Circulation

AHA STATISTICAL UPDATE

Heart Disease and Stroke Statistics—

2019 Update
A Report From the American Heart Association

WRITING GROUP MEMBERS

Each chapter listed in the Table of
Emelia J. Benjamin, MD, ScM, FAHA, Chair Kunihiro Matsushita, MD, PhD, FAHA
Contents (see next page) is a hy-
Paul Muntner, PhD, MHS, FAHA, Vice Chair Andrew E. Moran, MD, MPH, FAHA
perlink to that chapter. The reader
Alvaro Alonso, MD, PhD, FAHA Michael E. Mussolino, PhD, FAHA
clicks the chapter name to access
Marcio S. Bittencourt, MD, PhD, MPH Martin O’Flaherty, MD, MSc, PhD
that chapter.
Clifton W. Callaway, MD, FAHA Ambarish Pandey, MD, MSCS
April P. Carson, PhD, MSPH, FAHA Amanda M. Perak, MD, MS
Alanna M. Chamberlain, PhD Wayne D. Rosamond, PhD, MS, FAHA
Alexander R. Chang, MD, MS Gregory A. Roth, MD, MPH, FAHA
Susan Cheng, MD, MMSc, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH,
Sandeep R. Das, MD, MPH, MBA, FAHA FAHA
Francesca N. Delling, MD, MPH Gary M. Satou, MD, FAHA
Luc Djousse, MD, ScD, MPH Emily B. Schroeder, MD, PhD, FAHA
Mitchell S.V. Elkind, MD, MS, FAHA Svati H. Shah, MD, MHS, FAHA
Jane F. Ferguson, PhD, FAHA Nicole L. Spartano, PhD
Myriam Fornage, PhD, FAHA Andrew Stokes, PhD
Downloaded from http://ahajournals.org by on February 7, 2019

Lori Chaffin Jordan, MD, PhD, FAHA David L. Tirschwell, MD, MS, MSc, FAHA
Sadiya S. Khan, MD, MSc Connie W. Tsao, MD, MPH, Vice Chair Elect
Brett M. Kissela, MD, MS Mintu P. Turakhia, MD, MAS, FAHA
Kristen L. Knutson, PhD Lisa B. VanWagner, MD, MSc, FAST
Tak W. Kwan, MD, FAHA John T. Wilkins, MD, MS, FAHA
Daniel T. Lackland, DrPH, FAHA Sally S. Wong, PhD, RD, CDN, FAHA
Tené T. Lewis, PhD Salim S. Virani, MD, PhD, FAHA, Chair Elect
Judith H. Lichtman, PhD, MPH, FAHA On behalf of the American Heart Association
Chris T. Longenecker, MD Council on Epidemiology and Prevention
Matthew Shane Loop, PhD Statistics Committee and Stroke Statistics
Pamela L. Lutsey, PhD, MPH, FAHA Subcommittee
Seth S. Martin, MD, MHS, FAHA

Key Words:  AHA Scientific Statements

◼ cardiovascular diseases
◼ epidemiology ◼ risk factors ◼ statistics
◼ stroke

© 2019 American Heart Association, Inc.

https://www.ahajournals.org/journal/circ

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e1

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

TABLE OF CONTENTS advocates, and others seeking the best available data
CLINICAL STATEMENTS

on these factors and conditions. Cardiovascular disease

Each chapter listed here is a hyperlink. Click on the chapter
AND GUIDELINES

name to be taken to that chapter. (CVD) produces immense health and economic burdens
in the United States and globally. The Statistical Update
Summary . . . . . . . . . . . . . . . . . . . . . . . . . e2 also presents the latest data on a range of major clinical
1. About These Statistics . . . . . . . . . . . . . . . . e12 heart and circulatory disease conditions (including stroke,
2. Cardiovascular Health . . . . . . . . . . . . . . . . e15
congenital heart disease, rhythm disorders, subclinical
Health Behaviors atherosclerosis, coronary heart disease [CHD], heart fail-
3. Smoking/Tobacco Use . . . . . . . . . . . . . . . . e32 ure [HF], valvular disease, venous disease, and peripheral
4. Physical Inactivity . . . . . . . . . . . . . . . . . . e44
arterial disease) and the associated outcomes (including
5. Nutrition . . . . . . . . . . . . . . . . . . . . . . e64
6. Overweight and Obesity . . . . . . . . . . . . . . e83
quality of care, procedures, and economic costs). Since
2007, the annual versions of the Statistical Update have
Health Factors and Other Risk Factors
been cited >20 000 times in the literature.
7. High Blood Cholesterol and Other Lipids . . . . . . e106
8. High Blood Pressure . . . . . . . . . . . . . . . . e119
Each annual version of the Statistical Update under-
9. Diabetes Mellitus . . . . . . . . . . . . . . . . . . e138 goes revisions to include the newest nationally rep-
10. Metabolic Syndrome . . . . . . . . . . . . . . . . e157 resentative data, add additional relevant published
11. Kidney Disease . . . . . . . . . . . . . . . . . . . e178 scientific findings, remove older information, add new
12. Sleep . . . . . . . . . . . . . . . . . . . . . . . . e194 sections or chapters, and increase the number of ways
Cardiovascular Conditions/Diseases to access and use the assembled information. This
13. Total Cardiovascular Diseases . . . . . . . . . . . . e202 year-long process, which begins as soon as the previ-
14. Stroke (Cerebrovascular Disease) . . . . . . . . . . e226 ous Statistical Update is published, is performed by the
15. Congenital Cardiovascular Defects and AHA Statistics Committee faculty volunteers and staff
Kawasaki Disease . . . . . . . . . . . . . . . . . e272 and government agency partners. This year’s edition
16. Disorders of Heart Rhythm . . . . . . . . . . . . . e291 includes data on the monitoring and benefits of car-
17. Sudden Cardiac Arrest, Ventricular Arrhythmias, diovascular health in the population, metrics to assess
and Inherited Channelopathies . . . . . . . . . . . e322
and monitor healthy diets, a new chapter on sleep, an
18. Subclinical Atherosclerosis . . . . . . . . . . . . . e346
enhanced focus on social determinants of health, a
19. Coronary Heart Disease, Acute Coronary
Syndrome, and Angina Pectoris . . . . . . . . . . e360 substantively expanded focus on the global burden of
Downloaded from http://ahajournals.org by on February 7, 2019

20. Cardiomyopathy and Heart Failure . . . . . . . . . e383 CVD, and further evidence-based approaches to chang-
21. Valvular Diseases . . . . . . . . . . . . . . . . . . e400 ing behaviors, implementation strategies, and implica-
22. Venous Thromboembolism (Deep Vein tions of the AHA’s 2020 Impact Goals. Below are a few
Thrombosis and Pulmonary Embolism), Chronic highlights from this year’s Statistical Update.
Venous Insufficiency, Pulmonary Hypertension . . . . e417
23. Peripheral Artery Disease and Aortic Diseases . . . . e426
Outcomes
Cardiovascular Health (Chapter 2)
24. Quality of Care . . . . . . . . . . . . . . . . . . . e442 • New data expand the benefits of better cardio-
25. Medical Procedures . . . . . . . . . . . . . . . . e456 vascular health to include lower prevalence of
26. Economic Cost of Cardiovascular Disease . . . . . e461 aortic sclerosis and stenosis, improved progno-
Supplemental Materials sis after myocardial infarction (MI), lower risk of
27. At-a-Glance Summary Tables . . . . . . . . . . . . e467 atrial fibrillation, and greater positive psychologi-
28. Glossary . . . . . . . . . . . . . . . . . . . . . . e471 cal functioning (dispositional optimism).
• Among children, from 1999 to 2000 to 2015
to 2016, prevalence of nonsmoking, ideal total
SUMMARY cholesterol, and ideal BP improved. For example,
Each year, the American Heart Association (AHA), in con- nonsmoking among children aged 12 to 19 years
junction with the National Institutes of Health and other went from 76% to 94%. However, meeting ideal
government agencies, brings together in a single docu- levels for physical activity, body mass index (BMI),
ment the most up-to-date statistics related to heart dis- and blood glucose did not improve. For example,
ease, stroke, and the cardiovascular risk factors in the AHA’s prevalence of ideal BMI declined from 70% to
My Life Check − Life’s Simple 7 (Figure1), which include 60% over the same time period.
core health behaviors (smoking, physical activity, diet, and
weight) and health factors (cholesterol, blood pressure
[BP], and glucose control) that contribute to cardiovascular Smoking/Tobacco Use (Chapter 3)
health. The Statistical Update represents a critical resource • The prevalence of current smoking in the United
for the lay public, policy makers, media professionals, States in 2016 was 15.5% for adults, and 3.4% of
clinicians, healthcare administrators, researchers, health adolescents smoked cigarettes in the past month.

e2 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

CLINICAL STATEMENTS
AND GUIDELINES
Figure. AHA’s My Life Check – Life’s Simple 7.
Seven approaches to staying heart healthy: be active, keep a healthy weight, learn about cholesterol, don’t smoke or use
smokeless tobacco, eat a heart‐healthy diet, keep blood pressure healthy, and learn about blood sugar and diabetes mellitus.

Although there has been a consistent decline in adult television and tablet use has decreased
tobacco use in the United States, significant dispari- modestly in recent years, adult smartphone use
ties persist. Substantially higher tobacco use preva- increased from the 2012 to 2014 period to 2017
lence rates are observed in American Indian/Alaska by >1 hour each day.
Natives and lesbian, gay, bisexual, and transgender
populations, as well as among individuals with low
socioeconomic status, those with mental illness, Nutrition (Chapter 5)
individuals with HIV who are receiving medical care, • In a 2013 to 2014 nationally representative sam-
and those who are active-duty military. ple of 827 nonpregnant, noninstitutionalized US
• Tobacco use remains a leading cause of prevent- adults, estimated mean sodium intake by 24-hour
able death in the United States and globally. It urinary excretion was 4205 mg/d for males and
was estimated to account for 7.1 million deaths 3039 mg/d for females. In a diverse sample of
worldwide in 2016. 450 US adults in 3 geographic locations, ≈70%
Downloaded from http://ahajournals.org by on February 7, 2019

• Over the past 6 years, there has been a sharp of sodium was added to food outside the home,
increase in e-cigarette use among adolescents, 13% to 16% was inherent to food, 4% to 9%
and e-cigarettes are now the most commonly was added in home food preparation, 3% to 8%
used tobacco product in this demographic. was added at the table, and <1% was from dietary
• Policy-level interventions such as Tobacco 21 Laws supplements and home tap water; amounts var-
and MPOWER are being adopted and have been ied modestly by race/ethnicity.
associated with reductions in tobacco use inci- • After a 1 peso per liter excise tax on sugar-sweet-
dence and prevalence. ened beverages (SSBs) was implemented in Mexico
in January 2014, SSB purchases were reduced by
5.5% after 1 year and 9.7% after 2 years com-
Physical Inactivity (Chapter 4) pared with predicted SSB purchases based on pre-
• The trends in the prevalence of self-reported inac- tax trends. The effect of the SSB tax was greatest
tivity among adults decreased from 1998 to 2016, among households of the lowest socioeconomic
with the largest drop occurring in the past decade, status. A similar 1 cent per ounce excise tax on
from 40.1% to 26.9% between 2007 and 2016, SSBs was implemented in Berkeley, California, in
respectively. Despite this decrease in inactivity over January 2015, and SSB sales declined by 9.6%
recent years, currently, <23% of adults report par- after 1 year compared with predicted SSB pur-
ticipating in adequate leisure-time aerobic and chases based on pretax trends.
muscle-strengthening activity to meet the 2008 • The Special Supplemental Nutrition Program for
federal guidelines for physical activity. Women, Infants, and Children food package was
• Converging evidence from epidemiological stud- revised in 2009 to include more fruits, vegetables,
ies suggests that limiting sedentary time is asso- whole grains, and lower-fat milk. These food
ciated with a lower risk of cardiovascular events package revisions were associated with a signifi-
and mortality after accounting for other tradi- cant improvement in Healthy Eating Index-2010
tional risk factors and physical activity levels. score (3.7 higher Healthy Eating Index points;
• A Nielsen report from 2017 suggests that technol- 95% CI, 0.6–6.9). By contrast, participation in
ogy use is changing rapidly, with potential implica- the Supplemental Nutrition Assistance Program
tions for influencing sedentary behavior. Although (SNAP), which does not regulate nutritional

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e3

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

quality, was associated with less healthy house- using guideline thresholds from the Seventh
CLINICAL STATEMENTS

hold purchases (15–20 more calories from SSBs Report of the Joint National Committee on
AND GUIDELINES

per person per day, 174–195 more milligrams of Prevention, Detection, Evaluation, and Treatment
sodium per person per day, and 0.52 fewer grams of High Blood Pressure.
of fiber per person per day). • In prospective follow-up of the REGARDS, MESA
(Multi-Ethnic Study of Atherosclerosis), and JHS
(Jackson Heart Study) cohorts, 63.0% of incident
Overweight and Obesity (Chapter 6) CVD events occurred in participants with systolic BP
• According to NHANES (National Health and (SBP) <140 mm Hg and diastolic BP <90 mm Hg.
Nutrition Examination Survey) 2015 to 2016, • US non-Hispanic (NH) blacks (13.2%) are more
39.6% of US adults and 18.5% of youths were likely than NH Asians (11.0%), NH whites (8.6%),
obese, and 7.7% of adults and 5.6% of youth or Hispanics (7.4%) to use home BP monitoring
had severe obesity. The overall prevalence of obe- on a weekly basis.
sity and severe obesity in youth (aged 2–19 years) • In 2015, the worldwide prevalence of SBP ≥140
did not increase significantly from 2007 to 2008 mm Hg was estimated to be 20 526 per 100 000.
to 2015 to 2016. However, the age-standardized This represents an increase from 17  307 per
prevalence of obesity and severe obesity increased 100 000 in 1990. Also, the prevalence of SBP
significantly in the past decade (from 2007–2008 of 110 to 115 mm Hg or higher increased from
to 2015–2016) among adults. 73  119 per 100  000 to 81  373 per 100  000
• A recent mendelian randomization study of par- between 1990 and 2015. There were 3.47 billion
ticipants from 7 prospective cohorts demonstrated adults worldwide with SBP of 110 to 115 mm Hg
that genetic variants associated with higher BMI or higher in 2015.
were significantly associated with incident atrial • Among African Americans in the JHS not taking
fibrillation, which supports a causal relationship antihypertensive medication, the prevalence of
between obesity and atrial fibrillation. clinic hypertension (mean SBP ≥140 mm Hg or
• In a study of 189 672 participants from 10 US lon- mean diastolic BP ≥90 mm Hg) was 14.3%, the
gitudinal cohort studies, obesity was associated prevalence of daytime hypertension (mean day-
with a shorter total longevity and greater pro- time SBP ≥135 mm Hg or mean daytime diastolic
portion of life lived with CVD. Higher BMI was
Downloaded from http://ahajournals.org by on February 7, 2019

BP ≥85 mm Hg) was 31.8%, and the prevalence

associated with a significantly higher risk of death of nighttime hypertension (mean nighttime SBP
attributable to CVD. ≥120 mm Hg or mean nighttime diastolic BP ≥70
mm Hg) was 49.4%. Among JHS participants tak-
ing antihypertensive medication, the prevalence
High Blood Cholesterol and Other Lipids estimates were 23.1% for clinic hypertension,
(Chapter 7) 43.0% for daytime hypertension, and 61.7% for
• Between 1999 and 2016, mean total cholesterol nighttime hypertension.
levels declined overall and across all subgroups of
race.
Diabetes Mellitus (Chapter 9)
• Recent data from the REGARDS study (Reasons
for Geographic and Racial Differences in Stroke) • On the basis of data from NHANES 2013 to
indicate that even after accounting for access to 2016, of US adults, an estimated 26 million
medical care, there are disparities in the use of (9.8%) have diagnosed DM, 9.4 million (3.7%)
statins in individuals with diabetes mellitus (DM). have undiagnosed DM, and 91.8 million (37.6%)
White males with DM and low-density lipopro- have prediabetes.
tein cholesterol >100 mg/dL were more likely to • In 2017, the cost of DM was estimated at $327
be prescribed statins (66.0%) than black males billion (Table 9-1), up 26% from 2012, account-
(57.8%), white females (55.0%), and black ing for 1 in 4 healthcare dollars. Of these costs,
females (53.6%). $237 billion were direct medical costs and $90
billion resulted from reduced productivity.
• On the basis of NHANES 2013 to 2016 data for
High Blood Pressure (Chapter 8) adults with DM, 20.9% had their DM treated
• In 2011 to 2014, the prevalence of hypertension and controlled (fasting glucose <126 mg/dL),
among US adults was 45.6% (95% CI, 43.6%– 45.2% had their DM treated but uncontrolled,
47.6%) using the new BP thresholds from the 9.2% were aware they had DM but were not
2017 American College of Cardiology/AHA guide- treated, and 24.7% were undiagnosed and not
lines versus 31.9% (95% CI, 30.1%–33.7%) treated.

e4 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

Metabolic Syndrome (Chapter 10) hours per night; RR, 1.35; 95% CI, 1.29–1.41)

CLINICAL STATEMENTS
were associated with a greater risk of all-cause
• The overall prevalence of metabolic syndrome has

AND GUIDELINES
mortality. In addition, short sleep (<7 hours per
remained stable at 34.3% across all sex, age, and
night) was associated with total CVD (RR, 1.14;
racial/ethnic groups since 2008 according to data
95% CI, 1.09–1.20) and CHD (RR, 1.22; 95%
from NHANES 2007 to 2014. ​
CI, 1.13–1.31) but not stroke (RR, 1.09; 95% CI,
• In a recent meta-analysis of 26 609 young adults
0.99–1.19). Long sleep duration was associated
(aged 18–30 years) across 34 studies, the preva-
with total CVD (RR, 1.36; 95% CI, 1.26–1.48),
lence of metabolic syndrome was 4.8% to 7%
CHD (RR, 1.21; 95% CI, 1.12–1.30), and stroke
depending on the definition used.
(RR, 1.45; 95% CI, 1.30–1.62).
• In addition to well-established associations with
• A meta-analysis of 27 cohort studies found that
poor CVD outcomes and all-cause mortality,
mild obstructive sleep apnea (hazard ratio, 1.19;
the presence of metabolic syndrome also has
95% CI, 0.86–1.65), moderate obstructive sleep
been shown to be associated with poorer can-
apnea (1.28; 95% CI, 0.96–1.69), and severe
cer outcomes, including increased risk of cancer
obstructive sleep apnea (2.13; 95% CI, 1.68–
recurrence, cancer-related mortality, and overall
2.68) were associated with all-cause mortality in
mortality.​
a dose-response fashion. Only severe obstructive
sleep apnea was associated with cardiovascular
Kidney Disease (Chapter 11) mortality (hazard ratio, 2.73; 95% CI, 1.94–3.85).
• According to the United States Renal Data System,
the overall prevalence of chronic kidney disease Total Cardiovascular Diseases
in the United States among NHANES participants
(Chapter 13)
≥20 years of age was 14.8% (95% CI, 13.6%–
16.0%) in 2011 to 2014. • On the basis of NHANES 2013 to 2016 data,
• In 3 community-based cohort studies (JHS, the prevalence of CVD (comprising CHD, HF,
Cardiovascular Health Study, and MESA), abso- stroke, and hypertension) in adults ≥20 years of
lute incidence rates (per 1000 person-years) for age is 48.0% overall (121.5 million in 2016) and
HF, CHD, and stroke for participants with versus increases with advancing age in both males and
Downloaded from http://ahajournals.org by on February 7, 2019

without chronic kidney disease were 22 versus females. CVD prevalence excluding hypertension
6.2 for HF, 24.5 versus 8.4 for CHD, and 13.4 ver- (CHD, HF, and stroke only) is 9.0% overall (24.3
sus 4.8 for stroke. million in 2016).
• A recent meta-analysis of 43 studies examin- • In 2016, 2 744 248 resident deaths were registered
ing associations between socioeconomic indica- in the United States. Ten leading causes accounted
tors (income, education, and occupation) found for 74.1% of all registered deaths. The 10 leading
that lower socioeconomic status, particularly causes of death in 2016 were the same as in 2015;
income, was associated with a higher prevalence these include heart disease (No. 1), cancer (No. 2),
of chronic kidney disease and faster progres- unintentional injuries (No. 3), chronic lower respi-
sion to end-stage renal disease. This association ratory diseases (No. 4), stroke (No. 5), Alzheimer
was observed in higher- versus lower- or middle- disease (No. 6), DM (No. 7), influenza and pneu-
income countries and was more pronounced in monia (No. 8), kidney disease (No. 9), and suicide
the United States, relative to Europe. (No. 10). Seven of the 10 leading causes of death
had a decrease in age-adjusted death rates. The
age-adjusted death rates decreased 1.8% for
Sleep (Chapter 12) heart disease, 1.7% for cancer, 2.4% for chronic
• Data from the Centers for Disease Control and lower respiratory diseases, 0.8% for stroke, 1.4%
Prevention indicated that the age-adjusted prev- for DM, 11.2% for influenza and pneumonia, and
alence of healthy sleep duration (≥7 hours) was 2.2% for kidney disease. The age-adjusted rate
65.2% for all Americans and was lower among increased 9.7% for unintentional injuries, 3.1%
Native Hawaiians/Pacific Islanders (53.7%), NH for Alzheimer disease, and 1.5% for suicide.
blacks (54.2%), multiracial NH people (53.6%), • In 2016, ≈17.6 million (95% CI, 17.3–18.1 mil-
and American Indians/Alaska Natives (59.6%) lion) deaths were attributed to CVD globally,
compared with NH whites (66.8%), Hispanics which amounted to an increase of 14.5% (95%
(65.5%), and Asians (62.5%). CI, 12.1%–17.1%) from 2006. The age-adjusted
• A meta-analysis of 43 studies indicated that both death rate per 100 000 population was 277.9 (95%
short sleep (<7 hours per night; relative risk [RR], CI, 272.1–284.6), which represents a decrease of
1.13; 95% CI, 1.10–1.17) and long sleep (>8 14.5% (95% CI, −16.2% to −12.5%) from 2006.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e5

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

Stroke (Cerebrovascular Disease) heart disease surgery continue to decrease. In

CLINICAL STATEMENTS

(Chapter 14) a recent study from the Pediatric Cardiac Care

AND GUIDELINES

Consortium’s US-based multicenter data registry,

• An estimated 7.0 million Americans ≥20 years of which examined 35 998 patients with a median
age self-report having had a stroke, and the over- follow-up of 18 years, the overall standardized
all stroke prevalence was an estimated 2.5%. mortality ratio was 8.3% (95% CI, 8.0%–8.7%).
• In the National (Nationwide) Inpatient Sample,
hospitalizations for acute ischemic stroke increased
significantly for both males and females and for Disorders of Heart Rhythm (Chapter 16)
certain racial/ethnic groups among younger adults • The lifetime risk of atrial fibrillation recently has
aged 18 to 54 years. From 1995 through 2011 to been estimated to be ≈1 in 3 among whites and 1
2012, stroke hospitalization rates almost doubled in 5 among blacks in the United States.
for males aged 18 to 34 and 35 to 44 years, with a • Individuals with optimal cardiovascular health
41.5% increase among males aged 35 to 44 years have a 32% lower risk of atrial fibrillation.
from 2003 to 2004 through 2011 to 2012. • Approximately 0.7 million (13%) of the ≈5.3 mil-
• In analyses using data from the Global Burden of lion cases of atrial fibrillation in the United States
Disease Study, ≈90% of the stroke risk could be are undiagnosed.
attributed to modifiable risk factors (such as high • Obese individuals have a 51% increased risk of
BP, obesity, hyperglycemia, hyperlipidemia, and developing atrial fibrillation compared with their
renal dysfunction), and 74% could be attributed to nonobese counterparts.
behavioral risk factors, such as smoking, sedentary • Patients with atrial fibrillation admitted to rural
lifestyle, and an unhealthy diet. Globally, 29% of hospitals had a 17% higher risk of death than
the risk of stroke was attributable to air pollution. those admitted to urban hospitals.
• Although global age-adjusted mortality rates
for ischemic and hemorrhagic stroke decreased
between 1990 and 2015, the absolute number Sudden Cardiac Arrest, Ventricular
of people who have strokes annually, as well as Arrhythmias, and Inherited
related deaths and disability-adjusted life-years lost, Channelopathies (Chapter 17)
increased. The majority of global stroke burden is
Downloaded from http://ahajournals.org by on February 7, 2019

• Prevalence of reported current training in cardio-

in low-income and middle-income countries. pulmonary resuscitation was 18%, and prevalence
• In analyses of 1 165 960 Medicare fee-for-service of having cardiopulmonary resuscitation training at
beneficiaries hospitalized between 2009 and 2013 some point was 65% in a survey of 9022 people in
for ischemic stroke, patients treated at primary the United States in 2015. The prevalence of car-
stroke centers certified between 2009 and 2013 diopulmonary resuscitation training was lower in
had lower in-hospital (odds ratio [OR], 0.89; 95% Hispanic/Latino people, older people, people with
CI, 0.85–0.94), 30-day (hazard ratio, 0.90; 95% CI, less formal education, and the lower-income group.
0.89–0.92), and 1-year (hazard ratio, 0.91; 95% CI, • Incidence of emergency medical services–assessed
0.90–0.92) mortality than those treated at noncer- out-of-hospital cardiac arrest in people of any
tified hospitals, after adjustment for demographic age was 110.8 per 100 000 population (95%
and clinical factors. Hospitals certified between CI, 108.9–112.6), or 356  461 people (quasi-
2009 and 2013 also had lower in-hospital and CI, 350  349–362  252) based on extrapolation
30-day mortality than centers certified before 2009. from the ROC registry (Resuscitation Outcomes
Consortium) of out-of-hospital cardiac arrest
to the total population of the United States
Congenital Cardiovascular Defects and
(325 193 000 as of June 9, 2017).
Kawasaki Disease (Chapter 15) • Survival of hospitalization after cardiac arrest var-
• Although estimates of birth prevalence/overall ied between academic medical centers and was
prevalence of congenital cardiovascular defects higher in hospitals with higher cardiac arrest vol-
appear relatively stable, a general trend toward ume, higher surgical volume, greater availability
improved outcome/survival continues, which has of invasive cardiac services, and more affluent
led to an expanding population of adult congeni- catchment areas.
tal heart disease patients.
• Although there remains increased mortality in
patients with congenital cardiovascular defects Subclinical Atherosclerosis (Chapter 18)
compared with the general population, the • Coronary computed tomographic angiography,
standardized mortality ratios after congenital which includes assessment of the severity of

e6 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

coronary artery stenosis, plaque composition, compared with an estimated 5.7 million between

CLINICAL STATEMENTS
and coronary segment location, does not offer 2009 and 2012.

AND GUIDELINES
additional prognostic value for all-cause mortality • Primary prevention of HF can be augmented by
beyond traditional risk factors and coronary cal- greater adherence to the Life’s Simple 7 goals;
cium in asymptomatic individuals. optimal profiles in smoking, BMI, physical activity,
• In contrast to the US population, the majority diet, cholesterol, BP, and glucose are associated
(≈85%) of middle-aged people living a forager- with a lower lifetime risk of HF and more favor-
horticulturalist lifestyle in the Bolivian Amazon able cardiac structure and functional parameters
remain free of coronary artery calcium, which indi- by echocardiography.
cates that coronary atherosclerosis can typically be • Of incident hospitalized HF events, approximately
avoided by maintaining a low lifetime burden of half are characterized by reduced ejection frac-
risk factors. Even among those Bolivian Amazon tion and the other half by preserved ejection frac-
individuals >75 years of age, 65% remained free tion. The prevalence of HF with preserved ejection
of coronary artery calcium. fraction, compared with prevalence of HF with
reduced ejection fraction, appears to be increas-
ing over time along with aging of the population.
Coronary Heart Disease, Acute Coronary
Syndrome, and Angina Pectoris (Chapter 19)
Valvular Diseases (Chapter 21)
• Data from the BRFSS (Behavioral Risk Factor
Surveillance System) 2016 survey indicated that • Although rheumatic heart disease is uncommon
4.4% of respondents had been told that they had in high-income countries such as the United
had an MI and 4.1% of respondents had been States, it remains an important cause of morbidity
told that they had angina or CHD. and mortality in low- and middle-income coun-
• From 2006 to 2016, the annual death rate attrib- tries. In 2015, 33.4 million people were estimated
utable to CHD declined 31.8%. CHD age-adjusted to be living with rheumatic heart disease around
death rates per 100 000 were 132.3 for NH white the world, with sub-Saharan Africa, South Asia,
males, 146.5 for NH black males, and 95.6 for and Oceania having the highest concentration of
Hispanic males; for NH white females, the rate was disability-adjusted life-years attributable to rheu-
matic heart disease.
Downloaded from http://ahajournals.org by on February 7, 2019

67.9; for NH black females, it was 85.4; and for

Hispanic females, it was 54.6 (unpublished National • Admissions for endocarditis related to injection
Heart, Lung, and Blood Institute tabulation). drug use have risen in recent years in parallel
• Compared with nonparticipants, participants in with the opioid drug crisis. The prevalence of
SNAP have twice the risk of CVD mortality, which documented intravenous drug use among people
likely reflects differences in socioeconomic, envi- admitted to a hospital because of endocarditis in
ronmental, and behavioral characteristics. the National (Nationwide) Inpatient Sample rose
• In the BRFSS from 2005 to 2015, <40% of patients from 4.3% in 2008 to 10% in 2014.
self-reported participation in cardiac rehabilitation
after an acute MI. Between 2011 and 2015, com- Venous Thromboembolism (Deep Vein
pared with patients who did not participate in cardiac
Thrombosis and Pulmonary Embolism),
rehabilitation, those who declared such participa-
tion were less likely to be female (OR, 0.76; 95% CI, Chronic Venous Insufficiency, Pulmonary
0.65–0.90; P=0.002) or black (OR, 0.70; 95% CI, Hypertension (Chapter 22)
0.53–0.93; P=0.014), were less well educated (high • Traditional atherosclerotic risk factors, including
school versus college graduate: OR, 0.69; 95% CI, hypertension, hyperlipidemia, and DM, were not
0.59–0.81; P<0.001 and less than high school ver- associated with risk of venous thromboembo-
sus college graduate: OR, 0.47; 95% CI, 0.37–0.61; lism in a 2017 individual-level meta-analysis of
P<0.001), and were more likely to be retired or self- >240 000 participants from 9 cohorts. Cigarette
employed (OR, 1.39; 95% CI, 1.24–1.73; P=0.003). smoking was associated with provoked but not
with unprovoked venous thromboembolism
events.
Cardiomyopathy and Heart Failure • Emerging evidence suggests that autoimmune dis-
(Chapter 20) ease, such as lupus and Sjögren syndrome, could
• The prevalence of HF continues to rise over time be risk factors for venous thromboembolism.
with the aging population. In NHANES data, an • African Americans present with higher-sever-
estimated 6.2 million American adults ≥20 years ity chronic venous insufficiency and have less
of age (2.2%) had HF between 2013 and 2016 improvement with radiofrequency ablation.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e7

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

Peripheral Artery Disease and Aortic • The estimated direct costs of CVD and stroke
CLINICAL STATEMENTS

Diseases (Chapter 23) increased from $103.5 billion in 1996 to 1997 to

AND GUIDELINES

$213.8 billion in 2014 to 2015.

• A recent Danish trial in men aged 65 to 74 years • Between 2015 and 2035, the projected total
reported that screening of peripheral artery disease (direct and indirect) costs of total CVD are esti-
(with ankle-brachial index), abdominal aortic aneu- mated to remain relatively stable for 18- to
rysm (with abdominal ultrasound), and hypertension
44-year-olds, increase slightly for 45- to 64 year-
followed by optimal care resulted in a 7% lower risk
olds, and increase sharply for 65- to 79-year-olds
of 5-year mortality compared with no screening.
and adults aged ≥80 years.
• African Americans have a 37% higher amputa-
tion risk than white individuals. In adjusted analy-
ses, lower socioeconomic status was associated Conclusions
with a 12% higher risk for amputation. The AHA, through its Statistics Committee, continu-
• In 2017, the Centers for Medicare & Medicaid ously monitors and evaluates sources of data on heart
Services decided to cover supervised exercise ther- disease and stroke in the United States to provide the
apy (up to 36 sessions over 12 weeks) for eligible most current information available in the Statistical
symptomatic peripheral artery disease patients Update. The 2019 annual Statistical Update is the
with intermittent claudication. product of a full year’s worth of effort by dedicated
volunteer physicians and scientists, committed gov-
Quality of Care (Chapter 24) ernment professionals, and AHA staff members,
• Quality and performance measures for MI have been without whom publication of this valuable resource
relatively stable in recent years but have improved would be impossible. Their contributions are gratefully
longitudinally since data collection began. acknowledged.
• Among hospitals that care for Medicare fee-for- Emelia J. Benjamin, MD, ScM, FAHA, Chair
service beneficiaries, the implementation of hospi- Salim S. Virani, MD, PhD, FAHA, Chair Elect
tal readmission reduction programs was associated Paul Muntner, PhD, FAHA, Vice Chair
with a reduction in 30-day and 1-year hospitalization Connie W. Tsao, MD, MPH, Vice Chair Elect
rates but an increase in 30-day and 1-year mortality. Sally S. Wong, PhD, RD, CDN, FAHA, AHA Science and
Downloaded from http://ahajournals.org by on February 7, 2019

• According to national Medicare data from July Medicine Advisor

2015 through June 2016, the median (interquartile On behalf of the American Heart Association
range) hospital risk-standardized mortality rate for Epidemiology Council Statistics Committee and
MI was 13.1% (12.6%, 13.5%), and the median Stroke Statistics Subcommittee
(interquartile range) risk-standardized 30-day read-
mission rate was 15.8% (15.5%, 16.2%).
• According to national Medicare data from July ‍ARTICLE INFORMATION
2015 through June 2016, the median (interquartile The views expressed in this manuscript are those of the authors and do not
necessarily represent the views of the National Heart, Lung, and Blood Institute;
range) hospital risk-standardized mortality rate for
the National Institutes of Health; the US Department of Health and Human
HF was 11.6% (10.8%, 12.4%), and the median Services; or the US Department of Veterans Affairs.
(interquartile range) risk-standardized 30-day read- The American Heart Association makes every effort to avoid any actual or
mission rate was 21.4% (20.8%, 22.1%). potential conflicts of interest that may arise as a result of an outside relationship
or a personal, professional, or business interest of a member of the writing pan-
el. Specifically, all members of the writing group are required to complete and
Medical Procedures (Chapter 25) submit a Disclosure Questionnaire showing all such relationships that might be
perceived as real or potential conflicts of interest.
• Data from the Society of Thoracic Surgeons Adult A copy of the document is available at http://professional.heart.org/
statements by using either “Search for Guidelines & Statements” or the
Cardiac Surgery Database indicate that a total of “Browse by Topic” area. To purchase additional reprints, call 843-216-2533 or
159 869 procedures involved isolated coronary e-mail kelle.ramsay@wolterskluwer.com.
artery bypass grafting in 2016. The American Heart Association requests that this document be cited as
follows: Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Car-
• In 2017, 3244 heart transplantations were per- son AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L,
formed in the United States, the most ever. Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knut-
son KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop
MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O’Flaherty
Economic Cost of Cardiovascular Disease M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou
GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW,
(Chapter 26) Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; on behalf of the
• The average annual direct and indirect cost of American Heart Association Council on Epidemiology and Prevention Statistics
Committee and Stroke Statistics Subcommittee. Heart disease and stroke statis-
CVD and stroke in the United States was an esti- tics—2019 update: a report from the American Heart Association. Circulation.
mated $351.2 billion in 2014 to 2015. 2019;139:e1–e473. doi: 10.1161/CIR.0000000000000659.

e8 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

The expert peer review of AHA-commissioned documents (eg, scientific Permissions Request Form” appears in the second paragraph (https://www.

CLINICAL STATEMENTS
statements, clinical practice guidelines, systematic reviews) is conducted by heart.org/en/about-us/statements-and-policies/copyright-request-form).

AND GUIDELINES
the AHA Office of Science Operations. For more on AHA statements and
guidelines development, visit http://professional.heart.org/statements. Select
the “Guidelines & Statements” drop-down menu, then click “Publication Acknowledgments
Development.” We wish to thank our colleagues: Lucy Hsu, Michael Wolz, Sean Coady, and Dr
Permissions: Multiple copies, modification, alteration, enhancement, and/ Gina Wei, National Heart, Lung, and Blood Institute; Ian Golnik and Kathleen
or distribution of this document are not permitted without the express permis- Smith, AHA; and all the dedicated staff of the Centers for Disease Control and
sion of the American Heart Association. Instructions for obtaining permission Prevention and the National Heart, Lung, and Blood Institute for their valuable
are located at https://www.heart.org/permissions. A link to the “Copyright comments and contributions.

Disclosures
Writing Group Disclosures
Other Speakers’ Consultant/
Writing Group Research Bureau/ Expert Ownership Advisory
Member Employment Research Grant Support Honoraria Witness Interest Board Other
Emelia J. Benjamin Boston University School American Heart None None None None None None
of Medicine, Cardiology Association†; NIH/
Department NHLBI†; RWJF†; AHA/
NIH†
Paul Muntner University of Alabama at Amgen† None None None None None None
Birmingham, Department
of Epidemiology
Alvaro Alonso Emory University, NIH†; American Heart None None None None None None
Department of Association†
Epidemiology
Marcio S. University of Sao Paulo Sanofi* None None None None None None
Bittencourt
Clifton W. University of Pittsburgh,
Callaway Department of
Emergency Medicine
Downloaded from http://ahajournals.org by on February 7, 2019

April P. Carson University of Alabama at Centers for Disease None None None None None None
Birmingham, Department Control and Prevention†;
of Epidemiology National Heart, Lung,
and Blood Institute†;
National Institute for
Diabetes and Digestive
and Kidney Diseases†;
Amgen, Inc†
Alanna M. Mayo Clinic Health EpidStat Institute† None None None None None None
Chamberlain Sciences Research
Alexander R. Geisinger Health System None None None None None None None
Chang Nephrology
Susan Cheng Brigham and Women’s
Hospital, Cardiovascular
Medicine
Sandeep R. Das University of Texas None None None None None None None
Southwestern Medical
Center, Department of
Internal Medicine
Francesca N. University of California NHLBI† None None None None None None
Delling San Francisco,
Cardiovascular Research
Luc Djousse VA Boston Healthcare American Egg Board†; None None None None None American
System MAVERIC NIH† Egg Board
(salary)†
Mitchell S.V. Columbia University, BMS-Pfizer Alliance None None Auxilium†; None Abbott*; AHA/ASA
Elkind Department of for Eliquis*; Roche*; Merck/ Vascular (board
Neurology NINDS† Organon†; Dynamics* member)*;
LivaNova UpToDate
(Sorin)† (royalties)*;
Biogen*;
Medtronic*
(Continued )

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e9

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

Writing Group Disclosures Continued

CLINICAL STATEMENTS

Other Speakers’ Consultant/

AND GUIDELINES

Writing Group Research Bureau/ Expert Ownership Advisory

Member Employment Research Grant Support Honoraria Witness Interest Board Other
Jane F. Ferguson Vanderbilt University None None None None None None None
Medical Center, Division
of Cardiovascular
Medicine
Myriam Fornage University of Texas None None None None None None None
Health Science Center
at Houston, Institute of
Molecular Medicine
Lori Chaffin Vanderbilt University None None None None None None None
Jordan Medical Center,
Department of Pediatrics
Sadiya S. Khan Northwestern University NIH† None None None None None None
Brett M. Kissela University of Cincinnati None None None None None None None
College of Medicine
Kristen L. Knutson University of Chicago None None None None None Pfizer* None
Health Studies
Tak W. Kwan Mount Sinai Beth Israel, None None None None None None None
Department of Cardiology
Daniel T. Lackland Medical University None None None None None None None
of South Carolina,
Department of Neurology
Tené T. Lewis Emory University, None None None None None None None
Rollins School of Public
Health, Department of
Epidemiology
Judith H. Yale School of Public NIH* None None None None None None
Lichtman Health, Department
of Chronic Disease
Downloaded from http://ahajournals.org by on February 7, 2019

Epidemiology
Chris T. Case Western Reserve Medtronic None None None None None None
Longenecker University, School of Philanthropy*; Gilead
Medicine, Cardiology Sciences*
Matthew Shane University of North NHLBI (HCHS/SOL None None None None None None
Loop Carolina at Chapel Hill contract)†; NHLBI
(ARIC contract)†;
DENKA-SEIKEN†; Puget
Sound Bloodworks†
Pamela L. Lutsey University of Minnesota, NIH† None None None None None None
Division of Epidemiology
and Community Health
Seth S. Martin Johns Hopkins School of None None None None None None None
Medicine, Department
of Cardiology
Kunihiro Johns Hopkins Bloomberg Fukuda Denshi† None None None None Bristol-Myers None
Matsushita School of Public Squibb*;
Health, Department of Fukuda
Epidemiology Denshi*
Andrew E. Moran Columbia University None None None None None None None
Medicine
Michael E. NIH None None None None None None None
Mussolino
Martin O’Flaherty University of Liverpool, None None None None None None None
Department of Public
Health and Policy
Ambarish Pandey University of Texas Texas Health Resources None None None None None None
Southwestern Medical Clinical Scholarship†
Center, Cardiology

(Continued )

e10 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Summary

Writing Group Disclosures Continued

CLINICAL STATEMENTS
Other Speakers’ Consultant/

AND GUIDELINES
Writing Group Research Bureau/ Expert Ownership Advisory
Member Employment Research Grant Support Honoraria Witness Interest Board Other
Amanda M. Perak Lurie Children’s None None None None None None None
Wayne D. Gillings School of None None None None None None None
Rosamond Global Public Health,
University of North
Carolina, Department of
Epidemiology
Gregory A. Roth University of Washington, NHLBI†; Cardiovascular None None None None None None
Department of Medicine– Medical Research and
Cardiology Education Foundation†
Uchechukwu K.A. New York University, None None None None None None None
Sampson Department of
Population Health
Gary M. Satou UCLA None None None None None None None
Emily B. Schroeder Kaiser Permanente None None None None None None None
Colorado Institute for
Health Research
Svati H. Shah Duke University None None None None None None None
Medicine
Nicole L. Spartano Boston University, Alzheimer’s None None None None None None
Department of Association†; American
Preventative Medicine Heart Association†
and Epidemiology
Andrew Stokes Boston University Global Johnson & Johnson, None None None None None None
Health Inc†
David L. Tirschwell Harborview Medical None None None None None None None
Center, Department of
Neurology
Downloaded from http://ahajournals.org by on February 7, 2019

Connie W. Tsao Beth Israel Deaconess None None None None None None None
Medical Center
Department of Medicine
Mintu P. Turakhia Stanford University Janssen†; Apple†; None None None AliveCor* Medtronic*; JAMA
School of Medicine; AstraZeneca†; AHA† Abbott*; Cardiology
Veterans Affairs Palo iBeat* (income as
Alto Health Care System; editor)*
Center for Digital Health
Lisa B. VanWagner Northwestern University NIH†; Gore Medical† None Salix None None None None
Medicine Pharmaceuticals*
Salim S. Virani Michael E. DeBakey VA None None None None None None None
Medical Center, Baylor
College of Medicine
John T. Wilkins Northwestern University NIH K23† None None None None None None
Feinberg School of
Medicine, Preventive
Medicine
Sally S. Wong American Heart None None None None None None Hunter
Association College,
CUNY
(salary)*

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure
Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000
or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns
$10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*Modest.
†Significant.

REFERENCE
1. American Heart Association. My Life Check – Life’s Simple 7. https://www.
heart.org/en/healthy-living/healthy-lifestyle/my-life-check--lifes-simple-7.
Accessed November 9, 2018.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e11

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 1

1. ABOUT THESE STATISTICS • NAMCS—physician office visits

CLINICAL STATEMENTS

• National Home and Hospice Care Survey—staff,

AND GUIDELINES

Click here to return to the Table of Contents services, and patients of home health and hospice
agencies
• NHAMCS—hospital outpatient and ED visits
The AHA works with the NHLBI and other government
• NIS of the Agency for Healthcare Research and
agencies to derive the annual statistics in this Heart
Quality—hospital inpatient discharges, proce-
Disease and Stroke Statistics Update. This chapter
dures, and charges
describes the most important sources and the types of
• United States Renal Data System—kidney disease
data used from them. For more details, see Chapter 28
prevalence
of this document, the Glossary.
• WHO—mortality rates by country
The surveys used are the following:
• YRBSS—health-risk behaviors in youth and young
• ARIC—CHD and HF incidence rates
adults
• BRFSS—ongoing telephone health survey system
• GCNKSS—stroke incidence rates and outcomes
within a biracial population Disease Prevalence
• HCUP—hospital inpatient discharges and pro-
Prevalence is an estimate of how many people have a
cedures (discharged alive, dead, or status
condition at a given point or period in time. The NCHS/
unknown)
CDC conducts health examination and health interview
• MEPS—data on specific health services that
surveys that provide estimates of the prevalence of dis-
Americans use, how frequently they use them,
eases and risk factors. In this Update, the health inter-
the cost of these services, and how the costs are
view part of the NHANES is used for the prevalence of
paid
CVDs. NHANES is used more than the NHIS because in
• NHANES—disease and risk factor prevalence and
NHANES, AP is based on the Rose Questionnaire; esti-
nutrition statistics
mates are made regularly for HF; hypertension is based
• NHIS—disease and risk factor prevalence
on BP measurements and interviews; and an estimate
can be made for total CVD, including MI, AP, HF, stroke,
Abbreviations Used in Chapter 1
and hypertension.
AHA American Heart Association
A major emphasis of this Statistical Update is to
Downloaded from http://ahajournals.org by on February 7, 2019

AP angina pectoris
ARIC Atherosclerosis Risk in Communities Study
present the latest estimates of the number of people
BP blood pressure in the United States who have specific conditions to
BRFSS Behavioral Risk Factor Surveillance System provide a realistic estimate of burden. Most estimates
CDC Centers for Disease Control and Prevention based on NHANES prevalence rates are based on data
CHD coronary heart disease
collected from 2013 to 2016. These are applied to
CHS Cardiovascular Health Study
CVD cardiovascular disease
census population estimates for 2016. Differences in
DM diabetes mellitus population estimates cannot be used to evaluate pos-
ED emergency department sible trends in prevalence because these estimates are
FHS Framingham Heart Study based on extrapolations of rates beyond the data col-
GCNKSS Greater Cincinnati/Northern Kentucky Stroke Study lection period by use of more recent census population
HCUP Healthcare Cost and Utilization Project
estimates. Trends can only be evaluated by comparing
HD heart disease
HF heart failure
prevalence rates estimated from surveys conducted in
ICD International Classification of Diseases different years.
ICD-9-CM International Classification of Diseases, Clinical Modification, A major enhancement in the 2019 Statistical Update
9th Revision is the addition of a new chapter, Sleep (Chapter 12).
ICD-10 International Classification of Diseases, 10th Revision
Also this year, there is an emphasis on social deter-
MEPS Medical Expenditure Panel Survey
MI myocardial infarction
minants of health that are built across the various
NAMCS National Ambulatory Medical Care Survey chapters, and global estimates are provided where
NCHS National Center for Health Statistics available.
NHAMCS National Hospital Ambulatory Medical Care Survey
NHANES National Health and Nutrition Examination Survey
NHIS National Health Interview Survey Risk Factor Prevalence
NHLBI National Heart, Lung, and Blood Institute
NINDS National Institute of Neurological Disorders and Stroke
The NHANES 2013 to 2016 data are used in this
NIS National (Nationwide) Inpatient Sample Update to present estimates of the percentage of
PAD peripheral artery disease people with high lipid values, DM, overweight, and
WHO World Health Organization obesity. The NHIS 2015 data are used for the preva-
YRBSS Youth Risk Behavior Surveillance System lence of cigarette smoking and physical inactivity.

e12 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 1

Data for students in grades 9 through 12 are obtained numbers of deaths were tabulated from the electronic

CLINICAL STATEMENTS
from the YRBSS. mortality files of the NCHS/CDC website.

AND GUIDELINES
Incidence and Recurrent Attacks Population Estimates
An incidence rate refers to the number of new cases In this publication, we have used national population
of a disease that develop in a population per unit of estimates from the US Census Bureau for 20161 in the
time. The unit of time for incidence is not necessarily 1 computation of morbidity data. NCHS/CDC popula-
year, although incidence is often discussed in terms of tion estimates2 for 2016 were used in the computa-
1 year. For some statistics, new and recurrent attacks tion of death rate data. The Census Bureau website
or cases are combined. Our national incidence esti- contains these data, as well as information on the file
mates for the various types of CVD are extrapolations layout.
to the US population from the FHS, the ARIC study,
and the CHS, all conducted by the NHLBI, as well as
Hospital Discharges and Ambulatory
the GCNKSS, which is funded by the NINDS. The rates
change only when new data are available; they are Care Visits
not computed annually. Do not compare the incidence Estimates of the numbers of hospital discharges and
or the rates with those in past editions of the Heart numbers of procedures performed are for inpatients
Disease and Stroke Statistics Update (also known as discharged from short-stay hospitals. Discharges
the Heart and Stroke Statistical Update for editions include those discharged alive, dead, or with unknown
before 2005). Doing so can lead to serious misinter- status. Unless otherwise specified, discharges are listed
pretation of time trends. according to the first-listed (primary) diagnosis, and
procedures are listed according to all listed procedures
(primary plus secondary). These estimates are from the
Mortality HCUP 2014. Ambulatory care visit data include patient
Mortality data are generally presented according to visits to primary providers’ offices and hospital out-
the underlying cause of death. “Any-mention” mor- patient departments and EDs. Ambulatory care visit
tality means that the condition was nominally selected data reflect the first-listed (primary) diagnosis. These
Downloaded from http://ahajournals.org by on February 7, 2019

as the underlying cause or was otherwise mentioned estimates are from the NAMCS and NHAMCS of the
on the death certificate. For many deaths classified as NCHS/CDC. Data for community health centers, which
attributable to CVD, selection of the single most likely were included in estimates in previous years, were not
underlying cause can be difficult when several major available for 2015 NAMCS estimates included in this
comorbidities are present, as is often the case in the Update.
elderly population. It is useful, therefore, to know the
extent of mortality attributable to a given cause regard-
less of whether it is the underlying cause or a contribut- International Classification of Diseases
ing cause (ie, the “any-mention” status). The number Morbidity (illness) and mortality (death) data in the
of deaths in 2016 with any mention of specific causes United States have a standard classification system:
of death was tabulated by the NHLBI from the NCHS the ICD. Approximately every 10 to 20 years, the ICD
public-use electronic files on mortality. codes are revised to reflect changes over time in medi-
The first set of statistics for each disease in this cal technology, diagnosis, or terminology. If necessary
Update includes the number of deaths for which for comparability of mortality trends across the 9th and
the disease is the underlying cause. Two exceptions 10th ICD revisions, comparability ratios computed by
are Chapter 8 (High Blood Pressure) and Chapter the NCHS/CDC are applied as noted.3 Effective with
20 (Cardiomyopathy and Heart Failure). High BP, or mortality data for 1999, we are using the 10th revision
hypertension, increases the mortality risks of CVD (ICD-10).4 It will be a few more years before the 10th
and other diseases, and HF should be selected as an revision is systematically used for hospital discharge
underlying cause only when the true underlying cause data and ambulatory care visit data, which are based
is not known. In this Update, hypertension and HF on ICD-9-CM.5
death rates are presented in 2 ways: (1) As nominally
classified as the underlying cause and (2) as any-
mention mortality. Age Adjustment
National and state mortality data presented accord- Prevalence and mortality estimates for the United
ing to the underlying cause of death were computed States or individual states comparing demographic
from the mortality tables of the NCHS/CDC website groups or estimates over time are either age specific
or the CDC compressed mortality file. Any-mention or age adjusted to the year 2000 standard population

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e13

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 1

by the direct method.6 International mortality data are Race/Ethnicity

CLINICAL STATEMENTS

age adjusted to the European standard.7 Unless other-

Data published by governmental agencies for some
AND GUIDELINES

wise stated, all death rates in this publication are age

racial groups are considered unreliable because of the
adjusted and are deaths per 100 000 population.
small sample size in the studies. Because we try to
provide data for as many racial and ethnic groups as
Data Years for National Estimates possible, we show these data for informational and
comparative purposes.
In this Update, we estimate the annual number of new
(incidence) and recurrent cases of a disease in the United
States by extrapolating to the US population in 2014 Contacts
from rates reported in a community- or hospital-based
If you have questions about statistics or any points
study or multiple studies. Age-adjusted incidence rates
made in this Update, please contact the AHA National
by sex and race are also given in this report as observed in
Center, Office of Science & Medicine. Direct all media
the study or studies. For US mortality, most numbers and
inquiries to News Media Relations at http://newsroom.
rates are for 2016. For disease and risk factor prevalence,
heart.org/connect or 214-706-1173.
most rates in this report are calculated from the 2013
The AHA works diligently to ensure that this Update
to 2016 NHANES. Because NHANES is conducted only
is error free. If we discover errors after publication,
in the noninstitutionalized population, we extrapolated
we will provide corrections at http://www.heart.org/
the rates to the total US resident population on July 1,
statistics and in the journal Circulation.
2016, recognizing that this probably underestimates the
total prevalence, given the relatively high prevalence in
the institutionalized population. The numbers and rates REFERENCES
of hospital inpatient discharges for the United States are 1. US Census Bureau population estimates: historical data: 2000s. US Census
for 2014. Numbers of visits to primary providers’ offices Bureau website. http://www.census.gov/popest/. Accessed August 4,
and hospital EDs are for 2015, whereas hospital outpa- 2016.
2. Centers for Disease Control and Prevention. U.S. Census Populations With
tient department visits are for 2011. Except as noted, Bridged Race Categories. http://www.cdc.gov/nchs/nvss/bridged_race.
economic cost estimates are for 2014 to 2015. htm Accessed July 23, 2017.
3. National Center for Health Statistics. Health, United States, 2015: With
Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD:
Downloaded from http://ahajournals.org by on February 7, 2019

Cardiovascular Disease National Center for Health Statistics; 2015. http://www.cdc.gov/nchs/

data/hus/hus15.pdf. Accessed June 15, 2016.
For data on hospitalizations, primary provider office 4. World Health Organization. International Statistical Classification of
Diseases and Related Health Problems, Tenth Revision. 2008 ed. Geneva,
visits, and mortality, CVD is defined according to ICD Switzerland: World Health Organization; 2009.
codes given in Chapter 13 of the present document. 5. National Center for Health Statistics, Centers for Medicare and Medicaid
This definition includes all diseases of the circulatory Services. ICD-9-CM Official Guidelines for Coding and Reporting, 2011.
http://www.cdc.gov/nchs/data/icd/icd9cm_guidelines_2011.pdf.
system, as well as congenital CVD. Unless otherwise Accessed October 29, 2012.
specified, an estimate for total CVD does not include 6. Anderson RN, Rosenberg HM. Age standardization of death rates:
congenital CVD. Prevalence of CVD only includes implementation of the year 2000 standard. Natl Vital Stat Rep. 1998;
47:1–16, 20.
people with hypertension, HD, stroke, PAD, and dis- 7. World Health Organization. World Health Statistics Annual. Geneva,
eases of the veins. Switzerland: World Health Organization; 1998.

e14 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

2. CARDIOVASCULAR HEALTH health can also be represented as being ideal, inter-

CLINICAL STATEMENTS
mediate, or poor for each of the health behaviors and
See Tables 2-1 through 2-6 and Charts 2-1

AND GUIDELINES
health factors.1 Table  2-1 provides the specific defini-
through 2-12
tions for ideal, intermediate, and poor cardiovascular
health for each of the 7 metrics, both for adults and
Click here to return to the Table of Contents
for children.
This concept of cardiovascular health represented
In 2011, the AHA created a new set of central Strategic
a new focus for the AHA, with 3 central and novel
Impact Goals to drive organizational priorities for the
emphases:
current decade:
• An expanded focus on CVD prevention and pro-
By 2020, to improve the cardiovascular health motion of positive “cardiovascular health,” in
of all Americans by 20%, while reducing deaths addition to the treatment of established CVD.
from CVDs and stroke by 20%.1 • Efforts to promote both healthy behaviors (healthy
diet pattern, appropriate energy intake, PA, and
These goals introduced a new concept of cardiovascu-
nonsmoking) and healthy biomarker levels (opti-
lar health, characterized by 7 metrics (Life’s Simple 7),2
mal blood lipids, BP, glucose levels) throughout
including health behaviors (diet quality, PA, smoking,
the lifespan.
BMI) and health factors (blood cholesterol, BP, blood
• Population-level health promotion strategies to
glucose). Ideal cardiovascular health is defined by the
shift the majority of the public toward greater car-
absence of clinically manifest CVD together with the
diovascular health, in addition to targeting those
simultaneous presence of optimal levels of all 7 met-
individuals at greatest CVD risk, because healthy
rics, including not smoking and having a healthy diet
lifestyles in all domains are uncommon through-
pattern, sufficient PA, normal body weight, and nor-
out the US population.
mal levels of TC, BP, and fasting blood glucose, in the
Beginning in 2011, and recognizing the time lag in
absence of drug treatment (Table 2-1). Because a spec-
the nationally representative US data sets, this chap-
trum of cardiovascular health is possible and the ideal
ter in the annual Statistical Update has evaluated and
cardiovascular health profile is known to be rare in the
published metrics and information to provide insights
US population, a broader spectrum of cardiovascular
into both progress toward meeting the 2020 AHA
Downloaded from http://ahajournals.org by on February 7, 2019

Abbreviations Used in Chapter 2 goals and areas that require greater attention to meet
AF atrial fibrillation these goals. The AHA has advocated for raising the
AHA American Heart Association visibility of patient-reported cardiovascular health sta-
BMI body mass index tus, which includes symptom burden, functional sta-
BP blood pressure tus, and health-related quality of life, as an indicator
CAC coronary artery calcification
CHD coronary heart disease
of cardiovascular health in future organizational goal
CI confidence interval setting.3
CVD cardiovascular disease
DASH Dietary Approaches to Stop Hypertension
DBP diastolic blood pressure Relevance of Ideal Cardiovascular Health
DM diabetes mellitus • Since the AHA announced its 2020 Impact Goals,
F&V fruits and vegetables
multiple independent investigations (summaries
FPG fasting plasma glucose
HbA1c hemoglobin A1c (glycosylated hemoglobin)
below) have confirmed the importance of these
HBP high blood pressure metrics and the concept of cardiovascular health.
HF heart failure Findings include strong inverse, stepwise associa-
HR hazard ratio tions in the United States of the metrics and car-
IHD ischemic heart disease diovascular health with all-cause mortality, CVD
IMT intima-media thickness
mortality, and HF; with preclinical measures of ath-
MI myocardial infarction
NH non-Hispanic erosclerosis such as carotid IMT, arterial stiffness,
NHANES National Health and Nutrition Examination Survey and coronary artery calcium (CAC) prevalence
PA physical activity and progression; with physical functional impair-
PE pulmonary embolism ment and frailty4; and with cognitive decline and
REGARDS Reasons for Geographic and Racial Differences in Stroke
depression.4,5 Similar relationships have also been
RR relative risk
SBP systolic blood pressure
seen in non-US populations.4–9
SFat saturated fat • A recent study in a large Hispanic/Latino cohort
SSB sugar-sweetened beverage study in the United States found that associations
TC total cholesterol of CVD and cardiovascular health metrics com-
VTE venous thromboembolism pared favorably with existing national estimates;

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e15

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

however, some of the associations varied by sex — 7.5% (95% CI, 3.0%–14.7%) for abnormal
CLINICAL STATEMENTS

and heritage.10 glucose levels

AND GUIDELINES

• A recent study in blacks found that risk of incident • Data from the REGARDS cohort also demon-
HF was 61% lower among those with ≥4 ideal strated a stepwise association between cardiovas-
cardiovascular health metrics than among those cular health metrics and incident stroke. Using a
with 0 to 2 ideal metrics.11 cardiovascular health score scale ranging from 0
• Ideal health behaviors and ideal health factors are to 14, every unit increase in cardiovascular health
each independently associated with lower CVD was associated with an 8% lower risk of incident
risk in a stepwise fashion (Chart 2-1). In other stroke (HR, 0.92; 95% CI, 0.88–0.95), with a simi-
words, across any level of health behaviors, health lar effect size for white (HR, 0.91; 95% CI, 0.86–
factors are associated with incident CVD; con- 0.96) and black (HR, 0.93; 95% CI, 0.87–0.98)
versely, across any level of health factors, health participants.16
behaviors are still associated with incident CVD.12 • The Cardiovascular Lifetime Risk Pooling Project
• Analyses from the US Burden of Disease showed that adults with all-optimal risk factor lev-
Collaborators demonstrated that poor levels els (similar to having ideal cardiovascular health
of each of the 7 health factors and behaviors factor levels of cholesterol, blood sugar, and BP,
resulted in substantial mortality and morbidity as well as not smoking) have substantially longer
in the United States in 2010. The top risk factor overall and CVD-free survival than those who have
related to overall disease burden was suboptimal poor levels of ≥1 of these cardiovascular health
diet, followed by tobacco smoking, high BMI, factor metrics. For example, at an index age of 45
raised BP, high fasting plasma glucose, and physi- years, males with optimal risk factor profiles lived
cal inactivity.13 on average 14 years longer free of all CVD events,
• A stepwise association was present between and 12 years longer overall, than people with ≥2
the number of ideal cardiovascular health met- risk factors.17
rics and risk of death based on NHANES 1988 • Better cardiovascular health is associated with
to 2006 data.14 The HRs for people with 6 or less incident HF,18 less subclinical vascular dis-
7 ideal health metrics compared with 0 ideal ease,19,20 better global cognitive performance
health metrics were 0.49 (95% CI, 0.33–0.74) and cognitive function,21,22 lower prevalence23
for all-cause mortality, 0.24 (95% CI, 0.13–0.47) and incidence24 of depressive symptoms, lower
Downloaded from http://ahajournals.org by on February 7, 2019

for CVD mortality, and 0.30 (95% CI, 0.13–0.68) loss of physical functional status,25 longer leuko-
for IHD mortality.14 cyte telomere length,26 less end-stage renal dis-
• A recent meta-analysis of 9 prospective cohort ease,27 and less pneumonia, chronic obstructive
studies involving 12  878 participants reported pulmonary disease,28 VTE/PE,29 lower prevalence
that achieving the most ideal cardiovascular of aortic sclerosis and stenosis,30 better progno-
health metrics was associated with a lower risk of sis after MI,31 and lower risk of AF.32 In addition,
all-cause mortality (RR, 0.55; 95% CI, 0.37–0.80), a recent study among a sample of Hispanics/
cardiovascular mortality (RR, 0.25; 95% CI, 0.10– Latinos residing in the United States reported
0.63), CVD (RR, 0.20; 95% CI, 0.11–0.37), and that a measure of greater positive psychological
stroke (RR, 0.31; 95% CI, 0.25–0.38).15 functioning (dispositional optimism) was associ-
• The adjusted population attributable fractions for ated with higher cardiovascular health scores as
CVD mortality were as follows14: defined by the AHA.33
— 40.6% (95% CI, 24.5%–54.6%) for HBP • On the basis of NHANES 1999 to 2006 data, sev-
— 13.7% (95% CI, 4.8%–22.3%) for smoking eral social risk factors (low family income, low
— 13.2% (95% CI, 3.5%–29.2%) for poor diet education level, minority race, and single-living
— 11.9% (95% CI, 1.3%–22.3%) for insuffi- status) were related to lower likelihood of attain-
cient PA ing better cardiovascular health as measured by
— 8.8% (95% CI, 2.1%–15.4%) for abnormal Life’s Simple 7 scores.34
glucose levels • Cardiovascular health metrics are also asso-
• The adjusted population attributable fractions for ciated with lower healthcare costs. A recent
IHD mortality were as follows14: report from a large, ethnically diverse insured
— 34.7% (95% CI, 6.6%–57.7%) for HBP population35 found that people with 6 or 7 and
— 16.7% (95% CI, 6.4%–26.6%) for smoking those with 3 to 5 of the cardiovascular health
— 20.6% (95% CI, 1.2%–38.6%) for poor metrics in the ideal category had a $2021 and
diet $940 lower annual mean healthcare expendi-
— 7.8% (95% CI, 0%–22.2%) for insufficient ture, respectively, than those with 0 to 2 ideal
PA health metrics.

e16 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

Cardiovascular Health: Current — <1% of children meet all 7 criteria for ideal

CLINICAL STATEMENTS
Prevalence cardiovascular health.

AND GUIDELINES
• Charts 2-5 and 2-6 display the age-standardized
(See Table 2-2 and Charts 2-2
prevalence estimates of US adults meeting differ-
through 2-9) ent numbers of criteria for ideal cardiovascular
• The most up-to-date data on national prevalence health in 2013 to 2014, overall and stratified by
of ideal, intermediate, and poor levels of each of age, sex, and race.
the 7 cardiovascular health metrics are shown for — Approximately 2% of US adults meet 0 of
adolescents and teens (Chart 2-2) and for adults the 7 criteria at ideal levels, and another
(Chart 2-3). 15% meet only 1 of 7 criteria. Having ≤1
• For most metrics, the prevalence of ideal levels ideal metric is much more common among
of health behaviors and health factors is higher adults (17%) than among children (12–19
in US children than in US adults. The main years of age), for whom having ≤1 ideal met-
exceptions are diet and PA, for which the preva- ric is very rare (<1%).
lence of ideal levels in children is worse than in — Most US adults (≈62%) have 3 or fewer car-
adults. diovascular metrics in the ideal cardiovascu-
• Among US children aged 12 to 19 years (Chart lar health range.
2-2), the prevalence (unadjusted) of ideal levels of — Approximately 13% of US adults meet ideal
cardiovascular health behaviors and factors cur- levels in 5 categories, 5% have 6 ideal met-
rently varies from <1% for the healthy diet pat- rics, and virtually 0% meet all 7 criteria at
tern (ie, <1 in 100 US children meets at least 4 ideal levels.
of the 5 dietary components or a corresponding — Presence of ideal cardiovascular health by
AHA diet score of at least 80) to >85% for the age and sex is shown in Chart 2-5. Younger
smoking, BP, and fasting glucose metrics (unpub- adults are more likely to meet greater num-
lished AHA tabulation). bers of ideal metrics than are older adults.
• Among US adults (Chart 2-3), the age-standard- More than 60% of Americans >60 years of
ized prevalence of ideal levels of cardiovascular age have ≤2 metrics at ideal levels. At any
health behaviors and factors currently varies from age, females tend to have more metrics at
<1% for having a healthy diet pattern to up to ideal levels than do males.
Downloaded from http://ahajournals.org by on February 7, 2019

78% for never having smoked or being a former — Presence of ideal cardiovascular health
smoker who has quit for >12 months. In 2015 also varies by race (Chart 2-6). Blacks and
to 2016, only about half (49%) of all adults had Hispanics tend to have fewer metrics at
ideal levels of TC (<200 mg/dL). ideal levels than whites or other races.
• Age-standardized and age-specific prevalence Having ≥4 ideal metrics is most common
estimates for ideal cardiovascular health and among Asians (48%), followed by whites
for ideal levels of each of its components are (38%), Hispanics (34%), blacks (30%), and
shown for 2013 to 2014 and 2015 to 2016 in others (24%).
Table  2-2. NHANES 2013 to 2014 data were • Chart 2-7 displays the age-standardized percent-
used for some of the statistics that required ages of US adults and the percentages of children
nutritional data and for DM. The prevalence of who have ≥5 of the metrics (of 7 possible) at ideal
ideal levels across 7 health factors and health levels in 2007 to 2008 and 2013 to 2014.
behaviors generally was lower with increasing — Currently, nearly half (47%) of US children
age. The exception was diet, for which preva- 12 to 19 years of age have ≥5 metrics at ideal
lence of ideal levels was highest in older adults levels, with similar prevalence in boys (49%)
but still very low (<1%). and girls (46%).
• Chart 2-4 displays the prevalence estimates for — In comparison, only 18% of US adults have
the population of US children (12–19 years of ≥5 metrics at ideal levels, with lower preva-
age) meeting different numbers of criteria for lence in males (15%) than in females (22%).
ideal cardiovascular health (of 7 possible) in — All populations showed improvement com-
2013 to 2014. pared with baseline year 2007 to 2008.
— Few US children 12 to 19 years of age (≈4%) • Chart 2-8 displays the age-standardized percent-
meet <2 criteria for ideal cardiovascular ages of US adults and percentages of children by
health. race/ethnicity who have ≥5 of the metrics (of 7
— Approximately half of US children (48%) possible) at ideal levels.
meet 3 or 4 criteria for ideal cardiovascular — In adults, NH Asians tend to have a higher
health, and ≈47% meet 5 or 6 criteria. prevalence of having ≥5 metrics at ideal levels

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e17

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

than other racial/ethnic groups. In children, cardiovascular health is projected to improve by

CLINICAL STATEMENTS

the prevalence of ≥5 metrics at ideal levels 6% between 2010 and 2020, short of the AHA’s
AND GUIDELINES

is highest for NH whites (53%), followed by goal of 20% improvement.36 On the basis of
NH Asians (48%), Hispanics (40%), and NH current trends among individual metrics, antici-
blacks (36%). pated declines in prevalence of smoking, high
• Chart 2-9 displays the age-standardized percent- cholesterol, and HBP (in males) would be offset
ages of US adults meeting different numbers of by substantial increases in the prevalence of obe-
criteria for both poor and ideal cardiovascular sity and DM and smaller changes in ideal dietary
health in 2013 to 2014. Meeting the AHA 2020 patterns or PA.36
Strategic Impact Goals is predicated on reduc- • On the basis of these projections for cardiovascu-
ing the relative percentage of those with poor lar health factors and behaviors, CHD deaths are
levels while increasing the relative percentage projected to decrease by 30% between 2010 and
of those with ideal levels for each of the 7 2020 because of projected improvements in TC,
metrics. SBP, smoking, and PA (≈167 000 fewer deaths),
— Approximately 92% of US adults have ≥1 offset by increases in DM and BMI (≈24 000 more
metric at poor levels. deaths).37
— Approximately 36% of US adults have ≥3
metrics at poor levels.
Achieving the 2020 Impact Goals1
— Few US adults (3%) have ≥5 metrics at poor
levels. (See Tables 2-3 through 2-6 and
— More US adults have 4 to 6 ideal metrics than Chart 2-12)
4 to 6 poor metrics. To achieve the AHA’s 2020 Impact Goals of reduc-
ing deaths attributable to CVD and stroke by 20%,
continued emphasis is needed on the treatment of
Cardiovascular Health: Trends Over Time acute CVD events and secondary prevention through
(See Charts 2-10 and 2-11) treatment and control of health behaviors and risk
• The trends over the past decade in each of the factors.
7 cardiovascular health metrics (for diet, trends • Taken together, the data continue to demonstrate
from 1999–2000 through 2015–2016) are both the tremendous relevance of the AHA 2020
Downloaded from http://ahajournals.org by on February 7, 2019

shown in Chart 2-10 (for children 12–19 years Impact Goals for cardiovascular health and the
of age) and Chart 2-11 (for adults ≥20 years progress that will be needed to achieve these
of age). goals by the year 2020 (Chart 2-12).
— Among children, from 1999 to 2000 to 2015 • For each cardiovascular health metric, mod-
to 2016, the prevalence of nonsmoking, est shifts in the population distribution toward
ideal TC, and ideal BP improved. For exam- improved health would produce appreciable
ple, the prevalence of nonsmoking among increases in the proportion of Americans in both
children aged 12 to 19 years increased from ideal and intermediate categories. For example,
76% to 94%, and for ideal TC, the preva- on the basis of NHANES 2015 to 2016, the cur-
lence increased from 72% to 78%. However, rent prevalence of ideal levels of BP among US
there were no improvements in meeting adults is 41%. To achieve the 2020 goals, a 20%
ideal levels for PA, BMI, and blood glucose. relative improvement would require an increase
For example, the prevalence of ideal BMI in this proportion to 49.2% by 2020 (41% ×
declined from 70% in 1999 to 2000 to 60% 1.20). On the basis of NHANES data, a reduction
in 2015 to 2016. in population mean BP of just 5 mm Hg would
— Among adults, the prevalence of nonsmok- result in 52% of US adults having ideal levels
ing and ideal TC, BP, and PA improved. For of BP, which represents a 27% relative improve-
example, nonsmoking increased from 73% ment in this metric (Table  2-3). Larger popula-
of the adult population in 1999 to 2000 to tion reductions in BP would lead to even greater
79% in 2015 to 2016. For TC, the preva- numbers of people with ideal levels of BP. Such
lence of ideal levels increased from 45% small reductions in population BP could result
of the adult population in 1999 to 2000 from small health behavior changes at a popula-
to 49% of the adult population in 2015 to tion level, such as increased PA, increased fruit
2016. and vegetable consumption, decreased sodium
• On the basis of NHANES data from 1988 to intake, decreased adiposity, or some combina-
2008, if current trends continue, estimated tion of these and other lifestyle changes, with

e18 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

resulting substantial projected decreases in CVD local communities, and states, as well as

CLINICAL STATEMENTS
rates in US adults.38 throughout the nation (Table 2-6).

AND GUIDELINES
• A range of complementary strategies and • Such approaches can focus on both (1) improv-
approaches can lead to improvements in cardio- ing cardiovascular health among those who
vascular health.37 These include the following: currently have less than optimal levels and (2)
— Individual-focused approaches that target preserving cardiovascular health among those
lifestyle and treatments at the individual level who currently have ideal levels (in particular,
(Table 2-4). children, adolescents, and young adults) as
— Healthcare systems approaches that encour- they age.
age, facilitate, and reward efforts by provid- • The metrics with the greatest potential for improve-
ers to improve health behaviors and health ment in the United States are health behav-
factors (Table 2-5). iors, including diet quality, PA, and body weight.
— Population approaches that target lifestyle However, each of the 7 cardiovascular health met-
and treatments in schools or workplaces, rics can be improved and deserves major focus.

Table 2-1.  Definitions of Poor, Intermediate, and Ideal Cardiovascular Health for Each Metric in the AHA 2020 Goals

Level of Cardiovascular Health for Each Metric

Poor Intermediate Ideal
Current smoking

 Adults ≥20 y of age Yes Former ≥12 mo Never or quit >12 mo

 Children 12–19 y of age* Tried during the prior 30 d … Never tried; never smoked whole
cigarette
BMI†

 Adults ≥20 y of age ≥30 kg/m2 25–29.9 kg/m2 <25 kg/m2

 Children 2–19 y of age >95th percentile 85th–95th percentile <85th percentile

Downloaded from http://ahajournals.org by on February 7, 2019

Physical activity

 Adults ≥20 y of age None 1–149 min/wk moderate or ≥150 min/wk moderate or ≥75
1–74 min/wk vigorous or min/wk vigorous or ≥150 min/wk
1–149 min/wk moderate + 2× vigorous moderate + 2× vigorous
 Children 12–19 y of age None >0 and <60 min of moderate or vigorous ≥60 min of moderate or vigorous
every day every day
Healthy diet pattern, No. of components (AHA diet score)‡

 Adults ≥20 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

 Children 5–19 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Total cholesterol, mg/dL

 Adults ≥20 y of age ≥240 200–239 or treated to goal <200

 Children 6–19 y of age ≥200 170–199 <170

Blood pressure

 Adults ≥20 y of age SBP ≥140 mm Hg or DBP ≥90 mm Hg SBP 120–139 mm Hg or DBP 80–89 <120 mm Hg/<80 mm Hg
mm Hg or treated to goal
 Children 8–19 y of age >95th percentile 90th–95th percentile or SBP ≥120 mm Hg <90th percentile
or DBP ≥80 mm Hg
Fasting plasma glucose, mg/dL

 Adults ≥20 y of age ≥126 100–125 or treated to goal <100

 Children 12–19 y of age ≥126 100–125 <100

AHA indicates American Heart Association; BMI, body mass index; DBP, diastolic blood pressure; ellipses (…), data not available; and SBP, systolic blood pressure.
*Age ranges in children for each metric depend on guidelines and data availability.
†Represents appropriate energy balance, that is, appropriate dietary quantity and physical activity to maintain normal body weight.
‡In the context of a healthy dietary pattern that is consistent with a Dietary Approaches to Stop Hypertension (DASH)–type eating pattern, to consume ≥4.5 cups/d
of fruits and vegetables, ≥2 servings/wk of fish, and ≥3 servings/d of whole grains and no more than 36 oz/wk of sugar-sweetened beverages and 1500 mg/d of
sodium. The consistency of one’s diet with these dietary targets can be described using a continuous AHA diet score, scaled from 0 to 100 (see chapter on Nutrition).
Modified from Lloyd-Jones et al.1 Copyright © 2010, American Heart Association, Inc.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e19

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

Table 2-2.  Prevalence of Ideal Cardiovascular Health and Its Components in the US Population in Selected Age Strata: NHANES 2013 to 2014 and
CLINICAL STATEMENTS

2015 to 2016
AND GUIDELINES

NHANES
Cycle Age 12–19 y Age ≥20 y* Age 20–39 y Age 40–59 y Age ≥60 y
Ideal cardiovascular health profile (7/7) 2013–2014 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)

 ≥6 Ideal 2013–2014 9.4 (1.3) 5.1 (0.4) 9.0 (0.9) 4.2 (0.6) 0.6 (0.3)

 ≥5 Ideal 2013–2014 47.2 (2.0) 18.1 (1.0) 30.8 (1.8) 13.3 (1.5) 5.0 (0.9)

Ideal health factors (4/4) 2013–2014 57.7 (2.1) 18.4 (0.9) 32.6 (2.1) 13.1 (1.2) 2.9 (0.5)
 Total cholesterol <200 mg/dL 2015–2016 77.7 (1.3) 49.4 (1.1) 72.9 (1.4) 39.0 (1.7) 25.2 (1.2)
 SBP <120/DBP <80 mm  Hg 2015–2016 85.2 (1.0) 41.0 (1.2) 61.7 (1.7) 34.1 (2.0) 15.6 (2.1)
 Nonsmoker 2015–2016 93.6 (0.9) 78.8 (1.0) 75.0 (1.4) 77.0 (1.5) 86.5 (1.4)
 FPG <100 mg/dL and HbA1c <5.7% 2013–2014 87.6 (1.0) 60.8 (1.1) 78.5 (1.3) 57.7 (1.8) 35.4 (1.7)
Ideal health behaviors (4/4) 2013–2014 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
 PA at goal 2013–2014 27.7 (1.2) 36.7 (1.1) 45.0 (2.0) 34.2 (1.6) 26.7 (1.5)
 Nonsmoker 2015–2016 91.4 (1.4) 77.1 (1.2) 72.6 (1.4) 74.7 (2.1) 87.7 (1.2)
 BMI <25 kg/m2 2013–2014 63.1 (2.4) 29.6 (0.8) 36.3 (1.5) 25.4 (1.4) 25.6 (1.1)
 4–5 Diet goals met† 2013–2014 0.0 (0.0) 0.2 (0.1) 0.0 (0.0) 0.2 (0.1) 0.4 (0.2)

  F&V ≥4.5 C/d 2013–2014 6.5 (1.4) 10.3 (0.7) 8.5 (1.0) 9.7 (1.2) 13.8 (1.7)

  Fish ≥2 svg/wk 2013–2014 8.5 (1.4) 20.1 (1.6) 16.4 (1.7) 21.8 (2.1) 23.1 (2.2)

  Sodium <1500 mg/d 2013–2014 0.5 (0.5) 0.6 (0.2) 0.9 (0.3) 0.6 (0.4) 0.2 (0.1)
  SSB <36 oz/wk 2013–2014 37.0 (2.3) 51.2 (1.9) 41.8 (1.9) 53.0 (3.3) 64.5 (2.8)

  Whole grains ≥3 1-oz/d 2013–2014 3.4 (1.1) 7.1 (0.4) 5.3 (0.8) 6.6 (0.6) 10.4 (1.1)

Secondary diet metrics

 Nuts/legumes/seeds ≥4 svg/wk 2013–2014 31.7 (1.9) 49.7 (1.3) 46.8 (2.1) 51.0 (2.3) 53.5 (2.4)

 Processed meats ≤2 svg/wk 2013–2014 44.4 (3.2) 45.0 (1.3) 44.7 (1.5) 47.3 (2.4) 41.4 (2.3)
Downloaded from http://ahajournals.org by on February 7, 2019

 SFat <7% total kcal 2013–2014 8.9 (1.3) 9.2 (0.4) 9.7 (0.9) 9.4 (0.9) 8.4 (1.2)

Values are % (standard error). BMI indicates body mass index; DBP, diastolic blood pressure; F&V, fruits and vegetables; FPG, fasting plasma glucose; HbA1c,
hemoglobin A1c (glycosylated hemoglobin); NHANES, National Health and Nutrition Examination Survey; PA, physical activity; SBP, systolic blood pressure; SFat,
saturated fat; SSB, sugar-sweetened beverages; and svg, servings.
*Standardized to the age distribution of the 2000 US standard population.
†Scaled to 2000 kcal/d and in the context of appropriate energy balance and a DASH (Dietary Approaches to Stop Hypertension)–type eating pattern.

Table 2-3.  Reduction in BP Required to Increase Prevalence of Ideal BP

Among Adults ≥20 Years Old: NHANES 2015 to 2016

%
Percent BP ideal among adults, 2015–2016 41.0
20% Relative increase 49.2
Percent whose BP would be ideal if population mean BP were lowered by*:
 2 mm  Hg 44.6
 3 mm  Hg 47.2
 4 mm  Hg 49.0
 5 mm  Hg 52.0

Standardized to the age distribution of the 2000 US standard population.

BP indicates blood pressure; and NHANES, National Health and Nutrition
Examination Survey.
*Reduction in BP = (observed average systolic BP − X mm Hg) and (observed
average diastolic BP − X mm Hg).

e20 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

Table 2-4.  Evidence-Based Individual Approaches for Improving Table 2-5.  Evidence-Based Healthcare Systems Approaches to Support

CLINICAL STATEMENTS
Health Behaviors and Health Factors in the Clinic Setting and Facilitate Improvements in Health Behaviors and Health Factors41–43

AND GUIDELINES
Set specific, shared, proximal goals (Class I; Level of Evidence A): Set Electronic systems for scheduling and tracking initial visits and regular
specific, proximal goals with the patient, including a personalized plan to follow-up contacts for behavior change and treatments
achieve the goals (eg, over the next 3 mo, increase fruits by 1 serving/d,
Electronic medical records systems to help assess, track, and report on
reduce smoking by half a pack/d, or walk 30 min 3 times/wk).
specific health behaviors (diet, PA, tobacco, body weight) and health
Establish self-monitoring (Class I; Level of Evidence A): Develop a strategy factors (BP, cholesterol, glucose), as well as to provide feedback and the
for self-monitoring, such as a dietary or physical activity diary or web- latest guidelines to providers
based or mobile applications.
Practical paper or electronic toolkits for assessment of key health behaviors
Schedule regular follow-up (Class I; Level of Evidence A): Schedule regular and health factors, including during, before, and after provider visits
follow-up (in person, telephone, written, and electronic), with clear
Electronic systems to facilitate provision of feedback to patients on their
frequency and duration of contacts, to assess success, reinforce progress,
progress during behavior change and other treatment efforts
and set new goals as necessary.
Education and ongoing training for providers on evidence-based behavior
Provide feedback (Class I; Level of Evidence A): Provide feedback on
change strategies, as well as the most relevant behavioral targets,
progress toward goals, including using in-person, telephone, and/or
including training on relevant ethnic and cultural issues
electronic feedback.
Integrated systems to provide coordinated care by multidisciplinary teams
Increase self-efficacy (Class I; Level of Evidence A): Increase the patient’s
of providers, including physicians, nurse practitioners, dietitians, PA
perception that they can successfully change their behavior.*
specialists, and social workers
Use motivational interviewing† (Class I; Level of Evidence A): Use
Reimbursement guidelines and incentives that reward efforts to change
motivational interviewing when patients are resistant or ambivalent about
health behaviors and health factors. Restructuring of practice goals and
behavior change.
quality benchmarks to incorporate health behavior (diet, PA, tobacco,
Provide long-term support (Class I; Level of Evidence B): Arrange long-term body weight) and health factor (BP, cholesterol, glucose) interventions and
support from family, friends, or peers for behavior change, such as in other targets for both primary and secondary prevention
workplace, school, or community-based programs.
BP indicates blood pressure; and PA, physical activity.
Use a multicomponent approach (Class I; Level of Evidence A): Combine
≥2 of the above strategies into the behavior change efforts.

*Examples of approaches include mastery experiences (set a reasonable,

proximal goal that the person can successfully achieve); vicarious experiences
(have the person see someone with similar capabilities performing the behavior,
such as walking on a treadmill or preparing a healthy meal); physiological
feedback (explain to the patient when a change in their symptoms is related to
worse or improved behaviors); and verbal persuasion (persuade the person that
you believe in their capability to perform the behavior).
Downloaded from http://ahajournals.org by on February 7, 2019

†Motivational interviewing represents use of individual counseling to explore

and resolve ambivalence toward changing behavior. Major principles include
fostering the person’s own awareness and resolution of their ambivalence, as
well as their own self-motivation to change, in a partnership with the counselor
or provider.
Modified from Artinian et al.40 Copyright © 2010, American Heart
Association, Inc.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e21

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

Table 2-6.  Summary of Evidence-Based Population Approaches for Improving Diet, Increasing Physical Activity, and
CLINICAL STATEMENTS

Reducing Tobacco Use*

AND GUIDELINES

Diet
 Media and education Sustained, focused media and educational campaigns, using multiple modes, for increasing
consumption of specific healthful foods or reducing consumption of specific less healthful
foods or beverages, either alone (Class IIa; Level of Evidence B) or as part of multicomponent
strategies (Class I; Level of Evidence B)†‡§
On-site supermarket and grocery store educational programs to support the purchase of
healthier foods (Class IIa; Level of Evidence B)†
 Labeling and information Mandated nutrition facts panels or front-of-pack labels/icons as a means to influence industry
behavior and product formulations (Class IIa; Level of Evidence B)†
 Economic incentives Subsidy strategies to lower prices of more healthful foods and beverages (Class I; Level of
Evidence A)†
Tax strategies to increase prices of less healthful foods and beverages (Class IIa; Level of
Evidence B)†
Changes in both agricultural subsidies and other related policies to create an
infrastructure that facilitates production, transportation, and marketing of healthier
foods, sustained over several decades (Class IIa; Level of Evidence B)†
 Schools Multicomponent interventions focused on improving both diet and physical activity, including
specialized educational curricula, trained teachers, supportive school policies, a formal physical
education program, healthy food and beverage options, and a parental/family component
(Class I; Level of Evidence A)†
School garden programs, including nutrition and gardening education and hands-on
gardening experiences (Class IIa; Level of Evidence A)†
Fresh fruit and vegetable programs that provide free fruits and vegetables to students during
the school day (Class IIa; Level of Evidence A)†
 Workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco
cessation/prevention components (Class IIa; Level of Evidence A)†
Increased availability of healthier food/beverage options and/or strong nutrition standards
for foods and beverages served, in combination with vending machine prompts, labels, or
icons to make healthier choices (Class IIa; Level of Evidence B)†
Downloaded from http://ahajournals.org by on February 7, 2019

 Local environment Increased availability of supermarkets near homes (Class IIa; Level of Evidence B)†‡‖
 Restrictions and mandates Restrictions on television advertisements for less healthful foods or beverages advertised to
children (Class I; Level of Evidence B)†
Restrictions on advertising and marketing of less healthful foods or beverages near schools
and public places frequented by youths (Class IIa; Level of Evidence B)†
General nutrition standards for foods and beverages marketed and advertised to children in
any fashion, including on-package promotion (Class IIa; Level of Evidence B)†
Regulatory policies to reduce specific nutrients in foods (eg, trans fats, salt, certain fats) (Class
I; Level of Evidence B)†§
Physical activity
 Labeling and information Point-of-decision prompts to encourage use of stairs (Class IIa; Level of Evidence A)†
 Economic incentives Increased gasoline taxes to increase active transport/commuting (Class IIa; Level of Evidence
B)†
 Schools Multicomponent interventions focused on improving both diet and physical activity, including
specialized educational curricula, trained teachers, supportive school policies, a formal physical
education program, serving of healthy food and beverage options, and a parental/family
component (Class IIa; Level of Evidence A)†
Increased availability and types of school playground spaces and equipment (Class I; Level of
Evidence B)†
Increased number of physical education classes, revised physical education curricula to
increase time in at least moderate activity, and trained physical education teachers at
schools (Class IIa; Level of Evidence A/Class IIb; Level of Evidence A¶)†
Regular classroom physical activity breaks during academic lessons (Class IIa; Level of Evidence
A)†§
(Continued )

e22 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

Table 2-6. Continued

CLINICAL STATEMENTS
 Workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco

AND GUIDELINES
cessation/prevention components (Class IIa; Level of Evidence A)†
Structured worksite programs that encourage activity and also provide a set time for physical
activity during work hours (Class IIa; Level of Evidence B)†
Improving stairway access and appeal, potentially in combination with “skip-stop” elevators
that skip some floors (Class IIa; Level of Evidence B)†
Adding new or updating worksite fitness centers (Class IIa; Level of Evidence B)†
Physical activity Continued
 Local environment Improved accessibility of recreation and exercise spaces and facilities (eg, building of parks
and playgrounds, increasing operating hours, use of school facilities during nonschool
hours) (Class IIa; Level of Evidence B)†

Improved land-use design (eg, integration and interrelationships of residential, school, work,
retail, and public spaces) (Class IIa; Level of Evidence B)†

Improved sidewalk and street design to increase active commuting (walking or bicycling) to school
by children (Class IIa; Level of Evidence B)†

Improved traffic safety (Class IIa; Level of Evidence B)†

Improved neighborhood aesthetics (to increase activity in adults) (Class IIa; Level of Evidence
B)†

Improved walkability, a composite indicator that incorporates aspects of land-use mix, street
connectivity, pedestrian infrastructure, aesthetics, traffic safety, and crime safety (Class IIa;
Level of Evidence B)†

Smoking

 Media and education Sustained, focused media and educational campaigns to reduce smoking, either alone (Class
IIa; Level of Evidence B) or as part of larger multicomponent population-level strategies (Class
I; Level of Evidence A)†

 Labeling and information Cigarette package warnings, especially those that are graphic and health related (Class I; Level
of Evidence B)†‡§

 Economic incentives Higher taxes on tobacco products to reduce use and fund tobacco control programs (Class
Downloaded from http://ahajournals.org by on February 7, 2019

I; Level of
Evidence A)†‡§

 Schools and workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco
cessation/prevention components (Class IIa; Level of Evidence A)†

 Local environment Reduced density of retail tobacco outlets around homes and schools (Class I; Level of Evidence
B)†

Development of community telephone lines for cessation counseling and support services
(Class I; Level of
Evidence A)†

 Restrictions and mandates Community (city, state, or federal) restrictions on smoking in public places (Class I; Level of
Evidence A)†

Local workplace-specific restrictions on smoking (Class I; Level of Evidence A)†‡§

Stronger enforcement of local school-specific restrictions on smoking (Class IIa; Level of

Evidence B)†

Local residence-specific restrictions on smoking (Class IIa; Level of Evidence B)†§

Partial or complete restrictions on advertising and promotion of tobacco products (Class I;

Level of Evidence B)†

*The specific population interventions listed here are either a Class I or IIa recommendation with a Level of Evidence grade of
either A or B.
†At least some evidence from studies conducted in high-income Western regions and countries (eg, North America, Europe,
Australia, New Zealand).
‡At least some evidence from studies conducted in high-income non-Western regions and countries (eg, Japan, Hong Kong,
South Korea, Singapore).
§At least some evidence from studies conducted in low- or middle-income regions and countries (eg, Africa, China, Pakistan,
India).
‖Based on cross-sectional studies only; only 2 longitudinal studies have been performed, with no significant relations seen.
¶Class IIa; Level of Evidence A for improving physical activity; Class IIb; Level of Evidence B for reducing adiposity.
Reprinted from Mozaffarian et al.41 Copyright © 2012, American Heart Association, Inc.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e23

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2
CLINICAL STATEMENTS
AND GUIDELINES

Chart 2-1. Incidence of cardiovascular disease according to the number of ideal health behaviors and health factors.
Reprinted from Folsom et al12 with permission from the American College of Cardiology Foundation. Copyright © 2011, the American College of Cardiology
Foundation.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-2. Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular
health in the AHA 2020 goals, among US children aged 12 to 19 years.
AHA indicates American Heart Association.
*Healthy Diet Score reflects 2013 to 2014 NHANES (National Health and Nutrition Examination Survey).
Source: National Center for Health Statistics, NHANES, 2015 to 2016.

e24 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-3. Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular
health in the AHA 2020 goals among US adults aged 20 to 49 and ≥50 years.
AHA indicates American Heart Association.
*Healthy Diet Score reflects 2013 to 2014 NHANES (National Health and Nutrition Examination Survey).
Source: National Center for Health Statistics, NHANES, 2015 to 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-4. Proportion (unadjusted) of US children aged 12 to 19 years meeting different numbers of criteria for ideal cardiovascular health, overall
and by sex.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey, 2013 to 2014.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e25

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2
CLINICAL STATEMENTS
AND GUIDELINES

Chart 2-5. Age-standardized prevalence estimates of US adults aged ≥20 years meeting different numbers of criteria for ideal cardiovascular health,
overall and by age and sex subgroups.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey, 2013 to 2014.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-6. Age-standardized prevalence estimates of US adults aged ≥20 years meeting different numbers of criteria for ideal cardiovascular health,
overall and in selected race subgroups.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey 2013 to 2014.

e26 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-7. Prevalence of meeting ≥5 criteria for ideal cardiovascular health among US adults aged ≥20 years (age standardized) and US children
aged 12 to 19 years, overall and by sex.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey, 2007 to 2008 and 2013 to 2014.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-8. Prevalence of meeting ≥5 criteria for ideal cardiovascular health among US adults aged ≥20 years (age standardized) and US children
aged 12 to 19 years, by race/ethnicity.
NH indicates non-Hispanic.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey, 2013 to 2014.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e27

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2
CLINICAL STATEMENTS
AND GUIDELINES

Chart 2-9. Age-standardized prevalence estimates of US adults meeting different numbers of criteria for ideal and poor cardiovascular health for
each of the 7 metrics of cardiovascular health in the AHA 2020 goals among US adults aged ≥20 years.
AHA indicates American Heart Association.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey, 2013 to 2014.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-10. Trends in prevalence (unadjusted) of meeting criteria for ideal cardiovascular health for each of the 7 metrics among US children aged
12 to 19 years.
Data for the Healthy Diet Score, based on a 2-day average intake, were only available for the 2003 to 2004, 2005 to 2006, 2007 to 2008, 2009 to 2010, and
2011 to 2012 NHANES cycles at the time of this analysis.
NHANES indicates National Health and Nutrition Examination Survey.
*Because of changes in the physical activity questionnaire between different cycles of NHANES, trends over time for this indicator should be interpreted with
caution, and statistical comparisons should not be attempted.
Source: National Center for Health Statistics, NHANES, 1999 to 2000 through 2015 to 2016.

e28 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-11. Age-standardized trends in prevalence of meeting criteria for ideal cardiovascular health for each of the 7 metrics among US adults
aged ≥20 years.
Data for the Healthy Diet Score, based on a 2-day average intake, were only available for the 2003 to 2004, 2005 to 2006, 2007 to 2008, 2009 to 2010, and
2011 to 2012 NHANES cycles at the time of this analysis.
NHANES indicates National Health and Nutrition Examination Survey.
*Because of changes in the physical activity questionnaire between different cycles of NHANES, trends over time for this indicator should be interpreted with
caution, and statistical comparisons should not be attempted.
Source: National Center for Health Statistics, NHANES, 1999 to 2000 through 2015 to 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 2-12. Prevalence of ideal, intermediate, and poor cardiovascular health metrics in 2006 (AHA 2020 Strategic Impact Goals baseline year) and
2020 projections assuming current trends continue.
The 2020 targets for each cardiovascular health metric assume a 20% relative increase in ideal cardiovascular health prevalence metrics and a 20% relative
decrease in poor cardiovascular health prevalence metrics for males and females.
AHA indicates American Heart Association.
Reprinted from Huffman et al.36 Copyright © 2012, American Heart Association, Inc.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e29

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

REFERENCES 16. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM,
CLINICAL STATEMENTS

Muntner P, Hong Y, Safford MM, Goyal A, Cushman M. Life’s Simple

1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn
AND GUIDELINES

7 and risk of incident stroke: the Reasons for Geographic and

L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow Racial Differences in Stroke study. Stroke. 2013;44:1909–1914. doi:
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm 10.1161/STROKEAHA.111.000352
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart 17. Wilkins JT, Ning H, Berry J, Zhao L, Dyer AR, Lloyd-Jones DM. Lifetime risk
Association Strategic Planning Task Force and Statistics Committee. and years lived free of total cardiovascular disease. JAMA. 2012;308:1795–
Defining and setting national goals for cardiovascular health promotion
1801. doi: 10.1001/jama.2012.14312
and disease reduction: the American Heart Association’s strategic Impact
18. Folsom AR, Shah AM, Lutsey PL, Roetker NS, Alonso A, Avery CL,
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi:
Miedema MD, Konety S, Chang PP, Solomon SD. American Heart
10.1161/CIRCULATIONAHA.109.192703
Association’s Life’s Simple 7: avoiding heart failure and preserving car-
2. American Heart Association. My Life Check – Life’s Simple 7. https://www.
diac structure and function. Am J Med. 2015;128:970–976.e2. doi:
heart.org/en/healthy-living/healthy-lifestyle/my-life-check--lifes-simple-7.
10.1016/j.amjmed.2015.03.027
Accessed November 9, 2018.
19. Robbins JM, Petrone AB, Carr JJ, Pankow JS, Hunt SC, Heiss G, Arnett
3. Rumsfeld JS, Alexander KP, Goff DC Jr, Graham MM, Ho PM, Masoudi
DK, Ellison RC, Gaziano JM, Djoussé L. Association of ideal cardiovascular
FA, Moser DK, Roger VL, Slaughter MS, Smolderen KG, Spertus JA,
health and calcified atherosclerotic plaque in the coronary arteries: the
Sullivan MD, Treat-Jacobson D, Zerwic JJ; on behalf of the American Heart
National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J.
Association Council on Quality of Care and Outcomes Research, Council
2015;169:371–378.e1. doi: 10.1016/j.ahj.2014.12.017
on Cardiovascular and Stroke Nursing, Council on Epidemiology and
20. Saleem Y, DeFina LF, Radford NB, Willis BL, Barlow CE, Gibbons LW,
Prevention, Council on Peripheral Vascular Disease, and Stroke Council.
Khera A. Association of a favorable cardiovascular health profile with
Cardiovascular health: the importance of measuring patient-reported
the presence of coronary artery calcification. Circ Cardiovasc Imaging.
health status: a scientific statement from the American Heart Association.
2015;8:e001851. doi: 10.1161/CIRCIMAGING.114.001851
Circulation. 2013;127:2233–2249. doi: 10.1161/CIR.0b013e3182949a2e
21. Crichton GE, Elias MF, Davey A, Alkerwi A. Cardiovascular health and
4. Shay CM, Gooding HS, Murillo R, Foraker R. Understanding and improv-
cognitive function: the Maine-Syracuse Longitudinal Study. PLoS One.
ing cardiovascular health: an update on the American Heart Association’s
2014;9:e89317. doi: 10.1371/journal.pone.0089317
concept of cardiovascular health. Prog Cardiovasc Dis. 2015;58:41–49.
22. Thacker EL, Gillett SR, Wadley VG, Unverzagt FW, Judd SE, McClure LA,
doi: 10.1016/j.pcad.2015.05.003
Howard VJ, Cushman M. The American Heart Association Life’s Simple
5. Chang Y, Guo X, Chen Y, Guo L, Li Z, Yu S, Yang H, Sun G, Sun Y.
7 and incident cognitive impairment: the REasons for Geographic
Prevalence and metrics distribution of ideal cardiovascular health: a
And Racial Differences in Stroke (REGARDS) study. J Am Heart Assoc.
population-based, cross-sectional study in rural China. Heart Lung Circ.
2014;3:e000635. doi: 10.1161/JAHA.113.000635
2016;25:982–992. doi: 10.1016/j.hlc.2016.02.007
23. Kronish IM, Carson AP, Davidson KW, Muntner P, Safford MM.
6. Laitinen T. Cardiovascular Health From Childhood to Adulthood–With
Special Reference to Early Vascular Changes: The Cardiovascular Risk in Depressive symptoms and cardiovascular health by the American Heart
Young Finns Study [master’s thesis]. Helsinki, Finland; University of Turku; Association’s definition in the Reasons for Geographic and Racial
2015. Differences in Stroke (REGARDS) study. PLoS One. 2012;7:e52771. doi:
7. Laitinen TT, Pahkala K, Magnussen CG, Oikonen M, Viikari JS, Sabin MA, 10.1371/journal.pone.0052771
Daniels SR, Heinonen OJ, Taittonen L, Hartiala O, Mikkilä V, Hutri-Kähönen 24. España-Romero V, Artero EG, Lee DC, Sui X, Baruth M, Ruiz JR,
N, Laitinen T, Kähönen M, Raitakari OT, Juonala M. Lifetime measures Pate RR, Blair SN. A prospective study of ideal cardiovascular health
and depressive symptoms. Psychosomatics. 2013;54:525–535. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

of ideal cardiovascular health and their association with subclinical ath-

erosclerosis: The Cardiovascular Risk in Young Finns Study. Int J Cardiol. 10.1016/j.psym.2013.06.016
2015;185:186–191. doi: 10.1016/j.ijcard.2015.03.051 25. Dhamoon MS, Dong C, Elkind MS, Sacco RL. Ideal cardiovascular
8. Younus A, Aneni EC, Spatz ES, Osondu CU, Roberson L, Ogunmoroti O, health predicts functional status independently of vascular events: the
Malik R, Ali SS, Aziz M, Feldman T, Virani SS, Maziak W, Agatston AS, Northern Manhattan Study. J Am Heart Assoc. 2015;4:e001322. doi:
Veledar E, Nasir K. A systematic review of the prevalence and outcomes of 10.1161/JAHA.114.001322
ideal cardiovascular health in US and non-US populations. Mayo Clin Proc. 26. Gebreab SY, Manna ZG, Khan RJ, Riestra P, Xu R, Davis SK. Less than ideal
2016;91:649–670. doi: 10.1016/j.mayocp.2016.01.019 cardiovascular health is associated with shorter leukocyte telomere length:
9. Zhou L, Zhao L, Wu Y, Wu Y, Gao X, Li Y, Mai J, Nie Z, Ou Y, Guo M, Liu the National Health and Nutrition Examination Surveys, 1999–2002. J Am
X. Ideal cardiovascular health metrics and its association with 20-year car- Heart Assoc. 2017;6:e004105. doi: 10.1161/JAHA.116.004105
diovascular morbidity and mortality in a Chinese population. J Epidemiol 27. Han QL, Wu SL, Liu XX, An SS, Wu YT, Gao JS, Chen SH, Liu XK, Zhang
Community Health. 2018;72:752–758. doi: 10.1136/jech-2017-210396 Q, Mao RY, Shang XM, Jonas JB. Ideal cardiovascular health score and
10. González HM, Tarraf W, Rodríguez CJ, Gallo LC, Sacco RL, Talavera GA, incident end-stage renal disease in a community-based longitudi-
Heiss G, Kizer JR, Hernandez R, Davis S, Schneiderman N, Daviglus ML, nal cohort study: the Kailuan Study. BMJ Open. 2016;6:e012486. doi:
Kaplan RC. Cardiovascular health among diverse Hispanics/Latinos: 10.1136/bmjopen-2016-012486
Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results. 28. Fan W, Lee H, Lee A, Kieu C, Wong ND. Association of lung function and
Am Heart J. 2016;176:134–144. doi: 10.1016/j.ahj.2016.02.008 chronic obstructive pulmonary disease with American Heart Association’s
11. Spahillari A, Talegawkar S, Correa A, Carr JJ, Terry JG, Lima J, Freedman Life’s Simple 7 cardiovascular health metrics. Respir Med. 2017;131:85–
JE, Das S, Kociol R, de Ferranti S, Mohebali D, Mwasongwe S, Tucker KL, 93. doi: 10.1016/j.rmed.2017.08.001
Murthy VL, Shah RV. Ideal cardiovascular health, cardiovascular remodel- 29. Olson NC, Cushman M, Judd SE, McClure LA, Lakoski SG, Folsom AR,
ing, and heart failure in blacks: the Jackson Heart Study. Circ Heart Fail. Safford MM, Zakai NA. American Heart Association’s Life’s Simple 7
2017;10:e003682. doi: 10.1161/CIRCHEARTFAILURE.116.003682 and risk of venous thromboembolism: the Reasons for Geographic
12. Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond and Racial Differences in Stroke (REGARDS) study. J Am Heart Assoc.
WD; ARIC Study Investigators. Community prevalence of ideal car- 2015;4:e001494. doi: 10.1161/JAHA.114.001494
diovascular health, by the American Heart Association definition, and 30. Sengeløv M, Cheng S, Biering-Sørensen T, Matsushita K, Konety S,
relationship with cardiovascular disease incidence. J Am Coll Cardiol. Solomon SD, Folsom AR, Shah AM. Ideal cardiovascular health and the
2011;57:1690–1696. doi: 10.1016/j.jacc.2010.11.041 prevalence and severity of aortic stenosis in elderly patients. J Am Heart
13. US Burden of Disease Collaborators. The state of US health, 1990–2010: Assoc. 2018;7:e007234. doi: 10.1161/JAHA.117.007234
burden of diseases, injuries, and risk factors. JAMA. 2013;310:591–606. 31. Mok Y, Sang Y, Ballew SH, Rebholz CM, Rosamond WD, Heiss G, Folsom
doi: 10.1001/jama.2013.13805 AR, Coresh J, Matsushita K. American Heart Association’s Life’s Simple 7
14. Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, at middle age and prognosis after myocardial infarction in later life. J Am
Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and Heart Assoc. 2018;7:e007658. doi: 10.1161/JAHA.117.007658
associations with all-cause and CVD mortality among US adults. JAMA. 32. Garg PK, O’Neal WT, Chen LY, Loehr LR, Sotoodehnia N, Soliman EZ,
2012;307:1273–1283. doi: 10.1001/jama.2012.339 Alonso A. American Heart Association’s Life Simple 7 and risk of atrial
15. Fang N, Jiang M, Fan Y. Ideal cardiovascular health metrics and risk fibrillation in a population without known cardiovascular disease: the
of cardiovascular disease or mortality: a meta-analysis. Int J Cardiol. ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc.
2016;214:279–283. doi: 10.1016/j.ijcard.2016.03.210 2018;7:e008424. doi: 10.1161/JAHA.117.008424

e30 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 2

33. Hernandez R, González HM, Tarraf W, Moskowitz JT, Carnethon MR, on future cardiovascular disease. N Engl J Med. 2010;362:590–599. doi:

CLINICAL STATEMENTS
Gallo LC, Penedo FJ, Isasi CR, Ruiz JM, Arguelles W, Buelna C, Davis S, 10.1056/NEJMoa0907355

AND GUIDELINES
Gonzalez F, McCurley JL, Wu D, Daviglus ML. Association of dispositional 39. Fang J, Yang Q, Hong Y, Loustalot F. Status of cardiovascular health among
optimism with Life’s Simple 7’s Cardiovascular Health Index: results from adult Americans in the 50 States and the District of Columbia, 2009. J Am
the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Heart Assoc. 2012;1:e005371. doi: 10.1161/JAHA.112.005371.
Sociocultural Ancillary Study (SCAS). BMJ Open. 2018;8:e019434. doi: 40. Artinian NT, Fletcher GF, Mozaffarian D, Kris-Etherton P, Van Horn L,
10.1136/bmjopen-2017-019434 Lichtenstein AH, Kumanyika S, Kraus WE, Fleg JL, Redeker NS, Meininger
34. Caleyachetty R, Echouffo-Tcheugui JB, Muennig P, Zhu W, Muntner JC, Banks J, Stuart-Shor EM, Fletcher BJ, Miller TD, Hughes S, Braun
P, Shimbo D. Association between cumulative social risk and ideal car- LT, Kopin LA, Berra K, Hayman LL, Ewing LJ, Ades PA, Durstine JL,
diovascular health in US adults: NHANES 1999-2006. Int J Cardiol. Houston-Miller N, Burke LE; on behalf of the American Heart Association
2015;191:296–300. doi: 10.1016/j.ijcard.2015.05.007 Prevention Committee of the Council on Cardiovascular Nursing.
35. Osondu CU, Aneni EC, Valero-Elizondo J, Salami JA, Rouseff M, Das S, Interventions to promote physical activity and dietary lifestyle changes for
Guzman H, Younus A, Ogunmoroti O, Feldman T, Agatston AS, Veledar cardiovascular risk factor reduction in adults: a scientific statement from
E, Katzen B, Calitz C, Sanchez E, Lloyd-Jones DM, Nasir K. Favorable car- the American Heart Association. Circulation. 2010;122:406–441. doi:
diovascular health is associated with lower health care expenditures and 10.1161/CIR.0b013e3181e8edf1
resource utilization in a large US employee population: the Baptist Health 41. Mozaffarian D, Afshin A, Benowitz NL, Bittner V, Daniels SR, Franch HA,
South Florida Employee Study. Mayo Clin Proc. 2017;92:512–524. doi: Jacobs DR Jr, Kraus WE, Kris-Etherton PM, Krummel DA, Popkin BM,
10.1016/j.mayocp.2016.12.026 Whitsel LP, Zakai NA; on behalf of the American Heart Association Council
36. Huffman MD, Capewell S, Ning H, Shay CM, Ford ES, Lloyd-Jones on Epidemiology and Prevention, Council on Nutrition, Physical Activity
DM. Cardiovascular health behavior and health factor changes (1988- and Metabolism, Council on Clinical Cardiology, Council on Cardiovascular
2008) and projections to 2020: results from the National Health and Disease in the Young, Council on the Kidney in Cardiovascular Disease.
Nutrition Examination Surveys. Circulation. 2012;125:2595–2602. doi: Population approaches to improve diet, physical activity, and smok-
10.1161/CIRCULATIONAHA.111.070722 ing habits: a scientific statement from the American Heart Association.
37. Huffman MD, Lloyd-Jones DM, Ning H, Labarthe DR, Guzman Castillo M, Circulation. 2012;126:1514–1563. doi: 10.1161/CIR.0b013e318260a20b
O’Flaherty M, Ford ES, Capewell S. Quantifying options for reducing coro- 42. Bodenheimer T. Helping patients improve their health-related behaviors:
nary heart disease mortality by 2020. Circulation. 2013;127:2477–2484. what system changes do we need? Dis Manag. 2005;8:319–330. doi:
doi: 10.1161/CIRCULATIONAHA.112.000769 10.1089/dis.2005.8.319
38. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood 43. Simpson LA, Cooper J. Paying for obesity: a changing landscape.
JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions Pediatrics. 2009;123(suppl 5):S301–S307. doi: 10.1542/peds.2008-2780I
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e31

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

3. SMOKING/TOBACCO USE has risen dramatically, particularly among young peo-

CLINICAL STATEMENTS

ple. The variety of e-cigarette–related products has

See Table 3-1 and Charts 3-1 through 3-6
AND GUIDELINES

increased exponentially, giving rise to the more general

term electronic nicotine delivery systems.6 Use of cigars,
Click here to return to the Table of Contents
cigarillos, filtered cigars, and hookah also has become
increasingly common in recent years. Thus, each section
Tobacco use is one of the leading preventable causes
below will address the most recent statistical estimates
of death in the United States and globally.1 Tobacco
for combustible cigarettes, electronic nicotine delivery
smoking, the most common form of tobacco use, is
systems, and other forms of tobacco use if such esti-
a major risk factor for CVD and stroke.2 The AHA has
mates are available.
identified never having tried smoking or never having
smoked a whole cigarette (for children) and never hav-
ing smoked or having quit >12 months ago (for adults) Prevalence
as 1 of the 7 components of ideal cardiovascular health
(See Charts 3-1 through 3-4)
in Life’s Simple 7.3 Unless otherwise stated, throughout
the rest of the chapter we will report tobacco use and Youth
smoking estimates from the NSDUH4 for adolescents • Prevalence of cigarette use in the past month for
(12–17 years of age) and from the NHIS5 for adults adolescents aged 12 to 17 years by sex and race/
(≥18 years of age), because these data sources have ethnicity in 2014 and 2015 is shown in Chart 3-1.
more recent data. • According to the NSDUH 2016 data, for adoles-
Other forms of tobacco use are becoming increas- cents aged 12 to 17 years4:
ingly common. Electronic cigarette (e-cigarette) use, — 5.3% (1  319 541) used tobacco products,
which involves inhalation of a vaporized liquid that and 3.4% (846 498) smoked cigarettes in the
includes nicotine, solvents, and flavoring (“vaping”), past month.
— 1.4% (348 558) used smokeless tobacco in
the past month.
Abbreviations Used in Chapter 3
— Of adolescents who smoked, 15% (126 975)
ACS acute coronary syndrome smoked cigarettes daily.
AHA American Heart Association
— 1.8% (448 146) were current cigar smok-
Downloaded from http://ahajournals.org by on February 7, 2019

AIAN American Indian or Alaska Native

BRFSS Behavioral Risk Factor Surveillance System
ers, and 0.5% (124 485) were current pipe
CDC Centers for Disease Control and Prevention tobacco smokers.
CHD coronary heart disease • In 2015, tobacco use within the past month
CI confidence interval for youth 12 to 17 years of age varied slightly
CVD cardiovascular disease
by region: 6.2% in the Northeast, 7.0% in the
DALY disability-adjusted life-year
DM diabetes mellitus
Midwest, 6.0% in the South, and 4.9% in the
EAGLES Study Evaluating the Safety and Efficacy of Varenicline and West.4
Bupropion for Smoking Cessation in Subjects With and • In 2015, 21.6% of adults aged 18 to 20 years
Without a History of Psychiatric Disorders were current cigarette smokers compared with
EVITA Evaluation of Varenicline in Smoking Cessation for Patients
Post-Acute Coronary Syndrome
8.7% of adolescents aged 16 to 17 years.4
GBD Global Burden of Disease • The PATH study assessed the use of different
HD heart disease types of tobacco products, including cigarettes,
HIV human immunodeficiency virus e-cigarettes, cigars, cigarillos, filtered cigars,
HR hazard ratio
pipe tobacco, hookah, snus pouches, smokeless
NH non-Hispanic
NHANES National Health and Nutrition Examination Survey
tobacco, dissolvable tobacco, bidis, and kreteks.
NHIS National Health Interview Survey This study estimated that in 2013 to 2014, 8.9%
NNT number needed to treat of youth aged 12 to 18 years used some form
NSDUH National Survey on Drug Use and Health of tobacco in the past 30 days, and 1.6% were
OR odds ratio daily users.7
PAF population attributable fraction
• Data from the National Youth Tobacco Survey
PAR population attributable risk
PATH Population Assessment of Tobacco and Health
indicate that the percentage of high school stu-
RCT randomized controlled trial dents who used e-cigarettes (11.3%) exceeded
RR relative risk the proportion using cigarettes (8.0%) in 2016
SAH subarachnoid hemorrhage (Chart 3-2).8
SBP systolic blood pressure
SHS Strong Heart Study Adults
UI uncertainty interval • According to the NHIS 2016 data, among adults
WHO World Health Organization ≥18 years of age6:

e32 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

— 15.5% of adults (37.8 million) are current adult females were current users of some form

CLINICAL STATEMENTS
smokers. of tobacco.7

AND GUIDELINES
— 17.5% of males and 13.5% of females are • E-cigarette prevalence in 2016 is shown in
current smokers. Chart 3-4.
— 13.1% of those 18 to 24 years of age,
17.6% of those 25 to 44 years of age,
18.0% of those 45 to 64 years of age, and
Incidence
8.8% of those ≥65 years old are current • According to the 2015 NSDUH, approximately
smokers. 1.96 million people ≥12 years of age had smoked
— 31.8% of American Indians or Alaska Natives, cigarettes for the first time within the past 12
16.5% of blacks, 9% of Asians, 10.7% of months, a decrease from 2.3 million in 2012.4
Hispanics, and 16.6% of whites are current The 2015 estimate averages out to ≈5390 new
smokers. cigarette smokers every day. Of new smokers
— 25.3% of people below the poverty level in 2015, 823 000 (42.1%) were 12 to 17 years
based on family income and family size are old, 762 000 (39%) were 18 to 20 years old, and
current smokers. 287 000 (14.7%) were 21 to 25 years old; only
• 20.5% of lesbian/gay/bisexual individuals are cur- 84 000 (4.3%) were ≥26 years when they first
rent smokers. smoked cigarettes.
• By region, the prevalence of current cigarette • The number of new smokers 12 to 17 years of
smokers was highest in the Midwest (18.5%) and age (823 000) decreased from 2002 (1.3 million);
lowest in the West (12.3%).7 however, new smokers 18 to 25 years of age
• In 2009, 42.4% of adults with HIV receiving increased from ≈600  000 in 2002 to 1.05 million
medical care were current smokers.9 in 2015.
• Using data from BRFSS 2016, the state with the • According to the NHIS, in 2015, the average age
highest age-adjusted percentage of current ciga- for initiation of cigarette use was 17.9 years.5
rette smokers was West Virginia (26.2%). The • According to data from PATH, in youth 12 to 17
state with the lowest age-adjusted percentage years of age, use of an e-cigarette was indepen-
of current cigarette smokers was Utah (8.7%) dently associated with combustible cigarette use
(Chart 3-3).9a 1 year later (OR, 1.87; 95% CI, 1.15–3.05). For
Downloaded from http://ahajournals.org by on February 7, 2019

• In 2016, smoking prevalence was higher among youth who tried hookah, noncigarette combus-
adults ≥18 years of age who reported having tible tobacco, or smokeless tobacco, a similar
a disability or activity limitation (21.2%) than strength of association for tobacco use at 1 year
among those reporting no disability or limitation was observed.12
(14.4%).7
• 9.3% of males and 33.6% of females with men-
Lifetime Risk and Cumulative Incidence in
tal illness were current smokers.10
• Among females who gave birth in 2016, 7.2% Youth (12 to 17 Years Old) in 2015
smoked cigarettes during pregnancy. Smoking • Per NSDUH data for individuals aged 12 to 17
prevalence during pregnancy was greatest for years, overall, the lifetime use of tobacco prod-
females aged 20 to 24 years (10.7%), followed ucts declined from 18.5% to 17.3%, with lifetime
by females aged 15 to 19 years (8.5%) and 25 cigarette use declining from 14.2% to 13.2%
to 29 years (8.2%).11 Rates were highest among during the same time period (P<0.05 for both).4
NH American Indian or Alaska Native females • The lifetime use of tobacco products among
(16.7%) and lowest in NH Asian females (0.6%). adolescents 12 to 17 years old varied by the
With respect to differences by education, ciga- following4:
rette smoking prevalence was highest among — Sex: Lifetime use was higher among boys
females who completed high school (12.2%), (19.1%) than girls (15.3%).
followed by females with less than high school — Race/ethnicity: Lifetime use was highest among
education (11.7%). whites (19.9%), followed by American Indians
• The PATH study assessed the use of different or Alaska Natives (19.6%), Hispanics or Latinos
types of tobacco products, including cigarettes, (14.5%), African Americans (13.8%), and
e-cigarettes, cigars, cigarillos, filtered cigars, Asians (7.7%).
pipe tobacco, hookah, snus pouches, smoke- — Geographic division: The highest lifetime use
less tobacco, dissolvable tobacco, bidis, and was observed in the South (East South Central
kreteks. This study estimated that in 2013 to 22.8%), and the lowest was observed in the
2014, 34.8% of adult males and 20.8% of Pacific West (13.0%).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e33

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

Adults Secular Trends

CLINICAL STATEMENTS

• According to NSDUH data, the lifetime use of (See Charts 3-2 and 3-5)
AND GUIDELINES

tobacco products in individuals aged ≥18 years Youth

declined significantly (P<0.01) between 2014 The percentage of adolescents (12–17 years old) who
and 2015, from 71.1% to 68.7%, with cigarette reported smoking in the past month declined from 13%
use declining in the same interval from 65.9% to in 2002 to 3.4% in 2016 (Chart 3-5).22 The percentages
63.1% (both P<0.01).4 Similar to the patterns in for daily cigarette use among past-month cigarette-
youth, lifetime risk of tobacco products varied by smoking adolescents were 31.8% in 2002 and 15%
demographic factors: in 2016. Among high school students between 2011
— Sex: Lifetime use was higher in males (78.1%) and 2016, past-month cigarette smoking declined from
than females (60.0%). 15.8% to 8.0% (Chart 3-2).8
— Race/ethnicity: Lifetime use was high-
est in American Indians or Alaska Natives Adults
(75.9%) and whites (75.9%), followed by Since the US Surgeon General’s first report on the
blacks (58.4%), Native Hawaiian or Other health dangers of smoking, age-adjusted rates of smok-
Pacific Islander (56.8%), Hispanics or Latinos ing among adults have declined, from 51% of males
(56.7%), and Asians (37.9%). smoking in 1965 to 16.7% in 2015 and from 34% of
• In 2015, the lifetime use of smokeless tobacco for females in 1965 to 13.6% in 2015, according to NHIS
adults ≥18 years of age was 17.4%. data.10,12 The decline in smoking, along with other
• Lifetime tobacco use for people with psychiatric factors (including improved treatment and reductions
diagnoses was 56.1%, 55.6%, and 70.1% in in the prevalence of risk factors such as uncontrolled
patients with mood disorders, anxiety disorders, hypertension and high cholesterol), is a contributing
and schizophrenia, respectively.13 factor to secular declines in the HD death rate.16
• On the basis of weighted NHIS data, the current
smoking status among 18- to 24-year-old men
Mortality
declined 46.5%, from 28.0% in 2005 to 15.0%
• Of risk factors evaluated by the US Burden of in 2015; for 18- to 24-year-old females, smoking
Disease Collaborators, tobacco use was the sec- declined 47.0%, from 20.7% to 11.0%, over the
Downloaded from http://ahajournals.org by on February 7, 2019

ond-leading risk factor for death in the United same time period.10 On the basis of age-adjusted
States and the leading cause of DALYs, account- estimates in 2015, among people ≥65 years of
ing for 11% of DALYs, in 2016.14 age, 9.7% of males and 8.3% of females were
• Overall mortality among US smokers is 3 times current smokers.
higher than that for never-smokers.15 • From 2005 to 2015, adjusted prevalence rates
• On average, male smokers die 12 years earlier for tobacco use in individuals with serious psy-
than male never-smokers, and female smokers die chological distress (according to the Kessler Scale)
11 years earlier than female never-smokers.9a,16 went from 41.9% to 40.6%, which represents a
• Increased CVD mortality risks persist for older nonsignificant decline; however, rates for people
(≥60 years old) smokers as well. A meta-anal- without serious psychological stress declined sig-
ysis comparing CVD risks in 503 905 cohort nificantly, from 20.3% to 14.0%.10
participants ≥60 years of age reported an HR
for cardiovascular mortality of 2.07 (95% CI,
1.82–2.36) compared with never-smokers and Cardiovascular Health Impact
1.37 (95% CI, 1.25–1.49) compared with for- • A 2010 report of the US Surgeon General on how
mer smokers.18 tobacco causes disease summarized an extensive
• In a sample of Native Americans (SHS), among body of literature on smoking and CVD and the
whom the prevalence of tobacco use is highest in mechanisms through which smoking is thought
the United States, the PAR for total mortality was to cause CVD.21 There is a sharp increase in CVD
18.4% for males and 10.9% for females.19 risk with low levels of exposure to cigarette smoke,
• Since the first report on the dangers of smoking including secondhand smoke, and a less rapid fur-
was issued by the US Surgeon General in 1964, ther increase in risk as the number of cigarettes per
tobacco control efforts have contributed to a day increases. Similar health risks for CHD events
reduction of 8 million premature smoking-attrib- are reported with regular cigar smoking as well.23
utable deaths.20 • Smoking is an independent risk factor for CHD
• If current smoking trends continue, 5.6 million US and appears to have a multiplicative effect with
children will die of smoking prematurely during the other major risk factors for CHD: high serum
adulthood.21 levels of lipids, untreated hypertension, and DM.21

e34 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

• Cigarette smoking and other traditional CHD risk the majority of smokers start smoking, by limiting

CLINICAL STATEMENTS
factors might have a synergistic interaction in HIV- access, because most people who buy cigarettes

AND GUIDELINES
positive individuals.24 for adolescents are <21 years of age.37
• A meta-analysis of 75 cohort studies (≈2.4 million • In several towns where Tobacco 21 laws have
individuals) demonstrated a 25% greater risk for been enacted, 47% reductions in smoking preva-
CHD in female smokers than in male smokers (RR, lence among high school students have been
1.25; 95% CI, 1.12–1.39).25 reported.36
• Cigarette smoking is an independent risk factor • Furthermore, the National Academy of Medicine
for both ischemic stroke and SAH and has a syn- estimates that a nationwide Tobacco 21 law
ergistic effect on other stroke risk factors such as would result in 249 000 fewer premature deaths,
SBP26 and oral contraceptive use.27,28 45 000 fewer lung cancer deaths, and 4.2 mil-
• A meta-analysis comparing pooled data of ≈3.8 lion fewer lost life-years among Americans born
million smokers and nonsmokers found a similar between 2010 and 2019.38
risk of stroke associated with current smoking in • As of March 30, 2018, 5 states (California, New
females and males.26 Jersey, Oregon, Hawaii, and Maine) and at least
• Current smokers have a 2- to 4-times increased 300 localities, including New York City, Chicago,
risk of stroke compared with nonsmokers or those San Antonio, Boston, Cleveland, and both Kansas
who have quit for >10 years.29,30 Cities, have set the minimum age for the pur-
• Short-term exposure to water pipe smoking is asso- chase of tobacco to 21 years.39
ciated with a significant increase in SBP and heart
rate compared with nonsmoking control subjects,31
but long-term effects remain unclear. Current use of Awareness, Treatment, and Control
smokeless tobacco is associated with an increased Smoking Cessation
risk of CVD events in cigarette nonsmokers.32 • According to NHIS 2015 data, 59.1% of adult
• The CVD risks associated with e-cigarette use are ever-smokers had stopped smoking.40
not known.33,34 — The majority (68.0%) of adult smokers
wanted to quit smoking; 55.4% had tried
in the past year, 7.4% had stopped recently,
Healthcare Utilization: Hospital
Downloaded from http://ahajournals.org by on February 7, 2019

and 57.2% had received healthcare provider

Discharges/Ambulatory Care Visits advice to quit.
Cost — Receiving advice to quit smoking was lower
• Each year from 2005 to 2009, US smoking-attrib- in uninsured smokers and varied by race,
utable economic costs were between $289 billion with a lower prevalence in Asian (34.2%),
and $333 billion, including $133 billion to $176 American Indian/Alaska Native (38.1%),
billion for direct medical care of adults and $151 and Hispanic (42.2%) smokers than in white
billion for lost productivity related to premature smokers (60.2%).
death.16 — The period from 2000 to 2015 revealed sig-
• In the United States, cigarette smoking was asso- nificant increases in the prevalence of smok-
ciated with 8.7% of annual aggregated health- ers who had tried to quit in the past year, had
care spending from 2006 to 2010.35 stopped recently, had a health professional
• In 2016, $9.5 billion was spent on marketing recommend quitting, or had used cessation
cigarettes and smokeless tobacco in the United counseling or medication.
States.36 — In 2015, less than one-third of smokers
• 249 billion cigarettes were sold in the United attempting to quit used evidence-based
States in 2017, which is a 3.5% decrease from therapies: 4.7% used both counseling and
the number sold in 2016.36 medication, 6.8% used counseling, and 29.0%
• Cigarette prices in the United States increased used medication (16.6% nicotine patch, 12.5%
steeply between the early 1980s and 2016, in gum/lozenges, 2.4% nicotine spray/inhaler,
large part because of excise taxes on tobacco 2.7% bupropion, and 7.9% varenicline).
products.36 • Smoking cessation reduces the risk of cardiovas-
cular morbidity and mortality for smokers with
Smoking Prevention and without CHD.
Tobacco 21 laws increase the minimum age of sale for — There is no convincing evidence to date that
tobacco products from 18 to 21 years. smoking fewer cigarettes per day reduces the
• Such legislation would likely reduce the rates of risk of CVD, although in several studies, a dose-
smoking during adolescence, a time during which response relationship has been seen among

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e35

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

current smokers between the number of ciga- other counseling have contributed to smoking
CLINICAL STATEMENTS

rettes smoked per day and CVD incidence.15 cessation.40,46

AND GUIDELINES

— Quitting smoking at any age significantly • Mass media antismoking campaigns, such as the
lowers mortality from smoking-related dis- CDC’s Tips campaign (Tips From Former Smokers),
eases, and the risk declines more the longer have been shown to reduce smoking-attributable
the time since quitting smoking.2 Cessation morbidity and mortality and are cost-effective.47
appears to have both short-term (weeks to • Despite states having collected $25.6 billion in
months) and long-term (years) benefits for 2012 from the 1998 Tobacco Master Settlement
lowering CVD risk. Overall, CVD risk appears Agreement and tobacco taxes, <2% of those
to approach that of nonsmokers after ≈10 funds are spent on tobacco prevention and cessa-
years of cessation. tion programs.48
— Smokers who quit smoking at 25 to 34 years
of age gained 10 years of life compared with
those who continued to smoke. Those aged
Electronic Cigarettes
35 to 44 years gained 9 years and those aged (See Charts 3-2 and 3-5)
45 to 54 years gained 6 years of life, on aver- • Electronic nicotine delivery systems, more com-
age, compared with those who continued to monly called electronic cigarettes or e-cigarettes,
smoke.15 are battery-operated devices that deliver nico-
• Cessation medications (including sustained- tine, flavors, and other chemicals to the user in
release bupropion, varenicline, and nicotine gum, an aerosol. Although e-cigarettes were intro-
lozenge, nasal spray, and patch) are effective for duced less than a decade ago, there are currently
helping smokers quit.41 >450 e-cigarette brands on the market, and sales
• EVITA was an RCT that examined the efficacy of in the United States were projected to be $2 bil-
varenicline versus placebo for smoking cessation lion in 2014.
among smokers who were hospitalized for ACS. • Current e-cigarette user prevalence for 2016 is
At 24 weeks, rates of smoking abstinence and shown in Chart 3-4.
reduction were significantly higher among patients • According to the National Youth Tobacco Survey, in
randomized to varenicline. Point-prevalence absti- 2016, e-cigarettes were the most commonly used
nence rates were 47.3% in the varenicline group
Downloaded from http://ahajournals.org by on February 7, 2019

tobacco products in youth: in the prior 30 days,

and 32.5% in the placebo group (P=0.012; 4.3% of middle school and 11.3% of high school
NNT=6.8). Continuous abstinence rates and reduc- students endorsed use (Chart 3-2).8 Despite a gen-
tion rates (≥50% of daily cigarette consumption) eral trend of increased use between 2011 and
were also higher in the varenicline group.42 2016, the prevalence of e-cigarette use decreased
• The EAGLES trial43 demonstrated the efficacy and between 2015 and 2016, from 5.3% to 4.3% in
safety of 12 weeks of varenicline, bupropion, middle school students and from 16.0% to 11.3%
or nicotine patch in motivated-to-quit smoking in high school students. Among high school stu-
patients with major depressive disorder, bipolar dents, rates of use were most pronounced in males
disorder, anxiety disorders, posttraumatic stress (13.1%) and NH whites (13.7%). In middle school
disorder, obsessive-compulsive disorder, social students, higher rates were observed in males
phobia, psychotic disorders including schizophre- (5.1%) than females (3.4%) and in Hispanics
nia and schizoaffective disorders, and borderline (5.6%) than in other racial/ethnic groups (3.7% in
personality disorder. Of note, these participants NH white students and 4.0% in NH black students)
were all clinically stable from a psychiatric per- • In 2014, 18.3 million US middle and high school
spective and were believed not to be at high risk students (68.9%) were exposed to e-cigarette
for self-injury.43 advertising.4,49
• Extended use of a nicotine patch (24 weeks com- • Among US adults, awareness and use of e-cig-
pared with 8 weeks) has been demonstrated to arettes has increased considerably.50 In 2014,
be safe and efficacious in recent randomized clini- 12.6% of all adults and nearly half (49%) of
cal trials.44 current daily cigarette smokers had tried an
• An RCT demonstrated the effectiveness of indi- e-cigarette.51
vidual- and group-oriented financial incentives for • According to NHIS 2014 data, among US work-
tobacco abstinence through at least 12 months of ing adults, 3.8% (≈5.5 million) currently used
follow-up.45 e-cigarettes. The use of e-cigarettes was signifi-
• In addition to medications, smoke-free policies, cantly higher among current smokers (16.2%)
increases in tobacco prices, cessation advice than among past smokers (4.3%) or never-smok-
from healthcare professionals, and quit-lines and ers (0.5%). Similarly, prevalence was significantly

e36 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

higher among males (4.5%), NH whites (4.5%), Mexican Americans (23.9%). People living below

CLINICAL STATEMENTS
younger adults (18–24 years; 5.1%), individu- the poverty level (43.2%) and those living in rental

AND GUIDELINES
als without health insurance (5.9%), individuals housing (36.8%) had higher rates of secondhand
with incomes <$35 000, and those residing in the smoke exposure than their counterparts (21.1% of
Midwest (4.5%).52 those living above the poverty level and 19.0% of
• Effective August 8, 2016, the US Food and Drug those who owned their homes; NHANES).55
Administration’s Deeming Rule prohibited sale of
e-cigarettes to individuals <18 years of age.53
Family History and Genetics
• Genetic factors might contribute to smoking
Secondhand Smoke behavior; several loci have been identified that are
• Data from the US Surgeon General on the con- associated with smoking initiation, number of cig-
sequences of secondhand smoke indicate the arettes smoked per day, and smoking cessation.55
following: • Genetics might also modify adverse cardiovascular
— Nonsmokers who are exposed to secondhand health outcomes among smokers, with variation
smoke at home or at work increase their risk in ADAMTS7 associated with loss of cardioprotec-
of developing CHD by 25% to 30%.21 tion in smokers.56
— Exposure to secondhand smoke increases
the risk of stroke by 20% to 30%, and
it is associated with increased mortality
Global Burden of Tobacco Use
(adjusted mortality rate ratio, 2.11) after a (See Table 3-1 and Chart 3-6)
stroke.51 • Although tobacco use in the United States has
• A meta-analysis of 23 prospective and 17 case- been declining, the absolute number of tobacco
control studies of cardiovascular risks associated users worldwide has climbed steeply.42
with secondhand smoke exposure demonstrated • On the basis of the GBD synthesis of >2800 data
18%, 23%, 23%, and 29% increased risks for sources, the age-standardized global prevalence
total mortality, total CVD, CHD, and stroke, of daily smoking in 2016 was 25.1% (95% UI,
respectively, in those exposed to secondhand 22.7%–28.7%) in males and 7.9% (95% UI,
smoke.52 6.5%–10.6%) in females. The investigators
Downloaded from http://ahajournals.org by on February 7, 2019

• A meta-analysis of 24 studies demonstrates that estimate that since 1990, smoking rates have
secondhand smoke can increase risks for preterm declined globally by 29.6% in males and 28.6%
birth by 20%.53 in females.1
• As of April 1, 2018, 11 states (California, • The GBD 2016 study used statistical models and
Connecticut, Delaware, Hawaii, Maine, New data on incidence, prevalence, case fatality, excess
Jersey, New York, North Dakota, Oregon, Utah, mortality, and cause-specific mortality to estimate
and Vermont), the District of Columbia, and disease burden for 315 diseases and injuries in
Puerto Rico have passed comprehensive smoke- 195 countries and territories. Eastern and Central
free indoor air laws that include e-cigarettes. Europe, East Asia, Southeast Asia, and southern
These laws prohibit smoking and the use of e-cig- sub-Saharan Africa have the highest mortality
arettes in indoor areas of private work sites, res- rates attributable to tobacco (Chart 3-6).57
taurants, and bars.39 • The number of smokers was estimated to have
• Pooled data from 17 studies in North America, grown from 721 million in 1980 to 967 million in
Europe, and Australia suggest that smoke-free 2012.58
legislation can reduce the incidence of acute cor- • Worldwide, ≈80% of smokers live in low- and
onary events by 10%.54 middle-income countries.59
• The percentage of the US nonsmoking population • Tobacco smoking (including secondhand smoke)
with serum cotinine ≥0.05 ng/mL (which indi- caused an estimated 7.1 million deaths in 2016.
cates exposure to secondhand smoke) declined Among the leading risk factors for death, smok-
from 52.5% in 1999 to 2000 to 25.3% in 2011 ing ranked fourth in DALYs globally.14
to 2012, with declines occurring for both children • The WHO estimated that the economic cost of
and adults. During 2011 to 2012, the percentage smoking-attributable diseases accounted for US
of nonsmokers with detectable serum cotinine was $422 billion, which represented ≈5.7% of global
40.6% for those 3 to 11 years of age, 33.8% for health expenditures.60 The total economic costs,
those 12 to 19 years of age, and 21.3% for those including both health expenditures and lost pro-
≥20 years of age. The percentage was higher for ductivity, amounted to approximately US $1436
NH blacks (46.8%) than for NH whites (21.8%) and billion, which was roughly equal to 1.8% of the

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e37

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

world’s annual gross domestic product. The WHO outline the following strategies for nations to
CLINICAL STATEMENTS

further estimated that 40% of the expenditures reduce tobacco use: (1) monitor tobacco use and
AND GUIDELINES

were in developing countries. prevention policies; (2) protect individuals from

• To help combat the global problem of tobacco tobacco smoke; (3) offer to help with tobacco
exposure, in 2003 the WHO adopted the cessation; (4) warn about tobacco-related dan-
Framework Convention on Tobacco Control gers; (5) enforce bans on tobacco advertising; (6)
treaty. From this emerged a set of evidence-based raise taxes on tobacco; and (7) reduce the sale
policies with the goal of reducing the demand for of cigarettes. More than half of all nations have
tobacco, entitled MPOWER. MPOWER policies implemented at least 1 MPOWER policy.‍61

Table 3-1.  Deaths Caused by Tobacco Smoke Worldwide, by Sex

Males and Females Males Females

Total number of deaths in 2015, millions 7.2 (6.5 to 7.8) 5.2 (4.7 to 5.7) 1.9 (1.7 to 2.2)
Percent change in total number from 1990 to 2015 21.5 (15.8 to 27.2) 26.4 (20.4 to 32.9) 9.9 (1.2 to 19.1)
Percent change in total number from 2005 to 2015 4.2 (0.9 to 7.6) 6.8 (3.1 to 10.7) -2.3 (-7.5 to 3.7)
Mortality rate per 100 000 in 2015 110.7 (101.0 to 120.3) 177.2 (160.2 to 193.7) 55.2 (48.8 to 61.9)
Percent change in rate from 2005 to 2015 −20.3 (−22.8 to −17.7) −18.9 (−21.7 to −16.0) −25.2 (−29.1 to −20.5)
Percent change in rate from 1990 to 2015 −33.3 (−36.4 to −30.1) −32.8 (−35.8 to −29.5) −38.4 (−43.7 to −33.2)
PAF in 2015, % 12.8 (11.7 to 13.9) 16.9 (15.4 to 18.4) 7.8 (6.9 to 8.7)
Percent change in PAF from 1990 to 2015 4.4 (−0.1 to 8.5) 3.7 (−0.1 to 7.4) −0.4 (−7.9 to 7.0)
Percent change in PAF from 2005 to 2015 0.1 (−2.4 to 2.6) −0.1 (−2.4 to 2.2) −3.0 (−7.4 to 2.2)

Rates are most current data available as of 2015. Rates are per 100 000 people. Values in parentheses represent 95% CIs. PAF indicates
population attributable fraction.
Source: Global Burden of Disease Study 2015, Institute of Health Metrics and Evaluation.62
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 3-1. Prevalence (%) of cigarette use in the past month for adolescents aged 12 to 17 years by sex and race/ethnicity (NSDUH, 2014 and 2015).
Because of methodological differences among the NSDUH, the Youth Risk Behavior Survey, the National Youth Tobacco Survey, and other surveys, percentages of
cigarette smoking measured by these surveys are not directly comparable. Notably, school-based surveys might include students who are 18 years old, who are
legally permitted to smoke and have higher rates of smoking.
AIAN indicates American Indian or Alaska Native; NH, non-Hispanic; and NSDUH, National Survey on Drug Use and Health.
Data derived from Substance Abuse and Mental Health Services Administration, NSDUH.63

e38 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

CLINICAL STATEMENTS
AND GUIDELINES
Chart 3-2. Estimated percentage of high school students who have used any tobacco products,* ≥2 tobacco products,†‡ and select tobacco prod-
ucts§ in the past 30 days (National Youth Tobacco Survey, 2011–2016).
*Any tobacco use is defined as past 30-day use of cigarettes, cigars, smokeless tobacco, electronic cigarettes (e-cigarettes), hookahs, pipe tobacco, and/or bidis.
†Use of ≥2 tobacco products is defined as past 30-day use of ≥2 of the following product types: cigarettes, cigars, smokeless tobacco, e-cigarettes, hookahs, pipe
tobacco, or bidis. ‡Use of ≥2 tobacco products demonstrated a nonlinear change (P<0.05). §E-cigarettes and hookahs demonstrated a linear increase (P<0.05).
Cigarettes, cigars, and smokeless tobacco demonstrated a linear decrease (P<0.05). Pipe tobacco and bidis demonstrated a nonlinear decrease (P<0.05).
Data derived from the Centers for Disease Control and Prevention, National Youth Tobacco Survey.64
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 3-3. Age-adjusted prevalence (%) of current cigarette smoking for adults, by state: United States (BRFSS, 2016).
BRFSS indicates Behavior Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
Data derived from the Centers for Disease Control and Prevention.65

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e39

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3
CLINICAL STATEMENTS
AND GUIDELINES

Chart 3-4. Prevalence (age-adjusted) of current e-cigarette use (BRFSS, 2016).

BRFSS indicates Behavior Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 3-5. Past month cigarette use among people ≥12 years of age, by age group: percentages, 2002 to 2016 (NHIS, 2002–2016; NSDUH, 2002–
2016).
NSDUH indicates National Survey on Drug Use and Health; and NHIS, National Health Interview Survey.
Data derived from the Centers for Disease Control and Prevention/National Center for Health Statistics and the Substance Abuse and Mental Health Services
Administration (NSDUH).63

e40 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

CLINICAL STATEMENTS
AND GUIDELINES
Chart 3-6. Age-standardized global mortality rates attributable to tobacco per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016 with permission.57 Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

[published correction appears in N Engl J Med. 2018;378:492]. N Engl J

REFERENCES Med. 2017;376:342–353. doi: 10.1056/NEJMsa1607538
1. GBD 2016 Risk Factor Collaborators. Global, regional, and national com- 8. Jamal A, Gentzke A, Corey CG, Hu SS, Cullen KA, Apelberg BJ, Homa
parative risk assessment of 84 behavioural, environmental and occupa- DM,King BA. Tobacco use among middle and high school students:
tional, and metabolic risks or clusters of risks, 1990–2016: a systematic United States, 2011–2016 [published correction appears in MMWR
analysis for the Global Burden of Disease Study 2016 [published cor- Morb Mortal Wkly Rep. 2017;66:765]. MMWR Morb Mortal Wkly Rep.
rections appear in Lancet. 2017;390: E38 and Lancet. 2017;390:1736]. 2017;66:23;597–603. doi: 10.15585/mmwr.mm6623a1
Lancet. 2017;390:1345–1422. doi: 10.1016/S0140-6736(17)32366-8 9. Mdodo R, Frazier EL, Dube SR, Mattson CL, Sutton MY, Brooks JT, Skarbinski
2. Thun MJ, Carter BD, Feskanich D, Freedman ND, Prentice R, Lopez J. Cigarette smoking prevalence among adults with HIV compared with
AD, Hartge P, Gapstur SM. 50-Year trends in smoking-related mor- the general adult population in the United States: cross-sectional surveys.
tality in the United States. N Engl J Med. 2013;368:351–364. doi: Ann Intern Med. 2015;162:335–344. doi: 10.7326/M14-0954
10.1056/NEJMsa1211127 9a. Centers for Disease Control and Prevention, National Center for Chronic
3. American Heart Association. My Life Check – Life’s Simple 7. https://www. Disease Prevention and Health Promotion, Division of Population Health.
heart.org/en/healthy-living/healthy-lifestyle/my-life-check--lifes-simple-7. BRFSS Prevalence & Trends Data. 2016. https://www.cdc.gov/brfss/
Accessed November 9, 2018. brfssprevalence/index.html. Accessed October 28, 2018.
4. Center for Behavioral Health Statistics and Quality. Key Substance Use 10. Jamal A, King BA, Neff LJ, Whitmill J, Babb SD, Graffunder CM. Current
and Mental Health Indicators in the United States: Results From the 2015 cigarette smoking among adults: United States, 2005-2015. MMWR Morb
National Survey on Drug Use and Health. September 2016. HHS publi- Mortal Wkly Rep. 2016;65:1205–1211. doi: 10.15585/mmwr.mm6544a2
cation No. SMA 16-4984, NSDUH series H-51. https://www.samhsa.gov/ 11. Drake P, Driscoll AK, Mathews TJ. Cigarette smoking during pregnancy:
data/sites/default/files/NSDUH-FFR1-2015/NSDUH-FFR1-2015/NSDUH-
United States, 2016. NCHS Data Brief. 2018 Feb;(305):1–8.
FFR1-2015.pdf. Accessed August 1, 2018.
12. Watkins SL, Glantz SA, Chaffee BW. Association of noncigarette tobacco
5. Centers for Disease Control and Prevention, National Center for Health
product use with future cigarette smoking among youth in the Population
Statistics. National Health Interview Survey 2016 Data Release. https://www.
Assessment of Tobacco and Health (PATH) Study, 2013-2015. JAMA
cdc.gov/nchs/nhis/nhis_2016_data_release.htm. Accessed October 28,
Pediatr. 2018;172:181–187. doi: 10.1001/jamapediatrics.2017.4173
2018.
6. Centers for Disease Control and Prevention (CDC). Electronic Nicotine 13. Martins SS, Gorelick DA. Conditional substance abuse and depen-
Delivery Systems Key Facts. 2014. https://www.cdc.gov/tobacco/infographics/ dence by diagnosis of mood or anxiety disorder or schizophrenia in
policy/pdfs/electronic-nicotine-delivery-systems-key-facts-infographic.pdf. the U.S. population. Drug Alcohol Depend. 2011;119:28–36. doi:
Accessed June 8, 2016. 10.1016/j.drugalcdep.2011.05.010
7. Kasza KA, Ambrose BK, Conway KP, Borek N, Taylor K, Goniewicz ML, 14. US Burden of Disease Collaborators. The state of US health, 1990–2016:
Cummings KM, Sharma E, Pearson JL, Green VR, Kaufman AR, Bansal- burden of diseases, injuries, and risk factors among US states. JAMA.
Travers M, Travers MJ, Kwan J, Tworek C, Cheng YC, Yang L, Pharris-Ciurej 2018;319:1444–1472. doi: 10.1001/jama.2018.0158
N, van Bemmel DM, Backinger CL, Compton WM, Hyland AJ. Tobacco- 15. Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson
product use by adults and youths in the United States in 2013 and 2014 RN, McAfee T, Peto R. 21st-century hazards of smoking and benefits of

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e41

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

cessation in the United States. N Engl J Med. 2013;368:341–350. doi: 32. Yatsuya H, Folsom AR; and for the ARIC Investigators. Risk of inci-
CLINICAL STATEMENTS

10.1056/NEJMsa1211128 dent cardiovascular disease among users of smokeless tobacco in the

AND GUIDELINES

16. US Department of Health and Human Services. The Health Consequences Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol.
of Smoking—50 Years of Progress: A Report of the Surgeon General. 2010;172:600–605. doi: 10.1093/aje/kwq191
Atlanta, GA: US Department of Health and Human Services, Centers 33. Bhatnagar A, Whitsel LP, Ribisl KM, Bullen C, Chaloupka F, Piano MR,
for Disease Control and Prevention, National Center for Chronic Disease Robertson RM, McAuley T, Goff D, Benowitz N; on behalf of the American
Prevention and Health Promotion, Office on Smoking and Health; 2014. Heart Association Advocacy Coordinating Committee, Council on
17. Deleted in proof. Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and
18. Mons U, Müezzinler A, Gellert C, Schöttker B, Abnet CC, Bobak M, Council on Quality of Care and Outcomes Research. Electronic cigarettes:
de Groot L, Freedman ND, Jansen E, Kee F, Kromhout D, Kuulasmaa K, a policy statement from the American Heart Association. Circulation.
Laatikainen T, O’Doherty MG, Bueno-de-Mesquita B, Orfanos P, Peters 2014;130:1418–1436. doi: 10.1161/CIR.0000000000000107
A, van der Schouw YT, Wilsgaard T, Wolk A, Trichopoulou A, Boffetta 34. Bhatnagar A. E-cigarettes and cardiovascular disease risk: evaluation of
P, Brenner H; on behalf of the CHANCES Consortium. Impact of smok- evidence, policy implications, and recommendations. Curr Cardiovasc Risk
ing and smoking cessation on cardiovascular events and mortality among Rep. 2016;10:24. doi: 10.1007/s12170-016-0505-6
older adults: meta-analysis of individual participant data from prospective 35. Xu X, Bishop EE, Kennedy SM, Simpson SA, Pechacek TF. Annual health-
cohort studies of the CHANCES consortium. BMJ. 2015;350:h1551. doi: care spending attributable to cigarette smoking: an update. Am J Prev
10.1136/bmj.h1551 Med. 2015;48:326–333. doi: 10.1016/j.amepre.2014.10.012
19. Zhang M, An Q, Yeh F, Zhang Y, Howard BV, Lee ET, Zhao J. Smoking- 36. Trends in State and Federal Cigarette Tax and Retail Price in the United
attributable mortality in American Indians: findings from the Strong States: 1970-2016. https://www.cdc.gov/tobacco/infographics/economics/
Heart Study. Eur J Epidemiol. 2015;30:553–561. doi: 10.1007/ pdfs/linegraph2017.pdf?s_cid=bb-osh-economics-graphic-001. Accessed
s10654-015-0031-8 October 28, 2018.
20. Holford TR, Meza R, Warner KE, Meernik C, Jeon J, Moolgavkar SH, Levy 37. Kessel Schneider S, Buka SL, Dash K, Winickoff JP, O’Donnell L.
DT. Tobacco control and the reduction in smoking-related premature Community reductions in youth smoking after raising the minimum
deaths in the United States, 1964-2012. JAMA. 2014;311:164–171. doi: tobacco sales age to 21. Tob Control. 2016;25:355–359. doi: 10.1136/
10.1001/jama.2013.285112 tobaccocontrol-2014-052207
21. US Department of Health and Human Services. How Tobacco Smoke 38. Morain SR, Winickoff JP, Mello MM. Have Tobacco 21 laws come of age?
Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable N Engl J Med. 2016;374:1601–1604. doi: 10.1056/NEJMp1603294
Disease: A Report of the Surgeon General. Atlanta, GA: Centers for 39. States and localities that have raised the minimum legal sale age for
Disease Control and Prevention; 2010. tobacco products to 21. https://www.tobaccofreekids.org/content/
22. Substance Abuse and Mental Health Services Administration. Key what_we_do/state_local_issues/sales_21/states_localities_MLSA_21.pdf.
Substance Use and Mental Health Indicators in the United States: Results Accessed June 5, 2017.
from the 2016 National Survey on Drug Use and Health. 2017. https:// 40. Babb S, Malarcher A, Schauer G, Asman K, Jamal A. Quitting smoking
www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH- among adults: United States, 2000-2015. MMWR Morb Mortal Wkly Rep.
FFR1-2016.pdf. Accessed April 4, 2018. 2017;65:1457–1464. doi: 10.15585/mmwr.mm6552a1
23. Chang CM, Corey CG, Rostron BL, Apelberg BJ. Systematic review of cigar 41. Clinical Practice Guideline Treating Tobacco Use and Dependence Update
smoking and all cause and smoking related mortality. BMC Public Health. Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco
2015;15:390. doi: 10.1186/s12889-015-1617-5 use and dependence: 2008 update: a U.S. Public Health Service report.
24. Rasmussen LD, Helleberg M, May MT, Afzal S, Kronborg G, Larsen CS, Am J Prev Med. 2008;35:158–176. doi: 10.1016/j.amepre.2008.04.009
Downloaded from http://ahajournals.org by on February 7, 2019

Pedersen C, Gerstoft J, Nordestgaard BG, Obel N. Myocardial infarction 42. Eisenberg MJ, Windle SB, Roy N, Old W, Grondin FR, Bata I, Iskander A,
among Danish HIV-infected individuals: population-attributable frac- Lauzon C, Srivastava N, Clarke A, Cassavar D, Dion D, Haught H, Mehta
tions associated with smoking. Clin Infect Dis. 2015;60:1415–1423. doi: SR, Baril JF, Lambert C, Madan M, Abramson BL, Dehghani P; for the
10.1093/cid/civ013 EVITA Investigators. Varenicline for smoking cessation in hospitalized
25. Huxley RR, Woodward M. Cigarette smoking as a risk factor for coro- patients with acute coronary syndrome. Circulation. 2016;133:21–30.
nary heart disease in women compared with men: a systematic review doi: 10.1161/CIRCULATIONAHA.115.019634
and meta-analysis of prospective cohort studies. Lancet. 2011;378:1297– 43. Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D,
1305. doi: 10.1016/S0140-6736(11)60781-2 Ascher J, Russ C, Krishen A, Evins AE. Neuropsychiatric safety and effi-
26. Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke cacy of varenicline, bupropion, and nicotine patch in smokers with and
in women compared with men: a systematic review and meta-analysis of without psychiatric disorders (EAGLES): a double-blind, randomised,
81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke. placebo-controlled clinical trial. Lancet. 2016;387:2507–2520. doi:
2013;44:2821–2828. doi: 10.1161/STROKEAHA.113.002342 10.1016/S0140-6735(16)30272-0
27. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone 44. Schnoll RA, Goelz PM, Veluz-Wilkins A, Blazekovic S, Powers L, Leone FT,
Contraception. Ischaemic stroke and combined oral contraceptives: Gariti P, Wileyto EP, Hitsman B. Long-term nicotine replacement therapy:
results of an international, multicentre, case-control study. Lancet. a randomized clinical trial. JAMA Intern Med. 2015;175:504–511. doi:
1996;348:498–505. doi: 10.1016/S0140-6736(95)12393-8 10.1001/jamainternmed.2014.8313
28. WHO Collaborative Study of Cardiovascular Disease and Steroid 45. Halpern SD, French B, Small DS, Saulsgiver K, Harhay MO, Audrain-
Hormone Contraception. Haemorrhagic stroke, overall stroke risk, McGovern J, Loewenstein G, Brennan TA, Asch DA, Volpp KG. Randomized
and combined oral contraceptives: results of an international, multi- trial of four financial-incentive programs for smoking cessation. N Engl J
centre, case-control study. Lancet. 1996;348:505–510. doi: 10.1016/ Med. 2015;372:2108–2117. doi: 10.1056/NEJMoa1414293
S0140-6736(95)12394-6 46. Centers for Disease Control and Prevention (CDC). Quitting smoking
29. Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi among adults: United States, 2001–2010. MMWR Morb Mortal Wkly
S, Creager MA, Eckel RH, Elkind MS, Fornage M, Goldstein LB, Greenberg Rep. 2011;60:1513–1519.
SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA; on behalf of 47. Xu X, Alexander RL Jr, Simpson SA, Goates S, Nonnemaker JM, Davis
the American Heart Association Stroke Council; Council on Cardiovascular KC, McAfee T. A cost-effectiveness analysis of the first federally funded
and Stroke Nursing; Council on Clinical Cardiology; Council on Functional antismoking campaign. Am J Prev Med. 2015;48:318–325. doi:
Genomics and Translational Biology; Council on Hypertension. Guidelines 10.1016/j.amepre.2014.10.011
for the primary prevention of stroke: a statement for healthcare profes- 48. Antman E, Arnett D, Jessup M, Sherwin C. The 50th anniversary of the
sionals from the American Heart Association/American Stroke Association. US Surgeon General’s report on tobacco: what we’ve accomplished
Stroke. 2014;45:3754–3832. doi: 10.1161/STR.0000000000000046 and where we go from here. J Am Heart Assoc. 2014;3:e000740. doi:
30. Shah RS, Cole JW. Smoking and stroke: the more you smoke the 10.1161/JAHA.113.000740
more you stroke. Expert Rev Cardiovasc Ther. 2010;8:917–932. doi: 49. Singh T, Marynak K, Arrazola RA, Cox S, Rolle IV, King BA. Vital signs:
10.1586/erc.10.56 exposure to electronic cigarette advertising among middle school and
31. Azar RR, Frangieh AH, Mroué J, Bassila L, Kasty M, Hage G, Kadri high school students: United States, 2014. MMWR Morb Mortal Wkly
Z. Acute effects of waterpipe smoking on blood pressure and heart Rep. 2016;64:1403–1408. doi: 10.15585/mmwr.mm6452a3
rate: a real-life trial. Inhal Toxicol. 2016;28:339–342. doi: 10.3109/ 50. Zhu SH, Sun JY, Bonnevie E, Cummins SE, Gamst A, Yin L, Lee
08958378.2016.1171934 M. Four hundred and sixty brands of e-cigarettes and counting:

e42 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 3

implications for product regulation. Tob Control. 2014;23(suppl 3):iii3-iii9. of gene-smoking interactions. Circulation. 2017;135:2336–2353. doi:

CLINICAL STATEMENTS
doi: 10.1136/tobaccocontrol-2014-051670 10.1161/CIRCULATIONAHA.116.022069

AND GUIDELINES
51. Delnevo CD, Giovenco DP, Steinberg MB, Villanti AC, Pearson JL, 57. Global Burden of Disease Study 2016 (GBD 2016) results. Global Health
Niaura RS, Abrams DB. Patterns of electronic cigarette use among Data Exchange website. Seattle, WA: Institute for Health Metrics and
adults in the United States. Nicotine Tob Res. 2016;18:715–719. doi: Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
10.1093/ntr/ntv237 data.org/gbd-results-tool. Accessed May 1, 2018.
52. Syamlal G, Jamal A, King BA, Mazurek JM. Electronic cigarette use among 58. Ng M, Freeman MK, Fleming TD, Robinson M, Dwyer-Lindgren L,
working adults: United States, 2014. MMWR Morb Mortal Wkly Rep. Thomson B, Wollum A, Sanman E, Wulf S, Lopez AD, Murray CJ, Gakidou
2016;65:557–561. doi: 10.15585/mmwr.mm6522a1 E. Smoking prevalence and cigarette consumption in 187 countries, 1980-
53. FDA’s deeming regulations for e-cigarettes, cigars, and all other tobacco 2012. JAMA. 2014;311:183–192. doi: 10.1001/jama.2013.284692
products. US Food & Drug Administration website. https://www.fda.gov/ 59. World Health Organization. Tobacco Fact Sheet. 2017. http://www.who.
TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm394909.htm. int/mediacentre/factsheets/fs339/en/. Accessed June 5, 2017.
Accessed April 6, 2018. 60. Goodchild M, Nargis N, Tursan d’Espaignet E. Global economic cost
54. Mackay DF, Irfan MO, Haw S, Pell JP. Meta-analysis of the effect of of smoking-attributable diseases. Tob Control. 2017;27:58–64. doi:
comprehensive smoke-free legislation on acute coronary events. Heart. 10.1136/tobaccocontrol-2016-053305
2010;96:1525–1530. doi: 10.1136/hrt.2010.199026 61. World Health Organization. The WHO Framework Convention on Tobacco
55. Tobacco and Genetics Consortium. Genome-wide meta-analyses identify Control: An Overview. 2015. http://www.who.int/fctc/about/en/index.
multiple loci associated with smoking behavior. Nat Genet. 2010;42:441– html. Accessed July 18, 2016.
447. doi: 10.1038/ng.571 62. Global Burden of Disease Study 2015 (GBD 2015) results. Global Health
56. Saleheen D, Zhao W, Young R, Nelson CP, Ho W, Ferguson JF, Rasheed Data Exchange website. Seattle, WA: Institute for Health Metrics and
A, Ou K, Nurnberg ST, Bauer RC, Goel A, Do R, Stewart AFR, Hartiala Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
J, Zhang W, Thorleifsson G, Strawbridge RJ, Sinisalo J, Kanoni S, data.org/gbd-results-tool. Accessed May 30, 2017.
Sedaghat S, Marouli E, Kristiansson K, Hua Zhao J, Scott R, Gauguier 63. Center for Behavioral Health Statistics and Quality. Behavioral Health
D, Shah SH, Smith AV, van Zuydam N, Cox AJ, Willenborg C, Kessler Trends in the United States: Results From the 2014 National Survey on
T, Zeng L, Province MA, Ganna A, Lind L, Pedersen NL, White CC, Drug Use and Health. 2015. http://www.samhsa.gov/data/. Accessed
Joensuu A, Edi Kleber M, Hall AS, März W, Salomaa V, O’Donnell August 25, 2016.
C, Ingelsson E, Feitosa MF, Erdmann J, Bowden DW, Palmer CNA, 64. National Youth Tobacco Survey (NYTS). Centers for Disease Control and
Gudnason V, Faire U, Zalloua P, Wareham N, Thompson JR, Kuulasmaa Prevention website. http://www.cdc.gov/tobacco/data_statistics/surveys/
K, Dedoussis G, Perola M, Dehghan A, Chambers JC, Kooner J, nyts/. Accessed July 18, 2016.
Allayee H, Deloukas P, McPherson R, Stefansson K, Schunkert H, 65. State Tobacco Activities Tracking and Evaluation (STATE) System. Centers
Kathiresan S, Farrall M, Marcel Frossard P, Rader DJ, Samani NJ, Reilly for Disease Control and Prevention website. http://www.cdc.gov/
MP. Loss of cardioprotective effects at the ADAMTS7 locus as a result statesystem/cigaretteuseadult.html. Accessed July 18, 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e43

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

4. PHYSICAL INACTIVITY basis of survey interviews,4 only 27.1% of high school

CLINICAL STATEMENTS

students reported achieving at least 60 minutes of daily

See Charts 4-1 through 4-13
AND GUIDELINES

PA, which is likely an overestimation of those actually

meeting the guidelines.5,6 The 2008 federal guidelines
Click here to return to the Table of Contents
recommend that adults get at least 150 minutes of
moderate-intensity or 75 minutes of vigorous-intensity
Physical inactivity is a major risk factor for CVD and
aerobic activity (or an equivalent combination) per
stroke.1 Meeting the guidelines for PA is one of the
week and perform muscle-strengthening activities at
AHA’s 7 components of ideal cardiovascular health for
least 2 days per week.3 In a nationally representative
both children and adults.2 The AHA and 2008 federal
sample of adults, only 22.5% of adults reported par-
guidelines for PA recommend that children get at least
ticipating in adequate leisure-time aerobic and mus-
60 minutes of PA daily (including aerobic and muscle-
cle-strengthening activity to meet these criteria (Chart
and bone-strengthening activity).3 In 2015, on the
4-1), but they were not asked to report activity accumu-
lated during occupational, transportation, or domestic
Abbreviations Used in Chapter 4 duties.7 Being physically active is an important aspect
AF atrial fibrillation of overall health. PA not only reduces premature mor-
AHA American Heart Association tality but also improves risk factors for CVD (such as
AMI acute myocardial infarction
HBP and high cholesterol) and reduces the likelihood
BMI body mass index
BP blood pressure
of diseases related to CVD, including CHD, HF, stroke,
CAD coronary artery disease type 2 DM, and sudden heart attacks.3 Benefits from
CHD coronary heart disease PA are seen for all ages and groups, including chil-
CI confidence interval dren and older adults, pregnant females, and people
CVD cardiovascular disease with disabilities and chronic conditions. Therefore, the
DBP diastolic blood pressure
2008 federal guidelines recommend being as physi-
DM diabetes mellitus
ED emergency department cally active as abilities and conditions allow and, if not
EF ejection fraction currently meeting the recommendations, increasing PA
GBD Global Burden of Disease gradually.3 Ahead of the new 2018 federal guidelines,
GED General Educational Development the Physical Activity Guidelines Advisory Committee
HBP high blood pressure
Downloaded from http://ahajournals.org by on February 7, 2019

published a report providing an even clearer message

HDL high-density lipoprotein
HDL-C high-density lipoprotein cholesterol
for individuals not meeting the 150 minutes of mod-
HF heart failure erate PA per week guideline, stating that even small
HR hazard ratio increases in moderate-intensity PA or replacing seden-
LDL-C low-density lipoprotein cholesterol tary time with light-intensity PA could provide health
LIFE Lifestyle Interventions and Independence for Elders benefits.8
MET metabolic equivalent
MI myocardial infarction
MSA Metropolitan Statistical Area Defining and Measuring PA
NAVIGATOR Long-term Study of Nateglinide + Valsartan to Prevent
or Delay Type II Diabetes Mellitus and Cardiovascular There are 4 dimensions of PA (mode or type, frequency,
Complications duration, and intensity) and 4 common domains for
NH non-Hispanic
adults (occupational, domestic, transportation, and lei-
NHANES National Health and Nutrition Examination Survey
NHIS National Health Interview Survey
sure time).5 For children, there are additional consid-
OR odds ratio erations of structured PA in schools and communities.
PA physical activity The federal guidelines specify the suggested frequency,
PAD peripheral artery disease duration, and intensity of activity. Historically, recom-
PAR population attributable risk mendations on PA for health purposes have focused on
QALY quality-adjusted life-year
leisure-time activity. However, because all domains of
RCT randomized controlled trial
REGARDS Reasons for Geographic and Racial Differences in Stroke PA could have an impact on health, and because an
RR relative risk increase in 1 domain can sometimes be compensated
SBP systolic blood pressure for by a decrease in another domain, ideally data will be
SD standard deviation collected on all dimensions and domains of PA.5
SES socioeconomic status
There are 2 broad categories of methods to assess
TC total cholesterol
VTE venous thromboembolism
PA: (1) subjective methods that use questionnaires
WC waist circumference and diaries/logs and (2) objective methods that use
WHI Women’s Health Initiative wearable monitors (pedometers, accelerometers, etc).
WHO World Health Organization Studies that compare the findings between subjective
YRBSS Youth Risk Behavior Surveillance System and objective methods have found that there is marked

e44 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

discordance between self-reported and measured PA, per week was higher among NH white

CLINICAL STATEMENTS
with respondents often overstating their PA, especially boys (62.0%), NH black boys (52.2%),

AND GUIDELINES
the intensity.5,6 and Hispanic boys (53.5%) than NH
Another consideration in the measurement of PA white girls (43.5%), NH black girls
is that surveys often ask only about leisure-time PA, (33.4%), and Hispanic girls (33.1%)
which represents PA obtained from a single domain. (Chart 4-2).
People who obtain high PA in other domains might — 14.3% of students reported that they did not
be less likely to engage in leisure-time PA. Although participate in ≥60 minutes of any kind of PA
they might meet the federal PA guidelines, people on any 1 of the previous 7 days. Girls were
who spend considerable time and physical effort in more likely than boys to report this level of
occupational, domestic, or transportation activities/ inactivity (17.5% versus 11.1%), with black
domains might be less likely to be identified as meet- girls reporting the highest rate of inactivity
ing the guidelines. (25.2%) (Chart 4-3).
PA and cardiorespiratory fitness provide distinct • With regard to objectively measured moder-
metrics in assessment of CVD risk.9 Poor cardiorespira- ate to vigorous PA (based on age-specific cri-
tory (or aerobic) fitness might be a stronger predictor teria for accelerometer cutpoints; NHANES,
of adverse cardiometabolic and cardiovascular out- 2003–2004)6:
comes such as CHD, stroke, and HF than traditional risk — Only 8% of 12- to 19-year-olds accumu-
factors.10–12Although many studies have shown that lated ≥60 minutes of moderate to vigorous
increasing the amount and quality of PA can improve PA on ≥5 days per week, whereas 42% of
cardiorespiratory fitness, other factors can contribute, 6- to 11-year-olds achieved similar activity
such as a genetic predisposition to perform aerobic levels.6
exercise.13 Because cardiorespiratory fitness is directly — More boys than girls met PA recommenda-
measured and reflects both participation in PA and the tions (≥60 minutes of moderate to vigorous
state of physiological systems affecting performance, activity) on ≥5 days per week.6
the relationship between cardiorespiratory fitness and • With regard to objectively measured cardiorespi-
clinical outcomes is stronger than the relationship of PA ratory fitness (NHANES, 2012)15:
to a series of clinical outcomes.9 Unlike health behav- — For adolescents aged 12 to 15 years, boys
Downloaded from http://ahajournals.org by on February 7, 2019

iors such as PA and risk factors that are tracked by fed- in all age groups were more likely to have
erally funded programs (NHIS, NHANES, etc),6,14 there adequate levels of cardiorespiratory fitness
are no national data on adult cardiorespiratory fitness, than girls (Chart 4-4).15
although the development of a national cardiorespira-
• With regard to self-reported muscle-strengthening
tory fitness registry has been proposed.9 Such additional
activities (YRBSS, 2015)4:
data on the cardiorespiratory fitness levels of Americans
— The proportion of high school students who
could give a fuller and more accurate picture of physical
participated in muscle-strengthening activi-
fitness levels.9
ties on ≥3 days of the week was 53.4%
nationwide and declined from 9th grade
Prevalence (males 64.9%, females 48.2%) to 12th
grade (males 59.9%, females 39.9%).
Youth
— More high school boys (63.7%) than girls
Meeting the Activity Recommendations
(42.7%) reported having participated in
(See Charts 4-2 through 4-4)
muscle-strengthening activities on ≥3 days
• On the basis of self-reported PA (YRBSS, 2015)4:
of the week.
— The prevalence of high school students who
met aerobic activity recommendations of Structured Activity Participation in Schools and Sports
≥60 minutes of PA on all 7 days of the week • In 2015, only 29.8% of students attended physi-
was 27.1% nationwide and declined from cal education classes in school daily (33.8% of
9th (31.0%) to 12th (23.5%) grades. At boys and 25.5% of girls; YRBSS).4
each grade level, the prevalence was higher • Daily physical education class participation
in boys than in girls. declined from the 9th grade (44.6% for boys,
— More than double the percentage of high 39.5% for girls) through the 12th grade (27.9%
school–aged boys (36.0%) than girls (17.7%) for boys, 16.0% for girls; YRBSS).4
reported having been physically active ≥60 • Just over half (57.6%) of high school students
minutes per day on all 7 days (Chart 4-2). played on at least 1 school or community sports
▪ The prevalence of students meeting team in the previous year: 53.0% of girls and
activity recommendations on ≥5 days 62.2% of boys (YRBSS).4

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e45

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

Television/Video/Computers and 41.8% for Hispanic males and females,

CLINICAL STATEMENTS

(See Chart 4-5) respectively. Among both males and females,

AND GUIDELINES

Research suggests that screen time (watching television NH whites were more likely to meet the PA
or using a computer) can lead to less PA among chil- aerobic guidelines with leisure-time activ-
dren.16 In addition, television viewing time is associated ity than NH blacks and Hispanics. For each
with poor nutritional choices, overeating, and weight racial/ethnic group, males had higher PA
gain (Chapter 5, Nutrition). than females (Chart 4-6).
• In 2015 (YRBSS)4: — Among adults ≥25 years of age, 32.4% of
— Nationwide, 41.7% of high school students participants with no high school diploma,
used a computer for activities other than 40.8% of those with a high school diploma
school work (eg, videogames or other com- or GED high school equivalency credential,
puter games) for ≥3 hours per day on an 51.4% of those with some college, and
average school day. 64.9% of those with a bachelor’s degree or
— The prevalence of using computers ≥3 hours higher met the federal guidelines for aerobic
per day (for activities other than school work) PA through leisure-time activities (Chart 4-7).
was highest among NH black girls (48.4%), • Adults residing in urban areas (metropolitan sta-
followed by Hispanic girls (47.4%), Hispanic tistical areas) are more likely to meet the federal
boys (45.1%), NH black boys (41.2%), NH aerobic PA guidelines through leisure-time activi-
white boys (38.9%), and NH white girls ties than those residing in rural areas (53.7% ver-
(38.3%) (Chart 4-5). sus 46.2%) (Chart 4-8).7
— The prevalence of watching television ≥3 • Adults living below 200% of the poverty level
hours per day was highest among NH black are less likely to meet the federal PA guidelines
girls (41.5%) and boys (37.0%), followed by through leisure-time activities than adults living at
Hispanic girls (29.2%) and boys (27.4%) and >200% above the poverty level (Chart 4-9).7
NH white boys (21.4%) and girls (18.8%). • 13.5 % of people with disabilities and 24.3% of
• A report from the Kaiser Family Foundation (using people without disabilities meet both the aero-
data from 2009) reported that 8- to 18-year-olds bic and muscle-strengthening guidelines (Chart
spent an average of 33 minutes per day talking on 4-10).7
• In 2016, 26.9% of adults reported that they do
Downloaded from http://ahajournals.org by on February 7, 2019

the phone and 49 minutes using their phone to

access media (music, games, or videos).17 In addi- not engage in leisure-time PA (no sessions of lei-
tion to other cell phone use, 7th to 12th graders sure time PA of ≥10 minutes in duration; Chart
spent an average of 95 minutes per day text mes- 4-11).7
saging. Surveys such as YRBSS have not historically • Among adults 20 to 59 years of age, 3.8% of
asked about cell phone use specifically and are males and 3.2% of females met recommenda-
thus likely underestimates of total screen-time use. tions to engage in moderate to vigorous PA for
30 minutes (in sessions of ≥10 minutes) on ≥5 of
Adults 7 days.6 It is also important to consider that using
Meeting the Activity Recommendations data accumulated only in ≥10-minute bouts could
(See Charts 4-1 and 4-6 through 4-10) remove up to 75% of moderate activity.18
• With regard to self-reported leisure-time aerobic — These data also revealed that rural US resi-
and muscle-strengthening PA (NHIS, 2016)7: dents performed less moderate to vigorous
— 22.5% of adults met the 2008 federal PA PA than urban residents, but rural residents
guidelines for both aerobic and strength- spent more time in lighter-intensity PA (accel-
ening activity, an important component of erometer counts per minute: 760–2020)
overall physical fitness, based on only report- than their urban resident counterparts.19
ing leisure-time activity (Chart 4-1). — In a review examining self-reported versus
• For self-reported leisure-time aerobic PA (NHIS, directly measured PA (eg, accelerometers,
2016)7: pedometers, indirect calorimetry, doubly
— The age-adjusted proportion who reported labeled water, heart rate monitor), 60%
meeting the 2008 aerobic PA guidelines for of respondents self-reported higher values
Americans (≥150 minutes of moderate PA or of activity than what was measured by use
75 minutes of vigorous PA or an equivalent of direct methods.20 Among males, self-
combination each week) through leisure- reported PA was 44% greater than directly
time activities was 59.7% and 53.6% for NH measured values; among females, self-
white males and females, 51.0% and 39.1% reported activity was 138% greater than
for NH black males and females, and 46.4% directly measured PA.20

e46 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

• With regard to objectively measured moderate • A 1-day assessment indicated that the mean

CLINICAL STATEMENTS
to vigorous PA (accelerometer counts per minute prevalence of any active transportation was

AND GUIDELINES
>2020; NHANES, 2003–2004)6: 10.3% using 2012 data from the American Time
— Among those ≥60 years of age, adherence to Use Study. NH whites reported the lowest active
PA recommendations was 2.5% in males and transport, only 9.2%, of any racial/ethnic group.
2.3% in females.6 Roughly 11.0% of Hispanics, 13.4% of NH blacks,
— In contrast to self-reported PA, which sug- and 15.0% of other NH individuals reported par-
gested that NH whites had the higher lev- ticipating in any active transportation on the pre-
els of PA,14 data from objectively measured vious day.24
PA revealed that Hispanic participants had
higher total PA and moderate to vigorous
Mortality
PA compared with NH white or black partici-
pants (≥20 years old).6,21 Self-Reported Physical Inactivity and Mortality
• Levels of activity declined sharply after the age • Physical inactivity is the fourth-leading risk fac-
of 50 years in all groups.18 In a recent study of tor for global death, responsible for 1 to 2 mil-
almost 5000 British males, in those with low PA in lion deaths annually.25,26 The adjusted population
midlife, retirement and the development of car- attributable fraction for achieving <150 minutes
diovascular-related conditions were identified as of moderate to vigorous PA per week was 8.0%
factors predicting a decrease in PA over 20 years for all-cause and 4.6% for major CVD in a study
of follow-up, but for males who were more active of 17 low-, middle-, and high-income countries in
in middle age, retirement was observed to be a 130 843 participants without preexisting CVD.27
time of increasing PA.22 • A similar analysis in the US using NHIS data from
• A Nielsen Report using data from 2017 reported 1990 to 1991 (N=67 762) found that after 20
that adults spent an average of 5 hours 5 min- years of follow-up, 8.7% of all-cause mortality
utes per day watching television (including live was attributed to levels of PA that were <150
television and other television-connected devices minutes of moderate-intensity equivalent activity
such as DVDs or playing video games on a con- per week.28
sole) and an hour and a half each day on com- • A study of US adults that linked a large, nation-
ally representative sample of 10 535 participants
Downloaded from http://ahajournals.org by on February 7, 2019

puters or tablets.23 Adult smartphone app/web

use was reported as 2 hours 28 minutes per day (NHANES) to death records found that meeting the
using data collected from 12 500 smartphone aerobic PA guidelines reduced all-cause mortality,
users in 2017.23 These technology use behaviors with an HR of 0.64 (95% CI, 0.52–0.79), after
could influence time spent in PA and sedentary adjustment for potential confounding factors.
time. Furthermore, for adults not meeting the aerobic
— Of particular concern, black adults spent an PA guidelines, engaging in muscle-strengthening
average of 7 hours 13 minutes per day watch- activity ≥2 times a week was associated with a
ing television. Black and Hispanic adults had 44% lower adjusted HR for all-cause mortality.29
the highest smartphone use compared with • A meta-analysis of 9 cohort studies, represent-
other racial/ethnic groups.23 ing 122 417 patients, found that as little as 15
minutes of daily moderate to vigorous PA reduced
Structured Activity Participation in Leisure-Time, all-cause mortality in adults ≥60 years of age. This
Domestic, Occupational, and Transportation Activities protective effect of PA was dose dependent; the
• Individuals from urban areas who participated in most rapid reduction in mortality per minute of
NHANES 2003 to 2006 reported participating in added PA was for those at the lowest levels of
more transportation activity, but rural individuals PA. These findings suggest that older adults can
reported spending more time in household PA benefit from PA time far below the amount rec-
and more total PA than urban individuals, possi- ommended by the federal guidelines.30
bly explaining the higher levels of light activity of • In a pooled study of >600 000 participants,31 an
rural individuals observed by objective methods.19 inverse dose-response relationship was observed
• At this time, it is unclear which construct of PA between level of self-reported leisure-time PA (HR,
(domestic, occupational, or transportation) con- 0.80 [95% CI, 0.78–0.82] for less than the recom-
tributes to the higher objectively measured PA21 mended minimum of the PA guidelines; HR, 0.69
but lower subjectively measured PA14 for Hispanic [95% CI, 0.67–0.70] for 1–2 times the recom-
individuals, or whether these differences are mended minimum; and HR, 0.63 [95% CI, 0.62–
caused by overreporting or underreporting of 0.65] for 2–3 times the minimum) and mortality,
leisure-time PA. with the upper threshold for mortality benefit

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e47

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

occurring at 3 to 5 times the PA recommendations mortality, higher sedentary time was associated
CLINICAL STATEMENTS

(HR, 0.61; 95% CI, 0.59–0.62). Furthermore, with a 22% higher risk of all-cause mortality (HR,
AND GUIDELINES

there was no evidence of harm associated with 1.22; 95% CI, 1.09–1.41). This association was
performing ≥10 times the recommended mini- more pronounced at lower levels of PA than at
mum (HR, 0.68; 95% CI, 0.59–0.78).31 higher levels.39
• Similarly, a population-based cohort in New South • A meta-analysis that included >1 million par-
Wales, Australia, of 204 542 adults followed up ticipants across 16 studies compared the risk
for an average of 6.5 years evaluated the relation- associated with sitting time and television
ship of PA to mortality risk. It found that compared viewing in physically active and inactive study
with those who reported no moderate to vigor- participants. For inactive individuals (defined
ous PA, the adjusted HRs for all-cause mortality as the lowest quartile of PA), those sitting >8
were 0.66 (95% CI, 0.61–0.71) for those report- h/d had a higher all-cause mortality risk than
ing 10 to 149 min/wk, 0.53 (95% CI, 0.48–0.57) those sitting <4 h/d. For active individuals (top
for those reporting 150 to 299 min/wk, and 0.46 quartile for PA), sitting time was not associated
(95% CI, 0.43–0.49) for those reporting ≥300 with all-cause mortality, but active people who
min/wk of activity.32 watched television ≥5 h/d did have higher mor-
• In the Women’s Health Study (N=28 879; mean tality risk.40
age, 62 years), females participating in strength
Objectively Measured Physical Inactivity/
training (1–19, 20–59, and 60–149 min/wk com-
Sedentary Time and Mortality
pared with 0 min/wk) had lower risk of all-cause
• In a subsample of NHANES (participants with
mortality (HR [95% CI], 0.73 [0.65–0.82], 0.71
objectively measured PA and between the ages
[0.62–0.82], and 0.81 [0.67–0.97], respectively),
of 50 and 79 years [N=3029]), models that
but performing ≥150 min/wk strength training
replaced sedentary time with 10 min/d of mod-
was not associated with lower risk of all-cause
erate to vigorous PA were associated with lower
mortality (HR, 1.10; 95% CI, 0.77–1.56) because
all-cause mortality (HR, 0.70; 95% CI, 0.57–0.85)
of very wide CIs.33
after 5 to 8 years of follow-up. Even substitut-
• A meta-analysis also revealed an association
ing in 10 min/d of light activity was associated
between participating in more transportation-
with lower all-cause mortality (HR, 0.91; 95% CI,
related PA and lower all-cause mortality risk.34 In
Downloaded from http://ahajournals.org by on February 7, 2019

0.86–0.96).41
contrast, higher occupational PA has been asso-
• In an analysis from the Women’s Health Study,
ciated with higher mortality in males but not
objective measures of PA and sedentary behavior
females.35 It is unclear whether confounding fac-
using an accelerometer were associated with all-
tors such as fitness, SES, or other domains of PA
cause mortality. The highest levels of overall PA
might impact this relationship.
volume, as measured by the accelerometer, were
• In a longitudinal cohort study of 263 540 partici-
associated with 60% to 70% lower risk of all-
pants from the UK Biobank cohort, commuting by
cause mortality. This inverse association between
bicycle was associated with a lower risk of CVD
overall PA and all-cause mortality was largely
mortality and all-cause mortality (HR, 0.48 and
driven by the moderate to vigorous PA levels; light
0.59, respectively). Commuting by walking was
PA or sedentary behavior was not associated with
associated with a lower risk of CVD mortality (HR,
mortality risk in this cohort after accounting for
0.64) but not all-cause mortality.36
moderate to vigorous PA.42
• In a study involving 55 137 adults followed up
• In a cohort study of 7985 middle- and older-aged
over an average of 15 years, running even 5 to 10
US adults, the REGARDS study objectively mea-
min/d and at slow speeds (<6 mph) was associ-
sured total sedentary time (HR [95% CI] for high-
ated with a markedly reduced risk of CVD and of
est versus lowest quartile of total sedentary time,
death attributable to all causes.37
2.63 [1.60–4.30]) and longer sedentary bouts
• In the Southern Community Cohort Study of
(HR, 1.96; 95% CI, 1.31–2.93) were both associ-
63 308 individuals followed up for >6.4 years,
ated with higher risk of all-cause mortality.43
more time spent being sedentary (>12 h/d versus
<5.76 h/d) was associated with a 20% to 25% Cardiorespiratory Fitness and Mortality
increased risk of all-cause mortality in both black • The Cooper Center Longitudinal Study, an analy-
and white adults. Both PA (beneficial) and seden- sis conducted on 16 533 participants, revealed
tary time (detrimental) were associated with mor- that across all risk factor strata, the presence of
tality risk.38 low cardiorespiratory fitness was associated with
• In a meta-analysis of 13 studies evaluating the a greater risk of CVD death over a mean follow-
association between sedentary time and all-cause up of 28 years.44

e48 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

• In a longitudinal cohort study from the UK cardiorespiratory fitness (based on age- and sex-

CLINICAL STATEMENTS
Biobank data, the association between PA and all- specific standards) was 42.2% (Chart 4-3), down

AND GUIDELINES
cause mortality was strongest among those with from 52.4% in 1999 to 2000.15
lowest hand-grip strength and lowest cardiorespi-
Adults
ratory fitness, which suggests that strength and
(See Charts 4-11 and 4-12)
possibly cardiorespiratory fitness could moderate
• The prevalence of physical inactivity among
the association between PA and mortality.45
adults ≥18 years of age, overall and by sex, has
• In a retrospective cohort study of 57 085 individu-
decreased from 1998 to 2016, with the largest
als who were clinically referred for stress testing
(but without established CAD or HF), cardiore- drop occurring in the past decade, from 40.2%
spiratory fitness–associated “biologic age” was a to 26.9% between 2005 and 2016, respectively
stronger predictor of mortality over 10 years of (Chart 4-11).7,47 The prevalence of physical inac-
follow-up than chronological age.46 tivity has surpassed the target for Healthy People
2020, which was 32.6%.47
• A 2.3% decline in physical inactivity between
Secular Trends 1980 and 2000 was estimated to have prevented
Youth or postponed ≈17 445 deaths (≈5%) attributable
In 2015 (YRBSS)4: to CHD in the United States.48
• Among students nationwide, there was a sig- • The age-adjusted percentage of US adults who
nificant increase in the number of individuals reported meeting both the muscle-strengthening
reporting participation in muscle-strengthening and aerobic guidelines increased from 14.4% in
activities on ≥3 days per week, from 47.8% in 1998 to 21.4% in 2015 (Chart 4-12).14 The per-
1991 to 53.4% in 2015; however, the prevalence centage of US adults who reported meeting the
did not change substantively from 2013 (51.7%) aerobic guideline increased from 40.1% in 1998
to 2015 (53.4%). to 49.7% in 2015.14,49
• A significant increase occurred in the number of • Although it appears that leisure-time PA has been
youth reporting having used computers not for increasing in recent years, trends in technology
school work for ≥3 h/d compared with 2003 behavior could influence both PA and sedentary
(22.1% versus 41.7% in 2015). The prevalence time. Nielsen reports of adult smartphone app/
Downloaded from http://ahajournals.org by on February 7, 2019

increased from 2003 to 2009 (22.1% versus web use comparing data collected in 2012 and
24.9%) and then increased more rapidly from 2014 (48 min/d and 1 hour 25 minutes per day,
2009 to 2015 (24.9% versus 41.7%). respectively)47 to 2017 (2 hours 28 minutes per
— From 2004 to 2009, the Kaiser Family day)50 suggest extreme increases in use over the
Foundation reported that the proportion of past few years. Although they acknowledge that
8- to 18-year-olds who owned their own cell there were inconsistent methods in data collec-
phone increased from 39% to 66%,17 which tion among these different reports, the reported
could also contribute to higher exposure to changes in technology behavior over such a short
screen time in children. period of time are striking.
• Nationwide, the number of high school stu- — During this time period, from 2012 to 2017,
dents who reported attending physical education television viewing decreased from 5 hours 28
classes at least once per week did not change minutes per day to 5 hours 5 minutes per
substantively between 2013 (48.0%) and 2015 day. Time spent on a computer decreased
(51.6%). from 1 hour 3 minutes to <52 minutes in
— The number of high school students report- 2017. However, in 2017, tablet use was also
ing attending daily physical education measured and contributed to screen time, at
classes changed in nonlinear ways over time. 34 min/d.
Attendance initially decreased from 1991 to — The relationships between changes in tech-
1995 (from 41.6% to 25.4%) and did not nology habits and sedentary time have not
substantively change between 1995, 2013, been measured systematically.
and 2015 (25.4%, 29.4%, and 29.8%,
respectively).
Complications of Physical Inactivity: The
• The prevalence of high school students playing
≥1 team sport in the past year did not substan- Cardiovascular Health Impact
tively change between 2013 (54.0%) and 2015 Youth
(57.6%). In 2012, the prevalence of adolescents • In a study from the NHANES cohort, of par-
aged 12 to 15 years with adequate levels of ticipants aged 6 to 17 years with objective

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e49

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

measurement of PA levels by accelerometer, 10 years’ follow-up than among those using

CLINICAL STATEMENTS

young participants with the highest levels of PA passive modes of transportation.58

AND GUIDELINES

had lower SBP, lower glucose levels, and lower • A total of 120 to 150 min/wk of moderate-inten-
insulin levels than participants in the lowest PA sity activity, compared with none, can reduce the
group.51 risk of developing metabolic syndrome.3
• Similarly, a higher amount of objectively mea- • Even lighter-intensity activities, such as yoga,
sured sedentary duration assessed by accelerom- were reported to improve BMI, BP, triglycerides,
eter among children aged 10 to 14 years old is LDL-C, and HDL-C but not fasting blood glucose
associated with greater odds of hypertriglyceride- in a meta-analysis of 32 RCTs comparing yoga to
mia and cardiometabolic risk.52 nonexercise control groups.59
• For elementary school children, engagement in • In a sample of 466 605 participants in the China
organized sports for ≈1 year was associated with Kadoorie Biobank study, a 1-SD (1.5 h/d) increase
lower clustered cardiovascular risk.53 in sedentary time was associated with a 0.19-U
• In a study of 36 956 Brazilian adolescents, self- higher BMI, a 0.57-cm larger WC, and 0.44%
reported higher moderate to vigorous PA levels more body fat. Both higher sedentary leisure time
and lower screen time were associated with lower and lower PA were independently associated with
cardiometabolic risk. Furthermore, the association an increased BMI.60
of screen time with cardiometabolic risk was mod- • In a dose-response meta-analysis of 22 studies
ified by BMI. In contrast, the association between with 330 222 participants evaluating the associa-
moderate to vigorous PA and cardiometabolic risk tion between PA levels and risk of hypertension,
was independent of BMI.54 each 10 MET h/wk higher level of leisure time PA
• In a prospective study of 700 Norwegian 10-year- was associated with a 6% lower risk of hyperten-
old children with objective measures of PA, higher sion (RR, 0.94; 95% CI, 0.92–0.96)].61
levels of moderate PA at baseline were associated • In a meta-analysis of 17 trials with 5075 pregnant
with lower triglyceride levels and lower insulin female participants that evaluated the effects of
resistance at 7-month follow-up. In contrast, sed- exercise during pregnancy, aerobic exercise for
entary time duration was not associated with car- ≈30 to 60 minutes 2 to 7 times per week dur-
diometabolic risk factors on follow-up.55 ing pregnancy was associated with significantly
Downloaded from http://ahajournals.org by on February 7, 2019

lower risk of gestational hypertensive disorders

Adults (RR, 0.70; 95% CI, 0.53–0.83).62
Cardiovascular and Metabolic Risk • In a population-based study of Hispanic/Latino
• A review of the US Preventive Services Task Force adults with objective assessment of sedentary
recommendations examined the evidence on time, higher levels of sedentary time were asso-
whether relevant counseling interventions for a ciated with lower levels of HDL, higher triglycer-
healthful diet and PA in primary care modify inter- ides, and higher measures of insulin resistance
mediate physiological outcomes. It was concluded after adjustment for PA levels. Furthermore, the
that after 12 to 24 months, intensive lifestyle accrual of prolonged and uninterrupted bouts of
counseling for individuals selected because of risk sedentary time was particularly associated with
factors reduced TC levels by an average of 0.14 greater abnormalities in measures of glucose
mmol/L, LDL-C levels by 0.10 mmol/L, triglyceride regulation.63,64
levels by 0.09 mmol/L, SBP by 2.06 mm Hg, DBP
by 1.30 mm Hg, fasting glucose by 0.10 mmol/L, Cardiovascular Events
DM incidence by an RR of 0.54, and weight by a • In a dose-response meta-analysis of 9 prospec-
standardized difference of 0.24.56 tive cohort studies (N=720 425), higher levels of
• Results from NHANES 2011 to 2014 demon- sedentary time were associated with greater risk
strated that the prevalence of low HDL-C was of CVD in a nonlinear relationship (HR for high-
higher among adults who reported not meeting est versus lowest sedentary time, 1.14; 95% CI,
PA guidelines (21.0%) than among adults meet- 1.09–1.19).65
ing guidelines (17.7%).57 • A study of the factors related to declining CVD
• Engaging in active transport to work has been among Norwegian adults ≥25 years of age found
associated with lower cardiovascular risk factors. that increased PA (≥1 hour of strenuous PA per
— In a large Swedish cohort of 23 732 indi- week) accounted for 9% of the decline in hos-
viduals, bicycling to work at baseline was pitalized and nonhospitalized fatal and nonfatal
associated with a lower odds of developing CHD events.66
incident obesity, hypertension, hypertriglyc- • In a study that followed 1.1 million females in the
eridemia, and impaired glucose tolerance at United Kingdom without prior vascular disease

e50 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

for an average of 9 years, those who reported Furthermore, high domestic work in females (2.4

CLINICAL STATEMENTS
moderate activity were found to be at lower risk years) and high gardening in males (2 years) was

AND GUIDELINES
of CHD, a cerebrovascular event, or a thrombotic also associated with an increased CVD-free life
event. However, strenuous PA was not found to span.74
be as beneficial as moderate PA.67 • Cardiorespiratory fitness and PA levels are impor-
• In a prospective cohort study of 168 916 par- tant determinants of HF risk in the general popu-
ticipants from 17 countries, compared with low lation. In the Cooper Center Longitudinal Study
levels of self-reported PA (<150 min/wk of mod- population, higher levels of cardiorespiratory fit-
erate-intensity PA), moderate (150–750 min/wk) ness in midlife were associated with lower risk of
and high (>750 min/wk) levels of PA were associ- HF, MI, and stroke.75
ated with a graded lower risk of major cardiovas- — The inverse association between higher fit-
cular events (HR [95% CI] high versus low: 0.75 ness levels and risk of HF (HR per 1-MET
[0.69–0.82]; moderate versus low: 0.86 [0.78– higher fitness level, 0.79; 95% CI, 0.75–0.83
0.93]; high versus moderate: 0.88 [0.82–0.94]) for males) was stronger than observed for
over an average 6.9 years of follow-up time.27 risk of MI (HR, 0.91; 95% CI, 0.87–0.95).75
• In the 2-year LIFE study of older adults (mean — Cardiorespiratory fitness accounted for 47%
age, 78.9 years), higher levels of PA, measured by of the HF risk associated with higher BMI
accelerometer, were associated with lower risk of levels.11
adverse cardiovascular events.68 — Improvement in cardiorespiratory fitness in
• In a dose-response meta-analysis of 12 prospec- middle age was also strongly associated with
tive cohort studies (n=370 460), there was an lower risk of HF among the Cooper Center
inverse dose-dependent association between PA Longitudinal Study participants (HR per
levels and risk of HF. PA levels at the guideline- 1-MET increase in fitness levels, 0.83; 95%
recommended minimum (500 MET min/wk) were CI, 0.74–0.93).76
associated with 10% lower risk of HF. PA at twice • Lower levels of cardiorespiratory fitness have also
and 4 times the guideline-recommended levels been associated with higher risk of HF in a recent
was associated with 19% and 35% lower risk of study of 21 080 veterans, with a 91% higher risk
HF, respectively.69 of HF noted among low-fit participants (HR, 1.91;
• Furthermore, a recent individual level pooled
Downloaded from http://ahajournals.org by on February 7, 2019

95% CI, 1.74–2.09).77

analysis of 3 large cohort studies demonstrated • In a Swedish cohort of 773 925 young males
that the strong, dose-dependent association without history of VTE, cardiorespiratory fit-
between higher PA levels and lower risk of HF is ness was associated with a reduced risk of VTE
largely driven by lower risk of HF with preserved (HR, 0.81; 95% CI, 0.78–0.85) at ≥20 years of
EF but not HF with reduced EF.70 follow-up.78
• In a large clinical trial (NAVIGATOR) involving • In 5962 veterans, lower exercise capacity was
9306 people with impaired glucose tolerance, associated with a higher risk of developing AF. For
ambulatory activity as assessed by pedometer every 1-MET increase in exercise capacity, the risk
at baseline and 12 months was found to be of developing AF was 21% lower (HR, 0.79; 95%
inversely associated with risk of a cardiovascular CI, 0.76–0.82).79
event.71
• Domains of PA, other than leisure time, are under- Secondary Prevention
studied and often overlooked. A meta-analysis • A Cochrane systematic review of 63 studies con-
reported a protective relation of transportation cluded that exercise-based cardiac rehabilitation
activity to cardiovascular risk, which was greater programs for CHD patients reduced cardiovas-
in women.72 However, higher occupational PA cular mortality and hospital admissions but not
has recently been associated with higher MI inci- overall mortality.80
dence in males 19 to 70 years old.35,73 These rela- • In a prospective study that monitored 902 HF
tionships require further investigation, because patients (with preserved or reduced EF) for 3
a protective association of occupational activity years, reporting participation in any PA (≥1 min/
with MI has been reported in young males (19– wk) was associated with a lower risk of cardiac
44 years).73 death and all-cause death than no PA. Less televi-
• A recent analysis from the Rotterdam Study eval- sion screen time (<2 versus >4 h/d) was also asso-
uated the contribution of specific PA types on ciated with lower all-cause death.81
CVD-free life expectancy. Higher levels of cycling • In a prospective cohort study of 15  486 par-
were associated with a greater CVD-free life ticipants with stable CAD from 39 countries,
span in males (3.1 years) and females (2.4 years). higher levels of PA were associated with lower

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e51

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

risk of mortality such that doubling the exercise PA was associated with lower mortality at 7-year
CLINICAL STATEMENTS

volume was associated with 10% lower risk of follow-up.90

AND GUIDELINES

all-cause mortality after adjustment for potential

confounders.82
— Among 1746 CAD patients followed up Costs
for 2 years, those who remained inactive • The economic consequences of physical inactivity
or became inactive had a 4.9- and 2.4-fold are substantial. Using data derived primarily from
higher risk of cardiac death, respectively, WHO publications and data warehouses, one
than patients who remained at least irregu- study estimated that economic costs of physical
larly active during the follow-up period.83 inactivity account for 1.5% to 3.0% of total direct
— In a prospective cohort study of 3307 individ- healthcare expenditures in developed countries
uals with CHD, participants who maintained such as the United States.91
high PA levels over longitudinal follow-up • A global analysis of 142 countries (93.2% of
had a lower risk of mortality than those who the world’s population) concluded that physical
were inactive over time (HR, 0.64; 95% CI, inactivity cost healthcare systems $53.8 billion
0.50–0.83).84 in 2013, including $9.7 billion paid by individual
• In a cohort of patients with HF and preserved households.92
EF, compared with high levels of self-reported • A study of American adults reported that inad-
PA, poor and intermediate levels were associ- equate levels of aerobic PA (after adjustment for
ated with higher risk of HF hospitalization (HR BMI) were associated with an estimated 11.1%
[95% CI], 1.93 [1.16–3.22] for poor versus high of aggregate healthcare expenditures (including
PA and 1.84 [1.02–3.31] for intermediate versus expenditures for inpatient, outpatient, ED, office-
high PA) and cardiovascular mortality (HR [95% based, dental, vision, home health, prescription
CI], 4.36 [1.37–13.83] for poor versus high PA drug, and other services).93
and 4.05 [1.17–14.04] for intermediate versus • An evaluation of healthcare costs based on the
high PA).85 cardiovascular risk factor profile (including ≥30
• Using data from a registry of stable outpatients minutes of moderate to vigorous PA ≥5 times per
with symptomatic coronary disease, cerebro- week) found that among adults aged ≥40 years
vascular disease, or PAD, the mortality rate with CVD, the highest marginal expenditures
Downloaded from http://ahajournals.org by on February 7, 2019

of patients with a recent MI was significantly ($2853 in 2012) were for those not meeting the
lower in patients who participated in supervised PA guidelines. Healthcare costs included hospital-
(N=593) versus unsupervised (N=531) exercise izations, prescribed medications, outpatient visits
programming.86 (hospital outpatient visits and office-based visits),
• Early mortality after a first MI was lower for ED visits, and other expenditures (dental visits,
patients who had higher exercise capacity before vision aid, home health care, and other medical
the MI event. Every 1-MET-higher exercise capac- supplies).94
ity before the MI was associated with an 8% • A systematic review of population-based inter-
to 10% lower risk of mortality at 28 days, 90 ventions to encourage PA found that improving
days, and 365 days after MI.87 A study of 3572 biking trails, distributing pedometers, and school-
patients with recent MI demonstrated significant based PA were most cost-effective.95
sex differences in PA after AMI. Females were • Interventions and community strategies to
more likely to be inactive than males within 12 increase PA have been shown to be cost-effective
months after the AMI episode (OR, 1.37; 95% in terms of reducing medical costs96:
CI, 1.21–1.55).88 — Nearly $3 in medical cost savings is realized
• A recent study of participants included in the WHI for every $1 invested in building bike and
observational study who experienced a clinical MI walking trails.
during the study demonstrated that compared — The incremental cost-effectiveness ratio
with those who maintained low PA levels after the ranges from $14 000 to $69 000 per QALY
MI event, participants had lower risk of mortality gained from interventions such as pedom-
with improvement in PA levels (HR, 0.54; 95% CI, eter or walking programs compared with no
0.36–0.86) or with sustained high PA levels (HR, intervention, especially in high-risk groups.
0.52; 95% CI, 0.36–0.73).89
• Among 2370 individuals with CVD who
responded to the Taiwan National Health Strategies to Prevent Physical Inactivity
Interview Survey, achieving more total PA, The US Surgeon General has introduced “Step It Up!,
leisure-time PA, and domestic and work-related a Call to Action to Promote Walking and Walkable

e52 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

Communities” in recognition of the importance of PA.97 • Worksite interventions for sedentary occupa-

CLINICAL STATEMENTS
There are roles for communities, schools, and worksites. tions, such as providing “activity-permissive”

AND GUIDELINES
workstations and email contacts that promote
Communities
breaks, have reported increased occupational
• Community-level interventions have been shown
light activity, and the more adherent individu-
to be effective in promoting increased PA.
als observed improvements in cardiometabolic
Communities can encourage walking with street
outcomes.103,104
design that includes sidewalks, improved street
lighting, and landscaping design that reduces
traffic speed to improve pedestrian safety. Higher Family History and Genetics
neighborhood walkability has been associated
with lower prevalence of overweight, obesity, • It is clear that environmental factors can play a
and lower incidence of DM.98 Moving to a walk- role in PA and sedentary behavior and the context
able neighborhood was associated with a lower in which these behaviors occur. However, PA and
risk for incident hypertension in the Canadian sedentary behavior can also be determined in part
Community Health Survey.99 by genetics, with heritability estimates of up to
• Community-wide campaigns include a variety 47%, although few loci have been identified or
of strategies such as media coverage, risk factor replicated.105,106
screening and education, community events, and
policy or environmental changes.
• Educating the public on the recommended PA
Global Burden
guidelines could increase adherence. In a study (See Chart 4-13)
examining awareness of current US PA guidelines, • Physical inactivity is responsible for 12.2% of
only 33% of respondents had direct knowledge the global burden of MI after accounting for
of the recommended dosage of PA (ie, frequency/ other CVD risk factors such as cigarette smok-
duration).100 ing, DM, hypertension, abdominal obesity, lipid
profile, excessive alcohol intake, and psychosocial
Schools
factors.107
• Schools can provide opportunities for PA through
• Worldwide, the prevalence of physical inactiv-
Downloaded from http://ahajournals.org by on February 7, 2019

physical education, recess, before- and after-

school activity programs, and PA breaks.101 ity (35%) is now greater than the prevalence of
• According to the School Health Policies and smoking (26%). On the basis of the HRs associ-
Practices Study, <5% of elementary schools and ated with these 2 behaviors (1.57 for smoking
junior and senior high schools required daily phys- and 1.28 for inactivity), it was concluded that
ical education in 2014.47 the PAR was greater for inactivity (9%) than for
• In 2012, the School Health Policies and Practices smoking (8.7%). Inactivity was estimated to be
Study also reported that 58.9% of school districts responsible for 5.3 million deaths compared with
required regular elementary school recess.47 5.1 million deaths for smoking.108
• Healthy afterschool programs and active school • The GBD 2016 Study used statistical models
day policies have been shown to be cost-effective and data on incidence, prevalence, case fatal-
solutions to increase PA and prevent childhood ity, excess mortality, and cause-specific mortal-
obesity.102 ity to estimate disease burden for 315 diseases
and injuries in 195 countries and territories.
Worksites Mortality rates attributable to low PA are high
• Worksites can offer access to on-site exercise in Eastern Europe, the North Africa/Middle East
facilities or employer-subsidized off-site exercise region, and the Pacific Island countries (Chart
facilities to encourage PA among employees. 4-13).109

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e53

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4
CLINICAL STATEMENTS
AND GUIDELINES

Chart 4-1. Prevalence of meeting both the aerobic and muscle-strengthening guidelines for the 2008 Physical Activity Guidelines for Americans
among adults ≥18 years of age, overall and by sex and race/ethnicity.
Data are age adjusted for adults ≥18 years of age.
NH indicates non-Hispanic.
Source: National Health Interview Survey, 2016 (National Center for Health Statistics).7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-2. Prevalence of students in grades 9 to 12 who were active at least 60 min/d on all 7 days by race/ethnicity and sex.
“Currently recommended levels” was defined as activity that increased their heart rate and made them breathe hard some of the time for a total of ≥60 min/d on
all 7 days preceding the survey.
NH indicates non-Hispanic.
Source: Youth Risk Behavior Surveillance Survey, 2015.4

e54 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-3. Prevalence of students in grades 9 to 12 who did not participate in ≥60 minutes of physical activity on any day in the past 7 days by
race/ethnicity and sex.
NH indicates non-Hispanic.
Source: Youth Risk Behavior Surveillance Survey, 2015.4
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-4. Prevalence of children 12 to 15 years of age who had adequate levels of cardiorespiratory fitness by sex and age (NHANES, National
Youth Fitness Survey, 2012).
NHANES indicates National Health and Nutrition Examination Survey.
Source: NHANES, National Youth Fitness Survey, 2012.15

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e55

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4
CLINICAL STATEMENTS
AND GUIDELINES

Chart 4-5. Percentage of students in grades 9 to 12 who used a computer* for ≥3 hours on an average school day by race/ethnicity and sex.
NH indicates non-Hispanic.
*For something other than school work.
Source: Youth Risk Behavior Surveillance Survey, 2015.4
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-6. Prevalence of meeting the aerobic guideline of the 2008 Physical Activity Guidelines for Americans among adults ≥18 years of age by
race/ethnicity and sex (NHIS, 2016).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend engaging in moderate leisure-time
physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination.
NH indicates non-Hispanic; and NHIS, National Health Interview Survey.
Source: NHIS, 2016 (National Center for Health Statistics).7

e56 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-7. Prevalence of meeting the aerobic guideline of the 2008 Physical Activity Guidelines for Americans among adults ≥25 years of age by
educational attainment (NHIS, 2016).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend engaging in moderate leisure-time
physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination.
GED indicates General Educational Development; and NHIS, National Health Interview Survey.
Source: NHIS, 2016 (National Center for Health Statistics).7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-8. Prevalence of meeting the aerobic guideline for the 2008 Physical Activity Guidelines for Americans among adults ≥18 years of age by
location of residence (NHIS, 2016).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend engaging in moderate leisure-time
physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination.
MSA indicates metropolitan statistical area; and NHIS, National Health Interview Survey.
Source: NHIS, 2016 (National Center for Health Statistics).7

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e57

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4
CLINICAL STATEMENTS
AND GUIDELINES

Chart 4-9. Prevalence of meeting the aerobic and muscle-strengthening guidelines for the 2008 Physical Activity Guidelines for Americans among
adults ≥18 years of age by poverty level and type of activity (NHIS, 2016).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend engaging in moderate leisure-time
physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination and performing muscle-strengthening activities at least 2 days per week.
NHIS indicates National Health Interview Survey.
Source: NHIS, 2016 (National Center for Health Statistics).7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-10. Prevalence of meeting both the aerobic and muscle-strengthening guidelines for the 2008 Physical Activity Guidelines for Americans
among adults ≥18 years of age by disability status.
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend engaging in moderate leisure-time
physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination.
Source: National Health Interview Survey, 1998 to 2016 (National Center for Health Statistics).7

e58 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-11. Trends in the prevalence of physical inactivity among adults ≥18 years of age, overall and by sex (NHIS, 1998–2016).
Percentages are age adjusted. Physical inactivity is defined as reporting no engagement in leisure-time physical activity in bouts lasting ≥10 minutes.
NHIS indicates National Health Interview Survey.
Source: NHIS, 1998 to 2016 (National Center for Health Statistics).7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 4-12. Trends in meeting the physical activity guidelines of the 2008 Federal Physical Activity Guidelines for Americans through leisure-time
activity only among adults ≥18 years of age by type of activity (NHIS, 1998–2015).
Source: NHIS, 1998 to 2015 (National Center for Health Statistics).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e59

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4
CLINICAL STATEMENTS
AND GUIDELINES

Chart 4-13. Age-standardized global mortality rates attributable to low physical activity per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016 with permission.109 Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

and Cardiometabolic Health and Cardiovascular, Exercise, Cardiac

‍‍‍‍‍‍‍‍REFERENCES Rehabilitation and Prevention Committee of the Council on Clinical
1. Artinian NT, Fletcher GF, Mozaffarian D, Kris-Etherton P, Van Horn L, Cardiology, and Council on Cardiovascular and Stroke Nursing. Guide
Lichtenstein AH, Kumanyika S, Kraus WE, Fleg JL, Redeker NS, Meininger to the assessment of physical activity: clinical and research applications:
JC, Banks J, Stuart-Shor EM, Fletcher BJ, Miller TD, Hughes S, Braun a scientific statement from the American Heart Association. Circulation.
LT, Kopin LA, Berra K, Hayman LL, Ewing LJ, Ades PA, Durstine JL, 2013;128:2259–2279. doi: 10.1161/01.cir.0000435708.67487.da
Houston-Miller N, Burke LE; on behalf of the American Heart Association 6. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical
Prevention Committee of the Council on Cardiovascular Nursing. activity in the United States measured by accelerometer. Med Sci Sports
Interventions to promote physical activity and dietary lifestyle changes for Exerc. 2008;40:181–188. doi: 10.1249/mss.0b013e31815a51b3
cardiovascular risk factor reduction in adults: a scientific statement from 7. National Center for Health Statistics. National Health Interview Survey,
the American Heart Association. Circulation. 2010;122:406–441. doi: 2016. Public-use data file and documentation. https://ftp.cdc.gov/pub/
10.1161/CIR.0b013e3181e8edf1 Health_Statistics/NCHS/Dataset_Documentation/NHIS/2016/srvydesc.pdf.
2. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn Accessed September 7, 2018.
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow 8. 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm Activity Guidelines Advisory Committee Scientific Report. Washington,
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart DC: US Department of Health and Human Services; 2018.
Association Strategic Planning Task Force and Statistics Committee. 9. Kaminsky LA, Arena R, Beckie TM, Brubaker PH, Church TS, Forman DE,
Defining and setting national goals for cardiovascular health promotion Franklin BA, Gulati M, Lavie CJ, Myers J, Patel MJ, Piña IL, Weintraub
and disease reduction: the American Heart Association’s strategic Impact WS, Williams MA; on behalf of the American Heart Association Advocacy
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: Coordinating Committee, Council on Clinical Cardiology, and Council on
10.1161/CIRCULATIONAHA.109.192703 Nutrition, Physical Activity and Metabolism. The importance of cardiore-
3. US Department of Health and Human Services. 2008 Physical Activity spiratory fitness in the United States: the need for a national registry:
Guidelines for Americans. October 2008. ODPHP publication No. a policy statement from the American Heart Association. Circulation.
U0036. http://www.health.gov/paguidelines/pdf/paguide.pdf. Accessed 2013;127:652–662. doi: 10.1161/CIR.0b013e31827ee100
September 7, 2018. 10. Ross R, Blair SN, Arena R, Church TS, Després JP, Franklin BA, Haskell WL,
4. Kann L, McManus T, Harris WA, Shanklin SL, Flint KH, Hawkins J, Kaminsky LA, Levine BD, Lavie CJ, Myers J, Niebauer J, Sallis R, Sawada
Queen B, Lowry R, Olsen EO, Chyen D, Whittle L, Thornton J, Lim C, SS, Sui X, Wisløff U; on behalf of the American Heart Association Physical
Yamakawa Y, Brener N, Zaza S. Youth Risk Behavior Surveillance: United Activity Committee of the Council on Lifestyle and Cardiometabolic Health;
States, 2015 [published correction appears in MMWR Morb Mortal Council on Clinical Cardiology; Council on Epidemiology and Prevention;
Wkly Rep. 2016;65:610]. MMWR Surveill Summ. 2016;65:1–174. doi: Council on Cardiovascular and Stroke Nursing; Council on Functional
10.15585/mmwr.ss6506a1 Genomics and Translational Biology; Stroke Council. Importance of assess-
5. Strath SJ, Kaminsky LA, Ainsworth BE, Ekelund U, Freedson PS, Gary ing cardiorespiratory fitness in clinical practice: a case for fitness as a clini-
RA, Richardson CR, Smith DT, Swartz AM; on behalf of the American cal vital sign: a scientific statement from the American Heart Association.
Heart Association Physical Activity Committee of the Council on Lifestyle Circulation. 2016;134:e653–e699. doi: 10.1161/CIR.0000000000000461

e60 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

11. Pandey A, Cornwell WK 3rd, Willis B, Neeland IJ, Gao A, Leonard D, 29. Zhao G, Li C, Ford ES, Fulton JE, Carlson SA, Okoro CA, Wen XJ, Balluz LS.

CLINICAL STATEMENTS
DeFina L, Berry JD. Body mass index and cardiorespiratory fitness in mid- Leisure-time aerobic physical activity, muscle-strengthening activity and

AND GUIDELINES
life and risk of heart failure hospitalization in older age: findings from the mortality risks among US adults: the NHANES linked mortality study. Br J
Cooper Center Longitudinal Study. JACC Heart Fail. 2017;5:367–374. doi: Sports Med. 2014;48:244–249. doi: 10.1136/bjsports-2013-092731
10.1016/j.jchf.2016.12.021 30. Hupin D, Roche F, Gremeaux V, Chatard JC, Oriol M, Gaspoz JM,
12. Andersen K, Rasmussen F, Held C, Neovius M, Tynelius P, Sundstrom Barthélémy JC, Edouard P. Even a low-dose of moderate-to-vigorous
J. Exercise capacity and muscle strength and risk of vascular disease physical activity reduces mortality by 22% in adults aged ≥60 years: a sys-
and arrhythmia in 1.1 million young Swedish men: cohort study. BMJ. tematic review and meta-analysis. Br J Sports Med. 2015;49:1262–1267.
2015;351:h4543. doi: 10.1136/bmj.h4543 doi: 10.1136/bjsports-2014-094306
13. DeFina LF, Haskell WL, Willis BL, Barlow CE, Finley CE, Levine BD, Cooper 31. Arem H, Moore SC, Patel A, Hartge P, Berrington de Gonzalez A,
KH. Physical activity versus cardiorespiratory fitness: two (partly) distinct Visvanathan K, Campbell PT, Freedman M, Weiderpass E, Adami HO, Linet
components of cardiovascular health? Prog Cardiovasc Dis. 2015;57:324– MS, Lee IM, Matthews CE. Leisure time physical activity and mortality: a
329. doi: 10.1016/j.pcad.2014.09.008 detailed pooled analysis of the dose-response relationship. JAMA Intern
14. National Center for Health Statistics. National Health Interview Survey, Med. 2015;175:959–967. doi: 10.1001/jamainternmed.2015.0533
2015. Public-use data file, documentation, and NCHS tabulations. 32. Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect
https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2016_SHS_ of moderate to vigorous physical activity on all-cause mortality in mid-
Table_A-14.pdf. Accessed September 7, 2018 dle-aged and older Australians [published correction appears in JAMA
15. Gahche J, Fakhouri T, Carroll DD, Burt VL, Wang CY, Fulton JE. Intern Med. 2015;175:1248]. JAMA Intern Med. 2015;175:970–977. doi:
Cardiorespiratory fitness levels among U.S. youth aged 12–15 years: 10.1001/jamainternmed.2015.0541
United States, 1999–2004 and 2012. NCHS Data Brief. 2014;(153):1–8. 33. Kamada M, Shiroma EJ, Buring JE, Miyachi M, Lee IM. Strength train-
16. Lieberman DA, Chamberlin B, Medina E, Jr., Franklin BA, Sanner BM, ing and all-cause, cardiovascular disease, and cancer mortality in older
Vafiadis DK; on behalf of the Power of Play: Innovations in Getting women: a cohort study. J Am Heart Assoc. 2017;6:e007677. doi:
Active Summit Planning Committee. The Power of Play: Innovations in 10.1161/JAHA.117.007677
Getting Active Summit 2011: a science panel proceedings report from 34. Samitz G, Egger M, Zwahlen M. Domains of physical activity and all-cause
the American Heart Association. Circulation 2011;123:2507–2516. doi: mortality: systematic review and dose-response meta-analysis of cohort
10.1161/CIR.0b013e318219661d studies. Int J Epidemiol. 2011;40:1382–1400. doi: 10.1093/ije/dyr112
17. Rideout VJ, Foehr UG, Roberts DF. Generation M2: Media in the Lives of 35. Holtermann A, Marott JL, Gyntelberg F, Søgaard K, Suadicani P, Mortensen
8-18-Year-Olds: A Kaiser Family Foundation Study. Menlo Park, CA: Henry OS, Prescott E, Schnohr P. Occupational and leisure time physical activity:
J. Kaiser Family Foundation; 2010. risk of all-cause mortality and myocardial infarction in the Copenhagen
18. Luke A, Dugas LR, Durazo-Arvizu RA, Cao G, Cooper RS. Assessing physical City Heart Study: a prospective cohort study. BMJ Open. 2012;2:e000556.
activity and its relationship to cardiovascular risk factors: NHANES 2003- doi: 10.1136/bmjopen-2011-000556
2006. BMC Public Health. 2011;11:387. doi: 10.1186/1471-2458-11-387 36. Celis-Morales CA, Lyall DM, Welsh P, Anderson J, Steell L, Guo Y,
19. Fan JX, Wen M, Kowaleski-Jones L. Rural-urban differences in objective Maldonado R, Mackay DF, Pell JP, Sattar N, Gill JMR. Association
and subjective measures of physical activity: findings from the National between active commuting and incident cardiovascular disease, can-
Health and Nutrition Examination Survey (NHANES) 2003-2006. Prev cer, and mortality: prospective cohort study. BMJ. 2017;357:j1456. doi:
Chronic Dis. 2014;11:E141. doi: 10.5888/pcd11.140189 10.1136/bmj.j1456
20. Prince SA, Adamo KB, Hamel ME, Hardt J, Connor Gorber S, Tremblay 37. Lee DC, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN. Leisure-time run-
M. A comparison of direct versus self-report measures for assessing ning reduces all-cause and cardiovascular mortality risk [published cor-
Downloaded from http://ahajournals.org by on February 7, 2019

physical activity in adults: a systematic review. Int J Behav Nutr Phys Act. rection appears in J Am Coll Cardiol. 2014;64:1537]. J Am Coll Cardiol.
2008;5:56. doi: 10.1186/1479-5868-5-56 2014;64:472–481. doi: 10.1016/j.jacc.2014.04.058
21. Hawkins MS, Storti KL, Richardson CR, King WC, Strath SJ, Holleman RG, 38. Matthews CE, Cohen SS, Fowke JH, Han X, Xiao Q, Buchowski MS,
Kriska AM. Objectively measured physical activity of USA adults by sex, Hargreaves MK, Signorello LB, Blot WJ. Physical activity, sedentary behav-
age, and racial/ethnic groups: a cross-sectional study. Int J Behav Nutr Phys ior, and cause-specific mortality in black and white adults in the Southern
Act. 2009;6:31. doi: 10.1186/1479-5868-6-31 Community Cohort Study. Am J Epidemiol. 2014;180:394–405. doi:
22. Aggio D, Papachristou E, Papacosta O, Lennon LT, Ash S, Whincup 10.1093/aje/kwu142
PH, Wannamethee SG, Jefferis BJ. Trajectories of self-reported physi- 39. Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA.
cal activity and predictors during the transition to old age: a 20-year Sedentary time and its association with risk for disease incidence, mortal-
cohort study of British men. Int J Behav Nutr Phys Act. 2018;15:14. doi: ity, and hospitalization in adults: a systematic review and meta-analysis
10.1186/s12966-017-0642-4 [published correction appears in Ann Intern Med. 2015;163:400]. Ann
23. Nielsen Comparable Metrics Report Q2 2017. http://www.nielsen. Intern Med. 2015;162:123–132. doi: 10.7326/M14-1651
com/content/dam/corporate/us/en/reports-downloads/2017-reports/ 40. Ekelund U, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen
q2-2017-comparable-metrics-report.pdf. Accessed September 7, 2018. N, Powell KE, Bauman A, Lee IM; Lancet Physical Activity Series 2
24. Whitfield GP, Paul P, Wendel AM. Active transportation surveillance: Executive Committee; Lancet Sedentary Behaviour Working Group.
United States, 1999-2012. MMWR Surveill Summ. 2015;64:1–17. Does physical activity attenuate, or even eliminate, the detrimental
25. GBD 2013 Risk Factors Collaborators. Global, regional, and national association of sitting time with mortality? A harmonised meta-analysis
comparative risk assessment of 79 behavioural, environmental and occu- of data from more than 1 million men and women [published correc-
pational, and metabolic risks or clusters of risks in 188 countries, 1990– tion appears in Lancet. 2016;388:e6]. Lancet. 2016;388:1302–1310. doi:
2013: a systematic analysis for the Global Burden of Disease Study 2013. 10.1016/S0140-6736(16)30370-1
Lancet. 2015;386:2287–2323. doi: 10.1016/S0140-6736(15)00128-2 41. Fishman EI, Steeves JA, Zipunnikov V, Koster A, Berrigan D, Harris TA,
26. World Health Organization. Global Health Risks: Mortality and Burden of Murphy R. Association between objectively measured physical activity and
Disease Attributable to Selected Major Risks. Geneva, Switzerland: World mortality in NHANES. Med Sci Sports Exerc. 2016;48:1303–1311. doi:
Health Organization; 2009. 10.1249/MSS.0000000000000885
27. Lear SA, Hu W, Rangarajan S, Gasevic D, Leong D, Iqbal R, Casanova 42. Lee IM, Shiroma EJ, Evenson KR, Kamada M, LaCroix AZ, Buring JE.
A, Swaminathan S, Anjana RM, Kumar R, Rosengren A, Wei L, Yang Accelerometer-measured physical activity and sedentary behavior in
W, Chuangshi W, Huaxing L, Nair S, Diaz R, Swidon H, Gupta R, relation to all-cause mortality: the Women’s Health Study. Circulation.
Mohammadifard N, Lopez-Jaramillo P, Oguz A, Zatonska K, Seron P, 2018;137:203–205. doi: 10.1161/CIRCULATIONAHA.117.031300
Avezum A, Poirier P, Teo K, Yusuf S. The effect of physical activity on mor- 43. Diaz KM, Howard VJ, Hutto B, Colabianchi N, Vena JE, Safford MM,
tality and cardiovascular disease in 130 000 people from 17 high-income, Blair SN, Hooker SP. Patterns of sedentary behavior and mortality in U.S.
middle-income, and low-income countries: the PURE study [published middle-aged and older adults: a national cohort study. Ann Intern Med.
correction appears in Lancet. 2017;390:2626]. Lancet. 2017;390:2643– 2017;167:465–475. doi: 10.7326/M17-0212
2654. doi: 10.1016/S0140-6736(17)31634-3 44. Wickramasinghe CD, Ayers CR, Das S, de Lemos JA, Willis BL, Berry JD.
28. Carlson SA, Adams EK, Yang Z, Fulton JE. Percentage of deaths associated Prediction of 30-year risk for cardiovascular mortality by fitness and risk
with inadequate physical activity in the United States. Prev Chronic Dis. factor levels: the Cooper Center Longitudinal Study. Circ Cardiovasc Qual
2018;15:E38. doi: 10.5888/pcd18.170354 Outcomes. 2014;7:597–602. doi: 10.1161/CIRCOUTCOMES.113.000531

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e61

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

45. Celis-Morales CA, Lyall DM, Anderson J, Iliodromiti S, Fan Y, Ntuk UE, a systematic review and meta-analysis. Acta Obstet Gynecol Scand.
CLINICAL STATEMENTS

Mackay DF, Pell JP, Sattar N, Gill JM. The association between physical 2017;96:921–931. doi: 10.1111/aogs.13151
AND GUIDELINES

activity and risk of mortality is modulated by grip strength and cardiorespi- 63. Qi Q, Strizich G, Merchant G, Sotres-Alvarez D, Buelna C, Castañeda SF,
ratory fitness: evidence from 498 135 UK-Biobank participants. Eur Heart Gallo LC, Cai J, Gellman MD, Isasi CR, Moncrieft AE, Sanchez-Johnsen L,
J. 2017;38:116–122. doi: 10.1093/eurheartj/ehw249 Schneiderman N, Kaplan RC. Objectively measured sedentary time and
46. Blaha MJ, Hung RK, Dardari Z, Feldman DI, Whelton SP, Nasir K, Blumenthal cardiometabolic biomarkers in US Hispanic/Latino adults: the Hispanic
RS, Brawner CA, Ehrman JK, Keteyian SJ, Al-Mallah MH. Age-dependent Community Health Study/Study of Latinos (HCHS/SOL). Circulation.
prognostic value of exercise capacity and derivation of fitness-associated bio- 2015;132:1560–1569. doi: 10.1161/CIRCULATIONAHA.115.016938
logic age. Heart. 2016;102:431–437. doi: 10.1136/heartjnl-2015-308537 64. Diaz KM, Goldsmith J, Greenlee H, Strizich G, Qi Q, Mossavar-Rahmani Y,
47. National Center for Health Statistics. Chapter 33: Physical Activity. Healthy Vidot DC, Buelna C, Brintz CE, Elfassy T, Gallo LC, Daviglus ML, Sotres-
People 2020 Midcourse Review. Hyattsville, MD; US Department of Health Alvarez D, Kaplan RC. Prolonged, uninterrupted sedentary behavior
and Human Services, Centers for Disease Control and Prevention, National and glycemic biomarkers among US Hispanic/Latino adults: the HCHS/
Center for Health Statistics; 2016. DHHS publication No. 2017-1042. SOL (Hispanic Community Health Study/Study of Latinos). Circulation.
48. Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, Giles 2017;136:1362–1373. doi: 10.1161/CIRCULATIONAHA.116.026858
WH, Capewell S. Explaining the decrease in U.S. deaths from coro- 65. Pandey A, Salahuddin U, Garg S, Ayers C, Kulinski J, Anand V, Mayo H,
nary disease, 1980-2000. N Engl J Med. 2007;356:2388–2398. doi: Kumbhani DJ, de Lemos J, Berry JD. Continuous dose-response association
10.1056/NEJMsa053935 between sedentary time and risk for cardiovascular disease: a meta-analy-
49. National Center for Health Statistics. Health, United States, 2015: With sis. JAMA Cardiol. 2016;1:575–583. doi: 10.1001/jamacardio.2016.1567
Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD: 66. Mannsverk J, Wilsgaard T, Mathiesen EB, Løchen ML, Rasmussen K,
National Center for Health Statistics; 2016. http://www.cdc.gov/nchs/ Thelle DS, Njølstad I, Hopstock LA, Bønaa KH. Trends in modifiable risk
data/hus/hus15.pdf. Accessed September 7, 2018. factors are associated with declining incidence of hospitalized and non-
50. Shifts in Viewing: The Cross-Platform Report: September 2014. New hospitalized acute coronary heart disease in a population. Circulation.
York, NY: Nielsen Company; 2014. http://www.nielsen.com/content/dam/ 2016;133:74–81. doi: 10.1161/CIRCULATIONAHA.115.016960
corporate/us/en/reports-downloads/2014%20Reports/q2-2014-cross- 67. Armstrong ME, Green J, Reeves GK, Beral V, Cairns BJ; on behalf of the
platform-report-shifts-in-viewing.pdf. Accessed September 7, 2018. Million Women Study Collaborators. Frequent physical activity may not
51. Jenkins GP, Evenson KR, Herring AH, Hales D, Stevens J. Cardiometabolic reduce vascular disease risk as much as moderate activity: large prospec-
correlates of physical activity and sedentary patterns in U.S. youth. Med Sci tive study of women in the United Kingdom. Circulation. 2015;131:721–
Sports Exerc. 2017;49:1826–1833. doi: 10.1249/MSS.0000000000001310 729. doi: 10.1161/CIRCULATIONAHA.114.010296
52. Bailey DP, Charman SJ, Ploetz T, Savory LA, Kerr CJ. Associations between 68. Cochrane SK, Chen SH, Fitzgerald JD, Dodson JA, Fielding RA, King AC,
prolonged sedentary time and breaks in sedentary time with cardio- McDermott MM, Manini TM, Marsh AP, Newman AB, Pahor M, Tudor-
metabolic risk in 10-14-year-old children: the HAPPY study. J Sports Sci. Locke C, Ambrosius WT, Buford TW; for the LIFE Study Research Group.
2017;35:2164–2171. doi: 10.1080/02640414.2016.1260150 Association of accelerometry-measured physical activity and cardiovascu-
53. Hebert JJ, Klakk H, Møller NC, Grøntved A, Andersen LB, Wedderkopp N. lar events in mobility-limited older adults: the LIFE (Lifestyle Interventions
The prospective association of organized sports participation with cardio- and Independence for Elders) Study. J Am Heart Assoc. 2017;6:e007215.
vascular disease risk in children (the CHAMPS Study-DK). Mayo Clin Proc. doi: 10.1161/JAHA.117.007215
2017;92:57–65. doi: 10.1016/j.mayocp.2016.08.013 69. Pandey A, Garg S, Khunger M, Darden D, Ayers C, Kumbhani DJ,
54. Cureau FV, Ekelund U, Bloch KV, Schaan BD. Does body mass index modify Mayo HG, de Lemos JA, Berry JD. Dose-response relationship between
the association between physical activity and screen time with cardiomet- physical activity and risk of heart failure: a meta-analysis. Circulation.
Downloaded from http://ahajournals.org by on February 7, 2019

abolic risk factors in adolescents? Findings from a country-wide survey. Int 2015;132:1786–1794. doi: 10.1161/CIRCULATIONAHA.115.015853
J Obes (Lond). 2017;41:551–559. doi: 10.1038/ijo.2016.210 70. Pandey A, LaMonte M, Klein L, Ayers C, Psaty BM, Eaton CB, Allen NB,
55. Skrede T, Stavnsbo M, Aadland E, Aadland KN, Anderssen SA, Resaland de Lemos JA, Carnethon M, Greenland P, Berry JD. Relationship between
GK, Ekelund U. Moderate-to-vigorous physical activity, but not sedentary physical activity, body mass index, and risk of heart failure. J Am Coll
time, predicts changes in cardiometabolic risk factors in 10-y-old children: Cardiol. 2017;69:1129–1142. doi: 10.1016/j.jacc.2016.11.081
the Active Smarter Kids Study. Am J Clin Nutr. 2017;105:1391–1398. doi: 71. Yates T, Haffner SM, Schulte PJ, Thomas L, Huffman KM, Bales CW,
10.3945/ajcn.116.150540 Califf RM, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Davies
56. LeFevre ML; U.S. Preventive Services Task Force. Behavioral counseling MJ, Kraus WE. Association between change in daily ambulatory activ-
to promote a healthful diet and physical activity for cardiovascular dis- ity and cardiovascular events in people with impaired glucose tolerance
ease prevention in adults with cardiovascular risk factors: U.S. Preventive (NAVIGATOR trial): a cohort analysis. Lancet. 2014;383:1059–1066. doi:
Services Task Force Recommendation Statement. Ann Intern Med. 10.1016/S0140-6736(13)62061-9
2014;161:587–593. doi: 10.7326/M14-1796 72. Hamer M, Chida Y. Active commuting and cardiovascular risk: a meta-ana-
57. Zwald ML, Akinbami LJ, Fakhouri TH, Fryar CD. Prevalence of low high- lytic review. Prev Med. 2008;46:9–13. doi: 10.1016/j.ypmed.2007.03.006
density lipoprotein cholesterol among adults, by physical activity: United 73. Johnsen AM, Alfredsson L, Knutsson A, Westerholm PJ, Fransson EI.
States, 2011–2014. NCHS Data Brief. 2017;(276):1–8. Association between occupational physical activity and myocardial
58. Grontved A, Koivula RW, Johansson I, Wennberg P, Østergaard L, Hallmans infarction: a prospective cohort study. BMJ Open. 2016;6:e012692. doi:
G, Renström F, Franks PW. Bicycling to work and primordial prevention of 10.1136/bmjopen-2016-012692
cardiovascular risk: a cohort study among Swedish men and women. J Am 74. Dhana K, Koolhaas CM, Berghout MA, Peeters A, Ikram MA, Tiemeier
Heart Assoc. 2016;5:e004413. doi: 10.1161/jaha.116.004413 H, Hofman A, Nusselder W, Franco OH. Physical activity types and life
59. Chu P, Gotink RA, Yeh GY, Goldie SJ, Hunink MG. The effectiveness of yoga expectancy with and without cardiovascular disease: the Rotterdam Study.
in modifying risk factors for cardiovascular disease and metabolic syndrome: J Public Health (Oxf). 2017;39:e209–e218. doi: 10.1093/pubmed/fdw110
a systematic review and meta-analysis of randomized controlled trials. Eur J 75. Berry JD, Pandey A, Gao A, Leonard D, Farzaneh-Far R, Ayers C, DeFina L, Willis
Prev Cardiol. 2016;23:291–307. doi: 10.1177/2047487314562741 B. Physical fitness and risk for heart failure and coronary artery disease. Circ
60. Du H, Bennett D, Li L, Whitlock G, Guo Y, Collins R, Chen J, Bian Z, Heart Fail. 2013;6:627–634. doi: 10.1161/CIRCHEARTFAILURE.112.000054
Hong LS, Feng S, Chen X, Chen L, Zhou R, Mao E, Peto R, Chen Z; China 76. Pandey A, Patel M, Gao A, Willis BL, Das SR, Leonard D, Drazner MH, de
Kadoorie Biobank Collaborative Group. Physical activity and sedentary lei- Lemos JA, DeFina L, Berry JD. Changes in mid-life fitness predicts heart
sure time and their associations with BMI, waist circumference, and per- failure risk at a later age independent of interval development of cardiac
centage body fat in 0.5 million adults: the China Kadoorie Biobank study. and noncardiac risk factors: the Cooper Center Longitudinal Study. Am
Am J Clin Nutr. 2013;97:487–496. doi: 10.3945/ajcn.112.046854 Heart J. 2015;169:290–297.e1. doi: 10.1016/j.ahj.2014.10.017
61. Liu X, Zhang D, Liu Y, Sun X, Han C, Wang B, Ren Y, Zhou J, Zhao Y, Shi 77. Myers J, Kokkinos P, Chan K, Dandekar E, Yilmaz B, Nagare A, Faselis C,
Y, Hu D, Zhang M. Dose-response association between physical activity and Soofi M. Cardiorespiratory fitness and reclassification of risk for incidence
incident hypertension: a systematic review and meta-analysis of cohort stud- of heart failure: the Veterans Exercise Testing Study. Circulation Heart Fail.
ies. Hypertension. 2017;69:813–820. doi: 10.1161/HYPERTENSIONAHA. 2017;10:e003780. doi: 10.1161/CIRCHEARTFAILURE.116.003780
116.08994 78. Zöller B, Ohlsson H, Sundquist J, Sundquist K. Cardiovascular fitness in young
62. Magro-Malosso ER, Saccone G, Di Tommaso M, Roman A, Berghella V. males and risk of unprovoked venous thromboembolism in adulthood.
Exercise during pregnancy and risk of gestational hypertensive disorders: Ann Med. 2017;49:176–184. doi: 10.1080/07853890.2016.1252057

e62 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 4

79. Faselis C, Kokkinos P, Tsimploulis A, Pittaras A, Myers J, Lavie CJ, Kyritsi 95. Laine J, Kuvaja-Köllner V, Pietilä E, Koivuneva M, Valtonen H, Kankaanpää

CLINICAL STATEMENTS
F, Lovic D, Karasik P, Moore H. Exercise capacity and atrial fibrillation E. Cost-effectiveness of population-level physical activity interven-

AND GUIDELINES
risk in veterans: a cohort study. Mayo Clin Proc. 2016;91:558–566. doi: tions: a systematic review. Am J Health Promot. 2014;29:71–80. doi:
10.1016/j.mayocp.2016.03.002 10.4278/ajhp.131210-LIT-622
80. Anderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, 96. Weintraub WS, Daniels SR, Burke LE, Franklin BA, Goff DC Jr, Hayman
Taylor RS. Exercise-based cardiac rehabilitation for coronary heart dis- LL, Lloyd-Jones D, Pandey DK, Sanchez EJ, Schram AP, Whitsel LP;
ease: Cochrane systematic review and meta-analysis. J Am Coll Cardiol. on behalf of the American Heart Association Advocacy Coordinating
2016;67:1–12. doi: 10.1016/j.jacc.2015.10.044 Committee; Council on Cardiovascular Disease in the Young; Council
81. Doukky R, Mangla A, Ibrahim Z, Poulin MF, Avery E, Collado FM, Kaplan on the Kidney in Cardiovascular Disease; Council on Epidemiology
J, Richardson D, Powell LH. Impact of physical inactivity on mortality in and Prevention; Council on Cardiovascular Nursing; Council on
patients with heart failure. Am J Cardiol. 2016;117:1135–1143. doi: Arteriosclerosis; Thrombosis and Vascular Biology; Council on Clinical
10.1016/j.amjcard.2015.12.060 Cardiology, and Stroke Council. Value of primordial and primary
82. Stewart RAH, Held C, Hadziosmanovic N, Armstrong PW, Cannon CP, prevention for cardiovascular disease: a policy statement from the
Granger CB, Hagström E, Hochman JS, Koenig W, Lonn E, Nicolau JC, American Heart Association. Circulation. 2011;124:967–990. doi:
Steg PG, Vedin O, Wallentin L, White HD; STABILITY Investigators. Physical 10.1161/CIR.0b013e3182285a81
activity and mortality in patients with stable coronary heart disease. J Am 97. Step It Up! The Surgeon General’s Call to Action to Promote Walking and
Coll Cardiol. 2017;70:1689–1700. doi: 10.1016/j.jacc.2017.08.017 Walkable Communities. Washington, DC: US Dept of Health and Human
83. Lahtinen M, Toukola T, Junttila MJ, Piira OP, Lepojärvi S, Kääriäinen M, Services, Office of the Surgeon General; 2015.
Huikuri HV, Tulppo MP, Kiviniemi AM. Effect of changes in physical activity 98. Creatore MI, Glazier RH, Moineddin R, Fazli GS, Johns A, Gozdyra
on risk for cardiac death in patients with coronary artery disease. Am J P, Matheson FI, Kaufman-Shriqui V, Rosella LC, Manuel DG, Booth
Cardiol. 2018;121:143–148. doi: 10.1016/j.amjcard.2017.10.002 GL. Association of neighborhood walkability with change in over-
84. Moholdt T, Lavie CJ, Nauman J. Sustained physical activity, not weight weight, obesity, and diabetes. JAMA. 2016;315:2211–2220. doi:
loss, associated with improved survival in coronary heart disease [pub- 10.1001/jama.2016.5898
lished correction appears in J Am Coll Cardiol. 2018;71:1499]. J Am Coll 99. Chiu M, Rezai MR, Maclagan LC, Austin PC, Shah BR, Redelmeier DA,
Cardiol. 2018;71:1094–1101. doi: 10.1016/j.jacc.2018.01.011 Tu JV. Moving to a highly walkable neighborhood and incidence of hy-
85. Hegde SM, Claggett B, Shah AM, Lewis EF, Anand I, Shah SJ, Sweitzer NK, pertension: a propensity-score matched cohort study. Environ Health
Fang JC, Pitt B, Pfeffer MA, Solomon SD. Physical activity and prognosis in Perspect. 2016;124:754–760. doi: 10.1289/ehp.1510425
the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure 100. Bennett GG, Wolin KY, Puleo EM, Mâsse LC, Atienza AA. Awareness
With an Aldosterone Antagonist). Circulation. 2017;136:982–992. doi: of national physical activity recommendations for health promotion
10.1161/CIRCULATIONAHA.117.028002 among US adults. Med Sci Sports Exerc. 2009;41:1849–1855. doi:
86. Coll-Fernández R, Coll R, Muñoz-Torrero JF, Aguilar E, Ramón Álvarez 10.1249/MSS.0b013e3181a52100
L, Sahuquillo JC, Yeste M, Jiménez PE, Mujal A, Monreal M; FRENA 101. Centers for Disease Control and Prevention and SHAPE America–Society
Investigators. Supervised versus non-supervised exercise in patients with of Health and Physical Educators. Strategies for Recess in Schools.
recent myocardial infarction: a propensity analysis. Eur J Prev Cardiol. Atlanta, GA; Centers for Disease Control and Prevention, US Dept of
2016;23:245–252. doi: 10.1177/2047487315578443 Health and Human Services; 2017.
87. Shaya GE, Al-Mallah MH, Hung RK, Nasir K, Blumenthal RS, Ehrman JK, 102. Cradock AL, Barrett JL, Kenney EL, Giles CM, Ward ZJ, Long MW, Resch
Keteyian SJ, Brawner CA, Qureshi WT, Blaha MJ. High exercise capacity SC, Pipito AA, Wei ER, Gortmaker SL. Using cost-effectiveness analysis to
attenuates the risk of early mortality after a first myocardial infarction: the prioritize policy and programmatic approaches to physical activity promo-
Downloaded from http://ahajournals.org by on February 7, 2019

Henry Ford Exercise Testing (FIT) Project. Mayo Clin Proc. 2016;91:129– tion and obesity prevention in childhood. Prev Med. 2017;95(suppl):S17–
139. doi: 10.1016/j.mayocp.2015.11.012 S27. doi: 10.1016/j.ypmed.2016.10.017
88. Minges KE, Strait KM, Owen N, Dunstan DW, Camhi SM, Lichtman J, Geda 103. Carr LJ, Leonhard C, Tucker S, Fethke N, Benzo R, Gerr F. Total worker
M, Dreyer RP, Bueno H, Beltrame JF, Curtis JP, Krumholz HM. Gender dif- health intervention increases activity of sedentary workers. Am J Prev
ferences in physical activity following acute myocardial infarction in adults: Med. 2016;50:9–17. doi: 10.1016/j.amepre.2015.06.022
a prospective, observational study. Eur J Prev Cardiol. 2017;24:192–203. 104. Healy GN, Winkler EAH, Eakin EG, Owen N, Lamontagne AD, Moodie M,
doi: 10.1177/2047487316679905 Dunstan DW. A cluster RCT to reduce workers’ sitting time: impact on
89. Gorczyca AM, Eaton CB, LaMonte MJ, Manson JE, Johnston JD, Bidulescu cardiometabolic biomarkers. Med Sci Sports Exerc. 2017;49:2032–2039.
A, Waring ME, Manini T, Martin LW, Stefanick ML, He K, Chomistek AK. doi: 10.1249/MSS.0000000000001328
Change in physical activity and sitting time after myocardial infarction 105. Young DR, Hivert MF, Alhassan S,Camhi SM, Ferguson JF, Katzmarzyk
and mortality among postmenopausal women in the Women’s Health PT, Lewis CE, Owen N, Perry CK, Siddique J, Yong CM; on behalf
Initiative-Observational Study. J Am Heart Assoc. 2017;6:e005354. doi: of the Physical Activity Committee of the Council on Lifestyle and
10.1161/JAHA.116.005354 Cardiometabolic Health; Council on Clinical Cardiology; Council on
90. Ku PW, Chen LJ, Fox KR, Chen YH, Liao Y, Lin CH. Leisure-time, domestic, Epidemiology and Prevention; Council on Functional Genomics and
and work-related physical activity and their prospective associations with Translational Biology; and Stroke Council. Sedentary behavior and
all-cause mortality in patients with cardiovascular disease. Am J Cardiol. cardiovascular morbidity and mortality: a science advisory from the
2018;121:177–181. doi: 10.1016/j.amjcard.2017.10.003 American Heart Association. Circulation. 2016;134:e262–279. doi:
91. Oldridge NB. Economic burden of physical inactivity: healthcare costs 10.1161/CIR.0000000000000440
associated with cardiovascular disease. Eur J Cardiovasc Prev Rehabil. 106. den Hoed M, Brage S, Zhao JH, Westgate K, Nessa A, Ekelund U, Spector
2008;15:130–139. doi: 10.1097/HJR.0b013e3282f19d42 TD, Wareham NJ, Loos RJ. Heritability of objectively assessed daily physi-
92. Ding D, Lawson KD, Kolbe-Alexander TL, Finkelstein EA, Katzmarzyk cal activity and sedentary behavior. Am J Clin Nutr. 2013;98:1317–1325.
PT, van Mechelen W, Pratt M; Lancet Physical Activity Series 2 Executive doi: 10.3945/ajcn.113.069849
Committee. The economic burden of physical inactivity: a global analysis 107. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F,
of major non-communicable diseases. Lancet. 2016;388:1311–1324. doi: McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART
10.1016/S0140-6736(16)30383-X Study Investigators. Effect of potentially modifiable risk factors as-
93. Carlson SA, Fulton JE, Pratt M, Yang Z, Adams EK. Inadequate physical sociated with myocardial infarction in 52 countries (the INTERHEART
activity and health care expenditures in the United States. Prog Cardiovasc study): case-control study. Lancet. 2004;364:937–952. doi: 10.1016/
Dis. 2015;57:315–323. doi: 10.1016/j.pcad.2014.08.002 S0140-6736(04)17018-9
94. Valero-Elizondo J, Salami JA, Ogunmoroti O, Osondu CU, Aneni EC, 108. Wen CP, Wu X. Stressing harms of physical inactivity to promote exercise.
Malik R, Spatz ES, Rana JS, Virani SS, Blankstein R, Blaha MJ, Veledar Lancet. 2012;380:192–193. doi: 10.1016/S0140-6736(12)60954-4
E, Nasir K. Favorable cardiovascular risk profile is associated with lower 109. Global Burden of Disease Study 2016. Global Burden of Disease Study
healthcare costs and resource utilization: the 2012 Medical Expenditure 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
Panel Survey. Circ Cardiovasc Qual Outcomes. 2016;9:143–153. doi: Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
10.1161/CIRCOUTCOMES.115.002616 data.org/gbd-results-tool. Accessed September 7, 2018.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e63

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

5. NUTRITION diet pattern characterized by 5 primary and 3 second-

CLINICAL STATEMENTS

ary metrics (Table 5-1) that should be consumed within

See Table 5-1 and Charts 5-1 through 5-8
AND GUIDELINES

the context that is appropriate in energy balance and

consistent with a DASH-type eating plan.1
Click here to return to the Table of Contents
The AHA scoring system for ideal, intermediate,
and poor diet patterns uses a binary-based scoring
This chapter of the Update highlights national dietary hab-
system, which awards 1 point for meeting the ideal
its, focusing on key foods, nutrients, dietary patterns, and
target for each metric and 0 points otherwise.2 For
other dietary factors related to cardiometabolic health. It is
better consistency with other dietary pattern scores
intended to examine current intakes, trends and changes
such as DASH, an alternative continuous scoring sys-
in intakes, and estimated effects on disease to support and
tem has been developed to measure small improve-
further stimulate efforts to monitor and improve dietary
ments over time toward the AHA ideal target levels
habits in relation to cardiovascular health.
(Table 5-1). The dietary targets remain the same, and
progress toward each of these targets is assessed by
Prevalence and Trends in the AHA 2020 use of a more granular range of 1 to 10 (rather than
Healthy Diet Metrics 0 to 1).
(See Table 5-1 and Charts 5-1 and 5-2) Using the alternative scoring system, the mean AHA
healthy diet score improved between 2003 to 2004 and
The AHA’s 2020 Impact Goals prioritize improving car- 2011 to 2012 in the United States in both children and
diovascular health,1 which includes following a healthy
adults.3 In children, the poor diet (<40% adherence),
Abbreviations Used in Chapter 5
based on the AHA healthy diet score, decreased from
69.2% to 54.6%. In adults, the prevalence of a poor
AHA American Heart Association
BMI body mass index
diet decreased from 50.3% to 41.0%.4 Improvements
BP blood pressure were largely attributable to increased whole grain con-
CER cost-effectiveness ratio sumption and decreased SSB consumption in both
CHD coronary heart disease children and adults.4 Among adults, other significant
CI confidence interval improvements included increased consumption of
CVD cardiovascular disease
nuts, seeds, and legumes (0.54 to 0.81 servings/d)
DALY disability-adjusted life-year
Downloaded from http://ahajournals.org by on February 7, 2019

DASH Dietary Approaches to Stop Hypertension and decreased consumption of 100% fruit juice (0.43
DBP diastolic blood pressure to 0.32 servings/d) and white potatoes (0.39 to 0.32
DM diabetes mellitus servings/d).4 No major improvements in consumption of
GBD Global Burden of Disease sodium, fish, fruits and vegetables, processed meats,
HbA1c hemoglobin A1c (glycosylated hemoglobin)
and saturated fat were noted.
HDL high-density lipoprotein
HDL-C high-density lipoprotein cholesterol
Smaller improvements in AHA healthy diet scores
HEI Healthy Eating Index were seen in minority groups and those with lower
HF heart failure income or education (Charts 5-1 and 5-2).4 For exam-
HR hazard ratio ple, the proportion with a poor diet (<40% adher-
LDL low-density lipoprotein ence) decreased from 50.5% to 35.7% in adults with
LDL-C low-density lipoprotein cholesterol
income-to-poverty ratio ≥3.0, but only from 67.8%
MI myocardial infarction
MUFA monounsaturated fatty acid
to 60.6% in adults with income-to-poverty ratio <1.3
NH non-Hispanic (Chart 5-2).
NHANES National Health and Nutrition Examination Survey
PA physical activity
PREDIMED Prevención con Dieta Mediterránea Global Trends in Key Dietary Factors
PUFA polyunsaturated fatty acid Globally, between 1999 and 2010, SSB intake increased
RCT randomized controlled trial
in several countries.5 SSB consumption was highest in
REGARDS Reasons for Geographic and Racial Differences in Stroke
RR relative risk the Caribbean, with adults consuming on average 2
SBP systolic blood pressure servings per day, and lowest in East Asia, at 0.20 serv-
SCD sudden cardiac death ings per day. Adults in the United States had the 26th-
SES socioeconomic status highest consumption among 187 countries.
SFA saturated fatty acid
A number of countries and US cities have imple-
SNAP Supplemental Nutrition Assistance Program
SNP single-nucleotide polymorphism
mented SSB taxes.6 In Mexico, a 1 peso per liter excise
SSB sugar-sweetened beverage tax was implemented in January 2014. In a study using
TC total cholesterol store purchase data from 6645 Mexican households,
TOHP Trials of Hypertension Prevention posttax volume of beverages purchased decreased by
WHI Women’s Health Initiative 5.5% in 2014 and by 9.7% in 2015 compared with

e64 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

predicted volume of beverages purchased based on • Consumption of whole grains was 1.1 serv-

CLINICAL STATEMENTS
pretax trends. Although all socioeconomic groups ings per day by NH white males and females,

AND GUIDELINES
experienced declines in SSB purchases, the lowest 0.8 to 0.9 servings per day by NH black males
socioeconomic group had the greatest decline in SSB and females, and 0.6 to 0.8 servings per day by
purchases (9.0% in 2014 and 14.3% in 2015).7 In Mexican American males and females. For each
Berkeley, CA, a 1 cent per ounce SSB excise tax was of these groups, <10% of adults in 2011 to 2012
implemented in January 2015.8 Using store-level data, met guidelines of ≥3 servings per day.
posttax year 1 SSB sales declined by 9.6% compared • Fruit consumption ranged from 1.0 to 1.6 serv-
with predicted SSB sales based on pretax trends. By ings per day in these racial or ethnic subgroups:
comparison, SSB sales increased by 6.9% in non- ≈9% of NH whites, 7% of NH blacks, and 6%
Berkeley stores in adjacent cities. of Mexican Americans met guidelines of ≥2 cups
In 2010, mean sodium intake among adults world- per day. When 100% fruit juices were included,
wide was 3950 mg/d.9 Across world regions, mean the number of servings increased and the pro-
sodium intakes were highest in Central Asia (5510 portions of adults consuming ≥2 cups per day
mg/d) and lowest in eastern sub-Saharan Africa (2180 nearly doubled in NH whites, doubled in NH
mg/d). Across countries, the lowest observed mean blacks, and more than doubled in Mexican
national intakes were ≈1500 mg/d. Between 1990 and Americans.
2010, global mean sodium intake appeared to remain • Nonstarchy vegetable consumption ranged from
relatively stable, although data on trends in many world 1.7 to 2.7 servings per day. Across all racial/eth-
regions were suboptimal.9 nic subgroups, NH white females were the only
In a systematic review of population-level sodium group meeting the target of consuming ≥2.5
initiatives, reduction in mean sodium intake occurred cups per day.
in 5 of 10 initiatives.10 Successful population-level • Consumption of fish and shellfish was lowest
sodium initiatives tended to use multiple strategies among Mexican American females and white
and included structural activities, such as food product females (0.8 and 1.0 servings per week, respec-
reformulation. For example, Finland initiated a nation- tively) and highest among NH black females and
wide campaign in the late 1970s through public edu- NH black and Mexican American males (1.9 and
cation, collaboration with the food industry, and salt 1.7 servings per week, respectively). Generally,
labeling legislation. From 1979 to 2002, mean 24-hour only 15% to 27% of adults in each sex and racial
Downloaded from http://ahajournals.org by on February 7, 2019

urine sodium excretion in population-based samples or ethnic subgroup consumed ≥2 servings per
decreased in Finnish males (5.1 to 3.9 g/d) and females week.
(4.1 to 3.0 g/d), with concurrent decreases in mean • Weekly consumption of nuts and seeds was
SBP and prevalence of hypertension.11,12 Similarly, the ≈3.5 servings among NH whites and 2.5 serv-
United Kingdom initiated a nationwide salt reduction ings among NH blacks and Mexican Americans.
program in 2003 to 2004 that included consumer Approximately 1 in 4 whites, 1 in 6 NH blacks,
awareness campaigns, progressively lower salt targets and 1 in 8 Mexican Americans met guidelines of
for various food categories, clear nutritional label- ≥4 servings per week.
ing, and working with industry to reformulate foods. • Consumption of unprocessed red meats was
Mean sodium intake in the United Kingdom decreased higher in males than in females, up to 4.8 serv-
by 15% from 2003 to 2011,13 along with concurrent ings per week in Mexican American males.
decreases in BP (3.0/1.4 mm Hg) in patients not taking • Consumption of processed meats was lowest
antihypertensive medication, stroke mortality (42%), among Mexican American females (1.1 servings
and CHD mortality (40%) (P<0.001 for all compari- per week) and highest among NH black and NH
sons); these findings remained statistically significant white males (≈2.5 servings per week). Between
after adjustment for changes in demographics, BMI, 57% (NH white males) and 79% (Mexican
and other dietary factors. American females) of adults consumed ≤2 serv-
ings per week.
• Consumption of SSBs ranged from 6.8 servings
Dietary Habits in the United States: per week among NH white females to nearly
Current Intakes 12 servings per week among Mexican American
Foods and Nutrients males. Females generally consumed less than
Adults males. Some adults, from 33% of Mexican
The average dietary consumption by US adults of American males to 65% of NH white females,
selected foods and nutrients related to cardiometabolic consumed <36 oz/wk.
health based on data from 2011 to 2012 NHANES is • Consumption of sweets and bakery desserts
detailed below3: ranged from 3.9 servings per week (Mexican

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e65

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

American males) to >7 servings per week (white consuming ≥2 cups per day increased to nearly
CLINICAL STATEMENTS

females). Approximately 1 in 3 adults (1 in 2 25% of those 5 to 9 years of age, 20% of those

AND GUIDELINES

Mexican American males) consumed <2.5 serv- 10 to 14 years of age, and 15% of those 15 to
ings per week. 19 years of age.
• Consumption of eicosapentaenoic acid and doc- • Nonstarchy vegetable consumption was low,
osahexaenoic acid ranged from 0.058 to 0.117 ranging from 1.1 to 1.5 servings per day, with
g/d in each sex and racial or ethnic subgroup. <1.5% of children in different age and sex sub-
Fewer than 8% of NH whites, 14% of NH blacks, groups meeting guidelines of ≥2.5 cups per day.
and 11% of Mexican Americans consumed • Consumption of fish and shellfish was low,
≥0.250 g/d. ranging between 0.3 and 1.0 servings per week
• One-third to one-half of adults in each sex and in all age and sex groups. Among all ages, only
racial or ethnic subgroup consumed <10% of 7% to 14% of youths consumed ≥2 servings per
total calories from saturated fat, and approxi- week.
mately one-half to two-thirds consumed <300 • Consumption of nuts, seeds, and beans ranged
mg of dietary cholesterol per day. from 1.1 to 2.7 servings per week among differ-
• Only ≈7% to 10% of NH whites, 4% to 5% of ent age and sex groups, and generally <15% of
blacks, and 13% to 14% of Mexican Americans children in different age and sex subgroups con-
consumed ≥28 g of dietary fiber per day. sumed ≥4 servings per week.
• Only ≈6% to 8% of adults in each age and • Consumption of unprocessed red meats was
racial or ethnic subgroup consumed <2.3 g of higher in boys than in girls and increased with
sodium per day. Estimated mean sodium intake age, up to 3.6 and 2.5 servings per week in 15- to
in the US by 24-hour urinary excretion was 4205 19-year-old boys and girls, respectively.
mg/d for males and 3039 mg/d for females in • Consumption of processed meats ranged from
2013 to 2014. Estimates of sodium intake by 1.4 to 2.3 servings per week, and the majority of
race, sex, and source are shown in Charts 5-3 children consumed <2 servings per week of pro-
and 5-4.14 Sodium added to food outside the cessed meats.
home accounts for more than two-thirds of total • Consumption of SSBs was higher in boys than
sodium intake in the United States (Chart 5-4).15 in girls in the 5- to 9-year-old (7.7±6.2 versus
6.0±3.8 servings per week) and 10- to 14-year-
Downloaded from http://ahajournals.org by on February 7, 2019

Top sources of sodium intake vary by race/eth-

nicity, with the largest contributor being yeast old (11.6±5.3 versus 9.7±7.9 servings per week)
breads for NH whites, sandwiches for NH blacks, groups, but it was higher in girls than in boys
burritos and tacos for Hispanics, and soups for in the 15- to 19-year-old group (14±6.0 versus
NH Asians.16 12.4±5.8 servings per week). Only about half of
children 5 to 9 years of age and one-quarter of
Children and Teenagers boys 15 to 19 years of age consumed <4.5 serv-
On the basis of NHANES 2011 to 2012, the average ings per week.
dietary consumption by US children and teenagers of • Consumption of sweets and bakery desserts
selected foods and nutrients related to cardiometabolic was higher among 5- to 9-year-old and 10- to
health is detailed below3: 14-year-old boys and girls and modestly lower
• Whole grain consumption was <1 serving per day (4.7 to 6 servings per week) among 15- to
in all age and sex groups, with <5% of all chil- 19-year-olds. A minority of children in all age
dren in different age and sex subgroups meeting and sex subgroups consumed <2.5 servings
guidelines of ≥3 servings per day.17 per week.
• Fruit consumption was low and decreased with • Consumption of eicosapentaenoic acid and doco-
age: 1.7 to 1.9 servings per day in younger boys sahexaenoic acid was low, ranging from 0.034
and girls (5–9 years of age), 1.4 servings per to 0.065 g/d in boys and girls in all age groups.
day in adolescent boys and girls (10–14 years of Fewer than 7% of children and teenagers at any
age), and 0.9 to 1.3 servings per day in teen- age consumed ≥0.250 g/d.
age boys and girls (15–19 years of age). The pro- • Consumption of SFAs was ≈11% of calories
portion meeting guidelines of ≥2 cups per day in boys and girls in all age groups, and aver-
was also low and decreased with age: ≈8% to age consumption of dietary cholesterol ranged
14% in those 5 to 9 years of age, 3% to 8% in from ≈210 to 270 mg/d, increasing with age.
those 10 to 14 years of age, and 5% to 6% in Approximately 25% to 40% of youths con-
those 15 to 19 years of age. When 100% fruit sumed <10% energy from SFAs, and ≈70% to
juices were included, the number of servings 80% consumed <300 mg of dietary cholesterol
consumed increased by ≈50%, and proportions per day.

e66 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

• Consumption of dietary fiber ranged from ≈14 to • In an assessment of snacks served at YMCA after-

CLINICAL STATEMENTS
16 g/d. Fewer than 3% of children in all age and school programs from 2006 to 2008, healthful

AND GUIDELINES
sex subgroups consumed ≥28 g/d. snacks were ≈50% more expensive ($0.26 per
• Consumption of sodium ranged from 3.1 to 3.5 snack) than less healthful snacks.22
g/d. Only 2% to 11% of children in different age • In a 1-year (2013–2014) RCT of 30 after-school
and sex subgroups consumed <2.3 g/d. programs in South Carolina, site leaders in the
intervention group received assistance in estab-
lishing snack budgets and menus and identify-
Impact on US Mortality ing low-cost outlets to purchase snacks that
(See Chart 5-5) met healthy eating standards. The intervention
Comparable risk assessment methods and nation- was successful in increasing the number of days
ally representative data were used to estimate the fruits and vegetables were served (3.9 versus 0.7
impact of 10 specific dietary factors on cardiometa- d/wk) and decreasing the number of days SSBs
bolic mortality in the United States in 2002 and 2012 (0.1 versus 1.8 d/wk) and sugary foods (0.3 versus
(Chart 5-5).18 In 2012, 318 656 (45.4%) of 702 308 2.7 d/wk) were served.23 Cost in the intervention
cardiometabolic deaths were estimated to be attribut- group was minimized by identifying low-cost gro-
able to poor dietary habits. The largest numbers of cery outlets or large bulk warehouse stores; cost
deaths attributable to diet were estimated to be from increased by $0.02 per snack in the intervention
high sodium intake (66 508; 9.5% of all cardiometa- group compared with a $0.01 per snack decrease
bolic deaths), low consumption of nuts/seeds (59 374; in the control group.
8.5%), high consumption of processed meats (57 766;
Cost-Effectiveness of Sodium Reduction
8.2%), low intake of seafood omega-3 fats (54 626;
• In a cost-effectiveness analysis using the Coronary
7.8%), low consumption of vegetables (53 410; 7.6%)
Heart Disease Policy Model, a 1.2-g/d reduction in
and fruits (52 547; 7.5%), and high consumption of
dietary sodium was projected to reduce US annual
SSBs (51 694; 7.4%). Between 2002 and 2012, pop-
cases of incident CHD by 60 000 to 120 000,
ulation-adjusted US cardiometabolic deaths decreased
stroke by 32 000 to 66 000, and total mortality by
by 26.5%, with declines in estimated diet-associated
44 000 to 92 000.24 The projected benefits would
cardiometabolic deaths for PUFAs (−20.8%), nuts/
be greater in blacks than in nonblacks. If accom-
Downloaded from http://ahajournals.org by on February 7, 2019

seeds (−18.0%), and SSBs (−14.5%) and increases

in diet-associated cardiometabolic deaths for sodium plished through a regulatory intervention, esti-
(5.8%) and unprocessed red meats (14.4%). Estimated mated savings in healthcare costs would be $10
cardiometabolic mortality related to whole grains, billion to $24 billion annually.24
fruits, vegetables, seafood, omega-3 fats, and pro- • A global cost-effectiveness analysis modeled
cessed meats remained relatively stable. the cost-effectiveness of a so-called soft regula-
tion national policy to reduce sodium intake in
countries around the world, based on the United
Cost Kingdom experience (government-supported
(See Chart 5-6) industry agreements, government monitoring of
industry compliance, public health campaign).25
The US Department of Agriculture reported that the
Model estimates were based on sodium intake,
Consumer Price Index for all food increased by 0.9%
BP, and CVD data from 183 countries. Country-
in 2017.19 Prices for foods eaten at home decreased
specific cost data were used to estimate the CER,
by 0.2% in 2017, whereas prices for foods eaten
defined as purchasing power parity adjusted inter-
away from home increased by 2.3%.12 Using data
national dollars (I$, equivalent to country-specific
from Euromonitor International, the US Department of
Agriculture calculated the share of consumer expendi- purchasing power of $1 US) per DALY saved over
tures attributed to food in multiple countries in 2016. 10 years. Globally, the estimated average CER was
The proportion of consumer expenditures spent on I$204 per DALY (95% CI, I$149–I$322) saved.
food ranged from 6.3% in the United States to 9.1% in The estimated CER was highly favorable in high-,
Canada, 23.1% in Mexico, and 58.9% in Nigeria (Chart middle-, and low-income countries.
5-6).20
Cost of a Healthy Diet Secular Trends
• A meta-analysis of price comparisons of healthy Trends in Dietary Patterns
versus unhealthy diet patterns found that the (See Chart 5–7)
healthiest diet patterns cost, on average, ≈$1.50 In addition to individual foods and nutrients, over-
more per person per day to consume.21 all dietary patterns can be another useful tool for

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e67

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

assessing diet quality.26 Different dietary patterns have compared with low-income nations, high-income
CLINICAL STATEMENTS

been defined, such as Mediterranean, DASH-type, nations had better diet patterns based on healthful
AND GUIDELINES

HEI-2010, Alternate HEI, Western, prudent, and veg- foods but substantially worse diet patterns based on
etarian patterns. The original DASH diet was low fat; unhealthful foods. Between 1990 and 2010, both
a higher-MUFA DASH-type diet is even more health- types of dietary patterns improved in high-income
ful and similar to a traditional Mediterranean dietary Western countries but worsened or did not improve
pattern.27 in low-income countries in Africa and Asia. Middle-
Between 1999 and 2010, the average Alternate HEI– income countries showed the largest improvements
2010 score of US adults improved from 39.9 to 46.8.28 in dietary patterns based on healthful foods but
This was related to reduced intake of trans fat (account- the largest deteriorations in dietary patterns based
ing for more than half of the improvement), SSBs, and on unhealthful foods. Overall, global consumption
fruit juice, as well as an increased intake of whole fruit, of healthy foods improved but was outpaced by
whole grains, PUFAs, and nuts and legumes. Adults increased intake of unhealthy foods in most world
with greater family income and education had higher regions.
scores, and the gap between low and high SES wid-
ened over time, from 3.9 points in 1999 to 2000 to 7.8 Trends in Energy Intake
points in 2009 to 2010. Until 1980, total energy intake remained relatively
Between 1999 and 2012, the mean HEI-2010 constant33; however, data from NHANES indicate that
score in US children and adolescents aged 2 to 18 average energy intake among US adults increased
years improved from 42.5 to 50.9.29 One-third of the from 1971, peaked at 2004, and has since stabilized.
improvement was attributable to reduction in empty Average total energy intakes among US white adults
calorie intake; other HEI categories that improved in 1971, 2004, and 2010 were 1992, 2283, and 2200
included whole grains, fruit, seafood and plant pro- kcal/d, respectively. Average total energy intakes among
teins, greens and beans, and fatty acids (Chart 5-7). US black adults in 1971, 2004, and 2010 were 1780,
Participants in the National School Lunch Program and 2169, and 2134 kcal/d, respectively. This rise in energy
the School Breakfast Program had lower HEI-2010 intake was primarily attributable to increased carbohy-
scores than nonparticipants. There was also a trend drate intake, particularly of starches, refined grains, and
toward lower HEI-2010 in SNAP participants after the sugars.34,35
2003 to 2004 cycle. HEI-2010 scores were consistently In a study using 4 nationally representative US
Downloaded from http://ahajournals.org by on February 7, 2019

lower from 1999 to 2012 in NH blacks (39.6–48.4) Department of Agriculture surveys of food intake
than in NH whites (42.1–50.2) and were highest in among US children,36 average portion sizes among
Mexican Americans (44.1–51.9). In a study that used US children increased for many foods between 1977
household store purchase data (N=98 256 household- and 2006. For example, pizza portion size increased
by-quarter observations), SNAP participants purchased from 406 to 546 calories, with much of this increase
more calories from SSBs (15–20 kcal per person per occurring from the 1990s to the 2000s. Portion sizes
day), more sodium (174–195 mg per person per day), for other foods increased, including Mexican food
and fewer calories from fiber (−0.52 kcal per per- (from 373 to 512 calories), cheeseburgers (from 380
son per day) than income-eligible and higher-income to 473 calories), soft drinks (from 121 to 155 calo-
nonparticipants.30 ries), fruit drinks (from 106 to 133 calories), and salty
The impact of the October 2009 Special Supplemental snacks (from 124 to 165 calories). French fry portion
Nutrition Program for Women, Infants, and Children sizes increased at fast food locations but not stores
food package revision (more fruits, vegetables, whole and restaurants. Soft drink and pizza portion sizes
grains, and lower-fat milk) was examined using 2003 increased at all food sources (stores, restaurants, and
to 2008 and 2011 to 2012 NHANES data in 2- to fast food locations).
4-year-old children from low-income households.31 The In a quantitative analysis using various US sur-
Women, Infants, and Children food package revisions veys between 1977 and 2010, the relationships of
were associated with significant improvements in HEI- national changes in energy density, portion sizes, and
2010 score (3.7-higher HEI points; 95% CI, 0.6–6.9), number of daily eating/drinking occasions to changes
with the greatest improvement coming from a 3.4-fold in total energy intake were assessed.37 Total energy
increase (95% CI, 1.3–9.4) in the greens and beans intake increased by 108 kcal/day over this time period.
category. Changes in energy density were not consistently linked
Worldwide, 2 separate, relatively uncorrelated to energy intake over time. Rather, main contributors to
dietary patterns can be characterized, 1 by greater temporal changes in caloric intake included an increase
intakes of health-promoting foods (eg, fruits, veg- in the number of eating occasions from 3.9 to 5.1 from
etables, nuts, fish) and 1 by lower intakes of less 1977 to 2010 and decreases in average portion size of
optimal foods (eg, processed meats, SSBs).32 In 2010, foods and beverages since 1989 to 1991.

e68 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

Cardiovascular Health Impact of Dietary • In a meta-analysis of 34 RCTs with modest reduc-

CLINICAL STATEMENTS
Patterns tion of sodium for ≥4 weeks, a 100-mmol/d

AND GUIDELINES
(2300-mg/d) reduction in sodium was associated
Cardiovascular and Metabolic Risk with a 5.8-mm Hg lower SBP.44 The effects of
• In a systematic review and meta-analysis, RCTs sodium reduction on BP were stronger in individu-
in children demonstrated reductions in BMI gain als who were older, hypertensive, and black.45,46
when SSBs were replaced with noncaloric bev- • Compared with a usual Western diet, a DASH-
erages, and RCTs in adults showed weight gain type dietary pattern with low sodium reduced SBP
when SSBs were added.38 by 5.3, 7.5, 9.7, and 20.8 mm Hg in adults with
• In a meta-analysis of 61 trials (N=2582), tree nut baseline SBP <130, 130–139, 140–149, and ≥150
consumption lowered TC by 4.7 mg/dL, LDL-C by mm Hg, respectively.47
4.8 mg/dL, apolipoprotein B by 3.7 mg/dL, and • Compared with a higher-carbohydrate DASH diet,
triglycerides by 2.2 mg/dL. No heterogeneity by a DASH-type diet with higher protein lowered BP
nut type was observed.39 by 1.4 mm Hg, LDL by 3.3 mg/dL, and triglycerides
• After intentional weight loss in 21 overweight/ by 16 mg/dL but also lowered HDL by 1.3 mg/dL.
obese young adults, an isocaloric low-carbo- Compared with a higher-carbohydrate DASH diet,
hydrate diet resulted in smaller declines in total a DASH-type diet with higher unsaturated fat
energy expenditure than a low-fat diet, with a lowered BP by 1.3 mm Hg, increased HDL by 1.1
mean difference of >300 kcal/d.40 mg/dL, and lowered triglycerides by 10 mg/dL.48
• In a randomized trial of 609 nondiabetic partici- The DASH-type diet higher in unsaturated fat also
pants with BMI 28 to 40 kg/m2 that compared improved glucose-insulin homeostasis compared
the effects of healthy low-fat versus healthy low- with the higher-carbohydrate DASH diet.49
carbohydrate weight loss diets, weight loss at 12 • In a systematic review and meta-analysis of con-
months did not differ between groups. Neither trolled clinical trials of dietary pattern interven-
genotype pattern (3 SNP multilocus genotype tions, the DASH diet had the largest net effect
responsiveness pattern) nor insulin secretion (30 on SBP (−7.6 mm Hg) and DBP (−4.2 mm Hg),
minutes after glucose challenge) modified the whereas the Mediterranean diet had an effect on
effects of diet on weight loss.41 DBP (−1.4 mm Hg) but not SBP.50
• In the PREDIMED RCT, 7447 adults with type 2 • In a meta-analysis of 60 randomized controlled
Downloaded from http://ahajournals.org by on February 7, 2019

DM or ≥3 CVD risk factors were randomized to 3 feeding trials, consumption of 1% of calories

arms: Mediterranean diet supplemented by extra- from SFAs in place of carbohydrates raised LDL-C
virgin olive oil, Mediterranean diet supplemented concentrations but also raised HDL-C and low-
with nuts, or control diet (advice to reduce dietary ered triglycerides, with no significant effects on
fat).42 A significantly smaller decrease in central apolipoprotein B concentrations.51
adiposity occurred in the Mediterranean diet with • In a randomized crossover trial of 92 adults with
olive oil arm (−0.55 cm; 95% CI, −1.16 to −0.06) abdominal obesity, LDL was highest after a but-
and the Mediterranean diet with nuts arm (−0.94 ter-rich diet, followed by a cheese-rich diet, high-
cm; 95% CI, −1.60 to −0.27) than in the control carbohydrate diet, MUFA-rich diet, and PUFA-rich
arm. In a subgroup analysis of 3541 patients in diet. The butter-rich and cheese-rich diets similarly
PREDIMED without DM, HRs for incident DM were increased HDL (+4.7% and +3.8%, respectively),
0.60 (95% CI, 0.43–0.85) for the Mediterranean compared with the high-carbohydrate diet.52
diet with olive oil arm and 0.82 (0.61–1.10) for • In a meta-analysis of RCTs, consumption of 1%
the Mediterranean diet with nuts arm compared of calories from trans fat in place of SFAs, MUFAs,
with the control arm. or PUFAs, respectively, increased the ratio of TC
• In a randomized crossover trial of 118 overweight to HDL-C by 0.031, 0.054, and 0.67; increased
omnivores at low-moderate CVD risk, a reduced- apolipoprotein B levels by 3, 10, and 11 mg/L;
calorie lacto-ovo vegetarian diet was compared to decreased apolipoprotein A-1 levels by 7, 5, and
a reduced-calorie Mediterranean diet by provid- 3 mg/L; and increased lipoprotein(a) levels by 3.8,
ing face-to-face, individual counseling sessions. 1.4, and 1.1 mg/L.53
Both diets were equally successfully in reducing • In a meta-analysis of 70 RCTs, consumption of
body weight and fat mass. LDL-C, uric acid, and eicosapentaenoic acid and docosahexaenoic acid
vitamin B12 were lower during the vegetarian lowered BP by 1.5/1.0 mm Hg.54
diet, whereas triglycerides were lower during • A meta-analysis of 102 randomized controlled
the Mediterranean diet, without substantial dif- feeding trials evaluated the effects of exchanging
ferences between oxidative stress markers and different dietary fats and carbohydrates on mark-
inflammatory cytokines.43 ers of glucose-insulin homeostasis.55 Replacing

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e69

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

5% energy from carbohydrates with SFAs gen- glycemic load were associated with increased risk of
CLINICAL STATEMENTS

erally had no significant effects, whereas replac- stroke. Compared with the lowest 10th percentiles,
AND GUIDELINES

ing carbohydrates with unsaturated fats lowered risks for the 90th percentiles of glycemic index and
both HbA1c and insulin. On the basis of “gold glycemic load were 1.19 (95% CI, 1.04–1.36) and
standard” short-term insulin response in 10 trials, 1.27 (95% CI, 1.04–1.54), respectively.65
PUFAs improved insulin secretion compared with
Foods and Beverages
carbohydrates, SFAs, and even MUFAs.
• In meta-analyses of prospective cohort studies,
each daily serving of fruits or vegetables was
Cardiovascular Events associated with a 4% lower risk of CHD (RR, 0.96;
Fats and Carbohydrates 95% CI, 0.93–0.99), a 5% lower risk of stroke
• In the WHI RCT (N=48 835), reduction of total fat (RR, 0.95; 95% CI, 0.92–0.97), and a 4% lower
consumption from 37.8% energy (baseline) to risk of cardiovascular mortality (RR, 0.96; 95% CI,
24.3% energy (at 1 year) and 28.8% energy (at 0.92–0.99).66–68
6 years) had no effect on incidence of CHD (RR, • In a prospective study of 512 891 adults in China
0.98; 95% CI, 0.88–1.09), stroke (RR, 1.02; 95% (only 18% consumed fresh fruit daily), individuals
CI, 0.90–1.15), or total CVD (RR, 0.98; 95% CI, who ate fresh fruit daily had 40% lower risk of CVD
0.92–1.05) over a mean follow up of 8.1 years.56 death (RR, 0.60; 95% CI, 0.54–0.67), 34% lower
This was consistent with null results of 4 prior risk of incident CHD (RR, 0.66; 95% CI, 0.58–0.75),
RCTs and multiple large prospective cohort stud- 25% lower risk of ischemic stroke (RR, 0.75; 95%
ies that indicated little effect of total fat consump- CI, 0.72–0.79), and 36% lower risk of hemorrhagic
tion on CVD risk.57 stroke (RR, 0.64; 95% CI, 0.56–0.74).69
• In a meta-analysis of 21 studies, SFA consump- • In a meta-analysis of 45 prospective studies,
tion was not associated with increased risk of whole grain intake was associated with a lower
CHD, stroke, or total CVD.58 In comparison, in risk of CHD (HR, 0.81; 95% CI, 0.75–0.87) and
a pooled individual-level analysis of 11 prospec- CVD (HR, 0.78, 95% CI, 0.73–0.85) but was not
tive cohort studies, the specific exchange of PUFA significantly associated with stroke (HR, 0.88;
consumption in place of SFAs was associated with 95% CI, 0.75–1.03).70
lower CHD risk, with 13% lower risk for each 5% • In a meta-analysis of 16 prospective cohort stud-
Downloaded from http://ahajournals.org by on February 7, 2019

energy exchange (RR, 0.87; 95% CI, 0.70–0.97).59 ies, fish consumption was associated with signifi-
These findings are consistent with a meta-analysis cantly lower risk of CHD mortality.71 Compared
of RCTs in which increased PUFA consumption with no consumption, consumption of an esti-
in place of SFAs reduced CHD events, with 10% mated 0.250 g/d of long-chain omega-3 fatty
lower risk for each 5% energy exchange (RR, 0.90; acids was associated with 35% lower risk of CHD
95% CI, 0.83–0.97).60 Replacing SFAs with MUFAs death (P<0.001).
was not significantly associated with CHD risk.59 • Among 16 479 males and females in the REGARDS
• In a meta-analysis of 13 prospective cohort stud- study, individuals who consumed ≥2 servings of fried
ies, increased intake of PUFAs was associated with fish per week had a greater risk of CVD over 5.1
lower risk of CHD, whether it replaced SFAs or years of follow-up than those who consumed <1
carbohydrates.61 serving per month (HR, 1.63; 95% CI, 1.11–2.40).72
• In a meta-analysis of prospective cohort studies, • In a meta-analysis of prospective cohort and
each 2% of calories from trans fat was associated case-control studies from multiple countries,
with a 23% higher risk of CHD (RR, 1.23; 95% CI, consumption of unprocessed red meat was not
1.11–1.37).62 significantly associated with incidence of CHD. In
• In meta-analyses of prospective cohort studies, contrast, each 50-g serving per day of processed
greater consumption of refined complex carbo- meats (eg, sausage, bacon, hot dogs, deli meats)
hydrates, starches, and sugars, as assessed by was associated with a higher incidence of CHD
glycemic index or load, was associated with sig- (RR, 1.42; 95% CI, 1.07–1.89).73
nificantly higher risk of CHD and DM. When the • In a study of 169 310 female nurses and 41 526
highest category was compared with the lowest male physicians, consumption of 1 serving of nuts
category, risk of CHD was 36% greater (glycemic ≥5 times per week was associated with lower risk
load: RR, 1.36; 95% CI, 1.13–1.63) and risk of of CVD (HR, 0.86; 95% CI, 0.79, 0.93) and CHD
DM was 40% greater (glycemic index: RR, 1.40; (HR, 0.80; 95% CI, 0.72, 0.89), compared with
95% CI, 1.23–1.59).63,64 those who never or almost never consumed nuts.
• In a prospective cohort study of urban Chinese Results were largely consistent for peanuts, tree
females (N=64  328), high glycemic index and nuts, and walnuts.74

e70 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

• In a meta-analysis of 5 prospective observational products (32% of males and females reporting

CLINICAL STATEMENTS
studies, consumption of legumes (beans) was asso- such use).86 Supplement use is associated with

AND GUIDELINES
ciated with lower incidence of CHD (RR per 4 weekly older age, white race, higher education, greater
100-g servings, 0.86; 95% CI, 0.78–0.94).75 PA, moderate alcohol consumption, lower BMI,
• Results from a meta-analysis of 17 prospective abstinence from smoking, having health insur-
observational studies showed that neither dairy ance, and higher intake of most vitamins and
consumption nor dairy fat was significantly asso- minerals from food.87,88
ciated with higher or lower risk of CHD.76 • A meta-analysis of 4 RCTs and 27 prospective
• In a meta-analysis of 15 country-specific observa- cohort and nested case-control studies found
tional cohorts, consumption of butter had small no significant effect of calcium supplements or
or neutral overall associations with mortality, calcium plus vitamin D supplements with CVD
CVDs, and DM.77 events or mortality.89
• Observational studies have found that the antioxi-
Sodium and Potassium
dants vitamin C, beta-carotene, and vitamin E are
• Nearly all observational studies demonstrate an
associated with lower risk of CHD and mortality,
association between higher estimated sodium
but RCTs providing antioxidant supplementation
intakes (eg, >4000 mg/d) and a higher risk
have demonstrated no benefit on CVD outcomes
of CVD events, in particular stroke.78–84 Some
or mortality.90–95
studies have also observed higher CVD risk at
• A 2017 AHA scientific advisory statement sum-
estimated low intakes (eg, <3000 g/d), which
marized available evidence and suggested fish oil
suggests a potential J-shaped relationship with
supplementation only for secondary prevention
risk.
of CHD and SCD (Class IIa recommendation) and
• An AHA science advisory suggested that varia-
for secondary prevention of outcomes in patients
tion in methodology might account for inconsis-
with HF (Class IIa recommendation).96
tencies in the relationship between sodium and
• A meta-analysis of 77 917 participants in 10 RCTs
CVD in observational studies. Increased risk at
with ≥500 participants treated for ≥1 year found
low sodium intake in some observational studies
that fish oil supplementation (eicosapentaenoic
could be related to reverse causation (illness caus-
acid dose range 226–1800 mg/d; docosahexae-
ing low intake), imprecise estimation of sodium
Downloaded from http://ahajournals.org by on February 7, 2019

noic acid dose range 0–1700 mg/d) had no sig-

intake through a single dietary recall or a single
nificant effect on CHD death (RR, 0.94; 95%
urine excretion.82
CI, 0.81–1.03), nonfatal MI (RR, 0.97; 95% CI,
• Post hoc analyses of the TOHP with 10 to 15 years
0.87–1.08), or any CHD events (RR, 0.97; 95%
of follow-up found that participants randomized
CI, 0.93–1.01).97
to sodium reduction had a 25% decrease in CVD
risk (RR, 0.75; 95% CI, 0.57–0.99) compared with
those randomized to control.83 Dietary Patterns
• In an observational analysis of TOHP participants
The 2015 US Dietary Guidelines Advisory Committee
not assigned to an active sodium reduction inter-
summarized the evidence for benefits of healthful diet
vention, sodium-potassium ratio was linearly
patterns on a range of cardiometabolic and other dis-
associated with risk of CVD over 10 to 15 years of
ease outcomes.17 They concluded that a healthy dietary
follow-up (RR, 1.24 per unit; 95% CI, 1.05–1.46;
pattern is higher in vegetables, fruits, whole grains,
P=0.01).83
low-fat or nonfat dairy, seafood, legumes, and nuts;
• In a longer-term (median 24 years) post hoc analy-
moderate in alcohol (among adults); lower in red and
sis of the TOHP (median of five 24-hour urine mea-
processed meat; and low in sugar-sweetened foods
surements), every 1-U increase in sodium-potassium
and drinks and refined grains. The 2015 US Dietary
ratio was associated with a 13% higher risk of death
Guidelines also describe a healthy vegetarian dietary
(HR, 1.13; 95% CI, 1.01–1.27; P=0.04).84
pattern, which includes more legumes, soy products,
nuts and seeds, and whole grains but does not include
Dietary Supplement Trends and Outcomes meats, poultry, or seafood.17
Use of dietary supplements is common in the United • In a meta-analysis of 8 observational studies (3
States among both adults and children despite lack of Seventh-day Adventist cohorts [N=110 723] and 5
evidence to support the use of most dietary supple- other cohorts [N=72 598]), vegetarians had a 40%
ments in reducing risks of CVD or death85: lower risk of CHD in the Seventh-day Adventist
• Approximately half of US adults in 2007 to 2010 studies (RR, 0.60; 95% CI, 0.43–0.80) and a 16%
used ≥1 dietary supplement, with the most com- lower risk of CHD (RR, 0.84; 95% CI, 0.74–0.96)
mon supplement being multivitamin-multimineral in the other studies.98

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e71

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

• In a cohort of 200 272 US males and females, and (at least cross-sectionally) neighborhood
CLINICAL STATEMENTS

greater adherence to a plant-based dietary pat- availability of supermarkets.114–116

AND GUIDELINES

tern, defined by higher intake of plant-based • Other local food-environment characteristics,

foods and low intake of animal based foods, was such as availability of grocery stores (ie, smaller
associated with a 20% lower risk of DM (HR, stores than supermarkets), convenience stores,
0.80; 95% CI, 0.74–0.87).99 and fast food restaurants, are not consistently
• In a cohort of 380 296 US males and females, associated with diet quality or adiposity and
greater versus lower adherence to a Mediterranean could be linked to social determinants of health
dietary pattern was associated with a 22% lower for CVD.117
cardiovascular mortality (RR, 0.78; 95% CI, 0.69– • Disparities may be driven in part by overabundance
0.87).100 Similar findings have been seen for the of unhealthy food options. In a study of neighbor-
Mediterranean dietary pattern and risk of incident hood-level data from 4 US cities (Birmingham, AL,
CHD and stroke101 and for the DASH-type dietary Chicago, IL, Minneapolis, MN, and Oakland, CA),
pattern.102 past neighborhood-level income was inversely
• In a cohort of 72 113 US female nurses, a dietary associated with current density of convenience
pattern characterized by higher intakes of veg- stores.118 In low-income neighborhoods, the per-
etables, fruits, legumes, fish, poultry, and whole centage of white population was inversely asso-
grains was associated with a 28% lower cardio- ciated with density of fast food restaurants and
vascular mortality (RR, 0.72; 95% CI, 0.60–0.87), smaller grocery stores.
whereas a dietary pattern characterized by higher • In a study using NHANES and Nielsen Homescan
intakes of processed meat, red meat, refined data to examine disparities in calories from store-
grains, french fries, and sweets/desserts was asso- bought consumer packaged goods over time,
ciated with a 22% higher cardiovascular mortality calories from store-bought beverages decreased
(RR, 1.22; 95% CI, 1.01–1.48).103 Similar findings between 2003 to 2006 and 2009 to 2012. However,
have been seen in other cohorts and for other the decline in calories from consumer pack-
outcomes, including development of DM and aged goods was slower for NH blacks, Mexican
metabolic syndrome.104–110 Americans, and lowest-income households.119
• The observational findings for benefits of a
Downloaded from http://ahajournals.org by on February 7, 2019

healthy food–based dietary pattern have been

Global Burden
confirmed in 2 randomized clinical trials, includ-
ing a small secondary prevention trial in France (See Chart 5-8)
among patients with recent MI111 and a large • A report from the GBD Study estimated the
primary prevention trial in Spain among patients impact of 14 specific dietary factors on mortal-
with CVD risk factors.42 The latter trial, PREDIMED, ity worldwide in 2005 to 2015. In 2015, a total
demonstrated an ≈30% reduction in the risk of 6.9 million male deaths (237.4 deaths per
of stroke, MI, and death attributable to cardio- 100 000) and 5.2 million female deaths (147.0
vascular causes in those patients randomized to deaths per 100 000) worldwide were estimated to
Mediterranean-style diets supplemented with be attributable to poor dietary habits. The popu-
extra-virgin olive oil or mixed nuts.42 lation attributable fraction was 22.4% for males
and 20.7% for females. Although the estimated
mortality rate attributable to poor dietary factors
Family History and Genetics decreased by 15.0% in the worldwide population
• Although the interaction between genetics and from 2005 to 2015, the population attributable
nutrition is complex, genetic factors may contrib- fraction increased by 7.9% over the same time
ute to food preferences and modulate the asso- period.120
ciation between dietary components and adverse • The GBD 2016 Study used statistical models
cardiovascular health outcomes.112,113 and data on incidence, prevalence, case fatal-
ity, excess mortality, and cause-specific mortal-
ity to estimate disease burden for 315 diseases
Nutrition and Disparities in CVD Health and injuries in 195 countries and territories.
• Societal and environmental factors independently Mortality rates attributable to dietary risks were
associated with diet quality, adiposity, or weight highest in Eastern Europe, Russia, and Central
gain include education, income, race/ethnicity, Asia (Chart 5-8).121

e72 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

Table 5-1.  AHA Dietary Targets and Healthy Diet Score for Defining Cardiovascular Health

CLINICAL STATEMENTS
Consumption Range for

AND GUIDELINES
Alternative Healthy Diet Alternative Scoring
AHA Target Score* Range*
Primary dietary metrics†
  Fruits and vegetables ≥4.5 cups/d‡ 0 to ≥4.5 cups/d‡ 0–10

  Fish and shellfish 2 or more 3.5-oz servings/wk 0 to ≥7 oz/wk 0–10

(≥200 g/wk)
 Sodium ≤1500 mg/d ≤1500 to >4500 mg/d 10–0

 SSBs ≤36 fl oz/wk ≤36 to >210 fl oz/wk 10–0

  Whole grains 3 or more 1-oz-equivalent servings/d 0 to ≥3 oz/d 0–10

Secondary dietary metrics†

  Nuts, seeds, and legumes ≥4 servings/wk (nuts/seeds: 1 oz; legumes: ½ cup) 0 to ≥4 servings/d 0–10

  Processed meats 2 or fewer 1.75-oz servings/wk (≤100 g/wk) ≤3.5 to >17.5 oz/wk 10–0

  Saturated fat ≤7% energy ≤7 to >15 (% energy) 10–0

AHA Diet Score (primary) Ideal: 4 or 5 dietary targets (≥80%) Sum of scores for primary 0 (worst) to 100 (best)§
Intermediate: 2 or 3 dietary targets (40%–79%) metrics Ideal: 80–100
Poor: <2 dietary targets (<40%) Intermediate: 40–79
Poor: <40
AHA Diet Score (secondary) Ideal: 4 or 5 dietary targets (≥80%) Sum of scores for primary 0 (worst) to 100 (best)§
Intermediate: 2 or 3 dietary targets (40%–79%) and Ideal: 80–100
Poor: <2 dietary targets (<40%) secondary metrics Intermediate: 40–79
Poor: <40

AHA indicates American Heart Association; and SSBs, sugar-sweetened beverages.

*Consistent with other dietary pattern scores, the highest score (10) was given for meeting or exceeding the AHA target (eg, at least 4.5 cups of fruits and
vegetables per day; no more than 1500 mg/d of sodium), and the lowest score (0) was given for zero intake (protective factors) or for very high intake (harmful
factors). The score for each metric was scaled continuously within this range. For harmful factors, the level of high intake that corresponded to a zero score was
identified as approximately the 90th percentile distribution of US population intake.
†Selected by the AHA based on evidence for likely causal effects on cardiovascular events, diabetes mellitus, or obesity; a general prioritization of food rather
than nutrient metrics; consistency with US and AHA dietary guidelines; ability to measure and track these metrics in the US population; and parsimony, that is, the
Downloaded from http://ahajournals.org by on February 7, 2019

inclusion of as few components as possible that had minimal overlap with each other while at the same time having some overlap with the many other relevant
dietary factors that were not included.2 The AHA dietary metrics should be targeted in the context of a healthy diet pattern that is appropriate in energy balance and
consistent with a DASH (Dietary Approaches to Stop Hypertension)-type eating plan, including but not limited to these metrics.
‡Including up to one 8-oz serving per day of 100% fruit juice and up to 0.42 cups/d (3 cups/wk) of starchy vegetables such as potatoes or corn.
§The natural range of the primary AHA Diet Score is 0 to 50 (5 components), and the natural range of the secondary AHA Diet Score is 0 to 80 (8
components). Both scores are then rescaled to a range of 0 to 100 for comparison purposes. The ideal range of the primary AHA Diet Score corresponds
to the AHA scoring system of meeting at least 4 of 5 binary dietary targets (≥80%), the intermediate range corresponds to meeting 2 or 3 dietary targets
(40%–79%), and the poor range corresponds to meeting <2 dietary targets (<40%). The same ranges are used for the secondary AHA Diet Score for
consistency and comparison.
Sources: AHA’s My Life Check – Life’s Simple 71; Lloyd-Jones et al2; Rehm et al.4

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e73

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5
CLINICAL STATEMENTS
AND GUIDELINES

Chart 5-1. Trends in prevalence of poor AHA healthy diet score, by race/ethnicity.
Components of AHA healthy diet score are defined in Table 5-1. Poor diet was defined as <40% adherence, based on primary AHA continuous diet score.4
AHA indicates American Heart Association.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 5-2. Trends in prevalence of poor AHA healthy diet score, by ratio of family income to poverty level (<1.30, 1.30–1.849, 1.85–2.99, ≥3.0).
Components of AHA healthy diet score are defined in Table 5-1. Poor diet was defined as <40% adherence, based on primary AHA continuous diet score.4
AHA indicates American Heart Association.

e74 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

CLINICAL STATEMENTS
Women Men

AND GUIDELINES
5000

24-h Urine Sodium Excretion (mg/d) 4500

4000

3500

3000

2500

2000
l

te

te

c
Al

Al
ac

ni

ac

ni
ia

ia
hi

hi
pa

pa
As

As
bl

bl
w

w
is

is
c

c
c

c
ni

ni

ni

ni

H
ni

ni
pa

pa

pa

pa
pa

pa
is

is

is

is
is

is
-H

-H

-H

-H
-H

-H
on

on

on

on
on

on
N

N
N

N
Chart 5-3. Estimated mean sodium intake in the United States by 24-hour urinary excretion.
Estimates based on nationally representative sample of 827 nonpregnant, noninstitutionalized US adults aged 20 to 69 years who completed a 24-hour urine
collection in NHANES 2013 to 2014.14
NHANES indicates National Health and Nutrition Examination Survey.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 5-4. Sources of sodium intake in US adults in 3 geographic regions.

Sources of sodium intake determined by four 24-hour dietary recalls with special procedures, in which duplicate samples of salt added to food at the table and
in home food preparation were collected in 450 adults recruited in 3 geographic regions (Birmingham, AL, Palo Alto, CA, Minneapolis-St. Paul, MN) with equal
numbers of males and females from 4 racial/ethnic groups (Asians, blacks, Hispanics, non-Hispanic whites).15

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e75

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5
CLINICAL STATEMENTS
AND GUIDELINES

Chart 5-5. Absolute and proportional cardiometabolic disease mortality associated with overall suboptimal diet in the United States in 2012 by
population subgroups.
Bars represent absolute number (left) and percentage (right) of cardiometabolic deaths jointly related to suboptimal intakes of 10 dietary factors. The 10 factors
were low intakes of fruits, vegetables, nuts/seeds, whole grains, seafood omega-3 fats, and polyunsaturated fats (replacing saturated fats) and high intakes of
sodium, unprocessed red meats, processed meats, and sugar-sweetened beverages. Error bars indicate 95% uncertainty intervals.
CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Reprinted with permission from Micha et al.18 Copyright © 2017, American Medical Association. All rights reserved.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 5-6. Proportion of consumer expenditures spent on food at home in selected countries.
Data computed by the US Department of Agriculture Economic Research Service, August 2017.120

e76 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

CLINICAL STATEMENTS
AND GUIDELINES
Chart 5-7. Mean Healthy Eating Index (HEI)-2010 component scores in children and adolescents aged 2 to 18 years according to NHANES
survey cycles.
Downloaded from http://ahajournals.org by on February 7, 2019

Sizes of the study population were as follows: N=3590 for 1999 to 2000, N=4039 for 2001 to 2002, N=6841 for 2003 to 2004, N=7215 for 2005 to 2006,
N=5402 for 2007 to 2008, N=5751 for 2009 to 2010, and N=5649 for 2011 to 2012. For total fruit, whole fruit, total vegetables, greens and beans, whole
grains, dairy, total protein foods, seafood and plant proteins, and fatty acids, higher scores corresponded to higher intakes. For refined grains, sodium, and empty
calories, higher scores corresponded to lower intakes. The HEI-2010 component score increased by 3.8 points for empty calories; 1.1 points for whole grains;
0.9 points for dairy; 0.8 points for whole fruit; 0.6 points for total fruit; 0.5 points for seafood and plant proteins, greens and beans, and fatty acids; 0.4 points
for total protein foods (all P for linear trend <0.001); and 0.2 points for refined grains (P for linear trend=0.01). The HEI-2010 component score decreased by 0.2
points for sodium (P for trend <0.001). There was no significant improvement for total vegetable intake over the period.
Reprinted from Gu et al29 by permission of Oxford University Press.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e77

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5
CLINICAL STATEMENTS
AND GUIDELINES

Chart 5-8. Age-standardized global mortality rates attributable to dietary risks per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016 with permission.121 Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

regional, and national consumption of sugar-sweetened beverages,

REFERENCES fruit juices, and milk: a systematic assessment of beverage intake in
1. American Heart Association. My Life Check – Life’s Simple 7. https://www. 187 countries. PLoS One 2015;10:e0124845. doi: 10.1371/journal.
heart.org/en/healthy-living/healthy-lifestyle/my-life-check--lifes-simple-7. pone.0124845
Accessed November 9, 2018. 6. Popkin BM, Hawkes C. Sweetening of the global diet, particularly bever-
2. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn ages: patterns, trends, and policy responses. Lancet Diabetes Endocrinol.
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow 2016;4:174–186. doi: 10.1016/S2213-8587(15)00419-2
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm 7. Colchero MA, Rivera-Dommarco J, Popkin BM, Ng SW. In Mexico, evi-
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart dence of sustained consumer response two years after implementing a
Association Strategic Planning Task Force and Statistics Committee. sugar-sweetened beverage tax. Health Aff (Millwood). 2017;36:564–571.
Defining and setting national goals for cardiovascular health promotion doi: 10.1377/hlthaff.2016.1231
and disease reduction: the American Heart Association’s strategic Impact 8. Silver LD, Ng SW, Ryan-Ibarra S, Taillie LS, Induni M, Miles DR, Poti JM,
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: Popkin BM. Changes in prices, sales, consumer spending, and bev-
10.1161/CIRCULATIONAHA.109.192703 erage consumption one year after a tax on sugar-sweetened bever-
3. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng ages in Berkeley, California, US: a before-and-after study. PLoS Med.
S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson 2017;14:e1002283. doi: 10.1371/journal.pmed.1002283
JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, 9. Powles J, Fahimi S, Micha R, Khatibzadeh S, Shi P, Ezzati M, Engell RE, Lim
Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, SS, Danaei G, Mozaffarian D; on behalf of the Global Burden of Diseases
Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O’Flaherty Nutrition and Chronic Diseases Expert Group (NutriCoDE). Global, regional
M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, and national sodium intakes in 1990 and 2010: a systematic analysis of
Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah 24 h urinary sodium excretion and dietary surveys worldwide. BMJ Open.
SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins 2013;3:e003733. doi: 10.1136/bmjopen-2013-003733
JT, Wu JH, Alger HM, Wong SS, Muntner P; on behalf of the American 10. Barberio AM, Sumar N, Trieu K, Lorenzetti DL, Tarasuk V, Webster J,
Heart Association Council on Epidemiology and Prevention Statistics Campbell NRC, McLaren L. Population-level interventions in govern-
Committee and Stroke Statistics Subcommittee. Heart disease and stroke ment jurisdictions for dietary sodium reduction: a Cochrane Review. Int J
statistics–2018 update: a report from the American Heart Association Epidemiol. 2017;46:1551–1405. doi: 10.1093/ije/dyw361
[published correction appears in Circulation. 2018;137:e493]. Circulation. 11. Laatikainen T, Pietinen P, Valsta L, Sundvall J, Reinivuo H, Tuomilehto J.
2018;137:e67–e492. doi: 10.1161/CIR.0000000000000558 Sodium in the Finnish diet: 20-year trends in urinary sodium excretion
4. Rehm CD, Peñalvo JL, Afshin A, Mozaffarian D. Dietary intake among among the adult population. Eur J Clin Nutr. 2006;60:965–970. doi:
US adults, 1999-2012. JAMA. 2016;315:2542–2553. doi: 10.1001/ 10.1038/sj.ejcn.1602406
jama.2016.7491 12. Kastarinen MJ, Salomaa VV, Vartiainen EA, Jousilahti PJ, Tuomilehto
5. Singh GM, Micha R, Khatibzadeh S, Shi P, Lim S, Andrews KG, Engell JO, Puska PM, Nissinen AM. Trends in blood pressure levels and con-
RE, Ezzati M, Mozaffarian D; on behalf of the Global Burden of Diseases trol of hypertension in Finland from 1982 to 1997. J Hypertens.
Nutrition and Chronic Diseases Expert Group (NutriCoDE). Global, 1998;16:1379–1387.

e78 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

13. He FJ, Brinsden HC, MacGregor GA. Salt reduction in the United Kingdom: 32. Imamura F, Micha R, Khatibzadeh S, Fahimi S, Shi P, Powles J, Mozaffarian

CLINICAL STATEMENTS
a successful experiment in public health. J Hum Hypertens. 2014;28:345– D; Global Burden of Diseases Nutrition and Chronic Diseases Expert

AND GUIDELINES
352. doi: 10.1038/jhh.2013.105 Group (NutriCoDE). Dietary quality among men and women in 187 coun-
14. Cogswell ME, Loria CM, Terry AL, Zhao L, Wang CY, Chen TC, Wright tries in 1990 and 2010: a systematic assessment. Lancet Glob Health.
JD, Pfeiffer CM, Merritt R, Moy CS, Appel LJ. Estimated 24-hour urinary 2015;3:e132–e142. doi: 10.1016/S2214-109X(14)70381-X
sodium and potassium excretion in US adults. JAMA. 2018;319:1209– 33. Duffey KJ, Popkin BM. Energy density, portion size, and eating occasions:
1220. doi: 10.1001/jama.2018.1156 contributions to increased energy intake in the United States, 1977-2006.
15. Harnack LJ, Cogswell ME, Shikany JM, Gardner CD, Gillespie C, Loria PLoS Med. 2011;8:e1001050. doi: 10.1371/journal.pmed.1001050
CM, Zhou X, Yuan K, Steffen LM. Sources of sodium in US adults 34. Ford ES, Dietz WH. Trends in energy intake among adults in the United
from 3 Geographic regions. Circulation. 2017;135:1775–1783. doi: States: findings from NHANES. Am J Clin Nutr. 2013;97:848–853. doi:
10.1161/CIRCULATIONAHA.116.024446 10.3945/ajcn.112.052662
16. Quader ZS, Zhao L, Gillespie C, Cogswell ME, Terry AL, Moshfegh A, 35. Gross LS, Li L, Ford ES, Liu S. Increased consumption of refined carbo-
Rhodes D. Sodium intake among persons aged ≥2 years: United States, hydrates and the epidemic of type 2 diabetes in the United States:
2013–2014. MMWR Morb Wkly Rep. 2017;66:324. doi: 10.15585/ an ecologic assessment. Am J Clin Nutr. 2004;79:774–779. doi:
mmwr.mm6612a3 10.1093/ajcn/79.5.774
17. US Department of Agriculture and US Department of Health and 36. Piernas C, Popkin BM. Food portion patterns and trends among U.S. chil-
Human Services. Dietary Guidelines for Americans, 2015–2020. 8th ed. dren and the relationship to total eating occasion size, 1977–2006. J Nutr.
Washington, DC: US Government Printing Office; December 2015. https:// 2011;141:1159–1164. doi: 10.3945/jn.111.138727
health.gov/dietaryguidelines/2015/guidelines/. Accessed September 19, 37. Duffey KJ, Popkin BM. Causes of increased energy intake among chil-
2016. dren in the U.S., 1977-2010. Am J Prev Med. 2013;44:e1–e8. doi:
18. Micha R, Peñalvo JL, Cudhea F, Imamura F, Rehm CD, Mozaffarian D. 10.1016/j.amepre.2012.10.011
Association between dietary factors and mortality from heart disease, 38. Malik VS, Pan A, Willett WC, Hu FB. Sugar-sweetened beverages and
stroke, and type 2 diabetes in the United States. JAMA. 2017;317:912– weight gain in children and adults: a systematic review and meta-analysis.
924. doi: 10.1001/jama.2017.0947 Am J Clin Nutr. 2013;98:1084–1102. doi: 10.3945/ajcn.113.058362
19. USDA Economic Research Service. Food price outlook: changes in food 39. Del Gobbo LC, Falk MC, Feldman R, Lewis K, Mozaffarian D. Effects of
price indexes, 2015 through 2018. USDA Economic Research Service web- tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic
site. https://www.ers.usda.gov/data-products/food-price-outlook.aspx. review, meta-analysis, and dose-response of 61 controlled intervention tri-
Accessed August 30, 2017. als. Am J Clin Nutr. 2015;102:1347–1356. doi: 10.3945/ajcn.115.110965
20. USDA Economic Research Service. Food expenditures. USDA Economic 40. Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-
Research Service website. https://www.ers.usda.gov/data-products/food- Lago E, Ludwig DS. Effects of dietary composition on energy expendi-
expenditures.aspx. Accessed May 15, 2018. ture during weight-loss maintenance. JAMA. 2012;307:2627–2634. doi:
21. Rao M, Afshin A, Singh G, Mozaffarian D. Do healthier foods and 10.1001/jama.2012.6607
diet patterns cost more than less healthy options? A systematic 41. Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J,
review and meta-analysis. BMJ Open. 2013;3:e004277. doi: 10.1136/ Ioannidis JPA, Desai M, King AC. Effect of low-fat vs low-carbohydrate
bmjopen-2013-004277 diet on 12-month weight loss in overweight adults and the association
22. Mozaffarian RS, Andry A, Lee RM, Wiecha JL, Gortmaker SL. Price and with genotype pattern or insulin secretion: the DIETFITS randomized
healthfulness of snacks in 32 YMCA after-school programs in 4 US metro- clinical trial [published corrections appear in JAMA. 2018;319:1386 and
politan areas, 2006-2008. Prev Chronic Dis. 2012;9:E38. JAMA. 2018;319:1728]. JAMA. 2018;319:667–679. doi: 10.1001/jama.
Downloaded from http://ahajournals.org by on February 7, 2019

23. Beets MW, Weaver RG, Turner-McGrievy G, Huberty J, Ward DS, 2018.0245
Freedman D, Hutto B, Moore JB, Beighle A. Making healthy eat- 42. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Arós F, Gómez-Gracia
ing policy practice: a group randomized controlled trial on changes E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem
in snack quality, costs, and consumption in after-school pro- L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González
grams. Am J Health Promot. 2016;30:521–531. doi: 10.4278/ajhp. MA. Retraction and republication: primary prevention of cardiovascular
141001-QUAN-486 disease with a Mediterranean diet. N Engl J Med 2013;368:1279–90 [cor-
24. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood rected and republished in N Engl J Med. 2018;378:e34]. N Engl J Med.
JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions 2018;378:2441–2442. doi: 10.1056/NEJMc1806491
on future cardiovascular disease. N Engl J Med. 2010;362:590–599. doi: 43. Sofi F, Dinu M, Pagliai G, Cesari F, Gori AM, Sereni A, Becatti M, Fiorillo C,
10.1056/NEJMoa0907355 Marcucci R, Casini A. Low-calorie vegetarian versus Mediterranean diets for
25. Webb M, Fahimi S, Singh GM, Khatibzadeh S, Micha R, Powles J, reducing body weight and improving cardiovascular risk profile: CARDIVEG
Mozaffarian D. Cost effectiveness of a government supported policy strat- Study (Cardiovascular Prevention With Vegetarian Diet). Circulation.
egy to decrease sodium intake: global analysis across 183 nations. BMJ. 2018;137:1103–1113. doi: 10.1161/CIRCULATIONAHA.117.030088
2017;356:i6699. doi: 10.1136/bmj.i6699 44. He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction
26. Ahluwalia N, Andreeva VA, Kesse-Guyot E, Hercberg S. Dietary patterns, on blood pressure: Cochrane systematic review and meta-analysis of ran-
inflammation and the metabolic syndrome. Diabetes Metab. 2013;39:99– domised trials. BMJ. 2013;346:f1325. 10.1136/bmj.f1325
110. doi: 10.1016/j.diabet.2012.08.007 45. Mozaffarian D, Fahimi S, Singh GM, Micha R, Khatibzadeh S, Engell RE,
27. Harmon BE, Boushey CJ, Shvetsov YB, Ettienne R, Reedy J, Wilkens LR, Lim S, Danaei G, Ezzati M, Powles J; for the Global Burden of Diseases
Le Marchand L, Henderson BE, Kolonel LN. Associations of key diet- Nutrition and Chronic Diseases Expert Group. Global sodium consumption
quality indexes with mortality in the Multiethnic Cohort: the Dietary and death from cardiovascular causes. N Engl J Med. 2014;371:624–634.
Patterns Methods Project. Am J Clin Nutr. 2015;101:587–597. doi: doi: 10.1056/NEJMoa1304127
10.3945/ajcn.114.090688 46. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D,
28. Wang DD, Leung CW, Li Y, Ding EL, Chiuve SE, Hu FB, Willett WC. Trends Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N,
in dietary quality among adults in the United States, 1999 through 2010. Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood
JAMA Intern Med. 2014;174:1587–1595. doi: 10.1001/jamainternmed. pressure of reduced dietary sodium and the Dietary Approaches to Stop
2014.3422 Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group.
29. Gu X, Tucker KL. Dietary quality of the US child and adolescent popula- N Engl J Med. 2001;344:3–10. doi: 10.1056/NEJM200101043440101.
tion: trends from 1999 to 2012 and associations with the use of federal 47. Juraschek SP, Miller ER 3rd, Weaver CM, Appel LJ. Effects of sodium
nutrition assistance programs. Am J Clin Nutr. 2017;105:194–202. doi: reduction and the DASH diet in relation to baseline blood pressure. J Am
10.3945/ajcn.116.135095 Coll Cardiol. 2017;70:2841–2848. doi: 10.1016/j.jacc.2017.10.011
30. Grummon AH, Taillie LS. Nutritional profile of Supplemental Nutrition 48. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER 3rd,
Assistance Program household food and beverage purchases. Am J Clin Conlin PR, Erlinger TP, Rosner BA, Laranjo NM, Charleston J, McCarron
Nutr. 2017;105:1433–1442. doi: 10.3945/ajcn.116.147173 P, Bishop LM; for the OmniHeart Collaborative Research Group. Effects
31. Tester JM, Leung CW, Crawford PB. Revised WIC food package and chil- of protein, monounsaturated fat, and carbohydrate intake on blood pres-
dren’s diet quality. Pediatrics. 2016;137:e20153557. doi: 10.1542/peds. sure and serum lipids: results of the OmniHeart randomized trial. JAMA.
2015-3557 2005;294:2455–2464. doi: 10.1001/jama.294.19.2455

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e79

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

49. Gadgil MD, Appel LJ, Yeung E, Anderson CA, Sacks FM, Miller ER 3rd. in urban Chinese women. Am J Clin Nutr. 2016;104:1345–1351. doi:
CLINICAL STATEMENTS

The effects of carbohydrate, unsaturated fat, and protein intake on mea- 10.3945/ajcn.115.129379
AND GUIDELINES

sures of insulin sensitivity: results from the OmniHeart trial. Diabetes Care. 66. Dauchet L, Amouyel P, Dallongeville J. Fruit and vegetable consump-
2013;36:1132–1137. doi: 10.2337/dc12-0869 tion and risk of stroke: a meta-analysis of cohort studies. Neurology.
50. Gay HC, Rao SG, Vaccarino V, Ali MK. Effects of different dietary inter- 2005;65:1193–1197. doi: 10.1212/01.wnl.0000180600.09719.53
ventions on blood pressure: systematic review and meta-analysis of 67. Dauchet L, Amouyel P, Hercberg S, Dallongeville J. Fruit and vegetable
randomized controlled trials. Hypertension. 2016;67:733–739. doi: consumption and risk of coronary heart disease: a meta-analysis of cohort
10.1161/HYPERTENSIONAHA.115.06853 studies. J Nutr. 2006;136:2588–2593. doi: 10.1093/jn/136.10.2588
51. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids 68. Wang X, Ouyang Y, Liu J, Zhu M, Zhao G, Bao W, Hu FB. Fruit and vegeta-
and carbohydrates on the ratio of serum total to HDL cholesterol and on ble consumption and mortality from all causes, cardiovascular disease, and
serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. cancer: systematic review and dose-response meta-analysis of prospective
Am J Clin Nutr. 2003;77:1146–1155. doi: 10.1093/ajcn/77.5.1146 cohort studies [published correction appears in BMJ. 2014;349:5472].
52. Brassard D, Tessier-Grenier M, Allaire J, Rajendiran E, She Y, Ramprasath BMJ. 2014;349:g4490. doi: 10.1136/bmj.g4490
V, Gigleux I, Talbot D, Levy E, Tremblay A, Jones PJ, Couture P, Lamarche 69. Du H, Li L, Bennett D, Guo Y, Key TJ, Bian Z, Sherliker P, Gao H, Chen Y,
B. Comparison of the impact of SFAs from cheese and butter on car- Yang L, Chen J, Wang S, Du R, Su H, Collins R, Peto R, Chen Z; China
diometabolic risk factors: a randomized controlled trial. Am J Clin Nutr. Kadoorie Biobank Study. Fresh fruit consumption and major cardio-
2017;105:800–809. doi: 10.3945/ajcn.116.150300 vascular disease in China. N Engl J Med. 2016;374:1332–1343. doi:
53. Uauy R, Aro A, Clarke R. WHO Scientific Update on trans fatty acids: sum- 10.1056/NEJMoa1501451
mary and conclusions. Eur J Clin Nutr. 2009;63:S68–S75. 70. Aune D, Keum N, Giovannucci E, Fadnes LT, Boffetta P, Greenwood DC,
54. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure Tonstad S, Vatten LJ, Riboli E, Norat T. Whole grain consumption and risk
response to fish oil supplementation: metaregression analysis of random- of cardiovascular disease, cancer, and all cause and cause specific mor-
ized trials. J Hypertens. 2002;20:1493–1499. tality: systematic review and dose-response meta-analysis of prospective
55. Imamura F, Micha R, Wu JH, de Oliveira Otto MC, Otite FO, Abioye AI, studies. BMJ. 2016;353:i2716. doi: 10.1136/bmj.i2716
Mozaffarian D. Effects of saturated fat, polyunsaturated fat, monounsatu- 71. Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, Cunnane
rated fat, and carbohydrate on glucose-insulin homeostasis: a systematic SC, Holden JM, Klurfeld DM, Morris MC, Whelan J. Towards establish-
review and meta-analysis of randomised controlled feeding trials. PLoS ing dietary reference intakes for eicosapentaenoic and docosahexaenoic
Med. 2016;13:e1002087. doi: 10.1371/journal.pmed.1002087 acids. J Nutr. 2009;139:804S–819S. doi: 10.3945/jn.108.101329
56. Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil- 72. Nahab F, Pearson K, Frankel MR, Ard J, Safford MM, Kleindorfer D, Howard
Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher VJ, Judd S. Dietary fried fish intake increases risk of CVD: the REasons
MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips for Geographic And Racial Differences in Stroke (REGARDS) study. Public
L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar Health Nutr. 2016;19:3327–3336. doi: 10.1017/S136898001600152X
LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf 73. Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption
AR, Bassford T, Beresford SA, Black HR, Brunner RL, Brzyski RG, Caan B, and risk of incident coronary heart disease, stroke, and diabetes mellitus:
Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss a systematic review and meta-analysis. Circulation. 2010;121:2271–2283.
G, Hendrix SL, Hubbell FA, Johnson KC, Kotchen JM. Low-fat dietary doi: 10.1161/CIRCULATIONAHA.109.924977
pattern and risk of cardiovascular disease: the Women’s Health Initiative 74. Guasch-Ferré M, Liu X, Malik VS, Sun Q, Willett WC, Manson JE,
Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:655– Rexrode KM, Li Y, Hu FB, Bhupathiraju SN. Nut consumption and risk
666. doi: 10.1001/jama.295.6.655 of cardiovascular disease. J Am Coll Cardiol. 2017;70:2519–2532. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

57. Joint WHO/FAO Expert Consultation on Diet, Nutrition and the Prevention 10.1016/j.jacc.2017.09.035
of Chronic Diseases. Diet, nutrition and the prevention of chronic dis- 75. Afshin A, Micha R, Khatibzadeh S, Mozaffarian D. Consumption of
eases: report of a joint WHO/FAO expert consultation, Geneva, 28 January nuts and legumes and risk of incident ischemic heart disease, stroke,
– 1 February 2002. WHO Technical Report Series No. 916. 2003. http:// and diabetes: a systematic review and meta-analysis. Am J Clin Nutr.
www.who.int/dietphysicalactivity/publications/trs916/en/gsfao_introduc- 2014;100:278–288. doi: 10.3945/ajcn.113.076901
tion.pdf. Accessed June 14, 2016. 76. Chen M, Li Y, Sun Q, Pan A, Manson JE, Rexrode KM, Willett WC, Rimm EB,
58. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective Hu FB. Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults.
cohort studies evaluating the association of saturated fat with cardio- Am J Clin Nutr. 2016;104:1209–1217. doi: 10.3945/ajcn.116.134460
vascular disease. Am J Clin Nutr. 2010;91:535–546. doi: 10.3945/ajcn. 77. Pimpin L, Wu JH, Haskelberg H, Del Gobbo L, Mozaffarian D. Is butter
2009.27725 back? A systematic review and meta-analysis of butter consumption and
59. Jakobsen MU, O’Reilly EJ, Heitmann BL, Pereira MA, Bälter K, Fraser risk of cardiovascular disease, diabetes, and total mortality. PLoS One.
GE, Goldbourt U, Hallmans G, Knekt P, Liu S, Pietinen P, Spiegelman D, 2016;11:e0158118. doi: 10.1371/journal.pone.0158118
Stevens J, Virtamo J, Willett WC, Ascherio A. Major types of dietary fat 78. Kalogeropoulos AP, Georgiopoulou VV, Murphy RA, Newman AB, Bauer
and risk of coronary heart disease: a pooled analysis of 11 cohort studies. DC, Harris TB, Yang Z, Applegate WB, Kritchevsky SB. Dietary sodium
Am J Clin Nutr. 2009;89:1425–1432. doi: 10.3945/ajcn.2008.27124 content, mortality, and risk for cardiovascular events in older adults: the
60. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease Health, Aging, and Body Composition (Health ABC) Study. JAMA Intern
of increasing polyunsaturated fat in place of saturated fat: a systematic Med. 2015;175:410–419. doi: 10.1001/jamainternmed.2014.6278
review and meta-analysis of randomized controlled trials. PLoS Med. 79. Mente A, O’Donnell M, Rangarajan S, Dagenais G, Lear S, McQueen M,
2010;7:e1000252. doi: 10.1371/journal.pmed.1000252 Diaz R, Avezum A, Lopez-Jaramillo P, Lanas F, Li W, Lu Y, Yi S, Rensheng L,
61. Farvid MS, Ding M, Pan A, Sun Q, Chiuve SE, Steffen LM, Willett WC, Iqbal R, Mony P, Yusuf R, Yusoff K, Szuba A, Oguz A, Rosengren A, Bahonar
Hu FB. Dietary linoleic acid and risk of coronary heart disease: a system- A, Yusufali A, Schutte AE, Chifamba J, Mann JF, Anand SS, Teo K, Yusuf S;
atic review and meta-analysis of prospective cohort studies. Circulation. PURE, EPIDREAM and ONTARGET/TRANSCEND Investigators. Associations
2014;130:1568–1578. doi: 10.1161/CIRCULATIONAHA.114.010236 of urinary sodium excretion with cardiovascular events in individuals with
62. Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Trans and without hypertension: a pooled analysis of data from four studies.
fatty acids and cardiovascular disease. N Engl J Med. 2006;354:1601– Lancet. 2016;388:465–475. doi: 10.1016/S0140-6736(16)30467-6
1613. doi: 10.1056/NEJMra054035 80. O’Donnell M, Mente A, Rangarajan S, McQueen MJ, Wang X, Liu L, Yan
63. Barclay AW, Petocz P, McMillan-Price J, Flood VM, Prvan T, Mitchell P, H, Lee SF, Mony P, Devanath A, Rosengren A, Lopez-Jaramillo P, Diaz R,
Brand-Miller JC. Glycemic index, glycemic load, and chronic disease risk: a Avezum A, Lanas F, Yusoff K, Iqbal R, Ilow R, Mohammadifard N, Gulec
meta-analysis of observational studies. Am J Clin Nutr. 2008;87:627–637. S, Yusufali AH, Kruger L, Yusuf R, Chifamba J, Kabali C, Dagenais G, Lear
doi: 10.1093/ajcn/87.3.627 SA, Teo K, Yusuf S; for the PURE Investigators. Urinary sodium and potas-
64. Dong JY, Zhang YH, Wang P, Qin LQ. Meta-analysis of dietary glycemic sium excretion, mortality, and cardiovascular events [published correction
load and glycemic index in relation to risk of coronary heart disease. Am J appears in N Engl J Med. 2014;371:1267]. N Engl J Med. 2014;371:612–
Cardiol. 2012;109:1608–1613. doi: 10.1016/j.amjcard.2012.01.385 623. doi: 10.1056/NEJMoa1311889
65. Yu D, Zhang X, Shu XO, Cai H, Li H, Ding D, Hong Z, Xiang YB, Gao YT, 81. Whelton PK, Appel LJ, Sacco RL, Anderson CA, Antman EM, Campbell N,
Zheng W, Yang G. Dietary glycemic index, glycemic load, and refined car- Dunbar SB, Frohlich ED, Hall JE, Jessup M, Labarthe DR, MacGregor GA,
bohydrates are associated with risk of stroke: a prospective cohort study Sacks FM, Stamler J, Vafiadis DK, Van Horn LV. Sodium, blood pressure,

e80 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

and cardiovascular disease: further evidence supporting the American 97. Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse

CLINICAL STATEMENTS
Heart Association sodium reduction recommendations [published correc- JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington

AND GUIDELINES
tion appears in Circulation. 2013;127:e263]. Circulation. 2012;126:2880– S, Armitage J, Clarke R; Omega-3 Treatment Trialists’ Collaboration.
2889. doi: 10.1161/CIR.0b013e318279acbf Associations of omega-3 fatty acid supplement use with cardiovascu-
82. Cobb LK, Anderson CA, Elliott P, Hu FB, Liu K, Neaton JD, Whelton PK, lar disease risks: meta-analysis of 10 trials involving 77 917 individuals.
Woodward M, Appel LJ; on behalf of the American Heart Association JAMA Cardiol. 2018;3:225–234. doi: 10.1001/jamacardio.2017.5205
Council on Lifestyle and Metabolic Health. Methodological issues in cohort 98. Kwok CS, Umar S, Myint PK, Mamas MA, Loke YK. Vegetarian diet,
studies that relate sodium intake to cardiovascular disease outcomes: Seventh Day Adventists and risk of cardiovascular mortality: a system-
a science advisory from the American Heart Association. Circulation. atic review and meta-analysis. Int J Cardiol. 2014;176:680–686. doi:
2014;129:1173–1186. doi: 10.1161/CIR.0000000000000015 10.1016/j.ijcard.2014.07.080
83. Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika 99. Satija A, Bhupathiraju SN, Rimm EB, Spiegelman D, Chiuve SE, Borgi
SK, Appel LJ, Whelton PK; Trials of Hypertension Prevention L, Willett WC, Manson JE, Sun Q, Hu FB. Plant-based dietary patterns
Collaborative Research Group. Joint effects of sodium and potassium and incidence of type 2 diabetes in US men and women: results from
intake on subsequent cardiovascular disease: the Trials of Hypertension three prospective cohort studies. PLoS Med. 2016;13:e1002039. doi:
Prevention follow-up study. Arch Intern Med. 2009;169:32–40. doi: 10.1371/journal.pmed.1002039
10.1001/archinternmed.2008.523 100. Mitrou PN, Kipnis V, Thiébaut AC, Reedy J, Subar AF, Wirfält E, Flood
84. Cook NR, Appel LJ, Whelton PK. Sodium intake and all-cause mortality A, Mouw T, Hollenbeck AR, Leitzmann MF, Schatzkin A. Mediterranean
over 20 years in the Trials of Hypertension Prevention. J Am Coll Cardiol. dietary pattern and prediction of all-cause mortality in a US population:
2016;68:1609–1617. doi: 10.1016/j.jacc.2016.07.745 results from the NIH-AARP Diet and Health Study. Arch Intern Med.
85. Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich 2007;167:2461–2468. doi: 10.1001/archinte.167.22.2461
S, Hoffmann G, Chaimani A. Dietary supplements and risk of cause-spe- 101. Fung TT, Chiuve SE, McCullough ML, Rexrode KM, Logroscino G, Hu
cific death, cardiovascular disease, and cancer: a systematic review and FB. Adherence to a DASH-style diet and risk of coronary heart disease
meta-analysis of primary prevention trials. Adv Nutr. 2017;8:27–39. doi: and stroke in women [published correction appears in Arch Intern
10.3945/an.116.013516 Med. 2008;168:1276]. Arch Intern Med. 2008;168:713–720. doi:
86. Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults 10.1001/archinte.168.7.713
use dietary supplements. JAMA Intern Med. 2013;173:355–361. doi: 102. Fung TT, Rexrode KM, Mantzoros CS, Manson JAE, Willett WC, Hu
10.1001/jamainternmed.2013.2299 FB. Mediterranean diet and incidence of and mortality from coronary
87. Bailey RL, Fulgoni VL 3rd, Keast DR, Dwyer JT. Dietary supplement use is heart disease and stroke in women [published correction appears in
associated with higher intakes of minerals from food sources. Am J Clin Circulation. 2009;119:e379] Circulation. 2009;119:1093–1100. doi:
Nutr. 2011;94:1376–1381. doi: 10.3945/ajcn.111.020289 10.1161/CIRCULATIONAHA.108.816736
88. Bailey RL, Fulgoni VL 3rd, Keast DR, Dwyer JT. Examination of vitamin 103. Heidemann C, Schulze MB, Franco OH, van Dam RM, Mantzoros CS, Hu
intakes among US adults by dietary supplement use. J Acad Nutr Diet. FB. Dietary patterns and risk of mortality from cardiovascular disease,
2012;112:657–663.e4. doi: 10.1016/j.jand.2012.01.026 cancer, and all causes in a prospective cohort of women. Circulation.
89. Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ. Calcium intake and 2008;118:230–237. doi: 10.1161/CIRCULATIONAHA.108.771881
cardiovascular disease risk: an updated systematic review and meta-analy- 104. Brunner EJ, Mosdøl A, Witte DR, Martikainen P, Stafford M, Shipley MJ,
sis [published correction appears in Ann Intern Med. 2017;166:687]. Ann Marmot MG. Dietary patterns and 15-y risks of major coronary events,
Intern Med. 2016;165:856–866. doi: 10.7326/M16-1165 diabetes, and mortality. Am J Clin Nutr. 2008;87:1414–1421. doi:
90. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. 10.1093/ajcn/87.5.1414
Downloaded from http://ahajournals.org by on February 7, 2019

Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin 105. Fitzgerald KC, Chiuve SE, Buring JE, Ridker PM, Glynn RJ. Comparison
E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo of associations of adherence to a Dietary Approaches to Stop
Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. [published Hypertension (DASH)-style diet with risks of cardiovascular disease and
corrections appear in Lancet. 2001;357:642 and Lancet. 2007;369:106]. venous thromboembolism. J Thromb Haemost. 2012;10:189–198. doi:
Lancet. 1999;354:447–455. doi: 10.1016/S0140-6736(99)07072-5 10.1111/j.1538-7836.2011.04588.x
91. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, 106. Heidemann C, Hoffmann K, Spranger J, Klipstein-Grobusch K, Möhlig
Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W, Peto R. Lack M, Pfeiffer AF, Boeing H; European Prospective Investigation into Cancer
of effect of long-term supplementation with beta carotene on the inci- and Nutrition (EPIC)–Potsdam Study Cohort. A dietary pattern protec-
dence of malignant neoplasms and cardiovascular disease. N Engl J Med. tive against type 2 diabetes in the European Prospective Investigation
1996;334:1145–1149. doi: 10.1056/NEJM199605023341801 into Cancer and Nutrition (EPIC)–Potsdam Study cohort. Diabetologia.
92. Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement 2005;48:1126–1134. doi: 10.1007/s00125-005-1743-1
use and risk of all-cause and coronary heart disease mortality in older per- 107. Joosten MM, Grobbee DE, van der A DL, Verschuren WM, Hendriks HF,
sons: the Established Populations for Epidemiologic Studies of the Elderly. Beulens JW. Combined effect of alcohol consumption and lifestyle be-
Am J Clin Nutr. 1996;64:190–196. doi: 10.1093/ajcn/64.2.190 haviors on risk of type 2 diabetes. Am J Clin Nutr. 2010;91:1777–1783.
93. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, doi: 10.3945/ajcn.2010.29170
Willett WC. Vitamin E consumption and the risk of coronary dis- 108. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development
ease in women. N Engl J Med. 1993;328:1444–1449. doi: 10.1056/ of the metabolic syndrome: the Atherosclerosis Risk in Communities
NEJM199305203282003 study. Circulation. 2008;117:754–761. doi: 10.1161/CIRCULATIONAHA.
94. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant 107.716159
vitamins for the prevention of cardiovascular disease: meta-analysis of 109. Osler M, Heitmann BL, Gerdes LU, Jørgensen LM, Schroll M. Dietary pat-
randomised trials [published correction appears in Lancet. 2004;363:662]. terns and mortality in Danish men and women: a prospective observa-
Lancet. 2003;361:2017–2023. doi: 10.1016/S0140-6736(03)13637-9 tional study. Br J Nutr. 2001;85:219–225.
95. Ye Y, Li J, Yuan Z. Effect of antioxidant vitamin supplementation on cardio- 110. van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Dietary pat-
vascular outcomes: a meta-analysis of randomized controlled trials. PLoS terns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med.
One. 2013;8:e56803. doi: 10.1371/journal.pone.0056803 2002;136:201–209.
96. Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, 111. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.
Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Mediterranean diet, traditional risk factors, and the rate of cardiovascu-
Appel LJ, Mozaffarian D; on behalf of the American Heart Association lar complications after myocardial infarction: final report of the Lyon Diet
Nutrition Committee of the Council on Lifestyle and Cardiometabolic Heart Study. Circulation. 1999;99:779–785.
Health; Council on Epidemiology and Prevention; Council on 112. Ferguson JF, Allayee H, Gerszten RE, Ideraabdullah F, Kris-Etherton
Cardiovascular Disease in the Young; Council on Cardiovascular and PM, Ordovás JM, Rimm EB, Wang TJ, Bennett BJ; on behalf of the
Stroke Nursing; and Council on Clinical Cardiology. Omega-3 poly- American Heart Association Council on Functional Genomics and
unsaturated fatty acid (fish oil) supplementation and the preven- Translational Biology, Council on Epidemiology and Prevention, and
tion of clinical cardiovascular disease: a science advisory from the Stroke Council. Nutrigenomics, the microbiome, and gene-environ-
American Heart Association. Circulation. 2017;135:e867–e884. doi: ment interactions: new directions in cardiovascular disease research,
10.1161/CIR.0000000000000482 prevention, and treatment: a scientific statement from the American

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e81

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 5

Heart Association. Circ Cardiovasc Genet. 2016;9:291–313. doi: Advocacy Coordinating Committee. Population approaches to improve
CLINICAL STATEMENTS

10.1161/HCG.0000000000000030 diet, physical activity, and smoking habits: a scientific statement from
AND GUIDELINES

113. Pirastu N, Kooyman M, Traglia M, Robino A, Willems SM, Pistis G, Amin N, the American Heart Association. Circulation. 2012;126:1514–1563. doi:
Sala C, Karssen LC, Van Duijn C, Toniolo D, Gasparini P. A genome-wide 10.1161/CIR.0b013e318260a20b
association study in isolated populations reveals new genes associated to 118. Rummo PE, Guilkey DK, Ng SW, Popkin BM, Evenson KR, Gordon-
common food likings. Rev Endocr Metab Disord. 2016;17:209–219. doi: Larsen P. Beyond supermarkets: food outlet location selection in
10.1007/s11154-016-9354-3 four U.S. cities over time. Am J Prev Med. 2017;52:300–310. doi:
114. Kumanyika S, Grier S. Targeting interventions for ethnic minority and 10.1016/j.amepre.2016.08.042
low-income populations. Future Child. 2006;16:187–207. 119. Ng SW, Poti JM, Popkin BM. Trends in racial/ethnic and income disparities
115. Li F, Harmer PA, Cardinal BJ, Bosworth M, Acock A, Johnson-Shelton in foods and beverages consumed and purchased from stores among US
D, Moore JM. Built environment, adiposity, and physical activity in households with children, 2000-2013. Am J Clin Nutr. 2016;104:750–
adults aged 50-75. Am J Prev Med. 2008;35:38–46. doi: 10.1016/j. 759. doi: 10.3945/ajcn.115.127944
amepre.2008.03.021 120. GBD 2015 Risk Factors Collaborators. Global, regional, and national
116. Sallis JF, Glanz K. The role of built environments in physical activity, eat- comparative risk assessment of 79 behavioural, environmental and oc-
ing, and obesity in childhood. Future Child. 2006;16:89–108. cupational, and metabolic risks or clusters of risks, 1990–2015: a sys-
117. Mozaffarian D, Afshin A, Benowitz NL, Bittner V, Daniels SR, Franch tematic analysis for the Global Burden of Disease Study 2015 [published
HA, Jacobs DR Jr, Kraus WE, Kris-Etherton PM, Krummel DA, Popkin correction appears in Lancet. 2017;389:e1]. Lancet. 2016;388:1659–
BM, Whitsel LP, Zakai NA; on behalf of the American Heart Association 1724. doi: 10.1016/S0140-6736(16)31679-8
Council on Epidemiology and Prevention, Council on Nutrition, Physical 121. Global Burden of Disease Study 2016. Global Burden of Disease Study
Activity and Metabolism, Council on Clinical Cardiology, Council 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
on Cardiovascular Disease in the Young, Council on the Kidney in Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
Cardiovascular Disease, Council on Peripheral Vascular Disease, and the data.org/gbd-results-tool. Accessed May 1, 2018.
Downloaded from http://ahajournals.org by on February 7, 2019

e82 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

6. OVERWEIGHT AND OBESITY Abbreviations Used in Chapter 6 Continued

CLINICAL STATEMENTS
OR odds ratio
See Table 6-1 and Charts 6-1 through 6-12

AND GUIDELINES
PA physical activity
PCI percutaneous coronary intervention
Click here to return to the Table of Contents PSC Prospective Studies Collaboration
QALY quality-adjusted life-year
Overweight and obesity are major risk factors for RCT randomized controlled trial
RR relative risk
CVD, including CHD, stroke,1,2 AF,3 VTE,4,5 and CHF.
SBP systolic blood pressure
According to NHANES 2015 to 2016, the prevalence of SCD sudden cardiac death
obesity was 39.6% of US adults and 18.5% of youths, SD standard deviation
SES socioeconomic status
Abbreviations Used in Chapter 6 SNP single-nucleotide polymorphism
SOS Swedish Obese Subjects
ACTION Acute Coronary Treatment and Intervention Outcomes
Network STEMI ST-segment–elevation myocardial infarction
AF atrial fibrillation TC total cholesterol
AFFIRM Atrial Fibrillation Follow-up Investigation of Rhythm UI uncertainty interval
Management VTE venous thromboembolism
AHA American Heart Association WC waist circumference
APCSC Asia-Pacific Cohort Studies Collaboration WHI Women’s Health Initiative
APPROACH Alberta Provincial Project for Outcome Assessment in YRBSS Youth Risk Behavior Surveillance System
Coronary Heart Disease
ARIC Atherosclerosis Risk in Communities Study
ARISTOTLE Apixaban for Reduction in Stroke and Other with 7.7% of adults and 5.6% of youth having severe
Thromboembolic Events in Atrial Fibrillation obesity.6–8 The AHA has identified BMI <85th percentile
BMI body mass index
in youth (aged 2–19 years) and <25 kg/m2 in adults
BP blood pressure
BRFSS Behavioral Risk Factor Surveillance System
(aged ≥20 years) as 1 of the 7 components of ideal
CABG coronary artery bypass graft cardiovascular health.9 In 2013 to 2014, 63.1% of
CAC coronary artery calcification youth and 29.6% of adults met these criteria (Chapter
CAD coronary artery disease 2, Cardiovascular Health).
CARDIA Coronary Artery Risk Development in Young Adults
CDC Centers for Disease Control and Prevention
Downloaded from http://ahajournals.org by on February 7, 2019

CHD coronary heart disease Classification of Overweight and

CHF congestive heart failure
CI confidence interval
Obesity
CVD cardiovascular disease • For adults, NHLBI weight categories are as fol-
DBP diastolic blood pressure lows: overweight (25.0 ≤ BMI ≤ 29.9 kg/m2) and
DM diabetes mellitus
obese class I (BMI 30–35 kg/m2), class II (BMI
DNA deoxyribonucleic acid
ERFC Emerging Risk Factor Collaboration >35–39.9 kg/m2), and class III (BMI ≥40 kg/m2).
GBD Global Burden of Disease BMI cutoffs often misclassify obesity in those with
GWAS genome-wide association study muscle mass on the upper and lower tails of the
HbA1c hemoglobin A1c (glycosylated hemoglobin) distribution. BMI categories also vary in prognos-
HD heart disease
tic value by race/ethnicity; they appear to overesti-
HDL high-density lipoprotein
HDL-C high-density lipoprotein cholesterol
mate risk in African Americans and underestimate
HR hazard ratio risk in Asians.10 For this reason, lower BMI cutoffs
HUNT 2 Nord-Trøndelag Health Study have been recommended to classify obesity and
IHD ischemic heart disease associated health risks for Asian and South Asian
IMT intima-media thickness populations.11
IRR incidence rate ratio
• For youth, sex-specific BMI-for-age 2000 CDC
LDL-C low-density lipoprotein cholesterol
Look AHEAD Look: Action for Health in Diabetes
growth charts for the United States are used,12
MESA Multi-Ethnic Study of Atherosclerosis and overweight is defined as 85th to <95th per-
MHO metabolically healthy obesity centile and obesity as ≥95th percentile. These
MI myocardial infarction categories were previously called “at risk for over-
NCDR National Cardiovascular Data Registry weight” and “overweight.” The change in termi-
NCHS National Center for Health Statistics
NH non-Hispanic
nology reflects the labels used by organizations
NHANES National Health and Nutrition Examination Survey such as the Health and Medicine Division and the
NHDS National Hospital Discharge Survey American Academy of Pediatrics. More informa-
NHIS National Health Interview Survey tion is available elsewhere.13
NHLBI National Heart, Lung, and Blood Institute • A 2013 AHA scientific statement recommended
(Continued ) that the definition of severe obesity for children

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e83

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

≥2 years old and adolescents be changed to NH black (16.8%, 20.9%), and Hispanic (20.6%,
CLINICAL STATEMENTS

BMI ≥120% of the 95th percentile for age and 22.1%) boys and girls, respectively.18,20
AND GUIDELINES

sex or an absolute BMI ≥35 kg/m2, whichever is • The prevalence of childhood obesity varies by
lower.14 This definition of severe obesity among SES. According to 2011 to 2014 NHANES data,
children could better identify this small but for children 12 to 19 years old, the prevalence
important group compared with the other com- of obesity by percentage of poverty level was
mon definition of BMI ≥99th percentile for age 22.4% for those below 100%, 25.7% for 100%
and sex.14 to 199%, 19.7% for 200% to 399%, and 13.7%
• Current obesity guidelines define WC ≥40 inches for ≥400% of poverty level.19
(102 cm) for males and ≥35 inches (88 cm) for • In addition, obesity prevalence among adoles-
females as being associated with increased car- cents was higher for those whose parents had
diovascular risk15; however, lower cutoffs have a high school degree or less education (21.6%)
been recommended for various racial/ethnic than for adolescents whose parents had a bach-
groups, for example, ≥80 cm for Asian females elor’s degree or higher (9.6%).21,22
and ≥90 cm for Asian males.10,16 WC measure- • According to self-reported height and weight
ment is recommended for those with BMI of 25 data from the YRBSS 2015,23 13.9% of US high
to 34.9 kg/m2, to provide additional information school students had obesity and 16.0% were
on CVD risk.17 overweight. The percentages of obesity were
higher in boys (16.8%) than girls (10.8%) and
in blacks (16.8%) and Hispanics (16.4%) than in
Prevalence
whites (12.4%). Obesity rates varied by states:
Youth The highest rates of obesity in females were
(See Table 6-1 and Chart 6-1) observed in Kentucky and Mississippi (16.2%),
• According to 2015 to 2016 data from NHANES and in males, West Virginia (23.4%); the lowest
(NCHS/CDC), the overall prevalence of obesity rates in females were observed in Nevada (6.3%),
(≥95th percentile) was 18.5%. By age group, whereas for males, the lowest rates were seen in
the prevalence of obesity for children aged 2 Montana (13.0%).
to 5 years was 13.9%; for children aged 6 to • A systematic review and meta-analysis of 15 pro-
11 years, the prevalence was 18.4%; and for
Downloaded from http://ahajournals.org by on February 7, 2019

spective cohort studies with 200 777 participants

adolescents aged 12 to 19 years, the prevalence showed that children and adolescents who had
was 20.6%.8 obesity were ≈5 times more likely to have obesity
• According to 2013 to 2014 data from NHANES in adulthood than those who did not have obe-
(NCHS/CDC), the overall prevalence of over- sity. Approximately 55% of children with obesity
weight, including obesity, in children and ado- will remain with obesity in adolescence, 80% of
lescents aged 2 to 19 years was 33.4% based adolescents with obesity will remain with obesity
on a BMI-for-age value ≥85th percentile of the in their adulthood, and 70% of these adolescents
2000 CDC growth charts: 16.2% were over- will remain with obesity over age 30.
weight, and 17.2% had obesity (≥95th percen-
tile). There were no significant differences in Adults
overweight (including obesity) prevalence for (See Table 6-1 and Charts 6-2 through 6-8)
boys and girls.18 • According to NHANES 2015 to 2016, among US
• The prevalence of obesity was lower for NH Asian adults aged ≥20 years:
and NH white children than for NH black and
— The age-adjusted prevalence of obesity was
Hispanic children, without significant differences
39.6% (37.9% of males and 41.1% of fe-
between NH black and Hispanic children (Chart
males), and 7.7% had class III obesity (5.6%
6-1).7,19
• Extreme obesity, defined as BMI ≥120% of the of males and 9.7% of females).8
95th percentile for age and sex, was prevalent in • According to NHANES 2013 to 2014, among US
5.8% of youth aged 2 to 19 years, which was adults aged ≥20 years6:
similar for boys (5.7%) and girls (5.9%) but was — The age-adjusted prevalence of obesity
higher among Hispanic and NH black youth than was 37.7% (35.0% of males and 40.4%
among NH white youth.18 of females), and 7.7% had class III obesity
• According to 2013 to 2014 NHANES data, among (5.5% of males and 9.9% of females).
all children aged 2 to 19 years, the prevalence of — Among males, the age-adjusted prevalence
obesity was lower for NH Asian boys (12.1%) and of obesity and class III obesity was not sig-
girls (5.0%) than for NH white (15.9%, 14.6%), nificantly different for NH blacks (38.0% and

e84 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

7.2%), NH Asians (12.6% and data not avail- • Children and adolescents who are overweight

CLINICAL STATEMENTS
able for class III obesity), Hispanics (37.9% and have obesity are at increased risk for future

AND GUIDELINES
and 5.4%), and NH whites (34.7% and adverse health effects, including the following26:
5.6%). — Increased prevalence of traditional cardiovas-
— Among females, the age-adjusted preva- cular risk factors such as hypertension, hyper-
lence of obesity and class III obesity, respec- lipidemia, and DM. Among 8579 youths in
tively, was greater in NH blacks (57.2% and the NHANES study, higher BMI was associ-
16.8%), lower in NH Asians (12.4% and ated with higher SBP and DBP, lower HDL,
data not available for class III obesity), and and high triglyceride and HbA1c levels.27,28
similar in Hispanics (46.9% and 8.7%) com- — Poor school performance, tobacco use, alco-
pared with NH whites (38.2% and 9.7%). hol use, premature sexual behavior, and poor
• According to NHANES 2011 to 2014, the age- diet.
adjusted prevalence of obesity was higher — Other associated health conditions, such
among middle-aged (40–59 years: 40.2%) and as asthma, hepatic steatosis, sleep apnea,
older (≥60 years: 37.0%) adults than younger stroke, some cancers (breast, colon, and kid-
(20–39 years: 32.3%) adults. This pattern (lower ney), renal insufficiency, musculoskeletal dis-
prevalence of obesity among younger adults) orders, gallbladder disease, and reproductive
was similar for males and females, although the abnormalities.
prevalence of obesity was higher among females • Data from 4 Finnish cohort studies examining
(Chart 6-2).7 childhood and adult BMI with a mean follow-up
• Using NHANES 2011 to 2014 data, obesity prev- of 23 years found that children who were over-
alence was higher in females than males when weight or had obesity and had obesity in their
stratified by race/ethnicity (Table  6-1 and Chart adulthood had an increased risk of type 2 DM (RR,
6-3). By sex, the only significant differences were 5.4), hypertension (RR, 2.7), dyslipidemia (high
higher prevalence of obesity among NH black LDL-C: RR, 1.8; low HDL-C: RR, 2.1; high triglyc-
females than among NH black males and among erides: RR, 3.0), and carotid atherosclerosis (RR,
Hispanic females than among Hispanic males 1.7), whereas those who achieved normal weight
(Table 6-1 and Chart 6-3).7 by adulthood had risks comparable to individuals
Downloaded from http://ahajournals.org by on February 7, 2019

• Females have had a higher prevalence of class who never had obesity.29
III obesity and a lower prevalence of overweight • The CARDIA study showed that young adults
than males in all NHANES surveys from 1999 who were overweight or had obesity had lower
through 2014 (Chart 6-4).19 self-reported physical health-related quality of life
• In the United States, the prevalence of obesity, as than normal-weight participants 20 years later.30
estimated from self-reported height and weight
in the BRFSS/CDC (2016),24 varies by region and Adults
state. Self-reported estimates usually underes- (See Chart 6-9)
timate BMI and obesity. In 2016, by state, the • Obesity is associated with increased lifetime risk
prevalence of obesity was highest in Mississippi of CVD and increased prevalence of type 2 DM,
(37.3%) and West Virginia (37.7%) and lowest hypertension, dyslipidemia, sleep-disordered
in Colorado (22.3%) (Chart 6-5).24 When BRFSS breathing, VTE, AF, and dementia.31,32
data from 2014 to 2016 were combined, the • Analyses of continuous BMI show the risk of type
prevalence of obesity by state was higher for 2 DM increases with increasing BMI.33
Hispanic adults and substantially higher for NH • Among 68 070 adult participants across multiple
black adults than for white adults (Charts 6-6 NHANES surveys, the decline in BP in recent birth
through 6-8). cohorts slowed, mediated by BMI.34
• Another systematic review and meta-analysis of
37 studies showed that high childhood BMI was
Complications associated with an increased incidence of adult
Youth DM (OR, 1.70; 95% CI, 1.30–2.22), CHD (OR,
• According to the National Longitudinal Study of 1.20; 95% CI, 1.10–1.31), and a range of can-
Adolescent Health, compared with those with cers, but not stroke or breast cancer; however, the
normal weight or those who were overweight, accuracy of childhood BMI predicting any adult
adolescents who were obese had a 16-fold morbidity was low. Only 31% of future DM and
increased risk of having severe obesity as adults, 22% of future hypertension and CHD occurred
and 70.5% of adolescents with severe obesity in those who as youth aged ≥12 years had been
maintained this weight status into adulthood.25 classified as overweight or who had obesity. Only

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e85

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

20% of future adult cancers occurred in children • Obesity was cross-sectionally associated with sub-
CLINICAL STATEMENTS

classified as overweight or who had obesity.35 clinical atherosclerosis, including CAC and carotid
AND GUIDELINES

• Another study examining longitudinal data from IMT, among older adults in MESA, and this asso-
2.3 million adolescents (aged 16–19 years) dem- ciation persisted after adjustment for CVD risk
onstrated increased cardiovascular mortality in factors.40 In prospective analysis of younger adults
adulthood in youth with obesity compared with through midlife, greater duration of overall and
youth with BMI in the 5th to 24th percentile, with abdominal obesity was associated with presence
an HR of 4.9 (95% CI, 3.9–6.1) for death attrib- of and progression of subclinical atherosclerosis in
utable to CHD, 2.6 (95% CI, 1.7–4.1) for death the CARDIA study.41
attributable to stroke, 2.1 (95% CI, 1.5–2.9) for • A systematic review of 25 prospective studies
sudden death, and 3.5 (95% CI, 2.9–4.1) for examining overweight and obesity as predictors
death attributable to total cardiovascular causes, of major stroke subtypes in >2 million partici-
after adjustment for sex, age, birth year, sociode- pants with >30 000 events in ≥4 years found an
mographic characteristics, and height.36 adjusted RR for ischemic stroke of 1.22 (95% CI,
• A meta-analysis of 123 cohorts with 1.4 million 1.05–1.41) in overweight individuals and an RR
adults and 52 000 CVD events reported that asso- of 1.64 (95% CI, 1.36–1.99) for individuals with
ciations of BMI with IHD, hypertensive HD, stroke, obesity relative to normal-weight individuals. RRs
and DM declined with advancing age (Chart 6-9) for hemorrhagic stroke were 1.01 (95% CI, 0.88–
but were largely similar by sex and by region. 1.17) and 1.24 (95% CI, 0.99–1.54) for over-
The RRs for 5-kg/m2 higher BMI for ages 55 to weight individuals and individuals with obesity,
64 years ranged from 1.44 (95% CI, 1.40–1.48) respectively. These risks were graded with increas-
for IHD to 2.32 (95% CI, 2.04–2.63) for DM. On ing BMI and persisted after adjustment for age,
the basis of their data, the authors suggested that lifestyle, and other cardiovascular risk factors.42
the theoretical minimum-risk exposure distribu- • A recent mendelian randomization study of
tion for BMI is 21 to 23 kg/m2 ± 1.1 to 1.8 kg/m2 participants from 7 prospective cohorts dem-
(Chart 6-9).37 onstrated that genetic variants associated with
• Cardiovascular risks might be even higher with higher BMI were significantly associated with
class III obesity than with class I or class II obesity.38 incident AF, which supports a causal relationship
Among 156 775 postmenopausal females in the between obesity and AF.43
Downloaded from http://ahajournals.org by on February 7, 2019

WHI, for severe obesity versus normal BMI, HRs • A recent meta-analysis of 10 case-referent studies
(95% CIs) for mortality were 1.97 (1.77–2.20) and 4 prospective cohort studies (including ARIC)5
in white females, 1.55 (1.20–2.00) in African reported that when individuals with BMI ≥30 kg/
American females, and 2.59 (1.55–4.31) in m2 were compared with those with BMI <30 kg/
Hispanic females; for CHD, HRs were 2.05 (1.80– m2, obesity was associated with a significantly
2.35), 2.24 (1.57–3.19), and 2.95 (1.60–5.41), higher prevalence (OR, 2.45; 95% CI, 1.78–3.35)
respectively; and for CHF, HRs were 5.01 (4.33– and incidence (RR, 2.39; 95% CI, 1.79–3.17) of
5.80), 3.60 (2.30–5.62), and 6.05 (2.49–14.69), VTE, although there was significant heterogeneity
respectively. However, CHD risk was strongly in the studies.4
related to CVD risk factors across BMI categories, • A recent meta-analysis of 15 prospective studies
even in class III obesity, and CHD incidence was of midlife BMI demonstrated that the increased
similar by race/ethnicity with adjustment for dif- risk for Alzheimer disease or any dementia was
ferences in BMI and CVD risk factors.38 1.35 and 1.26 for overweight, respectively, and
• In a meta-analysis from 58 cohorts representing 2.04 and 1.64 for obesity, respectively.44 The
221 934 people in 17 developed countries with inclusion of obesity in dementia forecast models
14 297 incident CVD outcomes, BMI, WC, and increased the estimated prevalence of dementia
waist-to-hip ratio were strongly associated with through 2050 by 9% in the United States and
intermediate risk factors of DM, higher SBP and 19% in China.45
TC, and lower HDL-C. The associations of adipos- • A BMI paradox is often reported, with higher-
ity measures (BMI, WC, waist-to-hip ratio) with BMI patients demonstrating favorable outcomes
CVD outcomes were attenuated after adjustment among adults with prevalent CHF, hypertension,
for intermediate risk factors (DM, SBP, TC, and peripheral vascular disease, and CAD; similar
HDL-C), along with age, sex, and smoking status. findings have been seen for percent body fat.
Measures of adiposity also did not substantively However, recent studies suggest that the obesity
improve risk discrimination or reclassification paradox might be explained by lead-time bias,
when data on intermediate risk factors were because it is not present before the development
included.39 of CVD.32,46

e86 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

• The ARISTOTLE trial reported that in adjusted — Other reports suggest that obesity, especially

CLINICAL STATEMENTS
analyses, higher BMI was associated with lower long-lasting or severe obesity, without meta-

AND GUIDELINES
all-cause mortality (overweight HR, 0.67 [95% bolic abnormalities might not increase risk
CI, 0.59–0.78]; obesity HR, 0.63 [95% CI, 0.54– for MI but does increase risk for HF.53,54
0.74]), similar to an earlier study from the AFFIRM
trial.47
• In a study of 2625 participants with new-onset Mortality
DM pooled from 5 longitudinal cohort stud- • Childhood BMIs in the highest quartile were
ies, rates of total, CVD, and non-CVD mortality associated with premature death as an adult in a
were higher among normal-weight people than cohort of 4857 American Indian children during a
among overweight participants and participants median follow-up of 23.9 years (BMI for quartile 4
with obesity, with adjusted HRs of 2.08 (95% CI, versus quartile 1: IRR, 2.30; 95% CI, 1.46–3.62).55
1.52–2.85), 1.52 (95% CI, 0.89–2.58), and 2.32 • According to NHIS-linked mortality data, among
(95% CI, 1.55–3.48), respectively.48 young adults aged 18 to 39 years, the HR for all-
• In a study of 189 672 participants from 10 US lon- cause mortality was 1.07 (95% CI, 0.91–1.26) for
gitudinal cohort studies, obesity was associated self-reported overweight (not including obesity),
with a shorter total longevity and greater propor- 1.41 (95% CI, 1.16–1.73) for obesity, and 2.46
tion of life lived with CVD, and higher BMI was (95% CI, 1.91–3.16) for extreme obesity.56
associated with significantly higher risk of death • On the basis of NHANES I and II data, among
attributable to CVD.32 adults, obesity was associated with nearly
• Recent studies have evaluated risks for MHO ver- 112 000 excess deaths (95% CI, 53 754–170 064)
sus “metabolically unhealthy” or “metabolically relative to normal weight in 2000. Class I obe-
abnormal” obesity. The definition of MHO has sity was associated with almost 30 000 of these
varied across studies, but it has often comprised excess deaths (95% CI, 8534–68 220) and class
0 or 1 metabolic abnormality by metabolic syn- II and III obesity with >82 000 deaths (95% CI,
drome criteria, sometimes excluding WC. 44  843–119  289). Underweight was associ-
— Using strict criteria of 0 metabolic syndrome ated with nearly 34 000 excess deaths (95% CI,
components and no previous CVD diagno- 15 726–51 766).57 As other studies have found,58
sis, a recent report of 10 European cohort being overweight but not obese was not associ-
Downloaded from http://ahajournals.org by on February 7, 2019

studies (N=163 517 people) reported that ated with excess deaths.57

the prevalence of MHO varied from 7% to • A systematic review (2.88 million people and
28% in females and from 2% to 19% in >270 000 deaths) showed that relative to normal
males.49 BMI (18.5 to <25 kg/m2), all-cause mortality was
— MHO appears to be unstable over time, with lower for overweight individuals (BMI 18.5 to <25
1 study showing that 44.5% of MHO individ- kg/m2: HR, 0.94; 95% CI, 0.91–0.96) and was
uals transitioned to metabolically unhealthy not elevated for class I obesity (HR, 0.95; 95%
obesity over 8 years of follow-up.50 CI, 0.88–1.01). All-cause mortality was higher for
— Among younger adults in the CARDIA study, obesity overall (HR, 1.18; 95% CI, 1.12–1.25) and
after 20 years of follow-up, 47% of people for the subset of class II and III obesity (HR, 1.29;
were defined as being metabolically healthy 95% CI, 1.18–1.41).59
overweight (presence of 0 or 1 metabolic • Fluctuation of weight is associated with cardio-
risk factor).51 Among older adults in MESA, vascular events and death. In 9509 participants
approximately half of participants with MHO of the Treating to New Targets trial, those in the
developed metabolic syndrome and had quintile of highest body weight fluctuation had
increased odds of CVD (OR, 1.60; 95% CI, the highest rates of cardiovascular events, MI,
1.14–2.25) compared with those with stable stroke, and death.60
MHO or healthy normal weight.52 • Recent meta-analysis of 3.74 million deaths
— A recent meta-analysis of 22 prospective among 30.3 million participants found that over-
studies suggested that CVD risk was higher weight and obesity were associated with higher
in MHO than metabolically healthy normal- risk of all-cause mortality, with lowest risks at BMI
weight participants (RR, 1.45; 95% CI, 1.20– 22 to 23 kg/m2 in healthy never-smokers and 20
1.70); however, the risk in MHO individuals to 22 kg/m2 in never-smokers with ≥20 years of
was lower than in individuals who were met- follow-up.61
abolically unhealthy and normal weight (RR, • In a collaborative analysis of data from almost
2.07; 95% CI, 1.62–2.65) or obese (RR, 2.31; 900 000 adults in 57 prospective studies, mostly
95% CI, 1.99–2.69).31 in Western Europe and North America, overall

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e87

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

mortality was lowest at a BMI of ≈22.5 to 25 kg/ — In a comparison of 5 different anthropomet-

CLINICAL STATEMENTS

m2 in both sexes and at all ages, after exclusion of ric variables (BMI, WC, hip circumference,
AND GUIDELINES

early follow-up and adjustment for smoking sta- waist-to-hip ratio, and waist-to-height ratio)
tus. Above this range, each 5-kg/m2-higher BMI in 62 223 individuals from Norway with 12
was associated with ≈30% higher all-cause mor- years of follow-up from the HUNT 2 study,
tality, and no specific cause of death was inversely the risk of death per SD increase in each
associated with BMI. Below 22.5 to 25 kg/m2, the measure was 1.02 (95% CI, 0.99–1.06) for
overall inverse association with BMI was predomi- BMI, 1.10 (95% CI, 1.06–1.14) for WC,
nantly related to strong inverse associations for 1.01 (95% CI, 0.97–1.05) for hip circumfer-
smoking-related respiratory disease, and the only ence, 1.15 (95% CI, 1.11–1.19) for waist-
clearly positive association was for IHD.62 to-hip ratio, and 1.12 (95% CI, 1.08–1.16)
• In a meta-analysis of 1.46 million white adults, for waist-to-height ratio. For CVD mortality,
over a mean follow-up period of 10 years, all- the risk of death per SD increase was 1.12
cause mortality was lowest at BMI levels of 20.0 (95% CI, 1.06–1.20) for BMI, 1.19 (95% CI,
to 24.9 kg/m2. Among females, compared with 1.12–1.26) for WC, 1.06 (95% CI, 1.00–
a BMI of 22.5 to 24.9 kg/m2, the HRs for death 1.13) for hip circumference, 1.23 (95% CI,
were as follows: BMI 15.0 to 18.4 kg/m2, 1.47; 1.16–1.30) for waist-to-hip ratio, and 1.24
18.5 to 19.9 kg/m2, 1.14; 20.0 to 22.4 kg/m2, (95% CI, 1.16–1.31) for waist-to-height
1.00; 25.0 to 29.9 kg/m2, 1.13; 30.0 to 34.9 kg/ ratio.68
m2, 1.44; 35.0 to 39.9 kg/m2, 1.88; and 40.0 • However, because BMI and WC are strongly cor-
to 49.9 kg/m2, 2.51. Similar estimates were related, large samples are needed to evaluate
observed in males.63 their independent contributions to risk.15,69
• In 10 large population cohorts in the United — A recent pooled analysis of WC and mortality
States, individual-level data from adults aged in 650 386 adults followed up for a median
20 to 79 years with 3.2 million person-years of of 9 years revealed that a 5-cm increment in
follow-up (1964–2015) demonstrated that over- WC was associated with an increase in all-
weight and obesity were associated with early cause mortality at all BMI categories exam-
development of CVD and reinforced the greater ined from 20 to 50 kg/m2.70
mortality associated with obesity.32
Downloaded from http://ahajournals.org by on February 7, 2019

— Similarly, in an analysis of postmenopausal

• According to data from the NCDR ACTION females in the WHI limited to those with BMI
Registry–Get With The Guidelines, among ≥40 kg/m2, mortality, CHD, and CHF inci-
patients presenting with STEMI and a BMI ≥40 dence all increased with WC >115 and >122
kg/m2, in-hospital mortality rates were higher for cm compared with ≤108.4 cm.38
patients with class III obesity (OR, 1.64; 95% CI, — Finally, among 14 941 males and females in
1.32–2.03) when class I obesity was used as the ARIC, the risk of SCD was associated with
referent.64 In the APPROACH registry of individu- higher BMI and WC, with traditional risk fac-
als after CABG and PCI, overweight and class 1 tors mediating the association with BMI but
obesity (BMI 20–24.9 kg/m2) were associated with not with WC.71
lower mortality, whereas BMI ≥40 kg/m2 was asso-
ciated with elevated mortality.65 Similar results in
the National Adult Cardiac Surgery registry from Cost
2002 to 2013 showed lower mortality in over- Obesity costs the healthcare system, healthcare payers,
weight and obesity class I and II (OR, 0.81 [95% and individuals with obesity.
CI, 0.76–0.86] and 0.83 [95% CI, 0.74–0.94], • In the United States, the estimated annual medi-
respectively) relative to normal-weight individuals cal cost of obesity in 2008 was $147 billion; the
and greater mortality risk with underweight (OR, annual medical costs for individuals with obesity
1.51; 95% CI, 1.41–1.62), with these results per- were $1429 higher than for normal-weight indi-
sisting after adjustment for residual confounding viduals.72 A more recent study estimated mean
and reverse causation.66 annual per capita healthcare expenses associated
• In a study of 22 203 females and males from with obesity were $1160 for males and $1525 for
England and Scotland, metabolically unhealthy females.73
obese individuals were at an increased risk of all- • According to NHANES I data linked to Medicare
cause mortality compared with MHO individuals and mortality records, 45-year-old individuals with
(HR, 1.72; 95% CI, 1.23–2.41).67 obesity had lifetime Medicare costs of $163 000
• Relation of various anthropometric measures to compared with $117 000 for those who were at
mortality: normal weight at 65 years of age.74

e88 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

• According to data from the Medicare Current with increasing degree of obesity associated with

CLINICAL STATEMENTS
Beneficiary Survey from 1997 to 2006, in 1997, decreasing cost per QALY ($19 222/QALY in the

AND GUIDELINES
expenditures for Part A and Part B services per severely obese), which suggests that subsets of
beneficiary were $6832 for a normal-weight indications for bariatric surgery may be more
person, which was more than for overweight cost-effective.86
people ($5473) or people with obesity ($5790);
however, over time, expenses increased more
rapidly for overweight people and people with
Secular Trends
obesity.75 (See Charts 6-10 and 6-11)
• The costs of obesity are high: People with obesity Youth
paid on average $1429 (42%) more for health- • According to NHANES data, overall prevalence of
care costs than normal-weight people in 2006. obesity and severe obesity in youth (aged 2–19
For beneficiaries who are obese, Medicare pays years old) did not increase significantly between
$1723 more, Medicaid pays $1021 more, and pri- 2007 to 2008 and 2015 to 2016. Among chil-
vate insurers pay $1140 more annually than for dren 2 to 5 years old, a quadratic trend was seen,
beneficiaries who are at normal weight. Similarly, with obesity decreasing from 10.1% in 2007 to
people with obesity have 46% higher inpatient 2008 to 8.4% in 2011 to 2012 and increasing to
costs and 27% more outpatient visits and spend 13.9% in 2015 to 2016.8
80% more on prescription drugs.72 • According to NHANES 2011 to 2014 data, prev-
• Using 4 waves of NHANES data (through 2000), alence of obesity in youth (aged 2–19 years)
the total excess cost in 2007 US dollars related to increased from 1988 to 1994 until 2003 to 2004
the current prevalence of adolescent overweight but did not change significantly afterward. The
and obesity was estimated to be $254 billion prevalence of severe obesity increased between
($208 billion in lost productivity secondary to pre- 1988 to 1994 and 2013 to 2014.18
mature morbidity and mortality and $46 billion in • According to NCHS/CDC and NHANES surveys,
direct medical costs).76 the prevalence of obesity among children and
• A recent study recommended the use of $19 000 adolescents increased substantially from 1963 to
(2012 US dollars) as the incremental lifetime med- 1965 through 2009 to 2010, but this increase has
ical cost of a child with obesity relative to a nor-
Downloaded from http://ahajournals.org by on February 7, 2019

slowed (Chart 6-10).

mal-weight child who maintains normal weight • Specifically, according to NHANES data, from
throughout adulthood.77 1988 to 1994, 2003 to 2006, and 2011 to 2014,
• According to the 2006 NHDS, the incidence the percentage of children 12 to 19 years of age
of bariatric surgery was estimated at 113 000 with obesity increased from 10.5% to 17.6% to
cases per year, with costs of nearly $1.5 billion 20.5%, respectively19; however, during the same
annually.78 time periods, among children aged 2 to 5 years,
• A recent cost-effectiveness study of laparoscopic the prevalence of obesity changed from 7.2% in
adjustable gastric banding showed that after 5 1988 to 1994 to 12.5% in 2003 to 2006 to 8.9%
years, $4970 was saved in medical expenses; if in 2011 to 2014.18,19 Another analysis of NHANES
indirect costs were included (absenteeism and data showed that between 1988 to 1994 and
presenteeism), savings increased to $6180 and 2013 to 2014, extreme obesity increased among
$10 960, respectively.79 However, when expressed children aged 6 to 11 years (from 3.6% to 4.3%)
per QALY, only $6600 was gained for laparoscopic and among adolescents aged 12 to 19 years (from
gastric bypass, $6200 for laparoscopic adjustable 2.6% to 9.1%).18
gastric band, and $17 300 for open Roux-en-Y • Among infants and children from birth to >2 years
gastric bypass, none of which exceeded the stan- old, the prevalence of high weight for recumbent
dard $50 000 per QALY gained.80 Two other recent length (ie, ≥95th percentile of sex-specific CDC
large studies failed to demonstrate a cost benefit 2000 growth charts) was 9.5% in 2003 to 2004
for bariatric surgery versus matched patients over and 8.1% in 2011 to 2014. The decrease of 1.4%
6 years of follow-up.81,82 was not statistically significant.87
• The cost effectiveness of bariatric surgery among • According to the YRBSS, among US high school
individuals with DM is unclear, with 2 studies students between 1999 and 2015, there was a
showing cost savings83,84 but a recent study dem- significant linear increase in the prevalence of obe-
onstrating no improvement compared with inten- sity (from 10.6% to 13.9%) and in the prevalence
sive lifestyle and medical interventions.85 of overweight (from 14.1% to 16.0%). Between
• Bariatric surgery appears to be cost-effective for 1991 and 2015, there was a corresponding sig-
the treatment of nonalcoholic steatohepatitis, nificant linear increase of students who reported

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e89

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

they were trying to lose weight, from 41.8% to identified from systemic reviews, national strate-
CLINICAL STATEMENTS

45.6%.23 gies or action plans, or expert bodies.93 Obesity

AND GUIDELINES

reduction policies and programs implemented by

Adults
country are also provided online.94
• In the United States, the age-standardized preva-
lence of obesity and severe obesity increased sig-
nificantly in the past decade (from 2007–2008 to Awareness
2015–2016) among adults.8 • According to NHANES 2003 to 2006 data, ≈23%
• In the United States, the prevalence of obesity of adults who were overweight and with obe-
among adults, estimated using NHANES data, sity misperceived themselves to be at a healthier
increased from 1999 to 2000 through 2013 weight status, and those people were less likely to
to 2014 from 30.5% to 37.7%6 (Chart 6-11); have tried to lose weight in the prior year.95
however, from 2005 to 2006 through 2013 to • Recent studies show that parents’ perceptions of
2014, there was a significant linear trend for overweight and obesity differ according to the
the increase in obesity and class III obesity for child’s race and sex. Boys 6 to 15 years of age
females (from 35.6% to 41.1% and from 7.5% with obesity were more likely than girls to be
to 10.0%, respectively) but not males (from misperceived as being “about the right weight”
33.4% to 35.1% and from 7.5% to 10.0%, by their parents (OR, 1.40; 95% CI, 1.12–1.76;
respectively).6 P=0.004). Obesity was significantly less likely to
• From NHANES 1999 to 2002 to NHANES 2007 to be misperceived among girls 11 to 15 years of
2010, the prevalence of total and undiagnosed age than among girls 6 to 10 years of age (OR,
DM, total hypertension, total dyslipidemia, and 0.46; 95% CI, 0.29–0.74; P=0.002) and among
smoking did not change significantly within any of Hispanic males than among white males (OR,
the BMI categories, but there was a lower preva- 0.58; 95% CI, 0.36–0.93; P=0.02).95 Notification
lence of dyslipidemia (−3.4%; 95% CI, −6.3% to of a child’s unhealthy weight by healthcare prac-
−0.5%) among overweight adults. However, the titioners increased from 22% in 1999 to 34% in
prevalence of untreated hypertension decreased 2014.96
among adults with overweight or obesity, and the
prevalence of untreated dyslipidemia decreased
Downloaded from http://ahajournals.org by on February 7, 2019

for all BMI categories (normal, overweight, obe- Treatment and Control
sity, and BMI ≥35 kg/m2).88 • The randomized trial Look AHEAD showed that
• Another study reported that for females, but not among adults who were overweight, had obesity,
males, the increase in WC from NHANES 1999 to and had type 2 DM, an intensive lifestyle interven-
2000 to NHANES 2010 to 2011 was greater than tion produced a greater percentage of weight loss
expected based on the increase in BMI.89 at 4 years than DM support education.97
— After 8 years of intervention, the percentage
of weight loss ≥5% and ≥10% was greater
Prevention in the intensive lifestyle intervention than
• In adults, 2 prevention targets are the built envi- in DM support education groups (50.3%
ronment and the workplace. The built environ- and 26.9% versus 35.7% and 17.2%,
ment plays a role in promoting healthy lifestyles respectively).98
and preventing obesity.90 Similar to schools for — Look AHEAD was stopped early with a
children, the workplace can provide an oppor- median 9.6 years of follow-up for failure to
tunity to educate adults on methods to reduce show a significant difference in CVD events
weight and can also motivate individuals to lose between the intensive lifestyle intervention
weight through group participation.91 and control group.97
• 70% of adults with obesity did not have obesity in — Intensive lifestyle interventions produce
childhood or adolescence, so reducing the overall greater weight loss than education alone
burden of adult obesity might require interven- among those with class III obesity99 and child-
tions beyond targeting obesity reduction solely at hood obesity.100
overweight children and children with obesity.92 • A comprehensive review and meta-analysis of 54
• The CDC Prevention Status Reports highlight the RCTs suggests that dietary weight loss interven-
status of public health policies and practices to tions reduce all-cause mortality (34 trials, 685
address public health problems, including obe- events; RR, 0.82; 95% CI, 0.71–0.95), but the
sity, by state. Reports rate the extent to which the benefit on lowering cardiovascular mortality is
state has implemented the policies or practices less clear.101

e90 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

• Ten-year follow-up data from the nonrandom- surgery than for conventional medical therapy,

CLINICAL STATEMENTS
ized SOS bariatric intervention study (see Bariatric with follow-up of ≤2 years.108

AND GUIDELINES
Surgery) suggested that to maintain a favorable • The longest follow-up to date of 12 years in 1156
effect on cardiovascular risk factors, more than patients with severe obesity, including 418 indi-
the short-term goal of 5% weight loss is needed viduals who underwent gastric bypass, demon-
to overcome secular trends and aging effects.102 strated sustained weight loss and both remission
Long-term follow-up might be necessary to show and prevention of incident type 2 DM, hyperten-
reductions in CVD risk. sion, and dyslipidemia.109
• Lifestyle and surgical interventions are both bene- • An RCT demonstrated that weight loss from lapa-
ficial: After gastric bypass, individuals with regular roscopic sleeve gastrectomy was similar to that
PA had improved fat mass, insulin sensitivity, and achieved by traditional gastric bypass surgery,
HDL-C.103 although the latter achieved greater improvement
in lipid levels.110,111
• According to retrospective data, among 9949
Bariatric Surgery patients who underwent gastric bypass surgery,
• Lifestyle interventions often do not provide sus- after a mean of 7 years, long-term mortality
tained significant weight loss for people with obe- was 40% lower among the surgically treated
sity. Among adults with obesity, bariatric surgery patients than among control subjects with obe-
produces greater weight loss and maintenance of sity. Specifically, cancer mortality was reduced by
lost weight than lifestyle intervention, with some 60%, DM mortality by 92%, and CAD mortal-
variations depending on the type of procedure ity by 56%. Nondisease death rates (eg, acci-
and the patient’s initial weight.33 Gastric bypass dents, suicide) were 58% higher in the surgery
surgery is typically performed as a Roux-en-Y gas- group.112
tric bypass, vertical sleeve gastrectomy, adjustable • A recent DM consensus statement recommended
gastric banding, or biliopancreatic diversion with bariatric surgery to treat type 2 DM among adults
duodenal switch. with class III obesity and recommended it be con-
• Benefits reported for bariatric surgery include sidered to treat type 2 DM among adults with
substantial weight loss; remission of DM, hyper- class I obesity.99
tension, and dyslipidemia; reduced incidence of
Downloaded from http://ahajournals.org by on February 7, 2019

• The role of bariatric surgery to treat type 2 DM

mortality; reduction in microvascular disease; and in adolescence is controversial.113 Although bar-
fewer CVD events.104 Reported risks with bariatric iatric surgery improves insulin requirements and
surgery include not only perioperative mortality comorbidities in type 1 DM, there was minimal
and adverse events but also weight regain, DM sustained effect in glycemic control in long-term
recurrence (particularly for those with longer DM follow-up in a small series.114
duration before surgery), bone loss, increases in
substance use disorders, suicide, and nutritional
deficiencies. Outcomes vary by bariatric surgery Family History and Genetics
technique.105 • Overweight and obesity have considerable genetic
• Outcomes must be assessed cautiously, because components, with heritability estimates ranging
most bariatric surgery data come from nonran- from ≈40% to 75%.115 However, only ≈1.5% of
domized observational studies, with only a few interindividual variation of BMI is explained by
RCTs comparing bariatric surgery to medical treat- commonly occurring SNPs, which suggests a role
ment for patients with DM. Furthermore, studies for DNA methylation variants.116
have not always reported their definition of remis- • Monogenic or mendelian causes of obesity
sion or partial remission for comorbidities such as include mutations with strong effects in genes
DM, hypertension, and dyslipidemia, and many that control appetite and energy balance (eg, LEP,
have not reported laboratory values or medication MC4R), as well as obesity that occurs in the con-
use.105,106 text of syndromes.117
• In a large bariatric surgery cohort, the prevalence • Most cases of obesity are determined by the inter-
of high 10-year predicted CVD risk was 36.5%,91 action of genetic and epigenetic factors with an
but 76% of those with low 10-year risk had high obesogenic environment, including diet, PA, and
lifetime predicted CVD risk. The correspond- the microbiome. Although BMI is most com-
ing prevalence in US adults is 18% and 56%, monly used to define obesity at the population
respectively.107 level, measures of visceral adiposity more closely
• A meta-analysis of RCTs also showed substantially approximate the pathogenic form of excess body
higher weight loss and DM remission for bariatric weight.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e91

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

• GWASs in diverse populations have implicated 1980 and 2013, the proportion of adults with
CLINICAL STATEMENTS

multiple loci for obesity, mostly defined by BMI, overweight or obesity increased from 28.8%
AND GUIDELINES

WC, or waist-hip ratio. The FTO locus is the most (95% UI, 28.4%–29.3%) to 36.9% (95% UI,
well-established obesity locus, first reported in 36.3%–37.4%) among males and from 29.8%
2007118,119 and replicated in many studies with (95% UI, 29.3%–30.2%) to 38.0% (95% UI,
diverse populations and age groups since then.120– 37.5%–38.5%) among females. Since 2006, the
124
The mechanisms underlying the association increase in adult obesity in developed countries
remain incompletely elucidated but could be has slowed. The estimated prevalence of adult
related to mitochondrial thermogenesis11 or food obesity exceeded 50% of males in Tonga and
intake.125 females in Kuwait, Kiribati, the Federated States
• Other GWASs have reported numerous addi- of Micronesia, Libya, Qatar, Tonga, and Samoa.
tional loci,126 with >300 putative loci, most of In the sub-Saharan African country of Malawi,
which explain only a small proportion of the representative of rural but developing coun-
variance in obesity, have not been mechanisti- tries, the prevalence of overweight or obesity
cally defined, and have unclear clinical signifi- was 18% and 44% of urban males and females,
cance. Fine mapping of loci, including recent respectively, and 9% and 27% of rural males
efforts focused on GWASs in African ancestry, and females, respectively. Associated hyperten-
in addition to mechanistic studies, is required sion and DM are highly prevalent and under-
to define functionality of obesity-associated diagnosed.132 As of 2013, around the world,
loci.127 obesity rates are higher for females than males
• A large GWAS of obesity in >240 000 individu- and in developed countries than in developing
als of predominately European ancestry revealed countries. Higher obesity rates for females than
an interaction with smoking, which highlights the for males occur for age ≥45 years in developed
need to consider gene-environment interactions countries but for age ≥25 years in developing
in genetic studies of obesity.128 countries.133
• Epigenetic modifications such as DNA methyla- • Between 1980 and 2013, the prevalence of over-
tion have both genetic and environmental con- weight and obesity rose by 27.5% for adults.133
tributors and may contribute to risk of and adverse Over this same period, no declines in obesity
consequences of obesity. An epigenome-wide prevalence were detected. In 2008, an esti-
Downloaded from http://ahajournals.org by on February 7, 2019

association study in 479 people demonstrated mated 1.46 billion adults were overweight or
that increased methylation at the HIF3A locus in obese. The prevalence of obesity was estimated
circulating white blood cells and in adipose tissue at 205 million males and 297 million females in
was associated with increased BMI.129 2013. The highest prevalence of male obesity is
in the United States, southern and central Latin
America, Australasia, and Central and Western
Global Burden Europe, and the lowest prevalence is in South
(See Chart 6-12) and Southeast Asia and East, Central, and West
• The GBD 2016 Study used statistical models Africa. For females, the highest prevalence of obe-
and data on incidence, prevalence, case fatality, sity is in Southern and North Africa, the Middle
excess mortality, and cause-specific mortality to East, central and southern Latin America, and the
estimate disease burden for 315 diseases and United States, and the lowest is in South, East,
injuries in 195 countries and territories.130 The and Southeast Asia, the high-income Asia-Pacific
Pacific Island countries, Eastern Europe, Central subregion, and East, Central, and West Africa.134
Asia, and the North Africa/Middle East region • An appraisal of the prevalence of obesity in sub-
have the highest mortality rates attributable to Saharan Africa from 2009 to 2012 suggests an
high BMI (Chart 6-12).130 increase in BMI and WC, associated with hyper-
• Although there is considerable variability in tension. In 2726 university students in Cameroon,
overweight and obesity data methodology and the prevalence of obesity, overweight and obesity
quality worldwide, cross-country comparisons (combined), and hypertension was 3.5%, 21%,
can help reveal different patterns. Worldwide, and 6.3%, respectively. There was an increase
from 1975 to 2014, the prevalence of obesity over time in overweight and obesity in males and
increased from 3.2% in 1975 to 10.8% in 2014 an increase in prevalence of abdominal obesity in
in males and from 6.4% to 14.9% in females, females, which were both associated with inci-
and mean age-standardized BMI increased from dent hypertension.135
21.7 to 24.2 kg/m2 in males and from 22.1 to • In 2015, a total of 107.7 million youth and 603.7
24.4 kg/m2 in females.131 Worldwide, between million adults had obesity, with an overall obesity

e92 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

prevalence of 5.0% among children and 12.0% dissemination and implementation of evidence-based

CLINICAL STATEMENTS
among adults. High BMI contributed to 4.0 mil- interventions focusing on primordial prevention. In

AND GUIDELINES
lion deaths globally, with the leading cause of recent years, the rate of decline of CVD mortality has
death and disability being attributable to CVD.136 decelerated substantially, which might be attributable
to the obesity epidemic, and there are concerns about
the increasing future burden of CVD. Identification of
Future Research evidence-based strategies to maintain and achieve a
The dramatic increase in prevalence and disease bur- healthy body weight is necessary to reverse the slowing
den of obesity over the past several decades highlights progress in cardiovascular mortality rates and reduce
the ongoing need to focus on the development of and the overall burden of obesity.

Table 6-1.  Overweight and Obesity

Prevalence of Overweight Prevalence of

and Obesity, 2011–2014, Prevalence of Obesity, Overweight and Obesity, Prevalence of Obesity,
Age ≥20 y 2011–2014, Age ≥20 y 2011–2014, Ages 2–19 y 2011–2014, Ages 2–19 y
n % n % n % n % Cost, 2008*
Total 157 232 115 69.4 82 241 005 36.3 24 036 573 32.1 12 339 701 16.5 $147 billion
 Males 78 854 444 72.5 37 306 309 34.3 12 326 869 32.3 6 231 683 16.3 …
 Females 78 215 543 66.4 45 115 291 38.3 11 709 947 32.0 6 107 613 16.7 …
NH white
 Males 53 310 267 73.0 24 537 328 33.6 5 962 553 29.3 2 848 504 14.0 …
 Females 49 632 907 63.7 27 660 411 35.5 5 419 620 28.0 2 847 989 14.7 …
NH black
 Males 7 968 039 69.1 4 324 189 37.5 1 734 453 32.8 924 000 17.5 …
Downloaded from http://ahajournals.org by on February 7, 2019

 Females 11 782 661 82.2 8 156 124 56.9 1 929 861 37.6 1 026 805 20.0 …

NH Asian
 Males 2 504 566 46.6 601 956 11.2 416 430 24.9 190 805 11.4 …
 Females 2 165 586 34.6 744 811 11.9 245 206 15.0 86 088 5.3 …
Hispanic
 Males 13 015 852 79.6 6 377 113 39.0 3 601 223 40.4 1 939 812 21.7 …
 Females 12 721 527 77.1 7 540 516 45.7 3 400 898 39.8 1 798 951 21.0 …

Overweight and obesity in adults is defined as body mass index (BMI) ≥25 kg/m2. Obesity in adults is defined as BMI ≥30 kg/m2. In children, overweight and obesity
are based on BMI-for-age values at or above the 85th percentile of the 2000 Centers for Disease Control and Prevention (CDC) growth charts. In children, obesity
is based on BMI-for-age values at or above the 95th percentile of the CDC growth charts. In January 2007, the American Medical Association’s Expert Task Force on
Childhood Obesity recommended new definitions for overweight and obesity in children and adolescents137; however, statistics based on this new definition are not
yet available. Estimates for the total include those of “other” racial/ethnic groups.
Ellipses (…) indicate data not available; and NH, non-Hispanic.
*Data from Finkelstein et al.79
Sources: NHANES (National Health and Nutrition Examination Survey) 2011 to 2014 (adults), unpublished CDC tabulation; NHANES 2011 to 2014 (ages 2–19
years) from Ogden et al.7 Population count extrapolations calculated using the average of the 2011 and 2013 American Community Survey Summary File data.138

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e93

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6
CLINICAL STATEMENTS
AND GUIDELINES

Chart 6-1. US children and adolescents with obesity by race/ethnicity, 2011 to 2014.
Obesity is body mass index (BMI) at or above the sex-and age-specific 95th percentile BMI cutoff points from the 2000 CDC growth charts.
CDC indicates Centers for Disease Control and Prevention.
Source: CDC and National Center for Health Statistics. Data derived from the National Health and Nutrition Examination Survey, Table 59.7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-2. Age-adjusted prevalence of obesity in adults ≥20 years of age by sex and age group (NHANES, 2011–2014).
Totals were age-adjusted by the direct method to the 2000 US census population using the age groups 20 to 39, 40 to 59, and ≥60 years old. Crude estimates are
36.5% for all, 34.5% for males, and 38.5% for females.
NHANES indicates National Health and Nutrition Examination Survey.
*Significantly different from those aged 20 to 39 years.
†Significantly different from females of the same age group.
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, NHANES, 2011 to 2014.

e94 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-3. Age-adjusted prevalence of obesity in adults ≥20 years of age by sex and race/ethnicity (NHANES, 2011–2014).
NHANES indicates National Health and Nutrition Examination Survey.
*Significantly different from non-Hispanic Asian people.
†Significantly different from non-Hispanic white people.
‡Significantly different from females of the same race and Hispanic origin.
§Significantly different from non-Hispanic black people.
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, NHANES, 2011 to 2014.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-4. Trends in overweight and obesity between 1999 to 2002 and 2011 to 2014 among US adults aged ≥20 years, by sex.
Overweight but not obese (25 ≤ body mass index [BMI] <30 kg/m2); grade 1 obesity (30 ≤ BMI <35 kg/m2); grade 2 obesity (35 ≤ BMI <40 kg/m2); grade 3 obesity
(BMI ≥40 kg/m2).
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, Health, United States, 2015, Figure 9 and Table 58. Data from National
Health and Nutrition Examination Survey.19

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e95

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6
CLINICAL STATEMENTS
AND GUIDELINES

Chart 6-5. Prevalence† of self-reported obesity among US adults aged ≥20 years by state and territory, BRFSS, 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥30%.
†Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.
Source: Centers for Disease Control and Prevention, Obesity Prevalence Map, 2016.24
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-6. Prevalence of self-reported obesity among non-Hispanic white adults aged ≥20 years, by state and territory, BRFSS, 2014 to 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥30%.
Source: Centers for Disease Control and Prevention, Obesity Prevalence Map, 2014 to 2016.24

e96 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-7. Prevalence of self-reported obesity among Hispanic adults aged ≥20 years, by state and territory, BRFSS, 2014 to 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; and PR, Puerto Rico.
*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥30%.
Source: Centers for Disease Control and Prevention, Obesity Prevalence Map, 2014 to 2016.24
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-8. Prevalence of self-reported obesity among non-Hispanic black adults aged ≥20 years, by state and territory, BRFSS, 2014 to 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; and PR, Puerto Rico.
*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥30%.
Source: Centers for Disease Control and Prevention, Obesity Prevalence Map, 2014 to 2016.24

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e97

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6
CLINICAL STATEMENTS
AND GUIDELINES

Chart 6-9. Relative risks for diseases associated with body mass index by age group.
APCSC indicates Asia-Pacific Cohort Studies Collaboration; ERFC, Emerging Risk Factor Collaboration; IHD, ischemic heart disease; and PSC, Prospective Studies
Collaboration.
Reprinted from Singh et al.37 Copyright © 2013, Singh et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-10. US children and adolescents with obesity, 1963 to 2014.

Obesity is body mass index (BMI) at or above the sex- and age-specific 95th percentile BMI cutoff points from the 2000 CDC growth charts.
CDC indicates Centers for Disease Control and Prevention.
Source: CDC/National Center for Health Statistics, Health, United States, 2015, Figure 8 and Table 59. Data from the National Health and Nutrition Examination
Survey.19

e98 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-11. Trends in obesity prevalence among adults aged ≥20 years (age adjusted) and youth aged 2 to 19 years, United States, 1999 to 2000
through 2013 to 2014.
Data from the National Center for Health Statistics.19
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 6-12. Age-standardized global mortality rates attributable to high body mass index per 100 000, both sexes 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016 with permission.130 Copyright © 2017, University of Washington

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e99

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

REFERENCES 15. Cornier MA, Després JP, Davis N, Grossniklaus DA, Klein S, Lamarche B,
CLINICAL STATEMENTS

Lopez-Jimenez F, Rao G, St-Onge MP, Towfighi A, Poirier P; on behalf of

1. Klein S, Burke LE, Bray GA, Blair S, Allison DB, Pi-Sunyer X, Hong Y, Eckel
AND GUIDELINES

the American Heart Association Obesity Committee of the Council on

RH; on behalf of the American Heart Association Council on Nutrition, Nutrition; Physical Activity and Metabolism; Council on Arteriosclerosis;
Physical Activity, and Metabolism. Clinical implications of obesity with Thrombosis and Vascular Biology; Council on Cardiovascular Disease in the
specific focus on cardiovascular disease: a statement for profession- Young; Council on Cardiovascular Radiology and Intervention; Council on
als from the American Heart Association Council on Nutrition, Physical Cardiovascular Nursing, Council on Epidemiology and Prevention; Council
Activity, and Metabolism. Circulation. 2004;110:2952–2967. doi: on the Kidney in Cardiovascular Disease, and Stroke Council. Assessing
10.1161/01.CIR.0000145546.97738.1E adiposity: a scientific statement from the American Heart Association.
2. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH; Circulation. 2011;124:1996–2019. doi: 10.1161/CIR.0b013e318233bc6a
on behalf of the American Heart Association; Obesity Committee of 16. World Health Organization. Waist Circumference and Waist–Hip Ratio:
the Council on Nutrition, Physical Activity, and Metabolism. Obesity Report of a WHO Expert Consultation, Geneva, 8–11 December 2008.
and cardiovascular disease: pathophysiology, evaluation, and effect of Geneva, Switzerland: World Health Organization; 2011.
weight loss: an update of the 1997 American Heart Association Scientific 17. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato
Statement on Obesity and Heart Disease from the Obesity Committee of KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE,
the Council on Nutrition, Physical Activity, and Metabolism. Circulation. Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM,
2006;113:898–918. doi: 10.1161/CIRCULATIONAHA.106.171016 Yanovski SZ. 2013 AHA/ACC/TOS guideline for the management of
3. Aune D, Sen A, Schlesinger S, Norat T, Janszky I, Romundstad P, Tonstad overweight and obesity in adults: a report of the American College of
S, Riboli E, Vatten LJ. Body mass index, abdominal fatness, fat mass and Cardiology/American Heart Association Task Force on Practice Guidelines
the risk of atrial fibrillation: a systematic review and dose-response meta- and The Obesity Society [published correction appears in Circulation.
analysis of prospective studies. Eur J Epidemiol. 2017;32:181–192. doi: 2014;129(suppl 2):S139–140]. Circulation. 2014;129(suppl 2):S102–
10.1007/s10654-017-0232-4 S138. doi: 10.1161/01.cir.0000437739.71477.ee
4. Mi Y, Yan S, Lu Y, Liang Y, Li C. Venous thromboembolism has the 18. Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit
same risk factors as atherosclerosis: a PRISMA-compliant systemic BK, Flegal KM. Trends in obesity prevalence among children and ado-
review and meta-analysis. Medicine (Baltimore). 2016;95:e4495. doi: lescents in the United States, 1988-1994 through 2013-2014. JAMA.
10.1097/MD.0000000000004495 2016;315:2292–2299. doi: 10.1001/jama.2016.6361
5. Wattanakit K, Lutsey PL, Bell EJ, Gornik H, Cushman M, Heckbert 19. National Center for Health Statistics. Health, United States, 2015: With
SR, Rosamond WD, Folsom AR. Association between cardiovascu- Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD:
lar disease risk factors and occurrence of venous thromboembolism: a National Center for Health Statistics; 2016. http://www.cdc.gov/nchs/
time-dependent analysis. Thromb Haemost. 2012;108:508–515. doi: data/hus/hus15.pdf. Accessed August 24, 2016.
10.1160/TH11-10-0726 20. Fryar CD, Carroll MD, Ogden CL. Prevalence of overweight and obesity
6. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends among children and adolescents aged 2–19 years: United States, 1963–
in obesity among adults in the United States, 2005 to 2014. JAMA. 1965 through 2013–2014. National Center for Health Statistics: Health
2016;315:2284–2291. doi: 10.1001/jama.2016.6458 E-Stats. Centers for Disease Control and Prevention website. July 2016.
7. Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity https://www.cdc.gov/nchs/data/hestat/obesity_child_13_14/obesity_
among adults and youth: United States, 2011–2014. NCHS Data Brief. child_13_14.htm. Accessed September 1, 2018.
2015;(219):1–8. 21. Frederick CB, Snellman K, Putnam RD. Increasing socioeconomic dispari-
8. Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in
Downloaded from http://ahajournals.org by on February 7, 2019

ties in adolescent obesity. Proc Natl Acad Sci U S A. 2014;111:1338–1342.

obesity and severe obesity prevalence in US youth and adults by sex doi: 10.1073/pnas.1321355110
and age, 2007–2008 to 2015–2016. JAMA. 2018;319:1723–1725. doi: 22. Ogden CL, Carroll MD, Fakhouri TH, Hales CM, Fryar CD, Li X, Freedman
10.1001/jama.2018.3060 DS. Prevalence of obesity among youths by household income and edu-
9. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn cation level of head of household: United States 2011-2014. MMWR
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow Morb Mortal Wkly Rep. 2018;67:186–189. doi: 10.15585/mmwr.
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm mm6706a3
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart 23. Kann L, McManus T, Harris WA, Shanklin SL, Flint KH, Hawkins J, Queen
Association Strategic Planning Task Force and Statistics Committee. B, Lowry R, Olsen EO, Chyen D, Whittle L, Thornton J, Lim C, Yamakawa
Defining and setting national goals for cardiovascular health promotion Y, Brener N, Zaza S. Youth Risk Behavior Surveillance: United States, 2015.
and disease reduction: the American Heart Association’s strategic Impact MMWR Surveill Summ. 2016;65:1–174. doi: 10.15585/mmwr.ss6506a1
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: 24. BRFSS Prevalence & Trends Data. Centers for Disease Control and
10.1161/CIRCULATIONAHA.109.192703 Prevention website. https://www.cdc.gov/brfss/brfssprevalence/index.
10. Rao G, Powell-Wiley TM, Ancheta I, Hairston K, Kirley K, Lear SA, North html. Accessed June 30, 2018.
KE, Palaniappan L, Rosal MC; on behalf of the American Heart Association 25. The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P. Association
Obesity Committee of the Council on Lifestyle and Cardiometabolic Health. of adolescent obesity with risk of severe obesity in adulthood. JAMA.
Identification of Obesity and Cardiovascular Risk in Ethnically and Racially 2010;304:2042–2047. doi: 10.1001/jama.2010.1635
Diverse Populations: A Scientific Statement From the American Heart 26. Daniels SR, Jacobson MS, McCrindle BW, Eckel RH, Sanner BM. American
Association [published correction appears in Circulation. 2015;132:e130]. Heart Association Childhood Obesity Research Summit: executive sum-
Circulation. 2015;132:457–472. doi: 10.1161/CIR.0000000000000223 mary. Circulation. 2009;119:2114–2123. doi: 10.1161/CIRCULATIONAHA.
11. WHO Expert Consultation. Appropriate body-mass index for Asian popu- 109.192215
lations and its implications for policy and intervention strategies [published 27. Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic risks
correction appears in Lancet. 2004;363:902]. Lancet. 2004;363:157–163. and severity of obesity in children and young adults. N Engl J Med.
12. CDC growth charts. Centers for Disease Control and Prevention website. 2015;373:1307–1317. doi: 10.1056/NEJMoa1502821
http://www.cdc.gov/growthcharts/cdc_charts.htm. Accessed July 13, 28. Umer A, Kelley GA, Cottrell LE, Giacobbi P Jr, Innes KE, Lilly CL.
2016. Childhood obesity and adult cardiovascular disease risk factors: a sys-
13. Ogden CL, Flegal KM. Changes in terminology for childhood overweight tematic review with meta-analysis. BMC Public Health. 2017;17:683. doi:
and obesity. Natl Health Stat Report. 2010;(25):1–5. 10.1186/s12889-017-4691-z
14. Kelly AS, Barlow SE, Rao G, Inge TH, Hayman LL, Steinberger J, Urbina 29. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA,
EM, Ewing LJ, Daniels SR; on behalf of the American Heart Association Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari
Atherosclerosis, Hypertension, and Obesity in the Young Committee of JS, Dwyer T, Raitakari OT. Childhood adiposity, adult adiposity, and
the Council on Cardiovascular Disease in the Young, Council on Nutrition, cardiovascular risk factors. N Engl J Med. 2011;365:1876–1885. doi:
Physical Activity and Metabolism, and Council on Clinical Cardiology. 10.1056/NEJMoa1010112
Severe obesity in children and adolescents: identification, associated 30. Kozak AT, Daviglus ML, Chan C, Kiefe CI, Jacobs DR Jr, Liu K. Relationship
health risks, and treatment approaches: a scientific statement from the of body mass index in young adulthood and health-related quality of life
American Heart Association. Circulation. 2013;128:1689–1712. doi: two decades later: the Coronary Artery Risk Development in Young Adults
10.1161/CIR.0b013e3182a5cfb3 study. Int J Obes (Lond). 2011;35:134–141. doi: 10.1038/ijo.2010.120

e100 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

31. Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB. fibrillation: yet another obesity paradox. Am J Med. 2010;123:646–651.

CLINICAL STATEMENTS
Metabolically healthy obesity and cardiovascular events: a systematic doi: 10.1016/j.amjmed.2009.11.026

AND GUIDELINES
review and meta-analysis. Eur J Prev Cardiol. 2016;23:956–966. doi: 48. Carnethon MR, De Chavez PJ, Biggs ML, Lewis CE, Pankow JS, Bertoni
10.1177/2047487315623884 AG, Golden SH, Liu K, Mukamal KJ, Campbell-Jenkins B, Dyer AR.
32. Khan SS, Ning H, Wilkins JT, Allen N, Carnethon M, Berry JD, Sweis Association of weight status with mortality in adults with incident dia-
RN, Lloyd-Jones DM. Association of body mass index with lifetime risk betes [published correction appears in JAMA. 2012;308:2085]. JAMA.
of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2012;308:581–590. doi: 10.1001/jama.2012.9282
2018;3:280–287. doi: 10.1001/jamacardio.2018.0022 49. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K,
33. Guidelines (2013) for managing overweight and obesity in adults. Preface Foco L, Gaye A, Gögele M, Heier M, Hiekkalinna T, Joensuu A, Newby
to the Expert Panel Report (comprehensive version which includes sys- C, Pang C, Partinen E, Reischl E, Schwienbacher C, Tammesoo ML,
tematic evidence review, evidence statements, and recommendations). Swertz MA, Burton P, Ferretti V, Fortier I, Giepmans L, Harris JR, Hillege
Obesity (Silver Spring). 2014;22(suppl 2):S40. doi: 10.1002/oby.20822 HL, Holmen J, Jula A, Kootstra-Ros JE, Kvaløy K, Holmen TL, Männistö S,
34. Goff DC Jr, Gillespie C, Howard G, Labarthe DR. Is the obesity epidemic Metspalu A, Midthjell K, Murtagh MJ, Peters A, Pramstaller PP, Saaristo
reversing favorable trends in blood pressure? Evidence from cohorts T, Salomaa V, Stolk RP, Uusitupa M, van der Harst P, van der Klauw MM,
born between 1890 and 1990 in the United States. Ann Epidemiol. Waldenberger M, Perola M, Wolffenbuttel BH. The prevalence of meta-
2012;22:554–561. doi: 10.1016/j.annepidem.2012.04.021 bolic syndrome and metabolically healthy obesity in Europe: a collabora-
35. Llewellyn A, Simmonds M, Owen CG, Woolacott N. Childhood obesity tive analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.
as a predictor of morbidity in adulthood: a systematic review and meta- doi: 10.1186/1472-6823-14-9
analysis. Obes Rev. 2016;17:56–67. doi: 10.1111/obr.12316 50. Hamer M, Bell JA, Sabia S, Batty GD, Kivimäki M. Stability of metabolically
36. Twig G, Yaniv G, Levine H, Leiba A, Goldberger N, Derazne E, Ben-Ami healthy obesity over 8 years: the English Longitudinal Study of Ageing. Eur
Shor D, Tzur D, Afek A, Shamiss A, Haklai Z, Kark JD. Body-mass index in J Endocrinol. 2015;173:703–708. doi: 10.1530/EJE-15-0449
2.3 million adolescents and cardiovascular death in adulthood. N Engl J 51. Fung MD, Canning KL, Mirdamadi P, Ardern CI, Kuk JL. Lifestyle and
Med. 2016;374:2430–2440. doi: 10.1056/NEJMoa1503840 weight predictors of a healthy overweight profile over a 20-year
37. Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, follow-up. Obesity (Silver Spring). 2015;23:1320–1325. doi: 10.1002/
Kaptoge S, Whitlock G, Qiao Q, Lewington S, Di Angelantonio E, Vander oby.21087
Hoorn S, Lawes CM, Ali MK, Mozaffarian D, Ezzati M; Global Burden 52. Mongraw-Chaffin M, Foster MC, Anderson CAM, Burke GL, Haq N, Kalyani
of Metabolic Risk Factors of Chronic Diseases Collaborating Group; Asia- RR, Ouyang P, Sibley CT, Tracy R, Woodward M, Vaidya D. Metabolically
Pacific Cohort Studies Collaboration (APCSC); Diabetes Epidemiology: healthy obesity, transition to metabolic syndrome, and cardiovascular risk.
Collaborative analysis of Diagnostic criteria in Europe (DECODE); Emerging J Am Coll Cardiol. 2018;71:1857–1865. doi: 10.1016/j.jacc.2018.02.055
Risk Factor Collaboration (ERFC); Prospective Studies Collaboration (PSC). 53. Mørkedal B, Vatten LJ, Romundstad PR, Laugsand LE, Janszky I. Risk of
The age-specific quantitative effects of metabolic risk factors on cardiovas- myocardial infarction and heart failure among metabolically healthy but
cular diseases and diabetes: a pooled analysis. PLoS One. 2013;8:e65174. obese individuals: HUNT (Nord-Trøndelag Health Study), Norway. J Am
doi: 10.1371/journal.pone.0065174 Coll Cardiol. 2014;63:1071–1078. doi: 10.1016/j.jacc.2013.11.035
38. McTigue KM, Chang YF, Eaton C, Garcia L, Johnson KC, Lewis CE, Liu 54. Janszky I, Romundstad P, Laugsand LE, Vatten LJ, Mukamal KJ, Mørkedal
S, Mackey RH, Robinson J, Rosal MC, Snetselaar L, Valoski A, Kuller B. Weight and weight change and risk of acute myocardial infarction and
LH. Severe obesity, heart disease, and death among white, African heart failure: the HUNT Study. J Intern Med. 2016;280:312–322. doi:
American, and Hispanic postmenopausal women. Obesity (Silver Spring). 10.1111/joim.12494
2014;22:801–810. doi: 10.1002/oby.20224 55. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC.
Downloaded from http://ahajournals.org by on February 7, 2019

39. Emerging Risk Factors Collaboration. Separate and combined associations Childhood obesity, other cardiovascular risk factors, and premature death.
of body-mass index and abdominal adiposity with cardiovascular disease: N Engl J Med. 2010;362:485–493. doi: 10.1056/NEJMoa0904130
collaborative analysis of 58 prospective studies. Lancet. 2011;377:1085– 56. Ma J, Flanders WD, Ward EM, Jemal A. Body mass index in young adult-
1095. doi: 10.1016/S0140-6736(11)60105-0 hood and premature death: analyses of the US National Health Interview
40. Burke GL, Bertoni AG, Shea S, Tracy R, Watson KE, Blumenthal RS, Survey linked mortality files. Am J Epidemiol. 2011;174:934–944. doi:
Chung H, Carnethon MR. The impact of obesity on cardiovascular 10.1093/aje/kwr169
disease risk factors and subclinical vascular disease: the Multi-Ethnic 57. Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associ-
Study of Atherosclerosis. Arch Intern Med. 2008;168:928–935. doi: ated with underweight, overweight, and obesity. JAMA. 2005;293:1861–
10.1001/archinte.168.9.928 1867. doi: 10.1001/jama.293.15.1861
41. Reis JP, Loria CM, Lewis CE, Powell-Wiley TM, Wei GS, Carr JJ, Terry JG, Liu 58. McGee DL; Diverse Populations Collaboration. Body mass index and
K. Association between duration of overall and abdominal obesity begin- mortality: a meta-analysis based on person-level data from twenty-
ning in young adulthood and coronary artery calcification in middle age. six observational studies. Ann Epidemiol. 2005;15:87–97. doi:
JAMA. 2013;310:280–288. doi: 10.1001/jama.2013.7833 10.1016/j.annepidem.2004.05.012
42. Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. 59. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortal-
Excess body weight and incidence of stroke: meta-analysis of prospec- ity with overweight and obesity using standard body mass index catego-
tive studies with 2 million participants. Stroke. 2010;41:e418–e426. doi: ries: a systematic review and meta-analysis. JAMA. 2013;309:71–82. doi:
10.1161/STROKEAHA.109.576967 10.1001/jama.2012.113905
43. Chatterjee NA, Giulianini F, Geelhoed B, Lunetta KL, Misialek JR, 60. Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD.
Niemeijer MN, Rienstra M, Rose LM, Smith AV, Arking DE, Ellinor PT, Body-weight fluctuations and outcomes in coronary disease. N Engl J
Heeringa J, Lin H, Lubitz SA, Soliman EZ, Verweij N, Alonso A, Benjamin Med. 2017;376:1332–1340. doi: 10.1056/NEJMoa1606148
EJ, Gudnason V, Stricker BHC, Van Der Harst P, Chasman DI, Albert 61. Aune D, Sen A, Prasad M, Norat T, Janszky I, Tonstad S, Romundstad
CM. Genetic obesity and the risk of atrial fibrillation: causal estimates P, Vatten LJ. BMI and all cause mortality: systematic review and non-
from mendelian randomization. Circulation. 2017;135:741–754. doi: linear dose-response meta-analysis of 230 cohort studies with 3.74 mil-
10.1161/CIRCULATIONAHA.116.024921 lion deaths among 30.3 million participants. BMJ. 2016;353:i2156. doi:
44. Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife 10.1136/bmj.i2156
and late-life as a risk factor for dementia: a meta-analysis of prospec- 62. Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J,
tive studies. Obes Rev. 2011;12:e426–e437. doi: 10.1111/j.1467-789X. Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortal-
2010.00825.x ity in 900 000 adults: collaborative analyses of 57 prospective studies.
45. Loef M, Walach H. Midlife obesity and dementia: meta-analysis and Lancet. 2009;373:1083–1096. doi: 10.1016/S0140-6736(09)60318-4
adjusted forecast of dementia prevalence in the United States and China. 63. Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L,
Obesity (Silver Spring). 2013;21:E51–E55. doi: 10.1002/oby.20037 MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson
46. Chang VW, Langa KM, Weir D, Iwashyna TJ. The obesity paradox and WL, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson
incident cardiovascular disease: A population-based study. PLoS One. N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet
2017;12:e0188636. doi: 10.1371/journal.pone.0188636 MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ,
47. Badheka AO, Rathod A, Kizilbash MA, Garg N, Mohamad T, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ. Body-mass index
Afonso L, Jacob S. Influence of obesity on outcomes in atrial and mortality among 1.46 million white adults [published correction

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e101

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

appears in N Engl J Med. 2011;365:869]. N Engl J Med. 2010;363:2211– 83. Makary MA, Clark JM, Shore AD, Magnuson TH, Richards T, Bass
CLINICAL STATEMENTS

2219. doi: 10.1056/NEJMoa1000367 EB, Dominici F, Weiner JP, Wu AW, Segal JB. Medication utilization
AND GUIDELINES

64. Das SR, Alexander KP, Chen AY, Powell-Wiley TM, Diercks DB, Peterson and annual health care costs in patients with type 2 diabetes mel-
ED, Roe MT, de Lemos JA. Impact of body weight and extreme obesity on litus before and after bariatric surgery [published correction appears
the presentation, treatment, and in-hospital outcomes of 50,149 patients in Arch Surg. 2011;146:659]. Arch Surg. 2010;145:726–731. doi:
with ST-segment elevation myocardial infarction: results from the NCDR 10.1001/archsurg.2010.150
(National Cardiovascular Data Registry). J Am Coll Cardiol. 2011;58:2642– 84. Keating C, Neovius M, Sjöholm K, Peltonen M, Narbro K, Eriksson JK,
2650. doi: 10.1016/j.jacc.2011.09.030 Sjöström L, Carlsson LM. Health-care costs over 15 years after bariat-
65. Terada T, Forhan M, Norris CM, Qiu W, Padwal R, Sharma AM, Nagendran ric surgery for patients with different baseline glucose status: results
J, Johnson JA. Differences in short- and long-term mortality associ- from the Swedish Obese Subjects study [published correction appears
ated with BMI following coronary revascularization. J Am Heart Assoc. in Lancet Diabetes Endocrinol. 2015;3:e11]. Lancet Diabetes Endocrinol.
2017;6:e005335. doi: 10.1161/JAHA.116.005335 2015;3:855–865. doi: 10.1016/S2213-8587(15)00290-9
66. Mariscalco G, Wozniak MJ, Dawson AG, Serraino GF, Porter R, Nath M, 85. Banerjee S, Garrison LP Jr, Flum DR, Arterburn DE. Cost and health
Klersy C, Kumar T, Murphy GJ. Body mass index and mortality among care utilization implications of bariatric surgery versus intensive lifestyle
adults undergoing cardiac surgery: a nationwide study with a system- and medical intervention for type 2 diabetes. Obesity (Silver Spring).
atic review and meta-analysis. Circulation. 2017;135:850–863. doi: 2017;25:1499–1508. doi: 10.1002/oby.21927
10.1161/CIRCULATIONAHA.116.022840 86. Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur
67. Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all- C. Bariatric surgery for nonalcoholic steatohepatitis: a clinical and
cause and cardiovascular disease mortality. J Clin Endocrinol Metab. cost-effectiveness analysis. Hepatology. 2017;65:1156–1164. doi:
2012;97:2482–2488. doi: 10.1210/jc.2011-3475 10.1002/hep.28958
68. Petursson H, Sigurdsson JA, Bengtsson C, Nilsen TI, Getz L. Body con- 87. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and
figuration as a predictor of mortality: comparison of five anthropometric adult obesity in the United States, 2011-2012. JAMA. 2014;311:806–
measures in a 12 year follow-up of the Norwegian HUNT 2 study. PLoS 814. doi: 10.1001/jama.2014.732
One. 2011;6:e26621. doi: 10.1371/journal.pone.0026621 88. Saydah S, Bullard KM, Cheng Y, Ali MK, Gregg EW, Geiss L, Imperatore
69. Després JP. Excess visceral adipose tissue/ectopic fat the missing link G. Trends in cardiovascular disease risk factors by obesity level in adults
in the obesity paradox? J Am Coll Cardiol. 2011;57:1887–1889. doi: in the United States, NHANES 1999-2010. Obesity (Silver Spring).
10.1016/j.jacc.2010.10.063 2014;22:1888–1895. doi: 10.1002/oby.20761
70. Cerhan JR, Moore SC, Jacobs EJ, Kitahara CM, Rosenberg PS, Adami HO, 89. Freedman DS, Ford ES. Are the recent secular increases in the waist cir-
Ebbert JO, English DR, Gapstur SM, Giles GG, Horn-Ross PL, Park Y, Patel cumference of adults independent of changes in BMI? Am J Clin Nutr.
AV, Robien K, Weiderpass E, Willett WC, Wolk A, Zeleniuch-Jacquotte 2015;101:425–431. doi: 10.3945/ajcn.114.094672
A, Hartge P, Bernstein L, Berrington de Gonzalez A. A pooled analysis 90. Feng J, Glass TA, Curriero FC, Stewart WF, Schwartz BS. The built envi-
of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. ronment and obesity: a systematic review of the epidemiologic evi-
2014;89:335–345. doi: 10.1016/j.mayocp.2013.11.011 dence. Health Place. 2010;16:175–190. doi: 10.1016/j.healthplace.
71. Adabag S, Huxley RR, Lopez FL, Chen LY, Sotoodehnia N, Siscovick D, 2009.09.008
Deo R, Konety S, Alonso A, Folsom AR. Obesity related risk of sudden 91. Cooklin A, Joss N, Husser E, Oldenburg B. Integrated approaches to oc-
cardiac death in the atherosclerosis risk in communities study. Heart. cupational health and safety: a systematic review. Am J Health Promot.
2015;101:215–221. doi: 10.1136/heartjnl-2014-306238 2017;31:401–412. doi: 10.4278/ajhp.141027-LIT-542
72. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spend- 92. Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obe-
Downloaded from http://ahajournals.org by on February 7, 2019

ing attributable to obesity: payer-and service-specific estimates. Health Aff sity from childhood obesity: a systematic review and meta-analysis. Obes
(Millwood). 2009;28:w822–w831. doi: 10.1377/hlthaff.28.5.w822 Rev. 2016;17:95–107. doi: 10.1111/obr.12334
73. An R. Health care expenses in relation to obesity and smoking among 93. Centers for Disease Control and Prevention. Centers for Disease Control
U.S. adults by gender, race/ethnicity, and age group: 1998-2011. Public and Prevention website. Prevention Status Reports. 2016. http://www.
Health. 2015;129:29–36. doi: 10.1016/j.puhe.2014.11.003 cdc.gov/psr/. Accessed June 8, 2016.
74. Cai L, Lubitz J, Flegal KM, Pamuk ER. The predicted effects of chronic 94. World Obesity Federation. Policies and interventions. World Obesity
obesity in middle age on Medicare costs and mortality. Med Care. Federation website. 2015. http://www.worldobesity.org/resources/poli-
2010;48:510–517. doi: 10.1097/MLR.0b013e3181dbdb20 cies-and-interventions/. Accessed June 8, 2016.
75. Alley D, Lloyd J, Shaffer T, Stuart B. Changes in the association between 95. Duncan DT, Wolin KY, Scharoun-Lee M, Ding EL, Warner ET, Bennett GG.
body mass index and Medicare costs, 1997-2006. Arch Intern Med. Does perception equal reality? Weight misperception in relation to weight-
2012;172:277–278. doi: 10.1001/archinternmed.2011.702 related attitudes and behaviors among overweight and obese US adults.
76. Lightwood J, Bibbins-Domingo K, Coxson P, Wang YC, Williams L, Int J Behav Nutr Phys Act. 2011;8:20. doi: 10.1186/1479-5868-8-20
Goldman L. Forecasting the future economic burden of current adolescent 96. Hansen AR, Duncan DT, Baidal JA, Hill A, Turner SC, Zhang J. An in-
overweight: an estimate of the coronary heart disease policy model. Am J creasing trend in health care professionals notifying children of unhealthy
Public Health. 2009;99:2230–2237. doi: 10.2105/AJPH.2008.152595 weight status: NHANES 1999–2014. Int J Obes (Lond). 2016;40:1480–
77. Finkelstein EA, Graham WC, Malhotra R. Lifetime direct medical costs 1485. doi: 10.1038/ijo.2016.85
of childhood obesity. Pediatrics. 2014;133:854–862. doi: 10.1542/peds. 97. The Look AHEAD Research Group. Cardiovascular effects of intensive
2014-0063 lifestyle intervention in type 2 diabetes [published correction appears in
78. Livingston EH. The incidence of bariatric surgery has plateaued in the U.S. N Engl J Med. 2014;370:1866]. N Engl J Med. 2013;369:145–154. doi:
Am J Surg. 2010;200:378–385. doi: 10.1016/j.amjsurg.2009.11.007 10.1056/NEJMoa1212914
79. Finkelstein EA, Allaire BT, Dibonaventura MD, Burgess SM. Incorporating 98. Look AHEAD Research Group. Eight-year weight losses with an inten-
indirect costs into a cost-benefit analysis of laparoscopic adjustable gastric sive lifestyle intervention: the Look AHEAD study. Obesity (Silver Spring).
banding. Value Health. 2012;15:299–304. doi: 10.1016/j.jval.2011.12.004 2014;22:5–13. doi: 10.1002/oby.20662
80. Wang BC, Wong ES, Alfonso-Cristancho R, He H, Flum DR, Arterburn DE, 99. Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del
Garrison LP, Sullivan SD. Cost-effectiveness of bariatric surgical procedures Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-
for the treatment of severe obesity. Eur J Health Econ. 2014;15:253–263. Oldenburg G, Cummings DE; Delegates of the 2nd Diabetes Surgery
doi: 10.1007/s10198-013-0472-5 Summit. Metabolic surgery in the treatment algorithm for type 2 diabe-
81. Maciejewski ML, Livingston EH, Smith VA, Kahwati LC, Henderson WG, tes: a joint statement by international diabetes organizations. Diabetes
Arterburn DE. Health expenditures among high-risk patients after gas- Care. 2016;39:861–877. doi: 10.2337/dc16-0236
tric bypass and matched controls. Arch Surg. 2012;147:633–640. doi: 100. Ho M, Garnett SP, Baur L, Burrows T, Stewart L, Neve M, Collins C.
10.1001/archsurg.2012.818 Effectiveness of lifestyle interventions in child obesity: systematic re-
82. Weiner JP, Goodwin SM, Chang HY, Bolen SD, Richards TM, Johns view with meta-analysis. Pediatrics. 2012;130:e1647–e1671. doi:
RA, Momin SR, Clark JM. Impact of bariatric surgery on health care 10.1542/peds.2012-1176
costs of obese persons: a 6-year follow-up of surgical and comparison 101. Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C,
cohorts using health plan data. JAMA Surg. 2013;148:555–562. doi: Sharma P, Fraser C, MacLennan G. Effects of weight loss interventions
10.1001/jamasurg.2013.1504 for adults who are obese on mortality, cardiovascular disease, and

e102 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849. doi: Clarke R, Coin L, Connell J, Day IN, den Heijer M, Duan J, Ebrahim S,

CLINICAL STATEMENTS
10.1136/bmj.j4849 Elliott P, Elosua R, Eiriksdottir G, Erdos MR, Eriksson JG, Facheris MF, Felix

AND GUIDELINES
102. Sjöström CD, Lystig T, Lindroos AK. Impact of weight change, secu- SB, Fischer-Posovszky P, Folsom AR, Friedrich N, Freimer NB, Fu M, Gaget
lar trends and ageing on cardiovascular risk factors: 10-year experi- S, Gejman PV, Geus EJ, Gieger C, Gjesing AP, Goel A, Goyette P, Grallert
ences from the SOS study. Int J Obes (Lond). 2011;35:1413–1420. doi: H, Grässler J, Greenawalt DM, Groves CJ, Gudnason V, Guiducci C,
10.1038/ijo.2010.282 Hartikainen AL, Hassanali N, Hall AS, Havulinna AS, Hayward C, Heath
103. Wefers JF, Woodlief TL, Carnero EA, Helbling NL, Anthony SJ, Dubis GS, AC, Hengstenberg C, Hicks AA, Hinney A, Hofman A, Homuth G, Hui J,
Jakicic JM, Houmard JA, Goodpaster BH, Coen PM. Relationship among Igl W, Iribarren C, Isomaa B, Jacobs KB, Jarick I, Jewell E, John U,
physical activity, sedentary behaviors, and cardiometabolic risk factors Jørgensen T, Jousilahti P, Jula A, Kaakinen M, Kajantie E, Kaplan LM,
during gastric bypass surgery-induced weight loss. Surg Obes Relat Dis. Kathiresan S, Kettunen J, Kinnunen L, Knowles JW, Kolcic I, König IR,
2017;13:210–219. doi: 10.1016/j.soard.2016.08.493 Koskinen S, Kovacs P, Kuusisto J, Kraft P, Kvaløy K, Laitinen J, Lantieri O,
104. Shubeck S, Dimick JB, Telem DA. Long-term outcomes following bariatric Lanzani C, Launer LJ, Lecoeur C, Lehtimäki T, Lettre G, Liu J, Lokki ML,
surgery. JAMA. 2018;319:302–303. doi: 10.1001/jama.2017.20521 Lorentzon M, Luben RN, Ludwig B, Manunta P, Marek D, Marre M,
105. Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic Martin NG, McArdle WL, McCarthy A, McKnight B, Meitinger T, Melander
conditions in adults. BMJ. 2014;349:g3961. doi: 10.1136/bmj.g3961 O, Meyre D, Midthjell K, Montgomery GW, Morken MA, Morris AP, Mulic
106. Puzziferri N, Roshek TB 3rd, Mayo HG, Gallagher R, Belle SH, Livingston R, Ngwa JS, Nelis M, Neville MJ, Nyholt DR, O’Donnell CJ, O’Rahilly S,
EH. Long-term follow-up after bariatric surgery: a systematic review. Ong KK, Oostra B, Paré G, Parker AN, Perola M, Pichler I, Pietiläinen KH,
JAMA. 2014;312:934–942. doi: 10.1001/jama.2014.10706 Platou CG, Polasek O, Pouta A, Rafelt S, Raitakari O, Rayner NW,
107. Marma AK, Berry JD, Ning H, Persell SD, Lloyd-Jones DM. Distribution Ridderstråle M, Rief W, Ruokonen A, Robertson NR, Rzehak P, Salomaa V,
of 10-year and lifetime predicted risks for cardiovascular disease in US Sanders AR, Sandhu MS, Sanna S, Saramies J, Savolainen MJ, Scherag S,
adults: findings from the National Health and Nutrition Examination Schipf S, Schreiber S, Schunkert H, Silander K, Sinisalo J, Siscovick DS,
Survey 2003 to 2006. Circ Cardiovasc Qual Outcomes. 2010;3:8–14. doi: Smit JH, Soranzo N, Sovio U, Stephens J, Surakka I, Swift AJ, Tammesoo
10.1161/CIRCOUTCOMES.109.869727 ML, Tardif JC, Teder-Laving M, Teslovich TM, Thompson JR, Thomson B,
108. Gloy VL, Briel M, Bhatt DL, Kashyap SR, Schauer PR, Mingrone G, Bucher Tönjes A, Tuomi T, van Meurs JB, van Ommen GJ, Vatin V, Viikari J,
HC, Nordmann AJ. Bariatric surgery versus non-surgical treatment for Visvikis-Siest S, Vitart V, Vogel CI, Voight BF, Waite LL, Wallaschofski H,
obesity: a systematic review and meta-analysis of randomised controlled Walters GB, Widen E, Wiegand S, Wild SH, Willemsen G, Witte DR,
trials. BMJ. 2013;347:f5934. doi: 10.1136/bmj.f5934 Witteman JC, Xu J, Zhang Q, Zgaga L, Ziegler A, Zitting P, Beilby JP,
109. Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN, Farooqi IS, Hebebrand J, Huikuri HV, James AL, Kähönen M, Levinson DF,
Gutierrez JM, Frogley SJ, Ibele AR, Brinton EA, Hopkins PN, McKinlay Macciardi F, Nieminen MS, Ohlsson C, Palmer LJ, Ridker PM, Stumvoll M,
R, Simper SC, Hunt SC. Weight and metabolic outcomes 12 years Beckmann JS, Boeing H, Boerwinkle E, Boomsma DI, Caulfield MJ,
after gastric bypass. N Engl J Med. 2017;377:1143–1155. doi: Chanock SJ, Collins FS, Cupples LA, Smith GD, Erdmann J, Froguel P,
10.1056/NEJMoa1700459 Grönberg H, Gyllensten U, Hall P, Hansen T, Harris TB, Hattersley AT,
110. Salminen P, Helmiö M, Ovaska J, Juuti A, Leivonen M, Peromaa-Haavisto Hayes RB, Heinrich J, Hu FB, Hveem K, Illig T, Jarvelin MR, Kaprio J, Karpe
P, Hurme S, Soinio M, Nuutila P, Victorzon M. Effect of laparoscopic sleeve F, Khaw KT, Kiemeney LA, Krude H, Laakso M, Lawlor DA, Metspalu A,
gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss at 5 Munroe PB, Ouwehand WH, Pedersen O, Penninx BW, Peters A,
years among patients with morbid obesity: the SLEEVEPASS randomized Pramstaller PP, Quertermous T, Reinehr T, Rissanen A, Rudan I, Samani NJ,
clinical trial. JAMA. 2018;319:241–254. doi: 10.1001/jama.2017.20313 Schwarz PE, Shuldiner AR, Spector TD, Tuomilehto J, Uda M, Uitterlinden
111. Van Osdol AD, Grover BT, Borgert AJ, Kallies KJ, Kothari SN. Impact of A, Valle TT, Wabitsch M, Waeber G, Wareham NJ, Watkins H, Wilson JF,
Downloaded from http://ahajournals.org by on February 7, 2019

laparoscopic Roux-en-Y Gastric bypass versus sleeve gastrectomy on Wright AF, Zillikens MC, Chatterjee N, McCarroll SA, Purcell S, Schadt EE,
postoperative lipid values. Surg Obes Relat Dis. 2017;13:399–403. doi: Visscher PM, Assimes TL, Borecki IB, Deloukas P, Fox CS, Groop LC,
10.1016/j.soard.2016.09.031 Haritunians T, Hunter DJ, Kaplan RC, Mohlke KL, O’Connell JR, Peltonen
112. Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond L, Schlessinger D, Strachan DP, van Duijn CM, Wichmann HE, Frayling
WD, Lamonte MJ, Stroup AM, Hunt SC. Long-term mortal- TM, Thorsteinsdottir U, Abecasis GR, Barroso I, Boehnke M, Stefansson
ity after gastric bypass surgery. N Engl J Med. 2007;357:753–761. doi: K, North KE, McCarthy MI, Hirschhorn JN, Ingelsson E, Loos RJ; MAGIC;
10.1056/NEJMoa066603 Procardis Consortium. Association analyses of 249,796 individuals reveal
113. Viner R, White B, Christie D. Type 2 diabetes in adolescents: a severe 18 new loci associated with body mass index. Nat Genet. 2010;42:937–
phenotype posing major clinical challenges and public health burden. 948. doi: 10.1038/ng.686
Lancet. 2017;389:2252–2260. doi: 10.1016/S0140-6736(17)31371-5 117. Kaur Y, de Souza RJ, Gibson WT, Meyre D. A systematic review of
114. Vilarrasa N, Rubio MA, Miñambres I, Flores L, Caixàs A, Ciudin A, Bueno genetic syndromes with obesity. Obes Rev. 2017;18:603–634. doi:
M, García-Luna PP, Ballesteros-Pomar MD, Ruiz-Adana M, Lecube A. 10.1111/obr.12531.
Long-term outcomes in patients with morbid obesity and type 1 dia- 118. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren
betes undergoing bariatric surgery. Obes Surg. 2017;27:856–863. doi: CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett
10.1007/s11695-016-2390-y JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor
115. Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D,
influence on childhood adiposity despite the force of the obesogenic envi- Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon
ronment. Am J Clin Nutr. 2008;87:398–404. doi: 10.1093/ajcn/87.2.398 LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD,
116. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Hattersley AT, McCarthy MI. A common variant in the FTO gene is as-
Lango Allen H, Lindgren CM, Luan J, Mägi R, Randall JC, Vedantam S, sociated with body mass index and predisposes to childhood and adult
Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham obesity. Science. 2007;316:889–894. doi: 10.1126/science.1141634
HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segrè AV, 119. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja
Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpeläinen TO, Yang R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret
J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Raychaudhuri GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger
S, Scherag A, Smith AV, Welch R, Zhao JH, Aben KK, Absher DM, Amin D, Cao A, Lakatta E, Abecasis GR. Genome-wide association scan shows
N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, genetic variants in the FTO gene are associated with obesity-related
Hottenga JJ, Johansson A, Johnson T, Ketkar S, Lamina C, Li S, Moffatt traits. PLoS Genet. 2007;3:e115. doi: 10.1371/journal.pgen.0030115
MF, Myers RH, Narisu N, Perry JR, Peters MJ, Preuss M, Ripatti S, 120. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ,
Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, Tyrer JP, van Wingerden Park M, Cha SH, Kim JW, Han BG, Min H, Ahn Y, Park MS, Han HR, Jang
S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, HY, Cho EY, Lee JE, Cho NH, Shin C, Park T, Park JW, Lee JK, Cardon L,
Cooper MN, Jansson JO, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Clarke G, McCarthy MI, Lee JY, Lee JK, Oh B, Kim HL. A large-scale ge-
Thiering E, Alavere H, Alibrandi MT, Almgren P, Arnold AM, Aspelund T, nome-wide association study of Asian populations uncovers genetic fac-
Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman tors influencing eight quantitative traits. Nat Genet. 2009;41:527–534.
RN, Bergmann S, Biebermann H, Blakemore AI, Boes T, Bonnycastle LL, doi: 10.1038/ng.357
Bornstein SR, Brown MJ, Buchanan TA, Busonero F, Campbell H, 121. Wen W, Cho YS, Zheng W, Dorajoo R, Kato N, Qi L, Chen CH, Delahanty
Cappuccio FP, Cavalcanti-Proença C, Chen YD, Chen CM, Chines PS, RJ, Okada Y, Tabara Y, Gu D, Zhu D, Haiman CA, Mo Z, Gao YT, Saw SM,

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e103

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

Go MJ, Takeuchi F, Chang LC, Kokubo Y, Liang J, Hao M, Le Marchand JD, Hakonarson H, Levin AM, Nathanson KL, Ware EB, Weir DR, Zhao
CLINICAL STATEMENTS

L, Zhang Y, Hu Y, Wong TY, Long J, Han BG, Kubo M, Yamamoto K, Su W, Zhi D, Arnett DK, Grant SFA, Kardia SLR, Oloapde OI, Rao DC, Rotimi
AND GUIDELINES

MH, Miki T, Henderson BE, Song H, Tan A, He J, Ng DP, Cai Q, Tsunoda T, CN, Sale MM, Williams LK, Zemel BS, Becker DM, Borecki IB, Evans MK,
Tsai FJ, Iwai N, Chen GK, Shi J, Xu J, Sim X, Xiang YB, Maeda S, Ong RT, Harris TB, Hirschhorn JN, Li Y, Patel SR, Psaty BM, Rotter JI, Wilson JG,
Li C, Nakamura Y, Aung T, Kamatani N, Liu JJ, Lu W, Yokota M, Seielstad Bowden DW, Cupples LA, Haiman CA, Loos RJF, North KE; Bone Mineral
M, Fann CS, Wu JY, Lee JY, Hu FB, Tanaka T, Tai ES, Shu XO; Genetic Density in Childhood Study (BMDCS) Group. Discovery and fine-map-
Investigation of ANthropometric Traits (GIANT) Consortium. Meta- ping of adiposity loci using high density imputation of genome-wide
analysis identifies common variants associated with body mass index in association studies in individuals of African ancestry: African Ancestry
east Asians. Nat Genet. 2012;44:307–311. doi: 10.1038/ng.1087 Anthropometry Genetics Consortium. PLoS Genet. 2017;13:e1006719.
122. Okada Y, Kubo M, Ohmiya H, Takahashi A, Kumasaka N, Hosono doi: 10.1371/journal.pgen.1006719
N, Maeda S, Wen W, Dorajoo R, Go MJ, Zheng W, Kato N, GIANT 128. Justice AE, Winkler TW, Feitosa MF, Graff M, Fisher VA, Young K, Barata
Consortium,Wu JY, Lu Q, Tsunoda T, Yamamoto K, Nakamura Y, L, Deng X, Czajkowski J, Hadley D, Ngwa JS, Ahluwalia TS, Chu AY,
Kamatani N, Tanaka T. Common variants at CDKAL1 and KLF9 are as- Heard-Costa NL, Lim E, Perez J, Eicher JD, Kutalik Z, Xue L, Mahajan A,
sociated with body mass index in east Asian populations. Nat Genet. Renström F, Wu J, Qi Q, Ahmad S, Alfred T, Amin N, Bielak LF, Bonnefond
2012;44:302–306. doi: 10.1038/ng.1086 A, Bragg J, Cadby G, Chittani M, Coggeshall S, Corre T, Direk N, Eriksson
123. Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng J, Fischer K, Gorski M, Neergaard Harder M, Horikoshi M, Huang T,
MC, Adeyemo AA, Allison MA, Bielak LF, Chen G, Graff M, Irvin MR, Huffman JE, Jackson AU, Justesen JM, Kanoni S, Kinnunen L, Kleber ME,
Rhie SK, Li G, Liu Y, Liu Y, Lu Y, Nalls MA, Sun YV, Wojczynski MK, Yanek Komulainen P, Kumari M, Lim U, Luan J, Lyytikäinen LP, Mangino M,
LR, Aldrich MC, Ademola A, Amos CI, Bandera EV, Bock CH, Britton A, Manichaikul A, Marten J, Middelberg RPS, Müller-Nurasyid M, Navarro
Broeckel U, Cai Q, Caporaso NE, Carlson CS, Carpten J, Casey G, Chen P, Pérusse L, Pervjakova N, Sarti C, Smith AV, Smith JA, Stančáková A,
WM, Chen F, Chen YD, Chiang CW, Coetzee GA, Demerath E, Deming- Strawbridge RJ, Stringham HM, Sung YJ, Tanaka T, Teumer A, Trompet S,
Halverson SL, Driver RW, Dubbert P, Feitosa MF, Feng Y, Freedman BI, van der Laan SW, van der Most PJ, Van Vliet-Ostaptchouk JV, Vedantam
Gillanders EM, Gottesman O, Guo X, Haritunians T, Harris T, Harris SL, Verweij N, Vink JM, Vitart V, Wu Y, Yengo L, Zhang W, Hua Zhao
CC, Hennis AJ, Hernandez DG, McNeill LH, Howard TD, Howard BV, J, Zimmermann ME, Zubair N, Abecasis GR, Adair LS, Afaq S, Afzal
Howard VJ, Johnson KC, Kang SJ, Keating BJ, Kolb S, Kuller LH, Kutlar A, U, Bakker SJL, Bartz TM, Beilby J, Bergman RN, Bergmann S, Biffar R,
Langefeld CD, Lettre G, Lohman K, Lotay V, Lyon H, Manson JE, Maixner Blangero J, Boerwinkle E, Bonnycastle LL, Bottinger E, Braga D, Buckley
W, Meng YA, Monroe KR, Morhason-Bello I, Murphy AB, Mychaleckyj BM, Buyske S, Campbell H, Chambers JC, Collins FS, Curran JE, de Borst
JC, Nadukuru R, Nathanson KL, Nayak U, N’diaye A, Nemesure B, Wu SY, GJ, de Craen AJM, de Geus EJC, Dedoussis G, Delgado GE, den Ruijter
Leske MC, Neslund-Dudas C, Neuhouser M, Nyante S, Ochs-Balcom H, HM, Eiriksdottir G, Eriksson AL, Esko T, Faul JD, Ford I, Forrester T, Gertow
Ogunniyi A, Ogundiran TO, Ojengbede O, Olopade OI, Palmer JR, Ruiz- K, Gigante B, Glorioso N, Gong J, Grallert H, Grammer TB, Grarup N,
Narvaez EA, Palmer ND, Press MF, Rampersaud E, Rasmussen-Torvik LJ, Haitjema S, Hallmans G, Hamsten A, Hansen T, Harris TB, Hartman CA,
Rodriguez-Gil JL, Salako B, Schadt EE, Schwartz AG, Shriner DA, Siscovick Hassinen M, Hastie ND, Heath AC, Hernandez D, Hindorff L, Hocking LJ,
D, Smith SB, Wassertheil-Smoller S, Speliotes EK, Spitz MR, Sucheston L, Hollensted M, Holmen OL, Homuth G, Jan Hottenga J, Huang J, Hung J,
Taylor H, Tayo BO, Tucker MA, Van Den Berg DJ, Edwards DR, Wang Z, Hutri-Kähönen N, Ingelsson E, James AL, Jansson JO, Jarvelin MR, Jhun
Wiencke JK, Winkler TW, Witte JS, Wrensch M, Wu X, Yang JJ, Levin AM, MA, Jørgensen ME, Juonala M, Kähönen M, Karlsson M, Koistinen HA,
Young TR, Zakai NA, Cushman M, Zanetti KA, Zhao JH, Zhao W, Zheng Kolcic I, Kolovou G, Kooperberg C, Krämer BK, Kuusisto J, Kvaløy K,
Y, Zhou J, Ziegler RG, Zmuda JM, Fernandes JK, Gilkeson GS, Kamen DL, Lakka TA, Langenberg C, Launer LJ, Leander K, Lee NR, Lind L, Lindgren
Hunt KJ, Spruill IJ, Ambrosone CB, Ambs S, Arnett DK, Atwood L, Becker CM, Linneberg A, Lobbens S, Loh M, Lorentzon M, Luben R, Lubke G,
Downloaded from http://ahajournals.org by on February 7, 2019

DM, Berndt SI, Bernstein L, Blot WJ, Borecki IB, Bottinger EP, Bowden Ludolph-Donislawski A, Lupoli S, Madden PAF, Männikkö R, Marques-
DW, Burke G, Chanock SJ, Cooper RS, Ding J, Duggan D, Evans MK, Vidal P, Martin NG, McKenzie CA, McKnight B, Mellström D, Menni C,
Fox C, Garvey WT, Bradfield JP, Hakonarson H, Grant SF, Hsing A, Chu Montgomery GW, Musk AB, Narisu N, Nauck M, Nolte IM, Oldehinkel AJ,
L, Hu JJ, Huo D, Ingles SA, John EM, Jordan JM, Kabagambe EK, Kardia Olden M, Ong KK, Padmanabhan S, Peyser PA, Pisinger C, Porteous DJ,
SL, Kittles RA, Goodman PJ, Klein EA, Kolonel LN, Le Marchand L, Liu S, Raitakari OT, Rankinen T, Rao DC, Rasmussen-Torvik LJ, Rawal R, Rice T,
McKnight B, Millikan RC, Mosley TH, Padhukasahasram B, Williams LK, Ridker PM, Rose LM, Bien SA, Rudan I, Sanna S, Sarzynski MA, Sattar N,
Patel SR, Peters U, Pettaway CA, Peyser PA, Psaty BM, Redline S, Rotimi Savonen K, Schlessinger D, Scholtens S, Schurmann C, Scott RA, Sennblad
CN, Rybicki BA, Sale MM, Schreiner PJ, Signorello LB, Singleton AB, B, Siemelink MA, Silbernagel G, Slagboom PE, Snieder H, Staessen JA,
Stanford JL, Strom SS, Thun MJ, Vitolins M, Zheng W, Moore JH, Williams Stott DJ, Swertz MA, Swift AJ, Taylor KD, Tayo BO, Thorand B, Thuillier
SM, Ketkar S, Zhu X, Zonderman AB, Kooperberg C, Papanicolaou GJ, D, Tuomilehto J, Uitterlinden AG, Vandenput L, Vohl MC, Völzke H, Vonk
Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA; JM, Waeber G, Waldenberger M, Westendorp RGJ, Wild S, Willemsen
NABEC Consortium; UKBEC Consortium; BioBank Japan Project; AGEN G, Wolffenbuttel BHR, Wong A, Wright AF, Zhao W, Zillikens MC,
Consortium. A meta-analysis identifies new loci associated with body Baldassarre D, Balkau B, Bandinelli S, Böger CA, Boomsma DI, Bouchard
mass index in individuals of African ancestry. Nat Genet. 2013;45:690– C, Bruinenberg M, Chasman DI, Chen YD, Chines PS, Cooper RS, Cucca
696. doi: 10.1038/ng.2608 F, Cusi D, Faire U, Ferrucci L, Franks PW, Froguel P, Gordon-Larsen P,
124. Loos RJ, Yeo GS. The bigger picture of FTO: the first GWAS-identified Grabe HJ, Gudnason V, Haiman CA, Hayward C, Hveem K, Johnson AD,
obesity gene. Nat Rev Endocrinol. 2014;10:51–61. doi: 10.1038/ Wouter Jukema J, Kardia SLR, Kivimaki M, Kooner JS, Kuh D, Laakso M,
nrendo.2013.227 Lehtimäki T, Marchand LL, März W, McCarthy MI, Metspalu A, Morris
125. Speakman JR. The “fat mass and obesity related” (FTO) gene: mech- AP, Ohlsson C, Palmer LJ, Pasterkamp G, Pedersen O, Peters A, Peters U,
anisms of impact on obesity and energy balance. Curr Obes Rep. Polasek O, Psaty BM, Qi L, Rauramaa R, Smith BH, Sørensen TIA, Strauch
2015;4:73–91. doi: 10.1007/s13679-015-0143-1 K, Tiemeier H, Tremoli E, van der Harst P, Vestergaard H, Vollenweider
126. Fall T, Ingelsson E. Genome-wide association studies of obesity and P, Wareham NJ, Weir DR, Whitfield JB, Wilson JF, Tyrrell J, Frayling TM,
metabolic syndrome. Mol Cell Endocrinol. 2014;382:740–757. doi: Barroso I, Boehnke M, Deloukas P, Fox CS, Hirschhorn JN, Hunter DJ,
10.1016/j.mce.2012.08.018 Spector TD, Strachan DP, van Duijn CM, Heid IM, Mohlke KL, Marchini
127. Ng MCY, Graff M, Lu Y, Justice AE, Mudgal P, Liu CT, Young K, Yanek LR, J, Loos RJF, Kilpeläinen TO, Liu CT, Borecki IB, North KE, Cupples LA.
Feitosa MF, Wojczynski MK, Rand K, Brody JA, Cade BE, Dimitrov L, Duan Genome-wide meta-analysis of 241,258 adults accounting for smok-
Q, Guo X, Lange LA, Nalls MA, Okut H, Tajuddin SM, Tayo BO, Vedantam ing behaviour identifies novel loci for obesity traits. Nat Commun.
S, Bradfield JP, Chen G, Chen WM, Chesi A, Irvin MR, Padhukasahasram 2017;8:14977. doi: 10.1038/ncomms14977
B, Smith JA, Zheng W, Allison MA, Ambrosone CB, Bandera EV, Bartz 129. Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, Meduri E,
TM, Berndt SI, Bernstein L, Blot WJ, Bottinger EP, Carpten J, Chanock Morange PE, Gagnon F, Grallert H, Waldenberger M, Peters A, Erdmann
SJ, Chen YI, Conti DV, Cooper RS, Fornage M, Freedman BI, Garcia M, J, Hengstenberg C, Cambien F, Goodall AH, Ouwehand WH, Schunkert
Goodman PJ, Hsu YH, Hu J, Huff CD, Ingles SA, John EM, Kittles R, Klein H, Thompson JR, Spector TD, Gieger C, Trégouët DA, Deloukas P, Samani
E, Li J, McKnight B, Nayak U, Nemesure B, Ogunniyi A, Olshan A, Press NJ. DNA methylation and body-mass index: a genome-wide analysis.
MF, Rohde R, Rybicki BA, Salako B, Sanderson M, Shao Y, Siscovick DS, Lancet. 2014;383:1990–1998. doi: 10.1016/S0140-6736(13)62674-4
Stanford JL, Stevens VL, Stram A, Strom SS, Vaidya D, Witte JS, Yao J, Zhu 130. Global Burden of Disease Study 2016. Global Burden of Disease Study
X, Ziegler RG, Zonderman AB, Adeyemo A, Ambs S, Cushman M, Faul 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and

e104 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 6

Evaluation (IHME), University of Washington; 2016. http://ghdx.health- Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari

CLINICAL STATEMENTS
data.org/gbd-results-tool. Accessed May 1, 2018. TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T,

AND GUIDELINES
131. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC,
index in 200 countries from 1975 to 2014: a pooled analysis of 1698 Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray
population-based measurement studies with 19.2 million participants CJ, Gakidou E. Global, regional, and national prevalence of overweight
[published correction appears in Lancet. 2016;387:1998]. Lancet. and obesity in children and adults during 1980-2013: a systematic analy-
2016;387:1377–1396. doi: 10.1016/S0140-6736(16)30054-X sis for the Global Burden of Disease Study 2013 [published correction
132. Price AJ, Crampin AC, Amberbir A, Kayuni-Chihana N, Musicha C, appears in Lancet. 2014;384:746]. Lancet. 2014;384:766–781. doi:
Tafatatha T, Branson K, Lawlor DA, Mwaiyeghele E, Nkhwazi L, Smeeth 10.1016/S0140-6736(14)60460-8
L, Pearce N, Munthali E, Mwagomba BM, Mwansambo C, Glynn JR, 134. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek
Jaffar S, Nyirenda M. Prevalence of obesity, hypertension, and diabetes, CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM,
and cascade of care in sub-Saharan Africa: a cross-sectional, population- Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases
based study in rural and urban Malawi. Lancet Diabetes Endocrinol. Collaborating Group (Body Mass Index). National, regional, and global
2018;6:208–222. doi: 10.1016/S2213-8587(17)30432-1 trends in body-mass index since 1980: systematic analysis of health ex-
133. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany amination surveys and epidemiological studies with 960 country-years
EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, and 9.1 million participants. Lancet. 2011;377(9765):557–567. doi:
Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman 10.1016/S0140-6736(10)62037-5
NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, 135. Choukem SP, Kengne AP, Nguefack ML, Mboue-Djieka Y, Nebongo D,
Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville Guimezap JT, Mbanya JC. Four-year trends in adiposity and its association
KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama with hypertension in serial groups of young adult university students in
A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar urban Cameroon: a time-series study. BMC Public Health. 2017;17:499.
F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, doi: 10.1186/s12889-017-4449-7
Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay 136. The GBD 2015 Obesity Collaborators. Health effects of overweight and
S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal obesity in 195 countries over 25 years N Engl J Med. 2017;377:13–27.
SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, doi: 10.1056/NEJMoa1614362
Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen 137. Barlow SE; Expert Committee. Expert committee recommendations re-
S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo garding the prevention, assessment, and treatment of child and adoles-
PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, cent overweight and obesity: summary report. Pediatrics. 2007;120(suppl
Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson 4):S164–S192. doi: 10.1542/peds.2007-2329C
EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran 138. United States Census Bureau. American Community Survey (ACS): sum-
D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue mary file. https://www.census.gov/programs-surveys/acs/data/summary-
I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, file.html. Accessed August 22, 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e105

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

7. HIGH BLOOD CHOLESTEROL AND Prevalence of High TC

CLINICAL STATEMENTS

OTHER LIPIDS Youth

AND GUIDELINES

See Table 7-1 and Charts 7-1 through 7-5 Ages 6 to 11 years:

• Among children 6 to 11 years of age, the mean
TC level is 157.8 mg/dL. For boys, it is 157.9 mg/
Click here to return to the Table of Contents
dL; for girls, it is 157.7 mg/dL. The racial/ethnic
breakdown in NHANES 2013 to 2016 is as follows
Cholesterol is one of the primary causal risk factors for (unpublished NHLBI tabulation):
the development of atherosclerotic CVD. The AHA has — For NH whites, 157.1 mg/dL for boys and
defined untreated TC levels <200 mg/dL as one of the 159.1 mg/dL for girls
7 components of ideal cardiovascular health.1 Thus, — For NH blacks, 158.8 mg/dL for boys and
there is substantial interest in lowering average choles- 158.2 mg/dL for girls
terol levels in populations and in identifying individu- — For Hispanics, 158.7 mg/dL for boys and
als likely to benefit from targeted cholesterol-lowering 153.9 mg/dL for girls
interventions. — For NH Asians, 160.1 mg/dL for boys and
US-based population estimates of prevalence 161.5 mg/dL for girls
reported in this chapter are from unpublished NHLBI Adolescents, ages 12 to 19 years:
summary statistics that are derived from 2013 to 2016 • Among adolescents 12 to 19 years of age in
NHANES data for youth and adults for TC and HDL-C. NHANES 2013 to 2016, the mean TC level was
Data are from 2011 to 2014 for LDL-C and triglyc- 154.4 mg/dL; for boys, it was 151.6 mg/dL; for
erides. For statistics pertaining to dietary cholesterol, girls, it was 157.5 mg/dL. The racial/ethnic break-
fats, and other lifestyle factors that affect cholesterol down is as follows (unpublished NHLBI tabulation):
concentrations, see Chapter 4 (Physical Inactivity), — For NH whites, 150.6 mg/dL for boys and
Chapter 5 (Nutrition), and Chapter 6 (Overweight and 157.2 mg/dL for girls
Obesity). — For NH blacks, 150.8 mg/dL for boys and
156.0 mg/dL for girls
Abbreviations Used in Chapter 7 — For Hispanics, 152.7 mg/dL for boys and
ACC American College of Cardiology 156.0 mg/dL for girls
Downloaded from http://ahajournals.org by on February 7, 2019

AHA American Heart Association — For NH Asians, 155.4 mg/dL for boys and
ASCVD atherosclerotic cardiovascular disease 170.2 mg/dL for girls
BRFSS Behavioral Risk Factor Surveillance System
• From 1999 to 2016, mean serum TC for adoles-
CAD coronary artery disease
CETP cholesteryl ester transfer protein
cents 12 to 19 years of age decreased across all
CHD coronary heart disease subgroups of race and sex (Chart 7-1).
CI confidence interval • Fewer than 1% of adolescents are potentially eli-
CVD cardiovascular disease gible for pharmacological treatment on the basis
DALY disability-adjusted life-year of guidelines from the American Academy of
DM diabetes mellitus
Pediatrics.2,3
FH familial hypercholesterolemia
GBD Global Burden of Disease
Adults (Aged ≥20 Years)
GWAS genome wide association studies
HDL high-density lipoprotein
(See Table 7-1 and Charts 7-2 through 7-4)
HDL-C high-density lipoprotein cholesterol • An estimated 28.5 million adults ≥20 years of
LDL low-density lipoprotein age have serum TC levels ≥240 mg/dL (extrapo-
LDL-C low-density lipoprotein cholesterol lated for 2016 by use of NCHS/NHANES 2013–
MACE major adverse cardiovascular events 2016 data), with a prevalence of 11.7%. From
Mex. Am. Mexican American
1999 to 2016, mean serum TC for adults ≥20
NCHS National Center for Health Statistics
NH non-Hispanic
years of age decreased across all subgroups of
NHANES National Health and Nutrition Examination Survey race (Chart 7-2).
NHLBI National Heart, Lung, and Blood Institute • During the period from 2013 to 2016 (unpub-
PCSK9 proprotein convertase subtilisin kexin 9 lished NHLBI tabulation):
QALY quality-adjusted life-year — The percentage of adults with high TC (≥240
RCT randomized controlled trial
mg/dL) was lower for NH black than for NH
REGARDS Reasons for Geographic and Racial Differences in Stroke
RR relative risk
white and Hispanic adults; the same patterns
SES socioeconomic status were seen in males and females.
SOL Studies of Latinos — NH black males ≥20 years of age had the
TC total cholesterol lowest age-adjusted prevalence of serum TC
WHO World Health Organization ≥240 mg/dL (Chart 7-4).

e106 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

— Females had a higher prevalence of high TC — Among NH whites, mean LDL-C levels were

CLINICAL STATEMENTS
≥240 mg/dL (12.4%) than males (10.7%) 112.1 mg/dL for males and 114.9 mg/dL for

AND GUIDELINES
(Table 7-1). females.
• The prevalence of high TC has decreased over — Among NH blacks, mean LDL-C levels were
time, from 18.3% of adults in 1999 to 2000 to 110.4 mg/dL for males and 111.4 mg/dL for
11.0% of adults in 2013 to 2014.4 females.
• During 2013 to 2016, increases in the prevalence — Among Hispanics, mean LDL-C levels were
rates of high TC (≥240 mg/dL) were seen in NH 119.2 mg/dL for males and 112.6 mg/dL for
white and black males and females (Chart 7-4). females.
• However, the age-adjusted mean TC level for NH — Among NH Asians, mean LDL-C levels were
white adults ≥20 years of age declined linearly 112.4 mg/dL for males and 110.3 mg/dL for
from 1999 to 2016. Similar trends were seen females.
for NH white, NH black, and Mexican American • Mean levels of LDL-C decreased from 126.2 mg/
males and females (Chart 7-2). dL during 1999 to 2000 to 111.3 mg/dL during
• The Healthy People 2010 guideline of an age- 2013 to 2014. The age-adjusted prevalence of
adjusted mean TC level of ≤200 mg/dL has been high LDL-C (≥130 mg/dL) decreased from 42.9%
achieved in adults, in males, in females, and in during 1999 to 2000 to 28.5% during 2013 to
all race/ethnicity and sex subgroups.5 The Healthy 2014 (unpublished NHLBI tabulation).
People 2020 target is a mean total blood choles- HDL Cholesterol
terol of 177.9 mg/dL for adults, which had not Youth
been achieved in males or females as of 2011 to • Among children 6 to 11 years of age in NHANES
2014 NHANES data6 (Chart 7-2). 2013 to 2016, the mean HDL-C level was
• Overall, the decline in mean cholesterol levels 56.0 mg/dL. For boys, it was 57.4 mg/dL, and
in recent years likely reflects greater uptake of for girls, it was 54.5 mg/dL. The racial/ethnic
cholesterol-lowering medications rather than breakdown was as follows (unpublished NHLBI
changes in dietary patterns.7 tabulation):
— For NH whites, 56.6 mg/dL for boys and 54.7
Lipid Subfractions mg/dL for girls
Downloaded from http://ahajournals.org by on February 7, 2019

— For NH blacks, 62.5 mg/dL for boys and 58.1

LDL Cholesterol mg/dL for girls
Youth — For Hispanics, 55.9 mg/dL for boys and 52.2
• There are limited data available on LDL-C for chil- mg/dL for girls
dren 6 to 11 years of age. — For NH Asians, 58.1 mg/dL for boys and 54.4
• Among adolescents 12 to 19 years of age in mg/dL for girls
NHANES (2011–2014), the mean LDL-C level was • Among adolescents 12 to 19 years of age, the
87.7 mg/dL (boys, 85.7 mg/dL; girls, 89.8 mg/ mean HDL-C level was 51.8 mg/dL. For boys, it
dL). The racial/ethnic breakdown was as follows was 49.9 mg/dL, and for girls, it was 53.8 mg/
(unpublished NHLBI tabulation): dL. The racial/ethnic breakdown was as fol-
— For NH whites, 86.5 mg/dL for boys and 89.9 lows (NHANES 2013–2016, unpublished NHLBI
mg/dL for girls tabulation):
— For NH blacks, 86.6 mg/dL for boys and 90.9 — For NH whites, 49.2 mg/dL for boys and 53.5
mg/dL for girls mg/dL for girls
— For Hispanic Americans, 85.9 mg/dL for boys — For NH blacks, 54.4 mg/dL for boys and 56.9
and 87.8 mg/dL for girls mg/dL for girls
— For NH Asians, 84.5 mg/dL for boys and 96.9 — For Hispanics, 49.6 mg/dL for boys and 52.2
mg/dL for girls mg/dL for girls
• High levels of LDL-C occurred in 5.5% of male — For NH Asians, 52.8 mg/dL for boys and 56.6
adolescents and 7.5% of female adolescents dur- mg/dL for girls
ing 2011 to 2014 (unpublished NHLBI tabulation). • Low levels of HDL-C occurred in 20.4% of male
adolescents and 10.4% of female adolescents
Adults
in NHANES 2013 to 2016 (unpublished NHLBI
• The mean level of LDL-C for American adults ≥20
tabulation).
years of age was 113.4 mg/dL in 2011 to 2014
(unpublished NHLBI tabulation). Adults
• According to NHANES 2013 to 2014 (unpublished • According to NHANES 2013 to 2016 (unpub-
NHLBI tabulation): lished NHLBI tabulation), the mean level of

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e107

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

HDL-C for American adults ≥20 years of age is adolescents during 2011 to 2014 (unpublished
CLINICAL STATEMENTS

54.2 mg/dL. NHLBI tabulation).

AND GUIDELINES

— Among NH whites, mean HDL-C levels were

Adults
48.4 mg/dL for males and 60.9 mg/dL for
• The geometric mean of triglyceride levels for
females.
American adults ≥20 years of age was 103.5 mg/
— Among NH blacks, mean HDL-C levels were
dL in NHANES 2011 to 2014 (unpublished NHLBI
52.8 mg/dL for males and 60.1 mg/dL for
tabulation).
females.
• Approximately 24.2% of adults had high triglyc-
— Among Hispanics, mean HDL-C levels were
eride levels (≥150 mg/dL) in NHANES 2011 to
45.8 mg/dL for males and 54.4 mg/dL for
2014 (unpublished NHLBI tabulation).
females.
• Among males, the age-adjusted geometric mean
— Among NH Asians, mean HDL-C levels were
triglyceride level was 111.6 mg/dL in NHANES
47.7 mg/dL for males and 60.2 mg/dL for
2011 to 2014 (unpublished NHLBI tabulation),
females.
with the following racial/ethnic breakdown:
• The prevalence of low HDL-C (<40 mg/dL) was
— 113.2 mg/dL for NH white males
higher (24%) in those with lower education (<12
— 86.7 mg/dL for NH black males
years) than in those with higher education (>12
— 124.1 mg/dL for Hispanic males
years; 17%). Approximately 17% of adults (just
— 115.3 mg/dL for NH Asian males
over one-quarter of males and <10% of females)
• Among females, the age-adjusted geometric
had low HDL-C during 2011 to 2012. The per-
mean triglyceride level was 96.4 mg/dL in NHANES
centage of adults with low HDL-C has decreased
2011 to 2014 (unpublished NHLBI tabulation),
20% since 2009 to 2010.8
with the following racial/ethnic breakdown:
• According to NHANES 2013 to 2016 (unpublished
— 99.8 mg/dL for NH white females
NHLBI tabulations), the age-adjusted prevalence
— 75.1 mg/dL for NH black females
rates for HDL-C <40mg/dL were:
— 105.3 mg/dL for Hispanic females
— 29.0% in males and 9.9% in females
— 91.5 mg/dL for NH Asian females
— 29.7% in NH white males and 9.3% in NH
• The prevalence of high triglycerides (≥150 mg/
white females
dL) was higher (27%) in those with lower edu-
— 19.8% in NH black males and 8.1% in NH
Downloaded from http://ahajournals.org by on February 7, 2019

cation (<12 years) than in those with higher

black females
— 32.6 % in Hispanic males and 13.1% in education (>12 years; 23%) (unpublished NHLBI
Hispanic females tabulation).
— 25.9% in NH Asian males and 7.9% in NH
Asian females Screening
Triglycerides • The percentage of adults who reported having
Youth had a cholesterol check increased from 68.6%
• There are limited data available on triglycerides during 1999 to 2000 to 74.8% during 2005 to
for children 6 to 11 years of age. 2006.9
• Among adolescents 12 to 19 years of age in • Nearly 70% of adults (67% of males and nearly
NHANES 2011 to 2014, the geometric mean tri- 72% of females) had been screened for choles-
glyceride level was 79.4 mg/dL. For boys, it was terol (defined as being told by a doctor their cho-
81.9 mg/dL, and for girls, it was 76.8 mg/dL. The lesterol was high and indicating they had their
racial/ethnic breakdown was as follows (unpub- blood cholesterol checked <5 years ago) accord-
lished NHLBI tabulation): ing to data from NHANES 2011 to 2012, which
— Among NH whites, 82.3 mg/dL for boys and was unchanged since 2009 to 2010.8
77.3 mg/dL for girls — Among NH whites, 71.8% were screened
— Among NH blacks, 62.8 mg/dL for boys and (70.6% of males and 72.9% of females).
62.7 mg/dL for girls — Among NH blacks, 71.9% were screened
— Among Hispanics, 89.0 mg/dL for boys and (66.8% of males and 75.9% of females).
85.2 mg/dL for girls — Among NH Asians, 70.8% were screened
— Among NH Asians, 78.3 mg/dL for boys and (70.6% of males and 70.9% of females).
88.0 mg/dL for girls — Among Hispanic adults, 59.3% were
• High levels of triglycerides (≥150 mg/dL) occurred screened (54.6% of males and 64.2% of
in 8.7% of male adolescents and 6.3% of female females).

e108 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

— The percentage of adults screened for cho- discussion regarding statin therapy in 4 identi-

CLINICAL STATEMENTS
lesterol in the past 5 years was lower for fied groups in whom it has been clearly shown

AND GUIDELINES
Hispanic adults than for NH white, NH black, to reduce ASCVD risk. The 4 statin benefit
and NH Asian adults. groups are (1) people with clinical ASCVD, (2)
those with primary elevations of LDL-C >190
mg/dL, (3) people aged 40 to 75 years who
Awareness have DM with LDL-C 70 to 189 mg/dL and
• Awareness of high LDL-C increased from 48.9% without clinical ASCVD, and (4) those without
in 1999 to 2000 to 62.8% in 2003 to 2004; how- clinical ASCVD or DM with LDL-C 70 to 189 mg/
ever, awareness did not increase further through dL and estimated 10-year ASCVD risk ≥7.5%.
2009 to 2010 (61.5%). Treatment among those Approximately 31.9% of the ASCVD-free, non-
aware of having high LDL-C increased from pregnant US population between 40 and 79
41.3% in 1999 to 2000 to 72.6% in 2007 to years of age has a 10-year risk of a first hard
2008. In 2009 to 2010, it was 70.0%.10 CHD event of ≥10% or has DM.16
• According to 2015 BRFSS data11: • According to a recent analysis of NHANES data
— 36.4% of US adults have been told they have from 2005 to 2010, the number of people eligible
high cholesterol. for statin therapy would rise from 43.2 million US
— The percentage of adults told they had high adults (37.5%) to 56.0 million (48.6%) based on
cholesterol was highest in Alabama (42%) the 2013 ACC/AHA guidelines for the manage-
and lowest in Colorado (31.5%). ment of blood cholesterol.17 Most of the increase
• Almost half (49.6%) of Hispanic participants with comes from adults 60 to 75 years old without CVD
high cholesterol (LDL-C >130 mg/dL, TC >240 mg/ who have a 10-year ASCVD risk ≥7.5%; the net
dL, or taking cholesterol-lowering medications) in number of new statin prescriptions could poten-
the SOL baseline examination (2008–2011) were tially increase by 12.8 million, including 10.4 mil-
not aware of their condition. lion for primary prevention.17 Individuals eligible
for treatment under Adult Treatment Panel III but
not ACC/AHA guidelines had higher LDL-C levels
Treatment but were otherwise at lower risk than individuals
• In high-risk patients, the nonstatin medications eligible under both guidelines or only under ACC/
Downloaded from http://ahajournals.org by on February 7, 2019

ezetimibe, PCSK-9 inhibitors, and a CETP inhibitor, AHA guidelines.18

anacetrapib, demonstrated reductions in LDL-C • Data from NHANES 1999 to 2012 show that
and ASCVD risk in randomized, controlled clini- the use of cholesterol-lowering treatment has
cal trials. The PCSK-9 inhibitors evolocumab and increased substantially among adults, from 8% in
alirocumab reduced LDL-C by 40% to 50%, were 1999 to 2000 to 18% in 2011 to 2012.19 During
safe, and reduced the RR for ASCVD events by this period, the use of statins increased from 7%
15% in high-risk patients on maximum tolerated to 17%.19
doses of statins.12,13 Despite the promising effi- • Lower socioeconomic, nonwhite populations
cacy results, the substantial cost of PCSK9 inhibi- typically have a higher prevalence of elevated
tors (≈$14 000/year) remains a barrier to their risk; thus, the 2013 guidelines will be particularly
widespread use in the US population. The AHA/ beneficial in terms of reducing ASCVD events
ACC guideline committee issued an addendum to in these groups. However, improving access to
the 2013 recommendations (outlined below) on healthcare for lower SES populations is necessary
how nonstatin medications can be incorporated to realize this potential expansion of statin use
into clinic care.14 in primary prevention as recommended by these
• In 2013, the ACC/AHA released recommenda- guidelines.20,21
tions for statin treatment.15 AHA 2013 guide- • Recent data from the REGARDS study indicate
lines recommend lipid measurement at baseline, that even after accounting for access to medical
at 1 to 3 months after statin initiation, and then care, there are disparities in the use of statins in
annually to check for the expected percentage individuals with DM; white males with DM and
decrease of LDL-C levels (30% to <50% with LDL-C >100 mg/dL were more likely to be pre-
a moderate-intensity statin and ≥50% with a scribed statins (66.0% versus 57.8% for black
high-intensity statin). Unlike previous recom- males, 55.0% for white females, and 53.6%
mendations, which had LDL-C and non–HDL- for black females) and were more likely to have
C goals based on the patient’s risk category, LDL-C at goal than were African American males
the 2013 ACC/AHA guideline recommended a and females and white females.22

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e109

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

Adherence central adiposity, and poor diet, among others.

CLINICAL STATEMENTS

The interconnectedness of triglycerides with other

Youth
AND GUIDELINES

risk factors makes it challenging to determine the

• In 2011, the NHLBI Expert Panel recommended
isolated effect of serum triglyceride concentration
universal dyslipidemia screening for all chil-
on ASCVD risk.
dren between 9 and 11 years of age and again
• Although multiple clinical trials do not sug-
between 17 and 21 years of age.23
gest added benefit of triglyceride lowering with
• A 2015 study based on NCHS data found that
fibrate medications in statin-treated patients, sev-
21% of youths aged 6 to 19 years had at least
eral mendelian randomization studies suggest a
1 abnormal cholesterol measure during 2011 to
causal association between pathways that lead to
2014.24
high triglycerides and ASCVD.38
Adults
• From 2005 to 2010, among adults with high LDL-
C, age-adjusted control of LDL-C increased from Cost
22.3% to 29.5%.25 The prevalence of LDL-C • An analysis from the GBD study estimates that
control was lowest among people who reported high TC accounts for 88.7 million (95% CI, 74.6
receiving medical care less than twice in the previ- million to 105.7 million) DALYs.39
ous year (11.7%), being uninsured (13.5%), being • Compared with the Adult Treatment Panel
Mexican American (20.3%), or having income III cholesterol treatment guidelines, the AHA
below the poverty level (21.9%).26 2013 recommendations are estimated (from
years 2016 to 2025) to treat 12.24 million more
Americans with statin medications and increase
CVD Health Impact treatment costs by $3.9 billion. However, despite
• CHD risk can accumulate at normative cholesterol the higher costs, the AHA 2013 guideline is pre-
levels with or without the presence of other tradi- dicted to be cost-effective because it is estimated
tional risk factors.27 to save 183 000 more QALYs and prevent 43 700
• Long-term exposure to even modestly elevated deaths.40
cholesterol levels can lead to CHD later in life.1,28 • In patients with ASCVD, the addition of PCSK9
inhibitors to statin therapy was estimated to pre-
Downloaded from http://ahajournals.org by on February 7, 2019

HDL Cholesterol
vent 4.3 million more MACE than adding ezeti-
• Low levels of HDL-C and apolipoprotein A1 are
mibe to statin therapy. However, because of high
strongly associated with increased ASCVD risk
drug costs, the addition of PCSK9 is estimated to
in young and middle-aged adults.29 The associa-
cost $414 000 per QALY. To achieve cost-effective-
tion between CHD risk and HDL-C appears to be
ness, the PCSK9 inhibitor cost would need to be
inverse and linear until HDL-C values exceed 70
reduced to $4536 per year to achieve $100 000
to 80 mg/dL, at which point there may be a slight
per QALY.41
increase in CHD risk in some people.30,31
• In the United States, only 47% of prescriptions
• Negative RCTs and mendelian randomization
for PCSK9 inhibitors were approved between July
studies have suggested that HDL-C content is not
2015 and August 2016.42 Approval rates were
in the causal pathway of atheroprotection.32–34
• Metrics of HDL particle function, notably HDL highest for Medicare (60.9%) and lowest for pri-
efflux capacity, have been shown to have strong, vate third-party payers (24.4%).
independent associations with ASCVD risk in sev-
eral cohort studies.35,36 Family History and Genetics
• HDL efflux capacity may predict residual risk in
Familial Hypercholesterolemia
statin-treated patients.37
• There are several known monogenic or mende-
Triglycerides lian causes of high blood cholesterol and lipids,
• Triglyceride concentration has strong associa- the most common of which include FH, which
tions with ASCVD risk; however, in most studies affects up to ≈1 in 200 individuals.43 Patients with
the association is attenuated after adjustment for FH have elevated TC and LDL-C and a 20-fold
other traditional risk factors.29 increased risk of CVD.44 Similarly, individuals with
• Triglyceride levels are biologically linked to other the FH phenotype (LDL-C >190 mg/dL) experience
causal factors for ASCVD, notably LDL-C, LDL par- an acceleration in CHD risk by 10 to 20 years in
ticle concentration, insulin resistance, low HDL-C, males and 20 to 30 years in females.45

e110 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

• FH has been associated with mutations in LDLR, between genetic loci for triglyceride-rich lipopro-

CLINICAL STATEMENTS
APOB, LDLRAP1, and PCSK9, which affect teins and disease implicate triglycerides as causal

AND GUIDELINES
uptake and clearance of LDL-C. Individuals with in CVD.35,36,53,54
LDL-C >190 mg/dL and a confirmed FH muta-
Lipid Genetics and Drug Development
tion have substantially higher odds for CAD than
• Genetic studies of lipid traits have had some suc-
those with LDL-C >190 mg/dL without patho-
cess in identifying new drug targets, particularly
genic mutations. Similarly, individuals with an FH
the genetic interrogation of extremely high and
pathogenic mutation and an LDL-C <190 mg/ low LDL-C,55–57 which led to the development of
dL have substantially higher odds for CAD than PCSK9 inhibitors. Furthermore, identification of
those without a pathogenic FH mutation and variants in ANGPTL4 and ANGPTL3 that associ-
similar LDL-C levels.46 ate with increased triglycerides and CAD risk52,58
• Individuals who are homozygous for an FH muta- highlight inhibition of these genes as potentially
tion have severe CHD that becomes apparent in therapeutic.59
childhood and requires plasmapheresis; it may be • As highly effective LDL-C–lowering drugs, statins
best treated using novel therapies, including gene are widely prescribed to reduce CVD risk, but
therapy.47 However, the majority of FH cases are response to statins varies among individuals.
heterozygous for the causal mutation, and these Genetic variants that affect statin responsive-
patients remain underdiagnosed.43 ness could predict the lipid-modulating ability
• Cascade screening, which recommends choles- of statins60–62 and modulate cardioprotection.63
terol testing for all first-degree relatives of an FH Importantly, variation in SLCO1B1 predicts risk of
patient, can be an effective strategy to identify statin myopathy, a major potential adverse event,
affected family members who would benefit from which has prompted recommendations for geno-
therapeutic intervention.44 type-guided dosing of simvastatin.64,65
Familial Combined Hyperlipidemia
• Combined hyperlipidemia, which affects ≈1 in Global Burden of Hypercholesterolemia
100 individuals, is characterized by elevated (See Chart 7-5)
LDL-C and triglycerides. Unlike FH, there is little • The GBD 2016 Study used statistical models and
Downloaded from http://ahajournals.org by on February 7, 2019

evidence for monogenic causes of combined data on incidence, prevalence, case fatality, excess
hyperlipidemia, which indicates that most cases mortality, and cause-specific mortality to estimate
of combined hyperlipidemia might be complex disease burden for 315 diseases and injuries in
and polygenic.48 195 countries and territories. The highest mor-
• High cholesterol is heritable even in families that tality rates attributable to high TC are in Eastern
do not harbor one of these monogenic forms Europe and Central Asia (Chart 7-5).66
of disease. Extensive efforts have focused on • TC went from being the 14th-leading risk factor
GWASs for lipid traits in large numbers of subjects in 1990 for the global burden of disease, as quan-
to identify the genetic architecture of variability tified by DALYs, to the number 15 risk factor in
in cholesterol levels. With GWASs, 95 loci were 2010.67
identified using >100 000 subjects of European • The prevalence of elevated TC was highest
origin.49 Additional studies in even larger num- in the WHO European Region (54% for both
bers, including individuals of diverse ancestry, sexes), followed by the WHO Region of the
use of electronic health record–based samples, Americas (48% for both sexes). The WHO
and the addition of whole-exome sequencing African Region and the WHO South-East Asia
(which offers more comprehensive coverage of Region showed the lowest percentages (23%
the coding regions of the genome) have brought and 30%, respectively).39
the number of known lipid loci to >200.50–52 As • A report on trends in TC in 199 countries and ter-
expected for a causal biomarker, there is consid- ritories indicated that TC declined in high-income
erable overlap between the genetics of LDL-C regions of the world (Australasia, North America,
and the genetics of CHD. Furthermore, overlap and Western Europe).67

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e111

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

Table 7-1.  High TC and LDL-C and Low HDL-C

CLINICAL STATEMENTS

Prevalence of TC Prevalence of TC Prevalence of LDL-C Prevalence of HDL-C

AND GUIDELINES

≥200 mg/dL, 2013–2016 ≥240 mg/dL, 2013–2016 ≥130 mg/ dL, 2011–2014 <40 mg/dL, 2013–2016
Population Group Age ≥20 y Age ≥20 y Age ≥20 y Age ≥20 y
Both sexes, n (%)* 92 800 000 (38.2) 28 500 000 (11.7) 71 300 000 (30.3) 45 600 000 (19.2)
Males, n (%)* 41 200 000 (35.4) 12 400 000 (10.7) 34 000 000 (30.0) 33 700 000 (29.0)
Females, n (%)* 51 600 000 (40.4) 16 100 000 (12.4) 37 300 000 (30.4) 11 900 000 (9.9)
NH white males, % 35.4 10.5 29.3 29.7
NH white females, % 41.8 13.6 32.1 9.3
NH black males, % 29.8 8.9 29.9 19.8
NH black females, % 33.1 9.0 27.9 8.1
Hispanic males, % 39.9 13.0 36.6 32.6
Hispanic females, % 38.9 10.1 28.7 13.1
NH Asian males, % 38.7 11.7 29.2 25.9
NH Asian females, % 39.6 10.8 25.0 7.9

Prevalence of TC ≥200 mg/dL includes people with TC ≥240 mg/dL. In adults, levels of 200 to 239 mg/dL are considered borderline high. Levels of ≥240 mg/dL
are considered high.
HDL-C indicates high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NH, non-Hispanic; and TC, total cholesterol.
*Total data for TC are for Americans ≥20 years of age. Data for LDL-C, HDL-C, and all racial/ethnic groups are age adjusted for age ≥20 years.
Source for TC ≥200 mg/dL, ≥240 mg/dL, LDL-C, and HDL-C: National Health and Nutrition Examination Survey (2013–2016), National Center for Health Statistics,
and National Heart, Lung, and Blood Institute. Estimates from National Health and Nutrition Examination Survey 2013 to 2016 (National Center for Health Statistics)
were applied to 2016 population estimates.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 7-1. Trends in mean serum total cholesterol among adolescents 12 to 19 years of age by race, sex, and survey year (NHANES, 1999–2004,
2005–2010, and 2011–2016).
Values are in mg/dL.
Mex. Am. indicates Mexican American; NH, non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics was only used starting in 2007.
Consequently, for long-term trend data, the category Mexican American is used.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

e112 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

CLINICAL STATEMENTS
AND GUIDELINES
Chart 7-2. Age-adjusted trends in mean serum total cholesterol among adults ≥20 years old by race and survey year (NHANES, 1999–2004,
2005–2010, and 2011–2016).
Values are in mg/dL.
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics was only used starting in 2007.
Consequently, for long-term trend data, the category Mexican American is used.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 7-3. Age-adjusted trends in the prevalence of serum total cholesterol ≥200 mg/dL in adults ≥20 years of age by race/ethnicity, sex, and survey
year (NHANES, 2013–2014 and 2015–2016).
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e113

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7
CLINICAL STATEMENTS
AND GUIDELINES

Chart 7-4. Age-adjusted trends in the prevalence of serum total cholesterol ≥240 mg/dL in adults ≥20 years of age by race/ethnicity, sex, and survey
year (NHANES, 2013–2014 and 2015–2016).
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 7-5. Age-standardized global mortality rates attributable to high total cholesterol per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016 with permission.66 Copyright © 2017, University of Washington.

e114 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

REFERENCES 16. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons

CLINICAL STATEMENTS
R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz
1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn

AND GUIDELINES
JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow AHA guideline on the assessment of cardiovascular risk: a report of the
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm American College of Cardiology/American Heart Association Task Force
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart on Practice Guidelines [published correction appears in Circulation.
Association Strategic Planning Task Force and Statistics Committee. 2014;129(suppl 2):S74–S75]. Circulation. 2014;129(suppl 2):S49–S73.
Defining and setting national goals for cardiovascular health promotion doi: 10.1161/01.cir.0000437741.48606.98
and disease reduction: the American Heart Association’s strategic Impact 17. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, Williams K, Neely B,
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: Sniderman AD, Peterson ED. Application of new cholesterol guidelines
10.1161/CIRCULATIONAHA.109.192703 to a population-based sample. N Engl J Med. 2014;370:1422–1431. doi:
2. Centers for Disease Control and Prevention (CDC). Prevalence of abnor- 10.1056/NEJMoa1315665
mal lipid levels among youths: United States, 1999–2006 [published cor- 18. Bittner V. New ACC-AHA cholesterol guidelines significantly increase
rection appears in MMWR Morb Mortal Wkly Rep. 2010;59:78]. MMWR potential eligibility for statin treatment. Evid Based Med. 2014;19:198.
Morb Mortal Wkly Rep. 2010;59:29–33. doi: 10.1136/ebmed-2014-110029
3. Ford ES, Li C, Zhao G, Mokdad AH. Concentrations of low-density 19. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in pre-
lipoprotein cholesterol and total cholesterol among children and ado- scription drug use among adults in the United States from 1999–2012.
lescents in the United States. Circulation. 2009;119:1108–1115. doi: JAMA. 2015;314:1818–1831. doi: 10.1001/jama.2015.13766
10.1161/CIRCULATIONAHA.108.816769 20. Qureshi WT, Kaplan RC, Swett K, Burke G, Daviglus M, Jung M, Talavera
4. Carroll MD, Kit BK, Lacher DA, Shero ST, Mussolino ME. Trends in lipids GA, Chirinos DA, Reina SA, Davis S, Rodriguez CJ. American College of
and lipoproteins in US adults, 1988-2010. JAMA. 2012;308:1545–1554. Cardiology/American Heart Association (ACC/AHA) class I guidelines for
doi: 10.1001/jama.2012.13260 the treatment of cholesterol to reduce atherosclerotic cardiovascular risk:
5. US Department of Health and Human Services. Healthy People.gov web- implications for US Hispanics/Latinos based on findings from the Hispanic
site. Healthy People 2020: HDS-8: reduce the mean total blood choles- Community Health Study/Study of Latinos (HCHS/SOL). J Am Heart Assoc.
terol levels among adults. https://www.healthypeople.gov/node/4600/ 2017;6:e005045. doi: 10.1161/JAHA.116.005045
data_details. Accessed July 13, 2016. 21. Verma AA, Jimenez MP, Subramanian SV, Sniderman AD, Razak F. Race
6. US Department of Health and Human Services. Healthy People.gov web- and socioeconomic differences associated with changes in statin eligi-
site. Healthy People 2020 Topics & Objectives: Heart Disease and Stroke. bility under the 2013 American College of Cardiology/American Heart
https://www.healthypeople.gov/2020/topics-objectives/topic/heart-dis- Association cholesterol guidelines. Circ Cardiovasc Qual Outcomes.
ease-and-stroke/objectives. Accessed July 13, 2016. 2017;10:e003764. doi: 10.1161/CIRCOUTCOMES.117.003764
7. Ford ES, Capewell S. Trends in total and low-density lipoprotein choles- 22. Gamboa CM, Colantonio LD, Brown TM, Carson AP, Safford MM. Race-
terol among U.S. adults: contributions of changes in dietary fat intake and sex differences in statin use and low-density lipoprotein cholesterol control
use of cholesterol-lowering medications. PLoS One. 2013;8:e65228. doi: among people with diabetes mellitus in the Reasons for Geographic and
10.1371/journal.pone.0065228 Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6:e004264.
8. Carroll MD, Fryar CD, Kit BK. Total and high-density lipoprotein cholesterol doi: 10.1161/JAHA.116.004264
in adults: United States, 2011–2014. NCHS Data Brief. 2015;(226):1–8. 23. Expert Panel on Integrated Guidelines for Cardiovascular Health and
9. Ford ES, Li C, Pearson WS, Zhao G, Mokdad AH. Trends in hypercholester- Risk Reduction in Children and Adolescents. Expert Panel on Integrated
olemia, treatment and control among United States adults. Int J Cardiol.
Downloaded from http://ahajournals.org by on February 7, 2019

Guidelines for Cardiovascular Health and Risk Reduction in Children and

2010;140:226–235. doi: 10.1016/j.ijcard.2008.11.033 Adolescents: summary report. Pediatrics. 2011;128(suppl 5):S213–256.
10. Muntner P, Levitan EB, Brown TM, Sharma P, Zhao H, Bittner V, Glasser doi: 10.1542/peds.2009-2107C
S, Kilgore M, Yun H, Woolley JM, Farkouh ME, Rosenson RS. Trends 24. Nguyen D, Kit B, Carroll M. Abnormal cholesterol among children
in the prevalence, awareness, treatment and control of high low den- and adolescents in the United States, 2011–2014. NCHS Data Brief.
sity lipoprotein-cholesterol among United States adults from 1999- 2015;(228):1–8.
2000 through 2009-2010. Am J Cardiol. 2013;112:664–670. doi: 25. Johnson NB, Hayes LD, Brown K, Hoo EC, Ethier KA; Centers for Disease
10.1016/j.amjcard.2013.04.041 Control and Prevention. CDC National Health Report: leading causes of
11. Centers for Disease Control and Prevention, Division of Population Health. morbidity and mortality and associated behavioral risk and protective fac-
BRFSS Prevalence & Trends Data (2015). Centers for Disease Control and tors: United States, 2005–2013. MMWR Suppl. 2014;63:3–27.
Prevention website. http://www.cdc.gov/brfss/brfssprevalence/. Accessed 26. Centers for Disease Control and Prevention (CDC). Vital signs: prevalence,
May 17, 2017. treatment, and control of high levels of low-density lipoprotein choles-
12. Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, Schneider J, terol: United States, 1999–2002 and 2005–2008. MMWR Morb Mortal
Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Robinson JG, Wkly Rep. 2011;60:109–114.
Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. 27. Fernández-Friera L, Fuster V, López-Melgar B, Oliva B, García-Ruiz JM,
Cognitive function in a randomized trial of evolocumab. N Engl J Med. Mendiguren J, Bueno H, Pocock S, Ibáñez B, Fernández-Ortiz A, Sanz J.
2017;377:633–643. doi: 10.1056/NEJMoa1701131 Normal LDL-cholesterol levels are associated with subclinical atherosclero-
13. Schmidt AF, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. sis in the absence of risk factors [published correction appears in J Am Coll
PCSK9 monoclonal antibodies for the primary and secondary prevention of Cardiol. 2018;71:588–589]. J Am Coll Cardiol. 2017;70:2979–2991. doi:
cardiovascular disease. Cochrane Database Syst Rev. 2017;4:CD011748. 10.1016/j.jacc.2017.10.024
doi: 10.1002/14651858.CD011748.pub2 28. Navar-Boggan AM, Peterson ED, D’Agostino RB Sr, Neely B, Sniderman
14. Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, AD, Pencina MJ. Hyperlipidemia in early adulthood increases long-term
DePalma SM, Minissian MB, Orringer CE, Smith SC Jr. 2017 Focused risk of coronary heart disease. Circulation. 2015;131:451–458. doi:
update of the 2016 ACC expert consensus decision pathway on the role 10.1161/CIRCULATIONAHA.114.012477
of non-statin therapies for LDL-cholesterol lowering in the management 29. Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and
of atherosclerotic cardiovascular disease risk: a report of the American risk of vascular disease. JAMA. 2009;302:1993–2000. doi: 10.1001/jama.
College of Cardiology Task Force on Expert Consensus Decision Pathways. 2009.1619
J Am Coll Cardiol. 2017;70:1785–1822. doi: 10.1016/j.jacc.2017.07.745 30. Wilkins JT, Ning H, Stone NJ, Criqui MH, Zhao L, Greenland P, Lloyd-Jones
15. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, DM. Coronary heart disease risks associated with high levels of HDL
Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, cholesterol. J Am Heart Assoc. 2014;3:e000519. doi: 10.1161/JAHA.
Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/ 113.000519
AHA guideline on the treatment of blood cholesterol to reduce athero- 31. Ko DT, Alter DA, Guo H, Koh M, Lau G, Austin PC, Booth GL, Hogg
sclerotic cardiovascular risk in adults: a report of the American College of W, Jackevicius CA, Lee DS, Wijeysundera HC, Wilkins JT, Tu JV. High-
Cardiology/American Heart Association Task Force on Practice Guidelines density lipoprotein cholesterol and cause-specific mortality in indi-
[published corrections appear in Circulation. 2014;129(suppl 2):S46–S48 viduals without previous cardiovascular conditions: the CANHEART
and Circulation. 2015;132:e396]. Circulation. 2014;129(suppl 2):S1–45. Study. J Am Coll Cardiol. 2016;68:2073–2083. doi: 10.1016/j.jacc.
doi: 10.1161/01.cir.0000437738.63853.7a 2016.08.038

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e115

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

32. Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, Gibson heart disease and stroke. Circulation. 2017;136:1087–1098. doi:
CLINICAL STATEMENTS

CM, Granger C, Menon V, Montalescot G, Rader D, Tall AR, McErlean E, 10.1161/CIRCULATIONAHA.117.027067

AND GUIDELINES

Wolski K, Ruotolo G, Vangerow B, Weerakkody G, Goodman SG, Conde 41. Kazi DS, Moran AE, Coxson PG, Penko J, Ollendorf DA, Pearson SD, Tice
D, McGuire DK, Nicolau JC, Leiva-Pons JL, Pesant Y, Li W, Kandath D, JA, Guzman D, Bibbins-Domingo K. Cost-effectiveness of PCSK9 inhibi-
Kouz S, Tahirkheli N, Mason D, Nissen SE; ACCELERATE Investigators. tor therapy in patients with heterozygous familial hypercholesterolemia
Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N or atherosclerotic cardiovascular disease. JAMA. 2016;316:743–753. doi:
Engl J Med. 2017;376:1933–1942. doi: 10.1056/NEJMoa1609581 10.1001/jama.2016.11004
33. Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, 42. Hess GP, Natarajan P, Faridi KF, Fievitz A, Valsdottir L, Yeh RW. Proprotein
Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani convertase subtilisin/kexin type 9 inhibitor therapy: payer approvals and
NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, Newton- rejections, and patient characteristics for successful prescribing. Circulation.
Cheh C, Musunuru K, Pirruccello JP, Saleheen D, Chen L, Stewart A, 2017;136:2210–2219. doi: 10.1161/CIRCULATIONAHA.117.028430
Schillert A, Thorsteinsdottir U, Thorgeirsson G, Anand S, Engert JC, 43. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L,
Morgan T, Spertus J, Stoll M, Berger K, Martinelli N, Girelli D, McKeown Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A,
PP, Patterson CC, Epstein SE, Devaney J, Burnett MS, Mooser V, Ripatti S, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C,
Surakka I, Nieminen MS, Sinisalo J, Lokki ML, Perola M, Havulinna A, de Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P,
Faire U, Gigante B, Ingelsson E, Zeller T, Wild P, de Bakker PI, Klungel OH, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A; European
Maitland-van der Zee AH, Peters BJ, de Boer A, Grobbee DE, Kamphuisen Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is
PW, Deneer VH, Elbers CC, Onland-Moret NC, Hofker MH, Wijmenga C, underdiagnosed and undertreated in the general population: guidance for
Verschuren WM, Boer JM, van der Schouw YT, Rasheed A, Frossard P, clinicians to prevent coronary heart disease: consensus statement of the
Demissie S, Willer C, Do R, Ordovas JM, Abecasis GR, Boehnke M, Mohlke European Atherosclerosis Society. Eur Heart J. 2013;34:3478–390a. doi:
KL, Daly MJ, Guiducci C, Burtt NP, Surti A, Gonzalez E, Purcell S, Gabriel 10.1093/eurheartj/eht273
S, Marrugat J, Peden J, Erdmann J, Diemert P, Willenborg C, König IR, 44. Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG,
Fischer M, Hengstenberg C, Ziegler A, Buysschaert I, Lambrechts D, Van Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty
de Werf F, Fox KA, El Mokhtari NE, Rubin D, Schrezenmeir J, Schreiber S, PM, Cromwell WC, Ross JL, Ziajka PE. Familial hypercholesterolemia:
Schäfer A, Danesh J, Blankenberg S, Roberts R, McPherson R, Watkins H, screening, diagnosis and management of pediatric and adult patients:
Hall AS, Overvad K, Rimm E, Boerwinkle E, Tybjaerg-Hansen A, Cupples clinical guidance from the National Lipid Association Expert Panel on
LA, Reilly MP, Melander O, Mannucci PM, Ardissino D, Siscovick D, Elosua Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:133–140. doi:
R, Stefansson K, O’Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz 10.1016/j.jacl.2011.03.001
SM, Altshuler D, Kathiresan S. Plasma HDL cholesterol and risk of myo- 45. Perak AM, Ning H, de Ferranti SD, Gooding HC, Wilkins JT, Lloyd-Jones
cardial infarction: a mendelian randomisation study [published correc- DM. Long-term risk of atherosclerotic cardiovascular disease in US
tion appears in Lancet. 2012;380:564]. Lancet. 2012;380:572–580. doi: adults with the familial hypercholesterolemia phenotype. Circulation.
10.1016/S0140-6736(12)60312-2 2016;134:9–19. doi: 10.1161/CIRCULATIONAHA.116.022335
34. HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with 46. Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, van
laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–212. doi: Leeuwen EM, Natarajan P, Emdin CA, Bick AG, Morrison AC, Brody JA,
10.1056/NEJMoa1300955 Gupta N, Nomura A, Kessler T, Duga S, Bis JC, van Duijn CM, Cupples LA,
35. Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, Psaty B, Rader DJ, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins
Lukmanova D, Mucksavage ML, Luben R, Billheimer J, Kastelein JJ, H, Lander E, Wilson JG, Correa A, Boerwinkle E, Merlini PA, Ardissino
Boekholdt SM, Khaw KT, Wareham N, Rader DJ. Association of HDL cho- D, Saleheen D, Gabriel S, Kathiresan S. Diagnostic yield and clinical util-
Downloaded from http://ahajournals.org by on February 7, 2019

lesterol efflux capacity with incident coronary heart disease events: a pro- ity of sequencing familial hypercholesterolemia genes in patients with
spective case-control study. Lancet Diabetes Endocrinol. 2015;3:507–513. severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578–2589. doi:
doi: 10.1016/S2213-8587(15)00126-6 10.1016/j.jacc.2016.03.520
36. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland 47. Ajufo E, Cuchel M. Recent developments in gene therapy for homozy-
IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW. HDL cholesterol gous familial hypercholesterolemia. Curr Atheroscler Rep. 2016;18:22.
efflux capacity and incident cardiovascular events. N Engl J Med. doi: 10.1007/s11883-016-0579-0
2014;371:2383–2393. doi: 10.1056/NEJMoa1409065 48. Brahm AJ, Hegele RA. Combined hyperlipidemia: familial but not (usu-
37. Khera AV, Demler OV, Adelman SJ, Collins HL, Glynn RJ, Ridker PM, Rader ally) monogenic. Curr Opin Lipidol. 2016;27:131–140. doi: 10.1097/MOL.
DJ, Mora S. Cholesterol efflux capacity, high-density lipoprotein particle 0000000000000270
number, and incident cardiovascular events: an analysis from the JUPITER 49. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki
Trial (Justification for the Use of Statins in Prevention: An Intervention M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier
Trial Evaluating Rosuvastatin). Circulation. 2017;135:2494–2504. doi: SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS,
10.1161/CIRCULATIONAHA.116.025678 Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O,
38. Holmes MV, Asselbergs FW, Palmer TM, Drenos F, Lanktree MB, Nelson CP, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY,
Dale CE, Padmanabhan S, Finan C, Swerdlow DI, Tragante V, van Iperen EP, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA,
Sivapalaratnam S, Shah S, Elbers CC, Shah T, Engmann J, Giambartolomei Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang
C, White J, Zabaneh D, Sofat R, McLachlan S, Doevendans PA, Balmforth W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann
AJ, Hall AS, North KE, Almoguera B, Hoogeveen RC, Cushman M, Fornage HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider
M, Patel SR, Redline S, Siscovick DS, Tsai MY, Karczewski KJ, Hofker MH, P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson
Verschuren WM, Bots ML, van der Schouw YT, Melander O, Dominiczak JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH,
AF, Morris R, Ben-Shlomo Y, Price J, Kumari M, Baumert J, Peters A, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna
Thorand B, Koenig W, Gaunt TR, Humphries SE, Clarke R, Watkins H, S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM,
Farrall M, Wilson JG, Rich SS, de Bakker PI, Lange LA, Davey Smith G, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx
Reiner AP, Talmud PJ, Kivimäki M, Lawlor DA, Dudbridge F, Samani NJ, BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O’Donnell CJ,
Keating BJ, Hingorani AD, Casas JP; UCLEB Consortium. Mendelian Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson
randomization of blood lipids for coronary heart disease. Eur Heart J. R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino
2015;36:539–550. doi: 10.1093/eurheartj/eht571 M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G,
39. GBD 2015 Risk Factors Collaborators. Global, regional, and national com- Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg
parative risk assessment of 79 behavioural, environmental and occupa- F, König IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR,
tional, and metabolic risks or clusters of risks, 1990–2015: a systematic Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman
analysis for the Global Burden of Disease Study 2015 [published correc- A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie
tion appears in Lancet. 2017;389:e1]. Lancet. 2016;388:1659–1724. doi: ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC,
10.1016/S0140-6736(16)31679-8 Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe
40. Heller DJ, Coxson PG, Penko J, Pletcher MJ, Goldman L, Odden MC, KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de
Kazi DS, Bibbins-Domingo K. Evaluating the impact and cost-effec- Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt
tiveness of statin use guidelines for primary prevention of coronary NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso

e116 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, whites and blacks. Am J Hum Genet. 2014;94:223–232. doi: 10.1016/j.

CLINICAL STATEMENTS
Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor ajhg.2014.01.009

AND GUIDELINES
HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, 52. Dewey F, Murray M, Overton JD, Habegger L, Leader JB, Fetterolf SN,
Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner O’Dushlaine C, Van Hout CV, Staples J, Gonzaga-Jauregui C, Metpally
JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, R, Pendergrass SA, Giovanni MA, Kirchner HL, Balasubramanian S, Abul-
Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Husn NS, Hartzel DN, Lavage DR, Kost KA, Packer JS, Lopez AE, Penn J,
Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen Mukherjee S, Gosalia N, Kanagaraj M, Li AH, Mitnaul LJ, Adams LJ, Person
L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and popula- TN, Praveen K, Marcketta A, Lebo MS, Austin-Tse CA, Mason-Suares HM,
tion relevance of 95 loci for blood lipids. Nature. 2010;466:707–713. doi: Bruse S, Mellis S, Phillips R, Stahl N, Murphy A, Economides A, Skelding
10.1038/nature09270 KA, Still CD, Elmore JR, Borecki IB, Yancopoulos GD, Davis FD, Faucett
50. Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni WA, Gottesman O, Ritchie MD, Shuldiner AR, Reid JG, Ledbetter DH,
S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg- Baras A, Carey DJ. Distribution and clinical impact of functional variants
Gresham JL, Chang HY, Demirkan A, Den Hertog HM, Do R, Donnelly in 50,726 whole-exome sequences from the DiscovEHR study. Science.
LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser 2016;354(6319):aaf6814. doi: 10.1126/science.aaf6814
RM, Freitag DF, Gurdasani D, Heikkilä K, Hyppönen E, Isaacs A, Jackson 53. Triglyceride Coronary Disease Genetics Consortium and Emerging
AU, Johansson Å, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li Risk Factors Collaboration. Triglyceride-mediated pathways and coro-
X, Luan J, Lyytikäinen LP, Magnusson PKE, Mangino M, Mihailov E, nary disease: collaborative analysis of 101 studies [published correction
Montasser ME, Müller-Nurasyid M, Nolte IM, O’Connell JR, Palmer CD, appears in Lancet. 2010;376:90]. Lancet. 2010;375:1634–1639. doi:
Perola M, Petersen AK, Sanna S, Saxena R, Service SK, Shah S, Shungin 10.1016/S0140-6736(10)60545-4
D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, 54. TG and HDL Working Group of the Exome Sequencing Project, National
Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong Heart, Lung, and Blood Institute. Loss-of-function mutations in APOC3,
A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, triglycerides, and coronary disease. N Engl J Med. 2014;371:22–31. doi:
Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney 10.1056/NEJMoa1307095
ASF, Döring A, Elliott P, Epstein SE, Ingi Eyjolfsson G, Gigante B, Goodarzi 55. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M,
MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen AL, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier
Hayward C, Hernandez D, Hicks AA, Holm H, Hung YJ, Illig T, Jones MR, M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin
Kaleebu P, Kastelein JJP, Khaw KT, Kim E, Klopp N, Komulainen P, Kumari P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C.
M, Langenberg C, Lehtimäki T, Lin SY, Lindström J, Loos RJF, Mach F, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
McArdle WL, Meisinger C, Mitchell BD, Müller G, Nagaraja R, Narisu N, Nat Genet. 2003;34:154–156. doi: 10.1038/ng1161
Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou 56. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in
T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, PCSK9, low LDL, and protection against coronary heart disease. N Engl J
Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Med. 2006;354:1264–1272. doi: 10.1056/NEJMoa054013
Stančáková A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt 57. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low
LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, LDL cholesterol in individuals of African descent resulting from frequent
Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes nonsense mutations in PCSK9 [published correction appears in Nat Genet.
TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, 2005;37:328]. Nat Genet. 2005;37:161–165. doi: 10.1038/ng1509
Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti 58. Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia
A, Chambers JC, Chen YI, Collins FS, Cooper RS, Danesh J, Dedoussis Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and
Downloaded from http://ahajournals.org by on February 7, 2019

G, de Faire U, Feranil AB, Ferrières J, Ferrucci L, Freimer NB, Gieger C, the risk of coronary disease [published correction appears in N Engl
Groop LC, Gudnason V, Gyllensten U, Hamsten A, Harris TB, Hingorani J Med. 2016;374:1898]. N Engl J Med. 2016;374:1134–1144. doi:
A, Hirschhorn JN, Hofman A, Hovingh GK, Hsiung CA, Humphries SE, 10.1056/NEJMoa1507652
Hunt SC, Hveem K, Iribarren C, Järvelin MR, Jula A, Kähönen M, Kaprio 59. Graham MJ, Lee RG, Brandt TA, Tai LJ, Fu W, Peralta R, Yu R, Hurh E, Paz
J, Kesäniemi A, Kivimaki M, Kooner JS, Koudstaal PJ, Krauss RM, Kuh D, E, McEvoy BW, Baker BF, Pham NC, Digenio A, Hughes SG, Geary RS,
Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Lind L, Lindgren CM, Martin Witztum JL, Crooke RM, Tsimikas S. Cardiovascular and metabolic effects
NG, März W, McCarthy MI, McKenzie CA, Meneton P, Metspalu A, of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377:222–
Moilanen L, Morris AD, Munroe PB, Njølstad I, Pedersen NL, Power C, 232. doi: 10.1056/NEJMoa1701329
Pramstaller PP, Price JF, Psaty BM, Quertermous T, Rauramaa R, Saleheen 60. Postmus I, Trompet S, Deshmukh HA, Barnes MR, Li X, Warren HR,
D, Salomaa V, Sanghera DK, Saramies J, Schwarz PEH, Sheu WH, Chasman DI, Zhou K, Arsenault BJ, Donnelly LA, Wiggins KL, Avery CL,
Shuldiner AR, Siegbahn A, Spector TD, Stefansson K, Strachan DP, Tayo Griffin P, Feng Q, Taylor KD, Li G, Evans DS, Smith AV, de Keyser CE,
BO, Tremoli E, Tuomilehto J, Uusitupa M, van Duijn CM, Vollenweider Johnson AD, de Craen AJ, Stott DJ, Buckley BM, Ford I, Westendorp RG,
P, Wallentin L, Wareham NJ, Whitfield JB, Wolffenbuttel BHR, Ordovas Slagboom PE, Sattar N, Munroe PB, Sever P, Poulter N, Stanton A, Shields
JM, Boerwinkle E, Palmer CNA, Thorsteinsdottir U, Chasman DI, Rotter DC, O’Brien E, Shaw-Hawkins S, Chen YD, Nickerson DA, Smith JD, Dubé
JI, Franks PW, Ripatti S, Cupples LA, Sandhu MS, Rich SS, Boehnke M, MP, Boekholdt SM, Hovingh GK, Kastelein JJ, McKeigue PM, Betteridge
Deloukas P, Kathiresan S, Mohlke KL, Ingelsson E, Abecasis GR; Global J, Neil A, Durrington PN, Doney A, Carr F, Morris A, McCarthy MI, Groop
Lipids Genetics Consortium. Discovery and refinement of loci associated L, Ahlqvist E, Bis JC, Rice K, Smith NL, Lumley T, Whitsel EA, Stürmer
with lipid levels. Nat Genet. 2013;45:1274–1283. doi: 10.1038/ng.2797 T, Boerwinkle E, Ngwa JS, O’Donnell CJ, Vasan RS, Wei WQ, Wilke RA,
51. Peloso GM, Auer PL, Bis JC, Voorman A, Morrison AC, Stitziel NO, Brody Liu CT, Sun F, Guo X, Heckbert SR, Post W, Sotoodehnia N, Arnold AM,
JA, Khetarpal SA, Crosby JR, Fornage M, Isaacs A, Jakobsdottir J, Feitosa Stafford JM, Ding J, Herrington DM, Kritchevsky SB, Eiriksdottir G, Launer
MF, Davies G, Huffman JE, Manichaikul A, Davis B, Lohman K, Joon AY, LJ, Harris TB, Chu AY, Giulianini F, MacFadyen JG, Barratt BJ, Nyberg F,
Smith AV, Grove ML, Zanoni P, Redon V, Demissie S, Lawson K, Peters U, Stricker BH, Uitterlinden AG, Hofman A, Rivadeneira F, Emilsson V, Franco
Carlson C, Jackson RD, Ryckman KK, Mackey RH, Robinson JG, Siscovick OH, Ridker PM, Gudnason V, Liu Y, Denny JC, Ballantyne CM, Rotter JI,
DS, Schreiner PJ, Mychaleckyj JC, Pankow JS, Hofman A, Uitterlinden AG, Adrienne Cupples L, Psaty BM, Palmer CN, Tardif JC, Colhoun HM, Hitman
Harris TB, Taylor KD, Stafford JM, Reynolds LM, Marioni RE, Dehghan A, G, Krauss RM, Wouter Jukema J, Caulfield MJ; Welcome Trust Case
Franco OH, Patel AP, Lu Y, Hindy G, Gottesman O, Bottinger EP, Melander Control Consortium. Pharmacogenetic meta-analysis of genome-wide
O, Orho-Melander M, Loos RJ, Duga S, Merlini PA, Farrall M, Goel A, association studies of LDL cholesterol response to statins. Nat Commun.
Asselta R, Girelli D, Martinelli N, Shah SH, Kraus WE, Li M, Rader DJ, 2014;5:5068. doi: 10.1038/ncomms6068
Reilly MP, McPherson R, Watkins H, Ardissino D, Zhang Q, Wang J, 61. Postmus I, Warren HR, Trompet S, Arsenault BJ, Avery CL, Bis JC, Chasman
Tsai MY, Taylor HA, Correa A, Griswold ME, Lange LA, Starr JM, Rudan DI, de Keyser CE, Deshmukh HA, Evans DS, Feng Q, Li X, Smit RA, Smith
I, Eiriksdottir G, Launer LJ, Ordovas JM, Levy D, Chen YD, Reiner AP, AV, Sun F, Taylor KD, Arnold AM, Barnes MR, Barratt BJ, Betteridge J,
Hayward C, Polasek O, Deary IJ, Borecki IB, Liu Y, Gudnason V, Wilson Boekholdt SM, Boerwinkle E, Buckley BM, Chen YI, de Craen AJ,
JG, van Duijn CM, Kooperberg C, Rich SS, Psaty BM, Rotter JI, O’Donnell Cummings SR, Denny JC, Dubé MP, Durrington PN, Eiriksdottir G, Ford
CJ, Rice K, Boerwinkle E, Kathiresan S, Cupples LA; NHLBI GO Exome I, Guo X, Harris TB, Heckbert SR, Hofman A, Hovingh GK, Kastelein JJ,
Sequencing Project. Association of low-frequency and rare coding- Launer LJ, Liu CT, Liu Y, Lumley T, McKeigue PM, Munroe PB, Neil A,
sequence variants with blood lipids and coronary heart disease in 56,000 Nickerson DA, Nyberg F, O’Brien E, O’Donnell CJ, Post W, Poulter N, Vasan

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e117

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 7

RS, Rice K, Rich SS, Rivadeneira F, Sattar N, Sever P, Shaw-Hawkins S, 64. SEARCH Collaborative Group. SLCO1B1 variants and statin-induced
CLINICAL STATEMENTS

Shields DC, Slagboom PE, Smith NL, Smith JD, Sotoodehnia N, Stanton A, myopathy: a genomewide study. N Engl J Med. 2008;359:789–799. doi:
AND GUIDELINES

Stott DJ, Stricker BH, Stürmer T, Uitterlinden AG, Wei WQ, Westendorp 10.1056/NEJMoa0801936
RG, Whitsel EA, Wiggins KL, Wilke RA, Ballantyne CM, Colhoun HM, 65. Wilke RA, Ramsey LB, Johnson SG, Maxwell WD, McLeod HL, Voora
Cupples LA, Franco OH, Gudnason V, Hitman G, Palmer CN, Psaty BM, D, Krauss RM, Roden DM, Feng Q, Cooper-Dehoff RM, Gong L, Klein
Ridker PM, Stafford JM, Stein CM, Tardif JC, Caulfield MJ, Jukema JW, TE, Wadelius M, Niemi M; Clinical Pharmacogenomics Implementation
Rotter JI, Krauss RM. Meta-analysis of genome-wide association studies of Consortium (CPIC). The clinical pharmacogenomics implementation con-
HDL cholesterol response to statins. J Med Genet. 2016;53:835–845. doi: sortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy.
10.1136/jmedgenet-2016-103966 Clin Pharmacol Ther. 2012;92:112–117. doi: 10.1038/clpt.2012.57
62. Chu AY, Giulianini F, Barratt BJ, Ding B, Nyberg F, Mora S, Ridker 66. Global Burden of Disease Study 2016. Global Burden of Disease Study
PM, Chasman DI. Differential genetic effects on statin-induced 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
changes across low-density lipoprotein-related measures. Circ Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
Cardiovasc Genet. 2015;8:688–695. doi: 10.1161/CIRCGENETICS. data.org/gbd-results-tool. Accessed May 1, 2018.
114.000962 67. Farzadfar F, Finucane MM, Danaei G, Pelizzari PM, Cowan MJ, Paciorek
63. Shiffman D, Trompet S, Louie JZ, Rowland CM, Catanese JJ, Iakoubova CJ, Singh GM, Lin JK, Stevens GA, Riley LM, Ezzati M; Global Burden
OA, Kirchgessner TG, Westendorp RG, de Craen AJ, Slagboom PE, of Metabolic Risk Factors of Chronic Diseases Collaborating Group
Buckley BM, Stott DJ, Sattar N, Devlin JJ, Packard CJ, Ford I, Sacks FM, (Cholesterol). National, regional, and global trends in serum total choles-
Jukema JW. Genome-wide study of gene variants associated with differ- terol since 1980: systematic analysis of health examination surveys and
ential cardiovascular event reduction by pravastatin therapy. PLoS One. epidemiological studies with 321 country-years and 3·0 million partici-
2012;7:e38240. doi: 10.1371/journal.pone.0038240 pants. Lancet. 2011;377:578–586. doi: 10.1016/S0140-6736(10)62038-7
Downloaded from http://ahajournals.org by on February 7, 2019

e118 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

8. HIGH BLOOD PRESSURE Abbreviations Used in Chapter 8 Continued

CLINICAL STATEMENTS
PA physical activity
ICD-9 401 to 404; ICD-10 I10 to I15. See Tables 8-1

AND GUIDELINES
PAR population attributable risk
and 8-2 and Charts 8-1 through 8-6 QALY quality-adjusted life-year
REGARDS Reasons for Geographic and Racial Differences in Stroke
Click here to return to the Table of Contents RR relative risk
SBP systolic blood pressure
SES socioeconomic status
HBP is a major risk factor for CVD and stroke.1 The
SPRINT Systolic Blood Pressure Intervention Trial
AHA has identified untreated BP <90th percentile SSB sugar-sweetened beverage
(for children) and <120/<80 mm Hg (for adults aged
≥20 years) as 1 of the 7 components of ideal cardio-
vascular health.2 In 2013 to 2014, 88.7% of children Prevalence
and 45.4% of adults met these criteria (Chapter 2, (See Table 8-1, Chart 8-1, and Chart 8-2)
Cardiovascular Health).
• Although surveillance definitions vary widely in
the published literature, including for the CDC
Abbreviations Used in Chapter 8
and NHLBI, the following definition of HBP has
been proposed for surveillance3:
ACC American College of Cardiology
ACEI angiotensin-converting enzyme inhibitor
— SBP ≥130 mm Hg or DBP ≥80 mm Hg or self-
AHA American Heart Association reported antihypertensive medicine use, or
BMI body mass index — Having been told previously, at least twice,
BP blood pressure by a physician or other health professional
BRFSS Behavioral Risk Factor Surveillance System that one has HBP.
CARDIA Coronary Artery Risk Development in Young Adults
• With this definition, the age-adjusted preva-
CDC Centers for Disease Control and Prevention
CHD coronary heart disease
lence of hypertension among US adults ≥20
CI confidence interval years of age was estimated to be 46.0% in
CKD chronic kidney disease NHANES in 2013 to 2016 (49.0% for males and
CVD cardiovascular disease 42.8% for females). This equates to an esti-
DALY disability-adjusted life-year mated 116.4 million adults ≥20 years of age
DBP diastolic blood pressure
who have HBP (58.7 million males and 57.7
Downloaded from http://ahajournals.org by on February 7, 2019

DM diabetes mellitus
ED emergency department million females; Table  8-1; unpublished NHLBI
ESRD end-stage renal disease tabulation).
GBD Global Burden of Disease • In 2013 to 2016, the prevalence of HBP was
GWAS genome-wide association studies 26.1% among those 20 to 44 years of age,
HBP high blood pressure
59.2% among those 45 to 64 years of age, and
HCHS/SOL Hispanic Community Health Study/Study of Latinos
HCUP Healthcare Cost and Utilization Project
78.2% among those ≥65 years of age (unpub-
HF heart failure lished NHLBI tabulation).
HIV human immunodeficiency virus • The prevalence of HBP in adults ≥20 years of age
HR hazard ratio is presented by both age and sex in Chart 8-1.
ICD-9 International Classification of Diseases, 9th Revision • In 2013 to 2016, a higher percentage of males
ICD-9-CM International Classification of Diseases, Clinical
Modification, 9th Revision
than females had hypertension up to 64 years of
ICD-10 International Classification of Diseases, 10th Revision age. For those ≥65 years of age, the percentage
IDACO International Database on Ambulatory Blood Pressure of females with hypertension was higher than for
Monitoring in Relation to Cardiovascular Outcomes males (unpublished NHLBI tabulation).
JHS Jackson Heart Study • Data from NHANES 2013 to 2016 indicate
MEPS Medical Expenditure Panel Survey
that 35.3% of US adults with hypertension
MESA Multi-Ethnic Study of Atherosclerosis
MET metabolic equivalent are not aware they have it (unpublished NHLBI
MI myocardial infarction tabulation).
NAMCS National Ambulatory Medical Care Survey • The age-adjusted prevalence of hypertension in
NCHS National Center for Health Statistics 1999 to 2004, 2005 to 2010, and 2011 to 2016
NH non-Hispanic
is shown in race/sex subgroups in Chart 8-2.
NHAMCS National Hospital Ambulatory Medical Care Survey
NHANES National Health and Nutrition Examination Survey
• Data from the 2015 BRFSS/CDC indicate that the
NHIS National Health Interview Survey age-adjusted percentage of adults ≥18 years of
NHLBI National Heart, Lung, and Blood Institute age who had been told that they had HBP ranged
NIS National (Nationwide) Inpatient Sample from 24.2% in Minnesota to 39.9% in Mississippi.
OR odds ratio The age-adjusted percentage for the total United
(Continued ) States was 29.7%.4

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e119

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

• A meta-analysis of 24 studies (N=961 035) esti- SBP was 3.8 mm Hg (95% CI, 3.1–4.6 mm Hg)
CLINICAL STATEMENTS

mated the prevalence of apparent treatment- larger for each 10-year increase in age.13
AND GUIDELINES

resistant hypertension to be 13.7% (95% CI, • In the English Longitudinal Study of Ageing, the
11.2%–16.2%).5 prevalence, awareness, and treatment of hyper-
• In a cohort of patients with established kidney tension increased progressively between 1998
disease, 40.4% had resistant hypertension.6 and 2012 among octogenarians. Although BP
• An analysis of the Spanish Ambulatory Blood control (SBP/DBP <140/90 mm Hg) declined from
Pressure Monitoring Registry using 70  997 1998 to 2004 (37% to 31%), it increased to 47%
patients treated for hypertension estimated the by 2012.14
prevalence of resistant hypertension (SBP/DBP • Among adults in the REGARDS study ≥65 years of
≥140/90 mm Hg on at least 3 antihypertensive age with hypertension, having more indicators of
medications) was 16.9%, whereas the prevalence frailty (low BMI, cognitive impairment, depressive
of white-coat resistant hypertension was 37.1%. symptoms, exhaustion, impaired mobility, and
The prevalence of refractory hypertension (SBP/ history of falls) was associated with an increased
DBP ≥140/90 mm Hg on at least 5 antihyperten- risk for serious fall injuries (HR associated with
sive medications) was 1.4%, whereas the preva- 1, 2, and ≥3 versus 0 indicators of frailty, 1.18
lence of white-coat refractory hypertension was [95% CI, 0.99–1.40], 1.49 [95% CI, 1.19–1.87],
26.7%.7 and 2.04 [95% CI, 1.56–2.67], respectively). In
• SPRINT demonstrated that an SBP goal of <120 contrast, on-treatment SBP and DBP were not
mm  Hg resulted in fewer CVD events and a significantly associated with risk for serious fall
greater reduction in mortality than an SBP goal injuries.15
of <140 mm Hg among people with SBP ≥130 Children and Adolescents
mm Hg and increased cardiovascular risk.8 Using • In 2011 to 2012, 11.0% (95% CI, 8.8%–
NHANES 2007 to 2012 data, it was estimated 13.4%) of children and adolescents aged 8 to
that 7.6% (95% CI, 7.0%–8.3%) or 16.8 million 17 years had either HBP (SBP or DBP at the 95th
(95% CI, 15.7–17.8 million) US adults meet the percentile or higher) or borderline HBP (SBP or
SPRINT inclusion and exclusion criteria.9 DBP between the 90th and 95th percentile or
• Among 1677 participants in the IDACO cohort BP levels of 120/80 mm Hg or higher but <95th
Downloaded from http://ahajournals.org by on February 7, 2019

database aged 40 to 79 years with clinic-mea- percentile).16

sured SBP ≥140 mm Hg or DBP ≥90 mm Hg and • Among US children and adolescents, there was
not taking antihypertensive medication, 35.7% no evidence of a change in the prevalence of bor-
(95% CI, 23.5%–56.2%) had white-coat hyper- derline HBP (7.6% [95% CI, 5.8%–9.8%] versus
tension. Among 3320 participants from the same 9.4% [95% CI, 7.2%–11.9%]; P=0.90) or either
database with clinic SBP <140 mm Hg and clinic HBP or borderline HBP (10.6% [95% CI, 8.4%–
DBP <90 mm Hg and not taking antihypertensive 13.1%] versus 11.0% [95% CI, 8.8%–13.4%];
medication, 16.9% (95% CI, 8.8%–30.5%) had P=0.26) between 1999 to 2000 and 2011 to
masked hypertension.10 2012.16 In this age group, HBP declined from
• Using data from the 2011 to 2014 NHANES 3.0% to 1.6% between 1999 to 2000 and 2011
(N=9623), the prevalence of hypertension among to 2012.16
US adults was 45.6% (95% CI, 43.6%–47.6%) • In 2011 to 2012, HBP was more common
using BP thresholds from the 2017 ACC/AHA among boys (1.8%) than girls (1.4%) and
guidelines versus 31.9% (95% CI, 30.1%– among Hispanics (2.4%) than among NH blacks
33.7%) using Joint National Committee 7 guide- (1.9%), NH whites (1.1%), and NH Asians
line thresholds.11 (1.7%). Having either HBP or borderline HBP
• In a meta-analysis of people ≥16 years of age was more common among boys than girls. Also,
with HIV (49 studies; N=63 554), the prevalence NH blacks were more likely to have either HBP or
of hypertension was 25.2% (34.7% among those borderline HBP than Hispanic, NH white, or NH
who were taking or had taken antiretroviral ther- Asian boys or girls.16
apy and 12.7% among those who had not ever • In 2003 to 2010, for girls 8 to 11 years of age,
taken antiretroviral therapy).12 3.5% had poor BP, 5.0% had intermediate BP,
and 91.5% had ideal BP levels according to the
Older Adults AHA 2020 Strategic Impact Goals. For boys 8 to
• The white-coat effect (clinic minus out-of-clinic 11 years of age, 2.8% had poor BP, 4.8% had
BP) is larger at older ages. In IDACO, a pooled intermediate BP, and 92.5% had ideal BP accord-
analysis of 11 cohorts, the white-coat effect for ing to Life’s Simple 7.17

e120 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

• Analysis of data for children and adolescents individuals with a follow-up visit had a BP ≥95th

CLINICAL STATEMENTS
aged 8 to 17 years from NHANES 1999 to 2002 percentile at this visit.25

AND GUIDELINES
through NHANES 2009 to 2012 found that mean
SBP decreased from 105.6 to 104.9 mm Hg and
DBP decreased from 60.3 to 56.1 mm Hg.16,18 Race/Ethnicity and HBP
• In NHANES 1999 to 2012, the prevalence of (See Table 8-1 and Chart 8-2)
HBP was 9.9% among severely obese US ado- • The prevalence of hypertension in blacks in the
lescents (BMI ≥120% of 95th percentile of sex- United States is among the highest in the world.
specific BMI for age or BMI ≥35 kg/m2). The In 2011 to 2016, the age-adjusted prevalence
OR for HBP was 5.3 (95% CI, 3.8–7.3) when of hypertension among NH blacks was 57.6%
comparing severely obese versus normal-weight among males and 53.2% among females (Chart
adolescents.19 8-2) (unpublished NHLBI tabulation).
• Among normal-weight and overweight/obese • Among >4 million adults who were overweight or
US adolescents (12–19 years of age), mean SBP obese in 10 healthcare systems, the prevalence of
and DBP did not change between 1988 to 1994 hypertension was 47.3% among blacks, 39.6%
and 2007 to 2012. The unadjusted prevalence of among whites, 38.6% among Native Hawaiians/
pre-HBP was 11.4% and the prevalence of HBP Pacific Islanders, 38.3% among American
was 0.9% in 1988 to 1994; the prevalence of Indians/Native Americans, 34.8% among Asians,
pre-HBP was 11.1% and that of HBP was 1.4% and 24.8% among Hispanics. Within categories
in 2007 to 2012. Among overweight/obese ado- defined by BMI and after adjustment for age, sex,
lescents, the unadjusted prevalence of pre-HBP and healthcare system, each racial/ethnic group
was 15.5% and that of HBP was 6.4% in 1988 except Hispanics was more likely to have hyper-
to 1994; the unadjusted prevalence of pre-HBP tension than whites.26
was 21.4% and that of HBP was 3.4% in 2007 • During 10 years of follow-up in the REGARDS
to 2012.20 study, a higher percentage of black males (48%)
• The AHA has outlined conditions in which ambu- and females (54%) developed hypertension than
latory BP monitoring may be helpful in children white males (38%) or females (27% for those 45
and adolescents. These include secondary hyper- to 54 years of age and 40% for those ≥75 years
tension, CKD, type 1 and type 2 DM, obesity,
Downloaded from http://ahajournals.org by on February 7, 2019

old).27
sleep apnea, genetic syndromes, treated patients • Higher SBP explains ≈50% of the excess stroke
with hypertension, and for research.21 In a retro- risk among blacks compared with whites.28
spective study of 500 children screened for poten- • Data from the 2014 NHIS showed that black
tial hypertension with ambulatory BP monitoring, adults ≥18 years of age were more likely (33.0%)
12% had white-coat hypertension and 10% had to have been told on ≥2 occasions that they had
masked hypertension.22 hypertension than American Indian/Alaska Native
• In a systematic review of studies evaluating secu- adults (26.4%), white adults (23.5%), Hispanic or
lar trends in BP among children and adolescents Latino adults (22.9%), or Asian adults (19.5%).29
(N=18 studies with >2 million participants), BP • In HCHS/SOL, for US Hispanic or Latino males, the
decreased between 1963 and 2012 in 13 studies, age-standardized prevalence of hypertension in
increased in 4 studies, and did not change in 1 2008 to 2011 varied from a low of 19.9% among
study conducted.23 No formal pooling of data was individuals of South American background to a
conducted. high of 32.6% among individuals of Dominican
• Among adolescents (mean age 14 years) with background. For US Hispanic or Latino females,
CKD, 40% had masked hypertension (clinic the age-standardized prevalence of hypertension
SBP and DBP <90th percentile for age, sex, and was lowest for individuals of South American
height, and awake or asleep BP ≥95th percentile background (15.9%) and highest for individuals
or BP load ≥25%).24 of Puerto Rican background (29.1%).30
• Among 30 565 children and adolescents (3–17 • Also in HCHS/SOL, the prevalence of awareness,
years old) receiving health care between 2012 treatment, and control of hypertension among
and 2015, 51.2% of those with a first BP read- males was lowest in those of Central American
ing ≥95th percentile for age, sex, and height and background (57%, 39%, and 12%, respectively)
who had a second BP measurement had a mean and highest among those of Cuban background
BP based on 2 consecutive readings that was less (78%, 65%, and 40%, respectively). Among
than the 95th percentile. Of those with a visit BP females, those of South American background
≥95th percentile, 67.8% did not have a follow- had the lowest prevalence of awareness (72%)
up visit within 3 months, and only 2.3% of those and treatment (64%), whereas hypertension

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e121

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

control was lowest among females of Central for Hispanic females, 14.0 for NH Asian/Pacific
CLINICAL STATEMENTS

American background (32%). Only Hispanic Islander females, and 20.7 for NH American
AND GUIDELINES

females reporting mixed/other background had a Indian/Alaska Native females.38

hypertension control rate that exceeded 50%.31 • From 2006 to 2016, the death rate attributable
• Among adults with hypertension, blacks were to HBP increased 18.0%, and the actual number
more likely to have resistant hypertension (19.0%) of deaths attributable to HBP rose 46.3%. During
than whites (13.5%) or Hispanics (11.2%).32 this 10-year period, in NH whites, the HBP death
• Among 22 705 black adults with hypertension rate increased 19.3%, whereas the actual number
receiving care in the New York City Health and of deaths attributable to HBP increased 44.5%. In
Hospital Corporation outpatient clinics in 2004 NH blacks, the HBP death rate decreased 2.2%,
to 2009, the percentage with controlled BP whereas the actual number of deaths attribut-
(SBP/DBP <140/90 mm  Hg) was lower among able to HBP increased 31.2%. In Hispanics, the
Caribbean-born individuals (49.0%) than among HBP death rate increased 13.4%, and the actual
those born in the United States (58.3%) or West number of deaths attributable to HBP increased
Africa (58.4%).33 96.8% (unpublished NHLBI tabulation).
• In an analysis of NHANES participants from 2003 • When any mention of HBP was present, the
to 2014, foreign-born NH blacks (N=522) had overall age-adjusted death rate in 2016 was
lower adjusted odds of having hypertension than 115.8 per 100 000. Death rates were 126.5
US-born NH blacks (N=4511; OR, 0.61; 95% CI, for NH white males, 221.9 for NH black males,
0.49–0.77).34 87.8 for NH Asian or Pacific Islander males,
• In NHANES 2011 to 2014, US NH blacks (13.2%) 155.8 for NH American Indian or Alaska Native
were more likely than NH Asians (11.0%), NH males (underestimated because of underreport-
whites (8.6%), or Hispanics (7.4%) to use home ing), and 116.6 for Hispanic males. In females,
BP monitoring on a weekly basis.35 rates were 95.3 for NH white females, 153.8
• Among 559 participants who reported having for NH black females, 68.0 for NH Asian or
hypertension in the AHA’s Cardiovascular Health Pacific Islander females, 111.7 for NH American
Consumer Survey, 53.8% of participants reported Indian or Alaska Native females (underesti-
using a home BP monitor.36 mated because of underreporting), and 85.9 for
• Among 441 African Americans in the JHS not tak- Hispanic females.39,40
Downloaded from http://ahajournals.org by on February 7, 2019

ing antihypertensive medication, the prevalence • The hypertension-related death rate increased
of clinic hypertension (mean SBP ≥140 mm Hg or 6.8% from 523.8 per 100 000 in 2000 to 559.3 in
mean DBP ≥90 mm Hg) was 14.3%, the prevalence 2005 for NH blacks, and then it decreased 8.8%
of daytime hypertension (mean daytime SBP ≥135 to 509.9 in 2013. Among Hispanics, the rate
mm Hg or mean daytime DBP ≥85 mm Hg) was increased 21.9% from 233.7 in 2000 to 284.8
31.8%, and the prevalence of nighttime hyperten- in 2013. For the NH white population, the rate
sion (mean nighttime SBP ≥120 mm Hg or mean increased 29.8% from 228.5 in 2000 to 296.5 in
nighttime DBP ≥70 mm Hg) was 49.4%. Among 2013.41
575 African Americans taking antihypertensive • CHD, stroke, cancer, and DM accounted for 65%
medication, the prevalence estimates were 23.1% of all deaths with any mention of hypertension in
for clinic hypertension, 43.0% for daytime hyper- 2000 and for 54% in 2013.41
tension, and 61.7% for nighttime hypertension.37 • The elimination of hypertension could reduce CVD
mortality by 30.4% among males and 38.0%
among females.42 The elimination of hypertension
Mortality is projected to have a larger impact on CVD mor-
(See Table 8-1) tality than the elimination of all other risk factors
• Using data from the National Vital Statistics among females and all except smoking among
System, in 2016, there were 82 735 deaths pri- males.42
marily attributable to HBP (Table  8-1). The 2016 • Among US adults meeting the eligibility criteria
age-adjusted death rate primarily attributable for SPRINT, SBP treatment to a treatment goal of
to HBP was 21.6 per 100  000. Age-adjusted <120 mm Hg versus <140 mm Hg has been pro-
death rates attributable to HBP (per 100 000) in jected to prevent ≈107 500 deaths per year (95%
2016 were 21.1 for NH white males, 54.0 for CI, 93 300–121 200).43
NH black males, 20.1 for Hispanic males, 16.0 • On the basis of a Swedish cohort study from
for NH Asian/Pacific Islander males, 26.2 for NH 2006 to 2012, patients with treatment-resis-
American Indian/Alaska Native males, 17.3 for NH tant hypertension (N=4317) had a 12% higher
white females, 36.7 for NH black females, 15.6 risk of all-cause mortality (HR, 1.12; 95% CI,

e122 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

1.03–1.23) than patients with hypertension but 32.7%, 25.8% and 10.7% among participants

CLINICAL STATEMENTS
not treatment-resistant hypertension (N=32 282). with 2, 3, 4, 5, and 6 ideal components, respec-

AND GUIDELINES
Patients with treatment-resistant hypertension tively. No participants had 7 ideal Life’s Simple 7
also had a higher risk of cardiovascular mortality components. A strong and dose-response asso-
(HR, 1.20; 95% CI, 1.03–1.40) than participants ciation between having more ideal Life’s Simple 7
with hypertension but not treatment-resistant components and lower risk for hypertension was
hypertension.44 present after multivariable adjustment.53
• In a meta-analysis of 5 studies, each additional
250 mL of SSBs was associated with an RR for inci-
Risk Factors dent hypertension of 1.07 (95% CI, 1.04–1.10).54
• Participants with SSB consumption in the highest • In a meta-analysis of 36 trials, randomization to
versus lowest quantile had a risk ratio for hyper- reduction in alcohol consumption was associ-
tension of 1.12 (95% CI, 1.06–1.17) in a meta- ated with a reduction in SBP for participants who
analysis of 240 508 people.45 This equated to an at baseline consumed ≥6 drinks per day (−5.50
8.2% increased risk for hypertension for each mm Hg; 95% CI, −6.70 to −4.30 mm Hg), 4 or
additional SSB consumed per day. 5 drinks per day (−3.00 mm Hg; 95% CI, −3.98
• A systematic review identified 48 hypertension to −2.03 mm Hg), and 3 drinks per day (−1.18
risk prediction models reported in 26 studies mm Hg; 95% CI, −2.32 to −0.04 mm Hg) but not
(N=162 358 enrolled participants). The C statistics their counterparts who drank 2 or fewer drinks
from these models ranged from 0.60 to 0.90.46 per day (−0.18; 95% CI, −1.02 to 0.66 mm Hg).55
• In the JHS, intermediate and ideal versus poor • In the HCHS/SOL Sueño Sleep Ancillary Study of
levels of moderate to vigorous PA were associ- Hispanics (N=2148), a 10% higher sleep fragmen-
ated with HRs of hypertension of 0.84 (95% tation and frequent napping versus not napping
CI, 0.67–1.05) and 0.76 (95% CI, 0.58–0.99), were associated with a 5.2% and 11.6% higher
respectively.47 prevalence of hypertension, respectively. A 10%
• Also, anger, depressive symptoms, and stress higher sleep efficiency was associated with 7.2%
were associated with increased BP progression in lower prevalence of hypertension.56
the JHS.48 • In a meta-analysis of 24 cohort studies, each 10
• In the JHS, an additional social contact was associ-
Downloaded from http://ahajournals.org by on February 7, 2019

additional MET-hours per week in leisure-time

ated with a fully adjusted prevalence ratio of 0.87 PA was associated with an RR for hypertension
(95% CI, 0.74–1.0) for having treatment-resistant of 0.94 (95% CI, 0.92–0.96). In 5 cohort studies,
hypertension in a sample of 1392 participants each additional 50 MET-hours per week in total
with treated hypertension who self-reported PA time was associated with an RR for hyperten-
being adherent to antihypertensive medication.49 sion of 0.93 (95% CI, 0.88–0.98).57
• In NHANES 2013 to 2014, each additional 1000
mg of usual 24-hour sodium excretion (ie, a
marker of sodium consumption) was associated Aftermath
with 4.58 (95% CI, 2.64–6.51) mm Hg higher SBP • In a meta-analysis that included 95  772 US
and 2.25 (0.83–3.67) mm Hg higher DBP. Each females and 30 555 US males, each 10-mm Hg
additional 1000 mg usual 24-hour potassium higher SBP was associated with an effect size (eg,
intake was associated with 3.72 (95% CI, 1.42 - RR or HR) for CVD of 1.25 (95% CI, 1.18–1.32)
6.01) mm Hg lower SBP.50 among females and 1.15 (95% CI, 1.11–1.19)
• Among 1741 participants in the JHS with hyper- among males. Among 65 806 females and 92 515
tension, 20.1% of those without versus 30.5% of males in this meta-analysis, the RR for CVD mor-
those with CKD developed apparent treatment- tality associated with 10-mm Hg higher SBP was
resistant hypertension (multivariable-adjusted HR, 1.16 (95% CI, 1.10–1.23) among females and
1.45; 95% CI, 1.12–1.86).51 1.17 (95% CI, 1.12–1.22) among males.58
• In a meta-analysis of 9 population-based stud- • In a meta-analysis of 12 prospective studies
ies (N=102 408), the OR for having hypertension (N=2  170  265), participants with a history of
among participants with versus without restless hypertension were more likely to develop kidney
leg syndrome was 1.36 (95% CI, 1.18–1.57).52 cancer (RR, 1.67; 95% CI, 1.46–1.90).59
• Among 1878 participants in the JHS who were • In a study of >1 million adults with hyperten-
followed up for a median of 8 years, the cumula- sion, the lifetime risk of CVD at age 30 years was
tive incidence of hypertension was 80.9% among 63.3% compared with 46.1% for those without
those with 0 of 1 of the Life’s Simple 7 compo- hypertension. Those with hypertension developed
nents in the ideal range and 66.7%, 54.8%, CVD 5.0 years earlier than their counterparts

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e123

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

without hypertension.60 The largest lifetime risk a previous history of hypertension or SBP/DBP
CLINICAL STATEMENTS

differences between people with versus without ≥140/90 mm Hg was associated with an OR for
AND GUIDELINES

hypertension were for angina, MI, and stroke. At stroke of 2.98 (95% CI, 2.72–3.28). The PAR
age 60 years, the lifetime risk for CVD was 60.2% for stroke accounted for by hypertension was
for those with hypertension and 44.6% for their 47.9%.68
counterparts without hypertension. • Among adults 45 years of age without HF, HF-free
• In a cohort of older US adults, both isolated sys- survival was shorter among those with versus
tolic hypertension and systolic-diastolic hyperten- without hypertension in males (30.4 versus 34.3
sion were associated with an increased risk for years), females (33.5 versus 37.6 years), blacks
HF (multivariable-adjusted HR, 1.86; 95% CI, (33.2 versus 37.3 years), and whites (31.9 versus
1.51–2.30 and HR, 1.73; 95% CI, 1.24–2.42, 36.3 years).69
respectively) compared with participants without • In prospective follow-up of the REGARDS, MESA,
hypertension.61 and JHS cohorts (N=31 856), 63.0% (95% CI,
• Overall, in national data, the prevalence of healthy 54.9%–71.1%) of the 2584 incident CVD events
lifestyle behaviors varies widely among those with occurred in participants with SBP <140 and DBP
self-reported hypertension: 20.5% had a normal <90 mm Hg.70
weight, 82.3% did not smoke, 94.1% reported
no or limited alcohol intake, 14.1% consumed
the recommended amounts of fruits or vegeta- Hospital Discharges/Ambulatory Care
bles, and 46.6% engaged in the recommended Visits
amount of PA.62 (See Table 8-1)
• The association of hypertension with CHD has not
changed from 1983 to 1990 (HR, 1.14; 95% CI, • From 2004 to 2014, the number of inpatient
1.11–1.16) versus 1996 to 2002 (HR, 1.13; 95% discharges from short-stay hospitals with HBP
CI, 1.10–1.15). The PAR associated with hyper- as the principal diagnosis was stable at 285 000
tension was 39.6% in the early time period and and 292  000, respectively (HCUP, unpub-
40.0% in the later time period.63 lished NHLBI tabulation) The number of dis-
• Among 17 312 participants with hypertension, charges with any listing of HBP increased from
nondipping BP was associated with an HR for 12 461 000 to 15 638 000 (HCUP, unpublished
Downloaded from http://ahajournals.org by on February 7, 2019

CVD of 1.40 (95% CI, 1.20–1.63).64 NHLBI tabulation).

• In the JHS, a cohort composed exclusively of African • In 2014, there were 90 000 principal diagno-
Americans, masked hypertension was associated sis discharges for essential hypertension (HCUP,
with an HR for CVD of 2.49 (95% CI, 1.26–4.93).65 unpublished NHLBI tabulation).
• A meta-analysis (23 cohorts with 20 445 partici- • In 2014, there were 11 584 000 all-listed dis-
pants) showed that white- coat hypertension is charges for essential hypertension (HCUP, unpub-
associated with an increased risk for CVD among lished NHLBI tabulation).
untreated individuals (adjusted HR, 1.38; 95% • Data from the NIS from the years 2000 to
CI, 1.15–1.65) but not among treated individuals 2011 found the frequency of hospitalizations
(HR, 1.16; 95% CI, 0.91–1.49).66 for malignant hypertension and hypertensive
• In a pooled analysis of 63 559 people without encephalopathy increased, whereas hospital-
hypertension from 49 countries, sodium excre- izations for essential hospitalization decreased,
tion >7 g/d was associated with an HR for which coincided with the introduction of medi-
CVD of 1.23 (95% CI, 1.11–1.37), and sodium cal severity diagnosis-related group billing.
excretion <3 g/d was associated with an HR of Overall, the annual incidence of hypertension-
1.34 (95% CI, 1.23–1.47), each compared with related hospitalizations increased over the time
sodium excretion of 4.5 g/d.67 period from ≈87 000 in 2000 to ≈120 000 in
• Among adults with established CKD, apparent 2011.71
treatment-resistant hypertension has been associ- • In 2006 to 2010, 7.1% of patients with hyper-
ated with increased risk for CVD (HR, 1.38; 95% tension attending outpatient visits had treatment-
CI, 1.22–1.56), renal outcomes including a 50% resistant hypertension. The use of thiazide diuretic
decline in estimated glomerular filtration rate or agents and chlorthalidone was low (56.4% and
end-stage renal disease (HR, 1.28; 95% CI, 1.11– 1.2%, respectively).72
1.46), HF (HR, 1.66; 95% CI, 1.38–2.00), and all- • In 2015, 42 749 000 of 990 808 000 physician
cause mortality (HR, 1.24; 95% CI, 1.06–1.45).6 office visits had a primary diagnosis of essential
• In an international case-control study (N=13 447 hypertension (ICD-9-CM 401; NCHS, NAMCS,
cases of stroke and N=13 472 control subjects), NHLBI tabulation).73 A total of 1  182 000 of

e124 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

136 943 000 ED visits in 2015 and 3 743 000 of The use of calcium channel blockers remained the

CLINICAL STATEMENTS
125 721 000 hospital outpatient visits in 2011 same, at 6%.77

AND GUIDELINES
were for essential hypertension (NCHS, NHAMCS, • In a multinational study of 63 014 adults from
NHLBI tabulation).74 high-, middle-, and low-income countries, 55.6%
• Among REGARDS study participants ≥65 years of participants were aware of their diagnosis of
of age with hypertension, compared with those hypertension, 44.1% were treated, and 17.1%
without apparent treatment-resistant hyperten- had controlled BP. Awareness and control were
sion, participants with apparent treatment-resis- less common in upper-middle-income countries,
tant hypertension and uncontrolled BP had more whereas treatment was lowest in low-income
primary care visits (2.77 versus 2.27 per year) countries.78
and more cardiologist visits (0.50 versus 0.35 per • Among US adults in NHANES 2007 to 2012, 55%
year). In this same study, there were no statisti- of those with a usual source of care compared
cally significant differences in laboratory testing with 14% of their counterparts without a usual
for end-organ damage or secondary causes of source of care had controlled hypertension (SBP/
hypertension among participants with apparent DBP <140/90 mm Hg). In addition, 31% of those
treatment-resistant hypertension and uncon- who reported using the ED as their usual source
trolled BP (72.4%), apparent treatment-resistant of care had controlled hypertension.79
hypertension and controlled BP (76.5%), and • According to the 2006 to 2010 NAMCS, 16.3%
with hypertension but not apparent treatment- of patients with uncontrolled BP were pre-
resistant hypertension (71.8%).75 scribed a new antihypertensive medication.
Patients receiving care at community health
clinics versus private physician’s offices had a
Awareness, Treatment, and Control greater odds of being prescribed a new antihy-
(See Table 8-2 and Charts 8-3 pertensive medication (adjusted OR, 1.6; 95%
through 8-5) CI, 1.1–2.4).80
• Self-reported antihypertensive medication use
• Using NHANES 2013 to 2016 data, the extent increased from 2.2% in 1971 to 1975 to 7.7%
of awareness, treatment, and control of HBP is in 2009 to 2012 among US adults 25 to 49 years
provided by race/ethnicity (Chart 8-3), by age of age.81
Downloaded from http://ahajournals.org by on February 7, 2019

(Chart 8-4), and by race/ethnicity and sex (Chart • In a cohort study of Korean patients from 2009 to
8-5) (unpublished NHLBI tabulation). Awareness, 2013 with health insurance claims for hyperten-
treatment, and control of hypertension were sion (N=38 520), those with poor adherence to
higher at older ages (Chart 8-4). Overall, females antihypertensive medication (defined as <50% of
were more likely than males in all race/ethnic- days of follow up covered by a medication pre-
ity groups to be aware of their condition, under scription fill) had an adjusted risk ratio for stroke
treatment, or in control of their hypertension of 1.27 (95% CI, 1.17–1.38) compared with
(Chart 8-5). those with high adherence (>80% of days cov-
• Analysis of NHANES 1999 to 2006 and 2007 ered by prescription fill).82
to 2014 found the proportion of adults aware • Using national prescription data in Denmark, the
of their hypertension increased within each use of antihypertensive medications increased
race/ethnicity and sex subgroup. Similarly, large from 184 to 379 defined daily doses per 1000
increases in hypertension treatment and con- inhabitants per day. Over this time period,
trol (≈10%) occurred in each of these groups increases were present for ACEIs (29 to 105
(Table 8-2). defined daily doses), angiotensin II receptor block-
• Among US adults taking prescription antihyper- ers (13 to 73 defined daily doses), β-blockers (17
tensive medication, the age-adjusted percentage to 34 defined daily doses), and calcium channel
with BP control increased from 61.9% to 70.4% blockers (34 to 82 defined daily doses).83
from 2003 to 2004 to 2011 to 2012.76 • Among 3358 African Americans taking anti-
• Data from NHANES 1999 to 2012 show that the hypertensive medication in the JHS, 25.4% of
use of various classes of antihypertensive treat- participants reported not taking ≥1 of their pre-
ment had increased substantially among people scribed antihypertensive medications within the
≥20 years of age. During this period, the use of 24 hours before their baseline study visit in 2000
ACEIs increased from 6.3% of the US popula- to 2004. This percentage was 28.7% at examina-
tion to 12%, angiotensin receptor blockers from tion 2 (2005–2008) and 28.5% at examination 3
2.1% to 5.8%, β-blockers from 6.0% to 11%, (2009–2012). Nonadherence was associated with
and thiazide diuretic drugs from 5.6% to 9.4%. higher likelihood of having SBP ≥140 mm Hg or

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e125

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

DBP ≥90 mm Hg (prevalence ratio, 1.26; 95% CI, linked to increased risk of hypertension. Findings
CLINICAL STATEMENTS

1.16–1.37).84 were particularly pronounced for education, with

AND GUIDELINES

• In an analysis of 1590 healthcare providers who a 2-fold higher rate of hypertension observed in
completed the DocStyles survey, a web-based lower- compared with higher-educated individu-
survey of healthcare providers, 86.3% reported als. Associations were stronger among women
using a prescribing strategy to increase their and in higher-income countries.93 Additional
patients’ adherence. The most common strat- research among Hispanics has found that lower
egies were prescribing once-daily regimens education is also a risk factor for lower BP
(69.4%), prescribing medications covered by the dipping.94
patient’s insurance (61.8%), and using longer fills • Racial segregation (residing in a neighborhood
(59.9%).85 composed primarily of others from the same
racial/ethnic background) and neighborhood pov-
erty have also been linked to hypertension preva-
Cost lence, particularly among African Americans.95
(See Table 8-1) Recent data from the CARDIA study also found
• The estimated direct and indirect cost of HBP for that for African Americans, moving from highly
2014 to 2015 (annual average) was $55.9 billion segregated census tracts to areas lower in segre-
(MEPS, NHLBI tabulation). gation over a 25-year follow-up was associated
• Adjusted to 2012 US dollars, the monetary sav- with up to a 5.71 mm Hg reduction in SBP, even
ings and QALYs gained with lifetime treatment after adjustment for poverty and other relevant
were $7387 and 1.14 for white males, $7796 and risk factors.96
0.89 for white females, $8400 and 1.66 for black • Self-reported experiences of discrimination and
males, and $10 249 and 1.79 for black females, unfair treatment have also been linked to hyper-
respectively.86 tension and BP. In a meta-analysis of 44 studies,
• Projections show that by 2035, the total direct higher reports of discrimination were linked to a
costs of HBP could increase to an estimated greater prevalence of hypertension, particularly
$220.9 billion (based on methodology described among African Americans (compared with other
in Heidenreich et al87).88 racial/ethnic groups), participants of older ages,
Downloaded from http://ahajournals.org by on February 7, 2019

• According to IMS Health’s National Prescription males, and individuals with a lower versus higher
Audit, the number of prescriptions for antihy- level of education. Associations between reports
pertensive medication increased from 614 mil- of discrimination and BP were most striking for
lion to 653 million between 2010 and 2014. The ambulatory nighttime BP; effect sizes for overall
653 million antihypertensive prescriptions filled in associations between self-reported experiences of
2014 cost $28.81 billion.89 discrimination and resting SBP or DBP were not
• Among a 5% sample of US Medicare benefi- significant.97
ciaries initiating antihypertensive treatment in • At least 1 study has found that social integra-
2012 (N=41 135), 21.3% discontinued treatment tion, defined as the number of social contacts
within 1 year and an additional 31.7% had low of an individual, may be an important factor to
adherence.90 consider in treatment-resistant hypertension.
• Using data from MEPS for 2011 to 2014, among In the JHS, a study of African Americans, each
persons with a diagnosis code for hypertension additional social contact was associated with a
who were ≥18 years of age (N=26 049), the mean 19% lower prevalence of treatment-resistant
annual costs of hypertension ranged from $3914 hypertension.49
(95% CI, $3456–$4372) for those with no comor-
bidities to $13 920 (95% CI, $13 166–$14 674)
for those with ≥3 comorbidities.91
Family History and Genetics
• Among US adults, medical expenditures associ- • BP is a heritable trait; family studies have yielded
ated with having versus not having hypertension heritability estimates of 48% to 60% (SBP) and
were $1494 in 2012 to 2013 and $1399 in 2000 34% to 67% (DBP).98
to 2001. Outpatient expenditures increased from • Genetic studies have been conducted to identify
$322 in 2000 to 2001 to $416 in 2012 to 2013.92 the genetic architecture of hypertension. Several
large-scale GWASs and whole-exome studies,
with interrogation of common and rare variants in
Social Determinants >300 000 individuals, have established >100 well-
• In a meta-analysis of 51 studies, lower SES mea- replicated hypertension loci, with several hundred
sured by income, occupation, or education was additional suggestive loci.99–105

e126 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

• Genetic risk scores for hypertension are also asso- in low-middle-income countries. It was also

CLINICAL STATEMENTS
ciated with increased risk of CVD and MI.99 estimated that 1.39 billion adults worldwide

AND GUIDELINES
• Given strong effects of environmental factors on had hypertension in 2010 (349 million in high-
hypertension, gene-environment interactions are income countries and 1.04 billion in low- and
important in the pathophysiology of hyperten- middle-income countries).116
sion. Large-scale gene-environment interaction • In 2015, the prevalence of SBP ≥140 mm Hg
studies have not yet been conducted; however, was estimated to be 20 526 per 100 000. This
studies of several thousand people have to date represents an increase from 17 307 per 100 000
revealed several loci of interest that interact with in 1990.117 Also, the prevalence of SBP 110 to
smoking106,107 and with dietary intake of alcohol108 115 mm Hg or higher increased from 73 119 per
and sodium.109 100 000 to 81 373 per 100 000 between 1990
• The clinical implications and utility of hyperten- and 2015. There were 3.47 billion adults world-
sion genes remain unclear, although some genetic wide with SBP of 110 to 115 mm Hg or higher in
variants have been shown to influence response 2015. Of this group, 847 million adults had SBP
to antihypertensive agents.110 ≥140 mm Hg.117
• It has been estimated that 7.834 million deaths
and 143.037 million DALYs in 2015 could be
Global Burden of Hypertension attributed to SBP ≥140 mm Hg.117 In addition,
(See Chart 8-6) 10.7 million deaths and 211 million DALYs in
• From 1980 to 2008, the global age-adjusted prev- 2015 could be attributed to SBP of 110 to 115
alence of uncontrolled hypertension decreased mm Hg or higher.117
from 33% to 29% among males and from 29% • Between 1990 and 2015, the number of deaths
to 25% among females.111 related to SBP ≥140 mm Hg did not increase in
• HBP went from being the fourth-leading risk fac- high-income countries (from 2.197 to 1.956 mil-
tor for global disease burden in 1990, as quanti- lion deaths) but did in high-middle-income (from
fied by DALYs, to being the number 1 risk factor 1.288 to 2.176 million deaths), middle-income
in 2010.112 (from 1.044 to 2.253 million deaths), low-middle-
• In a cross-sectional study of 628 communities (3 income (from 0.512 to 1.151 million deaths), and
low-income (from 0.146 to 0.293 million deaths)
Downloaded from http://ahajournals.org by on February 7, 2019

high-income countries, 10 upper-middle-income

and low-middle-income countries, and 4 low- countries.117
income countries), low-income countries had the • The GBD 2016 Study used statistical models
lowest percentages of awareness (40.8%) and and data on incidence, prevalence, case fatal-
treatment (31.7%) of hypertension (self-reported ity, excess mortality, and cause-specific mortal-
treated hypertension or SBP/DBP ≥140/90 ity to estimate disease burden for 315 diseases
mm Hg). Low-middle-income countries had the and injuries in 195 countries and territories.
lowest percentage of controlled hypertension The highest mortality rates attributable to high
(9.9%).113 SBP are in Eastern Europe and Central Asia
• In 2010, HBP was 1 of the 5 leading risk fac- (Chart 8-6).118
tors for the burden of disease (years of life lost • Among ≈1.7 million participants from the Chinese
and DALYs) in all regions with the exception of mainland aged 35 to 75 years from 2014 to 2017,
Oceania.112 the age- and sex-standardized prevalence of
• In a meta-analysis of population-studies con- hypertension was 37.2%.119
ducted in Africa, the prevalence of hypertension • In a meta-analysis of 25 studies (N=54 196 partici-
was 55.2% among adults ≥55 years of age.114 pants aged 2 to 19 years) conducted in Africa, the
• In a systematic review, a higher percentage of pooled prevalence of SBP or DBP ≥95th percentile
hypertension guidelines developed in high-income was 5.5% and the pooled prevalence of SBP or
countries used high-quality systematic reviews of DBP ≥90th percentile was 12.7%. The prevalence
relevant evidence compared with low- and mid- of SBP/DBP ≥95th percentile was 30.8% among
dle-income countries (63.5% versus 10%).115 children with obesity versus 5.5% among normal-
• On the basis of data from 135 population- weight children.120
based studies (N=968 419 adults from 90 coun- • Among 12 971 Turkish adults who completed
tries), it was estimated that 31.1% (95% CI, the Chronic Diseases and Risk Factors Survey, a
30.0%–32.2%) of the world adult population nationwide study, the prevalence of hypertension
had hypertension in 2010. The prevalence was in 2011 was 27.1%, 65% of participants were
28.5% (95% CI, 27.3%–29.7%) in high-income aware they had hypertension, 59% were treated,
countries and 31.5% (95% CI, 30.2%–32.9%) and 30% had SBP/DBP <140/90 mm Hg.121

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e127

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

• In a meta-analysis of studies in Africa among older • Among US adults with prehypertension, between
CLINICAL STATEMENTS

adults (≥55 years of age; 91 studies with 54 198 1999 to 2000 and 2011 to 2012, there was an
AND GUIDELINES

participants), the prevalence of hypertension was increase in the prevalence of overweight (from
55.2%.114 33.5% to 37.3%), obesity (30.6% to 35.2%), no
weekly leisure-time PA (40.0% to 43.9%), pre-
DM (9.6% to 21.6%), and DM (6.0% to 8.5%).
Prehypertension There was a decrease in the prevalence of cur-
• Among adults without hypertension, prehyper- rent smoking over the time period (from 25.9%
tension is defined by an untreated SBP of 120 to to 23.2%).122
139 mm Hg or untreated DBP of 80 to 89 mm Hg. • Among young adults (18–30 years old at baseline)
• Between 1999 to 2000 and 2011 to 2012, the with and without prehypertension in CARDIA,
prevalence of prehypertension decreased among 23.1% and 3.8%, respectively, developed hyper-
US adults from 31.2% to 28.2%.122 In NHANES, tension over 5 years of follow-up.124
the prevalence of prehypertension decreased • Multiple meta-analyses have demonstrated that
in all age groups for US adults between 1999 prehypertension is associated with an increased
to 2000 through 2013 to 2014, with the larg- risk for CVD, ESRD, and mortality. These risks are
est decline occurring among those 18 to 39 greater for people in the upper (130–139/85–89
years of age (32.2% in 1999–2000 to 23.4% in mm Hg) versus lower (120–129/80–84 mm Hg)
2013–2014).123 range of prehypertension.125–133

Table 8-1.  High Blood Pressure in the United States

Prevalence, 2013–2016, Mortality,* 2016, Hospital Discharges, Estimated Cost,

Population Group Age ≥20 y All Ages 2014, All Ages 2014–2015
Both sexes 116 400 000 (46.0%) 82 735 292 000 $55.9 Billion
Males 58 700 000 (49.0%) 39 577 (47.8%)† 142 000 …
Females 57 700 000 (42.8%) 43 158 (52.2 %)† 150 000 …
NH white males 48.2% 26 402 … …
Downloaded from http://ahajournals.org by on February 7, 2019

NH white females 41.3% 30  638 … …

NH black males 58.6% 8429 … …
NH black females 56.0% 7897 … …
Hispanic males 47.4% 3063 … …
Hispanic females 40.8% 2856 … …
NH Asian males 46.4% 1153‡ … …
NH Asian females 36.4% 1362‡ … …
NH American Indian/Alaska Native … 520 … …

Hypertension is defined in terms of NHANES (National Health and Nutrition Examination Survey) blood pressure measurements and health
interviews. A subject was considered to have hypertension if systolic blood pressure was ≥130 mm Hg or diastolic blood pressure was ≥80 mm Hg, if
the subject said “yes” to taking antihypertensive medication, or if the subject was told on 2 occasions that he or she had hypertension. A previous
publication that used NHANES 2011 to 2014 data estimated there were 103.3 million noninstitutionalized US adults with hypertension.11 The
number of US adults with hypertension in this table includes both noninstitutionalized and institutionalized US individuals. Also, the previous study
did not include individuals who reported having been told on 2 occasions that they had hypertension as having hypertension unless they met another
criterion (systolic blood pressure was ≥130 mm Hg or diastolic blood pressure was ≥80 mm Hg, if the subject said “yes” to taking antihypertensive
medication). Ellipses indicate data not available; and NH, non-Hispanic.
*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of
inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have
shown underreporting on death certificates of American Indian or Alaska Native, Asian, and Pacific Islander, and Hispanic decedents, as well as
undercounts of these groups in censuses.
†These percentages represent the portion of total high blood pressure mortality that is for males vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
Sources: Prevalence: NHANES (2013–2016), National Center for Health Statistics (NCHS), and National Heart, Lung, and Blood Institute (NHLBI).
Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2016 US
population estimates. Mortality: Centers for Disease Control and Prevention/NCHS, 2016 Mortality Multiple Cause-of-Death–United States. These
data represent underlying cause of death only. Mortality for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization
Project, National (Nationwide) Inpatient Sample, 2014. Agency for Healthcare Research and Quality. Cost: Medical Expenditure Panel Survey data
include estimated direct costs for 2014 to 2015 (annual average); indirect costs calculated by NHLBI for 2014 to 2015 (annual average).

e128 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

Table 8-2.  Hypertension Awareness, Treatment, and Control: NHANES 1999 to 2004, 2005 to 2010, and 2011 to 2016 Age-Adjusted Percent With

CLINICAL STATEMENTS
Hypertension in Adults by Sex and Race/Ethnicity

AND GUIDELINES
Awareness, % Treatment, % Control, %
1999–2004 2005–2010 2011–2016 1999–2004 2005–2010 2011–2016 1999–2004 2005–2010 2011–2016
NH white males 46.7 55.8 61.2 35.0 45.7 48.9 13.3 20.4 24.8
NH white females 58.7 65.5 68.9 47.4 57.8 60.6 16.8 26.0 28.6
NH black males 47.6 59.1 62.3 35.5 46.5 48.4 11.2 18.0 17.2
NH black females 67.6 74.5 74.7 55.5 65.9 64.6 19.0 28.7 26.4
Mexican American males* 30.8 37.8 43.8 18.5 27.1 30.3 6.5 11.7 11.6
Mexican American females* 51.6 56.7 66.2 39.0 47.2 53.2 11.7 20.0 27.0

Values are percentages. Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A subject was considered to have
hypertension if systolic blood pressure was ≥140 mm Hg or diastolic blood pressure was ≥90 mm Hg, or if the subject said “yes” to taking antihypertensive
medication. NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics was only used starting in 2007.
Consequently, for long-term trend data, the category Mexican American is used.
Sources: NHANES (1999–2004, 2005–2010, 2011–2016) and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 8-1. Prevalence of hypertension in adults ≥20 years of age by sex and age (NHANES, 2013–2016).
Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A person was considered to have hypertension if he or she had
systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, if he or she said “yes” to taking antihypertensive medication, or if the person was told
on 2 occasions that he or she had hypertension.
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e129

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8
CLINICAL STATEMENTS
AND GUIDELINES

Chart 8-2. Age-adjusted prevalence trends for hypertension in adults ≥20 years of age by race/ethnicity, sex, and survey year (NHANES, 1999–2004,
2005–2010, and 2010–2016).
Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A person was considered to have hypertension if he or she had
systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, if he or she said “yes” to taking antihypertensive medication, or if the person was told
on 2 occasions that he or she had hypertension.
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics was only used starting in 2007.
Consequently, for long-term trend data, the category Mexican American is used.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 8-3. Extent of awareness, treatment, and control of high blood pressure by race/ethnicity (NHANES, 2013–2016).
Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A person was considered to have hypertension if he or she had
systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, if he or she said “yes” to taking antihypertensive medication, or if the person was told
on 2 occasions that he or she had hypertension.
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

e130 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

CLINICAL STATEMENTS
AND GUIDELINES
Chart 8-4. Extent of awareness, treatment, and control of high blood pressure by age (NHANES, 2013–2016).
Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A person was considered to have hypertension if he or she had systolic
blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, if he or she said “yes” to taking antihypertensive medication, or if the person was told on 2 occa-
sions that he or she had hypertension.
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 8-5. Extent of awareness, treatment, and control of high blood pressure by race/ethnicity and sex (NHANES, 2013–2016).
Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A person was considered to have hypertension if he or she had
systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, if he or she said “yes” to taking antihypertensive medication, or if the person was told
on 2 occasions that he or she had hypertension.
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e131

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8
CLINICAL STATEMENTS
AND GUIDELINES

Chart 8-6. Age-standardized global mortality rates attributable to high systolic blood pressure per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.118 Printed with permission.
Copyright © 2017, University of Washington.

J Med. 2017;377:2506]. N Engl J Med. 2015;373:2103–2116. doi:

REFERENCES 10.1056/NEJMoa1511939
9. Bress AP, Tanner RM, Hess R, Colantonio LD, Shimbo D, Muntner P.
1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo
Generalizability of SPRINT results to the U.S. adult population. J Am Coll
JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ;
Cardiol. 2016;67:463–472. doi: 10.1016/j.jacc.2015.10.037
National High Blood Pressure Education Program Coordinating
10. Melgarejo JD, Maestre GE, Thijs L, Asayama K, Boggia J, Casiglia E, Hansen
Committee. Seventh report of the Joint National Committee on
Downloaded from http://ahajournals.org by on February 7, 2019

TW, Imai Y, Jacobs L, Jeppesen J, Kawecka-Jaszcz K, Kuznetsova T, Li Y,

Prevention, Detection, Evaluation, and Treatment of High Blood
Malyutina S, Nikitin Y, Ohkubo T, Stolarz-Skrzypek K, Wang JG, Staessen
Pressure. Hypertension. 2003;42:1206–1252. doi: 10.1161/01.HYP.
JA; on behalf of the International Database on Ambulatory Blood Pressure
0000107251.49515.c2
in Relation to Cardiovascular Outcomes (IDACO) Investigators. Prevalence,
2. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn
treatment, and control rates of conventional and ambulatory hyperten-
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow
sion across 10 populations in 3 continents. Hypertension. 2017;70:50–58.
GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm
doi: 10.1161/HYPERTENSIONAHA.117.09188
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart
11. Muntner P, Carey RM, Gidding S, Jones DW, Taler SJ, Wright JT Jr,
Association Strategic Planning Task Force and Statistics Committee.
Whelton PK. Potential US population impact of the 2017 ACC/AHA
Defining and setting national goals for cardiovascular health promotion
high blood pressure guideline. Circulation. 2018;137:109–118. doi:
and disease reduction: the American Heart Association’s strategic Impact 10.1161/CIRCULATIONAHA.117.032582
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: 12. Xu Y, Chen X, Wang K. Global prevalence of hypertension among peo-
10.1161/CIRCULATIONAHA.109.192703 ple living with HIV: a systematic review and meta-analysis. J Am Soc
3. Crim MT, Yoon SS, Ortiz E, Wall HK, Schober S, Gillespie C, Sorlie P, Keenan Hypertens. 2017;11:530–540. doi: 10.1016/j.jash.2017.06.004
N, Labarthe D, Hong Y. National surveillance definitions for hypertension 13. Franklin SS, Thijs L, Asayama K, Li Y, Hansen TW, Boggia J, Jacobs L,
prevalence and control among adults. Circ Cardiovasc Qual Outcomes. Zhang Z, Kikuya M, Björklund-Bodegård K, Ohkubo T, Yang WY, Jeppesen
2012;5:343–351. doi: 10.1161/CIRCOUTCOMES.111.963439 J, Dolan E, Kuznetsova T, Stolarz-Skrzypek K, Tikhonoff V, Malyutina S,
4. Centers for Disease Control and Prevention, National Center for Chronic Casiglia E, Nikitin Y, Lind L, Sandoya E, Kawecka-Jaszcz K, Filipovský J, Imai
Disease Prevention and Health Promotion, Division of Population Health Y, Wang JG, O’Brien E, Staessen JA; IDACO Investigators. The cardiovascular
website. BRFSS Prevalence & Trends Data (2015). https://www.cdc.gov/ risk of white-coat hypertension. J Am Coll Cardiol. 2016;68:2033–2043.
brfss/brfssprevalence/index.html. Accessed April 30, 2018. doi: 10.1016/j.jacc.2016.08.035
5. Achelrod D, Wenzel U, Frey S. Systematic review and meta-analysis of the 14. Dregan A, Ravindrarajah R, Hazra N, Hamada S, Jackson SH, Gulliford MC.
prevalence of resistant hypertension in treated hypertensive populations. Longitudinal trends in hypertension management and mortality among
Am J Hypertens. 2015;28:355–361. doi: 10.1093/ajh/hpu151 octogenarians: prospective cohort study. Hypertension. 2016;68:97–105.
6. Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, Brecklin doi: 10.1161/HYPERTENSIONAHA.116.07246
CS, Drawz P, Flack JM, Miller ER 3rd, Steigerwalt SP, Townsend RR, 15. Bromfield SG, Ngameni CA, Colantonio LD, Bowling CB, Shimbo D,
Weir MR, Wright JT Jr, Rahman M; CRIC Study Investigators. Prevalence Reynolds K, Safford MM, Banach M, Toth PP, Muntner P. Blood pres-
and prognostic significance of apparent treatment resistant hyper- sure, antihypertensive polypharmacy, frailty, and risk for serious fall
tension in chronic kidney disease: report from the Chronic Renal injuries among older treated adults with hypertension. Hypertension.
Insufficiency Cohort Study. Hypertension. 2016;67:387–396. doi: 2017;70:259–266. doi: 10.1161/HYPERTENSIONAHA.116.09390
10.1161/HYPERTENSIONAHA.115.06487 16. Kit BK, Kuklina E, Carroll MD, Ostchega Y, Freedman DS, Ogden CL.
7. Armario P, Calhoun DA, Oliveras A, Blanch P, Vinyoles E, Banegas Prevalence of and trends in dyslipidemia and blood pressure among US
JR, Gorostidi M, Segura J, Ruilope LM, Dudenbostel T, de la Sierra A. children and adolescents, 1999-2012. JAMA Pediatr. 2015;169:272–279.
Prevalence and clinical characteristics of refractory hypertension. J Am doi: 10.1001/jamapediatrics.2014.3216
Heart Assoc. 2017;6:e007365. DOI: 10.1161/JAHA.117.007365. 17. Ning H, Labarthe DR, Shay CM, Daniels SR, Hou L, Van Horn L, Lloyd-
8. SPRINT Research Group. A randomized trial of intensive versus stan- Jones DM. Status of cardiovascular health in US children up to 11
dard blood-pressure control [published correction appears in N Engl years of age: the National Health and Nutrition Examination Surveys

e132 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

2003-2010. Circ Cardiovasc Qual Outcomes. 2015;8:164–171. doi: Blacks: National Health and Nutrition Examination Survey 2003-

CLINICAL STATEMENTS
10.1161/CIRCOUTCOMES.114.001274 2014 data. J Hypertens. 2017;35:2380–2387. doi: 10.1097/HJH.

AND GUIDELINES
18. Xi B, Zhang T, Zhang M, Liu F, Zong X, Zhao M, Wang Y. Trends in elevated 0000000000001489
blood pressure among US children and adolescents: 1999-2012. Am J 35. Ostchega Y, Zhang G, Kit BK, Nwankwo T. Factors associated with home
Hypertens. 2016;29:217–225. doi: 10.1093/ajh/hpv091 blood pressure monitoring among US adults: National Health and Nutrition
19. Li L, Pérez A, Wu LT, Ranjit N, Brown HS, Kelder SH. Cardiometabolic risk Examination Survey, 2011-2014. Am J Hypertens. 2017;30:1126–1132.
factors among severely obese children and adolescents in the United States, doi: 10.1093/ajh/hpx101
1999-2012. Child Obes. 2016;12:12–19. doi: 10.1089/chi.2015.0136 36. Ayala C, Tong X, Neeley E, Lane R, Robb K, Loustalot F. Home blood pres-
20. Yang Q, Zhong Y, Merritt R, Cogswell ME. Trends in high blood pres- sure monitoring among adults: American Heart Association Cardiovascular
sure among United States adolescents across body weight category Health Consumer Survey, 2012. J Clin Hypertens (Greenwich).
between 1988 and 2012. J Pediatr. 2016;169:166–173.e3. doi: 2017;19:584–591. doi: 10.1111/jch.12983
10.1016/j.jpeds.2015.10.007 37. Thomas SJ, Booth JN 3rd, Bromfield SG, Seals SR, Spruill TM, Ogedegbe
21. Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes G, Kidambi S, Shimbo D, Calhoun D, Muntner P. Clinic and ambulatory
M, Zachariah JP, Urbina EM; on behalf of the American Heart Association blood pressure in a population-based sample of African Americans: the
Atherosclerosis, Hypertension and Obesity in Youth Committee of the Jackson Heart Study. J Am Soc Hypertens. 2017;11:204–212.e5. doi:
Council on Cardiovascular Disease in the Young. Update: ambulatory 10.1016/j.jash.2017.02.001
blood pressure monitoring in children and adolescents: a scientific state- 38. National Center for Health Statistics. Centers for Disease Control and
ment from the American Heart Association. Hypertension. 2014;63:1116– Prevention website. National Vital Statistics System: public use data file
1135. doi: 10.1161/HYP.0000000000000007 documentation: mortality multiple cause-of-death micro-data files, 2016.
22. Lubrano R, Paoli S, Spiga S, Falsaperla R, Vitaliti G, Gentile I, Elli M. https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed
Impact of ambulatory blood pressure monitoring on the diagnosis of May 21, 2018.
hypertension in children. J Am Soc Hypertens. 2015;9:780–784. doi: 39. Kochanek KD, Murphy SL, Xu JQ, Tejada-Vera B. Deaths: final data for
10.1016/j.jash.2015.07.016 2014. National Vital Statistics Reports. 2016. Vol 65, No 4. Hyattsville,
23. Roulet C, Bovet P, Brauchli T, Simeoni U, Xi B, Santschi V, Paradis G, Chiolero MD: National Center for Health Statistics; 2016.
A. Secular trends in blood pressure in children: a systematic review. J Clin 40. Centers for Disease Control and Prevention website. About underlying
Hypertens (Greenwich). 2017;19:488–497. doi: 10.1111/jch.12955 cause of death, 1999-2016. https://wonder.cdc.gov/ucd-icd10.html.
24. Mitsnefes MM, Pierce C, Flynn J, Samuels J, Dionne J, Furth S, Accessed June 18, 2018.
Warady B; CKiD study group. Can office blood pressure readings pre- 41. Kung HC, Xu J. Hypertension-related mortality in the United States, 2000–
dict masked hypertension? Pediatr Nephrol. 2016;31:163–166. doi: 2013. NCHS Data Brief. 2015;(193):1–8.
10.1007/s00467-015-3212-5 42. Patel SA, Winkel M, Ali MK, Narayan KM, Mehta NK. Cardiovascular mor-
25. Koebnick C, Mohan Y, Li X, Porter AH, Daley MF, Luo G, Kuizon BD. Failure tality associated with 5 leading risk factors: national and state preventable
to confirm high blood pressures in pediatric care: quantifying the risks fractions estimated from survey data. Ann Intern Med. 2015;163:245–
of misclassification. J Clin Hypertens (Greenwich). 2018;20:174–182. doi: 253. doi: 10.7326/M14-1753
10.1111/jch.13159 43. Bress AP, Kramer H, Khatib R, Beddhu S, Cheung AK, Hess R, Bansal VK,
26. Young DR, Fischer H, Arterburn D, Bessesen D, Cromwell L, Daley MF, Cao G, Yee J, Moran AE, Durazo-Arvizu R, Muntner P, Cooper RS. Potential
Desai J, Ferrara A, Fitzpatrick SL, Horberg MA, Koebnick C, Nau CL, deaths averted and serious adverse events incurred from adoption of the
Oshiro C, Waitzfelder B, Yamamoto A. Associations of overweight/obe- SPRINT (Systolic Blood Pressure Intervention Trial) intensive blood pressure
sity and socioeconomic status with hypertension prevalence across racial regimen in the United States: projections from NHANES (National Health
Downloaded from http://ahajournals.org by on February 7, 2019

and ethnic groups. J Clin Hypertens (Greenwich). 2018;20:532–540. doi: and Nutrition Examination Survey). Circulation. 2017;135:1617–1628.
10.1111/jch.13217 doi: 10.1161/CIRCULATIONAHA.116.025322
27. Carson AP, Howard G, Burke GL, Shea S, Levitan EB, Muntner P. Ethnic dif- 44. Holmqvist L, Boström KB, Kahan T, Schiöler L, Hasselström J, Hjerpe
ferences in hypertension incidence among middle-aged and older adults: P, Wettermark B, Manhem K. Cardiovascular outcome in treat-
the Multi-ethnic Study of Atherosclerosis. Hypertension. 2011;57:1101– ment-resistant hypertension: results from the Swedish Primary Care
1107. doi: 10.1161/HYPERTENSIONAHA.110.168005 Cardiovascular Database (SPCCD). J Hypertens. 2018;36:402–409. doi:
28. Howard G, Safford MM, Moy CS, Howard VJ, Kleindorfer DO, Unverzagt 10.1097/HJH.0000000000001561
FW, Soliman EZ, Flaherty ML, McClure LA, Lackland DT, Wadley VG, Pulley 45. Jayalath VH, de Souza RJ, Ha V, Mirrahimi A, Blanco-Mejia S, Di Buono
L, Cushman M. Racial differences in the incidence of cardiovascular risk M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ,
factors in older black and white adults. J Am Geriatr Soc. 2017;65:83–90. Sievenpiper JL. Sugar-sweetened beverage consumption and incident
doi: 10.1111/jgs.14472 hypertension: a systematic review and meta-analysis of prospective cohorts.
29. National Center for Health Statistics. Centers for Disease Control and Am J Clin Nutr. 2015;102:914–921. doi: 10.3945/ajcn.115.107243
Prevention website. National Health Interview Survey: 2014 data release. 46. Sun D, Liu J, Xiao L, Liu Y, Wang Z, Li C, Jin Y, Zhao Q, Wen S. Recent
Public-use data file and documentation. http://www.cdc.gov/nchs/nhis/ development of risk-prediction models for incident hypertension:
nhis_2014_data_release.htm. Accessed April 30, 2018. an updated systematic review. PLoS One. 2017;12:e0187240. doi:
30. Daviglus ML, Talavera GA, Avilés-Santa ML, Allison M, Cai J, Criqui MH, 10.1371/journal.pone.0187240
Gellman M, Giachello AL, Gouskova N, Kaplan RC, LaVange L, Penedo 47. Diaz KM, Booth JN 3rd, Seals SR, Abdalla M, Dubbert PM, Sims M, Ladapo
F, Perreira K, Pirzada A, Schneiderman N, Wassertheil-Smoller S, Sorlie JA, Redmond N, Muntner P, Shimbo D. Physical activity and incident hyper-
PD, Stamler J. Prevalence of major cardiovascular risk factors and car- tension in African Americans: the Jackson Heart Study. Hypertension.
diovascular diseases among Hispanic/Latino individuals of diverse 2017;69:421–427. doi: 10.1161/HYPERTENSIONAHA.116.08398
backgrounds in the United States. JAMA. 2012;308:1775–1784. doi: 48. Ford CD, Sims M, Higginbotham JC, Crowther MR, Wyatt SB, Musani
10.1001/jama.2012.14517 SK, Payne TJ, Fox ER, Parton JM. Psychosocial factors are associated with
31. Sorlie PD, Allison MA, Avilés-Santa ML, Cai J, Daviglus ML, Howard AG, blood pressure progression among African Americans in the Jackson Heart
Kaplan R, Lavange LM, Raij L, Schneiderman N, Wassertheil-Smoller S, Study. Am J Hypertens. 2016;29:913–924. doi: 10.1093/ajh/hpw013
Talavera GA. Prevalence of hypertension, awareness, treatment, and 49. Shallcross AJ, Butler M, Tanner RM, Bress AP, Muntner P, Shimbo D,
control in the Hispanic Community Health Study/Study of Latinos. Am J Ogedegbe G, Sims M, Spruill TM. Psychosocial correlates of apparent
Hypertens. 2014;27:793–800. doi: 10.1093/ajh/hpu003 treatment-resistant hypertension in the Jackson Heart Study [published
32. Sim JJ, Bhandari SK, Shi J, Liu IL, Calhoun DA, McGlynn EA, Kalantar-Zadeh correction appears in J Hum Hypertens. 2017;31:486]. J Hum Hypertens.
K, Jacobsen SJ. Characteristics of resistant hypertension in a large, ethni- 2017;31:474–478. doi: 10.1038/jhh.2016.100
cally diverse hypertension population of an integrated health system. Mayo 50. Jackson SL, Cogswell ME, Zhao L, Terry AL, Wang CY, Wright J, Coleman
Clin Proc. 2013;88:1099–1107. doi: 10.1016/j.mayocp.2013.06.017 King SM, Bowman B, Chen TC, Merritt R, Loria CM. Association
33. Gyamfi J, Butler M, Williams SK, Agyemang C, Gyamfi L, Seixas A, Zinsou between urinary sodium and potassium excretion and blood pres-
GM, Bangalore S, Shah NR, Ogedegbe G. Blood pressure control and mor- sure among adults in the United States: National Health and Nutrition
tality in US- and foreign-born blacks in New York City. J Clin Hypertens Examination Survey, 2014. Circulation. 2018;137:237–246. doi:
(Greenwich). 2017;19:956–964. doi: 10.1111/jch.13045 10.1161/CIRCULATIONAHA.117.029193
34. Brown AGM, Houser RF, Mattei J, Mozaffarian D, Lichtenstein AH, 51. Tanner RM, Shimbo D, Irvin MR, Spruill TM, Bromfield SG, Seals SR,
Folta SC. Hypertension among US-born and foreign-born non-Hispanic Young BA, Muntner P. Chronic kidney disease and incident apparent

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e133

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

treatment-resistant hypertension among blacks: data from the Jackson 67. Mente A, O’Donnell M, Rangarajan S, Dagenais G, Lear S, McQueen M,
CLINICAL STATEMENTS

Heart Study. J Clin Hypertens (Greenwich). 2017;19:1117–1124. doi: Diaz R, Avezum A, Lopez-Jaramillo P, Lanas F, Li W, Lu Y, Yi S, Rensheng
AND GUIDELINES

10.1111/jch.13065 L, Iqbal R, Mony P, Yusuf R, Yusoff K, Szuba A, Oguz A, Rosengren

52. Shen Y, Liu H, Dai T, Guan Y, Tu J, Nie H. Association between restless legs A, Bahonar A, Yusufali A, Schutte AE, Chifamba J, Mann JF, Anand
syndrome and hypertension: a meta-analysis of nine population-based SS, Teo K, Yusuf S; PURE, EPIDREAM and ONTARGET/TRANSCEND
studies. Neurol Sci. 2018;39:235–242. doi: 10.1007/s10072-017-3182-4 Investigators. Associations of urinary sodium excretion with cardiovascu-
53. Booth JN 3rd, Abdalla M, Tanner RM, Diaz KM, Bromfield SG, Tajeu lar events in individuals with and without hypertension: a pooled analy-
GS, Correa A, Sims M, Ogedegbe G, Bress AP, Spruill TM, Shimbo D, sis of data from four studies. Lancet. 2016;388:465–475. doi: 10.1016/
Muntner P. Cardiovascular health and incident hypertension in blacks: S0140-6736(16)30467-6
JHS (the Jackson Heart Study). Hypertension. 2017;70:285–292. doi: 68. O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-
10.1161/HYPERTENSIONAHA.117.09278 Melacini P, Zhang X, Pais P, Agapay S, Lopez-Jaramillo P, Damasceno A,
54. Schwingshackl L, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, Andriolo Langhorne P, McQueen MJ, Rosengren A, Dehghan M, Hankey GJ, Dans
V, Bechthold A, Schlesinger S, Boeing H. Food groups and risk of hyper- AL, Elsayed A, Avezum A, Mondo C, Diener HC, Ryglewicz D, Czlonkowska
tension: a systematic review and dose-response meta-analysis of prospec- A, Pogosova N, Weimar C, Iqbal R, Diaz R, Yusoff K, Yusufali A, Oguz
tive studies. Adv Nutr. 2017;8:793–803. doi: 10.3945/an.117.017178 A, Wang X, Penaherrera E, Lanas F, Ogah OS, Ogunniyi A, Iversen HK,
55. Roerecke M, Kaczorowski J, Tobe SW, Gmel G, Hasan OSM, Rehm J. The Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, Magazi D, Nilanont
effect of a reduction in alcohol consumption on blood pressure: a system- Y, Ferguson J, Pare G, Yusuf S; INTERSTROKE Investigators. Global and
atic review and meta-analysis. Lancet Public Health. 2017;2:e108–e120. regional effects of potentially modifiable risk factors associated with
doi: 10.1016/S2468-2667(17)30003-8 acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet.
56. Ramos AR, Weng J, Wallace DM, Petrov MR, Wohlgemuth WK, Sotres- 2016;388:761–775. doi: 10.1016/S0140-6736(16)30506-2
Alvarez D, Loredo JS, Reid KJ, Zee PC, Mossavar-Rahmani Y, Patel 69. Ahmad FS, Ning H, Rich JD, Yancy CW, Lloyd-Jones DM, Wilkins JT.
SR. Sleep patterns and hypertension using actigraphy in the Hispanic Hypertension, obesity, diabetes, and heart failure-free survival: the
Community Health Study/Study of Latinos. Chest. 2018;153:87–93. doi: Cardiovascular Disease Lifetime Risk Pooling Project. JACC Heart Fail.
10.1016/j.chest.2017.09.028 2016;4:911–919. doi: 10.1016/j.jchf.2016.08.001
57. Liu X, Zhang D, Liu Y, Sun X, Han C, Wang B, Ren Y, Zhou J, Zhao Y, 70. Tajeu GS, Booth JN 3rd, Colantonio LD, Gottesman RF, Howard G, Lackland
Shi Y, Hu D, Zhang M. Dose-response association between physi- DT, O’Brien EC, Oparil S, Ravenell J, Safford MM, Seals SR, Shimbo D,
cal activity and incident hypertension: a systematic review and meta- Shea S, Spruill TM, Tanner RM, Muntner P. Incident cardiovascular dis-
analysis of cohort studies. Hypertension. 2017;69:813–820. doi: ease among adults with blood pressure <140/90 mm Hg. Circulation.
10.1161/HYPERTENSIONAHA.116.08994 2017;136:798–812. doi: 10.1161/CIRCULATIONAHA.117.027362
58. Wei YC, George NI, Chang CW, Hicks KA. Assessing sex differences in 71. Polgreen LA, Suneja M, Tang F, Carter BL, Polgreen PM. Increasing trend
the risk of cardiovascular disease and mortality per increment in sys- in admissions for malignant hypertension and hypertensive encepha-
tolic blood pressure: a systematic review and meta-analysis of follow- lopathy in the United States. Hypertension. 2015;65:1002–1007. doi:
up studies in the United States. PLoS One. 2017;12:e0170218. doi: 10.1161/HYPERTENSIONAHA.115.05241
10.1371/journal.pone.0170218 72. Fontil V, Pletcher MJ, Khanna R, Guzman D, Victor R, Bibbins-Domingo K.
59. Hidayat K, Du X, Zou SY, Shi BM. Blood pressure and kidney cancer risk: Physician underutilization of effective medications for resistant hyperten-
meta-analysis of prospective studies. J Hypertens. 2017;35:1333–1344. sion at office visits in the United States: NAMCS 2006-2010. J Gen Intern
doi: 10.1097/HJH.0000000000001286 Med. 2014;29:468–476. doi: 10.1007/s11606-013-2683-y
60. Rapsomaniki E, Timmis A, George J, Pujades-Rodriguez M, Shah AD, 73. Centers for Disease Control and Prevention website. National Ambulatory
Downloaded from http://ahajournals.org by on February 7, 2019

Denaxas S, White IR, Caulfield MJ, Deanfield JE, Smeeth L, Williams B, Medical Care Survey: 2015 State and National Summary Tables. https://
Hingorani A, Hemingway H. Blood pressure and incidence of twelve car- www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_
diovascular diseases: lifetime risks, healthy life-years lost, and age-specific tables.pdf. Accessed June 18, 2018.
associations in 1·25 million people. Lancet. 2014;383:1899–1911. doi: 74. Centers for Disease Control and Prevention website. National Hospital
10.1016/S0140-6736(14)60685-1 Ambulatory Medical Care Survey: 2015 Emergency Department Summary
61. Tsimploulis A, Sheriff HM, Lam PH, Dooley DJ, Anker MS, Papademetriou Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_
V, Fletcher RD, Faselis C, Fonarow GC, Deedwania P, White M, Valentova web_tables.pdf. Accessed June 18, 2018.
M, Blackman MR, Banach M, Morgan CJ, Alagiakrishnan K, Allman RM, 75. Vemulapalli S, Deng L, Patel MR, Kilgore ML, Jones WS, Curtis LH,
Aronow WS, Anker SD, Ahmed A. Systolic-diastolic hypertension versus Irvin MR, Svetkey LP, Shimbo D, Calhoun DA, Muntner P. National
isolated systolic hypertension and incident heart failure in older adults: patterns in intensity and frequency of outpatient care for apparent
Insights from the Cardiovascular Health Study [published correction treatment-resistant hypertension. Am Heart J. 2017;186:29–39. doi:
appears in Int J Cardiol. 2017;238:181]. Int J Cardiol. 2017;235:11–16. 10.1016/j.ahj.2017.01.008
doi: 10.1016/j.ijcard.2017.02.139 76. Yoon SS, Gu Q, Nwankwo T, Wright JD, Hong Y, Burt V. Trends in blood
62. Fang J, Moore L, Loustalot F, Yang Q, Ayala C. Reporting of adherence to pressure among adults with hypertension: United States, 2003 to 2012.
healthy lifestyle behaviors among hypertensive adults in the 50 states and Hypertension. 2015;65:54–61. doi: 10.1161/HYPERTENSIONAHA.
the District of Columbia, 2013. J Am Soc Hypertens. 2016;10:252–262. 114.04012
e3. doi: 10.1016/j.jash.2016.01.008 77. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in pre-
63. Navar AM, Peterson ED, Wojdyla D, et al. Temporal changes in the asso- scription drug use among adults in the United States from 1999–2012.
ciation between modifiable risk factors and coronary heart disease inci- JAMA. 2015;314:1818–1831. doi: 10.1001/jama.2015.13766
dence [published correction appears in JAMA. 2016;316:2433]. JAMA. 78. Yang F, Qian D, Hu D; Healthy Aging and Development Study Group,
2016;316:2041–2043. doi: 10.1001/jama.2016.13614 Nanjing Medical University; Data Mining Group of Biomedical Big Data,
64. Salles GF, Reboldi G, Fagard RH, Cardoso CR, Pierdomenico SD, Nanjing Medical University. Prevalence, awareness, treatment, and con-
Verdecchia P, Eguchi K, Kario K, Hoshide S, Polonia J, de la Sierra A, trol of hypertension in the older population: results from the multiple
Hermida RC, Dolan E, O’Brien E, Roush GC; ABC-H Investigators. national studies on ageing. J Am Soc Hypertens. 2016;10:140–148. doi:
Prognostic effect of the nocturnal blood pressure fall in hypertensive 10.1016/j.jash.2015.11.016
patients: the Ambulatory Blood Pressure Collaboration in Patients With 79. Dinkler JM, Sugar CA, Escarce JJ, Ong MK, Mangione CM. Does age mat-
Hypertension (ABC-H) meta-analysis. Hypertension. 2016;67:693–700. ter? Association between usual source of care and hypertension control
doi: 10.1161/HYPERTENSIONAHA.115.06981 in the US population: data from NHANES 2007-2012. Am J Hypertens.
65. Booth JN 3rd, Diaz KM, Seals SR, Sims M, Ravenell J, Muntner P, Shimbo D. 2016;29:934–940. doi: 10.1093/ajh/hpw010
Masked hypertension and cardiovascular disease events in a prospective 80. Fontil V, Bibbins-Domingo K, Nguyen OK, Guzman D, Goldman LE.
cohort of blacks: the Jackson Heart Study. Hypertension. 2016;68:501– Management of hypertension in primary care safety-net clinics in the
510. doi: 10.1161/HYPERTENSIONAHA.116.07553 United States: a comparison of community health centers and pri-
66. Huang Y, Huang W, Mai W, Cai X, An D, Liu Z, Huang H, Zeng J, Hu vate physicians’ offices. Health Serv Res. 2017;52:807–825. doi:
Y, Xu D. White-coat hypertension is a risk factor for cardiovascu- 10.1111/1475-6773.12516
lar diseases and total mortality. J Hypertens. 2017;35:677–688. doi: 81. Casagrande SS, Menke A, Cowie CC. Cardiovascular risk fac-
10.1097/HJH.0000000000001226 tors of adults age 20-49 years in the United States, 1971-2012: a

e134 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

series of cross-sectional studies. PLoS One. 2016;11:e0161770. doi: 97. Dolezsar CM, McGrath JJ, Herzig AJ, Miller SB. Perceived racial discrimi-

CLINICAL STATEMENTS
10.1371/journal.pone.0161770 nation and hypertension: a comprehensive systematic review. Health

AND GUIDELINES
82. Lee HJ, Jang SI, Park EC. Effect of adherence to antihypertensive medi- Psychol. 2014;33:20–34. doi: 10.1037/a0033718
cation on stroke incidence in patients with hypertension: a population- 98. Hottenga JJ, Boomsma DI, Kupper N, Posthuma D, Snieder H, Willemsen
based retrospective cohort study. BMJ Open. 2017;7:e014486. doi: G, de Geus EJ. Heritability and stability of resting blood pressure. Twin
10.1136/bmjopen-2016-014486 Res Hum Genet. 2005;8:499–508. doi: 10.1375/183242705774310123
83. Sundbøll J, Adelborg K, Mansfield KE, Tomlinson LA, Schmidt M. Seventeen- 99. Liu C, Kraja AT, Smith JA, Brody JA, Franceschini N, Bis JC, Rice K,
year nationwide trends in antihypertensive drug use in Denmark. Am J Morrison AC, Lu Y, Weiss S, Guo X, Palmas W, Martin LW, Chen YD,
Cardiol. 2017;120:2193–2200. doi: 10.1016/j.amjcard.2017.08.042 Surendran P, Drenos F, Cook JP, Auer PL, Chu AY, Giri A, Zhao W,
84. Butler MJ, Tanner RM, Muntner P, Shimbo D, Bress AP, Shallcross AJ, Jakobsdottir J, Lin LA, Stafford JM, Amin N, Mei H, Yao J, Voorman A,
Sims M, Ogedegbe G, Spruill TM. Adherence to antihypertensive medi- Larson MG, Grove ML, Smith AV, Hwang SJ, Chen H, Huan T, Kosova
cations and associations with blood pressure among African Americans G, Stitziel NO, Kathiresan S, Samani N, Schunkert H, Deloukas P, Li
with hypertension in the Jackson Heart Study. J Am Soc Hypertens. M, Fuchsberger C, Pattaro C, Gorski M, Kooperberg C, Papanicolaou
2017;11:581–588.e5. doi: 10.1016/j.jash.2017.06.011 GJ, Rossouw JE, Faul JD, Kardia SL, Bouchard C, Raffel LJ, Uitterlinden
85. Chang TE, Ritchey MD, Ayala C, Durthaler JM, Loustalot F. Use of strat- AG, Franco OH, Vasan RS, O’Donnell CJ, Taylor KD, Liu K, Bottinger EP,
egies to improve antihypertensive medication adherence within United Gottesman O, Daw EW, Giulianini F, Ganesh S, Salfati E, Harris TB, Launer
States outpatient health care practices, DocStyles 2015-2016. J Clin LJ, Dörr M, Felix SB, Rettig R, Völzke H, Kim E, Lee WJ, Lee IT, Sheu
Hypertens (Greenwich). 2018;20:225–232. doi: 10.1111/jch.13188 WH, Tsosie KS, Edwards DR, Liu Y, Correa A, Weir DR, Völker U, Ridker
86. Tajeu GS, Mennemeyer S, Menachemi N, Weech-Maldonado R, Kilgore PM, Boerwinkle E, Gudnason V, Reiner AP, van Duijn CM, Borecki IB,
M. Cost-effectiveness of antihypertensive medication: exploring race Edwards TL, Chakravarti A, Rotter JI, Psaty BM, Loos RJ, Fornage M, Ehret
and sex differences using data from the REasons for Geographic and GB, Newton-Cheh C, Levy D, Chasman DI; CHD Exome+ Consortium;
Racial Differences in Stroke study. Med Care. 2017;55:552–560. doi: ExomeBP Consortium; GoT2DGenes Consortium; T2D-GENES
10.1097/MLR.0000000000000719 Consortium; Myocardial Infarction Genetics and CARDIoGRAM Exome
87. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz Consortia; CKDGen Consortium. Meta-analysis identifies common and
MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, rare variants influencing blood pressure and overlapping with metabolic
Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ; on behalf of trait loci. Nat Genet. 2016;48:1162–1170. doi: 10.1038/ng.3660
the American Heart Association Advocacy Coordinating Committee; 100. Surendran P, Drenos F, Young R, Warren H, Cook JP, Manning AK, Grarup
Stroke Council; Council on Cardiovascular Radiology and Intervention; N, Sim X, Barnes DR, Witkowska K, Staley JR, Tragante V, Tukiainen T,
Council on Clinical Cardiology; Council on Epidemiology and Prevention; Yaghootkar H, Masca N, Freitag DF, Ferreira T, Giannakopoulou O, Tinker
Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on A, Harakalova M, Mihailov E, Liu C, Kraja AT, Fallgaard Nielsen S, Rasheed
Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council A, Samuel M, Zhao W, Bonnycastle LL, Jackson AU, Narisu N, Swift AJ,
on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Southam L, Marten J, Huyghe JR, Stančáková A, Fava C, Ohlsson T,
Disease; Council on Cardiovascular Surgery and Anesthesia, and Matchan A, Stirrups KE, Bork-Jensen J, Gjesing AP, Kontto J, Perola M,
Interdisciplinary Council on Quality of Care and Outcomes Research. Shaw-Hawkins S, Havulinna AS, Zhang H, Donnelly LA, Groves CJ, Rayner
Forecasting the future of cardiovascular disease in the United States: NW, Neville MJ, Robertson NR, Yiorkas AM, Herzig KH, Kajantie E, Zhang
a policy statement from the American Heart Association. Circulation. W, Willems SM, Lannfelt L, Malerba G, Soranzo N, Trabetti E, Verweij N,
2011;123:933–944. doi: 10.1161/CIR.0b013e31820a55f5 Evangelou E, Moayyeri A, Vergnaud AC, Nelson CP, Poveda A, Varga TV,
88. RTI International. Projections of Cardiovascular Disease Prevalence and Caslake M, de Craen AJ, Trompet S, Luan J, Scott RA, Harris SE, Liewald
Downloaded from http://ahajournals.org by on February 7, 2019

Costs: 2015–2035: Technical Report [report prepared for the American DC, Marioni R, Menni C, Farmaki AE, Hallmans G, Renström F, Huffman
Heart Association]. Research Triangle Park, NC: RTI International; JE, Hassinen M, Burgess S, Vasan RS, Felix JF, Uria-Nickelsen M, Malarstig
November 2016. RTI project number 021480.003.001.001. https:// A, Reily DF, Hoek M, Vogt T, Lin H, Lieb W, Traylor M, Markus HF, Highland
healthmetrics.heart.org/wp-content/uploads/2017/10/Projections-of- HM, Justice AE, Marouli E, Lindström J, Uusitupa M, Komulainen P, Lakka
Cardiovascular-Disease.pdf. Accessed May 4, 2017. TA, Rauramaa R, Polasek O, Rudan I, Rolandsson O, Franks PW, Dedoussis
89. Ritchey M, Tsipas S, Loustalot F, Wozniak G. Use of pharmacy sales data to G, Spector TD, Jousilahti P, Männistö S, Deary IJ, Starr JM, Langenberg C,
assess changes in prescription- and payment-related factors that promote Wareham NJ, Brown MJ, Dominiczak AF, Connell JM, Jukema JW, Sattar
adherence to medications commonly used to treat hypertension, 2009 and N, Ford I, Packard CJ, Esko T, Mägi R, Metspalu A, de Boer RA, van der
2014. PLoS One. 2016;11:e0159366. doi: 10.1371/journal.pone.0159366 Meer P, van der Harst P, Gambaro G, Ingelsson E, Lind L, de Bakker PI,
90. Tajeu GS, Kent ST, Kronish IM, Huang L, Krousel-Wood M, Bress AP, Numans ME, Brandslund I, Christensen C, Petersen ER, Korpi-Hyövälti E,
Shimbo D, Muntner P. Trends in antihypertensive medication discon- Oksa H, Chambers JC, Kooner JS, Blakemore AI, Franks S, Jarvelin MR,
tinuation and low adherence among Medicare beneficiaries initiating Husemoen LL, Linneberg A, Skaaby T, Thuesen B, Karpe F, Tuomilehto
treatment from 2007 to 2012. Hypertension. 2016;68:565–575. doi: J, Doney AS, Morris AD, Palmer CN, Holmen OL, Hveem K, Willer CJ,
10.1161/HYPERTENSIONAHA.116.07720 Tuomi T, Groop L, Käräjämäki A, Palotie A, Ripatti S, Salomaa V, Alam
91. Park C, Fang J, Hawkins NA, Wang G. Comorbidity status and annual DS, Shafi Majumder AA, Di Angelantonio E, Chowdhury R, McCarthy
total medical expenditures in U.S. hypertensive adults. Am J Prev Med. MI, Poulter N, Stanton AV, Sever P, Amouyel P, Arveiler D, Blankenberg S,
2017;53(6S2):S172–S181. doi: 10.1016/j.amepre.2017.07.014 Ferrières J, Kee F, Kuulasmaa K, Müller-Nurasyid M, Veronesi G, Virtamo
92. Zhang D, Wang G, Zhang P, Fang J, Ayala C. Medical expenditures J, Deloukas P, Elliott P, Zeggini E, Kathiresan S, Melander O, Kuusisto
associated with hypertension in the U.S., 2000-2013. Am J Prev Med. J, Laakso M, Padmanabhan S, Porteous D, Hayward C, Scotland G,
2017;53:S164–S171. doi: 10.1016/j.amepre.2017.05.014 Collins FS, Mohlke KL, Hansen T, Pedersen O, Boehnke M, Stringham
93. Leng B, Jin Y, Li G, Chen L, Jin N. Socioeconomic status and hyper- HM, Frossard P, Newton-Cheh C, Tobin MD, Nordestgaard BG, Caulfield
tension: a meta-analysis. J Hypertens. 2015;33:221–229. doi: MJ, Mahajan A, Morris AP, Tomaszewski M, Samani NJ, Saleheen D,
10.1097/HJH.0000000000000428 Asselbergs FW, Lindgren CM, Danesh J, Wain LV, Butterworth AS,
94. Rodriguez CJ, Jin Z, Schwartz JE, Turner-Lloveras D, Sacco RL, Di Tullio Howson JM, Munroe PB; CHARGE-Heart Failure Consortium; EchoGen
MR, Homma S. Socioeconomic status, psychosocial factors, race and Consortium; METASTROKE Consortium; GIANT Consortium; EPIC-
nocturnal blood pressure dipping in a Hispanic cohort. Am J Hypertens. InterAct Consortium; Lifelines Cohort Study; Wellcome Trust Case
2013;26:673–682. doi: 10.1093/ajh/hpt009 Control Consortium; Understanding Society Scientific Group; EPIC-CVD
95. Kershaw KN, Diez Roux AV, Burgard SA, Lisabeth LD, Mujahid MS, Schulz Consortium; CHARGE+ Exome Chip Blood Pressure Consortium; T2D-
AJ. Metropolitan-level racial residential segregation and black-white GENES Consortium; GoT2DGenes Consortium; ExomeBP Consortium;
disparities in hypertension. Am J Epidemiol. 2011;174:537–545. doi: CHD Exome+ Consortium. Trans-ancestry meta-analyses identify rare and
10.1093/aje/kwr116 common variants associated with blood pressure and hypertension. Nat
96. Kershaw KN, Robinson WR, Gordon-Larsen P, Hicken MT, Goff DC Jr, Genet. 2016;48:1151–1161. doi: 10.1038/ng.3654
Carnethon MR, Kiefe CI, Sidney S, Diez Roux AV. Association of changes 101. Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson
in neighborhood-level racial residential segregation with changes in blood T, Thorleifsson G, Luan J, Donnelly LA, Kanoni S, Petersen AK, Pihur
pressure among black adults: the CARDIA study. JAMA Intern Med. V, Strawbridge RJ, Shungin D, Hughes MF, Meirelles O, Kaakinen M,
2017;177:996–1002. doi: 10.1001/jamainternmed.2017.1226 Bouatia-Naji N, Kristiansson K, Shah S, Kleber ME, Guo X, Lyytikäinen

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e135

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

LP, Fava C, Eriksson N, Nolte IM, Magnusson PK, Salfati EL, Rallidis LS, C, Gansevoort RT, Guo X, Haiqing S, Hastie CE, Hofker MH, Hovingh
CLINICAL STATEMENTS

Theusch E, Smith AJP, Folkersen L, Witkowska K, Pers TH, Joehanes R, GK, Kim DS, Kirkland SA, Klein BE, Klein R, Li YR, Maiwald S, Newton-
AND GUIDELINES

Kim SK, Lataniotis L, Jansen R, Johnson AD, Warren H, Kim YJ, Zhao Cheh C, O’Brien ET, Onland-Moret NC, Palmas W, Parsa A, Penninx BW,
W, Wu Y, Tayo BO, Bochud M, Absher D, Adair LS, Amin N, Arking DE, Pettinger M, Vasan RS, Ranchalis JE, M Ridker P, Rose LM, Sever P, Shimbo
Axelsson T, Baldassarre D, Balkau B, Bandinelli S, Barnes MR, Barroso I, D, Steele L, Stolk RP, Thorand B, Trip MD, van Duijn CM, Verschuren
Bevan S, Bis JC, Bjornsdottir G, Boehnke M, Boerwinkle E, Bonnycastle WM, Wijmenga C, Wyatt S, Young JH, Zwinderman AH, Bezzina CR,
LL, Boomsma DI, Bornstein SR, Brown MJ, Burnier M, Cabrera CP, Boerwinkle E, Casas JP, Caulfield MJ, Chakravarti A, Chasman DI,
Chambers JC, Chang IS, Cheng CY, Chines PS, Chung RH, Collins FS, Davidson KW, Doevendans PA, Dominiczak AF, FitzGerald GA, Gums JG,
Connell JM, Döring A, Dallongeville J, Danesh J, de Faire U, Delgado G, Fornage M, Hakonarson H, Halder I, Hillege HL, Illig T, Jarvik GP, Johnson
Dominiczak AF, Doney ASF, Drenos F, Edkins S, Eicher JD, Elosua R, Enroth JA, Kastelein JJ, Koenig W, Kumari M, März W, Murray SS, O’Connell
S, Erdmann J, Eriksson P, Esko T, Evangelou E, Evans A, Fall T, Farrall M, JR, Oldehinkel AJ, Pankow JS, Rader DJ, Redline S, Reilly MP, Schadt
Felix JF, Ferrières J, Ferrucci L, Fornage M, Forrester T, Franceschini N, EE, Kottke-Marchant K, Snieder H, Snyder M, Stanton AV, Tobin MD,
Duran OHF, Franco-Cereceda A, Fraser RM, Ganesh SK, Gao H, Gertow Uitterlinden AG, van der Harst P, van der Schouw YT, Samani NJ, Watkins
K, Gianfagna F, Gigante B, Giulianini F, Goel A, Goodall AH, Goodarzi H, Johnson AD, Reiner AP, Zhu X, de Bakker PI, Levy D, Asselbergs FW,
MO, Gorski M, Gräßler J, Groves C, Gudnason V, Gyllensten U, Hallmans Munroe PB, Keating BJ. Gene-centric meta-analysis in 87,736 individuals
G, Hartikainen AL, Hassinen M, Havulinna AS, Hayward C, Hercberg S, of European ancestry identifies multiple blood-pressure-related loci. Am
Herzig KH, Hicks AA, Hingorani AD, Hirschhorn JN, Hofman A, Holmen J, J Hum Genet. 2014;94:349–360. doi: 10.1016/j.ajhg.2013.12.016
Holmen OL, Hottenga JJ, Howard P, Hsiung CA, Hunt SC, Ikram MA, Illig 105. Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I,
T, Iribarren C, Jensen RA, Kähönen M, Kang H, Kathiresan S, Keating BJ, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten
Khaw KT, Kim YK, Kim E, Kivimaki M, Klopp N, Kolovou G, Komulainen J, Karaman I, Lepe MP, O’Reilly PF, Knight J, Snieder H, Kato N, He J, Tai
P, Kooner JS, Kosova G, Krauss RM, Kuh D, Kutalik Z, Kuusisto J, Kvaløy ES, Said MA, Porteous D, Alver M, Poulter N, Farrall M, Gansevoort RT,
K, Lakka TA, Lee NR, Lee IT, Lee WJ, Levy D, Li X, Liang KW, Lin H, Lin Padmanabhan S, Mägi R, Stanton A, Connell J, Bakker SJ, Metspalu A,
L, Lindström J, Lobbens S, Männistö S, Müller G, Müller-Nurasyid M, Shields DC, Thom S, Brown M, Sever P, Esko T, Hayward C, van der Harst
Mach F, Markus HS, Marouli E, McCarthy MI, McKenzie CA, Meneton P, Saleheen D, Chowdhury R, Chambers JC, Chasman DI, Chakravarti A,
P, Menni C, Metspalu A, Mijatovic V, Moilanen L, Montasser ME, Morris Newton-Cheh C, Lindgren CM, Levy D, Kooner JS, Keavney B, Tomaszewski
AD, Morrison AC, Mulas A, Nagaraja R, Narisu N, Nikus K, O’Donnell CJ, M, Samani NJ, Howson JM, Tobin MD, Munroe PB, Ehret GB, Wain LV;
O’Reilly PF, Ong KK, Paccaud F, Palmer CD, Parsa A, Pedersen NL, Penninx International Consortium of Blood Pressure (ICBP) 1000G Analyses; BIOS
BW, Perola M, Peters A, Poulter N, Pramstaller PP, Psaty BM, Quertermous Consortium; Lifelines Cohort Study; Understanding Society Scientific
T, Rao DC, Rasheed A, Rayner NWNWR, Renström F, Rettig R, Rice Group; CHD Exome+ Consortium; ExomeBP Consortium; T2D-GENES
KM, Roberts R, Rose LM, Rossouw J, Samani NJ, Sanna S, Saramies J, Consortium; GoT2DGenes Consortium; Cohorts for Heart and Ageing
Schunkert H, Sebert S, Sheu WH, Shin YA, Sim X, Smit JH, Smith AV, Research in Genome Epidemiology (CHARGE) BP Exome Consortium;
Sosa MX, Spector TD, Stančáková A, Stanton A, Stirrups KE, Stringham International Genomics of Blood Pressure (iGEN-BP) Consortium; UK
HM, Sundstrom J, Swift AJ, Syvänen AC, Tai ES, Tanaka T, Tarasov KV, Biobank CardioMetabolic Consortium BP Working Group. Genome-
Teumer A, Thorsteinsdottir U, Tobin MD, Tremoli E, Uitterlinden AG, wide association analysis identifies novel blood pressure loci and offers
Uusitupa M, Vaez A, Vaidya D, van Duijn CM, van Iperen EPA, Vasan biological insights into cardiovascular risk [published correction ap-
RS, Verwoert GC, Virtamo J, Vitart V, Voight BF, Vollenweider P, Wagner pears in Nat Genet. 2017;49:1558]. Nat Genet. 2017;49:403–415. doi:
A, Wain LV, Wareham NJ, Watkins H, Weder AB, Westra HJ, Wilks R, 10.1038/ng.3768
Wilsgaard T, Wilson JF, Wong TY, Yang TP, Yao J, Yengo L, Zhang W, Zhao 106. Basson J, Sung YJ, Fuentes LL, Schwander K, Cupples LA, Rao DC.
Downloaded from http://ahajournals.org by on February 7, 2019

JH, Zhu X, Bovet P, Cooper RS, Mohlke KL, Saleheen D, Lee JY, Elliott P, Influence of smoking status and intensity on discovery of blood pressure
Gierman HJ, Willer CJ, Franke L, Hovingh GK, Taylor KD, Dedoussis G, loci through gene-smoking interactions. Genet Epidemiol. 2015;39:480–
Sever P, Wong A, Lind L, Assimes TL, Njølstad I, Schwarz PE, Langenberg 488. doi: 10.1002/gepi.21904
C, Snieder H, Caulfield MJ, Melander O, Laakso M, Saltevo J, Rauramaa 107. Sung YJ, de Las Fuentes L, Schwander KL, Simino J, Rao DC. Gene-
R, Tuomilehto J, Ingelsson E, Lehtimäki T, Hveem K, Palmas W, März W, smoking interactions identify several novel blood pressure loci in the
Kumari M, Salomaa V, Chen YI, Rotter JI, Froguel P, Jarvelin MR, Lakatta Framingham Heart Study. Am J Hypertens. 2015;28:343–354. doi:
EG, Kuulasmaa K, Franks PW, Hamsten A, Wichmann HE, Palmer CNA, 10.1093/ajh/hpu149
Stefansson K, Ridker PM, Loos RJF, Chakravarti A, Deloukas P, Morris AP, 108. Simino J SY, Kume R, Schwander K, Rao DC. Gene-alcohol interactions
Newton-Cheh C, Munroe PB; CHARGE-EchoGen consortium; CHARGE- identify several novel blood pressure loci including a promising locus near
HF consortium; Wellcome Trust Case Control Consortium. The genet- SLC16A9. Front Genet. 2013;12:277. doi: 10.3389/fgene.2013.00277
ics of blood pressure regulation and its target organs from association 109. Li C, He J, Chen J, Zhao J, Gu D, Hixson JE, Rao DC, Jaquish CE, Gu CC,
studies in 342,415 individuals. Nat Genet. 2016;48:1171–1184. doi: Chen J, Huang J, Chen S, Kelly TN. Genome-wide gene-sodium inter-
10.1038/ng.3667 action analyses on blood pressure: the Genetic Epidemiology Network
102. Hoffmann TJ, Ehret GB, Nandakumar P, Ranatunga D, Schaefer C, Kwok of Salt-Sensitivity study. Hypertension (Dallas, Tex: 1979). 2016;68:348–
PY, Iribarren C, Chakravarti A, Risch N. Genome-wide association analy- 355. doi: 10.1161/HYPERTENSIONAHA.115.06765
ses using electronic health records identify new loci influencing blood 110. Cooper-DeHoff RM, Johnson JA. Hypertension pharmacogenom-
pressure variation. Nat Genet. 2017;49:54–64. doi: 10.1038/ng.3715 ics: in search of personalized treatment approaches. Nat Rev Nephrol.
103. Yu B, Pulit SL, Hwang SJ, Brody JA, Amin N, Auer PL, Bis JC, Boerwinkle 2016;12:11–22. doi: 10.1038/nrneph.2015.176
E, Burke GL, Chakravarti A, Correa A, Dreisbach AW, Franco OH, Ehret 111. Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ,
GB, Franceschini N, Hofman A, Lin DY, Metcalf GA, Musani SK, Muzny Farzadfar F, Stevens GA, Lim SS, Riley LM, Ezzati M; Global Burden of
D, Palmas W, Raffel L, Reiner A, Rice K, Rotter JI, Veeraraghavan N, Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood
Fox E, Guo X, North KE, Gibbs RA, van Duijn CM, Psaty BM, Levy D, Pressure). National, regional, and global trends in systolic blood pressure
Newton-Cheh C, Morrison AC; on behalf of the CHARGE Consortium since 1980: systematic analysis of health examination surveys and epide-
and the National Heart, Lung, and Blood Institute GO ESP. Rare miological studies with 786 country-years and 5·4 million participants.
exome sequence variants in CLCN6 reduce blood pressure levels Lancet. 2011;377:568–577. doi: 10.1016/S0140-6736(10)62036-3
and hypertension risk. Circ Cardiovasc Genet. 2016;9:64–70. doi: 112. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H,
10.1161/CIRCGENETICS.115.001215 Amann M, Anderson HR, Andrews KG, Aryee M, Atkinson C, Bacchus
104. Tragante V, Barnes MR, Ganesh SK, Lanktree MB, Guo W, Franceschini LJ, Bahalim AN, Balakrishnan K, Balmes J, Barker-Collo S, Baxter A, Bell
N, Smith EN, Johnson T, Holmes MV, Padmanabhan S, Karczewski KJ, ML, Blore JD, Blyth F, Bonner C, Borges G, Bourne R, Boussinesq M,
Almoguera B, Barnard J, Baumert J, Chang YP, Elbers CC, Farrall M, Brauer M, Brooks P, Bruce NG, Brunekreef B, Bryan-Hancock C, Bucello
Fischer ME, Gaunt TR, Gho JM, Gieger C, Goel A, Gong Y, Isaacs A, Kleber C, Buchbinder R, Bull F, Burnett RT, Byers TE, Calabria B, Carapetis J,
ME, Mateo Leach I, McDonough CW, Meijs MF, Melander O, Nelson CP, Carnahan E, Chafe Z, Charlson F, Chen H, Chen JS, Cheng AT, Child JC,
Nolte IM, Pankratz N, Price TS, Shaffer J, Shah S, Tomaszewski M, van Cohen A, Colson KE, Cowie BC, Darby S, Darling S, Davis A, Degenhardt
der Most PJ, Van Iperen EP, Vonk JM, Witkowska K, Wong CO, Zhang L, L, Dentener F, Des Jarlais DC, Devries K, Dherani M, Ding EL, Dorsey
Beitelshees AL, Berenson GS, Bhatt DL, Brown M, Burt A, Cooper-DeHoff ER, Driscoll T, Edmond K, Ali SE, Engell RE, Erwin PJ, Fahimi S, Falder G,
RM, Connell JM, Cruickshanks KJ, Curtis SP, Davey-Smith G, Delles Farzadfar F, Ferrari A, Finucane MM, Flaxman S, Fowkes FG, Freedman G,

e136 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 8

Freeman MK, Gakidou E, Ghosh S, Giovannucci E, Gmel G, Graham K, hypertension and systolic blood pressure of at least 110 to 115 mm Hg,

CLINICAL STATEMENTS
Grainger R, Grant B, Gunnell D, Gutierrez HR, Hall W, Hoek HW, Hogan 1990-2015 [published correction appears in JAMA. 2017;317:648].

AND GUIDELINES
A, Hosgood HD 3rd, Hoy D, Hu H, Hubbell BJ, Hutchings SJ, Ibeanusi JAMA. 2017;317:165–182. doi: 10.1001/jama.2016.19043
SE, Jacklyn GL, Jasrasaria R, Jonas JB, Kan H, Kanis JA, Kassebaum N, 118. Global Burden of Disease Study 2016. Global Burden of Disease Study
Kawakami N, Khang YH, Khatibzadeh S, Khoo JP, Kok C, Laden F, Lalloo 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics
R, Lan Q, Lathlean T, Leasher JL, Leigh J, Li Y, Lin JK, Lipshultz SE, London and Evaluation (IHME), University of Washington; 2016. http://ghdx.
S, Lozano R, Lu Y, Mak J, Malekzadeh R, Mallinger L, Marcenes W, healthdata.org/gbd-results-tool. Accessed May 1, 2018.
March L, Marks R, Martin R, McGale P, McGrath J, Mehta S, Mensah GA, 119. Lu J, Lu Y, Wang X, Li X, Linderman GC, Wu C, Cheng X, Mu L, Zhang
Merriman TR, Micha R, Michaud C, Mishra V, Mohd Hanafiah K, Mokdad H, Liu J, Su M, Zhao H, Spatz ES, Spertus JA, Masoudi FA, Krumholz HM,
AA, Morawska L, Mozaffarian D, Murphy T, Naghavi M, Neal B, Nelson Jiang L. Prevalence, awareness, treatment, and control of hypertension
PK, Nolla JM, Norman R, Olives C, Omer SB, Orchard J, Osborne R, Ostro in China: data from 1·7 million adults in a population-based screening
B, Page A, Pandey KD, Parry CD, Passmore E, Patra J, Pearce N, Pelizzari study (China PEACE Million Persons Project) [published correction ap-
PM, Petzold M, Phillips MR, Pope D, Pope CA 3rd, Powles J, Rao M, pears in Lancet. 2017;390:2548]. Lancet. 2017;390:2549–2558. doi:
Razavi H, Rehfuess EA, Rehm JT, Ritz B, Rivara FP, Roberts T, Robinson C, 10.1016/S0140-6736(17)32478-9
Rodriguez-Portales JA, Romieu I, Room R, Rosenfeld LC, Roy A, Rushton 120. Noubiap JJ, Essouma M, Bigna JJ, Jingi AM, Aminde LN, Nansseu JR.
L, Salomon JA, Sampson U, Sanchez-Riera L, Sanman E, Sapkota A, Prevalence of elevated blood pressure in children and adolescents in
Seedat S, Shi P, Shield K, Shivakoti R, Singh GM, Sleet DA, Smith E, Smith Africa: a systematic review and meta-analysis. Lancet Public Health.
KR, Stapelberg NJ, Steenland K, Stöckl H, Stovner LJ, Straif K, Straney L, 2017;2:e375–e386. doi: 10.1016/S2468-2667(17)30123-8
Thurston GD, Tran JH, Van Dingenen R, van Donkelaar A, Veerman JL, 121. Dastan I, Erem A, Cetinkaya V. Awareness, treatment, control of hyper-
Vijayakumar L, Weintraub R, Weissman MM, White RA, Whiteford H, tension, and associated factors: results from a Turkish national study. Clin
Wiersma ST, Wilkinson JD, Williams HC, Williams W, Wilson N, Woolf Exp Hypertens. 2018;40:90–98. doi: 10.1080/10641963.2017.1334797
AD, Yip P, Zielinski JM, Lopez AD, Murray CJ, Ezzati M, AlMazroa MA, 122. Booth JN 3rd, Li J, Zhang L, Chen L, Muntner P, Egan B. Trends in prehyperten-
Memish ZA. A comparative risk assessment of burden of disease and sion and hypertension risk factors in US adults: 1999–2012. Hypertension.
injury attributable to 67 risk factors and risk factor clusters in 21 re- 2017;70:275–284. doi: 10.1161/HYPERTENSIONAHA.116.09004
gions, 1990-2010: a systematic analysis for the Global Burden of Disease 123. Zhang Y, Moran AE. Trends in the prevalence, awareness, treat-
Study 2010 [published corrections appear in Lancet. 2013;381:628 and ment, and control of hypertension among young adults in the
Lancet. 2013;381:1276]. Lancet. 2012;380:2224–2260. doi: 10.1016/ United States, 1999 to 2014. Hypertension. 2017;70:736–742. doi:
S0140-6736(12)61766-8 10.1161/HYPERTENSIONAHA.117.09801
113. Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, Bahonar A, 124. Carson AP, Lewis CE, Jacobs DR Jr, Peralta CA, Steffen LM, Bower JK,
Chifamba J, Dagenais G, Diaz R, Kazmi K, Lanas F, Wei L, Lopez-Jaramillo Person SD, Muntner P. Evaluating the Framingham hypertension risk pre-
P, Fanghong L, Ismail NH, Puoane T, Rosengren A, Szuba A, Temizhan A, diction model in young adults: the Coronary Artery Risk Development in
Wielgosz A, Yusuf R, Yusufali A, McKee M, Liu L, Mony P, Yusuf S; PURE Young Adults (CARDIA) study. Hypertension. 2013;62:1015–1020. doi:
(Prospective Urban Rural Epidemiology) Study Investigators. Prevalence, 10.1161/HYPERTENSIONAHA.113.01539
awareness, treatment, and control of hypertension in rural and ur- 125. Guo X, Zhang X, Guo L, Li Z, Zheng L, Yu S, Yang H, Zhou X, Zhang
ban communities in high-, middle-, and low-income countries. JAMA. X, Sun Z, Li J, Sun Y. Association between pre-hypertension and car-
2013;310:959–968. doi: 10.1001/jama.2013.184182 diovascular outcomes: a systematic review and meta-analysis of
114. Kaze AD, Schutte AE, Erqou S, Kengne AP, Echouffo-Tcheugui JB. prospective studies. Curr Hypertens Rep. 2013;15:703–716. doi:
Prevalence of hypertension in older people in Africa: a systematic re- 10.1007/s11906-013-0403-y
Downloaded from http://ahajournals.org by on February 7, 2019

view and meta-analysis. J Hypertens. 2017;35:1345–1352. doi: 126. Guo X, Zhang X, Zheng L, Guo L, Li Z, Yu S, Yang H, Zhou X, Zou L, Zhang
10.1097/HJH.0000000000001345 X, Sun Z, Li J, Sun Y. Prehypertension is not associated with all-cause
115. Owolabi M, Olowoyo P, Miranda JJ, Akinyemi R, Feng W, Yaria J, mortality: a systematic review and meta-analysis of prospective studies.
Makanjuola T, Yaya S, Kaczorowski J, Thabane L, Van Olmen J, Mathur PLoS One. 2013;8:e61796. doi: 10.1371/journal.pone.0061796
P, Chow C, Kengne A, Saulson R, Thrift AG, Joshi R, Bloomfield GS, 127. Huang Y, Cai X, Li Y, Su L, Mai W, Wang S, Hu Y, Wu Y, Xu D.
Gebregziabher M, Parker G, Agyemang C, Modesti PA, Norris S, Prehypertension and the risk of stroke: a meta-analysis. Neurology.
Ogunjimi L, Farombi T, Melikam ES, Uvere E, Salako B, Ovbiagele B; 2014;82:1153–1161. doi: 10.1212/WNL.0000000000000268
for the COUNCIL Initiative. Gaps in hypertension guidelines in low- 128. Huang YW, Gu F, Dombkowski A, Wang LS, Stoner GD. Black raspber-
and middle-income versus high-income countries: a systematic review. ries demethylate Sfrp4, a WNT pathway antagonist, in rat esophageal
Hypertension. 2016;68:1328–1337. doi: 10.1161/HYPERTENSIONAHA. squamous cell papilloma. Mol Carcinog. 2016;55:1867–1875. doi:
116.08290 10.1002/mc.22435
116. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, 129. Huang Y, Cai X, Zhang J, Mai W, Wang S, Hu Y, Ren H, Xu D. Prehypertension
He J. Global disparities of hypertension prevalence and control: a system- and incidence of ESRD: a systematic review and meta-analysis. Am J
atic analysis of population-based studies from 90 countries. Circulation. Kidney Dis. 2014;63:76–83. doi: 10.1053/j.ajkd.2013.07.024
2016;134:441–450. doi: 10.1161/CIRCULATIONAHA.115.018912 130. Huang Y, Su L, Cai X, Mai W, Wang S, Hu Y, Wu Y, Tang H, Xu D.
117. Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Association of all-cause and cardiovascular mortality with prehyper-
Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis- tension: a meta-analysis. Am Heart J. 2014;167:160–168.e1. doi:
Guzman N, Azzopardi P, Banerjee A, Bärnighausen T, Basu A, Bekele 10.1016/j.ahj.2013.10.023
T, Bennett DA, Biadgilign S, Catalá-López F, Feigin VL, Fernandes 131. Huang Y, Wang S, Cai X, Mai W, Hu Y, Tang H, Xu D. Prehypertension
JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd and incidence of cardiovascular disease: a meta-analysis. BMC Med.
SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, 2013;11:177. doi: 10.1186/1741-7015-11-177
Lopez A, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw 132. Shen L, Ma H, Xiang MX, Wang JA. Meta-analysis of cohort studies
A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo of baseline prehypertension and risk of coronary heart disease. Am J
T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos Cardiol. 2013;112:266–271. doi: 10.1016/j.amjcard.2013.03.023
IS, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, 133. Wang S, Wu H, Zhang Q, Xu J, Fan Y. Impact of baseline prehyperten-
Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, sion on cardiovascular events and all-cause mortality in the general
Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, population: a meta-analysis of prospective cohort studies. Int J Cardiol.
Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global burden of 2013;168:4857–4860. doi: 10.1016/j.ijcard.2013.07.063

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e137

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

9. DIABETES MELLITUS Abbreviations Used in Chapter 9 Continued

CLINICAL STATEMENTS

HF heart failure
ICD-9 250; ICD-10 E10 to E11. See Tables 9-1 and
AND GUIDELINES

HR hazard ratio
9-2 and Charts 9-1 through 9-10 ICD-9 International Classification of Diseases, 9th Revision
ICD-10 International Classification of Diseases, 10th Revision
Click here to return to the Table of Contents IHD ischemic heart disease
IRR incidence rate ratio
JHS Jackson Heart Study
DM is a heterogeneous mix of health conditions char-
LDL-C low-density lipoprotein cholesterol
acterized by glucose dysregulation. In the United LEADER Liraglutide Effect and Action in Diabetes: Evaluation of
States, the most common forms are type 2 DM, which Cardiovascular Outcome Results
affects 90% to 95% of those with DM,1 and type MACE major adverse cardiovascular events
1 DM, which constitutes 5% to 10% of DM.2 DM MEPS Medical Expenditure Panel Survey
MESA Multi-Ethnic Study of Atherosclerosis
is diagnosed based on fasting glucose ≥126 mg/dL,
MET metabolic equivalent
2-hour postchallenge glucose ≥200 mg/dL during an NCHS National Center for Health Statistics
oral glucose tolerance test, random glucose ≥200 mg/ NH non-Hispanic
dL with presentation of hyperglycemia symptoms, or NHANES National Health and Nutrition Examination Survey
HbA1c ≥6.5%.2a DM is a major risk factor for CVD, NHIS National Health Interview Survey
including CHD and stroke.3 The AHA has identified NHLBI National Heart, Lung, and Blood Institute
NIS National (Nationwide) Inpatient Sample
untreated fasting blood glucose levels of <100 mg/dL
OR odds ratio
for children and adults as 1 of the 7 components of PA physical activity
ideal cardiovascular health.4 PCSK9 proprotein convertase subtilisin kexin 9
PWV pulse-wave velocity
Abbreviations Used in Chapter 9 REGARDS Reasons for Geographic and Racial Differences in Stroke
RR relative risk
ABI ankle-brachial index SBP systolic blood pressure
ACC American College of Cardiology SD standard deviation
ACS acute coronary syndrome SEARCH SEARCH for Diabetes in Youth
ADVANCE Action in Diabetes and Vascular Disease: Preterax and SNP single-nucleotide polymorphism
Diamicron Modified Release Controlled Evaluation
SSB sugar-sweetened beverage
AF atrial fibrillation
SUSTAIN-6 Trial to Evaluate Cardiovascular and Other Long-term
Downloaded from http://ahajournals.org by on February 7, 2019

AHA American Heart Association Outcomes with Semaglutide in Subjects with Type 2
AP angina pectoris Diabetes
ARIC Atherosclerosis Risk in Communities Study TC total cholesterol
BMI body mass index TODAY Treatment Options for Type 2 Diabetes in Adolescents
BP blood pressure and Youth
CAC coronary artery calcification VTE venous thromboembolism
CAD coronary artery disease WC waist circumference
CANVAS Canagliflozin Cardiovascular Assessment Study
CARDIA Coronary Artery Risk Development in Young Adults
CDC Centers for Disease Control and Prevention Prevalence
CHD coronary heart disease Youth
CI confidence interval
CKD chronic kidney disease
• Approximately 193 000 people <20 years of age
CVD cardiovascular disease were diagnosed with DM in 2015.1
DM diabetes mellitus • During 2001 to 2009, the prevalence of type 1
ED emergency department DM increased 30% from 1.48 per 1000 youth to
eGFR estimated glomerular filtration rate 1.93 per 1000 youth.5
EMPA-REG BI 10773 (Empagliflozin) Cardiovascular Outcome Event
OUTCOME Trial in Type 2 Diabetes Mellitus Patients — Among youths with type 1 DM, the preva-
ESRD end-stage renal disease lence of overweight is 22.1% and the
EVEREST Efficacy of Vasopressin Antagonism in Heart Failure prevalence of obesity is 12.6%.6
Outcome Study With Tolvaptan
EXAMINE Examination of Cardiovascular Outcomes With Alogliptin • Type 2 DM, a disease usually diagnosed in adults
Versus Standard of Care ≥40 years of age, is being diagnosed among peo-
FOURIER Further Cardiovascular Outcomes Research With PCSK9
Inhibition in Subjects With Elevated Risk
ple <20 years of age. Between 2001 and 2009,
GBD Global Burden of Disease the prevalence of type 2 DM in youths increased
GWAS genome-wide association studies by 30.5%.5
GWTG Get With The Guidelines
— Among youths with type 2 DM, 10.4% are
HbA1c hemoglobin A1c (glycosylated hemoglobin)
HCHS/SOL Hispanic Community Health Study/Study of Latinos
overweight and 79.4% have obesity.6
HDL high-density lipoprotein • According to NHANES data from 1999 to 2000
(Continued ) through 2007 to 2008, among US adolescents

e138 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

aged 12 to 19 years, the prevalence of prediabe- descent aged 18 to 74 years were enrolled from

CLINICAL STATEMENTS
tes and type 2 DM increased from 9% to 23%.7 4 US metropolitan areas from 2008 to 2011. The

AND GUIDELINES
• Among US adolescents aged 12 to 19 years prevalence of DM varied for adults with different
in 2005 to 2014, the prevalence of DM was Hispanic backgrounds. DM prevalence ranged
0.8% (95% CI, 0.6%–1.1%). Of those with from 10.2% in South Americans to 13.4% in
DM, 28.5% (95% CI, 16.4%–44.8%) were Cubans, 17.7% in Central Americans, 18.0%
undiagnosed.8 in Dominicans and Puerto Ricans, and 18.3% in
• Among US adolescents aged 12 to 19 years in Mexicans.10
2005 to 2014, the prevalence of prediabetes • Among foreign-born participants of the US
was 17.7% (95% CI, 15.8%–19.8%).8 Males NHANES 1999 to 2012, the prevalence of DM
were more likely to have prediabetes than increased with duration of time spent in the
females (22.0% [95% CI, 19.5%–24.7%] ver- United States and was 6.1%, 9.3%, 11.1%,
sus 13.2% [95% CI, 10.4%–16.7%]). Also, the and 20.0% among those in the United States
prevalence of prediabetes was higher in NH for <1, 1 to 9, 10 to 19, and ≥20 years,
blacks (21.0% [95% CI, 17.7%–24.7%]) and respectively.11
Hispanics (22.9% [95% CI, 19.9%–26.3%]) • The prevalence of diagnosed DM in adults was
than in NH white participants (15.1% [95% CI, higher for both males and females in the 2013
12.3%–18.6%]).8 to 2016 NHANES data than in the 1988 to 1994
• Between 1996 and 2010, the number of youths NHANES data. Males had a higher prevalence
with type 1 DM increased by 5.7% per year.9 of diagnosed DM and undiagnosed DM than
females in 2013 to 2016. Prevalence of diagnosed
Adults and undiagnosed DM increased for both males
(See Table 9-1 and Charts 9-1 through 9-5) and females between study periods (Chart 9-3;
• On the basis of data from NHANES 2013 to 2016, unpublished NCHS/NHLBI tabulation). During this
an estimated 26 million adults have diagnosed time period, 2 DM diagnostic changes occurred:
DM, 9.4 million adults have undiagnosed DM, the threshold definition for diagnosed DM was
and 91.8 million adults (37.6%) have prediabe- lowered from ≥140 mg/dL to ≥126 mg/dL in
tes. The prevalence of prediabetes and DM differs 1997,12 and HbA1c ≥6.5% was added as a diag-
by sex and race/ethnicity (Table 9-1; unpublished nostic test in 2010.2a
Downloaded from http://ahajournals.org by on February 7, 2019

NHLBI tabulation). • Geographic variations in DM prevalence have

• After adjustment for population age differences, been reported in the United States (Chart 9-4).
2013 to 2016 NHANES national survey data for — Across counties in the United States during
people ≥20 years of age indicate that the preva- 1999 to 2012, the prevalence of diagnosed
lence of diagnosed DM was 9.4% in NH white DM ranged from 5.6% to 20.4%, the preva-
males and 7.3% in NH white females, 14.7% in lence of undiagnosed DM ranged from 3.2%
NH black males and 13.4% in NH black females, to 6.8%, and the prevalence of total DM
15.1% in Hispanic males and 14.1% in Hispanic ranged from 8.8% to 26.4%.14 The preva-
females, and 12.8% in NH Asian males and 9.9% lence of diagnosed DM was highest in the
in NH Asian females (Table  9-1 and Chart 9-1; Deep South, near the Texas-Mexico border,
unpublished NCHS/NHLBI tabulation). and in counties with Native American res-
• On the basis of 2015 data from the Indian ervations and was lowest in counties in the
Health Service, the age-adjusted prevalence of upper Midwest and parts of Alaska and New
diagnosed DM among American Indians/Alaska England.
Natives was 14.9% for males and 15.3% for — Using data from the REGARDS study, the
females.1 median (range) predicted prevalence of
• On the basis of NHANES 2013 to 2016 data, DM was 14% (10%–20%) among whites
the age-adjusted prevalence of diagnosed DM and 31% (28%–41%) among blacks.15 DM
in adults ≥20 years of age varies by race/ethnic- was most prevalent in the west and cen-
ity and years of education. NH white adults with tral Southeast among whites (Louisiana,
more than a high school education had the low- Arkansas, Mississippi, Alabama, Tennessee,
est prevalence (7.6%), and Hispanic adults with a and south Kentucky, as well as parts of North
high school education had the highest prevalence Carolina and South Carolina).
(17.7%; Chart 9-2; unpublished NCHS/NHLBI • The age-adjusted prevalence of diagnosed DM
tabulation). and undiagnosed DM increased from 5.0% and
• In the prospective, multicenter, population-based 3.5%, respectively, in 1999 to 2000 to 7.8%
HCHS/SOL, 16  415 adults of Hispanic/Latino and 4.4%, respectively, in 2009 to 2010.16 The

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e139

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

prevalence of diagnosed DM increased among • There were 258 852 deaths with DM listed as
CLINICAL STATEMENTS

NH whites and blacks over this time period. any cause of death in 2016.20 The 2016 over-
AND GUIDELINES

• The prevalence of diagnosed DM in adults was all underlying-cause, age-adjusted death rate
higher for NH black, NH white, and Hispanic attributable to DM was 21.0 per 100 000. For
adults in NHANES 1988 to 2010 than in NHANES males, the death rates per 100 000 population
1988 to 1994. Prevalence of undiagnosed DM were 23.5 for NH whites, 44.8 for NH blacks,
increased slightly between studies (Chart 9-5; 29.6 for Hispanics, 18.8 for NH Asian/Pacific
unpublished NCHS/NHLBI tabulation). Islanders, and 52.2 for NH American Indian/
Alaska Natives. For females, the death rates per
Incidence 100 000 population were 14.4 for NH whites,
Youth 32.7 for NH blacks, 20.7 for Hispanics, 13.0
for NH Asian/Pacific Islanders, and 40.6 for NH
• During 2011 to 2012, an estimated 17 900 peo- American Indian/Alaska Natives.20
ple <20 years of age in the United States were • In a study of NHIS 1997 to 2009 participants fol-
diagnosed with incident type 1 DM, and 5300 lowed up through 2011, DM was the underly-
individuals aged 10 to 19 years were newly diag- ing cause for 3.3% of deaths and a contributing
nosed with type 2 DM annually.1 cause for 10.8% of deaths. The population attrib-
• In the SEARCH study, the incidence rate of type utable fraction for death associated with DM was
1 DM increased by 1.4% annually (from 19.5 to 11.5%. Although DM was more often cited as
21.7 cases per 100 000 youths per year in 2003 an underlying and contributing cause of death
to 2012).17 The increase was larger for males for NH blacks and Hispanics than for NH whites,
than for females and for Hispanics and Asian or the population attributable fraction was similar in
Pacific Islanders than for other ethnic groups. each racial/ethnic group.21
Also, the incidence of type 2 DM increased • In a collaborative meta-analysis of 820 900 indi-
by 7.1% annually (from 9.0 to 12.5 cases per viduals from 97 prospective studies, DM was asso-
100 000 youths per year from 2003 to 2012). ciated with the following risks: all-cause mortality
The annual increase was larger among females (HR, 1.80 [95% CI, 1.71–1.90]), cancer death
than males and among NH blacks, Hispanics, (HR, 1.25 [95% CI, 1.19–1.31]), and vascular
Asian or Pacific Islanders, and Native Americans
Downloaded from http://ahajournals.org by on February 7, 2019

death (HR, 2.32 [95% CI, 2.11–2.56]). In particu-

compared with NH whites. lar, DM was associated with death attributable to
• Projecting disease burden for the US population the following cancers: liver, pancreatic, ovarian,
<20 years of age by 2050, the number of youths colorectal, lung, bladder, and breast. A 50-year-
with type 1 DM is expected to increase from old with DM dies on average 6 years earlier than
166 018 to 203 382, and the number with type 2 an individual without DM.22
DM will increase from 20 203 to 30 111. Less con- • Among NHIS participants enrolled in 2000 to
servative modeling projects the number of youths 2009 and followed up through 2011, males
with type 1 DM at 587 488 and those with type 2 and females with diagnosed DM had 1.56 and
DM at 84 131 by 2050.18 1.69 times as high risk of all-cause mortality as
Adults those without diagnosed DM (HR, 1.56 [95%
(See Table 9-1) CI, 1.49–1.64] and 1.69 [95% CI, 1.61–1.78],
• Approximately 1.5 million US adults ≥18 years respectively).23
old were diagnosed with incident DM in 2015 • In the Swedish National Diabetes Register, there
(Table 9-1).1 was a significant decline in all-cause mortality
• In the CARDIA study, the risk of DM was higher from 1998 to 2014 among patients with type
for black females than white females (HR, 2.86 1 DM (HR, 0.71 [95% CI, 0.66–0.78]), but this
[95% CI, 2.19–3.72]) and for black males than decline was not statistically different from the
white males (HR, 1.68 [95% CI, 1.28–2.17]) after decline observed among control subjects without
adjustment for age and field center.19 DM (HR, 0.77 [95% CI, 0.72–0.83]). In contrast,
the decline in all-cause mortality from 1998 to
2014 among patients with type 2 DM (HR, 0.79
Mortality [95% CI, 0.78–0.80]) was less than the decline
(See Table 9-1) observed among control subjects without DM
• DM was listed as the underlying cause of mor- (HR, 0.69 [95% CI, 0.68–0.70]).24
tality for 80  058 people (43 763 males and • In the Swedish National Diabetes Register, com-
36 295 females) in the United States in 2016 pared with control subjects without DM, the
(Table 9-1).20 adjusted HR for all-cause mortality for patients

e140 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

with type 1 DM who met all risk factor targets • On the basis of analyses of data from the NHIS,

CLINICAL STATEMENTS
was 1.31 (95% CI, 0.93–1.85), whereas the HR between 1995 and 2014, the rate of hospital-

AND GUIDELINES
for patients with type 1 DM who met no risk fac- izations for IHD declined 66.4% and the rate of
tor targets was 7.33 (95% CI, 5.08–10.57).25 hospitalization for stroke declined 35.6% among
• The leading cause of death among patients with patients with DM (Chart 9-6).31
type 1 DM is CVD, which accounted for 22% of • The HRs of CHD events comparing participants
deaths among those in the Allegheny County, PA, with DM only, DM and prevalent CHD, and neither
type 1 DM registry, followed by renal (20%) and DM nor prevalent CHD with those with prevalent
infectious (18%) causes.26 CHD were 0.65 (95% CI, 0.54–0.77), 1.54 (95%
CI, 1.30–1.83), and 0.41 (95% CI, 0.35–0.47),
respectively, after adjustment for demographics
Complications and risk factors.32 Compared with participants
(See Chart 9-6) who had prevalent CHD, the HR of CHD events
Microvascular Complications for participants with severe DM was 0.88 (95%
• Among those ≤21 years old with newly diag- CI, 0.72–1.09).
nosed DM in a US managed care network, 20% • In a meta-analysis of 19 studies, DM was not
of youth with type 1 DM and 7.2% of youth with associated with an increased risk for VTE (pooled
type 2 DM developed diabetic retinopathy over a RR, 1.10 [95% CI, 0.94–1.29]).33
median follow-up of 3 years.27 • Compared with those with normal glucose,
• On the basis of analyses of data from the NIS, carotid-femoral PWV was 95.8 (95% CI, 69.4–
the United States Renal Data System, and the US 122.1) and 21.3 (95% CI, −0.8 to 43.4) cm/s
National Vital Statistics System, between 1995 higher for participants with DM and prediabetes,
and 2014 (Chart 9-6), substantial declines have respectively.34 A similar pattern was present for
been observed in the age-standardized rates of brachial-ankle PWV.
hospitalization for lower-extremity amputation, • In MESA, 63% of participants with DM had a
incident DM-related ESRD, and mortality attribut- CAC >0 compared with 48% of those without
able to hyperglycemic crisis (32.8%, 40.7%, and DM.35
37.5%, respectively). • In CARDIA, a longer duration of DM was associ-
ated with CAC presence (per 5-year longer dura-
Downloaded from http://ahajournals.org by on February 7, 2019

• Among adults with DM in NHANES 2007 to

2012, the overall age-adjusted prevalence of CKD tion: HR, 1.15 [95% CI, 1.06–1.25]) and worse
was 40.2% in 2007 to 2008, 36.9% in 2009 to cardiac function, including early diastolic relax-
2010, and 37.6% in 2011 to 2012.28 The preva- ation and higher diastolic filling pressure.36
lence of CKD was 58.7% in US adults with DM • In a nationwide Danish registry, the adjusted IRRs
aged ≥65 years, 25.7% in those <65 years of age, (95% CIs) for AF comparing people with and
43.5% in NH blacks and Mexican Americans, and without DM were 2.34 (1.52–3.60), 1.52 (1.47–
38.7% in NH whites. 1.56), 1.20 (1.18–1.23), and 0.99 (0.97–1.01) for
• The prevalence of any diabetic kidney disease, adults 18 to 39, 40 to 64, 65 to 74, and 75 to 100
defined as persistent albuminuria, persistent years of age, respectively.37
reduced eGFR, or both, did not significantly • A meta-analysis of published observational data
change from the period 1988 to 1994 (28.4% comprising 11 studies and >1.6 million partici-
[95% CI, 23.8%–32.9%]) to 2009 to 2014 pants reported DM was associated with a 24%
(26.2% [95% CI, 22.6%–29.9%]). However, increased risk for AF (RR, 1.24 [95% CI, 1.06–
the prevalence of albuminuria decreased from 1.44]) after multivariable adjustment.38
20.8% (95% CI, 16.3%–25.3%) to 15.9% • In an analysis of NHANES 2001 to 2010, the prev-
(95% CI, 12.7%–19.0%) and the prevalence alence of AP among participants with CHD was
of reduced eGFR increased from 9.2% (95% similar for adults with and without DM (49% and
CI, 6.2%–12.2%) to 14.1% (95% CI, 11.3%– 46%, respectively).39
17.0%) over this time period.29 DM accounted • DM increases the risk of HF and adversely affects
outcomes among patients with HF.
for 46% of the new cases of ESRD in 2011 to
— DM alone qualifies for the most recent
2015.30
ACC/AHA diagnostic criteria for stages
CVD Complications A and B HF, a classification of patients
• Among NHIS participants enrolled in 2000 to without HF but at notably high risk for its
2009 and followed up through 2011, DM was development.40
associated with increased risk for CVD mortality — DM should be treated similarly for patients
among males and females.23 with HF as for the general population.40

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e141

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

— In a meta-analysis of 10 prospective cohort Healthcare Utilization

CLINICAL STATEMENTS

studies, the HR for HF per 1-mmol/L (≈18

• Among Medicare beneficiaries with type 2 DM
AND GUIDELINES

mg/dL) increase in fasting plasma glucose

hospitalized between 2012 and 2014, 17.1%
level was 1.11 (95% CI, 1.04–1.17), which
were readmitted within 30 days.52
suggests an independent and continuous
• According to the 2014 NIS, the rate of hospital-
positive association between fasting plasma
ization among adults with DM was 327.2 per
glucose and HF.41
1000 people with DM for any causes (7.2 million
— Post hoc analysis of data from the EVEREST
discharges), 70.4 per 1000 people with DM for
randomized trial of patients hospitalized
major CVD (1.5 million discharges), 5.0 per 1000
with decompensated systolic HF demon-
people with DM for lower-extremity amputation
strated that DM increased the risk of the
(108 000 discharges), and 7.7 per 1000 peo-
composite outcome of cardiovascular mor-
ple with DM for diabetic ketoacidosis (168 000
tality and HF hospitalization (HR, 1.17 [95%
discharges).1
CI, 1.04–1.31]) over a median 9.9 months of
• According to the 2014 Nationwide Emergency
follow-up.42
Department Sample, the rate of ED visits was
— The association between glycemia and out-
648.9 per 1000 people with DM for any causes
comes has been mixed in patients with HF,
(14.2 million visits), 11.2 per 1000 people with
and there is insufficient evidence to recom-
DM for hypoglycemia (245 000 visits), and 9.5 per
mend specific glucose treatment goals in
1000 people with DM for hyperglycemia (207 000
patients hospitalized with HF.43
visits).1
Hypoglycemia • Among participants in the ARIC study, without a
• Hypoglycemia is a major factor that lim- prior diagnosis of DM, hospitalization rates were
its glycemic control in DM. In 2010, among 163 (95% CI, 158–169), 217 (95% CI, 206–228),
Medicare beneficiaries with DM, hospitaliza- and 254 (95% CI, 226–281) per 1000 person-
tions for hypoglycemia and hyperglycemia years with HbA1c <5.7%, 5.7% to <6.5%, and
were 612 and 367 per 100 000 person-years, ≥6.5% respectively. Among those with diag-
respectively.44 nosed DM, the hospitalization rates were 340
• In ADVANCE, severe hypoglycemia was associ- (95% CI, 297–384) and 504 (95% CI, 462–547)
Downloaded from http://ahajournals.org by on February 7, 2019

ated with an increased risk of major macrovas- for participants with HbA1c <7.0% and ≥7.0%,
cular events (HR, 2.88 [95% CI, 2.01–4.12]), respectively.53
cardiovascular death (HR, 2.68 [95% CI, 1.72–
4.19]), and all-cause death (HR, 2.69 [95% CI,
Cost
1.97–3.67]), including nonvascular outcomes.
The lack of specificity of hypoglycemia with vas- (See Table 9-1)
cular outcomes suggests that it might be a marker • In 2017, the cost of DM was estimated at $327
for overall susceptibility or frailty.45 billion (Table 9-1), up 26% from 2012, account-
• In ARIC, severe hypoglycemia was associated ing for 1 in 4 healthcare dollars.30 Of these costs,
with an increased risk of CHD (HR, 2.02 [95% CI, $237 billion were direct medical costs and $90
1.27–3.20]), all-cause mortality (HR, 1.73 [95% billion resulted from reduced productivity.
CI, 1.38–2.17]), cardiovascular mortality (HR, 1.64 • After adjustment for age and sex, medical costs
[95% CI, 1.15–2.34]), and cancer mortality (HR, for patients with DM were 2.3 times higher than
2.49 [95% CI, 1.46–4.24]).46 for people without DM.30 In 2017, the average
• In the EXAMINE trial, severe hypoglycemia was medical expenditure for people with DM was
associated with an increased risk of MACE (HR, $16 752 per year, of which $9601 was attributed
2.42 [95% CI, 1.27–4.60]).47 to DM.30 Informal care is estimated to cost $1192
• Severe hypoglycemia is more common with to $1321 annually per person with DM.54
increasing age, with use of insulin or sulfonyl-
ureas, and in those with impaired renal function,
type 1 DM, and prior severe hypoglycemia.48 Risk Factors for Developing DM
HbA1c shows a U-shaped relationship with hypo- • In MESA, the incidence rate of DM per 1000
glycemia.49 Higher rates of hypoglycemia have person-years associated with having 0, 1, 2, 3,
also been reported in African Americans com- 4, and 5 to 6 ideal cardiovascular health factors
pared with NH whites.50 Furthermore, dementia was 21.8, 18.6, 13.0, 11.2, 4.7, and 3.6, respec-
and decreased cognitive function have been asso- tively.55 Lower DM risk was associated with more
ciated with hypoglycemia.45,51 ideal cardiovascular health factors for NH whites,

e142 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

Chinese Americans, African Americans, and • In the FOURIER trial, evolocumab, a PCSK9 inhibi-

CLINICAL STATEMENTS
Hispanic Americans. Ideal cardiovascular health tor, was not associated with an increased risk of

AND GUIDELINES
factors included TC, BP, dietary intake, tobacco DM (HR, 1.05 [95% CI, 0.94–1.17]) over a median
use, PA, and BMI. of 2.2 years of follow-up.64
• In CARDIA, adjustment for fasting glucose,
BMI, WC, SBP, use of antihypertensive medi-
cations, triglyceride to HDL ratio, and parental
Prediabetes and Prevention
history of DM explained the higher incidence • In 2015, 33.9% of US adults aged ≥18 years had
of DM observed for black adults compared prediabetes, defined as fasting glucose 100 to
with white adults, respectively, over 30 years of 125 mg/dL or HbA1c 5.7 to 6.4%.1 The prevalence
follow-up.19 of prediabetes increased with age and was higher
• In a meta-analysis, each 1-SD higher BMI in child- for males (36.6%) than females (29.3%).
hood was associated with an increased risk for • Among adults aged ≥20 years with overweight
developing DM as an adult (pooled OR, 1.23 or obesity from 4 integrated health systems in the
[95% CI, 1.10–1.37] for children ≤6 years of age; United States, 47.2% had prediabetes in 2012 to
1.78 [95% CI, 1.51–2.10] for age 7 to 11 years; 2013.65
and 1.70 [95% CI, 1.30 – 2.22] for those 12 to 18 • The awareness of prediabetes is low, with only
years).56 11.6% of adults with prediabetes reporting
• Compared with birth weight of 3.63 to 4.5 kg, being told they have prediabetes by a healthcare
low birth weight (<2.72 kg) increased the risk professional.1
of type 2 DM (OR, 2.15 [95% CI, 1.54–3.00]), • In the Diabetes Prevention Program of adults with
with 47% of this association mediated by insulin prediabetes (defined as 2-hour postchallenge
resistance.57 glucose of 140–199 mg/dL), the absolute risk
• Of the 20.9 million new cases of DM predicted reduction for DM was 20% for those adherent
to occur over 10 years in the United States, 1.8 to the lifestyle modification intervention and 9%
million could be attributable to consumption for those adherent to the metformin intervention
of SSBs. A recent meta-analysis showed that compared with placebo over a median 3-year
each 1 serving per day higher consumption of follow-up. Metformin was effective among those
SSBs was associated with an 18% increased risk with higher predicted risk at baseline, whereas
Downloaded from http://ahajournals.org by on February 7, 2019

for DM.58 lifestyle intervention was effective regardless of

• In a meta-analysis, 600 to 3999, 4000 to 7999, baseline predicted risk.66
and ≥8000 MET min/week of PA versus <600
MET min/week were associated with a decreased
Awareness, Treatment, and Control
risk for developing DM of 0.86 (95% CI, 0.82–
0.90), 0.75 (95% CI, 0.70–0.80), and 0.72 (95% (See Chart 9-7)
CI, 0.68–0.77), respectively.59 • From 2004 through 2011 in the TODAY study,
• In the CARDIA study, higher cardiorespiratory less than half of children (41.1% of Hispanic
fitness was associated with lower risk for inci- and 31.5% of NH black children) with recent-
dent prediabetes/DM (difference of 1 MET: HR, onset type 2 DM maintained durable glycemic
0.99898 [95% CI, 0.99861–0.99940]; P<0.01), control with metformin monotherapy, which is
which persisted after adjustment for covariates.60 a higher rate of treatment failure than observed
• A systematic review by Biswas et al61 identified in adult cohorts.67 Youths with recent-onset type
5 studies (4 were prospective) that assessed the 2 DM were sedentary >56 minutes longer per
association between sedentary time and type 2 day (via accelerometry) than obese youths from
DM and found that even after adjustment for NHANES.68
PA, higher sedentary time was associated with • On the basis of NHANES 2013 to 2016 data for
elevated risk of type 2 DM (RR, 1.91 [95% CI, adults with DM, 20.9% had their DM treated
1.64–2.22]). These findings suggest prolonged and controlled, 45.2% had their DM treated but
sedentary time might have deleterious metabolic uncontrolled, 9.2% were aware they had DM but
effects independent of PA.62 were not treated, and 24.7% were undiagnosed
• In the ARIC study, the risk of DM was higher for and not treated (Chart 9-7; unpublished NHLBI
participants with an ABI ≤0.9 (HR, 1.41 [95% CI, tabulations).
1.17–1.68]) than their counterparts with an ABI • In a pooled analysis of ARIC, MESA, and JHS,
of 1.11 to 1.20, but this association was attenu- 41.8%, 32.1%, and 41.9% of participants were
ated after multivariable adjustment (HR, 1.18 at target levels for BP, LDL-C, and HbA1c, respec-
[95% CI, 0.98–1.41]).63 tively; 41.1%, 26.5%, and 7.2% were at target

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e143

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

levels for any 1, 2, or all 3 factors, respectively. 2018, 9 cardiovascular outcomes trials have been
CLINICAL STATEMENTS

Having 1, 2, and 3 factors at goal was associated reported, all demonstrating noninferiority of the
AND GUIDELINES

with 36%, 52%, and 62%, respectively, lower new glucose-lowering agents relative to placebo
risk of CVD events compared with participants for their primary outcomes. Four of the trials
with no risk factors at goal.69 had a decrease in the primary cardiovascular end
• In 2007 to 2010 NHANES data, 52.5% of point.80
adults with DM had an HbA1c <7.0%, 51.1% — The LEADER trial had a decrease in MACE
achieved a BP <130/80 mm Hg, 56.2% had an events for liraglutide versus placebo (HR,
LDL-C <100 mg/dL, and 18.8% had reached 0.87 [95% CI, 0.78–0.97]).81
all 3 treatment targets. Compared with NH — The SUSTAIN-6 trial had a decrease in MACE
whites, Mexican Americans were less likely to events for semaglutide versus placebo (HR,
meet HbA1c and LDL-C goals, and NH blacks 0.74 [95% CI, 0.58–0.95]).82
were less likely to meet BP and LDL-C goals.70 — The EMPA-REG OUTCOME trial had a
Additionally, 22.3% of adults with DM reported decrease in MACE events for empa-
being current smokers.71 gliflozin versus placebo (HR, 0.86 [95% CI,
• Among HCHS/SOL study participants with 0.74–0.99]).83
DM, 43.0% had HbA1c <7.0%, 48.7% had — The CANVAS Program trial had a decrease
BP <130/80 mm Hg, 36.6% had LDL-C <100 in MACE events for canagliflozin versus pla-
mg/dL, and 8.4% had reached all 3 treatment cebo (HR, 0.86 [95% CI, 0.75–0.97]).84
targets.72
— HCHS/SOL participants in the lowest versus Family History and Genetics
highest tertile of sedentary time were more
• DM is heritable; twin or family studies have dem-
likely to have controlled their HbA1c to <7%
onstrated a range of heritability estimates from
(OR, 1.76 [95% CI, 1.10–2.82]) and their tri-
30% to 70% depending on age of onset.85,86 In
glycerides to <150 mg/dL (OR, 2.16 [95% CI,
the Framingham Heart Study, having a parent or
1.36–3.46]).73
sibling with DM conferred a 3.4 times increased
• According to NHANES 2007 to 2012, 17% of US risk of DM, which increased to 6.1 if both parents
adults with DM met the criteria for major depres- were affected.87
Downloaded from http://ahajournals.org by on February 7, 2019

sion or subsyndromal symptomatic depression. • There are parent-of-origin effects in DM, whereby
This represents 3.7 million US adults with these the effects of genetic variants depend on the par-
conditions.74 ent from whom they are inherited.88
• Treatment of hypercholesterolemia is recom- • There are monogenic forms of DM, such as matu-
mended for adults with DM, with statin ther- rity-onset DM of the young, that are caused by
apy recommended for all patients with DM genetic mutations in the GCK (glucokinase) and
40 to 75 years of age independent of baseline 28 other genes, but these affect <5% of patients
cholesterol.75 with DM; genetic testing can be considered in
• In the AHA’s GWTG Program, patients with ACS these patients.89,90
and DM were less likely to have LDL-C checked • The majority of DM is a complex disease character-
or a statin prescribed than patients with ACS but ized by multiple genetic variants with gene-gene
without DM.76 and gene-environment interactions. Genome-
• Treatment of hypertension is also recommended wide genetic studies of common DM conducted
for adults with DM, with a target BP of 130/80 in large sample sizes through meta-analyses have
mm Hg for most people with DM.77 identified >100 genetic variants associated with
• In MEPS, 70% (95% CI, 68%–71%), 67% (95% DM, with the most consistent being a common
CI, 66%–69%), and 68% (95% CI, 66%–71%) intronic variant in the TCF7L2 (transcription factor
of US adults with DM received appropriate DM 7 like 2) gene.91–93
care (HbA1c measurement, foot examination, and • Other risk loci for DM identified from GWAS
an eye examination) in 2002, 2007, and 2013, include variants in the genes SLC30A8 and HHEX
respectively78; however, only 39.6% of adults (related to β-cell development or function) and in
with DM reported receiving dilated eye examina- the NAT2 (N-acetyltransferase 2) gene, associated
tions annually.79 with insulin sensitivity.93,94
• In 2008, the US Food and Drug Administration • GWASs in non-European ethnicities have also
issued guidance to the pharmaceutical indus- identified significant risk loci for DM, including
try mandating cardiovascular outcomes trials for variants in the gene KCNQ1 (identified from a
new glucose-lowering medications. As of early GWAS in Japanese individuals and replicated in

e144 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

other ethnicities).93,95 Transethnic analyses have be able to discriminate type 1 DM from type 2

CLINICAL STATEMENTS
identified genetic variants that are specific to DM (area under the curve 0.87), which could be

AND GUIDELINES
certain ethnicities, for example, within the PEPD clinically useful given the increasing prevalence of
gene (specific to East Asian ancestry) and KLF14 obesity in young adults.102
(specific to European ancestry).91,92 • The risk of complications from DM is also heri-
• Lifestyle appears to overcome risk conferred by table. For example, diabetic kidney disease
a polygenic risk score composed of a combina- shows familial clustering, with diabetic siblings
tion of these common variants. In a recent study of patients with diabetic kidney disease having a
of the United Kingdom Biobank, genetic com- 2-fold increased risk of also developing diabetic
position and combined health behaviors had a kidney disease.103 Genetic variants have also been
log-additive effect on the risk of developing DM, identified that appear to increase the risk of CAD
but ideal lifestyle returned the risk of incident in patients with DM.104
DM toward the referent (low genetic risk) group
in both the intermediate- and high-genetic-risk
groups.96 Global Burden of DM
• Some studies have suggested that genetic vari- (See Table 9-2 and Charts 9-8 through 9-10)
ants may predict response to DM therapies. For • The GBD 2016 Study used statistical models and
example, the response to metformin is herita- data on incidence, prevalence, case fatality, excess
ble, and a SNP in the ATM (ataxia telangiecta- mortality, and cause-specific mortality to estimate
sia mutated) gene has been associated with this disease burden for 315 diseases and injuries in
response.97,98 195 countries and territories.105
• The utility of clinical genetic testing for common — The prevalence of DM increased 119.1%
DM is currently unclear. Recent genetic tech- for males and 106.1% for females between
nological advances, including whole-genome 1990 and 2016. Overall, 198.7 million males
sequencing, have enabled identification of novel and 184.7 million females worldwide have
genes that harbor rare variants associated with DM (Table 9-2).
common DM, with the strongest being for a vari- — Mortality rates attributable to high fast-
ant in the gene CCND2 (encoding a protein that ing plasma glucose are lowest in Western
Downloaded from http://ahajournals.org by on February 7, 2019

helps regulate cell cycle), which reduces the risk Europe, Australia, and New Zealand (Chart
of DM by half.99 9-8).
• Inactivation of rare variants in the ANGPTL4 — Mortality attributable to DM is high in the
(angiopoietin-like 4) gene, which leads to loss of Pacific Island countries, South Asia, sub-
the gene’s ability to inhibit lipoprotein lipase, has Saharan Africa, the North Africa/Middle
been associated with reduced DM risk.100 East region, and Central and Latin America
• Type 1 DM is also heritable. Early genetic studies (Chart 9-9).
identified the role of the MHC (major histocom- — The prevalence of DM is highest in the Pacific
patibility complex) gene in this disease, with the Island countries, Central Latin America, and
greatest contributor being the human leukocyte the North Africa/Middle East region (Chart
antigen region, estimated to contribute to ≈50% 9-10).
of the genetic risk.101 • The global economic burden of DM was $1.3 tril-
• A genotype risk score composed of 9 type 1 lion in 2015. It is estimated to increase to $2.1 to
DM–associated risk variants has been shown to 2.5 trillion by 2030.106

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e145

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

Table 9-1.  Diabetes Mellitus

CLINICAL STATEMENTS

Prevalence of Prevalence of Incidence of Hospital

AND GUIDELINES

Diagnosed DM, Undiagnosed Prevalence of Diagnosed Discharges,

2013–2016: Age DM, 2013–2016: Prediabetes, 2013– DM, 2015: Mortality, 2016: 2014: All
Population Group ≥20 y Age ≥20 y 2016: Age ≥20 y Age ≥18 y* All Ages† Ages Cost, 2017‡
Both sexes 26 000 000 (9.8%) 9 400 000 (3.7%) 91 800 000 (37.6%) 1 500 000 80 058 551 000 $327 Billion
Males 13 700 000 (10.9%) 5 500 000 (4.6%) 51 700 000 (44.0%) … 43 763 (54.7%)§ 301 000 …
Females 12 300 000 (8.9%) 3 900 000 (2.8%) 40 100 000 (31.3%) … 36 295 (45.3%)§ 250 000 …
NH white males 9.4% 4.7% 43.7% … 30 010 … …
NH white females 7.3% 2.6% 32.2% … 23 389 … …
NH black males 14.7% 1.7% 31.9% … 6976 … …
NH black females 13.4% 3.3% 24.0% … 7077 … …
Hispanic males 15.1% 6.3% 48.1% … 4603 … …
Hispanic females 14.1% 4.0% 31.7% … 3943 … …
NH Asian males 12.8% 6.1% 47.1% … 1414 … …
NH Asian females 9.9% 2.1% 29.4% … 1283 … …
NH American Indian … … … … 1078 … …
or Alaska Native

Undiagnosed DM is defined as those whose fasting glucose is ≥126 mg/dL but who did not report being told by a healthcare provider that they had DM.
Prediabetes is a fasting blood glucose of 100 to <126 mg/dL (impaired fasting glucose); prediabetes includes impaired glucose tolerance. DM indicates diabetes
mellitus; ellipses (…), data not available; and NH, non-Hispanic.
*Centers for Disease Control and Prevention (CDC), National Diabetes Statistics Report, 2017.1
†Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
‡American Diabetes Association.2a
§These percentages represent the portion of total DM mortality that is for males vs females.
Sources: Prevalence: Prevalence of diagnosed and undiagnosed DM: National Health and Nutrition Examination Survey 2013 to 2016, National Center for Health
Statistics (NCHS), and National Heart, Lung, and Blood Institute. Percentages for sex and racial/ethnic groups are age adjusted for Americans ≥20 years of age.
Mortality: CDC/NCHS, 2016 Mortality Multiple Cause-of-Death–US. These data represent underlying cause of death only. Mortality for NH Asians includes Pacific
Downloaded from http://ahajournals.org by on February 7, 2019

Islanders. Hospital discharges: Healthcare Cost and Utilization Project, Hospital Discharges, 2014.

Table 9-2.  Global Prevalence and Mortality of DM, 2016

Both Sexes Combined Males Females

Death Prevalence Death Prevalence Death Prevalence
Total number 1.4 383.5 0.7 198.7 0.8 184.7
(millions) (1.4 to 1.5) (352.6 to 414.6) (0.7 to 0.7) (182.9 to 215.3) (0.7 to 0.8) (169.6 to 199.5)
Percent change total 127.0 112.6 145.0 119.1 113.1 106.1
number 1990 to (120.3 to 133.0) (107.7 to 117.2) (137.2 to 152.3) (113.8 to 124.1) (102.9 to 121.8) (100.8 to 111.0)
2016
Percent change total 31.1 22.0 35.7 23.1 27.3 20.8
number 2006 to (28.9 to 33.4) (19.3 to 24.8) (32.8 to 38.6) (20.3 to 26.3) (23.7 to 30.9) (18.3 to 23.3)
2016
Rate per 100 000 22.1 5334.8 23.3 5672.5 21.2 5009.5
(21.6 to 22.7) (4908.6 to 5759.7) (22.6 to 24.0) (5225.5 to 6136.6) (20.4 to 21.9) (4612.8 to 5412.9)
Percent change rate 16.0 19.6 21.6 21.8 11.2 17.2
1990 to 2016 (12.6 to 19.1) (16.7 to 22.0) (17.8 to 25.1) (18.9 to 24.4) (5.9 to 15.8) (14.2 to 19.7)
Percent change rate −0.9 −1.9 1.3 −1.1 −3.0 −2.9
2006 to 2016 (−2.5 to 0.8) (−4.1 to 0.3) (−0.9 to 3.4) (−3.3 to 1.6) (−5.7 to −0.3) (−4.9 to −0.9)

DM indicates diabetes mellitus. Values in parentheses represent 95% confidence intervals.

Reprinted with permission from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.105
Copyright © 2017, University of Washington.

e146 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

CLINICAL STATEMENTS
AND GUIDELINES
Chart 9-1. Age-adjusted prevalence of diagnosed diabetes mellitus in adults ≥20 years of age by race/ethnicity and sex (NHANES, 2013–2016).
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 9-2. Age-adjusted prevalence of diagnosed diabetes mellitus in adults ≥20 years of age by race/ethnicity and years of education (NHANES,
2013–2016).
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e147

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9
CLINICAL STATEMENTS
AND GUIDELINES

Chart 9-3. Trends in diabetes mellitus prevalence in adults ≥20 years of age by sex (NHANES, 1988–1994, 2011–2014, and 2013–2016).
The definition of diabetes changed in 1997 (from glucose ≥140 mg/dL to ≥126 mg/dL).
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 9-4. Diagnosed diabetes (crude percentage) among adults with diabetes, US states and territories, 2015.
Source: Center for Disease Control and Prevention, Division of Diabetes Translation.

e148 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

CLINICAL STATEMENTS
AND GUIDELINES
Chart 9-5. Trends in the prevalence of diagnosed and undiagnosed diabetes mellitus (calibrated hemoglobin A1c levels >6.5%), by racial/ethnic group.
Data from US adults aged ≥20 years in NHANES 1988 to 1994, 1999 to 2004, and 2005 to 2010.
NHANES indicates National Health and Nutrition Examination Survey.
Reprinted from Selvin et al108 with the permission of the American College of Physicians, Inc. Copyright © 2014, American College of Physicians. All rights reserved.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 9-6. Trends in age-standardized rates of complications among US adults with and without diagnosed diabetes, 1995 to 2014.
ESRD indicates end-stage renal disease.
*Hospitalization rates; data from the National Inpatient Sample of the Agency for Healthcare Research and Quality.
†Diabetes-related ESRD; data from the United States Renal Data System.
‡Data from the Centers for Disease Control and Prevention’s National Vital Statistics System.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e149

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9
CLINICAL STATEMENTS
AND GUIDELINES

Chart 9-7. Diabetes mellitus awareness, treatment, and control in adults ≥20 years of age (NHANES, 2013–2016).
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 9-8. Age-standardized global mortality rates attributable to high fasting plasma glucose per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia,
Federated States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB,
Solomon Islands; SYC, Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa,
West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.105 Printed with permission.
Copyright © 2017, University of Washington.

e150 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

CLINICAL STATEMENTS
AND GUIDELINES
Chart 9-9. Age-standardized global mortality rates attributable to diabetes mellitus per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia,
Federated States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB,
Solomon Islands; SYC, Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa,
West Africa; and WSM, Samoa.
Downloaded from http://ahajournals.org by on February 7, 2019

Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.105 Printed with permission.
Copyright © 2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e151

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9
CLINICAL STATEMENTS
AND GUIDELINES

Chart 9-10. Age-standardized global prevalence rates of diabetes mellitus per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia,
Federated States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB,
Solomon Islands; SYC, Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa,
West Africa; and WSM, Samoa.
Downloaded from http://ahajournals.org by on February 7, 2019

Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.105 Printed with permission.
Copyright © 2017, University of Washington.

6. Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, Dabelea
REFERENCES D, Hamman R, Waitzfelder B, Kahn HS; SEARCH for Diabetes in Youth
1. National Center for Chronic Disease Prevention and Health Promotion, Study Group. Prevalence of overweight and obesity in youth with dia-
Division of Diabetes Translation. National Diabetes Statistics Report, betes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes.
2017: Estimates of Diabetes and Its Burden in the United States. Atlanta, 2010;11:4–11. doi: 10.1111/j.1399-5448.2009.00519.x
GA: Centers for Disease Control and Prevention, US Dept of Health and 7. May AL, Kuklina EV, Yoon PW. Prevalence of cardiovascular disease risk
Human Services; 2017. factors among US adolescents, 1999-2008. Pediatrics. 2012;129:1035–
2. Menke A, Orchard TJ, Imperatore G, Bullard KM, Mayer-Davis E, Cowie 1041. doi: 10.1542/peds.2011-1082
CC. The prevalence of type 1 diabetes in the United States. Epidemiology. 8. Menke A, Casagrande S, Cowie CC. Prevalence of diabetes in ado-
2013;24:773–774. doi: 10.1097/EDE.0b013e31829ef01a lescents aged 12 to 19 years in the United States, 2005-2014. JAMA.
2a. American Diabetes Association. Standards of medical care in diabetes: 2016;316:344–345. doi: 10.1001/jama.2016.8544
2010 [published correction appears in Diabetes Care. 2010;33:692]. 9. Hummel K, McFann KK, Realsen J, Messer LH, Klingensmith GJ, Chase
Diabetes Care. 2010;33(suppl 1):S11–S61. HP. The increasing onset of type 1 diabetes in children. J Pediatr.
3. The Emerging Risk Factors Collaboration. Diabetes mellitus, fasting 2012;161:652–7.e1. doi: 10.1016/j.jpeds.2012.03.061
blood glucose concentration, and risk of vascular disease: a collab- 10. Schneiderman N, Llabre M, Cowie CC, Barnhart J, Carnethon M,
orative meta-analysis of 102 prospective studies [published correction Gallo LC, Giachello AL, Heiss G, Kaplan RC, LaVange LM, Teng Y, Villa-
appears in Lancet. 2010;376:958]. Lancet. 2010;375:2215–2222. doi: Caballero L, Avilés-Santa ML. Prevalence of diabetes among Hispanics/
10.1016/S0140-6736(10)60484-9 Latinos from diverse backgrounds: the Hispanic Community Health Study/
4. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn Study of Latinos (HCHS/SOL). Diabetes Care. 2014;37:2233–2239. doi:
L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow 10.2337/dc13-2939
GC, Ho PM, Lauer MS, Masoudi FA, Robertson R M, Roger V, Schwamm 11. Tsujimoto T, Kajio H, Sugiyama T. Obesity, diabetes, and length of time in
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart the United States: analysis of National Health and Nutrition Examination
Association Strategic Planning Task Force and Statistics Committee. Survey 1999 to 2012. Medicine (Baltimore). 2016;95:e4578. doi:
Defining and setting national goals for cardiovascular health promotion 10.1097/MD.0000000000004578
and disease reduction: the American Heart Association’s strategic Impact 12. Expert Committee on the Diagnosis and Classification of Diabetes
Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: Mellitus. Report of the Expert Committee on the Diagnosis and
10.1161/CIRCULATIONAHA.109.192703 Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–1197.
5. Dabelea D, Mayer-Davis EJ, Saydah S, Imperatore G, Linder B, Divers J, Bell doi: 10.2337/diacare.20.7.1183
R, Badaru A, Talton JW, Crume T, Liese AD, Merchant AT, Lawrence JM, 13. Deleted in proof.
Reynolds K, Dolan L, Liu LL, Hamman RF; for the SEARCH for Diabetes in 14. Dwyer-Lindgren L, Mackenbach JP, van Lenthe FJ, Flaxman AD, Mokdad
Youth Study. Prevalence of type 1 and type 2 diabetes among children AH. Diagnosed and undiagnosed diabetes prevalence by county
and adolescents from 2001 to 2009. JAMA. 2014;311:1778–1786. doi: in the U.S., 1999-2012. Diabetes Care. 2016;39:1556–1562. doi:
10.1001/jama.2014.3201 10.2337/dc16-0678

e152 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

15. Loop MS, Howard G, de Los Campos G, Al-Hamdan MZ, Safford MM, equivalence: REasons for Geographic and Racial Differences in Stroke

CLINICAL STATEMENTS
Levitan EB, McClure LA. Heat maps of hypertension, diabetes mellitus, and (REGARDS). Am Heart J. 2016;181:43–51. doi: 10.1016/j.ahj.2016.08.002

AND GUIDELINES
smoking in the continental United States. Circ Cardiovasc Qual Outcomes. 33. Bell EJ, Folsom AR, Lutsey PL, Selvin E, Zakai NA, Cushman M, Alonso
2017;10:e003350. doi: 10.1161/CIRCOUTCOMES.116.003350 A. Diabetes mellitus and venous thromboembolism: a systematic review
16. Zhang N, Yang X, Zhu X, Zhao B, Huang T, Ji Q. Type 2 diabetes mel- and meta-analysis. Diabetes Res Clin Pract. 2016;111:10–18. doi:
litus unawareness, prevalence, trends and risk factors: National Health 10.1016/j.diabres.2015.10.019
and Nutrition Examination Survey (NHANES) 1999-2010. J Int Med Res. 34. Loehr LR, Meyer ML, Poon AK, Selvin E, Palta P, Tanaka H, Pankow JS,
2017;45:594–609. doi: 10.1177/0300060517693178 Wright JD, Griswold ME, Wagenknecht LE, Heiss G. Prediabetes and dia-
17. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, betes are associated with arterial stiffness in older adults: the ARIC study.
Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Am J Hypertens. 2016;29:1038–1045. doi: 10.1093/ajh/hpw036
Wagenknecht L; SEARCH for Diabetes in Youth Study. Incidence trends 35. Bertoni AG, Kramer H, Watson K, Post WS. Diabetes and clini-
of Type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med. cal and subclinical CVD. Glob Heart. 2016;11:337–342. doi:
2017;376:1419–1429. doi: 10.1056/NEJMoa1610187 10.1016/j.gheart.2016.07.005
18. Imperatore G, Boyle JP, Thompson TJ, Case D, Dabelea D, Hamman RF, 36. Reis JP, Allen NB, Bancks MP, Carr JJ, Lewis CE, Lima JA, Rana JS, Gidding
Lawrence JM, Liese AD, Liu LL, Mayer-Davis EJ, Rodriguez BL, Standiford SS, Schreiner PJ. Duration of diabetes and prediabetes during adulthood
D; SEARCH for Diabetes in Youth Study Group. Projections of type 1 and and subclinical atherosclerosis and cardiac dysfunction in middle age: the
type 2 diabetes burden in the U.S. population aged <20 years through CARDIA study. Diabetes Care. 2018;41:731–738. doi: 10.2337/dc17-2233
2050: dynamic modeling of incidence, mortality, and population growth. 37. Pallisgaard JL, Schjerning AM, Lindhardt TB, Procida K, Hansen ML, Torp-
Diabetes Care. 2012;35:2515–2520. doi: 10.2337/dc12-0669 Pedersen C, Gislason GH. Risk of atrial fibrillation in diabetes mellitus:
19. Bancks MP, Kershaw K, Carson AP, Gordon-Larsen P, Schreiner PJ, a nationwide cohort study. Eur J Prev Cardiol. 2016;23:621–627. doi:
Carnethon MR. Association of modifiable risk factors in young adulthood 10.1177/2047487315599892
with racial disparity in incident type 2 diabetes during middle adulthood. 38. Huxley RR, Filion KB, Konety S, Alonso A. Meta-analysis of cohort and
JAMA. 2017;318:2457–2465. doi: 10.1001/jama.2017.19546 case-control studies of type 2 diabetes mellitus and risk of atrial fibrilla-
20. National Center for Health Statistics. Centers for Disease Control and tion. Am J Cardiol. 2011;108:56–62. doi: 10.1016/j.amjcard.2011.03.004
Prevention website. National Vital Statistics System: public use data file 39. Hui G, Koch B, Calara F, Wong ND. Angina in coronary artery disease
documentation: mortality multiple cause-of-death micro-data files, 2016. patients with and without diabetes: US National Health and Nutrition
https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed Examination Survey 2001-2010. Clin Cardiol. 2016;39:30–36. doi:
May 21, 2018. 10.1002/clc.22488
21. Stokes A, Preston SH. Deaths attributable to diabetes in the United 40. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG,
States: comparison of data sources and estimation approaches. PLoS One. Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver
2017;12:e0170219. doi: 10.1371/journal.pone.0170219 MA, Stevenson LW, Yancy CW. 2009 Focused update incorporated into
22. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, the ACC/AHA 2005 Guidelines for the Diagnosis and Management of
Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njølstad I, Heart Failure in Adults: a report of the American College of Cardiology
Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Foundation/American Heart Association Task Force on Practice Guidelines
Sattar N, Selvin E, Hu FB, Danesh J; Emerging Risk Factors Collaboration. [published correction appears in Circulation. 2010;121:e258]. Circulation.
Diabetes mellitus, fasting glucose, and risk of cause-specific death [pub- 2009;119:e391–e479. doi: 10.1161/CIRCULATIONAHA.109.192065
lished correction appears in N Engl J Med. 2011;364:1281]. N Engl J Med. 41. Khan H, Kunutsor SK, Kauhanen J, Kurl S, Gorodeski EZ, Adler AI, Butler
2011;364:829–841. doi: 10.1056/NEJMoa1008862 J, Laukkanen JA. Fasting plasma glucose and incident heart failure risk:
Downloaded from http://ahajournals.org by on February 7, 2019

23. Liu L, Simon B, Shi J, Mallhi AK, Eisen HJ. Impact of diabetes mellitus on a population-based cohort study and new meta-analysis. J Card Fail.
risk of cardiovascular disease and all-cause mortality: evidence on health 2014;20:584–592. doi: 10.1016/j.cardfail.2014.05.011
outcomes and antidiabetic treatment in United States adults. World J 42. Sarma S, Mentz RJ, Kwasny MJ, Fought AJ, Huffman M, Subacius H,
Diabetes. 2016;7:449–461. doi: 10.4239/wjd.v7.i18.449 Nodari S, Konstam M, Swedberg K, Maggioni AP, Zannad F, Bonow RO,
24. Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj Gheorghiade M; EVEREST investigators. Association between diabetes
M, McGuire DK, Sattar N, Rosengren A, Gudbjörnsdottir S. Mortality mellitus and post-discharge outcomes in patients hospitalized with heart
and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. failure: findings from the EVEREST trial. Eur J Heart Fail. 2013;15:194–
2017;376:1407–1418. doi: 10.1056/NEJMoa1608664 202. doi: 10.1093/eurjhf/hfs153
25. Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj 43. Bozkurt B, Aguilar D, Deswal A, Dunbar SB, Francis GS, Horwich T,
M, McGuire DK, Sattar N, Rosengren A, Gudbjörnsdottir S. Range Jessup M, Kosiborod M, Pritchett AM, Ramasubbu K, Rosendorff C,
of risk factor levels: control, mortality, and cardiovascular outcomes Yancy C; on behalf of the American Heart Association Heart Failure and
in type 1 diabetes mellitus. Circulation. 2017;135:1522–1531. doi: Transplantation Committee of the Council on Clinical Cardiology; Council
10.1161/CIRCULATIONAHA.116.025961 on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular
26. Secrest AM, Becker DJ, Kelsey SF, Laporte RE, Orchard TJ. Cause-specific and Stroke Nursing; Council on Hypertension; and Council on Quality
mortality trends in a large population-based cohort with long-standing and Outcomes Research. Contributory risk and management of comor-
childhood-onset type 1 diabetes. Diabetes. 2010;59:3216–3222. doi: bidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and
10.2337/db10-0862 metabolic syndrome in chronic heart failure: a scientific statement from
27. Wang SY, Andrews CA, Herman WH, Gardner TW, Stein JD. Incidence the American Heart Association. Circulation. 2016;134:e535–e578. doi:
and risk factors for developing diabetic retinopathy among youths with 10.1161/CIR.0000000000000450
type 1 or type 2 diabetes throughout the United States. Ophthalmology. 44. Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, Huang
2017;124:424–430. doi: 10.1016/j.ophtha.2016.10.031 ES, Desai MM, Gill TM, Krumholz HM. National trends in US hospital
28. Wu B, Bell K, Stanford A, Kern DM, Tunceli O, Vupputuri S, Kalsekar I, admissions for hyperglycemia and hypoglycemia among Medicare ben-
Willey V. Understanding CKD among patients with T2DM: preva- eficiaries, 1999 to 2011. JAMA Intern Med. 2014;174:1116–1124. doi:
lence, temporal trends, and treatment patterns: NHANES 2007- 10.1001/jamainternmed.2014.1824
2012. BMJ Open Diabetes Res Care. 2016;4:e000154. doi: 10.1136/ 45. Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward
bmjdrc-2015-000154 M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M,
29. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH. Heller S; ADVANCE Collaborative Group. Severe hypoglycemia and risks
Clinical manifestations of kidney disease among US adults with diabetes, of vascular events and death. N Engl J Med. 2010;363:1410–1418. doi:
1988-2014. JAMA. 2016;316:602–610. doi: 10.1001/jama.2016.10924 10.1056/NEJMoa1003795
30. Economic costs of diabetes in the US in 2017. American Diabetes 46. Lee AK, Warren B, Lee CJ, McEvoy JW, Matsushita K, Huang ES, Sharrett
Association. Diabetes Care. 2018;41:917–928. doi: 10.2337/dci18-0007. AR, Coresh J, Selvin E. The association of severe hypoglycemia with inci-
31. Centers for Disease Control and Prevention, Division of Diabetes dent cardiovascular events and mortality in adults with type 2 diabetes.
Translation, US Diabetes Surveillance System. Diabetes Data and Statistics. Diabetes Care. 2018;41:104–111. doi: 10.2337/dc17-1669
2018. https://www.cdc.gov/diabetes/data. Accessed July 30, 2018. 47. Heller SR, Bergenstal RM, White WB, Kupfer S, Bakris GL, Cushman WC,
32. Mondesir FL, Brown TM, Muntner P, Durant RW, Carson AP, Safford MM, Mehta CR, Nissen SE, Wilson CA, Zannad F, Liu Y, Gourlie NM, Cannon
Levitan EB. Diabetes, diabetes severity, and coronary heart disease risk CP; EXAMINE Investigators. Relationship of glycated haemoglobin and

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e153

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

reported hypoglycaemia to cardiovascular outcomes in patients with type Risk in Communities (ARIC) study. Cardiovasc Diabetol. 2016;15:163. doi:
CLINICAL STATEMENTS

2 diabetes and recent acute coronary syndrome events: the EXAMINE trial. 10.1186/s12933-016-0476-4
AND GUIDELINES

Diabetes Obes Metab. 2017;19:664–671. doi: 10.1111/dom.12871 64. Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari
48. Schroeder EB, Xu S, Goodrich GK, Nichols GA, O’Connor PJ, Steiner GM, Murphy SA, Kuder JF, Gouni-Berthold I, Lewis BS, Handelsman Y,
JF. Predicting the 6-month risk of severe hypoglycemia among adults Pineda AL, Honarpour N, Keech AC, Sever PS, Pedersen TR. Cardiovascular
with diabetes: development and external validation of a predic- safety and efficacy of the PCSK9 inhibitor evolocumab in patients with
tion model. J Diabetes Complications. 2017;31:1158–1163. doi: and without diabetes and the effect of evolocumab on glycaemia and
10.1016/j.jdiacomp.2017.04.004 risk of new-onset diabetes: a prespecified analysis of the FOURIER ran-
49. Lipska KJ, Warton EM, Huang ES, Moffet HH, Inzucchi SE, Krumholz HM, domised controlled trial. Lancet Diabetes Endocrinol. 2017;5:941–950.
Karter AJ. HbA1c and risk of severe hypoglycemia in type 2 diabetes: doi: 10.1016/S2213-8587(17)30313-3
the Diabetes and Aging Study. Diabetes Care. 2013;36:3535–3542. doi: 65. Nichols GA, Horberg M, Koebnick C, Young DR, Waitzfelder B, Sherwood
10.2337/dc13-0610 NE, Daley MF, Ferrara A. Cardiometabolic risk factors among 1.3 million
50. Karter AJ, Lipska KJ, O’Connor PJ, Liu JY, Moffet HH, Schroeder EB, adults with overweight or obesity, but not diabetes, in 10 geographi-
Lawrence JM, Nichols GA, Newton KM, Pathak RD, Desai J, Waitzfelder cally diverse regions of the United States, 2012-2013. Prev Chronic Dis.
B, Butler MG, Thomas A, Steiner JF; SUPREME-DM Study Group. High 2017;14:E22. doi: 10.5888/pcd14.160438
rates of severe hypoglycemia among African American patients with dia- 66. Herman WH, Pan Q, Edelstein SL, Mather KJ, Perreault L, Barrett-Connor
betes: the Surveillance, Prevention, and Management of Diabetes Mellitus E, Dabelea DM, Horton E, Kahn SE, Knowler WC, Lorenzo C, Pi-Sunyer X,
(SUPREME-DM) network. J Diabetes Complications. 2017;31:869–873. Venditti E, Ye W; Diabetes Prevention Program Research Group. Impact of
doi: 10.1016/j.jdiacomp.2017.02.009 lifestyle and metformin interventions on the risk of progression to diabe-
51. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic tes and regression to normal glucose regulation in overweight or obese
episodes and risk of dementia in older patients with type 2 diabetes mel- people with impaired glucose regulation [published correction appears in
litus. JAMA. 2009;301:1565–1572. doi: 10.1001/jama.2009.460 Diabetes Care. 2018;41:913]. Diabetes Care. 2017;40:1668–1677. doi:
52. Collins J, Abbass IM, Harvey R, Suehs B, Uribe C, Bouchard J, Prewitt 10.2337/dc17-1116
T, DeLuzio T, Allen E. Predictors of all-cause-30-day-readmission 67. Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, Cuttler L,
among Medicare patients with type 2 diabetes. Curr Med Res Opin. Nathan DM, Tollefsen S, Wilfley D, Kaufman F; TODAY Study Group. A
2017;33:1517–1523. doi: 10.1080/03007995.2017.1330258 clinical trial to maintain glycemic control in youth with type 2 diabetes. N
53. Schneider AL, Kalyani RR, Golden S, Stearns SC, Wruck L, Yeh HC, Engl J Med. 2012;366:2247–2256. doi: 10.1056/NEJMoa1109333
Coresh J, Selvin E. Diabetes and prediabetes and risk of hospitalization: 68. Kriska A, Delahanty L, Edelstein S, Amodei N, Chadwick J, Copeland K,
the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. Galvin B, El ghormli L, Haymond M, Kelsey M, Lassiter C, Mayer-Davis E,
2016;39:772–779. doi: 10.2337/dc15-1335 Milaszewski K, Syme A. Sedentary behavior and physical activity in youth
54. Joo H, Zhang P, Wang G. Cost of informal care for patients with cardiovas- with recent onset of type 2 diabetes. Pediatrics. 2013;131:e850–e856.
cular disease or diabetes: current evidence and research challenges. Qual doi: 10.1542/peds.2012-0620
Life Res. 2017;26:1379–1386. doi: 10.1007/s11136-016-1478-0 69. Wong ND, Zhao Y, Patel R, Patao C, Malik S, Bertoni AG, Correa A, Folsom
55. Joseph JJ, Echouffo-Tcheugui JB, Carnethon MR, Bertoni AG, Shay CM, AR, Kachroo S, Mukherjee J, Taylor H, Selvin E. Cardiovascular risk factor
Ahmed HM, Blumenthal RS, Cushman M, Golden SH. The association targets and cardiovascular disease event risk in diabetes: a pooling project
of ideal cardiovascular health with incident type 2 diabetes mellitus: the of the Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of
Multi-Ethnic Study of Atherosclerosis. Diabetologia. 2016;59:1893–1903. Atherosclerosis, and Jackson Heart Study. Diabetes Care. 2016;39:668–
doi: 10.1007/s00125-016-4003-7 676. doi: 10.2337/dc15-2439
Downloaded from http://ahajournals.org by on February 7, 2019

56. Llewellyn A, Simmonds M, Owen CG, Woolacott N. Childhood obesity 70. Stark Casagrande S, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prev-
as a predictor of morbidity in adulthood: a systematic review and meta- alence of meeting A1C, blood pressure, and LDL goals among people
analysis. Obes Rev. 2016;17:56–67. doi: 10.1111/obr.12316 with diabetes, 1988-2010. Diabetes Care. 2013;36:2271–2279. doi:
57. Song Y, Huang YT, Song Y, Hevener AL, Ryckman KK, Qi L, LeBlanc ES, 10.2337/dc12-2258
Kazlauskaite R, Brennan KM, Liu S. Birthweight, mediating biomark- 71. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW.
ers and the development of type 2 diabetes later in life: a prospective Achievement of goals in U.S. diabetes care, 1999-2010 [published
study of multi-ethnic women. Diabetologia. 2015;58:1220–1230. doi: correction appears in N Engl J Med. 2013;369:587]. N Engl J Med.
10.1007/s00125-014-3479-2 2013;368:1613–1624. doi: 10.1056/NEJMsa1213829
58. Imamura F, O’Connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN, 72. Casagrande SS, Aviles-Santa L, Corsino L, Daviglus ML, Gallo LC, Espinoza
Forouhi NG. Consumption of sugar sweetened beverages, artificially Giacinto RA, Llabre MM, Reina SA, Savage PJ, Schneiderman N, Talavera
sweetened beverages, and fruit juice and incidence of type 2 dia- GA, Cowie CC. Hemoglobin A1c, blood pressure, and LDL-cholesterol
betes: systematic review, meta-analysis, and estimation of popula- control among Hispanic/Latino adults with diabetes: results from the
tion attributable fraction. Br J Sports Med. 2016;50:496–504. doi: Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Endocr
10.1136/bjsports-2016-h3576rep Pract. 2017;23:1232–1253. doi: 10.4158/EP171765.OR
59. Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, 73. Wang X, Strizich G, Hua S, Sotres-Alvarez D, Buelna C, Gallo LC,
Veerman JL, Delwiche K, Iannarone ML, Moyer ML, Cercy K, Vos T, Murray Gellman MD, Mossavar-Rahmani Y, O’Brien MJ, Stoutenberg M, Wang
CJ, Forouzanfar MH. Physical activity and risk of breast cancer, colon T, Avilés-Santa ML, Kaplan RC, Qi Q. Objectively measured sedentary
cancer, diabetes, ischemic heart disease, and ischemic stroke events: sys- time and cardiovascular risk factor control in US Hispanics/Latinos with
tematic review and dose-response meta-analysis for the Global Burden of diabetes mellitus: results from the Hispanic Community Health Study/
Disease Study 2013. BMJ. 2016;354:i3857. doi: 10.1136/bmj.i3857 Study of Latinos (HCHS/SOL). J Am Heart Assoc. 2017;6:e004324. doi:
60. Chow LS, Odegaard AO, Bosch TA, Bantle AE, Wang Q, Hughes J, 10.1161/JAHA.116.004324
Carnethon M, Ingram KH, Durant N, Lewis CE, Ryder J, Shay CM, Kelly 74. Albertorio-Diaz JR, Eberhardt MS, Oquendo M, Mesa-Frias M, He Y, Jonas
AS, Schreiner PJ. Twenty year fitness trends in young adults and inci- B, Kang K. Depressive states among adults with diabetes: findings from the
dence of prediabetes and diabetes: the CARDIA study. Diabetologia. National Health and Nutrition Examination Survey, 2007-2012. Diabetes
2016;59:1659–1665. doi: 10.1007/s00125-016-3969-5 Res Clin Pract. 2017;127:80–88. doi: 10.1016/j.diabres.2017.02.031
61. Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA. 75. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB,
Sedentary time and its association with risk for disease incidence, mortal- Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P,
ity, and hospitalization in adults: a systematic review and meta-analysis Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/
[published correction appears in Ann Intern Med. 2015;163:400]. Ann AHA guideline on the treatment of blood cholesterol to reduce athero-
Intern Med. 2015;162:123–132. doi: 10.7326/M14-1651 sclerotic cardiovascular risk in adults: a report of the American College of
62. Henson J, Dunstan DW, Davies MJ, Yates T. Sedentary behaviour as Cardiology/American Heart Association Task Force on Practice Guidelines
a new behavioural target in the prevention and treatment of type 2 [published corrections appear in Circulation. 2014;129:S46–S48 and
diabetes. Diabetes Metab Res Rev. 2016;32(suppl 1):213–220. doi: Circulation. 2015;132:e396]. Circulation. 2014;129(suppl 2):S1–S45. doi:
10.1002/dmrr.2759 10.1161/01.cir.0000437738.63853.7a
63. Hua S, Loehr LR, Tanaka H, Heiss G, Coresh J, Selvin E, Matsushita K. 76. Deedwania P, Acharya T, Kotak K, Fonarow GC, Cannon CP, Laskey
Ankle-brachial index and incident diabetes mellitus: the Atherosclerosis WK, Peacock WF, Pan W, Bhatt DL; GWTG Steering Committee and

e154 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

Investigators. Compliance with guideline-directed therapy in diabetic Scott LJ, Wiltshire S, Yengo L, Kinnunen L, Rossin EJ, Raychaudhuri S,

CLINICAL STATEMENTS
patients admitted with acute coronary syndrome: findings from the Johnson AD, Dimas AS, Loos RJ, Vedantam S, Chen H, Florez JC, Fox C,

AND GUIDELINES
American Heart Association’s Get With The Guidelines-Coronary Artery Liu CT, Rybin D, Couper DJ, Kao WH, Li M, Cornelis MC, Kraft P, Sun Q,
Disease (GWTG-CAD) program. Am Heart J. 2017;187:78–87. doi: van Dam RM, Stringham HM, Chines PS, Fischer K, Fontanillas P, Holmen
10.1016/j.ahj.2017.02.025 OL, Hunt SE, Jackson AU, Kong A, Lawrence R, Meyer J, Perry JR, Platou
77. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison CG, Potter S, Rehnberg E, Robertson N, Sivapalaratnam S, Stančáková
Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, A, Stirrups K, Thorleifsson G, Tikkanen E, Wood AR, Almgren P, Atalay
MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford M, Benediktsson R, Bonnycastle LL, Burtt N, Carey J, Charpentier G,
RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 Crenshaw AT, Doney AS, Dorkhan M, Edkins S, Emilsson V, Eury E, Forsen
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guide- T, Gertow K, Gigante B, Grant GB, Groves CJ, Guiducci C, Herder C,
line for the prevention, detection, evaluation, and management of high Hreidarsson AB, Hui J, James A, Jonsson A, Rathmann W, Klopp N, Kravic
blood pressure in adults: a report of the American College of Cardiology/ J, Krjutškov K, Langford C, Leander K, Lindholm E, Lobbens S, Männistö S,
American Heart Association Task Force on Clinical Practice Guidelines Mirza G, Mühleisen TW, Musk B, Parkin M, Rallidis L, Saramies J, Sennblad
[published correction appears in Hypertension. 2018;71:e140–e144]. B, Shah S, Sigurðsson G, Silveira A, Steinbach G, Thorand B, Trakalo J,
Hypertension. 2018;71:e13–e115. doi: 10.1161/HYP0000000000000065 Veglia F, Wennauer R, Winckler W, Zabaneh D, Campbell H, van Duijn C,
78. Levine DM, Linder JA, Landon BE. The quality of outpatient care deliv- Uitterlinden AG, Hofman A, Sijbrands E, Abecasis GR, Owen KR, Zeggini
ered to adults in the United States, 2002 to 2013. JAMA Intern Med. E, Trip MD, Forouhi NG, Syvänen AC, Eriksson JG, Peltonen L, Nöthen
2016;176:1778–1790. doi: 10.1001/jamainternmed.2016.6217 MM, Balkau B, Palmer CN, Lyssenko V, Tuomi T, Isomaa B, Hunter DJ, Qi
79. Tran EMT, Bhattacharya J, Pershing S. Self-reported receipt of dilated fun- L, Shuldiner AR, Roden M, Barroso I, Wilsgaard T, Beilby J, Hovingh K,
dus examinations among patients with diabetes: Medicare Expenditure Price JF, Wilson JF, Rauramaa R, Lakka TA, Lind L, Dedoussis G, Njølstad I,
Panel Survey, 2002-2013. Am J Ophthalmol. 2017;179:18–24. doi: Pedersen NL, Khaw KT, Wareham NJ, Keinanen-Kiukaanniemi SM, Saaristo
10.1016/j.ajo.2017.04.009 TE, Korpi-Hyövälti E, Saltevo J, Laakso M, Kuusisto J, Metspalu A, Collins
80. Cefalu WT, Kaul S, Gerstein HC, Holman RR, Zinman B, Skyler JS, Green FS, Mohlke KL, Bergman RN, Tuomilehto J, Boehm BO, Gieger C, Hveem
JB, Buse JB, Inzucchi SE, Leiter LA, Raz I, Rosenstock J, Riddle MC. K, Cauchi S, Froguel P, Baldassarre D, Tremoli E, Humphries SE, Saleheen
Cardiovascular outcomes trials in type 2 diabetes: where do we go from D, Danesh J, Ingelsson E, Ripatti S, Salomaa V, Erbel R, Jöckel KH, Moebus
here? Reflections from a Diabetes Care Editors’ Expert Forum. Diabetes S, Peters A, Illig T, de Faire U, Hamsten A, Morris AD, Donnelly PJ, Frayling
Care. 2018;41:14–31. doi: 10.2337/dci17-0057 TM, Hattersley AT, Boerwinkle E, Melander O, Kathiresan S, Nilsson PM,
81. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck Deloukas P, Thorsteinsdottir U, Groop LC, Stefansson K, Hu F, Pankow
MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, JS, Dupuis J, Meigs JB, Altshuler D, Boehnke M, McCarthy MI; Wellcome
Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trust Case Control Consortium; Meta-Analyses of Glucose and Insulin-
Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 dia- related traits Consortium (MAGIC) Investigators; Genetic Investigation of
betes. N Engl J Med. 2016;375:311–322. doi: 10.1056/NEJMoa1603827 ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology
82. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay Network–Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2
I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Diabetes (SAT2D) Consortium; DIAbetes Genetics Replication And Meta-
Pettersson J, Vilsbøll T; SUSTAIN-6 Investigators. Semaglutide and car- analysis (DIAGRAM) Consortium. Large-scale association analysis provides
diovascular outcomes in patients with type 2 diabetes. N Engl J Med. insights into the genetic architecture and pathophysiology of type 2 dia-
2016;375:1834–1844. doi: 10.1056/NEJMoa1607141 betes. Nat Genet. 2012;44:981–990. doi: 10.1038/ng.2383
83. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus 92. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium,
Downloaded from http://ahajournals.org by on February 7, 2019

M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D)
OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican
mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128. doi: American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic
10.1056/NEJMoa1504720 Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-
84. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, GENES) Consortium. Genome-wide trans-ancestry meta-analysis provides
Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative insight into the genetic architecture of type 2 diabetes susceptibility. Nat
Group. Canagliflozin and cardiovascular and renal events in type 2 diabe- Genet. 2014;46:234–244. doi: 10.1038/ng.2897
tes. N Engl J Med. 2017;377:644–657. doi: 10.1056/NEJMoa1611925 93. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent
85. Almgren P, Lehtovirta M, Isomaa B, Sarelin L, Taskinen MR, Lyssenko V, D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ,
Tuomi T, Groop L; Botnia Study Group. Heritability and familiality of type 2 Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre
diabetes and related quantitative traits in the Botnia Study. Diabetologia. D, Polychronakos C, Froguel P. A genome-wide association study identi-
2011;54:2811–2819. doi: 10.1007/s00125-011-2267-5 fies novel risk loci for type 2 diabetes. Nature. 2007;445:881–885. doi:
86. Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H. Heritability of type II (non- 10.1038/nature05616
insulin-dependent) diabetes mellitus and abnormal glucose tolerance–a 94. Knowles JW, Xie W, Zhang Z, Chennamsetty I, Assimes TL, Paananen J,
population-based twin study. Diabetologia. 1999;42:139–145. Hansson O, Pankow J, Goodarzi MO, Carcamo-Orive I, Morris AP, Chen
87. Meigs JB, Cupples LA, Wilson PW. Parental transmission of type 2 diabe- YD, Mäkinen VP, Ganna A, Mahajan A, Guo X, Abbasi F, Greenawalt DM,
tes: the Framingham Offspring Study. Diabetes. 2000;49:2201–2207. Lum P, Molony C, Lind L, Lindgren C, Raffel LJ, Tsao PS, Schadt EE, Rotter JI,
88. Kong A, Steinthorsdottir V, Masson G, Thorleifsson G, Sulem P, Sinaiko A, Reaven G, Yang X, Hsiung CA, Groop L, Cordell HJ, Laakso M,
Besenbacher S, Jonasdottir A, Sigurdsson A, Kristinsson KT, Jonasdottir A, Hao K, Ingelsson E, Frayling TM, Weedon MN, Walker M, Quertermous T;
Frigge ML, Gylfason A, Olason PI, Gudjonsson SA, Sverrisson S, Stacey SN, RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease)
Sigurgeirsson B, Benediktsdottir KR, Sigurdsson H, Jonsson T, Benediktsson Consortium; EUGENE (European Network on Functional Genomics of
R, Olafsson JH, Johannsson OT, Hreidarsson AB, Sigurdsson G, Ferguson- Type Diabetes) Study; GUARDIAN (Genetics UndeRlying DIAbetes in
Smith AC, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K; DIAGRAM HispaNics) Consortium; SAPPHIRe (Stanford Asian and Pacific Program for
Consortium. Parental origin of sequence variants associated with complex Hypertension and Insulin Resistance) Study. Identification and validation
diseases. Nature. 2009;462:868–874. doi: 10.1038/nature08625 of N-acetyltransferase 2 as an insulin sensitivity gene [published correction
89. Bonnefond A, Froguel P. Rare and common genetic events in type 2 dia- appears in J Clin Invest. 2016;126:403]. J Clin Invest. 2015;125:1739–
betes: what should biologists know? Cell Metab. 2015;21:357–368. doi: 1751. doi: 10.1172/JCI74692
10.1016/j.cmet.2014.12.020 95. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, Hirota Y,
90. Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Mori H, Jonsson A, Sato Y, Yamagata K, Hinokio Y, Wang HY, Tanahashi T,
Ellard S. Maturity-onset diabetes of the young (MODY): how many Nakamura N, Oka Y, Iwasaki N, Iwamoto Y, Yamada Y, Seino Y, Maegawa
cases are we missing? Diabetologia. 2010;53:2504–2508. doi: H, Kashiwagi A, Takeda J, Maeda E, Shin HD, Cho YM, Park KS, Lee HK,
10.1007/s00125-010-1799-4 Ng MC, Ma RC, So WY, Chan JC, Lyssenko V, Tuomi T, Nilsson P, Groop L,
91. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir Kamatani N, Sekine A, Nakamura Y, Yamamoto K, Yoshida T, Tokunaga K,
V, Strawbridge RJ, Khan H, Grallert H, Mahajan A, Prokopenko I, Kang Itakura M, Makino H, Nanjo K, Kadowaki T, Kasuga M. Variants in KCNQ1
HM, Dina C, Esko T, Fraser RM, Kanoni S, Kumar A, Lagou V, Langenberg are associated with susceptibility to type 2 diabetes mellitus. Nat Genet.
C, Luan J, Lindgren CM, Müller-Nurasyid M, Pechlivanis S, Rayner NW, 2008;40:1092–1097. doi: 10.1038/ng.207

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e155

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 9

96. Said MA, Verweij N, van der Harst P. Associations of combined ge- Damrauer S, Birtwell D, Brummett CM, Khera AV, Natarajan P, Orho-
CLINICAL STATEMENTS

netic and lifestyle risks with incident cardiovascular disease and dia- Melander M, Flannick J, Lotta LA, Willer CJ, Holmen OL, Ritchie MD,
AND GUIDELINES

betes in the UK Biobank Study. JAMA Cardiol. 2018;3:693–702. doi: Ledbetter DH, Murphy AJ, Borecki IB, Reid JG, Overton JD, Hansson O,
10.1001/jamacardio.2018.1717 Groop L, Shah SH, Kraus WE, Rader DJ, Chen YI, Hveem K, Wareham
97. Zhou K, Donnelly L, Yang J, Li M, Deshmukh H, Van Zuydam N, Ahlqvist NJ, Kathiresan S, Melander O, Stefansson K, Nordestgaard BG, Tybjærg-
E, Spencer CC, Groop L, Morris AD, Colhoun HM, Sham PC, McCarthy Hansen A, Abecasis GR, Altshuler D, Florez JC, Boehnke M, McCarthy MI,
MI, Palmer CN, Pearson ER; Wellcome Trust Case Control Consortium 2. Yancopoulos GD, Carey DJ, Shuldiner AR, Baras A, Dewey FE, Gromada
Heritability of variation in glycaemic response to metformin: a genome- J. Genetic inactivation of ANGPTL4 improves glucose homeostasis and
wide complex trait analysis. Lancet Diabetes Endocrinol. 2014;2:481– is associated with reduced risk of diabetes. Nat Commun. 2018;9:2252.
487. doi: 10.1016/S2213-8587(14)70050-6 doi: 10.1038/s41467-018-04611-z
98. The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; 101. Pociot F, Lernmark Å. Genetic risk factors for type 1 diabetes. Lancet.
Zhou K, Bellenguez C, Spencer CC, Bennett AJ, Coleman RL, Tavendale R, 2016;387:2331–2339. doi: 10.1016/S0140-6736(16)30582-7
Hawley SA, Donnelly LA, Schofield C, Groves CJ, Burch L, Carr F, Strange 102. Oram RA, Patel K, Hill A, Shields B, McDonald TJ, Jones A, Hattersley AT,
A, Freeman C, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Weedon MN. A type 1 diabetes genetic risk score can aid discrimination
Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Gray E, Hunt between type 1 and type 2 diabetes in young adults. Diabetes Care.
S, Jankowski J, Langford C, Markus HS, Mathew CG, Plomin R, Rautanen 2016;39:337–344. doi: 10.2337/dc15-1111
A, Sawcer SJ, Samani NJ, Trembath R, Viswanathan AC, Wood NW; 103. Langefeld CD, Beck SR, Bowden DW, Rich SS, Wagenknecht LE,
Harries LW, Hattersley AT, Doney AS, Colhoun H, Morris AD, Sutherland Freedman BI. Heritability of GFR and albuminuria in Caucasians with type
C, Hardie DG, Peltonen L, McCarthy MI, Holman RR, Palmer CN, Donnelly 2 diabetes mellitus. Am J Kidney Dis. 2004;43:796–800.
P, Pearson ER; Wellcome Trust Case Control Consortium 2. Common vari- 104. Qi L, Qi Q, Prudente S, Mendonca C, Andreozzi F, di Pietro N, Sturma
ants near ATM are associated with glycemic response to metformin in M, Novelli V, Mannino GC, Formoso G, Gervino EV, Hauser TH,
type 2 diabetes. Nat Genet. 2011;43:117–120. doi: 10.1038/ng.735 Muehlschlegel JD, Niewczas MA, Krolewski AS, Biolo G, Pandolfi A,
99. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Rimm E, Sesti G, Trischitta V, Hu F, Doria A. Association between a ge-
Sigurdsson A, Helgadottir HT, Johannsdottir H, Magnusson OT, Gudjonsson netic variant related to glutamic acid metabolism and coronary heart dis-
SA, Justesen JM, Harder MN, Jørgensen ME, Christensen C, Brandslund ease in individuals with type 2 diabetes. JAMA. 2013;310:821–828. doi:
I, Sandbæk A, Lauritzen T, Vestergaard H, Linneberg A, Jørgensen T, 10.1001/jama.2013.276305
Hansen T, Daneshpour MS, Fallah MS, Hreidarsson AB, Sigurdsson G, 105. Global Burden of Disease Study 2016. Global Burden of Disease Study
Azizi F, Benediktsson R, Masson G, Helgason A, Kong A, Gudbjartsson 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
DF, Pedersen O, Thorsteinsdottir U, Stefansson K. Identification of low-fre- Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
quency and rare sequence variants associated with elevated or reduced risk data.org/gbd-results-tool. Accessed May 1, 2018.
of type 2 diabetes. Nat Genet. 2014;46:294–298. doi: 10.1038/ng.2882 106. Bommer C, Sagalova V, Heesemann E, Manne-Goehler J, Atun R,
100. Gusarova V, O’Dushlaine C, Teslovich TM, Benotti PN, Mirshahi T, Bärnighausen T, Davies J, Vollmer S. Global economic burden of diabetes
Gottesman O, Van Hout CV, Murray MF, Mahajan A, Nielsen JB, Fritsche in adults: projections from 2015 to 2030. Diabetes Care. 2018;41:963–
L, Wulff AB, Gudbjartsson DF, Sjögren M, Emdin CA, Scott RA, Lee WJ, 970. doi: 10.2337/dc17-1962
Small A, Kwee LC, Dwivedi OP, Prasad RB, Bruse S, Lopez AE, Penn J, 107. Deleted in proof.
Marcketta A, Leader JB, Still CD, Kirchner HL, Mirshahi UL, Wardeh AH, 108. Selvin E, Parrinello CM, Sacks DB, Coresh J. Trends in prevalence and
Hartle CM, Habegger L, Fetterolf SN, Tusie-Luna T, Morris AP, Holm H, control of diabetes in the United States, 1988-1994 and 1999-2010.
Steinthorsdottir V, Sulem P, Thorsteinsdottir U, Rotter JI, Chuang LM, Ann Intern Med. 2014;160:517–525. doi: 10.7326/M13-2411
Downloaded from http://ahajournals.org by on February 7, 2019

e156 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

10. METABOLIC SYNDROME Abbreviations Used in Chapter 10 Continued

CLINICAL STATEMENTS
MHO metabolically healthy obesity
See Charts 10-1 through 10-10

AND GUIDELINES
MI myocardial infarction
MICROS Microisolates in South Tyrol Study
Click here to return to the Table of Contents MORGAM MONICA [Monitoring Trends and Determinants in
Cardiovascular Disease], Risk, Genetics, Archiving and
Definition Monograph Project
MRI magnetic resonance imaging
• Metabolic syndrome is a multicomponent risk NAFLD nonalcoholic fatty liver disease
factor for CVD and type 2 DM that reflects the NCDS National Child Development Study
clustering of individual cardiometabolic risk fac- NH non-Hispanic
tors related to abdominal obesity and insulin NHANES National Health and Nutrition Examination Survey
NHLBI National Heart, Lung, and Blood Institute
Abbreviations Used in Chapter 10 NIPPON DATA National Integrated Project for Prospective
Observation of Noncommunicable Disease and Its
AF atrial fibrillation Trends in Aged
AHA American Heart Association OR odds ratio
AIM-HIGH Atherothrombosis Intervention in Metabolic Syndrome OSA obstructive sleep apnea
With Low HDL/High Triglycerides and Impact on Global
PA physical activity
Health Outcomes
PAD peripheral artery disease
AMP adenosine monophosphate
PAR population attributable risk
ARIC Atherosclerosis Risk in Communities Study
PREMA Prediction of Metabolic Syndrome in Adolescence
ATP III Adult Treatment Panel III
PREVEND Prevention of Renal and Vascular End-Stage Disease
BioSHaRE Biobank Standardization and Harmonization for
Research Excellence in the European Union PUFA polyunsaturated fatty acid
BMI body mass index RCT randomized controlled trial
BP blood pressure REGARDS Reasons for Geographic and Racial Differences in
Stroke
CAC coronary artery calcification
RR relative risk
CAD coronary artery disease
RV right ventricular
Carbs carbohydrates
SBP systolic blood pressure
CDC Centers for Disease Control and Prevention
SCD sudden cardiac death
CHD coronary heart disease
SES socioeconomic status
CHRIS Collaborative Health Research in South Tyrol Study
SNP single-nucleotide polymorphism
CI confidence interval
SSB sugar-sweetened beverage
Downloaded from http://ahajournals.org by on February 7, 2019

CRP C-reactive protein

VTE venous thromboembolism
CT computed tomography
Waist circumf waist circumference
CVD cardiovascular disease
WC waist circumference
DBP diastolic blood pressure
WHO World Health Organization
DESIR Data from an Epidemiological Study on the Insulin
Resistance Syndrome
DILGOM Dietary, Lifestyle, and Genetics Determinants of Obesity resistance. Clinically, metabolic syndrome is a
and Metabolic Syndrome useful entity for communicating the nature of
DM diabetes mellitus lifestyle-related cardiometabolic risk to both
EGCUT Estonian Genome Center of the University of Tartu
patients and clinicians. Although several differ-
GFR glomerular filtration rate
HbA1c hemoglobin A1c (glycosylated hemoglobin) ent clinical definitions for metabolic syndrome
HCHS/SOL Hispanic Community Health Study/Study of Latinos have been proposed, the International Diabetes
HCUP-NIS Healthcare Cost and Utilization Project Nationwide Federation, NHLBI, AHA, and others proposed a
Inpatient Sample harmonized definition for metabolic syndrome.
HDL high-density lipoprotein
By this definition, metabolic syndrome is diag-
HDL-C high-density lipoprotein cholesterol
HF heart failure nosed when any 3 of the following 5 risk factors
HIV human immunodeficiency virus are present:
HR hazard ratio — Fasting plasma glucose ≥100 mg/dL or under-
HUNT2 Nord-Trøndelag Health Study going drug treatment for elevated glucose
IMT intima-media thickness
— HDL-C <40 mg/dL in males or <50 mg/dL in
JHS Jackson Heart Study
KORA Cooperative Health Research in the Region of
females or undergoing drug treatment for
Augsburg reduced HDL-C
LDL low-density lipoprotein — Triglycerides ≥150 mg/dL or undergoing drug
LDL-C low-density lipoprotein cholesterol treatment for elevated triglycerides
LV left ventricular
— WC >102 cm in males or >88 cm in females
MESA Multi-Ethnic Study of Atherosclerosis
MET metabolic equivalent
for people of most ancestries living in the
MetS metabolic syndrome United States. Ethnicity and country-spe-
Mex-Am Mexican American cific thresholds can be used for diagnosis
(Continued ) in other groups, particularly Asians and

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e157

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

individuals of non-European ancestry who • Approximately half of the 1098 adolescent par-
CLINICAL STATEMENTS

have predominantly resided outside the ticipants in the Princeton School District Study
AND GUIDELINES

United States. diagnosed with pediatric Adult Treatment Panel

— SBP ≥130 mm Hg or DBP ≥85 mm Hg or III metabolic syndrome lost the diagnosis over 3
undergoing drug treatment for hyperten- years of follow-up.7
sion, or antihypertensive drug treatment in • In children 6 to 17 years of age participating in
a patient with a history of hypertension research studies in a single clinical research hos-
• The harmonized metabolic syndrome definition pital, the diagnosis of metabolic syndrome was
identifies a comparable risk group and predicts unstable in 46% of cases after a mean of 5.6
CVD risk similarly to the prior metabolic syndrome years of follow-up.8
definitions.1 • In the HCHS/SOL Youth, the prevalence of meta-
• There are many adverse health conditions that are bolic syndrome among children 10 to 16 years
related to metabolic syndrome but are not part of age varied according to the clinical definition
of its clinical definition. These include NAFLD, used, with only 1 participant being classified
sexual/reproductive dysfunction (erectile dysfunc- as having metabolic syndrome by all 3 clinical
tion in males and polycystic ovarian syndrome in definitions.9
females), OSA, certain forms of cancer, and pos- • Although metabolic syndrome categoriza-
sibly osteoarthritis, as well as a general proinflam- tion is generally unstable at younger ages, a
matory and prothrombotic state.2 single grouping of cardiometabolic risk factors
• Those with a fasting blood glucose ≥126 mg/ was identified in a confirmatory factor analysis
dL, random or 2-hour postchallenge glucose and shown to be present across the spectrum
≥200 mg/dL, HbA1c ≥6.5%, or taking hypo- from children to adults.10 However, a sepa-
glycemic medication will normally be classified rate confirmatory factor analysis in HCHS/SOL
separately as having DM; many of these people Youth showed that SBP and fasting glucose
will also have metabolic syndrome because of did not cluster with other metabolic syndrome
the presence of ≥2 of the additional risk factors components.9
noted above. • Uncertainty remains concerning the definition of
• Identification and treatment of metabolic syn- the obesity component of metabolic syndrome
Downloaded from http://ahajournals.org by on February 7, 2019

drome fits closely with the current AHA 2020 in the pediatric population because it is age
Impact Goal, including emphasis on PA, healthy dependent. Therefore, use of BMI percentiles11
diet, and healthy weight for attainment of ideal and waist-height ratio12 has been recommended.
BP, serum cholesterol, and fasting blood glucose. Using standard CDC and FitnessGram standards
Monitoring the prevalence of metabolic syn- for pediatric obesity, the prevalence of metabolic
drome is a secondary metric in the 2020 Impact syndrome in obese youth ranges from 19% to
Goals. Identification of metabolic syndrome rep- 35%.11
resents a call to action for the healthcare provider
and patient to address the underlying lifestyle- Adults
related risk factors. A multidisciplinary team of (See Charts 10-1 and 10-2)
healthcare professionals is desirable to ade- The following estimates include many who also have
quately address these multiple issues in patients DM, in addition to those with metabolic syndrome
with metabolic syndrome.3 without DM:
• Despite its high prevalence (see Prevalence of • Prevalence of metabolic syndrome varies by the
Metabolic Syndrome), the public’s recognition of definition used, with definitions such as that from
metabolic syndrome is limited.4 Making a diag- the International Diabetes Federation and the
nosis of metabolic syndrome and communicat- harmonized definition suggesting lower thresh-
ing with the patient about it may increase risk olds for defining central obesity in European
perception and motivation toward a healthier whites, Asians (in particular, South Asians),
behavior.5 Middle Easterners, sub-Saharan Africans, and
Hispanics, which results in higher prevalence
estimates.13
Prevalence of Metabolic Syndrome • On the basis of NHANES 2007 to 2014, the over-
Youth all prevalence of metabolic syndrome was 34.3%
• Metabolic syndrome should be diagnosed with and was similar for males (35.3%) and females
caution in children and adolescents, because (33.3%).14 The prevalence of metabolic syndrome
its categorization is not stable in these age increased with age, from 19.3% among people
groups.6 20 to 39 years of age to 37.7% for people 40 to

e158 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

59 years of age and 54.9% among people ≥60 Secular Trends of Metabolic Syndrome

CLINICAL STATEMENTS
years of age.
Youth

AND GUIDELINES
• In a recent meta-analysis of 26 609 young adults
(See Chart 10-3)
(aged 18–30 years) across 34 studies, the preva- • Data from NHANES 2009 to 2012 suggest that the
lence of metabolic syndrome was 4.8% to 7% prevalence of metabolic syndrome is decreasing in
depending on the definition used.15 12- to 19-year-olds. This appears to be correlated
• Using data from HCHS/SOL 2008 to 2011, the with increases in HDL-C and decreases in levels of
overall prevalence of metabolic syndrome among triglycerides despite a persistently increasing level
Hispanics/Latinos living in the United States was of obesity. The lifestyle factors that correlate with
34% among males and 36% among females decreasing metabolic syndrome are less carbo-
(Chart 10-1); it increased with age, with the high- hydrate intake and more unsaturated fat intake
est prevalence in females 70 to 74 years of age (Chart 10-3).43
(Chart 10-2). In males and females, the lowest
prevalence of metabolic syndrome was observed Adults
among South Americans (27%). In males, the (See Charts 10-4 through 10-8)
highest prevalence was observed in Cubans • On the basis of data from NHANES 2001 to 2010,
(35%), and in females, the highest prevalence after declining from NHANES 2001 to 2002 to
was observed among Puerto Ricans (41%). Some NHANES 2005 to 2006, the age-adjusted prevalence
differences in individual components existed of metabolic syndrome in the United States went up
by specific Hispanic/Latino background (Chart in the 2007 to 2008 cycle and then declined again
10-1).16 in the 2009 to 2010 cycle (Chart 10-4).44
• Among African Americans in the JHS, the overall • In a recent updated analysis of NHANES 2007 to
prevalence of metabolic syndrome was 34%, and 2014, the prevalence of metabolic syndrome was
it was higher in females than in males (40% ver- stable for males and females (Chart 10-5).14 The
sus 27%, respectively).17 prevalence remained stable for all age and racial/
• Filipinos in the United States are at high risk for ethnic subgroups (P>0.10).
metabolic syndrome at lower BMI levels.18 • Prevalence of metabolic syndrome was lower in
• The prevalence of metabolic syndrome has NH black males than white males and Mexican
Downloaded from http://ahajournals.org by on February 7, 2019

been noted to be high among select special American males in the NHANES cycle 1999 to
populations, including those with schizophre- 2010 (Chart 10-6).45
nia spectrum disorders19; those taking atypical • Prevalence of metabolic syndrome was higher
antipsychotic drugs20; those receiving prior solid in Mexican American females than white and
organ transplants21; those receiving prior hema- black females in the NHANES cycle 1999 to 2010
topoietic cell transplantation22; HIV-infected (Chart 10-7).45
individuals23; those previously treated for blood • The changing trends in the age-adjusted preva-
cancers24; those with systemic inflammatory dis- lence of metabolic syndrome are attributable to
orders such as psoriasis,25 systemic lupus erythe- changes in the prevalence of its individual com-
matosus,26 and rheumatoid arthritis27; those with ponents. From NHANES data cycles 1999 through
multiple sclerosis28; individuals with well-con- 2010, hypertriglyceridemia and elevated BP were
trolled type 1 DM29; those with hypopituitarism30; lower in the total population, whereas hypergly-
those with prior gestational DM31; those with cemia and elevated WC were higher in the total
prior pregnancy-induced hypertension32; veter- population; however, these trends varied sig-
ans with war-related bilateral lower-limb ampu- nificantly by sex and race/ethnicity (Chart 10-8).
tation33 or spinal cord injury34; and individuals in Differences in the prevalence statistics are the
select professions, including law enforcement35 result of different handling of age adjustment as
and firefighters.36 the prevalence of metabolic syndrome increases
• Perhaps most important with respect to meet- with age and handling of medication therapy for
ing the 2020 goals, the prevalence of metabolic its component conditions.45
syndrome increases with greater cumulative
life-course exposure to sedentary behavior
and physical inactivity37; screen time, including
Natural History and Progression of
television viewing38; fast food intake39; short Metabolic Syndrome
sleep duration40; and intake of SSBs.41,42 Each (See Chart 10-9)
of these risk factors is reversible with lifestyle • Preclinical forms of metabolic syndrome are com-
change.37–42 monly progressive and precede the development

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e159

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

of overt metabolic syndrome. In the ARIC study, baseline metabolic syndrome status. Data from
CLINICAL STATEMENTS

a sex- and race/ethnicity-specific metabolic syn- 771 participants 6 to 19 years of age from the
AND GUIDELINES

drome severity score increased in 76% of par- NHLBI’s Lipid Research Clinics Princeton Prevalence
ticipants, with faster progression observed in Study and the Princeton Follow-up Study showed
younger participants and in females. The meta- that the risk of developing CVD was substantially
bolic syndrome severity score predicted time to higher among those with metabolic syndrome
development of incident metabolic syndrome than among those without this syndrome (OR,
over a mean 10-year follow-up (1987–1989 to 14.6 [95% CI, 4.8–45.3]) who were followed up
1996–1998). In ARIC, prevalence of metabolic for 25 years.52
syndrome increased from 33% to 50% over the • In an international childhood cardiovascular
mean 10-year follow-up, with differences by age cohort consortium that included 5803 partici-
and sex. The prevalence of metabolic syndrome pants in 4 cohort studies (Cardiovascular Risk
was lower in African American males than in in Young Finns, Bogalusa Heart Study, Princeton
white males at all time points and for all ages Lipid Research Study, and Insulin Study) with a
across the study. African American females had mean follow-up period of 22.3 years, childhood
higher prevalence of metabolic syndrome than metabolic syndrome and overweight were asso-
white females at baseline and subsequent time ciated with a >2.4-fold risk for adult metabolic
points for all ages except for those >60 years of syndrome from the age of 5 years onward.53 The
age (Chart 10-9).46 risk for type 2 DM was increased beginning at
• Isolated metabolic syndrome, which could be con- the age of 8 years (RR, 2.6 [95% CI, 1.4–6.8])
sidered an earlier form of metabolic syndrome, onward based on international cutoff values for
has been defined as those with ≥3 metabolic definition of childhood metabolic syndrome. Risk
syndrome components but without overt hyper- of carotid IMT was increased beginning at age
tension and DM. In a population-based random 11 years (RR, 2.44 [95% CI, 1.55–3.55]) using
sample of 2042 residents of Olmsted County, MN, the same definition. Notably, BMI measure-
those with isolated metabolic syndrome were ment alone at the same age points provided
found to be at increased risk of incident hyper- similar findings for type 2 DM and subclinical
tension, DM, diastolic dysfunction, and reduced atherosclerosis.
renal function (GFR <60 mL/min) compared with • In a study of 6328 subjects from 4 prospec-
Downloaded from http://ahajournals.org by on February 7, 2019

healthy control subjects (P<0.05). However, iso- tive studies, compared with people with nor-
lated metabolic syndrome was not significantly mal BMI as children and as adults, those with
associated with higher rates of mortality (P=0.12) consistently high adiposity from childhood to
or development of HF (P=0.64) over the 8-year adulthood had an increased risk of the follow-
follow-up.47 ing metabolic syndrome components: hyper-
tension (RR, 2.7 [95% CI, 2.2–3.3]), low HDL-C
(RR, 2.1 [95% CI, 1.8–2.5]), elevated triglyc-
Cost and Healthcare Utilization in erides (RR, 3.0 [95% CI, 2.4–3.8]), and type
Metabolic Syndrome 2 DM (RR, 5.4 [95% CI, 3.4–8.5]). Individuals
• Metabolic syndrome is associated with increased who were overweight or had obesity during
healthcare use and healthcare-related costs childhood but did not have obesity as adults
among individuals with and without DM. had no increased risk compared with those
Overall, healthcare costs increase by ≈24% for with consistently normal BMI.54
each additional metabolic syndrome component • Among 1757 youths from the Bogalusa Heart
present.48 Study and the Cardiovascular Risk in Young Finns
• The presence of metabolic syndrome increases Study, those with metabolic syndrome in youth
the risk for postoperative complications, and adulthood were at 3.4 times increased risk of
including prolonged hospital stay and risk high carotid IMT and 12.2 times increased risk of
for blood transfusion, surgical site infection, type 2 DM in adulthood as those without meta-
and respiratory failure, across various surgical bolic syndrome at either time. Adults whose met-
populations.49–51 abolic syndrome had resolved after their youth
were at no increased risk of having high IMT or
type 2 DM.55
Complications of Metabolic Syndrome • In the Princeton Lipid Research Cohort Study, met-
Youth abolic syndrome severity scores during childhood
• Few prospective pediatric studies have exam- were lowest among those who never developed
ined the future risk for CVD or DM according to CVD and were proportionally higher progressing

e160 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

from those who developed early CVD (mean 38 increased risk of all-cause mortality (RR, 1.20

CLINICAL STATEMENTS
years old) to those who developed CVD later in [95% CI, 1.05–1.38] for males and 1.22 [95% CI,

AND GUIDELINES
life (mean 50 years old).56 Metabolic syndrome 1.02–1.44] for females) and CVD mortality (RR,
severity score was also strongly associated with 1.29 [95% CI, 1.09–1.53] for males and 1.20
early onset of DM.57 Similarly, metabolic syndrome [95%, 0.91–1.60] for females).64 There was signif-
score, based on the number of components of icant heterogeneity across the studies (all-cause
metabolic syndrome, was associated with bio- mortality, I2=55.9%, P=0.001; CVD mortality,
markers of inflammation, endothelial damage, I2=58.1%, P=0.008). In subgroup analyses, the
and CVD risk in a separate cohort of 677 prepu- association of metabolic syndrome with CVD and
bertal children.58 all-cause mortality varied by geographic location,
sample size, definition of metabolic syndrome,
Adults and adjustment for frailty.
Metabolic Syndrome and CVD Morbidity and • The impact of the metabolic syndrome on mor-
Mortality tality has been shown to be modified by objec-
• A meta-analysis of prospective studies con- tive sleep duration.65 In data from the Penn State
cluded that metabolic syndrome increased the Adult Cohort, a prospective population‐based
risk of developing CVD (summary RR, 1.78 [95% study of sleep disorders, objectively measured
CI, 1.58–2.00]).59 The RR of CVD tended to short sleep duration (<6 hours) was associated
be higher in females (summary RR, 2.63) than with increased all-cause (HR, 1.99 [95% CI,
in males (summary RR, 1.98; P=0.09). On the 1.53–2.59]) and CVD mortality (HR, 2.10 [95%
basis of results from 3 studies, metabolic syn- CI, 1.39–3.16]), whereas sleep ≥6 hours was not
drome was associated with an increased risk of associated with increased all-cause (HR, 1.29
cardiovascular events after adjustment for the [95% CI, 0.89–1.87]) or CVD (HR, 1.49 [95% CI,
individual components of the syndrome (sum- 0.75–2.97]) mortality among participants with
mary RR, 1.54 [95% CI, 1.32–1.79]). Metabolic metabolic syndrome.
syndrome is also associated with incident CVD • In the INTERHEART case-control study of
independent of the baseline subclinical CVD.60 26 903 subjects from 52 countries, metabolic
A meta-analysis among 87 studies comprising syndrome was associated with an increased risk
951 083 subjects showed an even higher risk of of MI, both according to the WHO (OR, 2.69
Downloaded from http://ahajournals.org by on February 7, 2019

CVD associated with metabolic syndrome (sum- [95% CI, 2.45–2.95]) and the International
mary RR, 2.35 [95% CI, 2.02–2.73]), with sig- Diabetes Federation (OR, 2.20 [95% CI,
nificant increased risks (RRs ranging from 1.6 to 2.03–2.38]) definitions, with a PAR of 14.5%
2.9) for all-cause mortality, CVD mortality, MI, (95% CI, 12.7%–16.3%) and 16.8% (95% CI,
and stroke, as well as for those with metabolic 14.8%–18.8%), respectively, and associations
syndrome without DM.61 that were similar across all regions and ethnic
• The cardiovascular risk associated with meta- groups. In addition, the presence of ≥3 risk fac-
bolic syndrome varies on the basis of the com- tors with subthreshold values was associated
bination of metabolic syndrome components with increased risk of MI (OR, 1.50 [95% CI,
present. Of all possible ways to have 3 meta- 1.24–1.81]) compared with having “normal”
bolic syndrome components, the combination values. Similar results were observed when the
of central obesity, elevated BP, and hypergly- International Diabetes Federation definition
cemia conferred the greatest risk for CVD (HR, was used.66
2.36 [95% CI, 1.54–3.61]) and mortality (HR, • In the Three-City Study, among 7612 partici-
3.09 [95% CI, 1.93–4.94]) in the Framingham pants aged ≥65 years who were followed up for
Offspring Study.62 5.2 years, metabolic syndrome was associated
• Data from the Aerobics Center Longitudinal with increased total CHD (HR, 1.78 [95% CI,
Study indicate that risk for CVD mortality is 1.39–2.28]) and fatal CHD (HR, 2.40 [95% CI,
increased in males without DM who have meta- 1.41–4.09]); however, metabolic syndrome was
bolic syndrome (HR, 1.8 [95% CI, 1.5–2.0]); not associated with CHD beyond its individual risk
however, among those with metabolic syn- components.67
drome, the presence of DM is associated with • Among 3414 patients with stable CVD and ath-
even greater risk for CVD mortality (HR, 2.1 erogenic dyslipidemia who were treated inten-
[95% CI, 1.7–2.6]).63 sively with statins in the AIM-HIGH trial, neither
• In a recent meta-analysis of 20 prospective cohort the presence of metabolic syndrome or the num-
studies that included 57 202 adults aged ≥60 ber of metabolic syndrome components was asso-
years, metabolic syndrome was associated with ciated with cardiovascular outcomes, including

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e161

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

coronary events, ischemic stroke, nonfatal MI, calcification was 33% for people with metabolic
CLINICAL STATEMENTS

CAD death, or the composite end point.68 syndrome compared with 38% for those with
AND GUIDELINES

• Metabolic syndrome is also associated with risk DM (with and without metabolic syndrome) and
of incident stroke.69 In a recent meta-analysis of 24% of those with neither DM nor metabolic
16 studies including 116 496 participants who syndrome.82
were initially free of CVD, those with metabolic • In the DESIR cohort, metabolic syndrome was
syndrome had a significantly high risk of incident associated with an unfavorable hemodynamic
stroke (pooled RR, 1.70 [95% CI, 1.49–1.95]) com- profile, including increased brachial central
pared with those without metabolic syndrome. pulse pressure and increased pulse-pressure
This effect was most notable among females (RR, amplification, compared with similar individu-
1.83 [95% CI, 1.31–2.56]) compared with males als with isolated hypertension but without
(RR, 1.47 [95% CI, 1.22–1.78]). Finally, those metabolic syndrome.83 In MESA, metabolic syn-
with metabolic syndrome had the highest risk for drome was associated with major and minor
ischemic stroke (RR, 2.12 [95% CI, 1.46–3.08]) electrocardiographic abnormalities, although
rather than hemorrhagic stroke (RR, 1.48 [95% CI, this varied by sex.84 Metabolic syndrome is
0.98–2.24]). associated with reduced heart rate variability
• It is estimated that 13.3% to 44% of the excess and altered cardiac autonomic modulation in
CVD mortality in the United States, compared adolescents.85
with other countries such as Japan, is explained • Individuals with metabolic syndrome have a
by metabolic syndrome or metabolic syndrome– higher degree of endothelial dysfunction than
related existing CVD.70 individuals with a similar burden of traditional
• In the ARIC study, among 13 168 participants cardiovascular risk factors.86 Furthermore, indi-
with a median follow-up of 23.6 years, metabolic viduals with both metabolic syndrome and DM
syndrome was independently associated with an have demonstrated increased microvascular and
increased risk of SCD (adjusted HR, 1.70 [95% macrovascular dysfunction.87 Metabolic syn-
CI, 1.37–2.12]; P<0.001).71 In addition, the risk of drome is associated with increased thrombosis,
SCD varied according to the number of metabolic including increased resistance to aspirin88 and
syndrome components (HR=1.31 per additional clopidogrel loading.89
Downloaded from http://ahajournals.org by on February 7, 2019

component of the metabolic syndrome [95% CI, • In a recent meta-analysis of 8 population-based stud-
1.19–1.44]; P<0.001), independent of race or sex. ies that included 19 696 patients (22.2% with meta-
• Metabolic syndrome has also been associated bolic syndrome), metabolic syndrome was associated
with incident AF,72 recurrent AF after ablation,73 with higher carotid IMT (standard mean difference
HF,74 and PAD.75 0.28±0.06 [95% CI, 0.16–0.40]; P=0.00003) and
• Using the 36 cohorts represented in the MORGAM higher prevalence of carotid plaques than in individ-
Project, the association between metabolic syn- uals without metabolic syndrome (pooled OR, 1.61
drome and CVD varied by age for females but not [95% CI, 1.29–2.01]; P<0.0001).90
males.76 • In modern imaging studies using echocardiog-
raphy, MRI, cardiac CT, and positron emission
Metabolic Syndrome and Subclinical CVD
tomography, metabolic syndrome has been
• In MESA, among 6603 people aged 45 to 84
shown to be closely related to increased epicar-
years (1686 [25%] with metabolic syndrome
dial adipose tissues,91 regional neck fat distribu-
without DM and 881 [13%] with DM), subclini-
tion,92 increased visceral fat in other locations,93
cal atherosclerosis assessed by CAC was more
increased ascending aortic diameter,94 high-risk
severe in people with metabolic syndrome and
coronary plaque features including increased
DM than in those without these conditions, and
necrotic core,95 impaired coronary flow reserve,96
the extent of CAC was a strong predictor of
abnormal indices of LV strain,97 LV diastolic dys-
CHD and CVD events in these groups.77 There
function,98 LV dysynchrony,99 and subclinical RV
appears to be a synergistic relationship between
dysfunction.100
metabolic syndrome, NAFLD, and prevalence of
CAC,78,79 as well as a synergistic relationship with Metabolic Syndrome and Non-CVD Complications
smoking.80 Furthermore, the progression of CAC • Metabolic syndrome has been associated with erec-
was greater in people with metabolic syndrome tile dysfunction,101 DM,102 cancer103,104 (in particular,
and DM than in those without, and progression breast, endometrial, prostate, pancreatic, hepatic,
of CAC predicted future CVD event risk both colorectal, and renal), cirrhosis,105 and cognitive
in those with metabolic syndrome and in those decline.106 Data from case-control studies, but not
with DM.81 In MESA, the prevalence of thoracic prospective studies, support an association with

e162 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

VTE.107 There may be an association with increased • NAFLD, a spectrum of liver disease that ranges

CLINICAL STATEMENTS
incident asthma.108 In MESA, the prevalence of from isolated fatty liver to fatty liver plus inflam-

AND GUIDELINES
erectile dysfunction among participants aged 55 mation (nonalcoholic steatohepatitis), is hypoth-
to 65 years with metabolic syndrome was 16% esized to represent the hepatic manifestation of
compared with 10% in their counterparts without the metabolic syndrome. On the basis of data
metabolic syndrome (P<0.001).101 from NHANES 2011 to 2014, the overall preva-
• In data from ARIC and JHS, metabolic syndrome lence of NAFLD among US adults was 21.9%.113
was associated with an increased risk of DM In a prospective study of 4401 Japanese adults
(HR, 4.36 [95% CI, 3.83–4.97]), although the aged 21 to 80 years free of NAFLD at baseline, the
association was attenuated after adjustment for presence of metabolic syndrome increased the
the individual components of the metabolic syn- risk for NAFLD in both males (adjusted OR, 4.00
drome.102 However, use of a continuous sex- and [95% CI, 2.63–6.08]) and females (adjusted OR,
race-specific metabolic severity Z score was asso- 11.20 [95% CI, 4.85–25.87]).114 In cross-sectional
ciated with increased risk of DM independent of studies, an increase in the number of compo-
individual metabolic syndrome components, and nents of the metabolic syndrome was associated
increases in this score over time conferred addi- with underlying nonalcoholic steatohepatitis and
tional risk for DM independent of confounders. advanced fibrosis in NAFLD.113,115
• Metabolic syndrome is linked to poorer cancer out-
comes, including increased risk of recurrence and
overall mortality.104 For example, in a retrospective Risk Factors for Metabolic Syndrome
study of 3662 males with low-risk prostate can- Genetics and Family History
cer who were treated with radical prostatectomy, • Investigation of genetic factors related to meta-
metabolic syndrome was associated with higher bolic syndrome has shed some light on the
perioperative complications (OR, 1.24 [95% CI, underlying pathways and mediators. Several
1.04–1.49]; P=0.018).109 In addition, a recent meta- pleiotropic variants of genes of apolipoproteins
analysis of 24 studies that included 132 589 males (APOE, APOC1, APOC3, and APOA5), Wnt sig-
(17.4% with metabolic syndrome) showed that naling pathway (TCF7L2), lipoproteins (LPL, CETP),
metabolic syndrome was associated with worse mitochondrial proteins (TOMM40), gene tran-
oncologic outcomes including biochemical recur-
Downloaded from http://ahajournals.org by on February 7, 2019

scription regulation (PROX1), cell proliferation

rence and more aggressive tumor features in pros- (DUSP9), cyclic AMP signaling (ADCY5), oxida-
tate cancer.110 tive LDL metabolism (COLEC12), and expression
• In data obtained from HCUP-NIS, hospitalized of liver-specific genes (HNF1A) have been identi-
patients with a diagnosis of metabolic syndrome fied across various racial/ethnic populations that
and cancer had significantly increased odds of could explain some of the correlated architecture
adverse health outcomes, including increased of metabolic syndrome traits.116–119
postsurgical complications (OR, 1.20 [95% CI, • The minor G allele of the atrial natriuretic pep-
1.03–1.39] and 1.22 [95% CI, 1.09–1.37] for tide genetic variant rs5068, which is associated
breast and prostate cancer, respectively).49 with higher circulating atrial natriuretic peptide
• In 25 038 black and white participants from the levels, has been associated with lower prevalence
REGARDS study, metabolic syndrome was associ- of metabolic syndrome in whites and African
ated with increased risk of cancer-related mortality Americans.120
(HR, 1.22 [95% CI, 1.03–1.45]).103 In race-strati- • SNPs of inflammatory genes (encoding interleukin
fied analysis, black participants with metabolic 6, interleukin 1β, and interleukin 10) and plasma
syndrome had significantly increased risk of can- fatty acids, as well as interactions among these
cer mortality compared with those without meta- SNPs, are differentially associated with odds of
bolic syndrome (HR, 1.32 [95% CI, 1.01–1.72]). metabolic syndrome.121
The risk of cancer mortality increased more than
2-fold among those with 5 metabolic syndrome In Youth
components (HR, 2.35 [95% CI, 1.01–5.51]). • Risk of metabolic syndrome probably begins
• In data from NHANES III, metabolic syndrome was before birth. The PREMA Study showed that the
associated with total cancer mortality (HR, 1.33 coexistence of low birth weight, small head cir-
[95% CI, 1.04–1.70]) and breast cancer mortality cumference, and parental history of overweight
(HR, 2.1 [95% CI, 1.09–4.11]).111 or obesity places children at the highest risk for
• For some cancers, the risk estimate differs metabolic syndrome in adolescence. Other risk
between sexes, populations, and the definitions factors identified included parental history of DM,
of the metabolic syndrome used.112 gestational hypertension in the mother, and lack

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e163

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

of breastfeeding.122 However, a recent RCT that • The following factors have been reported as
CLINICAL STATEMENTS

tested a breastfeeding promotion intervention being inversely associated with incident meta-
AND GUIDELINES

did not lead to reduced childhood metabolic syn- bolic syndrome, defined by 1 of the major defi-
drome among healthy term infants.123 nitions, in prospective or retrospective cohort
• In NHANES, adolescents 12 to 19 years old were studies: muscular strength,182 increased PA or
at greater risk of metabolic syndrome if they had physical fitness,133,183 aerobic training,184 moder-
concurrent exposure to secondhand smoke and ate alcohol intake,185 fiber intake,186,187 fruits and
low exposure to certain nutrients (vitamin E and vegetables,188 white fish intake,189 Mediterranean
omega-3 polyunsaturated fatty acids)124 and if diet,190 dairy consumption138 (particularly yogurt
they consumed more sugar in their diet.125 and low-fat dairy products),191 consumption of
fermented milk with Lactobacillus plantarum,192
In Adults animal or fat protein,193 hot tea consumption
• There is a bidirectional relationship between meta- (but not sugar-sweetened iced tea),194 coffee
bolic syndrome and depression. In prospective stud- consumption,195 vitamin D intake,196 intake of
ies, the presence of depression increases the risk tree nuts,197 walnut intake,198 avocado intake,199
of metabolic syndrome (OR, 1.49 [95% CI, 1.19– intake of long-chain omega-3 PUFA,200 potassium
1.87]), whereas metabolic syndrome increases the intake,201 ability to interpret nutrition labels,130
risk of depression (OR, 1.52 [95% CI, 1.20–1.91]).126 living at geographically higher elevation,202
• In prospective or retrospective cohort studies, the insulin sensitivity,153 ratio of aspartate amino-
following factors have been reported as being transferase to alanine transaminase,203 total
directly associated with incident metabolic syn- testosterone,150,153,204 serum 25-hydroxyvitamin
drome, defined by 1 of the major definitions: age,45 D,205 sex hormone–binding globulin,150,153,204 and
low educational attainment,127,128 low SES,129 not Δ5-desaturase activity.206 In cross-sectional stud-
being able to understand or read food labels,130 ies, increased standing,207 a vegetarian diet,208
everyday discrimination,131 urbanization,132 smok- subclinical hypothyroidism in males,209 marijuana
ing,127,129,133 parental smoking,134 low levels of use,210 total antioxidant capacity from diet and
PA,127,129,133 low levels of physical fitness,135,136 dietary supplements,211 and organic food con-
intake of soft drinks,137 intake of diet soda,138 fruc- sumption212 were inversely associated with met-
tose intake,139 magnesium intake,140,141 energy abolic syndrome.
Downloaded from http://ahajournals.org by on February 7, 2019

intake,142 carbohydrate intake,128,133,143 total fat • In a pooled population of 117  020 patients
intake,144 meat intake (red but not white meat),145 (from 20 studies) with NAFLD diagnosed by
intake of fried foods,138 skipping breakfast,146 serum liver enzymes (aminotransferases or
heavy alcohol consumption,147 abstention from γ-glutamyltransferase) or ultrasonography who
alcohol use,128 parental history of DM,144 long- were followed up for a median of 5 years (range,
term stress at work,148 pediatric metabolic syn- 3–14.7  years), NAFLD was associated with an
drome,144 obesity or BMI,55,62 childhood obesity,149 increased risk of incident metabolic syndrome
intra-abdominal fat,150 gain in weight or BMI,142 with a pooled RR of 1.80 (95% CI, 1.72–1.89)
weight fluctuation,151 heart rate,152 homeosta- for alanine aminotransferase (last versus first
sis model assessment,153 fasting insulin,153 2-hour quartile or quintile), 1.98 (95% CI, 1.89–2.07) for
insulin,153 proinsulin,153 oxidized LDL-C,154,155 HDL γ-glutamyltransferase, and 3.22 (95% CI, 3.05–
particle concentration,156 LDL particle concentra- 3.41) for ultrasonography, respectively.161
tion,156,157 lipoprotein-associated phospholipase • During >6 years of follow-up in the ARIC study,
A2,158 uric acid,159,160 γ-glutamyltransferase,161,162 1970 individuals (25%) developed metabolic syn-
alanine transaminase,161 plasminogen activator drome, and compared with the normal-weight
inhibitor-1,163 fibroblast growth factor 21,164 aldo- group (BMI <25 kg/m2), the ORs of developing
sterone,163 leptin,165 ferritin,166 CRP,167,168 adipocyte– metabolic syndrome were 2.81 (95% CI, 2.50–
fatty acid binding protein,169 testosterone and sex 3.17) and 5.24 (95% CI, 4.50–6.12) for the over-
hormone–binding globulin,170,171 matrix metallo- weight (BMI 25–30 kg/m2) and obese (BMI ≥30
proteinase 9,172 active periodontitis,173 and urinary kg/m2) groups, respectively.213
bisphenol A levels.174 In cross-sectional studies, a • In a meta-analysis that included 76  699 par-
high-salt diet,175 stress,176 low cardiorespiratory ticipants and 13 871 incident cases of metabolic
fitness,177 cancer antigen 19-9,177,178 erythrocyte syndrome, there was a negative linear relation-
parameters179 such as hemoglobin level and red ship between leisure-time PA and development
blood cell distribution width, excessive dietary cal- of metabolic syndrome.214 For every increase in
cium (>1200 mg/d) in males,180 and OSA181 were 10 MET-hours per week (approximately equal to
significant predictors of metabolic syndrome. 150 minutes of moderate PA per week), risk of

e164 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

metabolic syndrome was reduced by 10% (RR, population, the prevalence of metabolic syndrome

CLINICAL STATEMENTS
0.90 [95% CI, 0.86–0.94]). far exceeded the prevalence of MHO, which had a

AND GUIDELINES
prevalence of 7% to 28% in females and 2% to
19% in males. The prevalence of metabolic syn-
Global Burden of Metabolic Syndrome drome varied considerably by European country in
(See Chart 10-10) the BioSHaRE consortium (Chart 10-10).228
• Metabolic syndrome is becoming hyperen- • The prevalence of metabolic syndrome has been
demic around the world. Recent evidence has reported to be low (14.6%) in a population-rep-
described the prevalence of metabolic syn- resentative study in France (the French Nutrition
drome in Canada,215 Latin America,216 India,217–219 and Health Survey, 2006–2007) compared with
Bangladesh,220 Iran,221 Nigeria,222 South Africa,223 other industrialized countries.229
Ecuador,224 Nigeria,225 and Vietnam,226 as well as • In a recent systematic review of 10 Brazilian stud-
many other countries. ies, the weighted mean prevalence of metabolic
• On the basis of data from NIPPON DATA (1990– syndrome in Brazil was 29.6%.230
2005), the age-adjusted prevalence of metabolic • In a report from a representative survey of the
syndrome in a Japanese population was 19.3%.70 northern state of Nuevo León, Mexico, the preva-
In a partially representative Chinese population, lence of metabolic syndrome in adults (≥16 years
the 2009 age-adjusted prevalence of metabolic old) for 2011 to 2012 was 54.8%. In obese adults,
syndrome in China was 21.3%,132 whereas in the prevalence reached 73.8%. The prevalence in
northwest China, the prevalence for 2010 was adult North Mexican females (60.4%) was higher
15.1%.227 than in adult North Mexican males (48.9%).231
• In a report from BioSHaRE, which harmonizes • Metabolic syndrome is highly prevalent in mod-
modern data from 10 different population-based ern indigenous populations, notably in Brazil and
cohorts in 7 European countries, the age-adjusted Australia. The prevalence of metabolic syndrome
prevalence of metabolic syndrome in obese sub- was estimated to be 41.5% in indigenous groups
jects ranged from 24% to 65% in females and in Brazil,230,231 33.0% in Australian Aborigines,
from ≈43% to ≈78% in males. In the obese and 50.3% in Torres Strait Islanders.232
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 10-1. Age-standardized prevalence of metabolic syndrome by sex and Hispanic/Latino background, 2008 to 2011.
Values were weighted for survey design and nonresponse and were age standardized to the population described by the 2010 US census.
Source: Hispanic Community Health Study/Study of Latinos.16

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e165

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10
CLINICAL STATEMENTS
AND GUIDELINES

Chart 10-2. Age-standardized prevalence of metabolic syndrome by age and sex in Hispanics/Latinos, 2008 to 2011.
Values were weighted for survey design and nonresponse and were age standardized to the population described by the 2010 US census.
Source: Hispanic Community Health Study/Study of Latinos.16
Downloaded from http://ahajournals.org by on February 7, 2019

e166 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 10-3. Prevalence of metabolic syndrome in youth.

ATP III indicates Adult Treatment Panel III; BMI, body mass index; Carbs, carbohydrates; HDL, high-density lipoprotein; and MetS, metabolic syndrome.
Reproduced with permission from Lee et al.43 Copyright © 2016, by the American Academy of Pediatrics.

Chart 10-4. Age-adjusted prevalence of metabolic syndrome in the United States, NHANES, 1999 to 2010.
NHANES indicates National Health and Nutrition Examination Survey.
Data derived from Beltrán-Sánchez et al.45

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e167

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10
CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 10-5. Sex-stratified trends in the age-adjusted weighted prevalence of metabolic syndrome and its components among US adults in 2007 to
2014, NHANES.
HDL indicates high-density lipoprotein; and NHANES, National Health and Nutrition Examination Survey.
Data derived from Shin et al.14

Chart 10-6. Age-adjusted prevalence of metabolic syndrome among males by race, NHANES, 1999 to 2010.
NHANES indicates National Health and Nutrition Examination Survey.
Data derived from Beltrán-Sánchez et al.45

e168 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-7. Age-adjusted prevalence of metabolic syndrome among females by race, NHANES, 1999 to 2010.
NHANES indicates National Health and Nutrition Examination Survey.
Data derived from Beltrán-Sánchez et al.45
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 10-8. Prevalence and trends of the 5 components of metabolic syndrome in the adult US population (≥20 years old), 1999 to 2010, by sex (first
column), race/ethnicity (second column), and race/ethnicity and sex (third and fourth columns).
Shaded areas represent 95% CIs.
HDL-C indicates high-density lipoprotein cholesterol; Mex-Am, Mexican American; and Waist circumf, waist circumference.
Reprinted from Beltrán-Sánchez et al45 with permission from Elsevier. Copyright © 2013.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e169

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10
CLINICAL STATEMENTS
AND GUIDELINES

Chart 10-9. Ten-year progression of metabolic syndrome in the ARIC study, stratified by age, sex, and race/ethnicity.
ARIC indicates Atherosclerosis Risk in Communities Study.
Adapted from Vishnu et al46 with permission from Elsevier. Copyright © 2015, Elsevier Ireland Ltd.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 10-10. Age-standardized prevalence of MetS and MHO among obese (body mass index ≥30 kg/m2) males (A) and females (B) in different cohorts.
CHRIS indicates Collaborative Health Research in South Tyrol Study; DILGOM, Dietary, Lifestyle, and Genetics Determinants of Obesity and Metabolic Syndrome;
EGCUT, Estonian Genome Center of the University of Tartu; HUNT2, Nord-Trøndelag Health Study; KORA, Cooperative Health Research in the Region of Augsburg;
MetS, metabolic syndrome; MHO, metabolically healthy obesity; MICROS, Microisolates in South Tyrol Study; NCDS, National Child Development Study; NL, the
Netherlands; and PREVEND, Prevention of Renal and Vascular End-Stage Disease.
Reprinted from van Vliet-Ostaptchouk et al.228 Copyright © 2014, van Vliet-Ostaptchouk et al; licensee BioMed Central Ltd. This is an Open Access article distrib-
uted under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited.46

e170 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

‍‍‍‍‍‍REFERENCES 18. Abesamis CJ, Fruh S, Hall H, Lemley T, Zlomke KR. Cardiovascular health

CLINICAL STATEMENTS
of Filipinos in the United States: a review of the literature. J Transcult Nurs.
1. Hari P, Nerusu K, Veeranna V, Sudhakar R, Zalawadiya S, Ramesh K, Afonso

AND GUIDELINES
2016;27:518–528. doi: 10.1177/1043659615597040
L. A gender-stratified comparative analysis of various definitions of meta- 19. Correll CU, Robinson DG, Schooler NR, Brunette MF, Mueser KT,
bolic syndrome and cardiovascular risk in a multiethnic U.S. population. Rosenheck RA, Marcy P, Addington J, Estroff SE, Robinson J, Penn DL,
Metab Syndr Relat Disord. 2012;10:47–55. doi: 10.1089/met.2011.0087 Azrin S, Goldstein A, Severe J, Heinssen R, Kane JM. Cardiometabolic risk
2. Tota-Maharaj R, Defilippis AP, Blumenthal RS, Blaha MJ. A practi- in patients with first-episode schizophrenia spectrum disorders: baseline
cal approach to the metabolic syndrome: review of current con- results from the RAISE-ETP study. JAMA Psychiatry. 2014;71:1350–1363.
cepts and management. Curr Opin Cardiol. 2010;25:502–512. doi: doi: 10.1001/jamapsychiatry.2014.1314
10.1097/HCO.0b013e32833cd474 20. Rojo LE, Gaspar PA, Silva H, Risco L, Arena P, Cubillos-Robles K, Jara B.
3. Bischoff SC, Boirie Y, Cederholm T, Chourdakis M, Cuerda C, Delzenne Metabolic syndrome and obesity among users of second generation
NM, Deutz NE, Fouque D, Genton L, Gil C, Koletzko B, Leon-Sanz M, antipsychotics: a global challenge for modern psychopharmacology.
Shamir R, Singer J, Singer P, Stroebele-Benschop N, Thorell A, Weimann Pharmacol Res. 2015;101:74–85. doi: 10.1016/j.phrs.2015.07.022
A, Barazzoni R. Towards a multidisciplinary approach to understand and 21. Sorice GP, Di Pizio L, Sun VA, Schirò T, Muscogiuri G, Mezza T, Cefalo
manage obesity and related diseases. Clin Nutr. 2017;36:917–938. doi: CM, Prioletta A, Pontecorvi A, Giaccari A. Metabolic syndrome in
10.1016/j.clnu.2016.11.007 transplant patients: an updating point of view. Minerva Endocrinol.
4. Lewis SJ, Rodbard HW, Fox KM, Grandy S; SHIELD Study Group. 2012;37:211–220.
Self-reported prevalence and awareness of metabolic syndrome: 22. DeFilipp Z, Duarte RF, Snowden JA, Majhail NS, Greenfield DM, Miranda JL,
findings from SHIELD. Int J Clin Pract. 2008;62:1168–1176. doi: Arat M, Baker KS, Burns LJ, Duncan CN, Gilleece M, Hale GA, Hamadani
10.1111/j.1742-1241.2008.01770.x M, Hamilton BK, Hogan WJ, Hsu JW, Inamoto Y, Kamble RT, Lupo-
5. Jumean MF, Korenfeld Y, Somers VK, Vickers KS, Thomas RJ, Lopez- Stanghellini MT, Malone AK, McCarthy P, Mohty M, Norkin M, Paplham
Jimenez F. Impact of diagnosing metabolic syndrome on risk perception. P, Ramanathan M, Richart JM, Salooja N, Schouten HC, Schoemans H,
Am J Health Behav. 2012;36:522–532. doi: 10.5993/AJHB.36.4.9 Seber A, Steinberg A, Wirk BM, Wood WA, Battiwalla M, Flowers ME,
6. Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle Savani BN, Shaw BE. Metabolic syndrome and cardiovascular disease fol-
B, Mietus-Snyder ML. Progress and challenges in metabolic syndrome lowing hematopoietic cell transplantation: screening and preventive prac-
in children and adolescents: a scientific statement from the American tice recommendations from CIBMTR and EBMT. Bone Marrow Transplant.
Heart Association Atherosclerosis, Hypertension, and Obesity in the 2017;52:173–182. doi: 10.1038/bmt.2016.203
Young Committee of the Council on Cardiovascular Disease in the 23. Calza L, Colangeli V, Magistrelli E, Rossi N, Rosselli Del Turco E, Bussini
Young; Council on Cardiovascular Nursing; and Council on Nutrition, L, Borderi M, Viale P. Prevalence of metabolic syndrome in HIV-infected
Physical Activity, and Metabolism. Circulation. 2009;119:628–647. doi: patients naive to antiretroviral therapy or receiving a first-line treat-
10.1161/CIRCULATIONAHA.108.191394 ment. HIV Clin Trials. 2017;18:110–117. doi: 10.1080/15284336.
7. Goodman E, Daniels SR, Meigs JB, Dolan LM. Instability in the diagnosis 2017.1311502
of metabolic syndrome in adolescents. Circulation. 2007;115:2316–2322. 24. Nottage KA, Ness KK, Li C, Srivastava D, Robison LL, Hudson MM.
doi: 10.1161/CIRCULATIONAHA.106.669994 Metabolic syndrome and cardiovascular risk among long-term survivors
8. Gustafson JK, Yanoff LB, Easter BD, Brady SM, Keil MF, Roberts MD, of acute lymphoblastic leukaemia: from the St. Jude Lifetime Cohort. Br J
Sebring NG, Han JC, Yanovski SZ, Hubbard VS, Yanovski JA. The stabil- Haematol. 2014;165:364–374. doi: 10.1111/bjh.12754
ity of metabolic syndrome in children and adolescents. J Clin Endocrinol 25. Rodríguez-Zúñiga MJM, García-Perdomo HA. Systematic review and meta-
Metab. 2009;94:4828–4834. doi: 10.1210/jc.2008-2665
Downloaded from http://ahajournals.org by on February 7, 2019

analysis of the association between psoriasis and metabolic syndrome. J Am

9. Reina SA, Llabre MM, Vidot DC, Isasi CR, Perreira K, Carnethon M, Acad Dermatol. 2017;77:657–666.e8. doi: 10.1016/j.jaad.2017.04.1133
Parrinello CM, Gallo LC, Ayala GX, Delamater A. Metabolic syndrome in 26. Sun C, Qin W, Zhang YH, Wu Y, Li Q, Liu M, He CD. Prevalence and
Hispanic Youth: results from the Hispanic Community Children’s Health risk of metabolic syndrome in patients with systemic lupus erythe-
Study/Study of Latino Youth. Metab Syndr Relat Disord. 2017;15:400– matosus: a meta-analysis. Int J Rheum Dis. 2017;20:917–928. doi:
406. doi: 10.1089/met.2017.0054 10.1111/1756-185X.13153
10. Viitasalo A, Lakka TA, Laaksonen DE, Savonen K, Lakka HM, Hassinen M, 27. Gomes KWP, Luz AJP, Felipe MRB, Beltrão LA, Sampaio AXC, Rodrigues
Komulainen P, Tompuri T, Kurl S, Laukkanen JA, Rauramaa R. Validation CEM. Prevalence of metabolic syndrome in rheumatoid arthritis
of metabolic syndrome score by confirmatory factor analysis in chil- patients from Northeastern Brazil: association with disease activity. Mod
dren and adults and prediction of cardiometabolic outcomes in adults. Rheumatol. 2018;28:258–263. doi: 10.1080/14397595.2017.1316813
Diabetologia. 2014;57:940–949. doi: 10.1007/s00125-014-3172-5 28. Sicras-Mainar A, Ruíz-Beato E, Navarro-Artieda R, Maurino J.
11. Laurson KR, Welk GJ, Eisenmann JC. Diagnostic performance of BMI Comorbidity and metabolic syndrome in patients with multiple sclero-
percentiles to identify adolescents with metabolic syndrome. Pediatrics. sis from Asturias and Catalonia, Spain. BMC Neurol. 2017;17:134. doi:
2014;133:e330–e338. doi: 10.1542/peds.2013-1308 10.1186/s12883-017-0914-2
12. Khoury M, Manlhiot C, McCrindle BW. Role of the waist/height ratio in the 29. Chillarón JJ, Flores Le-Roux JA, Benaiges D, Pedro-Botet J. Type 1 diabetes,
cardiometabolic risk assessment of children classified by body mass index. metabolic syndrome and cardiovascular risk. Metabolism. 2014;63:181–
J Am Coll Cardiol. 2013;62:742–751. doi: 10.1016/j.jacc.2013.01.026 187. doi: 10.1016/j.metabol.2013.10.002
13. Brown TM, Voeks JH, Bittner V, Safford MM. Variations in prevalent car- 30. Verhelst J, Mattsson AF, Luger A, Thunander M, Góth MI, Koltowska-
diovascular disease and future risk by metabolic syndrome classification in Häggström M, Abs R. Prevalence and characteristics of the metabolic
the REasons for Geographic and Racial Differences in Stroke (REGARDS) syndrome in 2479 hypopituitary patients with adult-onset GH deficiency
study. Am Heart J. 2010;159:385–391. doi: 10.1016/j.ahj.2009.12.022 before GH replacement: a KIMS analysis. Eur J Endocrinol. 2011;165:881–
14. Shin D, Kongpakpaisarn K, Bohra C. Trends in the prevalence of meta- 889. doi: 10.1530/EJE-11-0599
bolic syndrome and its components in the United States 2007-2014. Int J 31. Noctor E, Crowe C, Carmody LA, Kirwan B, O’Dea A, Glynn LG,
Cardiol. 2018;259:216–219. doi: 10.1016/j.ijcard.2018.01.139 McGuire BE, O’Shea PM, Dunne FP. ATLANTIC-DIP: prevalence of meta-
15. Nolan PB, Carrick-Ranson G, Stinear JW, Reading SA, Dalleck LC. bolic syndrome and insulin resistance in women with previous ges-
Prevalence of metabolic syndrome and metabolic syndrome components tational diabetes mellitus by International Association of Diabetes in
in young adults: a pooled analysis. Prev Med Rep. 2017;7:211–215. doi: Pregnancy Study Groups criteria. Acta Diabetol. 2015;52:153–160. doi:
10.1016/j.pmedr.2017.07.004 10.1007/s00592-014-0621-z
16. Heiss G, Snyder ML, Teng Y, Schneiderman N, Llabre MM, Cowie C, 32. Facca TA, Mastroianni-Kirsztajn G, Sabino ARP, Passos MT, Dos Santos
Carnethon M, Kaplan R, Giachello A, Gallo L, Loehr L, Avilés-Santa L. LF, Famá EAB, Nishida SK, Sass N. Pregnancy as an early stress test for
Prevalence of metabolic syndrome among Hispanics/Latinos of diverse cardiovascular and kidney disease diagnosis. Pregnancy Hypertens.
background: the Hispanic Community Health Study/Study of Latinos. 2018;12:169–173. doi: 10.1016/j.preghy.2017.11.008
Diabetes Care. 2014;37:2391–2399. doi: 10.2337/dc13-2505 33. Ejtahed HS, Soroush MR, Hasani-Ranjbar S, Angoorani P, Mousavi
17. Khan RJ, Gebreab SY, Sims M, Riestra P, Xu R, Davis SK. Prevalence, asso- B, Masumi M, Edjtehadi F, Soveid M. Prevalence of metabolic syn-
ciated factors and heritabilities of metabolic syndrome and its individual drome and health-related quality of life in war-related bilateral lower
components in African Americans: the Jackson Heart Study. BMJ Open. limb amputees. J Diabetes Metab Disord. 2017;16:17. doi: 10.1186j/
2015;5:e008675. doi: 10.1136/bmjopen-2015-008675 s40200-017-0298-2

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e171

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

34. Gater DR Jr, Farkas GJ, Berg AS, Castillo C. Prevalence of metabolic syn- 53. Koskinen J, Magnussen CG, Sinaiko A, Woo J, Urbina E, Jacobs DR Jr,
CLINICAL STATEMENTS

drome in veterans with spinal cord injury. J Spinal Cord Med. 2018:1–8. Steinberger J, Prineas R Sabin MA, Burns T, Berenson G, Bazzano L,
AND GUIDELINES

doi: 10.1080/10790268.2017 Venn A, Viikari JSA, Hutri-Kähönen N, Raitakari O, Dwyer T, Juonala

35. Zimmerman FH. Cardiovascular disease and risk factors in law enforce- M. Childhood age and associations between childhood metabolic syn-
ment personnel: a comprehensive review. Cardiol Rev. 2012;20:159–166. drome and adult risk for metabolic syndrome, type 2 diabetes mel-
doi: 10.1097/CRD.0b013e318248d631 litus and carotid intima media thickness: the International Childhood
36. Li K, Lipsey T, Leach HJ, Nelson TL. Cardiac health and fitness of Colorado Cardiovascular Cohort Consortium. J Am Heart Assoc. 2017;6:e005632.
male/female firefighters. Occup Med (Lond). 2017;67:268–273. doi: doi: 10.1161/JAHA.117.005632
10.1093/occmed/kqx033 54. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA,
37. Bankoski A, Harris TB, McClain JJ, Brychta RJ, Caserotti P, Chen KY, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari
Berrigan D, Troiano RP, Koster A. Sedentary activity associated with JS, Dwyer T, Raitakari OT. Childhood adiposity, adult adiposity, and
metabolic syndrome independent of physical activity. Diabetes Care. cardiovascular risk factors. N Engl J Med. 2011;365:1876–1885. doi:
2011;34:497–503. doi: 10.2337/dc10-0987 10.1056/NEJMoa1010112
38. Wennberg P, Gustafsson PE, Howard B, Wennberg M, Hammarström A. 55. Magnussen CG, Koskinen J, Juonala M, Chen W, Srinivasan SR, Sabin
Television viewing over the life course and the metabolic syndrome in mid- MA, Thomson R, Schmidt MD, Nguyen QM, Xu JH, Skilton MR, Kähönen
adulthood: a longitudinal population-based study. J Epidemiol Community M, Laitinen T, Taittonen L, Lehtimäki T, Rönnemaa T, Viikari JS, Berenson
Health. 2014;68:928–933. doi: 10.1136/jech-2013-203504 GS, Raitakari OT. A diagnosis of the metabolic syndrome in youth that
39. Bahadoran Z, Mirmiran P, Hosseini-Esfahani F, Azizi F. Fast food con- resolves by adult life is associated with a normalization of high carotid
sumption and the risk of metabolic syndrome after 3-years of follow-up: intima-media thickness and type 2 diabetes mellitus risk: the Bogalusa
Tehran Lipid and Glucose Study. Eur J Clin Nutr. 2013;67:1303–1309. doi: Heart and Cardiovascular Risk in Young Finns studies. J Am Coll Cardiol.
10.1038/ejcn.2013.217 2012;60:1631–1639. doi: 10.1016/j.jacc.2012.05.056
40. Xi B, He D, Zhang M, Xue J, Zhou D. Short sleep duration predicts risk of 56. DeBoer MD, Gurka MJ, Woo JG, Morrison JA. Severity of metabolic syn-
metabolic syndrome: a systematic review and meta-analysis. Sleep Med drome as a predictor of cardiovascular disease between childhood and
Rev. 2014;18:293–297. doi: 10.1016/j.smrv.2013.06.001 adulthood: the Princeton Lipid Research Cohort Study. J Am Coll Cardiol.
41. Barrio-Lopez MT, Martinez-Gonzalez MA, Fernandez-Montero A, Beunza 2015;66:755–757. doi: 10.1016/j.jacc.2015.05.061
JJ, Zazpe I, Bes-Rastrollo M. Prospective study of changes in sugar-sweet- 57. DeBoer MD, Gurka MJ, Woo JG, Morrison JA. Severity of the metabolic
ened beverage consumption and the incidence of the metabolic syndrome syndrome as a predictor of type 2 diabetes between childhood and
and its components: the SUN cohort. Br J Nutr. 2013;110:1722–1731. adulthood: the Princeton Lipid Research Cohort Study. Diabetologia.
doi: 10.1017/S0007114513000822 2015;58:2745–2752. doi: 10.1007/s00125-015-3759-5
42. Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB. Sugar- 58. Olza J, Aguilera CM, Gil-Campos M, Leis R, Bueno G, Valle M, Cañete R,
sweetened beverages and risk of metabolic syndrome and type 2 dia- Tojo R, Moreno LA, Gil Á. A continuous metabolic syndrome score is asso-
betes: a meta-analysis. Diabetes Care. 2010;33:2477–2483. doi: ciated with specific biomarkers of inflammation and CVD risk in prepuber-
10.2337/dc10-1079 tal children. Ann Nutr Metab. 2015;66:72–79. doi: 10.1159/000369981
43. Lee AM, Gurka MJ, DeBoer MD. Trends in metabolic syndrome severity 59. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori
and lifestyle factors among adolescents [published correction appears in VM. Metabolic syndrome and risk of incident cardiovascular events and
Pediatrics. 2016;137:e20161255]. Pediatrics. 2016;137:e20153177. doi: death: a systematic review and meta-analysis of longitudinal studies. J Am
10.1542/peds.2015-3177 Coll Cardiol. 2007;49:403–414. doi: 10.1016/j.jacc.2006.09.032
44. Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic 60. Xanthakis V, Sung JH, Samdarshi TE, Hill AN, Musani SK, Sims M,
Downloaded from http://ahajournals.org by on February 7, 2019

syndrome in the United States, 2003-2012. JAMA. 2015;313:1973–1974. Ghraibeh KA, Liebson PR, Taylor HA, Vasan RS, Fox ER. Relations between
doi: 10.1001/jama.2015.4260 subclinical disease markers and type 2 diabetes, metabolic syndrome, and
45. Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S. Prevalence incident cardiovascular disease: the Jackson Heart Study. Diabetes Care.
and trends of metabolic syndrome in the adult U.S. population, 2015;38:1082–1088. doi: 10.2337/dc14-2460
1999-2010. J Am Coll Cardiol. 2013;62:697–703. doi: 10.1016/j. 61. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S,
jacc.2013.05.064 Schiffrin EL, Eisenberg MJ. The metabolic syndrome and cardiovas-
46. Vishnu A, Gurka MJ, DeBoer MD. The severity of the metabolic syn- cular risk: a systematic review and meta-analysis. J Am Coll Cardiol.
drome increases over time within individuals, independent of baseline 2010;56:1113–1132. doi: 10.1016/j.jacc.2010.05.034
metabolic syndrome status and medication use: the Atherosclerosis 62. Franco OH, Massaro JM, Civil J, Cobain MR, O’Malley B, D’Agostino
Risk in Communities Study. Atherosclerosis. 2015;243:278–285. doi: RB Sr. Trajectories of entering the metabolic syndrome: the
10.1016/j.atherosclerosis.2015.09.025 Framingham Heart Study. Circulation. 2009;120:1943–1950. doi:
47. Patel PA, Scott CG, Rodeheffer RJ, Chen HH. The natural history of 10.1161/CIRCULATIONAHA.109.855817
patients with isolated metabolic syndrome. Mayo Clin Proc. 2016;91:623– 63. Church TS, Thompson AM, Katzmarzyk PT, Sui X, Johannsen N, Earnest
633. doi: 10.1016/j.mayocp.2016.02.026 CP, Blair SN. Metabolic syndrome and diabetes, alone and in combination,
48. Boudreau DM, Malone DC, Raebel MA, Fishman PA, Nichols GA, Feldstein as predictors of cardiovascular disease mortality among men. Diabetes
AC, Boscoe AN, Ben-Joseph RH, Magid DJ, Okamoto LJ. Health care uti- Care. 2009;32:1289–1294. doi: 10.2337/dc08-1871
lization and costs by metabolic syndrome risk factors. Metab Syndr Relat 64. Ju SY, Lee JY, Kim DH. Association of metabolic syndrome and its com-
Disord. 2009;7:305–314. doi: 10.1089/met.2008.0070 ponents with all-cause and cardiovascular mortality in the elderly: a
49. Akinyemiju T, Sakhuja S, Vin-Raviv N. In-hospital mortality and post-surgi- meta-analysis of prospective cohort studies. Medicine (Baltimore).
cal complications among cancer patients with metabolic syndrome. Obes 2017;96:e8491. doi: 10.1097/MD.0000000000008491
Surg. 2018;28:683–692. doi: 10.1007/s11695-017-2900-6 65. Fernandez-Mendoza J, He F, LaGrotte C, Vgontzas AN, Liao D, Bixler EO.
50. Shariq OA, Fruth KM, Hanson KT, Cronin PA, Richards ML, Farley DR, Impact of the metabolic syndrome on mortality is modified by objec-
Thompson GB, Habermann EB, McKenzie TJ. Metabolic syndrome is asso- tive short sleep duration [published correction appears in J Am Heart
ciated with increased postoperative complications and use of hospital Assoc. 2017;6:e002182]. J Am Heart Assoc. 2017;6:e005479. doi:
resources in patients undergoing laparoscopic adrenalectomy. Surgery. 10.1161/JAHA.117.005479
2018;163:167–175. doi: 10.1016/j.surg.2017.06.023 66. Mente A, Yusuf S, Islam S, McQueen MJ, Tanomsup S, Onen CL, Rangarajan
51. Tee MC, Ubl DS, Habermann EB, Nagorney DM, Kendrick ML, Sarr MG, S, Gerstein HC, Anand SS; INTERHEART Investigators. Metabolic syndrome
Truty MJ, Que FG, Reid-Lombardo K, Smoot RL, Farnell MB. Metabolic and risk of acute myocardial infarction a case-control study of 26,903
syndrome is associated with increased postoperative morbidity and subjects from 52 countries. J Am Coll Cardiol. 2010;55:2390–2398. doi:
hospital resource utilization in patients undergoing elective pancre- 10.1016/j.jacc.2009.12.053
atectomy. J Gastrointest Surg. 2016;20:189–98; discussion 198. doi: 67. Rachas A, Raffaitin C, Barberger-Gateau P, Helmer C, Ritchie K, Tzourio
10.1007/s11605-015-3007-9 C, Amouyel P, Ducimetière P, Empana JP. Clinical usefulness of the
52. Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in child- metabolic syndrome for the risk of coronary heart disease does not
hood predicts adult cardiovascular disease 25 years later: the Princeton exceed the sum of its individual components in older men and women:
Lipid Research Clinics Follow-up Study. Pediatrics. 2007;120:340–345. the Three-City (3C) Study. Heart. 2012;98:650–655. doi: 10.1136/
doi: 10.1542/peds.2006-1699 heartjnl-2011-301185

e172 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

68. Lyubarova R, Robinson JG, Miller M, Simmons DL, Xu P, Abramson BL, 83. Safar ME, Balkau B, Lange C, Protogerou AD, Czernichow S, Blacher

CLINICAL STATEMENTS
Elam MB, Brown TM, McBride R, Fleg JL, Desvigne-Nickens P, Ayenew J, Levy BI, Smulyan H. Hypertension and vascular dynamics in men and

AND GUIDELINES
W, Boden WE; Atherothrombosis Intervention in Metabolic Syndrome women with metabolic syndrome. J Am Coll Cardiol. 2013;61:12–19. doi:
with Low HDL/High Triglycerides and Impact on Global Health Outcomes 10.1016/j.jacc.2012.01.088
(AIM-HIGH) Investigators. Metabolic syndrome cluster does not provide 84. Ebong IA, Bertoni AG, Soliman EZ, Guo M, Sibley CT, Chen YD, Rotter
incremental prognostic information in patients with stable cardiovas- JI, Chen YC, Goff DC Jr. Electrocardiographic abnormalities associated
cular disease: a post hoc analysis of the AIM-HIGH trial. J Clin Lipidol. with the metabolic syndrome and its components: the Multi-Ethnic
2017;11:1201–1211. doi: 10.1016/j.jacl.2017.06.017 Study of Atherosclerosis. Metab Syndr Relat Disord. 2012;10:92–97. doi:
69. Li X, Li X, Lin H, Fu X, Lin W, Li M, Zeng X, Gao Q. Metabolic syndrome 10.1089/met.2011.0090
and stroke: a meta-analysis of prospective cohort studies. J Clin Neurosci. 85. Rodríguez-Colón SM, He F, Bixler EO, Fernandez-Mendoza J, Vgontzas
2017;40:34–38. doi: 10.1016/j.jocn.2017.01.018 AN, Calhoun S, Zheng ZJ, Liao D. Metabolic syndrome burden in appar-
70. Liu L, Miura K, Fujiyoshi A, Kadota A, Miyagawa N, Nakamura Y, Ohkubo ently healthy adolescents is adversely associated with cardiac autonomic
T, Okayama A, Okamura T, Ueshima H. Impact of metabolic syndrome modulation–Penn State Children Cohort. Metabolism. 2015;64:626–632.
on the risk of cardiovascular disease mortality in the United States doi: 10.1016/j.metabol.2015.01.018
and in Japan. Am J Cardiol. 2014;113:84–89. doi: 10.1016/j.amjcard. 86. Li J, Flammer AJ, Lennon RJ, Nelson RE, Gulati R, Friedman PA, Thomas
2013.08.042 RJ, Sandhu NP, Hua Q, Lerman LO, Lerman A. Comparison of the effect
71. Hess PL, Al-Khalidi HR, Friedman DJ, Mulder H, Kucharska-Newton A, of the metabolic syndrome and multiple traditional cardiovascular risk
Rosamond WR, Lopes RD, Gersh BJ, Mark DB, Curtis LH, Post WS, Prineas factors on vascular function. Mayo Clin Proc. 2012;87:968–975. doi:
RJ, Sotoodehnia N, Al-Khatib SM. The metabolic syndrome and risk of 10.1016/j.mayocp.2012.07.004
sudden cardiac death: the Atherosclerosis Risk in Communities Study. J 87. Walther G, Obert P, Dutheil F, Chapier R, Lesourd B, Naughton G,
Am Heart Assoc. 2017;6:e006103. doi: 10.1161/JAHA.117.006103 Courteix D, Vinet A. Metabolic syndrome individuals with and without
72. Chamberlain AM, Agarwal SK, Ambrose M, Folsom AR, Soliman EZ, type 2 diabetes mellitus present generalized vascular dysfunction: cross-
Alonso A. Metabolic syndrome and incidence of atrial fibrillation among sectional study. Arterioscler Thromb Vasc Biol. 2015;35:1022–1029. doi:
blacks and whites in the Atherosclerosis Risk in Communities (ARIC) Study. 10.1161/ATVBAHA.114.304591
Am Heart J. 2010;159:850–856. doi: 10.1016/j.ahj.2010.02.005 88. Smith JP, Haddad EV, Taylor MB, Oram D, Blakemore D, Chen Q, Boutaud
73. Lin KJ, Cho SI, Tiwari N, Bergman M, Kizer JR, Palma EC, Taub CC. Impact O, Oates JA. Suboptimal inhibition of platelet cyclooxygenase-1 by
of metabolic syndrome on the risk of atrial fibrillation recurrence after aspirin in metabolic syndrome. Hypertension. 2012;59:719–725. doi:
catheter ablation: systematic review and meta-analysis. J Interv Card 10.1161/HYPERTENSIONAHA.111.181404
Electrophysiol. 2014;39:211–223. doi: 10.1007/s10840-013-9863-x 89. Feldman L, Tubach F, Juliard JM, Himbert D, Ducrocq G, Sorbets E,
74. Perrone-Filardi P, Paolillo S, Costanzo P, Savarese G, Trimarco B, Bonow Triantafyllou K, Kerner A, Abergel H, Huisse MG, Roussel R, Esposito-Farèse
RO. The role of metabolic syndrome in heart failure. Eur Heart J. M, Steg PG, Ajzenberg N. Impact of diabetes mellitus and metabolic syn-
2015;36:2630–2634. doi: 10.1093/eurheartj/ehv350 drome on acute and chronic on-clopidogrel platelet reactivity in patients
75. Vidula H, Liu K, Criqui MH, Szklo M, Allison M, Sibley C, Ouyang P, Tracy with stable coronary artery disease undergoing drug-eluting stent place-
RP, Chan C, McDermott MM. Metabolic syndrome and incident peripheral ment. Am Heart J. 2014;168:940–7.e5. doi: 10.1016/j.ahj.2014.08.014
artery disease: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 90. Cuspidi C, Sala C, Tadic M, Gherbesi E, Grassi G, Mancia G. Association
2015;243:198–203. doi: 10.1016/j.atherosclerosis.2015.08.044 of metabolic syndrome with carotid thickening and plaque in the general
76. Vishram JK, Borglykke A, Andreasen AH, Jeppesen J, Ibsen H, Jørgensen population: a meta-analysis. J Clin Hypertens (Greenwich). 2018;20:4–10.
T, Palmieri L, Giampaoli S, Donfrancesco C, Kee F, Mancia G, Cesana G, doi: 10.1111/jch.13138
Downloaded from http://ahajournals.org by on February 7, 2019

Kuulasmaa K, Salomaa V, Sans S, Ferrieres J, Dallongeville J, Söderberg S, 91. Pierdomenico SD, Pierdomenico AM, Cuccurullo F, Iacobellis G. Meta-
Arveiler D, Wagner A, Tunstall-Pedoe H, Drygas W, Olsen MH; MORGAM analysis of the relation of echocardiographic epicardial adipose tissue
Project. Impact of age and gender on the prevalence and prognostic thickness and the metabolic syndrome. Am J Cardiol. 2013;111:73–78.
importance of the metabolic syndrome and its components in Europeans: doi: 10.1016/j.amjcard.2012.08.044
the MORGAM Prospective Cohort Project [published correct appears 92. Torriani M, Gill CM, Daley S, Oliveira AL, Azevedo DC, Bredella MA.
in PLoS One. 2015;10:e0128848]. PLoS One. 2014;9:e107294. doi: Compartmental neck fat accumulation and its relation to cardiovascular
10.1371/journal.pone.0107294 risk and metabolic syndrome. Am J Clin Nutr. 2014;100:1244–1251. doi:
77. Malik S, Budoff MJ, Katz R, Blumenthal RS, Bertoni AG, Nasir K, Szklo M, 10.3945/ajcn.114.088450
Barr RG, Wong ND. Impact of subclinical atherosclerosis on cardiovascu- 93. van der Meer RW, Lamb HJ, Smit JW, de Roos A. MR imaging evaluation
lar disease events in individuals with metabolic syndrome and diabetes: of cardiovascular risk in metabolic syndrome. Radiology. 2012;264:21–37.
the Multi-Ethnic Study of Atherosclerosis. Diabetes Care. 2011;34:2285– doi: 10.1148/radiol.12110772
2290. doi: 10.2337/dc11-0816 94. Chun H. Ascending aortic diameter and metabolic syndrome in
78. Hong HC, Hwang SY, Ryu JY, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik Korean men. J Investig Med. 2017;65:1125–1130. doi: 10.1136/
SH, Choi DS, Choi KM. The synergistic impact of nonalcoholic fatty jim-2016-000367
liver disease and metabolic syndrome on subclinical atherosclerosis. Clin 95. Marso SP, Mercado N, Maehara A, Weisz G, Mintz GS, McPherson
Endocrinol (Oxf). 2016;84:203–209. doi: 10.1111/cen.12940 J, Schiele F, Dudek D, Fahy M, Xu K, Lansky A, Templin B, Zhang Z, de
79. Al Rifai M, Silverman MG, Nasir K, Budoff MJ, Blankstein R, Szklo M, Bruyne B, Serruys PW, Stone GW. Plaque composition and clinical out-
Katz R, Blumenthal RS, Blaha MJ. The association of nonalcoholic comes in acute coronary syndrome patients with metabolic syndrome
fatty liver disease, obesity, and metabolic syndrome, with systemic or diabetes. JACC Cardiovasc Imaging. 2012;5(suppl):S42–S52. doi:
inflammation and subclinical atherosclerosis: the Multi-Ethnic Study 10.1016/j.jcmg.2012.01.008
of Atherosclerosis (MESA). Atherosclerosis. 2015;239:629–633. doi: 96. Di Carli MF, Charytan D, McMahon GT, Ganz P, Dorbala S, Schelbert HR.
10.1016/j.atherosclerosis.2015.02.011 Coronary circulatory function in patients with the metabolic syndrome. J
80. Lee YA, Kang SG, Song SW, Rho JS, Kim EK. Association between meta- Nucl Med. 2011;52:1369–1377. doi: 10.2967/jnumed.110.082883
bolic syndrome, smoking status and coronary artery calcification. PLoS 97. Almeida AL, Teixido-Tura G, Choi EY, Opdahl A, Fernandes VR, Wu CO,
One. 2015;10:e0122430. doi: 10.1371/journal.pone.0122430 Bluemke DA, Lima JA. Metabolic syndrome, strain, and reduced myo-
81. Wong ND, Nelson JC, Granston T, Bertoni AG, Blumenthal RS, Carr cardial function: Multi-Ethnic Study of Atherosclerosis. Arq Bras Cardiol.
JJ, Guerci A, Jacobs DR Jr, Kronmal R, Liu K, Saad M, Selvin E, Tracy R, 2014;102:327–335.
Detrano R. Metabolic syndrome, diabetes, and incidence and progres- 98. Aksoy S, Durmuş G, Özcan S, Toprak E, Gurkan U, Oz D, Canga Y,
sion of coronary calcium: the Multiethnic Study of Atherosclerosis Karatas B, Duman D. Is left ventricular diastolic dysfunction indepen-
study. JACC Cardiovasc Imaging. 2012;5:358–366. doi: 10.1016/j.jcmg. dent from presence of hypertension in metabolic syndrome? An echo-
2011.12.015 cardiographic study. J Cardiol. 2014;64:194–198. doi: 10.1016/j.jjcc.
82. Katz R, Budoff MJ, O’Brien KD, Wong ND, Nasir K. The metabolic 2014.01.002
syndrome and diabetes mellitus as predictors of thoracic aortic calci- 99. Crendal E, Walther G, Dutheil F, Courteix D, Lesourd B, Chapier R,
fication as detected by non-contrast computed tomography in the Multi- Naughton G, Vinet A, Obert P. Left ventricular myocardial dyssynchrony is
Ethnic Study of Atherosclerosis. Diabet Med. 2016;33:912–919. doi: already present in nondiabetic patients with metabolic syndrome. Can J
10.1111/dme.12958 Cardiol. 2014;30:320–324. doi: 10.1016/j.cjca.2013.10.019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e173

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

100. Tadic M, Cuspidi C, Sljivic A, Andric A, Ivanovic B, Scepanovic R, Ilic I, metabolic syndrome in the Moroccan population. Diabetes Metab Syndr.
CLINICAL STATEMENTS

Jozika L, Marjanovic T, Celic V. Effects of the metabolic syndrome on 2017;11 Suppl 2:S853–S857. doi: 10.1016/j.dsx.2017.07.005
118. Lakbakbi El Yaagoubi F, Charoute H, Morjane I, et al. Association analy-
AND GUIDELINES

right heart mechanics and function. Can J Cardiol. 2014;30:325–331.

doi: 10.1016/j.cjca.2013.12.006 sis of genetic variants with metabolic syndrome components in the
101. Besiroglu H, Otunctemur A, Ozbek E. The relationship between meta- Moroccan population. Curr Res Transl Med. 2017;65:121–125. doi:
bolic syndrome, its components, and erectile dysfunction: a system- 10.1016/j.retram.2017.08.001
atic review and a meta-analysis of observational studies. J Sex Med. 119. Carty CL, Bhattacharjee S, Haessler J, Cheng I, Hindorff LA, Aroda V,
2015;12:1309–1318. doi: 10.1111/jsm.12885 Carlson CS, Hsu CN, Wilkens L, Liu S, Selvin E, Jackson R, North KE,
102. Gurka MJ, Golden SH, Musani SK, Sims M, Vishnu A, Guo Y, Cardel Peters U, Pankow JS, Chatterjee N, Kooperberg C. Analysis of metabolic
M, Pearson TA, DeBoer MD. Independent associations between a syndrome components in >15 000 African Americans identifies pleiotro-
metabolic syndrome severity score and future diabetes by sex and pic variants: results from the Population Architecture using Genomics
race: the Atherosclerosis Risk In Communities Study and Jackson and Epidemiology study. Circ Cardiovasc Genet. 2014;7:505–513. doi:
Heart Study. Diabetologia. 2017;60:1261–1270. doi: 10.1007/ 10.1161/CIRCGENETICS.113.000386
s00125-017-4267-6 120. Cannone V, Cefalu’ AB, Noto D, Scott CG, Bailey KR, Cavera G,
103. Akinyemiju T, Moore JX, Judd S, Lakoski S, Goodman M, Safford Pagano M, Sapienza M, Averna MR, Burnett JC Jr. The atrial natriuretic
MM, Pisu M. Metabolic dysregulation and cancer mortality in a na- peptide genetic variant rs5068 is associated with a favorable cardio-
tional cohort of blacks and whites. BMC Cancer. 2017;17:856. doi: metabolic phenotype in a Mediterranean population. Diabetes Care.
10.1186/s12885-017-3807-2 2013;36:2850–2856. doi: 10.2337/dc12-2337
104. Micucci C, Valli D, Matacchione G, Catalano A. Current perspectives 121. Maintinguer Norde M, Oki E, Ferreira Carioca AA, Teixeira Damasceno
between metabolic syndrome and cancer. Oncotarget. 2016;7:38959– NR, Fisberg RM, Lobo Marchioni DM, Rogero MM. Influence of IL1B,
38972. doi: 10.18632/oncotarget.8341 IL6 and IL10 gene variants and plasma fatty acid interaction on meta-
105. Åberg F, Helenius-Hietala J, Puukka P, Färkkilä M, Jula A. Interaction be- bolic syndrome risk in a cross-sectional population-based study. Clin Nutr.
tween alcohol consumption and metabolic syndrome in predicting severe 2018;37:659–666. doi: 10.1016/j.clnu.2017.02.009
liver disease in the general population. Hepatology. 2018;67:2141– 122. Efstathiou SP, Skeva II, Zorbala E, Georgiou E, Mountokalakis TD.
2149. doi: 10.1002/hep.29631 Metabolic syndrome in adolescence: can it be predicted from na-
106. Raffaitin C, Féart C, Le Goff M, Amieva H, Helmer C, Akbaraly TN, tal and parental profile? The Prediction of Metabolic Syndrome in
Tzourio C, Gin H, Barberger-Gateau P. Metabolic syndrome and cognitive Adolescence (PREMA) study. Circulation. 2012;125:902–910. doi:
decline in French elders: the Three-City Study. Neurology. 2011;76:518– 10.1161/CIRCULATIONAHA.111.034546
525. doi: 10.1212/WNL.0b013e31820b7656 123. Martin RM, Patel R, Kramer MS, Vilchuck K, Bogdanovich N, Sergeichick
107. Ageno W, Di Minno MN, Ay C, Jang MJ, Hansen JB, Steffen LM, Vayà A, N, Gusina N, Foo Y, Palmer T, Thompson J, Gillman MW, Smith GD,
Rattazzi M, Pabinger I, Oh D, Di Minno G, Braekkan SK, Cushman M, Bonet Oken E. Effects of promoting longer-term and exclusive breastfeed-
E, Pauletto P, Squizzato A, Dentali F. Association between the metabolic ing on cardiometabolic risk factors at age 11.5 years: a cluster-
syndrome, its individual components, and unprovoked venous thrombo- randomized, controlled trial. Circulation. 2014;129:321–329. doi:
embolism: results of a patient-level meta-analysis. Arterioscler Thromb 10.1161/CIRCULATIONAHA.113.005160
Vasc Biol. 2014;34:2478–2485. doi: 10.1161/ATVBAHA.114.304085 124. Moore BF, Clark ML, Bachand A, Reynolds SJ, Nelson TL, Peel JL.
108. Brumpton BM, Camargo CA Jr, Romundstad PR, Langhammer A, Interactions between diet and exposure to secondhand smoke on meta-
Chen Y, Mai XM. Metabolic syndrome and incidence of asthma bolic syndrome among children: NHANES 2007-2010. J Clin Endocrinol
in adults: the HUNT study. Eur Respir J. 2013;42:1495–1502. doi: Metab. 2016;101:52–58. doi: 10.1210/jc.2015-2477
Downloaded from http://ahajournals.org by on February 7, 2019

10.1183/09031936.00046013 125. Rodriguez LA, Madsen KA, Cotterman C, Lustig RH. Added sugar intake
109. Colicchia M, Morlacco A, Rangel LJ, Carlson RE, Dal Moro F, Karnes RJ. and metabolic syndrome in US adolescents: cross-sectional analysis of
Role of metabolic syndrome on perioperative and oncological outcomes the National Health and Nutrition Examination Survey 2005–2012. Public
at radical prostatectomy in a low-risk prostate cancer cohort potentially Health Nutr. 2016;19:2424–2434. doi: 10.1017/S13689890016000057
eligible for active surveillance [published online January 3, 2018]. Eur 126. Pan A, Keum N, Okereke OI, Sun Q, Kivimaki M, Rubin RR, Hu FB.
Urol Focus. doi: 10.1016/j.euf.2017.12.005. https://www.eu-focus.euro- Bidirectional association between depression and metabolic syndrome: a
peanurology.com/article/S2405-4569(17)30292-4/fulltext. systematic review and meta-analysis of epidemiological studies. Diabetes
110. Gacci M, Russo GI, De Nunzio C, Sebastianelli A, Salvi M, Vignozzi L, Care. 2012;35:1171–1180. doi: 10.2337/dc11-2055
Tubaro A, Morgia G, Serni S. Meta-analysis of metabolic syndrome and 127. Wilsgaard T, Jacobsen BK. Lifestyle factors and incident metabolic
prostate cancer. Prostate Cancer Prostatic Dis. 2017;20:146–155. doi: syndrome: the Tromsø Study 1979-2001. Diabetes Res Clin Pract.
10.1038/pcan.2017.1 2007;78:217–224. doi: 10.1016/j.diabres.2007.03.006
111. Gathirua-Mwangi WG, Song Y, Monahan PO, Champion VL, Zollinger 128. Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K; Coronary
TW. Associations of metabolic syndrome and C-reactive protein with Artery Risk Development in Young Adults study. Risk factors for the met-
mortality from total cancer, obesity-linked cancers and breast cancer abolic syndrome: the Coronary Artery Risk Development in Young Adults
among women in NHANES III. Int J Cancer. 2018;143:535–542. doi: (CARDIA) study, 1985-2001. Diabetes Care. 2004;27:2707–2715.
10.1002/ijc.31344 129. Chichlowska KL, Rose KM, Diez-Roux AV, Golden SH, McNeill AM,
112. Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syn- Heiss G. Life course socioeconomic conditions and metabolic syn-
drome and risk of cancer: a systematic review and meta-analysis. drome in adults: the Atherosclerosis Risk in Communities (ARIC)
Diabetes Care. 2012;35:2402–2411. doi: 10.2337/dc12-0336 Study. Ann Epidemiol. 2009;19:875–883. doi: 10.1016/j.annepidem.
113. Wong RJ, Liu B, Bhuket T. Significant burden of nonalcoholic fatty liver 2009.07.094
disease with advanced fibrosis in the US: a cross-sectional analysis of 130. Kang HT, Shim JY, Lee YJ, Linton JA, Park BJ, Lee HR. Reading nutrition
2011-2014 National Health and Nutrition Examination Survey. Aliment labels is associated with a lower risk of metabolic syndrome in Korean
Pharmacol Ther. 2017;46:974–980. doi: 10.1111/apt.14327 adults: the 2007-2008 Korean NHANES. Nutr Metab Cardiovasc Dis.
114. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, 2013;23:876–882. doi: 10.1016/j.numecd.2012.06.007
Omatsu T, Nakajima T, Sarui H, Shimazaki M, Kato T, Okuda J, Ida K. The 131. Beatty Moody DL, Chang Y, Brown C, Bromberger JT, Matthews
metabolic syndrome as a predictor of nonalcoholic fatty liver disease. KA. Everyday discrimination and metabolic syndrome incidence
Ann Intern Med. 2005;143:722–728. in a racially/ethnically diverse sample: Study of Women’s Health
115. Xu ZJ, Shi JP, Yu DR, Zhu LJ, Jia JD, Fan JG. Evaluating the relationship be- Across the Nation. Psychosom Med. 2018;80:114–121. doi:
tween metabolic syndrome and liver biopsy-proven non-alcoholic steato- 10.1097/PSY.0000000000000516
hepatitis in China: a multicenter cross-sectional study design. Adv Ther. 132. Xi B, He D, Hu Y, Zhou D. Prevalence of metabolic syndrome and its
2016;33:2069–2081. doi: 10.1007/s12325-016-0416-4 influencing factors among the Chinese adults: the China Health
116. Lin E, Kuo PH, Liu YL, Yang AC, Tsai SJ. Detection of susceptibility loci and Nutrition Survey in 2009. Prev Med. 2013;57:867–871. doi:
on APOA5 and COLEC12 associated with metabolic syndrome using a 10.1016/j.ypmed.2013.09.023
genome-wide association study in a Taiwanese population. Oncotarget. 133. Wannamethee SG, Shaper AG, Whincup PH. Modifiable life-
2017;8:93349–93359. doi: 10.18632/oncotarget.20967 style factors and the metabolic syndrome in older men: effects
117. Morjane I, Kefi R, Charoute H, Lakbakbi El Yaagoubi F, Hechmi M, Saile R, of lifestyle changes. J Am Geriatr Soc. 2006;54:1909–1914. doi:
Abdelhak S, Barakat A. Association study of HNF1A polymorphisms with 10.1111/j.1532-5415.2006.00974.x

e174 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

134. Juonala M, Magnussen CG, Venn A, Gall S, Kähönen M, Laitinen T, syndrome in an adult cohort. Int J Obes (Lond). 2008;32:315–321. doi:

CLINICAL STATEMENTS
Taittonen L, Lehtimäki T, Jokinen E, Sun C, Viikari JS, Dwyer T, Raitakari 10.1038/sj.ijo.0803739
152. Tomiyama H, Yamada J, Koji Y, Yambe M, Motobe K, Shiina K, Yamamoto

AND GUIDELINES
OT. Parental smoking in childhood and brachial artery flow-mediated dil-
atation in young adults: the Cardiovascular Risk in Young Finns study and Y, Yamashina A. Heart rate elevation precedes the development of meta-
the Childhood Determinants of Adult Health study. Arterioscler Thromb bolic syndrome in Japanese men: a prospective study. Hypertens Res.
Vasc Biol. 2012;32:1024–1031. doi: 10.1161/ATVBAHA.111.243261 2007;30:417–426. doi: 10.1291/hypres.30.417
135. Ferreira I, Henry RM, Twisk JW, van Mechelen W, Kemper HC, Stehouwer 153. Palaniappan L, Carnethon MR, Wang Y, Hanley AJ, Fortmann SP, Haffner
CD; Amsterdam Growth and Health Longitudinal Study. The metabolic SM, Wagenknecht L; Insulin Resistance Atherosclerosis Study. Predictors
syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as inde- of the incident metabolic syndrome in adults: the Insulin Resistance
pendent determinants of arterial stiffness: the Amsterdam Growth and Atherosclerosis Study. Diabetes Care. 2004;27:788–793.
Health Longitudinal Study. Arch Intern Med. 2005;165:875–882. doi: 154. Koskinen J, Magnussen CG, Würtz P, Soininen P, Kangas AJ, Viikari JS,
10.1001/archinte.165.8.875 Kähönen M, Loo BM, Jula A, Ahotupa M, Lehtimäki T, Ala-Korpela M,
136. LaMonte MJ, Barlow CE, Jurca R, Kampert JB, Church TS, Blair SN. Juonala M, Raitakari OT. Apolipoprotein B, oxidized low-density lipopro-
Cardiorespiratory fitness is inversely associated with the incidence of met- tein, and LDL particle size in predicting the incidence of metabolic syn-
abolic syndrome: a prospective study of men and women. Circulation. drome: the Cardiovascular Risk in Young Finns study. Eur J Prev Cardiol.
2005;112:505–512. doi: 10.1161/CIRCULATIONAHA.104.503805 2012;19:1296–1303. doi: 10.1177/1741826711425343
137. Narain A, Kwok CS, Mamas MA. Soft drink intake and the risk of 155. Calcaterra V, De Giuseppe R, Biino G, Mantelli M, Marchini S, Bendotti
metabolic syndrome: a systematic review and meta-analysis [published G, Madè A, Avanzini MA, Montalbano C, Cossellu G, Larizza D, Cena
online January 10, 2017]. Int J Clin Pract. doi: 10.1111/ijcp.12927. H. Relation between circulating oxidized-LDL and metabolic syn-
https://onlinelibrary.wiley.com/doi/abs/10.1111/ijcp.12927. drome in children with obesity: the role of hypertriglyceridemic waist
138. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the devel- phenotype. J Pediatr Endocrinol Metab. 2017;30:1257–1263. doi:
opment of the metabolic syndrome: the Atherosclerosis Risk 10.1515/jpem-2017-0239
in Communities study. Circulation. 2008;117:754–761. doi: 156. Mani P, Ren HY, Neeland IJ, McGuire DK, Ayers CR, Khera A, Rohatgi A.
10.1161/CIRCULATIONAHA.107.716159 The association between HDL particle concentration and incident meta-
139. Kelishadi R, Mansourian M, Heidari-Beni M. Association of fructose con- bolic syndrome in the multi-ethnic Dallas Heart Study. Diabetes Metab
sumption and components of metabolic syndrome in human studies: a Syndr. 2017;11 Suppl 1:S175–S179. doi: 10.1016/j.dsx.2016.12.028
systematic review and meta-analysis. Nutrition. 2014;30:503–510. doi: 157. Tehrani DM, Zhao Y, Blaha MJ, Mora S, Mackey RH, Michos ED, Budoff
10.1016/j.nut.2013.08.014 MJ, Cromwell W, Otvos JD, Rosenblit PD, Wong ND. Discordance of
140. He K, Liu K, Daviglus ML, Morris SJ, Loria CM, Van Horn L, Jacobs low-density lipoprotein and high-density lipoprotein cholesterol par-
DR Jr, Savage PJ. Magnesium intake and incidence of metabolic syn- ticle versus cholesterol concentration for the prediction of cardiovascu-
drome among young adults. Circulation. 2006;113:1675–1682. doi: lar disease in patients with metabolic syndrome and diabetes mellitus
10.1161/CIRCULATIONAHA.105.588327 (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol.
141. Song Y, Ridker PM, Manson JE, Cook NR, Buring JE, Liu S. Magnesium 2016;117:1921–1927. doi: 10.1016/j.amjcard.2016.03.040
intake, C-reactive protein, and the prevalence of metabolic syndrome in 158. Acevedo M, Varleta P, Kramer V, Valentino G, Quiroga T, Prieto C, Parada
middle-aged and older U.S. women. Diabetes Care. 2005;28:1438–1444. J, Adasme M, Briones L, Navarrete C. Comparison of lipoprotein-associ-
142. Ferreira I, Twisk JW, van Mechelen W, Kemper HC, Stehouwer CD. ated phospholipase A2 and high sensitive C-reactive protein as determi-
Development of fatness, fitness, and lifestyle from adolescence to the nants of metabolic syndrome in subjects without coronary heart disease:
age of 36 years: determinants of the metabolic syndrome in young in search of the best predictor. Int J Endocrinol. 2015;2015:934681. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

adults: the Amsterdam Growth and Health Longitudinal Study. Arch 10.1155/2015/934681
Intern Med. 2005;165:42–48. doi: 10.1001/archinte.165.1.42 159. Ryu S, Song J, Choi BY, Lee SJ, Kim WS, Chang Y, Kim DI, Suh BS,
143. Kwon YJ, Lee HS, Lee JW. Association of carbohydrate and fat in- Sung KC. Incidence and risk factors for metabolic syndrome in Korean
take with metabolic syndrome. Clin Nutr. 2018;37:746–751. doi: male workers, ages 30 to 39. Ann Epidemiol. 2007;17:245–252. doi:
10.1016/j.clnu.2017.06.022 10.1016/j.annepidem.2006.10.001
144. Morrison JA, Friedman LA, Wang P, Glueck CJ. Metabolic syndrome 160. Sui X, Church TS, Meriwether RA, Lobelo F, Blair SN. Uric acid and the
in childhood predicts adult metabolic syndrome and type 2 diabe- development of metabolic syndrome in women and men. Metabolism.
tes mellitus 25 to 30 years later. J Pediatr. 2008;152:201–206. doi: 2008;57:845–852. doi: 10.1016/j.metabol.2008.01.030
10.1016/j.jpeds.2007.09.010 161. Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F,
145. Cocate PG, Natali AJ, de Oliveira A, Alfenas Rde C, Peluzio Mdo C, Longo Roverato A, Guaraldi G, Lonardo A. Nonalcoholic fatty liver disease
GZ, dos Santos EC, Buthers JM, de Oliveira LL, Hermsdorff HH. Red but is associated with an almost twofold increased risk of incident type 2
not white meat consumption is associated with metabolic syndrome, in- diabetes and metabolic syndrome: evidence from a systematic review
sulin resistance and lipid peroxidation in Brazilian middle-aged men. Eur and meta-analysis. J Gastroenterol Hepatol. 2016;31:936–944. doi:
J Prev Cardiol. 2015;22:223–230. doi: 10.1177/2047487313507684 10.1111/jgh.13264
146. Deshmukh-Taskar P, Nicklas TA, Radcliffe JD, O’Neil CE, Liu Y. The re- 162. Lin CM, Hsieh CH, Lee CH, Pei D, Lin JD, Wu CZ, Liang YJ, Hung
lationship of breakfast skipping and type of breakfast consumed with YJ, Chen YL. Predictive value of serum gamma-glutamyltranspep-
overweight/obesity, abdominal obesity, other cardiometabolic risk factors tidase for future cardiometabolic dysregulation in adolescents: a
and the metabolic syndrome in young adults: the National Health and 10-year longitudinal study. Sci Rep. 2017;7:9636. doi: 10.1038/
Nutrition Examination Survey (NHANES): 1999–2006. Public Health Nutr. s41598-017-09719-8
2013;16:2073–2082. doi: 10.1017/S1368980012004296 163. Ingelsson E, Pencina MJ, Tofler GH, Benjamin EJ, Lanier KJ, Jacques PF,
147. Baik I, Shin C. Prospective study of alcohol consumption and Fox CS, Meigs JB, Levy D, Larson MG, Selhub J, D’Agostino RB Sr, Wang
metabolic syndrome. Am J Clin Nutr. 2008;87:1455–1463. doi: TJ, Vasan RS. Multimarker approach to evaluate the incidence of the
10.1093/ajcn/87.5.1455 metabolic syndrome and longitudinal changes in metabolic risk factors:
148. Chandola T, Brunner E, Marmot M. Chronic stress at work and the the Framingham Offspring Study. Circulation. 2007;116:984–992. doi:
metabolic syndrome: prospective study. BMJ. 2006;332:521–525. doi: 10.1161/CIRCULATIONAHA.107.708537
10.1136/bmj.38693.435301.80 164. Lakhani I, Gong M, Wong WT, Bazoukis G, Lampropoulos K, Wong
149. Sun SS, Liang R, Huang TT, Daniels SR, Arslanian S, Liu K, Grave SH, Wu WKK, Wong MCS, Ong KL, Liu T, Tse G; International Health
GD, Siervogel RM. Childhood obesity predicts adult metabolic syn- Informatics Study (IHIS) Network. Fibroblast growth factor 21 in cardio-
drome: the Fels Longitudinal Study. J Pediatr. 2008;152:191–200. doi: metabolic disorders: a systematic review and meta-analysis. Metabolism.
10.1016/j.jpeds.2007.07.055 2018;83:11–17. doi: 10.1016/j.metabol.2018.01.017
150. Tong J, Boyko EJ, Utzschneider KM, McNeely MJ, Hayashi T, Carr DB, 165. Galletti F, Barbato A, Versiero M, Iacone R, Russo O, Barba G, Siani A,
Wallace TM, Zraika S, Gerchman F, Leonetti DL, Fujimoto WY, Kahn Cappuccio FP, Farinaro E, della Valle E, Strazzullo P. Circulating leptin
SE. Intra-abdominal fat accumulation predicts the development of the levels predict the development of metabolic syndrome in middle-aged
metabolic syndrome in non-diabetic Japanese-Americans. Diabetologia. men: an 8-year follow-up study. J Hypertens. 2007;25:1671–1677. doi:
2007;50:1156–1160. doi: 10.1007/s00125-007-0651-y 10.1097/HJH.0b013e3281afa09e
151. Vergnaud AC, Bertrais S, Oppert JM, Maillard-Teyssier L, Galan P, 166. Iwanaga S, Sakano N, Taketa K, Takahashi N, Wang DH, Takahashi
Hercberg S, Czernichow S. Weight fluctuations and risk for metabolic H, Kubo M, Miyatake N, Ogino K. Comparison of serum ferritin and

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e175

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

oxidative stress biomarkers between Japanese workers with and with- training effects on metabolic syndrome (from the Studies of a Targeted
CLINICAL STATEMENTS

out metabolic syndrome. Obes Res Clin Pract. 2014;8:e201–e298. doi: Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).
AND GUIDELINES

10.1016/j.orcp.2013.01.003 Am J Cardiol. 2011;108:838–844. doi: 10.1016/j.amjcard.2011.04.037

167. Hassinen M, Lakka TA, Komulainen P, Gylling H, Nissinen A, Rauramaa R. 185. Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB.
C-reactive protein and metabolic syndrome in elderly women: a 12-year Metabolic syndrome as a precursor of cardiovascular disease and
follow-up study. Diabetes Care. 2006;29:931–932. type 2 diabetes mellitus. Circulation. 2005;112:3066–3072. doi:
168. Laaksonen DE, Niskanen L, Nyyssönen K, Punnonen K, Tuomainen TP, 10.1161/CIRCULATIONAHA.105.539528
Valkonen VP, Salonen R, Salonen JT. C-reactive protein and the devel- 186. Grooms KN, Ommerborn MJ, Pham DQ, Djousse L, Clark CR.
opment of the metabolic syndrome and diabetes in middle-aged men. Dietary fiber intake and cardiometabolic risks among US adults,
Diabetologia. 2004;47:1403–1410. doi: 10.1007/s00125-004-1472-x NHANES 1999–2010. Am J Med. 2013;126:1059–1067.e4. doi:
169. Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, Yeung DC, 10.1016/j.amjmed.2013.07.023
Janus ED, Sham PC, Lam KS. Circulating adipocyte-fatty acid bind- 187. Wei B, Liu Y, Lin X, Fang Y, Cui J, Wan J. Dietary fiber intake and risk of meta-
ing protein levels predict the development of the metabolic syndrome: bolic syndrome: a meta-analysis of observational studies [published online
a 5-year prospective study. Circulation. 2007;115:1537–1543. doi: October 31, 2017]. Clin Nutr. doi: 10.1016/j.cinu.2017.10.019. https://
10.1161/CIRCULATIONAHA.106.647503 www.clinicalnutritionjournal.com/article/S0261-5614(17)31392-4/
170. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, fulltext.
Gaziano JM, Liu S. Sex hormone-binding globulin and risk of type 2 188. Shin JY, Kim JY, Kang HT, Han KH, Shim JY. Effect of fruits and veg-
diabetes in women and men. N Engl J Med. 2009;361:1152–1163. doi: etables on metabolic syndrome: a systematic review and meta-analysis of
10.1056/NEJMoa0804381 randomized controlled trials. Int J Food Sci Nutr. 2015;66:416–425. doi:
171. Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hor- 10.3109/09637486.2015.1025716
mone-binding globulin with metabolic syndrome and insulin resistance in 189. Vázquez C, Botella-Carretero JI, Corella D, Fiol M, Lage M, Lurbe E,
men. Diabetes Care. 2010;33:1618–1624. doi: 10.2337/dc09-1788 Richart C, Fernández-Real JM, Fuentes F, Ordóñez A, de Cos AI, Salas-
172. Yadav SS, Mandal RK, Singh MK, Verma A, Dwivedi P, Sethi R, Usman K, Salvadó J, Burguera B, Estruch R, Ros E, Pastor O, Casanueva FF; WISH-
Khattri S. High serum level of matrix metalloproteinase 9 and promoter CARE Study Investigators. White fish reduces cardiovascular risk factors in
polymorphism – 1562 C:T as a new risk factor for metabolic syndrome. patients with metabolic syndrome: the WISH-CARE study, a multicenter
DNA Cell Biol. 2014;33:816–822. doi: 10.1089/dna.2014.2511 randomized clinical trial. Nutr Metab Cardiovasc Dis. 2014;24:328–335.
173. Nibali L, Tatarakis N, Needleman I, Tu YK, D’Aiuto F, Rizzo M, Donos N. doi: 10.1016/j.numecd.2013.09.018
Clinical review: association between metabolic syndrome and periodon- 190. Echeverria G, McGee EE, Urquiaga I, Jiménez P, D’Acuña S, Villarroel
titis: a systematic review and meta-analysis. J Clin Endocrinol Metab. L, Velasco N, Leighton F, Rigotti A. Inverse associations between a lo-
2013;98:913–920. doi: 10.1210/jc.2012-3552 cally validated Mediterranean diet index, overweight/obesity, and
174. Teppala S, Madhavan S, Shankar A. Bisphenol A and metabolic syn- metabolic syndrome in Chilean adults. Nutrients. 2017;9:E862. doi:
drome: results from NHANES. Int J Endocrinol. 2012;2012:598180. doi: 10.3390/nu9080862
10.1155/2012/598180 191. Babio N, Becerra-Tomás N, Martínez-González MÁ, Corella D, Estruch R,
175. Oh SW, Han KH, Han SY, Koo HS, Kim S, Chin HJ. Association Ros E, Sayón-Orea C, Fitó M, Serra-Majem L, Arós F, Lamuela-Raventós
of sodium excretion with metabolic syndrome, insulin resis- RM, Lapetra J, Gómez-Gracia E, Fiol M, Díaz-López A, Sorlí JV, Martínez
tance, and body fat. Medicine (Baltimore). 2015;94:e1650. doi: JA, Salas-Salvadó J; PREDIMED Investigators. Consumption of yogurt,
10.1097/MD.0000000000001650 low-fat milk, and other low-fat dairy products is associated with lower
176. Janczura M, Bochenek G, Nowobilski R, Dropinski J, Kotula-Horowitz K, risk of metabolic syndrome incidence in an elderly Mediterranean popu-
Downloaded from http://ahajournals.org by on February 7, 2019

Laskowicz B, Stanisz A, Lelakowski J, Domagala T. The relationship of lation. J Nutr. 2015;145:2308–2316. doi: 10.3945/jn.115.214593
metabolic syndrome with stress, coronary heart disease and pulmonary 192. Barreto FM, Colado Simão AN, Morimoto HK, Batisti Lozovoy MA,
function: an occupational cohort-based study [published correction ap- Dichi I, Helena da Silva Miglioranza L. Beneficial effects of Lactobacillus
pears in PLoS One. 2015;10:e0139408]. PLoS One. 2015;10:e0133750. plantarum on glycemia and homocysteine levels in postmenopausal
doi: 10.1371/journal.pone.0133750 women with metabolic syndrome. Nutrition. 2014;30:939–942. doi:
177. Edwards MK, Loprinzi PD. High amounts of sitting, low cardiorespiratory 10.1016/j.nut.2013.12.004
fitness, and low physical activity levels: 3 key ingredients in the recipe 193. Hill AM, Harris Jackson KA, Roussell MA, West SG, Kris-Etherton PM.
for influencing metabolic syndrome prevalence. Am J Health Promot. Type and amount of dietary protein in the treatment of metabolic syn-
2018;32:587–594. doi: 10.1177/0890117116684889 drome: a randomized controlled trial. Am J Clin Nutr. 2015;102:757–
178. Du R, Cheng D, Lin L, Sun J, Peng K, Xu Y, Xu M, Chen Y, Bi Y, Wang 770. doi: 10.3945/ajcn.114.104026
W, Lu J, Ning G. Association between serum CA 19-9 and metabolic 194. Vernarelli JA, Lambert JD. Tea consumption is inversely associated with
syndrome: a cross-sectional study. J Diabetes. 2017;9:1040–1047. doi: weight status and other markers for metabolic syndrome in US adults.
10.1111/1753-0407.12523 Eur J Nutr. 2013;52:1039–1048. doi: 10.1007/s00394-012-0410-9
179. Huang LL, Dou DM, Liu N, Wang XX, Fu LY, Wu X, Wang P. Association of 195. Shang F, Li X, Jiang X. Coffee consumption and risk of the metabol-
erythrocyte parameters with metabolic syndrome in the Pearl River Delta ic syndrome: a meta-analysis. Diabetes Metab. 2016;42:80–87. doi:
region of China: a cross sectional study. BMJ Open. 2018;8:e019792. 10.1016/j.diabet.2015.09.001
doi: 10.1136/bmjopen-2017-019792 196. Maki KC, Fulgoni VL 3rd, Keast DR, Rains TM, Park KM, Rubin MR.
180. Kim MK, Chon SJ, Noe EB, Roh YH, Yun BH, Cho S, Choi YS, Lee Vitamin D intake and status are associated with lower prevalence of met-
BS, Seo SK. Associations of dietary calcium intake with metabolic abolic syndrome in U.S. adults: National Health and Nutrition Examination
syndrome and bone mineral density among the Korean popula- Surveys 2003-2006. Metab Syndr Relat Disord. 2012;10:363–372. doi:
tion: KNHANES 2008-2011. Osteoporos Int. 2017;28:299–308. doi: 10.1089/met.2012.0020
10.1007/s00198-016-3717-1 197. O’Neil CE, Fulgoni VL 3rd, Nicklas TA. Tree nut consumption is associ-
181. Xu S, Wan Y, Xu M, Ming J, Xing Y, An F, Ji Q. The association be- ated with better adiposity measures and cardiovascular and metabolic
tween obstructive sleep apnea and metabolic syndrome: a system- syndrome health risk factors in U.S. adults: NHANES 2005-2010. Nutr J.
atic review and meta-analysis. BMC Pulm Med. 2015;15:105. doi: 2015;14:64. doi: 10.1186/s12937-015-0052-x
10.1186/s12890-015-0102-3 198. Hosseinpour-Niazi S, Hosseini S, Mirmiran P, Azizi F. Prospective study of
182. Jurca R, Lamonte MJ, Barlow CE, Kampert JB, Church TS, Blair SN. nut consumption and incidence of metabolic syndrome: Tehran Lipid and
Association of muscular strength with incidence of metabolic syndrome Glucose Study. Nutrients. 2017;9(10):E1056. doi: 10.3390/nu9101056
in men. Med Sci Sports Exerc. 2005;37:1849–1855. 199. Fulgoni VL 3rd, Dreher M, Davenport AJ. Avocado consumption is as-
183. Lin X, Zhang X, Guo J, Roberts CK, McKenzie S, Wu WC, Liu S, Song sociated with better diet quality and nutrient intake, and lower meta-
Y. Effects of exercise training on cardiorespiratory fitness and biomark- bolic syndrome risk in US adults: results from the National Health and
ers of cardiometabolic health: a systematic review and meta-analysis of Nutrition Examination Survey (NHANES) 2001-2008. Nutr J. 2013;12:1.
randomized controlled trials. J Am Heart Assoc. 2015;4:e002014. doi: doi: 10.1186/1475-2891-12-1
10.1161/JAHA.115.002014 200. Kim YS, Xun P, He K. Fish consumption, long-chain omega-3 polyunsatu-
184. Bateman LA, Slentz CA, Willis LH, Shields AT, Piner LW, Bales CW, rated fatty acid intake and risk of metabolic syndrome: a meta-analysis.
Houmard JA, Kraus WE. Comparison of aerobic versus resistance exercise Nutrients. 2015;7:2085–2100. doi: 10.3390/nu7042085

e176 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 10

201. Shin D, Joh HK, Kim KH, Park SM. Benefits of potassium intake on Schmid H, Botero R, Urina M, Lara J, Foss MC, Márquez G, Harrap S,

CLINICAL STATEMENTS
metabolic syndrome: the fourth Korean National Health and Nutrition Ramírez AJ, Zanchetti A; Latin America Expert Group. Latin American

AND GUIDELINES
Examination Survey (KNHANES IV). Atherosclerosis. 2013;230:80–85. consensus on hypertension in patients with diabetes type 2 and meta-
doi: 10.1016/j.atherosclerosis.2013.06.025 bolic syndrome. J Hypertens. 2013;31:223–238. doi: 10.1097/HJH.
202. Lopez-Pascual A, Bes-Rastrollo M, Sayón-Orea C, Perez-Cornago A, 0b013e32835c5444
Díaz-Gutiérrez J, Pons JJ, Martínez-González MA, González-Muniesa P, 217. Sawant A, Mankeshwar R, Shah S, Raghavan R, Dhongde G, Raje
Martínez JA. Living at a geographically higher elevation is associated with H, D’souza S, Subramanium A, Dhairyawan P, Todur S, Ashavaid
lower risk of metabolic syndrome: prospective analysis of the SUN co- TF. Prevalence of metabolic syndrome in urban India. Cholesterol.
hort. Front Physiol. 2016;7:658. doi: 10.3389/fphys.2016.00658 2011;2011:920983. doi: 10.1155/2011/920983
203. Hanley AJ, Williams K, Festa A, Wagenknecht LE, D’Agostino RB Jr, Haffner 218. Yadav D, Mahajan S, Subramanian SK, Bisen PS, Chung CH, Prasad
SM. Liver markers and development of the metabolic syndrome: the GB. Prevalence of metabolic syndrome in type 2 diabetes mellitus us-
Insulin Resistance Atherosclerosis Study. Diabetes. 2005;54:3140–3147. ing NCEP-ATPIII, IDF and WHO definition and its agreement in Gwalior
204. Liu S, Sun Q. Sex differences, endogenous sex-hormone hormones, Chambal region of Central India. Glob J Health Sci. 2013;5:142–155.
sex-hormone binding globulin, and exogenous disruptors in diabetes doi: 10.5539/gjhs.v5n6p142
and related metabolic outcomes. J Diabetes. 2018;10:428–441. doi: 219. Barik A, Das K, Chowdhury A, Rai RK. Metabolic syndrome among
10.1111/1753-0407.12517 rural Indian adults. Clin Nutr ESPEN. 2018;23:129–135. doi:
205. Al-Khalidi B, Kimball SM, Rotondi MA, Ardern CI. Standardized serum 10.1016/j.clnesp.2017.11.002
25-hydroxyvitamin D concentrations are inversely associated with cardio- 220. Khanam MA, Qiu C, Lindeboom W, Streatfield PK, Kabir ZN, Wahlin
metabolic disease in U.S. adults: a cross-sectional analysis of NHANES, Å. The metabolic syndrome: prevalence, associated factors, and im-
2001-2010 [published correction appears in Nutr J. 2017;16:32]. Nutr J. pact on survival among older persons in rural Bangladesh. PLoS One.
2017;16:16. doi: 10.1186/s12937-017-0237-6 2011;6:e20259. doi: 10.1371/journal.pone.0020259
206. Mayneris-Perxachs J, Guerendiain M, Castellote AI, Estruch R, Covas MI, 221. Amirkalali B, Fakhrzadeh H, Sharifi F, Kelishadi R, Zamani F, Asayesh
Fitó M, Salas-Salvadó J, Martínez-González MA, Aros F, Lamuela-Raventós H, Safiri S, Samavat T, Qorbani M. Prevalence of metabolic syndrome
RM, López-Sabater MC; for PREDIMED Study Investigators. Plasma fatty and its components in the Iranian adult population: a systematic re-
acid composition, estimated desaturase activities, and their relation with view and meta-analysis. Iran Red Crescent Med J. 2015;17:e24723. doi:
the metabolic syndrome in a population at high risk of cardiovascular 10.5812/ircmj.24723
disease. Clin Nutr. 2014;33:90–97. doi: 10.1016/j.clnu.2013.03.001 222. Oguoma VM, Nwose EU, Richards RS. Prevalence of cardio-metabolic
207. Shuval K, Barlow CE, Finley CE, Gabriel KP, Schmidt MD, DeFina LF. syndrome in Nigeria: a systematic review. Public Health. 2015;129:413–
Standing, obesity, and metabolic syndrome: findings from the Cooper 423. doi: 10.1016/j.puhe.2015.01.017
Center Longitudinal Study. Mayo Clin Proc. 2015;90:1524–1532. doi: 223. Peer N, Lombard C, Steyn K, Levitt N. High prevalence of metabolic syn-
10.1016/j.mayocp.2015.07.022 drome in the Black population of Cape Town: the Cardiovascular Risk in
208. Sabaté J, Wien M. A perspective on vegetarian dietary patterns and risk Black South Africans (CRIBSA) study. Eur J Prev Cardiol. 2015;22:1036–
of metabolic syndrome. Br J Nutr. 2015;113(suppl 2):S136–S143. doi: 1042. doi: 10.1177/2047487314549744
10.1017/S0007114514004139 224. Orces CH, Gavilanez EL. The prevalence of metabolic syndrome among
209. Benseñor IM, Goulart AC, Molina Mdel C, de Miranda ÉJ, Santos IS, older adults in Ecuador: results of the SABE survey. Diabetes Metab
Lotufo PA. Thyrotropin levels, insulin resistance, and metabolic syn- Syndr. 2017;11 Suppl 2:S555–S560. doi: 10.1016/j.dsx.2017.04.004
drome: a cross-sectional analysis in the Brazilian Longitudinal Study of 225. Raimi TH, Odusan O, Fasanmade OA, Odewabi AO, Ohwovoriole AE.
Adult Health (ELSA-Brasil). Metab Syndr Relat Disord. 2015;13:362–369. Metabolic syndrome among apparently healthy Nigerians with the har-
Downloaded from http://ahajournals.org by on February 7, 2019

doi: 10.1089/met.2015.0045 monized criteria: prevalence and concordance with the International
210. Vidot DC, Prado G, Hlaing WM, Florez HJ, Arheart KL, Messiah SE. Diabetes Federation (IDF) and Third Report of the National Cholesterol
Metabolic syndrome among marijuana users in the United States: an Education Programme-Adult Treatment Panel III (NCEP-ATP III) criteria.” J
analysis of National Health and Nutrition Examination Survey data. Am J Cardiovasc Disease Res. 2017;8:145–150.
Med. 2016;129:173–179. doi: 10.1016/j.amjmed.2015.10.019 226. Binh TQ, Phuong PT, Nhung BT, Tung do D. Metabolic syndrome among
211. Kim S, Song Y, Lee JE, Jun S, Shin S, Wie GA, Cho YH, Joung H. Total a middle-aged population in the Red River Delta region of Vietnam. BMC
antioxidant capacity from dietary supplement decreases the likelihood of Endocr Disord. 2014;14:77. doi: 10.1186/1472-6823-14-77
having metabolic syndrome in Korean adults. Nutrients. 2017;9:E1055. 227. Zhao Y, Yan H, Yang R, Li Q, Dang S, Wang Y. Prevalence and determi-
doi: 10.3390/nu9101055 nants of metabolic syndrome among adults in a rural area of Northwest
212. Baudry J, Lelong H, Adriouch S, Julia C, Allès B, Hercberg S, Touvier China. PLoS One. 2014;9:e91578. doi: 10.1371/journal.pone.0091578
M, Lairon D, Galan P, Kesse-Guyot E. Association between organic 228. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K,
food consumption and metabolic syndrome: cross-sectional results Foco L, Gaye A, Gögele M, Heier M, Hiekkalinna T, Joensuu A, Newby C,
from the NutriNet-Santé study. Eur J Nutr. 2018;57:2477–2488. doi: Pang C, Partinen E, Reischl E, Schwienbacher C, Tammesoo ML, Swertz
10.1007/s00394-107-1520-1 MA, Burton P, Ferretti V, Fortier I, Giepmans L, Harris JR, Hillege HL,
213. Cheriyath P, Duan Y, Qian Z, Nambiar L, Liao D. Obesity, physical activity Holmen J, Jula A, Kootstra-Ros JE, Kvaløy K, Holmen TL, Männistö S,
and the development of metabolic syndrome: the Atherosclerosis Risk Metspalu A, Midthjell K, Murtagh MJ, Peters A, Pramstaller PP, Saaristo
in Communities study. Eur J Cardiovasc Prev Rehabil. 2010;17:309–313. T, Salomaa V, Stolk RP, Uusitupa M, van der Harst P, van der Klauw MM,
doi: 10.1097/HJR.0b013e32833189b8 Waldenberger M, Perola M, Wolffenbuttel BH. The prevalence of meta-
214. Zhang D, Liu X, Liu Y, Sun X, Wang B, Ren Y, Zhao Y, Zhou J, Han C, bolic syndrome and metabolically healthy obesity in Europe: a collabora-
Yin L, Zhao J, Shi Y, Zhang M, Hu D. Leisure-time physical activity and tive analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.
incident metabolic syndrome: a systematic review and dose-response doi: 10.1186/1472-6823-14-9
meta-analysis of cohort studies. Metabolism. 2017;75:36–44. doi: 229. Vernay M, Salanave B, de Peretti C, Druet C, Malon A, Deschamps V,
10.1016/j.metabol.2017.08.001 Hercberg S, Castetbon K. Metabolic syndrome and socioeconomic status
215. Leiter LA, Fitchett DH, Gilbert RE, Gupta M, Mancini GB, McFarlane in France: the French Nutrition and Health Survey (ENNS, 2006-2007). Int
PA, Ross R, Teoh H, Verma S, Anand S, Camelon K, Chow CM, Cox JL, J Public Health. 2013;58:855–864. doi: 10.1007/s00038-013-0501-2
Després JP, Genest J, Harris SB, Lau DC, Lewanczuk R, Liu PP, Lonn EM, 230. de Carvalho Vidigal F, Bressan J, Babio N, Salas-Salvadó J. Prevalence of
McPherson R, Poirier P, Qaadri S, Rabasa-Lhoret R, Rabkin SW, Sharma metabolic syndrome in Brazilian adults: a systematic review. BMC Public
AM, Steele AW, Stone JA, Tardif JC, Tobe S, Ur E; Cardiometabolic Health. 2013;13:1198. doi: 10.1186/1471-2458-13-1198
Risk Working Group: Executive Committee. Cardiometabolic risk in 231. Salas R, Bibiloni Mdel M, Ramos E, Villarreal JZ, Pons A, Tur JA, Sureda A.
Canada: a detailed analysis and position paper by the Cardiometabolic Metabolic syndrome prevalence among Northern Mexican adult popula-
Risk Working Group. Can J Cardiol. 2011;27:e1–e33. doi: 10.1016/j. tion. PLoS One. 2014;9:e105581. doi: 10.1371/journal.pone.0105581
cjca.2010.12.054 232. Li M, McCulloch B, McDermott R. Metabolic syndrome and incident cor-
216. López-Jaramillo P, Sánchez RA, Diaz M, Cobos L, Bryce A, Parra Carrillo onary heart disease in Australian indigenous populations. Obesity (Silver
JZ, Lizcano F, Lanas F, Sinay I, Sierra ID, Peñaherrera E, Bendersky M, Spring). 2012;20:1308–1312. doi: 10.1038/oby.2011.156

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e177

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

11. KIDNEY DISEASE Abbreviations Used in Chapter 11 Continued

CLINICAL STATEMENTS

NIS National (Nationwide) Inpatient Sample

ICD-10 N18.0. See Charts 11-1 through 11-15
AND GUIDELINES

OR odds ratio
OSA obstructive sleep apnea
PAD peripheral artery disease
Click here to return to the Table of Contents
PCI percutaneous coronary intervention
PE pulmonary embolism

Definition PI Pacific Islander

RR relative risk
CKD, defined as reduced GFR (<60 mL·min−1·1.73 SBP systolic blood pressure
m−2), excess urinary albumin excretion (≥30 mg/d or SCA sudden cardiac arrest
mg/gCr), or both, is a serious health condition and a SCD sudden cardiac death
SES socioeconomic status
worldwide public health problem that is associated
SHARP Study of Heart and Renal Protection
with poor outcomes and a high cost to the US health- SNP single-nucleotide polymorphism
care system.1 SPRINT Systolic Blood Pressure Intervention Trial
SR self-report
Abbreviations Used in Chapter 11 STS Society of Thoracic Surgeons
ACC American College of Cardiology TAVR transcatheter aortic valve replacement
ACR albumin-to-creatinine ratio TIA transient ischemic attack
AF atrial fibrillation TVT Transcatheter Valve Therapy
AHA American Heart Association USRDS United States Renal Data System
AI American Indian VA ventricular arrhythmia
AMI acute myocardial infarction VHD valvular heart disease
AN Alaska Native VTE venous thromboembolism
ARIC Atherosclerosis Risk in Communities Study
ASCVD atherosclerotic cardiovascular disease • GFR is usually estimated from the serum cre-
ASHD atherosclerotic heart disease
atinine level using equations that account for
BMI body mass index
BP blood pressure
age, sex, and race. The CKD-EPI equation more
CABG coronary artery bypass graft surgery accurately estimates GFR from serum creatinine
CAD coronary artery disease than the previously established MDRD Study
CARDIA Coronary Artery Risk Development in Young Adults equation.2
Downloaded from http://ahajournals.org by on February 7, 2019

CHD coronary heart disease • The spot urine ACR ratio is recommended as a
CHF congestive heart failure
measure of urine albumin excretion.
CHS Cardiovascular Health Study
CI confidence interval The KDIGO CKD 2012 guideline recommends charac-
CKD chronic kidney disease terizing CKD according to eGFR category (G1–G5) and
CKD-EPI Chronic Kidney Disease Epidemiology Collaboration albuminuria category (A1–A3), as well as cause of CKD
CVA cerebrovascular accident (Chart 11-1).3
CVD cardiovascular disease
ESRD is defined as severe CKD requiring chronic
DBP diastolic blood pressure
DM diabetes mellitus
renal replacement treatment such as hemodialysis, peri-
eGFR estimated glomerular filtration rate toneal dialysis, or kidney transplantation.1 ESRD is an
ESRD end-stage renal disease extremely high-risk population for cardiovascular mor-
GBD Global Burden of Disease bidity and mortality.
GFR glomerular filtration rate
GWAS Genome-Wide Association Study
HANDLS Health Aging in Neighborhoods of Diversity Across the Life Prevalence
Span
HBP high blood pressure (See Charts 11-1 through 11-4)
HF heart failure • According to the United States Renal Data
HR hazard ratio
System, the overall prevalence of CKD in the
HTN hypertension
ICD-10 International Classification of Diseases, 10th Revision United States among NHANES participants aged
IHD ischemic heart disease ≥20 years was 14.8% (95% CI, 13.6%–16.0%)
JHS Jackson Heart Study in 2011 to 2014.1 The prevalence of CKD by
KDIGO Kidney Disease: Improving Global Outcomes eGFR and albuminuria categories is shown in
MACE major adverse cardiovascular events
Chart 11-1.
MDRD Modification of Diet in Renal Disease
MESA Multi-Ethnic Study of Atherosclerosis
• The prevalence of CKD increases substantially
MR mitral regurgitation with age, as follows1:
NH non-Hispanic — 6.6% for those 20 to 39 years of age
NHANES National Health and Nutrition Examination Survey — 10.6% for those 40 to 59 years of age
(Continued ) — 32.6% for those ≥60 years of age

e178 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

• From 1999 to 2014, the prevalence of ACR ≥30 11-2). Despite improvements in incidence rate

CLINICAL STATEMENTS
mg/g was higher but prevalence of eGFR <60 among blacks and Native Americans, substantial

AND GUIDELINES
mL·min−1·1.73 m−2 was lower among NH blacks disparities persist (Chart 11-5).
than NH whites.1 • Among the very old (>80 years), the prevalence
• At the end of 2015, the unadjusted prevalence of an eGFR <60 mL·min−1·1.73 m−2 increased
of ESRD estimated from cases reported to the from 40.5% in 1988 to 1994 to 49.9% and
Centers for Medicare & Medicaid Services in 51.2% in 1999 to 2004 and 2005 to 2010,
the United States was 2128 per million (0.21%; respectively. The prevalence of albuminuria (ACR
Chart 11-2). Of the 703 243 total patients receiv- ≥30 mg/g) was 30.9%, 33.0%, and 30.6%
ing treatment for ESRD in the United States, in 1988 to 1994, 1999 to 2004, and 2005 to
63% were on hemodialysis, 7% were on peri- 2010, respectively.1
toneal dialysis, and 30% had received a kidney
transplant.1
Costs
• The prevalence of ESRD varies regionally across
the United States (Chart 11-3), mirroring the • In 2015, Medicare spent over $64 billion caring
prevalence of traditional risk factors such as DM for people with CKD. More than 70% of CKD
or hypertension.1 spending was attributable to patients who had
• ESRD prevalence is highest in Native Hawaiians/ comorbid DM or CHF.1
Pacific Islanders than in other races, and preva- • The total annual cost of treating ESRD in the
lence is higher among Hispanics than NH individ- United States was $33.9 billion in 2015, which
uals (Chart 11-4).1 represents >7% of total Medicare claims paid.1
In 2015, total spending per patient was $88 750
for patients on hemodialysis, $75 140 for those
Incidence receiving peritoneal dialysis, and $34 084 for
(See Chart 11-5) transplant patients.1
• For US adults aged 30 to 49, 50 to 64, and
≥65 years without CKD, the residual lifetime Risk Factors
incidences of CKD are projected to be 54%, (See Charts 11-6 and 11-7)
Downloaded from http://ahajournals.org by on February 7, 2019

52%, and 42%, respectively, in the CKD Health

• Many traditional CVD risk factors are also risk
Policy Model simulation based on 1999 to 2010
factors for CKD, including older age, male sex,
NHANES data.4
hypertension, DM, smoking, and family history
• The incidence of ESRD is higher among blacks than of CVD (Chart 11-6). In NHANES 2011 to 2014,
whites, a disparity that persists even after control- the prevalence of CKD was 32% in adults aged
ling for major ESRD risk factors and that might ≥20 years with HBP and 39% in adults with DM.
be explained in part by the higher prevalence of Among adults with obesity (BMI >30 kg/m2),
albuminuria and APOL1 in this population.5–7 nearly 18% had CKD.1
• Among those aged ≥60 years with CKD in
Secular Trends NHANES 2013 to 2014, 59% had HBP and 35%
had DM.9
(See Charts 11-2 and 11-5) • Even early stages of elevated BP and stage 1
• According to NHANES data, the prevalence of hypertension as defined by the 2017 ACC/AHA
CKD (eGFR 15–59 mL·min−1·1.73 m−2) in the guidelines (SBP of 120–139 mm Hg or DBP of
United States increased slowly over time until 80–89 mm Hg) were associated with incident
2003 to 2004 because of an aging population decreased eGFR (<60 mL·min−1·1.73 m−2) in a
and higher prevalence of risk factors, but the meta-analysis of observational cohorts (RR, 1.19
prevalence plateaued from 2004 to 2012.8 [95% CI, 1.07–1.33] over a mean follow-up of
• The prevalence of ESRD is now increasing more 6.5 years).10
rapidly primarily because of improved survival, • OSA is associated with CKD and CKD progres-
because the incidence rate appears to be stabiliz- sion independent of BMI and other traditional risk
ing or decreasing slightly (Chart 11-2).1 factors.11
• The prevalence of CKD in adults ≥30 years of age • Zip code–level poverty is associated with ≈25%
is projected to increase to 14.4% in 2020 and higher ESRD incidence after accounting for
16.7% in 2030.4 age, sex, and race/ethnicity, and this association
• The incidence of ESRD adjusted for age, sex, race, appears to be getting stronger over time (2005–
and ethnicity has been stable for >15 years (Chart 2010 versus 1995–2004).12

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e179

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

• Importantly, cardiovascular fitness and healthy age-standardized prevalence only increased

CLINICAL STATEMENTS

lifestyles are associated with decreased risk of 2.1%.

AND GUIDELINES

CKD.13–16 For example, having more of the AHA’s — CKD attributable to HBP rose 26% to 79 mil-
Life’s Simple 7 ideal health factors was associated lion (95% CI, 68–91 million), but age-stan-
with progressively lower risk of incident CKD in dardized prevalence only increased 0.2%.
the ARIC study (Chart 11-7).15 — CKD attributable to glomerulonephritis rose
29% to 67 million (95% CI, 58–77 mil-
lion), but age standardized prevalence only
Awareness increased 1.1%.
• Awareness of CKD status in NHANES was particu- — CKD attributable to other causes rose 26%
larly low, ranging from 3% to 5% for early-stage to 95 million (95% CI, 81–109 million), but
CKD to 53% for more advanced CKD (eGFR 15– age-standardized prevalence only increased
29 mL·min−1·1.73 m−2).17 by 0.1%.
• The prevalence of recognized CKD, meaning that • CKD rose from the 25th leading cause of death
a provider or billing coder recognized the preva- in 1990 to the 17th leading cause of death in
lence of CKD, was also low in the Medicare 5% 2015.19
sample, but it has increased over time, from 5.9%
in 2006 to 11.7% in 2015.1
Family History and Genetics
• There is evidence of moderate heritability for cre-
Global Burden of Kidney Disease atinine and GFR, which supports a genetic com-
(See Charts 11-8 through 11-11) ponent of CKD.20
• The GBD 2016 Study used statistical models and • GWASs have revealed several candidate loci
data on incidence, prevalence, case fatality, excess for CKD phenotypes, including GFR, albumin-
mortality, and cause-specific mortality to estimate uria, kidney injury, and diabetic kidney disease,
disease burden for 315 diseases and injuries in although the clinical implications and utility of
195 countries and territories.17 these genetic variants are not yet clear.20–28
• Race differences in CKD prevalence might be
— According to the GBD Study, the prevalence
attributable to differences in genetic risk. The
Downloaded from http://ahajournals.org by on February 7, 2019

of CKD is rising in almost every country of

APOL1 gene has been well studied as a kidney
the world, primarily because of aging popu-
disease locus in individuals of African ancestry.7
lations (Chart 11-8).17 SNPs in APOL1 that are present in individuals of
• In 2016, the total estimated prevalence is 276 African ancestry but absent in other racial groups
million people (95% CI, 252–300 million), a might have been subject to positive selection,
31% increase since 2006.17 Notably, there have conferring protection against trypanosome infec-
been downward revisions of estimated CKD tion but leading to increased risk of renal disease,
prevalence in recent years compared with prior potentially through disruption of mitochondrial
GBD estimates because of a refinement of mod- function.21
eling methods. The age-standardized prevalence • Although certain variants of APOL1 increase risk, it
of CKD is highest in the Middle East/North Africa only explains a portion of the disparity in ESRD risk
region, sub-Saharan Africa, and central Latin between blacks and nonblacks.22,23 For example,
America (Chart 11-9).17 eGFR decline was faster even for black subjects
• Globally, the burden of years lived with disability with low-risk APOL1 status (0–1 allele) than for
attributable to CKD is generally heaviest in high- whites in CARDIA; this difference was attenuated
income countries (Chart 11-10). Total years lived by adjustment for SES and traditional risk factors.24
with disability attributable to CKD were 8.8 mil- • APOL1 does not appear to be associated with
lion (95% CI, 6.6–11.1 million) in 2016.17 overall risk for CVD among blacks with hyperten-
• The Pacific Island countries had the highest mor- sion-attributed CKD.25
tality rates attributable to CKD in 2016 (Chart
11-11).17
• GBD 2015 has also estimated the global preva- Social Determinants of CKD
lence of CKD by cause and the percentage change • A recent meta-analysis of 43 studies examining
from 2005 to 201518: associations between socioeconomic indicators
— The prevalence of CKD attributable to (income, education and occupation) found that
DM rose 27% during this time period to lower SES, particularly income, was associated with
101 million (95% CI, 87–116 million), but a higher prevalence of CKD and faster progression

e180 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

to ESRD.26 This association was observed in higher- 57% of peritoneal dialysis patients and 42% of

CLINICAL STATEMENTS
versus lower- or middle-income countries and was transplant patients have any CVD (Chart 11-13).

AND GUIDELINES
more pronounced in the United States relative to
Incidence of CVD Events Among People With CKD
Europe.
• In 3 community-based cohort studies (JHS, CHS,
• In a cross-sectional analysis of 9126 lower-income
and MESA), absolute incidence rates for HF, CHD,
participants from NHANES 2003 to 2008, food
and stroke for participants with versus without
insecurity (ie, the inability to acquire nutritional
CKD were 22 versus 6.2 (per 1000 person-years)
foods) was associated with a 67% higher odds
for HF, 24.5 versus 8.4 for CHD, and 13.4 versus
of age-adjusted prevalent CKD in those with DM
4.8 for stroke.37
and a 37% higher odds of age-adjusted preva-
• Both eGFR and albuminuria appear to more
lent CKD in those with hypertension. A similar
strongly predict HF events than CHD or stroke
analysis in 1239 participants in the HANDLS
events.34
study revealed a marginally significant higher
• GFR predicts stroke risk but is not as strongly
odds of CKD in the full cohort, with no evidence
associated as albuminuria. In 4 community-based
of stronger associations in individuals with DM or
cohorts, lower eGFR (45 versus 95 mL·min−1·1.73
hypertension.27
m−2) was associated with an increased risk for
• In a study of 1620 participants from HANDLS with
ischemic stroke (HR, 1.30 [95% CI, 1.01–1.68])
preserved baseline kidney function, self-reported
but not hemorrhagic stroke (HR, 0.92 [95%
experiences of discrimination were associated
CI, 0.47–1.81]). Albuminuria (ACR of 300 ver-
with lower kidney function assessed via GFR,
sus 5 mg/g) was associated with both isch-
and associations were particularly pronounced
emic and hemorrhagic stroke (HR, 1.62 [95%
for African-American females relative to white
CI, 1.27–2.07] and 2.57 [95% CI, 1.37–4.83],
females, African-American males, and NH white
respectively).38 In a meta-analysis of 83 studies
males.28
of >30 000 strokes, there were linear relation-
ships of both eGFR and albuminuria with stroke
Kidney and CVD regardless of stroke subtype.33 Among people
with CKD, proteinuria but not eGFR indepen-
Impact of CKD on CVD Outcomes
dently predicted stroke risk.39
Downloaded from http://ahajournals.org by on February 7, 2019

• CKD is a risk factor for incident and recurrent CHD

• In one study of people with CKD aged 50 to 79
events, stroke, HF, VTE, and AF and is considered
years, the ACC/AHA pooled cohort risk equa-
to be a CHD risk equivalent for the purposes of
tions appeared to be well calibrated (Hosmer-
recommending primary prevention therapies such
Lemeshow χ2=2.7, P=0.45), with moderately
as statins or aggressive BP control.29–35
good discrimination (C index, 0.71 [95% CI,
• The association of reduced eGFR with cardiovas-
0.65–0.77]) for ASCVD events.40
cular risk is generally similar across age, race, and
• Females with CKD appear to have higher risk of
sex subgroups,36 although, albuminuria tends
incident PAD than males, particularly at younger
to be a stronger risk factor for females than for
ages.41
males and for older (>65 years) versus younger
• A patient-level pooled analysis of randomized tri-
people.34
als explored the effect of CKD on prognosis for
• The addition of eGFR or albuminuria improves
females who undergo PCI.42 Creatinine clearance
CVD prediction beyond traditional risk factors
<45 mL/min was an independent risk factor for
used in risk equations.34
3-year MACE (adjusted HR, 1.56) and all-cause
Prevalence of CVD Among People With CKD mortality (adjusted HR, 2.67).
(See Charts 11-12 and 11-13) • Despite higher overall event rates than NH whites,
• People with CKD, as well as those with ESRD, NH blacks with CKD have similar (or possibly
have an extremely high prevalence of comorbid lower) rates of ASCVD events, HF events, and
CVDs ranging from IHD and HF to arrhythmias death after adjustment for demographic factors,
and VTE (Charts 11-12 and 11-13).1 baseline kidney function, and cardiovascular risk
• Nearly two-thirds (65.8%) of CKD patients aged factors.43 However, the risk of HF associated with
66 years or older have CVD, compared with CKD might be greater for blacks and Hispanics
approximately one-third (31.9%) of patients than for whites.37
without CKD in this age group.1 • Clinically significant bradyarrhythmias appear to
• The prevalence of CVD in ESRD patients differs by be more common than ventricular arrhythmias
treatment modality. Approximately 70% of ESRD among hemodialysis patients and are highest in
patients on hemodialysis have any CVD, whereas the immediate hours before dialysis sessions.44

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e181

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

Mortality Attributable to CVD Among People Prevention and Treatment of CVD in People
CLINICAL STATEMENTS

With CKD With CKD

AND GUIDELINES

(See Charts 11-14 and 11-15) • One potential explanation for the higher CVD
• CVD is the leading cause of death among those event rate in people with CKD is the low uptake
with kidney disease. For those with ESRD, CVD of standard therapies. Furthermore, people with
accounts for more than half of deaths with known advanced CKD and ESRD are often excluded
causes, with arrhythmias and SCD accounting for from clinical trials of cardiovascular drugs and
nearly 40% (Chart 11-14).1 devices,51,52 although recent observational data
• For people with CKD, death attributable to CVD is from large registries can provide insight into the
more common than progression to ESRD.1 risks and benefits in this population.
• Mortality risk depends not only on eGFR but also • In a nationwide US cohort that included 4726 par-
on category of albuminuria (Chart 11-15). The ticipants with CKD, only 2366 (50%) were taking
adjusted RR of all-cause mortality and cardiovas- statins, whereas an additional 1984 participants
cular mortality is highest in those with eGFR 15 to (42%) met recommendations for statin treatment
30 mL·min−1·1.73 m−2 and those with ACR >300 according to the ACC/AHA guidelines but were
mg/g. not using statins.40
• For patients with severe valvular heart disease, • As shown in SPRINT in patients with hyperten-
CKD is a particularly strong risk factor for mor- sion but without DM, intensive SBP lowering (tar-
tality. In the Duke University Echocardiography get <120 mm Hg versus <140 mm Hg) reduced
Database (1999–2013), 5-year survival was rates of major cardiovascular events and all-cause
substantially lower for CKD than for non-CKD death to a similar extent among participants with
patients (42% versus 67% for severe aortic ste- and without CKD and had no effect on the pri-
nosis and 37% versus 65% for severe MR, CKD mary kidney end point of >50% decrease in eGFR
versus non-CKD, respectively).45 or ESRD (HR, 0.90 [95% CI, 0.44–1.83]).53
• Elevated levels of the alternative glomerular filtra- • For CKD and ESRD patients with multivessel
tion marker cystatin C have been associated with CAD, CABG may be associated with improved
increased risk for CVD and all-cause mortality in outcomes compared with PCI.54 Similar find-
studies from a broad range of cohorts. ings were seen in a Northern California Kaiser
Permanente cohort.55
Downloaded from http://ahajournals.org by on February 7, 2019

— The addition of cystatin C to the combination

of creatinine and ACR significantly improves • People with CKD are at higher risk of complica-
the prediction of all-cause mortality, cardio- tions after PCI, and accurate estimation of kidney
vascular death, and development of ESRD.46 function is required to dose antiplatelet and anti-
— Cystatin C–based eGFR was a stronger pre- thrombotic medications. Compared with older
dictor of HF than creatinine-based eGFR equations (Cockcroft-Gault), the CKD-EPI eGFR
among patients with CKD in the Chronic equation more accurately predicted kidney out-
Renal Insufficiency Cohort.47 comes and appropriate drug dosing in a large
— These strengthened associations with out- sample of nearly 130 000 patients undergoing PCI
comes might be explained in part by non- in Michigan.56
GFR determinants of cystatin C such as • In a study of >12 000 people undergoing hemo-
chronic inflammation.48 dialysis in the United States Renal Data System
who had AF, only 15% initiated warfarin therapy
Costs of CVD in People With CKD within 30 days, and 70% discontinued use within
• In 2015, admissions for CVD accounted for 26% 1 year.57 Warfarin was marginally associated with
of all inpatient spending for ESRD patients.1 reductions in ischemic stroke and mortality. In a
• In the SHARP study of patients in Europe, North large meta-analysis of observational studies of
America, and Australasia, nonfatal major car- people with AF, warfarin use was associated with
diovascular events were associated with £6133 reductions in thromboembolic events (HR, 0.70)
(95% CI, £5608–£6658) higher costs for and mortality (HR, 0.65) among those with less
ESRD patients on dialysis and £4350 (95% CI, severe CKD but was not associated with benefit
£3819–£4880) for other CKD patients in the (HR, 0.96 for mortality) in ESRD.58
year of the event (compared with years before • Low eGFR is an indication for reduced dosing
the event).49 of non–vitamin K antagonist oral anticoagu-
• Worse preoperative creatinine clearance was lant drugs. Among nearly 15 000 US Air Force
associated with higher total costs of CABG from patients prescribed non–vitamin K antago-
2000 to 2012 in the STS database ($1250 per 10 nist oral anticoagulant drugs in an administra-
mL/min lower clearance).50 tive database, 1473 had a renal indication for

e182 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

reduced dosing, and 43% of these were poten- approximately one-third will die and 1 in 6 will

CLINICAL STATEMENTS
tially overdosed. Potential overdosing was asso- require dialysis within a year.63

AND GUIDELINES
ciated with increased risk of major bleeding (HR, • In a large, nationally representative sample of
2.9 [95% CI, 1.07–4.46]).59 hemodialysis patients hospitalized for PAD, the
• Patients with eGFR <60 mL·min−1·1.73 m−2 and number of endovascular procedures increased
left bundle-branch block (but not other mor- nearly 3-fold and the number of surgical pro-
phologies) appear to derive greater absolute cedures dropped by more than two-thirds from
reductions in death and HF from cardiac resyn- 2000 to 2012.64
chronization with a defibrillator than patients Global Burden of CVD Among People With CKD
with higher eGFR.60 • In low- and middle-income countries, the bur-
• For patients undergoing TAVR in the United den of CKD is high (see Global Burden of Kidney
Kingdom, eGFR <45 mL·min−1·1.73 m−2 was Disease), but data on the magnitude of the asso-
associated with higher odds of in-hospital ciation between CKD and various cardiovascular
(adjusted OR, 1.45 [95% CI, 1.03–2.05]) and lon- outcomes are lacking. These data are necessary
ger-term (median, 543 days; adjusted OR, 1.36 to properly model the public health and economic
[95% CI, 1.17–1.58]) mortality compared with burden of CKD in these countries.
higher eGFR.61 Somewhat higher odds of in-hos-
pital mortality after TAVR were seen for those with
ESRD compared with all others in the NIS 2011 to FOOTNOTE
2014 (adjusted OR, 2.21 [95% CI, 1.81–2.69]).62 Disclosure: A portion of the data reported has been supplied by the United
States Renal Data System.1 The interpretation and reporting of these data are
• For patients with eGFR <60 but >15 mL·min−1· the responsibility of the authors and in no way should be seen as an official
1.73 m−2 undergoing TAVR in the TVT registry, policy or interpretation of the US government.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-1. Percentage of NHANES participants within the KDIGO 2012 prognosis of chronic kidney disease by GFR and albuminuria categories,
2011 to 2014 (2017 USRDS Annual Report, volume 1, Table 1.1).1
GFR indicates glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; NHANES, National Health and Nutrition Examination Survey; and
USRDS, United States Renal Data System.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e183

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11
CLINICAL STATEMENTS
AND GUIDELINES

Chart 11-2. Trends in unadjusted and standardized* end-stage renal disease (ESRD) prevalence (A) and incidence rates (B) from 1980 to 2015 in the
United States (2017 USRDS Annual Data Report, volume 2, Figures 1.7a and 1.1).1
USRDS indicates United States Renal Data System.
*Standardized for age, sex, and race. The standard population was the US population in 2011.
Source: Reference Tables A.2(2), B.2(2), and special analyses, USRDS ESRD database.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-3. Map of the standardized prevalence (per million/year) of end-stage renal disease (ESRD) by health service area in the US population,
2011 to 2015* (2017 USRDS Annual Data Report, volume 2, Figure 1.9).1
USRDS indicates United States Renal Data System.
*Standardized for age, sex, and race. The standard population was the US population in 2011. Three health service areas were suppressed because the ratio of
unadjusted rate to adjusted rate or adjusted rate to unadjusted rate was >3. Values for cells with ≤10 patients are suppressed.
Source: Special analyses, USRDS ESRD database.

e184 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-4. Trends in adjusted* prevalence (per million) of end-stage renal disease (ESRD), by race (A) and Hispanic ethnicity (B) in the US popula-
tion, 2000 to 2015 (2017 USRDS Annual Data Report, volume 2, Figure 1.11 and 1.12).1
AI indicates American Indian; AN, Alaska Native; NH, non-Hispanic; PI, Pacific Islander; and USRDS, United States Renal Data System.
*Year-end point prevalence standardized for age and sex; the ethnicity analysis (B) is further adjusted for race. The standard population was the US population
in 2011.
Source: Tables B.1, B.2(2), and special analyses, USRDS ESRD database.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-5. Trends in standardized* end-stage renal disease (ESRD) incidence rate (per million/year), by race, in the US population, 2000 to 2015
(2017 USRDS Annual Data Report, volume 2, Figure 1.5).1
AI indicates American Indian; AN, Alaska Native; NH, non-Hispanic; PI, Pacific Islander; and USRDS, United States Renal Data System.
*Standardized for age and sex. The standard population was the US population in 2011.
Source: Tables A.2(2) and special analyses, USRDS ESRD database.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e185

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11
CLINICAL STATEMENTS
AND GUIDELINES

Chart 11-6. Adjusted odds ratios of chronic kidney disease in NHANES participants by risk factor, 1999 to 2014 (2017 USRDS Annual Data Report,
volume 1, Figure 1.7b).1
Chronic kidney disease was defined as presence of estimated glomerular filtration rate (eGFR) <60 mL·min−1·1.73 m−2, urine albumin-to-creatinine ratio (ACR) ≥30
mg/g, and either eGFR <60 mL·min−1·1.73 m−2 or ACR ≥30 mg/g for each of the comorbid conditions. Adjusted for age, sex, and race; single-sample estimates of
eGFR and ACR; eGFR calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. Whisker lines indicate 95% CIs.
BMI indicates body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; HTN, hypertension; NHANES, National Health and Nutrition Examination
Survey; SR, self-report; and USRDS, US Renal Data System.
Source: NHANES, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2014 participants aged ≥20 years.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-7. Relationship of the AHA’s Life’s Simple 7 health factors and risk of incident CKD.
Hazard ratio adjusted for age, sex, race, and baseline estimated glomerular filtration rate. Error bars represent the 95% CI.15
AHA indicates American Heart Association, and CKD, chronic kidney disease.
Reprinted from Rebholz et al.14 Copyright 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open
access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited and is not used for commercial purposes.

e186 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-8. Annual percentage change in the prevalence of chronic kidney disease per 100 000 population, all ages, both sexes, 1990 to 2016.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.17 Printed with permission.
Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-9. Age-standardized global prevalence rates for chronic kidney disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.17 Printed with permission.
Copyright © 2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e187

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11
CLINICAL STATEMENTS
AND GUIDELINES

Chart 11-10. Years of life lived with disability attributable to chronic kidney disease, both sexes, all ages, 2016.
Years of life lived with disability per 100 000.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.17 Printed with permission.
Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-11. Age-standardized global mortality rates for chronic kidney disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.17 Printed with permission.
Copyright © 2017, University of Washington.

e188 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-12. Prevalence of CVD in patients with or without CKD, 2015 (2017 USRDS Annual Data Report, volume 1, Figure 4.1).1
AF indicates atrial fibrillation; AMI, acute myocardial infarction; CAD, coronary artery disease; CKD, chronic kidney disease; CVA, cerebrovascular accident; CVD,
cardiovascular disease; HF, heart failure; PAD, peripheral arterial disease; PE, pulmonary embolism; SCA, sudden cardiac arrest; TIA, transient ischemic attack;
USRDS, United States Renal Data System; VA, ventricular arrhythmia; VHD, valvular heart disease; and VTE, venous thromboembolism.
Source: Special analyses, Medicare 5% sample.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-13. Prevalence of CVD in patients with end-stage renal disease (ESRD) by treatment modality, 2015 (2017 USRDS Annual Data Report,
volume 2, Figure 9.2).1
Point prevalent hemodialysis, peritoneal dialysis, and transplant patients aged ≥22 years, who are continuously enrolled in Medicare Parts A and B, and with
Medicare as primary payer from January 1, 2015, to December 31, 2015, and ESRD service date is at least 90 days before January 1, 2015.
AF indicates atrial fibrillation; AMI, acute myocardial infarction; CAD, coronary artery disease; CVA, cerebrovascular accident; CVD, cardiovascular disease; HF, heart
failure; PAD, peripheral arterial disease; PE, pulmonary embolism; SCA, sudden cardiac arrest; TIA, transient ischemic attack; USRDS, United States Renal Data
System; VA, ventricular arrhythmia; VHD, valvular heart disease; and VTE, venous thromboembolism.
Source: Special analyses, USRDS ESRD database.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e189

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11
CLINICAL STATEMENTS
AND GUIDELINES

Chart 11-14. Causes of death in patients with end-stage renal disease (ESRD) among those with a known cause of death, 2014 (2017 USRDS Annual
Data Report, volume 2, Figure 5.4.a).1
Mortality among 2014 prevalent dialysis patients. Denominator excludes missing or unknown causes of death.
AMI indicates acute myocardial infarction; ASHD, atherosclerotic heart disease; CHF, congestive heart failure; CVA, cerebrovascular accident; and USRDS, US Renal
Data System.
Source: Special analysis using Reference Table H.12, USRDS ESRD database.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 11-15. Adjusted relative risk of (A) all-cause mortality and (B) cardiovascular mortality in the general population categorized by KDIGO 2012
categories of chronic kidney disease.
Data are derived from categorical meta-analysis of population cohorts. Pooled relative risks are expressed relative to the reference (Ref) cell. Colors represent the
ranking of the adjusted relative risks (green=low risk; yellow=moderate risk; orange=high risk; red=very high risk).
ACR indicates urine albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; and Ref, reference.
Modified from Levey et al3 with permission from International Society of Nephrology. Copyright © 2011, International Society of Nephrology.

e190 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

‍‍‍‍‍‍‍‍‍‍REFERENCES CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J

CLINICAL STATEMENTS
Kidney Dis. 2013;62:267–275. doi: 10.1053/j.ajkd.2013.02.363
1. United States Renal Data System. 2017 USRDS Annual Data Report:

AND GUIDELINES
17. Global Burden of Disease Study 2016. Global Burden of Disease Study
Epidemiology of Kidney Disease in the United States. Bethesda, MD: 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
National Institutes of Health, National Institute of Diabetes and Digestive Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
and Kidney Diseases; 2017. data.org/gbd-results-tool. Accessed May 1, 2018.
2. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, 18. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators.
Perrone RD, Lau J, Eknoyan G; National Kidney Foundation. National Global, regional, and national incidence, prevalence, and years lived with
Kidney Foundation practice guidelines for chronic kidney disease: evalua- disability for 310 diseases and injuries, 1990–2015: a systematic analy-
tion, classification, and stratification [published correction appears in Ann sis for the Global Burden of Disease Study 2015 [published correction
Intern Med. 2003;139:605]. Ann Intern Med. 2003;139:137–147. appears in Lancet. 2017;389:e1]. Lancet. 2016;388:1545–1602.
3. Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, 19. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional,
Gansevoort RT, Kasiske BL, Eckardt KU. The definition, classification, and and national life expectancy, all-cause mortality, and cause-specific mor-
prognosis of chronic kidney disease: a KDIGO Controversies Conference tality for 249 causes of death, 1980–2015: a systematic analysis for the
report [published correction appears in Kidney Int. 2011;80:1000]. Kidney Global Burden of Disease Study 2015 [published correction appears in
Int. 2011;80:17–28. doi: 10.1038/ki.2010.483 Lancet. 2017;389:e1]. Lancet. 2016;388:1459–1544.
4. Hoerger TJ, Simpson SA, Yarnoff BO, Pavkov ME, Ríos Burrows N, Saydah 20. Fox CS, Yang Q, Cupples LA, Guo CY, Larson MG, Leip EP, Wilson
SH, Williams DE, Zhuo X. The future burden of CKD in the United PW, Levy D. Genomewide linkage analysis to serum creatinine, GFR,
States: a simulation model for the CDC CKD Initiative. Am J Kidney Dis. and creatinine clearance in a community-based population: the
2015;65:403–411. doi: 10.1053/j.ajkd.2014.09.023 Framingham Heart Study. J Am Soc Nephrol. 2004;15:2457–2461. doi:
5. Lewis EF, Claggett B, Parfrey PS, Burdmann EA, McMurray JJ, Solomon 10.1097/01.ASN.0000135972.13396.6F
SD, Levey AS, Ivanovich P, Eckardt KU, Kewalramani R, Toto R, Pfeffer 21. Ma L, Chou JW, Snipes JA, Bharadwaj MS, Craddock AL, Cheng D,
MA. Race and ethnicity influences on cardiovascular and renal events Weckerle A, Petrovic S, Hicks PJ, Hemal AK, Hawkins GA, Miller LD,
in patients with diabetes mellitus. Am Heart J. 2015;170:322–329. doi: Molina AJ, Langefeld CD, Murea M, Parks JS, Freedman BI. APOL1
10.1016/j.ahj.2015.05.008 Renal-risk variants induce mitochondrial dysfunction. J Am Soc Nephrol.
6. McClellan WM, Warnock DG, Judd S, Muntner P, Kewalramani R, 2017;28:1093–1105. doi: 10.1681/ASN.2016050567
Cushman M, McClure LA, Newsome BB, Howard G. Albuminuria and 22. Grams ME, Rebholz CM, Chen Y, Rawlings AM, Estrella MM, Selvin
racial disparities in the risk for ESRD. J Am Soc Nephrol. 2011;22:1721– E, Appel LJ, Tin A, Coresh J. Race, APOL1 risk, and eGFR decline in
1728. doi: 10.1681/ASN.2010101085 the general population. J Am Soc Nephrol. 2016;27:2842–2850. doi:
7. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman 10.1681/ASN.2015070763
BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy 23. Foster MC, Coresh J, Fornage M, Astor BC, Grams M, Franceschini
AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays N, Boerwinkle E, Parekh RS, Kao WH. APOL1 variants associate with
E, Pollak MR. Association of trypanolytic ApoL1 variants with kid- increased risk of CKD among African Americans. J Am Soc Nephrol.
ney disease in African Americans. Science. 2010;329:841–845. doi: 2013;24:1484–1491. doi: 10.1681/ASN.2013010113
10.1126/science.1193032 24. Peralta CA, Bibbins-Domingo K, Vittinghoff E, Lin F, Fornage M, Kopp JB,
8. Murphy D, McCulloch CE, Lin F, Banerjee T, Bragg-Gresham JL, Eberhardt Winkler CA. APOL1 genotype and race differences in incident albuminuria
MS, Morgenstern H, Pavkov ME, Saran R, Powe NR, Hsu CY; Centers for and renal function decline. J Am Soc Nephrol. 2016;27:887–893. doi:
Disease Control and Prevention Chronic Kidney Disease Surveillance Team.
Downloaded from http://ahajournals.org by on February 7, 2019

10.1681/ASN.2015020124
Trends in prevalence of chronic kidney disease in the United States. Ann 25. Chen TK, Appel LJ, Grams ME, Tin A, Choi MJ, Lipkowitz MS, Winkler
Intern Med. 2016;165:473–481. doi: 10.7326/M16-0273 CA, Estrella MM. APOL1 risk variants and cardiovascular disease:
9. Centers for Disease Control and Prevention. Chronic Kidney Disease results from the AASK (African American Study of Kidney Disease and
Surveillance System—United States. http://nccd.cdc.gov/CKD. Accessed Hypertension). Arterioscler Thromb Vasc Biol. 2017;37:1765–1769. doi:
August 15, 2018. 10.1161/ATVBAHA.117.309384
10. Garofalo C, Borrelli S, Pacilio M, Minutolo R, Chiodini P, De Nicola L, 26. Zeng X, Liu J, Tao S, Hong HG, Li Y, Fu P. Associations between socio-
Conte G. Hypertension and prehypertension and prediction of devel- economic status and chronic kidney disease: a meta-analysis. J Epidemiol
opment of decreased estimated GFR in the general population: a Community Health. 2018;72:270–279. doi: 10.1136/jech-2017-209815
meta-analysis of cohort studies. Am J Kidney Dis. 2016;67:89–97. doi: 27. Crews DC, Kuczmarski MF, Grubbs V, Hedgeman E, Shahinian VB, Evans
10.1053/j.ajkd.2015.08.027 MK, Zonderman AB, Burrows NR, Williams DE, Saran R, Powe NR; Centers
11. Molnar MZ, Mucsi I, Novak M, Szabo Z, Freire AX, Huch KM, Arah OA, Ma for Disease Control and Prevention Chronic Kidney Disease Surveillance
JZ, Lu JL, Sim JJ, Streja E, Kalantar-Zadeh K, Kovesdy CP. Association of inci- Team. Effect of food insecurity on chronic kidney disease in lower-income
dent obstructive sleep apnoea with outcomes in a large cohort of US vet- Americans. Am J Nephrol. 2014;39:27–35. doi: 10.1159/000357595
erans. Thorax. 2015;70:888–895. doi: 10.1136/thoraxjnl-2015-206970 28. Beydoun MA, Poggi-Burke A, Zonderman AB, Rostant OS, Evans MK,
12. Garrity BH, Kramer H, Vellanki K, Leehey D, Brown J, Shoham DA. Time Crews DC. Perceived discrimination and longitudinal change in kidney
trends in the association of ESRD incidence with area-level poverty in the function among urban adults. Psychosom Med. 2017;79:824–834. doi:
US population. Hemodial Int. 2016;20:78–83. doi: 10.1111/hdi.12325 10.1097/PSY.0000000000000478
13. Kokkinos P, Faselis C, Myers J, Sui X, Zhang J, Tsimploulis A, Chawla 29. Cheung KL, Zakai NA, Folsom AR, Kurella Tamura M, Peralta CA, Judd
L, Palant C. Exercise capacity and risk of chronic kidney disease in US SE, Callas PW, Cushman M. Measures of kidney disease and the risk of
veterans: a cohort study. Mayo Clin Proc. 2015;90:461–468. doi: venous thromboembolism in the REGARDS (Reasons for Geographic and
10.1016/j.mayocp.2015.01.013 Racial Differences in Stroke) study. Am J Kidney Dis. 2017;70:182–190.
14. Ricardo AC, Anderson CA, Yang W, Zhang X, Fischer MJ, Dember doi: 10.1053/j.ajkd.2016.10.039
LM, Fink JC, Frydrych A, Jensvold NG, Lustigova E, Nessel LC, Porter 30. Wanner C, Tonelli M; Kidney Disease: Improving Global Outcomes
AC, Rahman M, Wright Nunes JA, Daviglus ML, Lash JP; CRIC Study Lipid Guideline Development Work Group Members. KDIGO clinical
Investigators. Healthy lifestyle and risk of kidney disease progression, ath- practice guideline for lipid management in CKD: summary of recom-
erosclerotic events, and death in CKD: findings from the Chronic Renal mendation statements and clinical approach to the patient. Kidney Int.
Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;65:412–424. 2014;85:1303–1309. doi: 10.1038/ki.2014.31
doi: 10.1053/j.ajkd.2014.09.016 31. Baber U, Gutierrez OM, Levitan EB, Warnock DG, Farkouh ME, Tonelli M,
15. Rebholz CM, Anderson CA, Grams ME, Bazzano LA, Crews DC, Chang Safford MM, Muntner P. Risk for recurrent coronary heart disease and all-
AR, Coresh J, Appel LJ. Relationship of the American Heart Association’s cause mortality among individuals with chronic kidney disease compared
impact goals (Life’s Simple 7) with risk of chronic kidney disease: results with diabetes mellitus, metabolic syndrome, and cigarette smokers. Am
from the Atherosclerosis Risk in Communities (ARIC) cohort study. J Am Heart J. 2013;166:373–380.e2. doi: 10.1016/j.ahj.2013.05.008
Heart Assoc. 2016;5:e003192. doi: 10.1161/JAHA.116.003192 32. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison
16. Chang A, Van Horn L, Jacobs DR Jr, Liu K, Muntner P, Newsome B, Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW,
Shoham DA, Durazo-Arvizu R, Bibbins-Domingo K, Reis J, Kramer H. MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC,
Lifestyle-related factors, obesity, and incident microalbuminuria: the Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e191

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/ 45. Samad Z, Sivak JA, Phelan M, Schulte PJ, Patel U, Velazquez EJ.
CLINICAL STATEMENTS

PCNA guideline for the prevention, detection, evaluation, and man- Prevalence and outcomes of left-sided valvular heart disease associated
AND GUIDELINES

agement of high blood pressure in adults: a report of the American with chronic kidney disease. J Am Heart Assoc. 2017;6. doi: 10.1161/
College of Cardiology/American Heart Association Task Force on Clinical JAHA.117.006044
Practice Guidelines [published correction appears in Hypertension. 46. Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Katz R, Polkinghorne KR,
2018;71:e140–e144]. Hypertension. 2018;71:e13–e115. DOI: 10.1161/ Rothenbacher D, Sarnak MJ, Astor BC, Coresh J, Levey AS, Gansevoort
HYP.0000000000000065 RT; CKD Prognosis Consortium. Cystatin C versus creatinine in determin-
33. Masson P, Webster AC, Hong M, Turner R, Lindley RI, Craig JC. Chronic kid- ing risk based on kidney function. N Engl J Med. 2013;369:932–943. doi:
ney disease and the risk of stroke: a systematic review and meta-analysis. 10.1056/NEJMoa1214234
Nephrol Dial Transplant. 2015;30:1162–1169. doi: 10.1093/ndt/gfv009 47. He J, Shlipak M, Anderson A, Roy JA, Feldman HI, Kallem RR, Kanthety
34. Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, Jafar T, R, Kusek JW, Ojo A, Rahman M, Ricardo AC, Soliman EZ, Wolf M, Zhang
Jassal SK, Landman GW, Muntner P, Roderick P, Sairenchi T, Schöttker X, Raj D, Hamm L; for the CRIC (Chronic Renal Insufficiency Cohort)
B, Shankar A, Shlipak M, Tonelli M, Townend J, van Zuilen A, Yamagishi Investigators. Risk factors for heart failure in patients with chronic kidney
K, Yamashita K, Gansevoort R, Sarnak M, Warnock DG, Woodward M, disease: the CRIC (Chronic Renal Insufficiency Cohort) study. J Am Heart
Ärnlöv J; CKD Prognosis Consortium. Estimated glomerular filtration rate Assoc. 2017;6:e005336. doi: 10.1161/JAHA.116.005336
and albuminuria for prediction of cardiovascular outcomes: a collaborative 48. Schei J, Stefansson VT, Mathisen UD, Eriksen BO, Solbu MD, Jenssen TG,
meta-analysis of individual participant data. Lancet Diabetes Endocrinol. Melsom T. Residual associations of inflammatory markers with eGFR after
2015;3:514–525. doi: 10.1016/S2213-8587(15)00040-6 accounting for measured GFR in a community-based cohort without CKD.
35. Alonso A, Lopez FL, Matsushita K, Loehr LR, Agarwal SK, Chen LY, Clin J Am Soc Nephrol. 2016;11:280–286. doi: 10.2215/CJN.07360715
Soliman EZ, Astor BC, Coresh J. Chronic kidney disease is associ- 49. Kent S, Schlackow I, Lozano-Kühne J, Reith C, Emberson J, Haynes R,
ated with the incidence of atrial fibrillation: the Atherosclerosis Risk in Gray A, Cass A, Baigent C, Landray MJ, Herrington W, Mihaylova B;
Communities (ARIC) study. Circulation. 2011;123:2946–2953. doi: SHARP Collaborative Group. What is the impact of chronic kidney dis-
10.1161/CIRCULATIONAHA.111.020982 ease stage and cardiovascular disease on the annual cost of hospital care
36. Hui X, Matsushita K, Sang Y, Ballew SH, Fülöp T, Coresh J. CKD and cardio- in moderate-to-severe kidney disease? BMC Nephrol. 2015;16:65. doi:
vascular disease in the Atherosclerosis Risk in Communities (ARIC) study: 10.1186/s12882-015-0054-0
interactions with age, sex, and race. Am J Kidney Dis. 2013;62:691–702. 50. LaPar DJ, Rich JB, Isbell JM, Brooks CH, Crosby IK, Yarboro LT, Ghanta
doi: 10.1053/j.ajkd.2013.04.010 RK, Kern JA, Brown M, Quader MA, Speir AM, Ailawadi G. Preoperative
37. Bansal N, Katz R, Robinson-Cohen C, Odden MC, Dalrymple L, Shlipak renal function predicts hospital costs and length of stay in coronary
MG, Sarnak MJ, Siscovick DS, Zelnick L, Psaty BM, Kestenbaum B, Correa artery bypass grafting. Ann Thorac Surg. 2016;101:606–612. doi:
A, Afkarian M, Young B, de Boer IH. Absolute rates of heart failure, coro- 10.1016/j.athoracsur.2015.07.079
nary heart disease, and stroke in chronic kidney disease: an analysis of 3 51. Konstantinidis I, Nadkarni GN, Yacoub R, Saha A, Simoes P, Parikh CR,
community-based cohort studies. JAMA Cardiol. 2017;2:314–318. doi: Coca SG. Representation of patients with kidney disease in trials of cardio-
10.1001/jamacardio.2016.4652 vascular interventions: an updated systematic review. JAMA Intern Med.
38. Mahmoodi BK, Yatsuya H, Matsushita K, Sang Y, Gottesman RF, Astor 2016;176:121–124. doi: 10.1001/jamainternmed.2015.6102
BC, Woodward M, Longstreth WT Jr, Psaty BM, Shlipak MG, Folsom 52. Konstantinidis I, Patel S, Camargo M, Patel A, Poojary P, Coca SG,
AR, Gansevoort RT, Coresh J. Association of kidney disease measures Nadkarni GN. Representation and reporting of kidney disease in cerebro-
with ischemic versus hemorrhagic strokes: pooled analyses of 4 pro- vascular disease: a systematic review of randomized controlled trials. PLoS
spective community-based cohorts. Stroke. 2014;45:1925–1931. doi: One. 2017;12:e0176145. doi: 10.1371/journal.pone.0176145
Downloaded from http://ahajournals.org by on February 7, 2019

10.1161/STROKEAHA.114.004900 53. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL,
39. Sandsmark DK, Messé SR, Zhang X, Roy J, Nessel L, Lee Hamm L, He Cushman WC, Hawfield AT, Johnson KC, Lewis CE, Oparil S, Rocco MV,
J, Horwitz EJ, Jaar BG, Kallem RR, Kusek JW, Mohler ER 3rd, Porter A, Sink KM, Whelton PK, Wright JT Jr, Basile J, Beddhu S, Bhatt U, Chang TI,
Seliger SL, Sozio SM, Townsend RR, Feldman HI, Kasner SE; CRIC Study Chertow GM, Chonchol M, Freedman BI, Haley W, Ix JH, Katz LA, Killeen
Investigators. Proteinuria, but not eGFR, predicts stroke risk in chronic AA, Papademetriou V, Ricardo AC, Servilla K, Wall B, Wolfgram D, Yee J;
kidney disease: Chronic Renal Insufficiency Cohort study. Stroke. SPRINT Research Group. Effects of intensive BP control in CKD. J Am Soc
2015;46:2075–2080. doi: 10.1161/STROKEAHA.115.009861 Nephrol. 2017;28:2812–2823. doi: 10.1681/ASN.2017020148
40. Colantonio LD, Baber U, Banach M, Tanner RM, Warnock DG, Gutiérrez 54. Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL.
OM, Safford MM, Wanner C, Howard G, Muntner P. Contrasting cho- Revascularization in patients with multivessel coronary artery disease
lesterol management guidelines for adults with CKD. J Am Soc Nephrol. and chronic kidney disease: everolimus-eluting stents versus coronary
2015;26:1173–1180. doi: 10.1681/ASN.2014040400 artery bypass graft surgery. J Am Coll Cardiol. 2015;66:1209–1220. doi:
41. Wang GJ, Shaw PA, Townsend RR, Anderson AH, Xie D, Wang X, Nessel 10.1016/j.jacc.2015.06.1334
LC, Mohler ER, Sozio SM, Jaar BG, Chen J, Wright J, Taliercio JJ, Ojo A, 55. Krishnaswami A, McCulloch CE, Tawadrous M, Jang JJ, Lee H, Melikian
Ricardo AC, Lustigova E, Fairman RM, Feldman HI, Ky B; for the CRIC Study V, Yee G, Leong TK, Go AS. Coronary artery bypass grafting and per-
Investigators. Sex differences in the incidence of peripheral artery disease cutaneous coronary intervention in patients with end-stage renal dis-
in the Chronic Renal Insufficiency Cohort. Circ Cardiovasc Qual Outcomes. ease. Eur J Cardiothorac Surg. 2015;47:e193–e198. doi: 10.1093/
2016;9(suppl 1):S86–S93. doi: 10.1161/CIRCOUTCOMES.115.002180 ejcts/ezv104
42. Baber U, Giustino G, Sartori S, Aquino M, Stefanini GG, Steg PG, 56. Parsh J, Seth M, Aronow H, Dixon S, Heung M, Mehran R, Gurm HS.
Windecker S, Leon MB, Wijns W, Serruys PW, Valgimigli M, Stone GW, Choice of estimated glomerular filtration rate equation impacts drug-
Dangas GD, Morice MC, Camenzind E, Weisz G, Smits PC, Kandzari dosing recommendations and risk stratification in patients with chronic
D, Von Birgelen C, Mastoris I, Galatius S, Jeger RV, Kimura T, Mikhail kidney disease undergoing percutaneous coronary interventions. J Am
GW, Itchhaporia D, Mehta L, Ortega R, Kim HS, Kastrati A, Chieffo A, Coll Cardiol. 2015;65:2714–2723. doi: 10.1016/j.jacc.2015.04.037
Mehran R. Effect of chronic kidney disease in women undergoing per- 57. Shen JI, Montez-Rath ME, Lenihan CR, Turakhia MP, Chang TI,
cutaneous coronary intervention with drug-eluting stents: a patient-level Winkelmayer WC. Outcomes after warfarin initiation in a cohort of hemo-
pooled analysis of randomized controlled trials. JACC Cardiovasc Interv. dialysis patients with newly diagnosed atrial fibrillation. Am J Kidney Dis.
2016;9:28–38. doi: 10.1016/j.jcin.2015.09.023 2015;66:677–688. doi: 10.1053/j.ajkd.2015.05.019
43. Lash JP, Ricardo AC, Roy J, Deo R, Fischer M, Flack J, He J, Keane M, Lora 58. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, major bleeding,
C, Ojo A, Rahman M, Steigerwalt S, Tao K, Wolf M, Wright JT Jr, Go and mortality outcomes in warfarin users with atrial fibrillation and
AS; CRIC Study Investigators. Race/ethnicity and cardiovascular outcomes chronic kidney disease: a meta-analysis of observational studies. Chest.
in adults with CKD: findings from the CRIC (Chronic Renal Insufficiency 2016;149:951–959. doi: 10.1378/chest.15-1719
Cohort) and Hispanic CRIC studies. Am J Kidney Dis. 2016;68:545–553. 59. Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-
doi: 10.1053/j.ajkd.2016.03.429 vitamin K antagonist oral anticoagulant dosing in patients with atrial fibril-
44. Roy-Chaudhury P, Tumlin JA, Koplan BA, Costea AI, Kher V, Williamson D, lation and renal dysfunction. J Am Coll Cardiol. 2017;69:2779–2790. doi:
Pokhariyal S, Charytan DM; MiD investigators and committees. Primary 10.1016/j.jacc.2017.03.600
outcomes of the Monitoring in Dialysis Study indicate that clinically signifi- 60. Daimee UA, Moss AJ, Biton Y, Solomon SD, Klein HU, McNitt S, Polonsky
cant arrhythmias are common in hemodialysis patients and related to dia- B, Zareba W, Goldenberg I, Kutyifa V. Long-term outcomes with car-
lytic cycle. Kidney Int. 2018;93:941–951. doi: 10.1016/j.kint.2017.11.019 diac resynchronization therapy in patients with mild heart failure with

e192 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 11

moderate renal dysfunction. Circ Heart Fail. 2015;8:725–732. doi: 63. Hansen JW, Foy A, Yadav P, Gilchrist IC, Kozak M, Stebbins A, Matsouaka

CLINICAL STATEMENTS
10.1161/CIRCHEARTFAILURE.115.002082 R, Vemulapalli S, Wang A, Wang DD, Eng MH, Greenbaum AB,

AND GUIDELINES
61. Ferro CJ, Chue CD, de Belder MA, Moat N, Wendler O, Trivedi U, Ludman P, O’Neill WO. Death and dialysis after transcatheter aortic valve replace-
Townend JN; UK TAVI Steering Group; National Institute for Cardiovascular ment: an analysis of the STS/ACC TVT registry. JACC Cardiovasc Interv.
Outcomes Research. Impact of renal function on survival after transcath- 2017;10:2064–2075. doi: 10.1016/j.jcin.2017.09.001
eter aortic valve implantation (TAVI): an analysis of the UK TAVI registry. 64. Garimella PS, Balakrishnan P, Correa A, Poojary P, Annapureddy N,
Heart. 2015;101:546–552. doi: 10.1136/heartjnl-2014-307041 Chauhan K, Patel A, Patel S, Konstantinidis I, Chan L, Agarwal SK, Jaar
62. Bhatia N, Agrawal S, Yang S, Yadav K, Agarwal M, Garg L, Agarwal N, Shirani BG, Gidwani U, Matsushita K, Nadkarni GN. Nationwide trends in hospi-
J, Fredi JL. In-hospital outcomes of transcatheter aortic valve implantation in tal outcomes and utilization after lower limb revascularization in patients
patients with end-stage renal disease on dialysis from a large national database. on hemodialysis. JACC Cardiovasc Interv. 2017;10:2101–2110. doi:
Am J Cardiol. 2017;120:1355–1358. doi: 10.1016/j.amjcard.2017.07.022 10.1016/j.jcin.2017.05.050
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e193

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

12. SLEEP of a healthy sleep duration (≥7 hours) in the

CLINICAL STATEMENTS

United States and found that 11.8% of peo-

See Charts 12-1 through 12-5
AND GUIDELINES

ple reported a sleep duration ≤5 hours, 23.0%

reported 6 hours, 29.5% reported 7 hours,
Click here to return to the Table of Contents
27.7% reported 8 hours, 4.4% reported 9
hours, and 3.6% reported ≥10 hours. Overall,
Sleep can be characterized in many different ways,
65.2% met the recommended sleep duration of
including quantity of sleep (sleep duration), quality
≥7 hours.3
of sleep, or the presence of a sleep disorder, such as
• Analysis of NHANES data (2005–2008) indi-
insomnia or OSA. All of these characteristics of sleep
cated that the proportion of adults getting
have been associated with CVD and stroke.
inadequate sleep (<7 hours) was 36.8%.
Younger people were more likely to report
Prevalence sleeping <7 hours, and males were more likely
(See Charts 12-1 through 12-4) to report sleeping <7 hours at younger ages
(20–59 years) (Chart 12-1).
• The American Academy of Sleep Medicine and the
• The prevalence of inadequate sleep (<7 hours)
Sleep Research Society published a consensus state-
varied by state or territory: in 2014, the lowest
ment recommending that adults obtain ≥7 hours
prevalence was seen in South Dakota (28.4%),
of sleep per night to promote optimal health.1
Colorado (28.5%), and Minnesota (29.2%), and
The American Academy of Sleep Medicine and
the highest was found in Guam (48.6%), Hawaii
Sleep Research Society also published guidelines
(43.6%), and Kentucky (39.4%).4
for pediatric populations: infants 4 to 12 months
• Analysis of time diaries indicated that the prev-
old should sleep 12 to 16 hours per day; children
alence of short sleepers was 7.6% in 1975 and
1 to 2 years old should sleep 11 to 14 hours per
9.3% in 2006 and that this increase in prevalence
day; children 3 to 5 years old should sleep 10 to
was observed predominantly in full-time workers.5
13 hours per day; children 6 to 12 years old should
• Prevalence of OSA varies by sex. On the basis of
sleep 9 to 12 hours per day; and adolescents 13 to
data from the Wisconsin Cohort Study, OSA prev-
18 years old should sleep 8 to 10 hours per day.2
alence estimates among 30- to 70-year-old sub-
• The CDC analyzed data from the 2014 BRFSS
jects in the United States in 2007 to 2010 were
Downloaded from http://ahajournals.org by on February 7, 2019

to determine the age-adjusted prevalence

33.9% among males and 17.4% among females
for AHI ≥5 (mild to severe OSA).6 Prevalence
Abbreviations Used in Chapter 12
estimates of moderate to severe OSA (AHI ≥15)
AF atrial fibrillation were 13.0% for males and 5.6% for females.
AHI apnea-hypopnea index
These estimates are higher than estimates for
AMI acute myocardial infarction
BMI body mass index
1988 to 1994 from the same study, which were
BRFSS Behavioral Risk Factor Surveillance System 26.4% in males and 8.8% in females for mild to
CARDIA Coronary Artery Risk Development in Young Adults severe OSA.6
CDC Centers for Disease Control and Prevention • The prevalence of insomnia symptoms, that is,
CHD coronary heart disease difficulty falling or staying asleep or nonrestor-
CI confidence interval
ative sleep, has been estimated to be 30% to
CPAP continuous positive airway pressure
CVD cardiovascular disease 48% in the general population, whereas the
DM diabetes mellitus prevalence of a diagnosis of insomnia was 6%.7
HF heart failure • The proportion of people who reported (a) trou-
Hisp Hispanic ble falling asleep often or almost always was
HR hazard ratio
17.3%, (b) trouble staying asleep often or almost
Mex Amer Mexican American
MI myocardial infarction
always was 20.4%, and (c) waking too early
NH non-Hispanic often or almost always was 16.8%. (unpublished
NHANES National Health and Nutrition Examination Survey NHANES 2005–2008). Females were more likely
NSTEMI non–ST-segment–elevation myocardial infarction to report these sleep problems than males at all
OR odds ratio ages (Charts 12-2 to 12-4).
OSA obstructive sleep apnea
• Females have a greater risk of insomnia than
PA physical activity
RCT randomized controlled trial
males. For example, a meta-analysis of 31 stud-
RR relative risk ies reported an RR of 1.41 (95% CI, 1.28–1.55)
STEMI ST-segment–elevation myocardial infarction comparing females to males.8 Furthermore, sex
TIA transient ischemic attack differences increased with age and were largest
UA unstable angina in those ≥65 years of age.8

e194 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

Children/Adolescents sleep quality in blacks and Hispanic/Latinos com-

CLINICAL STATEMENTS
• National poll data indicated that 63.3% of chil- pared with whites.

AND GUIDELINES
dren 6 to 11 years old and 56.7% of children 12 • In NHANES 2005 to 2008, blacks and individu-
to 17 years old obtained sufficient sleep, whereas als of other races were significantly more likely to
47.2% of children 6 to 11 years old and 38.5% report sleeping <7 hours than NH whites (unpub-
of children 12 to 17 years old had excellent sleep lished NHANES data; Chart 12-5).
quality.9 • In NHANES 2005 to 2008, whites were more
• The estimated prevalence of snoring in pedi- likely to report trouble falling asleep and trou-
atric populations (as reported by the parent) is ble staying asleep (unpublished NHANES data;
7.5%, whereas the prevalence of sleep-disor- Chart 12-5).
dered breathing using diagnostic testing is likely
between 1% and 4% (varies depending on defi-
nitions and methodologies used).10
Mortality
• A meta-analysis of 43 studies indicated that both
Adults: Young, Middle-Aged, and Old short sleep (<7 hours per night; RR, 1.13 [95% CI,
• Older adults are more likely to report adequate 1.10–1.17]) and long sleep (>8 hours per night;
sleep. Age-specific and age-adjusted percent- RR, 1.35 [95% CI, 1.29–1.41]) were associated
ages of adults who reported adequate sleep with a greater risk of all-cause mortality.13
(≥7 hours per 24-hour period) were as follows: — A prospective cohort study found that the
67.8% for 18- to 24-year-old adults, 62.1% association between sleep duration and
for 25- to 34-year-old adults, 61.7% for 35- to mortality varied with age.14 Among adults
44-year-old adults, 62.7% for 45- to 64-year- <65 years old, short sleep duration (≤5
old adults, and 73.7% for adults aged ≥65 hours per night) and long sleep duration
years.3 (≥8 hours per night) were both associated
• Prevalence of OSA is higher among older adults. with increased mortality risk (HR, 1.37 [95%
The prevalence of mild to severe OSA (AHI ≥5) CI, 1.09–1.71] and HR, 1.27 [95% CI, 1.08–
was 26.6% for 30- to 49-year-old males and 1.48], respectively). Sleep duration was not
43.2% for 50- to 70-year-old males, whereas significantly associated with mortality in
it was 8.7% for 30- to 49-year old females and adults >65 years of age.
Downloaded from http://ahajournals.org by on February 7, 2019

27.8% for 50 to 70-year-old females.6 • Data from NHANES indicated that long sleep
duration (>8 hours per night) was associated with
Race/Ethnicity and Sleep an increased risk of all-cause mortality in the full
sample (HR, 1.90 [95% CI, 1.38–2.60]), among
(See Chart 12-5) males (HR, 1.48 [95% CI, 1.05–2.09]), among
• Data from the CDC indicated that the age- females (HR, 2.32 [95% CI, 1.48–3.61]), and
adjusted prevalence of healthy sleep duration among those >65 years of age (HR, 1.80 [95%
was lower among Native Hawaiians/Pacific CI, 1.30–2.50]) but not among those <65 years of
Islanders (53.7%), NH blacks (54.2%), multira- age.15 No significant associations were observed
cial NH people (53.6%), and American Indians/ between short sleep (<7 hours per night) and all-
Alaska Natives (59.6%) compared with NH cause mortality in this analysis.
whites (66.8%), Hispanics (65.5%), and Asians • A meta-analysis of 27 cohort studies found that
(62.5%).3 mild OSA (HR, 1.19 [95% CI, 0.86–1.65]), mod-
• The CARDIA study estimated sleep duration using erate OSA (HR, 1.28 [95% CI, 0.96–1.69]), and
wrist activity monitoring and found that the aver- severe OSA (HR, 2.13 [95% CI, 1.68–2.68]) were
age sleep duration was 5.1 hours for black males, associated with all-cause mortality in a dose-
5.9 hours for black females, 5.8 hours for white response fashion. Only severe OSA was associ-
males, and 6.5 hours for white females, after ated with cardiovascular mortality (HR, 2.73 [95%
adjustment for numerous confounders includ- CI, 1.94–3.85]).16
ing socioeconomic indicators. This study also • A study of US males found that insomnia symp-
observed a similar race/sex pattern of sleep qual- toms were associated with increased risk of all-
ity measures.11 cause mortality. Specifically, mortality risk was
• The Chicago Area Health Study also used wrist higher for males who reported difficulty initiating
activity monitoring, and the adjusted mean sleep sleep (HR, 1.25 [95% CI, 1.04–1.50]) and non-
duration was 6.7 hours for blacks, 6.8 hours for restorative sleep (HR, 1.24 [95% CI, 1.05–1.46]).17
Asians, 6.9 hours for Hispanic/Latinos, and 7.5 • A study among males and females aged 21 to
hours for whites.12 This study also observed lower 75 years found that compared with those who

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e195

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

never reported insomnia symptoms, those who versus 18 to 44 years, high school degree (HR,
CLINICAL STATEMENTS

reported persistent insomnia symptoms at 2 time 1.44 [95% CI, 1.18–1.75]) versus college or more,
AND GUIDELINES

points ≈5 years apart had an increased risk of all- underweight (HR, 1.37 [95% CI, 1.06–1.77]) ver-
cause mortality (HR, 1.58 [95% CI, 1.02–2.45]), sus normal weight, greater comorbidities based
but those who reported insomnia at only 1 time on Charlson comorbidity index (HR, 1.69 [95%
point did not.18 CI, 1.45–1.98] for a score of 1 or 2 and HR, 1.76
[95% CI, 1.32–2.36] for a score ≥3), ever hav-
ing smoked (HR, 1.45 [95% CI, 1.20–1.76]) ver-
Risk Factors sus never having smoked, and physical inactivity
• In addition to age, sex, and race/ethnicity, char- (HR, 1.22 [95% CI, 1.06–1.42]) versus PA.20 The
acteristics associated with short sleep duration following are associated with reduced risk of
include lower education (OR, 0.68 [95% CI, incident diagnosed insomnia: male sex (HR, 0.57
0.56–0.84] for greater than high school ver- [95% CI, 0.48–0.69]) and having never been
sus less than high school), not being married married (HR, 0.73 [95% CI, 0.59–0.90]) versus
(OR, 1.43 [95% CI, 1.25–1.67] for not married being married or cohabitating.20
versus married), poverty (OR, 0.65 [95% CI,
0.54–0.79] for poverty/income ratio ≥2 versus
<1), smoking (OR, 0.063 [95% CI, 0.51–0.79] Family History and Genetics
for ex-smokers and OR, 0.68 [95% CI, 0.53– • Genetic factors can influence sleep either directly
0.85] for smokers versus never-smokers), physi- by controlling sleep disorders or indirectly through
cal inactivity (OR, 1.48 [95% CI, 1.15–1.86] modulation of risk factors such as obesity.
for no PA versus PA), poor diet (OR, 0.93 [95% • Heritability of sleep behaviors varies but is esti-
CI, 0.91–0.95] per point on nutrient adequacy mated to be ≈40%.21 Genetic studies have
scale), obesity (OR, 1.39 [95% CI, 1.17–1.65] identified variants associated with OSA.22 Data
for BMI ≥30 versus <25 kg/m2), fair/poor subjec- suggest genetic control of interindividual vari-
tive health (OR, 1.93 [95% CI, 1.63–2.32] ver- ability in circadian rhythms, with variants in clock
sus excellent, very good, and good combined), genes such as CRY1 and CRY2 being of particu-
and depressive symptoms (OR, 2.80 [95% CI, lar interest.23–25
2.01–3.90] for ≥10 versus <10 on the Patient
Downloaded from http://ahajournals.org by on February 7, 2019

Health Questionnaire).15
• In addition to age, sex, and race/ethnicity, charac- Aftermath
teristics associated with trouble sleeping include • Short sleep duration has been associated with
not being married (OR, 1.16 [95% CI, 1.01–1.36], several cardiovascular and metabolic health out-
not married versus married), smoking (OR, 0.39 comes, including prevalent obesity (OR, 1.55
[95% CI, 0.36–0.43] for never-smoker versus cur- [95% CI, 1.43–1.68])26, incident obesity (OR, 1.45
rent smoker), no alcohol consumption (OR, 0.39 [95% CI, 1.25–1.67]),27 incident DM (OR, 1.28
[95% CI, 0.36–0.43] for alcohol consumption [95% CI, 1.03–1.60]),28 CHD morbidity or mortal-
versus no consumption), obesity (OR, 1.25 [95% ity (RR, 1.48 [95% CI, 1.22–1.80]),29 and stroke
CI, 1.02–1.54] for BMI ≥30 versus <25 kg/m2), (RR, 1.15 [95% CI, 1.00–1.31]).29
fair/poor subjective health (OR, 1.97 [95% CI, • Long duration of sleep was also associated with
1.60–2.41] versus excellent/very good/good), and a greater risk of CHD morbidity or mortality (RR
depressive symptoms (OR, 4.71 [95% CI, 3.60– 1.38 [95% CI, 1.15–1.66]), stroke (RR, 1.65 [95%
6.17] for ≥10 versus <10 on the Patient Health CI, 1.45–1.87]), and total CVD (RR, 1.41 [95% CI,
Questionnaire).15 1.19–1.68]).29
• Predictors of OSA (AHI ≥15) include male sex (OR, • A meta-analysis examined sleep duration and
1.51 [95% CI, 1.50–1.90]), larger BMI (OR, 1.55 total CVD (26 articles), CHD (22 articles), and
[95% CI, 1.41–1.71] per 5.3 kg/m2), larger neck stroke (16 articles).13 Short sleep (<7 hours per
circumference (OR, 1.42 [95% CI, 1.25–1.61] per night) was associated with total CVD (RR, 1.14
1.7 inches), habitual snoring (OR, 1.75 [95% CI, [95% CI, 1.09–1.20]) and CHD (RR, 1.22 [95%
1.18–2.62]), and loud snoring (OR, 2.21 [95% CI, CI, 1.13–1.31]) but not stroke (RR, 1.09 [95% CI,
1.56–3.14]).19 0.99–1.19]). Long sleep duration was associated
• National data indicate that the following char- with total CVD (RR, 1.36 [95% CI, 1.26–1.48]),
acteristics are associated with increased risk of CHD (RR, 1.21 [95% CI, 1.12–1.30]), and stroke
incident diagnosed insomnia: age >45 years (HR, (RR, 1.45 [95% CI, 1.30–1.62]).
1.69 [95% CI, 1.40–2.03] for 45–64 years and • Insomnia symptoms have also been associated
HR, 2.11 [95% CI, 1.63–2.73] for ≥65 years) with incident DM, including difficulty falling

e196 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

asleep (OR, 1.57 [95% CI, 1.25–1.97]) and cardiovascular mortality (HR, 0.37 [95% CI, 0.16–

CLINICAL STATEMENTS
difficulty staying asleep (OR, 1.84 [95% CI, 0.54]) were significantly lower in CPAP-treated

AND GUIDELINES
1.39–2.43]).28 than in untreated patients.16
• The deepest stage of non–rapid-eye movement • An RCT tested the effect of early nasal CPAP
sleep, also called slow-wave sleep, is thought to treatment in patients with first-ever ischemic
be a restorative stage of sleep. In the Sleep Heart stroke and moderate to severe OSA over a
Health Study, which used in-home polysomnogra- 24-month period.36 Patients assigned to nasal
phy to characterize sleep, it was found that par- CPAP but who refused the treatment were
ticipants with a lower proportion of slow-wave excluded. The cardiovascular mortality rate was
sleep had significantly greater odds of incident 0% in the nasal CPAP group (0 of 57 patients)
hypertension (quartile 1 versus quartile 3: OR, compared with 4.3% in the control group (3
1.69 [95% CI, 1.21–2.36]).30 of 69 patients; P=0.16). The average time from
• Short sleep duration was associated with stroke onset until the appearance of the first
increased risk of incident hypertension in adults cardiovascular event was significantly longer
aged <65 years on the basis of a meta-analysis of in the nasal CPAP group than in the control
4 studies (OR, 1.33 [95% CI, 1.11–1.61]).31 group (14.9 versus 7.9 months; P=0.044). No
• A meta-analysis of 15 prospective studies observed differences were observed in CVD events or
a significant association between the presence of all-cause mortality.
OSA and the risk of cerebrovascular disease (HR, • Another RCT enrolled people aged 45 to 75
1.94 [95% CI, 1.31–2.89]).32 years with moderate-to-severe OSA without
• Among patients with AMI, the presence of excessive daytime sleepiness and who also had
moderate to severe OSA is associated with a coronary or cerebrovascular disease, to compare
greater likelihood of an NSTEMI versus STEMI CPAP plus usual care to usual care alone.37 A
(OR, 1.59 [95% CI, 1.07–2.37]), and the preva- total of 2687 patients were included in this sec-
lence of NSTEMI increases with increasing sever- ondary prevention trial and followed up for an
ity of OSA: 18.3% for no OSA, 35.4% for mild average of 3.7 years. No statistically significant
OSA, 33.9% for moderate OSA, and 41.6% for difference was observed for a composite of pri-
severe OSA.33 mary end points (HR, 1.10 [95% CI 0.91–1.32]),
• Central sleep apnea was associated with 2 to 3 including death attributable to cardiovascular
Downloaded from http://ahajournals.org by on February 7, 2019

times increased odds of incident AF, but OSA was causes, MI, stroke, or hospitalization for HF, UA,
not associated with incident AF.34 and TIA.

Awareness, Treatment, and Control Costs

• OSA is often undiagnosed. One study reported • Analysis of direct and indirect costs related to
that 93% of females and 82% of males with sleep disorders and other health consequences of
moderate to severe OSA have not been clinically sleep disorders suggested that the approximate
diagnosed.35 cost for a population the size of the United States
• A meta-analysis of 8 studies found that all-cause would have been approximately $109 billion in
mortality (HR, 0.66 [95% CI, 0.59–0.73]) and 2004.38

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e197

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12
CLINICAL STATEMENTS
AND GUIDELINES

Chart 12-1. Prevalence of inadequate sleep (<7 h) in US adults by age and sex.
Data source: National Health and Nutrition Examination Survey, 2015 to 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 12-2. Prevalence of trouble falling asleep in US adults by age and sex.
Data source: National Health and Nutrition Examination Survey, 2005 to 2008.

e198 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-3. Prevalence of trouble staying asleep in US adults by age and sex.
Data source: National Health and Nutrition Examination Survey, 2005 to 2008.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 12-4. Prevalence of waking too early in US adults by age and sex.
Data source: National Health and Nutrition Examination Survey, 2005 to 2008.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e199

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12
CLINICAL STATEMENTS
AND GUIDELINES

Chart 12-5. Prevalence of inadequate sleep (<7 h) and insomnia symptoms, trouble falling asleep, trouble staying asleep, and waking too early in
US adults by race/ethnicity.
Hisp indicates Hispanic; Mex Amer, Mexican American; and NH, non-Hispanic.
Data source: National Health and Nutrition Examination Survey, 2005 to 2008.

12. Carnethon MR, De Chavez PJ, Zee PC, Kim KY, Liu K, Goldberger JJ, Ng J,
‍‍‍REFERENCES Knutson KL. Disparities in sleep characteristics by race/ethnicity in a popu-
1. Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, Dinges lation-based sample: Chicago Area Sleep Study. Sleep Med. 2016;18:50–
DF, Gangwisch J, Grandner MA, Kushida C, Malhotra RK, Martin JL, 55. doi: 10.1016/j.sleep.2015.07.005
13. Yin J, Jin X, Shan Z, Li S, Huang H, Li P, Peng X, Peng Z, Yu K, Bao W, Yang
Downloaded from http://ahajournals.org by on February 7, 2019

Patel SR, Quan SF, Tasali E. Recommended amount of sleep for a healthy
adult: a joint consensus statement of the American Academy of Sleep W, Chen X, Liu L. Relationship of sleep duration with all-cause mortality
Medicine and Sleep Research Society. Sleep. 2015;38:843–844. doi: and cardiovascular events: a systematic review and dose-response meta-
10.5665/sleep.4716 analysis of prospective cohort studies. J Am Heart Assoc. 2017;6:e005947.
2. Paruthi S, Brooks LJ, D’Ambrosio C, Hall WA, Kotagal S, Lloyd RM, Malow doi: 10.1161/JAHA.117.005947
BA, Maski K, Nichols C, Quan SF, Rosen CL, Troester MM, Wise MS. 14. Åkerstedt T, Ghilotti F, Grotta A, Bellavia A, Lagerros YT, Bellocco R.
Consensus statement of the American Academy of Sleep Medicine on the Sleep duration, mortality and the influence of age. Eur J Epidemiol.
recommended amount of sleep for healthy children: methodology and dis- 2017;32:881–891. doi: 10.1007/s10654-017-0297-0
cussion. J Clin Sleep Med. 2016;12:1549–1561. doi: 10.5664/jcsm.6288 15. Beydoun HA, Beydoun MA, Chen X, Chang JJ, Gamaldo AA, Eid SM,
3. Liu Y, Wheaton AG, Chapman DP, Cunningham TJ, Lu H, Croft JB. Zonderman AB. Sex and age differences in the associations between sleep
Prevalence of healthy sleep duration among adults–United States, behaviors and all-cause mortality in older adults: results from the National
2014. MMWR Morb Mortal Wkly Rep. 2016;65:137–141. doi: Health and Nutrition Examination Surveys. Sleep Med. 2017;36:141–151.
10.15585/mmwr.mm6506a1 doi: 10.1016/j.sleep.2017.05.006
4. Gamble S, Mawokomatanda T, Xu F, Chowdhury PP, Pierannunzi C, Flegel 16. Fu Y, Xia Y, Yi H, Xu H, Guan J, Yin S. Meta-analysis of all-cause and car-
D, Garvin W, Town M. Surveillance for certain health behaviors and con- diovascular mortality in obstructive sleep apnea with or without continu-
ditions among states and selected local areas - Behavioral Risk Factor ous positive airway pressure treatment. Sleep Breath. 2017;21:181–189.
Surveillance System, United States, 2013 and 2014. MMWR Surveill doi: 10.1007/s11325-016-1393-1
Summ. 2017;66:1–144. doi: 10.15585/mmwr.ss6616a1 17. Li Y, Zhang X, Winkelman JW, Redline S, Hu FB, Stampfer M, Ma J,
5. Knutson KL, Van Cauter E, Rathouz PJ, DeLeire T, Lauderdale DS. Trends Gao X. Association between insomnia symptoms and mortality: a
in the prevalence of short sleepers in the USA: 1975-2006. Sleep. prospective study of U.S. men. Circulation. 2014;129:737–746. doi:
2010;33:37–45. 10.1161/CIRCULATIONAHA.113.004500
6. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased 18. Parthasarathy S, Vasquez MM, Halonen M, Bootzin R, Quan SF, Martinez
prevalence of sleep-disordered breathing in adults. Am J Epidemiol. FD, Guerra S. Persistent insomnia is associated with mortality risk. Am J
2013;177:1006–1014. doi: 10.1093/aje/kws342 Med. 2015;128:268–75.e2. doi: 10.1016/j.amjmed.2014.10.015
7. Ohayon MM. Epidemiology of insomnia: what we know and what we still 19. Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, Walsleben
need to learn. Sleep Med Rev. 2002;6:97–111. JA, Finn L, Enright P, Samet JM; Sleep Heart Health Study Research Group.
8. Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. Predictors of sleep-disordered breathing in community-dwelling adults:
2006;29:85–93. the Sleep Heart Health Study. Arch Intern Med. 2002;162:893–900.
9. Buxton OM, Chang AM, Spilsbury JC, Bos T, Emsellem H, Knutson KL. 20. Chen LJ, Steptoe A, Chen YH, Ku PW, Lin CH. Physical activity, smok-
Sleep in the modern family: protective family routines for child and ado- ing, and the incidence of clinically diagnosed insomnia. Sleep Med.
lescent sleep. Sleep Health. 2015;1:15–27. 2017;30:189–194. doi: 10.1016/j.sleep.2016.06.040
10. Lumeng JC, Chervin RD. Epidemiology of pediatric obstructive sleep apnea. 21. Mukherjee S, Saxena R, Palmer LJ. The genetics of obstructive sleep
Proc Am Thorac Soc. 2008;5:242–252. doi: 10.1513/pats.200708-135MG apnoea. Respirology. 2018;23:18–27. doi: 10.1111/resp.13212
11. Lauderdale DS, Knutson KL, Yan LL, Rathouz PJ, Hulley SB, Sidney S, 22. van der Spek A, Luik AI, Kocevska D, Liu C, Brouwer RWW, van Rooij
Liu K. Objectively measured sleep characteristics among early-middle- JGJ, van den Hout MCGN, Kraaij R, Hofman A, Uitterlinden AG, van
aged adults: the CARDIA study. Am J Epidemiol. 2006;164:5–16. doi: IJcken WFJ, Gottlieb DJ, Tiemeier H, van Duijn CM, Amin N. Exome-
10.1093/aje/kwj199 wide meta-analysis identifies rare 3′-UTR variant in ERCC1/CD3EAP

e200 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 12

associated with symptoms of sleep apnea. Front Genet. 2017;8:151. doi: meta-analysis. Hypertens Res. 2012;35:1012–1018. doi: 10.1038/

CLINICAL STATEMENTS
10.3389/fgene.2017.00151 hr.2012.91

AND GUIDELINES
23. Koskenvuo M, Hublin C, Partinen M, Heikkilä K, Kaprio J. Heritability of 32. Wu Z, Chen F, Yu F, Wang Y, Guo Z. A meta-analysis of obstructive
diurnal type: a nationwide study of 8753 adult twin pairs. J Sleep Res. sleep apnea in patients with cerebrovascular disease. Sleep Breath.
2007;16:156–162. doi: 10.1111/j.1365-2869.2007.00580.x 2018;22:729–742. doi: 10.1007/s11325-017-1604-4
24. Patke A, Murphy PJ, Onat OE, Krieger AC, Özçelik T, Campbell SS, 33. Ludka O, Stepanova R, Sert-Kuniyoshi F, Spinar J, Somers VK,
Young MW. Mutation of the human circadian clock gene CRY1 in Kara T. Differential likelihood of NSTEMI vs STEMI in patients with
familial delayed sleep phase disorder. Cell. 2017;169:203–215.e13. doi: sleep apnea. Int J Cardiol. 2017;248:64–68. doi: 10.1016/j.ijcard.
10.1016/j.cell.2017.03.027 2017.06.034
25. Hirano A, Shi G, Jones CR, Lipzen A, Pennacchio LA, Xu Y, Hallows WC, 34. Tung P, Levitzky YS, Wang R, Weng J, Quan SF, Gottlieb DJ, Rueschman
McMahon T, Yamazaki M, Ptacek LJ and Fu YH. A Cryptochrome 2 muta- M, Punjabi NM, Mehra R, Bertisch S, Benjamin EJ, Redline S. Obstructive
tion yields advanced sleep phase in humans. eLife. 2016;5:e16695. doi: and central sleep apnea and the risk of incident atrial fibrillation in a com-
10.7554/eLife.16695 munity cohort of men and women. J Am Heart Assoc. 2017;6:e004500.
26. Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller doi: 10.1161/JAHA.116.004500
MA. Meta-analysis of short sleep duration and obesity in children and 35. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed
adults. Sleep. 2008;31:619–626. proportion of sleep apnea syndrome in middle-aged men and women.
27. Wu Y, Zhai L, Zhang D. Sleep duration and obesity among adults: a meta- Sleep. 1997;20:705–706.
analysis of prospective studies. Sleep Med. 2014;15:1456–1462. doi: 36. Parra O, Sánchez-Armengol A, Bonnin M, Arboix A, Campos-Rodríguez
10.1016/j.sleep.2014.07.018 F, Pérez-Ronchel J, Durán-Cantolla J, de la Torre G, González Marcos
28. Cappuccio FP, D’Elia L, Strazzullo P, Miller MA. Quantity and quality of JR, de la Peña M, Carmen Jiménez M, Masa F, Casado I, Luz Alonso M,
sleep and incidence of type 2 diabetes: a systematic review and meta- Macarrón JL. Early treatment of obstructive apnoea and stroke outcome:
analysis. Diabetes Care. 2010;33:414–420. doi: 10.2337/dc09-1124 a randomised controlled trial. Eur Respir J. 2011;37:1128–1136. doi:
29. Cappuccio FP, Cooper D, D’Elia L, Strazzullo P, Miller MA. Sleep dura- 10.1183/09031936.00034410
tion predicts cardiovascular outcomes: a systematic review and meta- 37. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano
analysis of prospective studies. Eur Heart J. 2011;32:1484–1492. doi: O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S,
10.1093/eurheartj/ehr007 Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J,
30. Javaheri S, Zhao YY, Punjabi NM, Quan SF, Gottlieb DJ and Redline Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE
S. Slow-wave sleep is associated with incident hypertension: the Investigators and Coordinators. CPAP for prevention of cardiovascular
Sleep Heart Health Study. Sleep. 2018;41:zsx179. doi: 10.1093/ events in obstructive sleep apnea. N Engl J Med. 2016;375:919–931. doi:
sleep/zsx179 10.1056/NEJMoa1606599
31. Wang Q, Xi B, Liu M, Zhang Y, Fu M. Short sleep duration is associ- 38. Hillman DR, Murphy AS, Pezzullo L. The economic cost of sleep disorders.
ated with hypertension risk among adults: a systematic review and Sleep. 2006;29:299–305.
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e201

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

13. TOTAL CARDIOVASCULAR females. CVD prevalence excluding hyper-

CLINICAL STATEMENTS

tension (CHD, HF, and stroke only) is 9.0%

DISEASES
AND GUIDELINES

overall (24.3 million in 2016) (Table  13-1 and

ICD-9 390 to 459; ICD-10 I00 to I99. See Tables Chart 13-1).
13-1 through 13-4 and Charts 13-1 through 13-22 • The AHA’s 2020 Impact Goals are to improve the
cardiovascular health of all Americans by 20%
Click here to return to the Table of Contents
while reducing deaths attributable to CVDs and
stroke by 20%.1
Prevalence
(See Table 13-1 and Chart 13-1)
• On the basis of NHANES 2013 to 2016 data, Mortality
the prevalence of CVD (comprising CHD, HF, (See Tables 13-1 through 13-3 and Charts
stroke, and hypertension) in adults ≥20 years 13-2 through 13-17)
of age is 48.0% overall (121.5 million in 2016)
and increases with age in both males and
ICD-10 I00 to I99 for CVD; C00 to C97 for
cancer; C33 to C34 for lung cancer; C50
Abbreviations Used in Chapter 13
for breast cancer; J40 to J47 for CLRD;
AF atrial fibrillation
G30 for Alzheimer disease; E10 to E14 for
AHA American Heart Association DM; and V01 to X59 and Y85 to Y86 for
ARIC Atherosclerosis Risk in Communities Study accidents.
ASCVD atherosclerotic cardiovascular disease
BMI body mass index • Deaths attributable to diseases of the heart and
BP blood pressure CVD in the United States increased steadily dur-
CARDIA Coronary Artery Risk Development in Young Adults ing the 1900s to the 1980s and declined into the
CDC Centers for Disease Control and Prevention
2010s (Charts 13-2 through 13-4).
CHD coronary heart disease
CI confidence interval
• CHD (43.2%) is the leading cause of CVD death
CKD chronic kidney disease in the United States, followed by stroke (16.9%),
CLRD chronic lower respiratory disease HBP (9.8%), HF (9.3%), diseases of the arteries
CVD cardiovascular disease (3.0%), and other minor CVD causes combined
Downloaded from http://ahajournals.org by on February 7, 2019

DM diabetes mellitus
(17.7%) (Chart 13-4).
ED emergency department
FHS Framingham Heart Study
• The age-adjusted death rate attributable to CVD
GBD Global Burden of Disease decreased from 269.6 per 100 000 population
HBP high blood pressure in 2006 to 219.4 per 100 000 in 2016, which
HCUP Healthcare Cost and Utilization Project amounts to an 18.6% decrease.
HD heart disease • On the basis of 2016 mortality data2:
HDL high-density lipoprotein
— CVD currently claims more lives each year
HF heart failure
HIV human immunodeficiency virus than cancer and chronic lung disease com-
ICD-9 International Classification of Diseases, 9th Revision bined (Charts 13-5 through 13-15). More
ICD-10 International Classification of Diseases, 10th Revision than 360 000 people died in 2016 of CHD,
IHD ischemic heart disease the most common type of HD.
IMPACT International Model for Policy Analysis of Agricultural
Commodities and Trade
— In 2016, 2 744 248 resident deaths were
LDL-C low-density lipoprotein cholesterol registered in the United States. Ten lead-
MEPS Medical Expenditure Panel Survey ing causes accounted for 74.1% of all reg-
MESA Multi-Ethnic Study of Atherosclerosis istered deaths. The 10 leading causes of
MI myocardial infarction death in 2016 were the same as in 2015;
NAMCS National Ambulatory Medical Care Survey
these include HD (No. 1), cancer (No. 2),
NCHS National Center for Health Statistics
NH non-Hispanic
unintentional injuries (No. 3), CLRDs (No.
NHAMCS National Hospital Ambulatory Medical Care Survey 4), stroke (No. 5), Alzheimer disease (No. 6),
NHANES National Health and Nutrition Examination Survey DM (No. 7), influenza and pneumonia (No.
NHDS National Hospital Discharge Survey 8), kidney disease (No. 9), and suicide (No.
NHLBI National Heart, Lung, and Blood Institute
10). Seven of the 10 leading causes of death
PA physical activity
RR relative risk
had a decrease in age-adjusted death rates.
SBP systolic blood pressure The age-adjusted death rates decreased
SES socioeconomic status 1.8% for HD, 1.7% for cancer, 2.4% for
SNAP Supplemental Nutrition Assistance Program CLRDs, 0.8% for stroke, 1.4% for DM,
TC total cholesterol 11.2% for influenza and pneumonia, and

e202 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

2.2% for kidney disease. The age-adjusted from 5 797 000 to 4 791 000 (HCUP, hospital

CLINICAL STATEMENTS
rate increased 9.7% for unintentional inju- discharges 2014; NHDS, NCHS, and NHLBI;

AND GUIDELINES
ries, 3.1% for Alzheimer disease, and 1.5% Table  13-1). The CVD principal diagnosis dis-
for suicide.3 charges in 2014 comprised 2 571 000 males and
• HD accounted for 635 260 of all 840 678 CVD 2 220  000 females (unpublished NHDS, NCHS,
deaths in 2016. The number of CVD deaths and NHLBI tabulation).
was 428 434 for males and 412 244 for females • From 1993 to 2014, the number of hospital dis-
(Charts 13-2 and 13-3). The number was charges for CVD in the United States increased in
332 556 for NH white males, 52 874 for NH black the first decade and then began to decline in the
males, 27 801 for Hispanic males, 11 023 for NH second decade (Chart 13-18).
Asian and Pacific Islander males, 322 328 for • In 2014, cardiovascular causes were the leading
NH white females, 51 767 for NH black females, diagnostic group of hospital discharges in the
24 428 for Hispanic females, and 10 672 for NH United States (Chart 13-19).
Asian and Pacific Islander females. Among other • In 2015, there were 88 343 000 physician office
causes of death, cancer accounted for 598 031 visits with a primary diagnosis of CVD (NAMCS,
deaths; chronic lung disease, 154  592; acci- NHLBI tabulation).5 In 2015, there were 4 704 000
dents, 161 346; and Alzheimer disease, 116 103 ED visits with a primary diagnosis of CVD
(Chart 13-6). (NHAMCS, NHLBI tabulation).6
• Approximately 161  438 Americans, or 19.2%,
who were <65 years of age died of CVD, and
306 638, or 36.5% of deaths attributed to CVD, Operations and Procedures
occurred before the age of 75 years, which is well (See Chapter 25 for detailed
below the average US life expectancy of 78.6 information.)
years in 2016.3 • In 2014, an estimated 7 971 000 inpatient car-
• The CVD mortality trends for males and females diovascular operations and procedures were per-
in the United States declined from 1979 to 2016 formed in the United States (unpublished NHLBI
(Chart 13-16). tabulation of HCUP data).
• The age-adjusted death rates per 100 000 pop-
ulation for CVD, CHD, and stroke differ by US
Downloaded from http://ahajournals.org by on February 7, 2019

state (Chart 13-17; Table  13-2) and globally Cost

(Table 13-3). (See Chapter 26 for detailed
• CVD death rates also vary among United States information.)
counties. In 2014, the ratio between counties at
the 90th and 10th percentile was 2.0 for IHD • In the United States, 22.2% of adults (53 316 677
(119.1 versus 235.7 deaths per 100 000 people) people) report any disability. In 2006, 26.7%
and 1.7 for cerebrovascular disease (40.3 versus of resident adult healthcare expenditures were
68.1 deaths per 100 000 people). For other CVD associated with disability care and totaled
causes, the ratio ranged from 1.4 (aortic aneu- $397.8 billion.7 For people with disabilities in
rysm: 3.5 versus 5.1 deaths per 100 000 people) the United States, HD, stroke, and hyperten-
to 4.2 (hypertensive HD: 4.3 versus 17.9 deaths sion were among the 15 leading conditions
per 100 000 people). A region of higher CVD that caused those disabilities. Disabilities were
mortality extends from southeastern Oklahoma defined as difficulty with activities of daily living
along the Mississippi River Valley to eastern or instrumental activities of daily living, specific
Kentucky.4 functional limitations (except vision, hearing, or
speech), and limitation in ability to do house-
work or work at a job or business.8,9 The esti-
Hospital Discharges, Ambulatory Care mated direct and indirect cost of CVD for
Visits, Home Healthcare Patients, Nursing 2014 to 2015 was $351.2 billion (MEPS, NHLBI
Home Residents, and Hospice Care tabulation).
Discharges • In 2016, the AHA estimated that by 2035,
45.1% of the US population would have some
(See Table 13-1 and Charts 13-18 form of CVD. Total costs of CVD are expected
and 13-19) to reach $1.1 trillion in 2035, with direct
• From 2004 to 2014, the number of inpatient medical cost projected to reach $748.7 billion
discharges from short-stay hospitals with and indirect costs estimated to reach $368
CVD as the principal diagnosis decreased billion. 10

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e203

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Risk Factors in poor cardiovascular health explained in part by

CLINICAL STATEMENTS

individual and state-level factors such as policies,

• A recent study using the GBD methodology
AND GUIDELINES

food, and PA environments.19

examined the burden of CVD among US states
and found that a large proportion of CVD is
attributable to (in decreasing order of contribu- Impact of Healthy Lifestyle and Low Risk
tion) dietary risk, high SBP, high BMI, high TC Factor Levels
level, high fasting plasma glucose level, tobacco
(See Chapter 2 for more detailed
smoking, and low levels of PA.11
• It is estimated that 47% of all Americans have statistics regarding healthy lifestyle and
at least 1 of the 3 well-established key risk fac- low risk factor levels.)
tors for CVD, which are HBP, high cholesterol, and • A study of the decrease in US deaths attributable
smoking.12 to CHD from 1980 to 2000 suggested that ≈47%
• In 2005, HBP was the single largest risk factor for of the decrease was attributable to increased use
cardiovascular mortality in the United States and of evidence-based medical therapies for second-
was responsible for an estimated 395 000 (95% ary prevention and 44% to changes in risk fac-
CI, 372  000–414  000) cardiovascular deaths tors in the population attributable to lifestyle and
(45% of all cardiovascular deaths). Additional environmental changes.8
risk factors for cardiovascular mortality were • Approximately 80% of CVDs can be prevented
overweight/obesity, physical inactivity, high through not smoking, eating a healthy diet,
LDL-C, smoking, high dietary salt, high dietary engaging in PA, maintaining a healthy weight,
trans fatty acids, and low dietary omega-3 fatty and controlling HBP, DM, and elevated lipid lev-
acids.13 els. The presence of a greater number of optimal
• When added to traditional CVD risk factors, non- cardiovascular health metrics is associated with a
traditional CVD risk factors such as CKD, SBP vari- graded and significantly lower risk of total and
ability, migraine, severe mental illness, systemic CVD mortality.20
lupus erythematosus, use of corticosteroid or • During more than 5 million person-years of fol-
antipsychotic medications, or erectile dysfunc- low-up combined in the Nurses’ Health Studies
tion improved CVD prediction by the United and Health Professionals Follow-Up Study, regu-
Downloaded from http://ahajournals.org by on February 7, 2019

Kingdom–based QRISK score.14 lar consumption of peanuts and tree nuts (≥2
• In Nurses’ Health Study participants, compared times weekly) or walnuts (≥1 time weekly) was
with a more typical reproductive lifespan and age associated with a 13% to 19% lower risk of total
at first menarche, early age at menopause (age CVD.21
<40 years) was associated with a 32% higher • Seventeen-year mortality data from the
CVD risk; extremely early age at menarche (age NHANES II Mortality Follow-up Study indicated
≤10 years) was associated with a 22% higher that the RR for fatal CHD was 51% lower for
CVD risk.15 males and 71% lower for females with none
• People living with HIV are more likely to experi- of the 3 major risk factors (hypertension, cur-
ence CVD before age 60 years than uninfected rent smoking, and elevated TC [≥240 mg/dL])
people. Cumulative lifetime CVD risk in people liv- than for those with ≥1 risk factor. If all 3 major
ing with HIV (65% for males, 44% for females) is risk factors had not occurred, it is hypothesized
higher than in the general population and similar that 64% of all CHD deaths among females and
to that of people living with DM (67% for males, 45% of CHD deaths in males could have been
57% for females).16 avoided.22
• Patients living with type 1 DM are at increased • Data from the Cardiovascular Lifetime Risk
risk of early CVD. In Pittsburgh Epidemiology of Pooling Project, which involved 18 cohort stud-
Diabetes Complications Study participants with ies and combined data on 257 384 people (both
type 1 DM and aged 40 to 44 years at baseline, black and white males and females), indicate
mean absolute 10-year CVD risk was 14.8%. that at 45 years of age, participants with opti-
Mean absolute 10-year CVD risk was 6.3% in mal risk factor profiles had a substantially lower
those aged 30 to 39 years.17 lifetime risk of CVD events than those with 1
• Neighborhood-level socioeconomic deprivation major risk factor (1.4% versus 39.6% among
was associated with greater risk of CVD mortal- males; 4.1% versus 20.2% among females).
ity in older males in Britain, independent of indi- Having ≥2 major risk factors further increased
vidual social class or risk factors.18 In the United lifetime risk to 49.5% in males and 30.7% in
States, there are significant state-level variations females.23

e204 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

• In another study, FHS investigators conducted and these beneficial effects would likely be

CLINICAL STATEMENTS
follow-up of 2531 males and females who applicable not only for white but also for black

AND GUIDELINES
were examined between the ages of 40 and participants.29
50 years and observed their overall rates of • Mortality data from the National Vital Statistics
survival and survival free of CVD to 85 years System from 2001 to 2010 show that the avoid-
of age and beyond. Low levels of the major able death rate among blacks was nearly twice
risk factors in middle age were associated with that of whites.30
overall survival and morbidity-free survival to • Data from the CDC’s Vital and Health Statistics
≥85 years of age.24 2008 to 2010 showed that smokers with fam-
• In young adults aged 18 to 30 years in the CARDIA ily incomes below the poverty level were more
study and without clinical risk factors, a Healthy than twice as likely as adults in the highest
Heart Score combining self-reported information family income group to be current smokers
on modifiable lifestyle factors including smoking (29.2% versus 13.9%, respectively; NCHS/CDC,
status, alcohol intake, and healthful dietary pat- 2013).31
tern predicted risk for early ASCVD (before age 55 • The US IMPACT Food Policy Model, a computer
years).25 simulation model, projected that a national policy
• Data from NHANES 2005 to 2010 showed that combining a 30% fruit and vegetable subsidy
only 8.8% of adults complied with ≥6 heart- targeted to low-income SNAP recipients and a
healthy behaviors. Of the 7 factors studied, population-wide 10% price reduction in fruits
healthy diet was the least likely to be achieved and vegetables in the remaining population could
(only 22% of adults with a healthy diet).20 prevent ≈230 000 deaths by 2030 and reduce
• In the United States, higher whole grain con- the socioeconomic disparity in CVD mortality by
sumption was associated with lower CVD mor- 6%.32
tality, independent of other dietary and lifestyle • A study of nearly 1500 participants in MESA
factors. Every serving (28 g/d) of whole grain found that Hispanics with hypertension, hyper-
consumption was associated with a 9% (95% CI, cholesterolemia, or DM who spoke Spanish at
4%–13%) lower CVD mortality.26 home (as a proxy of lower levels of accultura-
tion) or had spent less than half a year in the
United States had higher SBP, LDL-C, and fast-
Downloaded from http://ahajournals.org by on February 7, 2019

Disparities in CVD Risk Factors ing blood glucose, respectively, than Hispanics
(See Chart 13-20) who were preferential English speakers and who
• Although traditional cardiovascular risk factors had lived a longer period of time in the United
are generally similar for males and females, there States.33
are several female-specific risk factors, such as • Findings from >15 000 Hispanics of diverse back-
disorders of pregnancy, adverse pregnancy out- grounds demonstrated that a sizeable proportion
comes, and menopause.27 of both males and females had major CVD risk
• CVD risk factor levels vary among counties and factors, with higher prevalence among Puerto
states within the continental United States. Rican subgroups and those with lower SES and a
Within-state differences in the county prevalence higher level of acculturation.34
of uncontrolled hypertension were as high as 7.8
percentage points in 2009.28
Family History and Genetics
• Analysis of >14 000 middle-aged participants
in the ARIC study sponsored by the NHLBI (See Table 13-4)
showed that ≈90% of CVD events in black • A family history of CVD increases risk of CVD,
participants, compared with ≈65% in white with the largest increase in risk if the family
participants, appeared to be explained by ele- member’s CVD was premature (Table 13-4).35
vated or borderline risk factors. Furthermore, • A reported family history of premature parental
the prevalence of participants with elevated CHD is associated with incident MI or CHD in
risk factors was higher in black participants; offspring. In FHS, the occurrence of a validated
after accounting for education and known premature atherosclerotic CVD event in either a
CVD risk factors, the incidence of CVD was parent36 or a sibling37 was associated with an ≈2-
identical in black and white participants. fold elevated risk for CVD, independent of other
Although organizational and social barriers traditional risk factors. Addition of a family history
to primary prevention do exist, the primary of premature CVD to a model that contained tra-
prevention of elevated risk factors might sub- ditional risk factors provided improved prognostic
stantially impact the future incidence of CVD, value in FHS.36

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e205

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

• The association of a family history of CVD with (95% CI, 272.1–284.6), which represents a
CLINICAL STATEMENTS

increased risk of CVD appears to be present across decrease of 14.5% (95% CI, −16.2% to −12.5%)
AND GUIDELINES

ethnic subgroups.38,39 from 2006. Overall, the crude prevalence of CVD

• Family history is also associated with subtypes of was 470.8 million (95% CI, 453.4–488.7 mil-
CVD, including HF,40 stroke, AF,41 and thoracic lion) in 2016, an increase of 26.7% (95% CI,
aortic disease.42 25.6%–27.8%) compared with 2006; however,
• Estimates of familial clustering of CVD are likely the age-adjusted prevalence was 6877.9 (95%
underestimated by self-report; in the multigen- CI, 6623.3–7141.3), a decrease of 0.8% (95%
erational FHS, only 75% of participants with a CI, −1.6% to −0.0%) from 2006.11
documented parental history of a heart attack • The GBD 2016 Study used statistical models and
before age 55 years reported that history when data on incidence, prevalence, case fatality, excess
asked.43 mortality, and cause-specific mortality to estimate
• A comprehensive scientific statement on the role disease burden for 315 diseases and injuries in
of genetics and genomics for the prevention and 195 countries and territories. CVD mortality and
treatment of CVD is available elsewhere.44 prevalence vary widely among world regions46:
— The highest mortality rates attributable to
CVD were in Eastern Europe and Central Asia
Awareness of Warning Signs and Risk (Chart 13-21).
Factors for CVD — CVD prevalence is highest in sub-Saharan
• Surveys conducted every 3 years since 1997 by Africa, the North Africa/Middle East region,
the AHA to evaluate trends in females’ aware- Eastern and Central Europe, and Central Asia
ness, knowledge, and perceptions related to CVD (Chart 13-22).
found most recently (in 2012) that awareness of • CVD is the leading global cause of death and is
HD as the leading cause of death among females expected to account for >23.6 million deaths by
was 56%, compared with 30% in 1997 (P<0.05). 2030.47 Deaths attributable to IHD increased by
Awareness among black and Hispanic females an estimated 41.7% from 1990 to 2013.48
• In 2011, data from the World Economic Forum
in 2012 was similar to that of white females in
found that CVD represented 50% of noncommu-
1997; however, awareness rates in 2012 among
nicable disease deaths.48 CVD represents 37% of
Downloaded from http://ahajournals.org by on February 7, 2019

black and Hispanic females remained below that

deaths of individuals <70 years of age that are
of white females. Awareness of heart attack signs
attributable to noncommunicable diseases.49
remained low for all racial/ethnic and age groups
• In 2013, ≈70% of CVD deaths occurred in low- to
surveyed during the same time.45
middle-income countries.50 CVD is a major cause
of death in both males and females worldwide.42
Global Burden of CVD • In May 2012, during the World Health Assembly,
(See Table 13-3 and Charts 13-21 ministers of health agreed to adopt a global
target to reduce premature (age 30–70 years)
and 13-22) noncommunicable disease mortality by 25% by
• The death rates for all causes and CVD in 31 2025.51 Targets for 6 risk factors (tobacco and
selected countries in 2016 are presented in alcohol use, salt intake, obesity, and raised BP and
Table 13-3. glucose) were also agreed on to address this goal.
• In 2016, ≈17.6 million (95% CI, 17.3–18.1 mil- It was projected that if the targets are met, pre-
lion) deaths were attributed to CVD globally, mature deaths attributable to CVDs in 2025 will
which amounted to an increase of 14.5% (95% be reduced by 34%, with 11.4 million and 15.9
CI, 12.1%–17.1%) from 2006. The age-adjusted million deaths delayed or prevented in those aged
death rate per 100 000 population was 277.9 30 to 69 years and ≥70 years, respectively.52

e206 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Table 13-1.  Cardiovascular Diseases

CLINICAL STATEMENTS
Prevalence, 2013–2016: Prevalence, 2013–2016: Mortality, 2016: All Hospital Discharge,

AND GUIDELINES
Population Group Age ≥20 y Age ≥20 y* Ages† 2014: All Ages Cost, 2014–2015
Both sexes 121 500 000 (48.0%) 24 300 000 (9.0%) 840 678 4 791 000 $351.2 Billion
Males 61 500 000 (51.2%) 12 300 000 (9.6%) 428 434 (51.0%)‡ 2 571 000 $224.7 Billion
Females 60 000 000 (44.7%) 12 000 000 (8.4%) 412 244 (49.0%)‡ 2 220 000 $126.5 Billion
NH white males 50.6% 9.7% 332 556 … …
NH white females 43.4% 8.1% 322 328 … …
NH black males 60.1% 10.7% 52 874 … …
NH black females 57.1% 10.5% 51 767 … …
Hispanic males 49.0% 7.8% 27 801 … …
Hispanic females 42.6% 8.0% 24 428 … …
NH Asian males 47.4% 6.5% 11 023§ … …
NH Asian females 37.2% 4.6% 10 672§ … …
NH American Indian/ … … 4313 … …
Alaska Native

Ellipses (…) indicate data not available; and NH, non-Hispanic.

*Prevalence excluding hypertension.
†Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
‡These percentages represent the portion of total cardiovascular disease mortality that is attributable to males vs females.
§Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2013 to 2016, National Center for Health Statistics (NCHS) and National Heart, Lung, and
Blood Institute. Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2014 US
population estimates. Mortality: Centers for Disease Control and Prevention/NCHS, 2016 Mortality Multiple Cause-of-Death–United States. These data represent
underlying cause of death only for International Classification of Diseases, 10th Revision codes I00 to I99 (diseases of the circulatory system). Mortality for NH Asians
includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, National (Nationwide) Inpatient Sample, 2014. Agency for Healthcare Research
and Quality. Cost: Medical Expenditure Panel Survey, average annual 2014 to 2015 (direct costs) and mortality data from NCHS and present value of lifetime earnings
from the Institute for Health and Aging, University of California, San Francisco (indirect costs).
Downloaded from http://ahajournals.org by on February 7, 2019

Table 13-2.  Age-Adjusted Death Rates per 100 000 Population for CVD, CHD, and Stroke by State, 2014 to 2016

CVD CHD Stroke

% Change, % Change, % Change,
Death 2004–2006 to Death 2004–2006 to Death 2004–2006 to
State Rank Rate 2014–2016 Rank Rate 2014–2016 Rank Rate 2014–2016
Alabama 51 295.4 −17.4 21 89.2 −31.1 52 50.7 −18.4
Alaska 13 197.2 −15.5 12 80.4 −14.1 26 36.2 −30.3
Arizona 6 186.2 −24.2 22 89.7 −34.9 7 29.6 −27.8
Arkansas 49 284.7 −14.2 51 133.7 −22.1 50 46.0 −26.5
California 14 198.0 −27.9 23 90.1 −39.5 23 35.7 −28.5
Colorado 3 178.5 −22.1 5 69.5 −33.7 19 34.5 −18.2
Connecticut 7 186.8 −21.3 9 77.1 −34.3 3 27.0 −27.0
Delaware 30 218.9 −23.4 34 101.9 −35.5 37 40.0 −7.1
District of Columbia 46 259.5 −23.9 46 117.9 −39.4 28 36.8 −8.2
Florida 17 199.8 −22.6 28 94.8 −35.9 24 35.9 −11.0
Georgia 39 242.9 −23.0 10 77.5 −36.2 46 44.1 −21.9
Hawaii 5 180.0 −20.7 2 67.2 −24.8 21 35.5 −25.5
Idaho 26 207.6 −17.9 17 84.6 −27.9 27 36.8 −31.8
Illinois 34 223.1 −22.3 26 90.7 −37.6 32 37.9 −22.5
Indiana 38 240.1 −20.8 35 102.6 −29.9 38 40.1 −23.3
Iowa 28 210.8 −19.6 38 105.0 −28.9 11 33.2 −30.5
Kansas 33 222.2 −17.1 19 87.7 −27.7 36 38.8 −22.4

(Continued )

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e207

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Table 13-2. Continued
CLINICAL STATEMENTS

CVD CHD Stroke

AND GUIDELINES

% Change, % Change, % Change,

Death 2004–2006 to Death 2004–2006 to Death 2004–2006 to
State Rank Rate 2014–2016 Rank Rate 2014–2016 Rank Rate 2014–2016
Kentucky 45 258.5 −21.0 41 107.4 −32.8 41 41.0 −24.2
Louisiana 48 275.2 −17.3 37 103.6 −31.9 48 45.9 −19.9
Maine 15 198.1 −19.9 14 82.7 −31.2 13 33.4 −26.7
Maryland 32 221.9 −21.2 30 96.6 −35.9 35 38.5 −19.6
Massachusetts 4 179.0 −24.7 7 74.5 −33.8 6 28.4 −30.2
Michigan 43 255.8 −17.0 47 121.6 −26.6 33 38.2 −21.4
Minnesota 2 164.3 −20.2 1 59.6 −31.3 12 33.3 −23.2
Mississippi 52 306.7 −19.1 42 107.7 −33.5 51 50.7 −12.5
Missouri 41 251.1 −19.5 45 111.7 −31.6 40 40.7 −23.3
Montana 19 201.2 −14.2 16 84.3 −16.4 16 34.2 −24.8
Nebraska 18 200.2 −19.0 8 76.0 −24.7 14 33.8 −28.4
Nevada 42 252.8 −18.7 44 110.9 −12.4 22 35.6 −25.5
New Hampshire 10 190.8 −24.0 15 84.1 −36.9 4 27.9 −29.7
New Jersey 27 210.7 −22.4 32 97.2 −36.6 8 30.9 −19.6
New Mexico 11 193.7 −19.5 29 95.4 −22.5 17 34.3 −14.6
New York 31 221.8 −25.3 49 123.2 −36.7 1 25.9 −18.9
North Carolina 29 218.8 −24.1 24 90.5 −33.9 45 43.6 −24.6
North Dakota 12 196.7 −20.8 18 86.4 −35.9 15 33.8 −31.4
Ohio 40 246.6 −18.4 43 107.8 −33.2 39 40.4 −18.3
Oklahoma 50 291.5 −17.5 52 139.7 −28.9 43 42.6 −27.7
Downloaded from http://ahajournals.org by on February 7, 2019

Oregon 9 190.0 −22.6 3 67.6 −35.5 30 37.6 −31.5

Pennsylvania 36 228.6 −21.4 33 100.0 −32.8 29 37.5 −20.6
Puerto Rico 1 157.8 −29.2 6 70.4 −36.5 5 28.0 −33.6
Rhode Island 16 198.4 −27.0 40 105.7 −41.0 2 26.5 −28.3
South Carolina 37 239.8 −20.2 27 91.0 −30.8 47 45.5 −24.3
South Dakota 22 205.4 −19.0 39 105.2 −27.6 25 35.9 −25.8
Tennessee 47 267.5 −20.0 50 129.3 −28.6 49 45.9 −24.9
Texas 35 226.9 −21.8 31 96.6 −34.8 42 42.1 −20.8
Utah 20 202.4 −12.7 4 68.3 −21.0 34 38.3 −13.7
Vermont 21 203.8 −15.7 36 102.7 −20.0 10 32.4 −19.7
Virginia 25 206.1 −25.3 13 82.2 −34.0 31 37.7 −29.4
Washington 8 187.6 −23.8 11 80.4 −35.4 20 34.8 −28.8
West Virginia 44 258.3 −22.1 48 122.1 −28.6 44 43.6 −16.4
Wisconsin 24 205.7 −19.5 20 88.5 −27.3 18 34.5 −27.2
Wyoming 23 205.6 −19..2 25 90.5 −23.5 9 31.2 −31.2
Total United States 220.7 −22.1 96.8 -33.9 37.2 −22.5

Rates are most current data available as of April 2018. Rates are per 100 000 people. International Classification of Diseases, 10th Revision codes used were I00
to I99 for CVD, I20 to I25 for CHD, and I60 to I69 for stroke. CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Sources: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

e208 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Table 13-3.  Death Rates for CVDs and All Causes in Selected Countries, 2016

CLINICAL STATEMENTS
Sorted Alphabetically Sorted by Descending

AND GUIDELINES
by Country CVD CHD Stroke Total CVD Death Rate CVD CHD Stroke Total
Males aged 35–74 y
 Australia (15) 112.5 66.0 16.3 515.6 Belarus (14) 979.5 710.6 175.9 1884.6
 Austria (16) 161.6 94.1 19.2 647.8 Ukraine (15) 972.1 661.3 187.7 1853.4
 Belarus (14) 979.5 710.6 175.9 1884.6 Russia (13) 956.8 536.2 234.4 2060.5
 Belgium (15) 138.2 58.3 23.6 669.8 Romania (16) 535.0 213.5 135.2 1366.5
 Croatia (16) 329.7 171.2 79.6 1003.3 Hungary (16) 500.2 257.4 82.7 1361.1
 Czech Republic (16) 301.3 156.4 45.1 914.3 Serbia (15) 466.0 131.9 101.4 1241.6
 Denmark (15) 128.9 49.6 28.3 655.0 Slovakia (14) 400.6 222.5 89.0 1173.6
 Finland (14) 217.6 124.7 35.4 698.1 Croatia (16) 329.7 171.2 79.6 1003.3
 France (14) 106.5 40.9 19.5 656.2 Czech Republic (16) 301.3 156.4 45.1 914.3
 Germany (15) 193.0 92.5 25.9 727.4 United States (16) 236.6 123.5 27.6 824.4
 Hungary (16) 500.2 257.4 82.7 1361.1 Finland (14) 217.6 124.7 35.4 698.1
 Ireland (13) 175.3 109.4 23.1 599.1 Germany (15) 193.0 92.5 25.9 727.4
 Israel (15) 100.3 45.8 20.4 541.2 Ireland (13) 175.3 109.4 23.1 599.1
 Italy (15) 134.7 59.5 23.9 541.0 Taiwan (16) 174.6 51.9 50.1 833.0
 Japan (15) 125.0 40.9 40.6 531.7 Austria (16) 161.6 94.1 19.2 647.8
 Korea, South (15) 104.1 32.4 42.0 611.6 United Kingdom (15) 161.4 97.7 23.1 613.9
 Netherlands (16) 111.9 38.9 21.0 546.1 Portugal (14) 160.9 68.3 46.6 733.6
 New Zealand (13) 153.1 93.8 22.1 548.0 New Zealand (13) 153.1 93.8 22.1 548.0
 Norway (15) 112.0 59.7 18.2 503.1 Sweden (15) 147.2 82.4 20.8 514.1
 Portugal (14) 160.9 68.3 46.6 733.6 Belgium (15) 138.2 58.3 23.6 669.8
 Romania (16) 535.0 213.5 135.2 1366.5 Italy (15) 134.7 59.5 23.9 541.0
Downloaded from http://ahajournals.org by on February 7, 2019

  Russia (!3) 956.8 536.2 234.4 2060.5 Spain (15) 131.3 59.5 23.2 598.7
 Serbia (15) 466.0 131.9 101.4 1241.6 Denmark (15) 128.9 49.6 28.3 655.0
 Slovakia (14) 400.6 222.5 89.0 1173.6 Japan (15) 125.0 40.9 40.6 531.7
 Spain (15) 131.3 59.5 23.2 598.6 Australia (15) 112.5 66.0 16.3 515.6
 Sweden (15) 147.2 82.4 20.8 514.1 Switzerland (13) 112.1 54.3 13.8 506.0
 Switzerland (13) 112.1 54.3 13.8 506.0 Norway (15) 112.0 59.7 18.2 503.1
 Taiwan (16) 174.6 51.9 50.1 833.0 Netherlands (16) 111.9 38.9 21.0 546.1
 Ukraine (15) 972.1 661.3 187.7 1853.4 France (14) 106.5 40.9 19.5 656.2
 United Kingdom (15) 161.4 97.7 23.1 613.9 Korea, South (15) 104.1 32.4 42.0 611.6
 United States (16) 236.6 123.5 27.6 824.4 Israel (15) 100.3 45.8 20.4 541.2
Females aged 35–74 y
 Australia (15) 46.7 18.2 11.6 310.7 Ukraine (15) 393.3 261.5 94.1 723.2
 Austria (16) 67.6 28.6 14.5 350.5 Russia (13) 374.1 183.9 117.2 793.5
 Belarus (14) 348.3 228.0 88.6 662.2 Belarus (14) 348.3 228.0 88.6 662.2
 Belgium (15) 62.4 17.6 15.3 391.5 Serbia (15) 234.1 49.9 63.4 663.6
 Croatia (16) 122.0 51.0 39.0 442.4 Romania (16) 232.4 77.4 71.9 605.0
 Czech Republic (16) 116.1 45.3 21.2 438.0 Hungary (16) 193.4 86.8 37.4 624.6
 Denmark (15) 58.1 17.0 17.3 422.5 Slovakia (14) 154.6 77.9 40.0 505.1
 Finland (14) 68.5 26.8 20.0 336.6 Croatia (16) 122.0 51.0 39.0 442.4
 France (13) 38.3 9.0 11.0 311.2 United States (16) 117.5 47.5 20.4 518.4
 Germany (15) 77.8 26.2 15.4 391.8 Czech Republic (16) 116.1 45.3 21.2 438.0
 Hungary (16) 193.4 86.8 37.4 624.6 Germany (15) 77.8 26.2 15.4 391.8
 Ireland (13) 65.7 29.2 15.1 372.1 United Kingdom (15) 71.4 30.1 18.1 404.3

(Continued )

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e209

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Table 13-3. Continued
CLINICAL STATEMENTS

Sorted Alphabetically Sorted by Descending

AND GUIDELINES

by Country CVD CHD Stroke Total CVD Death Rate CVD CHD Stroke Total
 Israel (15) 42.0 12.6 11.4 311.9 Finland (1) 68.5 26.8 20.0 336.6
 Italy (15) 55.0 15.9 14.4 300.6 Austria (16) 67.6 28.6 14.5 350.5
 Japan (15) 44.9 10.0 17.1 244.7 New Zealand (13) 67.5 30.3 16.1 367.5
 Korea, South (15) 42.1 8.6 20.4 245.1 Ireland (13) 65.7 29.2 19.7 372.1
 Netherlands (16) 54.9 13.1 15.5 388.4 Portugal (14) 63.7 17.0 23.9 315.9
 New Zealand (13) 67.5 30.3 16.1 367.5 Taiwan (16) 63.5 16.0 19.7 372.6
 Norway (15) 45.0 15.2 12.6 326.4 Belgium (15) 62.4 17.6 15.3 391.5
 Portugal (14) 63.7 17.0 23.9 315.9 Sweden (15) 61.2 24.5 14.1 336.1
 Romania (16) 232.4 77.4 71.9 605.0 Denmark (15) 58.1 17.0 17.3 422.5
  Russia (13) 374.1 183.9 117.2 793.5 Italy (15) 55.0 15.9 14.4 300.6
 Serbia (15) 234.1 49.9 63.4 663.6 Netherlands (16) 54.9 13.1 15.5 388.4
 Slovakia (14) 154.6 77.9 40.0 505.1 Australia (15) 46.7 18.2 11.6 310.7
 Spain (15) 46.7 13.6 12.7 269.9 Spain (15) 46.7 13.6 12.7 269.9
 Sweden (15) 61.2 24.5 14.1 336.1 Norway (15) 45.0 15.2 12.6 326.4
 Switzerland (13) 44.7 14.2 10.7 295.0 Japan (15) 44.9 10.0 17.1 244.7
 Taiwan (16) 63.5 16.0 19.7 372.6 Switzerland (13) 44.7 14.2 10.7 295.0
 Ukraine (15) 393.3 261.5 94.1 723.2 Korea, South (15) 42.1 8.6 20.4 245.1
 United Kingdom (15) 71.4 30.1 18.1 404.3 Israel (15) 42.0 12.6 11.4 311.9
 United States (16) 117.5 47.5 20.4 518.4 France (14) 38.3 9.0 11.0 311.2

Rates are for the most recent year available (shown in parentheses as last 2 digits of year); most current data available as of April 2018. Rates are per 100 000
people, adjusted to the European Standard population. International Classification of Diseases, 10th Revision codes used were I00 to I99 for cardiovascular disease,
I20 to I25 for coronary heart disease, and I60 to I69 for stroke. CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Sources: The World Health Organization; National Center for Health Statistics; and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Table 13-4.  OR for Combinations of Parental Heart Attack History

OR (95% CI)
No family history 1.00

One parent with heart attack ≥50 y of age 1.67 (1.55–1.81)

One parent with heart attack <50 y of age 2.36 (1.89–2.95)

Both parents with heart attack ≥50 y of age 2.90 (2.30–3.66)

Both parents with heart attack, one <50 y of age 3.26 (1.72–6.18)
Both parents with heart attack, both <50 y of age 6.56 (1.39–30.95)

OR indicates odds ratio.

Data derived from Chow et al.35

e210 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-1. Prevalence of cardiovascular disease in adults ≥20 years of age, by age and sex (NHANES, 2013–2016), with and without hypertension.
These data include coronary heart disease, heart failure, stroke, and with and without hypertension.
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-2. Deaths attributable to diseases of the heart (United States, 1900–2016).
See Glossary (Chapter 28) for an explanation of “diseases of the heart.” In the years 1900 to 1920, the International Classification of Diseases codes were 77 to
80; for 1925, 87 to 90; for 1930 to 1945, 90 to 95; for 1950 to 1960, 402 to 404 and 410 to 443; for 1965, 402 to 404 and 410 to 443; for 1970 to 1975, 390
to 398 and 404 to 429; for 1980 to 1995, 390 to 398, 402, and 404 to 429; and for 2000 to 2014, I00 to I09, I11, I13, and I20 to I51. Before 1933, data are for
a death registration area and not the entire United States. In 1900, only 10 states were included in the death registration area, and this increased over the years,
so part of the increase in numbers of deaths is attributable to an increase in the number of states.
Source: National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e211

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-3. Deaths attributable to cardiovascular disease (United States, 1910–2016).

Cardiovascular disease (International Classification of Diseases, 10th Revision codes I00–I99) does not include congenital heart disease. Before 1933, data are for a
death registration area and not the entire United States.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-4. Percentage breakdown of deaths attributable to cardiovascular disease (United States, 2016).
Total may not add to 100 because of rounding. Coronary heart disease includes International Classification of Diseases, 10th Revision (ICD-10) codes I20 to I25;
stroke, I60 to I69; heart failure, I50; high blood pressure, I10 to I15; diseases of the arteries, I70 to I78; and other, all remaining ICD-I0 I categories.
Source: National Heart, Lung, and Blood Institute from National Center for Health Statistics reports and data sets.

e212 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-5. CVD deaths vs cancer deaths by age (United States, 2016).
CVD includes International Classification of Diseases, 10th Revision codes I00 to I99; cancer, C00 to C97.
CVD indicates cardiovascular disease.
Source: National Center for Health Statistics.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-6. CVD and other major causes of death: all ages, <85 years of age, and ≥85 years of age.
Deaths among both sexes, United States, 2016. Heart disease includes International Classification of Diseases, 10th Revision codes I00 to I09, I11, I13, and I20 to
I51; stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97; CLRD, J40 to J47; Alzheimer disease, G30; and accidents, V01 to X59 and
Y85 and Y86.
CLRD indicates chronic lower respiratory disease; and CVD, cardiovascular disease.
Source: National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e213

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-7. CVD and other major causes of death in males: all ages, <85 years of age, and ≥85 years of age.
Deaths among males, United States, 2016. Heart disease includes International Classification of Diseases, 10th Revision codes I00 to I09, I11, I13, and I20 to I51;
stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97; CLRD, J40 to J47; and accidents, V01 to X59 and Y85 and Y86.
CLRD indicates chronic lower respiratory disease; and CVD, cardiovascular disease.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-8. CVD and other major causes of death in females: all ages, <85 years of age, and ≥85 years of age.
Deaths among females, United States, 2016. Heart disease includes International Classification of Diseases, 10th Revision codes I00 to I09, I11, I13, and I20 to I51;
stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97; CLRD, J40 to J47; and Alzheimer disease, G30.
CLRD indicates chronic lower respiratory disease; and CVD, cardiovascular disease.
Source: National Heart, Lung, and Blood Institute.

e214 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-9. CVD and other major causes of death for all males and females (United States, 2016).
Diseases included: CVD (International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86); CLRD
(J40–J47); diabetes mellitus (E10–E14); and Alzheimer disease (G30).
CLRD indicates chronic lower respiratory disease; and CVD, cardiovascular disease.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-10. CVD and other major causes of death for NH white males and females (United States, 2016).
Diseases included: CVD (International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); CLRD (J40–J47); accidents (V01–X59 andY85–Y86);
Alzheimer disease (G30); and diabetes mellitus (E10–E14).
CLRD indicates chronic lower respiratory disease; CVD, cardiovascular disease; and NH, non-Hispanic.
Source: National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e215

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-11. CVD and other major causes of death for NH black males and females (United States, 2016).
Diseases included: CVD (International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); CLRD (J40–J47); accidents (V01–X59 and Y85–Y86);
assault (X92-Y09); and diabetes mellitus (E10–E14).
CLRD indicates chronic lower respiratory disease; CVD, cardiovascular disease; and NH, non-Hispanic.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-12. CVD and other major causes of death for Hispanic or Latino males and females (United States, 2016).
Number of deaths shown may be lower than actual because of underreporting in this population. Diseases included: CVD (International Classification of Diseases,
10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86); diabetes mellitus (E10–E14); Alzheimer disease (G30); and chronic liver disease
(K70, K73, and K74).
CVD indicates cardiovascular disease.
Source: National Heart, Lung, and Blood Institute.

e216 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-13. CVD and other major causes of death for NH Asian or Pacific Islander males and females (United States, 2016).
“Asian or Pacific Islander” is a heterogeneous category that includes people at high CVD risk (eg, South Asian) and people at low CVD risk (eg, Japanese). More
specific data on these groups are not available. Number of deaths shown may be lower than actual because of underreporting in this population. Diseases
included: CVD (International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86); diabetes mellitus
(E10–E14); Alzheimer disease (G30); and influenza and pneumonia (J09-J18).
CVD indicates cardiovascular disease; and NH, non-Hispanic.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-14. CVD and other major causes of death for NH American Indian or Alaska Native males and females (United States, 2016).
Number of deaths shown may be lower than actual because of underreporting in this population. Diseases included: CVD (International Classification of Diseases,
10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86); diabetes mellitus (E10–E14); chronic liver disease (K70, K73, and K74); and
CLRD (J40–J47).
CLRD indicates chronic lower respiratory disease; CVD, cardiovascular disease; and NH, non-Hispanic.
Source: National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e217

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-15. Age-adjusted death rates for CHD, stroke, and lung and breast cancer for NH white and black females (United States, 2016).
CHD includes International Classification of Diseases, 10th Revision codes I20 to I25; stroke, I60 to I69; lung cancer, C33 to C34; and breast cancer, C50.
CHD indicates coronary heart disease; and NH, non-Hispanic.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-16. Cardiovascular disease (CVD) mortality trends for males and females (United States, 1979–2016).
CVD excludes congenital cardiovascular defects (International Classification of Diseases, 10th Revision [ICD-10] codes I00–I99). The overall comparability for cardio-
vascular disease between the International Classification of Diseases, 9th Revision (1979–1998) and ICD-10 (1999–2015) is 0.9962. No comparability ratios were
applied.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

e218 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-17. US maps corresponding to the state age-adjusted death rates per 100 000 population for cardiovascular disease, coronary heart disease,
and stroke (including the District of Columbia), 2016.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.2

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e219

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-18. Hospital discharges for cardiovascular disease (United States, 1993–2014).
Hospital discharges include people discharged alive, dead, and “status unknown.”
Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-19. Hospital discharges (International Classification of Diseases, 9th Revision) for the 10 leading diagnostic groups (United States, 2014).
Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, and National Heart, Lung, and Blood Institute.

e220 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 13-20. Estimated average 10-year cardiovascular disease risk in adults 50 to 54 years of age according to levels of various risk factors (FHS).
BP indicates blood pressure; FHS, Framingham Heart Study; and HDL, high-density lipoprotein.
Data derived from D’Agostino et al.53

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e221

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13
CLINICAL STATEMENTS
AND GUIDELINES

Chart 13-21. Age-standardized global mortality rates of cardiovascular diseases per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia,
Federated States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB,
Solomon Islands; SYC, Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa,
West Africa; and WSM, Samoa.
Downloaded from http://ahajournals.org by on February 7, 2019

Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.46 Printed with permission.
Copyright © 2017, University of Washington.

e222 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-22. Age-standardized global prevalence rates of cardiovascular diseases per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.46 Printed with permission.
Downloaded from http://ahajournals.org by on February 7, 2019

Copyright © 2017, University of Washington.

7. Centers for Disease Control and Prevention website. Disability and Health:
REFERENCES Data & Statistics: Healthcare Cost Data. https://www.cdc.gov/ncbddd/
disabilityandhealth/data-highlights.html. Accessed May 23, 2017.
1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van
8. Centers for Disease Control and Prevention (CDC). Prevalence and most
Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK,
common causes of disability among adults: United States, 2005. MMWR
Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger
Morb Mortal Wkly Rep. 2009;58:421–426.
V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of
9. Courtney-Long EA, Carroll DD, Zhang QC, Stevens AC, Griffin-Blake
the American Heart Association Strategic Planning Task Force and
S, Armour BS, Campbell VA. Prevalence of disability and disability type
Statistics Committee.. Defining and setting national goals for car-
among adults: United States, 2013. MMWR Morb Mortal Wkly Rep.
diovascular health promotion and disease reduction: the American
2015;64:777–783.
Heart Association’s strategic Impact Goal through 2020 and beyond.
10. RTI International. Projections of Cardiovascular Disease Prevalence and
Circulation. 2010;121:586–613. doi: 10.1161/CIRCULATIONAHA.
Costs: 2015–2035: Technical Report [report prepared for the American
109.192703
Heart Association]. Research Triangle Park, NC: RTI International;
2. National Center for Health Statistics. Centers for Disease Control and November 2016. RTI project number 021480.003.001.001. https://
Prevention website. National Vital Statistics System: public use data file healthmetrics.heart.org/wp-content/uploads/2017/10/Projections-of-
documentation: mortality multiple cause-of-death micro-data files, 2016. Cardiovascular-Disease.pdf. Accessed November 10, 2018.
https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed 11. Roth GA, Johnson CO, Abate KH, et al. The burden of cardiovascular dis-
May 21, 2018. eases among US states, 1990–2016. JAMA Cardiol. 2018;3:375–389. doi:
3. Kochanek KD, Murphy SL, Xu JQ, Arias E. Mortality in the United States, 10.1001/jamacardio.2018.0385
2016. NCHS Data Brief No. 293. Hyattsville, MD: National Center for 12. Fryar CD, Chen TC, Li X. Prevalence of uncontrolled risk factors for
Health Statistics; December 2017. https://www.cdc.gov/nchs/data/data- cardiovascular disease: United States, 1999–2010. NCHS Data Brief.
briefs/db293.pdf. Accessed June 18, 2018. 2012;(103):1–8.
4. Roth GA, Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, Morozoff C, 13. Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, Ezzati
Naghavi M, Mokdad AH, Murray CJL. Trends and Patterns of Geographic M. The preventable causes of death in the United States: comparative
Variation in Cardiovascular Mortality Among US Counties, 1980-2014. risk assessment of dietary, lifestyle, and metabolic risk factors [published
JAMA. 2017;317:1976–1992. doi: 10.1001/jama.2017.4150 correction appears in PLoS Med. 2011;8:10.1371/annotation/0ef47acd-
5. Centers for Disease Control and Prevention website. National Ambulatory 9dcc-4296-a897-872d182cde57]. PLoS Med. 2009;6:e1000058. doi:
Medical Care Survey: 2015 State and National Summary Tables. https:// 10.1371/journal.pmed.1000058
www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_ 14. Hippisley-Cox J, Coupland C, Brindle P. Development and validation
tables.pdf. Accessed June 14, 2018. of QRISK3 risk prediction algorithms to estimate future risk of cardio-
6. Centers for Disease Control and Prevention website. National Hospital vascular disease: prospective cohort study. BMJ. 2017;357:j2099. doi:
Ambulatory Medical Care Survey: 2015 Emergency Department Summary 10.1136/bmj.j2099
Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_ 15. Lisabeth LD, Beiser AS, Brown DL, Murabito JM, Kelly-Hayes M,
web_tables.pdf. Accessed June 14, 2018. Wolf PA. Age at natural menopause and risk of ischemic stroke:

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e223

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

the Framingham Heart Study. Stroke. 2009;40:1044–1049. doi: 33. Eamranond PP, Legedza AT, Diez-Roux AV, Kandula NR, Palmas W,
CLINICAL STATEMENTS

10.1161/STROKEAHA.108.542993 Siscovick DS, Mukamal KJ. Association between language and risk factor
AND GUIDELINES

16. Losina E, Hyle EP, Borre ED, Linas BP, Sax PE, Weinstein MC, Rusu C, levels among Hispanic adults with hypertension, hypercholesterolemia, or
Ciaranello AL, Walensky RP, Freedberg KA. Projecting 10-year, 20-year, and diabetes. Am Heart J. 2009;157:53–59. doi: 10.1016/j.ahj.2008.08.015
lifetime risks of cardiovascular disease in persons living with human immu- 34. Daviglus ML, Talavera GA, Avilés-Santa ML, Allison M, Cai J, Criqui MH,
nodeficiency virus in the United States. Clin Infect Dis. 2017;65:1266– Gellman M, Giachello AL, Gouskova N, Kaplan RC, LaVange L, Penedo
1271. doi: 10.1093/cid/cix547 F, Perreira K, Pirzada A, Schneiderman N, Wassertheil-Smoller S, Sorlie
17. Miller RG, Mahajan HD, Costacou T, Sekikawa A, Anderson SJ, Orchard PD, Stamler J. Prevalence of major cardiovascular risk factors and car-
TJ. A contemporary estimate of total mortality and cardiovascular disease diovascular diseases among Hispanic/Latino individuals of diverse
risk in young adults with type 1 diabetes: the Pittsburgh Epidemiology of backgrounds in the United States. JAMA. 2012;308:1775–1784. doi:
Diabetes Complications Study. Diabetes Care. 2016;39:2296–2303. doi: 10.1001/jama.2012.14517
10.2337/dc16-1162 35. Chow CK, Islam S, Bautista L, Rumboldt Z, Yusufali A, Xie C, Anand SS,
18. Ramsay SE, Morris RW, Whincup PH, Subramanian SV, Papacosta Engert JC, Rangarajan S, Yusuf S. Parental history and myocardial infarc-
AO, Lennon LT, Wannamethee SG. The influence of neighbourhood- tion risk across the world: the INTERHEART Study. J Am Coll Cardiol.
level socioeconomic deprivation on cardiovascular disease mortal- 2011;57:619–627. doi: 10.1016/j.jacc.2010.07.054
ity in older age: longitudinal multilevel analyses from a cohort of older 36. Lloyd-Jones DM, Nam BH, D’Agostino RB Sr, Levy D, Murabito JM,
British men. J Epidemiol Community Health. 2015;69:1224–1231. doi: Wang TJ, Wilson PW, O’Donnell CJ. Parental cardiovascular disease as a
10.1136/jech-2015-205542 risk factor for cardiovascular disease in middle-aged adults: a prospec-
19. Gebreab SY, Davis SK, Symanzik J, Mensah GA, Gibbons GH, Diez-Roux tive study of parents and offspring. JAMA. 2004;291:2204–2211. doi:
AV. Geographic variations in cardiovascular health in the United States: 10.1001/jama.291.18.2204
contributions of state- and individual-level factors. J Am Heart Assoc. 37. Murabito JM, Pencina MJ, Nam BH, D’Agostino RB Sr, Wang TJ, Lloyd-
2015;4:e001673. doi: 10.1161/JAHA.114.001673 Jones D, Wilson PW, O’Donnell CJ. Sibling cardiovascular disease as
20. Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, a risk factor for cardiovascular disease in middle-aged adults. JAMA.
Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and 2005;294:3117–3123. doi: 10.1001/jama.294.24.3117
associations with all-cause and CVD mortality among US adults. JAMA. 38. Yeboah J, Young R, McClelland RL, Delaney JC, Polonsky TS, Dawood FZ,
2012;307:1273–1283. doi: 10.1001/jama.2012.339 Blaha MJ, Miedema MD, Sibley CT, Carr JJ, Burke GL, Goff DC Jr, Psaty
21. Guasch-Ferré M, Liu X, Malik VS, Sun Q, Willett WC, Manson JE, BM, Greenland P, Herrington DM. Utility of nontraditional risk markers in
Rexrode KM, Li Y, Hu FB, Bhupathiraju SN. Nut consumption and risk atherosclerotic cardiovascular disease risk assessment. J Am Coll Cardiol.
of cardiovascular disease. J Am Coll Cardiol. 2017;70:2519–2532. doi: 2016;67:139–147. doi: 10.1016/j.jacc.2015.10.058
10.1016/j.jacc.2017.09.035 39. Valerio L, Peters RJ, Zwinderman AH, Pinto-Sietsma SJ. Association of
22. Mensah GA, Brown DW, Croft JB, Greenlund KJ. Major coronary risk fac- family history with cardiovascular disease in hypertensive individuals
tors and death from coronary heart disease: baseline and follow-up mor- in a multiethnic population. J Am Heart Assoc. 2016;5:e004260. doi:
tality data from the Second National Health and Nutrition Examination 10.1161/JAHA.116.004260
Survey (NHANES II). Am J Prev Med. 2005;29(5 Suppl 1):68–74. doi: 40. Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O’Donnell CJ, Nam BH,
10.1016/j.amepre.2005.07.030 Larson MG, D’Agostino RB, Vasan RS. Association of parental heart failure
23. Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van with risk of heart failure in offspring. N Engl J Med. 2006;355:138–147.
Horn L, Tracy RP, Lloyd-Jones DM. Lifetime risks of cardiovascular disease. doi: 10.1056/NEJMoa052948
N Engl J Med. 2012;366:321–329. doi: 10.1056/NEJMoa1012848 41. Fox CS, Parise H, D’Agostino RB Sr, Lloyd-Jones DM, Vasan RS, Wang
Downloaded from http://ahajournals.org by on February 7, 2019

24. Terry DF, Pencina MJ, Vasan RS, Murabito JM, Wolf PA, Hayes MK, Levy TJ, Levy D, Wolf PA, Benjamin EJ. Parental atrial fibrillation as a risk fac-
D, D’Agostino RB, Benjamin EJ. Cardiovascular risk factors predictive tor for atrial fibrillation in offspring. JAMA. 2004;291:2851–2855. doi:
for survival and morbidity-free survival in the oldest-old Framingham 10.1001/jama.291.23.2851
Heart Study participants. J Am Geriatr Soc. 2005;53:1944–1950. doi: 42. Olsson C, Granath F, Ståhle E. Family history, comorbidity and risk of
10.1111/j.1532-5415.2005.00465.x thoracic aortic disease: a population-based case-control study. Heart.
25. Gooding HC, Ning H, Gillman MW, Shay C, Allen N, Goff DC Jr, Lloyd- 2013;99:1030–1033. doi: 10.1136/heartjnl-2013-303654
Jones D, Chiuve S. Application of a Lifestyle-Based Tool to Estimate 43. Murabito JM, Nam BH, D’Agostino RB Sr, Lloyd-Jones DM, O’Donnell
Premature Cardiovascular Disease Events in Young Adults: The Coronary CJ, Wilson PW. Accuracy of offspring reports of parental cardiovascu-
Artery Risk Development in Young Adults (CARDIA) Study. JAMA Intern lar disease history: the Framingham Offspring Study. Ann Intern Med.
Med. 2017;177:1354–1360. doi: 10.1001/jamainternmed.2017.2922 2004;140:434–440.
26. Wu H, Flint AJ, Qi Q, van Dam RM, Sampson LA, Rimm EB, Holmes 44. Ganesh SK, Arnett DK, Assimes TL, Assimes TL, Basson CT, Chakravarti
MD, Willett WC, Hu FB, Sun Q. Association between dietary whole A, Ellinor PT, Engler MB, Goldmuntz E, Herrington DM, Hershberger RE,
grain intake and risk of mortality: two large prospective studies in Hong Y, Johnson JA, Kittner SJ, McDermott DA, Meschia JF, Mestroni L,
US men and women. JAMA Intern Med. 2015;175:373–384. doi: O’Donnell CJ, Psaty BM, Vasan RS, Ruel M, Shen WK, Terzic A, Waldman
10.1001/jamainternmed.2014.6283 SA; on behalf of the American Heart Association Council on Functional
27. Appelman Y, van Rijn BB, Ten Haaf ME, Boersma E, Peters SA. Sex differ- Genomics and Translational Biology; American Heart Association Council
ences in cardiovascular risk factors and disease prevention. Atherosclerosis. on Epidemiology and Prevention; American Heart Association Council
2015;241:211–218. doi: 10.1016/j.atherosclerosis.2015.01.027 on Basic Cardiovascular Sciences; American Heart Association Council
28. Olives C, Myerson R, Mokdad AH, Murray CJ, Lim SS. Prevalence, awareness, on Cardiovascular Disease in the Young; American Heart Association
treatment, and control of hypertension in United States counties, 2001- Council on Cardiovascular and Stroke Nursing; American Heart
2009. PLoS One. 2013;8:e60308. doi: 10.1371/journal.pone.0060308 Association Stroke Council. Genetics and genomics for the prevention
29. Hozawa A, Folsom AR, Sharrett AR, Chambless LE. Absolute and attrib- and treatment of cardiovascular disease: update: a scientific statement
utable risks of cardiovascular disease incidence in relation to optimal from the American Heart Association [published correction appears in
and borderline risk factors: comparison of African American with white Circulation. 2014;129:e398]. Circulation. 2013;128:2813–2851. doi:
subjects—Atherosclerosis Risk in Communities Study. Arch Intern Med. 10.1161/01.cir.0000437913.98912.1d
2007;167:573–579. doi: 10.1001/archinte.167.6.573 45. Mosca L, Hammond G, Mochari-Greenberger H, Towfighi A, Albert
30. Centers for Disease Control and Prevention (CDC). Vital signs: avoidable MA; on behalf of the American Heart Association Cardiovascular
deaths from heart disease, stroke, and hypertensive disease—United Disease and Stroke in Women and Special Populations Committee of
States, 2001–2010. MMWR Morb Mortal Wkly Rep. 2013;62:721–727. the Council on Clinical Cardiology, Council on Cardiovascular Nursing,
31. Schoenborn CA, Adams PF, Peregoy JA. Health behaviors of adults: United Council on High Blood Pressure Research, and Council on Nutrition,
States, 2008–2010. Vital Health Stat 10. 2013;(257):1–184. Physical Activity and Metabolism. Fifteen-year trends in aware-
32. Pearson-Stuttard J, Bandosz P, Rehm CD, Penalvo J, Whitsel L, Gaziano T, ness of heart disease in women: results of a 2012 American Heart
Conrad Z, Wilde P, Micha R, Lloyd-Williams F, Capewell S, Mozaffarian D, Association national survey. Circulation. 2013;127:1254–1263. doi:
O’Flaherty M. Reducing US cardiovascular disease burden and disparities 10.1161/CIR.0b013e318287cf2f
through national and targeted dietary policies: a modelling study. PLoS 46. Global Burden of Disease Study 2016. Global Burden of Disease Study
Med. 2017;14:e1002311. doi: 10.1371/journal.pmed.1002311 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and

e224 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 13

Evaluation (IHME), University of Washington; 2016. http://ghdx.healthdata. mortality from 1990 to 2013. Circulation. 2015;132:1667–1678. doi:

CLINICAL STATEMENTS
org/gbd-results-tool. Accessed May 1, 2018. 10.1161/CIRCULATIONAHA.114.008720

AND GUIDELINES
47. Global Status Report on Noncommunicable Diseases 2014. Geneva, 51. Smith SC Jr, Collins A, Ferrari R, Holmes DR Jr, Logstrup S, McGhie
Switzerland: World Health Organization; 2014. http://apps.who. DV, Ralston J, Sacco RL, Stam H, Taubert K, Wood DA, Zoghbi WA.
int/iris/bitstream/10665/148114/1/9789241564854_eng.pdf. Accessed Our time: a call to save preventable death from cardiovascular disease
September 2, 2016. (heart disease and stroke). Circulation. 2012;126:2769–2775. doi:
48. Bloom DE, Cafiero ET, Jane´-Llopis E, Abrahams-Gessel S, Bloom LR, 10.1161/CIR.0b013e318267e99f
Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Prettner K, 52. Kontis V, Mathers CD, Rehm J, Stevens GA, Shield KD, Bonita R, Riley
Rosenberg L, Seligman B, Stein AZ, Weinsteain C. The Global Economic LM, Poznyak V, Beaglehole R, Ezzati M. Contribution of six risk fac-
Burden of Non-communicable Diseases. Geneva, Switzerland: World tors to achieving the 25×25 non-communicable disease mortality
Economic Forum; 2011. reduction target: a modelling study. Lancet. 2014;384:427–437. doi:
49. World Health Organization (WHO) website. Cardiovascular diseases 10.1016/S0140-6736(14)60616-4
(CVDs). Fact sheet No. 317. http://www.who.int/mediacentre/factsheets/ 53. D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro
fs317/en/. Accessed April 10, 2015. JM, Kannel WB. General cardiovascular risk profile for use in primary
50. Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi care: the Framingham Heart Study. Circulation. 2008;117:743–753. doi:
M, Murray CJ. Global and regional patterns in cardiovascular 10.1161/CIRCULATIONAHA.107.699579
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e225

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

14. STROKE (CEREBROVASCULAR Abbreviations Used in Chapter 14 Continued

CLINICAL STATEMENTS

DISEASE) HR hazard ratio

AND GUIDELINES

ICD-9 International Classification of Diseases, 9th Revision

ICD-9 430 to 438; ICD-10 I60 to I69. See Table 14-1 ICD-9-CM International Classification of Diseases, 9th Revision,
Clinical Modification
and Charts 14-1 through 14-16
ICD-10 International Classification of Diseases, 10th Revision
ICH intracerebral hemorrhage
Click here to return to the Table of Contents
IMT intima-media thickness
IQ intelligence quotient
IQR interquartile range
Abbreviations Used in Chapter 14
IRR incidence rate ratio
ACCORD Action to Control Cardiovascular Risk in Diabetes LDL low-density lipoprotein
ACR albumin-creatinine ratio LDL­C low-density lipoprotein cholesterol
AF atrial fibrillation MEPS Medical Expenditure Panel Survey
AHA American Heart Association MESA Multi-Ethnic Study of Atherosclerosis
AHI apnea-hypopnea index MI myocardial infarction
ARIC Atherosclerosis Risk in Communities study MIDAS Myocardial Infarction Data Acquisition System
ATRIA Anticoagulation and Risk Factors in Atrial Fibrillation MONICA Monitoring Trends and Determinants of Cardiovascular
AVAIL Adherence Evaluation After Ischemic Stroke Longitudinal Disease
BASIC Brain Attack Surveillance in Corpus Christi MR CLEAN Multicenter Randomized Clinical Trial of Endovascular
BMI body mass index Treatment for Acute Ischemic Stroke in the Netherlands
BNP B-type natriuretic peptide MRI magnetic resonance imaging
BP blood pressure MUFA monounsaturated fatty acid
BRFSS Behavioral Risk Factor Surveillance System NAMCS National Ambulatory Medical Care Survey
CAD coronary artery disease NH non-Hispanic
CDC Centers for Disease Control and Prevention NHAMCS National Hospital Ambulatory Medical Care Survey
CHD coronary heart disease NHANES National Health and Nutrition Examination Survey
CHS Cardiovascular Health Study NHLBI National Heart, Lung, and Blood Institute
CI confidence interval NIHSS National Institutes of Health Stroke Scale
CKD chronic kidney disease NINDS National Institutes of Neurological Disorders and Stroke
CLRD chronic lower respiratory disease NIS National (Nationwide) Inpatient Sample
CREST Carotid Revascularization Endarterectomy Versus Stenting Trial NOMAS Northern Manhattan Study
CRP C-reactive protein ONTARGET Ongoing Telmisartan Alone and in Combination With
Downloaded from http://ahajournals.org by on February 7, 2019

CVD cardiovascular disease Ramipril Global Endpoint Trial

DALY disability-adjusted life-year OR odds ratio
DASH Dietary Approaches to Stop Hypertension OSA obstructive sleep apnea
DBP diastolic blood pressure PA physical activity
DM diabetes mellitus PAR population attributable risk
DVT deep vein thrombosis PE pulmonary embolism
ECG electrocardiogram PREVAIL Prevention of VTE After Acute Ischemic Stroke With LMWH
ED emergency department Enoxaparin
eGFR estimated glomerular filtration rate PREVEND Prevention of Renal and Vascular End-Stage Disease
EPIC European Prospective Investigation Into Cancer and Nutrition PROFESS Prevention Regimen for Effectively Avoiding Second Stroke
ESCAPE Endovascular Treatment for Small Core and Anterior RCT randomized controlled trial
Circulation Proximal Occlusion With Emphasis on REGARDS Reasons for Geographic and Racial Differences in Stroke
Minimizing CT to Recanalization Times REVASCAT Revascularization With Solitaire FR Device Versus Best
EXTEND-IA Extending the Time for Thrombolysis in Emergency Medical Therapy in the Treatment of Acute Stroke Due
Neurological Deficits–Intra-Arterial to Anterior Circulation Large Vessel Occlusion Presenting
FHS Framingham Heart Study Within Eight Hours of Symptom Onset
FINRISK Finnish Population Survey on Risk Factors for Chronic, RR relative risk
Noncommunicable Diseases SAH subarachnoid hemorrhage
FUTURE Follow-up of TIA and Stroke Patients and Unelucidated Risk SBP systolic blood pressure
Factor Evaluation SD standard deviation
GBD Global Burden of Disease SES socioeconomic status
GCNKSS Greater Cincinnati/Northern Kentucky Stroke Study SHS Strong Heart Study
GFR glomerular filtration rate SNP single-nucleotide polymorphism
GWAS genome wide association study SPRINT Systolic Blood Pressure Intervention Trial
GWTG Get With The Guidelines SPS3 Secondary Prevention of Small Subcortical Strokes
HBP high blood pressure STOP Stroke Prevention Trial in Sickle Cell Anemia
HCUP Healthcare Cost and Utilization Project SVT supraventricular tachycardia
HD heart disease SWIFT Solitaire With the Intention for Thrombectomy as Primary
HDL high-density lipoprotein PRIME Endovascular Treatment
HDL-C high-density lipoprotein cholesterol TC total cholesterol
HF heart failure TIA transient ischemic attack
HIV human immunodeficiency virus tPA tissue-type plasminogen activator
VTE venous thromboembolism
(Continued )

e226 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

Stroke Prevalence population >45 years of age reported at least 1

CLINICAL STATEMENTS
(See Table 14-1 and Chart 14-1) symptom. Stroke symptoms were more likely

AND GUIDELINES
among blacks than whites, among those with
• Stroke prevalence estimates may differ slightly lower income and lower educational attainment,
between studies because each study selects and and among those with fair to poor perceived
recruits a sample of participants to represent health status. Symptoms also were more likely in
the target study population (eg, state, region, or participants with higher Framingham stroke risk
country). scores (REGARDS, NINDS).3
• An estimated 7.0 million Americans ≥20 years of • Projections show that by 2030, an additional
age self-report having had a stroke (extrapolated 3.4 million US adults aged ≥18 years, represent-
to 2016 by use of NHANES 2013–2016 data). ing 3.9% of the adult population, will have had
Overall stroke prevalence during this period was a stroke, a 20.5% increase in prevalence from
an estimated 2.5% (NHANES, NHLBI tabulation; 2012. The highest increase (29%) is projected to
Table 14-1). be in white Hispanic males.4
• Prevalence of stroke in the United States increases • With the aging of the US population, prevalence
with advancing age in both males and females of stroke survivors is projected to increase, espe-
(Chart 14-1). cially among elderly females.5
• According to data from the 2016 BRFSS (CDC)1:
— 2.9% of males and 2.8% of females ≥18
years of age had a history of stroke; 2.7% Stroke Incidence
of NH whites, 4.1% of NH blacks, 1.2% of (See Table 14-1 and Chart 14-2)
Asian/Pacific Islanders, 2.3% of Hispanics (of
• Each year, ≈795 000 people experience a new
any race), 5.3% of American Indian/Alaska
or recurrent stroke (Table  14-1). Approximately
Natives, and 4.9% of other races or multira-
610 000 of these are first attacks, and 185 000 are
cial people had a history of stroke.
recurrent attacks (GCNKSS, NINDS, and NHLBI;
— Stroke prevalence in adults is 2.9% in the
GCNKSS and NINDS data for 1999 provided July
United States, with the lowest prevalence in
9, 2008; estimates compiled by NHLBI).
South Dakota (1.9%) and the highest preva-
• Of all strokes, 87% are ischemic and 10% are ICH
lence in Mississippi (4.5%).
Downloaded from http://ahajournals.org by on February 7, 2019

strokes, whereas 3% are SAH strokes (GCNKSS,

• Over the time period 2006 to 2010, data from
NINDS, 1999).
BRFSS show that the overall self-reported stroke
• On average, every 40 seconds, someone in the
prevalence did not change. Older adults, blacks,
United States has a stroke (AHA computation
people with lower levels of education, and peo-
based on the latest available data).
ple living in the southeastern United States had
higher stroke prevalence.2 Temporal Trends
• Analysis of temporal trends in age-, sex- and race/ • In the NIS, from 1995 to the period 2011 to 2012,
ethnicity-specific stroke prevalence rates from rates of hospitalization for acute ischemic stroke
2006 to 2010, according to BRFSS, revealed that almost doubled for males aged 18 to 34 and 35 to
stroke prevalence remained stable in individu- 44 years.6 Hospitalization rates for ICH and SAH
als aged 18 to 44 and 45 to 64 years but had remained stable, however, with the exception of
a declining trend among individuals ≥65 years declines among males and NH black patients aged
old across the study period (−1.2%, P=0.09). 45 to 54 with SAH (see Stroke in the Young).
From 2006 to 2010, stroke prevalence declined • In the multicenter ARIC study of black and white
in males (−3.6%, P<0.01) while remaining stable adults, stroke incidence rates decreased from
in females across the study period, such that in 1987 to 2011. The decreases varied across age
more recent years, stroke prevalence was similar groups but were similar across sex and race.7
in both males and females. From 2006 to 2010, • Data from the BASIC Project for the time period
there were no statistically significant temporal 2000 through 2010 demonstrated that ischemic
trends in stroke prevalence by race/ethnicity.2 stroke rates declined significantly in people aged
• The prevalence of stroke-related symptoms was ≥60 years but remained largely unchanged over
found to be relatively high in a general population time in those aged 45 to 59 years.
free of a prior diagnosis of stroke or TIA, which — Rates of stroke decline did not differ signifi-
suggests that stroke may be underdiagnosed cantly for NH whites and Mexican Americans
or that other conditions mimic stroke, or both. overall in any age group; however, ethnic
On the basis of data from 18 462 participants disparities in stroke rates persist between
enrolled in a national cohort study, 17.8% of the Mexican Americans and NH whites in the

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e227

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

45- to 59-year-old and 60- to 74-year-old atherosclerotic stroke was 5.85 (95% CI, 1.82–
CLINICAL STATEMENTS

age groups.8 18.73); extracranial atherosclerotic stroke, 3.18

AND GUIDELINES

— Data from the BASIC Project showed that the (95% CI, 1.42–7.13); lacunar stroke, 3.09 (95%
age-, sex-, and ethnicity-adjusted incidence CI, 1.86–5.11); and cardioembolic stroke, 1.58
of ICH decreased from 2000 to 2010, from (95% CI, 0.99–2.52). Among Hispanics com-
an annual incidence rate of 5.21 per 10 000 pared with whites, the relative rate of intracranial
(95% CI, 4.36–6.24) to 4.30 per 10 000 atherosclerotic stroke was 5.00 (95% CI, 1.69–
(95% CI, 3.21–5.76).9 14.76); extracranial atherosclerotic stroke, 1.71
• Analysis of data from the FHS suggests that stroke (95% CI, 0.80–3.63); lacunar stroke, 2.32 (95%
incidence is declining over time in this largely CI, 1.48–3.63); and cardioembolic stroke, 1.42
white cohort. Data from 1950 to 1977, 1978 to (95% CI, 0.97–2.09).15
1989, and 1990 to 2004 showed that the age- • Among 4507 American Indian or Alaska Native
adjusted incidence of first stroke per 1000 per- participants without a prior stroke in the SHS
son-years in each of the 3 periods was 7.6, 6.2, from 1989 to 1992, the age- and sex-adjusted
and 5.3 in males and 6.2, 5.8, and 5.1 in females, incidence of stroke through 2004 was 6.79 per
respectively. Lifetime risk for incident stroke at 65 100 person-years, with 86% of incident strokes
years of age decreased significantly in the latest being ischemic.16
data period compared with the first, from 19.5% • In the REGARDS study, the increased risk of ICH
to 14.5% in males and from 18.0% to 16.1% in with age differed between blacks and whites:
females.10 Data from the Tromsø Study found that there was a 2.25-fold (95% CI, 1.63–3.12)
changes in cardiovascular risk factors accounted increase per decade older age in whites but no
for 57% of the decrease in ischemic stroke inci- age association with ICH risk in blacks (HR, 1.09
dence for the time period from 1995 to 2012.11 [95% CI, 0.70–1.68] per decade older age).17
Race/Ethnicity Sex
• Annual age-adjusted incidence for first-ever stroke • Each year, ≈55 000 more females than males have
was higher in black individuals than white indi- a stroke (GCNKSS, NINDS).18
viduals in data collected in 1993 to 1994, 1999, • Females have a higher lifetime risk of stroke than
and 2005 for each of the following stroke types: males. In the FHS, lifetime risk of stroke among
Downloaded from http://ahajournals.org by on February 7, 2019

ischemic stroke, ICH, and SAH (Chart 14-2). those 55 to 75 years of age was 1 in 5 for females
• In the national REGARDS cohort, in 27 744 par- (95% CI, 20%–21%) and ≈1 in 6 for males (95%
ticipants followed up for 4.4 years (2003–2007), CI, 14%–17%).19
the overall age- and sex-adjusted black/white IRR • Age-specific incidence rates are substantially
was 1.51, but for ages 45 to 54 years, it was 4.02, lower in females than males in younger and mid-
whereas for those ≥85 years of age, it was 0.86.12 dle-age groups, but these differences narrow so
Similar trends for decreasing black/white IRR with that in the oldest age groups, incidence rates in
older age were seen in the GCNKSS.13 females are approximately equal to or even higher
• The BASIC Project (NINDS) demonstrated an than in males.5,20–24
increased incidence of stroke among Mexican • In the GCNKSS, sex-specific incidence rates
Americans compared with NH whites in a commu- between 1993 to 1994 and 2010 declined sig-
nity in southeast Texas. The crude 3-year cumula- nificantly for males but not for females. This trend
tive incidence (2000–2002) was 16.8 per 1000 in was seen for all strokes and ischemic stroke but
Mexican Americans and 13.6 per 1000 in NH whites. not for hemorrhagic stroke.25
Specifically, Mexican Americans had a higher cumu-
lative incidence of ischemic stroke than NH whites at
younger ages (45–59 years of age: RR, 2.04 [95% TIA: Prevalence, Incidence, and Prognosis
CI, 1.55–2.69]; 60–74 years of age: RR, 1.58 [95% • In a nationwide survey of US adults, the estimated
CI, 1.31–1.91]) but not at older ages (≥75 years prevalence of self-reported physician-diagnosed
of age: RR, 1.12 [95% CI, 0.94–1.32]). Mexican TIA increased with advancing age and was 2.3%
Americans also had a higher incidence of ICH and overall, which translates to ≈5 million people.
SAH than NH whites after adjustment for age.14 The true prevalence of TIA is likely to be greater,
• The age-adjusted incidence of first ischemic stroke because many patients who experience neurolog-
per 1000 was 0.88 in whites, 1.91 in blacks, and ical symptoms consistent with a TIA fail to report
1.49 in Hispanics according to data from NOMAS them to their healthcare provider.26
(NINDS) for 1993 to 1997. Among blacks, • A 2013 survey study of nearly 600 000 people
compared with whites, the RR of intracranial in China led to a neurologist-confirmed TIA

e228 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

prevalence of 1.03 per 1000 people, with a • Children with arterial ischemic stroke, particularly

CLINICAL STATEMENTS
slightly higher prevalence in females (1.15) than those with arteriopathy, remain at high risk for

AND GUIDELINES
males (0.92).27 recurrent arterial ischemic stroke despite increased
• In an Italian community-based registry (2007 to use of antithrombotic agents. The cumulative
2009), the crude TIA incidence rate was 0.52 per stroke recurrence rate was 6.8% (95% CI, 4.6%–
1000, and in a population-based registry from 10%) at 1 month and 12% (95% CI, 8.5%–15%)
Dijon, France (2013–2015), the incidence was at 1 year. The 1-year recurrence rate was 32%
0.61 per 1000.28 In China, 2013 TIA incidence (95% CI, 18%–51%) for moyamoya, 25% (95%
was 0.24 per 1000 person-years.27 CI, 12%–48%) for transient cerebral arteriopa-
• Incidence of TIA increases with age and varies by thy, and 19% (95% CI, 8.5%–40%) for arterial
sex and race/ethnicity. Males, blacks, and Mexican dissection.40
Americans have higher rates of TIA than their • A meta-analysis of 13 studies derived from hos-
female and NH white counterparts.14,29 Conversely, pital-based or community-based stroke registries
in China, incidence was slightly higher in females found a pooled cumulative stroke recurrence
(0.26 per 1000 person-years) than males (0.21).27 risk of 3.1% (95% CI, 1.7%–4.4%) at 30 days,
• Approximately 12% of all strokes are heralded by 11.1% (95% CI, 9.0%–13.3%) at 1 year, 26.4%
a TIA.30 (95% CI, 20.1%–32.8%) at 5 years, and 39.2%
• TIAs confer a substantial short-term risk of (95% CI, 27.2%–51.2%) at 10 years.41 There was
stroke, hospitalization for CVD events, and a temporal reduction in the 5-year risk of stroke
death. Of 1707 TIA patients evaluated in the recurrence from 32% to 16.2%, but substantial
EDs of Kaiser Permanente Northern California differences across studies in terms of case mix and
from 1997 to 1998, 180 (11%) experienced a definition of stroke recurrence were reported.
stroke within 90 days, and 91 (5%) had a stroke • Among 6700 patients with first-ever ischemic
within 2 days. Predictors of stroke included age stroke or ICH who survived the first 28 days in the
>60 years, DM, focal symptoms of weakness or Northern Sweden MONICA stroke registry from
speech impairment, and symptoms that lasted 1995 to 2008, the cumulative risk of recurrence
>10 minutes.31 was 6% at 1 year, 16% at 5 years, and 25% at
• Meta-analyses of cohorts of patients with TIA 10 years.42 The risk of stroke recurrence decreased
36% between 1995 to 1998 and 2004 to 2008.
Downloaded from http://ahajournals.org by on February 7, 2019

have shown the short-term risk of stroke after TIA

to be ≈3% to 10% at 2 days and 9% to 17% at Approximately 62% of all recurrent strokes after
90 days.32,33 ICH (63 of 101) were ischemic.
• Individuals who have a TIA and survive the ini- • Approximately 10% of participants with a prior
tial high-risk period have a 10-year stroke risk of stroke in the REGARDS study had a recurrent
roughly 19% and a combined 10-year stroke, MI, stroke during a mean follow-up of 6.8 years.43
or vascular death risk of 43% (4% per year).34 Although black participants aged 45 to 75
• In the GCNKSS, the 1-year mortality rate after a years had an increased risk of incident stroke
TIA was 12%.29 compared with white participants, there were
• In the community-based Oxford Vascular Study, no significant black/white differences in risk of
among patients with TIA, disability levels increased recurrent stroke.
from 14% (modified Rankin scale >2) before the • Using data for 12 392 patients aged 18 to 45
TIA to 23% at 5 years after the TIA (P=0.002). In years who were hospitalized with ischemic or
this same study, the 5-year risk of institutionaliza- hemorrhagic stroke and included in the 2013
tion after TIA was 11%.35 National Readmissions Database, the rate of
• In a meta-analysis of 47 studies,36 it was estimated recurrent stroke per 100 000 index hospitaliza-
that approximately one-third of TIA patients have tions was 1814.0 at 30 days, 2611.1 at 60 days,
an acute lesion present on diffusion-weighted and 2913.3 at 90 days.44 Among patients with-
MRI and thus would be classified as having had out vascular risk factors at the index stroke (ie,
a stroke under a tissue-based case definition37,38; hypertension, hypercholesterolemia, DM, smok-
however, substantial between-study heterogene- ing, AF/atrial flutter), rates per 100 000 hospital-
ity was noted. izations were 1461.9 at 30 days, 2203.6 at 60
days, and 2534.9 at 90 days. DM was associated
with greater risk of recurrent stroke in multivari-
Recurrent Stroke able analyses (HR, 1.5 [95% CI, 1.22–1.84]).
• In the North Dublin Population Stroke Study, the • In a meta-analysis of 34 studies published through
cumulative 2-year stroke recurrence rate was the end of 2016 and including a total of 73 184
10.8%, and case fatality was 38.6%.39 patients with either ischemic stroke or TIA, the

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e229

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

annual risk of recurrent stroke was 4.26% (95% — The decline in age-adjusted stroke death
CLINICAL STATEMENTS

CI, 3.43%–5.09%).45 Risk of stroke recurrence rates for males and females was similar
AND GUIDELINES

decreased with longer follow-up duration but did (−17.0% and −16.9%, respectively).
not vary over time or according to type of isch- — Crude stroke death rates declined most
emic event. Risk was higher in RCTs (4.58% [95% among people aged 65 to 74 years (−19.9%;
CI, 3.26%–5.91%]) and hospital-based studies from 94.9 to 76.0 per 100 000), 75 to 84
(4.54% [95% CI, 3.35%–5.72%]) than in com- years (−20.5%; from 333.9 to 265.5 per
munity-based studies (2.55% [95% CI, 0.50%– 100 000), and ≥85 years (−14.0%; from
4.60%]). The annual risk was 0.77% (95% CI, 1131.7 to 972.9 per 100 000). By compari-
0.45%–1.10%) for fatal stroke and 2.92% (95% son, crude stroke death rates declined more
CI, 2.22%–3.62%) for nonfatal stroke. modestly among those aged 25 to 34 years
(0%; 1.3 and 1.3 per 100 000), 35 to 44 years
(−9.8%; 5.1 to 4.6 per 100 000), 45 to 54
Stroke Mortality years (−14.4%; 14.6 to 12.5 per 100 000),
(See Table 14-1 and Charts 14-3 and 55 to 64 years (−9.7%; 32.9 and 29.7
through 14-6) per 100  000). Despite the improvements
noted since 2006, there has been a recent
See “Factors Influencing the Decline in Stroke Mortality:
flattening or increase in death rates among
A Statement From the American Heart Association/
all age groups (Charts 14-4 and 14-5).
American Stroke Association”46 for more in-depth cov- — Age-adjusted stroke death rates declined
erage of factors contributing to the decline in stroke by ≈14% or more among all racial/ethnic
mortality over the past several decades. groups; however, in 2016, rates remained
• In 201647,48: higher among NH blacks (51.9 per 100 000;
— On average, every 3 minutes 42 seconds, change since 2006: −19.3%) than among
someone died of a stroke. NH whites (36.1 per 100 000; −15.9%), NH
— Stroke accounted for ≈1 of every 19 deaths Asians/Pacific Islanders (31.0 per 100 000;
in the United States. −21.5%), NH American Indians/Alaska
— When considered separately from other Natives (30.7 per 100 000; −20.7%), and
CVDs, stroke ranks fifth among all causes of Hispanics (32.1 per 100 000; −13.7%).
Downloaded from http://ahajournals.org by on February 7, 2019

death, behind diseases of the heart, cancer, • There are substantial geographic disparities in
CLRD, and unintentional injuries/accidents. stroke mortality, with higher rates in the south-
— The number of deaths with stroke as an eastern United States, known as the “stroke
underlying cause was 142 142 (Table  14-1); belt” (Chart 14-6). This area is usually defined to
the age-adjusted death rate for stroke as include the 8 southern states of North Carolina,
an underlying cause of death was 37.3 per South Carolina, Georgia, Tennessee, Mississippi,
100 000, whereas the age-adjusted rate for Alabama, Louisiana, and Arkansas. These geo-
any mention of stroke as a cause of death graphic differences have existed since at least
was 62.6 per 100 000. 1940, and despite some minor shifts, they per-
— Approximately 62% of stroke deaths sist.49 Historically, the overall average stroke mor-
occurred outside of an acute care hospital. tality has been ≈30% higher in the stroke belt
— In 2016, NH black males and females had than in the rest of the nation and ≈40% higher
higher age-adjusted death rates for stroke in the stroke “buckle” (North Carolina, South
than NH white, NH Asian, NH Indian or Alaska Carolina and Georgia).46
Native, and Hispanic males and females in • The risk of dementia is also increased in the
the United States (Chart 14-3). Southeastern United States, the geographic area
— More females than males die of stroke each of excess stroke risk.50,51
year because of a larger number of elderly • More recent analyses of the geographic dispari-
females than males. Females accounted for ties determined that stroke risks are highest for
58% of US stroke deaths in 2016. residents of the stroke belt who were born and
• Conclusions about changes in stroke death rates resided in the Southeast for the first 2 decades of
from 2006 to 2016 are as follows47: their life.52
— The age-adjusted stroke death rate decreased • On the basis of pooled data from several large
16.7% (from 44.8 per 100 000 to 37.3 per studies, the probability of death within 1 year or 5
100  000), whereas the actual number of years after a stroke was highest in individuals ≥75
stroke deaths increased 3.7% (from 137 119 years of age (Charts 14-7 and 14-8). The probabil-
deaths to 142 142 deaths). ity of death within 1 year of a stroke was lowest

e230 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

in black males aged 45 to 64 years (Chart 14-7). increases among the population aged ≥65 years.

CLINICAL STATEMENTS
The probability of death within 5 years of a stroke Moreover, the trend-based projection method

AND GUIDELINES
was lowest for white males aged 45 to 64 years reveals that the disparity in stroke deaths among
(Chart 14-9). NH blacks compared with NH whites could
• In examining trends in stroke mortality by US cen- increase from an RR of 1.10 (95% CI, 1.08–1.13)
sus divisions from 1999 to 2007 for people ≥45 in 2012 to 1.30 (95% CI, 0.45–2.44) in 2030.55
years of age, the rate of decline varied by geo-
graphic region and racial/ethnic group. Among
black and white females and white males, rates Stroke Risk Factors
declined by ≥2% annually in every census divi- For prevalence and other information on any of these
sion, but among black males, rates declined little specific risk factors, refer to the specific risk factor
in the East and West South Central divisions.53 chapters.
• On the basis of national death statistics for the • In analyses using data from the GBD Study, ≈90%
time period 1990 to 2009, stroke mortality rates of the stroke risk could be attributed to modifiable
among American Indian and Alaska Native people risk factors, such as HBP, obesity, hyperglycemia,
were higher than among whites for both males hyperlipidemia, and renal dysfunction, and 74%
and females in contract health services deliv- could be attributed to behavioral risk factors, such
ery area counties in the United States and were as smoking, sedentary lifestyle, and an unhealthy
highest in the youngest age groups (35–44 years diet.56 Globally, 29% of the risk of stroke was
old). Stroke mortality rates and the rate ratios for attributable to air pollution.
American Indians/Alaska Natives to whites var-
ied by region, with the lowest in the Southwest High BP
and the highest in Alaska. Starting in 2001, rates (See Chapter 8 for more information.)
among American Indian/Alaska Native people • BP is a powerful determinant of risk for both isch-
decreased in all regions.54 emic stroke and intracranial hemorrhage. The evi-
• Data from the ARIC study (1987–2011; 4 US cit- dence-based 2017 “ACC/AHA/AAPA/ABC/ACPM/
ies) showed that the cumulative all-cause mor- AGS/APhA/ASH/ASPC/NMA/PCNA Guideline
tality rate after a stroke was 10.5% at 30 days, for the Prevention, Detection, Evaluation, and
21.2% at 1 year, 39.8% at 5 years, and 58.4% at Management of High Blood Pressure in Adults”
Downloaded from http://ahajournals.org by on February 7, 2019

the end of 24 years of follow-up. Mortality rates recommends intensive BP control for primary
were higher after an incident hemorrhagic stroke and secondary stroke prevention. The guideline
(67.9%) than after ischemic stroke (57.4%). proposes a target BP of <130/80 mm Hg.57 The
Age-adjusted mortality after an incident stroke recommendations are supported by an exten-
decreased over time (absolute decrease of 8.1 sive evidence document accompanying the
deaths per 100 strokes after 10 years), which guideline.58
was mainly attributed to the decrease in mortality • In a recent meta-analysis, 9 trials showed high-
among those aged ≤65 years (absolute decrease strength evidence that BP control to <150/90
of 14.2 deaths per 100 strokes after 10 years).7 mm Hg reduces stroke (RR, 0.74 [95% CI, 0.65–
• Data from the BASIC Project showed there was no 0.84]), and 6 trials yielded low- to moderate-
change in ICH case fatality or long-term mortality strength evidence that lower targets (≤140/85
from 2000 to 2010 in a South Texas community. mm Hg) are associated with significant decreases
Yearly age-, sex-, and ethnicity-adjusted 30-day in stroke (RR, 0.79 [95% CI, 0.59–0.99]).59
case fatality ranged from a low of 28.3% (95% • A recent special report identified the highly signif-
CI, 19.9%–40.3%) in 2006 to 46.5% (95% CI, icant and global implications of the hypertension
35.5%–60.8%) in 2008.9 treatment and control clinical guidelines on stroke
• Projections of stroke mortality from 2012 to 2030 risk reduction around the world.60
differ based on what factors are included in the — There was agreement across meta-analyses
forecasting.55 Conventional projections that only that intensive BP lowering appears to be most
incorporate expected population growth and beneficial for reduction in risk of stroke.61–63
aging reveal that the number of stroke deaths — Median SBP declined 16 mm Hg between
in 2030 may increase by ≈50% compared with 1959 and 2010 for different age groups in
the number of stroke deaths in 2012. However, if association with large accelerated reductions
previous stroke mortality trends are also incorpo- in stroke mortality.46 In a meta-analysis of
rated into the forecasting, the number of stroke clinical trials, antihypertensive therapy was
deaths among the entire population is projected associated with an average decline of 41%
to remain stable through 2030, with potential (95% CI, 33%–48%) in stroke incidence

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e231

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

with SBP reductions of 10 mm Hg or DBP 6.58–18.23]) compared with whites (treated: OR,
CLINICAL STATEMENTS

reductions of 5 mm Hg.64 1.57 [95% CI, 1.24–1.98]; untreated: OR, 8.79

AND GUIDELINES

• Three recent additional meta-analyses65–67 were [95% CI, 5.66–13.66]), as well as among blacks
consistent with the results of the aforementioned compared with whites and Hispanics (P for inter-
studies; the more intense BP-lowering strategy action <0.0001).76
was associated with a significant reduction in • In the SPS3 trial, black participants were more
the cumulative risk of stroke. Taken together, the likely to have SBP ≥150 mm Hg at both study entry
evidence from these meta-analyses suggests that (40%) and end-study visit (17%; mean follow-up,
SBP <130 mm Hg may be most clinically advanta- 3.7 years) than whites (9%) and Hispanics (11%)
geous BP target in the prevention of stroke. at end-study visit.77
• Risk prediction models identify elevated BP as a
key parameter in the assessment of cardiovascular Diabetes Mellitus
and stroke risk.68 (See Chapter 9 for more information.)
— People with DM with BP <120/80 mm Hg • DM increases ischemic stroke incidence at all
have approximately half the lifetime risk of ages, but this risk is most prominent (risk ratio >5)
stroke of diabetics with hypertension. The before 65 years of age in both blacks and whites.
treatment and lowering of BP among hyper- Overall, ischemic stroke patients with DM are
tensive individuals with DM was associated younger, more likely to be black, and more likely
with a significant reduction in stroke risk.69,70 to have HBP, MI, and high cholesterol than non-
— A review identified the benefit of intense BP diabetic patients.78
reduction and reduced stroke outcome risks • The association between DM and stroke risk dif-
in recent clinical trials.71 Combined results fers between sexes. A systematic review of 64
from SPRINT and ACCORD demonstrated cohort studies representing 775 385 individuals
that intensive BP control (<120 mm  Hg) and 12 539 strokes revealed that the pooled, fully
compared with standard treatment (<140 adjusted RR of stroke associated with DM was
mm Hg) resulted in a significantly lower risk 2.28 (95% CI, 1.93–2.69) in females and 1.83
of stroke (RR, 0.75 [95% CI, 0.58–0.97]).69 (95% CI, 1.60–2.08) in males. Compared with
• Cross-sectional baseline data from the SPS3 trial males with DM, females with DM had a 27%
showed that more than half of all patients with greater RR for stroke when baseline differences in
Downloaded from http://ahajournals.org by on February 7, 2019

symptomatic lacunar stroke had uncontrolled other major cardiovascular risk factors were taken
hypertension at 2.5 months after stroke.72 into account (pooled ratio of RR, 1.27 [95% CI,
• A meta-analysis of 19 prospective cohort studies 1.10–1.46]; I2=0%).79
(including 762 393 participants) found that prehy- • Prediabetes, defined as impaired glucose toler-
pertension is associated with incident stroke. The ance or a combination of impaired fasting glucose
risk is particularly noted in those with BP values in and impaired glucose tolerance, may be associ-
the higher prehypertension range.73 ated with a higher future risk of stroke, but the
• Several studies have shown significantly lower RRs are modest. A meta-analysis of 15 prospec-
rates of recurrent stroke with lower BPs. Most tive cohort studies including 760 925 participants
recently, the BP-reduction component of the SPS3 revealed that when prediabetes was defined as
trial showed that targeting an SBP <130 mm Hg fasting glucose of 110 to 125 mg/dL (5 studies),
(versus a higher group at 130–149 mm Hg) was the adjusted RR for stroke was 1.21 (95% CI,
likely to reduce recurrent stroke by ≈20% (HR, 1.02–1.44; P=0.03).80
0.81 [95% CI, 0.64–1.03]; P=0.08) and signifi- • DM is an independent risk factor for stroke recur-
cantly reduced ICH by two-thirds (HR, 0.37 [95% rence; a meta-analysis of 18 studies involving
CI, 0.14–0.89]; P=0.03) compared with an SBP 43  899 participants with prior stroke revealed
goal of 130 to 149 mm Hg.74 higher stroke recurrence in patients with DM than
• Results from the SPS3 study showed the lowest in those without (HR, 1.45 [95% CI, 1.32–1.59]).81
risk of events was observed at an SBP of 120 to • A Swedish population-based stroke registry of
128 mm Hg and a DBP of 65 to 70 mm Hg.75 12 375 first-ever stroke patients 25 to 74 years
• In the Ethnic/Racial Variations of Intracerebral old who were followed up to 23 years found
Hemorrhage study, both treated and untreated that patients with DM at stroke onset (21%)
hypertension conferred a greater risk of ICH had a higher risk of death than patients without
among blacks (treated: OR, 3.02 [95% CI, 2.16– DM (adjusted HR, 1.67 [95% CI, 1.58–1.76]).82
4.22]; untreated: OR, 12.46 [95% CI, 8.08– The reduced survival of stroke patients with DM
19.20]) and Hispanics (treated: OR, 2.50 [95% was more pronounced in females (P=0.02) and
CI, 1.73–3.62]; untreated: OR, 10.95 [95% CI, younger individuals (P<0.001).

e232 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

• In a meta-analysis of 11 RCTs that included 56 161 The percentage of strokes attributable to AF

CLINICAL STATEMENTS
patients with type 2 DM and 1835 stroke cases, increases steeply from 1.5% at 50 to 59 years of

AND GUIDELINES
those who were randomized to intensive glucose age to 23.5% at 80 to 89 years of age.89,90
control did not have a reduction in stroke risk • An analysis from the FHS demonstrated that the
compared with those with conventional glucose risk of stroke associated with AF declined by 73%
control (RR, 0.94 [95% CI, 0.84–1.06]; P=0.33; in the 50 years from 1958 to 2007.91 However,
I2 P=0.20); however, there was a 10% reduction analysis from the Olmsted County, MN, data-
in all MI (RR, 0.90 [95% CI, 0.820.98]; P=0.02; I2 base suggests that AF-associated stroke risk has
P=0.20).83 not changed over the past decade (from 2000 to
• A meta-analysis of 40 RCTs of BP lowering among 2010).92
100 354 participants with DM revealed a lower • Because AF is often asymptomatic93,94 and likely
risk of stroke (combined RR, 0.73 [95% CI, 0.64– frequently undetected clinically,95 the stroke risk
0.83]; absolute risk reduction, 4.06 [95% CI, attributed to AF could be substantially underesti-
2.53–5.40]).84 mated.96 Screening for AF in patients with crypto-
• A subsequent meta-analysis of 28 RCTs involv- genic stroke or TIA by use of outpatient telemetry
ing 96 765 participants with DM revealed that for 21 to 30 days has resulted in an AF detection
a decrease in SBP by 10 mm Hg was associated rate of 12% to 23%.95–97
with a lower risk of stroke (RR from 21 studies, • In an RCT among patients with cryptogenic stroke,
0.74 [95% CI, 0.66–0.83]). Significant interac- the cumulative incidence of AF detected with an
tions were observed, with lower RRs (RR, 0.71 implantable cardiac monitor was 30% by 3 years.
[95% CI, 0.63–0.80]) observed among trials with Approximately 80% of the first AF episodes were
mean baseline SBP ≥140 mm Hg and no signifi- asymptomatic.98
cant associations among trials with baseline SBP • Among 2580 participants ≥65 years of age with
<140 mm Hg (RR, 0.90 [95% CI, 0.69–1.17]). The hypertension in whom a cardiac rhythm device
associations between BP lowering and stroke risk that included an atrial lead was implanted, 35%
reduction were present for both the achieved SBP developed subclinical tachyarrhythmias (defined
of <130 mm Hg and the ≥130 mm Hg stratum.85 as an atrial rate ≥190 beats per minute that lasted
• The ACCORD study showed that in patients with ≥6 minutes). These subclinical events were asso-
ciated with a 2.5-fold increased risk of ischemic
Downloaded from http://ahajournals.org by on February 7, 2019

type 2 DM, targeting SBP to <120 mm Hg did not

reduce the rate of cardiovascular events com- stroke or systemic embolism. The authors esti-
pared with subjects in whom the SBP target was mated that subclinical atrial tachyarrhythmias
<140 mm Hg, except for the end point of stroke, were associated with a 13% PAR for stroke or
for which intensive therapy reduced the risk of systemic embolism.99
any stroke (HR, 0.59 [95% CI, 0.39–0.89]) and • An analysis of patients from the Veterans
nonfatal stroke (HR, 0.63 [95% CI, 0.41–0.96]).70 Administration showed that among patients with
• ONTARGET revealed that in both patients with device-documented AF, the presence of relatively
and without DM, the adjusted risk of stroke con- brief amounts of AF raised the short-term risk of
tinued to decrease down to achieved SBP values stroke 4- to 5-fold. This risk was highest in the
of 115 mm Hg, whereas there was no benefit for initial 5 to 10 days after the episode of AF and
other fatal or nonfatal cardiovascular outcomes declined rapidly after longer periods.100
below an SBP of 130 mm Hg.86 • Important risk factors for stroke in the setting
• In NOMAS, duration of DM was associated with of AF include advancing age, hypertension,
ischemic stroke risk (adjusted HR per year with HF, DM, previous stroke or TIA, vascular dis-
DM, 1.03 [95% CI, 1.02–1.04]).87 ease, renal dysfunction, and female sex.84,101–104
• The ATRIA Study demonstrated that the duration Additional biomarkers, including high levels
of DM is a stronger predictor of ischemic stroke of troponin and BNP, are associated with an
than glycemic control for patients with DM and increased risk of stroke in the setting of AF in
AF.88 Duration of DM ≥3 years was associated models adjusted for well-established clinical
with an increased rate of ischemic stroke (HR, characteristics.105
1.74 [95% CI, 1.10–2.76]) compared with a dura- • In patients with AF on anticoagulation, presence
of persistent AF versus paroxysmal AF is associ-
tion of <3 years.
ated with higher risk of stroke.106,107
Disorders of Heart Rhythm • A significant obesity paradox has been noted for
(See Chapter 16 for more information.) stroke risk among AF patients in a meta-analysis
• AF is a powerful risk factor for stroke, indepen- of RCTs with newer oral anticoagulant trials such
dently increasing risk ≈5-fold throughout all ages. that overweight to obese participants had lower

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e233

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

risk of stroke and systemic embolism.108 However, risk of hemorrhagic stroke (HR, 0.85 [95% CI,
CLINICAL STATEMENTS

this relationship was not observed in the observa- 0.80–0.91]).121

AND GUIDELINES

tional studies.109 • Data from the Honolulu Heart Program/NHLBI

• Other cardiac arrhythmias and ECG findings asso- found that in Japanese males 71 to 93 years of
ciated with an increased risk of stroke include age, low concentrations of HDL-C were more
paroxysmal SVT; short, irregular SVTs without P likely to be associated with a future risk of throm-
waves; short-run atrial tachyarrhythmia (episodes boembolic stroke than were high concentra-
of supraventricular ectopic beats <5 seconds); PR tions.122 However, a meta-analysis of 23 studies
interval prolongation >200 ms; abnormal P-wave performed in the Asia-Pacific region showed no
axis (any value outside 0° to 75° using 12-lead significant association between low HDL-C and
ECGs); elevated P-wave terminal force; and maxi- stroke risk,123 although another meta-analysis
mal P-wave area.110 without geographic restriction demonstrated a
• Left atrial enlargement is associated with AF, caus- protective association of HDL-C with stroke.116 A
ing the 2 conditions to often coexist. A system- Finnish study of 27 703 males and 30 532 females
atic review of 9 cohort studies including 67 875 followed up for >20 years for ischemic stroke
participants revealed that those with left atrial found an independent inverse association of
enlargement in the setting of sinus rhythm had HDL-C with the risks of total and ischemic stroke
stroke rates ranging from 0.64 to 2.06 per 100 in females.113 In the CHS, higher HDL-C was
person-years. Two studies found potential indica- associated with a lower risk of ischemic stroke in
tions of modification by sex, with only positive males but not in females.124 In the SHS, a possible
associations observed in females.111 interaction was noted between DM status and
HDL-C for risk of stroke such that higher HDL-C
High Blood Cholesterol and Other Lipids was protective against stroke risk in patients with
(See Chapter 7 for more information.) DM (HR per 1-SD higher HDL-C, 0.72 [95% CI,
• Overall, the association of each cholesterol sub- 0.53–0.97]) but not in those without DM (HR per
fraction with total stroke has shown inconsistent 1-SD higher HDL-C, 0.93 [95% CI, 0.69–1.26]).125
results, and the data are limited on associations In a recent meta-analysis, no significant associa-
with specific ischemic stroke subtypes. Further tion was observed between HDL-C levels and risk
research is needed to identify the association of of hemorrhagic stroke.121
Downloaded from http://ahajournals.org by on February 7, 2019

cholesterol with ischemic stroke subtypes, as well • Data from the Dallas Heart Study suggest that
as the association of lobar versus deep ICH.112–116 higher HDL-C efflux capacity is strongly associ-
For clarity, results for different types of cholesterol ated with lower risk of stroke.126
(TC, subfractions) are described in this section. • In an analysis by the Emerging Risk Factors
• An association between TC and ischemic stroke Collaboration of individual records on 302 430
has been found in some prospective studies117–119 people without initial vascular disease from 68
but not others.112,113,116 In the Women’s Pooling long-term prospective studies, HR for ischemic
Project, including those <55 years of age with- stroke was 1.12 (95% CI, 1.04–1.20) for non–
out CVD, TC was associated with an increased HDL-C in analyses using the lowest quantile as
risk of stroke at the highest quintile (mean cho- the referent group127 and 0.93 (95% CI, 0.84–
lesterol 7.6 mmol/L) in black (RR, 2.58 [95% CI, 1.02) for HDL-C. In the Women’s Health Study,
1.05–6.32]) but not white (RR, 1.47 [95% CI, LDL-C was associated with an increased risk of
0.57–3.76]) females.114 An association of elevated stroke,117 and LDL-C may have a stronger asso-
TC with risk of stroke was noted to be present ciation for large-artery atherosclerotic subtype.128
in those 40 to 49 years old and 50 to 59 years In a pooled analysis of CHS and ARIC, low LDL­ C
old but not in other age groups in the Prospective (<158.8 mg/dL) was associated with an increased
Studies Collaboration.115 In a recent meta-analy- risk of ICH.129
sis of data from 61 cohorts, TC was only weakly • Among 13  951 patients in the Copenhagen
associated with risk of stroke, with no significant Heart Study followed up for 33 years for ischemic
difference between males and females (HR [95% stroke, increasing stepwise levels of nonfasting
CI] for ischemic stroke per 1 mmol/L higher TC: triglycerides were associated with increased risk
1.01 [0.98–1.05] in females and 1.03 [1.00–1.05] of ischemic stroke in both males and females,130
in males).120 although in ARIC, the Physician’s Health Study,
• Elevated TC is inversely associated in multiple and the SHS, there was no association.125,131,132 In
studies with hemorrhagic stroke. In a meta-anal- the Rotterdam Study (N=9068), increasing quar-
ysis of 23 prospective cohort studies, 1 mmol tiles of serum triglycerides were associated with a
higher TC was associated with a 15% lower reduced risk of ICH.133

e234 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

• A mendelian randomization study of lipid genet- among nonsmokers who had secondhand

CLINICAL STATEMENTS
ics suggested an increased risk of large-artery smoke exposure during adulthood (95% CI,

AND GUIDELINES
ischemic stroke with increased LDL and a lower 2%–67%).148
risk of small-vessel ischemic stroke with increased — Data from another large-scale prospective
HDL.134 cohort study of females in Japan showed
that secondhand tobacco smoke exposure
Smoking/Tobacco Use
at home during adulthood was associated
(See Chapter 3 for more information.)
with an increased risk of stroke mortality in
• Current smokers have a 2 to 4 times increased risk
those aged ≥80 years (HR, 1.24 [95% CI,
of stroke compared with nonsmokers or those
1.05–1.46]). Overall, the increased risk was
who have quit for >10 years.135,136
most evident for SAH (HR, 1.66 [95% CI,
• Cigarette smoking is a risk factor for ischemic
1.02–2.70]) in all age groups.149
stroke and SAH.135–137
— A study using NHANES data found that indi-
• Smoking is perhaps the most important modifi-
viduals with a prior stroke have a greater
able risk factor in preventing SAH, with the high-
odds of having been exposed to secondhand
est PAR (38%–43%) of any SAH risk factor.138
smoke (OR, 1.46 [95% CI, 1.05–2.03]), and
• In a large Danish cohort study, among people
secondhand smoke exposure was associated
with AF, smoking was associated with a higher
with a 2-fold increase in mortality among
risk of ischemic stroke/arterial thromboembolism
stroke survivors compared with stroke sur-
or death, even after adjustment for other tradi-
vivors without the exposure (age-adjusted
tional risk factors.139
mortality rate: 96.4±20.8 versus 56.7±4.8
• Although some studies have reported a dose-
per 100 person-years; P=0.026).150
response relationship between smoking and risk
• The FINRISK study found a strong association
of stroke across old and young age groups,137,140
between current smoking and SAH compared
a recent meta-analysis of 141 cohort studies
with nonsmokers (HR, 2.77 [95% CI, 2.22–3.46])
showed that low cigarette consumption (≈1 ciga-
and reported a dose-dependent and cumulative
rette per day) carries a risk of developing stroke as
association with SAH risk that was highest in
large as 50% of that of high cigarette consump-
females who were heavy smokers.151
tion (≈20 cigarette per day).141 This is much higher
Downloaded from http://ahajournals.org by on February 7, 2019

• Use of smokeless tobacco is associated with an

than what would be predicted from a linear or
increased risk of fatal stroke.
log-linear dose-response relationship between
— In recent meta-analyses of studies from
smoking and risk of stroke.141
Europe, North America, and Asia, adult ever-
• A meta-analysis that compared pooled data of
users of smokeless tobacco had a higher
almost 4 million smokers and nonsmokers found
risk of fatal stroke (OR, 1.39 [95% CI,
a similar risk of stroke associated with current
1.29–1.49]).152,153
smoking in females and males.142
— No association has been reported between
• Discontinuation of smoking has been shown
use of smokeless tobacco and nonfatal
to reduce stroke risk across sex, race, and age
stroke.152
groups.140,142
• Smoking may impact the effect of other stroke Physical Inactivity
risk factors on stroke risk. For example, a syn- (See Chapter 4 for more information.)
ergistic effect on the risk of stroke appears to • Over a mean follow-up of 17 years, the ARIC
exist between smoking and SBP143 and oral study found a significant trend among African-
contraceptives.144,145 Americans toward reduced incidence of stroke
• Exposure to secondhand smoke, also termed pas- with increasing level of PA; a similar trend was
sive smoking or secondhand tobacco smoke, is a observed for whites in the study, although it was
risk factor for stroke. not statistically significant. Data from this study
— Meta-analyses have estimated a pooled RR showed that although the highest levels of activ-
of 1.25 for exposure to spousal smoking ity were most protective, even modest levels of PA
(or nearest equivalent) and risk of stroke. A appeared to be beneficial.154
dose-response relationship between expo- • Among individuals >80 years of age in NOMAS,
sure to secondhand smoke and stroke risk physical inactivity was associated with higher risk
was also reported.146,147 of stroke (physical inactivity versus PA: HR, 1.60
— Data from REGARDS found that after [95% CI, 1.05–2.42]).155
adjustment for other stroke risk factors, • In the CHS, a greater amount of leisure-time PA
the risk of overall stroke was 30% higher (across quintiles, Ptrend=0.001), as well as exercise

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e235

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

intensity (categories: high, moderate, low versus • Recent studies have also demonstrated a signifi-
CLINICAL STATEMENTS

none, Ptrend<0.001), were both associated with cant association between sedentary time duration
AND GUIDELINES

lower risk of stroke among individuals >65 years and risk of CVD including stroke, independent of
of age. The relation between greater PA and PA levels.162,163 In the REGARDS study, screen time
lower risk of stroke was even observed in indi- >4 h/d was associated with 37% higher risk (HR,
viduals ≥75 years of age.155a 1.37 [95% CI, 1.10–1.71]) of stroke over a 7-year
• In the Cooper Center Longitudinal Study of follow-up.164
participants who underwent evaluation at the • In a population-based study of 74 913 Japanese
Cooper Clinic in Dallas, TX, investigators found people aged 50 to 79 years and without histories of
that cardiorespiratory fitness in mid-life as mea- CVD or cancer, there was a nonlinear dose-response
sured by exercise treadmill testing was inversely relationship between daily total PA and stroke risk.
associated with risk of stroke in older age, includ- Individuals with moderate levels of total PA had the
ing in models that were adjusted for the interim lowest risk of total stroke (HR, 0.83 [95% CI, 0.75–
development of stroke risk factors such as DM, 0.93]), hemorrhagic stroke (HR, 0.79 [95% CI,
hypertension, and AF.156 0.66–0.94]), and ischemic stroke (HR, 0.79 [95%
• Similarly, a prospective study of young Swedish CI, 0.69–0.90]). The associations of total PA level
males demonstrated that the highest compared with hemorrhagic stroke showed a U or J shape,
with the lowest tertile of fitness (HR, 1.70 [95% and that with ischemic stroke showed a L shape.165
CI, 1.50–1.93]) and lower muscle strength (HR,
1.39 [95% CI, 1.27–1.53]) were associated with Nutrition
higher risk of stroke over 42 years of follow-up.157 (See Chapter 5 for more information.)
• Several recent prospective studies found associa- • Adherence to a Mediterranean-style diet that was
tions of PA and stroke risk in females. higher in nuts and olive oil was associated with
— In the Million Women Study, a prospective a reduced risk of stroke (diet with nuts: HR, 0.54
cohort study among females in England and [95% CI, 0.35–0.82]; diet with olive oil: HR, 0.65
Scotland, over an average follow-up of 9 [95% CI, 0.44–0.95]; Mediterranean diets com-
years, self-report of any PA at baseline was bined versus control: HR, 0.58 [95% CI, 0.42–
associated with reduced risk of any stroke, 0.82]) in an RCT conducted in Spain.165a
as well as stroke subtypes; however, more • In the Nurses Health and Health Professionals
Downloaded from http://ahajournals.org by on February 7, 2019

frequent or strenuous activity was not asso- Follow-up Studies, each 1-serving increase in
ciated with increased protection against sugar-sweetened soda beverage was associated
stroke.158 with a 13% increased risk of ischemic stroke, and
— Similarly, a low level of leisure-time PA was each 1-serving increase in low-calorie or diet soda
associated with a 1.5 times higher risk of was associated with a 7% increased risk of isch-
stroke and a 2.4 times higher risk of fatal emic stroke and a 27% increased risk of hemor-
stroke compared with intermediate to high rhagic stroke.166
levels of activity in a cohort of ≈1500 Swedish • A meta-analysis of >94 000 people with 34 817
females followed up for up to 32 years.159 stroke events demonstrated that eating ≥5 serv-
— The EPIC-Heidelberg cohort included ings of fish per week versus eating <1 serving per
25 000 males and females and identified week was associated with a 12% reduction in
stroke outcomes over a mean of 13 years stroke risk; however, these results were not con-
of follow-up. Among females, participa- sistent across all cohort studies.167
tion in any level of PA was associated with • According to registry data from Sweden, people
a nearly 50% reduction in stroke risk com- eating ≥7 servings of fruits and vegetables per
pared with inactivity; no similar pattern was day had a 19% reduced risk of stroke compared
seen for males.160 with those eating only 1 serving per day among
• A dose-response effect was seen for total number people who did not have hypertension.168 Results
of hours spent walking per week, and increased from 2 prospective cohorts from Sweden, com-
walking time was associated with reduced risk of prising 74 404 males and females 45 to 83 years
incident stroke among 4000 males in the British of age free of stroke at baseline, found that high
Regional Heart Study. Those reporting ≥22 hours adherence to the modified DASH diet is associ-
of walking per week had one-third the risk of ated with a reduced risk of ischemic stroke (RR,
incident stroke as those who walked <4 hours 0.86 [95% CI, 0.78–0.94] for the highest versus
per week. No clear association between stroke lowest quartile of diet adherence).169
and walking speed or distance walked was seen • A Nordic diet, including fish, apples and
in this study.161 pears, cabbages, root vegetables, rye bread, and

e236 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

oatmeal, was associated with a decreased risk potassium intake, there was a 10% reduction in

CLINICAL STATEMENTS
of stroke among 55 338 males and females (HR, stroke risk (RR, 0.90 [95% CI, 0.84–0.96]).178

AND GUIDELINES
0.86 [95% CI, 0.76–0.98] for high versus low diet • A systematic meta-analysis from 19 indepen-
adherence).170 dent cohort samples from 13 studies determined
• A meta-analysis of case-control, prospective a higher salt intake was associated with greater
cohort studies and an RCT investigating the asso- risk of stroke (pooled RR, 1.23 [95% CI, 1.06 to
ciation between olive oil consumption and the 1.43]), with no significant evidence of publication
risk of stroke (N=38 673 participants) revealed bias.179
a reduction in stroke risk (RR, 0.74 [95% CI, • A meta-analysis of 8 studies (N=280 174) indicated
0.60–0.92]).171 an inverse association between flavonol intake
• A meta-analysis of 10 prospective cohort stud- and stroke (summary RR, 0.86 [95% CI, 0.75–
ies including 314 511 nonoverlapping individuals 0.99]). An increase in flavonol intake of 20 mg/d
revealed that higher MUFA intake was not associ- was associated with a 14% decrease in the risk
ated with risk of overall stroke (RR, 0 .86 [95% for developing stroke (summary RR, 0.86 [95%
CI, 0.74–1.00]) or risk of ischemic stroke (RR, 0.92 CI, 0.77–0.96]). Subgroup analyses suggested
[95% CI, 0.79–1.08]) but was associated with a an inverse association between highest flavonol
reduced risk of hemorrhagic stroke (RR, 0.68 intake and stroke risk among males (summary RR,
[95% CI, 0.49–0.96]).172 0.74 [95% CI, 0.56–0.97]) but not females (sum-
• A meta-analysis of prospective cohort studies mary RR, 0.99 [95% CI, 0.85–1.16]).180
evaluating the impact of dairy intake on CVD • In a population of Chinese adults, folate therapy
noted that total dairy intake and calcium from combined with enalapril was associated with a sig-
dairy were associated with an inverse summary nificant reduction in ischemic stroke risk (HR, 0.76
RR estimate for stroke (0.91 [95% CI, 0.83–0.99] [95% CI, 0.64–0.91]). Although the US popula-
and 0.69 [95% CI, 0.60–0.81], respectively).173 tion is not as likely to be at risk of folate deficiency
• A meta-analysis of 20 prospective cohort studies because of folate fortification of grains, this study
of the association between nut consumption and demonstrates the importance of adequate folate
cardiovascular outcomes (N=467 389) revealed no levels for stroke prevention.181
association between nut consumption and stroke • A study using Framingham data found that recent
(2 studies; RR, 1.05 [95% CI, 0.69–1.61]) but did
Downloaded from http://ahajournals.org by on February 7, 2019

consumption and an increased cumulative intake

find an association with stroke mortality (3 stud- of artificially sweetened soft drinks was associ-
ies; RR, 0.83 [95% CI, 0.69–1.00]).174 ated with a higher risk of stroke, with the stron-
• A meta-analysis of 8 prospective studies gest association observed for ischemic stroke; no
(N=410 921) revealed no significant association association was observed for sugary beverages or
between consumption of refined grains and risk of sugar-sweetened soft drinks.182
stroke.175 A second meta-analysis176 of 8 prospec-
tive studies (N=468 887) revealed that a diet that Family History and Genetics
contained greater amounts of legumes was not • Ischemic stroke is a heritable disease; family his-
associated with a lower risk of stroke; however, tory of stroke is associated with increased risk
a diet with greater amounts of nuts was associ- of ischemic stroke, stroke subtypes, and carotid
ated with lower risk of stroke (summary RR, 0.90 atherosclerosis.183
[95% CI, 0.81–0.99]). Sex significantly modified • In the Family Heart Study, the adjusted ORs of
the effects of nut consumption on stroke risk, and stroke for a positive paternal and maternal his-
high nut intake was associated with reduced risk tory of stroke were 2.0 and 1.4, respectively, with
of stroke in females (summary RR, 0.85 [95% CI, similar patterns seen in African Americans and
0.75–0.97]) but not in males (summary RR, 0.95 European Americans.184
[95% CI, 0.82–1.11]).176 • Heritability of stroke appears to play a larger role
• A meta-analysis of 21 studies (N=13 033) evaluat- in strokes that occur in younger people.185
ing the effect of vitamin D on cardiovascular out- • Genetic factors appear to be more important in
comes revealed that vitamin D supplementation large-artery and small-vessel stroke than in cryp-
was not associated with a lower risk of stroke (HR, togenic or cardioembolic stroke.185
1.07 [95% CI, 0.91–1.29]).177 • Genetic studies have identified genetic variants
• A meta-analysis of 14 cohorts (N=333  250) associated with risk of ischemic stroke, with dis-
revealed that potassium intake is associated with tinct genetic associations186 for different stroke
lower risk of stroke (RR, 0.80 [95% CI, 0.72–0.90]). subtypes.
In addition, the dose-response analysis showed — For example, variants in the paired-like
that for every 1 g/d (25.6 mmol/d) increase in homeodomain transcription factor 2 (PITX2)

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e237

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

gene discovered through an unbiased • Monogenic forms of ischemic stroke have much
CLINICAL STATEMENTS

genome-wide approach for AF have been higher risk associated with the underlying genetic
AND GUIDELINES

shown to be associated with cardioembolic variant but are rare.195

stroke.187 — For example, cerebral autosomal dominant
— Variants in the HDAC9 gene have been asso- arteriopathy with subcortical infarcts and leu-
ciated with large-artery stroke, as have vari- koencephalopathy (CADASIL), an autosomal
ants in the chromosome 9p21 locus originally dominant disease presenting with stroke,
identified through a genome-wide approach progressive cognitive impairment, and char-
for CAD.188,189 acteristic bilateral involvement of the anterior
• The largest multiethnic GWAS of stroke conducted temporal white matter and external capsule,
to date reports 32 genetic loci, including 22 not is caused by mutations in the NOTCH3 gene
previously reported.190 These novel loci point to a on chromosome 19q12.196
major role of cardiac mechanisms beyond estab- — Other monogenic causes of stroke include
lished sources of cardioembolism. Approximately Fabry disease, sickle cell disease, homocys-
half of the stroke genetic loci share genetic asso- tinuria, Marfan syndrome, vascular Ehlers-
ciations with other vascular traits, most notably Danlos syndrome (type IV), pseudoxanthoma
BP. The identified loci were also enriched for tar- elasticum, retinal vasculopathy with cerebral
gets of antithrombotic drugs, including alteplase leukodystrophy and systemic manifestations,
and cilostazol. and mitochondrial myopathy, encephalopa-
• Some genetic loci were subtype specific. For thy, lactic acidosis, and stroke (MELAS).186
example, EDNRA and LINC01492 were exclu- • ICH also appears to have a genetic compo-
sively associated with large-artery stroke. But nent, with heritability estimates of 34% to 74%
shared genetic influences between stroke sub- depending on the subtype.197 A GWAS of ICH
types were also evident. For example, SH2B3 suggests that 15% of this heritability is attrib-
showed shared influence on large-artery and utable to genetic variants in the apolipoprotein
small-vessel stroke and ABO on large-artery E (APOE) gene and 29% is attributable to non-
and cardioembolic stroke; PMF1-SEMA4A has APOE genetic variants.197
been associated with both nonlobar ICH and • Genetic variants that predispose to hypertension
ischemic stroke
Downloaded from http://ahajournals.org by on February 7, 2019

also have been associated with ICH risk.185 The

• A recent GWAS focused on small-vessel stroke other strongest genes associated with ICH are
from the International Stroke Consortium identi- PMF1 and SLC25A44, which have been linked to
fied a novel association with a region on chromo- ICH with small-vessel disease.198,199
some 16q24.2.191
• Studies have also identified genetic loci unique to Kidney Disease
non-European ethnicity populations. For exam- (See Chapter 11 for more information.)
ple, one study of African Americans from MESA • A meta-analysis of 21 studies including >280 000
found that variants within the SERGEF gene were patients showed a 43% (RR, 1.43 [95% CI,
associated with carotid artery IMT, as well as with 1.31–1.57]) increased incident stroke risk among
stroke.192 patients with a GFR <60 mL·min−1·1.73 m−2.200
• Low-frequency genetic variants (ie, allele fre- • A meta-analysis showed that a higher albumin-
quency <5%) may also contribute to risk of uria level confers greater stroke risk, providing evi-
large- and small-vessel stroke. GUCY1A3, for dence that albuminuria is strongly linked to stroke
example, with an allele frequency in the lead risk, and suggested that people with elevated
SNP of 1.5%, was associated with large-vessel levels of urinary albumin excretion could benefit
stroke.193 The gene encodes the α1-subunit of from more intensive vascular risk reduction.201
soluble guanylyl cyclase, which plays a role both • A meta-analysis showed stroke risk increases lin-
in nitric oxide–induced vasodilation and plate- early and additively with declining GFR (RR per 10
let inhibition, and has been associated with mL·min−1·1.73 m−2 decrease in GFR, 1.07 [95%
early MI. CI, 1.04–1.09]) and increasing albuminuria (RR
• The gene GCH1, also with an allele frequency per 25 mg/mmol increase in ACR, 1.10 [95% CI,
of only 1.5%, was associated with small-vessel 1.01–1.20]), which indicates that CKD staging
stroke. This gene encodes GTP cyclohydrolase might also be a useful clinical tool to identify peo-
1, which plays a role in endothelial nitric oxide ple who might benefit most from interventions to
synthase.194 Rare variants thus may account reduce stroke risk.202
for some of the unexplained heritability in • A pooled analysis of 4 prospective community-
stroke risk. based cohorts (ARIC, MESA, CHS, and PREVEND)

e238 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

including 29 595 participants showed that low ≤10 years and those experiencing menarche at

CLINICAL STATEMENTS
eGFR (45 mL·min−1·1.73 m−2) was significantly age ≥17 years had an increased risk of stroke (RR,

AND GUIDELINES
associated with increased risk of ischemic stroke 1.16 [95% CI, 1.09–1.24] and RR, 1.13 [95% CI,
(HR, 1.30 [95% CI, 1.01–1.68]) but not hemor- 1.03 -1.24], respectively).
rhagic stroke (HR, 0.92 [95% CI, 0.47–1.81]) • In a recent meta-analysis of 32 studies, females
compared with normal GFR (95 mL·min−1·1.73 who experienced menopause before age 45 years
m−2). A high ACR of 300 mg/g was associated had an increased risk of stroke compared with
with both ischemic stroke (HR, 1.62 [95% CI, females 45 years or older at menopause onset
1.27–2.07]) and hemorrhagic stroke (HR, 2.57 (OR, 1.23 [95% CI, 0.98–1.53]). This association
[95% CI, 1.37–4.83]) compared with 5 mg/g.203 was not observed for stroke mortality (OR, 0.99
• Proteinuria and albuminuria are better predictors [95% CI, 0.92–1.07]).215
of stroke risk than eGFR in patients with kidney • Overall, randomized clinical trial data indicate
disease.204 that the use of estrogen plus progestin, as well as
• Among 232 236 patients in the GWTG–Stroke estrogen alone, increases stroke risk in postmeno-
registry, admission eGFR (in mL·min−1·1.73 m−2) pausal, generally healthy females and provides
was inversely associated with mortality and poor no protection for postmenopausal females with
functional outcomes. After adjustment for poten- established CHD216–219 and recent stroke or TIA.220
tial confounders, lower eGFR was associated • In a nested case-control study of the United
with increased mortality, with the highest mortal- Kingdom’s General Practice Research Database,
ity among those with eGFR <15 without dialysis stroke risk was not increased for users of low-
(OR, 2.52 [95% CI, 2.07–3.07]) compared with dose (≤50 µg) estrogen patches (RR, 0.81 [95%
eGFR ≥60. Lower eGFR was also associated with CI, 0.62–1.05]) but was increased for users of
decreased likelihood of being discharged home.205 high-dose (>50 µg) patches (RR, 1.89 [95% CI,
• In a Chinese stroke registry, low eGFR (<60 1.15–3.11]) compared with nonusers.221
mL·min−1·1.73 m−2) compared with eGFR ≥90 • Migraine with aura is associated with ischemic
mL·min−1·1.73 m−2 was similarly associated with stroke in younger females, particularly if they
increased mortality among patients with and smoke or use oral contraceptives. The combi-
without hypertension, but there was an inter- nation of all 3 factors increases the risk ≈9-fold
action between eGFR and hypertension for the compared with females without any of these
Downloaded from http://ahajournals.org by on February 7, 2019

effect on functional outcomes. In 5082 patients factors.222,223

without hypertension, the risk of a poor func- • The peripartum period extending from 2 days
tional outcome (defined as modified Rankin Scale before to 1 day after delivery and, to a lesser
score of 3–6) was approximately twice as high for extent, up to 6 weeks postpartum is associated
those with low eGFR (adjusted OR, 2.14 [95% with an increased risk of ischemic stroke and
CI, 1.45–3.16]). In 1378 patients with previously ICH.224
diagnosed hypertension, the magnitude of risk of • In the Baltimore-Washington Cooperative Young
a poor functional outcome associated with low Stroke Study, the risk of ischemic stroke or ICH
eGFR was less (adjusted OR, 1.30 [95% CI, 1.11– during pregnancy and the first 6 weeks after giv-
1.52]; P for interaction 0.046).206 ing birth was 2.4 times greater than for nonpreg-
nant females of similar age and race. The excess
Risk Factor Issues Specific to Females risk of stroke (all types except SAH) attributable to
See the “Guidelines for the Prevention of Stroke in the combined pregnancy/postpregnancy period
Women: A Statement for Healthcare Professionals was 8.1 per 100 000 pregnancies.225
From the American Heart Association/American Stroke • Analyses of the US NIS from 1994 to 1995 and
Association” for more in-depth coverage of stroke risk from 2006 to 2007 showed a temporal increase
factors unique to females.207 in the proportion of pregnancy hospitalizations
• On average, females are ≈4 years older at stroke that were associated with a stroke, with a 47%
onset than males (≈75 years compared with 71 increase for antenatal hospitalizations and an
years).208 83% increase for postpartum hospitalizations.
• In the setting of AF, females have a significantly Increases in the prevalence of HD and hyper-
higher risk of stroke than males.209–213 tensive disorders accounted for almost all the
• In the UK Million Women Study, there was a increase in postpartum stroke hospitalizations but
U-shaped relationship between age at menarche not the antenatal stroke hospitalizations.117
and risk of incident stroke.214 Compared with • Preeclampsia is a risk factor for ischemic stroke
females experiencing menarche at 13 years of remote from pregnancy.176 The increase in stroke
age, both those experiencing menarche at age risk related to preeclampsia could be mediated by

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e239

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

later risk of hypertension and DM.226 A case-con- an HR of 1.45 (95% CI, 1.30–1.62) after adjust-
CLINICAL STATEMENTS

trol study of females aged 12 to 55 years admit- ment for demographics, vascular risk factors, and
AND GUIDELINES

ted to New York State hospitals found several comorbidities.240 In this same meta-analysis, short
factors increased the risk of pregnancy-associated sleep, defined as sleep ≤5 to 6 hours per night,
stroke in females with preeclampsia, including was also associated with incident stroke (HR, 1.15
infections present on admission (OR, 3.0 [95% CI, [95% CI, 1.07–1.24]) after adjustment for similar
1.6–5.8]), prothrombotic states (OR, 3.5 [95% CI, factors.
1.3–9.2]), coagulopathies (OR, 3.1 [95% CI, 1.3– • In a 2017 meta-analysis that included 20 reports
7.1]), and chronic hypertension (OR, 3.2 [95% CI, related to stroke outcomes, there was an approxi-
1.8–5.5]).227 mate U‐shaped association between sleep dura-
• Among people living with HIV, females had a tion and stroke risk, with the lowest risk at a
higher incidence of stroke or TIA than males, sleep duration of ≈6 to 7 hours daily. Both short
especially at younger ages.228 Compared with and long sleep duration were associated with
HIV-uninfected females, females living with increased stroke risk of stroke. For every hour of
HIV had a 2-fold higher incidence of ischemic sleep reduction below 7 hours, after adjustment
stroke.229 for other risk factors, the pooled RR was 1.05
(95% CI, 1.01–1.09) and for each 1-hour incre-
Sleep-Disordered Breathing and Sleep Duration
ment of sleep above 7 hours, the RR was 1.18
(See Chapter 12 for more information)
(95% CI, 1.14–1.21).241
• Sleep-disordered breathing is associated with
• In a meta-analysis of 10 studies, a J-shaped rela-
stroke risk. In a 2017 meta-analysis including
tionship was reported between sleep duration
16 cohort studies (N=24 308 individuals), severe
and stroke risk, with the lowest risk among those
OSA was associated with a doubling in stroke risk
with a sleep duration of 6 to 7 h/d.242
(RR, 2.15 [95% CI, 1.42–3.24]). Severe OSA was
independently associated with stroke risk among Psychosocial Factors
males, but not females, in stratified analyses. • Depression was associated with a nearly 2-fold
Neither mild nor moderate OSA was associated increased odds of stroke after adjustment for
with stroke risk.230 age, SES, lifestyle, and physiological risk factors
• OSA is also common after stroke.219,231,232 In a (OR, 1.94 [95% CI, 1.37–2.74]) in a cohort of
Downloaded from http://ahajournals.org by on February 7, 2019

2017 meta-analysis that included 43 studies, the 10 547 females aged 47 to 52 years who were
prevalence of OSA (AHI >10) after stroke and TIA followed up for 12 years as part of the Australian
ranged from 24% to 92%, with a pooled esti- Longitudinal Study on Women’s Health.243
mate of 59%.233 The proportion of cerebrovas- • A meta-analysis of 28 prospective cohort studies
cular disease patients with severe OSA (AHI >30) comprising 317 540 participants with a follow-
ranged from 8% to 64%. up period that ranged from 2 to 29 years found
• In the BASIC Project, Mexican Americans had a that depression was associated with an increased
higher prevalence of poststroke sleep-disordered risk of total stroke (pooled HR, 1.45 [95% CI,
breathing, defined as an AHI ≥10, than NH whites 1.29–1.63]), fatal stroke (pooled HR, 1.55 [95%
after adjustment for confounders (prevalence CI, 1.25–1.93]), and ischemic stroke (pooled HR,
ratio, 1.21 [95% CI, 1.01–1.46]).231 1.25 [95% CI, 1.11–1.40]).244
• Also in the BASIC Project, acute infarction involv- • A meta-analysis of 14 studies found a 33% (95%
ing the brainstem (versus no brainstem involve- CI, 17%–50%) increased risk of total stroke for
ment) was associated with increased odds of those with general or work stress and those
sleep-disordered breathing, defined as an AHI who experienced stressful life events, although
≥10, with OR 3.76 (95% CI, 1.44–9.81) after there was significant statistical heterogeneity
adjustment for demographics, risk factors, and between studies.245 Among 10 studies reporting
stroke severity.234 In this same study, ischemic sex-specific analyses, 6 of 7 showed a positive
stroke subtype was not found to be associated association, with a pooled HR of 1.24 (95% CI,
with the presence or severity of sleep-disordered 1.12–1.36 for males); 3 studies reporting results
breathing.235 for females only showed a pooled HR of 1.90
• OSA is associated with higher poststroke mortal- (95% CI, 1.40–2.56), and 1 case-control study
ity236–238 and worse functional outcome.239 showed no difference by sex.
• Sleep duration is also associated with stroke risk. • In a meta-analysis that included 46 studies (30
In a meta-analysis of 11 studies, long sleep, mostly on psychological factors, 13 on vocational fac-
defined as self-reported sleep of ≥8 to 9 hours per tors, 10 on interpersonal factors, and 2 on behav-
night, was associated with incident stroke, with ioral factors), the risk of stroke increased by 39%

e240 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

with psychological factors (HR, 1.39 [95% CI, • In a study of patients with AF, there was a lack

CLINICAL STATEMENTS
1.27–1.51]), 35% with vocational factors (HR, of knowledge about stroke subtypes, common

AND GUIDELINES
1.35 [95% CI, 1.20–1.51]), and 16% with inter- symptoms of stroke, and the increased risk of
personal factors (HR, 1.16 [95% CI 1.03–1.31]); stroke associated with AF.252 Only 68% of patients
there was no significant relationship with behav- without a prior stroke history were able to identify
ior factors (HR, 0.94 [95% CI 0.20–4.31]).246 the most common symptoms of stroke.
• Among 13 930 ischemic stroke cases and 28 026 • Among 2975 stroke/TIA cases in the GCNKSS,
controls in the NINDS Stroke Genetics Network, symptoms of weakness, decreased level of con-
each 1-SD increase in the Psychiatric Genomics sciousness, speech/language abnormalities, and
Consortium polygenic risk score for major depres- dizziness increased the odds that 9-1-1 was called
sive disorder was associated with a 3% increase for emergency transport to the hospital, indepen-
in the odds of ischemic stroke (OR, 1.03 [95% CI, dent of age, prior stroke, location of patients,
1.00–1.05]) for those of European ancestry and stroke subtype, stroke severity, and prestroke dis-
an 8% increase (OR, 1.08 [95% CI, 1.04–1.13]) ability. Numbness and vision disturbances were
for those of African ancestry.247 The risk score was associated with decreased odds of calling 9-1-1;
associated with increased odds of small-artery headache was not associated with 9-1-1 use.253
occlusion in both ancestry samples (European:
OR, 1.08 [95% CI, 1.03–1.13]; African: OR, 1.09
[95% CI, 1.01–1.19]), cardioembolic stroke in
Complications and Recovery
those of European ancestry (OR, 1.04 [95% CI (See Charts 14-7 through 14-9)
1.00–1.08]), and large-artery atherosclerosis in • Stroke is a leading cause of serious long-term dis-
those of African ancestry (OR, 1.12 [95% CI, ability in the United States (Survey of Income and
1.01–1.25]). Program Participation, a survey of the US Census
Bureau).254 Approximately 3% of males and 2%
of females reported that they were disabled
Awareness of Stroke Warning Signs and
because of stroke.
Risk Factors • In data from the NIS (2010 to 2012), among
• Knowledge on stroke risk factors and symptoms 395 411 stroke patients, 6.2% had a palliative
Downloaded from http://ahajournals.org by on February 7, 2019

is limited in children; stroke knowledge is lowest care encounter. There was wide variability in use
for those living in communities with greater eco- of palliative care, with higher use among patients
nomic need and sociodemographic distress and who were older, female, and white; for those
lower school performance.248 with hemorrhagic stroke; and for those at larger,
• A study of CVD awareness performed by the nonprofit hospitals.255
AHA among females in the United States who • Stroke was among the top 18 diseases contribut-
were >75 years old (N=1205) showed that low ing to years lived with disability in 2010; of these
proportions of females identified severe head- 18 causes, only the age-standardized rates for
ache (23%), unexplained dizziness (20%), and stroke increased significantly between 1990 and
vision loss/changes (18%) as stroke warning 2010 (P<0.05).256
symptoms.249 • Common complications after stroke include both
• In a single-center study of 144 stroke survivors, short-term complications, such as seizures, DVT,
Hispanics scored lower on a test of stroke symp- PE, urinary infection, aspiration pneumonia, decu-
toms and the appropriate response to those bitus ulcers, and constipation, as well as chronic
symptoms than NH whites (72.5% versus 79.1% sequelae including pain syndromes, pseudobulbar
of responses correct) and were less often aware affect, depression and anxiety, cognitive impair-
of tPA as a treatment for stroke (91.5% versus ment and dementia, epilepsy, gait instability, and
79.2%).250 falls and fractures.
• In the 2009 BRFSS (N=132 604), 25% of males • Among 1075 patients undergoing rehabilitation
versus 21% of females had low stroke symp- after stroke in a Polish cohort, at least 1 com-
tom knowledge scores (correct response to 0–4 plication was reported by 77% of patients, and
of the 7 survey questions).251 Sudden confusion 20% experienced ≥3 complications.257 Urinary
or difficulty speaking and sudden numbness or tract infection (23.2%), depression (18.9%), falls
weakness of the face, arm, or leg were the most (17.9%), unstable hypertension (17.6%), and
commonly correctly identified stroke symptoms, shoulder pain (14.9%) were the most common
whereas sudden headache was the least; 60% of complications.
females and 58% of males incorrectly identified • DVT and PE are well-known complications of
sudden chest pain as a stroke symptom. stroke, particularly in the acute phase. The

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e241

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

incidence of DVT is lower now than in older stud- • Patients with stroke are at increased risk of depres-
CLINICAL STATEMENTS

ies because of the use of prophylactic treatment sion. Approximately one-third of stroke survivors
AND GUIDELINES

with subcutaneous heparin and pneumatic com- develop poststroke depression, and the fre-
pression boots. In the PREVAIL trial, among 1762 quency is highest in the first year after a stroke.265
ischemic stroke patients unable to walk without Suicidality is also increased after stroke.266
assistance, the incidence of symptomatic DVT was • A 2014 meta-analysis involving 61 studies
≤1% in patients treated with either enoxaparin or (N=25 488) revealed depression in 33% (95%
unfractionated heparin.258 PE occurred in only 1 CI, 26%–39%) of patients at 1 year after stroke,
of 666 patients (0.2%) treated with enoxaparin with a decline at 1 to 5 years to 25% (95% CI,
and 6 of 669 patients (1%) treated with unfrac- 16%–33%) and to 23% (95% CI, 14%–31%) at
tionated heparin. 5 years.267
• The risk of VTE ranged from 16% to 30% for • Poststroke depression is associated with higher
those with severe strokes (NIHSS score ≥14) to mortality. A meta-analysis of 13 studies involving
8% to 14% for those with mild and moderate 59 598 individuals revealed a pooled OR for mor-
strokes (NIHSS score <14) in PREVAIL. tality at follow-up of 1.22 (95% CI, 1.02–1.47).268
• In a meta-analysis that included 7 studies, the Cognitive impairment and dementia are common
incidence density of late-onset poststroke sei- after stroke, with the incidence increasing with
zure (ie, seizure occurring at least 14 days after duration of follow-up. In 2 prospective studies,
a stroke) was 1.12 (95% CI, 0.95–1.32) per 100 11% to 23% of patients with incident lacunar
person-years.259 stroke developed vascular dementia during 3-year
• In the PROFESS trial, among 15 754 participants follow-up.269 Vascular dementia may develop
with ischemic stroke, 1665 patients (10.6%) annually in 3% to 5% of patients with lacunar
reported new chronic poststroke pain, including stroke.270
431 (2.7%) with central poststroke pain, 238 • Twelve RCTs (N=1121 subjects) suggested that
(1.5%) with peripheral neuropathic pain, 208 antidepressant medications might be effective in
(1.3%) with pain from spasticity, and 136 (0.9%) treating poststroke depression, with a beneficial
with pain from shoulder subluxation.260 Chronic effect of antidepressants on remission (pooled OR
pain was associated with greater dependence for meeting criteria for depression: 0.47 [95% CI,
Downloaded from http://ahajournals.org by on February 7, 2019

(OR, 2.16 [95% CI, 1.82–2.56]). 0.22–0.98]) and response, measured as a >50%
• Patients with stroke are at increased risk of frac- reduction in mood scores (pooled OR, 0.22 [95%
tures compared with those with TIA or no stroke CI, 0.09–0.52]).271
history. In the Ontario Stroke Registry, which • Seven trials (N=775 subjects) suggested that
included 23 751 stroke and 11 240 TIA patients, brief psychosocial interventions could be use-
the risk of low-trauma fractures was 5.7% dur- ful and effective in treatment of poststroke
ing the 2 years after stroke, compared with depression.271–275
4.8% in those with TIA and 4.1% in age- and • A meta-analysis of 8 RCTs assessing the efficacy
sex-matched control subjects.261 The risk among of preventive pharmacological interventions
stroke survivors compared with healthy control among 776 initially nondepressed stroke patients
subjects was ≈50% higher (adjusted HR for those revealed that the likelihood of developing post-
with stroke versus control subjects, 1.47 [95% CI stroke depression was reduced among subjects
1.35–1.60]). receiving active pharmacological treatment (OR,
• Chronic insomnia occurred in 16% of stroke 0.34 [95% CI, 0.22–0.53]), especially after a
survivors in an Australian cohort. Insomnia was 1-year treatment (OR, 0.31 [95% CI, 0.18–0.56])
associated with depression, anxiety, disability, and and with the use of a selective serotonin reup-
failure to return to work.262 take inhibitor (OR, 0.37 [95% CI, 0.22–0.61]).
• In a meta-analysis of 8 studies with data available All studies excluded those with aphasia or sig-
on constipation after stroke, which included  1385 nificant cognitive impairment, which limits their
participants, the pooled incidence of constipation generalizability.276
was 48% (95% CI, 33%–63%).263 • Five RCTs (N=1078 subjects) suggested that psy-
• Among 190 mild to moderately disabled survivors chosocial therapies could prevent the develop-
>6 months after stroke, aged 40 to 84 years, the ment of poststroke depression; however, the
prevalence of sarcopenia (loss of muscle mass) studies were limited by heterogeneity in design,
ranged between 14% and 18%, which was analysis, inclusion and exclusion criteria, inad-
higher than for control subjects matched on age, equate concealment of randomization, and high
sex, race, and BMI.264 numbers of dropouts.271,277

e242 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

• Of 127 Swedish survivors assessed for cognition • In the multicenter AVAIL registry, among 1444

CLINICAL STATEMENTS
at 10 years after stroke, poststroke cognitive patients, depression was associated with wors-

AND GUIDELINES
impairment was found in 46% using a Mini– ening function during the first year after stroke.
Mental State Examination threshold of <27, and Those whose depression resolved were less likely
in 61% using a Montreal Cognitive Assessment to have functional decline over time than those
threshold of <25.278 Data from prospective stud- without depression.285
ies provide evidence that after an initial period of • In CHS, among 509 participants with recovery
recovery, function, cognition, and quality of life data, prestroke walking speed and grip strength
decline over several years after stroke, even in were associated with poststroke declines in
the absence of definite new clinical strokes.279–281 both cognition and activities of daily living.286
In NOMAS, 210 of 3298 participants had an Inflammatory biomarkers (CRP, interleukin 6)
ischemic stroke during follow-up and had func- were associated with poststroke cognitive decline
tional assessments using the Barthel index before among males, and frailty was associated with
and after stroke.281 Among those with Medicaid decline in activities of daily living among females.
or no insurance, in a fully adjusted model, the • In data from 2011, 19% of Medicare patients
slope of functional decline increased after stroke were discharged to inpatient rehabilitation facili-
compared with before stroke (P=0.04), with ties, 25% were discharged to skilled nursing facil-
a decline of 0.58 Barthel index points per year ities, and 12% received home health care.287
before stroke (P=0.02) and 1.94 Barthel index • The 30-day readmission rate for Medicare fee-for-
points after stroke (P=0.001). There was no service beneficiaries with ischemic stroke in 2006
effect among those with private insurance or was 14.4%.288
Medicare. • The 30-day hospital readmission rate after dis-
• In the REGARDS prospective cohort, 515 of 23 572 charge from post-acute rehabilitation for stroke
participants ≥45 years of age without baseline was 12.7% among fee-for-service Medicare
cognitive impairment underwent repeated cogni- patients. The mean rehabilitation length of stay
tive testing.282 Incident stroke was associated with for stroke was 14.6 days.289
a short-term decline in cognitive function as well • After stroke, females often have greater disability
as accelerated and persistent cognitive decline than males. For example, an analysis of commu-
over 6 years. Participants with stroke had faster nity-living adults (>65 years of age) found that
Downloaded from http://ahajournals.org by on February 7, 2019

declines in global cognition and executive func- females were half as likely to be independent in
tion, but not in new learning and verbal memory, activities of daily living after stroke, even after
compared with prestroke slopes, in contrast to controlling for age, race, education, and marital
those without stroke. The rate of incident cog- status.290
nitive impairment also increased compared with • A meta-analysis of >25 studies examining sex dif-
the prestroke rate (OR, 1.23 per year [95% CI, ferences in long-term outcomes among stroke
1.10–1.38]). survivors found that females had worse func-
• In a meta-analysis of 14 longitudinal studies tional recovery and greater long-term disability
with at least 2 assessments of cognitive function and handicap. However, confidence in these con-
after stroke, there was a trend toward significant clusions was limited by the quality of the stud-
deterioration in cognition in stroke survivors in 8 ies and variability in the statistical approach to
studies, although cognitive stability was found confounding.291
in 3 studies and improvement in 3 studies.283 • A national study of inpatient rehabilitation after
Follow-up time tended to be shorter in studies first stroke found that blacks were younger, had
without evidence of decline. a higher proportion of hemorrhagic stroke, and
• Stroke also appears to accelerate natural age- were more disabled on admission. Compared
related functional decline. In the CHS, 382 of with NH whites, blacks and Hispanics also had
5888 participants (6.5%) had ischemic stroke a poorer functional status at discharge but were
during follow-up with ≥1 disability assessments more likely to be discharged to home rather than
afterwards. The annual increase in disability to another institution, even after adjustment for
before stroke (0.06 points on the Barthel index age and stroke subtype. After adjustment for
per year [95% CI, 0.002–0.12]) more than tripled the same covariates, compared with NH whites,
after stroke (0.15 additional points per year [95% blacks also had less improvement in functional
CI, 0.004–0.30]). Notably, the annual increase status per inpatient day.292
in disability before MI (0.04 points per year) did • Blacks were less likely to report independence in
not change significantly after MI (0.02 additional activities of daily living and instrumental activities
points per year [95% CI, −0.07 to 0.11]).284 of daily living than whites 1 year after stroke after

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e243

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

controlling for stroke severity and comparable • Diagnostic delays are more common in isch-
CLINICAL STATEMENTS

rehabilitation use.293 emic than hemorrhagic stroke in children, with a

AND GUIDELINES

• In a study of 90-day poststroke outcomes among median time from symptom onset to diagnostic
ischemic stroke patients in the BASIC Project, neuroimaging of 3 hours for hemorrhagic and 24
Mexican Americans scored worse on neurologi- hours for ischemic stroke in a population-based
cal, functional, and cognitive outcomes than NH study from the south of England.300
whites after multivariable adjustment.294 • The most common cause of arterial ischemic
• Hospital characteristics also predict functional stroke in children is a cerebral arteriopathy, found
outcomes after stroke. In an analysis of the AVAIL in more than half of all cases.301,302 Childhood
study, which included 2083 ischemic stroke arteriopathies are heterogeneous and can be dif-
patients enrolled from 82 US hospitals participat- ficult to distinguish from a partially thrombosed
ing in GWTG–Stroke, patients treated at teaching artery in the setting of a cardioembolic stroke;
hospitals (OR, 0.72 [95% CI, 0.54–0.96]) and cer- incorporation of clinical data and serial vascular
tified primary stroke centers (OR, 0.69 [95% CI, imaging is important for diagnosis.303
0.53–0.91]) had lower rates of 3-month death or • In a retrospective population-based study in
dependence.295 northern California, 7% of childhood ischemic
• In a survey among 391 stroke survivors, the vast strokes and 2% of childhood hemorrhagic strokes
majority (87%) reported unmet needs in at least 1 were attributable to congenital heart defects.
of 5 domains (activities and participation, environ- Congenital heart defects increased a child’s risk
mental factors, body functions, post-acute care, of stroke 19-fold (OR, 19 [95% CI, 4.2–83]). The
and secondary prevention).296 The greatest area of majority of children with stroke related to congen-
unmet need was in secondary prevention (71% ital heart defects were outpatients at the time of
of respondents). Older age, greater functional the stroke.304 In a single-center Australian study,
ability, and reporting that the general practitio- infants with cyanotic congenital heart defects
ner was the most important health professional undergoing palliative surgery were the highest-
providing care were associated with fewer unmet risk group to be affected by arterial ischemic
needs, and depression and receipt of community stroke during the periprocedural period; stroke
services after stroke were associated with more occurred in 22 per 2256 cardiac surgeries (1%).305
unmet needs. • In another study of the northern Californian pop-
Downloaded from http://ahajournals.org by on February 7, 2019

• Stroke also takes its toll on caregivers. In a ulation, adolescents with migraine had a 3-fold
meta-analysis of 12 studies that included 1756 increased odds of ischemic stroke compared with
caregivers, the pooled prevalence of depressive those without migraine (OR, 3.4 [95% CI, 1.2–
symptoms among caregivers was 40% (95% CI, 9.5]); younger children with migraine had no sig-
30%–51%). Symptoms of anxiety were present in nificant difference in stroke risk.306
21% (95% CI, 12%–36%).297 • In a post hoc analysis, head or neck trauma in the
prior week was a strong risk factor for childhood
arterial ischemic stroke (adjusted OR, 36 [95% CI,
Stroke in Children 5–281]), present in 10% of cases.307
• On the basis of pathogenic differences, pediatric • Exposure to minor infection in the prior month
strokes are typically classified as either perina- was also associated with stroke and was present
tal (occurring at ≤28 days of life and including in one-third of cases (adjusted OR, 3.9 [95% CI,
in utero strokes) or (later) childhood. Presumed 2.0–7.4]).307 The effect of infection on pediatric
perinatal strokes are diagnosed in children with stroke risk is short-lived, lasting for days; 80% of
no symptoms in the newborn period presenting infections preceding childhood stroke are respira-
with hemiparesis or other neurological symp- tory.308 A prospective study of 326 children with
toms later in infancy. arterial stroke revealed that serologic evidence
• The prevalence of perinatal strokes is 29 per of acute herpesvirus infection doubled the odds
100 000 live births, or 1 per 3500 live births in of childhood arterial ischemic stroke, even after
the 1997 to 2003 Kaiser Permanente of Northern adjustment for age, race, and SES (OR, 2.2 [95%
California population.298 CI, 1.2–4.0]; P=0.007).309 Among 187 cases with
• A history of infertility, preeclampsia, prolonged acute and convalescent blood samples, 85 (45%)
rupture of membranes, and chorioamnionitis showed evidence of acute herpesvirus infection;
are independent maternal risk factors for peri- herpes simplex virus 1 was found most often.
natal arterial ischemic stroke.263 However, mater- Most infections were asymptomatic.
nal health and pregnancies are normal in most • Thrombophilias (genetic and acquired) are risk
cases.299 factors for childhood stroke, with summary ORs

e244 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

ranging from 1.6 to 8.8 in a meta-analysis.310 In part of a multicenter study with a median follow-

CLINICAL STATEMENTS
contrast, a population-based, controlled study sug- up of 2 years, the cumulative stroke recurrence

AND GUIDELINES
gested a minimal association between perinatal rate was 6.8% (95% CI, 4.6%–10%) at 1 month
stroke and thrombophilia,311 and therefore, routine and 12% (95% CI, 8.5%–15%) at 1 year.42 The
testing is not recommended in very young children. sole predictor of recurrence was the presence of
• In a prospective Swiss registry,312 atherosclerotic an arteriopathy, which increased the risk of recur-
risk factors were less common in children with rence 5-fold compared with an idiopathic acute
arterial ischemic stroke than in young adults; the ischemic stroke (HR, 5.0 [95% CI, 1.8–14]). In a
most common of these factors in children was retrospective cohort, with a cerebral arteriopathy,
hyperlipidemia (15%). However, an analysis of the 5-year recurrence risk was as high as 60%
the NIS suggests a low but rising prevalence of among children with abnormal arteries on vascu-
these factors among US adolescents and young lar imaging.325 The recurrence risk after perinatal
adults hospitalized for ischemic stroke (1995 ver- stroke, however, was negligible.325
sus 2008).313 • Among 59 long-term survivors of pediatric
• Compared with girls, US boys have a 25% brain aneurysms, 41% developed new or recur-
increased risk of ischemic stroke and a 34% rent aneurysm during a median follow-up of 34
increased risk of ICH, whereas a study in the years; of those, one-third developed multiple
United Kingdom found no sex difference in aneurysms.326
childhood ischemic stroke.314 Compared with • More than 25% of survivors of perinatal ischemic
white children, black children in both the United strokes develop delayed seizures within 3 years;
States and United Kingdom have a >2-fold risk those with larger strokes are at higher risk.327
of stroke.315 The increased risk among blacks is The cumulative risk of delayed seizures after later
not fully explained by the presence of sickle cell childhood stroke is 13% at 5 years and 30% at
disease, nor is the excess risk among boys fully 10 years.328 Children with acute seizures (within
explained by trauma.315 7 days of their stroke) have the highest risk for
• The excess ischemic stroke mortality in US black delayed seizures, >70% by 5 years after the
children compared with white children has dimin- stroke.329 In survivors of ICH in childhood, 13%
ished since 1998 when the STOP trial was pub- developed delayed seizures and epilepsy within 2
lished, which established a method for primary years.330 Elevated intracranial pressure requiring
Downloaded from http://ahajournals.org by on February 7, 2019

stroke prevention in children with sickle cell short-term intervention at the time of acute ICH is
disease.316 a risk factor for delayed seizures and epilepsy.
• Among young adult survivors of childhood stroke, • Pediatric stroke teams and stroke centers331 are
37% had a normal modified Rankin score, 42% developing worldwide. In a study of 124 children
had mild deficits, 8% had moderate deficits, and presenting to a children’s hospital ED with stroke
15% had severe deficits.317 Concomitant involve- symptoms where a “stroke alert” was paged,
ment of the basal ganglia, cerebral cortex, and 24% had a final diagnosis of stroke, 2% were
posterior limb of the internal capsule predicts a TIAs, and 14% were other neurological emer-
persistent hemiparesis.318 gencies, which underscores the need for prompt
• Survivors of childhood arterial ischemic stroke evaluation of children with “brain attacks.”332
have, on average, low-normal cognitive per- Implementation of a pediatric stroke clinical path-
formance,319,320 with poorest performance in way improved time to MRI from 17 hours to 4
visual-constructive skills, short-term memory, and hours at 1 center.333
processing speed. Younger age at stroke and • In a study of 111 pediatric stroke cases admit-
seizures, but not laterality of stroke (left versus ted to a single US children’s hospital, the median
right), predict worse cognitive outcome.320 1-year direct cost of a childhood stroke (inpatient
• Compared with referent children with asthma, and outpatient) was ≈$50 000, with a maximum
childhood stroke survivors have greater impair- approaching $1 000 000. More severe neurologi-
ments in adaptive behaviors, social adjustment, cal impairment after a childhood stroke correlated
and social participation, even if their IQ is nor- with higher direct costs of a stroke at 1 year and
mal.321 Severity of disability after perinatal stroke poorer quality of life in all domains.334
correlates with maternal psychosocial outcomes • A prospective study at 4 centers in the United
such as depression and quality of life.322 States and Canada found that the median
• Despite current treatment, at least 1 of 10 chil- 1-year out-of-pocket cost incurred by the fam-
dren with ischemic or hemorrhagic stroke will ily of a child with a stroke was $4354 (maximum
have a recurrence within 5 years.323,324 Of 355 $38 666), which exceeded the median American
children with stroke followed up prospectively as household cash savings of $3650 at the time of

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e245

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

the study and represented 6.8% of the family’s per 100 000 person-years in the period 1995 to
CLINICAL STATEMENTS

annual income.335 1999 to 23.6 strokes per 100 000 person-years

AND GUIDELINES

from 2010 to 2014 (rate ratio, 2.47 [95% CI,

2.07–2.96; P<0.0001).337 Rates of stroke in
Stroke in the Young those aged 40 to 44, 45 to 49, and 50 to 54
• Approximately 10% of all strokes occur in indi- years also increased significantly. Strokes rates in
viduals 18 to 50 years of age.336 those >55 years of age decreased during these
• In the NIS, hospitalizations for acute ischemic time periods.
stroke increased significantly for both males • Vascular risk factors are common among stroke
and females and for certain racial/ethnic groups patients aged 20 to 54 years. During 2005, in
among younger adults, aged 18 to 54 years.6 the biracial GCNKSS, hypertension prevalence
From 1995 to 2011 through 2012, hospitaliza- was estimated at 52%, hyperlipidemia at 18%,
tion rates almost doubled for males aged 18 to DM at 20%, CHD at 12%, and current smoking
34 and 35 to 44 years, with a 41.5% increase at 46% among stroke patients 20 to 54 years of
among males aged 35 to 44 years from 2003 age.208
to 2004 through 2011 to 2012. Hospitalization • In the FUTURE study, the 30-day case fatality rate
rates for ICH and SAH remained stable, how- among stroke patients 18 to 50 years of age was
ever, with the exception of declines among 4.5%. One-year mortality among 30-day survi-
males and NH black patients aged 45 to 54 vors was 1.2% (95% CI, 0.0%–2.5%) for TIA,
years with SAH. 2.4% (95% CI, 1.2%–3.7%) for ischemic stroke,
• In the NIS, the prevalence of stroke risk factors also and 2.9% (95% CI, 0.0%–6.8%) for ICH.338
increased from 2003 to 2004 through 2011 to • In the FUTURE study, after a mean follow-up of
2012 among those hospitalized for stroke.6 These 13.9 years, 44.7% of young stroke patients had
increases in prevalence were seen among both poor functional outcome, defined as a modified
males and females aged 18 to 64 years. Absolute Rankin score >2. The strongest baseline predictors
increases in prevalence were seen for hyperten- of poor outcome were female sex (OR, 2.7 [95%
sion (range of absolute increase 4%–11%), lipid CI, 1.5–5.0]) and baseline NIHSS score (OR, 1.1
disorders (12%–21%), DM (4%–7%), tobacco [95% CI, 1.1–1.2] per point increase).339
use (5%–16%), and obesity (4%–9%).
Downloaded from http://ahajournals.org by on February 7, 2019

• The prevalence of having 3 to 5 risk factors

increased from 2003 to 2004 through 2011 to Stroke in Older Adults
2012, as well.6 Among males, the prevalence • Stroke patients >85 years of age make up 17% of
of 3 or more risk factors among stroke patients all stroke patients, and in this age group, stroke is
increased from 9% to 16% at 18 to 34 years, more prevalent in females than in males.340,341
19% to 35% at 35 to 44 years, 24% to 44% • Risk factors for stroke may be different in older
at 45 to 54 years, and 26% to 46% at 55 to 64 adults. In the population-based multiethnic
years. Among females, the prevalence of ≥3 risk NOMAS cohort, the risk effect of physical inac-
factors among stroke patients increased from 6% tivity was modified by age, and there was a sig-
to 13% at 18 to 34 years, 15% to 32% at 35 to nificant risk only in stroke patients >80 years of
44 years, 25% to 44% at 45 to 54 years, and 27% age.155 Also, the proportion of ischemic strokes
to 48% at 55 to 65 years (P for trend <0.001). attributable to AF increases with age and may
• In the 2005 GCNKSS study period, the sex- reach 40% or higher in very elderly stroke
adjusted incidence rate of first-ever stroke was patients.342
48 per 100 000 (95% CI, 42–53) among whites • Very elderly patients have a higher risk-adjusted
aged 20 to 54 years compared with 128 per mortality,343 have greater disability,343 have longer
100 000 (95% CI, 106–149) among blacks of the hospitalizations,344 receive less evidence-based
same age. Both races had a significant increase care,251,252 and are less likely to be discharged to
in the incidence rate from 1993 to 1994.208 their original place of residence.344,345
Similarly, other studies suggest an increase in the • According to analyses from the US NIS, over
incidence of stroke in young adults. According to the past decade, in-hospital mortality rates after
MIDAS 29, an administrative database contain- stroke have declined for every age and sex group
ing hospital records of all patients discharged except males aged >84 years.346
from nonfederal hospitals in New Jersey with a • Over the period from 2010 to 2050, the number
diagnosis of CVD or an invasive cardiovascular of incident strokes is expected to more than dou-
procedure, the rate of stroke more than doubled ble, with the majority of the increase among the
in patients aged 35 to 39 years, from 9.5 strokes elderly (aged ≥75 years) and minority groups.347

e246 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

• A Danish stroke registry reported on 39 cen- demographic and clinical factors.352 Hospitals

CLINICAL STATEMENTS
tenarians (87% females; age range, 100–107 certified between 2009 and 2013 also had

AND GUIDELINES
years) hospitalized with acute stroke. Although lower in-hospital and 30-day mortality than cen-
they had more favorable risk profiles than other ters certified before 2009.
age groups (lower prevalence of previous MI, • Implementation of Target Stroke, a national qual-
stroke, and DM), their strokes were more severe ity improvement initiative to improve the timeli-
and were associated with high 1-month mortal- ness of tPA administration, found that among
ity (38.5%).348 71 169 patients with acute ischemic stroke treated
with tPA at 1030 GWTG–Stroke participating hos-
pitals, participation in the program was associated
Organization of Stroke Care
with a decreased door-to-needle time, lower in-
• A study of 36 981 patients admitted with a pri- hospital mortality (OR, 0.89 [95% CI, 0.83–0.94])
mary diagnosis of ICH or SAH in New Jersey and intracranial hemorrhage (OR, 0.83 [95% CI,
between 1996 and 2012 found that patients 0.76–0.91]), and an increase in the percentage
admitted to a comprehensive stroke center were of patients discharged home (OR, 1.14 [95% CI,
more likely to have neurosurgical or endovascular 1.09–1.19]).353
treatments and had lower 90-day mortality (OR,
0.93 [95% CI, 0.89–0.97]) than patients admitted
to other hospitals.349 Hospital Discharges and Ambulatory
• A Cochrane review of 28 trials involving 5855 Care Visits
participants concluded that stroke patients who (See Table 14-1)
receive organized inpatient care in a stroke unit
had better outcomes, including decreased odds • From 2004 to 2014, the number of inpatient
of mortality (median of 1 year; OR, 0.81 [95% CI, discharges from short-stay hospitals with stroke
0.69–0.94]), death or institutionalized care (0.78 as the principal diagnosis remained stable, with
[95% CI, 0.68–0.89]), and death or dependency 897 000 and 888 000 (Table  14-1), respectively
(OR, 0.79 [95% CI, 0.68–0.90]), than patients (HCUP, NHLBI tabulation).
treated in an alternative form of inpatient care. • In 2014, the average length of stay for discharges
The findings were adjusted for patient age, sex, with stroke as the principal diagnosis was 4.7
Downloaded from http://ahajournals.org by on February 7, 2019

initial stroke severity, and stroke type.350 days (HCUP, NHLBI tabulation).
• A GWTG–Stroke study found differences in • In 2015, there were 664 000 ED visits with
the quality measures and in-hospital outcomes stroke as the principal diagnosis, and in 2011,
among hospitals that received primary stroke there were 209 000 outpatient visits with stroke
center certification, depending on the differ- as the first-listed diagnosis (NHAMCS, unpub-
ent certification bodies (Joint Commission, lished NHLBI tabulation). In 2015, physician
Healthcare Facilities Accreditation Program, Det office visits for a first-listed diagnosis of stroke
Norske Veritas, or state-based agencies).351 State totaled 2 506 000 (NAMCS, unpublished NHLBI
agency–certified hospitals had lower intravenous tabulation).
tPA utilization rates (OR, 0.76 [95% CI, 0.68– • In 2014, males and females accounted for
0.86]) and higher risk-adjusted in-hospital mor- roughly the same number of inpatient hospital
tality rates (OR, 1.23 [95% CI, 1.07–1.41]) than stays for stroke in the 18- to 44-year-old and 65-
Joint Commission–certified centers; Healthcare to 84-year-old age groups. Among people 45 to
Facilities Accreditation Program–accredited hos- 64 years of age, 55.6% of stroke patients were
pitals were less likely to achieve door-to-needle males. Among those ≥85 years of age, females
times within 60 minutes (OR, 0.49 [95% CI, constituted 66.0% of all stroke patients (HCUP,
0.31–0.77]) but had lower mortality rates (OR, NHLBI tabulation).
0.66 [95% CI, 0.47–0.92]). • Age-specific acute ischemic stroke hospitaliza-
• In analyses of 1 165 960 Medicare fee-for-ser- tion rates from 2000 to 2010 decreased for
vice beneficiaries hospitalized between 2009 individuals aged 65 to 84 years (−28.5%) and
and 2013 for ischemic stroke, patients treated ≥85 years (−22.1%) but increased for individuals
at primary stroke centers certified between aged 25 to 44 years (43.8%) and 45 to 64 years
2009 and 2013 had lower in-hospital (OR, 0.89 (4.7%). Age-adjusted acute ischemic stroke hos-
[95% CI, 0.84–0.94]), 30-day (HR, 0.90 [95% pitalization rates were lower in females, and
CI, 0.89–0.91]), and 1-year (HR, 0.90 [95% females had a greater rate of decrease from
CI, 0.89–0.91]) mortality than those treated 2000 to 2010 than males (−22% versus −17.8%,
at noncertified hospitals after adjustment for respectively).354

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e247

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

• An analysis of the 2011 to 2012 NIS for acute isch- thrombolysis.366 Retrospective analyses of patient
CLINICAL STATEMENTS

emic stroke found that after risk adjustment, all databases have found similar results.367
AND GUIDELINES

racial/ethnic minorities except Native Americans • Within a large telestroke network, of 234 patients
had a significantly higher likelihood of length of who met the inclusion criteria, 51% were trans-
stay ≥4 days than whites.355 ferred for mechanical thrombectomy by ambu-
lance and 49% by helicopter; 27% underwent
Operations and Procedures thrombectomy. The median actual transfer time
was 132 minutes (IQR, 103–165 minutes). Longer
(See Chart 14-10)
transfer time was associated with lower rates of
• In 2014, an estimated 86 000 inpatient endarter- thrombectomy, and transfer at night rather than
ectomy procedures were performed in the United during the day was associated with significantly
States. Carotid endarterectomy is the most fre- longer delay. Metrics and protocols for more effi-
quently performed surgical procedure to prevent cient transfer, especially at night, could shorten
stroke (HCUP, NHLBI tabulation).
transfer times.368
• Although rates of carotid endarterectomy
decreased between 1997 and 2014 (Chart 14-10),
the use of carotid stenting increased dramatically Cost
from 2004 to 2014 (HCUP, NHLBI tabulation). (See Table 14-1)
• In-hospital mortality for carotid endarterectomy
decreased steadily from 1993 to 2014 (HCUP, • In 2014 to 2015 (average annual):
NHLBI tabulation). — The direct and indirect cost of stroke was
• In the Medicare population, in-hospital stroke $45.5 billion (MEPS, NHLBI tabulation;
rate and mortality are similar for carotid endarter- Table 14-1).
ectomy and carotid stenting.356,357 — The estimated direct medical cost of stroke
• Similarly, a recent study from the NIS database was $28.0 billion. This includes hospital
demonstrated significant improvement in the in- outpatient or office-based provider visits,
hospital outcomes associated with carotid artery hospital inpatient stays, ED visits, prescribed
stenting over the past decade.358 medicines, and home health care.369
Downloaded from http://ahajournals.org by on February 7, 2019

• In the Medicare population, 30-day readmission — The mean expense per patient for direct care
rates and long-term risk of adverse clinical out- for any type of service (including hospital
comes associated with carotid artery stenting inpatient stays, outpatient and office-based
were similar to those for carotid endarterectomy visits, ED visits, prescribed medicines, and
after adjustment for patient- and provider-level home health care) in the United States was
factors.356,357,359,360 estimated at $7902.370
• Evidence on comparative costs of carotid endar- • Between 2015 and 2035, total direct medical
terectomy and stenting are mixed; whereas some stroke-related costs are projected to more than
studies found carotid stenting to be associated double, from $36.7 billion to $94.3 billion, with
with significantly higher costs than carotid end-
much of the projected increase in costs arising
arterectomy,361 particularly among asymptomatic
from those ≥80 years of age.371
patients,362 and that they might be less cost-effec-
• The total cost of stroke in 2035 (in 2015 dollars)
tive in general,363 CREST found that the overall
is projected to be $81.1 billion for NH whites,
cost of carotid stenting was not different from
$32.2 billion for NH blacks, and $16.0 billion for
that of carotid endarterectomy (US $15 055 ver-
sus US $14 816).364 Hispanics.371
• The percentage of patients undergoing carotid • During 2001 to 2005, the average cost for out-
endarterectomy within 2 weeks of the onset of patient stroke rehabilitation services and medica-
stroke increased from 13% in 2007 to 47% in tions the first year after inpatient rehabilitation
2010.365 discharge was $11 145. The corresponding aver-
• Meta-analyses of 5 trials that investigated the effi- age yearly cost of medication was $3376, whereas
cacy of modern endovascular therapies for stroke the average cost of yearly rehabilitation service
(MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND-IA utilization was $7318.372
and REVASCAT) have provided strong evidence to • In adjusted models that controlled for relevant
support the use of thrombectomy initiated within covariates, the attributable 1-year cost of post-
6 hours of stroke onset, irrespective of patient stroke aphasia was estimated at $1703 in 2004
age, NIHSS score, or receipt of intravenous dollars.373

e248 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

Social Determinants — Countries in Eastern Europe, Central Asia,

CLINICAL STATEMENTS
and East Asia have the highest prevalence
• Adverse work conditions, including job loss and

AND GUIDELINES
rates of ischemic stroke (Chart 14-13).
unemployment, have been linked to stroke risk.
In a cohort of 21 902 Japanese males and 19 826 Incidence
females followed up for 19 years, job loss (change • In 2010, there were an estimated 11.6 million
in job status within the first 5 years of data col- incident ischemic strokes and 5.3 million incident
lection) was associated with a >50% increase in hemorrhagic strokes; 63% of ischemic strokes
incident stroke and a >2-fold increase in stroke and 80% of hemorrhagic strokes occurred in low-
mortality over follow-up.374 Long work hours have and middle-income countries.378
also been linked to stroke. Meta-analytic findings • Between 1990 and 2010378:
from 24 cohort studies from the United States, — Incidence of ischemic stroke was significantly
Europe, and Australia revealed a dose-response reduced by 13% (95% CI, 6%–18%) in high-
relationship between working longer than 40 income countries. No significant change was
hours per week and incident stroke.374a seen in low- or middle-income countries.
• In ARIC, having smaller social networks (ie, con- — Incidence of hemorrhagic stroke decreased
tact with fewer family members, friends, and by 19% (95% CI, 1%–15%) in high-income
neighbors) was linked to a 44% higher risk of countries. Rates increased by 22% (95% CI,
incident stroke over the 18.6-year follow-up, even 5%–30%) in low- and middle-income coun-
after controlling for demographics and other rel- tries, with a 19% increase in those aged
evant risk factors.375 <75 years.
• Findings from MESA have documented linkages
Mortality
between other psychosocial factors, including • In 2016377:
depressive symptoms, chronic stress, and hostil- — There were 5.5 million deaths attributable to
ity, and incident stroke, with participants in the cerebrovascular disease worldwide.
highest- versus lowest-scoring categories having — The absolute number of cerebrovascular
a 1.5- to >2-fold increased risk of stroke over a disease deaths worldwide increased 28.2%
median follow-up of 8.5 years.376 between 1990 and 2016; however, the age-
Downloaded from http://ahajournals.org by on February 7, 2019

standardized death rate decreased 36.2%.

Global Burden of Stroke — The absolute number of cerebrovascular
(See Charts 14-11 through 14-16) disease deaths worldwide increased 5.1%
between 2006 and 2016; however, the
Prevalence age-standardized death rate for the 10-year
• In 2016,377 period decreased 21.0%.
— Global prevalence of cerebrovascular disease — Globally, a total of 2.7 million individuals
was 80.1 million people, whereas that of died of ischemic stroke, and 2.8 million died
ischemic stroke was 67.6 million and that of of hemorrhagic stroke.
hemorrhagic stroke was 15.3 million. • The GBD 2016 Study used statistical models and
— Globally, there was a 2.7% increase in isch- data on incidence, prevalence, case fatality, excess
emic stroke prevalence from 2006 to 2016 mortality, and cause-specific mortality to estimate
and a 0.1% decrease from 1990 to 2016. disease burden for 315 diseases and injuries in
— Globally, there was a 1.7% decrease in hem- 195 countries and territories.377
orrhagic stroke prevalence from 2006 to — Eastern Europe, East Asia, and parts of
2016 and a 6.8% decrease from 1990 to Southeast Asia, Central Asia, and sub-Saha-
2016. ran Africa have the highest rates of stroke
• The GBD 2016 Study used statistical models and mortality (Chart 14-14).
data on incidence, prevalence, case fatality, excess — Hemorrhagic stroke mortality is highest in
mortality, and cause-specific mortality to estimate East Asia, the Pacific Islands, Southeast Asia,
disease burden for 315 diseases and injuries in Central Asia, and parts of sub-Saharan Africa
195 countries and territories.377 (Chart 14-15).
— Age-standardized prevalence rates of stroke — Countries in Eastern Europe and central
are higher in Eastern Europe and East Asia East Asia have among the highest mortal-
(Chart 14-11). ity rates attributable to ischemic stroke
— The prevalence of hemorrhagic stroke is high (Chart 14-16).
in Eastern Europe, Central Asia, and East • In 2010, 39.4 million DALYs were lost because
Asia (Chart 14-12). of ischemic stroke and 62.8 million because of

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e249

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

hemorrhagic stroke (64% and 86%, respectively, • Between 1990 and 2010, ischemic stroke mor-
CLINICAL STATEMENTS

in low- and middle-income countries).378 tality decreased 37% in high-income countries

AND GUIDELINES

• In 2010, the mean age of stroke-related death and 14% in low- and middle-income countries.
in high-income countries was 80.4 years com- Hemorrhagic stroke mortality decreased 38% in
pared with 72.1 years in low- and middle-income high-income countries and 23% in low- and mid-
countries.379 dle-income countries.378

Table 14-1. Stroke

Prevalence, 2013–2016: New and Recurrent Mortality, Hospital Discharges,

Population Group Age ≥20 y Attacks, All Ages 2016: All Ages* 2014: All Ages Cost, 2014–2015
Both sexes 7 000 000 (2.5%) 795 000 142 142 888 000 $45.5 Billion
Males 3 200 000 (2.5%) 370 000 (46.5%)† 59 355 (41.8%)† 434 000 …
Females 3 800 000 (2.6%) 425 000 (53.5%)† 82 787 (58.2%)† 454 000 …
NH white males 2.4% 325 000‡ 43 713 … …
NH white females 2.5% 365 000‡ 63 778 … …
NH black males 3.1% 45 000‡ 8115 … …
NH black females 3.8% 60 000‡ 10 074 … …
Hispanic males 2.0% … 4798 … …
Hispanic females 2.2% … 5485 … …
NH Asian males 1.1% … 2268§ … …
NH Asian females 1.6% … 2949§ … …
NH American Indian or … … 632 … …
Alaska Native

Ellipses (…) indicate data not available; and NH, non-Hispanic.

*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of
Downloaded from http://ahajournals.org by on February 7, 2019

inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have
shown underreporting on death certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as
undercounts of these groups in censuses.
†These percentages represent the portion of total stroke incidence or mortality that applies to males vs females.
‡Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
§Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2013 to 2016 and National Heart, Lung, and Blood Institute (NHLBI).
Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2016 US
population. Incidence: Greater Cincinnati/Northern Kentucky Stroke Study/National Institutes of Neurological Disorders and Stroke data for 1999
provided on August 1, 2007. US estimates compiled by NHLBI. See also Kissela et al.380 Data include children. Mortality: Centers for Disease Control
and Prevention/National Center for Health Statistics, 2016 Mortality Multiple Cause-of-Death–United States. These data represent underlying cause
of death only. Mortality for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, Agency for Healthcare
Research and Quality. Data include those inpatients discharged alive, dead, or status unknown. Cost: NHLBI. Data include estimated direct and indirect
costs for 2014 to 2015 (average annual).

e250 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-1. Prevalence of stroke by age and sex (NHANES, 2013–2016).
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-2. Annual age-adjusted incidence of first-ever stroke by race.

Hospital plus out-of-hospital ascertainment, 1993 to 1994, 1999, and 2005.
ICH indicates intracerebral hemorrhage; and SAH, subarachnoid hemorrhage.
Data derived from Kleindorfer et al.18

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e251

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14
CLINICAL STATEMENTS
AND GUIDELINES

Chart 14-3. Age-adjusted death rates for stroke by sex and race/ethnicity, 2016.
Death rates for the American Indian or Alaska Native and Asian or Pacific Islander populations are known to be underestimated. Stroke includes International
Classification of Diseases, 10th Revision codes I60 through I69 (cerebrovascular disease). Mortality for NH Asians includes Pacific Islanders.
NH indicates non-Hispanic.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-4. Crude stroke mortality rates among young US adults (aged 25–64 years), 2006 to 2016.
Source: Centers for Disease Control and Prevention.47

e252 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-5. Crude stroke mortality rates among older US adults (aged ≥65 years), 2006 to 2016.
Source: Centers for Disease Control and Prevention.47
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-6. Stroke death rates, 2014 through 2016, all ages, by county.
Rates are spatially smoothed to enhance the stability of rates in counties with small populations. International Classification of Diseases, 10th Revision codes for
stroke: I60 through I69.
Data source: National Vital Statistics System and National Center for Health Statistics.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e253

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14
CLINICAL STATEMENTS
AND GUIDELINES

Chart 14-7. Probability of death within 1 year after first stroke.

Source: Pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Multi-Ethnic Study of
Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study of the National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-8. Probability of death within 5 years after first stroke.

Source: Pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Multi-Ethnic Study of
Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study of the National Heart, Lung, and Blood Institute.

e254 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-9. Probability of death with recurrent stroke in 5 years after first stroke.
Source: Pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Multi-Ethnic Study of
Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study of the National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-10. Trends in carotid endarterectomy and carotid stenting procedures (United States, 1993–2014).
Carotid endarterectomy: International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) 38.12 (all-listed); carotid stenting: ICD-9-CM 00.63
(all-listed).
Source: Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e255

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14
CLINICAL STATEMENTS
AND GUIDELINES

Chart 14-11. Age-standardized global prevalence rates of cerebrovascular disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-12. Age-standardized global prevalence rates of hemorrhagic stroke per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.

e256 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-13. Age-standardized global prevalence rates of ischemic stroke per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-14. Age-standardized global mortality rates of cerebrovascular disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e257

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14
CLINICAL STATEMENTS
AND GUIDELINES

Chart 14-15. Age-standardized global mortality rates of hemorrhagic stroke per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 14-16. Age-standardized global mortality rates of ischemic stroke per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.377 Printed with permission.
Copyright © 2017, University of Washington.

e258 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

REFERENCES 18. Kleindorfer DO, Khoury J, Moomaw CJ, Alwell K, Woo D, Flaherty ML,

CLINICAL STATEMENTS
Khatri P, Adeoye O, Ferioli S, Broderick JP, Kissela BM. Stroke incidence
1. 2016 BRFSS survey data and documentation. Centers for Disease

AND GUIDELINES
is decreasing in whites but not in blacks: a population-based estimate
Control and Prevention website. https://www.cdc.gov/brfss/annual_data/ of temporal trends in stroke incidence from the Greater Cincinnati/
annual_2016.html. Accessed March 13, 2018. Northern Kentucky Stroke Study. Stroke. 2010;41:1326–1331. doi:
2. Centers for Disease Control and Prevention. Prevalence of stroke: United 10.1161/STROKEAHA.109.575043
States, 2006–2010. MMWR Morb Mortal Wkly Rep. 2012;61:379–382. 19. Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, Wolf PA.
3. Howard VJ, McClure LA, Meschia JF, Pulley L, Orr SC, Friday GH. High
The lifetime risk of stroke: estimates from the Framingham Study. Stroke.
prevalence of stroke symptoms among persons without a diagnosis of
2006;37:345–350. doi: 10.1161/01.STR.0000199613.38911.b2
stroke or transient ischemic attack in a general population: the REasons
20. Hollander M, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A, Breteler
for Geographic And Racial Differences in Stroke (REGARDS) study. Arch
MM. Incidence, risk, and case fatality of first ever stroke in the elderly
Intern Med. 2006;166:1952–1958. doi: 10.1001/archinte.166.18.1952
population: the Rotterdam Study. J Neurol Neurosurg Psychiatry.
4. Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC,
2003;74:317–321.
Khavjou OA, Lackland DT, Lichtman JH, Mohl S, Sacco RL, Saver JL,
21. Lewsey JD, Gillies M, Jhund PS, Chalmers JW, Redpath A, Briggs A,
Trogdon JG; on behalf of the American Heart Association Advocacy
Walters M, Langhorne P, Capewell S, McMurray JJ, Macintyre K. Sex
Coordinating Committee and Stroke Council. Forecasting the future
differences in incidence, mortality, and survival in individuals with
of stroke in the United States: a policy statement from the American
stroke in Scotland, 1986 to 2005. Stroke. 2009;40:1038–1043. doi:
Heart Association and American Stroke Association [published correc-
10.1161/STROKEAHA.108.542787
tion appears in Stroke. 2015;46:e179]. Stroke. 2013;44:2361–2375. doi:
22. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE,
10.1161/STR.0b031829734f2
Redgrave JN, Bull LM, Welch SJ, Cuthbertson FC, Binney LE, Gutnikov SA,
5. Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G,
Anslow P, Banning AP, Mant D, Mehta Z; Oxford Vascular Study. Population-
Khatiwoda A, Lisabeth L. Sex differences in stroke: epidemiology, clinical
based study of event-rate, incidence, case fatality, and mortality for all
presentation, medical care, and outcomes. Lancet Neurol. 2008;7:915–
acute vascular events in all arterial territories (Oxford Vascular Study).
926. doi: 10.1016/S1474-4422(08)70193-5
Lancet. 2005;366:1773–1783. doi: 10.1016/S0140-6736(05)67702-1
6. George MG, Tong X, Bowman BA. Prevalence of cardiovascular risk fac-
23. Sealy-Jefferson S, Wing JJ, Sánchez BN, Brown DL, Meurer WJ,
tors and strokes in younger adults. JAMA Neurol. 2017;74:695–703. doi:
Smith MA, Morgenstern LB, Lisabeth LD. Age- and ethnic-specific
10.1001/jamaneurol.2017.0020
sex differences in stroke risk. Gend Med. 2012;9:121–128. doi:
7. Koton S, Schneider AL, Rosamond WD, Shahar E, Sang Y, Gottesman RF,
10.1016/j.genm.2012.02.002
Coresh J. Stroke incidence and mortality trends in US communities, 1987
24. Vega T, Zurriaga O, Ramos JM, Gil M, Alamo R, Lozano JE, López A,
to 2011. JAMA. 2014;312:259–268. doi: 10.1001/jama.2014.7692
Miralles MT, Vaca P, Alvarez Mdel M; Group of Research for the RECENT
8. Morgenstern LB, Smith MA, Sánchez BN, Brown DL, Zahuranec DB,
Project. Stroke in Spain: epidemiologic incidence and patterns; a health
Garcia N, Kerber KA, Skolarus LE, Meurer WJ, Burke JF, Adelman EE,
Baek J, Lisabeth LD. Persistent ischemic stroke disparities despite declin- sentinel network study. J Stroke Cerebrovasc Dis. 2009;18:11–16. doi:
ing incidence in Mexican Americans. Ann Neurol. 2013;74:778–785. doi: 10.1016/j.jstrokecerebrovasdis.2008.06.010
10.1002/ana.23972 25. Madsen TE, Khoury J, Alwell K, Moomaw CJ, Rademacher E, Flaherty ML,
9. Zahuranec DB, Lisabeth LD, Sánchez BN, Smith MA, Brown Woo D, Mackey J, De Los Rios La Rosa F, Martini S, Ferioli S, Adeoye O,
DL, Garcia NM, Skolarus LE, Meurer WJ, Burke JF, Adelman EE, Khatri P, Broderick JP, Kissela BM, Kleindorfer D. Sex-specific stroke inci-
Morgenstern LB. Intracerebral hemorrhage mortality is not chang- dence over time in the Greater Cincinnati/Northern Kentucky Stroke Study.
Neurology. 2017;89:990–996. doi: 10.1212/WNL.0000000000004325
Downloaded from http://ahajournals.org by on February 7, 2019

ing despite declining incidence. Neurology. 2014;82:2180–2186. doi:

10.1212/WNL.0000000000000519 26. Johnston SC, Fayad PB, Gorelick PB, Hanley DF, Shwayder P, van Husen
10. Carandang R, Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Kannel WB, D, Weiskopf T. Prevalence and knowledge of transient ischemic attack
Wolf PA. Trends in incidence, lifetime risk, severity, and 30-day mortal- among US adults. Neurology. 2003;60:1429–1434.
ity of stroke over the past 50 years. JAMA. 2006;296:2939–2946. doi: 27. Jiang B, Sun H, Ru X, Sun D, Chen Z, Liu H, Li Y, Zhang M, Wang L,
10.1001/jama.296.24.2939 Wang L, Wu S, Wang W. Prevalence, incidence, prognosis, early stroke
11. Vangen-Lønne AM, Wilsgaard T, Johnsen SH, Løchen ML, Njølstad I, risk, and stroke-related prognostic factors of definite or probable tran-
Mathiesen EB. Declining incidence of ischemic stroke: what is the impact sient ischemic attacks in China, 2013. Front Neurol. 2017;8:309. doi:
of changing risk factors? The Tromsø study 1995 to 2012. Stroke. 10.3389/fneur.2017.00309
2017;48:544–550. doi: 10.1161/STROKEAHA.116.014377 28. Béjot Y, Brenière C, Graber M, Garnier L, Durier J, Blanc-Labarre C, Delpont
12. Howard VJ, Kleindorfer DO, Judd SE, McClure LA, Safford MM, Rhodes B, Giroud M. Contemporary epidemiology of transient ischemic attack in
JD, Cushman M, Moy CS, Soliman EZ, Kissela BM, Howard G. Disparities Dijon, France (2013-2015). Neuroepidemiology. 2017;49:135–141. doi:
in stroke incidence contributing to disparities in stroke mortality. Ann 10.1159/000484638
Neurol. 2011;69:619–627. doi: 10.1002/ana.22385 29. Kleindorfer D, Panagos P, Pancioli A, Khoury J, Kissela B, Woo D,
13. Kleindorfer D, Broderick J, Khoury J, Flaherty M, Woo D, Alwell K, Moomaw Schneider A, Alwell K, Jauch E, Miller R, Moomaw C, Shukla R,
CJ, Schneider A, Miller R, Shukla R, Kissela B. The unchanging incidence Broderick JP. Incidence and short-term prognosis of transient ischemic
and case-fatality of stroke in the 1990s: a population-based study. Stroke. attack in a population-based study. Stroke. 2005;36:720–723. doi:
2006;37:2473–2478. doi: 10.1161/01.STR.0000242766.65550.92 10.1161/01.STR.0000158917.59233.b7
14. Morgenstern LB, Smith MA, Lisabeth LD, Risser JM, Uchino K, Garcia N, 30. Hankey GJ. Impact of treatment of people with transient ischaemic attacks
Longwell PJ, McFarling DA, Akuwumi O, Al-Wabil A, Al-Senani F, Brown on stroke incidence and public health. Cerebrovasc Dis. 1996;6(suppl
DL, Moyé LA. Excess stroke in Mexican Americans compared with non- 1):26–33.
Hispanic whites: the Brain Attack Surveillance in Corpus Christi Project. 31. Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after
Am J Epidemiol. 2004;160:376–383. doi: 10.1093/aje/kwh225 emergency department diagnosis of TIA. JAMA. 2000;284:2901–2906.
15. White H, Boden-Albala B, Wang C, Elkind MS, Rundek T, Wright CB, 32. Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA.
Sacco RL. Ischemic stroke subtype incidence among whites, blacks, and Early risk of stroke after transient ischemic attack: a systematic review
Hispanics: the Northern Manhattan Study. Circulation. 2005;111:1327– and meta-analysis. Arch Intern Med. 2007;167:2417–2422. doi:
1331. doi: 10.1161/01.CIR.0000157736.19739.D0 10.1001/archinte.167.22.2417
16. Zhang Y, Galloway JM, Welty TK, Wiebers DO, Whisnant JP, Devereux 33. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack:
RB, Kizer JR, Howard BV, Cowan LD, Yeh J, Howard WJ, Wang W, Best a systematic review and meta-analysis. Lancet Neurol. 2007;6:1063–
L, Lee ET. Incidence and risk factors for stroke in American Indians: 1072. doi: 10.1016/S1474-4422(07)70274-0
the Strong Heart Study. Circulation. 2008;118:1577–1584. doi: 34. Clark TG, Murphy MF, Rothwell PM. Long term risks of stroke, myo-
10.1161/CIRCULATIONAHA.108.772285 cardial infarction, and vascular death in “low risk” patients with a
17. Howard G, Cushman M, Howard VJ, Kissela BM, Kleindorfer DO, Moy CS, non-recent transient ischaemic attack. J Neurol Neurosurg Psychiatry.
Switzer J, Woo D. Risk factors for intracerebral hemorrhage: the REasons 2003;74:577–580.
for Geographic and Racial Differences in Stroke (REGARDS) study [pub- 35. Luengo-Fernandez R, Paul NL, Gray AM, Pendlebury ST, Bull LM, Welch
lished correction appears in Stroke. 2013;44:e63]. Stroke. 2013;44:1282– SJ, Cuthbertson FC, Rothwell PM; on behalf of the Oxford Vascular Study.
1287. doi: 10.1161/STROKEAHA.111.000529 Population-based study of disability and institutionalization after transient

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e259

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

ischemic attack and stroke: 10-year results of the Oxford Vascular Study. 50. Gilsanz P, Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA.
CLINICAL STATEMENTS

Stroke. 2013;44:2854–2861. doi: 10.1161/STROKEAHA.113.001584 Association between birth in a high stroke mortality state, race,
AND GUIDELINES

36. Brazzelli M, Chappell FM, Miranda H, Shuler K, Dennis M, Sandercock and risk of dementia. JAMA Neurol. 2017;74:1056–1062. doi:
PA, Muir K, Wardlaw JM. Diffusion-weighted imaging and diagno- 10.1001/jamaneurol.2017.1553
sis of transient ischemic attack. Ann Neurol. 2014;75:67–76. doi: 51. Lackland DT. Impact of birth place and geographic location on risk dis-
10.1002/ana.24026 parities in cerebrovascular disease: implications for future research. JAMA
37. Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, Neurol. 2017;74:1043–1045. doi: 10.1001/jamaneurol.2017.1560
Hatsukami TS, Higashida RT, Johnston SC, Kidwell CS, Lutsep HL, Miller 52. Howard VJ, McClure LA, Glymour MM, Cunningham SA, Kleindorfer DO,
E, Sacco RL. Definition and evaluation of transient ischemic attack: a Crowe M, Wadley VG, Peace F, Howard G, Lackland DT. Effect of duration
scientific statement for healthcare professionals from the American and age at exposure to the Stroke Belt on incident stroke in adulthood.
Heart Association/American Stroke Association Stroke Council; Council Neurology. 2013;80:1655–1661. doi: 10.1212/WNL.0b013e3182904d59
on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular 53. Gillum RF, Kwagyan J, Obisesan TO. Ethnic and geographic varia-
Radiology and Intervention; Council on Cardiovascular Nursing; and tion in stroke mortality trends. Stroke. 2011;42:3294–3296. doi:
the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 10.1161/STROKEAHA.111.625343
2009;40:2276–2293. doi: 10.1161/STROKEAHA.108.192218 54. Schieb LJ, Ayala C, Valderrama AL, Veazie MA. Trends and dispari-
38. Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, ties in stroke mortality by region for American Indians and Alaska
Elkind MS, George MG, Hamdan AD, Higashida RT, Hoh BL, Janis LS, Natives. Am J Public Health. 2014;104 Suppl 3:S368–S376. doi:
Kase CS, Kleindorfer DO, Lee JM, Moseley ME, Peterson ED, Turan TN, 10.2105/AJPH.2013.301698
Valderrama AL, Vinters HV; on behalf of the American Heart Association 55. Pearson-Stuttard J, Guzman-Castillo M, Penalvo JL, Rehm CD, Afshin
Stroke Council, Council on Cardiovascular Surgery and Anesthesia; A, Danaei G, Kypridemos C, Gaziano T, Mozaffarian D, Capewell S,
Council on Cardiovascular Radiology and Intervention; Council on O’Flaherty M. Modeling future cardiovascular disease mortality in the
Cardiovascular and Stroke Nursing; Council on Epidemiology and United States: national trends and racial and ethnic disparities. Circulation.
Prevention; Council on Peripheral Vascular Disease; Council on Nutrition, 2016;133:967–978. doi: 10.1161/CIRCULATIONAHA.115.019904
Physical Activity and Metabolism. An updated definition of stroke for the 56. Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S,
21st century: a statement for healthcare professionals from the American Mensah GA, Norrving B, Shiue I, Ng M, Estep K, Cercy K, Murray CJL,
Heart Association/American Stroke Association. Stroke. 2013;44:2064– Forouzanfar MH; Global Burden of Diseases, Injuries and Risk Factors Study
2089. doi: 10.1161/STR.0b013e318296aeca 2013 and Stroke Experts Writing Group. Global burden of stroke and risk
39. Callaly E, Ni Chroinin D, Hannon N, Marnane M, Akijian L, Sheehan O, factors in 188 countries, during 1990-2013: a systematic analysis for the
Merwick A, Hayden D, Horgan G, Duggan J, Murphy S, O’Rourke K, Dolan Global Burden of Disease Study 2013. Lancet Neurol. 2016;15:913–924.
E, Williams D, Kyne L, Kelly PJ. Rates, predictors, and outcomes of early doi: 10.1016/S1474-4422(16)30073-4
and late recurrence after stroke: the North Dublin Population Stroke study. 57. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison
Stroke. 2016;47:244–246. doi: 10.1161/STROKEAHA.115.011248 Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW,
40. Fullerton HJ, Wintermark M, Hills NK, Dowling MM, Tan M, Rafay MF, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC,
Elkind MS, Barkovich AJ, deVeber GA; and the VIPS Investigators. Risk Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright
of recurrent arterial ischemic stroke in childhood: a prospective inter- JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/
national study. Stroke. 2016;47:53–59. doi: 10.1161/STROKEAHA. PCNA guideline for the prevention, detection, evaluation, and manage-
115.011173 ment of high blood pressure in adults: executive summary: a report of the
41. Mohan KM, Wolfe CD, Rudd AG, Heuschmann PU, Kolominsky-Rabas American College of Cardiology/American Heart Association Task Force
Downloaded from http://ahajournals.org by on February 7, 2019

PL, Grieve AP. Risk and cumulative risk of stroke recurrence: a sys- on Clinical Practice Guidelines. Hypertension. 2018;71:1269–1324. doi:
tematic review and meta-analysis. Stroke. 2011;42:1489–1494. doi: 10.1161/HYP.0000000000000066
10.1161/STROKEAHA.110.602615 58. Reboussin DM, Allen NB, Griswold ME, Guallar E, Hong Y, Lackland DT,
42. Pennlert J, Eriksson M, Carlberg B, Wiklund PG. Long-term risk and predic- Miller EPR 3rd, Polonsky T, Thompson-Paul AM, Vupputuri S. Systematic
tors of recurrent stroke beyond the acute phase. Stroke. 2014;45:1839– review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/
1841. doi: 10.1161/STROKEAHA.114.005060 ASPC/NMA/PCNA guideline for the prevention, detection, evalua-
43. Howard G, Kissela BM, Kleindorfer DO, McClure LA, Soliman EZ, Judd SE, tion, and management of high blood pressure in adults: a report of the
Rhodes JD, Cushman M, Moy CS, Sands KA, Howard VJ. Differences in American College of Cardiology/American Heart Association Task Force
the role of black race and stroke risk factors for first vs. recurrent stroke. on Clinical Practice Guidelines. Hypertension. 2018;71:e116–e135. doi:
Neurology. 2016;86:637–642. doi: 10.1212/WNL.0000000000002376 10.1161/HYP.0000000000000067
44. Jin P, Matos Diaz I, Stein L, Thaler A, Tuhrim S, Dhamoon MS. Intermediate 59. Weiss J, Freeman M, Low A, Fu R, Kerfoot A, Paynter R, Motu’apuaka M,
risk of cardiac events and recurrent stroke after stroke admission in young Kondo K, Kansagara D. Benefits and harms of intensive blood pressure
adults. Int J Stroke. 2017;13:576–584. doi: 10.1177/1747493017733929 treatment in adults aged 60 years or older: a systematic review and meta-
45. Boulanger M, Bejot Y, Rothwell PM, Touze E. Long-term risk of myocardial analysis. Ann Intern Med. 2017;166:419–429. doi: 10.7326/M16-1754
infarction compared to recurrent stroke after transient ischemic attack 60. Lackland DT, Carey RM, Conforto AB, Rosendorff C, Whelton PK, Gorelick
and ischemic stroke: systematic review and meta-analysis. J Am Heart PB. Implications of recent clinical trials and hypertension guidelines on
Assoc. 2018;7:e007267. doi: 10.1161/JAHA.117.007267 stroke and future cerebrovascular research. Stroke. 2018;49:772–779.
46. Lackland DT, Roccella EJ, Deutsch AF, Fornage M, George MG, Howard G, doi: 10.1161/STROKEAHA.117.019379
Kissela BM, Kittner SJ, Lichtman JH, Lisabeth LD, Schwamm LH, Smith EE, 61. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J,
Towfighi A; on behalf of the American Heart Association Stroke Council; Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention
Council on Cardiovascular and Stroke Nursing; Council on Quality of Care of cardiovascular disease and death: a systematic review and meta-analy-
and Outcomes Research; Council on Functional Genomics and Translational sis. Lancet. 2016;387:957–967. doi: 10.1016/S0140-6736(15)01225-8
Biology. Factors influencing the decline in stroke mortality: a statement 62. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering
from the American Heart Association/American Stroke Association. on outcome incidence in hypertension: 7. Effects of more vs. less intensive
Stroke. 2014;45:315–353. doi: 10.1161/01.str.0000437068.30550.cf blood pressure lowering and different achieved blood pressure levels -
47. Centers for Disease Control and Prevention, National Center for Health updated overview and meta-analyses of randomized trials. J Hypertens.
Statistics. Underlying cause of death, 1999-2016. CDC WONDER Online 2016;34:613–622. doi: 10.1097/HJH.0000000000000881
Database [database online]. Released January 2013. Atlanta, GA: Centers 63. Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, Woodward M,
for Disease Control and Prevention. https://wonder.cdc.gov/ucd-icd10. MacMahon S, Turnbull F, Hillis GS, Chalmers J, Mant J, Salam A, Rahimi K,
html. Accessed March 13, 2018. Perkovic V, Rodgers A. Effects of intensive blood pressure lowering on car-
48. Kochanek KD, Murphy SL, Xu JQ, Arias E. Mortality in the United States, diovascular and renal outcomes: updated systematic review and meta-anal-
2016. NCHS Data Brief No. 293. Hyattsville, MD: National Center for ysis. Lancet. 2016;387:435–443. doi: 10.1016/S0140-6736(15)00805-3
Health Statistics; December 2017. 64. Law M, Morris J, Wald N. Use of blood pressure lowering drugs in the pre-
49. Howard G, Evans GW, Pearce K, Howard VJ, Bell RA, Mayer EJ, Burke GL. vention of cardiovascular disease: meta-analysis of 147 randomized trials
Is the stroke belt disappearing? An analysis of racial, temporal, and age in the context of expectations from prospective epidemiological studies.
effects. Stroke. 1995;26:1153–1158. BMJ. 2009;338:b1665. doi: 10.1136/bmj.b1665

e260 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

65. Verdecchia P, Angeli F, Gentile G, Reboldi G. More versus less inten- 83. Fang HJ, Zhou YH, Tian YJ, Du HY, Sun YX, Zhong LY. Effects of inten-

CLINICAL STATEMENTS
sive blood pressure-lowering strategy: cumulative evidence and sive glucose lowering in treatment of type 2 diabetes mellitus on car-

AND GUIDELINES
trial sequential analysis. Hypertension. 2016;68:642–653. doi: diovascular outcomes: a meta-analysis of data from 58,160 patients
10.1161/HYPERTENSIONAHA.116.07608 in 13 randomized controlled trials. Int J Cardiol. 2016;218:50–58. doi:
66. Bangalore S, Toklu B, Gianos E, Schwartzbard A, Weintraub H, Ogedegbe 10.1016/j.ijcard.2016.04.163
G, Messerli FH. Optimal systolic blood pressure target after SPRINT: 84. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pres-
insights from a network meta-analysis of randomized trials. Am J Med. sure lowering in type 2 diabetes: a systematic review and meta-analysis.
2017;130:707–719.e8. doi: 10.1016/j.amjmed.2017.01.004 JAMA. 2015;313:603–615. doi: 10.1001/jama.2014.18574
67. Bundy JD, Li C, Stuchlik P, Bu X, Kelly TN, Mills KT, He H, Chen J, Whelton 85. Xie XX, Liu P, Wan FY, Lin SG, Zhong WL, Yuan ZK, Zou JJ, Liu LB. Blood
PK, He J. Systolic blood pressure reduction and risk of cardiovascular dis- pressure lowering and stroke events in type 2 diabetes: a network meta-
ease and mortality: a systematic review and network meta-analysis. JAMA analysis of randomized controlled trials. Int J Cardiol. 2016;208:141–146.
Cardiol. 2017;2:775–781. doi: 10.1001/jamacardio.2017.1421 doi: 10.1016/j.ijcard.2016.01.197
68. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons 86. Redon J, Mancia G, Sleight P, Schumacher H, Gao P, Pogue J, Fagard R,
R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz Verdecchia P, Weber M, Böhm M, Williams B, Yusoff K, Teo K, Yusuf S;
JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/ ONTARGET Investigators. Safety and efficacy of low blood pressures among
AHA guideline on the assessment of cardiovascular risk: a report of the patients with diabetes: subgroup analyses from the ONTARGET (ONgoing
American College of Cardiology/American Heart Association Task Force Telmisartan Alone and in combination with Ramipril Global Endpoint
on Practice Guidelines [published correction appears in Circulation. Trial). J Am Coll Cardiol. 2012;59:74–83. doi: 10.1016/j.jacc.2011.09.040
2014;129(suppl 2):S75–S75]. Circulation. 2014;129(suppl 2):S49–S73. 87. Banerjee C, Moon YP, Paik MC, Rundek T, Mora-McLaughlin C, Vieira JR,
doi: 10.1161/01.cir.0000437741.48606.98 Sacco RL, Elkind MS. Duration of diabetes and risk of ischemic stroke:
69. Perkovic V, Rodgers A. Redefining blood-pressure targets: SPRINT the Northern Manhattan Study. Stroke. 2012;43:1212–1217. doi:
starts the marathon. N Engl J Med. 2015;373:2175–2178. doi: 10.1161/STROKEAHA.111.641381
10.1056/NEJMe1513301 88. Ashburner JM, Go AS, Chang Y, Fang MC, Fredman L, Applebaum KM,
70. The ACCORD Study Group. Effects of intensive blood-pressure control Singer DE. Effect of diabetes and glycemic control on ischemic stroke risk
in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–1585. doi: in AF patients: ATRIA study. J Am Coll Cardiol. 2016;67:239–247. doi:
10.1056/NEJMoa1001286 10.1016/j.jacc.2015.10.080
71. Lackland DT, Voeks JH, Boan AD. Hypertension and stroke: an appraisal of the 89. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Agostino RB,
evidence and implications for clinical management. Expert Rev Cardiovasc Larson MG, Kannel WB, Benjamin EJ. A risk score for predicting stroke
Ther. 2016;14:609–616. doi: 10.1586/14779072.2016.1143359 or death in individuals with new-onset atrial fibrillation in the commu-
72. White CL, Pergola PE, Szychowski JM, Talbert R, Cervantes-Arriaga A, nity: the Framingham Heart Study. JAMA. 2003;290:1049–1056. doi:
Clark HD, Del Brutto OH, Godoy IE, Hill MD, Pelegrí A, Sussman CR, 10.1001/jama.290.8.1049
Taylor AA, Valdivia J, Anderson DC, Conwit R, Benavente OR; for the 90. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk
SPS3 Investigators. Blood pressure after recent stroke: baseline findings factor for stroke: the Framingham Study. Stroke. 1991;22:983–988.
from the Secondary Prevention of Small Subcortical Strokes trial. Am J 91. Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD,
Hypertens. 2013;26:1114–1122. doi: 10.1093/ajh/hpt076 Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf
73. Huang Y, Cai X, Li Y, Su L, Mai W, Wang S, Hu Y, Wu Y, Xu D. PA, Vasan RS, Benjamin EJ, Levy D. 50 year trends in atrial fibrillation
Prehypertension and the risk of stroke: a meta-analysis. Neurology. prevalence, incidence, risk factors, and mortality in the Framingham
2014;82:1153–1161. doi: 10.1212/WNL.0000000000000268 Heart Study: a cohort study. Lancet. 2015;386:154–162. doi: 10.1016/
Downloaded from http://ahajournals.org by on February 7, 2019

74. SPS3 Study Group. Blood-pressure targets in patients with recent S0140-6736(14)61774-8
lacunar stroke: the SPS3 randomised trial [published correction 92. Chamberlain AM, Brown RD Jr, Alonso A, Gersh BJ, Killian JM, Weston SA,
appears in Lancet. 2013;382:506]. Lancet. 2013;382:507–515. doi: Roger VL. No decline in the risk of stroke following incident atrial fibrilla-
10.1016/S0140-6736(13)60852-1 tion since 2000 in the community: a concerning trend. J Am Heart Assoc.
75. Odden MC, McClure LA, Sawaya BP, White CL, Peralta CA, Field TS, Hart 2016;5:e00348. doi: 10.1161/JAHA.116.003408
RG, Benavente OR, Pergola PE. Achieved blood pressure and outcomes in 93. Page RL, Wilkinson WE, Clair WK, McCarthy EA, Pritchett EL. Asymptomatic
the Secondary Prevention of Small Subcortical Strokes trial. Hypertension. arrhythmias in patients with symptomatic paroxysmal atrial fibrilla-
2016;67:63–69. doi: 10.1161/HYPERTENSIONAHA.115.06480 tion and paroxysmal supraventricular tachycardia. Circulation. 1994;89:
76. Walsh KB, Woo D, Sekar P, Osborne J, Moomaw CJ, Langefeld CD, Adeoye 224–227.
O. Untreated hypertension: a powerful risk factor for lobar and nonlobar 94. Strickberger SA, Ip J, Saksena S, Curry K, Bahnson TD, Ziegler PD.
intracerebral hemorrhage in whites, blacks, and Hispanics. Circulation. Relationship between atrial tachyarrhythmias and symptoms. Heart
2016;134:1444–1452. doi: 10.1161/CIRCULATIONAHA.116.024073 Rhythm. 2005;2:125–131. doi: 10.1016/j.hrthm.2004.10.042
77. Pergola PE, White CL, Szychowski JM, Talbert R, Brutto OD, Castellanos 95. Tayal AH, Tian M, Kelly KM, Jones SC, Wright DG, Singh D, Jarouse J,
M, Graves JW, Matamala G, Pretell EJ, Yee J, Rebello R, Zhang Y, Brillman J, Murali S, Gupta R. Atrial fibrillation detected by mobile car-
Benavente OR; SPS3 Investigators. Achieved blood pressures in the diac outpatient telemetry in cryptogenic TIA or stroke. Neurology.
Secondary Prevention of Small Subcortical Strokes (SPS3) study: chal- 2008;71:1696–1701. doi: 10.1212/01.wnl.0000325059.86313.31
lenges and lessons learned. Am J Hypertens. 2014;27:1052–1060. doi: 96. Elijovich L, Josephson SA, Fung GL, Smith WS. Intermittent atrial fibrilla-
10.1093/ajh/hpu027 tion may account for a large proportion of otherwise cryptogenic stroke:
78. Khoury JC, Kleindorfer D, Alwell K, Moomaw CJ, Woo D, Adeoye O, a study of 30-day cardiac event monitors. J Stroke Cerebrovasc Dis.
Flaherty ML, Khatri P, Ferioli S, Broderick JP, Kissela BM. Diabetes mel- 2009;18:185–189. doi: 10.1016/j.jstrokecerebrovasdis.2008.09.005
litus: a risk factor for ischemic stroke in a large biracial population. Stroke. 97. Flint AC, Banki NM, Ren X, Rao VA, Go AS. Detection of paroxysmal atrial
2013;44:1500–1504. doi: 10.1161/STROKEAHA.113.001318 fibrillation by 30-day event monitoring in cryptogenic ischemic stroke:
79. Peters SA, Huxley RR, Woodward M. Diabetes as a risk factor for stroke the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke.
in women compared with men: a systematic review and meta-analysis 2012;43:2788–2790. doi: 10.1161/STROKEAHA.112.665844
of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet. 98. Brachmann J, Morillo CA, Sanna T, Di Lazzaro V, Diener HC, Bernstein
2014;383:1973–1980. doi: 10.1016/S0140-6736(14)60040-4 RA, Rymer M, Ziegler PD, Liu S, Passman RS. Uncovering atrial fibrilla-
80. Lee M, Saver JL, Hong KS, Song S, Chang KH, Ovbiagele B. Effect of pre- tion beyond short-term monitoring in cryptogenic stroke patients:
diabetes on future risk of stroke: meta-analysis. BMJ. 2012;344:e3564. three-year results from the Cryptogenic Stroke and Underlying Atrial
doi: 10.1136/bmj.e3564 Fibrillation trial. Circ Arrhythm Electrophysiol. 2016;9:e003333. doi:
81. Shou J, Zhou L, Zhu S, Zhang X. Diabetes is an independent risk factor for 10.1161/CIRCEP.115.003333
stroke recurrence in stroke patients: a meta-analysis. J Stroke Cerebrovasc Dis. 99. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A,
2015;24:1961–1968. doi: 10.1016/j.jstrokecerebrovasdis.2015.04.004 Lau CP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E,
82. Eriksson M, Carlberg B, Eliasson M. The disparity in long-term survival Kaufman ES, Hohnloser SH; ASSERT Investigators. Subclinical atrial
after a first stroke in patients with and without diabetes persists: the fibrillation and the risk of stroke [published correction appears in N
Northern Sweden MONICA study. Cerebrovasc Dis. 2012;34:153-160. Engl J Med. 2016;374:998]. N Engl J Med. 2012;366:120–129. doi:
doi: 10.1159/000339763 10.1056/NEJMoa1105575

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e261

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

100. Turakhia MP, Ziegler PD, Schmitt SK, Chang Y, Fan J, Than CT, Keung 115. Prospective Studies Collaboration. Blood cholesterol and vascular mortal-
CLINICAL STATEMENTS

EK, Singer DE. Atrial fibrillation burden and short-term risk of stroke: ity by age, sex, and blood pressure: a meta-analysis of individual data
AND GUIDELINES

case-crossover analysis of continuously recorded heart rhythm from from 61 prospective studies with 55,000 vascular deaths [published cor-
cardiac electronic implanted devices. Circ Arrhythm Electrophysiol. rection appears in Lancet. 2008;372:292]. Lancet. 2007;370:1829–1839.
2015;8:1040–1047. doi: 10.1161/CIRCEP.114.003057 116. Amarenco P, Labreuche J, Touboul PJ. High-density lipoprotein-choles-
101. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford terol and risk of stroke and carotid atherosclerosis: a systematic review.
MJ. Validation of clinical classification schemes for predicting stroke: Atherosclerosis. 2008;196:489–496. doi: 10.1016/j.atherosclerosis.
results from the National Registry of Atrial Fibrillation. JAMA. 2007.07.033
2001;285:2864–2870. 117. Kurth T, Everett BM, Buring JE, Kase CS, Ridker PM, Gaziano JM. Lipid lev-
102. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk els and the risk of ischemic stroke in women. Neurology. 2007;68:556–
stratification for predicting stroke and thromboembolism in atrial fibrilla- 562. doi: 10.1212/01.wnl.0000254472.41810.0d
tion using a novel risk factor-based approach: the Euro Heart Survey on 118. Eastern Stroke and Coronary Heart Disease Collaborative Research
atrial fibrillation. Chest. 2010;137:263–272. doi: 10.1378/chest.09-1584 Group. Blood pressure, cholesterol, and stroke in eastern Asia. Lancet.
103. Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen 1998;352:1801–1807.
J, Selmer C, Ahlehoff O, Olsen AM, Gislason GH, Torp-Pedersen C. 119. Tirschwell DL, Smith NL, Heckbert SR, Lemaitre RN, Longstreth WT Jr,
Validation of risk stratification schemes for predicting stroke and throm- Psaty BM. Association of cholesterol with stroke risk varies in stroke sub-
boembolism in patients with atrial fibrillation: nationwide cohort study. types and patient subgroups. Neurology. 2004;63:1868–1875.
BMJ. 2011;342:d124. doi: 10.1136/bmj.d124 120. Peters SA, Singhateh Y, Mackay D, Huxley RR, Woodward M. Total choles-
104. Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, Patel terol as a risk factor for coronary heart disease and stroke in women com-
MR, Mahaffey KW, Halperin JL, Breithardt G, Hankey GJ, Hacke W, pared with men: a systematic review and meta-analysis. Atherosclerosis.
Becker RC, Nessel CC, Fox KA, Califf RM; for the ROCKET AF Steering 2016;248:123–131. doi: 10.1016/j.atherosclerosis.2016.03.016
Committee and Investigators. Renal dysfunction as a predictor of 121. Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of
stroke and systemic embolism in patients with nonvalvular atrial fi- hemorrhagic stroke: a systematic review and meta-analysis. Stroke.
brillation: validation of the R(2)CHADS(2) index in the ROCKET AF 2013;44:1833–1839. doi: 10.1161/STROKEAHA.113.001326
(Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared 122. Curb JD, Abbott RD, Rodriguez BL, Masaki KH, Chen R, Popper JS,
with vitamin K antagonism for prevention of stroke and Embolism Trial Petrovitch H, Ross GW, Schatz IJ, Belleau GC, Yano K. High den-
in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In sity lipoprotein cholesterol and the risk of stroke in elderly men: the
Atrial fibrillation) study cohorts. Circulation. 2013;127:224–232. doi: Honolulu Heart Program. Am J Epidemiol. 2004;160:150–157. doi:
10.1161/CIRCULATIONAHA.112.107128 10.1093/aje/kwh177
105. Oldgren J, Hijazi Z, Lindbäck J, Alexander JH, Connolly SJ, Eikelboom 123. Huxley RR, Barzi F, Lam TH, Czernichow S, Fang X, Welborn T, Shaw
JW, Ezekowitz MD, Granger CB, Hylek EM, Lopes RD, Siegbahn A, Yusuf J, Ueshima H, Zimmet P, Jee SH, Patel JV, Caterson I, Perkovic V,
S, Wallentin L; on behalf of the RE-LY and ARISTOTLE Investigators. Woodward M; for the Asia Pacific Cohort Studies Collaboration and
Performance and validation of a novel biomarker-based stroke risk the Obesity in Asia Collaboration. Isolated low levels of high-density li-
score for atrial fibrillation. Circulation. 2016;134:1697–1707. doi: poprotein cholesterol are associated with an increased risk of coronary
10.1161/CIRCULATIONAHA.116.022802 heart disease: an individual participant data meta-analysis of 23 stud-
106. Link MS, Giugliano RP, Ruff CT, Scirica BM, Huikuri H, Oto A, Crompton ies in the Asia-Pacific region. Circulation. 2011;124:2056–2064. doi:
AE, Murphy SA, Lanz H, Mercuri MF, Antman EM, Braunwald E; on 10.1161/CIRCULATIONAHA.111.028373
behalf of the ENGAGE AF-TIMI 48 Investigators. Stroke and mortality 124. Psaty BM, Anderson M, Kronmal RA, Tracy RP, Orchard T, Fried LP, Lumley
Downloaded from http://ahajournals.org by on February 7, 2019

risk in patients with various patterns of atrial fibrillation: results from T, Robbins J, Burke G, Newman AB, Furberg CD. The association be-
the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor tween lipid levels and the risks of incident myocardial infarction, stroke,
Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial and total mortality: the Cardiovascular Health Study. J Am Geriatr Soc.
Infarction 48). Circ Arrhythm Electrophysiol. 2017;10:e004267. doi: 2004;52:1639–1647. doi: 10.1111/j.1532-5415.2004.52455.x
10.1161/CIRCEP.116.004267 125. Lee JS, Chang PY, Zhang Y, Kizer JR, Best LG, Howard BV. Triglyceride
107. Steinberg BA, Hellkamp AS, Lokhnygina Y, Patel MR, Breithardt G, and HDL-C dyslipidemia and risks of coronary heart disease and ischemic
Hankey GJ, Becker RC, Singer DE, Halperin JL, Hacke W, Nessel CC, stroke by glycemic dysregulation status: the Strong Heart Study. Diabetes
Berkowitz SD, Mahaffey KW, Fox KA, Califf RM, Piccini JP; ROCKET- Care. 2017;40:529–537. doi: 10.2337/dc16-1958
AF Steering Committee and Investigators. Higher risk of death and 126. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ,
stroke in patients with persistent vs. paroxysmal atrial fibrillation: re- Yuhanna IS, Rader DR, de Lemos JA, Shaul PW. HDL cholesterol efflux ca-
sults from the ROCKET-AF Trial. Eur Heart J. 2015;36:288–296. doi: pacity and incident cardiovascular events. N Engl J Med. 2014;371:2383–
10.1093/eurheartj/ehu359 2393. doi: 10.1056/NEJMoa1409065
108. Proietti M, Guiducci E, Cheli P, Lip GY. Is there an obesity paradox for out- 127. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson
comes in atrial fibrillation? A systematic review and meta-analysis of non- A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson
vitamin K antagonist oral anticoagulant trials. Stroke. 2017;48:857–866. SG, Danesh J; Emerging Risk Factors Collaboration. Major lipids, apolipo-
doi: 10.1161/STROKEAHA.116.015984 proteins, and risk of vascular disease. JAMA. 2009;302:1993–2000. doi:
109. Pandey A, Gersh BJ, McGuire DK, Shrader P, Thomas L, Kowey PR, 10.1001/jama.2009.1619
Mahaffey KW, Hylek E, Sun S, Burton P, Piccini J, Peterson E, Fonarow 128. Imamura T, Doi Y, Arima H, Yonemoto K, Hata J, Kubo M, Tanizaki Y,
GC. Association of body mass index with care and outcomes in patients Ibayashi S, Iida M, Kiyohara Y. LDL cholesterol and the development
with atrial fibrillation: results from the ORBIT-AF registry. JACC Clin of stroke subtypes and coronary heart disease in a general Japanese
Electrophysiol. 2016;2:355–363. doi: 10.1016/j.jacep.2015.12.001 population: the Hisayama study. Stroke. 2009;40:382–388. doi:
110. Kamel H, Elkind MS, Bhave PD, Navi BB, Okin PM, Iadecola C, 10.1161/STROKEAHA.108.529537
Devereux RB, Fink ME. Paroxysmal supraventricular tachycardia 129. Sturgeon JD, Folsom AR, Longstreth WT Jr, Shahar E, Rosamond
and the risk of ischemic stroke. Stroke. 2013;44:1550–1554. doi: WD, Cushman M. Risk factors for intracerebral hemorrhage in
10.1161/STROKEAHA.113.001118 a pooled prospective study. Stroke. 2007;38:2718–2725. doi:
111. Overvad TF, Nielsen PB, Larsen TB, Søgaard P. Left atrial size and risk of 10.1161/STROKEAHA.107.487090
stroke in patients in sinus rhythm: a systematic review. Thromb Haemost. 130. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting
2016;116:206–219. doi: 10.1160/TH15-12-0923 triglycerides and risk of ischemic stroke in the general population. JAMA.
112. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure, 2008;300:2142–2152. doi: 10.1001/jama.2008.621
and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. 131. Bowman TS, Sesso HD, Ma J, Kurth T, Kase CS, Stampfer MJ, Gaziano
Lancet. 1995;346:1647–1653. JM. Cholesterol and the risk of ischemic stroke. Stroke. 2003;34:2930–
113. Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. 2934. doi: 10.1161/01.STR.0000102171.91292.DC
Total and high-density lipoprotein cholesterol and stroke risk. Stroke. 132. Shahar E, Chambless LE, Rosamond WD, Boland LL, Ballantyne CM,
2012;43:1768–1774. doi: 10.1161/STROKEAHA.111.646778 McGovern PG, Sharrett AR. Plasma lipid profile and incident ischemic
114. Horenstein RB, Smith DE, Mosca L. Cholesterol predicts stroke mortality stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke.
in the Women’s Pooling Project. Stroke. 2002;33:1863–1868. 2003;34:623–631. doi: 10.1161/01.STR.0000057812.51734.FF

e262 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

133. Wieberdink RG, Poels MM, Vernooij MW, Koudstaal PJ, Hofman A, van 148. Malek AM, Cushman M, Lackland DT, Howard G, McClure LA.

CLINICAL STATEMENTS
der Lugt A, Breteler MM, Ikram MA. Serum lipid levels and the risk of in- Secondhand smoke exposure and stroke: the REasons for Geographic

AND GUIDELINES
tracerebral hemorrhage: the Rotterdam Study. Arterioscler Thromb Vasc and Racial Differences in Stroke (REGARDS) study. Am J Prev Med.
Biol. 2011;31:2982–2989. doi: 10.1161/ATVBAHA.111.234948 2015;49:e89–e97. doi: 10.1016/j.amepre.2015.04.014
134. Hindy G, Engström G, Larsson SC, Traylor M, Markus HS, Melander O, 149. Nishino Y, Tsuji I, Tanaka H, Nakayama T, Nakatsuka H, Ito H, Suzuki T,
Orho-Melander M; on behalf of the Stroke Genetics Network (SiGN). Katanoda K, Sobue T, Tominaga S; Three-Prefecture Cohort Study Group.
Role of blood lipids in the development of ischemic stroke and its sub- Stroke mortality associated with environmental tobacco smoke among
types: a Mendelian randomization study. Stroke. 2018;49:820–827. doi: never-smoking Japanese women: a prospective cohort study. Prev Med.
10.1161/STROKEAHA.117.019653 2014;67:41–45. doi: 10.1016/j.ypmed.2014.06.029
135. Shah RS, Cole JW. Smoking and stroke: the more you smoke the 150. Lin MP, Ovbiagele B, Markovic D, Towfighi A. Association of second-
more you stroke. Expert Rev Cardiovasc Ther. 2010;8:917–932. doi: hand smoke with stroke outcomes. Stroke. 2016;47:2828–2835. doi:
10.1586/erc.10.56 10.1161/STROKEAHA.116.014099
136. Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, 151. Lindbohm JV, Kaprio J, Jousilahti P, Salomaa V, Korja M. Sex, smoking,
Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, Goldstein and risk for subarachnoid hemorrhage. Stroke. 2016;47:1975–1981.
LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson doi: 10.1161/STROKEAHA.116.012957
JA; on behalf of the American Heart Association Stroke Council; Council 152. Vidyasagaran AL, Siddiqi K, Kanaan M. Use of smokeless tobacco and risk
on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; of cardiovascular disease: a systematic review and meta-analysis. Eur J Prev
Council on Functional Genomics and Translational Biology; Council on Cardiol. 2016;23:1970–1981. doi: 10.1177/2047487316654026
Hypertension. Guidelines for the primary prevention of stroke: a state- 153. Boffetta P, Straif K. Use of smokeless tobacco and risk of myocar-
ment for healthcare professionals from the American Heart Association/ dial infarction and stroke: systematic review with meta-analysis. BMJ.
American Stroke Association. Stroke. 2014;45:3754–3832. doi: 2009;339:b3060. doi: 10.1136/bmj.b3060
10.1161/STR.0000000000000046 154. Bell EJ, Lutsey PL, Windham BG, Folsom AR. Physical activity and car-
137. Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi diovascular disease in African Americans in Atherosclerosis Risk
S, Creager MA, Culebras A, Eckel RH, Hart RG, Hinchey JA, Howard in Communities. Med Sci Sports Exerc. 2013;45:901–907. doi:
VJ, Jauch EC, Levine SR, Meschia JF, Moore WS, Nixon JV, Pearson TA; 10.1249/MSS.0b013e31827d87ec
on behalf of the American Heart Association Stroke Council; Council 155. Willey JZ, Moon YP, Sacco RL, Greenlee H, Diaz KM, Wright CB,
on Cardiovascular Nursing; Council on Epidemiology and Prevention; Elkind MS, Cheung YK. Physical inactivity is a strong risk factor for
Council for High Blood Pressure Research, Council on Peripheral Vascular stroke in the oldest old: findings from a multi-ethnic population (the
Disease, and Interdisciplinary Council on Quality of Care and Outcomes Northern Manhattan Study). Int J Stroke. 2017;12:197–200. doi:
Research. Guidelines for the primary prevention of stroke: a guideline for 10.1177/1747493016676614
healthcare professionals from the American Heart Association/American 155a. Soares-Miranda L, Siscovick DS, Psaty BM, Longstreth WT, Mozaffarian
Stroke Association [published correction appears in Stroke. 2011;42:e26]. D. Physical activity and risk of coronary heart disease and stroke in older
Stroke. 2011;42:517–584. doi: 10.1161/STR.0b013e3181fcb238 adults: the Cardiovascular Health Study. Circulation. 2016;133:147–155.
138. Kissela BM, Sauerbeck L, Woo D, Khoury J, Carrozzella J, Pancioli A, Jauch 156. Pandey A, Patel MR, Willis B, Gao A, Leonard D, Das SR, Defina L,
E, Moomaw CJ, Shukla R, Gebel J, Fontaine R, Broderick J. Subarachnoid Berry JD. Association between midlife cardiorespiratory fitness and risk
hemorrhage: a preventable disease with a heritable component. Stroke. of stroke: the Cooper Center Longitudinal Study [published correction
2002;33:1321–1326. appears in Stroke. 2016;47:e203]. Stroke. 2016;47:1720–1726. doi:
139. Albertsen IE, Rasmussen LH, Lane DA, Overvad TF, Skjøth F, Overvad K, 10.1161/STROKEAHA.115.011532
Downloaded from http://ahajournals.org by on February 7, 2019

Lip GY, Larsen TB. The impact of smoking on thromboembolism and 157. Åberg ND, Kuhn HG, Nyberg J, Waern M, Friberg P, Svensson J,
mortality in patients with incident atrial fibrillation: insights from the Torén K, Rosengren A, Åberg MA, Nilsson M. Influence of cardiovas-
Danish Diet, Cancer, and Health study. Chest. 2014;145:559–566. doi: cular fitness and muscle strength in early adulthood on long-term
10.1378/chest.13-1740 risk of stroke in Swedish men. Stroke. 2015;46:1769–1776. doi:
140. Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH, 10.1161/STROKEAHA.115.009008
Stern BJ, Kittner SJ. Dose-response relationship between cigarette smok- 158. Armstrong ME, Green J, Reeves GK, Beral V, Cairns BJ; on behalf of the
ing and risk of ischemic stroke in young women. Stroke. 2008;39:2439– Million Women Study Collaborators. Frequent physical activity may not
2443. doi: 10.1161/STROKEAHA.107.510073 reduce vascular disease risk as much as moderate activity: large prospec-
141. Hackshaw A, Morris JK, Boniface S, Tang JL, Milenkovic D. Low ciga- tive study of women in the United Kingdom. Circulation. 2015;131:721–
rette consumption and risk of coronary heart disease and stroke: 729. doi: 10.1161/CIRCULATIONAHA.114.010296
meta-analysis of 141 cohort studies in 55 study reports [published cor- 159. Blomstrand A, Blomstrand C, Ariai N, Bengtsson C, Björkelund C. Stroke
rection appears in BMJ. 2018;361:k1611]. BMJ. 2018;360:j5855. doi: incidence and association with risk factors in women: a 32-year follow-
10.1136/bmj.j5855 up of the Prospective Population Study of Women in Gothenburg. BMJ
142. Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke Open. 2014;4:e005173. doi: 10.1136/bmjopen-2014-005173
in women compared with men: a systematic review and meta-analysis of 160. Tikk K, Sookthai D, Monni S, Gross ML, Lichy C, Kloss M, Kaaks R.
81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke. Primary preventive potential for stroke by avoidance of major life-
2013;44:2821–2828. doi: 10.1161/STROKEAHA.113.002342 style risk factors: the European Prospective Investigation into Cancer
143. Nakamura K, Barzi F, Lam TH, Huxley R, Feigin VL, Ueshima H, Woo J, and Nutrition-Heidelberg cohort. Stroke. 2014;45:2041–2046. doi:
Gu D, Ohkubo T, Lawes CM, Suh I, Woodward M; for the Asia Pacific 10.1161/STROKEAHA.114.005025
Cohort Studies Collaboration. Cigarette smoking, systolic blood pres- 161. Jefferis BJ, Whincup PH, Papacosta O, Wannamethee SG. Protective
sure, and cardiovascular diseases in the Asia-Pacific region. Stroke. effect of time spent walking on risk of stroke in older men. Stroke.
2008;39:1694–1702. doi: 2014;45:194–199. doi: 10.1161/STROKEAHA.113.002246
144. WHO Collaborative Study of Cardiovascular Disease and Steroid 162. Chomistek AK, Manson JE, Stefanick ML, Lu B, Sands-Lincoln M, Going
Hormone Contraception. Ischaemic stroke and combined oral contracep- SB, Garcia L, Allison MA, Sims ST, LaMonte MJ, Johnson KC, Eaton CB.
tives: results of an international, multicentre, case-control study. Lancet. Relationship of sedentary behavior and physical activity to incident car-
1996;348:498–505. diovascular disease: results from the Women’s Health Initiative. J Am Coll
145. WHO Collaborative Study of Cardiovascular Disease and Steroid Cardiol. 2013;61:2346–2354. doi: 10.1016/j.jacc.2013.03.031
Hormone Contraception. Haemorrhagic stroke, overall stroke risk, and 163. Pandey A, Salahuddin U, Garg S, Ayers C, Kulinski J, Anand V, Mayo
combined oral contraceptives: results of an international, multicentre, H, Kumbhani DJ, de Lemos J, Berry JD. Continuous dose-response
case-control study. Lancet. 1996;348:505–510. association between sedentary time and risk for cardiovascu-
146. Lee PN, Forey BA. Environmental tobacco smoke exposure and risk of lar disease: a meta-analysis. JAMA Cardiol. 2016;1:575–583. doi:
stroke in nonsmokers: a review with meta-analysis. J Stroke Cerebrovasc 10.1001/jamacardio.2016.1567
Dis. 2006;15:190–201. doi: 10.1016/j.jstrokecerebrovasdis.2006.05.002 164. McDonnell MN, Hillier SL, Judd SE, Yuan Y, Hooker SP, Howard VJ.
147. Oono IP, Mackay DF, Pell JP. Meta-analysis of the association be- Association between television viewing time and risk of incident stroke
tween secondhand smoke exposure and stroke. J Public Health (Oxf). in a general population: results from the REGARDS study. Prev Med.
2011;33:496–502. doi: 10.1093/pubmed/fdr025 2016;87:1–5. doi: 10.1016/j.ypmed.2016.02.013

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e263

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

165. Kubota Y, Iso H, Yamagishi K, Sawada N, Tsugane S; on behalf of the JPHC 182. Pase MP, Himali JJ, Beiser AS, Aparicio HJ, Satizabal CL, Vasan RS,
CLINICAL STATEMENTS

Study Group. Daily total physical activity and incident stroke: the Japan Seshadri S, Jacques PF. Sugar- and artificially sweetened beverages and
AND GUIDELINES

Public Health Center-Based Prospective Study. Stroke. 2017;48:1730– the risks of incident stroke and dementia: a prospective cohort study.
1736. doi: 10.1161/STROKEAHA.117.017560 Stroke. 2017;48:1139–1146. doi: 10.1161/STROKEAHA.116.016027
165a. Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, Gómez- 183. Fox CS, Polak JF, Chazaro I, Cupples A, Wolf PA, D’Agostino RA,
Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, O’Donnell CJ. Genetic and environmental contributions to atheroscle-
Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, rosis phenotypes in men and women: heritability of carotid intima-
Fitó M, Gea A, Hernán MA, Martínez-González MA, for the PREDIMED media thickness in the Framingham Heart Study. Stroke. 2003;34:
Study Investigators. Primary prevention of cardiovascular disease with a 397–401.
Mediterranean diet supplemented with extra-virgin olive oil or nuts. N 184. Liao D, Myers R, Hunt S, Shahar E, Paton C, Burke G, Province M, Heiss G.
Engl J Med. 2018;378:e34. doi: 10.1056/NEJMoa1800389 Familial history of stroke and stroke risk: the Family Heart Study. Stroke.
166. Bernstein AM, de Koning L, Flint AJ, Rexrode KM, Willett WC. Soda con- 1997;28:1908–1912.
sumption and the risk of stroke in men and women. Am J Clin Nutr. 185. Schulz UG, Flossmann E, Rothwell PM. Heritability of ischemic stroke
2012;95:1190–1199. doi: 10.3945/ajcn.111.030205 in relation to age, vascular risk factors, and subtypes of incident
167. Chowdhury R, Stevens S, Gorman D, Pan A, Warnakula S, Chowdhury S, stroke in population-based studies. Stroke. 2004;35:819–824. doi:
Ward H, Johnson L, Crowe F, Hu FB, Franco OH. Association between fish 10.1161/01.STR.0000121646.23955.0f
consumption, long chain omega 3 fatty acids, and risk of cerebrovascu- 186. Markus HS, Bevan S. Mechanisms and treatment of ischaemic stroke–
lar disease: systematic review and meta-analysis. BMJ. 2012;345:e6698. insights from genetic associations. Nat Rev Neurol. 2014;10:723–730.
doi: 10.1136/bmj.e6698 doi: 10.1038/nrneurol.2014.196
168. Larsson SC, Virtamo J, Wolk A. Total and specific fruit and vegetable 187. Gretarsdottir S, Thorleifsson G, Manolescu A, Styrkarsdottir U,
consumption and risk of stroke: a prospective study. Atherosclerosis. Helgadottir A, Gschwendtner A, Kostulas K, Kuhlenbäumer G, Bevan S,
2013;227:147–152. doi: 10.1016/j.atherosclerosis.2012.12.022 Jonsdottir T, Bjarnason H, Saemundsdottir J, Palsson S, Arnar DO, Holm H,
169. Larsson SC, Wallin A, Wolk A. Dietary approaches to stop hypertension Thorgeirsson G, Valdimarsson EM, Sveinbjörnsdottir S, Gieger C, Berger
diet and incidence of stroke: results from 2 prospective cohorts. Stroke. K, Wichmann HE, Hillert J, Markus H, Gulcher JR, Ringelstein EB, Kong A,
2016;47:986–990. doi: 10.1161/STROKEAHA.116.012675 Dichgans M, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Risk vari-
170. Hansen CP, Overvad K, Kyrø C, Olsen A, Tjønneland A, Johnsen SP, ants for atrial fibrillation on chromosome 4q25 associate with ischemic
Jakobsen MU, Dahm CC. Adherence to a healthy Nordic diet and stroke. Ann Neurol. 2008;64:402–409. doi: 10.1002/ana.21480
risk of stroke: a Danish cohort study. Stroke. 2017;48:259–264. doi: 188. Anderson CD, Biffi A, Rost NS, Cortellini L, Furie KL, Rosand J. Chromosome
10.1161/STROKEAHA.116.015019 9p21 in ischemic stroke: population structure and meta-analysis. Stroke.
171. Martínez-González MA, Dominguez LJ, Delgado-Rodríguez M. Olive oil 2010;41:1123–1131. doi: 10.1161/STROKEAHA.110.580589
consumption and risk of CHD and/or stroke: a meta-analysis of case- 189. Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S,
control, cohort and intervention studies. Br J Nutr. 2014;112:248–259. Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O’Donnell CJ, Fornage
doi: 10.1017/S0007114514000713 M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J,
172. Cheng P, Wang J, Shao W. Monounsaturated fatty acid intake Bis JC, Peters A, Boncoraglio GB, März W, Meschia JF, Kathiresan S, Ikram
and stroke risk: a meta-analysis of prospective cohort studies. MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR,
J Stroke Cerebrovasc Dis. 2016;25:1326–1334. doi: 10.1016/j. Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts
jstrokecerebrovasdis.2016.02.017 R, Markus HS, Samani NJ, Farrall M, Schunkert H; and the METASTROKE
173. Alexander DD, Bylsma LC, Vargas AJ, Cohen SS, Doucette A, Mohamed Consortium; CARDIoGRAM Consortium; C4D Consortium; International
Downloaded from http://ahajournals.org by on February 7, 2019

M, Irvin SR, Miller PE, Watson H, Fryzek JP. Dairy consumption and Stroke Genetics Consortium. Shared genetic susceptibility to ischemic
CVD: a systematic review and meta-analysis [published correction ap- stroke and coronary artery disease: a genome-wide analysis of common
pears in Br J Nutr. 2016;115:2268]. Br J Nutr. 2016;115:737–750. doi: variants. Stroke. 2014;45:24–36. doi: 10.1161/STROKEAHA.113.002707
10.1017/S0007114515005000 190. Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A,
174. Mayhew AJ, de Souza RJ, Meyre D, Anand SS, Mente A. A system- Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson
atic review and meta-analysis of nut consumption and incident risk CD, Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz
of CVD and all-cause mortality. Br J Nutr. 2016;115:212–225. doi: TM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth
10.1017/S0007114515004316 AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A,
175. Wu D, Guan Y, Lv S, Wang H, Li J. No evidence of increased risk of Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PIW, DeStefano AL, den
stroke with consumption of refined grains: a meta-analysis of prospec- Hoed M, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP,
tive cohort studies. J Stroke Cerebrovasc Dis. 2015;24:2738–2746. doi: Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS,
10.1016/j.jstrokecerebrovasdis.2015.08.004 Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA,
176. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW,
C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, Mamas MA. Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M,
Preeclampsia and future cardiovascular health: a systematic review and Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R,
meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10:e003497. doi: Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK,
10.1161/CIRCOUTCOMES.116.003497 Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley
177. Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M; TH, Nalls MA, Ninomiya T, O’Donnell MJ, Psaty BM, Pulit SL, Rannikmäe
RECORD Trial Group. Cardiovascular disease and vitamin D supplementa- K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell
tion: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr. PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V,
2014;100:746–755. doi: 10.3945/ajcn.113.082602 Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A,
178. D’Elia L, Iannotta C, Sabino P, Ippolito R. Potassium-rich diet and risk of Sudlow CLM, Tanislav C, Tatlisumak T, Taylor KD, Thijs VNS, Thorleifsson
stroke: updated meta-analysis. Nutr Metab Cardiovasc Dis. 2014;24:585– G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM,
587. doi: 10.1016/j.numecd.2014.03.001 Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL,
179. Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, Yang Q, Yusuf S, Bis JC, Pastinen T, Ruusalepp A, Schadt EE, Koplev S,
and cardiovascular disease: meta-analysis of prospective studies. BMJ. Björkegren JLM, Codoni V, Civelek M, Smith NL, Trégouët DA,
2009;339:b4567. doi: 10.1136/bmj.b4567 Christophersen IE, Roselli C, Lubitz SA, Ellinor PT, Tai ES, Kooner JS, Kato
180. Wang ZM, Zhao D, Nie ZL, Zhao H, Zhou B, Gao W, Wang LS, Yang N, He J, van der Harst P, Elliott P, Chambers JC, Takeuchi F, Johnson AD,
ZJ. Flavonol intake and stroke risk: a meta-analysis of cohort studies. Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I,
Nutrition. 2014;30:518–523. doi: 10.1016/j.nut.2013.10.009 Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC,
181. Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M,
Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Markus HS, Howson JMM, Kamatani Y, Debette S, Dichgans M, Malik R,
Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-
J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators. Efficacy of folic acid Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD,
therapy in primary prevention of stroke among adults with hypertension Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz TM,
in China: the CSPPT randomized clinical trial. JAMA. 2015;313:1325– Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS,
1335. doi: 10.1001/jama.2015.2274 Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A,

e264 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PIW, DeStefano AL, Hoed Lemmens R, Levi CR, Lichtner P, Lindgren A, Liu J, Meschia JF, Mitchell

CLINICAL STATEMENTS
MD, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, BD, Oliveira SA, Pera J, Reiner AP, Rothwell PM, Sharma P, Slowik A,

AND GUIDELINES
Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Sudlow CL, Tatlisumak T, Thijs V, Vicente AM, Woo D, Seshadri S,
Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Saleheen D, Rosand J, Markus HS, Worrall BB, Dichgans M; ISGC
Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Analysis Group; METASTROKE collaboration; Wellcome Trust Case
Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Control Consortium 2 (WTCCC2); NINDS Stroke Genetics Network
Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, (SiGN). Low-frequency and common genetic variation in ischemic
Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, stroke: the METASTROKE collaboration [published correction appears
Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley in Neurology. 2016;87:1306]. Neurology. 2016;86:1217–1226. doi:
TH, Nalls MA, Ninomiya T, O’Donnell MJ, Psaty BM, Pulit SL, Rannikmäe 10.1212/WNL.0000000000002528
K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell 194. Erdmann J, Stark K, Esslinger UB, Rumpf PM, Koesling D, de Wit C,
PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Kaiser FJ, Braunholz D, Medack A, Fischer M, Zimmermann ME,
Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Tennstedt S, Graf E, Eck S, Aherrahrou Z, Nahrstaedt J, Willenborg
Sudlow CLM, Tanislav C, Tatlisumak T, Taylor KD, Thijs VNS, Thorleifsson C, Bruse P, Brænne I, Nöthen MM, Hofmann P, Braund PS, Mergia E,
G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Reinhard W, Burgdorf C, Schreiber S, Balmforth AJ, Hall AS, Bertram L,
Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Steinhagen-Thiessen E, Li SC, März W, Reilly M, Kathiresan S, McPherson
Yang Q, Yusuf S, Amin N, Aparicio HS, Arnett DK, Attia J, Beiser AS, Berr R, Walter U, Ott J, Samani NJ, Strom TM, Meitinger T, Hengstenberg C,
C, Buring JE, Bustamante M, Caso V, Cheng YC, Choi SH, Chowhan A, Schunkert H; CARDIoGRAM. Dysfunctional nitric oxide signalling in-
Cullell N, Dartigues JF, Delavaran H, Delgado P, Dörr M, Engström G, Ford creases risk of myocardial infarction. Nature. 2013;504:432–436. doi:
I, Gurpreet WS, Hamsten A, Heitsch L, Hozawa A, Ibanez L, Ilinca A, 10.1038/nature12722
Ingelsson M, Iwasaki M, Jackson RD, Jood K, Jousilahti P, Kaffashian S, 195. Dichgans M. Genetics of ischaemic stroke. Lancet Neurol. 2007;6:149–
Kalra L, Kamouchi M, Kitazono T, Kjartansson O, Kloss M, Koudstaal PJ, 161. doi: 10.1016/S1474-4422(07)70028-5
Krupinski J, Labovitz DL, Laurie CC, Levi CR, Li L, Lind L, Lindgren CM, 196. Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P,
Lioutas V, Liu YM, Lopez OL, Makoto H, Martinez-Majander N, Matsuda Alamowitch S, Domenga V, Cécillion M, Marechal E, Maciazek J,
K, Minegishi N, Montaner J, Morris AP, Muiño E, Müller-Nurasyid M, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach
Norrving B, Ogishima S, Parati EA, Peddareddygari LR, Pedersen NL, Pera JF, Bousser MG, Tournier-Lasserve E. Notch3 mutations in CADASIL, a
J, Perola M, Pezzini A, Pileggi S, Rabionet R, Riba-Llena I, Ribasés M, hereditary adult-onset condition causing stroke and dementia. Nature.
Romero JR, Roquer J, Rudd AG, Sarin AP, Sarju R, Sarnowski C, Sasaki M, 1996;383:707–710. doi: 10.1038/383707a0
Satizabal CL, Satoh M, Sattar N, Sawada N, Sibolt G, Sigurdsson Á, Smith 197. Devan WJ, Falcone GJ, Anderson CD, Jagiella JM, Schmidt H, Hansen
A, Sobue K, Soriano-Tárraga C, Stanne T, Stine OC, Stott DJ, Strauch K, BM, Jimenez-Conde J, Giralt-Steinhauer E, Cuadrado-Godia E, Soriano C,
Takai T, Tanaka H, Tanno K, Teumer A, Tomppo L, Torres-Aguila NP, Touze Ayres AM, Schwab K, Kassis SB, Valant V, Pera J, Urbanik A, Viswanathan
E, Tsugane S, Uitterlinden AG, Valdimarsson EM, van der Lee SJ, Völzke A, Rost NS, Goldstein JN, Freudenberger P, Stögerer EM, Norrving B,
H, Wakai K, Weir D, Williams SR, Wolfe CDA, Wong Q, Xu H, Yamaji T, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF,
Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Kidwell CS, Montaner J, Fernandez-Cadenas I, Delgado P, Greenberg SM,
Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Roquer J, Lindgren A, Slowik A, Schmidt R, Woo D, Rosand J, Biffi A;
Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, on behalf of the International Stroke Genetics Consortium. Heritability
Markus HS, Howson JMM, Kamatani Y, Debette S, Dichgans M; AFGen estimates identify a substantial genetic contribution to risk and out-
Consortium; Cohorts for Heart and Aging Research in Genomic come of intracerebral hemorrhage. Stroke. 2013;44:1578–1583. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

Epidemiology (CHARGE) Consortium; International Genomics of Blood 10.1161/STROKEAHA.111.000089

Pressure (iGEN-BP) Consortium; INVENT Consortium; STARNET; BioBank 198. Carpenter AM, Singh IP, Gandhi CD, Prestigiacomo CJ. Genetic risk
Japan Cooperative Hospital Group; COMPASS Consortium; EPIC-CVD factors for spontaneous intracerebral haemorrhage. Nat Rev Neurol.
Consortium; EPIC-InterAct Consortium; International Stroke Genetics 2016;12:40–49. doi: 10.1038/nrneurol.2015.226
Consortium (ISGC); METASTROKE Consortium; Neurology Working 199. Woo D, Falcone GJ, Devan WJ, Brown WM, Biffi A, Howard TD,
Group of the CHARGE Consortium; NINDS Stroke Genetics Network Anderson CD, Brouwers HB, Valant V, Battey TW, Radmanesh F, Raffeld
(SiGN); UK Young Lacunar DNA Study; MEGASTROKE Consortium; MR, Baedorf-Kassis S, Deka R, Woo JG, Martin LJ, Haverbusch M,
MEGASTROKE Consortium:. Multiancestry genome-wide association Moomaw CJ, Sun G, Broderick JP, Flaherty ML, Martini SR, Kleindorfer
study of 520,000 subjects identifies 32 loci associated with stroke DO, Kissela B, Comeau ME, Jagiella JM, Schmidt H, Freudenberger
and stroke subtypes. Nat Genet. 2018;50:524–537. doi: 10.1038/ P, Pichler A, Enzinger C, Hansen BM, Norrving B, Jimenez-Conde J,
s41588-018-0058-3 Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano C, Roquer
191. Traylor M, Malik R, Nalls MA, Cotlarciuc I, Radmanesh F, Thorleifsson G, J, Kraft P, Ayres AM, Schwab K, McCauley JL, Pera J, Urbanik A, Rost
Hanscombe KB, Langefeld C, Saleheen D, Rost NS, Yet I, Spector TD, Bell NS, Goldstein JN, Viswanathan A, Stögerer EM, Tirschwell DL, Selim M,
JT, Hannon E, Mill J, Chauhan G, Debette S, Bis JC, Longstreth WT Jr, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Montaner J,
Ikram MA, Launer LJ, Seshadri S, Hamilton-Bruce MA, Jimenez-Conde Fernandez-Cadenas I, Delgado P, Malik R, Dichgans M, Greenberg SM,
J, Cole JW, Schmidt R, Słowik A, Lemmens R, Lindgren A, Melander Rothwell PM, Lindgren A, Slowik A, Schmidt R, Langefeld CD, Rosand
O, Grewal RP, Sacco RL, Rundek T, Rexrode K, Arnett DK, Johnson JA, J; International Stroke Genetics Consortium. Meta-analysis of genome-
Benavente OR, Wasssertheil-Smoller S, Lee JM, Pulit SL, Wong Q, Rich wide association studies identifies 1q22 as a susceptibility locus for
SS, de Bakker PI, McArdle PF, Woo D, Anderson CD, Xu H, Heitsch L, intracerebral hemorrhage. Am J Hum Genet. 2014;94:511–521. doi:
Fornage M, Jern C, Stefansson K, Thorsteinsdottir U, Gretarsdottir S, 10.1016/j.ajhg.2014.02.012
Lewis CM, Sharma P, Sudlow CL, Rothwell PM, Boncoraglio GB, Thijs V, 200. Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B. Low
Levi C, Meschia JF, Rosand J, Kittner SJ, Mitchell BD, Dichgans M, Worrall glomerular filtration rate and risk of stroke: meta-analysis. BMJ.
BB, Markus HS; METASTROKE, UK Young Lacunar DNA Study, NINDS 2010;341:c4249. doi: 10.1136/bmj.c4249
Stroke Genetics Network, Neurology Working Group of the CHARGE 201. Lee M, Saver JL, Chang KH, Ovbiagele B. Level of albuminuria and
Consortium; International Stroke Genetics Consortium. Genetic varia- risk of stroke: systematic review and meta-analysis. Cerebrovasc Dis.
tion at 16q24.2 is associated with small vessel stroke. Ann Neurol. 2010;30:464–469. doi: 10.1159/000317069
2017;81:383–394. doi: 10.1002/ana.24840 202. Masson P, Webster AC, Hong M, Turner R, Lindley RI, Craig JC.
192. Shendre A, Wiener H, Irvin MR, Zhi D, Limdi NA, Overton ET, Wassel CL, Chronic kidney disease and the risk of stroke: a systematic review and
Divers J, Rotter JI, Post WS, Shrestha S. Admixture mapping of subclinical meta-analysis. Nephrol Dial Transplant. 2015;30:1162–1169. doi:
atherosclerosis and subsequent clinical events among African Americans 10.1093/ndt/gfv009
in 2 large cohort studies. Circ Cardiovasc Genet. 2017;10:e001569. doi: 203. Mahmoodi BK, Yatsuya H, Matsushita K, Sang Y, Gottesman RF, Astor
10.1161/CIRCGENETICS.116.001569 BC, Woodward M, Longstreth WT Jr, Psaty BM, Shlipak MG, Folsom
193. Malik R, Traylor M, Pulit SL, Bevan S, Hopewell JC, Holliday EG, Zhao W, AR, Gansevoort RT, Coresh J. Association of kidney disease measures
Abrantes P, Amouyel P, Attia JR, Battey TW, Berger K, Boncoraglio GB, with ischemic versus hemorrhagic strokes: pooled analyses of 4 pro-
Chauhan G, Cheng YC, Chen WM, Clarke R, Cotlarciuc I, Debette S, spective community-based cohorts. Stroke. 2014;45:1925–1931. doi:
Falcone GJ, Ferro JM, Gamble DM, Ilinca A, Kittner SJ, Kourkoulis CE, 10.1161/STROKEAHA.114.004900

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e265

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

204. Sandsmark DK, Messé SR, Zhang X, Roy J, Nessel L, Lee Hamm L, He KC, Kotchen JM, Ockene J; Writing Group for the Women’s Health
CLINICAL STATEMENTS

J, Horwitz EJ, Jaar BG, Kallem RR, Kusek JW, Mohler ER 3rd, Porter A, Initiative Investigators. Risks and benefits of estrogen plus proges-
AND GUIDELINES

Seliger SL, Sozio SM, Townsend RR, Feldman HI, Kasner SE; CRIC Study tin in healthy postmenopausal women: principal results from the
Investigators. Proteinuria, but not eGFR, predicts stroke risk in chron- Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:
ic kidney disease: Chronic Renal Insufficiency Cohort study. Stroke. 321–333.
2015;46:2075–2080. doi: 10.1161/STROKEAHA.115.009861 218. Hendrix SL, Wassertheil-Smoller S, Johnson KC, Howard BV, Kooperberg
205. El Husseini N, Fonarow GC, Smith EE, Ju C, Schwamm LH, Hernandez C, Rossouw JE, Trevisan M, Aragaki A, Baird AE, Bray PF, Buring JE,
AF, Schulte PJ, Xian Y, Goldstein LB. Renal dysfunction is associated Criqui MH, Herrington D, Lynch JK, Rapp SR, Torner J; for the WHI
with poststroke discharge disposition and in-hospital mortality: findings Investigators. Effects of conjugated equine estrogen on stroke in the
from Get With The Guidelines-Stroke. Stroke. 2017;48:327–334. doi: Women’s Health Initiative. Circulation. 2006;113:2425–2434. doi:
10.1161/STROKEAHA.116.014601 10.1161/CIRCULATIONAHA.105.594077
206. Wang X, Wang Y, Patel UD, Barnhart HX, Li Z, Li H, Wang C, Zhao X, 219. Simon JA, Hsia J, Cauley JA, Richards C, Harris F, Fong J, Barrett-Connor
Liu L, Wang Y, Laskowitz DT. Comparison of associations of reduced E, Hulley SB. Postmenopausal hormone therapy and risk of stroke: the
estimated glomerular filtration rate with stroke outcomes between Heart and Estrogen-progestin Replacement Study (HERS). Circulation.
hypertension and no hypertension. Stroke. 2017;48:1691–1694. doi: 2001;103:638–642.
10.1161/STROKEAHA.117.016864 220. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clini-
207. Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie cal trial of estrogen-replacement therapy after ischemic stroke. N Engl J
KL, Howard VJ, Lichtman JH, Lisabeth LD, Piña IL, Reeves MJ, Rexrode Med. 2001;345:1243–1249. doi: 10.1056/NEJMoa010534
KM, Saposnik G, Singh V, Towfighi A, Vaccarino V, Walters MR; on 221. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hor-
behalf of the American Heart Association Stroke Council; Council on mone replacement therapy and the risk of stroke: a nested case-control
Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; study. BMJ. 2010;340:c2519. doi: 10.1136/bmj.c2519
Council on Epidemiology and Prevention; Council for High Blood Pressure 222. MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, Kittner
Research. Guidelines for the prevention of stroke in women: a state- SJ. Probable migraine with visual aura and risk of ischemic stroke: the
ment for healthcare professionals from the American Heart Association/ Stroke Prevention in Young Women study. Stroke. 2007;38:2438–2445.
American Stroke Association [published corrections appear in Stroke. doi: 10.1161/STROKEAHA.107.488395
2014;45:e95 and Stroke. 2014;45:e214]. Stroke. 2014;45:1545–1588. 223. Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine
doi: 10.1161/01.str.0000442009.06663.48 and cardiovascular disease: systematic review and meta-analysis. BMJ.
208. Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, 2009;339:b3914. doi: 10.1136/bmj.b3914
Flaherty ML, Khatri P, Ferioli S, De Los Rios La Rosa F, Broderick JP, 224. Demel SL, Kittner S, Ley SH, McDermott M, Rexrode KM. Stroke
Kleindorfer DO. Age at stroke: temporal trends in stroke incidence in risk factors unique to women. Stroke. 2018;49:518–523. doi:
a large, biracial population. Neurology. 2012;79:1781–1787. doi: 10.1161/STROKEAHA.117.018415
10.1212/WNL.0b013e318270401d 225. Kittner SJ, Stern BJ, Feeser BR, Hebel R, Nagey DA, Buchholz DW,
209. Friberg J, Scharling H, Gadsbøll N, Truelsen T, Jensen GB; Copenhagen Earley CJ, Johnson CJ, Macko RF, Sloan MA, Wityk RJ, Wozniak MA.
City Heart Study. Comparison of the impact of atrial fibrillation on Pregnancy and the risk of stroke. N Engl J Med. 1996;335:768–774. doi:
the risk of stroke and cardiovascular death in women versus men (the 10.1056/NEJM199609123351102
Copenhagen City Heart Study). Am J Cardiol. 2004;94:889–894. doi: 226. Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ.
10.1016/j.amjcard.2004.06.023 Hypertensive pregnancy disorders and subsequent cardiovascular
210. Fang MC, Singer DE, Chang Y, Hylek EM, Henault LE, Jensvold NG, Go morbidity and type 2 diabetes mellitus in the mother. Hypertension.
Downloaded from http://ahajournals.org by on February 7, 2019

AS. Gender differences in the risk of ischemic stroke and peripheral 2009;53:944–951. doi: 10.1161/HYPERTENSIONAHA.109.130765
embolism in atrial fibrillation: the AnTicoagulation and Risk factors In 227. Miller EC, Gatollari HJ, Too G, Boehme AK, Leffert L, Marshall RS,
Atrial fibrillation (ATRIA) study. Circulation. 2005;112:1687–1691. doi: Elkind MSV, Willey JZ. Risk factors for pregnancy-associated stroke
10.1161/CIRCULATIONAHA.105.553438 in women with preeclampsia. Stroke. 2017;48:1752–1759. doi:
211. Dagres N, Nieuwlaat R, Vardas PE, Andresen D, Lévy S, Cobbe S, 10.1161/STROKEAHA.117.017374
Kremastinos DT, Breithardt G, Cokkinos DV, Crijns HJ. Gender- 228. Chow FC, Wilson MR, Wu K, Ellis RJ, Bosch RJ, Linas BP. Stroke incidence
related differences in presentation, treatment, and outcome of pa- is highest in women and non-Hispanic blacks living with HIV in the AIDS
tients with atrial fibrillation in Europe: a report from the Euro Heart Clinical Trials Group Longitudinal Linked Randomized Trials cohort. AIDS.
Survey on Atrial Fibrillation. J Am Coll Cardiol. 2007;49:572–577. doi: 2018;32:1125–1135. doi: 10.1097/QAD.0000000000001799
10.1016/j.jacc.2006.10.047 229. Chow FC, Regan S, Zanni MV, Looby SE, Bushnell CD, Meigs JB,
212. Poli D, Antonucci E, Grifoni E, Abbate R, Gensini GF, Prisco D. Gender dif- Grinspoon SK, Feske SK, Triant VA. Elevated ischemic stroke risk
ferences in stroke risk of atrial fibrillation patients on oral anticoagulant among women living with HIV infection. AIDS. 2018;32:59–67. doi:
treatment. Thromb Haemost. 2009;101:938–942. 10.1097/QAD.0000000000001650
213. Avgil Tsadok M, Jackevicius CA, Rahme E, Humphries KH, Behlouli H, 230. Xie C, Zhu R, Tian Y, Wang K. Association of obstructive sleep apnoea
Pilote L. Sex differences in stroke risk among older patients with re- with the risk of vascular outcomes and all-cause mortality: a meta-analy-
cently diagnosed atrial fibrillation. JAMA. 2012;307:1952–1958. doi: sis. BMJ Open. 2017;7:e013983. doi: 10.1136/bmjopen-2016-013983
10.1001/jama.2012.3490 231. Lisabeth LD, Sánchez BN, Chervin RD, Morgenstern LB, Zahuranec DB,
214. Canoy D, Beral V, Balkwill A, Wright FL, Kroll ME, Reeves GK, Green Tower SD, Brown DL. High prevalence of poststroke sleep-disordered
J, Cairns BJ; for the Million Women Study Collaborators. Age breathing in Mexican Americans. Sleep Med. 2017;33:97–102. doi:
at menarche and risks of coronary heart and other vascular dis- 10.1016/j.sleep.2016.01.010
eases in a large UK cohort. Circulation. 2015;131:237–244. doi: 232. Broadley SA, Jørgensen L, Cheek A, Salonikis S, Taylor J, Thompson
10.1161/CIRCULATIONAHA.114.010070 PD, Antic R. Early investigation and treatment of obstructive sleep
215. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, apnoea after acute stroke. J Clin Neurosci. 2007;14:328–333. doi:
Chowdhury R, Kavousi M, Franco OH. Association of age at onset of 10.1016/j.jocn.2006.01.017
menopause and time since onset of menopause with cardiovascular 233. Wu Z, Chen F, Yu F, Wang Y, Guo Z. A meta-analysis of obstructive
outcomes, intermediate vascular traits, and all-cause mortality: a sys- sleep apnea in patients with cerebrovascular disease. Sleep Breath.
tematic review and meta-analysis. JAMA Cardiol. 2016;1:767–776. doi: 2017;22:729–742. doi: 10.1007/s11325-017-1604-4
10.1001/jamacardio.2016.2415 234. Nicholson JS, McDermott MJ, Huang Q, Zhang H, Tyc VL. Full and home
216. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, smoking ban adoption after a randomized controlled trial targeting sec-
Baird A, Kotchen T, Curb JD, Black H, Rossouw JE, Aragaki A, Safford ondhand smoke exposure reduction. Nicotine Tob Res. 2015;17:612–
M, Stein E, Laowattana S, Mysiw WJ; WHI Investigators. Effect of estro- 616. doi: 10.1093/ntr/ntu201
gen plus progestin on stroke in postmenopausal women: the Women’s 235. Brown DL, Mowla A, McDermott M, Morgenstern LB, Hegeman G
Health Initiative: a randomized trial. JAMA. 2003;289:2673–2684. doi: 3rd, Smith MA, Garcia NM, Chervin RD, Lisabeth LD. Ischemic stroke
10.1001/jama.289.20.2673 subtype and presence of sleep-disordered breathing: the BASIC
217. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg sleep apnea study. J Stroke Cerebrovasc Dis. 2015;24:388–393. doi:
C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson 10.1016/j.jstrokecerebrovasdis.2014.09.007

e266 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

236. Martínez-García MA, Soler-Cataluña JJ, Ejarque-Martínez L, Soriano 255. Singh T, Peters SR, Tirschwell DL, Creutzfeldt CJ. Palliative care for

CLINICAL STATEMENTS
Y, Román-Sánchez P, Illa FB, Canal JM, Durán-Cantolla J. Continuous hospitalized patients with stroke: results from the 2010 to 2012

AND GUIDELINES
positive airway pressure treatment reduces mortality in patients with National Inpatient Sample. Stroke. 2017;48:2534–2540. doi: 10.1161/
ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. STROKEAHA.117.016893
Am J Respir Crit Care Med. 2009;180:36–41. doi: 10.1164/rccm. 256. US Burden of Disease Collaborators. The state of US health, 1990-2010:
200808-1341OC burden of diseases, injuries, and risk factors. JAMA. 2013;310:591–608.
237. Parra O, Arboix A, Montserrat JM, Quintó L, Bechich S, García-Eroles L. doi: 10.1001/jama.2013.13805
Sleep-related breathing disorders: impact on mortality of cerebrovascular 257. Janus-Laszuk B, Mirowska-Guzel D, Sarzynska-Dlugosz I, Czlonkowska A.
disease. Eur Respir J. 2004;24:267–272. Effect of medical complications on the after-stroke rehabilitation outcome.
238. Sahlin C, Sandberg O, Gustafson Y, Bucht G, Carlberg B, Stenlund H, NeuroRehabilitation. 2017;40:223–232. doi: 10.3233/NRE-161407
Franklin KA. Obstructive sleep apnea is a risk factor for death in patients 258. Sherman DG, Albers GW, Bladin C, Fieschi C, Gabbai AA, Kase CS,
with stroke: a 10-year follow-up. Arch Intern Med. 2008;168:297–301. O’Riordan W, Pineo GF; PREVAIL Investigators. The efficacy and safety
doi: 10.1001/archinternmed.2007.70 of enoxaparin versus unfractionated heparin for the prevention of ve-
239. Turkington PM, Bamford J, Wanklyn P, Elliott MW. Prevalence and predic- nous thromboembolism after acute ischaemic stroke (PREVAIL Study): an
tors of upper airway obstruction in the first 24 hours after acute stroke. open-label randomised comparison. Lancet. 2007;369:1347–1355. doi:
Stroke. 2002;33:2037–2042. 10.1016/S0140-6736(07)60633-3
240. Leng Y, Cappuccio FP, Wainwright NW, Surtees PG, Luben R, Brayne C, 259. Chan L, Hu CJ, Fan YC, Li FY, Hu HH, Hong CT, Bai CH. Incidence of
Khaw KT. Sleep duration and risk of fatal and nonfatal stroke: a pro- poststroke seizures: a meta-analysis. J Clin Neurosci. 2018;47:347–351.
spective study and meta-analysis. Neurology. 2015;84:1072–1079. doi: doi: 10.1016/j.jocn.2017.10.088
10.1212/WNL.0000000000001371 260. O’Donnell MJ, Diener HC, Sacco RL, Panju AA, Vinisko R, Yusuf S; PRoFESS
241. Yin J, Jin X, Shan Z, Li S, Huang H, Li P, Peng X, Peng Z, Yu K, Bao Investigators. Chronic pain syndromes after ischemic stroke: PRoFESS tri-
W, Yang W, Chen X, Liu L. Relationship of sleep duration with all-cause al. Stroke. 2013;44:1238–1243. doi: 10.1161/STROKEAHA.111.671008
mortality and cardiovascular events: a systematic review and dose-re- 261. Kapral MK, Fang J, Alibhai SM, Cram P, Cheung AM, Casaubon LK,
sponse meta-analysis of prospective cohort studies. J Am Heart Assoc. Prager M, Stamplecoski M, Rashkovan B, Austin PC. Risk of fractures
2017;6:e005947. doi: 10.1161/JAHA.117.005947 after stroke: results from the Ontario Stroke Registry. Neurology.
242. Li W, Wang D, Cao S, Yin X, Gong Y, Gan Y, Zhou Y, Lu Z. Sleep duration 2017;88:57–64. doi: 10.1212/WNL.0000000000003457
and risk of stroke events and stroke mortality: a systematic review and 262. Glozier N, Moullaali TJ, Sivertsen B, Kim D, Mead G, Jan S, Li Q, Hackett
meta-analysis of prospective cohort studies. Int J Cardiol. 2016;223:870– ML. The course and impact of poststroke insomnia in stroke survivors aged
876. doi: 10.1016/j.ijcard.2016.08.302 18 to 65 years: results from the Psychosocial Outcomes In StrokE (POISE)
243. Jackson CA, Mishra GD. Depression and risk of stroke in midaged wom- Study. Cerebrovasc Dis Extra. 2017;7:9–20. doi: 10.1159/000455751
en: a prospective longitudinal study. Stroke. 2013;44:1555–1560. doi: 263. Li J, Yuan M, Liu Y, Zhao Y, Wang J, Guo W. Incidence of constipation
10.1161/STROKEAHA.113.001147 in stroke patients: a systematic review and meta-analysis. Medicine
244. Pan A, Sun Q, Okereke OI, Rexrode KM, Hu FB. Depression and risk (Baltimore). 2017;96:e7225. doi: 10.1097/MD.0000000000007225
of stroke morbidity and mortality: a meta-analysis and systematic re- 264. Ryan AS, Ivey FM, Serra MC, Hartstein J, Hafer-Macko CE. Sarcopenia
view [published correction appears in JAMA. 2011;306:2565]. JAMA. and physical function in middle-aged and older stroke survivors.
2011;306:1241–1249. doi: 10.1001/jama.2011.1282 Arch Phys Med Rehabil. 2017;98:495–499. doi: 10.1016/j.apmr.
245. Booth J, Connelly L, Lawrence M, Chalmers C, Joice S, Becker C, 2016.07.015
Dougall N. Evidence of perceived psychosocial stress as a risk factor 265. Towfighi A, Ovbiagele B, El Husseini N, Hackett ML, Jorge RE, Kissela
Downloaded from http://ahajournals.org by on February 7, 2019

for stroke in adults: a meta-analysis. BMC Neurol. 2015;15:233. doi: BM, Mitchell PH, Skolarus LE, Whooley MA, Williams LS; on behalf of the
10.1186/s12883-015-0456-4 American Heart Association Stroke Council; Council on Cardiovascular and
246. Lightbody CE, Clegg A, Patel K, Lucas JC, Storey H, Hackett ML, Stroke Nursing; and Council on Quality of Care and Outcomes Research.
Watkins DCL. Systematic review and meta-analysis of psychoso- Poststroke depression: a scientific statement for healthcare profession-
cial risk factors for stroke. Semin Neurol. 2017;37:294–306. doi: als from the American Heart Association/American Stroke Association.
10.1055/s-0037-1603758 Stroke. 2017;48:e30–e43. doi: 10.1161/STR.0000000000000113
247. Wassertheil-Smoller S, Qi Q, Dave T, Mitchell BD, Jackson RD, Liu 266. Harnod T, Lin CL, Kao CH. Risk of suicide attempt in poststroke patients:
S, Park K, Salinas J, Dunn EC, Leira EC, Xu H, Ryan K, Smoller JW. a population-based cohort study. J Am Heart Assoc. 2018;7:e007830.
Polygenic risk for depression increases risk of ischemic stroke: from doi: 10.1161/JAHA.117.007830
the Stroke Genetics Network Study. Stroke. 2018;49:543–548. doi: 267. Hackett ML, Pickles K. Part I: frequency of depression after stroke: an
10.1161/STROKEAHA.117.018857 updated systematic review and meta-analysis of observational studies.
248. Simmons C, Noble JM, Leighton-Herrmann E, Hecht MF, Williams O. Int J Stroke. 2014;9:1017–1025. doi: 10.1111/ijs.12357
Community-level measures of stroke knowledge among children: find- 268. Bartoli F, Lillia N, Lax A, Crocamo C, Mantero V, Carrà G, Agostoni E,
ings from Hip Hop Stroke. J Stroke Cerebrovasc Dis. 2017;26:139–142. Clerici M. Depression after stroke and risk of mortality: a systematic
doi: 10.1016/j.jstrokecerebrovasdis.2016.08.045 review and meta-analysis. Stroke Res Treat. 2013;2013:862978. doi:
249. Mochari-Greenberger H, Towfighi A, Mosca L. National women’s knowl- 10.1155/2013/862978
edge of stroke warning signs, overall and by race/ethnic group. Stroke. 269. Samuelsson M, Lindell D, Norrving B. Presumed pathogenetic mecha-
2014;45:1180–1182. doi: 10.1161/STROKEAHA.113.004242 nisms of re-current stroke after lacunar infarction. Cerebrovasc Dis.
250. Martinez M, Prabhakar N, Drake K, Coull B, Chong J, Ritter L, Kidwell 1996;6:6:128–136.
C. Identification of barriers to stroke awareness and risk factor manage- 270. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in re-
ment unique to Hispanics. Int J Environ Res Public Health. 2015;13:ijer lation to prognosis for patients with lacunar infarction. Stroke.
ph13010023. doi: 10.3390/ijerph13010023 1992;23:1434–1438.
251. Madsen TE, Baird KA, Silver B, Gjelsvik A. Analysis of gender differ- 271. Hackett ML, Anderson CS, House A, Xia J. Interventions for treating de-
ences in knowledge of stroke warning signs. J Stroke Cerebrovasc Dis. pression after stroke. Cochrane Database Syst Rev. 2008;(4):CD003437.
2015;24:1540–1547. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.017 doi: 10.1002/14651858.CD003437.pub3
252. Frankel DS, Parker SE, Rosenfeld LE, Gorelick PB. HRS/NSA 2014 Survey 272. Alexopoulos GS, Wilkins VM, Marino P, Kanellopoulos D, Reding M, Sirey
of Atrial Fibrillation and Stroke: gaps in knowledge and perspective, op- JA, Raue PJ, Ghosh S, O’Dell MW, Kiosses DN. Ecosystem focused thera-
portunities for improvement. J Stroke Cerebrovasc Dis. 2015;24:1691– py in poststroke depression: a preliminary study. Int J Geriatr Psychiatry.
1700. doi: 10.1016/j.jstrokecerebrovasdis.2015.06.026 2012;27:1053–1060. doi: 10.1002/gps.2822
253. Kleindorfer D, Lindsell CJ, Moomaw CJ, Alwell K, Woo D, Flaherty ML, 273. Kirkness CJ, Becker KJ, Cain KC, Kohen R, Tirschwell DL, Teri L, Veith
Adeoye O, Zakaria T, Broderick JP, Kissela BM. Which stroke symp- RR,Mitchell PH. Abstract W P125: Telephone versus in-person psychoso-
toms prompt a 911 call? A population-based study. Am J Emerg Med. cial behavioral treatment in post-stroke depression. Stroke. 2015;46(sup-
2010;28:607–612. doi: 10.1016/j.ajem.2009.02.016 pl 1):AWP125.
254. Centers for Disease Control and Prevention (CDC). Prevalence and most 274. Mitchell PH, Veith RC, Becker KJ, Buzaitis A, Cain KC, Fruin M, Tirschwell
common causes of disability among adults: United States, 2005. MMWR D, Teri L. Brief psychosocial-behavioral intervention with antidepressant
Morb Mortal Wkly Rep. 2009;58:421–426. reduces poststroke depression significantly more than usual care with

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e267

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

antidepressant: living well with stroke: randomized, controlled trial. functional outcomes. Arch Phys Med Rehabil. 2015;96:84–90. doi:
CLINICAL STATEMENTS

Stroke. 2009;40:3073–3078. doi: 10.1161/STROKEAHA.109.549808 10.1016/j.apmr.2014.08.018

AND GUIDELINES

275. Thomas SA, Walker MF, Macniven JA, Haworth H, Lincoln NB. 294. Lisabeth LD, Sánchez BN, Baek J, Skolarus LE, Smith MA, Garcia N,
Communication and Low Mood (CALM): a randomized controlled trial Brown DL, Morgenstern LB. Neurological, functional, and cognitive
of behavioural therapy for stroke patients with aphasia. Clin Rehabil. stroke outcomes in Mexican Americans. Stroke. 2014;45:1096–1101.
2013;27:398–408. doi: 10.1177/0269215512462227 doi: 10.1161/STROKEAHA.113.003912
276. Salter KL, Foley NC, Zhu L, Jutai JW, Teasell RW. Prevention of post- 295. Bettger JP, Thomas L, Liang L, Xian Y, Bushnell CD, Saver JL, Fonarow
stroke depression: does prophylactic pharmacotherapy work? GC, Peterson ED. Hospital variation in functional recovery after
J Stroke Cerebrovasc Dis. 2013;22:1243–1251. doi: 10.1016/j. stroke. Circ Cardiovasc Qual Outcomes. 2017;10:e002391. doi:
jstrokecerebrovasdis.2012.03.013 10.1161/CIRCOUTCOMES.115.002391
277. Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, 296. Olaiya MT, Cadilhac DA, Kim J, Nelson MR, Srikanth VK, Andrew NE, Bladin
Fonzetti P, Hegel M, Arndt S. Escitalopram and problem-solving ther- CF, Gerraty RP, Fitzgerald SM, Phan T, Frayne J, Thrift AG; STANDFIRM
apy for prevention of poststroke depression: a randomized controlled (Shared Team Approach Between Nurses and Doctors for Improved Risk
trial [published correction appears in JAMA. 2009;301:1024]. JAMA. Factor Management) Investigators. Long-term unmet needs and associ-
2008;299:2391–2400. doi: 10.1001/jama.299.20.2391 ated factors in stroke or TIA survivors: an observational study. Neurology.
278. Delavaran H, Jönsson AC, Lövkvist H, Iwarsson S, Elmståhl S, Norrving B, 2017;89:68–75. doi: 10.1212/WNL.0000000000004063
Lindgren A. Cognitive function in stroke survivors: a 10-year follow-up 297. Loh AZ, Tan JS, Zhang MW, Ho RC. The global prevalence of anxi-
study. Acta Neurol Scand. 2017;136:187–194. doi: 10.1111/ane.12709 ety and depressive symptoms among caregivers of stroke sur-
279. Dhamoon MS, Moon YP, Paik MC, Boden-Albala B, Rundek T, Sacco vivors. J Am Med Dir Assoc. 2017;18:111–116. doi: 10.1016/j.
RL, Elkind MS. Long-term functional recovery after first ischemic stroke: jamda.2016.08.014
the Northern Manhattan Study. Stroke. 2009;40:2805–2811. doi: 298. Agrawal N, Johnston SC, Wu YW, Sidney S, Fullerton HJ. Imaging data
10.1161/STROKEAHA.109.549576 reveal a higher pediatric stroke incidence than prior US estimates. Stroke.
280. Dhamoon MS, Moon YP, Paik MC, Boden-Albala B, Rundek T, Sacco 2009;40:3415–3421. doi: 10.1161/STROKEAHA.109.564633
RL, Elkind MS. Quality of life declines after first ischemic stroke: 299. Kirton A, Armstrong-Wells J, Chang T, Deveber G, Rivkin MJ, Hernandez
the Northern Manhattan Study. Neurology. 2010;75:328–334. doi: M, Carpenter J, Yager JY, Lynch JK, Ferriero DM; International Pediatric
10.1212/WNL.0b013e3181ea9f03 Stroke Study Investigators. Symptomatic neonatal arterial ischemic stroke:
281. Dhamoon MS, Moon YP, Paik MC, Sacco RL, Elkind MS. Trajectory the International Pediatric Stroke Study. Pediatrics. 2011;128:e1402–
of functional decline before and after ischemic stroke: the Northern e1410. doi: 10.1542/peds.2011-1148
Manhattan Study. Stroke. 2012;43:2180–2184. doi: 10.1161/ 300. Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T,
STROKEAHA.112.658922 Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, O’Callaghan FJ.
282. Levine DA, Galecki AT, Langa KM, Unverzagt FW, Kabeto MU, Giordani Diagnostic delays in paediatric stroke. J Neurol Neurosurg Psychiatry.
B, Wadley VG. Trajectory of cognitive decline after incident stroke. JAMA. 2015;86:917–921. doi: 10.1136/jnnp-2014-309188
2015;314:41–51. doi: 10.1001/jama.2015.6968 301. Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan
283. Tang EY, Amiesimaka O, Harrison SL, Green E, Price C, Robinson V; International Pediatric Stroke Study Group. Arterial ischemic stroke
L, Siervo M, Stephan BC. Longitudinal effect of stroke on cogni- risk factors: the International Pediatric Stroke Study. Ann Neurol.
tion: a systematic review. J Am Heart Assoc. 2018;7:e006443. doi: 2011;69:130–140. doi: 10.1002/ana.22224
10.1161/JAHA.117.006443 302. Ganesan V, Prengler M, McShane MA, Wade AM, Kirkham FJ.
284. Dhamoon MS, Longstreth WT Jr, Bartz TM, Kaplan RC, Elkind MSV. Investigation of risk factors in children with arterial ischemic stroke. Ann
Downloaded from http://ahajournals.org by on February 7, 2019

Disability trajectories before and after stroke and myocardial infarction: Neurol. 2003;53:167–173. doi: 10.1002/ana.10423
the Cardiovascular Health Study. JAMA Neurol. 2017;74:1439–1445. 303. Wintermark M, Hills NK, deVeber GA, Barkovich AJ, Elkind MS, Sear
doi: 10.1001/jamaneurol.2017.2802 K, Zhu G, Leiva-Salinas C, Hou Q, Dowling MM, Bernard TJ, Friedman
285. El Husseini N, Goldstein LB, Peterson ED, Zhao X, Olson DM, Williams JW NR, Ichord RN, Fullerton HJ; VIPS Investigators. Arteriopathy diagnosis
Jr, Bushnell C, Laskowitz DT. Depression status is associated with function- in childhood arterial ischemic stroke: results of the Vascular Effects of
al decline over 1-year following acute stroke. J Stroke Cerebrovasc Dis. Infection in Pediatric Stroke study. Stroke. 2014;45:3597–3605. doi:
2017;26:1393–1399. doi: 10.1016/j.jstrokecerebrovasdis.2017.03.026 10.1161/STROKEAHA.114.007404
286. Winovich DT, Longstreth WT Jr, Arnold AM, Varadhan R, Zeki Al Hazzouri 304. Fox CK, Sidney S, Fullerton HJ. Community-based case-control study of
A, Cushman M, Newman AB, Odden MC. Factors associated with isch- childhood stroke risk associated with congenital heart disease. Stroke.
emic stroke survival and recovery in older adults. Stroke. 2017;48:1818– 2015;46:336–340. doi: 10.1161/STROKEAHA.114.007218
1826. doi: 10.1161/STROKEAHA.117.016726 305. Asakai H, Cardamone M, Hutchinson D, Stojanovski B, Galati
287. Medicare Payment Advisory Commission (MedPAC). Report to the JC, Cheung MM, Mackay MT. Arterial ischemic stroke in chil-
Congress: Medicare payment policy. Washington, DC: Medicare Payment dren with cardiac disease. Neurology. 2015;85:2053–2059. doi:
Advisory Commission; 2013. http://medpac.gov/docs/default-source/re- 10.1212/WNL.0000000000002036
ports/mar13_entirereport.pdf. Accessed August 23, 2016. 306. Gelfand AA, Fullerton HJ, Jacobson A, Sidney S, Goadsby PJ, Kurth T,
288. Lichtman JH, Leifheit-Limson EC, Jones SB, Wang Y, Goldstein LB. Pressman A. Is migraine a risk factor for pediatric stroke? Cephalalgia.
Preventable readmissions within 30 days of ischemic stroke among 2015;35:1252–1260. doi: 10.1177/0333102415576222
Medicare beneficiaries. Stroke. 2013;44:3429–3435. doi: 10.1161/ 307. Hills NK, Johnston SC, Sidney S, Zielinski BA, Fullerton HJ. Recent trauma
STROKEAHA.113.003165 and acute infection as risk factors for childhood arterial ischemic stroke.
289. Ottenbacher KJ, Karmarkar A, Graham JE, Kuo YF, Deutsch A, Reistetter Ann Neurol. 2012;72:850–858. doi: 10.1002/ana.23688
TA, Al Snih S, Granger CV. Thirty-day hospital readmission following dis- 308. Hills NK, Sidney S, Fullerton HJ. Timing and number of minor infec-
charge from postacute rehabilitation in fee-for-service Medicare patients. tions as risk factors for childhood arterial ischemic stroke. Neurology.
JAMA. 2014;311:604–614. doi: 10.1001/jama.2014.8 2014;83:890–897. doi: 10.1212/WNL.0000000000000752
290. Whitson HE, Landerman LR, Newman AB, Fried LP, Pieper CF, Cohen 309. Elkind MS, Hills NK, Glaser CA, Lo WD, Amlie-Lefond C, Dlamini N,
HJ. Chronic medical conditions and the sex-based disparity in disabil- Kneen R, Hod EA, Wintermark M, deVeber GA, Fullerton HJ; and the
ity: the Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci. VIPS Investigators. Herpesvirus infections and childhood arterial ischemic
2010;65:1325–1331. doi: 10.1093/gerona/glq139 stroke: results of the VIPS study. Circulation. 2016;133:732–741. doi:
291. Gall SL, Tran PL, Martin K, Blizzard L, Srikanth V. Sex differences in long-term 10.1161/CIRCULATIONAHA.115.018595
outcomes after stroke: functional outcomes, handicap, and quality of life. 310. Kenet G, Lütkhoff LK, Albisetti M, Bernard T, Bonduel M, Brandao L,
Stroke. 2012;43:1982–1987. doi: 10.1161/STROKEAHA.111.632547 Chabrier S, Chan A, deVeber G, Fiedler B, Fullerton HJ, Goldenberg
292. Ottenbacher KJ, Campbell J, Kuo YF, Deutsch A, Ostir GV, Granger NA, Grabowski E, Günther G, Heller C, Holzhauer S, Iorio A,
CV. Racial and ethnic differences in postacute rehabilitation outcomes Journeycake J, Junker R, Kirkham FJ, Kurnik K, Lynch JK, Male C,
after stroke in the United States. Stroke. 2008;39:1514–1519. doi: Manco-Johnson M, Mesters R, Monagle P, van Ommen CH, Raffini L,
10.1161/STROKEAHA.107.501254 Rostásy K, Simioni P, Sträter RD, Young G, Nowak-Göttl U. Impact of
293. Ellis C, Boan AD, Turan TN, Ozark S, Bachman D, Lackland DT. thrombophilia on risk of arterial ischemic stroke or cerebral sinove-
Racial differences in poststroke rehabilitation utilization and nous thrombosis in neonates and children: a systematic review and

e268 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

meta-analysis of observational studies. Circulation. 2010;121:1838– 331. Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, Chan AK,

CLINICAL STATEMENTS
1847. doi: 10.1161/CIRCULATIONAHA.109.913673 Hovinga CA, Ichord RN, Grotta JC, Jordan LC, Benedict S, Friedman NR,

AND GUIDELINES
311. Curtis C, Mineyko A, Massicotte P, Leaker M, Jiang XY, Floer A, Kirton Dowling MM, Elbers J, Torres M, Sultan S, Cummings DD, Grabowski EF,
A. Thrombophilia risk is not increased in children after perinatal McMillan HJ, Beslow LA, Amlie-Lefond C; on behalf of the Thrombolysis
stroke [published correction appears in Blood. 2017;130:382]. Blood. in Pediatric Stroke Study. Emergence of the primary pediatric stroke
2017;129:2793–2800. doi: 10.1182/blood-2016-11-750893 center: impact of the thrombolysis in pediatric stroke trial. Stroke.
312. Bigi S, Fischer U, Wehrli E, Mattle HP, Boltshauser E, Bürki S, Jeannet 2014;45:2018–2023. doi: 10.1161/STROKEAHA.114.004919
PY, Fluss J, Weber P, Nedeltchev K, El-Koussy M, Steinlin M, Arnold M. 332. Ladner TR, Mahdi J, Gindville MC, Gordon A, Harris ZL, Crossman K,
Acute ischemic stroke in children versus young adults. Ann Neurol. Pruthi S, Abramo TJ, Jordan LC. Pediatric acute stroke protocol activation
2011;70:245–254. doi: 10.1002/ana.22427 in a children’s hospital emergency department. Stroke. 2015;46:2328–
313. George MG, Tong X, Kuklina EV, Labarthe DR. Trends in stroke hospital- 2331. doi: 10.1161/STROKEAHA.115.009961
izations and associated risk factors among children and young adults, 333. DeLaroche AM, Sivaswamy L, Farooqi A, Kannikeswaran N.
1995-2008. Ann Neurol. 2011;70:713–721. doi: 10.1002/ana.22539 Pediatric stroke clinical pathway improves the time to diagnosis in
314. Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane an emergency department. Pediatr Neurol. 2016;65:39–44. doi:
T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, Tilling K, 10.1016/j.pediatrneurol.2016.09.005
O’Callaghan FJ. Childhood arterial ischaemic stroke incidence, present- 334. Hamilton W, Huang H, Seiber E, Lo W. Cost and outcome in pe-
ing features, and risk factors: a prospective population-based study. diatric ischemic stroke. J Child Neurol. 2015;30:1483–1488. doi:
Lancet Neurol. 2014;13:35–43. doi: 10.1016/S1474-4422(13)70290-4 10.1177/0883073815570673
315. Fullerton HJ, Wu YW, Zhao S, Johnston SC. Risk of stroke in children: 335. Plumb P, Seiber E, Dowling MM, Lee J, Bernard TJ, deVeber G, Ichord RN,
ethnic and gender disparities. Neurology. 2003;61:189–194. Bastian R, Lo WD. Out-of-pocket costs for childhood stroke: the impact
316. Lehman LL, Fullerton HJ. Changing ethnic disparity in ischemic of chronic illness on parents’ pocketbooks. Pediatr Neurol. 2015;52:73–
stroke mortality in US children after the STOP trial. JAMA Pediatr. 6.e2. doi: 10.1016/j.pediatrneurol.2014.09.010
2013;167:754–758. doi: 10.1001/jamapediatrics.2013.89 336. Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle
317. Elbers J, deVeber G, Pontigon AM, Moharir M. Long-term outcomes of HP, Schroth G, Remonda L, Sturzenegger M, Fischer U, Baumgartner
pediatric ischemic stroke in adulthood. J Child Neurol. 2014;29:782–788. RW. Ischaemic stroke in young adults: predictors of outcome and re-
doi: 10.1177/0883073813484358 currence. J Neurol Neurosurg Psychiatry. 2005;76:191–195. doi:
318. Boardman JP, Ganesan V, Rutherford MA, Saunders DE, Mercuri E, Cowan 10.1136/jnnp.2004.040543
F. Magnetic resonance image correlates of hemiparesis after neonatal 337. Swerdel JN, Rhoads GG, Cheng JQ, Cosgrove NM, Moreyra AE, Kostis
and childhood middle cerebral artery stroke. Pediatrics. 2005;115:321– JB, Kostis WJ; Myocardial Infarction Data Acquisition System (MIDAS 29)
326. doi: 10.1542/peds.2004-0427 Study Group. Ischemic stroke rate increases in young adults: evidence for
319. Hajek CA, Yeates KO, Anderson V, Mackay M, Greenham M, Gomes a generational effect? J Am Heart Assoc. 2016;5:e004245.
A, Lo W. Cognitive outcomes following arterial ischemic stroke 338. Rutten-Jacobs LC, Arntz RM, Maaijwee NA, Schoonderwaldt HC,
in infants and children. J Child Neurol. 2014;29:887–894. doi: Dorresteijn LD, van Dijk EJ, de Leeuw FE. Long-term mortality after stroke
10.1177/0883073813491828 among adults aged 18 to 50 years. JAMA. 2013;309:1136–1144. doi:
320. Studer M, Boltshauser E, Capone Mori A, Datta A, Fluss J, Mercati D, 10.1001/jama.2013.842
Hackenberg A, Keller E, Maier O, Marcoz JP, Ramelli GP, Poloni C, Schmid 339. Synhaeve NE, Arntz RM, van Alebeek ME, van Pamelen J, Maaijwee
R, Schmitt-Mechelke T, Wehrli E, Heinks T, Steinlin M. Factors affecting NA, Rutten-Jacobs LC, Schoonderwaldt HC, de Kort PL, van Dijk EJ, de
cognitive outcome in early pediatric stroke. Neurology. 2014;82:784– Leeuw FE. Women have a poorer very long-term functional outcome af-
Downloaded from http://ahajournals.org by on February 7, 2019

792. doi: 10.1212/WNL.0000000000000162 ter stroke among adults aged 18-50 years: the FUTURE study. J Neurol.
321. Lo W, Gordon A, Hajek C, Gomes A, Greenham M, Perkins E, Zumberge 2016;263:1099–1105. doi: 10.1007/s00415-016-8042-2
N, Anderson V, Yeates KO, Mackay MT. Social competence following 340. Dehlendorff C, Andersen KK, Olsen TS. Sex disparities in stroke: women
neonatal and childhood stroke. Int J Stroke. 2014;9:1037–1044. doi: have more severe strokes but better survival than men. J Am Heart Assoc.
10.1111/ijs.12222 2015;4:e001967. doi: 10.1161/JAHA.115.001967
322. Bemister TB, Brooks BL, Dyck RH, Kirton A. Parent and family impact 341. Russo T, Felzani G, Marini C. Stroke in the very old: a systematic re-
of raising a child with perinatal stroke. BMC Pediatr. 2014;14:182. doi: view of studies on incidence, outcome, and resource use. J Aging Res.
10.1186/1471-2431-14-182 2011;2011:108785. doi: 10.4061/2011/108785
323. Danchaivijitr N, Cox TC, Saunders DE, Ganesan V. Evolution of cere- 342. Ay H, Arsava EM, Andsberg G, Benner T, Brown RD Jr, Chapman SN,
bral arteriopathies in childhood arterial ischemic stroke. Ann Neurol. Cole JW, Delavaran H, Dichgans M, Engström G, Giralt-Steinhauer E,
2006;59:620–626. doi: 10.1002/ana.20800 Grewal RP, Gwinn K, Jern C, Jimenez-Conde J, Jood K, Katsnelson
324. Tuppin P, Samson S, Woimant F, Chabrier S. Management and 2-year M, Kissela B, Kittner SJ, Kleindorfer DO, Labovitz DL, Lanfranconi S,
follow-up of children aged 29 days to 17 years hospitalized for a first Lee JM, Lehm M, Lemmens R, Levi C, Li L, Lindgren A, Markus HS,
stroke in France (2009-2010). Arch Pediatr. 2014;21:1305–1315. doi: McArdle PF, Melander O, Norrving B, Peddareddygari LR, Pedersén
10.1016/j.arcped.2014.08.023 A, Pera J, Rannikmäe K, Rexrode KM, Rhodes D, Rich SS, Roquer
325. Fullerton HJ, Wu YW, Sidney S, Johnston SC. Risk of recurrent child- J, Rosand J, Rothwell PM, Rundek T, Sacco RL, Schmidt R, Schürks
hood arterial ischemic stroke in a population-based cohort: the impor- M, Seiler S, Sharma P, Slowik A, Sudlow C, Thijs V, Woodfield R,
tance of cerebrovascular imaging. Pediatrics. 2007;119:495–501. doi: Worrall BB, Meschia JF. Pathogenic ischemic stroke phenotypes
10.1542/peds.2006-2791 in the NINDS-Stroke Genetics Network [published correction ap-
326. Koroknay-Pál P, Niemelä M, Lehto H, Kivisaari R, Numminen J, Laakso pears in Stroke. 2015;46:e17]. Stroke. 2014;45:3589–3596. doi:
A, Hernesniemi J. De novo and recurrent aneurysms in pediatric pa- 10.1161/STROKEAHA.114.007362
tients with cerebral aneurysms. Stroke. 2013;44:1436–1439. doi: 343. Forti P, Maioli F, Procaccianti G, Nativio V, Lega MV, Coveri M, Zoli
10.1161/STROKEAHA.111.676601 M, Sacquegna T. Independent predictors of ischemic stroke in the el-
327. Wusthoff CJ, Kessler SK, Vossough A, Ichord R, Zelonis S, Halperin A, derly: prospective data from a stroke unit [published correction ap-
Gordon D, Vargas G, Licht DJ, Smith SE. Risk of later seizure after peri- pears in Neurology. 2013;81:1882]. Neurology. 2013;80:29–38. doi:
natal arterial ischemic stroke: a prospective cohort study. Pediatrics. 10.1212/WNL.0b013e31827b1a41
2011;127:e1550–e1557. doi: 10.1542/peds.2010-1577 344. Saposnik G, Black S; Stroke Outcome Research Canada (SORCan)
328. Fox CK, Glass HC, Sidney S, Lowenstein DH, Fullerton HJ. Acute seizures Working Group. Stroke in the very elderly: hospital care, case fatal-
predict epilepsy after childhood stroke. Ann Neurol. 2013;74:249–256. ity and disposition. Cerebrovasc Dis. 2009;27:537–543. doi: 10.1159/
doi: 10.1002/ana.23916 000214216
329. Hsu CJ, Weng WC, Peng SS, Lee WT. Early-onset seizures are correlated 345. Kammersgaard LP, Jørgensen HS, Reith J, Nakayama H, Pedersen PM,
with late-onset seizures in children with arterial ischemic stroke. Stroke. Olsen TS; Copenhagen Stroke Study. Short- and long-term prognosis
2014;45:1161–1163. doi: 10.1161/STROKEAHA.113.004015 for very old stroke patients: the Copenhagen Stroke Study. Age Ageing.
330. Beslow LA, Abend NS, Gindville MC, Bastian RA, Licht DJ, Smith SE, 2004;33:149–154. doi: 10.1093/ageing/afh052
Hillis AE, Ichord RN, Jordan LC. Pediatric intracerebral hemorrhage: acute 346. Ovbiagele B, Markovic D, Towfighi A. Recent age- and gender-specific
symptomatic seizures and epilepsy. JAMA Neurol. 2013;70:448–454. trends in mortality during stroke hospitalization in the United States. Int
doi: 10.1001/jamaneurol.2013.1033 J Stroke. 2011;6:379–387. doi: 10.1111/j.1747-4949.2011.00590.x

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e269

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

347. Howard G, Goff DC. Population shifts and the future of stroke: forecasts surgical risk: results from the Carotid Revascularization Endarterectomy
CLINICAL STATEMENTS

of the future burden of stroke. Ann N Y Acad Sci. 2012;1268:14–20. doi: Versus Stenting Trial (CREST). Stroke. 2012;43:2408–2416. doi:
AND GUIDELINES

10.1111/j.1749-6632.2012.06665.x 10.1161/STROKEAHA.112.661355
348. Olsen TS, Andersen KK. Stroke in centenarians. Geriatr Gerontol Int. 365. Witt AH, Johnsen SP, Jensen LP, Hansen AK, Hundborg HH, Andersen
2014;14:84–88. doi: 10.1111/ggi.12058 G. Reducing delay of carotid endarterectomy in acute ischemic stroke
349. McKinney JS, Cheng JQ, Rybinnik I, Kostis JB. Comprehensive stroke patients: a nationwide initiative. Stroke. 2013;44:686–690. doi:
centers may be associated with improved survival in hemorrhagic 10.1161/STROKEAHA.111.678565
stroke. J Am Heart Assoc. 2015;4:e001448. doi: 10.1161/JAHA. 366. Mokin M, Rojas H, Levy EI. Randomized trials of endovascular therapy
114.001448 for stroke: impact on stroke care. Nat Rev Neurol. 2016;12:86–94. doi:
350. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) 10.1038/nrneurol.2015.240
care for stroke. Cochrane Database Syst Rev. 2013;9:CD000197. doi: 367. Rebello LC, Haussen DC, Grossberg JA, Belagaje S, Lima A, Anderson A,
10.1002/14651858.CD000197.pub3 Frankel MR, Nogueira RG. Early endovascular treatment in intravenous
351. Man S, Cox M, Patel P, Smith EE, Reeves MJ, Saver JL, Bhatt DL, Xian Y, tissue plasminogen activator-ineligible patients. Stroke. 2016;47:1131–
Schwamm LH, Fonarow GC. Differences in acute ischemic stroke quality 1134. doi: 10.1161/STROKEAHA.115.012586
of care and outcomes by primary stroke center certification organization. 368. Regenhardt RW, Mecca AP, Flavin SA, Boulouis G, Lauer A, Zachrison KS,
Stroke. 2017;48:412–419. doi: 10.1161/STROKEAHA.116.014426 Boomhower J, Patel AB, Hirsch JA, Schwamm LH, Leslie-Mazwi TM. Delays
352. Man S, Schold JD, Uchino K. Impact of stroke center certification on in the air or ground transfer of patients for endovascular thrombectomy.
mortality after ischemic stroke: the Medicare cohort from 2009 to 2013. Stroke. 2018;49:1419–1425. doi: 10.1161/STROKEAHA.118.020618
Stroke. 2017;48:2527–2533. doi: 10.1161/STROKEAHA.116.016473 369. Agency for Healthcare Research and Quality. Total expenditures in mil-
353. Fonarow GC, Zhao X, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Xian Y, lions by condition, United States, 1996–2015: Medical Expenditure Panel
Hernandez AF, Peterson ED, Schwamm LH. Door-to-needle times for tis- Survey. https://meps.ahrq.gov/mepstrends/hc_cond/. Accessed March
sue plasminogen activator administration and clinical outcomes in acute 13, 2018.
ischemic stroke before and after a quality improvement initiative. JAMA. 370. Agency for Healthcare Research and Quality. Mean expenditure per
2014;311:1632–1640. doi: 10.1001/jama.2014.3203 person with care by condition, United States, 1996–2015: Medical
354. Ramirez L, Kim-Tenser MA, Sanossian N, Cen S, Wen G, He S, Expenditure Panel Survey. https://meps.ahrq.gov/mepstrends/hc_cond/.
Mack WJ, Towfighi A. Trends in acute ischemic stroke hospitaliza- Accessed March 13, 2018.
tions in the United States. J Am Heart Assoc. 2016;5:e003233. doi: 371. RTI International. Projections of Cardiovascular Disease Prevalence and
10.1161/JAHA.116.003233 Costs: 2015–2035: Technical Report [report prepared for the American
355. Kumar N, Khera R, Pandey A, Garg N. Racial differences in out- Heart Association]. Research Triangle Park, NC: RTI International;
comes after acute ischemic stroke hospitalization in the United November 2016. RTI project number 021480.003.001.001. https://
States. J Stroke Cerebrovasc Dis. 2016;25:1970–1977. doi: healthmetrics.heart.org/wp-content/uploads/2017/10/Projections-of-
10.1016/j.jstrokecerebrovasdis.2016.03.049 Cardiovascular-Disease.pdf. Accessed November 14, 2018.
356. Wang FW, Esterbrooks D, Kuo YF, Mooss A, Mohiuddin SM, 372. Godwin KM, Wasserman J, Ostwald SK. Cost associated with stroke:
Uretsky BF. Outcomes after carotid artery stenting and endarterec- outpatient rehabilitative services and medication. Top Stroke Rehabil.
tomy in the Medicare population. Stroke. 2011;42:2019–2025. doi: 2011;18(suppl 1):676–684. doi: 10.1310/tsr18s01-676
10.1161/STROKEAHA.110.608992 373. Ellis C, Simpson AN, Bonilha H, Mauldin PD, Simpson KN. The one-year
357. Jalbert JJ, Nguyen LL, Gerhard-Herman MD, Kumamaru H, Chen CY, attributable cost of poststroke aphasia. Stroke. 2012;43:1429–1431.
Williams LA, Liu J, Rothman AT, Jaff MR, Seeger JD, Benenati JF, Schneider doi: 10.1161/STROKEAHA.111.647339
Downloaded from http://ahajournals.org by on February 7, 2019

PA, Aronow HD, Johnston JA, Brott TG, Tsai TT, White CJ, Setoguchi S. 374. Eshak ES, Honjo K, Iso H, Ikeda A, Inoue M, Sawada N, Tsugane S.
Comparative effectiveness of carotid artery stenting versus carotid endar- Changes in the employment status and risk of stroke and stroke types.
terectomy among Medicare beneficiaries. Circ Cardiovasc Qual Outcomes. Stroke. 2017;48:1176–1182. doi: 10.1161/STROKEAHA.117.016967
2016;9:275–285. doi: 10.1161/CIRCOUTCOMES.115.002336 374a. Kivimäki M, Jokela M, Nyberg ST, Singh-Manoux A, Fransson EI,

358. Kim LK, Yang DC, Swaminathan RV, Minutello RM, Okin PM, Lee MK, Alfredsson L, Bjorner JB, Borritz M, Burr H, Casini A, Clays E, De Bacquer
Sun X, Wong SC, McCormick DJ, Bergman G, Allareddy V, Singh H, D, Dragano N, Erbel R, Geuskens GA, Hamer M, Hooftman WE, Houtman
Feldman DN. Comparison of trends and outcomes of carotid artery IL, Jöckel KH, Kittel F, Knutsson A, Koskenvuo M, Lunau T, Madsen IE,
stenting and endarterectomy in the United States, 2001 to 2010. Circ Nielsen ML, Nordin M, Oksanen T, Pejtersen JH, Pentti J, Rugulies R, Salo
Cardiovasc Interv. 2014;7:692–700. doi: 10.1161/CIRCINTERVENTIONS. P, Shipley MJ, Siegrist J, Steptoe A, Suominen SB, Theorell T, Vahtera J,
113.001338 Westerholm PJ, Westerlund H, O’Reilly D, Kumari M, Batty GD, Ferrie JE,
359. Al-Damluji MS, Dharmarajan K, Zhang W, Geary LL, Stilp E, Dardik A, Virtanen M; for the IPD-Work Consortium. Long working hours and risk
Mena-Hurtado C, Curtis JP. Readmissions after carotid artery revascular- of coronary heart disease and stroke: a systematic review and meta-anal-
ization in the Medicare population. J Am Coll Cardiol. 2015;65:1398– ysis of published and unpublished data for 603.838 individuals. Lancet.
1408. doi: 10.1016/j.jacc.2015.01.048 2015;386:1739–1746. doi: 10.1016/S0140-6736(15)60295-1
360. Bangalore S, Bhatt DL, Röther J, Alberts MJ, Thornton J, Wolski K, Goto 375. Nagayoshi M, Everson-Rose SA, Iso H, Mosley TH Jr, Rose KM,
S, Hirsch AT, Smith SC, Aichner FT, Topakian R, Cannon CP, Steg PG; Lutsey PL. Social network, social support, and risk of incident stroke:
for the REACH Registry Investigators. Late outcomes after carotid ar- Atherosclerosis Risk in Communities study. Stroke. 2014;45:2868–2873.
tery stenting versus carotid endarterectomy: insights from a propensity- doi: 10.1161/STROKEAHA.114.005815
matched analysis of the Reduction of Atherothrombosis for Continued 376. Everson-Rose SA, Roetker NS, Lutsey PL, Kershaw KN, Longstreth WT Jr,
Health (REACH) Registry. Circulation. 2010;122:1091–1100. doi: Sacco RL, Diez Roux AV, Alonso A. Chronic stress, depressive symptoms,
10.1161/CIRCULATIONAHA.109.933341 anger, hostility, and risk of stroke and transient ischemic attack in the
361. Obeid T, Alshaikh H, Nejim B, Arhuidese I, Locham S, Malas M. Fixed Multi-Ethnic Study of Atherosclerosis. Stroke. 2014;45:2318–2323. doi:
and variable cost of carotid endarterectomy and stenting in the United 10.1161/STROKEAHA.114.004815
States: a comparative study. J Vasc Surg. 2017;65:1398–1406.e1. doi: 377. Global Burden of Disease Study 2016. Global Burden of Disease Study
10.1016/j.jvs.2016.11.062 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
362. McDonald RJ, Kallmes DF, Cloft HJ. Comparison of hospitalization costs Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
and Medicare payments for carotid endarterectomy and carotid stenting data.org/gbd-results-tool. Accessed May 1, 2018.
in asymptomatic patients. AJNR Am J Neuroradiol. 2012;33:420–425. 378. Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M,
doi: 10.3174/ajnr.A2791 Bennett DA, Moran AE, Sacco RL, Anderson LM, Truelsen T, O’Donnell M,
363. Sternbergh WC 3rd, Crenshaw GD, Bazan HA, Smith TA. Carotid endar- Venketasubramanian N, Barker-Collo S, Lawes CM, Wang W, Shinohara
terectomy is more cost-effective than carotid artery stenting. J Vasc Surg. Y, Witt E, Ezzati M, Naghavi M, Murray C; Global Burden of Diseases,
2012;55:1623–1628. doi: 10.1016/j.jvs.2011.12.045 Injuries, Risk Factors Study 2010 (GBD 2010); GBD Stroke Experts
364. Vilain KR, Magnuson EA, Li H, Clark WM, Begg RJ, Sam AD 2nd, Group. Global and regional burden of first-ever ischaemic and haem-
Sternbergh WC 3rd, Weaver FA, Gray WA, Voeks JH, Brott TG, Cohen orrhagic stroke during 1990-2010: findings from the Global Burden
DJ; on behalf of the CREST Investigators. Costs and cost-effectiveness of Disease Study 2010. Lancet Glob Health. 2013;1:e259–e281. doi:
of carotid stenting versus endarterectomy for patients at standard 10.1016/S2214-109X(13)70089-5

e270 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 14

379. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P,

CLINICAL STATEMENTS
Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, O’Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B,

AND GUIDELINES
Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce
Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm
Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC,
M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel
Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith
Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T,
MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner
Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson
ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD,
V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality
Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez- from 235 causes of death for 20 age groups in 1990 and 2010: a sys-
Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen tematic analysis for the Global Burden of Disease Study 2010 [published
B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, correction appears in Lancet. 2013;381:628]. Lancet. 2012;380:2095–
Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton 2128. doi: 10.1016/S0140-6736(12)61728-0
LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz 380. Kissela BM, Khoury J, Kleindorfer D, Woo D, Schneider A, Alwell K,
SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks Miller R, Ewing I, Moomaw CJ, Szaflarski JP, Gebel J, Shukla R, Broderick
GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, JP. Epidemiology of ischemic stroke in patients with diabetes: the
McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Greater Cincinnati/Northern Kentucky Stroke Study. Diabetes Care.
Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, 2005;28:355–359.
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e271

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

15. CONGENITAL CARDIOVASCULAR has led to a population shift into adulthood. There is
CLINICAL STATEMENTS

a growing population of adults with both congenital

DEFECTS AND KAWASAKI DISEASE
AND GUIDELINES

heart defects and the more usual adult medical diag-

ICD-9 745 to 747; ICD-10 Q20 to Q28. See noses,6 which adds to the management complex-
Tables 15-1 through 15-4 and Charts 15-1 ity of this group of patients7,8 and emphasizes the
through 15-7 importance of specialty care by adult congenital HD
specialists.9
Click here to return to the Table of Contents

CCDs arise from abnormal formation of the heart or Overall Lifespan Prevalence
major blood vessels. CCDs range in severity from very (See Tables 15-1 through 15-3)
minor abnormalities that will never require medical The 32nd Bethesda Conference estimated that the total
therapy or intervention to complex malformations, number of adults living with CCDs in the United States
including absent or atretic portions of the heart, that in 2000 was 800 000.1,10 In 2002, the estimated preva-
could require multiple surgeries and interventions, lence of CCDs was 650 000 to 1.3 million in all age
or even cardiac transplantation. Thus, there is sig- groups.10 The annual birth prevalence of CCDs ranged
nificant variability in their presentation and require- from 2.4 to 13.7 per 1000 live births (Table  15-2). In
ments for care that can have a significant impact on the United States, 1 in 150 adults is expected to have
morbidity, mortality, and healthcare costs in children some form of congenital heart defect, including mild
and adults.1 Some types of CCDs are associated with lesions such as a well-functioning bicuspid aortic valve
diminished quality of life,2 on par with what is seen in and more severe disease such as HLHS.7 The estimated
other chronic pediatric health conditions,3 as well as prevalence of CCDs ranges from 2.5% for hypoplas-
deficits in cognitive functioning4 and neurodevelop- tic right heart syndrome to 20.1% for VSD in children
mental outcomes.5 Health outcomes generally con- and from 1.8% for TGA to 20.1% for VSD in adults
tinue to improve for CCDs, including survival, which (Table 15-3). In population data from Canada, the mea-
Abbreviations Used in Chapter 15
sured prevalence of CCDs in the general population
was 13.11 per 1000 children and 6.12 per 1000 adults
ACS acute coronary syndrome
in the year 2010.11 The expected growth rates of the
AHA American Heart Association
Downloaded from http://ahajournals.org by on February 7, 2019

AMI acute myocardial infarction congenital heart defects population vary from 1% to
ASD atrial septal defect 5% per year depending on age and the distribution of
AV atrioventricular lesions.12
CABG coronary artery bypass graft Estimates of the distribution of lesions in the CCD
CCD congenital cardiovascular defect
population using available data vary based on pro-
CDC Centers for Disease Control and Prevention
CI confidence interval
posed assumptions. If all those born with CCDs
DM diabetes mellitus between 1940 and 2002 were treated, there would be
GBD Global Burden of Disease ≈750 000 survivors with simple lesions, 400 000 with
HCUP Healthcare Cost and Utilization Project moderate lesions, and 180 000 with complex lesions;
HD heart disease in addition, there would be 3.0 million people alive
HLHS hypoplastic left heart syndrome
with bicuspid aortic valves.12 Without treatment, the
HR hazard ratio
ICD-9 International Classification of Diseases, 9th Revision
number of survivors in each group would be 400 000,
ICD-10 International Classification of Diseases, 10th Revision 220 000, and 30 000, respectively. The actual numbers
ICU intensive care unit surviving were projected to be between these 2 sets of
IHD ischemic heart disease estimates as of more than a decade ago.12 The most
IQR interquartile range common types of defects in children are VSD, 620 000
IVIG intravenous immunoglobulin
people; ASD, 235 000 people; valvar pulmonary ste-
KD Kawasaki disease
NH non-Hispanic
nosis, 185 000 people; and patent ductus arteriosus,
NHIS National Health Interview Survey 173 000 people.12 The most common lesions seen in
NHLBI National Heart, Lung, and Blood Institute adults are ASD and TOF.10
NIS National (Nationwide) Inpatient Sample
OR odds ratio
RR relative risk Birth Prevalence
RV right ventricle
STS Society of Thoracic Surgeons
The incidence of disorders present before birth, such
TGA transposition of the great arteries as CCDs, is generally described as the birth prevalence.
TOF tetralogy of Fallot The birth prevalence of CCDs is reported as 6.9 per 1000
UI uncertainty interval live births in North America, 8.2 per 1000 live births
VSD ventricular septal defect in Europe, and 9.3 per 1000 live births in Asia.15 The

e272 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

overall birth prevalence of CCDs at the Bhabha Atomic • Bicuspid aortic valve occurs in 13.7 of every 1000

CLINICAL STATEMENTS
Research Centre Hospital in Mumbai, India, from 2006 people; these defects might not require treatment

AND GUIDELINES
through 2011 was 13.28 per 1000 live births.16 in infancy or childhood but could require care
Variations in birth prevalence rates may be related later in adulthood.23
to the age at detection; major defects can be identified
in the prenatal or neonatal period, but minor defects Mortality
might not be detected until later in childhood or, in
fact, adulthood, which makes it challenging to esti-
(See Tables 15-1 and 15-4 and Charts 15-1
mate birth prevalence and population prevalence. To through 15-5)
distinguish more serious defects, some studies report Overall mortality attributable to CCDs:
the number of new cases of sufficient severity to result • In 2016 (NHLBI tabulation):
in death or an invasive procedure within the first year — Mortality related to CCDs was 3063 deaths
of life (in addition to the overall birth prevalence). (Table 15-1), a 13.3% decrease from 2006.
Birth prevalence rates are likely to increase over time — CCDs (ICD-10 Q20–Q28) were the most
because of improved technological advancements common cause of infant deaths result-
in diagnosis and screening, particularly fetal cardiac ing from birth defects (ICD-10 Q00–Q99);
ultrasound,17 pulse oximetry,18 and echocardiography 22.0% of infants who died of a birth defect
during infancy. had a heart defect (ICD-10 Q20-Q24).
— The age-adjusted death rate (deaths per
Overall Birth Prevalence
100 000 people) attributable to CCDs was
(See Table 15-2)
1.0, a 16.7% decrease from 2006.
• According to population-based data from the
• According to a review of Norwegian national
Metropolitan Atlanta Congenital Defects Program
mortality data in live-born children with CCDs
(Atlanta, GA), a CCD occurred in 1 of every 111
from 1994 to 2009, the all-cause mortality rate
to 125 births (live, still, or >20 weeks’ gestation)
was 17.4% for children with severe congeni-
from 1995 to 1997 and from 1998 to 2005.
tal heart defects and 3.0% for children with
Some defects showed variations by sex and racial
milder forms of CCDs, with declining mortality
distribution.19
rates over the analysis period related to declining
• According to population-based data from
Downloaded from http://ahajournals.org by on February 7, 2019

operative mortality and more frequent pregnancy

Alberta, Canada, there was a total birth preva-
terminations.24
lence of 12.42 per 1000 total births (live, still, or
• Death rates attributed to CCDs decrease as
>20 weeks’ gestation).20
gestational age advances toward 40 weeks.25
• An estimated minimum of 40 000 infants are
In-hospital mortality of infants with major CCDs is
expected to be affected by CCDs each year in the
independently associated with late-preterm birth
United States. Of these, ≈25%, or 2.4 per 1000
(OR, 2.70 [95% CI, 1.69–4.33]) compared with
live births, require invasive treatment in the first
delivery at later gestational ages.26,27
year of life (Table 15-2).
• Similarly, postoperative mortality of infants with
Birth Prevalence of Specific Defects CCDs born near term (37 weeks) is 1.34 (95%
• The National Birth Defects Prevention Network CI, 1.05–1.71; P=0.02) higher than for those
showed the average birth prevalence of 21 born full term,28,29 with higher complication rates
selected major birth defects for 13 states in and longer lengths of stay. The presence of CCDs
the United States from 2004 to 2006. These substantially increases mortality of very low-birth-
data indicated that there are >6100 estimated weight infants; in a study of very low-birth-weight
annual cases of 5 CCDs: truncus arteriosus (0.07 infants, the mortality rate with serious congenital
per 1000 births), TGA (0.3 per 1000 births), TOF heart defects was 44% compared with 12.7%
(0.4 per 1000 births), AV septal defect (0.47 in very low-birth-weight infants without serious
per 1000 births), and HLHS (0.23 per 1000 CCDs.30
births).21,22 • Analysis of the STS Congenital Heart Surgery
• Metropolitan Atlanta Congenital Defects Database, a voluntary registry with self-reported
Program data for specific defects at birth showed data for a 3-year cycle (2013–2016) from 116
the following: VSD, 4.2 per 1000 births; ASD, centers performing CCD surgery (112 based in 40
1.3 per 1000 births; valvar pulmonic stenosis, US states, 3 in Canada, and 1 in Turkey),31 showed
0.6 per 1000 births; TOF, 0.5 per 1000 births; that of 122 193 total patients who underwent an
aortic coarctation, 0.4 per 1000 births; AV sep- operation with analyzable data, the aggregate
tal defect, 0.4 per 1000 births; and TGA (0.2 per hospital discharge mortality rate was 3.0% (95%
1000 births).19 CI, 2.9%–3.1%).32 The mortality rate was 8.6%

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e273

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

(95% CI, 8.2%–9.1%) for neonates,32 2.8% NH people.37 Similarly, another study found that a
CLINICAL STATEMENTS

(95% CI, 2.6%–3.0%) for infants, 1.0% (95% higher risk of in-hospital mortality was associated
AND GUIDELINES

CI, 0.9%–1.1%) for children (>1 year to 18 years with nonwhite race (OR, 1.36 [95% CI, 1.19–
of age),32 and 1.5% (95% CI, 1.3%–1.8%) for 1.54]) and Medicaid insurance (OR, 1.26 [95% CI,
adults (>18 years of age).32 1.09–1.46]).38 One center’s experience suggested
• Another recent analysis of mortality after CCD race was independently associated with neonatal
surgery, culled from the Pediatric Cardiac Care surgical outcomes only in patients with less com-
Consortium’s US-based multicenter data registry, plex CCDs.39 Another center found that a home
demonstrated that although standardized mor- monitoring program can reduce mortality even in
tality ratios continue to decrease, there remains this vulnerable population.40
increased mortality in CCD patients compared • The population-weighted mortality rate for sur-
with the general population. The data included gery for congenital heart defects is slightly higher
35 998 patients with median follow-up of 18 in males (5.1%) than females (4.6%) <20 years
years and an overall standardized mortality ratio old (Table 15-4).
of 8.3% (95% CI, 8.0%–8.7%).33 • Data from the HCUP’s Kids’ Inpatient Database
• The Japan Congenital Cardiovascular Surgery from 2000, 2003, and 2006 show male chil-
Database reported similar surgical outcomes for dren had more CCD surgeries in infancy, more
congenital HD from 28 810 patients operated on high-risk surgeries, and more procedures to
between 2008 and 2012, with 2.3% and 3.5% correct multiple cardiac defects. Female infants
mortality at 30 and 90 days, respectively.34 with high-risk CCDs had a 39% higher adjusted
• In population-based data from Canada, 8123 mortality than males.40,41 According to CDC mul-
deaths occurred among 71 686 patients with CCDs tiple-cause death data from 1999 to 2006, sex
followed up for nearly 1 million patient-years.7 differences in mortality over time varied with age.
• Among 12 644 adults with CCDs followed up at Between the ages of 18 and 34 years, mortality
a single Canadian center from 1980 to 2009, 308 over time decreased significantly in females but
patients in the study cohorts (19%) died.35 not in males.42
• Trends in age-adjusted death rates attributable • In studies that examined trends since 1979,
to CCD mortality showed a decline from 1999 to age-adjusted death rates declined 22% for criti-
2016 (Chart 15-1); this varied by race/ethnicity cal CCDs43 and 39% for all CCDs,44 and deaths
Downloaded from http://ahajournals.org by on February 7, 2019

and sex (Charts 15-2 and 15-3). tended to occur at progressively older ages. CDC
• From 1999 to 2016, there was a decline in the mortality data from 1979 to 2005 showed all-
age-adjusted death rates attributable to CCDs in age death rates had declined by 60% for VSD
black, white, and Hispanic people (Chart 15-2), and 40% for TOF.45 Population-based data from
in both males and females (Chart 15-3), and in Canada showed overall mortality decreased by
age groups 1 to 4 years, 5 to 14 years, 15 to 24 31% and the median age of death increased from
years, and ≥25 years (Chart 15-4) in the United 2 to 23 years between 1987 and 2005.7
States. • Further analysis of the Kids’ Inpatient Database
• CCD-related mortality varies substantially by age, from 2000 to 2009 showed a decrease in HLHS
with infants showing the highest mortality rates stage 3 mortality by 14% and a decrease in
from 1999 to 2016 (Chart 15-4). stage 1 mortality by 6%.46 Surgical interven-
• The US 2016 age-adjusted death rate (deaths tions are the primary treatment for reducing
per 100  000 people) attributable to CCDs mortality. A Pediatric Heart Network study of
was 1.0 for NH white males, 1.3 for NH black 15 North American centers revealed that even
males, 1.0 for Hispanic males, 0.8 for NH white in lesions associated with the highest mortality,
females, 1.1 for NH black females, and 0.8 for such as HLHS, aggressive palliation can lead to an
Hispanic females. Infant (<1 year of age) mortal- increase in the 12-month survival rate, from 64%
ity rates were 28.9 for NH white infants, 42.0 for to 74%.47
NH black infants, and 31.0 for Hispanic infants • Surgical interventions are common in adults with
(Chart 15-5).36 CCDs. Mortality rates for 12 CCD procedures
• Mortality after congenital heart surgery also dif- were examined with data from 1988 to 2003
fers between races/ethnicities, even after adjust- reported in the NIS. A total of 30 250 operations
ment for access to care. The risk of in-hospital were identified, which yielded a national estimate
mortality for minority patients compared with of 152  277±7875 operations. Of these, 27%
white patients is 1.22 (95% CI, 1.05–1.41) for were performed in patients ≥18 years of age. The
Hispanics, 1.27 (95% CI, 1.09–1.47) for NH overall in-hospital mortality rate for adult patients
blacks, and 1.56 (95% CI, 1.37–1.78) for other with CCDs was 4.71% (95% CI, 4.19%–5.23%),

e274 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

with a significant reduction in mortality observed — The mean cost of CCDs was higher in infancy

CLINICAL STATEMENTS
when surgery was performed on such adult ($36 601) than in older ages and in those with

AND GUIDELINES
patients by pediatric versus nonpediatric heart critical congenital heart defects ($52 899).
surgeons (1.87% versus 4.84%; P<0.0001).48 For • Other studies confirm the high cost of HLHS. An
adults with CCDs, specialist care is a key deter- analysis of 1941 neonates with HLHS showed
minant of mortality and morbidity. In a single- a median cost of $99 070 for stage 1 palliation
center report of 4461 adult patients with CCDs (Norwood or Sano procedure), $35 674 for stage
with 48 828 patient-years of follow-up, missed 2 palliation (Glenn procedure), $36 928 for stage
appointments and delay in care were predictors 3 palliation (Fontan procedure), and $289 292 for
of mortality.49 transplantation.53
• Other CCD lesions are less costly. In 2124 patients
undergoing congenital heart operations between
Hospitalizations 2001 and 2007, total costs for the other surgeries
(See Table 15-1) were $12 761 (ASD repair), $18 834 (VSD repair),
$28 223 (TOF repair), and $55 430 (arterial switch
• In 2014, the total number of hospital dis-
operation).54
charges for CCDs for all ages was 39  000 • A recent Canadian study demonstrated increasing
(Table 15-1). hospitalization costs for children and adults with
• Hospitalization of infants with CCDs is com- CCDs, particularly those with complex lesions,
mon; one-third of patients with congenital heart which appears independent from inflation or
defects require hospitalization during infancy,45,50 length of stay.55
often in an ICU.
• Although the most common CCD lesions were
shunts, including patent ductus arteriosus, Risk Factors
VSDs, and ASDs, TOF accounted for a higher • Numerous intrinsic and extrinsic nongenetic risk
proportion of in-hospital death than any other factors are thought to contribute to CCDs.56,57
birth defect. • Intrinsic risk factors for CCDs include various
genetic syndromes. Twins are at higher risk for
CCDs58; one report from Kaiser Permanente data
Downloaded from http://ahajournals.org by on February 7, 2019

Cost showed monochorionic twins were at particu-

• Using HCUP 2013 NIS data, one study noted that lar risk (RR, 11.6 [95% CI, 9.2–14.5]).59 Known
hospitalization costs for individuals of all ages risks generally focus on maternal exposures, but
with CCDs exceeded $6.1 billion in 2013, which a study of paternal occupational exposure docu-
represents 27% of all birth defect–associated mented a higher incidence of CCDs with paternal
hospital costs.51 exposure to phthalates.60
• Among pediatric hospitalizations (age 0–20 • Other paternal exposures that increase risk for
years) in the HCUP 2012 Kids’ Inpatient CCDs include paternal anesthesia, which has
Database52: been implicated in TOF (3.6%); sympathomimetic
— Pediatric hospitalizations with CCDs (4.4% medication and coarctation of the aorta (5.8%);
of total pediatric hospitalizations) accounted pesticides and VSDs (5.5%); and solvents and
HLHS (4.6%).61
for $6.6 billion in hospitalization spend-
• Known maternal risks include smoking62,63 during
ing (23% of total pediatric hospitalization
the first trimester of pregnancy, which has also
costs).
been associated with a ≥30% increased risk of
— 26.7% of all CCD costs were attributed to
the following lesions in the fetus: ASD, pulmo-
critical CCDs, with the highest costs attrib- nary valvar stenosis, truncus arteriosus, TGA,64
utable to HLHS, coarctation of the aorta, and septal defects (particularly for heavy smokers
and TOF. [≥25 cigarettes daily]).65 Maternal smoking might
— Median (IQR) hospital cost was $51  302 account for 1.4% of all congenital heart defects.
($32 088–$100 058) in children who under- • Exposure to secondhand smoke has also been
went cardiac surgery, $21  920 ($13  068– implicated as a risk factor.66
$51 609) in children who underwent cardiac • Air pollutants can also increase the risk of CCDs.
catheterization, $4134 ($1771–$10 253) in In a retrospective review of singleton infants born
children who underwent noncardiac surgery, in Florida from 2000 to 2009, maternal exposure
and $23 062 ($5529–$71 887) in children during pregnancy to the air pollutant benzene
admitted for medical treatments. was associated with an increased risk in the fetus

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e275

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

of critical and noncritical CCDs (1.33 [95% CI, arteriosus and ASD contributed to the increased
CLINICAL STATEMENTS

1.07–1.65]).67 prevalence.80
AND GUIDELINES

• Maternal binge drinking68 is also associated with

an increased risk of CCDs, and the combination
of binge drinking and smoking can be particularly
Screening
deleterious: Mothers who smoke and report any Pulse oximetry screening for CCDs was recommended
binge drinking in the 3 months before pregnancy by the US Department of Health and Human Services
are at an increased risk of giving birth to a child in 2010.81 It was incorporated as part of the US rec-
with a CCD (adjusted OR, 12.65).68 ommended uniform screening panel for newborns
• Maternal obesity is also associated with CCDs. A in 2011 and has been endorsed by the AHA and the
meta-analysis of 14 studies of females without American Academy of Pediatrics.82 At present, all 50
gestational DM showed infants born to moth- states and the District of Columbia have laws or regula-
ers who were moderately and severely obese, tions mandating newborn screening for identification
respectively, had 1.1 and 1.4 times greater risk of of previously unidentified (by fetal cardiac ultrasound)
CCDs than infants born to normal-weight moth- newborn CCDs,83 and several studies have demon-
ers.69–71 The risk of TOF was 1.9 times higher strated the benefit of such screening.84–86
among infants born to mothers with severe obe- • Several key factors contribute to effective screen-
sity than among infants born to normal-weight ing, including probe placement (postductal),
mothers.70 oximetry cutoff (<95%), timing (>24 hours of
• Maternal DM, including gestational DM, has also life), and altitude (<2643 ft, 806 m).
been associated with CCDs, both isolated (CCD[s] • If fully implemented, screening would predict
as the only major congenital anomaly) and mul- identification of 1189 additional infants with criti-
tiple (CCD[s] plus ≥1 noncardiac major congenital cal congenital heart defects and yield 1975 false-
anomalies).72,73 Pregestational DM is also associ- positive results.87
ated with CCDs, specifically TOF.74 • A simulation model estimates that screening the
• Preeclampsia is considered a risk factor for CCDs, entire United States for critical CCDs with pulse
although not critical defects.75 oximetry would uncover 875 infants (95% UI,
• Folate deficiency is a well-documented risk for 705–1060) who truly have nonsyndromic CCDs
congenital malformations, including CCDs, and versus 880 (95% UI, 700–1080) false-negative
Downloaded from http://ahajournals.org by on February 7, 2019

folic acid supplementation is routinely recom- screenings (no CCDs).88

mended during pregnancy.56 An observational • It has been estimated that 29.5% (95% CI,
study of folic acid supplementation in Hungarian 28.1%–31.0%) of nonsyndromic children with
females showed a decrease in the incidence of critical CCDs are diagnosed after 3 days and thus
CCDs, including VSD (OR, 0.57 [95% CI, 0.45– might benefit from pulse oximetry screening.89
0.73]), TOF (OR, 0.53 [95% CI, 0.17–0.94]), dex- • A meta-analysis of 13 studies that included
tro-TGA (OR, 0.47 [95% CI, 0.26–0.86]), and ASD 229 421 newborns found pulse oximetry had a
secundum (OR, 0.63 [95% CI, 0.40–0.98]).75 A US sensitivity of 76.5% (95% CI, 67.7%–83.5%)
population-based case-control study showed an for detection of critical CCDs and a specificity of
inverse relationship between folic acid use and 99.9% (95% CI, 99.7%–99.9%), with a false-
the risk of TGA (Baltimore-Washington Infant positive rate of 0.14% (95% CI, 0.06%–0.33%).90
Study, 1981–1989).76 • A recent observational study demonstrated that
• An observational study from Quebec, Canada, statewide implementation of mandatory policies for
of 1.3 million births from 1990 to 2005 found newborn screening for critical CCDs was associated
a 6% per year reduction in severe congenital with a significant decrease (33.4% [95% CI, 10.6%–
heart defects using a time-trend analysis before 50.3%]) in infant cardiac deaths between 2007 and
and after public health measures were instituted 2013 compared with states without such policies.91
that mandated folic acid fortification of grain and • The cost of identifying a newborn with a critical
flour products in Canada.77 CCD has been estimated at $20 862 per newborn
• Maternal infections, including rubella and chla- detected and $40 385 per life-year gained (2011
mydia, have been associated with congenital US dollars).88
heart defects.78,79 • Reports outside of the United States have shown
• High altitude has also been described as a risk similar performance of pulse oximetry screening
factor for CCDs. Tibetan children living at 4200 in identifying critical CCDs,92 with a sensitivity and
to 4900 m had a higher prevalence of congenital specificity of pulse oximetry screening for critical
heart defects (12.09 per 1000) than those living at congenital heart defects of 100% and 99.7%,
lower altitudes of 3500 to 4100 m; patent ductus respectively.

e276 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Genetics and Family History Global Burden of CCDs

CLINICAL STATEMENTS
• CCDs have a heritable component. There is a (See Charts 15-6 and 15-7)

AND GUIDELINES
greater concordance of CCDs in monozygotic • In 2016101:
than dizygotic twins.93 Among parents with ASD — Prevalence of congenital heart anomalies
or VSD, 2.6% and 3.7%, respectively, have chil- was an estimated 15.4 million people.
dren who are similarly affected, 21 times the esti- — There were 200  000 deaths attributed to
mated population frequency.94 However, a large congenital heart anomalies worldwide.
fraction of CCDs occur in families with no other • The GBD 2016 Study used statistical models and
history of CCDs, which suggests the possibility of data on incidence, prevalence, case fatality, excess
de novo genetic events. mortality, and cause-specific mortality to estimate
• Large chromosomal abnormalities are associated disease burden for 315 diseases and injuries in
with some CCDs. For example, aneuploidies such 195 countries and territories.101
as trisomy 13, 18, and 21 account for 9% to 18% — Age-standardized mortality rates of CCDs
of CCDs.89 The specific genes responsible for are lowest in high-income countries (Chart
CCDs that are disrupted by these abnormalities 15-6).
are difficult to identify. There are studies that sug- — The prevalence of congenital heart anoma-
gest that DSCAM and COL6A contribute to Down lies is highest in Northern and Central Europe
syndrome–associated CCDs.95 (Chart 15-7).
• Copy number variants also contribute to CCDs
and have been shown to be overrepresented in
larger cohorts of patients with specific forms of
Kawasaki Disease
CCDs.96 The most common copy number vari- ICD-9 446.1; ICD-10 M30.3.
ant is del22q11, which encompasses the T-box 2016 Mortality: Underlying Mortality—5, All-Cause
transcription factor (TBX1) gene and presents Mortality—7 (NHLBI tabulation)
as DiGeorge syndrome and velocardiofacial syn- KD is an acute inflammatory illness characterized by
drome. Others include del17q11, which causes fever, rash, nonexudative limbal-sparing conjunctivitis,
William syndrome.97 extremity changes, red lips and strawberry tongue, and
Downloaded from http://ahajournals.org by on February 7, 2019

• Single point mutations are also a cause of CCDs a swollen lymph node. In areas where bacille Calmette-
and include mutations in a core group of cardiac Guerin vaccination is common, the site can reactivate in
transcription factors (NKX2.5, TBX1, TBX5, and KD.102 The most feared consequence of this vasculitis is
MEF2),97 ZIC3, and the NOTCH1 gene (dominantly coronary artery aneurysms, which can result in coronary
inherited and found in ≈5% of cases of bicuspid ischemic events and other cardiovascular outcomes in
aortic valve) and related NOTCH signaling genes.98 the acute period or years later.103 The cause of KD is
• Recent advances in whole-exome sequencing unknown, but it could be an immune response to an
have suggested that 10% of sporadic severe acute infectious illness based in part on genetic sus-
cases of CCDs are caused by de novo mutations,99 ceptibilities.104,105 This is supported by the occurrence
particularly in chromatin-regulating genes. of epidemics and variation in incidence by age, geog-
• Rare monogenic CCDs also exist, including mono- raphy, and season, but also by race/ethnicity, sex, and
genic forms of ASD, heterotaxy, severe mitral family history.105,106 The Nationwide Longitudinal Survey
valve prolapse, and bicuspid aortic valve.97 in Japan has shown that breastfeeding is protective
• There is no exact consensus currently on the against developing KD.107
role, type, and utility of clinical genetic testing in
Prevalence
people with CCDs,97 but it should be offered to
• KD is the most common cause of acquired
patients with multiple congenital abnormalities
HD in children in the US and other developed
or congenital syndromes (including CCD lesions countries.106
associated with a high prevalence of 22q11 dele-
tion or DiGeorge syndrome), and it can be con- Incidence
sidered in patients with a family history, in those • The incidence was 20.8 per 100 000 US children
with developmental delay, and in patients with aged <5 years in 2006.108 This is the most recent
left-sided obstructive lesions.1 national estimate available and is limited by
• A Pediatric Cardiac Genomics Consortium has reliance on weighted hospitalization data from
been developed to provide and better understand 38 states.
phenotype and genotype data from large cohorts • Boys have a 1.5-fold higher incidence of KD than
of patients with CCDs.100 girls.108

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e277

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

• Although KD can occur into adolescence (and resistance to IVIG treatment, and rarely, long-
CLINICAL STATEMENTS

rarely beyond), 76.8% of US children with KD are term myocardial dysfunction or death.106,113
AND GUIDELINES

<5 years of age.108 — It is estimated that even with current therapy

• Race-specific incidence rates indicate that KD is (high-dose IVIG within the first 10 days of
most common among Americans of Asian and illness), 20% of children develop transient
Pacific Island descent (30.3 per 100 000 children coronary artery dilation (Z score >2), 5%
<5 years old), occurs with intermediate frequency develop coronary artery aneurysms (Z score
in NH blacks (17.5 per 100 000 children <5 years ≥2.5), and 1% develop giant aneurysms
old) and Hispanics (15.7 per 100 000 children <5 (Z score ≥10 or >8 mm).107 Estimates are
years old), and is least common in whites (12.0 complicated by variability in ascertainment
per 100 000 children <5 years old).108 method (administrative codes or research
• There is also geographic variation in KD incidence measurement), size criteria, timing (because
within the United States. States with higher Asian the majority of dilated segments and approx-
American populations have higher rates of KD; imately half of aneurysms reduce to normal
for example, rates are 2.5-fold higher in Hawaii dimensions over time), and therapeutic regi-
(50.4 per 100 000 children <5 years old) than in mens in the underlying studies. In the most
the continental United States.109 Within Hawaii, recent US data from 2 centers in 2004 to
the race-specific rates of KD per 100 000 chil- 2008, maximal coronary artery dimensions
dren <5 years old in 1996 to 2006 were 210.5 reached Z scores ≥2.5 in 30% of KD cases
for Japanese, 86.9 for Native Hawaiian, 83.2 for up to 12 weeks from fever onset, including
Chinese, 64.5 for Filipino, and 13.7 for white medium (Z score ≥5 to <10) and giant aneu-
children.109 rysms in ≈6% and ≈3% of KD cases, respec-
• There are seasonal variations in KD; KD is more tively.114 Risk factors for coronary artery
common during the winter and early spring abnormalities include younger age, male sex,
months, except in Hawaii, where no clear sea- late treatment, and failure to respond to ini-
sonal trend is seen.108,109 tial IVIG with defervescence.114–117
• KD can recur. Recurrence rates are not available — Peak KD-associated mortality occurs during
for US children, but incidence of first recurrence the acute phase but is rare, estimated at 0 to
0.17% in older US data and 0.03% in recent
Downloaded from http://ahajournals.org by on February 7, 2019

among children with a history of KD has been

reported as 6.5 per 1000 person-years in Japan data from Japan.118–120 Mortality is related to
(2007–2010) and 2.6 per 1000 person-years in thrombosis or rupture of rapidly expanding
Canada (2004–2014).110,111 Recurrences con- aneurysms, or less commonly, shock or mac-
stitute 2% to 4% of total KD cases in both the rophage activation syndrome with multior-
United States and Japan.112 gan failure.118,119,121
• Long term, IHD and death are related to coronary
Hospital Discharges artery stenosis or thrombosis.
• In 2014, there were 6000 all-listed diagnoses dis- — Prognosis is predicted largely by coronary
charges for KD, with 4000 males and 2000 females artery size 1 month from illness onset. In a
(HCUP, unpublished NHLBI tabulation). Taiwanese study of 1073 KD cases from 1980
Secular Trends to 2012, coronary artery aneurysms were
• Although the incidence of KD is rising worldwide, present in 18.3% beyond 1 month, includ-
there is no clear secular trend in the United States. ing 11.6% with small, 4.1% with medium,
US hospitalizations for KD were 17.5 and 20.8 per and 2.5% with giant aneurysms. Among
100 000 children aged <5 years in 1997 and 2006, those with persistent aneurysms beyond 1
respectively, but the test for linear trend was not month, IHD death occurred in 2%, nonfatal
significant.108 AMI occurred in another 2%, and myocar-
dial ischemia occurred in another 3%, for a
Complications of KD total 7% ischemic event rate during 1 to 46
• In the acute phase (up to ≈6 weeks from fever years of follow-up. Nearly all events occurred
onset), several important cardiovascular complica- in those with giant aneurysms, for whom
tions can occur. the ischemia event–free survival rates were
— KD shock syndrome, with variable contri- 0.63 and 0.36 at 10 and 20 years, respec-
butions from myocardial dysfunction and tively, after KD onset.122 Findings were simi-
decreased peripheral resistance, occurs in lar in a Canadian study of 1356 KD patients
5% to 7% of KD cases and is associated diagnosed in 1990 to 2007 and followed
with higher risk of coronary arterial dilation, for up to 15 years, and in a Japanese study

e278 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

of 76 patients with giant aneurysms diag- thromboprophylaxis. Successful coronary inter-

CLINICAL STATEMENTS
nosed since 1972 and followed up through vention for late coronary stenosis or thrombosis

AND GUIDELINES
2011.123,124 has been accomplished percutaneously and surgi-
— A recent Japanese multicenter cohort study cally (eg, CABG).124,128
of 1006 individuals identified risk factors
Global Burden of KD
for 10-year incidence of coronary events
• The annual incidence of KD is highest in Japan,
(thrombosis, stenosis, obstruction, acute
at 308.0 per 100 000 children <5 years of age
ischemic events, or coronary intervention).125
in 2014, followed by South Korea at 194.7 per
Significant risk factors included giant-sized
100 000 children <5 years of age in 2014 and
aneurysm (HR, 8.9 [95% CI, 5.1–15.4]),
Taiwan at 55.9 per 100 000 in children <5 years
male sex (HR, 2.8 [95% CI, 1.7–4.8]), and
of age for the period 2000 to 2014.120,129,130
resistance to IVIG therapy (HR, 2.2 [95% CI,
National incidence data are lacking for China,
1.4–3.6]).
but the most recent estimates for Shanghai are
— Among 261 adults <40 years old with ACS
71.9 per 100 000 children <5 years of age in
who underwent coronary angiography in
2012.131
San Diego, CA, from 2005 to 2009, 5% had
• In Japan, the cumulative incidence of KD at age
aneurysms consistent with late sequelae of
10 years has been calculated with national survey
KD.126
data as >1%, at 1.5 per 100 boys and 1.2 per 100
Treatment and Control girls for 2007 to 2010.132 Using different meth-
• Treatment of acute KD rests on diminishing the odology with complete capture of cases through
inflammatory response with IVIG, which clearly the national health insurance program, Taiwan
reduces the incidence of coronary artery aneu- recorded a cumulative incidence of 2.78% by age
rysms. Aspirin is routinely used for its anti-inflam- 5 years in 2014.130
matory and antiplatelet effects, but it does not • The incidence of KD is lower in Canada, at 19.6
reduce the incidence of coronary artery aneu- per 100 000 children <5 years of age for the
rysms.106 On the basis of a Cochrane review, addi- period 2004 to 2014, and in European countries,
tion of prednisolone to the standard IVIG regimen such as Italy with 14.7 per 100 000 children <5
could further reduce the incidence of coronary years of age in 2008 to 2013, Spain with 8 per
Downloaded from http://ahajournals.org by on February 7, 2019

artery abnormalities (RR, 0.29 [95% CI, 0.18– 100 000 children <5 years of age in 2004 to 2014,
0.46]), but the applicability of these data to non- and Germany with 7.2 per 100 000 children <5
Asian and less severe KD cases is not certain.127 years of age in 2011 to 2012.111,133–136
Other anti-inflammatory treatments have also • The incidence of KD is rising worldwide, with
been used, based on limited data.106 potential contributions from improved recogni-
• Management of established coronary artery aneu- tion, diagnosis of incomplete KD more often, and
rysms in the short- and long-term is centered on true increasing incidence.120,130,135

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e279

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Table 15-1.  Congenital Cardiovascular Defects

CLINICAL STATEMENTS

Estimated Prevalence, Mortality, 2016, All Hospital Discharges,

AND GUIDELINES

Population Group 2002, All Ages Ages* 2014, All Ages

Both sexes 2.4 million137 3063 39 000
Males … 1670 (54.5%)† 21 000
Females … 1393 (45.5%)† 18 000
NH white males … 973 …
NH white females … 821 …
NH black males … 284 …
NH black females … 248 …
Hispanic males … 322 …
Hispanic females … 245 …
NH Asian or Pacific Islander males … 66 …
NH Asian or Pacific Islander females … 54 …
NH American Indian or Alaska Native … 38 …

Ellipses (…) indicate data not available; and NH, non-Hispanic.

*Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted
with caution because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses,
surveys, and birth certificates. Studies have shown underreporting on death certificates of American Indian or Alaska Native,
Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total congenital cardiovascular mortality that is for males vs females.
Sources: Mortality: Centers for Disease Control and Prevention/National Center for Health Statistics, 2016 Mortality Multiple
Cause-of-Death—United States. These data represent underlying cause of death only. Hospital discharges: Healthcare Cost and
Utilization Project, National (Nationwide) Inpatient Sample, 2014, Agency for Healthcare Research and Quality; data include those
inpatients discharged alive, dead, or status unknown.

Table 15-2.  Annual Birth Prevalence of CCDs in the United States15,21

Downloaded from http://ahajournals.org by on February 7, 2019

Estimated Number
Rate per 1000 (Variable With
Type of Presentation Live Births Yearly Birth Rate)
Fetal loss Unknown Unknown
Invasive procedure during the 2.4 9200
first year
Detected during first year* 8 36 000
Bicuspid aortic valve 13.7 54 800

CCD indicates congenital cardiovascular defect.

*Includes stillbirths and pregnancy termination at <20 weeks’ gestation;
includes some defects that resolve spontaneously or do not require treatment.

e280 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Table 15-3.  Estimated Prevalence of CCDs and Percent Distribution by Type, United States, 2002* (in Thousands)

CLINICAL STATEMENTS
Prevalence, N Percent of Total

AND GUIDELINES
Type Total Children Adults Total Children Adults
Total 994 463 526 100 100 100
VSD† 199 93 106 20.1 20.1 20.1
ASD 187 78 109 18.8 16.8 20.6
Patent ductus arteriosus 144 58 86 14.2 12.4 16.3
Valvular pulmonic stenosis 134 58 76 13.5 12.6 14.4
Coarctation of aorta 76 31 44 7.6 6.8 8.4
Valvular aortic stenosis 54 25 28 5.4 5.5 5.2
TOF 61 32 28 6.1 7 5.4
AV septal defect 31 18 13 3.1 3.9 2.5
TGA 26 17 9 2.6 3.6 1.8
Hypoplastic right heart syndrome 22 12 10 2.2 2.5 1.9
Double-outlet RV 9 9 0 0.9 1.9 0.1
Single ventricle 8 6 2 0.8 1.4 0.3
Anomalous pulmonary venous connection 9 5 3 0.9 1.2 0.6
Truncus arteriosus 9 6 2 0.7 1.3 0.5
HLHS 3 3 0 0.3 0.7 0
Other 22 12 10 2.1 2.6 1.9

ASD indicates atrial septal defect; AV, atrioventricular; CCD, congenital cardiovascular defect; HLHS, hypoplastic left heart
syndrome; RV, right ventricle; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; and VSD, ventricular septal
defect.
*Excludes an estimated 3 million bicuspid aortic valve prevalence (2 million in adults and 1 million in children).
†Small VSD, 117 000 (65 000 adults and 52 000 children); large VSD, 82 000 (41 000 adults and 41 000 children).
Source: Data derived from Hoffman et al.12
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e281

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Table 15-4.  Surgery for Congenital Heart Disease

CLINICAL STATEMENTS

Population,
AND GUIDELINES

Sample Weighted
Surgery for congenital heart disease, n 14 888 25 831
  Deaths, n 736 1253
  Mortality rate, % 4.9 4.8
By sex (81 missing in sample)
  Male, n 8127 14 109
  Deaths, n 420 714
   Mortality rate, % 5.2 5.1
  Female, n 6680 11 592
  Deaths, n 315 539
   Mortality rate, % 4.7 4.6
By type of surgery
  ASD secundum surgery, n 834 1448
  Deaths, n 3 6
   Mortality rate, % 0.4 0.4
  Norwood procedure for HLHS, n 161 286
  Deaths, n 42 72
   Mortality rate, % 26.1 25.2

In 2003, 25 000 cardiovascular operations for congenital cardiovascular

defects were performed on children <20 years of age. Inpatient mortality rate
after all types of cardiac surgery was 4.8%. Nevertheless, mortality risk varies
substantially for different defect types, from 0.4% for ASD repair to 25.2% for
first-stage palliation for HLHS. Fifty-five percent of operations were performed
in males. In unadjusted analysis, mortality after cardiac surgery was somewhat
higher for males than for females (5.1% vs 4.6%). ASD indicates atrial septal
Downloaded from http://ahajournals.org by on February 7, 2019

defect; and HLHS, hypoplastic left heart syndrome.

Source: Data derived from Ma et al.138

Chart 15-1. Trends in age-adjusted death rates attributable to congenital cardiovascular defects, 1999 to 2016.
Source: National Center for Health Statistics, National Vital Statistics System.

e282 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

CLINICAL STATEMENTS
AND GUIDELINES
Chart 15-2. Trends in age-adjusted death rates attributable to congenital cardiovascular defects by race/ethnicity, 1999 to 2016.
Source: National Center for Health Statistics, National Vital Statistics System.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 15-3. Trends in age-adjusted death rates attributable to congenital cardiovascular defects by sex, 1999 to 2016.
Source: National Center for Health Statistics, National Vital Statistics System.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e283

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15
CLINICAL STATEMENTS
AND GUIDELINES

Chart 15-4. Trends in age-specific death rates attributable to congenital cardiovascular defects by age at death, 1999 to 2016.
Source: National Center for Health Statistics, National Vital Statistics System.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 15-5. Age-adjusted death rates attributable to congenital cardiovascular defects, by sex and race/ethnicity, 2016.
NH indicates non-Hispanic.
Source: National Center for Health Statistics, National Vital Statistics System.

e284 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

CLINICAL STATEMENTS
AND GUIDELINES
Chart 15-6. Age-standardized global mortality rates of congenital heart anomalies per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.101 Printed with permission.
Copyright © 2017, University of Washington
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 15-7. Age-standardized global prevalence rates of congenital heart anomalies per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.101 Printed with permission. Copyright ©
2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e285

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

REFERENCES 16. Sawant SP, Amin AS, Bhat M. Prevalence, pattern and outcome of congen-
CLINICAL STATEMENTS

ital heart disease in Bhabha Atomic Research Centre Hospital, Mumbai.

1. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani
AND GUIDELINES

Indian J Pediatr. 2013;80:286–291. doi: 10.1007/s12098-012-0910-x

JA, del Nido P, Fasules JW, Graham TP Jr, Hijazi ZM, Hunt SA, King ME, 17. Botto LD, Correa A, Erickson JD. Racial and temporal variations in the
Landzberg MJ, Miner PD, Radford MJ, Walsh EP, Webb GD. ACC/AHA 2008 prevalence of heart defects. Pediatrics. 2001;107:E32.
guidelines for the management of adults with congenital heart disease: a
18. Koppel RI, Druschel CM, Carter T, Goldberg BE, Mehta PN, Talwar R,
report of the American College of Cardiology/American Heart Association
Bierman FZ. Effectiveness of pulse oximetry screening for congenital heart
Task Force on Practice Guidelines (writing committee to develop guidelines
disease in asymptomatic newborns. Pediatrics. 2003;111:451–455.
on the management of adults with congenital heart disease). Circulation.
19. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A.
2008;118:e714–e833. doi: 10.1161/CIRCULATIONAHA.108.190690
Prevalence of congenital heart defects in metropolitan Atlanta, 1998-
2. Fteropoulli T, Stygall J, Cullen S, Deanfield J, Newman SP. Quality of life of
2005. J Pediatr. 2008;153:807–813. doi: 10.1016/j.jpeds.2008.05.059
adult congenital heart disease patients: a systematic review of the literature.
20. Bedard T, Lowry RB, Sibbald B, Harder JR, Trevenen C, Horobec V, Dyck
Cardiol Young. 2013;23:473–485. doi: 10.1017/S1047951112002351
JD. Congenital heart defect case ascertainment by the Alberta Congenital
3. Mellion K, Uzark K, Cassedy A, Drotar D, Wernovsky G, Newburger
Anomalies Surveillance System. Birth Defects Res A Clin Mol Teratol.
JW, Mahony L, Mussatto K, Cohen M, Limbers C, Marino BS; Pediatric
2012;94:449–458. doi: 10.1002/bdra.23007
Cardiac Quality of Life Inventory Testing Study Consortium. Health-
21. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE,
related quality of life outcomes in children and adolescents with
Anderson P, Mason CA, Collins JS, Kirby RS, Correa A; National Birth
congenital heart disease. J Pediatr. 2014;164:781–788.e1. doi:
Defects Prevention Network. Updated national birth prevalence esti-
10.1016/j.jpeds.2013.11.066
mates for selected birth defects in the United States, 2004-2006.
4. Karsdorp PA, Everaerd W, Kindt M, Mulder BJ. Psychological and cog-
Birth Defects Res A Clin Mol Teratol. 2010;88:1008–1016. doi:
nitive functioning in children and adolescents with congenital heart
10.1002/bdra.20735
disease: a meta-analysis. J Pediatr Psychol. 2007;32:527–541. doi:
22. Mai CT, Riehle-Colarusso T, O’Halloran A, Cragan JD, Olney RS, Lin A,
10.1093/jpepsy/jsl047
Feldkamp M, Botto LD, Rickard R, Anderka M, Ethen M, Stanton C,
5. Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor
Ehrhardt J, Canfield M; National Birth Defects Prevention Network.
JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH Jr, Li J, Smith SE,
Selected birth defects data from population-based birth defects surveil-
Bellinger DC, Mahle WT; on behalf of the American Heart Association
lance programs in the United States, 2005–2009: featuring critical con-
Congenital Heart Defects Committee, Council on Cardiovascular Disease
genital heart defects targeted for pulse oximetry screening. Birth Defects
in the Young, Council on Cardiovascular Nursing, and Stroke Council.
Res A Clin Mol Teratol. 2012;94:970–983.
Neurodevelopmental outcomes in children with congenital heart dis-
23. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll
ease: evaluation and management: a scientific statement from the
Cardiol. 2002;39:1890–1900.
American Heart Association. Circulation. 2012;126:1143–1172. doi:
24. Jortveit J, Øyen N, Leirgul E, Fomina T, Tell GS, Vollset SE, Eskedal L, Døhlen
10.1161/CIR.0b013e318265ee8a
6. Roche SL, Silversides CK. Hypertension, obesity, and coronary artery G, Birkeland S, Holmstrøm H. Trends in mortality of congenital heart
disease in the survivors of congenital heart disease. Can J Cardiol. defects. Congenit Heart Dis. 2016;11:160–168. doi: 10.1111/chd.12307
2013;29:841–848. doi: 10.1016/j.cjca.2013.03.021 25. Cnota JF, Gupta R, Michelfelder EC, Ittenbach RF. Congenital heart dis-
7. Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli ease infant death rates decrease as gestational age advances from
AJ. Changing mortality in congenital heart disease. J Am Coll Cardiol. 34 to 40 weeks. J Pediatr. 2011;159:761–765. doi: 10.1016/j.jpeds.
2010;56:1149–1157. doi: 10.1016/j.jacc.2010.03.085 2011.04.020
Downloaded from http://ahajournals.org by on February 7, 2019

8. Sable C, Foster E, Uzark K, Bjornsen K, Canobbio MM, Connolly 26. Swenson AW, Dechert RE, Schumacher RE, Attar MA. The effect of late
HM, Graham TP, Gurvitz MZ, Kovacs A, Meadows AK, Reid GJ, preterm birth on mortality of infants with major congenital heart defects.
Reiss JG, Rosenbaum KN, Sagerman PJ, Saidi A, Schonberg R, J Perinatol. 2012;32:51–54. doi: 10.1038/jp.2011.50
Shah S, Tong E, Williams RG; on behalf of the American Heart 27. Best KE, Tennant PWG, Rankin J. Survival, by birth weight and gestational
Association Congenital Heart Defects Committee of the Council age, in individuals with congenital heart disease: a population-based study.
on Cardiovascular Disease in the Young, Council on Cardiovascular J Am Heart Assoc. 2017;6:e005213. doi: 10.1161/JAHA.116.005213
Nursing, Council on Clinical Cardiology, and Council on Peripheral 28. Costello JM, Polito A, Brown DW, McElrath TF, Graham DA, Thiagarajan
Vascular Disease. Best practices in managing transition to adulthood RR, Bacha EA, Allan CK, Cohen JN, Laussen PC. Birth before 39 weeks’
for adolescents with congenital heart disease: the transition process gestation is associated with worse outcomes in neonates with heart dis-
and medical and psychosocial issues: a scientific statement from the ease. Pediatrics. 2010;126:277–284. doi: 10.1542/peds.2009-3640
American Heart Association. Circulation. 2011;123:1454–1485. doi: 29. Costello JM, Pasquali SK, Jacobs JP, He X, Hill KD, Cooper DS, Backer CL,
10.1161/CIR.0b013e3182107c56 Jacobs ML. Gestational age at birth and outcomes after neonatal car-
9. Gurvitz M, Valente AM, Broberg C, Cook S, Stout K, Kay J, Ting J, Kuehl diac surgery: an analysis of the Society of Thoracic Surgeons Congenital
K, Earing M, Webb G, Houser L, Opotowsky A, Harmon A, Graham Heart Surgery Database. Circulation. 2014;129:2511–2517. doi:
D, Khairy P, Gianola A, Verstappen A, Landzberg M; Alliance for Adult 10.1161/CIRCULATIONAHA.113.005864
Research in Congenital Cardiology (AARCC) and Adult Congenital Heart 30. Archer JM, Yeager SB, Kenny MJ, Soll RF, Horbar JD. Distribution of and
Association. Prevalence and predictors of gaps in care among adult con- mortality from serious congenital heart disease in very low birth weight
genital heart disease patients: HEART-ACHD (The Health, Education, infants. Pediatrics. 2011;127:293–299. doi: 10.1542/peds.2010-0418
and Access Research Trial). J Am Coll Cardiol. 2013;61:2180–2184. doi: 31. Shahian DM, Jacobs JP, Edwards FH, Brennan JM, Dokholyan RS, Prager
10.1016/j.jacc.2013.02.048 RL, Wright CD, Peterson ED, McDonald DE, Grover FL. The Society of
10. Warnes CA, Liberthson R, Danielson GK, Dore A, Harris L, Hoffman Thoracic Surgeons national database. Heart. 2013;99:1494–1501. doi:
JI, Somerville J, Williams RG, Webb GD. Task force 1: the chang- 10.1136/heartjnl-2012-303456
ing profile of congenital heart disease in adult life. J Am Coll Cardiol. 32. The Society of Thoracic Surgeons (STS) National Database: Congenital
2001;37:1170–1175. Heart Surgery Database participants, Spring 2017 Harvest. Society of
11. Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache Thoracic Surgeons website. https://www.sts.org/sites/default/files/docu-
M. Lifetime prevalence of congenital heart disease in the general ments/CHSD_ExecutiveSummary_AllPatients_Spring2017.pdf. Accessed
population from 2000 to 2010. Circulation. 2014;130:749–756. doi: November 5, 2017.
10.1161/CIRCULATIONAHA.113.008396 33. Jacobs ML, Jacobs JP, Hill KD, Hornik C, O’Brien SM, Pasquali SK, Vener
12. Hoffman JI, Kaplan S, Liberthson RR. Prevalence of congenital heart dis- D, Kumar SR, Habib RH, Shahian DM, Edwards FH, Fernandez FG. The
ease. Am Heart J. 2004;147:425–439. doi: 10.1016/j.ahj.2003.05.003 Society of Thoracic Surgeons Congenital Heart Surgery Database:
13. Deleted in proof. 2017 update on research. Ann Thorac Surg. 2017;104:731–741. doi:
14. Deleted in proof. 10.1016/j.athoracsur.2017.07.001
15. van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, 34. Spector LG, Menk JS, Knight JH, McCracken C, Thomas AS, Vinocur JM,
Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart Oster ME, St Louis JD, Moller JH, Kochilas L. Trends in long-term mortality
disease worldwide: a systematic review and meta-analysis. J Am Coll after congenital heart surgery. J Am Coll Cardiol. 2018;71:2434–2446.
Cardiol. 2011;58:2241–2247. doi: 10.1016/j.jacc.2011.08.025 doi: 10.1016/j.jacc.2018.03.491

e286 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

35. Hoashi T, Miyata H, Murakami A, Hirata Y, Hirose K, Matsumura G, 52. Faraoni D, Nasr VG, DiNardo JA. Overall hospital cost estimates

CLINICAL STATEMENTS
Ichikawa H, Sawa Y, Takamoto S. The current trends of mortality fol- in children with congenital heart disease: analysis of the 2012

AND GUIDELINES
lowing congenital heart surgery: the Japan Congenital Cardiovascular Kid’s Inpatient Database. Pediatr Cardiol. 2016;37:37–43. doi:
Surgery Database. Interact Cardiovasc Thorac Surg. 2015;21:151–156. 10.1007/s00246-015-1235-0
doi: 10.1093/icvts/ivv109 53. Dean PN, Hillman DG, McHugh KE, Gutgesell HP. Inpatient costs and
36. Greutmann M, Tobler D, Kovacs AH, Greutmann-Yantiri M, Haile SR, charges for surgical treatment of hypoplastic left heart syndrome.
Held L, Ivanov J, Williams WG, Oechslin EN, Silversides CK, Colman Pediatrics. 2011;128:e1181–e1186. doi: 10.1542/peds.2010-3742
JM. Increasing mortality burden among adults with complex con- 54. Pasquali SK, Sun JL, d’Almada P, Jaquiss RD, Lodge AJ, Miller N, Kemper
genital heart disease. Congenit Heart Dis. 2015;10:117–127. doi: AR, Lannon CM, Li JS. Center variation in hospital costs for patients
10.1111/chd.12201 undergoing congenital heart surgery. Circ Cardiovasc Qual Outcomes.
37. National Center for Health Statistics. Centers for Disease Control and 2011;4:306–312. doi: 10.1161/CIRCOUTCOMES.110.958959
Prevention website. National Vital Statistics System: public use data file 55. Mackie AS, Tran DT, Marelli AJ, Kaul P. Cost of congenital heart disease
documentation: mortality multiple cause-of-death micro-data files, 2016. hospitalizations in Canada: a population-based study. Can J Cardiol.
https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed 2017;33:792–798. doi: 10.1016/j.cjca.2017.01.024
May 21, 2018. 56. Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR, Elixson
38. Oster ME, Strickland MJ, Mahle WT. Racial and ethnic disparities in M, Warnes CA, Webb CL. Noninherited risk factors and congenital
post-operative mortality following congenital heart surgery. J Pediatr. cardiovascular defects: current knowledge: a scientific statement from
2011;159:222–226. doi: 10.1016/j.jpeds.2011.01.060 the American Heart Association Council on Cardiovascular Disease
39. Chan T, Pinto NM, Bratton SL. Racial and insurance disparities in hos- in the Young: endorsed by the American Academy of Pediatrics.
pital mortality for children undergoing congenital heart surgery. Pediatr Circulation. 2007;115:2995–3014. doi: 10.1161/CIRCULATIONAHA.
Cardiol. 2012;33:1026–1039. doi: 10.1007/s00246-012-0221-z 106.183216
40. Lasa JJ, Cohen MS, Wernovsky G, Pinto NM. Is race associated with 57. Patel SS, Burns TL. Nongenetic risk factors and congenital heart defects.
morbidity and mortality after hospital discharge among neonates Pediatr Cardiol. 2013;34:1535–1555. doi: 10.1007/s00246-013-0775-4
undergoing heart surgery? Pediatr Cardiol. 2013;34:415–423. doi: 58. Herskind AM, Almind Pedersen D, Christensen K. Increased prevalence of
10.1007/s00246-012-0475-5 congenital heart defects in monozygotic and dizygotic twins. Circulation.
41. Castellanos DA, Herrington C, Adler S, Haas K, Ram Kumar S, Kung 2013;128:1182–1188. doi: 10.1161/CIRCULATIONAHA.113.002453
GC. Home monitoring program reduces mortality in high-risk sociode- 59. Pettit KE, Merchant M, Machin GA, Tacy TA, Norton ME. Congenital heart
mographic single-ventricle patients [published correction appears in defects in a large, unselected cohort of monochorionic twins. J Perinatol.
Pediatr Cardiol. 2017;38:206]. Pediatr Cardiol. 2016;37:1575–1580. doi: 2013;33:457–461. doi: 10.1038/jp.2012.145
10.1007/s00246-016-1472-x 60. Snijder CA, Vlot IJ, Burdorf A, Obermann-Borst SA, Helbing WA,
42. Gilboa SM, Salemi JL, Nembhard WN, Fixler DE, Correa A. Mortality Wildhagen MF, Steegers EA, Steegers-Theunissen RP. Congenital heart
resulting from congenital heart disease among children and adults in the defects and parental occupational exposure to chemicals. Hum Reprod.
United States, 1999 to 2006. Circulation. 2010;122:2254–2263. doi: 2012;27:1510–1517. doi: 10.1093/humrep/des043
10.1161/CIRCULATIONAHA.110.947002 61. Wilson PD, Loffredo CA, Correa-Villaseñor A, Ferencz C. Attributable frac-
43. Oster ME, Lee KA, Honein MA, Riehle-Colarusso T, Shin M, Correa tion for cardiac malformations. Am J Epidemiol. 1998;148:414–423.
A. Temporal trends in survival among infants with critical con- 62. Lee LJ, Lupo PJ. Maternal smoking during pregnancy and the risk of con-
genital heart defects. Pediatrics. 2013;131:e1502–e1508. doi: genital heart defects in offspring: a systematic review and metaanalysis.
10.1542/peds.2012-3435 Pediatr Cardiol. 2013;34:398–407. doi: 10.1007/s00246-012-0470-x
Downloaded from http://ahajournals.org by on February 7, 2019

44. Boneva RS, Botto LD, Moore CA, Yang Q, Correa A, Erickson JD. Mortality 63. Sullivan PM, Dervan LA, Reiger S, Buddhe S, Schwartz SM. Risk
associated with congenital heart defects in the United States: trends and of congenital heart defects in the offspring of smoking mothers:
racial disparities, 1979-1997. Circulation. 2001;103:2376–2381. a population-based study. J Pediatr. 2015;166:978–984.e2. doi:
45. Marino BS, Bird GL, Wernovsky G. Diagnosis and management of the 10.1016/j.jpeds.2014.11.042
newborn with suspected congenital heart disease. Clin Perinatol. 64. Alverson CJ, Strickland MJ, Gilboa SM, Correa A. Maternal smoking
2001;28:91–136. and congenital heart defects in the Baltimore-Washington Infant Study.
46. Czosek RJ, Anderson JB, Heaton PC, Cassedy A, Schnell B, Cnota JF. Staged Pediatrics. 2011;127:e647–e653. doi: 10.1542/peds.2010-1399
palliation of hypoplastic left heart syndrome: trends in mortality, cost, and 65. Malik S, Cleves MA, Honein MA, Romitti PA, Botto LD, Yang S, Hobbs
length of stay using a national database from 2000 through 2009. Am J CA; National Birth Defects Prevention Study. Maternal smoking and
Cardiol. 2013;111:1792–1799. doi: 10.1016/j.amjcard.2013.02.039 congenital heart defects. Pediatrics. 2008;121:e810–e816. doi:
47. Ohye RG, Sleeper LA, Mahony L, Newburger JW, Pearson GD, Lu M, 10.1542/peds.2007-1519
Goldberg CS, Tabbutt S, Frommelt PC, Ghanayem NS, Laussen PC, Rhodes 66. Patel SS, Burns TL, Botto LD, Riehle-Colarusso TJ, Lin AE, Shaw GM,
JF, Lewis AB, Mital S, Ravishankar C, Williams IA, Dunbar-Masterson C, Romitti PA; National Birth Defects Prevention Study. Analysis of selected
Atz AM, Colan S, Minich LL, Pizarro C, Kanter KR, Jaggers J, Jacobs JP, maternal exposures and non-syndromic atrioventricular septal defects in
Krawczeski CD, Pike N, McCrindle BW, Virzi L, Gaynor JW; Pediatric Heart the National Birth Defects Prevention Study, 1997-2005. Am J Med Genet
Network Investigators. Comparison of shunt types in the Norwood proce- A. 2012;158A:2447–2455. doi: 10.1002/ajmg.a.35555
dure for single-ventricle lesions. N Engl J Med. 2010;362:1980–1992. doi: 67. Tanner JP, Salemi JL, Stuart AL, Yu H, Jordan MM, DuClos C, Cavicchia
10.1056/NEJMoa0912461 P, Correia JA, Watkins SM, Kirby RS. Associations between exposure
48. Karamlou T, Diggs BS, Person T, Ungerleider RM, Welke KF. National prac- to ambient benzene and PM(2.5) during pregnancy and the risk of
tice patterns for management of adult congenital heart disease: opera- selected birth defects in offspring. Environ Res. 2015;142:345–353. doi:
tion by pediatric heart surgeons decreases in-hospital death. Circulation. 10.1016/j.envres.2015.07.006
2008;118:2345–2352. doi: 10.1161/CIRCULATIONAHA.108.776963 68. Mateja WA, Nelson DB, Kroelinger CD, Ruzek S, Segal J. The association
49. Kempny A, Diller GP, Dimopoulos K, Alonso-Gonzalez R, Uebing A, between maternal alcohol use and smoking in early pregnancy and con-
Li W, Babu-Narayan S, Swan L, Wort SJ, Gatzoulis MA. Determinants genital cardiac defects. J Womens Health (Larchmt). 2012;21:26–34. doi:
of outpatient clinic attendance amongst adults with congenital 10.1089/jwh.2010.2582
heart disease and outcome. Int J Cardiol. 2016;203:245–250. doi: 69. Baardman ME, Kerstjens-Frederikse WS, Corpeleijn E, de Walle HE,
10.1016/j.ijcard.2015.10.081 Hofstra RM, Berger RM, Bakker MK. Combined adverse effects of
50. Dorfman AT, Marino BS, Wernovsky G, Tabbutt S, Ravishankar C, Godinez maternal smoking and high body mass index on heart development
RI, Priestley M, Dodds KM, Rychik J, Gruber PJ, Gaynor JW, Levy RJ, Nicolson in offspring: evidence for interaction? Heart. 2012;98:474–479. doi:
SC, Montenegro LM, Spray TL, Dominguez TE. Critical heart disease in the 10.1136/heartjnl-2011-300822
neonate: presentation and outcome at a tertiary care center. Pediatr Crit 70. Cai GJ, Sun XX, Zhang L, Hong Q. Association between mater-
Care Med. 2008;9:193–202. doi: 10.1097/PCC.0b013e318166eda5 nal body mass index and congenital heart defects in offspring: a
51. Arth AC, Tinker SC, Simeone RM, Ailes EC, Cragan JD, Grosse SD. systematic review. Am J Obstet Gynecol. 2014;211:91–117. doi:
Inpatient hospitalization costs associated with birth defects among per- 10.1016/j.ajog.2014.03.028
sons of all ages: United States, 2013. MMWR Morb Mortal Wkly Rep. 71. Waller DK, Shaw GM, Rasmussen SA, Hobbs CA, Canfield MA,
2017;66:41–46. doi: 10.15585/mmwr.mm6602a1 Siega-Riz AM, Gallaway MS, Correa A; National Birth Defects

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e287

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Prevention Study. Prepregnancy obesity as a risk factor for structural 88. Ailes EC, Gilboa SM, Honein MA, Oster ME. Estimated number of
CLINICAL STATEMENTS

birth defects. Arch Pediatr Adolesc Med. 2007;161:745–750. doi: infants detected and missed by critical congenital heart defect screening.
AND GUIDELINES

10.1001/archpedi.161.8.745 Pediatrics. 2015;135:1000–1008. doi: 10.1542/peds.2014-3662

72. Øyen N, Diaz LJ, Leirgul E, Boyd HA, Priest J, Mathiesen ER, Quertermous 89. Hartman RJ, Rasmussen SA, Botto LD, Riehle-Colarusso T, Martin
T, Wohlfahrt J, Melbye M. Prepregnancy diabetes and offspring risk CL, Cragan JD, Shin M, Correa A. The contribution of chromo-
of congenital heart disease: a nationwide cohort study. Circulation. somal abnormalities to congenital heart defects: a population-
2016;133:2243–2253. doi: 10.1161/CIRCULATIONAHA.115.017465 based study. Pediatr Cardiol. 2011;32:1147–1157. doi: 10.1007/
73. Simeone RM, Devine OJ, Marcinkevage JA, Gilboa SM, Razzaghi H, s00246-011-0034-5
Bardenheier BH, Sharma AJ, Honein MA. Diabetes and congenital heart 90. Peterson C, Ailes E, Riehle-Colarusso T, Oster ME, Olney RS, Cassell CH,
defects: a systematic review, meta-analysis, and modeling project. Am J Fixler DE, Carmichael SL, Shaw GM, Gilboa SM. Late detection of criti-
Prev Med. 2015;48:195–204. doi: 10.1016/j.amepre.2014.09.002 cal congenital heart disease among US infants: estimation of the poten-
74. Priest JR, Yang W, Reaven G, Knowles JW, Shaw GM. Maternal midpreg- tial impact of proposed universal screening using pulse oximetry. JAMA
nancy glucose levels and risk of congenital heart disease in offspring. JAMA Pediatr. 2014;168:361–370. doi: 10.1001/jamapediatrics.2013.4779
Pediatr. 2015;169:1112–1116. doi: 10.1001/jamapediatrics.2015.2831 91. Abouk R, Grosse SD, Ailes EC, Oster ME. Association of US state im-
75. Auger N, Fraser WD, Healy-Profitós J, Arbour L. Association between pre- plementation of newborn screening policies for critical congenital
eclampsia and congenital heart defects. JAMA. 2015;314:1588–1598. heart disease with early infant cardiac deaths [published correction ap-
doi: 10.1001/jama.2015.12505 pears in JAMA. 2018;320:1288]. JAMA. 2017;318:2111–2118. doi:
76. Scanlon KS, Ferencz C, Loffredo CA, Wilson PD, Correa-Villaseñor A, 10.1001/jama.2017.17627
Khoury MJ, Willett WC. Preconceptional folate intake and malformations 92. Jawin V, Ang HL, Omar A, Thong MK. Beyond critical congenital heart
of the cardiac outflow tract: Baltimore-Washington Infant Study Group. disease: newborn screening using pulse oximetry for neonatal sep-
Epidemiology. 1998;9:95–98. sis and respiratory diseases in a middle-income country. PLoS One.
77. Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L. Prevalence of severe 2015;10:e0137580. doi: 10.1371/journal.pone.0137580
congenital heart disease after folic acid fortification of grain products: 93. Wang X, Li P, Chen S, Xi L, Guo Y, Guo A, Sun K. Influence of genes
time trend analysis in Quebec, Canada. BMJ. 2009;338:b1673. doi: and the environment in familial congenital heart defects. Mol Med Rep.
10.1136/bmj.b1673 2014;9:695–700. doi: 10.3892/mmr.2013.1847
78. Dong DY, Binongo JN, Kancherla V. Maternal chlamydia infection during 94. Nora JJ, Dodd PF, McNamara DG, Hattwick MA, Leachman RD, Cooley
pregnancy and risk of cyanotic congenital heart defects in the offspring. DA. Risk to offspring of parents with congenital heart defects. JAMA.
Matern Child Health J. 2016;20:66–76. doi: 10.1007/s10995-015-1804-0 1969;209:2052–2053.
79. Oster ME, Riehle-Colarusso T, Correa A. An update on cardiovascular mal- 95. Korbel JO, Tirosh-Wagner T, Urban AE, Chen XN, Kasowski M, Dai L,
Grubert F, Erdman C, Gao MC, Lange K, Sobel EM, Barlow GM, Aylsworth
formations in congenital rubella syndrome. Birth Defects Res A Clin Mol
AS, Carpenter NJ, Clark RD, Cohen MY, Doran E, Falik-Zaccai T, Lewin
Teratol. 2010;88:1–8. doi: 10.1002/bdra.20621
SO, Lott IT, McGillivray BC, Moeschler JB, Pettenati MJ, Pueschel SM,
80. Zheng JY, Tian HT, Zhu ZM, Li B, Han L, Jiang SL, Chen Y, Li DT, He JC,
Rao KW, Shaffer LG, Shohat M, Van Riper AJ, Warburton D, Weissman S,
Zhao Z, Cao Y, Qiu YG, Li TC. Prevalence of symptomatic congenital heart
Gerstein MB, Snyder M, Korenberg JR. The genetic architecture of Down
disease in Tibetan school children. Am J Cardiol. 2013;112:1468–1470.
syndrome phenotypes revealed by high-resolution analysis of human
doi: 10.1016/j.amjcard.2013.07.028
segmental trisomies. Proc Natl Acad Sci U S A. 2009;106:12031–12036.
81. US Department of Health and Human Services, Secretary’s Advisory
doi: 10.1073/pnas.0813248106
Downloaded from http://ahajournals.org by on February 7, 2019

Committee on Heritable Disorders in Newborns and Children. The addi-

96. Soemedi R, Wilson IJ, Bentham J, Darlay R, Töpf A, Zelenika D, Cosgrove
tion of critical congenital cyanotic heart disease to the committee’s rec-
C, Setchfield K, Thornborough C, Granados-Riveron J, Blue GM, Breckpot
ommended uniform screening panel. October 15, 2010. https://www.
J, Hellens S, Zwolinkski S, Glen E, Mamasoula C, Rahman TJ, Hall D,
hrsa.gov/sites/default/files/hrsa/advisory-committees/heritable-disorders/
Rauch A, Devriendt K, Gewillig M, O’ Sullivan J, Winlaw DS, Bu’Lock F,
reports-recommendations/letter-to-sec-congenital-cyanotic.pdf. Accessed
Brook JD, Bhattacharya S, Lathrop M, Santibanez-Koref M, Cordell HJ,
July 31, 2014.
Goodship JA, Keavney BD. Contribution of global rare copy-number vari-
82. Mahle WT, Martin GR, Beekman RH 3rd, Morrow WR; Section on
ants to the risk of sporadic congenital heart disease. Am J Hum Genet.
Cardiology and Cardiac Surgery Executive Committee. Endorsement of
2012;91:489–501. doi: 10.1016/j.ajhg.2012.08.003
Health and Human Services recommendation for pulse oximetry screening
97. Zaidi S, Brueckner M. Genetics and genomics of congenital heart
for critical congenital heart disease. Pediatrics. 2012;129:190–192. doi: disease. Circ Res. 2017;120:923–940. doi: 10.1161/CIRCRESAHA.
10.1542/peds.2011-3211 116.309140
83. Glidewell J, Olney RS, Hinton C, Pawelski J, Sontag M, Wood T, Kucik 98. Preuss C, Capredon M, Wünnemann F, Chetaille P, Prince A, Godard
JE, Daskalov R, Hudson J; Centers for Disease Control and Prevention B, Leclerc S, Sobreira N, Ling H, Awadalla P, Thibeault M, Khairy P,
(CDC). State legislation, regulations, and hospital guidelines for newborn Samuels ME, Andelfinger G; MIBAVA Leducq Consortium. Family based
screening for critical congenital heart defects: United States, 2011-2014. whole exome sequencing reveals the multifaceted role of notch signal-
MMWR Morb Mortal Wkly Rep. 2015;64:625–630. ing in congenital heart disease. PLoS Genet. 2016;12:e1006335. doi:
84. de-Wahl Granelli A, Wennergren M, Sandberg K, Mellander M, Bejlum 10.1371/journal.pgen.1006335
C, Inganäs L, Eriksson M, Segerdahl N, Agren A, Ekman-Joelsson BM, 99. Zaidi S, Choi M, Wakimoto H, Ma L, Jiang J, Overton JD, Romano-
Sunnegårdh J, Verdicchio M, Ostman-Smith I. Impact of pulse oxim- Adesman A, Bjornson RD, Breitbart RE, Brown KK, Carriero NJ, Cheung
etry screening on the detection of duct dependent congenital heart dis- YH, Deanfield J, DePalma S, Fakhro KA, Glessner J, Hakonarson H,
ease: a Swedish prospective screening study in 39,821 newborns. BMJ. Italia MJ, Kaltman JR, Kaski J, Kim R, Kline JK, Lee T, Leipzig J, Lopez
2009;338:a3037. doi: 10.1136/bmj.a3037 A, Mane SM, Mitchell LE, Newburger JW, Parfenov M, Pe’er I, Porter
85. Meberg A, Brügmann-Pieper S, Due R Jr, Eskedal L, Fagerli I, Farstad G, Roberts AE, Sachidanandam R, Sanders SJ, Seiden HS, State MW,
T, Frøisland DH, Sannes CH, Johansen OJ, Keljalic J, Markestad T, Subramanian S, Tikhonova IR, Wang W, Warburton D, White PS,
Nygaard EA, Røsvik A, Silberg IE. First day of life pulse oximetry screen- Williams IA, Zhao H, Seidman JG, Brueckner M, Chung WK, Gelb BD,
ing to detect congenital heart defects [published correction appears Goldmuntz E, Seidman CE, Lifton RP. De novo mutations in histone-
in J Pediatr. 2009;154:629]. J Pediatr. 2008;152:761–765. doi: modifying genes in congenital heart disease. Nature. 2013;498:220–
10.1016/j.jpeds.2007.12.043 223. doi: 10.1038/nature12141
86. Riede FT, Wörner C, Dähnert I, Möckel A, Kostelka M, Schneider P. 100. Hoang TT, Goldmuntz E, Roberts AE, Chung WK, Kline JK, Deanfield
Effectiveness of neonatal pulse oximetry screening for detection of JE, Giardini A, Aleman A, Gelb BD, Mac Neal M, Porter GA Jr, Kim
critical congenital heart disease in daily clinical routine: results from a R, Brueckner M, Lifton RP, Edman S, Woyciechowski S, Mitchell LE,
prospective multicenter study. Eur J Pediatr. 2010;169:975–981. doi: Agopian AJ. The Congenital Heart Disease Genetic Network Study: co-
10.1007/s00431-010-1160-4 hort description. PLoS One. 2018;13:e0191319. doi: 10.1371/journal.
87. Peterson C, Grosse SD, Oster ME, Olney RS, Cassell CH. Cost-effectiveness pone.0191319
of routine screening for critical congenital heart disease in US newborns. 101. Global Burden of Disease Study 2016. Global Burden of Disease Study
Pediatrics. 2013;132:e595–e603. doi: 10.1542/peds.2013-0332 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and

e288 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

Evaluation (IHME), University of Washington; 2016. http://ghdx.health- Kawasaki disease in Japan, 2013–2014. Pediatr Int. 2018;60:581–587.

CLINICAL STATEMENTS
data.org/gbd-results-tool. Accessed May 1, 2018. doi: 10.1111/ped.13544

AND GUIDELINES
102. Kumar A, Singh S. BCG site reactivation in Kawasaki disease. Arthritis 121. García-Pavón S, Yamazaki-Nakashimada MA, Báez M, Borjas-Aguilar KL,
Rheumatol. 2016;68:2026. doi: 10.1002/art.39708 Murata C. Kawasaki disease complicated with macrophage activation
103. Gordon JB, Daniels LB, Kahn AM, Jimenez-Fernandez S, Vejar M, syndrome: a systematic review. J Pediatr Hematol Oncol. 2017;39:445–
Numano F, Burns JC. The spectrum of cardiovascular lesions requiring 451. doi: 10.1097/MPH.0000000000000872
intervention in adults after Kawasaki disease. JACC Cardiovasc Interv. 122. Lin MT, Sun LC, Wu ET, Wang JK, Lue HC, Wu MH. Acute and late coro-
2016;9:687–696. doi: 10.1016/j.jcin.2015.12.011 nary outcomes in 1073 patients with Kawasaki disease with and without
104. Xie X, Shi X, Liu M. The roles of genetic factors in Kawasaki dis- intravenous γ-immunoglobulin therapy. Arch Dis Child. 2015;100:542–
ease: a systematic review and meta-analysis of genetic asso- 547. doi: 10.1136/archdischild-2014-306427
ciation studies. Pediatr Cardiol. 2018;39:207–225. doi: 10.1007/ 123. Manlhiot C, Millar K, Golding F, McCrindle BW. Improved classifica-
s00246-017-1760-0 tion of coronary artery abnormalities based only on coronary artery z-
105. Nakamura Y. Kawasaki disease: epidemiology and the lessons from it. Int scores after Kawasaki disease. Pediatr Cardiol. 2010;31:242–249. doi:
J Rheum Dis. 2018;21:16–19. doi: 10.1111/1756-185X.13211 10.1007/s00246-009-9599-7
106. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz 124. Suda K, Iemura M, Nishiono H, Teramachi Y, Koteda Y, Kishimoto
M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, S, Kudo Y, Itoh S, Ishii H, Ueno T, Tashiro T, Nobuyoshi M, Kato H,
Saji TT, Pahl E; on behalf of the American Heart Association Rheumatic Matsuishi T. Long-term prognosis of patients with Kawasaki dis-
Fever, Endocarditis, and Kawasaki Disease Committee of the Council ease complicated by giant coronary aneurysms: a single-institu-
on Cardiovascular Disease in the Young; Council on Cardiovascular and tion experience. Circulation. 2011;123:1836–1842. doi: 10.1161/
Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and CIRCULATIONAHA.110.978213
Council on Epidemiology and Prevention. Diagnosis, treatment, and 125. Miura M, Kobayashi T, Kaneko T, Ayusawa M, Fukazawa R, Fukushima
long-term management of Kawasaki disease: a scientific statement for N, Fuse S, Hamaoka K, Hirono K, Kato T, Mitani Y, Sato S, Shimoyama
health professionals from the American Heart Association. Circulation. S, Shiono J, Suda K, Suzuki H, Maeda J, Waki K, Kato H, Saji T,
2017;135:e927–e999. doi: 10.1161/CIR.0000000000000484 Yamagishi H, Ozeki A, Tomotsune M, Yoshida M, Akazawa Y, Aso K,
107. Yorifuji T, Tsukahara H, Doi H. Breastfeeding and risk of Kawasaki Doi S, Fukasawa Y, Furuno K, Hayabuchi Y, Hayashi M, Honda T, Horita
disease: a nationwide longitudinal survey in Japan. Pediatrics. N, Ikeda K, Ishii M, Iwashima S, Kamada M, Kaneko M, Katyama H,
2016;137:e20153919. doi: 10.1542/peds.2015-3919 Kawamura Y, Kitagawa A, Komori A, Kuraishi K, Masuda H, Matsuda
108. Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, S, Matsuzaki S, Mii S, Miyamoto T, Moritou Y, Motoki N, Nagumo K,
Schonberger LB. Hospitalizations for Kawasaki syndrome among children
Nakamura T, Nishihara E, Nomura Y, Ogata S, Ohashi H, Okumura K,
in the United States, 1997–2007. Pediatr Infect Dis J. 2010;29:483–488.
Omori D, Sano T, Suganuma E, Takahashi T, Takatsuki S, Takeda A, Terai
doi: 10.1097/INF.0b013e318cf8705
M, Toyono M, Watanabe K, Watanabe M, Yamamoto M, Yamamura K;
109. Holman RC, Christensen KY, Belay ED, Steiner CA, Effler PV, Miyamura
and the Z-score Project 2nd Stage Study Group. Association of severity
J, Forbes S, Schonberger LB, Melish M. Racial/ethnic differences in the
of coronary artery aneurysms in patients with Kawasaki disease and
incidence of Kawasaki syndrome among children in Hawaii. Hawaii Med
risk of later coronary events. JAMA Pediatr. 2018;172:e180030. doi:
J. 2010;69:194–197.
10.1001/jamapediatrics.2018.0030
110. Sudo D, Nakamura Y. Nationwide surveys show that the incidence of
126. Daniels LB, Tjajadi MS, Walford HH, Jimenez-Fernandez S, Trofimenko
recurrent Kawasaki disease in Japan has hardly changed over the last 30
V, Fick DB Jr, Phan HA, Linz PE, Nayak K, Kahn AM, Burns JC, Gordon
years. Acta Paediatr. 2017;106:796–800. doi: 10.1111/apa.13773
Downloaded from http://ahajournals.org by on February 7, 2019

JB. Prevalence of Kawasaki disease in young adults with suspect-

111. Manlhiot C, O’Shea S, Bernknopf B, LaBelle M, Chahal N, Dillenburg
ed myocardial ischemia. Circulation. 2012;125:2447–2453. doi:
RF, Lai LS, Bock D, Lew B, Masood S, Mathew M, McCrindle BW.
10.1161/CIRCULATIONAHA.111.082107
Epidemiology of Kawasaki disease in Canada 2004 to 2014: comparison
127. Wardle AJ, Connolly GM, Seager MJ, Tulloh RM. Corticosteroids for the
of surveillance using administrative data vs periodic medical record re-
treatment of Kawasaki disease in children. Cochrane Database Syst Rev.
view. Can J Cardiol. 2018;34:303–309. doi: 10.1016/j.cjca.2017.12.009
2017;1:CD011188. doi: 10.1002/14651858.CD011188.pub2
112. Maddox RA, Holman RC, Uehara R, Callinan LS, Guest JL, Schonberger
128. Dionne A, Bakloul M, Manlhiot C, McCrindle BW, Hosking M,
LB, Nakamura Y, Yashiro M, Belay ED. Recurrent Kawasaki disease: USA
Houde C, Pepelassis D, Dahdah N. Coronary artery bypass graft-
and Japan. Pediatr Int. 2015;57:1116–1120. doi: 10.1111/ped.12733
113. Taddio A, Rossi ED, Monasta L, et al. Describing Kawasaki shock syn- ing and percutaneous coronary intervention after Kawasaki disease:
drome: results from a retrospective study and literature review. Clin the Pediatric Canadian Series. Pediatr Cardiol. 2017;38:36–43. doi:
Rheumatol. 2017;36:223–228. doi: 10.1007/s10067-016-3316-8 10.1007/s00246-016-1480-x
114. Ogata S, Tremoulet AH, Sato Y, Ueda K, Shimizu C, Sun X, Jain S, 129. Kim GB, Park S, Eun LY, Han JW, Lee SY, Yoon KL, Yu JJ, Choi JW,
Silverstein L, Baker AL, Tanaka N, Ogihara Y, Ikehara S, Takatsuki S, Lee KY. Epidemiology and clinical features of Kawasaki disease in
Sakamoto N, Kobayashi T, Fuse S, Matsubara T, Ishii M, Saji T, Newburger South Korea, 2012-2014. Pediatr Infect Dis J. 2017;36:482–485. doi:
JW, Burns JC. Coronary artery outcomes among children with Kawasaki 10.1097/INF.0000000000001474
disease in the United States and Japan. Int J Cardiol. 2013;168:3825– 130. Wu MH, Lin MT, Chen HC, Kao FY, Huang SK. Postnatal risk of acquiring
3828. doi: 10.1016/j.ijcard.2013.06.027 Kawasaki disease: a nationwide birth cohort database study. J Pediatr.
115. Salgado AP, Ashouri N, Berry EK, Sun X, Jain S, Burns JC, Tremoulet AH. 2017;180:80–86.e2. doi: 10.1016/j.jpeds.2016.09.052
High risk of coronary artery aneurysms in infants younger than 6 months 131. Chen JJ, Ma XJ, Liu F, Yan WL, Huang MR, Huang M, Huang GY;
of age with Kawasaki disease. J Pediatr. 2017;185:112–116.e1. doi: Shanghai Kawasaki Disease Research Group. Epidemiologic features of
10.1016/j.jpeds.2017.03.025 Kawasaki disease in Shanghai from 2008 through 2012. Pediatr Infect
116. Satoh K, Wakejima Y, Gau M, Kiguchi T, Matsuda N, Takasawa R, Dis J. 2016;35:7–12. doi: 10.1097/INF.0000000000000914
Takasawa K, Nishioka M, Shimohira M. Risk of coronary artery lesions in 132. Nakamura Y, Yashiro M, Yamashita M, Aoyama N, Otaki U, Ozeki Y,
young infants with Kawasaki disease: need for a new diagnostic method. Sano T, Kojo T, Ae R, Aoyama Y, Makino N, Kotani K. Cumulative in-
Int J Rheum Dis. 2018;21:746–754. doi: 10.1111/1756-185X.13223 cidence of Kawasaki disease in Japan. Pediatr Int. 2018;60:19–22. doi:
117. Yamashita M, Ae R, Yashiro M, Aoyama Y, Sano T, Makino N, Nakamura 10.1111/ped.13450
Y. Difference in risk factors for subtypes of acute cardiac lesions result- 133. Jakob A, Whelan J, Kordecki M, Berner R, Stiller B, Arnold R, von Kries
ing from Kawasaki disease. Pediatr Cardiol. 2017;38:375–380. doi: R, Neumann E, Roubinis N, Robert M, Grohmann J, Höhn R, Hufnagel
10.1007/s00246-016-1525-1 M. Kawasaki disease in Germany: a prospective, population-based study
118. Holman RC, Curns AT, Belay ED, Steiner CA, Schonberger LB. Kawasaki adjusted for underreporting. Pediatr Infect Dis J. 2016;35:129–134. doi:
syndrome hospitalizations in the United States, 1997 and 2000. 10.1097/INF.0000000000000953
Pediatrics. 2003;112(pt 1):495–501. 134. Singh S, Vignesh P, Burgner D. The epidemiology of Kawasaki dis-
119. Chang RK. Hospitalizations for Kawasaki disease among children in the ease: a global update. Arch Dis Child. 2015;100:1084–1088. doi:
United States, 1988-1997. Pediatrics. 2002;109:e87. 10.1136/archdischild-2014-307536
120. Makino N, Nakamura Y, Yashiro M, Sano T, Ae R, Kosami K, Kojo T, 135. Cimaz R, Fanti E, Mauro A, Voller F, Rusconi F. Epidemiology
Aoyama Y, Kotani K, Yanagawa H. Epidemiological observations of of Kawasaki disease in Italy: surveillance from national

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e289

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 15

hospitalization records. Eur J Pediatr. 2017;176:1061–1065. doi: 10.1007/ 137. Gilboa SM, Devine OJ, Kucik JE, Oster ME, Riehle-Colarusso T, Nembhard
CLINICAL STATEMENTS

s00431-017-2947-3 WN, Xu P, Correa A, Jenkins K, Marelli AJ. Congenital heart defects in the
AND GUIDELINES

136. Sánchez-Manubens J, Antón J, Bou R, Iglesias E, Calzada-Hernandez J, United States: estimating the magnitude of the affected population in 2010.
Rodó X, Morguí JA; el Grupo de Trabajo en Enfermedad de Kawasaki Circulation. 2016;134:101–109. doi: 10.1161/CIRCULATIONAHA.115.019307
en Cataluña. Kawasaki disease is more prevalent in rural areas of 138. Ma M, Gauvreau K, Allan CK, Mayer JE Jr, Jenkins KJ. Causes of death
Catalonia (Spain) [in Spanish]. An Pediatr (Barc). 2017;87:226–231. doi: after congenital heart surgery. Ann Thorac Surg. 2007;83:1438–1445.
10.1016/j.anpedi.2016.12.009 doi: 10.1016/j.athoracsur.2006.10.073
Downloaded from http://ahajournals.org by on February 7, 2019

e290 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

16. DISORDERS OF HEART RHYTHM Abbreviations Used in Chapter 16 Continued

CLINICAL STATEMENTS
HD heart disease
See Table 16-1 and Charts 16-1 through 16-11

AND GUIDELINES
HF heart failure
HR hazard ratio
Click here to return to the Table of Contents ICD-9 International Classification of Diseases, 9th Revision
ICD-9-CM International Classification of Diseases, 9th Revision,
Clinical Modification

Arrhythmias (Disorders of Heart ICD-10 International Classification of Diseases, 10th Revision

IQR interquartile range
Rhythm) IRR incidence rate ratio
2016: Mortality—52 
015. Any-mention mortality— Look AHEAD Look: Action for Health in Diabetes
LVEF left ventricular ejection fraction
536 092.
LVH left ventricular hypertrophy
Abbreviations Used in Chapter 16 MESA Multi-Ethnic Study of Atherosclerosis
MET metabolic equivalent
ACCORD Action to Control Cardiovascular Risk in Diabetes MI myocardial infarction
AF atrial fibrillation NAMCS National Ambulatory Medical Care Survey
AMI acute myocardial infarction NCDR National Cardiovascular Data Registry
ARIC Atherosclerosis Risk in Communities NCHS National Center for Health Statistics
ASSERT Asymptomatic Atrial Fibrillation and Stroke Evaluation in NH non-Hispanic
Pacemaker Patients and the Atrial Fibrillation Reduction
NHAMCS National Hospital Ambulatory Medical Care Survey
Atrial Pacing Trial
NHDS National Hospital Discharge Survey
AV atrioventricular
NHLBI National Heart, Lung, and Blood Institute
BiomarCaRE Biomarker for Cardiovascular Risk Assessment in Europe
NIS National (Nationwide) Inpatient Sample
BMI body mass index
NSTEMI non–ST-segment–elevation myocardial infarction
BNP B-type natriuretic peptide
OHCA out-of-hospital cardiac arrest
BP blood pressure
OR odds ratio
CABG coronary artery bypass graft
ORBIT-AF Outcomes Registry for Better Informed Treatment of
CAD coronary artery disease
Atrial Fibrillation
CARDIA Coronary Artery Risk Development in Young Adults
OSA obstructive sleep apnea
CHA2DS2-VASc Clinical prediction rule for estimating the risk of stroke
PA physical activity
based on congestive heart failure, hypertension,
diabetes mellitus, and sex (1 point each); age ≥75 y and PAD peripheral artery disease
stroke/transient ischemic attack/thromboembolism (2 PAR population attributable risk
Downloaded from http://ahajournals.org by on February 7, 2019

points each); plus history of vascular disease, age 65–74 PINNACLE Practice Innovation and Clinical Excellence
y, and (female) sex category PREDIMED Prevención con Dieta Mediterránea
CHADS2 Clinical prediction rule for estimating the risk of stroke PREVEND Prevention of Renal and Vascular End-Stage Disease
based on congestive heart failure, hypertension, age QALY quality-adjusted life-year
≥75 y, diabetes mellitus (1 point each), and prior stroke/ REGARDS Reasons for Geographic and Racial Differences in
transient ischemic attack/thromboembolism (2 points) Stroke
CHARGE-AF Cohorts for Heart and Aging Research in Genomic RE-LY Randomized Evaluation of Long-term Anticoagulant
Epidemiology–Atrial Fibrillation Therapy
CHD coronary heart disease RR relative risk
CHS Cardiovascular Health Study SBP systolic blood pressure
CI confidence interval SCD sudden cardiac death
CKD chronic kidney disease SES socioeconomic status
CPAP continuous positive airway pressure SNP single-nucleotide polymorphism
CVD cardiovascular disease STEMI ST-segment–elevation myocardial infarction
DALY disability-adjusted life-year STROKESTOP Systematic ECG Screening for Atrial Fibrillation Among
DM diabetes mellitus 75-Year-Old Subjects in the Region of Stockholm and
DNA deoxyribonucleic acid Halland, Sweden
ECG electrocardiogram SVT supraventricular tachycardia
ED emergency department UI uncertainty interval
EF ejection fraction USD US dollars
EMPHASIS-HF Eplerenone in Mild Patients Hospitalization and Survival VF ventricular fibrillation
Study in Heart Failure WPW Wolff-Parkinson-White
EPIC European Prospective Investigation Into Cancer and
Nutrition
ESRD end-stage renal disease
FHS Framingham Heart Study
GBD Global Burden of Disease Bradyarrhythmias
GWAS genome-wide association studies ICD-9 426.0, 426.1, 427.81; ICD-10 I44.0
GWTG
HbA1c
Get With The Guidelines
hemoglobin A1c (glycosylated hemoglobin)
to I44.3, I49.5.
HCM hypertrophic cardiomyopathy 2016: Mortality—1163. Any-mention mortality—6411.
HCUP Healthcare Cost and Utilization Project 2014: Hospital discharges—94 000.
(Continued ) Pacemakers: ICD-9-CM 37.7 to 37.8, 00.50, 00.53.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e291

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Mean hospital charges: $83 521; in-hospital death Compared with people with a PR interval ≤200
CLINICAL STATEMENTS

rate: 1.46%; mean length of stay: 5.1 days. ms, those with a PR interval >200 ms had an
AND GUIDELINES

absolute increased risk per year of 1.0% for AF,

0.5% for pacemaker implantation, and 2.1% for
AV Block death (Chart 16-1).11
Prevalence and Incidence • Decisions about the need for a pacemaker are
• In a healthy sample of participants from the influenced by the presence or absence of symp-
ARIC study (mean age 53 years), the prevalence toms directly attributable to bradycardia and the
of first-degree AV block was 7.8% in black likelihood of the arrhythmia to progress to com-
males, 3.0% in black females, 2.1% in white plete heart block. Permanent pacing improves
males, and 1.3% in white females.1 Lower survival in patients with third-degree AV block,
prevalence estimates were noted in the rela- especially if syncope has occurred.12
tively younger population (mean age 45 years) • In a large, prospective, regional French registry of
of the CARDIA study at its year 20 follow-up 6662 STEMI patients (2006–2013), high-degree
examination: 2.6% in black males, 1.9% in AV block was noted in 3.5% of individuals. In
black females, 1.2% in white males, and 0.1% 64% of cases, high-degree AV block was pres-
in white females.2 ent on admission. Although patients with high-
• The prevalence of PR interval prolongation was degree AV block on admission or occurring during
observed to be 2.1% in Finnish middle-aged the first 24 hours of hospitalization had higher
adults, but the authors noted that the PR inter- in-hospital mortality rates than patients without
val normalized in follow-up in 30% of these heart block, it was not an independent predictor
people.3 of mortality after multivariable analysis (HR, 0.99
• No population-based studies have reported the [95% CI, 0.60–1.66]).13
prevalence of second-degree AV block. On the • Little evidence exists to suggest that pacemak-
basis of results from clinical series, Mobitz II sec- ers improve survival in patients with isolated
ond-degree AV block is rare in healthy individu- first-degree AV block.14 However, marked first-
als (≈0.003%), whereas Mobitz I (Wenckebach) is degree AV block (PR >300 ms) can lead to symp-
observed in 1% to 2% of healthy young people, toms even in the absence of higher degrees of
Downloaded from http://ahajournals.org by on February 7, 2019

especially during sleep.4 AV block, with uncontrolled studies suggest-

• The prevalence of third-degree AV block in the ing that those patients benefit from pacemaker
general adult population is very low. The preva- implantation.12,15
lence was 0.04% in the Tecumseh Study5 and the
Icelandic Reykjavik Study6 and 0.6% in a large Risk Factors
sample of people with hypertension and without • In healthy individuals without CVD or its risk
factors from MESA, PR interval was longer with
DM enrolled with Veterans Health Administration
advancing age, in males compared with females,
hospitals.7
and in blacks compared with whites.16
• In 122  815 recordings from 122  454 unique
• Although first-degree AV block and Mobitz type I
patients prescribed 14-day continuous electro-
second-degree AV block can occur in apparently
cardiographic monitoring with the Zio patch
healthy people, presence of Mobitz II second- or
device between 2011 and 2013, prevalence of
third-degree AV block usually indicates underlying
high-grade AV block (defined as either Mobitz II
HD, including CHD, and HF.4
or complete heart block) was 1.2% (1486 of all
• Reversible causes of AV block include electro-
tracings).8
lyte abnormalities, drug-induced AV block, peri-
• An English registry study estimated the incidence
operative AV block attributable to hypothermia,
of infant complete AV block as 2.1 per 100 000
or inflammation near the AV conduction system
live births.9 Congenital complete heart block
after surgery in this region. Some conditions
could be attributable to transplacental transfer of
may warrant pacemaker implantation because
maternal anti-SSA/Ro or SSB/La antibodies.10
of the potential for disease progression even
Complications if the AV block reverses transiently (eg, sar-
(See Chart 16-1) coidosis, amyloidosis, and neuromuscular
• In the FHS, PR interval prolongation (>200 ms) diseases).12
was associated with increased risk of AF (HR, • Long sinus pauses and AV block can occur during
2.06 [95% CI, 1.36–3.12]), pacemaker implan- sleep apnea. In the absence of symptoms, these
tation (HR, 2.89 [95% CI, 1.83–4.57]), and all- abnormalities are reversible and do not require
cause mortality (HR, 1.44 [95% CI, 1.09–1.91]).11 pacing.12,17

e292 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Prevention only was 63% compared with 40% among those

CLINICAL STATEMENTS
• Detection and correction of reversible causes of with DDD pacing at 7-year follow-up.

AND GUIDELINES
acquired AV block could be of potential impor- • In 19 893 males and females >45 years of age
tance in preventing symptomatic bradycardia and from the ARIC and CHS cohorts, incidence of sick
other complications of AV block.12 sinus syndrome was associated with increased
mortality (HR, 1.4 [95% CI, 1.1–1.7]), CHD (HR,
1.7 [95% CI, 1.1–2.7]), HF (HR, 2.9 [95% CI, 2.2–
Sinus Node Dysfunction 3.8]), stroke (HR, 1.6 [95% CI, 1.0–2.5]), AF (HR,
Prevalence and Incidence 5.8 [95% CI, 4.4–7.5]), and pacemaker implanta-
• There are no accurate estimates of the preva- tion (HR, 53.7 [95% CI, 42.9–67.2]).29
lence of sinus node dysfunction in the general • In a multicenter study from the Netherlands of
population. people with bradycardia treated with pacemaker
• According to a survey of members of the North implantation, the actuarial 1-, 3-, 5-, and 7-year
American Society of Pacing and Electrophysiology, survival rates were 93%, 81%, 69%, and 61%,
sick sinus syndrome accounted for 48% of respectively. Individuals without CVD at baseline
implantations of first permanent pacemakers in had similar survival rates as age- and sex-matched
the United States in 1997.18,19 control subjects.30
• Sinus node dysfunction is commonly present • With sinus node dysfunction, the incidence of
with other causes of bradyarrhythmias (carotid sudden death is extremely low, and pacemaker
sinus hypersensitivity in 42% of patients and implantation does not appear to alter longev-
advanced AV conduction abnormalities in ity.12,31 SVT including AF was prevalent in 53% of
17%).20,21 patients with sinus node dysfunction.26
• Incidence rates of sinus node dysfunction hos- • On the basis of records from the NIS, pacemaker
pitalization among Medicare beneficiaries >65 implantation rates per million increased from
years of age were 207 per 100 000 person-years 291 in 1993 to 616 in 2009, although overall
in 1998. Rates increased with age and were use plateaued in 2001. The patients’ mean age
higher in males than females and in whites than and number of comorbidities at implantation
blacks.22 increased over time. Total hospital charges asso-
Downloaded from http://ahajournals.org by on February 7, 2019

• The incidence rate of sick sinus syndrome was ciated with pacemaker implantation increased
0.8 per 1000 person-years of follow-up in 2 bira- 45% from $53 693 in 1993 to $78 015 in 2009
cial US cohorts, ARIC and CHS.23 The incidence (in 2011 dollars).32
increased with advancing age (HR, 1.73 [95% • On the basis of NHDS data, the escalating
CI, 1.47–2.05] per 5-year increment), and blacks implantation rate was attributable to increasing
were at 41% lower risk of sick sinus syndrome implantation for isolated sinus node dysfunction;
than their white counterparts (HR, 0.59 [95% CI, implantation for sinus node dysfunction increased
0.37–0.98]). Investigators projected that in the by 102%, whereas implantation for all other indi-
United States, the number of new cases of sick cations did not increase (Chart 16-2).33
sinus syndrome per year would rise from 78 000 • A study at a single academic institution com-
in 2012 to 172 000 in 2060.23 pared older adult outpatients (>60 years old)
Complications with (N=470) and without (N=2090) asymp-
(See Chart 16-2) tomatic bradycardia. Over a mean follow-up of
• In a small prospective study of 35 patients ≥45 7.2 years, patients with asymptomatic brady-
years of age with sinus node dysfunction that was cardia had a higher adjusted incidence of pace-
left untreated, 57% experienced cardiovascular maker insertion (HR, 2.14 [95% CI, 1.30–3.51];
events over a 4-year follow-up period; 31% expe- P=0.003), which appeared after a lag time of 4
rienced syncope over the same period.24 years. However, the absolute rate of pacemaker
• The survival of patients with sinus node dysfunc- implantation was low (<1% per year), and
tion appears to depend primarily on the severity asymptomatic bradycardia was not associated
of underlying cardiac disease, is not different from with a higher risk of death.34
survival in the general population when treated • In 5831 participants of the MESA cohort, a heart
with pacemaker, and is not significantly changed rate lower than 50 beats per minute was not
by type of pacemaker therapy.25–27 associated with mortality or incident CVD among
• In a retrospective study28 of patients with sinus individuals not taking heart rate–modifying drugs
node dysfunction who had pacemaker therapy, compared with those with heart rate between 50
mortality among those with ventricular pacing and 59 beats per minute.35

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e293

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Risk Factors • The prevalence of SVT that is clinically undetected

CLINICAL STATEMENTS

• The causes of sinus node dysfunction can be is likely much greater than the estimates from ED
AND GUIDELINES

classified as intrinsic (secondary to pathological visits and electrophysiology procedures would

conditions involving the sinus node) or extrinsic suggest. Among 26 751 individual patients receiv-
(caused by depression of sinus node function ing a Zio Patch monitor (a 14-day single-lead elec-
by external factors such as drugs or autonomic trocardiographic monitor) for clinical indications,
influences).36 prevalence of SVT defined as at least a single run
• Idiopathic degenerative disease is probably the of ≥8 beats was 31%.41
most common cause of sinus node dysfunction.37 • Of 1383 participants in the Baltimore Longitudinal
• Investigators collected data from 28 different Study of Aging undergoing maximal exercise test-
studies on atrial pacing for sinus node dysfunc- ing, 6% exhibited SVT during the test; increas-
tion that showed a median annual incidence ing age was a significant risk factor. Only 16%
of second- and third-degree AV block of 0.6% exhibited >10 beats of SVT, and only 4% were
(range, 0%–4.5%) and an overall prevalence of symptomatic. Over an average of 6 years of fol-
2.1% (range, 0%–11.9%). This suggests that the low-up, people with exercise-induced SVT were
degenerative process also affects the specialized more likely to develop SVT or AF.42
conduction system, although the rate of progres- • In a study of 3554 consecutive males 17 to 21
sion is slow and does not dominate the clinical years of age applying for a pilot’s license, the sur-
course of disease.38 face ECG revealed that the prevalence of ectopic
• In the CHS and ARIC studies, factors associated atrial tachycardia was estimated to be 0.34% in
with incident sick sinus syndrome included white asymptomatic applicants and 0.46% in symptom-
(versus black) race, higher mean BMI, height, prev- atic applicants.43
alent hypertension, lower heart rate, right bundle-
Complications
branch block, N-terminal pro-BNP, cystatin C, and
• Rare cases of incessant SVT can lead to a tachy-
history of a major cardiovascular event.23
cardia-induced cardiomyopathy,44 and rare cases
of sudden death attributed to SVT as a trigger
SVT (Excluding AF and Atrial Flutter) have been described.45
ICD-9 427.0; ICD-10 I47.1. • Among 2 350 328 pregnancies included in Taiwan’s
Downloaded from http://ahajournals.org by on February 7, 2019

national insurance database between 2001 and

2016: Mortality—146. Any-mention mortality—1440.
2012, 769 females experienced paroxysmal SVT
Hospital discharges—15 000 (6000 male; 9000 female).
during pregnancy. Compared with those females
Prevalence and Incidence without paroxysmal SVT during pregnancy, parox-
(See Chart 16-3) ysmal SVT during pregnancy was associated with
• Data from the Marshfield Epidemiologic Study a higher risk for poor maternal outcomes (severe
Area in Wisconsin suggested the incidence of morbidity and cesarean delivery) and poor fetal
documented paroxysmal SVT was 35 per 100 000 outcomes (low birth weight, preterm labor, fetal
person-years, whereas the prevalence was 225 stress, and obvious fetal abnormalities).46
per 100 000 people. The mean age at SVT onset • A California administrative database study of
was 57 years, and both female sex (RR, 2.0) and almost 5 million patients suggested that after
age ≥65 years (versus <65 years: RR, 5.3) were the exclusion of people with diagnosed AF, SVT
significant risk factors (Chart 16-3).39 was associated with an adjusted doubling of the
• A review of ED visits in US hospitals using risk of stroke in follow-up (HR, 2.10 [95% CI,
NHAMCS data from 1993 to 2003 revealed that 1.69–2.62]). The absolute stroke rate was low,
an estimated 550 000 visits were for SVT (0.05% however. The cumulative stroke rate was 0.94%
of all visits [95% CI, 0.04%–0.06%]), or ≈50 000 (95% CI, 0.76%–1.16%) over 1 year in patients
visits per year (incidence rate of 1.8 ED visits with SVT versus 0.21% (95% CI, 0.21%–0.22%;
per 10 000 person-years [95% CI, 1.4–2.3]). Of P<0.001, log-rank test) in those without SVT.47
these patients, 24% (95% CI, 15%–34%) were • In a Swedish study of 214 patients (51% females)
admitted to the hospital, and 44% (95% CI, with paroxysmal SVT undergoing ablation,
32%–56%) were discharged without specific females had a longer history of symptomatic
follow-up.40 Rates were higher in individuals ≥65 arrhythmia (16.2±14.6 versus 9.9±13.1 years),
years of age than in those <65 years of age (3.9 were more likely to report not being taken seri-
versus 1.5 per 10 000 person-years) and lower in ously when consulting for their symptoms (17%
males than in females (1.1 versus 2.6 per 10 000 versus 7%), and were more symptomatic after 6
person-years). months of ablation than males.48

e294 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Specific Types Complications

CLINICAL STATEMENTS
• Among those presenting for invasive electrophysi- • WPW syndrome, a diagnosis reserved for those

AND GUIDELINES
ological study and ablation, AV nodal reentrant with both ventricular preexcitation (evidence of
tachycardia (a circuit that requires 2 AV nodal an anterograde conducting AV accessory pathway
pathways) is the most common mechanism of on a 12-lead ECG) and tachyarrhythmias, deserves
SVT49,50 and usually represents the majority of special attention because of the associated risk of
cases (56% in one series of 1754 cases).50 sudden death. Sudden death is generally attrib-
• AV reentrant tachycardia (an arrhythmia that uted to rapid heart rates in AF conducting down
requires the presence of an extranodal connec- an accessory pathway and leading to VF.57
tion between the atria and ventricles or spe- • A cohort study from Intermountain Healthcare
cialized conduction tissue) is the second most with ≈8 years of follow-up reported that rates of
common type of SVT (27% in the study by Porter cardiac arrest were low and similar between WPW
et al50), and atrial tachycardia is the third most and control patients without WPW. In follow-up,
common (17% in the series of 1754 SVT cases WPW was associated with a significantly higher
from Porter et al50). risk of AF (HR, 1.55 [95% CI, 1.29–1.87]); 7.0%
• In a US-based national pediatric electrophysiology of the WPW patients developed AF compared
registry study, AV reentrant tachycardia was the with 3.8% of those without WPW.58
most common SVT mechanism (68%), whereas • Asymptomatic adults with ventricular preexcita-
the remainder of the patients had AV nodal reen- tion appear to be at no increased risk of sudden
trant tachycardia (32%).51 death compared with the general population,59–62
• AV reentrant tachycardia prevalence decreases although certain characteristics found during
with age, whereas AV nodal reentrant tachycardia an invasive electrophysiological study (includ-
and atrial tachycardia prevalence increase with ing inducibility of AV reentrant tachycardia or
advancing age.50 AF, accessory pathway refractory period, and the
• The majority of patients with AV reentrant tachy- shortest R-R interval during AF) can help risk strat-
cardia were males (55%), whereas females con- ify these patients.59
stituted the majority with AV nodal reentrant • In a single-center prospective registry study of
tachycardia (70%) or atrial tachycardia (62%) in 2169 patients who agreed to undergo an electro-
physiology study for WPW syndrome from 2005 to
Downloaded from http://ahajournals.org by on February 7, 2019

the study by Porter et al.50

• Multifocal atrial tachycardia is an arrhythmia that 2010, 1168 patients (206 asymptomatic) under-
is commonly confused with AF and is character- went radiofrequency ablation, none of whom had
ized by 3 distinct P-wave morphologies, irregular malignant arrhythmias or VF in up to 8 years of
R-R intervals, and a rate >100 beats per minute. follow-up. Of those who did not receive radiofre-
It is uncommon in both children52 and adults,53 quency ablation (N=1001; 550 asymptomatic) in
with a prevalence in hospitalized adults estimated follow-up, 1.5% had VF, most of whom (13 of
at 0.05% to 0.32%.53 The average age of onset 15) were children. The authors noted that poor
in adults is 70 to 72 years. Adults with multifo- prognosis was related to accessory pathway elec-
cal atrial tachycardia have a high mortality rate, trophysiological properties rather than patient
with estimates around 45%, but this is gener- symptoms.63
ally ascribed to the underlying condition(s).53 In a • In a meta-analysis of 20 studies involving 1869
study of older ambulatory adults in a Greece, the asymptomatic patients with a WPW electrocar-
mortality in follow-up did not differ by whether diographic pattern followed up for a total of
or not multifocal atrial rhythms were detected on 11 722 person-years, the rate of sudden death in
baseline ECG.54 a random effects model that was used because of
heterogeneity across studies was estimated to be
WPW Syndrome 1.25 (95% CI, 0.57–2.19) per 1000 person-years.
Prevalence Risk factors for sudden death included male sex,
• A WPW electrocardiographic pattern was observed inclusion in a study of children (<18 years of age),
in 0.11% of males and 0.04% of females among and inclusion in an Italian study.64
47 358 ECGs from adults participating in 4 large • Several studies in asymptomatic children with ven-
Belgian epidemiological studies.55 In a study of tricular preexcitation detected by screening sug-
32 837 Japanese students who were required by gested a benign prognosis.62,65 A referral-based
law to receive ECGs before entering school, a registry study reported that electrophysiological
WPW electrocardiographic pattern was reported in testing can identify a group of asymptomatic chil-
0.07%, 0.07%, and 0.17% of elementary, junior dren with a risk of sudden death or VF as high as
high, and high school students, respectively.56 11% over 19 months of follow-up.66 In a pediatric

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e295

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

hospital retrospective review of 446 children with • Data from California administrative databases
CLINICAL STATEMENTS

WPW syndrome, 64% were symptomatic at pre- were analyzed with regard to racial variation in
AND GUIDELINES

sentation, and 20% had onset of symptoms dur- incidence of AF. After adjustment for AF risk fac-
ing a median of 3 years follow-up. The incidence tors, compared with their white counterparts,
of sudden death was 1.1 per 1000 person-years lower incidence rates were found in blacks (HR,
in patients without structural HD.67 0.84 [95% CI, 0.82–0.85]; P<0.001), Hispanics
(HR, 0.78 [95% CI, 0.77–0.79]; P<0.001), and
Asians (HR, 0.78 [95% CI, 0.77–0.79]; P<0.001)
AF and Atrial Flutter (Chart 16-5).75
Prevalence • Racial variation in AF incidence is also observed
(See Chart 16-4) in other countries. For instance, in a study of the
• Estimates of the prevalence of AF in the United UK Clinical Practice Research Datalink cohort ≥45
States ranged from ≈2.7 million to 6.1 million in years of age, the incidence rates per 1000 person-
2010,68,69 and AF prevalence is estimated to rise to years standardized to the UK population were 8.1
12.1 million in 2030 (Chart 16-4).70 (95% CI, 8.1–8.2) in whites versus 5.4 (95% CI,
• In the European Union, the prevalence of AF in 4.6–6.3) in Asians and 4.6 (95% CI, 4.0–5.3) in
adults >55 years of age was estimated to be 8.8 black patients.76
million (95% CI, 6.5–12.3 million) in 2010 and • Using data from a health insurance claims data-
was projected to rise to 17.9 million in 2060 base covering 5% of the United States, the inci-
(95% CI, 13.6–23.7 million).71 dence of AF was estimated at 1.2 million cases in
• Data from a California health plan suggested 2010 and was projected to increase to 2.6 million
that compared with whites, blacks (OR, 0.49 cases in 2030.70
[95% CI, 0.47–0.52]), Asians (OR, 0.68 [95% CI, Lifetime Risk and Cumulative Risk
0.64–0.72]), and Hispanics (OR, 0.58 [95% CI, (See Chart 16-6)
0.55–0.61]) have a significantly lower adjusted • Previously, the lifetime risks of AF have been esti-
prevalence of AF.72 mated to be ≈1 in 4 in individuals from the FHS
• Among Medicare patients aged ≥65 years and Rotterdam Study.77,78
who were diagnosed from 1993 to 2007, the • However, in more recent studies from Framingham
Downloaded from http://ahajournals.org by on February 7, 2019

prevalence of AF increased ≈5% per year, from and the European BiomarCaRE Consortium, the
≈41.1 per 1000 beneficiaries to 85.5 per 1000 lifetime risk estimates for AF in individuals of
beneficiaries.73 European ancestry have increased to ≈1 in 3.
— In 2007 in the 5% Medicare sample, there — In the BiomarCaRE study based on 4
were 105 701 older adults with AF: 3.7% European community-based studies, the inci-
were black, 93.8% were white, and 2.6% dence increased after age 50 years in males
were other/unknown race.73 and 60 years in females, but the cumulative
— The prevalence rate per 1000 beneficiaries incidence of AF was similar, at >30%, by age
was 46.3 in blacks, 90.8 in whites, and 47.5 90 years.79
in other/unknown race.73 — In an FHS report based on participants with
DNA collected after 1980, the lifetime risk of
Incidence AF after age 55 years was 37.1%, which was
(See Table 16-1 and Chart 16-5) influenced by both clinical and genetic risk.80
• In a Medicare sample, per 1000 person-years, In a subsequent study from Framingham, the
the age- and sex-standardized incidence of AF lifetime risk of AF varied by risk factor bur-
was 27.3 in 1993 and 28.3 in 2007, represent- den. In individuals with optimal risk profile,
ing a 0.2% mean annual change (P=0.02). Of the lifetime risk was 23.4% (95% CI, 1.8%–
individuals with incident AF in 2007, ≈55% were 34.5%), whereas the risk was 33.4% (95%
females, 91% were white, 84% had hyperten- CI, 27.9–38.9) with a borderline risk profile
sion, 36% had HF, and 30% had cerebrovascular and 38.4% (95% CI, 35.5%–41.4%) with
disease.73 an elevated risk profile.81
• Investigators from MESA estimated the age- and • In a medical insurance database study from the
sex-adjusted incidence rate of hospitalized AF Yunnan Province in China, the estimated lifetime
per 1000 person-years (95% CI) as 11.2 (9.8– risk of AF at age 55 years was 21.1% (95% CI,
12.8) in NH whites, 6.1 (4.7–7.8) in Hispanics, 19.3%–23.0%) for females and 16.7% (95% CI,
5.8 (4.8–7.0) in NH blacks, and 3.9 (2.5–6.1) in 15.4%–18.0%) for males.82 In a Taiwanese study,
Chinese.74 the lifetime risk of AF was estimated to be 16.9

e296 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

(95% CI, 16.7–14.2) in males and 14.6 (95% CI, — Individuals with AF have increased mortal-

CLINICAL STATEMENTS
14.4–14.9) in females.83 ity with concomitant HF,98,99 HF with pre-

AND GUIDELINES
• Investigators from the NHLBI-sponsored ARIC served EF,100,101 and HF with reduced EF.100
study observed that the lifetime risk of AF was In a meta-analysis that examined the timing
36% in white males (95% CI, 32%–38%), 30% of AF in relation to HF onset with regard to
in white females (95% CI, 26%–32%), 21% in mortality, the risk of death associated with
African American males (95% CI, 13%–24%), incident AF was higher (RR, 2.21 [95% CI,
and 22% in African American females (95% CI, 1.96–2.49]) than with prevalent AF (RR, 1.19
16%–25%).84 [95% CI, 1.03–1.38]; Pinteraction<0.001).102
— AF is also associated with an increased
Mortality
risk of death in other conditions, including
(See Chart 16-7)
DM,103,104 ESRD,105 sepsis,106,107 and noncar-
2016 ICD-9 427.3; ICD-10 I48.
diac surgery.108
In 2016, AF was the underlying cause of death in 24 855
people and was listed on 15 816 US death certificates • In a Medicare unadjusted analysis, blacks and
(any-mention mortality). Hispanics had a higher risk of death than their
• The age-adjusted mortality rate from AF was 6.5 white counterparts with AF; however, after
per 100 000 people in 2016.85 adjustment for comorbidities, blacks (HR, 0.95
• In adjusted analyses from the FHS, AF was associ- [95% CI, 0.93–0.96]; P<0.001) and Hispanics
ated with an increased risk of death in both males (HR, 0.82 [95% CI, 0.80–0.84]; P<0.001) had
(OR, 1.5 [95% CI, 1.2–1.8]) and females (OR, 1.9 a lower risk of death than whites with AF.109 In
[95% CI, 1.5–2.2]).86 Furthermore, there was an contrast, in the population-based ARIC study,
interaction with sex, such that AF appeared to the rate difference for all-cause mortality for
diminish the survival advantage typically observed individuals with versus without AF per 1000 per-
in females. son-years was 106.0 (95% CI, 86.0–125.9)103 in
• Although there was significant between-study blacks, which was higher than the 55.9 (95% CI,
heterogeneity (P<0.001), a meta-analysis con- 48.1–63.7) rate difference in mortality observed
firmed that the adjusted risk of death was signifi- for whites.110
cantly stronger in females than in males with AF • In a US-based study, there was substantial varia-
Downloaded from http://ahajournals.org by on February 7, 2019

(RR, 1.12 [95% CI, 1.07–1.17]).87 tion in mortality with AF in US counties from
• In Medicare beneficiaries ≥65 years of age with 1980 to 2014.111 Investigators estimated there
new-onset AF, mortality decreased modestly but were ≈22 700 (95% UI, 19 300–26 300) deaths
significantly between 1993 and 2007. In 2007, attributable to AF in 2014 and 191 500 (95% UI,
the age- and sex-adjusted mortality at 30 days 168 000–215 300) years of life lost. In an exami-
was 11%, and at 1 year, it was 25%.73 nation of county-level data, the age-standardized
• An observational study of Olmsted County, MN, CVD mortality rates were 5.6 per 100 000 for
residents with first diagnosis of AF or atrial flut- the 10th percentile and 9.7 per 100 000 for the
ter between 2000 and 2010 reported a high early 90th percentile. The counties with age-standard-
mortality compared with individuals of similar age ized death rates greater than the 90th percentile
and sex; the standardized mortality ratio was 19.4 were clustered in Oregon, California, Utah, Idaho,
(95% CI, 17.3–21.7) in the first 30 days and 4.2 northeastern Montana, areas east of Kansas City,
(95% CI, 3.5–5.0) for days 31 to 90.88 MO, and southwest West Virginia.111
• Although stroke is the most feared complication • In a Swedish study based on 75 primary care
of AF, the RE-LY clinical trial reported that stroke centers, an adjusted analysis of patients diag-
accounted for only ≈7.0% of deaths in AF, with nosed with AF revealed that males living in low
SCD (22.25%), progressive HF (15.1%), and non- SES neighborhoods were 49% (HR, 1.49 [95%
cardiovascular death (35.8%) accounting for the CI, 1.13–1.96]) more likely to die than their
majority of deaths.89 counterparts living in middle-income neighbor-
• AF is also associated with increased mortal- hoods. The results were similar in models that
ity in subgroups of individuals, including the additionally adjusted for anticoagulant and statin
following: treatment (HR, 1.39 [95% CI, 1.05–1.83]).112 In
— Individuals with other cardiovascular con- another study from the same group, unmarried
ditions and procedures, including HCM,90 and divorced males and males with lower edu-
MI,91,92 post-CABG91–94 (both short-term93 cational levels with AF had higher risk of mortal-
and long-term93,94), post– transcatheter aor- ity than their married and better-educated male
tic valve implantation,95 PAD,96 and stroke.97 counterparts.113

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e297

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Complications to AF increased significantly. In the FHS, AF

CLINICAL STATEMENTS

• Five years after diagnosis with AF, the cumulative accounted for ≈1.5% of strokes in individuals 50
AND GUIDELINES

incidence rate of mortality, HF, MI, stroke, and to 59 years of age and ≈23.5% in those 80 to 89
gastrointestinal bleeding was higher in older age years of age.119
groups (80–84, 85–89, and ≥90 years of age) than • AF was also an independent risk factor for isch-
in younger age groups (67–69, 70–74, and 75–79 emic stroke severity, recurrence, and mortality.97
years of age) (Table 16-1).114 In an observational study, at 5 years only 39.2%
(95% CI, 31.5%–46.8%) of ischemic stroke
Extracranial Systemic Embolic Events
patients with AF were alive, and 21.5% (95%
• In a Danish population-based registry of individ-
CI, 14.5%–31.3%) had experienced recurrent
uals 50 to 89 years of age discharged from the
stroke.120
hospital, individuals with new-onset AF had an
• In Medicare analyses that were adjusted for
elevated risk of thromboembolic events to the
comorbidities, blacks (HR, 1.46 [95% CI, 1.38–
aorta and renal mesenteric, pelvic, and peripheral
1.55]; P<0.001) and Hispanics (HR, 1.11 [95%
arteries. The excess thromboembolic event rate
CI, 1.03–1.18]; P<0.001) had a higher risk of
was 3.6 in males and 6.3 in females per 1000 per-
son-years of follow-up. Compared with referents stroke than whites with AF.109 The increased risk
in the Danish population, the RR of diagnosed persisted in analyses adjusted for anticoagulant
extracranial embolism was 4.0 (95% CI, 3.5–4.6) therapy status.109 Additional analyses from the
in males and 5.7 (95% CI, 5.1–6.3) in females.115 Medicare registry demonstrated that the addition
• Investigators pooled data from 4 large, contem- of African American race to the CHA2DS2-VASc
porary, randomized anticoagulation trials and scoring system significantly improved the predic-
observed 221 systemic emboli in 91 746 person- tion of stroke events among newly diagnosed AF
years of follow-up. The systemic embolic event patients ≥65 years of age.121
rate was 0.24 versus a stroke rate of 1.92 per 100 • A meta-analysis that examined stroke risk by sex
person-years. Compared with individuals expe- and presence of AF reported that AF conferred
riencing stroke, patients experiencing systemic a multivariable-adjusted 2-fold stroke risk in
emboli were more likely to be females (56% ver- females compared with males (RR, 1.99 [95% CI,
sus 47%; P=0.01) but had similar mean age and 1.46–2.71]); however, the studies were noted to
Downloaded from http://ahajournals.org by on February 7, 2019

CHADS2 score as those with stroke. Both stroke be significantly heterogeneous.87

(RR, 6.79 [95% CI, 6.22–7.41]) and systemic Cognition
emboli (RR, 4.33 [95% CI, 3.29–5.70]) were asso- • A meta-analysis of 21 studies indicated that
ciated with an increased risk of death compared AF was associated with increased risk of cogni-
with patients with neither event.116 tive impairment in patients with (RR, 2.70 [95%
Stroke CI, 1.82–4.00]) and without (RR 1.37 [95% CI,
(See Chart 16-7) 1.08–1.73]) a history of stroke. The risk of demen-
• Using a 5% Medicare sample from 2008 to 2014, tia was similarly increased (RR, 1.38 [95% CI,
investigators reported the annual stroke rate to 1.22–1.56]).122
be 2.02% (95% CI, 1.99%–2.05%) in patients • In individuals with AF without evidence of cogni-
with AF and 1.38% (95% CI, 1.22%–1.57%) in tive dysfunction or stroke from Olmsted County,
patients with atrial flutter. After adjustment for MN, the cumulative rate of dementia at 1 and 5
demographics and vascular risk factors, the risk years was 2.7% and 10.5%, respectively.123
of stroke was significantly lower in patients with Physical Disability and Subjective Health
atrial flutter than in those with AF (HR, 0.69 [95% • AF has been associated with physical disability,
CI, 0.61–0.79]).117 poor subjective health,124,125 and diminished qual-
• A systematic review of prospective studies found ity of life.126 A recent systematic review suggested
wide variability in stroke risk between studies and that among people with AF, moderate-intensity
between AF patients, ranging between 0.5% and activity improved exercise capacity and quality of
9.3% per year.118 life.127
• Before the widespread use of anticoagulant
drugs, after accounting for standard stroke risk Falls
factors, AF was associated with a 4- to 5-fold • In the REGARDS study, AF was significantly asso-
increased risk of ischemic stroke. Although the RR ciated with an adjusted higher risk of falls (10%)
of stroke associated with AF did not vary (≈3- to than among those without AF (6.6%; OR, 1.22
5-fold increased risk) substantively with advanc- [95% CI, 1.04–1.44]). The presence of a his-
ing age, the proportion of strokes attributable tory of both AF and falls was associated with a

e298 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

significantly higher risk of mortality (per 1000 • A meta-analysis of 9 studies reported that indi-

CLINICAL STATEMENTS
person-years: AF plus falls, 51.2; AF and no falls, viduals with AF have a 5-fold increased risk of HF

AND GUIDELINES
34.4; no AF and falls, 29.8; no AF and no falls, (RR, 4.62 [95% CI, 3.13–6.83).133
15.6). Compared with those with neither AF nor
Myocardial Infarction
falls, those with both conditions had an adjusted
(See Chart 16-7)
2-fold increased risk of death (HR, 2.12 [95% CI,
A meta-analysis of 16 cohort studies reported that
1.64–2.74]).128
AF was associated with a 1.54 (95% CI, 1.26–1.85)
• A systematic review and Markov decision analytic
increased risk of MI in follow-up.133
modeling report focused on people with AF ≥65
• In the REGARDS study in individuals with AF, the
years of age noted that warfarin treatment was
age-adjusted MI incidence rate per 1000 person-
associated with 12.9 QALYs per patient with typi-
years was 12.0 (95% CI, 9.6–14.9) in those with
cal risks of stroke and falls versus 10.2 QALYs for
AF compared with 6.0 (95% CI, 5.6–6.6) in those
those treated with neither warfarin nor aspirin. Of
without AF.134
interest, sensitivity analyses of the probability of
• Both REGARDS134 and the ARIC study135 observed
falls or stroke did not substantively influence the
that the risk of MI after AF was higher in females
results.129
than in males.
• A Medicare study noted that patients at high risk
• For individuals with AF in both REGARDS134 and the
for falls with a CHADS2 score of at least 2 who
CHS,136 a higher risk of MI was observed in blacks
had been prescribed warfarin had a 25% lower
than whites. For instance, the CHS observed that
risk (HR, 0.75 [95% CI, 0.61–0.91]; P=0.004)
individuals with AF who were black had a higher
of a composite cardiovascular outcome (out-of-
risk of MI (HR, 3.1 [95% CI, 1.7–5.6]) than whites
hospital death or hospitalization for stroke, MI,
(HR, 1.6 [95% CI, 1.2–2.1]; Pinteraction=0.03).136
or hemorrhage) than those who did not receive
• In ARIC, AF was associated with an adjusted
anticoagulant drugs.130
increased risk of NSTEMI (HR, 1.80 [95% CI,
Heart Failure 1.39–2.31]) but not STEMI (HR, 0.49 [95% CI,
(See Chart 16-7) 0.18–0.34]; P for comparison of HR=0.004).135
• AF and HF share many antecedent risk factors,
Chronic Kidney Disease
and ≈40% of people with either AF or HF will
Downloaded from http://ahajournals.org by on February 7, 2019

• In a Japanese community-based study, individuals

develop the other condition.99
with AF had approximately a doubling in increased
• In the community, estimates of the incidence
risk of developing kidney dysfunction or protein-
of HF in individuals with AF ranged from 3.399
uria, even in those without baseline DM or hyper-
to 5.8131 per 100 person-years of follow-up. In
tension. Per 1000 person-years of follow-up, the
Olmsted County, MN, in individuals with AF, per
incidence of kidney dysfunction was 6.8 in those
100 person-years of follow-up, the incidence of
without and 18.2 in those with AF at baseline.137
HF with preserved EF was 3.3 (95% CI, 3.0–3.7),
• In a Kaiser Permanente study of people with CKD,
which was more common than HF with reduced
new-onset AF was associated with an adjusted
EF (2.1 [95% CI, 1.9–2.4]).131
1.67-fold increased risk of developing ESRD com-
• Among older adults with AF in Medicare, the
pared with those without AF (74 versus 64 per
5-year event rate was high, with rates of death
1000 person-years of follow-up).138
and HF exceeding those for stroke (Chart 16-7).
Higher event rates after new-onset AF were asso- SCD and VF
ciated with older age and higher mean CHADS2 • In a study that examined data from 2 population-
score.114 based studies, AF was associated with a doubling
• Investigators examined the incidence rate of in the risk of SCD after accounting for baseline
HF with systolic dysfunction versus preserved and time-varying confounders. In ARIC, the unad-
LVEF (<40% versus >50%, respectively) in a justed incidence rate per 1000 person-years was
Netherlands community-based cohort study 1.30 (95% CI, 1.14–1.47) in those without AF
(PREVEND) by AF status. Per 1000 person-years, and 2.89 (95% CI, 2.00–4.05) in those with AF;
the incidence rate of systolic HF was 12.75 versus corresponding rates in CHS were 3.82 (95% CI,
1.99 for those with versus those without AF, with 3.35–4.35) and 12.00 (95% CI, 9.45–15.25),
a multivariable-adjusted HR of AF of 5.79 (95% respectively. The multivariable-adjusted HR associ-
CI, 2.40–13.98). Corresponding numbers for pre- ated with AF for sudden death was 2.47 (95% CI,
served EF were 4.90 versus 0.85 with and without 1.95–3.13).139
AF, with a multivariable-adjusted HR of AF of 4.80 • An increased risk of VF was observed in a
(95% CI, 1.30–17.70).132 community-based case-control study from the

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e299

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Netherlands. Individuals with ECG-documented • In 2015, there were 6 431 000 physician office
CLINICAL STATEMENTS

VF during OHCA were matched with non-VF visits and 499  000 ED visits for AF (NAMCS,
AND GUIDELINES

community control subjects. The prevalence of NHAMCS, NHLBI tabulation).147,148

AF in the 1397 VF cases was 15.4% versus 2.6% • Using cross-sectional data (2006–2014) from
in the community referents. Individuals with AF the HCUP’s Nationwide Emergency Department
had an overall adjusted 3-fold increased risk of VF Sample, the NIS, and the National Vital Statistics
(adjusted OR, 3.1 [95% CI, 2.1–4.5]). The associa- System, investigators estimated that in 2014,
tion was similar across age and sex categories and AF listed as a primary diagnosis accounted for
was observed in analyses of individuals without ≈599 790 ED visits and 453 060 hospitalizations,
comorbidities, without AMI, and not using antiar- with a mean length of stay of 3.5 days. Including
rhythmic or QT-prolonging drugs.140 AF listed as a comorbid condition, there were ≈4
• In a meta-analysis of 7 studies, individuals million (3.6% of total) ED visits and 3.5 million
with AF had an RR of SCD of 1.88 (95% CI, (12.0% of total) hospitalizations.149
1.36–2.60).141 • On the basis of Medicare and MarketScan data-
AF Type and Complications bases, annually, people with AF (37.5%) are
• A meta-analysis of 12 studies reported that com- approximately twice as likely to be hospitalized as
pared with paroxysmal AF, nonparoxysmal AF was age- and sex-matched referents (17.5%).150
associated with a multivariable-adjusted increased Cost
risk of thromboembolism (HR, 1.38 [95% CI, (See Chart 16-8)
1.19–1.61]; P<0.001) and death (HR, 1.22 [95% • Investigators examined Medicare and Optum
CI, 1.09–1.37]; P<0.001).142 Touchstone databases (2004–2010) to estimate
• In the Canadian Registry of AF, 755 patients with costs attributed to nonvalvular AF versus propen-
paroxysmal AF were followed up for a median of sity-matched control subjects in 2014 US dollars151:
6.35 years. At 1, 5, and 10 years, 8.6%, 24.3%, — For patients aged 18 to 64 years, average
and 36.3% had progressed to persistent AF. per capita medical spending was $38 861
Within 10 years, >50% of the patients had pro- (95% CI, $35 781–$41 950) versus $28 506
gressed to persistent AF or had died.143 (95% CI, $28  409–$28  603) for matched
• In the FHS, atrial flutter had a much lower inci- patients without AF. Corresponding numbers
Downloaded from http://ahajournals.org by on February 7, 2019

dence rate (36 per 100 000 person-years) than AF for patients ≥65 years old were $25 322 for
(578 per 100 000 person-years). Although based those with AF (95% CI, $25 049–$25 595)
on only 112 individuals, in age- and sex-adjusted versus $21 706 (95% CI, $21 563–$21 849)
analyses, incident atrial flutter was associated for matched non-AF patients.
with a 5-fold hazard of AF (HR, 5.0 [95% CI, — The authors estimated that the incremental
3.1–8.0]).144 cost of AF was $10 355 for commercially
• A national Taiwanese study compared the prog- insured patients and $3616 for Medicare
nosis of 175 420 patients with AF and 6239 patients.
patients with atrial flutter. Using propensity scor- — Estimating that the prevalence of diagnosed
ing, they observed that compared with atrial flut- versus undiagnosed nonvalvular AF, respec-
ter, individuals with AF had significantly higher tively, was 0.83% versus 0.07% for individu-
incidences of ischemic stroke (1.63-fold), HF hos- als 18 to 64 years of age and 8.8% versus
pitalization (1.70-fold), and all-cause mortality 1.1% for those ≥65 years of age, the inves-
(1.08-fold).145 tigators estimated that the incremental cost
Hospitalizations and Ambulatory Care Visits of undiagnosed AF was $3.1 billion (95% CI,
• According to HCUP data in 2014, there were $2.7–3.7 billion).
454 000 hospital discharges with AF and atrial • Investigators examined Medicare and MarketScan
flutter as the principal diagnosis, evenly split databases (2004–2006) to estimate costs attrib-
between males and females (unpublished NHLBI uted to AF in 2008 US dollars (Chart 16-8):152
tabulation).146 — Extrapolating to the US population, it was
— The rate per 100 000 discharges increased estimated that the incremental cost of AF
with advancing age, from 16.4 in those aged was ≈$26 billion, of which $6 billion was
18 to 44 years, 149.6 in those 45 to 64 years, attributed to AF, $9.9 billion to other cardio-
and 593.1 in those 65 to 84 years, to 1159.5 vascular expenses, and $10.1 billion to non-
in individuals ≥85 years; however, 52.4% cardiovascular expenses.
of all hospital discharges for AF occurred in — Using cross-sectional data (2006–2014)
patients 65 to 84 years old.146 from the HCUP’s Nationwide Emergency

e300 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

Department Sample, the NIS, and the 2.0–5.0 days), did not change, the mortality

CLINICAL STATEMENTS
National Vital Statistics System, investigators declined by 4% per year, and hospital readmis-

AND GUIDELINES
estimated that in 2014, for AF listed as a pri- sions at 30 days declined by 1% per year. During
mary diagnosis, the mean charge for ED visits the same years, median Medicare inpatient costs
was ≈$4000, and the mean cost of hospital- per hospitalization increased substantially, from
izations was about $8819.149 $2932 (IQR, $2232–$3870) to $4719 (IQR,
• A systematic review that examined costs of isch- $3124–$7209).149
emic stroke in individuals with AF included 16
studies from 9 countries. In international dol- Risk Factors
lars adjusted to 2015 values, they estimated (See Chart 16-9)
that stroke-related healthcare costs were $8184, • On the basis of data from ARIC, the highest popu-
$12 895, and $41 420 for lower middle, middle- lation attributable fraction for AF was hyperten-
and high-income economies, respectively.153 sion, followed by BMI, smoking, cardiac disease,
• Costs of AF have been estimated for many other and DM (Chart 16-9).157
countries. Investigators estimated that the 3-year Smoking
societal costs of AF were approximately €20 403 • A meta-analysis of 8 studies suggested that cur-
to €26 544 per person and €219 to 295 million rent smoking was associated with an increased
for Denmark as a whole.154 risk of AF (pooled RR, 1.39 [95% CI, 1.11–1.75]).
Secular Trends Compared with noncurrent smokers, current
• During 50 years of observation of the FHS smokers had a 21% higher risk of incident AF
(1958–1967 to 1998–2007), the age-adjusted (pooled RR, 1.21 [95% CI, 1.03–1.42]), which sug-
prevalence and incidence of AF approximately gests that smoking cessation is associated with a
quadrupled. However, when only AF that was reduced risk of AF.158
ascertained on ECGs routinely collected in the Activity and Exercise
FHS was considered, the prevalence but not the • Data from some studies suggested that vigor-
incidence increased, which suggests that part of ous-intensity exercise 5 to 7 days per week was
the changing epidemiology was attributable to associated with a slightly increased risk of AF.127
enhanced surveillance. Although the prevalence
Downloaded from http://ahajournals.org by on February 7, 2019

In contrast, a meta-analysis suggested that more

of most risk factors changed over time, the haz- intensive PA was not associated with excess risk of
ards associated with specific risk factors did not AF (RR, 1.0 [95% CI, 0.82–1.22]), but the hetero-
change. Hence, the PAR associated with BMI, geneity statistic was significant.159
hypertension treatment, and DM increased (con- • A multiracial longitudinal study from Detroit, MI,
sistent with increasing prevalence). Over time, the reported a dose-response relation between objec-
multivariable-adjusted hazards of stroke and mor- tively assessed exercise capacity and lower risk of
tality associated with AF declined by 74% and new-onset AF.160 In unadjusted analyses, the inci-
25%, respectively.155 dence rates of AF over 5 years were 3.7%, 5.0%,
• Between 2000 and 2010 in Olmsted County, 9.5%, and 18.8% for >11, 10 to 11, 6 to 9, and
MN, age- and sex-adjusted incidence rates and <6 METs, respectively. Every 1-higher peak MET
survival did not change over time.88 However, was associated with an adjusted 7% lower risk of
over a similar time frame in the United Kingdom AF (HR, 0.93 [95% CI, 0.92–0.94]). The protec-
(2001–2013), the incidence of nonvalvular AF in tive association of fitness was observed in all sub-
people ≥45 years of age increased modestly from groups examined but was particularly beneficial in
5.9 (95% CI, 5.8–6.1) to 6.9 (95% CI, 6.8–7.1) obese individuals.
per 1000 patient-years, with the largest increase
observed in those >80 years of age.76 BMI and Obesity
• In data from the ARIC study, the prevalence of AF • In a meta-analysis of 16 studies involving
in the setting of MI increased slightly, from 11% >580  000 individuals, of whom ≈91 000 had
to 15%, between 1987 and 2009; however, the obesity, AF developed in 6.3% of those who had
increased risk of death (OR, 1.47 [95% CI, 1.07– obesity and 3.1% of those without it. Individuals
2.01]) in the year after MI accompanied by AF did with obesity had an RR of 1.51 for developing AF
not change over time.156 (95% CI, 1.35–1.68) compared with those with-
• Between 1999 and 2013, among Medicare fee- out obesity.161
for-service beneficiaries, rates of hospitaliza- • Another meta-analysis of 29 studies examined
tion for AF increased ≈1% per year. Although various anthropometric components in relation
the median hospital length of stay, 3 days (IQR, to incident AF. A 5-unit increment in BMI was

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e301

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

associated with an RR of 1.28 (95% CI, 1.20– were cardiothoracic surgery (30%), infection
CLINICAL STATEMENTS

1.38) in relation to AF. The risk was nonlinear (23%), and AMI (18%). Paroxysmal AF in the
AND GUIDELINES

(P<0.0001), with stronger associations observed context of a secondary precipitant frequently

at higher BMIs, but a BMI of 22 to 24 kg/m2 was recurred over follow-up.174
still associated with excess risk compared with — Sepsis is associated with an increased risk of
a BMI of 20 kg/m2. Waist, waist-hip ratio, fat AF. In a Medicare sample, 25.5% of patients
mass, and waist gain were also associated with with sepsis had AF; 18.3% of AF was pre-
increased risk of AF.162 existing, and 7.2% was newly diagnosed.175
• A causal relationship between higher BMI and AF occurring in the context of sepsis is asso-
incident AF gained further support from a genetic ciated with an increased risk of stroke and
mendelian randomization study, which observed death.106
that a BMI gene score that included 39 SNPs was — A meta-analysis reported that new-onset
associated with a higher risk of AF.163 AF has been observed in 10.9% of patients
undergoing noncardiac general surgery.176
BP and Hypertension • Prevalence of AF is particularly elevated in adults
• Hypertension accounted for ≈22%157 of AF with congenital heart disease.177
cases.
• In MESA, the population attributable fraction Risk Prediction of AF
of AF attributable to hypertension appeared • In the biracial REGARDS study, better cardiovascu-
to be higher in US NH blacks (33.1%), Chinese lar health, as classified by Life’s Simple 7, predicted
(46.3%), and Hispanics (43.9%) than in NH decreased risk of AF similarly between sexes and
whites (22.2%).74 in blacks and whites. Individuals with optimal car-
diovascular health (score 10–14 points) had an
DM and HbA1c adjusted 32% lower risk of AF (OR, 0.68 [95%
• In a meta-analysis restricted to prospective stud- CI, 0.47 to 0.99]).178
ies, HbA1c was associated with an increased risk • ARIC,179 the FHS,180 and the Women’s Health
of AF when analyzed as a continuous (RR, 1.11 Study181 have developed risk prediction models to
[95% CI, 1.06–1.16]) or categorical (RR, 1.09 predict new-onset AF. Predictors of increased risk
[95% CI, 1.00–1.18]) variable.164 of new-onset AF include advancing age, European
Downloaded from http://ahajournals.org by on February 7, 2019

• In a meta-analysis of observational studies ancestry, body size (greater height and BMI), elec-
(excluding a large outlier study) the RR of inci- trocardiographic features (LVH, left atrial enlarge-
dent AF was 1.28 (31 cohort studies [95% CI, ment), DM, BP (SBP and hypertension treatment),
1.22–1.35]) for DM and 1.20 (4 studies [95% CI, and presence of CVD (CHD, HF, valvular HD).
1.03–1.39]) for prediabetes.165 • More recently, the ARIC, CHS, and FHS investi-
Miscellaneous Risk Factors gators developed and validated a risk prediction
• Other consistently reported risk factors for AF model for AF in blacks and whites, which was rep-
include clinical and subclinical166 hyperthyroid- licated in 2 European cohorts.182 The CHARGE-AF
ism, CKD,167,168 and moderate169 or heavy alcohol model has been validated in US multiethnic
consumption.170 cohorts including Hispanics,183 in MESA,184 and in
• Central sleep apnea also is associated with an a United Kingdom cohort (EPIC Norfolk).185
increased risk of incident AF.171 For instance, in the Borderline Risk Factors
Sleep Heart Health Study, a central sleep apnea • Data from the ARIC study indicated that having
index ≥5 was associated with an adjusted 3-fold at least 1 elevated risk factor explained 50% and
higher odds (OR, 3.00 [95% CI, 1.40–6.44]) of having at least 1 borderline risk factor explained
incident AF.172 6.5% of incident AF cases. The estimated overall
• Investigators from the Danish Diet, Cancer, and incidence rate per 1000 person-years at a mean
Health cohort reported that individuals with age of 54.2 years was 2.19 for those with optimal
higher exposure to NO2, a traffic-related air pol- risk, 3.68 for those with borderline risk, and 6.59
lutant, had higher risk of AF (adjusted IRR, 1.08 for those with elevated risk factors.157
[95% CI, 1.01–1.14] per 10 mcg/m3 higher
10-year time-weighted mean exposure to NO2).173 Subclinical Atrial Tachyarrhythmias,
• AF frequently occurs secondary to other Unrecognized AF, Screening for AF
comorbidities. Device-Detected AF
— In the FHS, 31% of AF was diagnosed in • Cardiac implantable electronic devices (eg, pace-
the context of a secondary, reversible con- makers and defibrillators) have increased clini-
dition. The most common triggers of AF cian awareness of the frequency of subclinical AF

e302 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

and atrial high-rate episodes in people without a million AF cases in the United States were undiag-

CLINICAL STATEMENTS
documented history of AF. Several studies have nosed. Of the undiagnosed AF cases, investigators

AND GUIDELINES
suggested that device-detected high-rate atrial estimated 535 400 (95% CI, 331 900–804 400;
tachyarrhythmias are surprisingly frequent and 1.3%) were in individuals ≥65 years of age, and
are associated with an increased risk of AF and 163 500 (95% CI, 17 700–400 000; 0.09%) were
total mortality.186,187 in individuals 18 to 64 years old.191
• Investigators in the ASSERT study prospectively • The incidence of detecting previously undiag-
enrolled 2580 patients with a recent pacemaker nosed AF by screening depends on the underlying
or defibrillator implantation who were ≥65 years risk of AF in the population studied, the intensity
of age, had a history of hypertension, and had no and duration of screening, and the method used
history of AF. They classified individuals by pres- to detect AF.192
ence versus absence of subclinical atrial tachyar- • Methods vary in their sensitivity and specific-
rhythmias (defined as atrial rate >190 beats per ity in the detection of undiagnosed AF, increas-
minute for >6 minutes in the first 3 months) and ing from palpation, to devices such as handheld
conducted follow-up for 2.5 years.188 Subclinical single-lead ECGs, modified BP devices, and
atrial tachyarrhythmias in the first 3 months plethysmographs.192
occurred in 10.1% of the patients and were asso- • There has been increasing interest in the use of
ciated with the following188: smart phone technology to aid in community
— An almost 6-fold higher risk of clinical AF screening.193,194
(HR, 5.6 [95% CI, 3.8–8.2]) • In a community-based study in Sweden
— A more than doubling in the adjusted risk of (STROKESTOP), half of the population 75 to 76
the primary end point, ischemic stroke or sys- years of age were invited to a stepwise screen-
temic embolism (HR, 2.5 [95% CI, 1.3–4.9]) ing program for AF, and 7173 participated in the
— An annual ischemic stroke or systemic embo- screening, of whom 218 had newly diagnosed AF
lism rate of 1.7% (versus 0.7% in those (3.0% [95% CI, 2.7%–3.5%]) and an additional
without) 666 (9.3% [95% CI, 8.6%–10.0%]) had previ-
— A 13% PAR for ischemic stroke or systemic ously diagnosed AF. Of the 218 newly diagnosed
embolism AF cases, only 37 were diagnosed by screening
electrocardiography, whereas intermittent moni-
Downloaded from http://ahajournals.org by on February 7, 2019

— Over the subsequent 2.5 years of follow-

up, an additional 35% of the patients had toring detected 4 times as many cases. Of those
subclinical atrial tachyarrhythmias, which individuals with newly diagnosed AF, 93% initi-
were 8-fold more frequent than clinical AF ated treatment with oral anticoagulant drugs.195
episodes. • There have been 2 systematic reviews regard-
• A pooled analysis of 5 prospective studies in ing the effectiveness of screening to detect
patients without permanent AF revealed that over unknown AF.
2 years of follow-up, cardiac implanted electronic — Lowres et al196 identified 30 separate studies
devices detected ≥5 minutes of AF in 43% of the that included outpatient clinics or community
patients (total N=10 016). AF burden was associ- screening. In individuals without a prior diag-
ated with an increased risk of stroke after adjust- nosis of AF, they observed that 1.0% (95%
ment for CHADS2 score and anticoagulation.189 CI, 0.89%–1.04%) of those screened had
• The temporal association of AF and stroke risk AF (14 studies, N=67 772), whereas among
was evaluated in a case-crossover analysis among those individuals ≥65 years of age, 1.4%
9850 patients with cardiac implantable elec- (95% CI, 1.2%–1.6%; 8 studies, N=18 189)
tronic devices enrolled in the Veterans Health had AF.
Administration healthcare system. The OR for an — Another systematic review by Moran et al197
acute ischemic stroke was the highest within a observed that in individuals >65 years of
5-day period after a qualifying AF episode, which age, systematic screening (OR, 1.57 [95% CI,
was defined as at least 5.5 hours of AF on a given 1.08–2.26]) and opportunistic screening (OR,
day. This estimate reduced as the period after the 1.58 [95% CI, 1.10–2.29]) were associated
with enhanced detection of AF. The number
AF occurrence extended beyond 30 days.190
needed to screen by either method was ≈170
Community Screening individuals.
• The prevalence of undiagnosed AF in the com- • At present, the detection of AF, even in an asymp-
munity is unknown. Using Medicare and com- tomatic stage, is the basis for risk stratification for
mercials claims data, investigators have estimated stroke and appropriate decision making on the
that in 2009, ≈0.7 million (13.1%) of the ≈5.3 need for anticoagulant drugs. Ongoing trials are

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e303

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

evaluating the risks and benefits of anticoagula- transcription factor 2 (PITX2) gene.205 The study
CLINICAL STATEMENTS

tion among patients at high risk for stroke but identified a total of 26 loci, which were in or near
AND GUIDELINES

without a prior history of AF. The findings from genes encoding ion channels, sarcomeric proteins,
these studies will help to determine optimal and transcription factors. Japanese investigators
strategies for subclinical AF screening and treat- were able to replicate 7 loci previously reported in
ment.192 To date, no studies have demonstrated cohorts predominantly of European ancestry and
that AF screening reduces mortality or incidence were able to identify 6 new loci.206
of thromboembolic complications. • A subsequent GWAS, which included >65 000
patients with AF, reported 97 AF-associated loci,
Family History and Genetics 67 of which were novel in combined-ancestry
Family History analyses.207
• Although unusual, early-onset lone AF has long • Whole exome/genome sequencing studies have
been recognized to cluster in families.12,198 In the identified rare mutations in additional genes,
past decade, the heritability of AF in the commu- including MYL4.208
nity has been appreciated. • Investigators in the FHS examined the lifetime
• In studies from the FHS: risk of AF at age 55 years using both clinical
— Adjusted for coexistent risk factors, having at and genetic risk factors. They derived polygenic
least 1 parent with AF was associated with risk scores of 1000 variants (many were sub-
a 1.85-fold increased risk of AF in the adult threshold hits) associated with AF in the UK
offspring (multivariable-adjusted 95% CI, Biobank. They divided participants into tertiles
1.12–3.06; P=0.02).199 of clinical and genetic risk and reported that
— A history of a first-degree relative with AF individuals within the lowest tertile of clinical
also was associated with an increased risk and of polygenic risk had a lifetime risk of AF
of AF (HR, 1.40 [95% CI, 1.13–1.74]). The of 22.3% (95% CI, 15.4%–29.1%), whereas
risk was greater if the first-degree relative’s those in the highest tertile of clinical and poly-
age of onset was ≤65 years (HR, 2.01 [95% genic risk had a lifetime risk of 48.2% (95% CI,
CI, 1.49–2.71]) and with each additional 41.3%–55.1%).80
affected first-degree relative (HR, 1.24 [95% • Some studies suggest that genetic markers of AF
CI, 1.05–1.46]).200 Similar findings were could improve risk prediction for AF over models
Downloaded from http://ahajournals.org by on February 7, 2019

reported from Sweden.201 that include clinical factors.181

• A Taiwanese population-based study reported • Genetic risk scores could also identify patients at
that a history of a first-degree relative with AF higher risk of cardioembolic stroke209; however,
was associated with a 1.92-fold (95% CI, 1.84– the utility of clinical genetic testing for AF-related
1.99) increased risk of newly diagnosed AF. They genetic variants is unclear.
estimated that 19.9% of the increased risk was
Prevention
attributable to genetic (heritability) factors, with
(See Chart 16-9)
the remaining risk related to shared (3.5%) and
nonshared (76.5%) environmental factors.202 Primary Prevention: Observational Data
• A study from the UK Biobank estimated that the • An observational prospective Swedish study
heritability of AF was 22.1% (95% CI, 15.6%– revealed that individuals having bariatric surgery
28.5%). The heritability was similar by sex and had a 29% lower risk (HR, 0.79 [95% CI, 0.60–
in older (>65 years) versus younger (≤65 years) 0.83]; P<0.001) of developing AF in 19 years of
people. Most of the variation was explained by median follow-up than matched referents.210
common (minor allele frequency ≥5%) genetic Secondary Prevention of AF: Observational Data
variation.203 • There are increasingly more data supporting the
• Racial variation in AF incidence is complex and not importance of risk factor modification for second-
fully understood. One study of blacks and whites ary prevention of AF recurrence and improved
from CHS and ARIC suggested that genetic mark- symptoms.
ers of European ancestry were associated with an — In individuals referred for catheter abla-
increased risk of incident AF.204 tion, those who agreed to aggressive risk
• A recent meta-analysis of genetic studies in AF factor modification had lower symptom
included GWASs with >17 000 case subjects and burden in follow-up and higher adjusted
>115 000 referents and exome-wide association AF-free survival (HR, 4.8 [95% CI, 2.0–11.4];
studies of >22 000 AF cases and >132 000 refer- P<0.001).211
ents. The strongest common variant associated — The same Australian investigators reported
with AF was near the paired-like homeodomain that overweight and obese individuals with

e304 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

symptomatic AF who opted to participate enrolled were eligible for at least 1 cardiovascular

CLINICAL STATEMENTS
in weight loss and aggressive risk factor evidence-based therapy. The proportions receiv-

AND GUIDELINES
management interventions had fewer hos- ing evidence-based therapy varied by diagnosis,
pitalizations, cardioversions, and ablation at 40.8% of those with CAD, 48.9% of those
procedures than their counterparts who with DM, 40.2% of those with HF, and 96.7% of
declined enrollment. The risk factor man- those with hypertension.219
agement group was associated with a pre-
Prevention: Randomized Data
dicted 10-year cost savings of $12 094 per
• Intensive glycemic control was not found to pre-
patient.212
vent incident AF in the ACCORD study.104
— In adjusted analyses, overweight and obese
• In the Look AHEAD randomized trial of individuals
individuals with paroxysmal or persistent AF
with type 2 DM who were overweight to obese,
who achieved at least 10% weight loss were
an intensive lifestyle intervention associated with
6-fold more likely to be AF free (86.2% AF
modest weight loss did not significantly affect the
free; HR, 5.9 [95% CI, 3.4–10.3]; P<0.001)
rate of incident AF (6.1 versus 6.7 cases per 1000
than those with <3% weight loss (39.6% AF
person-years of follow-up; multivariable HR, 0.99
free). In addition, individuals losing at least
[95% CI, 0.77–1.28]); however, AF was not pre-
10% weight reported fewer symptoms.213
specified as a primary or secondary outcome.220
— The same Australian group also reported that
• Randomized trials of overweight or obese patients
among consecutive overweight and obese
referred to an Adelaide, Australia, arrhythmia
patients with AF who agreed to participate
clinic for management of symptomatic parox-
in an exercise program, those who achieved
ysmal or persistent AF demonstrated that indi-
less improvement in cardiorespiratory fitness
viduals randomized to a weight loss intervention
(<2 METs gain) had lower AF-free survival
reported lower symptom burden.221
(40%; HR, 3.9 [95% CI, 2.1–7.3]; P<0.001)
• Meta-analyses have suggested that BP lowering
than those with greater improvement in fit-
might be useful in prevention of AF in trials of
ness (≥2 METs gain, 89% AF free).214
hypertension, after MI, in HF, and after cardiover-
• Treatment of OSA has been noted to decrease
sion.222,223 However, the studies were primarily
risk of progression to permanent AF.215 In a meta-
secondary or post hoc analyses, the intervention
analysis, CPAP was reported to be associated with
Downloaded from http://ahajournals.org by on February 7, 2019

duration was modest, and the results were fairly

a reduced risk of recurrent AF after ablation.216
heterogeneous.
However, there is a lack of robust randomized
• Recently, in an analysis of the EMPHASIS-HF trial,
data supporting the role of CPAP in the primary
in one of many secondary outcomes, eplerenone
and secondary prevention of AF in individuals
was nominally observed to reduce the incidence
with sleep-disordered breathing.
of new-onset AF. However, the number of AF
• In a national outpatient registry of AF patients
events was modest.224
(ORBIT-AF), 94% had indications for guideline-
• A post hoc analysis of the PREDIMED randomized
based primary or secondary prevention in addition
primary prevention study suggested a significant
to oral anticoagulant drugs; however, only 47%
reduction in incident AF with the Mediterranean
received all guideline-indicated therapies, consis-
diet including extra virgin olive oil (HR, 0.62 [95%
tent with an underutilization of evidence-based
CI, 0.45–0.85]).225
preventive therapies for comorbid conditions in
• Although heterogeneous in their findings, mod-
individuals with AF.217 Predictors of not receiving
est-sized short-term studies suggested that the
all guideline-indicated therapies included frailty,
use of statins might prevent AF; however, larger
comorbid illness, geographic region, and anti-
longer-term studies do not provide support
arrhythmic drug therapy. Factors most strongly
for the concept that statins are effective in AF
associated with the 17% warfarin discontinua-
prevention.226
tion rate in the first year prescribed included hos-
pitalization because of bleeding (OR, 10.9 [95% Awareness
CI, 7.9–15.0]), prior catheter ablation (OR, 1.8 • In REGARDS, a US national biracial study, com-
[95% CI, 1.4–2.4]), noncardiovascular/nonbleed- pared with whites, blacks had approximately
ing hospitalization (OR, 1.8 [95% CI, 1.4–2.2]), one-third the likelihood (OR, 0.32 [95% CI, 0.20–
cardiovascular hospitalization (OR, 1.6 [95% CI, 0.52]) of being aware that they had AF.227 The
1.3–2.0]), and permanent AF (OR, 0.25 [95% CI, REGARDS investigators also reported that com-
0.17–0.36]).218 pared with individuals aware of their diagnosis,
• A study of 2 national Canadian primary care individuals who were unaware of their AF had a
audits similarly observed that 84.3% of individuals 94% higher risk of mortality in follow-up.228

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e305

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

• A study from Kaiser Permanente in California 34.8%. Although over the time period, the
CLINICAL STATEMENTS

examined the relation between AF diagnosis prevalence of oral anticoagulation treatment

AND GUIDELINES

(2006–2009) and self-report questionnaire data increased from 52.4% to 60.7%, substantive
(2010). Of the more than 12 000 individuals with gaps remain.235
diagnosed AF, 14.5% were unaware of their diag- — In the PINNACLE registry, females were sig-
nosis and 20.4% had inadequate health literacy. nificantly less likely to receive oral anticoag-
In adjusted analyses, low health literacy was ulants at all levels of CHA2DS2-VASc scores
associated with a lack of awareness of their AF (56.7% versus 61.3%; P<0.001).236
diagnosis (literacy prevalence ratio, 0.96 [95% CI, — The PINNACLE registry investigators also
0.94–0.98]).229 reported that receipt of warfarin versus a
direct oral anticoagulant varied significantly
Treatment and Control
by type of insurance, with military, private,
Anticoagulation Undertreatment and Medicare insured patients more likely to
• Studies have demonstrated underutilization of receive newer anticoagulants than individu-
oral anticoagulation therapy. In a meta-analysis, als with Medicaid and other insurance.237
males and individuals with prior stroke were more • Disparities in treatment patterns have also been
likely to receive warfarin, whereas factors associ- observed in Sweden. In adjusted analyses, com-
ated with lower use included alcohol and drug pared with individuals with AF living in middle-
abuse, noncompliance, warfarin contraindica- income neighborhoods, those living in high-SES
tions, dementia, falls, both gastrointestinal and neighborhoods were more likely to be prescribed
intracranial hemorrhage, renal impairment, and warfarin (males: OR, 1.44 [95% CI, 1.27–1.67];
advancing age.230 The underutilization of antico- females: OR, 1.19 [95% CI, 1.05–1.36]) and
agulation in AF has been demonstrated to be a statins (males: OR, 1.23 [95% CI, 1.07–1.41];
global problem.231 females: OR, 1.23 [95% CI, 1.05–1.44]).238
• The GWTG–Stroke program conducted a ret- • Investigators conducted multivariable cross-sec-
rospective analysis consisting of 1622 hospitals tional analyses of the NIS between 2012 and 2014
and 94 474 patients with acute ischemic stroke and observed that patients admitted to rural hos-
in the setting of known AF from 2012 to 2015. pitals had a 17% higher risk of death than those
In that analysis, 79  008 of patients (83.6%)
Downloaded from http://ahajournals.org by on February 7, 2019

admitted to urban hospitals (OR, 1.17 [95% CI,

were not receiving therapeutic anticoagulation: 1.04–1.32]).239
13.5% had a subtherapeutic international nor- • A systematic review and meta-analysis identified
malized ratio, 39.9% were receiving antiplatelet 3 studies of coordinated care systems of care
treatment only, and 30.3% were not receiving that included 1383 patients.240 The investigators
any antithrombotic therapy. In adjusted analy- reported that AF integrated care approaches were
ses versus patients receiving no antithrombotic associated with reduced all-cause mortality (OR,
medications, patients receiving antecedent ther- 0.51 [95% CI, 0.32 to 0.80]; P=0.003) and car-
apeutic warfarin, non–vitamin K antagonist oral diovascular hospitalizations (OR, 0.58 [95% CI,
anticoagulants, or antiplatelet therapy had lower 0.44 to 0.77]; P=0.0002).
odds of moderate or severe stroke (adjusted OR
[95% CI], 0.56 [0.51–0.60], 0.65 [0.61–0.71], Global Burden of AF
and 0.88 [0.84–0.92], respectively) and lower in- (See Charts 16-10 and 16-11)
hospital mortality.232 • The vast majority of research on the epidemiol-
• Individuals who had AF and were not treated with ogy of AF has been conducted in Europe and
anticoagulant drugs had a 2.1-fold increase in risk North America. Investigators from the GBD proj-
for recurrent stroke and a 2.4-fold increase in risk ect noted that the global prevalence, incidence,
for recurrent severe stroke.233 mortality, and DALYs associated with AF increased
• In the NCDR PINNACLE registry of outpatients from 1990 to 2010.241
with AF: • The GBD 2016 Study used statistical models and
— Less than half of high-risk patients, defined as data on incidence, prevalence, case fatality, excess
those with a CHA2DS2-VASc score ≥4, were mortality, and cause-specific mortality to estimate
receiving an oral anticoagulant prescription.234 disease burden for 315 diseases and injuries in
— Between 2008 and 2014, in individuals with 195 countries and territories.242
a CHA2DS2-VASc score >1, direct anticoag- — Total number of global deaths attributable
ulant use increased from 0 to 24.8%, and to AF/atrial flutter was 200  000 in 2016
use of warfarin decreased from 52.4% to (100 000 in females and 100 000 in males).

e306 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

— Globally, 46.3 million individuals had preva- • Investigators conducted a prospective registry of

CLINICAL STATEMENTS
lent AF/atrial flutter in 2016 (23.1 million >15 000 AF patients presenting to EDs in 47 coun-

AND GUIDELINES
females and 23.2 million males). tries. They observed substantial regional variabil-
— Mortality attributable to AF is highest in ity in annual AF mortality: South America (17%)
Northern Europe (Chart 16-10). and Africa (20%) had double the mortality rate
— Prevalence of AF is highest in Northern of North America, Western Europe, and Australia
Europe and the United States (Chart (10%; P<0.001). HF deaths (30%) exceeded
16-11). deaths attributable to stroke (8%).243

Table 16-1.  Cumulative Incidence Rate Over 5 Years After AF

Diagnosis, by Age*

Age Heart Myocardial Gastrointestinal

Group, y Mortality Failure Infarction Stroke Bleeding
67–69 28.8 11.0 3.3 5.0 4.4
70–74 32.3 12.1 3.6 5.7 4.9
75–79 40.1 13.3 3.9 6.9 5.9
80–84 52.1 15.1 4.3 8.1 6.4
85–89 67.0 15.8 4.4 8.9 6.6
≥90 84.3 13.7 3.6 6.9 5.4

All values are percentages. AF indicates atrial fibrillation.

*See Chart 16-7.
Adapted from Piccini et al114 by permission of the European Society of
Cardiology. Copyright © 2013, The Authors.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-1. Long-term outcomes in individuals with prolonged PR interval (>200 ms; first-degree atrioventricular block) compared with individuals
with normal PR interval in the FHS.
FHS indicates Framingham Heart Study.
Data derived from Cheng et al.11

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e307

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16
CLINICAL STATEMENTS
AND GUIDELINES

Chart 16-2. Primary indications (in thousands) for pacemaker placement between 1990 and 2002 from the NHDS, NCHS.
AV indicates atrioventricular; NCHS, National Center for Health Statistics; and NHDS, National Hospital Discharge Survey.
Data derived from Birnie et al.33
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-3. Incidence rate of paroxysmal supraventricular tachycardia per 100 000 person-years by age and sex.
Data derived from Orejarena et al.39

e308 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

CLINICAL STATEMENTS
AND GUIDELINES
Chart 16-4. Current and future US prevalence projections for AF.
Projections assume no increase (red dashed line) or logarithmic growth (blue dashed line) in incidence of AF from 2007.
AF indicates atrial fibrillation.
Data derived from Go et al68; and modified from Colilla et al70 with permission from Elsevier. Copyright © 2013, Elsevier Inc.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-5. Atrial fibrillation incidence by race.

Incidence increases with advancing age among different races and sexes in the United States.
Data derived from Dewland et al.75

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e309

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16
CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-6. Lifetime cumulative risk for atrial fibrillation at different ages (through age 94 years) by sex.
Reprinted from Weng et al.80 Copyright © 2018, American Heart Association, Inc.

e310 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

CLINICAL STATEMENTS
AND GUIDELINES
Chart 16-7. Cumulative incidence of events in the 5 years after diagnosis of incident AF in Medicare patients.
AF indicates atrial fibrillation.
Reprinted from Piccini et al114 by permission of the European Society of Cardiology. Copyright © 2013, The Authors.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-8. AF cost estimates, where AF is diagnosed in inpatient and outpatient encounters.
Indirect costs are incremental costs of inpatient and outpatient visits.
AF indicates atrial fibrillation; and USD, US dollars.
Adapted from Kim et al,150 copyright © 2011, American Heart Association, Inc.; and from Coyne et al152 with permission from the International Society for
Pharmacoeconomics and Outcomes Research (ISPOR), copyright © 2006, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e311

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16
CLINICAL STATEMENTS
AND GUIDELINES

Chart 16-9. Population attributable fraction of major risk factors for atrial fibrillation in the ARIC study.
ARIC indicates Atherosclerosis Risk in Communities; BMI, body mass index (in kg/m2); cardiac disease, patients with history of coronary artery disease or heart
failure; and smoking, current smoker.
Data derived from Huxley et al.157
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 16-10. Age-standardized global mortality rates of atrial fibrillation and flutter per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.242 Printed with permission.
Copyright © 2017, University of Washington.

e312 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

CLINICAL STATEMENTS
AND GUIDELINES
Chart 16-11. Age-standardized global prevalence rates of atrial fibrillation per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.242 Printed with permission. Copyright ©
Downloaded from http://ahajournals.org by on February 7, 2019

2017, University of Washington.

10. Bordachar P, Zachary W, Ploux S, Labrousse L, Haissaguerre M, Thambo

‍‍‍‍‍‍‍‍REFERENCES JB. Pathophysiology, clinical course, and management of congenital
1. Vitelli LL, Crow RS, Shahar E, Hutchinson RG, Rautaharju PM, Folsom AR; complete atrioventricular block. Heart Rhythm. 2013;10:760–766. doi:
for the Atherosclerosis Risk in Communities (ARIC) Study Investigators. 10.1016/j.hrthm.2012.12.030
Electrocardiographic findings in a healthy biracial population. Am J 11. Cheng S, Keyes MJ, Larson MG, McCabe EL, Newton-Cheh C, Levy D,
Cardiol. 1998;81:453–459. Benjamin EJ, Vasan RS, Wang TJ. Long-term outcomes in individuals
2. Walsh JA 3rd, Prineas R, Daviglus ML, Ning H, Liu K, Lewis CE, Sidney with prolonged PR interval or first-degree atrioventricular block. JAMA.
S, Schreiner PJ, Iribarren C, Lloyd-Jones DM. Prevalence of electrocardio- 2009;301:2571–2577. doi: 10.1001/jama.2009.888
graphic abnormalities in a middle-aged, biracial population: Coronary 12. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes
Artery Risk Development in Young Adults study. J Electrocardiol. LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby
2010;43:385.e1–385.e9. doi: 10.1016/j.jelectrocard.2010.02.001 LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. 2012
3. Aro AL, Anttonen O, Kerola T, Junttila MJ, Tikkanen JT, Rissanen HA, Reunanen ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS
A, Huikuri HV. Prognostic significance of prolonged PR interval in the general 2008 guidelines for device-based therapy of cardiac rhythm abnormalities:
population. Eur Heart J. 2014;35:123–129. doi: 10.1093/eurheartj/eht176 a report of the American College of Cardiology Foundation/American Heart
4. Wolbrette D, Naccarelli G. Bradycardias: sinus nodal dysfunction and Association Task Force on Practice Guidelines and the Heart Rhythm Society.
atrioventricular conduction disturbances. In: Topol. EJ, ed. Textbook of Circulation. 2013;127:e283–e352. doi: 10.1161/CIR.0b013e318276ce9b
Cardiovascular Medicine. 3rd ed. Philadelphia, PA: Lippincott Williams & 13. Auffret V, Loirat A, Leurent G, Martins RP, Filippi E, Coudert I, Hacot
Wilkins; 2007:1038–1049. JP, Gilard M, Castellant P, Rialan A, Delaunay R, Rouault G, Druelles P,
5. Ostrander LD Jr, Brandt RL, Kjelsberg MO, Epstein FH. Electrocardiographic Boulanger B, Treuil J, Avez B, Bedossa M, Boulmier D, Le Guellec M,
findings among the adult population of a total natural community, Daubert JC, Le Breton H. High-degree atrioventricular block complicat-
Tecumseh, Michigan. Circulation. 1965;31:888–898. ing ST segment elevation myocardial infarction in the contemporary era.
6. Kojic EM, Hardarson T, Sigfusson N, Sigvaldason H. The prevalence and Heart. 2016;102:40–49. doi: 10.1136/heartjnl-2015-308260
prognosis of third-degree atrioventricular conduction block: the Reykjavik 14. Mymin D, Mathewson FA, Tate RB, Manfreda J. The natural his-
study. J Intern Med. 1999;246:81–86. tory of primary first-degree atrioventricular heart block. N Engl J Med.
7. Movahed MR, Hashemzadeh M, Jamal MM. Increased prevalence of third- 1986;315:1183–1187. doi: 10.1056/NEJM198611063151902
degree atrioventricular block in patients with type II diabetes mellitus. 15. Barold SS, Ilercil A, Leonelli F, Herweg B. First-degree atrioventricular
Chest. 2005;128:2611–2614. doi: 10.1378/chest.128.4.2611 block. Clinical manifestations, indications for pacing, pacemaker man-
8. Solomon MD, Yang J, Sung SH, Livingston ML, Sarlas G, Lenane JC, Go AS. agement & consequences during cardiac resynchronization. J Interv Card
Incidence and timing of potentially high-risk arrhythmias detected through Electrophysiol. 2006;17:139–152. doi: 10.1007/s10840-006-9065-x
long term continuous ambulatory electrocardiographic monitoring. BMC 16. Soliman EZ, Alonso A, Misialek JR, Jain A, Watson KE, Lloyd-Jones DM,
Cardiovasc Disord. 2016;16:35. doi: 10.1186/s12872-016-0210-x Lima J, Shea S, Burke GL, Heckbert SR. Reference ranges of PR duration
9. Turner CJ, Wren C. The epidemiology of arrhythmia in infants: a pop- and P-wave indices in individuals free of cardiovascular disease: the Multi-
ulation-based study. J Paediatr Child Health. 2013;49:278–281. doi: Ethnic Study of Atherosclerosis (MESA). J Electrocardiol. 2013;46:702–
10.1111/jpc.12155 706. doi: 10.1016/j.jelectrocard.2013.05.006

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e313

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

17. Grimm W, Koehler U, Fus E, Hoffmann J, Menz V, Funck R, Peter JH, incident cardiovascular disease and mortality: the Multi-Ethnic Study
CLINICAL STATEMENTS

Maisch B. Outcome of patients with sleep apnea-associated severe of Atherosclerosis (MESA). JAMA Intern Med. 2016;176:219–227. doi:
AND GUIDELINES

bradyarrhythmias after continuous positive airway pressure therapy. Am 10.1001/jamainternmed.2015.7655

J Cardiol. 2000;86:688–692, A9. 36. Issa Z, Miller J, Zipes D. Clinical Arrhythmology and Electrophysiology:
18. Bernstein AD, Parsonnet V. Survey of cardiac pacing and implanted A Companion to Braunwald’s Heart Disease. Philadelphia, PA: Saunders
defibrillator practice patterns in the United States in 1997. Pacing Clin Elsevier; 2008.
Electrophysiol. 2001;24:842–855. 37. Dobrzynski H, Boyett MR, Anderson RH. New insights into pacemaker
19. Rodriguez RD, Schocken DD. Update on sick sinus syndrome, a cardiac activity: promoting understanding of sick sinus syndrome. Circulation.
disorder of aging. Geriatrics. 1990;45:26–30, 33. 2007;115:1921–1932. doi: 10.1161/CIRCULATIONAHA.106.616011
20. Brignole M, Menozzi C, Lolli G, Oddone D, Gianfranchi L, Bertulla A. 38. Rosenqvist M, Obel IW. Atrial pacing and the risk for AV block: is there
Pacing for carotid sinus syndrome and sick sinus syndrome. Pacing Clin a time for change in attitude? Pacing Clin Electrophysiol. 1989;12(pt
Electrophysiol. 1990;13(pt 2):2071–2075. 1):97–101.
21. Sutton R, Kenny RA. The natural history of sick sinus syndrome. Pacing 39. Orejarena LA, Vidaillet H Jr, DeStefano F, Nordstrom DL, Vierkant RA,
Clin Electrophysiol. 1986;9(pt 2):1110–1114. Smith PN, Hayes JJ. Paroxysmal supraventricular tachycardia in the general
22. Baine WB, Yu W, Weis KA. Trends and outcomes in the hospitalization of population. J Am Coll Cardiol. 1998;31:150–157.
older Americans for cardiac conduction disorders or arrhythmias, 1991- 40. Murman DH, McDonald AJ, Pelletier AJ, Camargo CA Jr. U.S. emergency
1998. J Am Geriatr Soc. 2001;49:763–770. department visits for supraventricular tachycardia, 1993-2003. Acad
23. Jensen PN, Gronroos NN, Chen LY, Folsom AR, deFilippi C, Heckbert Emerg Med. 2007;14:578–581. doi: 10.1197/j.aem.2007.01.013
SR, Alonso A. Incidence of and risk factors for sick sinus  syndrome in 41. Turakhia MP, Hoang DD, Zimetbaum P, Miller JD, Froelicher VF, Kumar
the general population. J Am Coll Cardiol. 2014;64:531–538. doi: UN, Xu X, Yang F, Heidenreich PA. Diagnostic utility of a novel leadless
10.1016/j.jacc.2014.03.056 arrhythmia monitoring device. Am J Cardiol. 2013;112:520–524. doi:
24. Menozzi C, Brignole M, Alboni P, Boni L, Paparella N, Gaggioli G, Lolli 10.1016/j.amjcard.2013.04.017
G. The natural course of untreated sick sinus syndrome and identifica- 42. Maurer MS, Shefrin EA, Fleg JL. Prevalence and prognostic significance of
tion of the variables predictive of unfavorable outcome. Am J Cardiol. exercise-induced supraventricular tachycardia in apparently healthy volun-
1998;82:1205–1209. teers. Am J Cardiol. 1995;75:788–792.
25. Alt E, Völker R, Wirtzfeld A, Ulm K. Survival and follow-up after pace- 43. Poutiainen AM, Koistinen MJ, Airaksinen KE, Hartikainen EK, Kettunen
maker implantation: a comparison of patients with sick sinus syndrome, RV, Karjalainen JE, Huikuri HV. Prevalence and natural course of ectopic
complete heart block, and atrial fibrillation. Pacing Clin Electrophysiol. atrial tachycardia. Eur Heart J. 1999;20:694–700.
1985;8:849–855. 44. Wu EB, Chia HM, Gill JS. Reversible cardiomyopathy after radiofrequency
26. Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak ablation of lateral free-wall pathway-mediated incessant supraventricular
RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, tachycardia. Pacing Clin Electrophysiol. 2000;23:1308–1310.
Ellenbogen K, Ehlert F, Freedman RA, Estes NA 3rd, Greenspon A, 45. Wang YS, Scheinman MM, Chien WW, Cohen TJ, Lesh MD, Griffin JC.
Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular Patients with supraventricular tachycardia presenting with aborted sud-
pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. den death: incidence, mechanism and long-term follow-up. J Am Coll
2002;346:1854–1862. doi: 10.1056/NEJMoa013040 Cardiol. 1991;18:1711–1719.
27. Simon AB, Janz N. Symptomatic bradyarrhythmias in the adult: natu- 46. Chang SH, Kuo CF, Chou IJ, See LC, Yu KH, Luo SF, Chiou MJ, Zhang
ral history following ventricular pacemaker implantation. Pacing Clin W, Doherty M, Wen MS, Chen WJ, Yeh YH. Outcomes associated with
Electrophysiol. 1982;5:372–383. paroxysmal supraventricular tachycardia during pregnancy. Circulation.
Downloaded from http://ahajournals.org by on February 7, 2019

28. Hesselson AB, Parsonnet V, Bernstein AD, Bonavita GJ. Deleterious effects 2017;135:616–618. doi: 10.1161/CIRCULATIONAHA.116.025064
of long-term single-chamber ventricular pacing in patients with sick sinus 47. Kamel H, Elkind MS, Bhave PD, Navi BB, Okin PM, Iadecola C,
syndrome: the hidden benefits of dual-chamber pacing. J Am Coll Cardiol. Devereux RB, Fink ME. Paroxysmal supraventricular tachycardia
1992;19:1542–1549. and the risk of ischemic stroke. Stroke. 2013;44:1550–1554. doi:
29. Alonso A, Jensen PN, Lopez FL, Chen LY, Psaty BM, Folsom AR, Heckbert 10.1161/STROKEAHA.113.001118
SR. Association of sick sinus syndrome with incident cardiovascular 48. Carnlöf C, Iwarzon M, Jensen-Urstad M, Gadler F, Insulander P. Women
disease and mortality: the Atherosclerosis Risk in Communities study with PSVT are often misdiagnosed, referred later than men, and have
and Cardiovascular Health Study. PLoS One. 2014;9:e109662. doi: more symptoms after ablation. Scand Cardiovasc J. 2017;51:299–307.
10.1371/journal.pone.0109662 doi: 10.1080/14017431.2017.1385837
30. Udo EO, van Hemel NM, Zuithoff NP, Doevendans PA, Moons KG. 49. Brembilla-Perrot B, Houriez P, Beurrier D, Claudon O, Burger G, Vançon
Prognosis of the bradycardia pacemaker recipient assessed at first implan- AC, Mock L. Influence of age on the electrophysiological mechanism of
tation: a nationwide cohort study. Heart. 2013;99:1573–1578. doi: paroxysmal supraventricular tachycardias. Int J Cardiol. 2001;78:293–298.
10.1136/heartjnl-2013-304445 50. Porter MJ, Morton JB, Denman R, Lin AC, Tierney S, Santucci PA, Cai JJ,
31. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Madsen N, Wilber DJ. Influence of age and gender on the mechanism
Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, of supraventricular tachycardia. Heart Rhythm. 2004;1:393–396. doi:
Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney 10.1016/j.hrthm.2004.05.007
MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac 51. Anand RG, Rosenthal GL, Van Hare GF, Snyder CS. Is the mecha-
rhythm abnormalities: a report of the American College of Cardiology/ nism of supraventricular tachycardia in pediatrics influenced by age,
American Heart Association Task Force on Practice Guidelines (Writing gender or ethnicity? Congenit Heart Dis. 2009;4:464–468. doi:
Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for 10.1111/j.1747-0803.2009.00336.x
Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) [pub- 52. Bradley DJ, Fischbach PS, Law IH, Serwer GA, Dick M 2nd. The clinical
lished correction appears in Circulation. 2009;120:e34–35]. Circulation. course of multifocal atrial tachycardia in infants and children. J Am Coll
2008;117:e350–e408. doi: 10.1161/CIRCUALTIONAHA.108.189742 Cardiol. 2001;38:401–408.
32. Greenspon AJ, Patel JD, Lau E, Ochoa JA, Frisch DR, Ho RT, Pavri BB, Kurtz 53. McCord J, Borzak S. Multifocal atrial tachycardia. Chest. 1998;113:
SM. Trends in permanent pacemaker implantation in the United States 203–209.
from 1993 to 2009: increasing complexity of patients and procedures. J 54. Lazaros G, Chrysohoou C, Oikonomou E, Tsiachris D, Mazaris S, Venieri
Am Coll Cardiol. 2012;60:1540–1545. doi: 10.1016/j.jacc.2012.07.017 E, Zisimos K, Zaromytidou M, Kariori M, Kioufis S, Pitsavos C, Stefanadis
33. Birnie D, Williams K, Guo A, Mielniczuk L, Davis D, Lemery R, Green M, C. The natural history of multifocal atrial rhythms in elderly outpa-
Gollob M, Tang A. Reasons for escalating pacemaker implants. Am J tients: insights from the “Ikaria study.” Ann Noninvasive Electrocardiol.
Cardiol. 2006;98:93–97. doi: 10.1016/j.amjcard.2006.01.069 2014;19:483–489. doi: 10.1111/anec.12165
34. Goldberger JJ, Johnson NP, Gidea C. Significance of asymptomatic 55. De Bacquer D, De Backer G, Kornitzer M. Prevalences of ECG find-
bradycardia for subsequent pacemaker implantation and mortality ings in large population based samples of men and women. Heart.
in patients >60 years of age. Am J Cardiol. 2011;108:857–861. doi: 2000;84:625–633.
10.1016/j.amjcard.2011.04.035 56. Sano S, Komori S, Amano T, Kohno I, Ishihara T, Sawanobori T, Ijiri H,
35. Dharod A, Soliman EZ, Dawood F, Chen H, Shea S, Nazarian S, Bertoni Tamura K. Prevalence of ventricular preexcitation in Japanese schoolchil-
AG; MESA Investigators. Association of asymptomatic bradycardia with dren. Heart. 1998;79:374–378.

e314 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

57. Blomström-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, 73. Piccini JP, Hammill BG, Sinner MF, Jensen PN, Hernandez AF, Heckbert

CLINICAL STATEMENTS
Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, SR, Benjamin EJ, Curtis LH. Incidence and prevalence of atrial fibril-

AND GUIDELINES
Shaeffer CW Jr, Stevenson WG, Tomaselli GF. ACC/AHA/ESC guidelines lation and associated mortality among Medicare beneficiaries,
for the management of patients with supraventricular arrhythmias–exec- 1993-2007. Circ Cardiovasc Qual Outcomes. 2012;5:85–93. doi:
utive summary: a report of the American College of Cardiology/American 10.1161/CIRCOUTCOMES.111.962688
Heart Association Task Force on Practice Guidelines and the European 74. Rodriguez CJ, Soliman EZ, Alonso A, Swett K, Okin PM, Goff DC Jr,
Society of Cardiology Committee for Practice Guidelines (Writing Heckbert SR. Atrial fibrillation incidence and risk factors in relation to
Committee to Develop Guidelines for the Management of Patients With race-ethnicity and the population attributable fraction of atrial fibrillation
Supraventricular Arrhythmias). Circulation. 2003;108:1871–1909. doi: risk factors: the Multi-Ethnic Study of Atherosclerosis. Ann Epidemiol.
10.1161/01.CIR.0000091380.04100.84 2015;25:71–6, 76.e1. doi: 10.1016/j.annepidem.2014.11.024
58. Bunch TJ, May HT, Bair TL, Anderson JL, Crandall BG, Cutler MJ, Jacobs 75. Dewland TA, Olgin JE, Vittinghoff E, Marcus GM. Incident atrial fibrillation
V, Mallender C, Muhlestein JB, Osborn JS, Weiss JP, Day JD. Long-term among Asians, Hispanics, blacks, and whites. Circulation. 2013;128:2470–
natural history of adult Wolff-Parkinson-White syndrome patients 2477. doi: 10.1161/CIRCULATIONAHA.113.002449
treated with and without catheter ablation. Circ Arrhythm Electrophysiol. 76. Martinez C, Katholing A, Wallenhorst C, Granziera S, Cohen AT,
2015;8:1465–1471. doi: 10.1161/CIRCEP.115.003013 Freedman SB. Increasing incidence of non-valvular atrial fibrillation
59. Leitch JW, Klein GJ, Yee R, Murdock C. Prognostic value of electrophysiol- in the UK from 2001 to 2013. Heart. 2015;101:1748–1754. doi:
ogy testing in asymptomatic patients with Wolff-Parkinson-White pattern 10.1136/heartjnl-2015-307808
[published correction appears in Circulation. 1991;83:1124]. Circulation. 77. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D’Agostino
1990;82:1718–1723. RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for devel-
60. Krahn AD, Manfreda J, Tate RB, Mathewson FA, Cuddy TE. The natu- opment of atrial fibrillation: the Framingham Heart Study. Circulation.
ral history of electrocardiographic preexcitation in men: the Manitoba 2004;110:1042–1046. doi: 10.1161/01.CIR.0000140263.20897.42
Follow-up Study. Ann Intern Med. 1992;116:456–460. 78. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker
61. Munger TM, Packer DL, Hammill SC, Feldman BJ, Bailey KR, Ballard DJ, BH, Stijnen T, Lip GY, Witteman JC. Prevalence, incidence and lifetime risk
Holmes DR Jr, Gersh BJ. A population study of the natural history of Wolff- of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27:949–953.
Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989. doi: 10.1093/eurheartj/ehi825.
Circulation. 1993;87:866–873. 79. Magnussen C, Niiranen TJ, Ojeda FM, Gianfagna F, Blankenberg S,
62. Goudevenos JA, Katsouras CS, Graekas G, Argiri O, Giogiakas V, Sideris Njølstad I, Vartiainen E, Sans S, Pasterkamp G, Hughes M, Costanzo S,
DA. Ventricular pre-excitation in the general population: a study on the Donati MB, Jousilahti P, Linneberg A, Palosaari T, de Gaetano G, Bobak
mode of presentation and clinical course. Heart. 2000;83:29–34. M, den Ruijter HM, Mathiesen E, Jørgensen T, Söderberg S, Kuulasmaa
63. Pappone C, Vicedomini G, Manguso F, Saviano M, Baldi M, Pappone K, Zeller T, Iacoviello L, Salomaa V, Schnabel RB; on behalf of the
A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Cuko A, BiomarCaRE Consortium. Sex differences and similarities in atrial fibril-
Calovic Z, Fundaliotis A, Moscatiello M, Tavazzi L, Santinelli V. Wolff- lation epidemiology, risk factors, and mortality in community cohorts:
Parkinson-White syndrome in the era of catheter ablation: insights from results from the BiomarCaRE Consortium (Biomarker for Cardiovascular
a registry study of 2169 patients. Circulation. 2014;130:811–819. doi: Risk Assessment in Europe). Circulation. 2017;136:1588–1597. doi:
10.1161/CIRCULATIONAHA.114.011154 10.1161/CIRCULATIONAHA.117.028981
64. Obeyesekere MN, Leong-Sit P, Massel D, Manlucu J, Modi S, Krahn AD, 80. Weng LC, Preis SR, Hulme OL, Larson MG, Choi SH, Wang B, Trinquart
Skanes AC, Yee R, Gula LJ, Klein GJ. Risk of arrhythmia and sudden death L, McManus DD, Staerk L, Lin H, Lunetta KL, Ellinor PT, Benjamin EJ,
in patients with asymptomatic preexcitation: a meta-analysis. Circulation. Lubitz SA. Genetic predisposition, clinical risk factor burden, and life-
Downloaded from http://ahajournals.org by on February 7, 2019

2012;125:2308–2315. doi: 10.1161/CIRCULATIONAHA.111.055350 time risk of atrial fibrillation. Circulation. 2018;137:1027–1038. doi:
65. Inoue K, Igarashi H, Fukushige J, Ohno T, Joh K, Hara T. Long-term pro- 10.1161/CIRCULATIONAHA.117.031431
spective study on the natural history of Wolff-Parkinson-White syndrome 81. Staerk L, Wang B, Preis SR, Larson MG, Lubitz SA, Ellinor PT, McManus DD,
detected during a heart screening program at school. Acta Paediatr. Ko D, Weng LC, Lunetta KL, Frost L, Benjamin EJ, Trinquart L. Lifetime risk
2000;89:542–545. of atrial fibrillation according to optimal, borderline, or elevated levels of
66. Pappone C, Manguso F, Santinelli R, Vicedomini G, Sala S, Paglino G, risk factors: cohort study based on longitudinal data from the Framingham
Mazzone P, Lang CC, Gulletta S, Augello G, Santinelli O, Santinelli Heart Study. BMJ. 2018;361:k1453. doi: 10.1136/bmj.k1453
V. Radiofrequency ablation in children with asymptomatic Wolff- 82. Guo Y, Tian Y, Wang H, Si Q, Wang Y, Lip GYH. Prevalence, incidence,
Parkinson-White syndrome. N Engl J Med. 2004;351:1197–1205. doi: and lifetime risk of atrial fibrillation in China: new insights into the
10.1056/NEJMoa040625 global burden of atrial fibrillation. Chest. 2015;147:109–119. doi:
67. Cain N, Irving C, Webber S, Beerman L, Arora G. Natural history of 10.1378/chest.14-0321
Wolff-Parkinson-White syndrome diagnosed in childhood. Am J Cardiol. 83. Chao TF, Liu CJ, Tuan TC, Chen TJ, Hsieh MH, Lip GYH, Chen SA. Lifetime
2013;112:961–965. doi: 10.1016/j.amjcard.2013.05.035 risks, projected numbers, and adverse outcomes in Asian patients with
68. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. atrial fibrillation: a report from the Taiwan Nationwide AF Cohort Study.
Prevalence of diagnosed atrial fibrillation in adults: national implications Chest. 2018;153:453–466. doi: 10.1016/j.chest.2017.10.001
for rhythm management and stroke prevention: the AnTicoagulation 84. Mou L, Norby FL, Chen LY, O’Neal WT, Lewis TT, Loehr LR, Soliman
and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285: EZ, Alonso A. Lifetime risk of atrial fibrillation by race and socioeco-
2370–2375. nomic status: the Atherosclerosis Risk in Communities (ARIC) study.
69. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna Circ Arrhythm Electrophysiol. 2018;11:e006350. doi: 10.1161/CIRCEP.
WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrilla- 118.006350
tion in Olmsted County, Minnesota, 1980 to 2000, and implications 85. National Center for Health Statistics. Centers for Disease Control and
on the projections for future prevalence [published correction appears Prevention website. National Vital Statistics System: public use data file
in Circulation. 2006;114:e498]. Circulation. 2006;114:119–125. doi: documentation: mortality multiple cause-of-death micro-data files, 2016.
10.1161/CIRCULATIONAHA.105.595140 https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed
70. Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of May 21, 2018.
current and future incidence and prevalence of atrial fibrillation in 86. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D.
the U.S. adult population. Am J Cardiol. 2013;112:1142–1147. doi: Impact of atrial fibrillation on the risk of death: the Framingham Heart
10.1016/j.amjcard.2013.05.063 Study. Circulation. 1998;98:946–952.
71. Krijthe BP, Kunst A, Benjamin EJ, Lip GY, Franco OH, Hofman A, Witteman 87. Emdin CA, Wong CX, Hsiao AJ, Altman DG, Peters SA, Woodward M,
JC, Stricker BH, Heeringa J. Projections on the number of individuals with Odutayo AA. Atrial fibrillation as risk factor for cardiovascular disease and
atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J. death in women compared with men: systematic review and meta-analy-
2013;34:2746–2751. doi: 10.1093/eurheartj/eht280 sis of cohort studies. BMJ. 2016;532:h7013. doi: 10.1136/bmj.h7013
72. Shen AY, Contreras R, Sobnosky S, Shah AI, Ichiuji AM, Jorgensen MB, 88. Chamberlain AM, Gersh BJ, Alonso A, Chen LY, Berardi C, Manemann SM,
Brar SS, Chen W. Racial/ethnic differences in the prevalence of atrial Killian JM, Weston SA, Roger VL. Decade-long trends in atrial fibrillation
fibrillation among older adults: a cross-sectional study. J Natl Med Assoc. incidence and survival: a community study. Am J Med. 2015;128:260–7.
2010;102:906–913. e1. doi: 10.1016/j.amjmed.2014.10.030

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e315

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

89. Marijon E, Le Heuzey JY, Connolly S, Yang S, Pogue J, Brueckmann outcomes of atrial fibrillation in patients on dialysis [published correc-
CLINICAL STATEMENTS

M, Eikelboom J, Themeles E, Ezekowitz M, Wallentin L, Yusuf S; for tion appears in Nephrol Dial Transplant. 2014;29:2152]. Nephrol Dial
AND GUIDELINES

the RE-LY Investigators. Causes of death and influencing factors in Transplant. 2012;27:3816–3822. doi: 10.1093/ndt/gfs416
patients with atrial fibrillation: a competing-risk analysis from the 106. Walkey AJ, Hammill BG, Curtis LH, Benjamin EJ. Long-term outcomes fol-
randomized evaluation of long-term anticoagulant therapy study. lowing development of new-onset atrial fibrillation during sepsis. Chest.
Circulation. 2013;128:2192–2201. doi: 10.1161/CIRCULATIONAHA. 2014;146:1187–1195. doi: 10.1378/chest.14-0003
112.000491 107. Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident
90. Masri A, Kanj M, Thamilarasan M, Wazni O, Smedira NG, Lever HM, stroke and mortality associated with new-onset atrial fibrillation in pa-
Desai MY. Outcomes in hypertrophic cardiomyopathy patients with and tients hospitalized with severe sepsis. JAMA. 2011;306:2248–2254. doi:
without atrial fibrillation: a survival meta-analysis. Cardiovasc Diagn Ther. 10.1001/jama.2011.1615
2017;7:36–44. doi: 10.21037/cdt.2016.11.23 108. van Diepen S, Bakal JA, McAlister FA, Ezekowitz JA. Mortality
91. Jabre P, Jouven X, Adnet F, Thabut G, Bielinski SJ, Weston SA, and readmission of patients with heart failure, atrial fibrillation,
Roger VL. Atrial fibrillation and death after myocardial infarc- or coronary artery disease undergoing noncardiac surgery: an
tion: a community study. Circulation. 2011;123:2094–2100. doi: analysis of 38  047 patients. Circulation. 2011;124:289–296. doi:
10.1161/CIRCULATIONAHA.110.990192 10.1161/CIRCULATIONAHA.110.011130
92. Jabre P, Roger VL, Murad MH, Chamberlain AM, Prokop L, Adnet F, 109. Kabra R, Cram P, Girotra S, Vaughan Sarrazin M. Effect of race on out-
Jouven X. Mortality associated with atrial fibrillation in patients with comes (stroke and death) in patients >65 years with atrial fibrillation. Am
myocardial infarction: a systematic review and meta-analysis. Circulation. J Cardiol. 2015;116:230–235. doi: 10.1016/j.amjcard.2015.04.012
2011;123:1587–1593. doi: 10.1161/CIRCULATIONAHA.110.986661 110. Magnani JW, Norby FL, Agarwal SK, Soliman EZ, Chen LY, Loehr LR,
93. Kaw R, Hernandez AV, Masood I, Gillinov AM, Saliba W, Blackstone EH. Alonso A. Racial differences in atrial fibrillation-related cardiovascular dis-
Short- and long-term mortality associated with new-onset atrial fibril- ease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study.
lation after coronary artery bypass grafting: a systematic review and JAMA Cardiol. 2016;1:433–441. doi: 10.1001/jamacardio.2016.1025
meta-analysis. J Thorac Cardiovasc Surg. 2011;141:1305–1312. doi: 111. Roth GA, Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, Morozoff C,
10.1016/j.jtcvs.2010.10.040 Naghavi M, Mokdad AH, Murray CJL. Trends and patterns of geographic
94. Phan K, Ha HS, Phan S, Medi C, Thomas SP, Yan TD. New-onset atrial variation in cardiovascular mortality among US counties, 1980-2014.
fibrillation following coronary bypass surgery predicts long-term mor- JAMA. 2017;317:1976–1992. doi: 10.1001/jama.2017.4150
tality: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 112. Wändell P, Carlsson AC, Gasevic D, Sundquist J, Sundquist K.
2015;48:817–824. doi: 10.1093/ejcts/ezu551 Neighbourhood socio-economic status and all-cause mortality in
95. Mojoli M, Gersh BJ, Barioli A, Masiero G, Tellaroli P, D’Amico G, Tarantini adults with atrial fibrillation: a cohort study of patients treated in
G. Impact of atrial fibrillation on outcomes of patients treated by trans- primary care in Sweden. Int J Cardiol. 2016;202:776–781. doi:
catheter aortic valve implantation: a systematic review and meta-analysis. 10.1016/j.ijcard.2015.09.027
Am Heart J. 2017;192:64–75. doi: 10.1016/j.ahj.2017.07.005 113. Wandell P, Carlsson AC, Gasevic D, Holzmann MJ, Arnlov J, Sundquist J,
96. Vrsalović M, Presečki AV. Atrial fibrillation and risk of cardiovascular Sundquist K. Socioeconomic factors and mortality in patients with atrial
events and mortality in patients with symptomatic peripheral artery dis- fibrillation-a cohort study in Swedish primary care [published online May
ease: a meta-analysis of prospective studies. Clin Cardiol. 2017;40:1231– 9, 2018]. Eur J Public Health. doi: 10.1093/eurpub/cky075
1235. doi: 10.1002/clc.22813 114. Piccini JP, Hammill BG, Sinner MF, Hernandez AF, Walkey AJ, Benjamin
97. Lin HJ, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ, EJ, Curtis LH, Heckbert SR. Clinical course of atrial fibrillation in older
D’Agostino RB. Stroke severity in atrial fibrillation: the Framingham adults: the importance of cardiovascular events beyond stroke. Eur Heart
Downloaded from http://ahajournals.org by on February 7, 2019

Study. Stroke. 1996;27:1760–1764. J. 2014;35:250–256. doi: 10.1093/eurheartj/eht483

98. Mamas MA, Caldwell JC, Chacko S, Garratt CJ, Fath-Ordoubadi F, 115. Frost L, Engholm G, Johnsen S, Møller H, Henneberg EW, Husted S.
Neyses L. A meta-analysis of the prognostic significance of atrial fibril- Incident thromboembolism in the aorta and the renal, mesenteric, pelvic,
lation in chronic heart failure. Eur J Heart Fail. 2009;11:676–683. doi: and extremity arteries after discharge from the hospital with a diagnosis
10.1093/eurjhf/hfp085 of atrial fibrillation. Arch Intern Med. 2001;161:272–276.
99. Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D’Agostino RB, 116. Bekwelem W, Connolly SJ, Halperin JL, Adabag S, Duval S, Chrolavicius
Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibril- S, Pogue J, Ezekowitz MD, Eikelboom JW, Wallentin LG, Yusuf S, Hirsch
lation and congestive heart failure and their joint influence on mortality: AT. Extracranial systemic embolic events in patients with nonvalvular
the Framingham Heart Study. Circulation. 2003;107:2920–2925. doi: atrial fibrillation: incidence, risk factors, and outcomes. Circulation.
10.1161/01.CIR.0000072767.89944.6E 2015;132:796–803. doi: 10.1161/CIRCULATIONAHA.114.013243
100. Cheng M, Lu X, Huang J, Zhang J, Zhang S, Gu D. The prognostic signifi- 117. Al-Kawaz M, Omran SS, Parikh NS, Elkind MSV, Soliman EZ, Kamel
cance of atrial fibrillation in heart failure with a preserved and reduced H. Comparative risks of ischemic stroke in atrial flutter versus atri-
left ventricular function: insights from a meta-analysis. Eur J Heart Fail. al fibrillation. J Stroke Cerebrovasc Dis. 2018;27:839–844. doi:
2014;16:1317–1322. doi: 10.1002/ejhf.187 10.1016/j.jstrokecerebrovasdis.2017.10.025
101. Zakeri R, Chamberlain AM, Roger VL, Redfield MM. Temporal relation- 118. Quinn GR, Severdija ON, Chang Y, Singer DE. Wide variation in reported
ship and prognostic significance of atrial fibrillation in heart failure rates of stroke across cohorts of patients with atrial fibrillation. Circulation.
patients with preserved ejection fraction: a community-based study [pub- 2017;135:208–219. doi: 10.1161/CIRCULATIONAHA.116.024057
lished correction appears in Circulation. 2013;128:e465]. Circulation. 119. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk
2013;128:1085–1093. doi: 10.1161/CIRCULATIONAHA.113.001475 factor for stroke: the Framingham Study. Stroke. 1991;22:983–988.
102. Odutayo A, Wong CX, Williams R, Hunn B, Emdin CA. Prognostic im- 120. Hayden DT, Hannon N, Callaly E, Ní Chróinín D, Horgan G, Kyne
portance of atrial fibrillation timing and pattern in adults with conges- L, Duggan J, Dolan E, O’Rourke K, Williams D, Murphy S, Kelly PJ.
tive heart failure: a systematic review and meta-analysis. J Card Fail. Rates and determinants of 5-year outcomes after atrial fibrillation-
2017;23:56–62. doi: 10.1016/j.cardfail.2016.08.005 related stroke: a population study. Stroke. 2015;46:3488–3493. doi:
103. Echouffo-Tcheugui JB, Shrader P, Thomas L, Gersh BJ, Kowey PR, Mahaffey 10.1161/STROKEAHA.115.011139
KW, Singer DE, Hylek EM, Go AS, Peterson ED, Piccini JP, Fonarow GC. 121. Kabra R, Girotra S, Vaughan Sarrazin M. Refining stroke prediction
Care patterns and outcomes in atrial fibrillation patients with and with- in atrial  fibrillation patients by addition of  African-American ethnic-
out diabetes: ORBIT-AF registry. J Am Coll Cardiol. 2017;70:1325–1335. ity to CHA2DS2-VASc score. J Am Coll Cardiol. 2016;68:461–470. doi:
doi: 10.1016/j.jacc.2017.07.755 10.1016/j.jacc.2016.05.044
104. Fatemi O, Yuriditsky E, Tsioufis C, Tsachris D, Morgan T, Basile J, Bigger T, 122. Kalantarian S, Stern TA, Mansour M, Ruskin JN. Cognitive impairment asso-
Cushman W, Goff D, Soliman EZ, Thomas A, Papademetriou V. Impact of ciated with atrial fibrillation: a meta-analysis. Ann Intern Med. 2013;158(5
intensive glycemic control on the incidence of atrial fibrillation and asso- Pt 1):338–346. doi: 10.7326/0003-4819-158-5-201303050-00007
ciated cardiovascular outcomes in patients with type 2 diabetes mellitus 123. Miyasaka Y, Barnes ME, Petersen RC, Cha SS, Bailey KR, Gersh BJ,
(from the Action to Control Cardiovascular Risk in Diabetes Study). Am J Casaclang-Verzosa G, Abhayaratna WP, Seward JB, Iwasaka T, Tsang TS.
Cardiol. 2014;114:1217–1222. doi: 10.1016/j.amjcard.2014.07.045 Risk of dementia in stroke-free patients diagnosed with atrial fibrillation:
105. Zimmerman D, Sood MM, Rigatto C, Holden RM, Hiremath S, Clase data from a community-based cohort. Eur Heart J. 2007;28:1962–1967.
CM. Systematic review and meta-analysis of incidence, prevalence and doi: 10.1093/eurheartj/ehm012

e316 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

124. Rienstra M, Lubitz SA, Mahida S, Magnani JW, Fontes JD, Sinner death: systematic review and meta-analysis. BMJ. 2016;354:i4482. doi:

CLINICAL STATEMENTS
MF, Van Gelder IC, Ellinor PT, Benjamin EJ. Symptoms and func- 10.1136/bmj.j4482

AND GUIDELINES
tional status of patients with atrial fibrillation: state of the art and fu- 142. Ganesan AN, Chew DP, Hartshorne T, Selvanayagam JB, Aylward
ture research opportunities. Circulation. 2012;125:2933–2943. doi: PE, Sanders P, McGavigan AD. The impact of atrial fibrillation type
10.1161/CIRCULATIONAHA.111.069450 on the risk of thromboembolism, mortality, and bleeding: a system-
125. Rienstra M, Lyass A, Murabito JM, Magnani JW, Lubitz SA, Massaro JM, atic review and meta-analysis. Eur Heart J. 2016;37:1591–1602. doi:
Ellinor PT, Benjamin EJ. Reciprocal relations between physical disability, 10.1093/eurheartj/ehw007
subjective health, and atrial fibrillation: the Framingham Heart Study. Am 143. Padfield GJ, Steinberg C, Swampillai J, Qian H, Connolly SJ, Dorian
Heart J. 2013;166:171–178. doi: 10.1016/j.ahj.2013.02.025 P, Green MS, Humphries KH, Klein GJ, Sheldon R, Talajic M, Kerr CR.
126. Zhang L, Gallagher R, Neubeck L. Health-related quality of life in Progression of paroxysmal to persistent atrial fibrillation: 10-year fol-
atrial fibrillation patients over 65 years: a review. Eur J Prev Cardiol. low-up in the Canadian Registry of Atrial Fibrillation. Heart Rhythm.
2015;22:987–1002. doi: 10.1177/2047487314538855 2017;14:801–807. doi: 10.1016/j.hrthm.2017.01.038
127. Giacomantonio NB, Bredin SS, Foulds HJ, Warburton DE. A system- 144. Rahman F, Wang N, Yin X, Ellinor PT, Lubitz SA, LeLorier PA, McManus DD,
atic review of the health benefits of exercise rehabilitation in persons Sullivan LM, Seshadri S, Vasan RS, Benjamin EJ, Magnani JW. Atrial flutter:
living with atrial fibrillation. Can J Cardiol. 2013;29:483–491. doi: clinical risk factors and adverse outcomes in the Framingham Heart Study.
10.1016/j.cjca.2012.07.003 Heart Rhythm. 2016;13:233–240. doi: 10.1016/j.hrthm.2015.07.031
128. O’Neal WT, Qureshi WT, Judd SE, Bowling CB, Howard VJ, Howard 145. Lin YS, Chen TH, Chi CC, Lin MS, Tung TH, Liu CH, Chen YL, Chen
G, Soliman EZ. Effect of falls on frequency of atrial fibrillation MC. Different implications of heart failure, ischemic stroke, and mor-
and mortality risk (from the REasons for Geographic And  Racial tality between nonvalvular atrial fibrillation and atrial flutter: a view
Differences in Stroke Study). Am J Cardiol. 2015;116:1213–1218. doi: from a national cohort study. J Am Heart Assoc. 2017;6:e006406. doi:
10.1016/j.amjcard.2015.07.036 10.1161/JAHA.117.006406
129. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic 146. Agency for Healthcare Research and Quality website. Weighted nation-
therapy for elderly patients with atrial fibrillation who are at risk for falls. al estimates from HCUP National (Nationwide) Inpatient Sample (NIS),
Arch Intern Med. 1999;159:677–685. [2014], Agency for Healthcare Research and Quality (AHRQ), based on
130. Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich data collected by individual States and provided to AHRQ by the states.
MW. Incidence of intracranial hemorrhage in patients with atrial fi- https://www.ahrq.gov/data/hcup/index.html. Accessed November 14,
brillation who are prone to fall. Am J Med. 2005;118:612–617. doi: 2018.
10.1016/j.amjmed.2005.02.022 147. Centers for Disease Control and Prevention website. National Ambulatory
131. Chamberlain AM, Gersh BJ, Alonso A, Kopecky SL, Killian JM, Weston SA, Medical Care Survey: 2015 State and National Summary Tables. https://
Roger VL. No decline in the risk of heart failure after incident atrial fibrilla- www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_ta-
tion: a community study assessing trends overall and by ejection fraction. bles.pdf. Accessed June 14, 2018.
Heart Rhythm. 2017;14:791–798. doi: 10.1016/j.hrthm.2017.01.031 148. Centers for Disease Control and Prevention website. National Hospital
132. Vermond RA, Geelhoed B, Verweij N, Tieleman RG, Van der Harst P, Ambulatory Medical Care Survey: 2015 Emergency Department Summary
Hillege HL, Van Gilst WH, Van Gelder IC, Rienstra M. Incidence of atrial Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_
fibrillation and relationship with cardiovascular events, heart failure, and web_tables.pdf. Accessed June 14, 2018.
mortality: a community-based study from the Netherlands. J Am Coll 149. Jackson SL, Tong X, Yin X, George MG, Ritchey MD. Emergency depart-
Cardiol. 2015;66:1000–1007. doi: 10.1016/j.jacc.2015.06.1314 ment, hospital inpatient, and mortality burden of atrial fibrillation in the
133. Ruddox V, Sandven I, Munkhaugen J, Skattebu J, Edvardsen T, Otterstad United States, 2006 to 2014. Am J Cardiol. 2017;120:1966–1973. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

JE. Atrial fibrillation and the risk for myocardial infarction, all-cause mor- 10.1016/j.amjcard.2017.08.017
tality and heart failure: a systematic review and meta-analysis. Eur J Prev 150. Kim MH, Johnston SS, Chu BC, Dalal MR, Schulman KL. Estimation of
Cardiol. 2017;24:1555–1566. doi: 10.1177/2047487317715769 total incremental health care costs in patients with atrial fibrillation in
134. Soliman EZ, Safford MM, Muntner P, Khodneva Y, Dawood FZ, Zakai NA, the United States. Circ Cardiovasc Qual Outcomes. 2011;4:313–320. doi:
Thacker EL, Judd S, Howard VJ, Howard G, Herrington DM, Cushman 10.1161/CIRCOUTCOMES.110.958165
M. Atrial fibrillation and the risk of myocardial infarction [published cor- 151. Turakhia MP, Shafrin J, Bognar K, Goldman DP, Mendys PM, Abdulsattar
rection appears in JAMA Intern Med. 2014;174:308]. JAMA Intern Med. Y, Wiederkehr D, Trocio J. Economic burden of undiagnosed nonvalvular
2014;174:107–114. doi: 10.1001/jamainternmed.2013.11912 atrial fibrillation in the United States. Am J Cardiol. 2015;116:733–739.
135. Soliman EZ, Lopez F, O’Neal WT, Chen LY, Bengtson L, Zhang ZM, doi: 10.1016/j.amjcard.2015.05.045
Loehr L, Cushman M, Alonso A. Atrial fibrillation and risk of ST- 152. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M,
segment-elevation versus non-ST-segment-elevation myocardial Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial
infarction: the Atherosclerosis Risk in Communities (ARIC) Study. fibrillation in the United States. Value Health. 2006;9:348–356. doi:
Circulation. 2015;131:1843–1850. doi: 10.1161/CIRCULATIONAHA. 10.1111/j.1524-4733.2006.00124.x
114.014145 153. Li X, Tse VC, Au-Doung LW, Wong ICK, Chan EW. The impact of isch-
136. O’Neal WT, Sangal K, Zhang ZM, Soliman EZ. Atrial fibrillation and inci- aemic stroke on atrial fibrillation-related healthcare cost: a systematic
dent myocardial infarction in the elderly. Clin Cardiol. 2014;37:750–755. review. Europace. 2017;19:937–947. doi: 10.1093/europace/euw093
doi: 10.1002/clc.22339 154. Johnsen SP, Dalby LW, Täckström T, Olsen J, Fraschke A. Cost of illness of
137. Watanabe H, Watanabe T, Sasaki S, Nagai K, Roden DM, Aizawa Y. atrial fibrillation: a nationwide study of societal impact. BMC Health Serv
Close bidirectional relationship between chronic kidney disease and Res. 2017;17:714. doi: 10.1186/s12913-017-2652-y
atrial fibrillation: the Niigata preventive medicine study. Am Heart J. 155. Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD,
2009;158:629–636. doi: 10.1016/j.ahj.2009.06.031 Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf
138. Bansal N, Fan D, Hsu CY, Ordonez JD, Marcus GM, Go AS. Incident PA, Vasan RS, Benjamin EJ, Levy D. 50 year trends in atrial fibrillation
atrial fibrillation and risk of end-stage renal disease in adults with prevalence, incidence, risk factors, and mortality in the Framingham
chronic kidney disease. Circulation. 2013;127:569–574. doi: Heart Study: a cohort study. Lancet. 2015;386:154–162. doi:
10.1161/CIRCULATIONAHA.112.123992 10.1016/S0140-6736(14)61774-8
139. Chen LY, Sotoodehnia N, Bůžková P, Lopez FL, Yee LM, Heckbert SR, Prineas 156. Bengtson LG, Chen LY, Chamberlain AM, Michos ED, Whitsel EA, Lutsey
R, Soliman EZ, Adabag S, Konety S, Folsom AR, Siscovick D, Alonso A. PL, Duval S, Rosamond WD, Alonso A. Temporal trends in the occur-
Atrial fibrillation and the risk of sudden cardiac death: the Atherosclerosis rence and outcomes of atrial fibrillation in patients with acute myocar-
Risk in Communities Study and Cardiovascular Health Study. JAMA Intern dial infarction (from the Atherosclerosis Risk in Communities Surveillance
Med. 2013;173:29–35. doi: 10.1001/2013.jamainternmed.744 Study). Am J Cardiol. 2014;114:692–697. doi: 10.1016/j.amjcard.
140. Bardai A, Blom MT, van Hoeijen DA, van Deutekom HW, Brouwer HJ, Tan 2014.05.059
HL. Atrial fibrillation is an independent risk factor for ventricular fibrilla- 157. Huxley RR, Lopez FL, Folsom AR, Agarwal SK, Loehr LR, Soliman EZ,
tion: a large-scale population-based case-control study. Circ Arrhythm Maclehose R, Konety S, Alonso A. Absolute and attributable risks
Electrophysiol. 2014;7:1033–1039. doi: 10.1161/CIRCEP.114.002094 of atrial fibrillation in relation to optimal and borderline risk factors:
141. Odutayo A, Wong CX, Hsiao AJ, Hopewell S, Altman DG, Emdin CA. the Atherosclerosis Risk in Communities (ARIC) study. Circulation.
Atrial fibrillation and risks of cardiovascular disease, renal disease, and 2011;123:1501–1508. doi: 10.1161/CIRCULATIONAHA.110.009035

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e317

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

158. Zhu W, Yuan P, Shen Y, Wan R, Hong K. Association of smoking traffic-related air pollution and risk of incident atrial fibrillation: a cohort
CLINICAL STATEMENTS

with the risk of incident atrial fibrillation: a meta-analysis of prospec- study. Environ Health Perspect. 2017;125:422–427. doi: 10.1289/EHP392
AND GUIDELINES

tive studies. Int J Cardiol. 2016;218:259–266. doi: 10.1016/j.ijcard. 174. Lubitz SA, Yin X, Rienstra M, Schnabel RB, Walkey AJ, Magnani JW,
2016.05.013 Rahman F, McManus DD, Tadros TM, Levy D, Vasan RS, Larson MG,
159. Kwok CS, Anderson SG, Myint PK, Mamas MA, Loke YK. Physical activity Ellinor PT, Benjamin EJ. Long-term outcomes of secondary atrial fibril-
and incidence of atrial fibrillation: a systematic review and meta-analysis. lation in the community: the Framingham Heart Study. Circulation.
Int J Cardiol. 2014;177:467–476. doi: 10.1016/j.ijcard.2014.09.104 2015;131:1648–1655. doi: 10.1161/CIRCULATIONAHA.114.014058
160. Qureshi WT, Alirhayim Z, Blaha MJ, Juraschek SP, Keteyian SJ, Brawner CA, 175. Walkey AJ, Greiner MA, Heckbert SR, Jensen PN, Piccini JP, Sinner MF,
Al-Mallah MH. Cardiorespiratory fitness and risk of incident atrial fibrilla- Curtis LH, Benjamin EJ. Atrial fibrillation among Medicare beneficia-
tion: results from the Henry Ford Exercise Testing (FIT) Project. Circulation. ries hospitalized with sepsis: incidence and risk factors. Am Heart J.
2015;131:1827–1834. doi: 10.1161/CIRCULATIONAHA.114.014833 2013;165:949–955.e3. doi: 10.1016/j.ahj.2013.03.020
161. Asad Z, Abbas M, Javed I, Korantzopoulos P, Stavrakis S. Obesity is 176. Chebbout R, Heywood EG, Drake TM, Wild JRL, Lee J, Wilson M, Lee MJ.
associated with incident atrial fibrillation independent of gender: a A systematic review of the incidence of and risk factors for postoperative
meta-analysis. J Cardiovasc Electrophysiol. 2018;29:725–732. doi: atrial fibrillation following general surgery. Anaesthesia. 2018;73:490–
10.1111/jce.13458 498. doi: 10.1111/anae.14118
162. Aune D, Sen A, Schlesinger S, Norat T, Janszky I, Romundstad P, Tonstad 177. Loomba RS, Buelow MW, Aggarwal S, Arora RR, Kovach J, Ginde S.
S, Riboli E, Vatten LJ. Body mass index, abdominal fatness, fat mass and Arrhythmias in adults with congenital heart disease: what are risk factors
the risk of atrial fibrillation: a systematic review and dose-response meta- for specific arrhythmias? Pacing Clin Electrophysiol. 2017;40:353–361.
analysis of prospective studies. Eur J Epidemiol. 2017;32:181–192. doi: doi: 10.1111/pace.12983
10.1007/s10654-017-0232-4 178. Garg PK, O’Neal WT, Ogunsua A, Thacker EL, Howard G, Soliman EZ,
163. Chatterjee NA, Giulianini F, Geelhoed B, Lunetta KL, Misialek JR, Cushman M. Usefulness of the American Heart Association’s Life Simple
Niemeijer MN, Rienstra M, Rose LM, Smith AV, Arking DE, Ellinor PT, 7 to predict the risk of atrial fibrillation (from the REasons for Geographic
Heeringa J, Lin H, Lubitz SA, Soliman EZ, Verweij N, Alonso A, Benjamin And Racial Differences in Stroke [REGARDS] Study). Am J Cardiol.
EJ, Gudnason V, Stricker BHC, Van Der Harst P, Chasman DI, Albert 2018;121:199–204. doi: 10.1016/j.amjcard.2017.09.033
CM. Genetic obesity and the risk of atrial fibrillation: causal estimates 179. Chamberlain AM, Agarwal SK, Folsom AR, Soliman EZ, Chambless LE,
from mendelian randomization. Circulation. 2017;135:741–754. doi: Crow R, Ambrose M, Alonso A. A clinical risk score for atrial fibrilla-
10.1161/CIRCULATIONAHA.116.024921 tion in a biracial prospective cohort (from the Atherosclerosis Risk
164. Qi W, Zhang N, Korantzopoulos P, Letsas KP, Cheng M, Di F, Tse G, Liu T, in Communities [ARIC] study). Am J Cardiol. 2011;107:85–91. doi:
Li G. Serum glycated hemoglobin level as a predictor of atrial fibrillation: 10.1016/j.amjcard.2010.08.049
a systematic review with meta-analysis and meta-regression. PLoS One. 180. Schnabel RB, Aspelund T, Li G, Sullivan LM, Suchy-Dicey A, Harris TB,
2017;12:e0170955. doi: 10.1371/journal.pone.0170955 Pencina MJ, D’Agostino RB Sr, Levy D, Kannel WB, Wang TJ, Kronmal
165. Aune D, Feng T, Schlesinger S, Janszky I, Norat T, Riboli E. Diabetes RA, Wolf PA, Burke GL, Launer LJ, Vasan RS, Psaty BM, Benjamin EJ,
mellitus, blood glucose and the risk of atrial fibrillation: a systematic Gudnason V, Heckbert SR. Validation of an atrial fibrillation risk algorithm
review and meta-analysis of cohort studies. J Diabetes Complications. in whites and African Americans. Arch Intern Med. 2010;170:1909–
2018;32:501–511. doi: 10.1016/j.jdiacomp.2018.02.004 1917. doi: 10.1001/archinternmed.2010.434
166. Baumgartner C, da Costa BR, Collet TH, Feller M, Floriani C, Bauer DC, 181. Everett BM, Cook NR, Conen D, Chasman DI, Ridker PM, Albert CM.
Cappola AR, Heckbert SR, Ceresini G, Gussekloo J, den Elzen WPJ, Novel genetic markers improve measures of atrial fibrillation risk predic-
Peeters RP, Luben R, Völzke H, Dörr M, Walsh JP, Bremner A, Iacoviello tion. Eur Heart J. 2013;34:2243–2251. doi: 10.1093/eurheartj/eht033
Downloaded from http://ahajournals.org by on February 7, 2019

M, Macfarlane P, Heeringa J, Stott DJ, Westendorp RGJ, Khaw KT, 182. Alonso A, Krijthe BP, Aspelund T, Stepas KA, Pencina MJ, Moser CB,
Magnani JW, Aujesky D, Rodondi N; Thyroid Studies Collaboration. Sinner MF, Sotoodehnia N, Fontes JD, Janssens AC, Kronmal RA, Magnani
Thyroid function within the normal range, subclinical hypothyroidism, JW, Witteman JC, Chamberlain AM, Lubitz SA, Schnabel RB, Agarwal SK,
and the risk of atrial fibrillation. Circulation. 2017;136:2100–2116. doi: McManus DD, Ellinor PT, Larson MG, Burke GL, Launer LJ, Hofman A,
10.1161/CIRCULATIONAHA.117.028753 Levy D, Gottdiener JS, Kääb S, Couper D, Harris TB, Soliman EZ, Stricker
167. Alonso A, Lopez FL, Matsushita K, Loehr LR, Agarwal SK, Chen LY, BH, Gudnason V, Heckbert SR, Benjamin EJ. Simple risk model predicts in-
Soliman EZ, Astor BC, Coresh J. Chronic kidney disease is associ- cidence of atrial fibrillation in a racially and geographically diverse popu-
ated with the incidence of atrial fibrillation: the Atherosclerosis Risk lation: the CHARGE-AF consortium. J Am Heart Assoc. 2013;2:e000102.
in Communities (ARIC) study. Circulation. 2011;123:2946–2953. doi: doi: 10.1161/JAHA.112.000102
10.1161/CIRCULATIONAHA.111.020982 183. Shulman E, Kargoli F, Aagaard P, Hoch E, Di Biase L, Fisher J, Gross J, Kim
168. Bansal N, Zelnick LR, Alonso A, Benjamin EJ, de Boer IH, Deo R, Katz R, S, Krumerman A, Ferrick KJ. Validation of the Framingham Heart Study
Kestenbaum B, Mathew J, Robinson-Cohen C, Sarnak MJ, Shlipak MG, and CHARGE-AF risk scores for atrial fibrillation in Hispanics, African-
Sotoodehnia N, Young B, Heckbert SR. eGFR and albuminuria in relation Americans, and non-Hispanic whites. Am J Cardiol. 2016;117:76–83.
to risk of incident atrial fibrillation: a meta-analysis of the Jackson Heart doi: 10.1016/j.amjcard.2015.10.009
Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular 184. Alonso A, Roetker NS, Soliman EZ, Chen LY, Greenland P and Heckbert SR.
Health Study. Clin J Am Soc Nephrol. 2017;12:1386–1398. doi: Prediction of atrial fibrillation in a racially diverse cohort: the Multi-Ethnic
10.2215/CJN.01860217 Study of Atherosclerosis (MESA). J Am Heart Assoc. 2016;5:e003077.
169. Larsson SC, Drca N, Wolk A. Alcohol consumption and risk of atrial fibril- doi: 10.1161/JAHA.115.003077
lation: a prospective study and dose-response meta-analysis. J Am Coll 185. Pfister R, Brägelmann J, Michels G, Wareham NJ, Luben R, Khaw KT.
Cardiol. 2014;64:281–289. doi: 10.1016/j.jacc.2014.03.048 Performance of the CHARGE-AF risk model for incident atrial fibrillation
170. Kodama S, Saito K, Tanaka S, Horikawa C, Saito A, Heianza Y, Anasako in the EPIC Norfolk cohort. Eur J Prev Cardiol. 2015;22:932–939. doi:
Y, Nishigaki Y, Yachi Y, Iida KT, Ohashi Y, Yamada N, Sone H. Alcohol con- 10.1177/2047487314544045
sumption and risk of atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 186. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak
2011;57:427–436. doi: 10.1016/j.jacc.2010.08.641 R, Cook J, Paraschos A, Love J, Radoslovich G, Lee KL, Lamas GA; for
171. May AM, Blackwell T, Stone PH, Stone KL, Cawthon PM, Sauer WH, the MOST Investigators. Atrial high rate episodes detected by pacemaker
Varosy PD, Redline S, Mehra R; MrOS Sleep (Outcomes of Sleep Disorders diagnostics predict death and stroke: report of the Atrial Diagnostics
in Older Men) Study Group. Central sleep-disordered breathing pre- Ancillary Study of the MOde Selection Trial (MOST). Circulation.
dicts incident atrial fibrillation in older men. Am J Respir Crit Care Med. 2003;107:1614–1619. doi: 10.1161/01.CIR.0000057981.70380.45
2016;193:783–791. doi: 10.1164/rccm.201508-1523OC 187. Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hilker C,
172. Tung P, Levitzky YS, Wang R, Weng J, Quan SF, Gottlieb DJ, Rueschman Miller C, Qi D, Ziegler PD. The relationship between daily atrial tachyar-
M, Punjabi NM, Mehra R, Bertisch S, Benjamin EJ, Redline S. Obstructive rhythmia burden from implantable device diagnostics and stroke risk:
and central sleep apnea and the risk of incident atrial fibrillation in a com- the TRENDS study. Circ Arrhythm Electrophysiol. 2009;2:474–480. doi:
munity cohort of men and women. J Am Heart Assoc. 2017;6:004500. 10.1161/CIRCEP.109.849638
doi: 10.1161/JAHA.116.004500 188. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci
173. Monrad M, Sajadieh A, Christensen JS, Ketzel M, Raaschou-Nielsen O, A, Lau CP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles
Tjønneland A, Overvad K, Loft S, Sørensen M. Long-term exposure to E, Kaufman ES, Hohnloser SH; ASSERT Investigators. Subclinical

e318 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

atrial fibrillation and the risk of stroke [published correction appears in 204. Marcus GM, Alonso A, Peralta CA, Lettre G, Vittinghoff E, Lubitz SA, Fox

CLINICAL STATEMENTS
N Engl J Med. 2016;374:998]. N Engl J Med. 2012;366:120–129. doi: ER, Levitzky YS, Mehra R, Kerr KF, Deo R, Sotoodehnia N, Akylbekova

AND GUIDELINES
10.1056/NEJMoa1105575 M, Ellinor PT, Paltoo DN, Soliman EZ, Benjamin EJ, Heckbert SR; for the
189. Boriani G, Glotzer TV, Santini M, West TM, De Melis M, Sepsi M, Candidate-Gene Association Resource (CARe) Study. European ancestry
Gasparini M, Lewalter T, Camm JA, Singer DE. Device-detected atrial fi- as a risk factor for atrial fibrillation in African Americans. Circulation.
brillation and risk for stroke: an analysis of >10,000 patients from the 2010;122:2009–2015. doi: 10.1161/CIRCULATIONAHA.110.958306
SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation 205. Christophersen IE, Rienstra M, Roselli C, Yin X, Geelhoed B, Barnard J,
information from implanted devices). Eur Heart J. 2014;35:508–516. doi: Lin H, Arking DE, Smith AV, Albert CM, Chaffin M, Tucker NR, Li M,
10.1093/eurheartj/eht491 Klarin D, Bihlmeyer NA, Low SK, Weeke PE, Müller-Nurasyid M, Smith
190. Turakhia MP, Ziegler PD, Schmitt SK, Chang Y, Fan J, Than CT, Keung JG, Brody JA, Niemeijer MN, Dörr M, Trompet S, Huffman J, Gustafsson
EK, Singer DE. Atrial fibrillation burden and short-term risk of stroke: S, Schurmann C, Kleber ME, Lyytikäinen LP, Seppälä I, Malik R, Horimoto
case-crossover analysis of continuously recorded heart rhythm from ARVR, Perez M, Sinisalo J, Aeschbacher S, Thériault S, Yao J, Radmanesh
cardiac electronic implanted devices. Circ Arrhythm Electrophysiol. F, Weiss S, Teumer A, Choi SH, Weng LC, Clauss S, Deo R, Rader DJ, Shah
2015;8:1040–1047. doi: 10.1161/CIRCEP.114.003057 SH, Sun A, Hopewell JC, Debette S, Chauhan G, Yang Q, Worrall BB,
191. Turakhia MP, Shafrin J, Bognar K, Trocio J, Abdulsattar Y, Wiederkehr Paré G, Kamatani Y, Hagemeijer YP, Verweij N, Siland JE, Kubo M, Smith
D, Goldman DP. Estimated prevalence of undiagnosed atrial fibril- JD, Van Wagoner DR, Bis JC, Perz S, Psaty BM, Ridker PM, Magnani JW,
lation in the United States. PLoS One. 2018;13:e0195088. doi: Harris TB, Launer LJ, Shoemaker MB, Padmanabhan S, Haessler J, Bartz
10.1371/journal.pone.0195088 TM, Waldenberger M, Lichtner P, Arendt M, Krieger JE, Kähönen M,
192. Freedman B, Camm J, Calkins H, Healey JS, Rosenqvist M, Wang J, Albert Risch L, Mansur AJ, Peters A, Smith BH, Lind L, Scott SA, Lu Y, Bottinger
CM, Anderson CS, Antoniou S, Benjamin EJ, Boriani G, Brachmann J, EB, Hernesniemi J, Lindgren CM, Wong JA, Huang J, Eskola M, Morris
Brandes A, Chao TF, Conen D, Engdahl J, Fauchier L, Fitzmaurice DA, AP, Ford I, Reiner AP, Delgado G, Chen LY, Chen YI, Sandhu RK, Li M,
Friberg L, Gersh BJ, Gladstone DJ, Glotzer TV, Gwynne K, Hankey GJ, Boerwinkle E, Eisele L, Lannfelt L, Rost N, Anderson CD, Taylor KD,
Harbison J, Hillis GS, Hills MT, Kamel H, Kirchhof P, Kowey PR, Krieger D, Campbell A, Magnusson PK, Porteous D, Hocking LJ, Vlachopoulou E,
Lee VWY, Levin LÅ, Lip GYH, Lobban T, Lowres N, Mairesse GH, Martinez Pedersen NL, Nikus K, Orho-Melander M, Hamsten A, Heeringa J, Denny
C, Neubeck L, Orchard J, Piccini JP, Poppe K, Potpara TS, Puererfellner JC, Kriebel J, Darbar D, Newton-Cheh C, Shaffer C, Macfarlane PW,
H, Rienstra M, Sandhu RK, Schnabel RB, Siu CW, Steinhubl S, Svendsen Heilmann-Heimbach S, Almgren P, Huang PL, Sotoodehnia N, Soliman EZ,
JH, Svennberg E, Themistoclakis S, Tieleman RG, Turakhia MP, Tveit A, Uitterlinden AG, Hofman A, Franco OH, Völker U, Jöckel KH, Sinner MF,
Uittenbogaart SB, Van Gelder IC, Verma A, Wachter R, Yan BP; AF-Screen Lin HJ, Guo X, Dichgans M, Ingelsson E, Kooperberg C, Melander O, Loos
Collaborators. Screening for atrial fibrillation: a report of the AF-SCREEN RJF, Laurikka J, Conen D, Rosand J, van der Harst P, Lokki ML, Kathiresan
International Collaboration. Circulation. 2017;135:1851–1867. doi: S, Pereira A, Jukema JW, Hayward C, Rotter JI, März W, Lehtimäki T,
10.1161/CIRCULATIONAHA.116.026693 Stricker BH, Chung MK, Felix SB, Gudnason V, Alonso A, Roden DM,
193. Lowres N, Neubeck L, Salkeld G, Krass I, McLachlan AJ, Redfern J, Kääb S, Chasman DI, Heckbert SR, Benjamin EJ, Tanaka T, Lunetta KL,
Bennett AA, Briffa T, Bauman A, Martinez C, Wallenhorst C, Lau JK, Lubitz SA, Ellinor PT; METASTROKE Consortium of the ISGC; Neurology
Brieger DB, Sy RW, Freedman SB. Feasibility and cost-effectiveness of Working Group of the CHARGE Consortium; AFGen Consortium. Large-
stroke prevention through community screening for atrial fibrillation us- scale analyses of common and rare variants identify 12 new loci associ-
ing iPhone ECG in pharmacies: the SEARCH-AF study. Thromb Haemost. ated with atrial fibrillation [published correction appears in Nat Genet.
2014;111:1167–1176. doi: 10.1160/TH14-03-0231 2017;49:1286]. Nat Genet. 2017;49:946–952. doi: 10.1038/ng.3843
194. McManus DD, Lee J, Maitas O, Esa N, Pidikiti R, Carlucci A, Harrington 206. Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT,
Downloaded from http://ahajournals.org by on February 7, 2019

J, Mick E, Chon KH. A novel application for the detection of an irregular Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M,
pulse using an iPhone 4S in patients with atrial fibrillation. Heart Rhythm. Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M,
2013;10:315–319. doi: 10.1016/j.hrthm.2012.12.001 Ito K, Kamatani Y, Tanaka T; AFGen Consortium. Identification of six new
195. Svennberg E, Engdahl J, Al-Khalili F, Friberg L, Frykman V, genetic loci associated with atrial fibrillation in the Japanese population.
Rosenqvist M. Mass screening for untreated atrial fibrillation: Nat Genet. 2017;49:953–958. doi: 10.1038/ng.3842
the STROKESTOP Study. Circulation. 2015;131:2176–2184. doi: 207. Roselli C, Chaffin MD, Weng LC, Aeschbacher S, Ahlberg G, Albert CM,
10.1161/CIRCULATIONAHA.114.014343 Almgren P, Alonso A, Anderson CD, Aragam KG, Arking DE, Barnard J,
196. Lowres N, Neubeck L, Redfern J, Freedman SB. Screening to iden- Bartz TM, Benjamin EJ, Bihlmeyer NA, Bis JC, Bloom HL, Boerwinkle E,
tify unknown atrial fibrillation: a systematic review. Thromb Haemost. Bottinger EB, Brody JA, Calkins H, Campbell A, Cappola TP, Carlquist J,
2013;110:213–222. doi: 10.1160/TH13-02-0165 Chasman DI, Chen LY, Chen YI, Choi EK, Choi SH, Christophersen IE,
197. Moran PS, Flattery MJ, Teljeur C, Ryan M, Smith SM. Effectiveness of Chung MK, Cole JW, Conen D, Cook J, Crijns HJ, Cutler MJ, Damrauer
systematic screening for the detection of atrial fibrillation. Cochrane SM, Daniels BR, Darbar D, Delgado G, Denny JC, Dichgans M, Dörr M,
Database Syst Rev. 2013;4:CD009586. doi: 10.1002/14651858. Dudink EA, Dudley SC, Esa N, Esko T, Eskola M, Fatkin D, Felix SB, Ford
CD009586.pub2 I, Franco OH, Geelhoed B, Grewal RP, Gudnason V, Guo X, Gupta N,
198. Wolff L. Familial auricular fibrillation. N Engl J Med. 1943;229:396–398. Gustafsson S, Gutmann R, Hamsten A, Harris TB, Hayward C, Heckbert
199. Fox CS, Parise H, D’Agostino RB Sr, Lloyd-Jones DM, Vasan RS, Wang SR, Hernesniemi J, Hocking LJ, Hofman A, Horimoto ARVR, Huang J,
TJ, Levy D, Wolf PA, Benjamin EJ. Parental atrial fibrillation as a risk fac- Huang PL, Huffman J, Ingelsson E, Ipek EG, Ito K, Jimenez-Conde J,
tor for atrial fibrillation in offspring. JAMA. 2004;291:2851–2855. doi: Johnson R, Jukema JW, Kääb S, Kähönen M, Kamatani Y, Kane JP, Kastrati
10.1001/jama.291.23.2851 A, Kathiresan S, Katschnig-Winter P, Kavousi M, Kessler T, Kietselaer BL,
200. Lubitz SA, Yin X, Fontes JD, Magnani JW, Rienstra M, Pai M, Villalon Kirchhof P, Kleber ME, Knight S, Krieger JE, Kubo M, Launer LJ, Laurikka J,
ML, Vasan RS, Pencina MJ, Levy D, Larson MG, Ellinor PT, Benjamin EJ. Lehtimäki T, Leineweber K, Lemaitre RN, Li M, Lim HE, Lin HJ, Lin H, Lind
Association between familial atrial fibrillation and risk of new-onset atrial L, Lindgren CM, Lokki ML, London B, Loos RJF, Low SK, Lu Y, Lyytikäinen
fibrillation. JAMA. 2010;304:2263–2269. doi: 10.1001/jama.2010.1690 LP, Macfarlane PW, Magnusson PK, Mahajan A, Malik R, Mansur AJ,
201. Zöller B, Ohlsson H, Sundquist J, Sundquist K. High familial risk of Marcus GM, Margolin L, Margulies KB, März W, McManus DD, Melander
atrial fibrillation/atrial flutter in multiplex families: a nationwide O, Mohanty S, Montgomery JA, Morley MP, Morris AP, Müller-Nurasyid
family study in Sweden. J Am Heart Assoc. 2012;2:e003384. doi: M, Natale A, Nazarian S, Neumann B, Newton-Cheh C, Niemeijer MN,
10.1161/JAHA.112.003384 Nikus K, Nilsson P, Noordam R, Oellers H, Olesen MS, Orho-Melander M,
202. Chang SH, Kuo CF, Chou IJ, See LC, Yu KH, Luo SF, Huang LH, Zhang Padmanabhan S, Pak HN, Paré G, Pedersen NL, Pera J, Pereira A, Porteous
W, Doherty M, Wen MS, Kuo CT, Yeh YH. Association of a family history D, Psaty BM, Pulit SL, Pullinger CR, Rader DJ, Refsgaard L, Ribasés M,
of atrial fibrillation with incidence and outcomes of atrial fibrillation: a Ridker PM, Rienstra M, Risch L, Roden DM, Rosand J, Rosenberg MA,
population-based family cohort study. JAMA Cardiol. 2017;2:863–870. Rost N, Rotter JI, Saba S, Sandhu RK, Schnabel RB, Schramm K, Schunkert
doi: 10.1001/jamacardio.2017.1855 H, Schurman C, Scott SA, Seppälä I, Shaffer C, Shah S, Shalaby AA, Shim
203. Weng LC, Choi SH, Klarin D, Smith JG, Loh PR, Chaffin M, Roselli C, Hulme J, Shoemaker MB, Siland JE, Sinisalo J, Sinner MF, Slowik A, Smith AV,
OL, Lunetta KL, Dupuis J, Benjamin EJ, Newton-Cheh C, Kathiresan S, Smith BH, Smith JG, Smith JD, Smith NL, Soliman EZ, Sotoodehnia N,
Ellinor PT, Lubitz SA. Heritability of atrial fibrillation. Circ Cardiovasc Genet. Stricker BH, Sun A, Sun H, Svendsen JH, Tanaka T, Tanriverdi K, Taylor
2017;10:e001838–2015. doi: 10.1161/CIRCGENETICS.117.001838 KD, Teder-Laving M, Teumer A, Thériault S, Trompet S, Tucker NR, Tveit

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e319

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

A, Uitterlinden AG, Van Der Harst P, Van Gelder IC, Van Wagoner DR, therapy for cardiovascular risk factors in Canadian outpatients with atrial
CLINICAL STATEMENTS

Verweij N, Vlachopoulou E, Völker U, Wang B, Weeke PE, Weijs B, Weiss fibrillation: from the Facilitating Review and Education to Optimize Stroke
AND GUIDELINES

R, Weiss S, Wells QS, Wiggins KL, Wong JA, Woo D, Worrall BB, Yang PS, Prevention in Atrial Fibrillation (FREEDOM AF) and Co-ordinated National
Yao J, Yoneda ZT, Zeller T, Zeng L, Lubitz SA, Lunetta KL, Ellinor PT. Multi- Network to Engage Physicians in the Care and Treatment of Patients
ethnic genome-wide association study for atrial fibrillation. Nat Genet. With Atrial Fibrillation (CONNECT AF). Am J Cardiol. 2017;120:582–587.
2018;50:1225–1233. doi: 10.1038/s41588-018-0133-9 doi: 10.1016/j.amjcard.2017.05.027
208. Gudbjartsson DF, Helgason H, Gudjonsson SA, Zink F, Oddson A, 220. Alonso A, Bahnson JL, Gaussoin SA, Bertoni AG, Johnson KC, Lewis CE,
Gylfason A, Besenbacher S, Magnusson G, Halldorsson BV, Hjartarson Vetter M, Mantzoros CS, Jeffery RW, Soliman EZ; Look AHEAD Research
E, Sigurdsson GT, Stacey SN, Frigge ML, Holm H, Saemundsdottir J, Group. Effect of an intensive lifestyle intervention on atrial fibrillation risk
Helgadottir HT, Johannsdottir H, Sigfusson G, Thorgeirsson G, Sverrisson in individuals with type 2 diabetes: the Look AHEAD randomized trial.
JT, Gretarsdottir S, Walters GB, Rafnar T, Thjodleifsson B, Bjornsson Am Heart J. 2015;170:770–777.e5. doi: 10.1016/j.ahj.2015.07.026
ES, Olafsson S, Thorarinsdottir H, Steingrimsdottir T, Gudmundsdottir 221. Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B, Middeldorp ME,
TS, Theodors A, Jonasson JG, Sigurdsson A, Bjornsdottir G, Jonsson Lorimer MF, Lau DH, Antic NA, Brooks AG, Abhayaratna WP, Kalman
JJ, Thorarensen O, Ludvigsson P, Gudbjartsson H, Eyjolfsson GI, JM, Sanders P. Effect of weight reduction and cardiometabolic risk fac-
Sigurdardottir O, Olafsson I, Arnar DO, Magnusson OT, Kong A, Masson tor management on symptom burden and severity in patients with atrial
G, Thorsteinsdottir U, Helgason A, Sulem P, Stefansson K. Large-scale fibrillation: a randomized clinical trial. JAMA. 2013;310:2050–2060. doi:
whole-genome sequencing of the Icelandic population. Nat Genet. 10.1001/jama.2013.280521
2015;47:435–444. doi: 10.1038/ng.3247 222. Emdin CA, Callender T, Cao J, Rahimi K. Effect of antihypertensive agents
209. Lubitz SA, Parsons OE, Anderson CD, Benjamin EJ, Malik R, Weng LC, on risk of atrial fibrillation: a meta-analysis of large-scale randomized tri-
Dichgans M, Sudlow CL, Rothwell PM, Rosand J, Ellinor PT, Markus HS, als. Europace. 2015;17:701–710. doi: 10.1093/europace/euv021
Traylor M; on behalf of the WTCCC2, International Stroke Genetics 223. Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S,
Consortium, and AFGen Consortia. Atrial fibrillation genetic risk Connolly SJ. Prevention of atrial fibrillation with angiotensin-convert-
and ischemic stroke mechanisms. Stroke. 2017;48:1451–1456. doi: ing enzyme inhibitors and angiotensin receptor blockers: a meta-
10.1161/STROKEAHA.116.016198 analysis. J Am Coll Cardiol. 2005;45:1832–1839. doi: 10.1016/j.
210. Jamaly S, Carlsson L, Peltonen M, Jacobson P, Sjöström L, Karason jacc.2004.11.070
K. Bariatric surgery and the risk of new-onset atrial fibrillation in 224. Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Shi
Swedish  obese subjects. J Am Coll Cardiol. 2016;68:2497–2504. doi: H, Vincent J, Pitt B; EMPHASIS-HF Study Investigators. Eplerenone and
10.1016/j.jacc.2016.09.940 atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-
211. Pathak RK, Middeldorp ME, Lau DH, Mehta AB, Mahajan R, Twomey D, HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study
Alasady M, Hanley L, Antic NA, McEvoy RD, Kalman JM, Abhayaratna WP, in Heart Failure) study. J Am Coll Cardiol. 2012;59:1598–1603. doi:
Sanders P. Aggressive risk factor reduction study for atrial fibrillation and 10.1016/j.jacc.2011.11.063
implications for the outcome of ablation: the ARREST-AF cohort study. J 225. Martínez-González MÁ, Toledo E, Arós F, Fiol M, Corella D, Salas-Salvadó
Am Coll Cardiol. 2014;64:2222–2231. doi: 10.1016/j.jacc.2014.09.028 J, Ros E, Covas MI, Fernández-Crehuet J, Lapetra J, Muñoz MA, Fitó M,
212. Pathak RK, Evans M, Middeldorp ME, Mahajan R, Mehta AB, Meredith Serra-Majem L, Pintó X, Lamuela-Raventós RM, Sorlí JV, Babio N, Buil-
M, Twomey D, Wong CX, Hendriks JML, Abhayaratna WP, Kalman JM, Cosiales P, Ruiz-Gutierrez V, Estruch R, Alonso A; PREDIMED Investigators.
Lau DH, Sanders P. Cost-effectiveness and clinical effectiveness of the risk Extravirgin olive oil consumption reduces risk of atrial fibrillation: the
factor management clinic in atrial fibrillation: the CENT Study. JACC Clin PREDIMED (Prevención con Dieta Mediterránea) trial. Circulation.
Electrophysiol. 2017;3:436–447. doi: 10.1016/j.jacep.2016.12.015 2014;130:18–26. doi: 10.1161/CIRCULATIONAHA.113.006921
Downloaded from http://ahajournals.org by on February 7, 2019

213. Pathak RK, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, Wong 226. Rahimi K, Emberson J, McGale P, Majoni W, Merhi A, Asselbergs FW,
CX, Twomey D, Elliott AD, Kalman JM, Abhayaratna WP, Lau DH, Sanders Krane V, Macfarlane PW; PROSPER Executive. Effect of statins on atrial
P. Long-term effect of goal-directed weight management in an atrial fibrillation: collaborative meta-analysis of published and unpublished
fibrillation cohort: a long-term follow-up study (LEGACY). J Am Coll evidence from randomised controlled trials. BMJ. 2011;342:d1250. doi:
Cardiol. 2015;65:2159–2169. doi: 10.1016/j.jacc.2015.03.002 10.1136/bmj.d1250
214. Pathak RK, Elliott A, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, 227. Meschia JF, Merrill P, Soliman EZ, Howard VJ, Barrett KM, Zakai NA,
Hendriks JM, Twomey D, Kalman JM, Abhayaratna WP, Lau DH, Sanders Kleindorfer D, Safford M, Howard G. Racial disparities in awareness and
P. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in treatment of atrial fibrillation: the REasons for Geographic and Racial
Obese Individuals With Atrial Fibrillation: the CARDIO-FIT Study. J Am Differences in Stroke (REGARDS) study. Stroke. 2010;41:581–587. doi:
Coll Cardiol. 2015;66:985–996. doi: 10.1016/j.jacc.2015.06.488 10.1161/STROKEAHA.109.573907
215. Holmqvist F, Guan N, Zhu Z, Kowey PR, Allen LA, Fonarow GC, Hylek EM, 228. O’Neal WT, Efird JT, Judd SE, McClure LA, Howard VJ, Howard G, Soliman
Mahaffey KW, Freeman JV, Chang P, Holmes DN, Peterson ED, Piccini EZ. Impact of awareness and patterns of nonhospitalized atrial fibrilla-
JP, Gersh BJ. Impact of obstructive sleep apnea and continuous positive tion on the risk of mortality: the Reasons for Geographic And Racial
airway pressure therapy on outcomes in patients with atrial fibrillation: Differences in Stroke (REGARDS) Study. Clin Cardiol. 2016;39:103–110.
results from the Outcomes Registry for Better Informed Treatment of doi: 10.1002/clc.22501
Atrial Fibrillation (ORBIT-AF). Am Heart J. 2015;169:647–654.e2. doi: 229. Reading SR, Go AS, Fang MC, Singer DE, Liu IA, Black MH, Udaltsova N,
10.1016/j.ahj.2014.12.024 Reynolds K; for the Anticoagulation and Risk Factors in Atrial Fibrillation–
216. Qureshi WT, Nasir UB, Alqalyoobi S, O’Neal WT, Mawri S, Sabbagh S, Cardiovascular Research Network (ATRIA-CVRN) Investigators.
Soliman EZ, Al-Mallah MH. Meta-analysis of continuous positive airway Health literacy and awareness of atrial fibrillation. J Am Heart Assoc.
pressure as a therapy of atrial fibrillation in obstructive sleep apnea. Am 2017;6:e005128. doi: 10.1161/JAHA.116.005128
J Cardiol. 2015;116:1767–1773. doi: 10.1016/j.amjcard.2015.08.046 230. Baczek VL, Chen WT, Kluger J, Coleman CI. Predictors of warfarin use
217. Hess PL, Kim S, Piccini JP, Allen LA, Ansell JE, Chang P, Freeman JV, in atrial fibrillation in the United States: a systematic review and meta-
Gersh BJ, Kowey PR, Mahaffey KW, Thomas L, Peterson ED, Fonarow analysis. BMC Fam Pract. 2012;13:5. doi: 10.1186/1471-2296-13-5
GC. Use of evidence-based cardiac prevention therapy among outpa- 231. Gamra H, Murin J, Chiang CE, Naditch-Brûlé L, Brette S, Steg PG;
tients with atrial fibrillation. Am J Med. 2013;126:625–32.e1. doi: RealiseAF investigators. Use of antithrombotics in atrial fibrillation in
10.1016/j.amjmed.2013.01.037 Africa, Europe, Asia and South America: insights from the International
218. O’Brien EC, Simon DN, Allen LA, Singer DE, Fonarow GC, Kowey PR, RealiseAF Survey. Arch Cardiovasc Dis. 2014;107:77–87. doi:
Thomas LE, Ezekowitz MD, Mahaffey KW, Chang P, Piccini JP, Peterson 10.1016/j.acvd.2014.01.001
ED. Reasons for warfarin discontinuation in the Outcomes Registry for 232. Xian Y, O’Brien EC, Liang L, Xu H, Schwamm LH, Fonarow GC, Bhatt DL,
Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J. Smith EE, Olson DM, Maisch L, Hannah D, Lindholm B, Lytle BL, Pencina
2014;168:487–494. doi: 10.1016/j.ahj.2014.07.002 MJ, Hernandez AF, Peterson ED. Association of preceding antithrombotic
219. Silberberg A, Tan MK, Yan AT, Angaran P, Dorian P, Bucci C, Gregoire JC, treatment with acute ischemic stroke severity and in-hospital outcomes
Bell AD, Gladstone DJ, Green MS, Gross PL, Skanes A, Demchuk AM, Kerr among patients with atrial fibrillation. JAMA. 2017;317:1057–1067. doi:
CR, Mitchell LB, Cox JL, Talajic M, Essebag V, Heilbron B, Ramanathan K, 10.1001/jama.2017.1371
Fournier C, Wheeler BH, Lin PJ, Berall M, Langer A, Goldin L, Goodman 233. Penado S, Cano M, Acha O, Hernández JL, Riancho JA. Atrial fibrillation
SG; FREEDOM AF and CONNECT AF Investigators. Use of evidence-based as a risk factor for stroke recurrence. Am J Med. 2003;114:206–210.

e320 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 16

234. Hsu JC, Maddox TM, Kennedy KF, Katz DF, Marzec LN, Lubitz SA, Gehi 239. O’Neal WT, Sandesara PB, Kelli HM, Venkatesh S, Soliman EZ.

CLINICAL STATEMENTS
AK, Turakhia MP, Marcus GM. Oral anticoagulant therapy prescription in Urban-rural differences in mortality for atrial fibrillation hospitaliza-

AND GUIDELINES
patients with atrial fibrillation across the spectrum of stroke risk: insights tions in the United States. Heart Rhythm. 2018;15:175–179. doi:
from the NCDR PINNACLE Registry. JAMA Cardiol. 2016;1:55–62. doi: 10.1016/j.hrthm.2017.10.019
10.1001/jamacardio.2015.0374 240. Gallagher C, Elliott AD, Wong CX, Rangnekar G, Middeldorp ME,
235. Marzec LN, Wang J, Shah ND, Chan PS, Ting HH, Gosch KL, Hsu JC, Mahajan R, Lau DH, Sanders P, Hendriks JML. Integrated care in atrial fi-
Maddox TM. Influence of direct oral anticoagulants on rates of oral anti- brillation: a systematic review and meta-analysis. Heart. 2017;103:1947–
coagulation for atrial fibrillation. J Am Coll Cardiol. 2017;69:2475–2484. 1953. doi: 10.1136/heartjnl-2016-310952
doi: 10.1016/j.jacc.2017.03.540 241. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin
236. Thompson LE, Maddox TM, Lei L, Grunwald GK, Bradley SM, Peterson PN, EJ, Gillum RF, Kim YH, McAnulty JH Jr, Zheng ZJ, Forouzanfar MH,
Masoudi FA, Turchin A, Song Y, Doros G, Davis MB, Daugherty SL. Sex dif- Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology
ferences in the use of oral anticoagulants for atrial fibrillation: a report from of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation.
the National Cardiovascular Data Registry (NCDR) PINNACLE Registry. J Am 2014;129:837–847. doi: 10.1161/CIRCULATIONAHA.113.005119
Heart Assoc. 2017;6:e005801. doi: 10.1161/JAHA.117.005801 242. Global Burden of Disease Study 2016. Global Burden of Disease Study
237. Yong CM, Liu Y, Apruzzese P, Doros G, Cannon CP, Maddox TM, Gehi A, 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
Hsu JC, Lubitz SA, Virani S, Turakhia MP; ACC PINNACLE Investigators. Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
Association of insurance type with receipt of oral anticoagulation in in- data.org/gbd-results-tool. Accessed May 1, 2018.
sured patients with atrial fibrillation: a report from the American College 243. Healey JS, Oldgren J, Ezekowitz M, Zhu J, Pais P, Wang J, Commerford
of Cardiology NCDR PINNACLE registry. Am Heart J. 2018;195:50–59. P, Jansky P, Avezum A, Sigamani A, Damasceno A, Reilly P, Grinvalds
doi: 10.1016/j.ahj.2017.08.010 A, Nakamya J, Aje A, Almahmeed W, Moriarty A, Wallentin L, Yusuf
238. Carlsson AC, Wändell P, Gasevic D, Sundquist J, Sundquist K. S, Connolly SJ; RE-LY Atrial Fibrillation Registry and Cohort Study
Neighborhood deprivation and warfarin, aspirin and statin prescrip- Investigators. Occurrence of death and stroke in patients in 47 countries
tion: a cohort study of men and women treated for atrial fibrilla- 1 year after presenting with atrial fibrillation: a cohort study [published
tion in Swedish primary care. Int J Cardiol. 2015;187:547–552. doi: correction appears in Lancet. 2017;389:602]. Lancet. 2016;388:1161–
10.1016/j.ijcard.2015.04.005 1169. doi: 10.1016/S0140-6736(16)30968-0
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e321

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

17. SUDDEN CARDIAC ARREST, Abbreviations Used in Chapter 17 Continued

CLINICAL STATEMENTS

VENTRICULAR ARRHYTHMIAS, AND LQTS long-QT syndrome

AND GUIDELINES

LV left ventricular
INHERITED CHANNELOPATHIES LVEF left ventricular ejection fraction
LVH left ventricular hypertrophy
See Tables 17-1 through 17-5 and Charts 17-1 MI myocardial infarction
through 17-4 NH non-Hispanic
NIS National (Nationwide) Inpatient Sample
Click here to return to the Table of Contents OHCA out-of-hospital cardiac arrest
OR odds ratio
Cardiac Arrest (Including VF and PEA pulseless electrical activity
PVC premature ventricular contraction
Ventricular Flutter) PVT polymorphic ventricular tachycardia
ICD-9 427.4, 427.5; ICD-10 I46.0, I46.1, QTc corrected QT interval

I46.9, I49.0. RMVT repetitive monomorphic ventricular tachycardia

ROC Resuscitation Outcomes Consortium
2016: Mortality—17 
661. Any-mention mortality— RR relative risk
366 494. RV right ventricular
RYR2 ryanodine receptor 2
Abbreviations Used in Chapter 17 SBP systolic blood pressure
AED automated external defibrillator SCA sudden cardiac arrest
AF atrial fibrillation SCD sudden cardiac death
AHA American Heart Association SD standard deviation
AMI acute myocardial infarction SE standard error
ARIC Atherosclerosis Risk in Communities Study STEMI ST-segment–elevation myocardial infarction
ARVC arrhythmogenic right ventricular cardiomyopathy SUDS Sudden Unexpected Death Study
AV atrioventricular TdP torsade de pointes
BMI body mass index VF ventricular fibrillation
BP blood pressure VT ventricular tachycardia
CAD coronary artery disease WPW Wolff-Parkinson-White
CARDIA Coronary Artery Risk Development in Young Adults
CARES Cardiac Arrest Registry to Enhance Survival
CASQ2 calsequestrin 2 Tachycardia
Downloaded from http://ahajournals.org by on February 7, 2019

CHS Cardiovascular Health Study ICD-9 427.0, 427.1, 427.2; ICD-10 I47.1,
CI confidence interval
I47.2, I47.9.
CLRD chronic lower respiratory disease
CPC Cerebral Performance Index 2016: Mortality—957. Any-mention mortality—7563.
CPR cardiopulmonary resuscitation 2014: Hospital discharges— 64 000 (42 000 male,
CPVT catecholaminergic polymorphic ventricular tachycardia 22 000 female).
CVD cardiovascular disease
Cardiac arrest is the cessation of cardiac mechani-
DCM dilated cardiomyopathy
DM diabetes mellitus cal activity, as confirmed by the absence of signs of
ECG electrocardiogram circulation.1 An operational definition of SCA is unex-
ED emergency department pected cardiac arrest that results in attempts to restore
eGFR estimated glomerular filtration rate circulation. If resuscitation attempts are unsuccessful,
EMS emergency medical services
this situation is referred to as SCD. SCA results from
ERP early repolarization pattern
GWAS genome-wide association studies
many disease processes; a consensus statement by the
GWTG Get With The Guidelines International Liaison Committee on Resuscitation rec-
HCM hypertrophic cardiomyopathy ommends categorizing cardiac arrest into events with
HCUP Healthcare Cost and Utilization Project external causes (drowning, trauma, asphyxia, electrocu-
HD heart disease tion, and drug overdose) or medical causes.2 Because
HDL-C high-density lipoprotein cholesterol
of fundamental differences in underlying pathogenesis
HF heart failure
HR hazard ratio
and the system of care, epidemiological data for OHCA
ICD-9 International Classification of Diseases, 9th Revision and IHCA are collected and reported separately. For
ICD-9-CM International Classification of Diseases, 9th Revision, similar reasons, data for infants (aged <1 year), children
Clinical Modification (aged 1–18 years), and adults are reported separately.
ICD-10 International Classification of Diseases, 10th Revision
• In a Swedish registry of 70 846 OHCAs from
ICU intensive care unit
IHCA in-hospital cardiac arrest
1992 to 2014, 92% of cases had medical causes.
IQR interquartile range Among nonmedical cases, trauma was the most
IRR incidence rate ratio common cause.3
KD Kawasaki disease • Adjudication of cause of death in 179 cases of
(Continued ) SCA in middle school, high school, college, and

e322 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

professional athletes from 2014 to 2016 iden- (95% CI, 175 759–184 399) in the ROC registry.

CLINICAL STATEMENTS
tified a cause in 117 (65.4%): HCM (16.2%), Approximately 52% of EMS-assessed adult OHCA

AND GUIDELINES
coronary artery anomalies (13.7%), idiopathic had resuscitation attempted (ROC Investigators,
cardiomyopathy (11.1%), autopsy-negative sud- unpublished data, July 7, 2016).
den unexplained death (6.8%), WPW syndrome • In 2015, the incidence of EMS-treated OHCA
(6.8%). and LQTS (6.0%).4 was 66 per 100 000. Incidence of EMS-treated
OHCA with initial shockable rhythm was 13.5 per
100 000 (ROC Investigators, unpublished data,
Incidence July 7, 2016).
(See Tables 17-1 through 17-5) • Ten ambulance services serving almost 54 000 000
• The ROC clinical trial network maintained a reg- residents of England attended 28  729 EMS-
istry of EMS-assessed and EMS-treated OHCA in treated cardiac arrests in 2014 (annual incidence
multiple regions of the United States from 2005 53 per 100 000 residents).9
to 2015 (Table 17-1). • Location of OHCA in adults is most often a home
• The ongoing CARES registry estimates the inci- or residence (69.5%), followed by public settings
dence of EMS-treated OHCA among individuals (18.8%) and nursing homes (11.7%) (Table  17-
of any age in >1400 EMS agencies in the United 2).10 OHCA in adults is witnessed by a layper-
States (Tables 17-1 through 17-4). son in 37% of cases or by an EMS provider in
• Incidence of EMS-assessed OHCA in people of 12% of cases. For 51% of cases, collapse is not
any age is 110.8 individuals per 100 000 popula- witnessed.10
tion (95% CI, 108.9–112.6), or 356 461 people • Initial recorded cardiac rhythm was VF or VT or
(quasi CI, 350 349–362 252), based on extrapo- shockable by an AED in 18.7% of EMS-treated
lation from the ROC registry of OHCA (ROC OHCAs in 2017 (Table 17-2).
Investigators, unpublished data, July 7, 2016) • Of 4729 patients with STEMI in Los Angeles
to the total population of the United States County, CA, from 2011 to 2014, 422 (9%) had
(325 193 000 as of June 9, 2017).5 OHCA.11
• Incidence of EMS-treated OHCA of suspected car-
IHCA: Adults
diac cause in people of any age is 57 individuals
(See Table 17-2)
Downloaded from http://ahajournals.org by on February 7, 2019

per 100 000 population, based on the CARES reg-

• Incidence of IHCA is 209 000 people each year
istry of EMS-treated OHCA.6
based on extrapolation of 2003 to 2007 GWTG
• Among 3 686 296 hospital discharges from aca-
data to the total population of hospitalized
demic medical centers in 2012, 33 700 (0.91%)
patients in the United States.12
included a cardiac arrest diagnosis.7
• Incidence of adult IHCA events was a mean of
• In the NIS for 2014, the weighted national estimate
8.27 (SD, 10.01) per 1000 hospital admissions
of hospital discharges that included ICD-9-CM
and 1.56 (SD, 1.36) per 1000 inpatient days in the
codes for CPR was 116 205 (SE, 2055; incidence
2017 GWTG data (GWTG–Resuscitation, unpub-
rate, 36 [SE, 0.6] per 100  000 people) (ROC
lished data, 2017).
Investigators, unpublished data, July 7, 2016).8
• Incidence of IHCA was 1.6 per 1000 hospital
• In the National Emergency Department Sample
admissions, with a median across hospitals of 1.5
for 2014, the weighted national estimate of ED
(IQR, 1.2–2.2) in the UK National Cardiac Arrest
visits that included a diagnosis of “cardiac arrest
Audit database between 2011 and 2013 (144
or ventricular fibrillation” was 405 200 (incidence
hospitals and 22 628 patients ≥16 years of age).13
rate, 127 per 100 000 people).8
• IHCA incidence was 2.85 per 1000 hospital
OHCA: Adults admissions, based on 838 465 patients in the
(See Table 17-2) United States ≥18 years old with IHCA in the NIS
• Incidence of EMS-assessed OHCA in adults is from 2003 to 2011.14
140.7 individuals per 100 000 population (95% • Incidence of CPR in the hospital increased from
CI, 138.3–143.1), or 347 322 adults (95% CI, 1.81 to 2.37 per 1000 hospitalizations from 2007
341 397–353 246) based on extrapolation from to 2012, based on 235 959 hospitalized patients
the ROC registry of OHCA to the total population aged 18 to 64 years in the NIS.15
of the United States (ROC Investigators, unpub- • Incidence of IHCA was 4.0 per 1000 hospital-
lished data, July 7, 2016).5 izations (range, 1.4–11.8 per 1000 hospitaliza-
• Incidence of EMS-treated OHCA in adults tions) based on 2 205 123 hospitalizations at 101
was 73.0 individuals per 100  000 popula- Veterans Health Administration hospitals between
tion (95% CI, 71.2–74.7), or 180  202 adults 2008 and 2012.16

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e323

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

• According to 2017 GWTG data (GWTG– 2002 and 2015 that included 186 SCAs in young
CLINICAL STATEMENTS

Resuscitation, unpublished data, 2017), location of people (5–34 years old).22

AND GUIDELINES

adult IHCA was 53.5% in the ICU, operating room, • Incidence of SCA or SCD was 1 per 44 832 athlete-
or ED and 46.5% in noncritical care areas among years for males and 1 per 237 510 athlete-years for
26 178 events at 311 hospitals (Table 17-4). females based on a 2007 to 2013 registry of 104
• Initial recorded cardiac rhythm was VF or VT cases of SCA and SCD in high school athletes.23
or shockable in 15.3% of adult IHCAs in 2017 • Incidence of SCA during competitive sports in
GWTG data (GWTG–Resuscitation, unpublished people 12 to 45 years old was 0.76 per 100 000
data, 2017) (Table 17-2). athlete-years in a population-based registry of all
paramedic responses in Toronto, Canada, from
OHCA: Children
2009 to 2014.24
(See Tables 17-2 and 17-3)
• In the US National Registry of Sudden Death in
• Age- and sex-adjusted incidence rate of EMS-
Athletes from 1980 to 2011, there were 1306
assessed OHCA in children was 8.3 per 100 000
person-years (75.3 for infants [<1 years], 3.7 for SCDs in young athletes (mean 19±6 years of age)
children [1–11 years], and 6.3 for adolescents participating in organized sports. The most com-
[12–19 years] per 100 000 person-years) in the mon causes of SCD in 842 young athletes with
ROC Epistry from 2007 to 2012.17 confirmed diagnoses were HCM (36%), coronary
• Incidence of EMS-assessed OHCA was 7037 artery anomalies (19%), myocarditis (7%), ARVC
(quasi CI, 6214–7861) children in the United (5%), CAD (4%), and commotio cordis (3%).25
States based on extrapolation from ROC for indi- • In 45 cases of SCD among National Collegiate
viduals <18 years of age in the United States (ROC Athletic Association athletes from 2004 to 2008,
Investigators, unpublished data, July 7, 2016). adjudication revealed a cause of death in 36
• Location of EMS-treated OHCA was at home for (80%): autopsy-negative sudden unexplained
90.6% of children ≤1 year old, 80.2% of children death (31%), coronary artery abnormalities
1 to 12 years old, and 74.7% of children 13 to 18 (14%), DCM (8%), myocarditis related (8%), aor-
years old in the CARES 2017 data. Location was in tic dissection (8%), and idiopathic LVH/possible
a public place for 9.3% of children ≤1 years old, HCM (8%), HCM (3%), ARVC (3%), LQTS (3%),
19.6% of children 1 to 12 years old, and 25.0% commotio cordis (3%), and KD (3%).26
Downloaded from http://ahajournals.org by on February 7, 2019

of children 13 to 18 years old (Table 17-2).10 • In a 2007 to 2013 registry of 104 cases of SCA and
• Annual incidence of pediatric OHCA was 8.7 per SCD in high school athletes, adjudication revealed
100 000 population in Western Australia from a cause of death in 50 cases (73%): idiopathic
2011 to 2014.18 LVH or possible cardiomyopathy (26%), autopsy-
negative sudden unexplained death (18%), HCM
Sports-Related SCA/SCD (14%), and myocarditis (14%).23
• Incidence of SCD was 0.24 per 100 000 athlete- • Adjudication of cause of death in 179 cases of
years in high school athletes screened every 3 SCA in middle school, high school, college, and
years between 1993 and 2012 with standard pre- professional athletes from 2014 to 2016 iden-
participation evaluations during Minnesota State tified a cause in 117 (65.4%): HCM (16.2%),
High School League activities.19 coronary artery anomalies (13.7%), idiopathic
• Incidence of nontraumatic OHCA was 1 per cardiomyopathy (11.1%), autopsy-negative sud-
43 770 athlete participant-years in a longitudinal den unexplained death (6.8%), WPW (6.8%),
study of students 17 to 24 years of age partici- and LQTS (6.0%).4
pating in National Collegiate Athletic Association
sports from 2004 to 2008. Incidence of cardiac IHCA: Children
arrest was higher among blacks than among (See Table 17-2)
whites and among males than among females.20 • Incidence of IHCA for children (30 days to 18 years
• Incidence of SCA was 0.54 per 100 000 partici- old) was a mean 9.65 (SD, 16.92) per 1000 admis-
pants (95% CI, 0.41–0.70) among 10.9 million sions and 1.75 (SD, 3.03) per 1000 inpatient days
registered participants in 40 marathons and 19 in 92 hospitals according to 2017 GWTG data
half marathons.21 Those with cardiac arrest were (GWTG–Resuscitation, unpublished data, 2017).
more often male and were running a marathon • Incidence of pediatric IHCA was 0.78 per 1000
versus a half marathon. discharges based on 29 577 children with IHCA in
• Sports-related SCA accounted for 39% of SCAs the Kids’ Inpatient Database from 1997 to 2012.
for ages ≤18 years, 13% for ages 19 to 25 years, Incidence of pediatric IHCA increased from 0.57
and 7% for ages 25 to 34 years in a prospective per 1000 discharges in 1997 to 1.01 per 1000
registry of 3775 SCAs in Portland, OR, between discharges in 2012.27

e324 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

• Per 2017 GWTG data (GWTG–Resuscitation, — SCD rate varied by age, from 0.49 per

CLINICAL STATEMENTS
unpublished data, 2017), location of IHCA for 100 000 (1–10 years) to 2.76 per 100 000

AND GUIDELINES
children (30 days to 18 years old) was 87.8% in (26–34 years).31
the ICU, operating room, or ED and 12.2% in — The rate of SCD declined from 1999 to 2015,
noncritical care areas among 897 events at 92 from 1.48 to 1.13 per 100 000 individuals.31
hospitals (Table 17-2). • Among hospitalized patients aged 18 to 64 years
• Incidence of IHCA was 1.8 CPR events per 100 in the NIS from 2007 to 2012, 235 959 adults had
pediatric (<18 years) ICU admissions (sites range CPR in the hospital, and 30.4% survived to hospi-
from 0.6 to 2.3 per 100 ICU admissions) in the tal discharge.15
Collaborative Pediatric Critical Care Research • Mortality rates for any mention of SCD by age are
Network dataset of 10 078 pediatric ICU admis- provided in Chart 17-1.
sions from 2011 to 2013.28
• In a registry of 23 cardiac ICUs of the Pediatric OHCA: Adults
Critical Care Consortium including 15 098 chil- (See Tables 17-1, 17-2, and 17-4)
dren between 2014 and 2016, 3.1% of children • Survival to hospital discharge after EMS-treated
in ICUs had a cardiac arrest, with substantial vari- OHCA was 10.4%, and survival with good func-
ation between centers (range 1%– 5.5%), for a tional status was 8.4% based on 73 910 cases in
mean incidence of 4.8 cardiac arrests per 1000 CARES for 2017.10
cardiac ICU days (range, 1.1–10.4 per 1000 car- • Survival to hospital discharge after EMS-treated
diac ICU days).29 cardiac arrest was 11.4% (95% CI, 10.4%–
• Initial recorded cardiac arrest rhythm was VF 12.4%) for patients of any age and 11.4% (95%
or VT or shockable in 9.9% of 897 events at CI, 10.3%–12.4%) for adults in the ROC Epistry
92 hospitals in GWTG–Resuscitation in 2017 (ROC Investigators, unpublished data, July 7,
(GWTG–Resuscitation, unpublished data, 2017) 2016) (Table 17-1).
(Table 17-2). • Large regional variations in survival to hospital
discharge (range, 3.4%–22.0%) and survival
with functional recovery (range, 0.8%–20.1%)
Lifetime Risk are observed between 132 counties in the United
• SCD appears among the multiple causes of death States.32 Variation in rates of layperson CPR and
Downloaded from http://ahajournals.org by on February 7, 2019

on 13.4% of death certificates in 2016 (366 494 AED use explained much of this variation.
of 2 744 248), which suggests that 1 of every • Age-adjusted survival to hospital admission was
7.5 people in the United States will die of SCD.30 lower for blacks (6.0%) and Hispanics (8.6%) than
Because some people survive SCA, the lifetime for whites (11.3%) among 4053 cardiac arrests in
risk of cardiac arrest is even higher. New York City in 2002 to 2003.33 This disparity
• Infants have a higher incidence of SCD (12.8 per persisted to 30 days after hospital discharge.
100 000) than older children (1.1–2.0 per 100 000). • Survival to hospital admission after EMS-treated
Among adults, risk of SCD increases exponentially nontraumatic OHCA was 29.0% for all presenta-
with age, surpassing the risk for infants by age 40 tions, with higher survival rates in public places
years (20.3 per 100 000) (Chart 17-1). (39.5%) and lower survival rates in homes/resi-
dences (27.5%) and nursing homes (18.2%) in
the 2017 CARES registry (Table 17-4).
Mortality • Survival to hospital discharge varies between
(See Table 17-5 and Chart 17-1) regions of the United States, being higher in the
• In 2016, primary-cause SCD mortality was 17 661, Midwest (adjusted OR, 1.16 [95% CI, 1.02–1.32])
and any-mention SCD mortality in the United and the South (1.24 [95% CI, 1.09–1.40]) relative
States was 366 494 (Table 17-5).30 to the Northeast, in 154 177 patients hospitalized
• Survival of hospitalization after cardiac arrest var- after OHCA in the NIS (2002–2013).34
ied between academic medical centers and was • Survival at 1, 5, 10, and 15 years, respectively,
higher in hospitals with higher cardiac arrest vol- was 92.2%, 81.4%, 70.1%, and 62.3% among
ume, higher surgical volume, greater availability 3449 patients surviving to hospital discharge
of invasive cardiac services, and more affluent after OHCA from 2000 to 2014 in Victoria,
catchment areas.7 Australia.35
• Of 1 452 808 death certificates from 1999 to • Patients with STEMI who had OHCA had higher
2015 for US residents aged 1 to 34 years, 31 492 in-hospital mortality (38%) than STEMI patients
listed SCD (2%) as the cause of death, for an SCD without OHCA (6%) in a Los Angeles, CA, registry
rate of 1.32 per 100 000 individuals.31 of 4729 STEMI patients from 2011 to 2014.11

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e325

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

Sports-Related SCA/SCD to 18 years old in CARES 2017 data (Tables 17-2

CLINICAL STATEMENTS

• Among runners with cardiac arrest during mara- and 17-3).

AND GUIDELINES

thons or half marathons, 71% died; those who • Mortality was lower in teaching hospitals (OR,
died were younger (mean±SD, 39±9 years of age) 0.57 [95% CI, 0.50–0.66), trauma centers (OR,
than those who did not die (mean±SD, 49±10 0.76 [95% CI, 0.67–0.86]), and urban hospitals
years of age), were more often male, and were (OR, 0.78 [95% CI, 0.63–0.97]) relative to non-
more often running a full marathon.21 teaching, non-trauma, or rural hospitals, respec-
• In a population-based registry of all paramedic tively, among 42 036 presentations of children 0 to
responses for SCA from 2009 to 2014, 43.8% of 18 years old for cardiac or respiratory failure in the
athletes with SCA during competitive sports sur- HCUP’s National Emergency Department Sample.39
vived to hospital discharge.24
IHCA: Children
IHCA: Adults • Survival to hospital discharge after pulseless IHCA
(See Table 17-2 and Chart 17-2) was 37.2% in 611 children 0 to 18 years old and
• Survival to hospital discharge was 25.6% of 26 178 22.6% in 214 neonates (0–30 days old) per 2017
adult IHCAs at 311 hospitals in GWTG 2017 GWTG data (GWTG–Resuscitation, unpublished
(GWTG–Resuscitation, unpublished data, 2017) data, 2017) (Table 17-2).
data (Table  17-2, Chart 17-2). Among survivors, • Survival to hospital discharge for children with
81.7% had good functional status (cerebral per- IHCA in the ICU was 45% in the Collaborative
formance category 1 or 2) at hospital discharge. Pediatric Critical Care Research Network from
• Unadjusted survival rate after IHCA was 18.4% 2011 to 2013.28
in the UK National Cardiac Arrest Audit database • The in-hospital mortality rate was 46% among
between 2011 and 2013. Survival was 49% when 29 577 children with IHCA in the Kids’ Inpatient
the initial rhythm was shockable and 10.5% when Database from 1997 to 2012.27
the initial rhythm was not shockable.13
• Survival to discharge is lower for black patients
(25.2%) than for white patients (37.4%) after Secular Trends
IHCA.36 Lower rates of survival to discharge for (See Tables 17-2 and 17-3 and Charts 17-2
blacks reflect lower rates of both successful and 17-3)
Downloaded from http://ahajournals.org by on February 7, 2019

resuscitation (55.8% for blacks versus 67.4% for • Incidence of EMS-treated OHCA increased from
whites) and postresuscitation survival (45.2% ver- 47 per 100 000 to 66 per 100 000 between 2008
sus 55.5%). The hospital where patients received and 2015 in the ROC Epistry (ROC Investigators,
care explained much of the racial variation in unpublished data, July 7, 2016).
postresuscitation survival (adjusted RR for hospi-
• Incidence of pediatric OHCA has declined from
tal, 0.92 [95% CI, 0.88–0.96]; adjusted RR for
1997 to 2014 in Perth, Western Australia, par-
race, 0.99 [95% CI, 0.92–1.06]).
ticularly in children <1 years of age.18
• Survival to hospital discharge after IHCA was
• Incidence of pediatric IHCA increased from 0.57
lower for males than for females (adjusted OR,
per 1000 discharges in 1997 to 1.01 per 1000
0.90 [95% CI, 0.83–0.99]) in a Swedish registry
discharges in 2012 based on 29 577 children with
of 14 933 cases of IHCA from 2007 to 2014.37
IHCA in the Kids’ Inpatient Database.27
• Mortality was lower among 348 368 patients with
• Age-adjusted death rates for any mention of SCD
IHCA managed in teaching hospitals (55.3%) than
declined from 138 per 100 000 person-years in
among 376 035 managed in nonteaching hospi-
1999 to 98 per 100 000 person-years by 2016
tals (58.8%), even after adjustment for baseline
(Chart 17-3).
patient and hospital characteristics (adjusted OR,
• Unadjusted survival to hospital discharge after
0.917 [95% CI, 0.899–0.937]).38
EMS-treated OHCA increased from 10.2% in
OHCA: Children 2006 to 12.4% in 2015 in the ROC Epistry (ROC
(See Tables 17-1 through 17-3) Investigators, unpublished data, July 7, 2016)
• Survival to hospital discharge after EMS-treated (Table 17-1).
nontraumatic cardiac arrest was 13.2% (95% • Survival to hospital discharge for patients hospital-
CI, 7.0%–19.4%) for children in the ROC Epistry ized after OHCA increased from 49.9% (39.8%–
(ROC Investigators, unpublished data, July 7, 60.0%) in 1995 to 54.0% (46.3%–61.8%) in
2016) (Table 17-1). 2013 among 247 684 patients hospitalized in the
• Survival to hospital discharge was 5.4% for 1197 NIS from 1995 to 2013.40
children ≤1 year old, 18.2% for 484 children 1 • Survival to hospital discharge in patients with
to 12 years old, and 20.7% for 376 children 13 VT/VF OHCA increased from 2000 to 2012 from

e326 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

46.9% to 60.1%, both in those with ST-segment premorbid activities, and 27% of those who were

CLINICAL STATEMENTS
elevation (59.2%–74.3%) and in those without working before the OHCA were on sick leave at 6

AND GUIDELINES
ST-segment elevation (43.3%–56.8%), based on months.51
407 974 patients from the NIS.41 • Among 195 family caregivers of cardiac arrest
• Survival after IHCA increased between 2000 and survivors, anxiety was present in 33 caregivers
2016 in GWTG data (Chart 17-2). (25%) and depression in 18 caregivers (14%) at
• The in-hospital mortality rate decreased each year 12 months.52
from 69.6% in 2001 to 57.8% in 2009 among
1 190 860 patients hospitalized with a diagnosis
of cardiac arrest in the NIS.42
Healthcare Utilization and Cost
• The in-hospital mortality rate declined from 51% • In the Oregon SUDS, the estimated societal bur-
in 1997 to 40% in 2012 among 29 577 children den of SCD in the United States was 2 million
with IHCA in the Kids’ Inpatient Database.27 years of potential life lost for males and 1.3 million
• Rates of layperson-initiated CPR and layperson years of potential life lost for females, accounting
use of AEDs have increased over time (Table 17-1). for 40% to 50% of the years of potential life lost
from all cardiac disease.53
• Among males, estimated deaths attributable
Complications to SCD exceeded all other individual causes of
(See Tables 17-2 through 17-4) death, including lung cancer, accidents, CLRD,
• Survivors of cardiac arrest experience multiple cerebrovascular disease, DM, prostate cancer, and
medical problems related to critical illness, includ- colorectal cancer.53
ing impaired consciousness and cognitive deficits.
As many as 18% of survivors of OHCA, 40% of Risk Factors
adult survivors of IHCA, and 72% of child survi-
vors of IHCA have moderate to severe functional
(See Chart 17-4)
impairment at hospital discharge (Tables  17-2 Age
through 17-4). • The underlying cause of OHCA varies by age
• Functional impairments are associated with group. Chart 17-4 illustrates the causes of OHCA
by age group based on a retrospective cohort of
Downloaded from http://ahajournals.org by on February 7, 2019

reduced function, reduced quality of life, and

shortened lifespan.43,44 OHCA patients 0 to 35 years of age treated in King
• Functional recovery continues over at least the County, WA, between 1980 and 2009.54
first 12 months after OHCA in children and over
Sex
the first 6 to 12 months after OHCA in adults.45,46
• In Denmark from 2000 to 2009, incidence of
• Among 366 patients discharged after IHCA in a
SCD in people aged 1 to 35 years was greater for
Veterans Administration hospital between 2014
males (3.6 per 100 000) than for females (1.8 per
and 2015, 55 (15%) endorsed suicidal ideation
100 000; IRR, 2.0 [95% CI, 1.7–2.4]).55
during the first 12 months.47
• Among 66 cases of arrhythmogenic right ventric-
• Among the 2855 patients who were 30-day sur-
ular dysplasia detected after SCA or SCD, 65%
vivors of OHCA between 2001 and 2012 in a
were males, with a mean±SD age of 29.3±13.8
nationwide registry in Denmark, 10.5% had brain
years; SCA occurred during exertion in 72%, and
damage or were admitted to a nursing home, and
antecedent cardiac symptoms had been reported
9.7% died during the 1-year follow-up period.48
by 41%.56
• Serial testing in a cohort of 141 people who sur-
vived hospitalization after SCA revealed severe Race
cognitive deficits in 14 (13%), anxiety and depres- • In patients with implanted defibrillators, rate of
sion in 16 (15%), posttraumatic stress symptoms first ventricular dysrhythmia or death within 4
in 29 (28%), and severe fatigue in 55 (52%).49 years was higher among black patients (42%)
Subjective symptoms declined over time after than whites (34%; adjusted HR, 1.60 [95% CI,
SCA, although 10% to 22% had cognitive impair- 1.18–2.17]).57
ments at 12 months, with executive functioning • A study in New York City, NY, found the age-
being most affected.50 adjusted incidence of OHCA per 10 000 adults
• Of 141 individuals who survived hospitalization was 10.1 among blacks, 6.5 among Hispanics,
after SCA, 41 (72%) returned to work by 12 and 5.8 among whites.33
months.49 • The US National Registry of Sudden Death in
• Of 287 people who survived hospitalization Athletes (1980–2011) of 2406 SCDs in com-
after OHCA, 47% had reduced participation in petitive athletes (mean age, 19 years) revealed a

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e327

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

higher estimated incidence of SCD in black ath- • A meta-analysis of 24 trials of statins in patients
CLINICAL STATEMENTS

letes than in white athletes and in males than in with HF, which included a total of 11 463 patients,
AND GUIDELINES

females. Of these deaths among athletes, 842 concluded that statins did not reduce the risk of
(35%) were adjudicated to have a cardiovascular SCD (RR, 0.92 [95% CI, 0.70–1.21]).65
cause, including HCM (36%), anomalous coro- • In a registry of 2119 SCAs in Portland, OR, from
nary artery (19%), myocarditis (7%), ARVC (5%), 2002 to 2015, prior syncope was present in 6.8%
CAD (4%), mitral valve prolapse (4%), aortic rup- cases, and history of syncope was associated with
ture (3%), aortic stenosis (2%), DCM (2%), and increased risk of SCA relative to 746 geographi-
LQTS (2%).25 cally matched control subjects (OR, 2.8 [95% CI,
1.68–4.85]).66
Socioeconomic Factors • In a cohort of 5211 Finnish people >30 years old
• OHCA rates were higher in census tracts from in 2000 to 2001 followed up for a median of 13.2
the lowest socioeconomic quartile relative to the years, high baseline thyroid-stimulating hormone
highest socioeconomic quartile (IRR, 1.9 [95% CI, was independently associated with greater risk of
1.8–2.0]) in 9235 cases from the ROC Epistry (from SCD (HR, 2.28 [95% CI, 1.13–4.60]).67
2006 to 2007).58 • In a meta-analysis that included 17 studies
HD, Cardiac Risk Factors, and Other Comorbidities with 118 954 subjects, presence of depression
• A large proportion of patients with OHCA have or depressive symptoms was associated with
coronary atherosclerosis.59 increased risk of SCD (HR, 1.62 [95% CI, 1.37–
1.92]), and specifically for VT/VF (HR, 1.47 [95%
• Approximately 5% to 10% of SCD cases occur in
CI, 1.23–1.76]).68
the absence of CAD or structural HD.60
• Risk of SCD in prospective cohorts who were ini- Prodromal Symptoms
tially free of CVD when recruited in 1987 to 1993 • Twenty-five percent of those with EMS-treated
was associated with male sex, black race, DM, OHCA have no symptoms before the onset of
current smoking, and SBP.61 arrest.69
• Prior HD was associated with risk for OHCA in • Abnormal vital signs during the 4 hours preceding
1275 health maintenance organization enrollees IHCA occurred in 59.4% and at least 1 severely
50 to 79 years of age. Incidence of OHCA was abnormal vital sign occurred in 13.4% of 7851
Downloaded from http://ahajournals.org by on February 7, 2019

6.0 per 1000 person-years in subjects with any patients in the 2007 to 2010 GWTG data.70
clinically recognized HD compared with 0.8 per • Early warning score systems using both clinical cri-
1000 person-years in subjects without HD. In sub- teria and vital signs can identify hospital patients
groups with HD, incidence was 13.7 per 1000 with a higher risk of IHCA.71
person-years in subjects with prior MI and 21.9 ECG Abnormalities
per 1000 person-years in subjects with HF.62 • Among 12 241 subjects from the ARIC study, in
• A logistic model incorporating age, sex, race, cur- which 346 subjects had SCD during a median
rent smoking, SBP, use of antihypertensive medi- follow-up of 23.6 years, prolongation of the
cation, DM, serum potassium, serum albumin, QT interval at baseline was associated with risk
HDL-C, eGFR, and QTc interval, derived in 13 677 of SCD (HR, 1.49 [95% CI, 1.01–2.18]), and
adults, correctly stratified 10-year risk of SCD in a this association was driven specifically by the
separate cohort of 4207 adults (C statistic, 0.820 T-wave onset to T-peak component of the total
in ARIC and 0.745 in CHS).61 interval.72
• Four lifestyle factors (smoking, exercise, diet, • In a cohort of 4176 subjects with no known HD,
and weight) were associated with SCD in a study 687 (16.5%) had early repolarization with termi-
of 81 722 females in the Nurses’ Health Study nal J wave, but this pattern had no association
who were followed up from 1984 to 2010. RR with cardiac deaths (0.8%) over 6 years of follow-
of SCD (N=321) was 0.54 (95% CI, 0.34–0.86) up compared with matched control subjects.73
for females with 1 low-risk factor, 0.41 (95% CI, • Among 11  956 residents of rural Liaoning
0.25–0.65) for those with 2 low-risk factors, 0.33 Province, China, who were ≥35 years old, 1.3%
(95% CI, 0.20–0.54) for 3 low-risk factors, and had ERP, with higher prevalence in males (2.6%)
0.08 (95% CI, 0.03–0.23) for 4 low-risk factors.63 than females (0.2%).74
• According to data from the Kids’ Inpatient Data • In an Italian public health screening project, 24%
Sample from 2000, 2003, and 2006, IHCA of 13 016 students aged 16 to 19 years had at
occurred in 0.74% of hospitalized children with least 1 of the following electrocardiographic
CVD versus 0.05% of hospitalized children with- abnormalities: ventricular ectopic beats, AV block,
out CVD (OR, 13.8 [95% CI, 12.8–15.0]).64 Brugada-like ECG pattern, left anterior/posterior

e328 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

fascicular block, LVH/RV hypertrophy, long/short Long-QT Syndrome

CLINICAL STATEMENTS
QT interval, left atrial enlargement, right atrial
• Hereditary LQTS is a genetic channelopathy char-

AND GUIDELINES
enlargement, short PQ interval, and ventricular
acterized by prolongation of the QT interval (typi-
pre-excitation WPW syndrome.75
cally >460 ms) and susceptibility to ventricular
tachyarrhythmias that lead to syncope and SCD.
Genetics and Family History Associated Investigators have identified mutations in 15
With SCD genes leading to this phenotype (LQT1 through
LQT15).87,88 LQT1 (KCNQ1), LQT2 (KCNH2), and
• A large proportion of OHCA in the general popu-
LQT3 (SCN5A) mutations account for the majority
lation results directly from CAD. Risk factors are
(≈80%) of the typed mutations.89,90
thus similar to those for CAD.76
• The prevalence of LQTS was estimated at 1 per
• Arrhythmic cardiac arrest not attributable to CAD
2000 live births from ECG-guided molecular
is associated with structural HD in about one-third
screening of 44 596 infants (mostly white) born
of cases and primary arrhythmic disorders, often
in Italy.91 A similar prevalence was found among
with a genetic basis, in the other two-thirds of
7961 Japanese schoolchildren screened by use of
cases.77
an ECG-guided molecular screening approach.92
• A family history of cardiac arrest in a first-degree
LQTS has been reported among those of African
relative is associated with an ≈2-fold increase in
descent, but its prevalence is not well assessed.93
risk of cardiac arrest.78,79
• Age- and sex-adjusted prevalence of electrocar- • There is variable penetrance and a sex-time inter-
diographic abnormalities associated with SCD action for LQTS symptoms. Therefore, frequency
was 0.6% to 1.1% in a sample of 7889 Spanish of LQTS mutations without clinically apparent or
citizens aged ≥40 years, including Brugada syn- forme pleine LQTS might be much higher. Risk
drome in 0.13%, QTc <340 ms in 0.18%, and QTc of cardiac events is 21% among males and 14%
≥480 ms in 0.42%.80 among females by 12 years of age. Risk of events
• Exome sequencing in younger (<51 years old) during adolescence (ages 12–18 years) is equiva-
decedents who died of sudden unexplained lent between sexes (≈25% for both sexes). Risk of
death or suspected arrhythmic death has revealed cardiac events in young adulthood (ages 18–40
years) is 16% among males and 39% among
Downloaded from http://ahajournals.org by on February 7, 2019

likely pathogenic variants in channelopathy-or

cardiomyopathy-related genes for 29% to 34% females.89
of cases.81,82 Among children with exertion-related • Individuals can be risk stratified for increased
deaths, pathogenic mutations were present in 10 risk of SCD94 according to their specific long-QT
of 11 decedents (91%) 1 to 10 years old and 4 of mutation and their response to β-blockers.95
21 decedents (19%) 11 to 19 years old.83 • Among 403 patients from the LQTS Registry
• Screening of 398 first-degree relatives of 186 from birth through age 40 years, multivariate
unexplained SCA and 212 unexplained SCD pro- analysis demonstrated that patients with multiple
bands revealed cardiac abnormalities in 30.2%: LQTS gene mutations had a 2.3-fold (P=0.015)
LQTS (13%), CPVT (4%), ARVC (4%), and increased risk for life-threatening cardiac events
Brugada syndrome (3%).84 (comprising aborted cardiac arrest, implant-
• In a registry of 109 families of probands with able defibrillator shock, or SCD) compared with
unexplained SCD from 2007 to 2012, screening patients with a single mutation.96
of 411 relatives revealed a diagnosis in 18% of • In 201 cases of sudden infant death syndrome
families: LQTS (15%), Brugada syndrome (3%), from Norway, molecular screening revealed 19
and CPVT (1%).85 cases (9.5% [95% CI, 5.8%–14.4%) with likely
• In a registry of 52 families of probands with unex- contributing mutations of genes associated with
plained cardiac arrest, screening of 91 relatives LQTS (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2,
revealed a diagnosis in 62% of families: LQTS KCNJ2, CAV3).97
(21%), Brugada syndrome (17%), CPVT (6%), • LQTS can be associated with a number of child-
early repolarization (6%), HCM (6%), ARVC hood genetic syndromes, although most cases
(4%), and short-QT syndrome (2%).85 are not. The Jervell and Lange-Nielson autoso-
• In a registry of families of probands with unex- mal recessive syndrome of sensorineural hear-
plained SCD before 45 years of age from 2009 to ing loss and long QT has a prevalence of 1 in
2014, screening of 230 people from 64 families 200 000.98
revealed a diagnosis in 25% of families: Brugada • Approximately 5% of sudden infant death syn-
syndrome (11%), LQTS (7.8%), DCM (3.1%), and drome and some cases of intrauterine fetal death
HCM (3.1%).86 could be attributable to LQTS.97,99,100

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e329

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

Short-QT Syndrome prevalence of 0.9%, 0.3%, and 0.2% in Asia,

CLINICAL STATEMENTS

Europe, and North America, respectively.110

Prevalence and Incidence
AND GUIDELINES

Prevalence is higher in males (0.9%) than females

• Short-QT syndrome is an inherited mendelian
(0.1%).108,111–113
condition characterized by shortening of the QT
interval (typically QT <320 ms) and predisposition Complications
to AF, ventricular tachyarrhythmias, and sudden • Cardiac event rates for Brugada syndrome patients
death. Mutations in 5 ion channel genes have followed up prospectively in Northern Europe
been described (SQT1–SQT5).101 (31.9 months) and Japan (48.7 months) were
• Prevalence of a QTc Bazett interval shorter than similar: 8% to 10% in patients with prior aborted
320 ms in a population of 41 767 young, pre- sudden death, 1% to 2% in those with history
dominantly male Swiss conscripts was 0.02%,102 of syncope, and 0.5% in asymptomatic patients.
which was identical to prevalence from a Portugal Predictors of poor outcome include clinical history
sudden death registry.103 of syncope or ventricular tachyarrhythmias, family
• Prevalence of QT interval ≤320 ms in 18 825 appar- history of sudden death, and a spontaneous ERP
ently healthy people from the United Kingdom on ECG.111,114,115
aged 14 to 35 years between 2005 and 2013 was • Among patients with Brugada syndrome, first-
0.1%.104 Short QT intervals were associated with degree AV block, syncope, and spontaneous
male sex and Afro-Caribbean ethnicity. type 1 ST-segment elevation were indepen-
• Prevalence of QT interval ≤340 ms in 99 380 dently associated with risk of sudden death or
unique patients aged ≤21 years at Cincinnati implantable cardioverter-defibrillator–appropriate
Children’s Hospital between 1993 and 2013 was therapies.116,117
0.05%.105 Of these children, 15 of 45 (33%) were
symptomatic.105
• Among 53 patients from the European Short QT Catecholaminergic PVT
Syndrome Registry (75% males, median age 26 Prevalence and Incidence
years),106 89% had a familial or personal history • CPVT is a familial condition characterized by
of cardiac arrest. Twenty-four patients received adrenergically induced ventricular arrhythmias
an implantable cardioverter-defibrillator, and 12 associated with syncope and sudden death.
Downloaded from http://ahajournals.org by on February 7, 2019

received long-term prophylaxis with hydroquini- Arrhythmias include frequent ectopy, bidirectional
dine. During a median follow-up of 64 months, 2 VT, and PVT with exercise or catecholaminergic
patients received an appropriate implantable car- stimulation (such as emotion, or medicines such
dioverter-defibrillator shock, and 1 patient expe- as isoproterenol). Mutations in genes encoding
rienced syncope. Nonsustained PVT was recorded RYR2 (CPVT1) are found in the majority of patients
in 3 patients. and result in a dominant pattern of inheritance.118
• In an international case series of 15 centers that Mutations in genes encoding CASQ2 (CPVT2) are
included 25 patients ≤21 years of age with short- found in a small minority and result in a recessive
QT syndrome who were followed up for 5.9 years pattern of inheritance. Mutations have also been
(IQR, 4–7.1 years), 6 patients had aborted sudden described in KCNJ2 (CPVT3), TRDN, ANK2, and
death (24%) and 4 (16%) had syncope.107 Sixteen CALM1.118
patients (84%) had a familial or personal history • Prevalence of CPVT is not known. Estimates of
of cardiac arrest. A gene mutation associated 1:5000 to 1:10 000 have been proposed, but this
with short-QT syndrome was identified in 5 of 21 could be an underestimate if childhood cases of
probands (24%). sudden death are uncounted from the numerator
and denominator.118
Brugada Syndrome Complications
Prevalence and Incidence • Of 101 patients with CPVT, the majority had expe-
• Brugada syndrome is an acquired or inher- rienced symptoms before 21 years of age.119
ited channelopathy characterized by persistent • In small series (N=27 to N=101) of patients fol-
ST-segment elevation in the precordial leads (V1– lowed up over a mean of 6.8 to 7.9 years, 27%
V3), right bundle-branch block, and susceptibility to 62% experienced cardiac symptoms, and
to ventricular arrhythmias and SCD.108 Brugada fatal or near-fatal events occurred in 13% to
syndrome is associated with mutations in at least 31%.119–121
12 ion channel–related genes.108,109 • Risk factors for cardiac events included younger
• In a meta-analysis of 24 studies, prevalence was age at diagnosis and absence of β-blocker
estimated at 0.4% worldwide, with regional therapy. A history of aborted cardiac arrest and

e330 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

absence of β-blocker therapy were risk factors for Complications

CLINICAL STATEMENTS
fatal or near-fatal events.119 • Over a mean follow-up of 8±7 years, 6% of 744

AND GUIDELINES
• In a cohort of 34 patients with CPVT, 20.6% HCM patients experienced SCD.127
developed fatal cardiac events during 7.4 years of • Among 1866 sudden deaths in athletes between
follow up.122 1980 and 2006, HCM was the most common
cause of cardiovascular sudden death (in 251
cases, or 36% of the 690 deaths that could be
Arrhythmogenic RV Dysplasia/ reliably attributed to a cardiovascular cause).128
Cardiomyopathy • The risk of sudden death increases with increas-
Prevalence and Incidence ing maximum LV wall thickness,129,130 and the risk
• Arrhythmogenic RV dysplasia or cardiomyopathy for those with wall thickness ≥30 mm is 18.2
is a form of genetically inherited structural HD per 1000 patient-years (95% CI, 7.3–37.6),130 or
that presents with fibrofatty replacement of the approximately twice that of those with maximal
myocardium, which increases risk for palpitations, wall thickness <30 mm.129–131 Of note, an asso-
syncope, and sudden death. Twelve ARVC loci ciation between maximum wall thickness and
have been described (ARVC1–ARVC12). Disease- sudden death has not been found in every HCM
causing genes for 8 of these loci have been iden- population.130
tified, the majority of which are in desmosomally • Nonsustained VT is a risk factor for sudden
related proteins.123 death,132,133 particularly in younger patients.
• The prevalence of ARVC has not been systemati- Nonsustained VT in those ≤30 years of age is
cally estimated, but is thought to be between 1 in associated with a 4.35-greater odds of sudden
1000 and 1 in 5000.123 death (95% CI, 1.5–12.3).133
• Of 100 patients in the Johns Hopkins • A history of syncope is also a risk factor for sud-
Arrhythmogenic Right Ventricular Dysplasia den death in HCM,134 particularly if the syncope
Registry, 51 were males and 95 were white, with was recent before the initial evaluation and not
the rest being of black, Hispanic, or Middle Eastern attributable to a neurally mediated event.135
origin. Twenty-two percent of the 87 index cases • The presence of LV outflow tract obstruction
and 32% of all the identified cases had evidence with pressure gradients ≥30 mm Hg appears to
increase the risk of sudden death by ≈2-fold.136,137
Downloaded from http://ahajournals.org by on February 7, 2019

of the familial form of ARVC.124

The presence of LV outflow tract obstruction has
Complications a low positive predictive value (7%–8%) but a
• The most common presenting symptoms were high negative predictive value (92%–95%) for
palpitations (27%), syncope (26%), and SCD predicting sudden death.136,138
(23%).124 • The rate of malignant ventricular arrhythmias
• During a median follow-up of 100 patients with detected by implantable cardioverter-defibrillators
arrhythmogenic right ventricular dysplasia for appears to be similar between HCM patients with
6 years, 47 patients received an implantable a family history of sudden death in ≥1 first-degree
cardioverter-defibrillator, 29 of whom received relative and those with at least 1 of the risk fac-
appropriate implantable cardioverter-defibrillator tors described above.139
shocks. At the end of follow-up, 66 patients were • The risk of sudden death increases with the num-
alive. Twenty-three patients died at study entry, ber of risk factors.140
and 11 died during follow-up (91% of deaths
were attributable to SCA).124 Similarly, the annual
mortality rate was 2.3% for 130 patients with Early Repolarization Syndrome
ARVC from Paris, France, who were followed up Prevalence and Incidence
for a mean of 8.1 years.125 • There is no single electrocardiographic defini-
• In a cohort of 301 patients with ARVC from a sin- tion or set of criteria for ERP. Studies have used
gle center in Italy, probability of a first life-threat- a range of criteria including ST elevation, termi-
ening arrhythmic event was 14% at 5 years, 23% nal QRS slurring, terminal QRS notching, J-point
at 10 years, and 30% at 15 years.126 elevation, J waves, and other variations. Although
the Brugada ECG pattern is considered an early
repolarization variant, it is generally not included
Hypertrophic Cardiomyopathy in epidemiology assessments of ERP or early repo-
(Please refer to Chapter 20, Cardiomyopathy and Heart larization syndrome.141
Failure, for statistics regarding the general epidemiol- • Because of the high variation in early repolariza-
ogy of HCM.) tion definitions and heterogeneity in published

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e331

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

outcomes, systematic screening for ERP has not • Evidence from families with a high penetrance
CLINICAL STATEMENTS

been recommended.142 of the early repolarization syndrome associated

AND GUIDELINES

• A syndrome in which ≥1-mm positive deflections with a high risk of sudden death suggests that
(sometimes referred to as J waves) occurred in the syndrome can be inherited in an autosomal
the S wave of ≥2 consecutive inferior or lateral dominant fashion.148 A meta-analysis of GWASs
leads was significantly more common among performed in population-based cohorts failed to
patients with idiopathic VF than among control identify any genetic variants.149
subjects.142,143
• ERP is observed in 4% to 19% of the population
(more commonly in young males and in athletes)
Genome-Wide Association Studies
and conventionally has been considered a benign • GWASs on cases of arrhythmic death attempt to
finding.141–145 identify previously unidentified genetic variants
• In CARDIA, 18.6% of 5069 participants had early and biological pathways associated with poten-
repolarization restricted to the inferior and lateral tially lethal ventricular arrhythmias and risk of
leads at baseline; by year 20, only 4.8% exhib- sudden death. Limitations of these studies are
ited an ERP.144 Younger age, black race, male sex, the small number of samples available for analy-
longer exercise duration and QRS duration, and sis and the heterogeneity of case definition. The
lower BMI, heart rate, QT index, and Cornell volt- number of loci uniquely associated with SCD is
age were associated with the presence of baseline much smaller than for other complex diseases. In
early repolarization. Persistence of the electrocar- addition, studies do not consistently identify the
diographic pattern from baseline to year 20 was same variants. A pooled analysis of case-control
associated with black race (OR, 2.62 [95% CI, and cohort GWASs identified a rare (1.4% minor
1.61–4.25]), BMI (OR, 0.62 per 1 SD [95% CI, allele frequency) novel marker at the BAZ2B locus
0.40–0.94]), serum triglyceride levels (OR, 0.66 (bromodomain adjacent zinc finger domain 2B)
per 1 SD [95% CI, 0.45–0.98]), and QRS dura- that was associated with a risk of arrhythmic death
tion (OR, 1.68 per 1 SD [95% CI, 1.37–2.06]) at (OR, 1.9 [95% CI, 1.6–2.3]).149
baseline.144
Complications Premature Ventricular Contractions
Downloaded from http://ahajournals.org by on February 7, 2019

• Shocks from an automatic implantable cardio- • In a study of 1139 older adults in the CHS with-
verter-defibrillator occur more often and earlier in out HF or systolic dysfunction studied by Holter
survivors of idiopathic VF with inferolateral early monitor (median duration, 22.2 hours), 0.011%
repolarization syndrome.146,147 of all heartbeats were PVCs, and 5.5% of par-
• In an analysis of the Social Insurance Institution’s ticipants had nonsustained VT. Over follow-up,
Coronary Disease Study in Finland, J-point eleva- the highest quartile of ambulatory ECG PVC
tion was identified in 5.8% of 10 864 people.144 burden was associated with an adjusted odds of
Those with inferior lead J-point elevation more decreased LVEF (OR, 1.13 [95% CI, 1.05–1.21])
often were male and more often were smokers; and incident HF (HR, 1.06 [95% CI, 1.02–1.09])
had a lower resting heart rate, lower BMI, lower and death (HR, 1.04 [95% CI, 1.02–1.06]).150
BP, shorter QTc, and longer QRS duration; and Although PVC ablation has been shown to
were more likely to have electrocardiographic evi- improve cardiomyopathy, the association with
dence of CAD. Those with lateral J-point elevation death may be complex, representing both a
were more likely to have LVH. Before and after potential cause and a noncausal marker for coro-
multivariable adjustment, subjects with J-point nary or structural HD.
elevation ≥1 mm in the inferior leads (N=384)
had a higher risk of cardiac death (adjusted RR,
1.28 [95% CI, 1.04–1.59]) and arrhythmic death Monomorphic VT
(adjusted RR, 1.43 [95% CI, 1.06–1.94]); how- Prevalence and Incidence
ever, these patients did not have a significantly • Monomorphic VT can be reentrant or focal.
higher rate of all-cause mortality. Before and after Reentrant monomorphic VT is generally caused
multivariable adjustment, subjects with J-point by scar, usually in the setting of prior MI, and is
elevation >2 mm (N=36) had an increased risk of considered malignant and increases the risk of
cardiac death (adjusted RR, 2.98 [95% CI, 1.85– SCD. Focal RMVT is the most common form of
4.92]), arrhythmic death (adjusted RR, 3.94 [95% idiopathic VT and is generally not considered a
CI, 1.96–7.90]), and death of any cause (adjusted risk factor for SCD. RMVT and paroxysmal exer-
RR, 1.54 [95% CI, 1.06–2.24]). cise-induced VT are often grouped together for

e332 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

the purposes of risk stratification because they • In the setting of AMI, PVT is associated with

CLINICAL STATEMENTS
generally do not increase risk of SCD. increased mortality (17.8%).163

AND GUIDELINES
• The overall prevalence of reentrant monomorphic • PVT resulting in cardiac arrest outside of the hos-
VT is not known, because VT can precede SCD pital has a 28% survival rate.165
and therefore not be ascertained. It is more preva-
Risk Factors
lent in diseases more likely to have scar, including
prior MI, cardiomyopathy and HF, infiltrative dis- • PVT in the setting of a normal QT interval is most
eases, myocarditis, and ARVC. frequently seen in the context of acute ischemia or
• In 634 patients with implantable cardioverter- MI.166
defibrillators who had structural HD (including
both primary and secondary prevention patients) Torsade de Pointes
followed up for a mean 11±3 months, 81% of
Prevalence and Incidence
potentially clinically relevant ventricular tachyar-
• Among 14 756 patients exposed to QT-prolonging
rhythmias were attributable to VT amenable to
drugs in 36 studies, 6.3% developed QT prolon-
antitachycardia pacing (which implies a stable cir-
gation, and 0.33% developed TdP.167
cuit and therefore monomorphic VT).151 Because
• A prospective, active surveillance, Berlin-based
therapy might have been delivered before spon-
registry of 51 hospitals observed that the
taneous resolution occurred, the proportion of
these VT episodes with definite clinical relevance annual incidence of symptomatic drug-induced
is not known. QT prolongation in adults was 2.5 per million
• Among 2099 subjects (mean age 52 years; 52.2% males and 4.0 per million females. The authors
male) without known CVD, exercise-induced non- reported 42 potentially associated drugs,
sustained VT occurred in 3.7% and was not inde- including metoclopramide, amiodarone, melp-
pendently associated with total mortality.152 erone, citalopram, and levomethadone. The
• RMVT most commonly arises from the RV outflow mean age of patients with QT prolongation/TdP
tract. The incidence or prevalence of RMVT is not was 57±20 years, and the majority of the cases
known, but it is a relatively common diagnosis in occurred in females (66%) and out of the hos-
cardiac electrophysiology referral practices. RMVT pital (60%).168
occurs almost exclusively in young to middle-aged • The prevalence of drug-induced prolongation
Downloaded from http://ahajournals.org by on February 7, 2019

patients without structural HD. It has been per- of QT interval and TdP is 2 to 3 times higher in
ceived to be more common in athletes, which females than in males.169,170 Other risk factors
might be because of a higher likelihood of exer- include hypokalemia, hypomagnesemia, and
cise-triggered manifestation than in the general bradycardia.171
population.153 Complications
Complications • In a cohort of 459 614 Medicaid and Medicaid-
• Although the prognosis of those with VT or fre- Medicare enrollees aged 30 to 75 years who were
quent PVCs in the absence of structural HD is taking antipsychotic medications, the incidence of
good,154,155 a potentially reversible cardiomyopa- sudden death was 3.4 per 1000 person-years, and
thy can develop in patients with very frequent the incidence of ventricular arrhythmia was 35.1
PVCs,156,157 and some cases of sudden death per 1000 person-years.172
attributable to short-coupled PVCs have been Risk Factors
described.158,159 • TdP is usually related to administration of
QT-interval–prolonging drugs.173 An up-to-date
Polymorphic VT list of drugs with the potential to cause TdP is
available at a website maintained by the University
Prevalence and Incidence
of Arizona Center for Education and Research on
• Among patients who developed SCD during
Therapeutics.174
ambulatory cardiac monitoring, PVT was detected
• Specific risk factors for drug-induced TdP include
in 30% to 43%.160–162
prolonged QT interval, female sex, advanced
• In the setting of AMI, the prevalence of PVT was
age, bradycardia, hypokalemia, hypomagne-
4.4%.163
semia, LV systolic dysfunction, and conditions
Complications that lead to elevated plasma concentrations of
• The presentation of PVT can range from a brief, causative drugs, such as kidney disease, liver dis-
asymptomatic, self-terminating episode to recur- ease, drug interactions, or some combination of
rent syncope or SCD.160–162,164 these.170,173,175

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e333

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

• Drug-induced TdP rarely occurs in patients with- CI, 0.41–0.58])186 or in predominantly Hispanic
CLINICAL STATEMENTS

out concomitant risk factors. An analysis of 144 neighborhoods (OR, 0.62 [95% CI, 0.44–0.89])
AND GUIDELINES

published articles describing TdP associated with than in high-income white neighborhoods.187
noncardiac drugs revealed that 100% of the • Laypeople from Hispanic and Latino neighbor-
patients had at least 1 risk factor, and 71% had at hoods in Denver, CO, report that barriers to learn-
least 2 risk factors.170 ing or providing CPR include lack of recognition
• Both common and rare genetic variants have of cardiac arrest events and lack of understanding
been shown to increase the propensity for drug- about what a cardiac arrest is and how CPR can
induced QT-interval prolongation.176,177 save a life, as well as fear of becoming involved
with law enforcement.188
Prevention • A survey of 5456 households in Beijing, China,
• Appropriate monitoring when a QT-interval– Shanghai, China, and Bangalore, India, revealed
prolonging drug is administered is essential. Also, that 26%, 15%, and 3% of respondents, respec-
prompt withdrawal of the offending agent should tively, were trained in CPR.189
be initiated.173

Global Burden
Awareness and Treatment
• International comparisons of cardiac arrest epi-
• Median annual CPR training rate for US coun- demiology must take into account differences in
ties was 2.39% (25th–75th percentiles, 0.88%– case ascertainment. OHCA usually is identified
5.31%) and ranged from 0.00% to >4.07% through EMS systems, and regional and cultural
(median, 6.81%), based on training data from the differences in use of EMS affect results.190
AHA, the American Red Cross, and the Health & • A systematic review of international epidemiology
Safety Institute, the largest providers of CPR train- of OHCA from 1991 to 2007 included 30 studies
ing in the United States.178 Training rates were from Europe, 24 from North America, 7 from Asia,
lower in rural areas, counties with high propor- and 6 from Australia.191 Estimated incidence per
tions of black or Hispanic residents, and counties 100 000 population of EMS-assessed OHCA was
with lower median household income. 86.4 in Europe, 98.1 in North America, 52.5 in
• Prevalence of reported current training in CPR was Asia, and 112.9 in Australia. Estimated incidence
Downloaded from http://ahajournals.org by on February 7, 2019

18% and prevalence of having CPR training at per 100 000 population of EMS-treated OHCA
some point was 65% in a survey of 9022 people was 40.6 in Europe, 47.3 in North America, 45.9
in the United States in 2015.179 The prevalence of in Asia, and 51.1 in Australia. The proportion of
CPR training was lower in Hispanic/Latino people, cases with VF was highest in Europe (35.2%) and
older people, people with less formal education, lowest in Asia (11.2%).
and lower-income groups. • A prospective data collection concerning
• Those with prior CPR training include 90% of 10 682 OHCA cases from 27 European coun-
citizens in Norway,180 68% of citizens in Victoria, tries in October 2014 found an incidence of 84
Australia,181 61.1% of laypeople in the United per 100 000 people, with CPR attempted in 19
Kingdom,182 and 49% of people in the Republic to 104 cases per 100 000 people.192 Return of
of Korea,183 according to surveys. pulse occurred in 28.6% (range for countries,
• Laypeople with knowledge of AEDs include 9%–50%), with 10.3% (range, 1.1%–30.8%) of
69.3% of people in the United Kingdom, 66% people on whom CPR was attempted surviving to
in Philadelphia, PA, and 32.6% in the Republic hospital discharge or 30 days.
of Korea.182–184 A total of 58% of Philadelphia • Western Australia reports an age- and sex-
respondents184 but only 2.1% of United Kingdom adjusted incidence of 65.9 EMS-attended cardiac
respondents182 reported that they would actually arrests per 100 000 population, with resuscita-
use an AED during a cardiac arrest. tion attempted in 43%.193 Survival to hospital
• Laypeople in the United States initiated CPR in discharge was 8.7%. Among children (<18 years
34.4% of OHCAs recorded in the 2005 to 2014 old), crude incidence was 5.6 per 100 000.18
CARES dataset and in 39.4% of OHCAs in CARES • Hospitals in Beijing, China, reported IHCA inci-
2017 data11 (Table 17-1). dence of 17.5 events per 1000 admissions.194
• Layperson CPR rates in Asian countries range
from 10.5% to 40.9%.185
• Laypeople in the United States are less likely Future Research
to initiate CPR for people with OHCA in low- • The absence of standards for monitoring and
income black neighborhoods (OR, 0.49 [95% reporting the incidence and outcomes of cardiac

e334 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

arrest remains a barrier to population research in administrative data. Finally, regional and cultural

CLINICAL STATEMENTS
the United States.6 Cardiac arrest is a syndrome differences in use of EMS systems could affect

AND GUIDELINES
that results from many disease processes, and ascertainment of OHCA in current registries.
diagnosis codes are often assigned to those dis- Regimenting and increasing the rigor of reporting
eases rather than to cardiac arrest. Consequently, of cardiac arrest will improve the understanding of
incidence of cardiac arrest is underestimated from the epidemiology of this syndrome.

Table 17-1.  Trends in Layperson Response and Outcomes for EMS-Treated OHCA10

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Survival to hospital discharge, %
 ROC 10.2 10.1 11.9 10.3 11.1 11.3 12.4 11.9 12.7 12.4 … ...
 CARES … … … … … 10.5 10 10.6 10.8 10.6 10.8 10.5
Survival if first rhythm shockable, %
 ROC 25.9 29 33.6 27.8 30.1 30.9 34.1 32.7 33.5 30.2 … ...
 CARES … … … … … … … … 29.3 29.1 29.5 29.3
First rhythm shockable, %
 ROC 23.7 21.7 21.9 20.9 20.8 21.4 21.7 20.2 20.8 21.3 … ...
 CARES … … … … … 23.2 23.1 23.2 20.4 20.1 19.8 18.4
Layperson-initiated CPR, %
 ROC 36.5 37.9 37.4 39.1 38.6 38.6 42.8 43 44.5 43.6 … ...
 CARES … … … … … 38 37.8 40.4 40.4 40.6 40.7 39.4
Layperson use of AED, %
 ROC 3.2 3.3 3.9 4.5 4 3.9 5.1 6 6.6 6.7 … ...
 CARES … … … … … 4.4 4 4.6 4.9 5.4 5.7 6.0
AED shock by layperson, %
Downloaded from http://ahajournals.org by on February 7, 2019

 ROC 2 1.6 1.8 1.8 2 1.8 2 2.2 2.2 2.3 … ...

 CARES … … … … … 1.7 1.6 1.6 1.6 1.7 1.7 1.6

AED indicates automated external defibrillator; CARES, Cardiac Arrest Registry to Enhance Survival; CPR, cardiopulmonary resuscitation;
ellipses (…), data not available; EMS, emergency medical services, OHCA, out-of-hospital cardiac arrest; and ROC, Resuscitation Outcomes
Consortium.
Source: Data reported by ROC (ROC Investigators, unpublished data, July 7, 2016) and CARES.10

Table 17-2.  Characteristics of and Outcomes for OHCA and IHCA

OHCA IHCA
Adults Children Adults Children
Survival to hospital discharge 10.4 11.1 25.6 48.9
Good functional status at hospital discharge 8.4 9.9 22.0 16.8
VF/VT/shockable 18.7 8.0 15.3 9.9
PEA … … 53.1 48.8
Asystole … … 23.9 25.8
Unknown … … 7.7 15.5
Public setting 18.8 14.6 … …
Home 69.5 85.3 … …
Nursing home 11.7 0.1 … …
Arrest in ICU, operating room, or ED … … 53.5 87.8
Noncritical care area … … 46.5 12.2

Values are percentages. ED indicates emergency department; ellipses (…), data not available; ICU, intensive care
unit; IHCA, in-hospital cardiac arrest; OHCA, out-of-hospital cardiac arrest; PEA, pulseless electrical activity; VF,
ventricular fibrillation; and VT, ventricular tachycardia.
OHCA data are from CARES (Cardiac Arrest Registry to Enhance Survival)10 2017, based on 76 040 emergency
medical services (EMS)–treated OHCA adult cases and 2057 EMS-treated OHCA child cases. IHCA data are from Get
With The Guidelines 2017, based on 26 178 adult IHCAs in 311 hospitals and 897 child IHCAs in 92 hospitals.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e335

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

Table 17-3.  Outcomes of EMS-Treated Nontraumatic OHCA in Table 17-5.  Sudden Cardiac Arrest (ICD-10 Codes 146.0, 146.1, 146.9,
CLINICAL STATEMENTS

Children: CARES Registry 2017 149.0)

AND GUIDELINES

Survival Number of Number of

With Good Deaths as Deaths as Any-
Survival to Survival to Neurological Underlying Mention Cause,
Age Hospital Hospital Function (CPC In-Hospital Population Group Cause, All Ages All Ages
Groups (n) Admission Discharge 1 or 2) Mortality*
Both sexes 17 661 366 494
<1 y (1197) 19.1 5.4 4.7 71.6
Males 9354 187 671
1–12 y (484) 34.9 18.2 15.7 47.9
Females 8307 178 823
13–18 y (376) 42.3 20.7 18.9 50.9
NH white males 7153 135 832
Values are percentages. CARES indicates Cardiac Arrest Registry to Enhance NH white females 6236 127 696
Survival; CPC, Cerebral Performance Category; EMS, emergency medical
services; and OHCA, out-of-hospital cardiac arrest. NH black males 1529 24 748
*Percentage of patients admitted to hospital who die before hospital
NH black females 1500 25 957
discharge.
Data derived from CARES.10 Hispanic males 400 17 700
Hispanic females 313 16 590

Table 17-4.  Outcomes of EMS-Treated Nontraumatic OHCA in Adults NH Asian/Pacific Islander males 210 7233
(Age ≥18 Years), CARES Registry 2017
NH Asian/Pacific Islander females 221 6924
Survival NH American Indian/Alaska Natives 70 2402
With Good
Presenting Survival to Survival to Neurological ICD-10 indicates International Classification of Diseases, 10th Revision; and
Characteristics Hospital Hospital Function In-Hospital NH, non-Hispanic.
(N) Admission Discharge (CPC 1 or 2) Mortality* Data derived from 2016 Centers for Disease Control and Prevention
WONDER (Wide-ranging Online Data for Epidemiologic Research) database.
All presentations 28.2 10.4 8.4 63.0 Accessed April 17, 2018.30
(73 910)
Home/residence 26.5 8.7 6.9 67.1
(51 344)
Nursing home 18.4 4.1 2.0 77.9
(8655)
Public setting 40.3 20.6 17.8 48.8
Downloaded from http://ahajournals.org by on February 7, 2019

(13 911)
Unwitnessed 18.3 4.6 3.3 75.0
(37 397)
Bystander 37.4 15.9 13.2 57.4
witnessed
(27 296)
EMS provider 40.9 18.0 14.6 56.1
witnessed (9217)
Shockable 48.6 29.1 25.7 40.2
presenting
rhythm (13 792)
Nonshockable 23.5 6.1 4.4 73.8
presenting
rhythm (60 112)
Layperson CPR 28.3 11.7 9.8 58.6
(29 034)
No layperson 24.7 7.4 5.6 70.1
CPR (35 657)

Values are percentages. CARES indicates Cardiac Arrest Registry to Enhance

Survival; CPC, Cerebral Performance Index; CPR, cardiopulmonary resuscitation;
EMS, emergency medical services; and OHCA, out-of-hospital cardiac arrest.
*Percentage of patients admitted to hospital who die before hospital
discharge.
Modified from CARES.10

e336 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

CLINICAL STATEMENTS
AND GUIDELINES
Chart 17-1. Age-specific death rates for any mention of sudden cardiac death by age, 2016.
Data derived from Centers for Disease Control and Prevention WONDER (Wide-ranging Online Data for Epidemiologic Research) database. Accessed June 7,
2018.30
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 17-2. Temporal trends in survival to hospital discharge after pulseless IHCA in GWTG–Resuscitation from 2000 to 2016.
GWTG indicates Get With The Guidelines; IHCA, in-hospital cardiac arrest; PEA, pulseless electrical activity; VF, ventricular fibrillation; and VT, ventricular tachycardia.
Source: GWTG–Resuscitation; unpublished data, 2017.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e337

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17
CLINICAL STATEMENTS
AND GUIDELINES

Chart 17-3. Age-adjusted death rates for any mention of sudden cardiac death, 1999 to 2016.
Data derived from Centers for Disease Control and Prevention WONDER (Wide-ranging Online Data for Epidemiologic Research) database. Accessed June 7,
2018.30
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 17-4. Detailed causes of cardiac arrest by age group in children and young adults in King County, WA (1980–2009).
CAD indicates coronary artery disease; DCM, dilated cardiomyopathy; and HCM, hypertrophic cardiomyopathy. “Other” corresponds to all other causes.
Reprinted from Meyer et al.54 Copyright © 2012, American Heart Association, Inc.

e338 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

REFERENCES JA, Fonarow GC. Regional variation in the incidence and outcomes of in-

CLINICAL STATEMENTS
hospital cardiac arrest in the United States. Circulation. 2015;131:1415–
1. Jacobs I, Nadkarni V; and the ILCOR Task Force on Cardiac Arrest and

AND GUIDELINES
1425. doi: 10.1161/CIRCULATIONAHA.114.014542
Cardiopulmonary Resuscitation Outcomes. Cardiac arrest and cardiopul- 15. Mallikethi-Reddy S, Briasoulis A, Akintoye E, Jagadeesh K, Brook RD,
monary resuscitation outcome reports: update and simplification of the Rubenfire M, Afonso L, Grines CL. Incidence and survival after in-hos-
Utstein templates for resuscitation registries: a statement for healthcare pital cardiopulmonary resuscitation in nonelderly adults: US experience,
professionals from a task force of the International Liaison Committee 2007 to 2012. Circ Cardiovasc Qual Outcomes. 2017;10:e003194. doi:
on Resuscitation (American Heart Association, European Resuscitation
10.1161/CIRCOUTCOMES.116.003194
Council, Australian Resuscitation Council, New Zealand Resuscitation
16. Bradley SM, Kaboli P, Kamphuis LA, Chan PS, Iwashyna TJ, Nallamothu BK.
Council, Heart and Stroke Foundation of Canada, InterAmerican Heart
Temporal trends and hospital-level variation of inhospital cardiac arrest
Foundation, Resuscitation Councils of Southern Africa). Circulation.
incidence and outcomes in the Veterans Health Administration. Am Heart
2004;110:3385–3397. doi: 10.1161/01.CIR.0000147236.85306.15
J. 2017;193:117–123. doi: 10.1016/j.ahj.2017.05.018
2. Perkins GD, Jacobs IG, Nadkarni VM, Berg RA, Bhanji F, Biarent D,
17. Fink EL, Prince DK, Kaltman JR, Atkins DL, Austin M, Warden C, Hutchison
Bossaert LL, Brett SJ, Chamberlain D, de Caen AR, Deakin CD, Finn JC,
J, Daya M, Goldberg S, Herren H, Tijssen JA, Christenson J, Vaillancourt
Gräsner JT, Hazinski MF, Iwami T, Koster RW, Lim SH, Huei-Ming Ma
C, Miller R, Schmicker RH, Callaway CW; Resuscitation Outcomes
M, McNally BF, Morley PT, Morrison LJ, Monsieurs KG, Montgomery
Consortium. Unchanged pediatric out-of-hospital cardiac arrest incidence
W, Nichol G, Okada K, Eng Hock Ong M, Travers AH, Nolan JP; for the
and survival rates with regional variation in North America. Resuscitation.
Utstein Collaborators. Cardiac arrest and cardiopulmonary resuscitation
2016;107:121–128. doi: 10.1016/j.resuscitation.2016.07.244
outcome reports: update of the Utstein Resuscitation Registry templates
18. Inoue M, Tohira H, Williams T, Bailey P, Borland M, McKenzie N, Brink D,
for out-of-hospital cardiac arrest: a statement for healthcare professionals
Finn J. Incidence, characteristics and survival outcomes of out-of-hospi-
from a task force of the International Liaison Committee on Resuscitation
tal cardiac arrest in children and adolescents between 1997 and 2014
(American Heart Association, European Resuscitation Council, Australian
in Perth, Western Australia. Emerg Med Australas. 2017;29:69–76. doi:
and New Zealand Council on Resuscitation, Heart and Stroke Foundation
10.1111/1742-6723.12657
of Canada, InterAmerican Heart Foundation, Resuscitation Council of
19. Roberts WO, Stovitz SD. Incidence of sudden cardiac death in Minnesota
Southern Africa, Resuscitation Council of Asia); and the American Heart
high school athletes 1993-2012 screened with a standardized pre-
Association Emergency Cardiovascular Care Committee and the Council
participation evaluation. J Am Coll Cardiol. 2013;62:1298–1301. doi:
on Cardiopulmonary, Critical Care, Perioperative and Resuscitation [pub-
10.1016/j.jacc.2013.05.080
lished correction appears in Circulation. 2015;132:e168–e169. Circulation.
20. Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of sudden
2015;132:1286–1300. doi: 10.1161/CIR.0000000000000144
cardiac death in National Collegiate Athletic Association athletes.
3. Claesson A, Djarv T, Nordberg P, Ringh M, Hollenberg J, Axelsson
Circulation. 2011;123:1594–1600. doi: 10.1161/CIRCULATIONAHA.
C, Ravn-Fischer A, Stromsoe A. Medical versus non medical etiol-
110.004622
ogy in out-of-hospital cardiac arrest-Changes in outcome in relation
to the revised Utstein template. Resuscitation. 2017;110:48–55. doi: 21. Kim JH, Malhotra R, Chiampas G, d’Hemecourt P, Troyanos C, Cianca
10.1016/j.resuscitation.2016.10.019 J, Smith RN, Wang TJ, Roberts WO, Thompson PD, Baggish AL; Race
4. Peterson DF, Siebert DM, Kucera KL, et al. Etiology of sudden cardiac Associated Cardiac Arrest Event Registry (RACER) Study Group. Cardiac
arrest and death in US competitive athletes: a 2-year prospective sur- arrest during long-distance running races. N Engl J Med. 2012;366:130–
veillance study [published online April 9, 2018]. Clin J Sport Med. doi: 140. doi: 10.1056/NEJMoa1106468
10.1097/JSM.0000000000000598 22. Jayaraman R, Reinier K, Nair S, Aro AL, Uy-Evanado A, Rusinaru C, Stecker
EC, Gunson K, Jui J, Chugh SS. Risk factors of sudden cardiac death
Downloaded from http://ahajournals.org by on February 7, 2019

5. US population data (population clock). United States Census Bureau web-

site. http://www.census.gov. Accessed June 8, 2018. in the young: multiple-year community-wide assessment. Circulation.
6. Graham R, McCoy MA, Schultz AM, eds. Committee on the Treatment 2018;137:1561–1570. doi: 10.1161/CIRCULATIONAHA.117.031262
of Cardia Arrest: Current Status and Future Directions; Board on Health 23. Harmon KG, Asif IM, Maleszewski JJ, Owens DS, Prutkin JM, Salerno JC,
Sciences Policy; Institute of Medicine. Strategies to Improve Cardiac Arrest Zigman ML, Ellenbogen R, Rao AL, Ackerman MJ,Drezner JA. Incidence
Survival: A Time to Act. Washington, DC: National Academy of Sciences; and etiology of sudden cardiac arrest and death in high school ath-
June 2015. letes in the United States. Mayo Clin Proc. 2016;91:1493–1502. doi:
7. Kurz MC, Donnelly JP, Wang HE. Variations in survival after cardiac 10.1016/j.mayocp.2016.07.021
arrest among academic medical center-affiliated hospitals. PLoS One. 24. Landry CH, Allan KS, Connelly KA, Cunningham K, Morrison LJ,
2017;12:e0178793. doi: 10.1371/journal.pone.0178793 Dorian P; Rescu Investigators. Sudden cardiac arrest during participa-
8. HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare tion in competitive sports. N Engl J Med. 2017;377:1943–1953. doi:
Research and Quality, Rockville, MD. https://hcupnet.ahrq.gov/. Accessed 10.1056/NEJMoa1615710
September 11, 2018. 25. Maron BJ, Haas TS, Ahluwalia A, Murphy CJ, Garberich RF. Demographics
9. Hawkes C, Booth S, Ji C, Brace-McDonnell SJ, Whittington A, and epidemiology of sudden deaths in young competitive athletes: from
Mapstone J, Cooke MW, Deakin CD, Gale CP, Fothergill R, Nolan JP, the United States National Registry. Am J Med. 2016;129:1170–1177.
Rees N, Soar J, Siriwardena AN, Brown TP, Perkins GD; OHCAO col- doi: 10.1016/j.amjmed.2016.02.031
laborators. Epidemiology and outcomes from out-of-hospital car- 26. Harmon KG, Drezner JA, Maleszewski JJ, Lopez-Anderson M, Owens
diac arrests in England. Resuscitation. 2017;110:133–140. doi: D, Prutkin JM, Asif IM, Klossner D, Ackerman MJ. Pathogeneses of
10.1016/j.resuscitation.2016.10.030 sudden cardiac death in National Collegiate Athletic Association
10. Cardiac Arrest Registry to Enhance Survival. https://mycares.net. Accessed athletes. Circ Arrhythm Electrophysiol. 2014;7:198–204. doi:
April 17, 2017. 10.1161/CIRCEP.113.001376
11. Shavelle DM, Bosson N, Thomas JL, Kaji AH, Sung G, French WJ, Niemann 27. Martinez PA, Totapally BR. The epidemiology and outcomes of
JT. Outcomes of ST elevation myocardial infarction complicated by out- pediatric in-hospital cardiopulmonary arrest in the United States
of-hospital cardiac arrest (from the Los Angeles County Regional System). during 1997 to 2012. Resuscitation. 2016;105:177–181. doi:
Am J Cardiol. 2017;120:729–733. doi: 10.1016/j.amjcard.2017.06.010 10.1016/j.resuscitation.2016.06.010
12. Merchant RM, Yang L, Becker LB, Berg RA, Nadkarni V, Nichol G, Carr 28. Berg RA, Nadkarni VM, Clark AE, Moler F, Meert K, Harrison RE, Newth
BG, Mitra N, Bradley SM, Abella BS, Groeneveld PW; American Heart CJ, Sutton RM, Wessel DL, Berger JT, Carcillo J, Dalton H, Heidemann
Association Get With The Guidelines-Resuscitation Investigators. Incidence S, Shanley TP, Zuppa AF, Doctor A, Tamburro RF, Jenkins TL, Dean JM,
of treated cardiac arrest in hospitalized patients in the United States. Crit Holubkov R, Pollack MM; Eunice Kennedy Shriver National Institute of
Care Med. 2011;39:2401-2406. doi: 10.1097/CCM.0b013e3182257459 Child Health and Human Development Collaborative Pediatric Critical
13. Nolan JP, Soar J, Smith GB, Gwinnutt C, Parrott F, Power S, Harrison Care Research Network. Incidence and outcomes of cardiopulmo-
DA, Nixon E, Rowan K; National Cardiac Arrest Audit. Incidence nary resuscitation in PICUs. Crit Care Med. 2016;44:798–808. doi:
and outcome of in-hospital cardiac arrest in the United Kingdom 10.1097/CCM.0000000000001484
National Cardiac Arrest Audit. Resuscitation. 2014;85:987–992. doi: 29. Alten JA, Klugman D, Raymond TT, Cooper DS, Donohue JE, Zhang W,
10.1016/j.resuscitation.2014.04.002 Pasquali SK, Gaies MG. Epidemiology and outcomes of cardiac arrest in
14. Kolte D, Khera S, Aronow WS, Palaniswamy C, Mujib M, Ahn C, Iwai pediatric cardiac ICUs. Pediatr Crit Care Med. 2017;18:935–943. doi:
S, Jain D, Sule S, Ahmed A, Cooper HA, Frishman WH, Bhatt DL, Panza 10.1097/PCC.0000000000001273

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e339

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

30. Centers for Disease Control and Prevention, National Center for Health 47. Bucy RA, Hanisko KA, Kamphuis LA, Nallamothu BK, Iwashyna TJ,
CLINICAL STATEMENTS

Statistics. Multiple Cause of Death, 1999–2016. CDC WONDER Online Pfeiffer PN. Suicide risk management protocol in post-cardiac arrest
AND GUIDELINES

Database [database online]. Released December 2017. Atlanta, GA: survivors: development, feasibility, and outcomes. Ann Am Thorac Soc.
Centers for Disease Control and Prevention. http://wonder.cdc.gov/mcd- 2017;14:363–367. doi: 10.1513/AnnalsATS.201609-694BC
icd10.html Accessed September 11, 2018 9:57:28 PM. 48. Kragholm K, Wissenberg M, Mortensen RN, Hansen SM, Malta Hansen C,
31. El-Assaad I, Al-Kindi SG, Aziz PF. Trends of out-of-hospital sudden cardiac Thorsteinsson K, Rajan S, Lippert F, Folke F, Gislason G, Køber L, Fonager
death among children and young adults. Pediatrics. 2017;140:e20171438. K, Jensen SE, Gerds TA, Torp-Pedersen C, Rasmussen BS. Bystander efforts
doi: 10.1542/peds.2017-1438 and 1-year outcomes in out-of-hospital cardiac arrest. N Engl J Med.
32. Girotra S, van Diepen S, Nallamothu BK, Carrel M, Vellano K, Anderson 2017;376:1737–1747. doi: 10.1056/NEJMoa1601891
ML, McNally B, Abella BS, Sasson C, Chan PS; in collaboration with 49. Moulaert VRM, van Heugten CM, Gorgels TPM, Wade DT, Verbunt JA.
CARES Surveillance Group and the HeartRescue Project. Regional Long-term outcome after survival of a cardiac arrest: a prospective longi-
variation in out-of-hospital cardiac arrest survival in the United States. tudinal cohort study. Neurorehabil Neural Repair. 2017;31:530–539. doi:
Circulation. 2016;133:2159–2168. doi: 10.1161/CIRCULATIONAHA. 10.1177/1545968317697032
115.018175 50. Steinbusch CVM, van Heugten CM, Rasquin SMC, Verbunt JA, Moulaert
33. Galea S, Blaney S, Nandi A, Silverman R, Vlahov D, Foltin G, Kusick M, VRM. Cognitive impairments and subjective cognitive complaints after sur-
Tunik M, Richmond N. Explaining racial disparities in incidence of and sur- vival of cardiac arrest: a prospective longitudinal cohort study. Resuscitation.
vival from out-of-hospital cardiac arrest. Am J Epidemiol. 2007;166:534– 2017;120:132–137. doi: 10.1016/j.resuscitation.2017.08.007
543. doi: 10.1093/aje/kwm102 51. Lilja G, Nielsen N, Bro-Jeppesen J, Dunford H, Friberg H, Hofgren C, Horn
34. Albaeni A, Beydoun MA, Beydoun HA, Akinyele B, RaghavaKurup L, J, Insorsi A, Kjaergaard J, Nilsson F, Pelosi P, Winters T, Wise MP, Cronberg
Chandra-Strobos N, Eid SM. Regional variation in outcomes of hos- T. Return to work and participation in society after out-of-hospital car-
pitalized patients having out-of-hospital cardiac arrest. Am J Cardiol. diac arrest. Circ Cardiovasc Qual Outcomes. 2018;11:e003566. doi:
2017;120:421–427. doi: 10.1016/j.amjcard.2017.04.045 10.1161/CIRCOUTCOMES.117.003566
35. Andrew E, Nehme Z, Wolfe R, Bernard S, Smith K. Long-term survival fol- 52. van Wijnen HG, Rasquin SM, van Heugten CM, Verbunt JA, Moulaert
lowing out-of-hospital cardiac arrest. Heart. 2017;103:1104–1110. doi: VR. The impact of cardiac arrest on the long-term wellbeing and care-
10.1136/heartjnl-2016-310485 giver burden of family caregivers: a prospective cohort study. Clin Rehabil.
36. Chan PS, Nichol G, Krumholz HM, Spertus JA, Jones PG, Peterson ED, 2017;31:1267–1275. doi: 10.1177/0269215516686155
Rathore SS, Nallamothu BK; American Heart Association National Registry 53. Stecker EC, Reinier K, Marijon E, Narayanan K, Teodorescu C, Uy-Evanado
of Cardiopulmonary Resuscitation (NRCPR) Investigators. Racial differ- A, Gunson K, Jui J, Chugh SS. Public health burden of sudden cardiac
ences in survival after in-hospital cardiac arrest. JAMA. 2009;302:1195– death in the United States. Circ Arrhythm Electrophysiol. 2014;7:212–
1201. doi: 10.1001/jama.2009.1340 217. doi: 10.1161/CIRCEP.113.001034
37. Al-Dury N, Rawshani A, Israelsson J, Strömsöe A, Aune S, Agerström J, 54. Meyer L, Stubbs B, Fahrenbruch C, Maeda C, Harmon K, Eisenberg
Karlsson T, Ravn-Fischer A, Herlitz J. Characteristics and outcome among M, Drezner J. Incidence, causes, and survival trends from cardiovascu-
14,933 adult cases of in-hospital cardiac arrest: a nationwide study with lar-related sudden cardiac arrest in children and young adults 0 to 35
the emphasis on gender and age. Am J Emerg Med. 2017;35:1839–1844. years of age: a 30-year review. Circulation. 2012;126:1363–1372. doi:
doi: 10.1016/j.ajem.2017.06.012 10.1161/CIRCULATIONAHA.111.076810
38. Dolmatova EV, Moazzami K, Klapholz M, Kothari N, Feurdean M, Waller 55. Winkel BG, Risgaard B, Bjune T, Jabbari R, Lynge TH, Glinge C, Bundgaard
AH. Impact of hospital teaching status on mortality, length of stay and H, Haunsø S, Tfelt-Hansen J. Gender differences in sudden cardiac death
cost among patients with cardiac arrest in the United States. Am J Cardiol. in the young: a nationwide study. BMC Cardiovasc Disord. 2017;17:19.
Downloaded from http://ahajournals.org by on February 7, 2019

2016;118:668–672. doi: 10.1016/j.amjcard.2016.05.062 doi: 10.1186/s12872-016-0446-5

39. Hansen M, Fleischman R, Meckler G, Newgard CD. The associa- 56. Gupta R, Tichnell C, Murray B, Rizzo S, Te Riele A, Tandri H, Judge DP,
tion between hospital type and mortality among critically ill chil- Thiene G, Basso C, Calkins H, James CA. Comparison of features of fatal
dren in US EDs. Resuscitation. 2013;84:488–491. doi: 10.1016/ versus nonfatal cardiac arrest in patients with arrhythmogenic right ven-
j.resuscitation.2016.07.032 tricular dysplasia/cardiomyopathy. Am J Cardiol. 2017;120:111–117. doi:
40. Eid SM, Abougergi MS, Albaeni A, Chandra-Strobos N. Survival, expen- 10.1016/j.amjcard.2017.03.251
diture and disposition in patients following out-of-hospital cardiac 57. Sabbag A, Goldenberg I, Moss AJ, McNitt S, Glikson M, Biton Y, Jackson
arrest: 1995-2013. Resuscitation. 2017;113:13–20. doi: 10.1016/ L, Polonsky B, Zareba W, Kutyifa V. Predictors and risk of ventricular
j.resuscitation.2016.12.027 tachyarrhythmias or death in black and white cardiac patients: a MADIT-
41. Patel N, Patel NJ, Macon CJ, Thakkar B, Desai M, Rengifo-Moreno P, CRT Trial substudy. JACC Clin Electrophysiol. 2016;2:448–455. doi:
Alfonso CE, Myerburg RJ, Bhatt DL, Cohen MG. Trends and outcomes 10.1016/j.jacep.2016.03.003
of coronary angiography and percutaneous coronary intervention after 58. Reinier K, Thomas E, Andrusiek DL, Aufderheide TP, Brooks SC, Callaway
out-of-hospital cardiac arrest associated with ventricular fibrillation or CW, Pepe PE, Rea TD, Schmicker RH, Vaillancourt C, Chugh SS;
pulseless ventricular tachycardia. JAMA Cardiol. 2016;1:890–899. doi: Resuscitation Outcomes Consortium Investigators. Socioeconomic status
10.1001/jamacardio.2016.2860 and incidence of sudden cardiac arrest. CMAJ. 2011;183:1705–1712. doi:
42. Fugate JE, Brinjikji W, Mandrekar JN, Cloft HJ, White RD, Wijdicks EF, 10.1503/cmaj.101512
Rabinstein AA. Post-cardiac arrest mortality is declining: a study of the US 59. Chelly J, Mongardon N, Dumas F, Varenne O, Spaulding C, Vignaux
National Inpatient Sample 2001 to 2009. Circulation. 2012;126:546–550. O, Carli P, Charpentier J, Pène F, Chiche JD, Mira JP, Cariou A.
doi: 10.1161/CIRCULATIONAHA.111.088807 Benefit of an early and systematic imaging procedure after cardiac
43. Geri G, Dumas F, Bonnetain F, Bougouin W, Champigneulle B, Arnaout arrest: insights from the PROCAT (Parisian Region Out of Hospital
M, Carli P, Marijon E, Varenne O, Mira JP, Empana JP, Cariou A. Predictors Cardiac Arrest) registry. Resuscitation. 2012;83:1444–1450. doi:
of long-term functional outcome and health-related quality of life after 10.1016/j.resuscitation.2012.08.321
out-of-hospital cardiac arrest. Resuscitation. 2017;113:77–82. doi: 60. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M,
10.1016/j.resuscitation.2017.01.028 Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA,
44. Elmer J, Rittenberger JC, Coppler PJ, Guyette FX, Doshi AA, Callaway Roden DM, Silka MJ, Tracy C. ACC/AHA/ESC 2006 guidelines for man-
CW; Pittsburgh Post-Cardiac Arrest Service. Long-term survival benefit agement of patients with ventricular arrhythmias and the prevention of
from treatment at a specialty center after cardiac arrest. Resuscitation. sudden cardiac death: a report of the American College of Cardiology/
2016;108:48–53. doi: 10.1016/j.resuscitation.2016.09.008 American Heart Association Task Force and the European Society of
45. Silverstein FS, Slomine BS, Christensen J, Holubkov R, Page K, Dean JM, Cardiology Committee for Practice Guidelines (Writing Committee
Moler FW; Therapeutic Hypothermia to Improve Survival After Cardiac to Develop Guidelines for Management of Patients With Ventricular
Arrest Trial Group. Functional outcome trajectories after out-of-hospital Arrhythmias and the Prevention of Sudden Cardiac Death). Circulation.
pediatric cardiac arrest. Crit Care Med. 2016;44:e1165–e1174. doi: 2006;114:e385–e484. doi: 10.1161/CIRCULATIONAHA.106.178233
10.1097/CCM.0000000000002003 61. Deo R, Norby FL, Katz R, Sotoodehnia N, Adabag S, DeFilippi
46. Tong JT, Eyngorn I, Mlynash M, Albers GW, Hirsch KG. Functional neuro- CR, Kestenbaum B, Chen LY, Heckbert SR, Folsom AR, Kronmal
logic outcomes change over the first 6 months after cardiac arrest. Crit Care RA, Konety S, Patton KK, Siscovick D, Shlipak MG, Alonso A.
Med. 2016;44:e1202–e1207. doi: 10.1097/CCM.0000000000001963 Development and validation of a sudden cardiac death prediction

e340 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

model for the general population. Circulation. 2016;134:806–816. doi: an acute coronary event. Circulation. 2006;114:1462–1467. doi:

CLINICAL STATEMENTS
10.1161/CIRCULATIONAHA.116.023042 10.1161/CIRCULATIONAHA.106.624593

AND GUIDELINES
62. Rea TD, Pearce RM, Raghunathan TE, Lemaitre RN, Sotoodehnia N, Jouven 80. Awamleh Garcia P, Alonso Martin JJ, Graupner Abad C, Jiménez
X, Siscovick DS. Incidence of out-of-hospital cardiac arrest. Am J Cardiol. Hernández RM, Curcio Ruigómez A, Talavera Calle P, Cristóbal Varela C,
2004;93:1455–1460. doi: 10.1016/j.amjcard.2004.03.002 Serrano Antolín J, Muñiz J, Gómez Doblas JJ, Roig E; Investigators of the
63. Chiuve SE, Fung TT, Rexrode KM, Spiegelman D, Manson JE, Stampfer OFRECE study. Prevalence of electrocardiographic patterns associated with
MJ, Albert CM. Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death in the Spanish population aged 40 years or older.
sudden cardiac death among women. JAMA. 2011;306:62–69. doi: results of the OFRECE Study. Rev Esp Cardiol (Engl Ed). 2017;70:801–807.
10.1001/jama.2011.907 doi: 10.1016/j.rec.2016.11.039
64. Lowry AW, Knudson JD, Cabrera AG, Graves DE, Morales DL, Rossano 81. Christiansen SL, Hertz CL, Ferrero-Miliani L, Dahl M, Weeke PE, LuCamp,
JW. Cardiopulmonary resuscitation in hospitalized children with cardio- Ottesen GL, Frank-Hansen R, Bundgaard H, Morling N. Genetic inves-
vascular disease: estimated prevalence and outcomes from the Kids’ tigation of 100 heart genes in sudden unexplained death victims
Inpatient Database. Pediatr Crit Care Med. 2013;14:248–255. doi: in a forensic setting. Eur J Hum Genet. 2016;24:1797–1802. doi:
10.1097/PCC.0b013e3182713329 10.1038/ejhg.2016.118
65. Al-Gobari M, Le HH, Fall M, Gueyffier F, Burnand B. No benefits of 82. Nunn LM, Lopes LR, Syrris P, Murphy C, Plagnol V, Firman E, Dalageorgou
statins for sudden cardiac death prevention in patients with heart fail- C, Zorio E, Domingo D, Murday V, Findlay I, Duncan A, Carr-White
ure and reduced ejection fraction: a meta-analysis of randomized con- G, Robert L, Bueser T, Langman C, Fynn SP, Goddard M, White A,
trolled trials. PLoS One. 2017;12:e0171168. doi: 10.1371/journal. Bundgaard H, Ferrero-Miliani L, Wheeldon N, Suvarna SK, O’Beirne A,
pone.0171168 Lowe MD, McKenna WJ, Elliott PM, Lambiase PD. Diagnostic yield of
66. Aro AL, Rusinaru C, Uy-Evanado A, Reinier K, Phan D, Gunson K, Jui J, molecular autopsy in patients with sudden arrhythmic death syndrome
Chugh SS. Syncope and risk of sudden cardiac arrest in coronary artery using targeted exome sequencing. Europace. 2016;18:888–896. doi:
disease. Int J Cardiol. 2017;231:26–30. doi: 10.1016/j.ijcard.2016.12.021 10.1093/europace/euv285
67. Langén VL, Niiranen TJ, Puukka P, Lehtonen AO, Hernesniemi JA, Sundvall 83. Anderson JH, Tester DJ, Will ML, Ackerman MJ. Whole-exome molec-
J, Salomaa V, Jula AM. Thyroid-stimulating hormone and risk of sudden ular autopsy after exertion-related sudden unexplained death in
cardiac death, total mortality and cardiovascular morbidity. Clin Endocrinol the young. Circ Cardiovasc Genet. 2016;9:259–265. doi: 10.1161/
(Oxf). 2018;88:105–113. doi: 10.1111/cen.13472 CIRCGENETICS.115.001370
68. Shi S, Liu T, Liang J, Hu D, Yang B. Depression and risk of sudden cardiac 84. Steinberg C, Padfield GJ, Champagne J, Sanatani S, Angaran P, Andrade
death and arrhythmias: a meta-analysis. Psychosom Med. 2017;79:153– JG, Roberts JD, Healey JS, Chauhan VS, Birnie DH, Janzen M, Gerull B,
161. doi: 10.1097/PSY.0000000000000382 Klein GJ, Leather R, Simpson CS, Seifer C, Talajic M, Gardner M, Krahn
69. Müller D, Agrawal R, Arntz HR. How sudden is sudden cardiac death? AD. Cardiac abnormalities in first-degree relatives of unexplained cardiac
Circulation. 2006;114:1146–1150. doi: 10.1161/CIRCULATIONAHA. arrest victims: a report from the Cardiac Arrest Survivors With Preserved
106.616318 Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2016;9:e004274.
70. Andersen LW, Kim WY, Chase M, Berg KM, Mortensen SJ, Moskowitz A, doi: 10.1161/CIRCEP.115.004274
Novack V, Cocchi MN, Donnino MW; American Heart Association’s Get With 85. Kumar S, Peters S, Thompson T, Morgan N, Maccicoca I, Trainer A, Zentner
the Guidelines–Resuscitation Investigators. The prevalence and significance D, Kalman JM, Winship I, Vohra JK. Familial cardiological and targeted
of abnormal vital signs prior to in-hospital cardiac arrest. Resuscitation. genetic evaluation: low yield in sudden unexplained death and high yield
2016;98:112–117. doi: 10.1016/j.resuscitation.2015.08.016 in unexplained cardiac arrest syndromes. Heart Rhythm. 2013;10:1653–
71. Smith GB, Prytherch DR, Jarvis S, Kovacs C, Meredith P, Schmidt PE, Briggs 1660. doi: 10.1016/j.hrthm.2013.08.022
Downloaded from http://ahajournals.org by on February 7, 2019

J. A comparison of the ability of the physiologic components of medical 86. Quenin P, Kyndt F, Mabo P, Mansourati J, Babuty D, Thollet A, Guyomarch
emergency team criteria and the U.K. National Early Warning Score to B, Redon R, Barc J, Schott JJ, Sacher F, Probst V, Gourraud JB. Clinical yield
discriminate patients at risk of a range of adverse clinical outcomes. Crit of familial screening after sudden death in young subjects: the French expe-
Care Med. 2016;44:2171–2181. doi: 10.1097/CCM.0000000000002000 rience. Circ Arrhythm Electrophysiol. 2017;10:e005236. doi: 10.1161/
72. O’Neal WT, Singleton MJ, Roberts JD, Tereshchenko LG, Sotoodehnia N, CIRCEP.117.005236.
Chen LY, Marcus GM, Soliman EZ. Association between QT-interval com- 87. Bezzina CR, Lahrouchi N, Priori SG. Genetics of sudden cardiac death. Circ
ponents and sudden cardiac death: the ARIC study (Atherosclerosis Risk Res. 2015;116:1919–1936. doi: 10.1161/CIRCRESAHA.116.304030
in Communities). Circ Arrhythm Electrophysiol. 2017;10:e005485. doi: 88. Nakano Y, Shimizu W. Genetics of long-QT syndrome. J Hum Genet.
10.1161/CIRCEP.117.005485 2016;61:51–55. doi: 10.1038/jhg.2015.74
73. Lanza GA, Argirò A, Mollo R, De Vita A, Spera F, Golino M, Rota E, Filice 89. Goldenberg I, Zareba W, Moss AJ. Long QT syndrome. Curr Probl Cardiol.
M, Crea F. Six-year outcome of subjects without overt heart disease with 2008;33:629–694. doi: 10.1016/j.cpcardiol.2008.07.002
an early repolarization/J wave electrocardiographic pattern. Am J Cardiol. 90. Wedekind H, Burde D, Zumhagen S, Debus V, Burkhardtsmaier G,
2017;120:2073–2077. doi: 10.1016/j.amjcard.2017.08.028 Mönnig G, Breithardt G, Schulze-Bahr E. QT interval prolongation and
74. Sun GZ, Ye N, Chen YT, Zhou Y, Li Z, Sun YX. Early repolarization pattern risk for cardiac events in genotyped LQTS-index children. Eur J Pediatr.
in the general population: prevalence and associated factors. Int J Cardiol. 2009;168:1107–1115. doi: 10.1007/s00431-008-0896-6
2017;230:614–618. doi: 10.1016/j.ijcard.2016.12.045 91. Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi
75. De Lazzari C, Genuini I, Gatto MC, Cinque A, Mancone M, D’Ambrosi A, G, Gabbarini F, Goulene K, Insolia R, Mannarino S, Mosca F, Nespoli
Silvetti E, Fusto A, Pisanelli DM, Fedele F. Screening high school students in L, Rimini A, Rosati E, Salice P, Spazzolini C. Prevalence of the con-
Italy for sudden cardiac death prevention by using a telecardiology device: genital long-QT syndrome. Circulation. 2009;120:1761–1767. doi:
a retrospective observational study. Cardiol Young. 2017;27:74–81. doi: 10.1161/CIRCULATIONAHA.109.863209
10.1017/S1047951116000147 92. Hayashi K, Fujino N, Uchiyama K, Ino H, Sakata K, Konno T, Masuta E,
76. Deo R, Albert CM. Epidemiology and genetics of sudden cardiac death. Funada A, Sakamoto Y, Tsubokawa T, Nakashima K, Liu L, Higashida
Circulation. 2012;125:620–637. doi: 10.1161/CIRCULATIONAHA. H, Hiramaru Y, Shimizu M, Yamagishi M. Long QT syndrome and asso-
111.023838 ciated gene mutation carriers in Japanese children: results from ECG
77. Krahn AD, Healey JS, Chauhan V, Birnie DH, Simpson CS, Champagne J, screening examinations. Clin Sci (Lond). 2009;117:415–424. doi:
Gardner M, Sanatani S, Exner DV, Klein GJ, Yee R, Skanes AC, Gula LJ, Gollob 10.1042/CS20080528
MH. Systematic assessment of patients with unexplained cardiac arrest: 93. Fugate T 2nd, Moss AJ, Jons C, McNitt S, Mullally J, Ouellet G,
Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER) Goldenberg I, Zareba W, Robinson JL; for the U.S. portion of International
[published correction appears in Circulation. 2010;121:e460]. Circulation. Long QT Syndrome Registry Investigators. Long QT syndrome in African-
2009;120:278–285. doi: 10.1161/CIRCULATIONAHA.109.853143 Americans. Ann Noninvasive Electrocardiol. 2010;15:73–76. doi:
78. Hookana E, Junttila MJ, Kaikkonen KS, Ukkola O, Kesäniemi YA, 10.1111/j.1542-474X.2009.00342.x
Kortelainen ML, Huikuri HV. Comparison of family history of sudden 94. Jons C, O-Uchi J, Moss AJ, Reumann M, Rice JJ, Goldenberg I, Zareba
cardiac death in nonischemic and ischemic heart disease. Circ Arrhythm W, Wilde AA, Shimizu W, Kanters JK, McNitt S, Hofman N, Robinson JL,
Electrophysiol. 2012;5:757–761. doi: 10.1161/CIRCEP.112.971465 Lopes CM. Use of mutant-specific ion channel characteristics for risk strat-
79. Kaikkonen KS, Kortelainen ML, Linna E, Huikuri HV. Family his- ification of long QT syndrome patients. Sci Transl Med. 2011;3:76ra28.
tory and the risk of sudden cardiac death as a manifestation of doi: 10.1126/scitranslmed.3001551

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e341

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

95. Barsheshet A, Goldenberg I, O-Uchi J, Moss AJ, Jons C, Shimizu W, 110. Quan XQ, Li S, Liu R, Zheng K, Wu XF, Tang Q. A meta-analytic review
CLINICAL STATEMENTS

Wilde AA, McNitt S, Peterson DR, Zareba W, Robinson JL, Ackerman of prevalence for Brugada ECG patterns and the risk for death. Medicine
AND GUIDELINES

MJ, Cypress M, Gray DA, Hofman N, Kanters JK, Kaufman ES, Platonov (Baltimore). 2016;95:e5643. doi: 10.1097/MD.0000000000005643
PG, Qi M, Towbin JA, Vincent GM, Lopes CM. Mutations in cytoplas- 111. Baron RC, Thacker SB, Gorelkin L, Vernon AA, Taylor WR, Choi K. Sudden
mic loops of the KCNQ1 channel and the risk of life-threatening events: death among Southeast Asian refugees: an unexplained nocturnal phe-
implications for mutation-specific response to β-blocker therapy in nomenon. JAMA. 1983;250:2947–2951.
type 1 long-QT syndrome. Circulation. 2012;125:1988–1996. doi: 112. Gilbert J, Gold RL, Haffajee CI, Alpert JS. Sudden cardiac death in a
10.1161/CIRCULATIONAHA.111.048041 southeast Asian immigrant: clinical, electrophysiologic, and biopsy char-
96. Mullally J, Goldenberg I, Moss AJ, Lopes CM, Ackerman MJ, Zareba W, acteristics. Pacing Clin Electrophysiol. 1986;9(pt 1):912–914.
McNitt S, Robinson JL, Benhorin J, Kaufman ES, Towbin JA, Barsheshet A. 113. Hermida JS, Lemoine JL, Aoun FB, Jarry G, Rey JL, Quiret JC. Prevalence
Risk of life-threatening cardiac events among patients with long QT syn- of the Brugada syndrome in an apparently healthy population. Am J
drome and multiple mutations. Heart Rhythm. 2013;10:378–382. doi: Cardiol. 2000;86:91–94.
10.1016/j.hrthm.2012.11.006 114. Miyasaka Y, Tsuji H, Yamada K, Tokunaga S, Saito D, Imuro Y, Matsumoto
97. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, N, Iwasaka T. Prevalence and mortality of the Brugada-type electrocardio-
Vege A, Wang DW, Rhodes TE, George AL Jr, Schwartz PJ. Prevalence gram in one city in Japan. J Am Coll Cardiol. 2001;38:771–774.
of long-QT syndrome gene variants in sudden infant death syndrome. 115. Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, Ogawa
Circulation. 2007;115:361–367. doi: 10.1161/CIRCULATIONAHA. S, Okumura K, Tsuchihashi K, Sugi K, Makita N, Hagiwara N, Inoue H,
106.658021 Atarashi H, Aihara N, Shimizu W, Kurita T, Suyama K, Noda T, Satomi
98. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical K, Okamura H, Tomoike H; Brugada Syndrome Investigators in Japan.
implications. J Am Coll Cardiol. 2000;36:1–12. Long-term prognosis of probands with Brugada-pattern ST-elevation
99. Crotti L, Tester DJ, White WM, Bartos DC, Insolia R, Besana A, Kunic in leads V1-V3. Circ Arrhythm Electrophysiol. 2009;2:495–503. doi:
JD, Will ML, Velasco EJ, Bair JJ, Ghidoni A, Cetin I, Van Dyke DL, Wick 10.1161/CIRCEP.108.816892
MJ, Brost B, Delisle BP, Facchinetti F, George AL, Schwartz PJ, Ackerman 116. Maury P, Rollin A, Sacher F, Gourraud JB, Raczka F, Pasquié JL, Duparc
MJ. Long QT syndrome-associated mutations in intrauterine fetal death. A, Mondoly P, Cardin C, Delay M, Derval N, Chatel S, Bongard V, Sadron
JAMA. 2013;309:1473–1482. doi: 10.1001/jama.2013.3219 M, Denis A, Davy JM, Hocini M, Jaïs P, Jesel L, Haïssaguerre M, Probst V.
100. Tester DJ, Wong LCH, Chanana P, Jaye A, Evans JM, FitzPatrick DR, Prevalence and prognostic role of various conduction disturbances in pa-
Evans MJ, Fleming P, Jeffrey I, Cohen MC, Tfelt-Hansen J, Simpson tients with the Brugada syndrome. Am J Cardiol. 2013;112:1384–1389.
MA, Behr ER, Ackerman MJ. Cardiac genetic predisposition in sudden doi: 10.1016/j.amjcard.2013.06.033
infant death syndrome. J Am Coll Cardiol. 2018;71:1217–1227. doi: 117. Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, Babuty
10.1016/j.jacc.2018.01.030 D, Sacher F, Giustetto C, Schulze-Bahr E, Borggrefe M, Haissaguerre
101. Cross B, Homoud M, Link M, Foote C, Garlitski AC, Weinstock J, Estes NA M, Mabo P, Le Marec H, Wolpert C, Wilde AA. Long-term prognosis of
3rd. The short QT syndrome. J Interv Card Electrophysiol. 2011;31:25– patients diagnosed with Brugada syndrome: results from the FINGER
31. doi: 10.1007/s10840-011-9566-0 Brugada Syndrome Registry. Circulation. 2010;121:635–643. doi:
102. Kobza R, Roos M, Niggli B, Abächerli R, Lupi GA, Frey F, Schmid JJ, Erne 10.1161/CIRCULATIONAHA.109.887026
P. Prevalence of long and short QT in a young population of 41,767 pre- 118. Lieve KV, Wilde AA. Inherited ion channel diseases: a brief review.
dominantly male Swiss conscripts. Heart Rhythm. 2009;6:652–657. doi: Europace. 2015;17(suppl 2):ii1–ii6. doi: 10.1093/europace/euv105
10.1016/j.hrthm.2009.01.009 119. Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff JM,
103. Providência R, Karim N, Srinivasan N, Honarbakhsh S, Vidigal Ferreira Klug D, Hayashi M, Takatsuki S, Villain E, Kamblock J, Messali A, Guicheney
Downloaded from http://ahajournals.org by on February 7, 2019

MJ, Gonçalves L, Marijon E, Lambiase PD. Impact of QTc formulae in P, Lunardi J, Leenhardt A. Incidence and risk factors of arrhythmic events
the prevalence of short corrected QT interval and impact on probabil- in catecholaminergic polymorphic ventricular tachycardia. Circulation.
ity and diagnosis of short QT syndrome. Heart. 2018;104:502–508. doi: 2009;119:2426–2434. doi: 10.1161/CIRCULATIONAHA.108.829267
10.1136/heartjnl-2017-311673 120. Sumitomo N, Harada K, Nagashima M, Yasuda T, Nakamura Y, Aragaki
104. Dhutia H, Malhotra A, Parpia S, Gabus V, Finocchiaro G, Mellor G, Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S, Matsuoka S,
Merghani A, Millar L, Narain R, Sheikh N, Behr ER, Papadakis M, Sharma Oono T, Hayakawa S, Miura M, Ushinohama H, Shibata T, Niimura I.
S. The prevalence and significance of a short QT interval in 18,825 low- Catecholaminergic polymorphic ventricular tachycardia: electrocardio-
risk individuals including athletes. Br J Sports Med. 2016;50:124–129. graphic characteristics and optimal therapeutic strategies to prevent sud-
doi: 10.1136/bjsports-2015-094827 den death. Heart. 2003;89:66–70.
105. Guerrier K, Kwiatkowski D, Czosek RJ, Spar DS, Anderson JB, Knilans 121. Sy RW, Gollob MH, Klein GJ, Yee R, Skanes AC, Gula LJ, Leong-
TK. Short QT interval prevalence and clinical outcomes in a pediat- Sit P, Gow RM, Green MS, Birnie DH, Krahn AD. Arrhythmia
ric population. Circ Arrhythm Electrophysiol. 2015;8:1460–1464. doi: characterization and long-term outcomes in catecholaminergic poly-
10.1161/CIRCEP.115.003256 morphic ventricular tachycardia. Heart Rhythm. 2011;8:864–871. doi:
106. Giustetto C, Schimpf R, Mazzanti A, Scrocco C, Maury P, Anttonen O, 10.1016/j.hrthm.2011.01.048
Probst V, Blanc JJ, Sbragia P, Dalmasso P, Borggrefe M, Gaita F. Long- 122. Kawata H, Ohno S, Aiba T, Sakaguchi H, Miyazaki A, Sumitomo N,
term follow-up of patients with short QT syndrome. J Am Coll Cardiol. Kamakura T, Nakajima I, Inoue YY, Miyamoto K, Okamura H, Noda T,
2011;58:587–595. doi: 10.1016/j.jacc.2011.03.038 Kusano K, Kamakura S, Miyamoto Y, Shiraishi I, Horie M, Shimizu W.
107. Villafañe J, Atallah J, Gollob MH, Maury P, Wolpert C, Gebauer R, Catecholaminergic polymorphic ventricular tachycardia (CPVT) associat-
Watanabe H, Horie M, Anttonen O, Kannankeril P, Faulknier B, Bleiz J, ed with ryanodine receptor (RyR2) gene mutations: long-term prognosis
Makiyama T, Shimizu W, Hamilton RM, Young ML. Long-term follow- after initiation of medical treatment. Circ J. 2016;80:1907–1915. doi:
up of a pediatric cohort with short QT syndrome. J Am Coll Cardiol. 10.1253/circj.CJ-16-0250
2013;61:1183–1191. doi: 10.1016/j.jacc.2012.12.025 123. Hamilton RM. Arrhythmogenic right ventricular cardiomyopa-
108. Benito B, Brugada J, Brugada R, Brugada P. Brugada syndrome [published thy. Pacing Clin Electrophysiol. 2009;32(suppl 2):S44–S51. doi:
correction appears in Rev Esp Cardiol. 2010;63:620]. Rev Esp Cardiol. 10.1111/j.1540-8159.2009.02384.x
2009;62:1297–1315. 124. Dalal D, Nasir K, Bomma C, Prakasa K, Tandri H, Piccini J, Roguin A,
109. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Tichnell C, James C, Russell SD, Judge DP, Abraham T, Spevak PJ,
Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge Bluemke DA, Calkins H. Arrhythmogenic right ventricular dysplasia:
DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin a United States experience. Circulation. 2005;112:3823–3832. doi:
JA, Watkins H, Wilde A, Wolpert C, Zipes DP; Heart Rhythm Society 10.1161/CIRCULATIONAHA.105.542266
(HRS); European Heart Rhythm Association (EHRA). HRS/EHRA expert 125. Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural his-
consensus statement on the state of genetic testing for the chan- tory and risk stratification of arrhythmogenic right ventricular dys-
nelopathies and cardiomyopathies: this document was developed plasia/cardiomyopathy. Circulation. 2004;110:1879–1884. doi:
as a partnership between the Heart Rhythm Society (HRS) and the 10.1161/01.CIR.0000143375.93288.82
European Heart Rhythm Association (EHRA) [published correction ap- 126. Mazzanti A, Ng K, Faragli A, Maragna R, Chiodaroli E, Orphanou N,
pears in Europace. 2012;14:277]. Europace. 2011;13:1077–1109. doi: Monteforte N, Memmi M, Gambelli P, Novelli V, Bloise R, Catalano O,
10.1093/europace/eur245 Moro G, Tibollo V, Morini M, Bellazzi R, Napolitano C, Bagnardi V, Priori

e342 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

SG. Arrhythmogenic right ventricular cardiomyopathy: clinical course and 142. Haïssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L,

CLINICAL STATEMENTS
predictors of arrhythmic risk. J Am Coll Cardiol. 2016;68:2540–2550. Pasquié JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P,

AND GUIDELINES
doi: 10.1016/j.jacc.2016.09.951 Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J,
127. Maron BJ, Olivotto I, Spirito P, Casey SA, Bellone P, Gohman TE, Graham Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A,
KJ, Burton DA, Cecchi F. Epidemiology of hypertrophic cardiomyopathy- Anselme F, O’Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD,
related death: revisited in a large non-referral-based patient population. Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Clémenty
Circulation. 2000;102:858–864. J. Sudden cardiac arrest associated with early repolarization. N Engl J
128. Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden Med. 2008;358:2016–2023. doi: 10.1056/NEJMoa071968
deaths in young competitive athletes: analysis of 1866 deaths in the 143. Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser
United States, 1980-2006. Circulation. 2009;119:1085–1092. doi: D, Halkin A, Steinvil A, Heller K, Glikson M, Katz A, Viskin S. J-point
10.1161/CIRCULATIONAHA.108.804617 elevation in survivors of primary ventricular fibrillation and matched
129. Elliott PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. control subjects: incidence and clinical significance. J Am Coll Cardiol.
Relation between severity of left-ventricular hypertrophy and prognosis 2008;52:1231–1238. doi: 10.1016/j.jacc.2008.07.010
in patients with hypertrophic cardiomyopathy. Lancet. 2001;357:420– 144. Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA,
424. doi: 10.1016/S0140-6736(00)04005-8 Reunanen A, Huikuri HV. Long-term outcome associated with early repo-
130. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude larization on electrocardiography. N Engl J Med. 2009;361:2529–2537.
of left ventricular hypertrophy and risk of sudden death in hyper- doi: 10.1056/NEJMoa0907589
trophic cardiomyopathy. N Engl J Med. 2000;342:1778–1785. doi: 145. Walsh JA 3rd, Ilkhanoff L, Soliman EZ, Prineas R, Liu K, Ning H, Lloyd-Jones
10.1056/NEJM200006153422403 DM. Natural history of the early repolarization pattern in a biracial cohort:
131. Blomström-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, CARDIA (Coronary Artery Risk Development in Young Adults) Study. J
Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Am Coll Cardiol. 2013;61:863–869. doi: 10.1016/j.jacc.2012.11.053
Shaeffer CW, Stevenson WG, Tomaselli GF. ACC/AHA/ESC guidelines for 146. Kamakura T, Kawata H, Nakajima I, Yamada Y, Miyamoto K, Okamura
the management of patients with supraventricular arrhythmias: execu- H, Noda T, Satomi K, Aiba T, Takaki H, Aihara N, Kamakura S, Kimura T,
tive summary: a report of the American College of Cardiology/American Shimizu W. Significance of non-type 1 anterior early repolarization in pa-
Heart Association Task Force on Practice Guidelines and the European tients with inferolateral early repolarization syndrome. J Am Coll Cardiol.
Society of Cardiology Committee for Practice Guidelines (Writing 2013;62:1610–1618. doi: 10.1016/j.jacc.2013.05.081
Committee to Develop Guidelines for the Management of Patients With 147. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E,
Supraventricular Arrhythmias). Circulation. 2003;108:1871–1909. doi: Sattler S, Fichtner S, Estner HL, Kääb S, Wakili R. Early repolarization
10.1161/01.CIR.0000091380.04100.84 pattern is the strongest predictor of arrhythmia recurrence in patients
132. Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ. Spectrum with idiopathic ventricular fibrillation: results from a single centre
and prognostic significance of arrhythmias on ambulatory Holter elec- long-term follow-up over 20 years. Europace. 2016;18:718–725. doi:
trocardiogram in hypertrophic cardiomyopathy. J Am Coll Cardiol. 10.1093/europace/euv301
2005;45:697–704. doi: 10.1016/j.jacc.2004.11.043 148. Gourraud JB, Le Scouarnec S, Sacher F, Chatel S, Derval N, Portero V,
133. Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna Chavernac P, Sandoval JE, Mabo P, Redon R, Schott JJ, Le Marec H,
WJ. Non-sustained ventricular tachycardia in hypertrophic cardiomyopa- Haïssaguerre M, Probst V. Identification of large families in early re-
thy: an independent marker of sudden death risk in young patients. J Am polarization syndrome. J Am Coll Cardiol. 2013;61:164–172. doi:
Coll Cardiol. 2003;42:873–879. 10.1016/j.jacc.2012.09.040
134. Kofflard MJ, Ten Cate FJ, van der Lee C, van Domburg RT. Hypertrophic 149. Sinner MF, Porthan K, Noseworthy PA, Havulinna AS, Tikkanen JT, Müller-
Downloaded from http://ahajournals.org by on February 7, 2019

cardiomyopathy in a large community-based population: clinical out- Nurasyid M, Peloso G, Ulivi S, Beckmann BM, Brockhaus AC, Cooper
come and identification of risk factors for sudden cardiac death and clini- RR, Gasparini P, Hengstenberg C, Hwang SJ, Iorio A, Junttila MJ, Klopp
cal deterioration. J Am Coll Cardiol. 2003;41:987–993. N, Kähönen M, Laaksonen MA, Lehtimäki T, Lichtner P, Lyytikäinen
135. Spirito P, Autore C, Rapezzi C, Bernabò P, Badagliacca R, Maron MS, LP, Martens E, Meisinger C, Meitinger T, Merchant FM, Nieminen
Bongioanni S, Coccolo F, Estes NA, Barillà CS, Biagini E, Quarta G, MS, Peters A, Pietilä A, Perz S, Oikarinen L, Raitakari O, Reinhard W,
Conte MR, Bruzzi P, Maron BJ. Syncope and risk of sudden death in Silander K, Thorand B, Wichmann HE, Sinagra G, Viikari J, O’Donnell
hypertrophic cardiomyopathy. Circulation. 2009;119:1703–1710. doi: CJ, Ellinor PT, Huikuri HV, Kääb S, Newton-Cheh C, Salomaa V. A meta-
10.1161/CIRCULATIONAHA.108.798314 analysis of genome-wide association studies of the electrocardiographic
136. Elliott PM, Gimeno JR, Tomé MT, Shah J, Ward D, Thaman R, Mogensen early repolarization pattern. Heart Rhythm. 2012;9:1627–1634. doi:
J, McKenna WJ. Left ventricular outflow tract obstruction and sudden 10.1016/j.hrthm.2012.06.008
death risk in patients with hypertrophic cardiomyopathy. Eur Heart J. 150. Dukes JW, Dewland TA, Vittinghoff E, Mandyam MC, Heckbert SR,
2006;27:1933–1941. doi: 10.1093/eurheartj/ehl041 Siscovick DS, Stein PK, Psaty BM, Sotoodehnia N, Gottdiener JS, Marcus
137. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi GM. Ventricular ectopy as a predictor of heart failure and death. J Am
F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical Coll Cardiol. 2015;66:101–109. doi: 10.1016/j.jacc.2015.04.062
outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003;348:295– 151. Wathen MS, DeGroot PJ, Sweeney MO, Stark AJ, Otterness MF, Adkisson
303. doi: 10.1056/NEJMoa021332 WO, Canby RC, Khalighi K, Machado C, Rubenstein DS, Volosin KJ;
138. Efthimiadis GK, Parcharidou DG, Giannakoulas G, Pagourelias ED, PainFREE Rx II Investigators. Prospective randomized multicenter trial of
Charalampidis P, Savvopoulos G, Ziakas A, Karvounis H, Styliadis IH, empirical antitachycardia pacing versus shocks for spontaneous rapid
Parcharidis GE. Left ventricular outflow tract obstruction as a risk factor ventricular tachycardia in patients with implantable cardioverter-defi-
for sudden cardiac death in hypertrophic cardiomyopathy. Am J Cardiol. brillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies
2009;104:695–699. doi: 10.1016/j.amjcard.2009.04.039 (PainFREE Rx II) trial results. Circulation. 2004;110:2591–2596. doi:
139. Bos JM, Maron BJ, Ackerman MJ, Haas TS, Sorajja P, Nishimura RA, Gersh 10.1161/01.CIR.0000145610.64014.E4
BJ, Ommen SR. Role of family history of sudden death in risk stratifica- 152. Marine JE, Shetty V, Chow GV, Wright JG, Gerstenblith G, Najjar SS,
tion and prevention of sudden death with implantable defibrillators in Lakatta EG, Fleg JL. Prevalence and prognostic significance of exercise-
hypertrophic cardiomyopathy. Am J Cardiol. 2010;106:1481–1486. doi: induced nonsustained ventricular tachycardia in asymptomatic volun-
10.1016/j.amjcard.2010.06.077 teers: BLSA (Baltimore Longitudinal Study of Aging). J Am Coll Cardiol.
140. Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava 2013;62:595–600. doi: 10.1016/j.jacc.2013.05.026
A, Mahon NG, McKenna WJ. Sudden death in hypertrophic car- 153. Belhassen B, Viskin S. Idiopathic ventricular tachycardia and fibrillation. J
diomyopathy: identification of high risk patients. J Am Coll Cardiol. Cardiovasc Electrophysiol. 1993;4:356–368.
2000;36:2212–2218. 154. Lemery R, Brugada P, Bella PD, Dugernier T, van den Dool A, Wellens
141. Patton KK, Ellinor PT, Ezekowitz M, Kowey P, Lubitz SA, Perez M, Piccini HJ. Nonischemic ventricular tachycardia: clinical course and long-term
J, Turakhia M, Wang P, Viskin S; on behalf of the American Heart follow-up in patients without clinically overt heart disease. Circulation.
Association Electrocardiography and Arrhythmias Committee of the 1989;79:990–999.
Council on Clinical Cardiology and Council on Functional Genomics 155. Sacher F, Tedrow UB, Field ME, Raymond JM, Koplan BA, Epstein LM,
and Translational Biology. Electrocardiographic early repolarization: a Stevenson WG. Ventricular tachycardia ablation: evolution of patients
scientific statement from the American Heart Association. Circulation. and procedures over 8 years. Circ Arrhythm Electrophysiol. 2008;1:153–
2016;133:1520–1529. doi: 10.1161/CIR.0000000000000388 161. doi: 10.1161/CIRCEP.108.769471

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e343

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

156. Baman TS, Lange DC, Ilg KJ, Gupta SK, Liu TY, Alguire C, Armstrong 174. QTDrugs list. Credible Meds website. Arizona Center for Education and
CLINICAL STATEMENTS

W, Good E, Chugh A, Jongnarangsin K, Pelosi F Jr, Crawford T, Ebinger Research on Therapeutics. https://crediblemeds.org/healthcare-provid-
AND GUIDELINES

M, Oral H, Morady F, Bogun F. Relationship between burden of prema- ers/. Accessed September 11, 2018.
ture ventricular complexes and left ventricular function. Heart Rhythm. 175. Gupta A, Lawrence AT, Krishnan K, Kavinsky CJ, Trohman RG. Current
2010;7:865–869. doi: 10.1016/j.hrthm.2010.03.036 concepts in the mechanisms and management of drug-induced QT pro-
157. Yarlagadda RK, Iwai S, Stein KM, Markowitz SM, Shah BK, Cheung longation and torsade de pointes. Am Heart J. 2007;153:891–899. doi:
JW, Tan V, Lerman BB, Mittal S. Reversal of cardiomyopathy in patients 10.1016/j.ahj.2007.01.040
with repetitive monomorphic ventricular ectopy originating from the 176. Jamshidi Y, Nolte IM, Dalageorgou C, Zheng D, Johnson T, Bastiaenen R,
right ventricular outflow tract. Circulation. 2005;112:1092–1097. doi: Ruddy S, Talbott D, Norris KJ, Snieder H, George AL, Marshall V, Shakir
10.1161/CIRCULATIONAHA.105.546432 S, Kannankeril PJ, Munroe PB, Camm AJ, Jeffery S, Roden DM, Behr
158. Noda T, Shimizu W, Taguchi A, Aiba T, Satomi K, Suyama K, Kurita T, ER. Common variation in the NOS1AP gene is associated with drug-
Aihara N, Kamakura S. Malignant entity of idiopathic ventricular fibrilla- induced QT prolongation and ventricular arrhythmia. J Am Coll Cardiol.
tion and polymorphic ventricular tachycardia initiated by premature ex- 2012;60:841–850. doi: 10.1016/j.jacc.2012.03.031
trasystoles originating from the right ventricular outflow tract. J Am Coll 177. Ramirez AH, Shaffer CM, Delaney JT, Sexton DP, Levy SE, Rieder MJ,
Cardiol. 2005;46:1288–1294. doi: 10.1016/j.jacc.2005.05.077 Nickerson DA, George AL Jr, Roden DM. Novel rare variants in con-
159. Viskin S, Rosso R, Rogowski O, Belhassen B. The “short-coupled” vari- genital cardiac arrhythmia genes are frequent in drug-induced tor-
ant of right ventricular outflow ventricular tachycardia: a not-so-benign sades de pointes. Pharmacogenomics J. 2013;13:325–329. doi:
form of benign ventricular tachycardia? J Cardiovasc Electrophysiol. 10.1038/tpj.2012.14
2005;16:912–916. doi: 10.1111/j.1540-8167.2005.50040.x 178. Anderson ML, Cox M, Al-Khatib SM, Nichol G, Thomas KL, Chan PS,
160. Panidis IP, Morganroth J. Sudden death in hospitalized patients: cardiac Saha-Chaudhuri P, Fosbol EL, Eigel B, Clendenen B, Peterson ED. Rates of
rhythm disturbances detected by ambulatory electrocardiographic moni- cardiopulmonary resuscitation training in the United States. JAMA Intern
toring. J Am Coll Cardiol. 1983;2:798–805. Med. 2014;174:194–201. doi: 10.1001/jamainternmed.2013.11320
161. Lewis BH, Antman EM, Graboys TB. Detailed analysis of 24 hour am- 179. Blewer AL IS, Leary M, Dutwin D, McNally B, Anderson ML, Morrison
bulatory electrocardiographic recordings during ventricular fibrillation or LJ, Aufderheide TA, Daya M, Idris A, Callaway CW, Kudenchuk PJ, Vilke
torsade de pointes. J Am Coll Cardiol. 1983;2:426–436. GM, Abella BS. Cardiopulmonary resuscitation training disparities in
162. Gang UJ, Jøns C, Jørgensen RM, Abildstrøm SZ, Haarbo J, Messier MD, the United States. Journal of Am Heart Assoc. 2017;6:e006124. doi:
Huikuri HV, Thomsen PE; CARISMA Investigators. Heart rhythm at the 10.1161/JAHA.117.006124
time of death documented by an implantable loop recorder. Europace. 180. Bakke HK, Steinvik T, Angell J, Wisborg T. A nationwide survey of first aid
2010;12:254–260. doi: 10.1093/europace/eup383 training and encounters in Norway. BMC Emerg Med. 2017;17:6. doi:
163. Hai JJ, Un KC, Wong CK, Wong KL, Zhang ZY, Chan PH, Lau CP, Siu 10.1186/s12873-017-0116-7
CW, Tse HF. Prognostic implications of early monomorphic and non- 181. Bray JE, Smith K, Case R, Cartledge S, Straney L, Finn J. Public cardio-
monomorphic tachyarrhythmias in patients discharged with acute coro- pulmonary resuscitation training rates and awareness of hands-only car-
nary syndrome. Heart Rhythm. 2018;15:822–829. doi: 10.1016/j.hrthm. diopulmonary resuscitation: a cross-sectional survey of Victorians. Emerg
2018.02.016 Med Australas. 2017;29:158–164. doi: 10.1111/1742-6723.12720
164. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syn- 182. Brooks B, Chan S, Lander P, Adamson R, Hodgetts GA, Deakin CD. Public
drome, and torsades de pointes. Med Clin North Am. 2001;85:321–341. knowledge and confidence in the use of public access defibrillation.
165. Brady WJ, DeBehnke DJ, Laundrie D. Prevalence, therapeutic response, Heart. 2015;101:967–971. doi: 10.1136/heartjnl-2015-307624
and outcome of ventricular tachycardia in the out-of-hospital setting: 183. Lee MJ, Hwang SO, Cha KC, Cho GC, Yang HJ, Rho TH. Influence of
Downloaded from http://ahajournals.org by on February 7, 2019

a comparison of monomorphic ventricular tachycardia, polymorphic nationwide policy on citizens’ awareness and willingness to perform by-
ventricular tachycardia, and torsades de pointes. Acad Emerg Med. stander cardiopulmonary resuscitation. Resuscitation. 2013;84:889–894.
1999;6:609–617. doi: 10.1016/j.resuscitation.2013.01.009
166. Choudhuri I, Pinninti M, Marwali MR, Sra J, Akhtar M. Polymorphic ventric- 184. Gonzalez M, Leary M, Blewer AL, Cinousis M, Sheak K, Ward M,
ular tachycardia, part I: structural heart disease and acquired causes. Curr Merchant RM, Becker LB, Abella BS. Public knowledge of automatic
Probl Cardiol. 2013;38:463–496. doi: 10.1016/j.cpcardiol.2013.07.001 external defibrillators in a large U.S. urban community. Resuscitation.
167. Arunachalam K, Lakshmanan S, Maan A, Kumar N, Dominic P. Impact 2015;92:101–106. doi: 10.1016/j.resuscitation.2015.04.022
of drug induced long QT syndrome: a systematic review. J Clin Med Res. 185. Ong ME, Shin SD, De Souza NN, Tanaka H, Nishiuchi T, Song KJ, Ko
2018;10:384–390. doi: 10.14740/jocmr3338w PC, Leong BS, Khunkhlai N, Naroo GY, Sarah AK, Ng YY, Li WY,
168. Sarganas G, Garbe E, Klimpel A, Hering RC, Bronder E, Haverkamp Ma MH; PAROS Clinical Research Network. Outcomes for out-of-
W. Epidemiology of symptomatic drug-induced long QT syndrome hospital cardiac arrests across 7 countries in Asia: the Pan Asian
and Torsade de Pointes in Germany. Europace. 2014;16:101–108. doi: Resuscitation Outcomes Study (PAROS) [published correction appears in
10.1093/europace/eut214 Resuscitation. 2016;98:125–126]. Resuscitation. 2015;96:100–108. doi:
169. Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. 10.1016/j.resuscitation.2015.07.026
Female gender as a risk factor for torsades de pointes associated with 186. Sasson C, Magid DJ, Chan P, Root ED, McNally BF, Kellermann AL, Haukoos
cardiovascular drugs. JAMA. 1993;270:2590–2597. JS; CARES Surveillance Group. Association of neighborhood characteris-
170. Zeltser D, Justo D, Halkin A, Prokhorov V, Heller K, Viskin S. Torsade tics with bystander-initiated CPR. N Engl J Med. 2012;367:1607–1615.
de pointes due to noncardiac drugs: most patients have easily iden- doi: 10.1056/NEJMoa1110700
tifiable risk factors. Medicine (Baltimore). 2003;82:282–290. doi: 187. Moon S, Bobrow BJ, Vadeboncoeur TF, Kortuem W, Kisakye M, Sasson C,
10.1097/01.md.0000085057.63483.9b Stolz U, Spaite DW. Disparities in bystander CPR provision and survival from
171. Kannankeril P, Roden DM, Darbar D. Drug-induced long QT syndrome. out-of-hospital cardiac arrest according to neighborhood ethnicity. Am J
Pharmacol Rev. 2010;62:760–781. doi: 10.1124/pr.110.003723 Emerg Med. 2014;32:1041–1045. doi: 10.1016/j.ajem.2014.06.019
172. Leonard CE, Freeman CP, Newcomb CW, Bilker WB, Kimmel SE, Strom 188. Sasson C, Haukoos JS, Ben-Youssef L, Ramirez L, Bull S, Eigel B, Magid
BL, Hennessy S. Antipsychotics and the risks of sudden cardiac death and DJ, Padilla R. Barriers to calling 911 and learning and performing cardio-
all-cause death: cohort studies in Medicaid and dually-eligible Medicaid- pulmonary resuscitation for residents of primarily Latino, high-risk neigh-
Medicare beneficiaries of five states. J Clin Exp Cardiolog. 2013;(suppl borhoods in Denver, Colorado. Ann Emerg Med. 2015;65:545–552.e2.
10):1–9. doi: 10.4172/2155-9880.S10-006 doi: 10.1016/j.annemergmed.2014.10.028
173. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, 189. Duber HC, McNellan CR, Wollum A, Phillips B, Allen K, Brown JC, Bryant
Philippides GJ, Roden DM, Zareba W; on behalf of the American Heart M, Guptam RB, Li Y, Majumdar P, Roth GA, Thomson B, Wilson S,
Association Acute Cardiac Care Committee of the Council on Clinical Woldeab A, Zhou M, Ng M. Public knowledge of cardiovascular disease
Cardiology; Council on Cardiovascular Nursing; American College of and response to acute cardiac events in three cities in China and India.
Cardiology Foundation. Prevention of torsade de pointes in hospital set- Heart. 2018;104:67–72. doi: 10.1136/heartjnl-2017-311388
tings: a scientific statement from the American Heart Association and the 190. Nishiyama C, Brown SP, May S, Iwami T, Koster RW, Beesems SG, Kuisma
American College of Cardiology Foundation [published correction ap- M, Salo A, Jacobs I, Finn J, Sterz F, Nürnberger A, Smith K, Morrison L,
pears in Circulation. 2010;122:e440]. Circulation. 2010;121:1047–1060. Olasveengen TM, Callaway CW, Shin SD, Gräsner JT, Daya M, Ma MH,
doi: 10.1161/CIRCULATIONAHA.109.192704 Herlitz J, Strömsöe A, Aufderheide TP, Masterson S, Wang H, Christenson

e344 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 17

J, Stiell I, Davis D, Huszti E, Nichol G. Apples to apples or apples to orang- Markota A, Strömsöe A, Burkart R, Perkins GD, Bossaert LL; EuReCa ONE

CLINICAL STATEMENTS
es? International variation in reporting of process and outcome of care Collaborators. EuReCa ONE-27 Nations, ONE Europe, ONE Registry: a

AND GUIDELINES
for out-of-hospital cardiac arrest. Resuscitation. 2014;85:1599–1609. prospective one month analysis of out-of-hospital cardiac arrest out-
doi: 10.1016/j.resuscitation.2014.06.031 comes in 27 countries in Europe. Resuscitation. 2016;105:188–195. doi:
191. Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of 10.1016/j.resuscitation.2016.06.004
out-of-hospital cardiac arrest and survival rates: Systematic review 193. Bray JE, Di Palma S, Jacobs I, Straney L, Finn J. Trends in the inci-
of 67 prospective studies. Resuscitation. 2010;81:1479–1487. doi: dence of presumed cardiac out-of-hospital cardiac arrest in Perth,
10.1016/j.resuscitation.2010.08.006 Western Australia, 1997-2010. Resuscitation. 2014;85:757–761. doi:
192. Gräsner JT, Lefering R, Koster RW, Masterson S, Böttiger BW, Herlitz 10.1016/j.resuscitation.2014.02.017
J, Wnent J, Tjelmeland IB, Ortiz FR, Maurer H, Baubin M, Mols P, 194. Shao F, Li CS, Liang LR, Qin J, Ding N, Fu Y, Yang K, Zhang GQ, Zhao L,
Hadžibegović I, Ioannides M, Škulec R, Wissenberg M, Salo A, Hubert Zhao B, Zhu ZZ, Yang LP, Yu DM, Song ZJ, Yang QL. Incidence and out-
H, Nikolaou NI, Lóczi G, Svavarsdóttir H, Semeraro F, Wright PJ, Clarens come of adult in-hospital cardiac arrest in Beijing, China. Resuscitation.
C, Pijls R, Cebula G, Correia VG, Cimpoesu D, Raffay V, Trenkler S, 2016;102:51–56. doi: 10.1016/j.resuscitation.2016.02.002
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e345

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

18. SUBCLINICAL ATHEROSCLEROSIS Abbreviations Used in Chapter 18 Continued

CLINICAL STATEMENTS

RR relative risk
See Charts 18-1 through 18-4
AND GUIDELINES

SBP systolic blood pressure

SD standard deviation
Click here to return to the Table of Contents TC total cholesterol
TIA transient ischemic attack
Multiple complementary imaging modalities allow TIPS The Indian Polycap Study
WC waist circumference
detection and quantification of atherosclerosis through
its stages and in multiple different vascular beds. Early
identification of subclinical atherosclerosis can guide medical treatment (eg, aspirin, antihypertensive ther-
preventive care, including lifestyle modifications and apy, lipid-lowering therapy) to prevent clinical manifes-
tations of atherosclerosis such as MI, stroke, or PAD.
Abbreviations Used in Chapter 18 Although several invasive and noninvasive imaging
ABI ankle-brachial index
modalities can be used for imaging atherosclerosis,
ACC American College of Cardiology 2 modalities, CT of the chest for evaluation of CAC
AF atrial fibrillation and B-mode ultrasound of the neck for evaluation
AHA American Heart Association of carotid artery IMT, have been used in large studies
ARIC Atherosclerosis Risk in Communities Study with outcomes data and can help define the burden
ASCVD atherosclerotic cardiovascular disease
of atherosclerosis in individuals before they develop
BMI body mass index
BNP B-type natriuretic peptide
symptoms or clinical events such as heart attack or
BP blood pressure stroke. Data on cardiovascular outcomes are beginning
CAC coronary artery calcification to emerge for additional modalities that measure ana-
CAD coronary artery disease tomic and functional measures of subclinical disease,
CARDIA Coronary Artery Risk Development in Young Adults including brachial artery reactivity testing, aortic and
CHD coronary heart disease
carotid MRI, and tonometric methods of measuring
CHS Cardiovascular Health Study
CKD chronic kidney disease vascular compliance or microvascular reactivity. Further
CI confidence interval research could help to define the role of these tech-
CONFIRM Coronary CT Angiography Evaluation for Clinical niques in cardiovascular risk assessment. Some guide-
Outcomes: An International Multicenter Registry lines have recommended that assessing for subclinical
CRP C-reactive protein
Downloaded from http://ahajournals.org by on February 7, 2019

atherosclerosis, especially by CAC, might be appropri-

CT computed tomography
CVD cardiovascular disease
ate as a decision aid in people at intermediate risk for
DBP diastolic blood pressure ASCVD (eg, 10-year estimated risk of 10%–20%) but
DM diabetes mellitus not for lower-risk general population screening or for
EF ejection fraction people with preexisting CHD or most other high-risk
ESRD end-stage renal disease
conditions.1,2
FHS Framingham Heart Study
FMD flow-mediated dilation
According to the 2018 ACC/AHA cholesterol man-
FRS Framingham Risk Score agement guideline, in intermediate-risk or selected bor-
HBP high blood pressure derline-risk adults, if the decision about statin therapy
HDL-C high-density lipoprotein cholesterol remains uncertain after 10-year risk calculation and
HF heart failure after accounting for risk enhancers, it is reasonable to
HR hazard ratio
use a CAC score in the decision to withhold, postpone,
IMT intima-media thickness
JHS Jackson Heart Study
or initiate statin therapy.3 A large-scale randomized trial
JUPITER Justification for the Use of Statins in Primary Prevention: showed that coronary calcium scanning, compared
An Intervention Trial Evaluating Rosuvastatin with no scanning, led to improved risk factor control
LDL-C low-density lipoprotein cholesterol without increasing downstream medical costs.4 In addi-
LV left ventricular
tion, a cost-effectiveness analysis based on MESA5 data
LVH left ventricular hypertrophy
MACE major adverse cardiovascular event(s)
reported that CAC testing and statin treatment for
MASALA Mediators of Atherosclerosis in South Asians Living in those with CAC >0 was cost-effective (<$50 000 per
America QALY) in intermediate-risk scenarios even when consid-
MESA Multi-Ethnic Study of Atherosclerosis ering less favorable statin assumptions ($1.00 per pill).
MI myocardial infarction
MRI magnetic resonance imaging
NHLBI National Heart, Lung, and Blood Institute Coronary Artery Calcification
NNT5 5-year number needed to treat
PAD peripheral artery disease Background
PWV pulse wave velocity • CAC is a measure of the burden of atheroscle-
QALY quality-adjusted life-year rosis in the heart arteries and is measured by CT.
(Continued ) Other components of the atherosclerotic plaque,

e346 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

including fatty (eg, cholesterol-rich components) — The prevalence and 75th percentile levels of

CLINICAL STATEMENTS
and fibrotic components, often accompany CAC CAC were highest in white males and low-

AND GUIDELINES
and can be present even in the absence of CAC. est in black and Hispanic females. Significant
• The presence of any CAC, which indicates that ethnic differences persisted after adjustment
at least some atherosclerotic plaque is present, for risk factors, with the RR of coronary cal-
is defined by an Agatston score >0. Clinically cium being 22% less in blacks, 15% less in
significant plaque, frequently an indication for Hispanics, and 8% less in Chinese than in
more aggressive risk factor management, is often whites.
defined by an Agatston score ≥100 or a score • In a comparison of MESA with the MASALA study,
≥75th percentile for one’s age and sex; however, which is a community-based cohort of South
although they predict short- to intermediate-term Asians in the United States and on average 5 years
risk, absolute CAC cutoffs offer more prognostic younger than MESA, the age-adjusted prevalence
information across all age groups in both males of CAC was similar among white (68.8%) and
andfemales.6 South Asian (67.9%) males, with these groups
having a greater prevalence of CAC than Chinese
Prevalence (57.8%), African American (51.2%), and Hispanic
(See Charts 18-1 through 18-3) (57.9%) males. In contrast, the age-adjusted
• The NHLBI’s FHS reported CAC measured in 3238 prevalence of CAC was lower in South Asian
white adults in age groups ranging from <45 to females (36.8%) than in white females (42.6%)
≥75 years of age.6a and females of other races/ethnicities.10
— Overall, 32.0% of females and 52.9% of • Further illustrating the variability of CAC based on
males had prevalent CAC. population and habits, a forager-horticulturalist
— Among participants at intermediate risk population of 705 individuals living in the Bolivian
according to FRS, 58% of females and 67% Amazon had the lowest reported levels of CAC of
of males had prevalent CAC. any population recorded to date.11 Overall in the
• The NHLBI’s CARDIA study measured CAC in population (mean age 58 years; 50% females),
3043 black and white adults 33 to 45 years of 85% of individuals were free from any CAC,
age (at the CARDIA year 15 examination).7 and even in individuals >75 years of age, 65%
— Overall, 15.0% of males, 5.1% of females, remained free of CAC. These unique data indicate
Downloaded from http://ahajournals.org by on February 7, 2019

5.5% of those 33 to 39 years of age, and that coronary atherosclerosis can be typically be
13.3% of those 40 to 45 years of age had avoided by maintaining a low lifetime burden of
prevalent CAC. Overall, 1.6% of participants CAD risk factors.11
had an Agatston score that exceeded 100. • To date, sparse research exists on the prevalence
• Chart 18-1 shows the prevalence of CAC by eth- of subclinical atherosclerosis, including CAC,
nicity and sex in adults 33 to 45 years of age. in rural areas of the United States.12 A study
The prevalence of CAC was lower in black versus reported the distribution of CAC scores among
white males but was similar in black versus white 1607 (mean age 56 years; 56% females) commu-
females at these ages.7 nity-dwelling asymptomatic individuals from cen-
• The NHLBI’s JHS assessed outcomes with presence tral Appalachia. Overall, 44% had a CAC score
of elevated CAC (>100) in 4416 African American of 0, whereas the prevalence of those with mild
participants (mean age 54 years; 64% females) (1–99), moderate (100–399), and severe (≥400)
followed up for 6 years.8 CAC was 29%, 15%, and 11%, respectively.12
• CAC >100 was noted in 14% of those without any • The prevalence of CAC varies widely according
metabolic syndrome or DM, 26% of those with to baseline risk profile. In recent studies from
metabolic syndrome, and 41% of those with DM. MESA, the prevalence of CAC in those with no
• The NHLBI’s MESA measured CAC in 6814 par- lipid abnormalities was 42% versus 50% in those
ticipants 45 to 84 years of age (mean 63), includ- with 3 lipid abnormalities,13 and 32% of people in
ing white (n=2619), black (n=1898), Hispanic MESA with no known traditional CVD risk factors
(n=1494), and Chinese (n=803) males and had presence of CAC versus 65% of those with 3
females.9 risk factors.14
— The overall prevalence of CAC in these 4 eth- • The 10-year trends in CAC among individuals with-
nic groups was 70.4%, 52.1%, 56.5%, and out clinical CVD in MESA were assessed15 (Chart
59.2%, respectively. 18-3). After adjustment for age, sex, ethnicity,
— Chart 18-2 shows the prevalence of CAC by and type of CT scanner, the proportion of par-
sex and ethnicity in US adults 45 to 84 years ticipants with no CAC decreased over time from
of age in MESA. 40.7% to 32.6% (P=0.007), and the proportions

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e347

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

increased from 29.9% to 37.0% (P=0.01) for • In a study of healthy adults 60 to 72 years of age
CLINICAL STATEMENTS

those with a CAC score ranging from 1 to 99 and who were free of clinical CAD, predictors of the
AND GUIDELINES

from 14.7% to 17.7% (P=0.14) for those with a progression of CAC were assessed. Predictors
CAC score of 100 to 399, whereas the propor- tested included age, sex, race/ethnicity, smoking
tion with a CAC score ≥400 decreased from 9.1% status, BMI, family history of CAD, CRP, several
to 7.2% (P=0.11). Trends in CAC among the 4 measures of DM, insulin levels, BP, and lipids.
racial/ethnic groups revealed a significant trend Insulin resistance, in addition to the traditional
toward increased prevalence of CAC in African cardiac risk factors, independently predicts pro-
Americans but not in any other group. Among gression of CAC.19 Clinically, however, it is not
African Americans, the CAC prevalence ratio recommended to conduct serial scanning of CAC
(year 10 versus baseline) was 1.27 (P<0.001 for to measure effects of therapeutic interventions.
test for trend). Adjustment for risk factors made • It is noteworthy, as demonstrated in MESA in
no notable difference in CAC trends in any ethnic 5878 participants with a median of 5.8 years of
group.15 follow-up, that the addition of CAC to standard
risk factors resulted in significant improvement
CAC and Incidence of Cardiovascular Events of classification of risk for incident CHD events,
(See Chart 18-4) placing 77% of people in the highest or lowest
• In a landmark study, the NHLBI’s MESA reported risk categories compared with 69% based on risk
on the association of CAC scores with first CHD factors alone. An additional 23% of those who
events over a median follow-up of 3.9 years experienced events were reclassified as high risk,
among a population-based sample of 6722 indi- and 13% with events were reclassified as low
viduals (39% white, 27% black, 22% Hispanic, risk.20 The contribution of CAC to risk prediction
and 12% Chinese).16 has also been observed in other cohorts, includ-
— Chart 18-4 shows the HRs associated with ing both the Heinz Nixdorf Recall Study21 and the
CAC scores of 1 to 100, 101 to 300, and Rotterdam Study.22
>300 compared with those without CAC • The prospective Dallas Heart Study reported the
(score=0), after adjustment for standard risk prognostic value of CAC scores in a relatively
factors. People with CAC scores of 1 to 100 younger cohort (44.4±9.0 years of age). Among
had ≈4 times greater risk and those with the 2084 participants who were followed up for
Downloaded from http://ahajournals.org by on February 7, 2019

CAC scores >100 were 7 to 10 times more a median of 9 years, compared with individuals
likely to experience a coronary event than with CAC=0, those with CAC scores of 10 to 100
those without CAC. and >100 were associated with an HR (95% CI) of
— CAC provided similar predictive value for 3.43 (1.36–8.56) and 5.64 (2.28–13.97) for CHD
coronary events in whites, Chinese, blacks, events, respectively. The addition of CAC to the
and Hispanics (HRs ranging from 1.15–1.39 traditional risk factor model resulted in significant
for each doubling of coronary calcium). improvement in the C statistic (Δ=0.03; P=0.003),
• In a more recent MESA analysis with 12-year as well as a net correct reclassification of 22%.23
follow-up, machine learning was used to assess • In the Heinz Nixdorf Recall Study of 4180 individu-
predictors of cardiovascular events. Among 735 als,21 CAC independently predicted stroke during
variables from imaging and noninvasive tests, a mean follow-up of 7.9 years. Cox proportional
questionnaires, and biomarker panels, CAC hazards regressions were used to examine CAC
emerged as the strongest predictor of CHD and as a predictor of stroke in addition to established
ASCVD events.17 vascular risk factors (age, sex, SBP, LDL-C, HDL-
• In MESA, CAC was noted to be highly predic- C, DM, smoking, and AF). Study participants who
tive of CHD event risk across in both young and had a stroke had significantly higher CAC values at
elderly MESA participants in a follow-up that baseline than the remaining participants (median
extended to 8.5 years, which suggests that 104.8 [quartile 1, 14.0; quartile 3, 482.2] versus
once CAC is known, chronological age has less 11.2 [quartile 1, 0; quartile 3, 106.2]; P<0.001).
importance. Compared with a CAC score of 0, In a multivariable Cox regression, log10(CAC+1)
CAC >100 was associated with an increased was a stroke predictor (HR, 1.52 [95% CI, 1.19–
multivariable-adjusted CHD event risk in the 1.92]; P=0.001) independent of traditional risk
younger individuals (45–54 years old), with an factors in low- and intermediate-risk individuals.21
HR of 12.4 (95% CI, 5.1–30.0). The respective • A meta-analysis24 also highlighted the utility of
risk was similar even in the very elderly (75–84 CAC testing in the diabetic population. In this
years of age), with an HR of 12.1 (95% CI, meta-analysis, 8 studies were included (n=6521;
2.9–50.2).18 802 events; mean follow-up 5.2 years). The RR for

e348 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

all-cause mortality or cardiovascular events or both for CHD events during a median of 4.1 years

CLINICAL STATEMENTS
comparing a total CAC score ≥10 with a score of follow-up among people with no detectable

AND GUIDELINES
<10 was 5.47 (95% CI, 2.59–11.53; I2=82.4%, CAC.30
P<0.001). For people with a CAC score <10, the • The value of CAC=0 has been confirmed in vari-
posttest probability of the composite outcome ous high-risk groups. For example, in MESA, 38%
was ≈1.8%, which represents a 6.8-fold reduc- of those with DM had CAC=0, and the annual-
tion from the pretest probability. This suggests ized CHD and CVD event rates were 0.4% and
that low or absent CAC could facilitate risk strati- 0.8%, respectively.31 A publication14 from MESA
fication by enabling the identification of people at demonstrated a low hard CHD event rate per
low risk within this high-risk population.24 1000 years during a median follow-up of 7.1
• CAC also appears to have predictive value for years across the entire spectrum of baseline FRS
cardiac events beyond stroke and MI. In the (0%–6%: 0.9; 6%–10%: 1.1; 10%–20%: 1.9;
Rotterdam Study, CAC independently predicted >20%: 2.5). Among high-risk individuals consid-
incident HF during a median follow-up of 6.8 ered for various polypill criteria in MESA, based
years. After adjustment for risk factors, those on age and risk factors, the prevalence of CAC=0
with severe CAC (>400) had a 4.1-fold higher risk ranged from 39% to 59%, and the respective
(95% CI, 1.7–10.1) of HF than those with CAC rate of CHD events varied from 1.2 to 1.9 events
scores of 0 to 10.25 In addition, CAC substantially per 1000 person-years during a median follow-up
improved the risk classification (net reclassification of 7.6 years.32
index, 34.0%). A recent MESA analysis examin- • A recent meta-analysis that pooled data from
ing prediction of HF with preserved EF found that 3 studies evaluated 13 262 asymptomatic indi-
CAC >300 was a significant independent predic- viduals (mean age 60 years, 50% males) without
tor in females (HR, 2.82 [95% CI, 1.32–6.00]) but apparent CVD. During a mean follow-up of 7.2
not in males (HR, 0.91 [95% CI, 0.46–1.82]).26 years, the pooled RR of incident stroke with CAC
• In MESA, during a median follow-up of 8.5 >0 was 2.95 (95% CI, 2.18–4.01; P<0.001) com-
years, after accounting for risk factors, higher pared with CAC=0. Furthermore, there was an
CAC scores were associated with increased risk increasing risk with higher CAC score (0.12% per
for AF (CAC=0: HR, 1.0 [referent]; CAC=1–100: year for CAC=0, 0.26% per year for CAC 1–99,
HR, 1.4 [95% CI, 1.01–2.0]; CAC=101–300: HR,
Downloaded from http://ahajournals.org by on February 7, 2019

0.41% per year for CAC 100–399, and 0.70%

1.6 [95% CI, 1.1–2.4]; CAC >300: HR, 2.1 [95% per year for CAC ≥400).33
CI, 1.4–2.9]). The addition of CAC to a risk score
yielded relative integrated discrimination improve- CAC Progression and Risk
ment of 0.10 (95% CI, 0.061–0.15).27 • Data from 6778 people in MESA showed annual
• A MESA analysis also showed that a higher CAC progression averaged 25±65 Agatston
CAC burden was associated with non-CVD out- units, and among those without CAC at base-
comes. During a median follow-up of 10.2 years, line, a 5-U annual change in CAC was associated
accounting for demographics and traditional risk with HRs of 1.4 and 1.5 for total and hard CHD
factors, participants with severe CAC (>400) were events, respectively. Among those with CAC >0
at an increased risk of cancer (HR, 1.53 [95% CI, at baseline, HRs per 100-U annual change in CAC
1.18–1.99]), CKD (HR, 1.70 [95% CI, 1.21–2.39]), were 1.2 and 1.3, respectively, and for those with
pneumonia (HR, 1.97 [95% CI, 1.37–2.82]), annual progression ≥300 versus no progression,
chronic obstructive pulmonary disease (HR, 2.71 HRs were 3.8 and 6.3, respectively.34 Progression
[95% CI, 1.60–4.57]), and hip fracture (HR, 4.29 of CAC in MESA was greater in those with meta-
[95% CI, 1.47–12.50]) compared with those with bolic syndrome and DM than in those with nei-
CAC=0.28 ther condition, and progression of CAC in each
• In a meta-analysis of 13 studies assessing the of these conditions was associated with a greater
relationship of CAC with adverse cardiovascu- future risk of CHD events.35
lar outcomes that included 71 595 asymptom- • Furthermore, in MESA, CAC progression was
atic individuals, 29 312 (41%) did not have any associated with incident AF. Presence of any CAC
evidence of CAC.29 In a mean follow-up of 4.3 progression (>0 per year) in the 5-year follow-up
years, 154 of 29 312 individuals without CAC was associated with 1.55-fold higher risk for AF
(0.47%) experienced a cardiovascular event com- (95% CI, 1.10–2.19). The risk of AF increased
pared with 1749 of 42 283 individuals with CAC with higher levels of CAC progression: (1–100
(4.14%). The cumulative RR was 0.15 (95% CI, per year: HR, 1.47 [95% CI, 1.03–2.09]; 101–300
0.11–0.21; P<0.001). These findings were con- per year: HR, 1.92 [95% CI, 1.15–3.20]; >300 per
firmed in MESA, which reported a rate of 0.52% year: HR, 3.23 [95% CI, 1.48–7.05]).27

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e349

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

• In MESA, greater adherence to a healthy lifestyle, DBP, and LDL-C. Carotid IMT was inversely
CLINICAL STATEMENTS

based on a healthy lifestyle score, was associ- correlated with HDL-C levels. Participants
AND GUIDELINES

ated with slower progression of CAC and lower with greater numbers of adverse risk factors
mortality rates relative to those with the most (0, 1, 2, 3, or more) had stepwise increases in
unhealthy lifestyle.36 mean carotid IMT levels.
• In a subsequent analysis, the Bogalusa investi-
gators examined the association of risk factors
Carotid IMT measured since childhood with carotid IMT mea-
Background sured in these young adults.40 Higher BMI and
• Carotid IMT measures the thickness of 2 layers LDL-C levels measured at 4 to 7 years of age were
(the intima and media) of the wall of the carotid associated with increased risk for being >75th
arteries, the largest conduits of blood going to percentile for carotid IMT in young adulthood.
the brain. Carotid IMT is thought to be an even Higher SBP and LDL-C and lower HDL-C in young
earlier manifestation of atherosclerosis than adulthood were also associated with having high
CAC, because thickening precedes the develop- carotid IMT.
ment of frank atherosclerotic plaque. Carotid • A similar pattern of association between risk fac-
IMT methods are still being refined, so it is tors at a younger age and carotid IMT in adult-
important to know which part of the artery was hood have also been demonstrated in a large
measured (common carotid, internal carotid, or Finnish cohort study.41 These data highlight the
bulb) and whether near and far walls were both importance of adverse risk factor levels in early
measured. Additionally, measurement can be childhood and young adulthood in the early
reported as the average thickness or maximum development of atherosclerosis.
thickness, although the average is more com- • Updates from an individual-participant meta-anal-
monly reported. ysis involving 15 population-based cohorts world-
• Unlike CAC, everyone has some thickness to wide that included 60 211 individuals (46 788
the layers of their arteries, but people who whites, 7200 blacks, 3816 Asians, and 2407
develop atherosclerosis have greater thickness. Hispanics) demonstrated differing associations
Additionally, the thickness is expected to increase between risk factors and burden of carotid IMT
according to racial/ethnic groups.42 Specifically,
Downloaded from http://ahajournals.org by on February 7, 2019

with age and for males. Thus, high-risk levels of

thickening might be considered as those in the association between age and carotid IMT was
highest quartile or quintile for one’s age and weaker in blacks and Hispanics, SBP was more
sex, or ≥1 mm. Ultrasound of the carotid arter- strongly associated with carotid IMT in Asians,
ies can also detect plaques and determine the and HDL-C and smoking were associated less
degree of narrowing of the artery they might with carotid IMT in blacks.
cause. Although this is commonly used to diag- • Among both females and males in MESA, blacks
nose plaque in the carotid arteries in people who had the highest common carotid IMT, but they
have had strokes or who have bruits (sounds of were similar to whites and Hispanics in internal
turbulence in the artery), current primary preven- carotid IMT. Chinese participants had the lowest
tion guidelines do not recommend screening of carotid IMT, in particular in the internal carotid, of
asymptomatic people using either the presence of the 4 ethnic groups.43
atherosclerotic plaque or carotid IMT to quantify • The CHS reported follow-up of 4476 males and
atherosclerosis or predict risk.37,38 females ≥65 years of age (mean age 72 years)
who were free of CVD at baseline.44 Mean maxi-
Prevalence and Association With Incident mal common carotid IMT was 1.03±0.20 mm,
Cardiovascular Events and mean internal carotid IMT was 1.37±0.55
• In the Bogalusa Heart Study,39 carotid IMT was mm. After a mean follow-up of 6.2 years, those
measured in 518 black and white males and with maximal combined carotid IMT in the highest
females at a mean age of 32±3 years. These quintile had a 4- to 5-fold greater risk for incident
males and females were healthy but overweight. heart attack or stroke than those in the bottom
— Males had significantly higher carotid IMT in quintile. After adjustment for other risk factors,
all segments than females, and blacks had there was still a 2- to 3-fold greater risk for the
higher common carotid and carotid bulb top versus the bottom quintile.
IMTs than whites. • In MESA, during a median follow-up of 3.3 years,
— Even at this young age, after adjustment for an IMT rate of change of 0.5 mm per year was
age, race, and sex, carotid IMT was associ- associated with an HR of 1.23 (95% CI, 1.02–
ated significantly and positively with WC, SBP, 1.48) for incident stroke. The upper quartile of

e350 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

IMT rate of change had an HR of 2.18 (95% CI, risk score resulted in a small but statistically sig-

CLINICAL STATEMENTS
1.07–4.46) compared with the lower 3 quartiles nificant improvement in risk prediction.50

AND GUIDELINES
combined.45 • In a recent study, however, carotid plaque burden
• Despite this evidence, conflicting data have been measured via 3-dimensional carotid ultrasound
reported on the contribution of carotid IMT to showed promise in improving CVD risk predic-
risk prediction. A recent study from a consor- tion. The prospective BioImage Study enrolled
tium of 14 population-based cohorts consisting 5808 asymptomatic US adults (mean age 69
of 45 828 individuals followed up for a median years; 56.5% females). Carotid plaque areas from
of 11 years demonstrated little additive value of both carotid arteries were summed as the carotid
common carotid IMT to FRS for purposes of dis- plaque burden. The primary end point was the
crimination and reclassification as far as incident composite of MACE (cardiovascular death, MI,
MI and stroke were concerned. The C statistics of and ischemic stroke). After adjustment for risk
the model with FRS alone (0.757 [95% CI, 0.749– factors, the HRs for MACE were 1.45 (95% CI,
0.764]) and with addition of common carotid IMT 0.67–3.14) and 2.36 (95% CI, 1.13–4.92) with
(0.759 [95% CI, 0.752–0.766]) were similar. The increasing carotid plaque burden tertile. Net
net reclassification improvement with the addition reclassification improved significantly with carotid
of common carotid IMT was small (0.8% [95% plaque burden (0.23).51
CI, 0.1%–1.6%]). In those at intermediate risk, • Two large, population-based prospective studies
the net reclassification improvement was 3.6% have aimed to elucidate the association of carotid
among all individuals (95% CI, 2.7%–4.6%).46 ultrasound findings with outcomes with shared
• Interestingly, the ability of carotid IMT to predict pathogenesis of atherosclerosis.52,53 Among
incident CVD events might also depend on how 13 197 individuals aged 45 to 64 years (26%
the data are modeled. In MESA, the use of an blacks, 56% females) followed up for a median of
age-, sex-, and race-adjusted carotid IMT score 22.7 years, mean carotid IMT in the fourth quar-
that combined data from both the internal and tile (≥0.81 mm) versus first quartile (<0.62) was
common carotid artery resulted in a significant significantly associated with ESRD.52,53
improvement in the net reclassification improve- • Investigators from the FHS demonstrated that
ment of 4.9% (P=0.024), with a particularly additional information obtained from carotid
higher impact in individuals with an intermediate
Downloaded from http://ahajournals.org by on February 7, 2019

ultrasound regarding the degree of carotid

FRS, in whom the net reclassification improve- stenotic burden was predictive of cerebral
ment was 11.5%.47 microbleeds detected on brain MRI, which are
• Among 13 590 participants in the ARIC study recognized as a marker of stroke and dementia,
aged 45 to 64 years, each 1-SD increase in carotid in 1243 participants (56.9±8.8 years old; 53%
IMT was associated with incident HF (HR, 1.20 females). Carotid stenosis ≥25% was associated
[95% CI, 1.16–1.25) in a 20-year follow-up after with a 2.2-fold (95% CI, 1.10–4.40) increased risk
accounting for major CVD risk factors and CHD. of cerebral microbleed, whereas no association
Similar associations were also noted across all was noted with carotid IMT.52
race and sex groups.48 This relationship was found
to be much stronger among those without estab-
lished DM.48 CAC and Carotid IMT
• A recent study49 from 3 population-based cohorts • In the NHLBI’s MESA, a study of white, black,
(ARIC, N=13  907; MESA, N=6640; and the Chinese, and Hispanic adults 45 to 84 years of
Rotterdam Study, N=5220) demonstrated that age, carotid IMT and CAC were found to be com-
both a higher carotid IMT and presence of carotid monly associated, but patterns of association dif-
plaque were independently associated with an fered somewhat by sex and race.43
increased risk of incident AF. In this study, a 1-SD — Common and internal carotid IMT were
increase in carotid IMT and presence of carotid greater in females and males who had CAC
plaque were associated with a meta-analyzed HR than in those who did not, regardless of
(95% CI) of 1.12 (1.08–1.16) and 1.30 (1.19– ethnicity.
1.42), respectively.49 — Overall, CAC prevalence and scores were
• A study from a consortium of population-based associated with carotid IMT, but associations
cohorts reported no added value of measurement were somewhat weaker in blacks than in
of mean common carotid IMT in individuals with other ethnic groups.
HBP for improving cardiovascular risk prediction. — In general, blacks had the thickest carotid
For those at intermediate risk, the addition of mean IMT of all 4 ethnic groups, regardless of the
common carotid IMT to an existing cardiovascular presence of CAC.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e351

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

— Common carotid IMT differed little by race/ artery IMT progression in people with DM ranged
CLINICAL STATEMENTS

ethnicity in females with any CAC, but between −0.09 and 0.04 mm per year in a follow-up of
AND GUIDELINES

among females with no CAC, IMT was 3.6 years; however, this change was not associated with
higher among blacks (0.86 mm) than in the cardiovascular outcomes. The HR for a 1-SD increase in
other 3 groups (0.76–0.80 mm). common carotid artery IMT progression was 0.99 (95%
• In a more recent analysis from MESA, the investi- CI, 0.91–1.08).56
gators reported on follow-up of 6779 males and
females in 4 ethnic groups over 9.5 years and
compared the predictive utility of carotid IMT,
CT Angiography
carotid plaque, and CAC (presence and burden).54 • CT angiography is widely used to aid in the diag-
— CAC presence was a stronger predictor of nosis of CAD in symptomatic individuals because
incident CVD and CHD than carotid ultra- of its ability to detect and possibly quantitate
sound measures. overall plaque burden and certain characteristics
— Mean IMT ≥75th percentile (for age, sex, and of plaques that might make them prone to rup-
race) alone did not predict events. Compared ture, such as positive remodeling, low attenua-
with traditional risk factors, C statistics for tion, and spotty calcifications.57
CVD (C=0.756) and CHD (C=0.752) increased • Compared with the established value of CAC
the most by the addition of CAC presence scanning for risk reclassification in asymptomatic
(CVD, 0.776; CHD, 0.784; P<0.001), fol- patients, there are limited data regarding the util-
lowed by carotid plaque presence (CVD, ity of CT angiography in asymptomatic people.
C=0.760; CHD, C=0.757; P<0.05). In a recent study from the CONFIRM registry, CT
— Compared with risk factors (C=0.782), angiography data on the presence, extent, and
carotid plaque presence (C=0.787; P=0.045) severity of CAD improved risk prediction over
but not CAC (C=0.785; P=0.438) improved traditional risk factors. However, no additional
prediction of stroke/TIA. prognostic value was added by coronary CT angi-
• Investigators from the NHLBI’s CARDIA and ography data for the prediction of all-cause death
MESA studies examined the burden and pro- once traditional risk factors and CAC scores were
gression of subclinical atherosclerosis among included in the model.58 In another analysis of the
CONFIRM data, it was noted that coronary CT
Downloaded from http://ahajournals.org by on February 7, 2019

adults <50 years of age. Ten-year and lifetime

risks for CVD were estimated for each partici- angiography only provided incremental prognos-
pant, and the participants were stratified into 3 tic utility for prediction of mortality and nonfatal
groups: (1) those with low 10-year (<10%) and MI for asymptomatic individuals with moderately
low lifetime (<39%) predicted risk for CVD; (2) high CAC scores, but not for those with lower or
those with low 10-year (<10%) but high life- higher CAC scores.59
time (≥39%) predicted risk; and (3) those with • Because of this limited impact on the prediction
high 10-year risk (>10%). The latter group had of outcomes in asymptomatic individuals, current
the highest burden and greatest progression of guidelines do not recommend its use as a screen-
subclinical atherosclerosis. Given the young age ing tool for assessment of cardiovascular risk in
of those studied, ≈90% of participants were at asymptomatic individuals.2
low 10-year risk, but of these, half had high pre-
dicted lifetime risk. Compared with those with
Measures of Vascular Function and
low short-term/low lifetime predicted risks, those
with low short-term/high lifetime predicted risk Incident CVD Events
had significantly greater burden and progres- Background
sion of CAC and significantly greater burden of • Measures of arterial tonometry (stiffness) are
carotid IMT, even at these younger ages. These based on the concept that pulse pressure has
data confirm the importance of early exposure been shown to be an important risk factor for
to risk factors for the onset and progression of CVD. Arterial tonometry offers the ability to
subclinical atherosclerosis.55 directly and noninvasively measure central PWV in
the thoracic and abdominal aorta.
• Brachial FMD is a marker for nitric oxide release
Carotid IMT Progression and Risk from the endothelium that can be measured by
To date, few studies have comprehensively studied the ultrasound. Impaired FMD is an early marker of
impact of carotid IMT progression on CVD outcomes. CVD.
Data from a comprehensive meta-analysis of individual • Recommendations have not been specific, how-
participant data demonstrated that common carotid ever, as to which, if any, measures of vascular

e352 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

function might be useful for CVD risk stratifica- CAC, ABI, high-sensitivity CRP, and family history

CLINICAL STATEMENTS
tion in selected patient subgroups. Because of the were independently associated with incident CHD

AND GUIDELINES
absence of significant prospective data relating in multivariable analyses (HRs of 2.6, 0.79, 1.28,
these measures to outcomes, the latest guidelines and 2.18, respectively), but carotid IMT and bra-
do not recommend measuring either FMD or arte- chial FMD were not. CAC provided the highest
rial stiffness for cardiovascular risk assessment in incremental improvement over the FRS (0.784 for
asymptomatic adults.2 both CAC and FRS versus 0.623 for FRS alone), as
well as the greatest net reclassification improve-
Arterial Tonometry and CVD ment (0.659).65
• The Rotterdam Study measured arterial stiffness • Additionally, in MESA, the values of 12 negative
in 2835 elderly participants (mean age 71 years).60 markers (CAC score of 0, carotid IMT <25th per-
They found that as aortic PWV increased, the RR centile, absence of carotid plaque, brachial FMD
of CHD was 1.72 (second versus first tertile) and >5% change, ABI >0.9 and <1.3, high-sensi-
2.45 (third versus first tertile). Results remained tivity CRP <2 mg/L, homocysteine <10 µmol/L,
robust even after accounting for carotid IMT, ABI, N-terminal pro-BNP <100 pg/mL, no microal-
and pulse pressure. buminuria, no family history of CHD [any/pre-
• A study from Denmark of 1678 individuals aged mature], absence of metabolic syndrome, and
40 to 70 years found that each 1-SD increment in healthy lifestyle) were compared for all and
aortic PWV (3.4 m/s) increased CVD risk by 16% hard CHD and all CVD events over the 10-year
to 20%.61 follow-up. After accounting for CVD risk fac-
• The FHS measured several indices of arterial tor, absence of CAC had the strongest negative
stiffness, including PWV, wave reflection, and predictive value, with an adjusted mean diag-
central pulse pressure.62 They found that not nostic likelihood ratio of 0.41 (SD, 0.12) for all
only was higher PWV associated with a 48% CHD and 0.54 (SD, 0.12) for CVD, followed by
increased risk of incident CVD events, but PWV carotid IMT <25th percentile (diagnostic likeli-
additionally improved CVD risk prediction (inte- hood ratio, 0.65 [SD, 0.04] and 0.75 [SD, 0.04],
grated discrimination improvement of 0.7%, respectively).66
P<0.05). • Similar findings were also noted in the Rotterdam
• An analysis from the JHS suggested peripheral Study, in which among 12 CHD risk markers,
Downloaded from http://ahajournals.org by on February 7, 2019

arterial tonometry to be associated with LVH. A improvements in FRS predictions were most sta-
total of 440 African American participants (mean tistically and clinically significant with the addition
age 59±10 years, 60% females) underwent both of CAC scores.67
peripheral arterial tonometry and cardiac MRI
evaluations between 2007 and 2013. Age- and
sex-adjusted Pearson correlation analysis sug- Utility for Risk Stratification for
gested that natural log-transformed LV mass Treatment
index measured by MRI was negatively correlated • CAC has been examined in multiple studies for
with reactive hyperemia index (coefficient −0.114; its potential to identify those most likely and not
P=0.02) after accounting for age, sex, BMI, DM, likely to benefit from pharmacological treatment
hypertension, ratio of TC and HDL-C, smoking, for the primary prevention of CVD.
and history of CVD.63 • A total of 950 participants from MESA who met
FMD and CVD JUPITER clinical trial entry criteria (risk factors plus
• A recent meta-analysis assessed the relation of LDL-C <130 mg/dL and high-sensitivity CRP ≥2
FMD with CVD events. Thirteen studies involving mg/L) were identified and stratified according to
11 516 individuals without established CVD, with CAC scores of 0, 1 to 100, or >100; CHD event
a mean duration of 2 to 7.2 years and adjusted for rates were calculated, and the NNT5 was calcu-
age, sex, and risk factors, reported a multivariate lated by applying the benefit found in JUPITER to
RR of 0.93 (95% CI, 0.90–0.96) per 1% increase the event rates found in each of these groups. For
in brachial FMD.64 CHD, the predicted NNT5 was 549 for those with
CAC of 0, 94 for scores of 1 to 100, and 24 for
Comparison of Measures scores >100.68
• In MESA, a comparison of 6 risk markers—CAC, • In a similar fashion, 2 studies extrapolated the
ABI, high-sensitivity CRP, carotid IMT, brachial NNT5 for LDL-C lowering by statins, applying the
FMD, and family history of CHD—and their clini- 30% RR reduction associated with a 1 mmol/L
cal utility over FRS was evaluated in 1330 interme- (39 mg/dL) reduction in LDL-C from a Cochrane
diate-risk individuals. After 7.6 years of follow-up, meta-analysis of statin therapy in primary

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e353

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

prevention across the spectrum of lipid abnor- to 269 for patients with CAC=0, from 58 to
CLINICAL STATEMENTS

malities (LDL-C ≥130 mg/dL, HDL-C <40 mg/dL 79 for those with CAC scores from 1 to 100,
AND GUIDELINES

for males or <50 mg/dL for females, and triglyc- and from 25 to 27 for those with CAC scores
erides ≥150 mg/dL), as well as across 10-year >100,32 which enabled significant reductions in
FRS categories (0%–6%, 6%–10%, 10%–20%, the population considered for treatment with
and >20%). The estimated NNT5 for prevent- more selective use of the polypill and, as a result,
ing 1 CVD event across dyslipidemia categories avoidance of treatment of those who were
in this MESA cohort ranged from 23 to 30 in unlikely to benefit.
those with CAC ≥100.13 The NNT5 was 30 in • Within the scope of the 2013 ACC/AHA guide-
participants with no lipid abnormality and CAC lines, data from MESA demonstrated that among
>100, whereas it was 154 in those with 3 lipid those for whom statins were recommended,
abnormalities and CAC of 0.13 A very high NNT5 41% had CAC=0 and had 5.2 ASCVD events
of 186 and 222, respectively, was estimated to per 1000 person-years. Among 589 partici-
prevent 1 CHD event in the absence of CAC pants (12%) considered for moderate-intensity
among those with 10-year FRS of 11% to 20% statin treatment, 338 (57%) had CAC=0, with
and >20%. The respective estimated NNT5 was an ASCVD event rate of 1.5 per 1000 person-
as low as 36 and 50 with the presence of a very years. Of participants eligible (recommended
high CAC score (>300) among those with 10-year or considered) for statins, 44% (1316 of 2966)
FRS of 0% to 6% and 6% to 10%, respectively.13 had CAC=0 at baseline and an observed 10-year
These collective data show the utility of CAC in ASCVD event rate of 4.2 per 1000 person-years.
identifying those most likely to benefit from statin The study results highlighted that among the
treatment across the spectrum of risk profiles intermediate-risk range of 5% to 20%, nearly
with an appropriate NNT5. half (48%) had CAC=0, and their 10-year
• Similarly, CAC testing also identified appropriate ASCVD risk was below the threshold recom-
candidates who might derive the highest benefit mended for statin therapy (4.5%).70 These find-
with aspirin therapy. In MESA, individuals with ings were recently confirmed in the JHS. Among
CAC ≥100 had an estimated net benefit with 2812 African American individuals aged 40 to
aspirin regardless of their traditional risk status; 75 years without prevalent ASCVD followed up
the estimated NNT5 was 173 for individuals clas- for a median of 10 years, participants who were
Downloaded from http://ahajournals.org by on February 7, 2019

sified as having <10% FRS and 92 for individu- statin eligible by ACC/AHA guidelines experi-
als with ≥10% FRS, and the estimated 5-year enced a 10-year ASCVD event rate of 8.1 per
number needed to harm was 442 for a major 1000 person-years. However, in the absence
bleed.69 Conversely, individuals with zero CAC of CAC, the 10-year observed ASCVD risk
had unfavorable estimates (estimated NNT5 of was below the threshold of statin recommen-
2036 for individuals with <10% FRS and 808 dation set by the guidelines, at 3.1 per 1000
for individuals with ≥10% FRS; estimated 5-year person-years.71
number needed to harm of 442 for a major
bleed). Sex-specific and age-stratified analyses
showed similar results. Family History and Genetics
• A study from MESA also examined the role of • There is evidence for genetic control of subclini-
CAC testing to define the target population to cal atherosclerosis, with several loci identified that
treat with a polypill.32 The NNT5 to prevent 1 associate with CAC and carotid artery IMT.72–75
event was estimated by applying the expected On the basis of the identified genes and variants,
62% CHD event reduction associated with the there are considerable shared genetic components
use of the polypill (based on TIPS). The estimated to subclinical disease and other risk factors (such
NNT5 to prevent 1 CHD event ranged from 170 as blood lipids) and incident disease.

e354 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-1. Prevalence (%) of detectable coronary calcium in the CARDIA study: US adults 33 to 45 years of age (2000–2001).
P<0.0001 across race-sex groups.
CARDIA indicates Coronary Artery Risk Development in Young Adults.
Data derived from Loria et al.7
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 18-2. Prevalence (%) of detectable coronary calcium in MESA: US adults 45 to 84 years of age.
P<0.0001 across ethnic groups in both males and females.
MESA indicates Multi-Ethnic Study of Atherosclerosis.
Data derived from Bild et al.9

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e355

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18
CLINICAL STATEMENTS
AND GUIDELINES

Chart 18-3. Ten-year trends in coronary artery calcification in individuals without clinical cardiovascular disease in MESA.
MESA indicates Multi-Ethnic Study of Atherosclerosis.
Adapted from Bild et al.15
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 18-4. HRs for CHD events associated with CAC scores: US adults 45 to 84 years of age (reference group, CAC=0).
All HRs P<0.0001. Major CHD events included myocardial infarction and death attributable to CHD; any CHD events included major CHD events plus definite
angina or definite or probable angina followed by revascularization.
CAC indicates coronary artery calcification; CHD, coronary heart disease; and HR, hazard ratio.
Data derived from Detrano et al.16

e356 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

‍‍‍REFERENCES 13. Martin SS, Blaha MJ, Blankstein R, Agatston A, Rivera JJ, Virani SS,

CLINICAL STATEMENTS
Ouyang P, Jones SR, Blumenthal RS, Budoff MJ, Nasir K. Dyslipidemia,
1. Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland

AND GUIDELINES
coronary artery calcium, and incident atherosclerotic cardiovascu-
P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE. lar disease: implications for statin therapy from the Multi-Ethnic
Assessment of coronary artery disease by cardiac computed tomography: Study of Atherosclerosis. Circulation. 2014;129:77–86. doi:
a scientific statement from the American Heart Association Committee 10.1161/CIRCULATIONAHA.113.003625
on Cardiovascular Imaging and Intervention, Council on Cardiovascular 14. Silverman MG, Blaha MJ, Krumholz HM, Budoff MJ, Blankstein R, Sibley
Radiology and Intervention, and Committee on Cardiac Imaging,
CT, Agatston A, Blumenthal RS, Nasir K. Impact of coronary artery calcium
Council on Clinical Cardiology. Circulation. 2006;114:1761–1791. doi:
on coronary heart disease events in individuals at the extremes of tradi-
10.1161/CIRCULATIONAHA.106.178458
tional risk factor burden: the Multi-Ethnic Study of Atherosclerosis. Eur
2. Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster
Heart J. 2014;35:2232–2241. doi: 10.1093/eurheartj/eht508
E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC
15. Bild DE, McClelland R, Kaufman JD, Blumenthal R, Burke GL, Carr
Jr, Taylor AJ, Weintraub WS, Wenger NK. 2010 ACCF/AHA guideline for
JJ, Post WS, Register TC, Shea S, Szklo M. Ten-year trends in coronary
assessment of cardiovascular risk in asymptomatic adults: a report of the
calcification in individuals without clinical cardiovascular disease in the
American College of Cardiology Foundation/American Heart Association
Multi-Ethnic Study of Atherosclerosis [published correction appears
Task Force on Practice Guidelines. Circulation. 2010;122:e584–e636. doi:
in PLoS One. 2014;9:e103666]. PLoS One. 2014;9:e94916. doi:
10.1161/CIR.0b013e3182051b4c
10.1371/journal.pone.0094916
3. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS,
16. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K,
Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R,
Shea S, Szklo M, Bluemke DA, O’Leary DH, Tracy R, Watson K, Wong
Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N,
ND, Kronmal RA. Coronary calcium as a predictor of coronary events in
Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling
four racial or ethnic groups. N Engl J Med. 2008;358:1336–1345. doi:
L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/
10.1056/NEJMoa072100
AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cho-
17. Ambale-Venkatesh B, Yang X, Wu CO, Liu K, Hundley WG, McClelland
lesterol: a report of the American College of Cardiology/American Heart
R, Gomes AS, Folsom AR, Shea S, Guallar E, Bluemke DA, Lima JAC.
Association Task Force on Clinical Practice Guidelines. Circulation. 2018;
Cardiovascular event prediction by machine learning: the Multi-
doi: 10.1161/CIR.0000000000000625
Ethnic Study of Atherosclerosis. Circ Res. 2017;121:1092–1101. doi:
4. Rozanski A, Gransar H, Shaw LJ, Kim J, Miranda-Peats L, Wong ND, Rana
10.1161/CIRCRESAHA.117.311312
JS, Orakzai R, Hayes SW, Friedman JD, Thomson LE, Polk D, Min J, Budoff
18. Tota-Maharaj R, Blaha MJ, Blankstein R, Silverman MG, Eng J, Shaw LJ,
MJ, Berman DS. Impact of coronary artery calcium scanning on coronary risk
Blumenthal RS, Budoff MJ, Nasir K. Association of coronary artery calcium
factors and downstream testing: the EISNER (Early Identification of Subclinical
and coronary heart disease events in young and elderly participants in the
Atherosclerosis by Noninvasive Imaging Research) prospective randomized
Multi-Ethnic Study of Atherosclerosis: a secondary analysis of a prospec-
trial. J Am Coll Cardiol. 2011;57:1622–1632. doi: 10.1016/j.jacc.2011.01.019
5. Pletcher MJ, Pignone M, Earnshaw S, McDade C, Phillips KA, Auer R, tive, population-based cohort. Mayo Clin Proc. 2014;89:1350–1359. doi:
Zablotska L, Greenland P. Using the coronary artery calcium score to 10.1016/j.mayocp.2014.05.017
guide statin therapy: a cost-effectiveness analysis. Circ Cardiovasc Qual 19. Lee KK, Fortmann SP, Fair JM, Iribarren C, Rubin GD, Varady A, Go AS,
Outcomes. 2014;7:276–284. doi: 10.1161/CIRCOUTCOMES.113.000799 Quertermous T, Hlatky MA. Insulin resistance independently predicts the
6. Budoff MJ, Nasir K, McClelland RL, Detrano R, Wong N, Blumenthal RS, progression of coronary artery calcification. Am Heart J. 2009;157:939–
Kondos G, Kronmal RA. Coronary calcium predicts events better with 945. doi: 10.1016/j.ahj.2009.02.006
20. Polonsky TS, McClelland RL, Jorgensen NW, Bild DE, Burke GL, Guerci
Downloaded from http://ahajournals.org by on February 7, 2019

absolute calcium scores than age-sex-race/ethnicity percentiles: MESA

(Multi-Ethnic Study of Atherosclerosis) [published correction appears in AD, Greenland P. Coronary artery calcium score and risk classification
J Am Coll Cardiol. 2009;53:1474]. J Am Coll Cardiol. 2009;53:345–352. for coronary heart disease prediction. JAMA. 2010;303:1610–1616. doi:
doi: 10.1016/j.jacc.2008.07.072 10.1001/jama.2010.461
6a. Hoffmann U, Massaro JM, Fox CS, Manders E, O’Donnell CJ. Defining 21. Hermann DM, Gronewold J, Lehmann N, Moebus S, Jöckel KH, Bauer
normal distributions of coronary artery calcium in women and men (from M, Erbel R; on behalf of the Heinz Nixdorf Recall Study Investigative
the Framingham Heart Study). Am J Cardiol. 2008;102:1136–1141. doi: Group. Coronary artery calcification is an independent stroke pre-
10.1016/j.amjcard.2008.06.038 dictor in the general population. Stroke. 2013;44:1008–1013. doi:
7. Loria CM, Liu K, Lewis CE, Hulley SB, Sidney S, Schreiner PJ, Williams OD, 10.1161/STROKEAHA.111.678078
Bild DE, Detrano R. Early adult risk factor levels and subsequent coronary 22. Elias-Smale SE, Proença RV, Koller MT, Kavousi M, van Rooij FJ, Hunink
artery calcification: the CARDIA Study. J Am Coll Cardiol. 2007;49:2013– MG, Steyerberg EW, Hofman A, Oudkerk M, Witteman JC. Coronary cal-
2020. doi: 10.1016/j.jacc.2007.03.009 cium score improves classification of coronary heart disease risk in the
8. Xanthakis V, Sung JH, Samdarshi TE, Hill AN, Musani SK, Sims M, elderly: the Rotterdam study. J Am Coll Cardiol. 2010;56:1407–1414. doi:
Ghraibeh KA, Liebson PR, Taylor HA, Vasan RS, Fox ER. Relations between 10.1016/j.jacc.2010.06.029
subclinical disease markers and type 2 diabetes, metabolic syndrome, and 23. Paixao AR, Ayers CR, El Sabbagh A, Sanghavi M, Berry JD, Rohatgi A,
incident cardiovascular disease: the Jackson Heart Study. Diabetes Care. Kumbhani DJ, McGuire DK, Das SR, de Lemos JA, Khera A. Coronary artery
2015;38:1082–1088. doi: 10.2337/dc14-2460 calcium improves risk classification in younger populations. JACC Cardiovasc
9. Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, Ouyang P, Imaging. 2015;8:1285–1293. doi: 10.1016/j.jcmg.2015.06.015
Jackson S, Saad MF. Ethnic differences in coronary calcification: the Multi- 24. Kramer CK, Zinman B, Gross JL, Canani LH, Rodrigues TC, Azevedo MJ,
Ethnic Study of Atherosclerosis (MESA). Circulation. 2005;111:1313– Retnakaran R. Coronary artery calcium score prediction of all cause mor-
1320. doi: 10.1161/01.CIR.0000157730.94423.4B tality and cardiovascular events in people with type 2 diabetes: systematic
10. Kanaya AM, Kandula NR, Ewing SK, Herrington D, Liu K, Blaha MJ, review and meta-analysis. BMJ. 2013;346:f1654. doi: 10.1136/bmj.f1654
Srivastava S, Dave SS, Budoff MJ. Comparing coronary artery calcium 25. Leening MJ, Elias-Smale SE, Kavousi M, Felix JF, Deckers JW, Vliegenthart
among U.S. South Asians with four racial/ethnic groups: the MASALA R, Oudkerk M, Hofman A, Steyerberg EW, Stricker BH, Witteman JC.
and MESA studies [published correction appears in Atherosclerosis. Coronary calcification and the risk of heart failure in the elderly: the
2014;235:36–37]. Atherosclerosis. 2014;234:102–107. doi: 10.1016/j. Rotterdam Study. JACC Cardiovasc Imaging. 2012;5:874–880. doi:
atherosclerosis.2014.02.017 10.1016/j.jcmg.2012.03.016
11. Kaplan H, Thompson RC, Trumble BC, Wann LS, Allam AH, Beheim 26. Sharma K, Al Rifai M, Ahmed HM, Dardari Z, Silverman MG, Yeboah
B, Frohlich B, Sutherland ML, Sutherland JD, Stieglitz J, Rodriguez DE, J, Nasir K, Sklo M, Yancy C, Russell SD, Blumenthal RS, Blaha MJ.
Michalik DE, Rowan CJ, Lombardi GP, Bedi R, Garcia AR, Min JK, Narula Usefulness of coronary artery calcium to predict heart failure with pre-
J, Finch CE, Gurven M, Thomas GS. Coronary atherosclerosis in indig- served ejection fraction in men versus women (from the Multi-Ethnic
enous South American Tsimane: a cross-sectional cohort study. Lancet. Study of Atherosclerosis). Am J Cardiol. 2017;120:1847–1853. doi:
2017;389:1730–1739. doi: 10.1016/S0140-6736(17)30752-3 10.1016/j.amjcard.2017.07.089
12. Mamudu HM, Paul TK, Wang L, Veeranki SP, Panchal HB, Alamian A, 27. O’Neal WT, Efird JT, Qureshi WT, Yeboah J, Alonso A, Heckbert SR,
Sarnosky K, Budoff M. The effects of multiple coronary artery disease risk Nazarian S, Soliman EZ. Coronary artery calcium progression and atrial
factors on subclinical atherosclerosis in a rural population in the United fibrillation: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc
States. Prev Med. 2016;88:140–146. doi: 10.1016/j.ypmed.2016.04.003 Imaging. 2015;8:e003786. doi: 10.1161/CIRCIMAGING.115.003786

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e357

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

28. Handy CE, Desai CS, Dardari ZA, Al-Mallah MH, Miedema MD, Ouyang Risk in Young Finns study. Eur Heart J. 2010;31:1745–1751. doi:
CLINICAL STATEMENTS

P, Budoff MJ, Blumenthal RS, Nasir K, Blaha MJ. The association of coro- 10.1093/eurheartj/ehq141
AND GUIDELINES

nary artery calcium with noncardiovascular disease: the Multi-Ethnic 42. Gijsberts CM, Groenewegen KA, Hoefer IE, Eijkemans MJ, Asselbergs FW,
Study of Atherosclerosis. JACC Cardiovasc Imaging. 2016;9:568–576. doi: Anderson TJ, Britton AR, Dekker JM, Engström G, Evans GW, de Graaf
10.1016/j.jcmg.2015.09.020 J, Grobbee DE, Hedblad B, Holewijn S, Ikeda A, Kitagawa K, Kitamura
29. Sarwar A, Shaw LJ, Shapiro MD, Blankstein R, Hoffmann U, Cury RC, A, de Kleijn DP, Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki
Abbara S, Brady TJ, Budoff MJ, Blumenthal RS, Nasir K. Diagnostic and S, O’Leary DH, Pasterkamp G, Peters SA, Polak JF, Price JF, Robertson C,
prognostic value of absence of coronary artery calcification [published Rembold CM, Rosvall M, Rundek T, Salonen JT, Sitzer M, Stehouwer CD,
correction appears in JACC Cardiovasc Imaging. 2010;3:1089]. JACC Bots ML, den Ruijter HM. Race/ethnic differences in the associations of the
Cardiovasc Imaging. 2009;2:675–688. doi: 10.1016/j.jcmg.2008.12.031 Framingham risk factors with carotid IMT and cardiovascular events. PLoS
30. Budoff MJ, McClelland RL, Nasir K, Greenland P, Kronmal RA, Kondos GT, One. 2015;10:e0132321. doi: 10.1371/journal.pone.0132321
Shea S, Lima JA, Blumenthal RS. Cardiovascular events with absent or 43. Manolio TA, Arnold AM, Post W, Bertoni AG, Schreiner PJ, Sacco RL,
minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis Saad MF, Detrano RL, Szklo M. Ethnic differences in the relationship
(MESA). Am Heart J. 2009;158:554–561. doi: 10.1016/j.ahj.2009.08.007 of carotid atherosclerosis to coronary calcification: the Multi-Ethnic
31. Malik S, Budoff MJ, Katz R, Blumenthal RS, Bertoni AG, Nasir K, Szklo M, Study of Atherosclerosis. Atherosclerosis. 2008;197:132–138. doi:
Barr RG, Wong ND. Impact of subclinical atherosclerosis on cardiovascu- 10.1016/j.atherosclerosis.2007.02.030
lar disease events in individuals with metabolic syndrome and diabetes: 44. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK
the Multi-Ethnic Study of Atherosclerosis. Diabetes Care. 2011;34:2285– Jr; for the Cardiovascular Health Study Collaborative Research Group.
2290. doi: 10.2337/dc11-0816 Carotid-artery intima and media thickness as a risk factor for myocardial
32. Bittencourt MS, Blaha MJ, Blankstein R, Budoff M, Vargas JD, Blumenthal infarction and stroke in older adults. N Engl J Med. 1999;340:14–22. doi:
RS, Agatston AS, Nasir K. Polypill therapy, subclinical atherosclerosis, and 10.1056/NEJM199901073400103
cardiovascular events-implications for the use of preventive pharmaco- 45. Polak JF, Pencina MJ, O’Leary DH, D’Agostino RB. Common carotid
therapy: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. artery intima-media thickness progression as a predictor of stroke in
2014;63:434–443. doi: 10.1016/j.jacc.2013.08.1640 Multi-Ethnic Study of Atherosclerosis. Stroke. 2011;42:3017–3021. doi:
33. Chaikriangkrai K, Jhun HY, Palamaner Subash Shantha G, Bin Abdulhak A, 10.1161/STROKEAHA.111.625186
Sigurdsson G, Nabi F, Mahmarian JJ, Chang SM. Coronary artery calcium 46. Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM,
score as a predictor for incident stroke: systematic review and meta-anal- Eijkemans MJ, Engström G, Evans GW, de Graaf J, Grobbee DE, Hedblad
ysis. Int J Cardiol. 2017;236:473–477. doi: 10.1016/j.ijcard.2017.01.132 B, Hofman A, Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A,
34. Budoff MJ, Young R, Lopez VA, Kronmal RA, Nasir K, Blumenthal RS, Koffijberg H, Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki
Detrano RC, Bild DE, Guerci AD, Liu K, Shea S, Szklo M, Post W, Lima J,
S, O’Leary DH, Polak JF, Price JF, Robertson C, Rembold CM, Rosvall M,
Bertoni A, Wong ND. Progression of coronary calcium and incident coro-
Rundek T, Salonen JT, Sitzer M, Stehouwer CD, Witteman JC, Moons
nary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).
KG, Bots ML. Common carotid intima-media thickness measurements
J Am Coll Cardiol. 2013;61:1231–1239. doi: 10.1016/j.jacc.2012.12.035
in cardiovascular risk prediction: a meta-analysis [published correction
35. Wong ND, Nelson JC, Granston T, Bertoni AG, Blumenthal RS, Carr
appears in JAMA. 2013;310:1739]. JAMA. 2012;308:796–803. doi:
JJ, Guerci A, Jacobs DR Jr, Kronmal R, Liu K, Saad M, Selvin E, Tracy R,
10.1001/jama.2012.9630
Detrano R. Metabolic syndrome, diabetes, and incidence and progression
47. Polak JF, Szklo M, O’Leary DH. Carotid intima-media thickness score,
of coronary calcium: the Multiethnic Study of Atherosclerosis study. JACC
positive coronary artery calcium score, and incident coronary heart dis-
Cardiovasc Imaging. 2012;5:358–366. doi: 10.1016/j.jcmg.2011.12.015
Downloaded from http://ahajournals.org by on February 7, 2019

ease: the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc.

36. Ahmed HM, Blaha MJ, Nasir K, Jones SR, Rivera JJ, Agatston A, Blankstein
2017;6:e004612. doi: 10.1161/JAHA.116.004612
R, Wong ND, Lakoski S, Budoff MJ, Burke GL, Sibley CT, Ouyang P,
48. Effoe VS, McClendon EE, Rodriguez CJ, Wagenknecht LE, Evans
Blumenthal RS. Low-risk lifestyle, coronary calcium, cardiovascular events,
GW, Chang PP, Bertoni AG. Diabetes status modifies the association
and mortality: results from MESA. Am J Epidemiol. 2013;178:12–21. doi:
between carotid intima-media thickness and incident heart failure:
10.1093/aje/kws453
the Atherosclerosis Risk in Communities study. Diabetes Res Clin Pract.
37. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons
2017;128:58–66. doi: 10.1016/j.diabres.2017.04.009
R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz
49. Chen LY, Leening MJ, Norby FL, Roetker NS, Hofman A, Franco OH, Pan
JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/
AHA guideline on the assessment of cardiovascular risk: a report of the W, Polak JF, Witteman JC, Kronmal RA, Folsom AR, Nazarian S, Stricker
American College of Cardiology/American Heart Association Task Force BH, Heckbert SR, Alonso A. Carotid intima-media thickness and arte-
on Practice Guidelines [published correction appears in Circulation. rial stiffness and the risk of atrial fibrillation: the Atherosclerosis Risk in
2014;129(suppl 2):S74–S75]. Circulation. 2014;129(suppl XXX2):S49– Communities (ARIC) Study, Multi-Ethnic Study of Atherosclerosis (MESA),
S73. doi: 10.1161/01.cir.0000437741.48606.98 and the Rotterdam Study. J Am Heart Assoc. 2016;5:e002907. doi:
38. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, 10.1161/JAHA.115.002907
Cooney MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs 50. Bots ML, Groenewegen KA, Anderson TJ, Britton AR, Dekker JM,
FDR, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon Engström G, Evans GW, de Graaf J, Grobbee DE, Hedblad B, Hofman
J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis A, Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A, Ikram MA,
I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki S, O’Leary
European Guidelines on cardiovascular disease prevention in clinical prac- DH, Polak JF, Price JF, Robertson C, Rembold CM, Rosvall M, Rundek T,
tice: the Sixth Joint Task Force of the European Society of Cardiology and Salonen JT, Sitzer M, Stehouwer CD, Franco OH, Peters SA, den Ruijter
Other Societies on Cardiovascular Disease Prevention in Clinical Practice HM. Common carotid intima-media thickness measurements do not
(constituted by representatives of 10 societies and by invited experts) improve cardiovascular risk prediction in individuals with elevated blood
Developed with the special contribution of the European Association pressure: the USE-IMT collaboration. Hypertension. 2014;63:1173–1181.
for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. doi: 10.1161/HYPERTENSIONAHA.113.02683
2016;37:2315–2381. doi: 10.1093/eurheartj/ehw106 51. Baber U, Mehran R, Sartori S, Schoos MM, Sillesen H, Muntendam P,
39. Urbina EM, Srinivasan SR, Tang R, Bond MG, Kieltyka L, Berenson GS; Garcia MJ, Gregson J, Pocock S, Falk E, Fuster V. Prevalence, impact, and
Bogalusa Heart Study. Impact of multiple coronary risk factors on the predictive value of detecting subclinical coronary and carotid athero-
intima-media thickness of different segments of carotid artery in healthy sclerosis in asymptomatic adults: the BioImage study. J Am Coll Cardiol.
young adults (the Bogalusa Heart Study). Am J Cardiol. 2002;90:953–958. 2015;65:1065–1074. doi: 10.1016/j.jacc.2015.01.017
40. Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, Berenson 52. Romero JR, Preis SR, Beiser A, DeCarli C, D’Agostino RB, Wolf PA, Vasan
GS. Childhood cardiovascular risk factors and carotid vascular changes RS, Polak JF, Seshadri S. Carotid atherosclerosis and cerebral microbleeds:
in adulthood: the Bogalusa Heart Study [published correction appears in the Framingham Heart Study. J Am Heart Assoc. 2016;5:e002377. doi:
JAMA. 2003;290:2943]. JAMA. 2003;290:2271–2276. 10.1161/JAHA.115.002377
41. Juonala M, Viikari JS, Kähönen M, Taittonen L, Laitinen T, Hutri-Kähönen 53. Pang Y, Sang Y, Ballew SH, Grams ME, Heiss G, Coresh J, Matsushita
N, Lehtimäki T, Jula A, Pietikäinen M, Jokinen E, Telama R, Räsänen L, K. Carotid intima-media thickness and incident ESRD: the Atherosclerosis
Mikkilä V, Helenius H, Kivimäki M, Raitakari OT. Life-time risk factors and Risk in Communities (ARIC) Study. Clin J Am Soc Nephrol. 2016;11:1197–
progression of carotid atherosclerosis in young adults: the Cardiovascular 1205. doi: 10.2215/CJN.11951115

e358 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 18

54. Gepner AD, Young R, Delaney JA, Tattersall MC, Blaha MJ, Post WS, 66. Blaha MJ, Cainzos-Achirica M, Greenland P, McEvoy JW, Blankstein

CLINICAL STATEMENTS
Gottesman RF, Kronmal R, Budoff MJ, Burke GL, Folsom AR, Liu K, R, Budoff MJ, Dardari Z, Sibley CT, Burke GL, Kronmal RA, Szklo M,

AND GUIDELINES
Kaufman J, Stein JH. Comparison of coronary artery calcium presence, carotid Blumenthal RS, Nasir K. Role of coronary artery calcium score of zero and
plaque presence, and carotid intima-media thickness for cardiovascular dis- other negative risk markers for cardiovascular disease: the Multi-Ethnic
ease prediction in the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Study of Atherosclerosis (MESA). Circulation. 2016;133:849–858. doi:
Imaging. 2015;8:e002262. doi: 10.1161/CIRCIMAGING.114.002262 10.1161/CIRCULATIONAHA.115.018524
55. Berry JD, Liu K, Folsom AR, Lewis CE, Carr JJ, Polak JF, Shea S, Sidney 67. Kavousi M, Elias-Smale S, Rutten JH, Leening MJ, Vliegenthart R, Verwoert
S, O’Leary DH, Chan C, Lloyd-Jones DM. Prevalence and progres- GC, Krestin GP, Oudkerk M, de Maat MP, Leebeek FW, Mattace-Raso
sion of subclinical atherosclerosis in younger adults with low short- FU, Lindemans J, Hofman A, Steyerberg EW, van der Lugt A, van den
term but high lifetime estimated risk for cardiovascular disease: the Meiracker AH, Witteman JC. Evaluation of newer risk markers for cor-
Coronary Artery Risk Development in Young Adults study and Multi- onary heart disease risk classification: a cohort study. Ann Intern Med.
Ethnic Study of Atherosclerosis. Circulation. 2009;119:382–389. doi: 2012;156:438–444. doi: 10.7326/0003-4819-156-6-201203200-00006
10.1161/CIRCULATIONAHA.108.800235 68. Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A,
56. Lorenz MW, Price JF, Robertson C, Bots ML, Polak JF, Poppert H, Kavousi O’Leary DH, Lima J, Blumenthal RS, Nasir K. Associations between C-reactive
M, Dörr M, Stensland E, Ducimetiere P, Ronkainen K, Kiechl S, Sitzer M, protein, coronary artery calcium, and cardiovascular events: implications
Rundek T, Lind L, Liu J, Bergström G, Grigore L, Bokemark L, Friera A, Yanez for the JUPITER population from MESA, a population-based cohort study.
D, Bickel H, Ikram MA, Völzke H, Johnsen SH, Empana JP, Tuomainen Lancet. 2011;378:684–692. doi: 10.1016/S0140-6736(11)60784-8
TP, Willeit P, Steinmetz H, Desvarieux M, Xie W, Schmidt C, Norata GD, 69. Miedema MD, Duprez DA, Misialek JR, Blaha MJ, Nasir K, Silverman
Suarez C, Sander D, Hofman A, Schminke U, Mathiesen E, Plichart M, MG, Blankstein R, Budoff MJ, Greenland P, Folsom AR. Use of coronary
Kauhanen J, Willeit J, Sacco RL, McLachlan S, Zhao D, Fagerberg B, artery calcium testing to guide aspirin utilization for primary prevention:
Catapano AL, Gabriel R, Franco OH, Bülbül A, Scheckenbach F, Pflug A, estimates from the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc
Gao L, Thompson SG. Carotid intima-media thickness progression and risk Qual Outcomes. 2014;7:453–460. doi: 10.1161/CIRCOUTCOMES.
of vascular events in people with diabetes: results from the PROG-IMT col- 113.000690
laboration. Diabetes Care. 2015;38:1921–1929. doi: 10.2337/dc14-2732 70. Nasir K, Bittencourt MS, Blaha MJ, Blankstein R, Agatson AS, Rivera JJ,
57. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, Naruse H, Ishii Miedema MD, Sibley CT, Shaw LJ, Blumenthal RS, Budoff MJ, Krumholz
J, Hishida H, Wong ND, Virmani R, Kondo T, Ozaki Y, Narula J. Computed HM. Implications of coronary artery calcium testing among statin can-
tomographic angiography characteristics of atherosclerotic plaques didates according to American College of Cardiology/American Heart
subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. Association cholesterol management guidelines: MESA (Multi-Ethnic
2009;54:49–57. doi: 10.1016/j.jacc.2009.02.068 Study of Atherosclerosis) [published correction appears in J Am Coll
58. Cho I, Al’Aref SJ, Berger A, Ó Hartaigh B, Gransar H, Valenti V, Lin Cardiol. 2015;66:2686]. J Am Coll Cardiol. 2015;66:1657–1668. doi:
FY, Achenbach S, Berman DS, Budoff MJ, Callister TQ, Al-Mallah 10.1016/j.jacc.2015.07.066
MH, Cademartiri F, Chinnaiyan K, Chow BJW, DeLago A, Villines TC, 71. Shah RV, Spahillari A, Mwasongwe S, Carr JJ, Terry JG, Mentz RJ,
Hadamitzky M, Hausleiter J, Leipsic J, Shaw LJ, Kaufmann PA, Feuchtner Addison D, Hoffmann U, Reis J, Freedman JE, Lima JAC, Correa A,
G, Kim YJ, Maffei E, Raff G, Pontone G, Andreini D, Marques H, Murthy VL. Subclinical atherosclerosis, statin eligibility, and outcomes in
Rubinshtein R, Chang HJ, Min JK. Prognostic value of coronary computed African American individuals: the Jackson Heart Study. JAMA Cardiol.
tomographic angiography findings in asymptomatic individuals: a 6-year 2017;2:644–652. doi: 10.1001/jamacardio.2017.0944
follow-up from the prospective multicentre international CONFIRM study. 72. Natarajan P, Bis JC, Bielak LF, Cox AJ, Dörr M, Feitosa MF, Franceschini N,
Eur Heart J. 2018;39:934–941. doi: 10.1093/eurheartj/ehx774 Guo X, Hwang SJ, Isaacs A, Jhun MA, Kavousi M, Li-Gao R, Lyytikäinen
Downloaded from http://ahajournals.org by on February 7, 2019

59. Cho I, Chang HJ, Ó Hartaigh B, Shin S, Sung JM, Lin FY, Achenbach S, LP, Marioni RE, Schminke U, Stitziel NO, Tada H, van Setten J, Smith AV,
Heo R, Berman DS, Budoff MJ, Callister TQ, Al-Mallah MH, Cademartiri F, Vojinovic D, Yanek LR, Yao J, Yerges-Armstrong LM, Amin N, Baber U,
Chinnaiyan K, Chow BJ, Dunning AM, DeLago A, Villines TC, Hadamitzky Borecki IB, Carr JJ, Chen YI, Cupples LA, de Jong PA, de Koning H, de Vos
M, Hausleiter J, Leipsic J, Shaw LJ, Kaufmann PA, Cury RC, Feuchtner G, Kim BD, Demirkan A, Fuster V, Franco OH, Goodarzi MO, Harris TB, Heckbert
YJ, Maffei E, Raff G, Pontone G, Andreini D, Min JK. Incremental prognostic SR, Heiss G, Hoffmann U, Hofman A, Išgum I, Jukema JW, Kähönen M,
utility of coronary CT angiography for asymptomatic patients based upon Kardia SL, Kral BG, Launer LJ, Massaro J, Mehran R, Mitchell BD, Mosley
extent and severity of coronary artery calcium: results from the COronary TH Jr, de Mutsert R, Newman AB, Nguyen KD, North KE, O’Connell JR,
CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter Oudkerk M, Pankow JS, Peloso GM, Post W, Province MA, Raffield LM,
(CONFIRM) study [published correction appears in Eur Heart J. 2015;36:3287]. Raitakari OT, Reilly DF, Rivadeneira F, Rosendaal F, Sartori S, Taylor KD,
Eur Heart J. 2015;36:501–508. doi: 10.1093/eurheartj/ehu358 Teumer A, Trompet S, Turner ST, Uitterlinden AG, Vaidya D, van der Lugt
60. Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, A, Völker U, Wardlaw JM, Wassel CL, Weiss S, Wojczynski MK, Becker
Bos ML, Schalekamp MA, Asmar R, Reneman RS, Hoeks AP, Breteler DM, Becker LC, Boerwinkle E, Bowden DW, Deary IJ, Dehghan A, Felix
MM, Witteman JC. Arterial stiffness and risk of coronary heart disease SB, Gudnason V, Lehtimäki T, Mathias R, Mook-Kanamori DO, Psaty BM,
and stroke: the Rotterdam Study. Circulation. 2006;113:657–663. doi: Rader DJ, Rotter JI, Wilson JG, van Duijn CM, Völzke H, Kathiresan S,
10.1161/CIRCULATIONAHA.105.555235 Peyser PA, O’Donnell CJ; CHARGE Consortium. Multiethnic exome-wide
61. Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, association study of subclinical atherosclerosis. Circ Cardiovasc Genet.
Ibsen H, Jeppesen J. Prognostic value of aortic pulse wave velocity as index 2016;9:511–520. doi: 10.1161/CIRCGENETICS.116.001572
of arterial stiffness in the general population. Circulation. 2006;113:664– 73. Divers J, Palmer ND, Langefeld CD, Brown WM, Lu L, Hicks PJ, Smith SC,
670. doi: 10.1161/CIRCULATIONAHA.105.579342 Xu J, Terry JG, Register TC, Wagenknecht LE, Parks JS, Ma L, Chan GC,
62. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg Buxbaum SG, Correa A, Musani S, Wilson JG, Taylor HA, Bowden DW,
NM, Vita JA, Levy D, Benjamin EJ. Arterial stiffness and cardiovascular Carr JJ, Freedman BI. Genome-wide association study of coronary artery
events: the Framingham Heart Study. Circulation. 2010;121:505–511. calcified atherosclerotic plaque in African Americans with type 2 diabetes.
doi: 10.1161/CIRCULATIONAHA.109.886655 BMC Genet. 2017;18:105. doi: 10.1186/s12863-017-0572-9
63. Tripathi A, Benjamin EJ, Musani SK, Hamburg NM, Tsao CW, Saraswat A, 74. Wojczynski MK, Li M, Bielak LF, Kerr KF, Reiner AP, Wong ND, Yanek
Vasan RS, Mitchell GF, Fox ER. The association of endothelial function and LR, Qu L, White CC, Lange LA, Ferguson JF, He J, Young T, Mosley
tone by digital arterial tonometry with MRI left ventricular mass in African TH, Smith JA, Kral BG, Guo X, Wong Q, Ganesh SK, Heckbert SR,
Americans: the Jackson Heart Study. J Am Soc Hypertens. 2017;11:258– Griswold ME, O’Leary DH, Budoff M, Carr JJ, Taylor HA Jr, Bluemke
264. doi: 10.1016/j.jash.2017.03.005 DA, Demissie S, Hwang SJ, Paltoo DN, Polak JF, Psaty BM, Becker DM,
64. Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, Rigatto Province MA, Post WS, O’Donnell CJ, Wilson JG, Harris TB, Kavousi
C, Komenda P, Sood MM, Tangri N. Non-invasive endothelial func- M, Cupples LA, Rotter JI, Fornage M, Becker LC, Peyser PA, Borecki
tion testing and the risk of adverse outcomes: a systematic review and IB, Reilly MP. Genetics of coronary artery calcification among African
meta-analysis. Eur Heart J Cardiovasc Imaging. 2014;15:736–746. doi: Americans, a meta-analysis. BMC Med Genet. 2013;14:75. doi:
10.1093/ehjci/jet256 10.1186/1471-2350-14-75
65. Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O’Leary D, Carr 75. Vargas JD, Manichaikul A, Wang XQ, Rich SS, Rotter JI, Post WS, Polak JF,
JJ, Goff DC, Greenland P, Herrington DM. Comparison of novel risk mark- Budoff MJ, Bluemke DA. Common genetic variants and subclinical athero-
ers for improvement in cardiovascular risk assessment in intermediate-risk sclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis.
individuals. JAMA. 2012;308:788–795. doi: 10.1001/jama.2012.9624 2016;245:230–236. doi: 10.1016/j.atherosclerosis.2015.11.034

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e359

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

19. CORONARY HEART DISEASE, Abbreviations Used in Chapter 19 Continued

CLINICAL STATEMENTS

ACUTE CORONARY SYNDROME, AND FRS Framingham Risk Score

AND GUIDELINES

GBD Global Burden of Disease

ANGINA PECTORIS GWAS genome-wide association studies
GWTG Get With The Guidelines
See Tables 19-1 through 19-3 and Charts 19-1 HCHS/SOL Hispanic Community Health Study/Study of
through 19-11 Latinos
HCUP Healthcare Cost and Utilization Project
HDL-C high-density lipoprotein cholesterol
Click here to return to the Table of Contents
HD heart disease
HF heart failure
Coronary Heart Disease HR hazard ratio
ICD-9 International Classification of Diseases, 9th
ICD-9 410 to 414, 429.2; ICD-10 I20 to I25 Revision
(includes MI ICD-10 I21 to I22). ICD-10 International Classification of Diseases, 10th
Revision
Prevalence IHD ischemic heart disease
(See Tables 19-1 and 19-2 and Charts 19-1 JHS Jackson Heart Study
through 19-4) JUPITER Justification for the Use of Statins in Primary
Prevention: An Intervention Trial Evaluating
• On the basis of data from NHANES 2013 to 2016 Rosuvastatin
(unpublished NHLBI tabulation), an estimated 18.2 LDL-C low-density lipoprotein cholesterol
million Americans ≥20 years of age have CHD LV left ventricular
(Table 19-1). The prevalence of CHD was higher for MEPS Medical Expenditure Panel Survey
males than females for all ages (Chart 19-1). MESA Multi-Ethnic Study of Atherosclerosis
MI myocardial infarction
MI-GENES Myocardial Infarction Genes Study
Abbreviations Used in Chapter 19
NAMCS National Ambulatory Medical Care Survey
ACC American College of Cardiology NCDR National Cardiovascular Data Registry
ACS acute coronary syndrome NCHS National Center for Health Statistics
ACTION Acute Coronary Treatment and Intervention NH non-Hispanic
Outcomes Network NHAMCS National Hospital Ambulatory Medical Care
AHA American Heart Association Survey
AMI acute myocardial infarction NHANES National Health and Nutrition Examination
Downloaded from http://ahajournals.org by on February 7, 2019

AP angina pectoris Survey

ARIC Atherosclerosis Risk in Communities Study NHIS National Health Interview Study
ASCOT Anglo-Scandinavian Cardiac Outcomes Trial NHLBI National Heart, Lung, and Blood Institute
ASCVD atherosclerotic cardiovascular disease NIS National (Nationwide) Inpatient Sample
BEST Randomized Comparison of Coronary Artery NSTEMI non–ST-segment–elevation myocardial infarction
Bypass Surgery and Everolimus-Eluting Stent OR odds ratio
Implantation in the Treatment of Patients With PCI percutaneous coronary intervention
Multivessel Coronary Artery Disease
PRECOMBAT Premier of Randomized Comparison of Bypass
BP blood pressure Surgery Versus Angioplasty Using Sirolimus
BRFSS Behavioral Risk Factor Surveillance System Stents in Patients With Left Main Coronary
CABG coronary artery bypass graft Artery Disease
CAC coronary artery calcium PROVE IT-TIMI 22 Pravastatin or Atorvastatin Evaluation and
CAD coronary artery disease Infection Therapy–Thrombolysis in Myocardial
CARDIA Coronary Artery Risk Development in Young Infarction 22
Adults RCT randomized controlled trial
CARDIoGRAM Coronary Artery Disease Genome-Wide REGARDS Reasons for Geographic and Racial Differences
Replication and Meta-Analysis in Stroke
CARDIoGRAMplusC4D Coronary Artery Disease Genome-Wide RR relative risk
Replication and Meta-Analysis (CARDIoGRAM) SBP systolic blood pressure
plus the Coronary Artery Disease Genetics SE standard error
(C4D) SES socioeconomic status
CARE Cholesterol and Recurrent Events SHS Strong Heart Study
CHD coronary heart disease SNAP Supplemental Nutrition Assistance Program
CHS Cardiovascular Health Study SNP single-nucleotide polymorphism
CI confidence interval STEMI ST-segment–elevation myocardial infarction
CKD chronic kidney disease SYNTAX Synergy Between PCI With Taxus and Cardiac
CVD cardiovascular disease Surgery
DM diabetes mellitus TC total cholesterol
ED emergency department TRACE-CORE Transitions, Risks, and Actions in Coronary
FHS Framingham Heart Study Events–Center for Outcomes Research and
FINRISK Finnish population survey on risk factors for Education
chronic, noncommunicable diseases UA unstable angina
(Continued ) WHI Women’s Health Initiative

e360 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

• Total CHD prevalence is 6.7% in US adults ≥20 • In the REGARDS study, 37% of adjudicated MIs

CLINICAL STATEMENTS
years of age. CHD prevalence is 7.4% for males had a primary hospital discharge diagnosis of MI,

AND GUIDELINES
and 6.2% for females. CHD prevalence by sex whereas 63% had a primary hospital discharge
and ethnicity is shown in Table 19-1. diagnosis other than MI, which suggests that
• On the basis of data from the 2016 NHIS1: most MIs that result in hospitalization might be
— Among American Indian/Alaska Natives ≥18 occurring during hospitalization for other acute
years of age, the CHD prevalence estimate is illnesses.5
12.1%. • Self-reported income and education were asso-
• According to data from NHANES 2013 to 2016 ciated with incident CHD (defined as definite
(unpublished NHLBI tabulation), the overall preva- or probable MI or acute CHD death) in the
lence for MI is 3.0% in US adults ≥20 years of REGARDS study. Those reporting low income
age. Males have a higher prevalence of MI than and low education had twice the incidence of
females for all age groups except 20 to 39 years CHD as those reporting high income and high
(Chart 19-2). MI prevalence is 4.0% for males and education (10.1 versus 5.2 per 1000 person-
2.3% for females. MI prevalence by sex and eth- years, respectively).6
nicity is shown in Table 19-1. • Annual numbers for MI or fatal CHD in the NHLBI-
• According to data from NHANES 2013 to 2016 sponsored ARIC study and CHS stratified by age
(unpublished NHLBI tabulation), the overall preva- and sex are displayed in Chart 19-5. Incidence of
lence for angina is 3.6% in US adults ≥20 years of heart attacks or fatal CHD stratified by age, race,
age (Table 19-2). and sex is displayed in Chart 19-6.
• According to data from NHANES for the period • Incidence of MI by age, sex, and race in the NHLBI-
1988 to 2012, angina prevalence declined in sponsored ARIC study is displayed in Chart 19-7.
NH whites (from 4.0% to 2.1%) but not in NH Black males have a higher incidence of MI in all
blacks (from 4.9% to 4.4%) and in both males age groups.
and females ≥65 years old (males from 5.1% to • HRs for incident fatal CHD were higher for black
2.9%, females from 5.6% to 2.4%).2 males than for white males aged 45 to 65 years
• Data from the BRFSS 2016 survey indicated that (ARIC: 2.09 [95% CI, 1.42–3.06]; REGARDS:
4.4% of respondents had been told that they 2.11 [95% CI, 1.32–3.38]). Nonfatal CHD risk
Downloaded from http://ahajournals.org by on February 7, 2019

had had an MI. The highest prevalence was was lower (ARIC: 0.82 [95% CI, 0.64–1.05];
in Kentucky (6.4%), and the lowest was in the REGARDS: 0.94 [95% CI, 0.69–1.28]). However,
District of Columbia and California (2.8%; age- after adjustment for social determinants of health
adjusted) (Chart 19-3).3 and cardiovascular risk factors, black males and
• In the same survey, 4.1% of respondents had females have similar risk for fatal CHD but lower
been told that they had angina or CHD. The risk for nonfatal CHD.7
highest prevalence was in Puerto Rico (7.0%) • In 9498 participants in the ARIC study, whites
and West Virginia (6.5%), and the lowest was in had a higher rate of clinically recognized MI than
the District of Columbia and Utah (2.6%; age- blacks (5.04 versus 3.24 per 1000 person-years,
adjusted) (Chart 19-4).3 P=0.002).8
Incidence Trends in Incidence
(See Table 19-1 and Charts 19-5 through 19-7) • The overall body of literature suggests that
• Approximately every 40 seconds, an American the incidence of MI has declined significantly
will have an MI (AHA computation). over time, including over the past decade.9
• On the basis of data from the 2005 to 2014 ARIC Geographic differences in patient populations,
study of the NHLBI4: temporal changes in the criteria used to diag-
— This year, ≈720 000 Americans will have a nose MI, and differences in study methodology
new coronary event (defined as first hospi- increase the complexity of interpreting these
talized MI or CHD death), and ≈335 000 will studies, however.
have a recurrent event. • In Olmsted County, MN, between 1995 and
— The estimated annual incidence of MI is 2012, the population rate of MI declined 3.3%
605 000 new attacks and 200 000 recurrent per year; however, these declines varied among
attacks. Of these 805 000 first and recur- types of MI, with the greatest declines occurring
rent events, it is estimated that 170 000 for prehospital fatal MI.10
are silent. • According to data from ARIC and the REGARDS
— Average age at first MI is 65.6 years for males study, between 1987 to 1996 and 2003 to 2009,
and 72.0 years for females. the incidence of CHD declined from 3.9 to 2.2

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e361

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

per 1000 person-years in people without DM and CHD risk prediction more since the publication
CLINICAL STATEMENTS

from 11.1 to 5.4 per 1000 person-years among of the 2013 ACC/AHA cholesterol management
AND GUIDELINES

those with DM.11 guideline.19

• Among Medicare beneficiaries between 2002 • The ASCVD tool might overestimate risk across all
and 2011, the incidence of MI hospitalization strata of risk compared with external contempo-
declined from 1485 to 1122 per 100 000 per- rary cohorts (Physicians’ Health Study, Women’s
son-years. The incidence of MI as the primary Health Study, and WHI Observational Study),
reason for hospitalization decreased over time as well as in reanalysis of the original validation
(from 1063 to 677 per 100 000 person-years cohorts. However, some of the subsequent analy-
between 2002 and 2011), whereas the percent- ses were not conducted in comparable popula-
age of MIs as a secondary reason for hospital- tions as the original study cohorts.20
ization increased (from 190 to 245 per 100 000
Mortality
person-years). The percentage of MIs that were
(See Table 19-1)
attributable to a secondary diagnosis increased
• On the basis of 2016 mortality data21:
from 28% to 40%.12
— CHD mortality was 363 452, and CHD any-
• Among Medicare beneficiaries, the incidence of
mention mortality was 533 126 (unpublished
primary hospitalization for MI between 2002 and
NHLBI tabulation) (Table 19-1).
2011 declined by 36.6% among NH whites (from
— MI mortality was 111 777. MI any-mention
1057 to 670 per 100 000 person-years between
mortality was 149 615 (unpublished NHLBI
2002 and 2011) and by 26.4% among NH blacks
tabulation) (Table 19-1).
(from 966 to 711 per 100  000 person-years
• From 2006 to 2016, the annual death rate attrib-
between 2002 and 2011).13
utable to CHD declined 31.8% and the actual
Predicted Risk number of deaths declined 14.6% (unpublished
• The percentage of US adults with a 10-year pre- NHLBI tabulation).
dicted ASCVD risk (using pooled-cohort risk • CHD age-adjusted death rates per 100 000 were
equations) ≥20% decreased from 13.0% in 1999 132.3 for NH white males, 146.5 for NH black
to 2000 to 9.4% in 2011 to 2012. The proportion males, and 95.6 for Hispanic males; for NH white
of US adults with 10-year predicted ASCVD risk of females, the rate was 67.9; for NH black females,
Downloaded from http://ahajournals.org by on February 7, 2019

7.5% to <20% was 23.9% in 1999 to 2000 and it was 85.4; and for Hispanic females, it was 54.6
26.8% in 2011 to 2012.14 (unpublished NHLBI tabulation).
• For adults with optimal risk factors (TC of 170 • 77% of CHD deaths occurred out of the hospital.
mg/dL, HDL-C of 50 mg/dL, SBP of 110 mm Hg According to NCHS mortality data, 279 171 CHD
without antihypertensive medication use, no DM, deaths occur out of the hospital or in hospital EDs
and not a smoker), 10-year CVD risk ≥7.5% will annually (NCHS, AHA tabulation).
occur at age 65 years for white males, 70 years • The estimated average number of years of life
for black males and females, and 75 years for lost because of an MI death is 16.2 (unpublished
white females.15 NHLBI tabulation).
• In the REGARDS study, the adjusted HR for CHD • Approximately 35% of the people who experi-
death associated with any versus no stroke symp- ence a coronary event in a given year will die as a
toms was 1.50 (95% CI, 1.10–2.06).16 Individuals result of it, and ≈14% who experience an MI will
with atherosclerotic stroke should be included die of it (AHA computation).
among those deemed to be at high risk (20% • Life expectancy after AMI treated in hospitals
over 10 years) of further atherosclerotic coronary with high performance on 30-day mortality
events. For primary prevention, ischemic stroke measures compared with low-performing hos-
should be included among CVD outcomes in pitals was on average between 0.74 and 1.14
absolute risk assessment algorithms. The inclusion years longer.22
of atherosclerotic ischemic stroke as a high-risk • Among 194 071 adults who were hospitalized for
condition has important implications, because the an AMI in the 2009 to 2010 NIS, in-hospital mor-
number of people considered to be at high risk tality for those <65 years of age was higher for
will increase over time.17 Hispanic females (3.7%) than for black females
• A survey of US family physicians, general inter- (3.1%) and white females (2.5%). Differences
nists, and cardiologists published in 2012 found were smaller for males <65 years of age. Among
that 41% of respondents reported using global older adults (≥65 years), in-hospital mortality was
CHD risk assessment at least occasionally.18 It 8.0% for white females and between 6% and
is unclear whether physicians are using global 8% for other race-sex groups.23

e362 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

• In a study using data from the Cooperative reduction in HF and mortality after MI. In a nation-

CLINICAL STATEMENTS
Cardiovascular Project, survival and life expec- wide Swedish registry of 199 851 patients admit-

AND GUIDELINES
tancy after AMI were higher in whites than in ted with AMI from 1996 to 2008, the incidence of
blacks (7.4% versus 5.7%). White patients living HF decreased from 46% to 28%, with a greater
in high SES areas showed the longest life expec- decline in individuals with STEMI compared with
tancy. Gaps in life expectancy between white and NSTEMI.32 The in-hospital, 30-day, and 1-year
black patients were largest among high SES areas, mortality rates for those with HF decreased from
with smaller differences in medium and low SES 19% to 13%, 23% to 17%, and 36% to 31%,
areas. These differences were attenuated but did respectively (all P<0.001). In Olmsted County,
not disappear after adjustment for patient and MN, from 1990 to 2010, there was a decline in
treatment characteristics.24 mortality associated with HF after MI, but this risk
• Compared with nonparticipants, participants in was greater for delayed HF than for early-onset
SNAP have twice the risk of CVD mortality, which HF after MI.33
likely reflects differences in socioeconomic, envi- • Taking into account past trends in CHD mortal-
ronmental, and behavioral characteristics.25 ity from 1980, and considering age-period and
cohort effects, CHD mortality is likely to con-
Temporal Trends in Mortality tinue its decades-long decline, with a reduction
• The decline in CHD mortality rates in part reflects in deaths by 2030 of 27%; however, race dispari-
the shift in the pattern of clinical presentations of ties will persist.34 Recent reports have suggested
AMI. There has been a marked decline in STEMI a slowing down of all CVD and HD mortality in
(from 133 to 50 cases per 100 000 person-years recent years.35,36
from 1999 to 2008).26
• In Olmsted County, MN, the age- and sex- Awareness of Warning Signs and Risk for HD
adjusted 30-day case fatality rate decreased by • In 2012, NH black and Hispanic females had
56% from 1987 to 2006.27 Among Medicare lower awareness than white females that HD/
fee-for-service beneficiaries, between 1999 and heart attack is the leading cause of death for
2011, the 30-day mortality rate after hospitalized females.37
MI declined by 29.4%.28 • The percentages of females in 2012 identifying
• In a community-based study of Worcester, MA, warning signs for a heart attack were as fol-
Downloaded from http://ahajournals.org by on February 7, 2019

the percentage of patients dying after cardiogenic lows: pain in the chest—56%; pain that spreads
shock during their hospitalization for MI declined to the shoulder, neck, or arm—60%; shortness
from 47.1% in 2001 to 2003 to 28.6% in 2009 of breath—38%; chest tightness—17%; nau-
to 2011.29 sea—18%; and fatigue—10%.37
• Between 2001 and 2011 in the NIS, in-hospital • The 5 most commonly cited HD prevention strat-
mortality did not change for patients with STEMI egies in 2012 were maintaining a healthy BP
with a PCI (3.40% and 3.52% in 2001 and 2011, (78%), seeing the doctor (78%), and increasing
respectively) or CABG (5.79% and 5.70% in 2001 fiber intake, eating food with antioxidants, and
and 2011, respectively) and increased for patients maintaining healthy cholesterol levels (each
with no intervention (12.43% and 14.91% in 66%).37
2001 and 2011, respectively). In-hospital mortal- • Among online survey participants, 21%
ity declined for patients with NSTEMI undergoing responded that their doctor had talked to them
CABG (from 4.97% to 2.91%) or no procedure about HD risk. Rates were lower among Hispanic
(from 8.87% to 6.26%) but did not change for females (12%) than whites (22%) or blacks (22%)
and increased with age from 6% (25–34 years) to
patients with NSTEMI undergoing PCI (1.73%
33% (≥65 years).37
and 1.45%).30
• Among 2009 females and 976 males <55
• Among US males <55 years of age, CHD mortal-
years of age hospitalized for MI, only 48.7%
ity declined an annual 5.5% per year between
of females and 52.9% of males reported being
1979 and 1989; a smaller decline was present
told they were at risk for HD or a heart problem.
in 1990 to 1999 (1.2% per year) and in 2000 to
Also, 50.3% of females and 59.7% of males
2011 (1.8% per year). Among US females <55
reported their healthcare provider discussing HD
years of age, CHD mortality declined an annual
and things they could do to take care of their
4.6% per year in 1979 to 1989, with no decline
heart.38
between 1990 and 1999 and a decline of 1.0%
in 2000 to 2011.31 Time of Symptom Onset and Arrival at Hospital
• Reflecting trends in change in type and severity • Data from Worcester, MA, indicate that the
of AMI, studies worldwide have documented a median time from symptom onset to hospital

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e363

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

arrival did not improve from 2001 through 2011. coronary arteries (<50% stenosis) had lower
CLINICAL STATEMENTS

In 2009 to 2011, 48.9% of patients reached the in-hospital mortality than patients with obstruc-
AND GUIDELINES

hospital within 2 hours of symptom onset com- tive CAD (1.1% versus 2.9%; P<0.001).
pared with 45.8% in 2001 to 2003.39 Nonobstructive coronary arteries were more
• Among patients hospitalized for ACS between common in females than males (10.5% versus
2001 and 2011 in the NIS, those with STEMI 3.4%; P<0.001), but no difference in in-hospital
admitted on the weekend versus on a weekday mortality was observed between females and
had a 3% higher odds of in-hospital mortality. males with nonobstructive coronary arteries
Those admitted on the weekend versus weekday (P=0.84).47
for non–ST-elevation ACS had a 15% higher odds • On the basis of pooled data from the FHS, ARIC,
of in-hospital mortality. The excess mortality asso- CHS, MESA, CARDIA, and JHS studies of the
ciated with weekend versus weekday admission NHLBI (1995–2012), within 1 year after a first MI
decreased over time.40 (unpublished NHLBI tabulation):
• A retrospective analysis of the NHAMCS data — At ≥45 years of age, 18% of males and 23%
from 2004 to 2011 that reviewed 15 438 visits of females will die.
related to ACS symptoms suggested that blacks — At 45 to 64 years of age, 3% of white males,
have a 30% longer waiting time than whites, the 5% of white females, 9% of black males,
reasons for which are unclear.41 and 10% of black females will die.
• The timing of hospital admission influences man- — At 65 to 74 years of age, 14% of white
agement of MI. A study of the NIS database from males, 18% of white females, 22% of black
2003 to 2011 indicated that admission on a males, and 21% of black females will die.
weekend for NSTEMI was associated with a sig- — At ≥75 years of age, 27% of white males,
nificantly reduced odds for coronary angiography 29% of white females, 19% of black males,
(OR, 0.88 [95% CI, 0.89–0.90]; P<0.001) and and 31% of black females will die.
early invasive strategy (OR, 0.48 [95% CI, 0.47– • In part because females have MIs at older ages
0.48]; P<0.001), with consequences of greater than males, they are more likely to die of MI
mortality.42 within a few weeks.
• Within 5 years after a first MI:
Complications — At ≥45 years of age, 36% of males and 47%
Downloaded from http://ahajournals.org by on February 7, 2019

• In a pooled analysis of individuals after PCI in sev- of females will die.

eral RCTs, those with STEMI had a greater risk of — At 45 to 64 years of age, 11% of white
death within the first 30 days after PCI than those males, 17% of white females, 16% of
with stable IHD, whereas those with NSTEMI had black males, and 28% of black females
a greater risk of death during the entire 2 years of will die.
follow up.43 — At 65 to 74 years of age, 25% of white
• From the NCDR registry, in 2014 the unadjusted males, 30% of white females, 33% of black
rate of acute kidney injury was 2.6% (versus males, and 44% of black females will die.
2.3% in 2011), of blood transfusion was 1.4% — At ≥75 years of age, 55% of white males,
(versus 1.9% in 2011), of postprocedural stroke 60% of white females, 61% of black males,
was 0.2% (versus 0.2% in 2011), of emergency and 64% of black females will die.
CABG surgery was 0.2% (versus 0.3% in 2011), • Of those who have a first MI, the percentage with
and of vascular access site injury was 1.3% (ver- a recurrent MI or fatal CHD within 5 years is as
sus 1.2% in 2011).44 follows:
• STEMI confers greater in-hospital risks than — At ≥45 years of age, 17% of males and 21%
NSTEMI, including death (6.4% for STEMI, 3.4% of females.
for NSTEMI), cardiogenic shock (4.4% versus — At 45 to 64 years of age, 11% of white
1.6%, respectively), and bleeding (8.5% versus males, 15% of white females, 22% of black
5.5%, respectively).45 males, and 32% of black females.
• Among females with AMI, those with spontane- — At 65 to 74 years of age, 12% of white
ous coronary artery dissection had higher odds males, 17% of white females, 30% of black
of in-hospital mortality (6.8%) than females males, and 30% of black females.
without spontaneous coronary artery dissec- — At ≥75 years of age, 21% of white males,
tion (3.8%; OR, 1.87 [95% CI, 1.65–2.11]; 20% of white females, 45% of black males,
P<0.001).46 and 20% of black females.
• In the NCDR ACTION Registry–GWTG, patients • The percentage of people with a first MI who will
with STEMI or NSTEMI with nonobstructive have HF in 5 years is as follows:

e364 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

— At ≥45 years of age, 16% of males and 22% 31.5% in 2001 to 2003 to 27.3% in 2009 to

CLINICAL STATEMENTS
of females. 2011.51 Crude 30-day rehospitalization rates

AND GUIDELINES
— At 45 to 64 years of age, 6% of white males, decreased from 20.5% in 2001 to 2003 to 15.8%
10% of white females, 13% of black males, in 2009 to 2011.52
and 25% of black females.
Cardiac Rehabilitation
— At 65 to 74 years of age, 12% of white
• In the NCDR ACTION Registry–GWTG, cardiac
males, 16% of white females, 20% of black
rehabilitation referral after patients were admit-
males, and 32% of black females.
ted with a primary diagnosis of STEMI or NSTEMI
— At ≥75 years of age, 25% of white males,
increased from 72.9% to 80.7% between 2007
27% of white females, 23% of black males,
and 2012.53
and 19% of NH black females.
• In the NCDR between 2009 and 2012, 59%
• The percentage of people with a first MI who of individuals were referred to cardiac reha-
will have an incident stroke within 5 years is as bilitation after PCI, with significant site-specific
follows: variation.54
— At ≥45 years of age, 4% of males and 7% of • In a community-based analysis of residents in
females. Olmsted County, MN, discharged with first MI
— At ≥45 years of age, 5% of white males, 6% between 1987 and 2010, 52.5% participated in
of white females, 4% of black males, and cardiac rehabilitation. The overall rate of partici-
10% of black females. pation did not change during the study period.
• The median survival time (in years) after a first MI Cardiac rehabilitation was associated with reduc-
is as follows: tions in all-cause mortality and readmission.55 A
— At ≥45 years of age, 8.2 for males and 5.5 dose-response association between rehabilita-
for females. tion session attendance and lower risk of MI
— At ≥45 years of age, 8.4 for white males, 5.6 and death was similarly seen in elderly Medicare
for white females, 7.0 for black males, and beneficiaries.56
5.5 for black females. • In the BRFSS from 2005 to 2015, <40% of
Rehospitalizations patients self-reported participation in cardiac
• The burden of rehospitalizations for AMI may rehabilitation after AMI. Between 2011 and
Downloaded from http://ahajournals.org by on February 7, 2019

be substantial: A retrospective cohort study of 2015, patients who declared participation in car-
78 085 Medicare beneficiaries ≥66 years of age diac rehabilitation were less likely to be female
without recent CHD history who were hospi- (OR, 0.76 [95% CI, 0.65–0.90]; P=0.002) or
talized for AMI in 2000 to 2010 reported that black (OR, 0.70 [95% CI, 0.53–0.93]; P=0.014),
20.6% had at least 1 rehospitalization during were less well educated (high school versus col-
the 10 years after the index MI. Among patients lege graduate: OR, 0.69 [95% CI, 0.59–0.81],
with a CHD rehospitalization, 35.9% had ≥2 P<0.001; less than high school versus col-
CHD rehospitalizations. Males and patients ≥85 lege graduate: OR, 0.47 [95% CI 0.37–0.61],
years of age had greater rate ratios for first P<0.001), and were more likely to be retired or
rehospitalization.48 self-employed (OR, 1.39 [95% CI, 1.24–1.73];
• A study of 3  250  194 Medicare beneficiaries P=0.003) than patients who did not participate
admitted for PCI found that readmission rates in cardiac rehabilitation.57
declined slightly from 16.1% in 2000 to 15.4% in Hospital Discharges and Ambulatory Care Visits
2012. The majority of readmissions were because (See Table 19-1 and Chart 19-8)
of chronic IHD (26.6%), HF (12%), and chest • From 2004 to 2014, the number of inpatient dis-
pain/angina (7.9%). A minority (<8%) of total charges from short-stay hospitals with CHD as the
readmissions were for AMI, UA, or cardiac arrest/ first-listed diagnosis decreased from 1 879 000
cardiogenic shock.49 to 1  021 000 (unpublished NHLBI tabulation)
• Rehospitalization can be influenced by clinical, (Table 19-1).
psychosocial, and sociodemographic characteris- • From 1997 through 2014, the number of hospi-
tics not accounted for in traditional Centers for tal discharges for CHD was higher for males than
Medicare & Medicaid Services claims-based mod- females (Chart 19-8).
els, including prior PCI, CKD, low health literacy, • In 2015, there were 11 682 000 physician office
lower serum sodium levels, and lack of cigarette visits for CHD (NAMCS, NHLBI tabulation).58
smoking.50 In 2015, there were 463 000 ED visits with a
• In a study of 3 central Massachusetts hospitals, primary diagnosis of CHD (NHAMCS, NHLBI
the 90-day rehospitalization rate declined from tabulation).59

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e365

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

• Total office visits for angina declined from 3.6 stroke (HR, 1.43 [95% CI, 1.05–1.95]; P=0.026),
CLINICAL STATEMENTS

million per year in 1995 to 1998 to 2.3 million cardiovascular death (HR, 2.17 [95% CI, 1.24–
AND GUIDELINES

per year in 2007 to 2010 based on data from the 3.81]; P=0.007), and major adverse cardiovascu-
NAMCS and NHAMCS.60 lar and cerebrovascular events (HR, 1.68 [95% CI,
• In the CathPCI registry, a composite of use of 1.31–2.15]; P<0.001).65
evidence-based medical therapies, including • In the NIS, isolated CABG procedures decreased
aspirin, P2Y12 inhibitors, and statins, was high by 25.4% from 2007 to 2011 (326 to 243 cases
(89.1% in 2011 and 93.3% in 2014). However, per million adults), particularly at higher-volume
in the ACTION–GWTG registry, metrics that centers. Low-volume centers were associated
were shown to need improvement were defect- with greater risk of all-cause in-hospital mortal-
free care (median hospital performance rate of ity in multivariable analysis (OR, 1.39 [95% CI,
78.4% in 2014), P2Y12 inhibitor use in eligible 1.24–1.56]; P<0.001).66
medically treated patients with AMI (56.7%), • According to the NIS, the number of PCI proce-
and the use of aldosterone antagonists in dures declined by 38% between 2006 and 2011.
patients with LV systolic dysfunction and either Among patients with stable IHD, a 61% decline in
DM or HF (12.8%).44 PCI occurred over this time period.67
Operations and Procedures • In Washington State, the overall number of PCIs
• In 2014, an estimated 480  000 percutaneous decreased by 6.8% between 2010 and 2013,
transluminal coronary angioplasties, 371  000 with a 43% decline in the number of PCIs per-
inpatient bypass procedures, 1 016 000 inpatient formed for elective indications.68
diagnostic cardiac catheterizations, 86 000 carotid • Among Medicare fee-for-service beneficiaries, the
endarterectomies, and 351 000 pacemaker proce- total number of revascularization procedures per-
dures were performed for inpatients in the United formed peaked in 2010 and declined by >4% per
States (unpublished NHLBI tabulation). year through 2012. In-hospital and 90-day mor-
• In an analysis of the BEST, PRECOMBAT, and tality rates declined after CABG surgery overall,
SYNTAX trials comparing individuals with MI as well as among patients presenting for elective
and who had left main or multivessel CAD, the CABG or CABG after NSTEMI.69
outcomes of CABG versus PCI were examined. • Between 2011 and 2014, the use of femo-
Downloaded from http://ahajournals.org by on February 7, 2019

CABG was associated with a lower risk of recur- ral access declined (from 88.8% to 74.5%)
rent MI and repeat revascularizations.61 In patients and radial access increased (from 10.9% to
with multivessel CAD, CABG was associated with 25.2%).44
lower all-cause and cardiovascular mortality; • In a meta-analysis of 13 observational studies
however, no differences in all-cause and cardio- and 3 RCTs, a transradial approach for PCI was
vascular mortality between CABG and PCI were associated with a reduction in vascular complica-
observed among patients with multivessel plus tions (OR, 0.36 [95% CI, 0.30–43]) and stroke
left main CAD.62 (OR, 0.79 [95% CI, 0.64–0.97]) compared with
• In a meta-analysis of 6 randomized trials that a transfemoral approach. A transradial approach
included 4686 patients with unprotected left was also associated with a reduced risk of death
main CAD, no significant differences in all- (OR, 0.56 [95% CI, 0.45–0.69]), although this
cause and cardiovascular mortality or a com- was driven by the observational studies, because
posite outcome of death, MI, or stroke were no association with death was observed in the
observed between patients treated with PCI randomized trials.70
versus CABG. However, PCI was associated with • In 2014, from the CathPCI registry, median door-
a lower risk of the composite outcome within to-balloon time for primary PCI for STEMI was 59
the first 30 days of follow-up (HR, 0.64 [95% CI, minutes for patients receiving PCI in the present-
0.47–0.87]).63 ing hospital and 107 minutes for patients trans-
• In 5-year follow-up of the SYNTAX trial, greater ferred from another facility for therapy.44
MI-related death in PCI patients was associated • The importance of adherence to optimal medical
with the presence of DM, 3-vessel disease, or high therapy was highlighted in an 8-hospital study of
SYNTAX scores.64 NSTEMI patients, in which medication nonadher-
• At 5 years of follow-up in the SYNTAX and BEST ence was associated with a composite outcome
randomized trials, patients with multivessel CAD of all-cause mortality, nonfatal MI, and reinter-
involving the proximal left anterior descending vention (HR, 2.79 [95% CI, 2.19–3.54]; P<0.001).
coronary artery, PCI was associated with increased In propensity-matched analysis, CABG outcomes
composite outcome of all-cause death, MI, or were favorable compared with PCI in patients

e366 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

nonadherent to medical therapy (P=0.001), but • In a study using the NIS and the State Inpatient

CLINICAL STATEMENTS
outcomes were similar in medicine-adherent Databases for the year 2009, mean charge per

AND GUIDELINES
patients (P=0.574).71 ACS discharge was $63 578 (median $41 816).
Mean charges, however, were greater for the first
Cost
compared with the second admission ($71 336
• The estimated direct costs of HD in 2014 to 2015
versus $53 290, respectively).76
(average annual) were $109.4 billion (MEPS,
• On the basis of medical, pharmacy, and disabil-
NHLBI tabulation).
ity insurance claims data from 2007 to 2010,
• The estimated direct and indirect cost of HD in
short-term productivity losses associated with
2014 to 2015 (average annual) was $218.7 billion
ACS were estimated at $7943 per disability claim,
(MEPS, NHLBI tabulation).
• A study of the NIS from 2001 to 2011 showed with long-term productivity losses of $52 473 per
that costs per hospitalization increased signifi- disability claim. ACS also resulted in substantial
cantly for patients who underwent intervention, wage losses, from $2263 to $20 609 per dis-
but not for those without intervention.30 ability claim, for short- and long-term disability,
• MI ($12.1 billion) and CHD ($9.0 billion) were 2 respectively.77
of the 10 most expensive conditions treated in US • According to data from the NIS, between 2001
hospitals in 2013.72 and 2011, the use of PCI for patients with ACS
• Between 2015 and 2030, medical costs of CHD declined by 15%.67
are projected to increase by ≈100%.73 • In a report from the TRACE-CORE study, per-
• In a multipayer administrative claims data- sons with recurrent ACS were more likely to
base of patients with incident inpatient PCI report anxiety, depression, higher perceived
admissions between 2008 and 2011, post-PCI stress, and lower mental and physical qual-
angina and chest pain were common and costly ity of life; were more likely to have impaired
($32 437 versus $17 913; P<0.001 at 1 year cognition; and had lower levels of health liter-
comparing those with and without angina or acy and health numeracy than persons with a
chest pain).74 first ACS.78
• Among Medicare beneficiaries linked to the NCDR • In the NIS from 2012 to 2013, females with
CathPCI Registry with inpatient or outpatient PCI non–ST-elevation ACS treated with an early
Downloaded from http://ahajournals.org by on February 7, 2019

between July 2009 and December 2012, costs invasive strategy had lower in-hospital mortality
were $3502 (95% CI, $3347–$3648; P<0.001) than females treated conservatively (2.1% versus
lower for patients with same-day discharge com- 3.8%). However, the survival advantage for inva-
pared with those not discharged the same day. sive management was restricted to females with
Although a minority of patients receive transra- NSTEMI (OR, 0.52 [95% CI, 0.46–0.58]), and no
dial intervention and same-day discharge (1.2%), differences in in-hospital survival for invasive ver-
a cost savings of $3689 (95% CI, $3486-$3902; sus conservative treatment were observed among
P<0.001) was observed compared with patients females with UA.79
with transfemoral intervention not discharged the • In a meta-analysis of 8 randomized trials, the risk
same day.75 of long-term all-cause mortality at a mean of 10.3
years of follow-up was similar for non–ST-eleva-
tion ACS patients treated with a routine strategy
Acute Coronary Syndrome (coronary angiography within 24 to 96 hours of
ICD-9 410, 411; ICD-10 I20.0, I21, I22. presentation) versus a selective invasive strat-
• In 2014, there were 633 000 ACS principal diag- egy (medical stabilization with or without coro-
nosis discharges. Of these, an estimated 389 000 nary angiography in those who demonstrated
were males, and 244 000 were females. This esti- evidence of ischemia on noninvasive stress test
mate was derived by adding the principal diag- or with ongoing symptoms) at 28.5% for both
noses for MI (609 000) to those for UA (24 000; strategies.80
HCUP, NHLBI).
• When secondary discharge diagnoses in 2014
Stable AP
were included, the corresponding number of
inpatient hospital discharges was 1  339 000 ICD-9 413; ICD-10 I20.1 to I20.9.
unique hospitalizations for ACS; 785 000 were Prevalence
males, and 554 000 were females. Of the total, (See Table 19-2 and Charts 19-9)
957 000 were for MI alone, and 382 000 were for • According to data from NHANES 2013 to
UA alone (HCUP, NHLBI). 2016, the prevalence of AP among adults

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e367

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

(≥20 years of age) is 3.6% (9.4 million adults) power, and resources throughout local communi-
CLINICAL STATEMENTS

(Table 19-2). ties, nations, and the world.83

AND GUIDELINES

• The prevalence of AP increased with age from • In an analysis of a population-based register

<1% among males and females 20 to 39 years sample of adults aged 40 to 60 years in Finland
of age to >10% among males and females ≥80 in 1995 (N=302  885) followed up until the
years of age (Chart 19-9). end of 2007, MI incidence and mortality were
• On the basis of data from NHANES from 1998 examined in relation to living arrangements
to 2004 and the six 2-year surveys from 2001 to (living with a marital partner was contrasted
2012, in 2009 to 2012, there were an average of to 3 alternatives: cohabiting with nonmarital
3.4 million people ≥40 years of age in the United partner, coresidence with people other than a
States with angina each year, compared with 4 partner, and living alone). Living arrangements
million in 1988 to 1994. Declines in angina symp-
were strong determinants for survival after MI
toms have occurred for NH whites but not for NH
independent of other sociodemographic fac-
blacks.2
tors. The results demonstrated greater fatal-
• In Americans ≥40 years of age with health insur-
ity associated with living alone in males (HR.
ance, age-adjusted angina prevalence declined
from 7.8% in 2001 to 2002 to 5.5% in 2011 1.50 [95% CI, 1.29–1.75]) and suggested that
to 2012 (P for trend <0.001), whereas in those cohabitation in midlife might be associated with
without health insurance, there was an increase a greater fatality risk in females (HR, 2.00 [95%
from 4.7% to 7.6%, albeit not statistically CI 1.26–3.17]).84
significant.81 • In an analysis of nationally representative longi-
• Among patients with a history of CAD (ACS, prior tudinal register data to examine how childhood
coronary revascularization procedure, or stable socioeconomic factors and later socioeconomic
angina), 32.7% self-reported at least 1 episode attainment were associated with MI incidence
of angina over the past month. Of those report- and fatality in Finnish adults who experienced
ing angina, 23.3% reported daily or weekly symp- their childhoods during the period from 1940
toms of angina, and 56.3% of these patients with to the 1950s, when the country was still poor,
daily or weekly angina were taking at least 2 anti- MI hospitalizations and mortality in 1988 to
Downloaded from http://ahajournals.org by on February 7, 2019

anginal medications.82 2010 were studied in those who were up to 14

Incidence years of age at the time of the census and resi-
(See Table 19-2) dent in Finland in 1987 (N= 94 501). Crowding
• The annual rates per 1000 population of new increased the risk of MI incidence by 16%
episodes of AP for NH black males are 28.3 (95% CI, 5%–29%) in males and 25% (95%
for those 65 to 74 years of age, 36.3 for those CI, 3%–50%) in females. Most aspects of child-
75 to 84 years of age, and 33.0 for those ≥85 hood circumstances did not strongly influence
years of age. For nonblack females in the same long-term fatality risk. Income and education
age groups, the rates are 14.1, 20.0, and 22.9, remained associated with MI incidence when
respectively. For black males, the rates are 22.4, adjusted for unobserved shared family factors
33.8, and 39.5, and for black females, the rates in siblings. Low adult socioeconomic resources
are 15.3, 23.6, and 35.9, respectively (CHS, remained a strong determinant of MI incidence
NHLBI). and fatality.85
• The incidence of AP for adults ≥45 years of age • Among US adults aged 45 to 74 years in 2009 to
is higher in males (370 000) than it is in females 2013, factors accounting for the US county varia-
(195 000) (Table 19-2). tion in CVD mortality included demographic com-
position (36% of the variation in county CVD);
Social Determinants economic/social conditions (32%); and health-
• Social determinants of health are complex, inte- care utilization, features of the environment, and
grated, and overlapping social structures and health indicators (6%).86
economic systems that are responsible for most • In a follow-up study of consecutive patients ≤65
health inequities.83 These social structures and years old discharged from 8 hospitals after first MI
economic systems include the social environment, in central Israel, living in poor SES neighborhoods
physical environment, health services, and struc- was associated with greater risk for recurrent MI
tural and societal factors. Social determinants of (HR, 1.55 [95% CI, 1.13–2.14) and UA (HR, 1.48
health are shaped by the distribution of money, [95% CI, 1.22–1.79).87

e368 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

Genetics and Family History but very few have identified consistent, repli-

CLINICAL STATEMENTS
cated, and independent genetic variants, and all
Family History as a Risk Factor

AND GUIDELINES
have had small effect sizes. The total number
• Among adults ≥20 years of age, 12.4% (SE
of CAD-associated regions is 73, with 15 novel
0.5%) reported having a parent or sibling with
CAD associations related to atherosclerosis and
a heart attack or angina before the age of 50
years. The racial/ethnic breakdown from NHANES traditional risk factors but also highlighting the
2013 to 2016 is as follows (unpublished NHLBI importance of key biological process in the arte-
tabulation): rial wall.93
— For NH whites, 12.2% (SE 1.0%) for males, • Over the past decade, the application of GWASs
15.0% (SE 0.9%) for females. to large cohorts of CHD case and control subjects
— For NH blacks, 7.1% (SE 0.9%) for males, has identified many consistent genetic variants
14.0% (SE 1.3%) for females. associated with CHD.
— For Hispanics, 7.7% (SE 0.6%) for males, • The first GWAS identified the now most consis-
10.7% (SE 0.5%) for females. tently replicated genetic marker for CHD and MI
— For NH Asians, 6.3% (SE 0.9%) for males, in European-derived populations, on chromo-
4.6% (SE 0.8%) for females. some 9p21.3.94 The frequency of the primary SNP
• HD occurs as people age, so the prevalence of is very common (50% of the white population is
family history will vary depending on the age at estimated to harbor 1 risk allele, and 23% har-
which it is assessed. The breakdown of reported bors 2 risk alleles).95
family history of heart attack by age of survey — The 10-year HD risk for a 65-year-old male
respondent in the US population as measured by with 2 risk alleles at 9p21.3 and no other
NHANES 2013 to 2016 is as follows (unpublished traditional risk factors is ≈13.2%, whereas
NHLBI tabulation): a similar male with 0 alleles would have a
— Age 20 to 39 years, 8.5% (SE 1.0%) for 10-year risk of ≈9.2%. The 10-year HD risk
males, 9.9% (SE 0.6%) for females. for a 40-year-old female with 2 alleles and
— Age 40 to 59 years, 11.4% (SE 1.4%) for no other traditional risk factors is ≈2.4%,
males, 16.9% (SE 1.2%) for females. whereas a similar female with 0 alleles would
— Age 60 to 79 years, 13.6% (SE 1.7%) for have a 10-year risk of ≈1.7%.95
Downloaded from http://ahajournals.org by on February 7, 2019

males, 16.6% (SE 1.6%) for females. • The association of SNPs with incident CHD was
— Age ≥80 years, 12.5% (SE 2.7%) for males, investigated in a large multiethnic study of mul-
13.6% (SE 2.6%) for females. tiple cohorts in the United States (including
• Family history of premature angina, MI, angio- NHANES, WHI, the Multiethnic Cohort Study,
plasty, or bypass surgery increases lifetime risk by CHS, ARIC, CARDIA, HCHS/SOL, and SHS). SNPs,
≈50% for both HD (from 8.9% to 13.7%) and including in 9p21, APOE, and LPL, were associ-
CVD mortality (from 14.1% to 21%).88 ated with incident CHD in individuals of European
• In the FHS, addition of a family history of prema- ancestry but not African Americans. Effect sizes
ture CVD provided improved prognostic value were greater for those ≤55 years of age and in
over traditional risk factors.89 females.96
• Among people with a family history, CAC is a • More recently, genetic studies of CHD have
robust marker of ASCVD risk.90 focused on the coding regions of the genome
• In premature ACS (age ≤55 years), a greater per- (exons) and have identified additional genes and
centage of females (28%) than males (20%) have SNPs for CHD, including loss-of-function muta-
a family history of CAD (P=0.008). Compared tions in the angiopoietin-like 4 (ANGPTL4) gene,
with patients without a family history, patients which is an inhibitor of lipoprotein lipase. These
with a family history of CAD have a higher preva- mutations are associated with low plasma triglyc-
lence of traditional CVD risk factors.91 erides and high HDL-C.97
• Among patients with STEMI in the NIS between • In a discovery analysis of common SNPs (minor
2003 and 2011, those with a family history of allele frequency of >5%) on an exome array, 6
CAD were more likely to undergo coronary inter- new loci associated with CAD were identified,
vention and had lower in-hospital mortality than including SNPs on the KCNJ13-GIGYF2, C2,
patients without a family history (OR, 0.45 [95% MRVI1-CTR9, LRP1, SCARB1, and CETP genes.98
CI, 0.43–0.47]; P<0.001).92 • In the DiscovEHR study, loss-of-function variants
• For the past 20 years, candidate gene studies in the angiopoietin-like 3 gene (ANGPTL3) were
have been conducted to identify the genetic less common in patients with CAD than in con-
variants underlying the heritability of CHD, trol subjects (0.33% versus 0.45%) and were

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e369

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

associated with 27% lower triglyceride levels, 9% in 4 studies across 55 685 participants, genetic
CLINICAL STATEMENTS

lower LDL-C, and 4% lower HDL-C.99 and lifestyle factors were independently associ-
AND GUIDELINES

• Protein-truncating variants at the CETP gene are ated with CHD, but even in participants at high
associated with increased HDL-C and lower LDL-C genetic risk, a favorable lifestyle was associated
and triglycerides. Compared with noncarriers, car- with a nearly 50% lower RR of CHD than was an
riers of protein-truncating variants at CETP had a unfavorable lifestyle.107
lower risk of CHD (OR, 0.70 [95% CI, 0.54–0.90]; • Collectively, these results may suggest future roles
P=5.1×10−3).100 for incorporation of genetic risk score in clinical
• Using a network mendelian randomization practice and emphasize the need for traditional
analysis, a 1-unit longer genetically determined primary prevention measures even in patients
telomere length was associated with a lower with a high genetic risk.
risk of CHD in the CARDIoGRAM Consortium
(OR, 0.79 [95% CI, 0.65–0.97; P=0.016) and
the CARDIoGRAMplusC4D 1000 Genome Global Burden
Consortium (OR, 0.89 [95% CI, 0.79–1.00; (See Table 19-3 and Charts 19-10
P=0.052). Fasting insulin can partially mediate and 19-11)
the association of telomere length with CHD,
• Globally, it is estimated that 153.5 million people
accounting for 18.4% of the effect of telomere
live with IHD, and it is more prevalent in males
length on CHD.101
than in females (86.5 and 67.0 million people,
• Whole-genome sequencing studies, which offer
respectively). The number of people with IHD
a deeper and more comprehensive coverage of
increased by 74.7% from 1990 to 2016, although
the genome, have recently identified 13 variants
the rate per 100 000 decreased 8.6% over the
with large effects on blood lipids, with 5 of these
same time period (Table 19-3).108
also being associated with CHD (PCSK9, APOA1,
• The GBD 2016 Study used statistical models and
ANGPTL4, and LDLR).102
data on incidence, prevalence, case fatality, excess
Clinical Utility of Genetic Markers mortality, and cause-specific mortality to estimate
• Recent advances have demonstrated the utility disease burden for 315 diseases and injuries in
of genetics in CAD risk prediction. In 48 421 indi- 195 countries and territories.108
Downloaded from http://ahajournals.org by on February 7, 2019

viduals enrolled in the Malmo Diet and Cancer — IHD mortality rates exceed 275 per 100 000
Study and 2 primary prevention trials (JUPITER, in Eastern Europe, Central Asia, and parts of
ASCOT) and 2 secondary prevention trials of lipid- the North Africa/Middle East region (Chart
lowering (CARE, PROVE-IT TIMI22), a genetic risk 19-10).
score consisting of 27 variants of genetic risk for — Eastern Europe and the North Africa/Middle
CAD improved risk prediction above models that East region have the highest prevalence rates
incorporated traditional risk factors and family of IHD in the world (Chart 19-11).
history.103
• In the Malmo Diet and Cancer Study, application
of an additional 23 SNPs known to be associated Future Research
with CAD resulted in greater discrimination and Although the incidence of CHD has decreased over the
reclassification (both P<0.0001).104 In the FINRISK past decade, it remains the leading cause of mortal-
and FHS cohorts, with a sample size of 12 676 ity in both the underdeveloped and developed world.
individuals, a genetic risk score incorporating However, more cases are expected to occur because
49 310 SNPs based on the CARDIoGRAMplusC4D of population aging, which makes prevention of CHD
Consortium data showed that the combination of a continuing priority. Taking action to develop and
genetic risk score with the FRS improved 10-year fully implement strategies to significantly reduce CHD
cardiac risk prediction, particularly in those ≥60 burden is likely to require new evidence and insights
years of age.105 to understand what interventions and programs will
• In the MI-GENES trial of intermediate-risk be needed to achieve prevention targets, such as the
patients, patient knowledge of their genetic risk 50×50×50 strategy, and to engage with diverse com-
score resulted in lower levels of LDL-C than a con- munities to develop and evaluate programs and across
trol group managed by conventional risk factors sectors.109
alone, which suggests the influence of genetic • More granularity of morbidity and mortality sta-
risk score in risk prevention.106 tistics is needed, ideally at the city level. Cities are
• Even in individuals with high genetic risk, preven- becoming important geographic, political, and
tion strategies have added benefit. For example, administrative units to implement CVD prevention

e370 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

initiatives, such as evaluating and modeling the disparities originate and are maintained over the

CLINICAL STATEMENTS
implementations of sugar levies or CVD preven- life course will be essential to design comprehen-

AND GUIDELINES
tion programs at the city level.110,111 sive strategies to improve CVD health in the com-
• There are substantial gaps in our knowledge of ing years.
the determinants of social disparities in the occur- • It is becoming increasingly important to under-
rence and outcomes of CHD that might have pro- stand influences on CHD risk across the life course,
found implications for prevention and health care. because it might have important implications for
Crucially, a better understanding of how these prevention of CHD by intervening in early years.

Table 19-1.  Coronary Heart Disease

New and Hospital

Prevalence, CHD, Prevalence, MI, Recurrent MI New and Mortality,* Mortality,* Discharges:
2013–2016 2013–2016 and Fatal CHD, Recurrent MI, CHD, 2016 MI, 2016 CHD, 2014
Population Group Age ≥20 y Age ≥20 y Age ≥35 y Age ≥35 y All Ages All Ages All Ages
Both sexes 18 200 000 (6.7%) 8 400 000 (3.0%) 1 055 000 805 000 363 452 111 777 1 021 000
Males 9 400 000 (7.4%) 5 100 000 (4.0%) 610 000 470 000 210 156 (57.8%)† 64 713 (57.9%)† 649 000
Females 8 800 000 (6.2%) 3 300 000 (2.3%) 445 000 335 000 153 296 (42.2%)† 47 064 (42.1%)† 372 000
NH white males 7.7% 4.0% 520 000‡ … 167 036 51 594 …
NH white females 6.1% 2.2% 370 000‡ … 119 996 36 664 …
NH black males 7.2% 4.0% 90 000‡ … 21 900 6587 …
NH black females 6.5% 2.2% 75 000‡ … 18 256 5750 …
Hispanic males 6.0% 3.4% … … 13 696 4331 …
Hispanic females 6.0% 2.0% … … 9878 3086 …
NH Asian males 4.8% 2.4% … … 5262 1601§ …
NH Asian females 3.2% 1.0% … … 3827 1197§ …
NH American Indian … … … … 2069 606 …
Downloaded from http://ahajournals.org by on February 7, 2019

or Alaska Native

CHD includes people who responded “yes” to at least 1 of the questions in “Has a doctor or other health professional ever told you that you had coronary heart
disease, angina or angina pectoris, heart attack, or myocardial infarction?” Those who answered “no” but were diagnosed with Rose angina are also included (the
Rose questionnaire is only administered to survey participants >40 years of age). CHD indicates coronary heart disease; ellipses (…), data not available; MI, myocardial
infarction; and NH, non-Hispanic.
*Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total CHD and MI mortality that is for males vs females.
‡Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
§Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2013 to 2016 (National Center for Health Statistics [NCHS]) and National Heart, Lung, and
Blood Institute (NHLBI). Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2016
US population estimates. These data are based on self-reports. Incidence: Atherosclerosis Risk in Communities Study (2005–2014), NHLBI. Mortality: Centers for
Disease Control and Prevention/NCHS, 2016 Mortality Multiple Cause-of-Death–United States. Mortality for NH Asians includes Pacific Islanders. Hospital discharges:
Healthcare Cost and Utilization Project, Hospital Discharges, 2014 (data include those inpatients discharged alive, dead, or status unknown).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e371

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

Table 19-2.  Angina Pectoris*

CLINICAL STATEMENTS

Prevalence, Incidence of Hospital Discharges,

AND GUIDELINES

Population Group 2013–2016, Age ≥20 y Stable AP, Age ≥45 y 2014, All Ages
Both sexes 9 400 000 (3.6%) 565 000 10 000
Males 4 300 000 (3.5%) 370 000 5000
Females 5 100 000 (3.7%) 195 000 5000
NH white males 3.8% … …
NH white females 3.8% … …
NH black males 3.6% … …
NH black females 3.8% … …
Hispanic males 2.6% … …
Hispanic females 3.6% … …
NH Asian or Pacific Islander males 2.0% … …
NH Asian or Pacific Islander females 1.6% … …

AP includes people who either answered “yes” to the question of ever having angina or AP or who were diagnosed
with Rose angina (the Rose questionnaire is only administered to survey participants >40 years of age). AP indicates angina
pectoris; ellipses (…), data not available; and NH, non-Hispanic.
*AP is chest pain or discomfort that results from insufficient blood flow to the heart muscle. Stable AP is predictable
chest pain on exertion or under mental or emotional stress. The incidence estimate is for AP without myocardial infarction.
Sources: Prevalence: NHANES (National Health and Nutrition Examination Survey) 2013 to 2016 (National Center for
Health Statistics [NCHS]) and National Heart, Lung, and Blood Institute (NHLBI). Percentages for racial/ethnic groups are age
adjusted for US adults ≥20 years of age. Estimates from NHANES 2013 to 2016 (NCHS) were applied to 2016 population
estimates (≥20 years of age). Incidence: AP uncomplicated by a myocardial infarction or with no myocardial infarction
(Framingham Heart Study [the original cohort and the Offspring Cohort 1986–2009], NHLBI). Hospital discharges:
Healthcare Cost and Utilization Project, Hospital Discharges, 2014; data include those inpatients discharged alive, dead,
or status unknown.

Table 19-3.  Global Burden of Ischemic Heart Disease and Trends108

Both Sexes Combined Males Females

Downloaded from http://ahajournals.org by on February 7, 2019

Death Prevalence Death Prevalence Death Prevalence

(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)
Total number (millions) 9.5 153.5 5.1 86.5 4.4 67.0
(9.2 to 9.8) (146.0 to 160.8) (5.0 to 5.3) (82.1 to 90.8) (4.2 to 4.6) (63.8 to 70.2)
Percent change total number 55.0 74.7 63.9 75.2 45.7 74.0
1990 to 2016 (50.7 to 59.4) (72.2 to 77.5) (58.6 to 69.2) (72.3 to 78.4) (39.1 to 53.1) (71.7 to 76.7)
Percent change total number 19.0 24.5 21.8 23.8 16.0 25.3
2006 to 2016 (16.2 to 22.1) (22.2 to 26.7) (18.6 to 25.3) (21.3 to 26.2) (11.5 to 21.2) (23.3 to 27.5)
Rate per 100 000 149.7 2,270.2 182.8 2,730.8 121.7 1,861.9
(145.8 to 154.1) (2158.4 to 2380.2) (177.4 to 188.3) (2594.2 to 2864.8) (116.3 to 127.2) (1771.8 to 1950.5)
Percent change rate −11.6 −3.8 −9.8 −5.4 −13.9 −2.3
2006 to 2016 (−13.6 to −9.3) (−5.6 to −2.0) (−12.0 to −7.4) (−7.3 to −3.5) (−17.2 to −10.1) (−3.9 to −0.5)
Percent change rate −26.2 −8.6 −23.6 −11.3 −29.8 −6.7
1990 to 2016 (−28.2 to −24.2) (−9.9 to −7.0) (−25.8 to −21.4) (−12.8 to −9.6) (−32.9 to −26.3) (−7.9 to −5.2)

e372 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

CLINICAL STATEMENTS
AND GUIDELINES
Chart 19-1. Prevalence of coronary heart disease by age and sex (NHANES, 2013–2016).
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 19-2. Prevalence of myocardial infarction by age and sex (NHANES, 2013–2016).
Myocardial infarction includes people who answered “yes” to the question of ever having had a heart attack or myocardial infarction.
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e373

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19
CLINICAL STATEMENTS
AND GUIDELINES

Chart 19-3. ”Ever told you had a heart attack (myocardial infarction)?” Age-adjusted prevalence by state, BRFSS Prevalence & Trends Data, 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
Source: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Population Health.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 19-4. ”Ever told you had angina or coronary heart disease?” Age-adjusted prevalence by state, BRFSS Prevalence & Trends Data, 2016.
BRFSS indicates Behavioral Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
Source: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Population Health.

e374 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

CLINICAL STATEMENTS
AND GUIDELINES
Chart 19-5. Annual number of adults per 1000 having diagnosed heart attack or fatal CHD by age and sex (ARIC surveillance, 2005–2014 and CHS).
These data include myocardial infarction and fatal CHD but not silent myocardial infarction.
ARIC indicates Atherosclerosis Risk in Communities; CHD, coronary heart disease; and CHS, Cardiovascular Health Study.
Source: National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 19-6. Incidence of heart attack or fatal CHD by age, sex, and race (ARIC Surveillance, 2005–2014).
ARIC indicates Atherosclerosis Risk in Communities; CHD, coronary heart disease; and MI, myocardial infarction.
Source: National Heart, Lung, and Blood Institute.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e375

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19
CLINICAL STATEMENTS
AND GUIDELINES

Chart 19-7. Incidence of myocardial infarction by age, sex, and race (ARIC Surveillance, 2005–2014).
ARIC indicates Atherosclerosis Risk in Communities.
Source: Unpublished data from ARIC, National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 19-8. Hospital discharges for coronary heart disease by sex (United States, 1997–2014).
Hospital discharges include people discharged alive, dead, and “status unknown.
”Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute.

e376 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

CLINICAL STATEMENTS
AND GUIDELINES
Chart 19-9. Prevalence of angina pectoris by age and sex (NHANES, 2013–2016).
Angina pectoris includes people who either answered “yes” to the question of ever having angina or angina pectoris or who were diagnosed with Rose angina.
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 19-10. Age-standardized global mortality rates of ischemic heart disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.108 Printed with permission.
Copyright © 2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e377

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19
CLINICAL STATEMENTS
AND GUIDELINES

Chart 19-11. Age-standardized global prevalence rates of ischemic heart disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.108 Printed with permission. Copyright ©
Downloaded from http://ahajournals.org by on February 7, 2019

2017, University of Washington.

in the Atherosclerosis Risk in Communities (ARIC) Study. Circulation.

REFERENCES 2016;133:2141–2148. doi: 10.1161/CIRCULATIONAHA.115.021177
9. Ford ES, Roger VL, Dunlay SM, Go AS, Rosamond WD. Challenges of
1. Centers for Disease Control and Prevention website. National Center for
ascertaining national trends in the incidence of coronary heart dis-
Health Statistics. National Health Interview Survey, 2016: Summary Health
ease in the United States. J Am Heart Assoc. 2014;3:e001097. doi:
Statistics, Table A-1. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/
10.1161/JAHA.114.001097
SHS/2016_SHS_Table_A-1.pdf. Accessed September 11, 2018.
10. Gerber Y, Weston SA, Jiang R, Roger VL. The changing epidemiology of
2. Will JC, Yuan K, Ford E. National trends in the prevalence and medi-
myocardial infarction in Olmsted County, Minnesota, 1995-2012. Am J
cal history of angina: 1988 to 2012. Circ Cardiovasc Qual Outcomes.
Med. 2015;128:144–151. doi: 10.1016/j.amjmed.2014.09.012
2014;7:407–413. doi: 10.1161/CIRCOUTCOMES.113.000779
11. Carson AP, Tanner RM, Yun H, Glasser SP, Woolley JM, Thacker EL, Levitan
3. Centers for Disease Control and Prevention, National Center for Chronic
EB, Farkouh ME, Rosenson RS, Brown TM, Howard G, Safford MM,
Disease Prevention and Health Promotion, Division of Population Health
Muntner P. Declines in coronary heart disease incidence and mortality
website. BRFSS Prevalence & Trends Data [online] (2016). https://www.
among middle-aged adults with and without diabetes. Ann Epidemiol.
cdc.gov/brfss/brfssprevalence/. Accessed June 15, 2018. 2014;24:581–587. doi: 10.1016/j.annepidem.2014.05.007
4. Atherosclerosis Risk in Communities Study, 2005–2014. http://www.cscc. 12. Sacks NC, Ash AS, Ghosh K, Rosen AK, Wong JB, Rosen AB. Trends in
unc.edu/aric/displaydata.php?pg_id=37. Accessed September 1, 2017. acute myocardial infarction hospitalizations: are we seeing the whole pic-
5. Levitan EB, Olubowale OT, Gamboa CM, Rhodes JD, Brown TM, Muntner ture? Am Heart J. 2015;170:1211–1219. doi: 10.1016/j.ahj.2015.09.009
P, Deng L, Safford MM. Characteristics and prognosis of acute myocardial 13. Sacks NC, Ash AS, Ghosh K, Rosen AK, Wong JB, Cutler DM, Rosen AB.
infarction by discharge diagnosis: the Reasons for Geographic and Racial Recent national trends in acute myocardial infarction hospitalizations
Differences in Stroke study. Ann Epidemiol. 2015;25:499–504.e1. doi: in Medicare: shrinking declines and growing disparities. Epidemiology.
10.1016/j.annepidem.2015.02.004 2015;26:e46–e47. doi: 10.1097/EDE.0000000000000298
6. Lewis MW, Khodneva Y, Redmond N, Durant RW, Judd SE, Wilkinson 14. Ford ES, Will JC, Mercado CI, Loustalot F. Trends in predicted risk for ath-
LL, Howard VJ, Safford MM. The impact of the combination of income erosclerotic cardiovascular disease using the pooled cohort risk equations
and education on the incidence of coronary heart disease in the pro- among US adults from 1999 to 2012. JAMA Intern Med. 2015;175:299–
spective Reasons for Geographic and Racial Differences in Stroke 302. doi: 10.1001/jamainternmed.2014.6403
(REGARDS) cohort study. BMC Public Health. 2015;15:1312. doi: 15. Karmali KN, Goff DC Jr, Ning H, Lloyd-Jones DM. A systematic examina-
10.1186/s12889-015-2630-4 tion of the 2013 ACC/AHA pooled cohort risk assessment tool for athero-
7. Colantonio LD, Gamboa CM, Richman JS, Levitan EB, Soliman EZ, Howard sclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64:959–968. doi:
G, Safford MM. Black-white differences in incident fatal, nonfatal, and 10.1016/j.jacc.2014.06.1186
total coronary heart disease. Circulation. 2017;136:152–166. doi: 16. Colantonio LD, Gamboa CM, Kleindorfer DO, Carson AP, Howard VJ,
10.1161/CIRCULATIONAHA.116.025848 Muntner P, Cushman M, Howard G, Safford MM. Stroke symptoms and
8. Zhang ZM, Rautaharju PM, Prineas RJ, Rodriguez CJ, Loehr L, Rosamond risk for incident coronary heart disease in the REasons for Geographic And
WD, Kitzman D, Couper D, Soliman EZ. Race and sex differences in the Racial Differences in Stroke (REGARDS) study. Int J Cardiol. 2016;220:122–
incidence and prognostic significance of silent myocardial infarction 128. doi: 10.1016/j.ijcard.2016.06.030

e378 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

17. Lackland DT, Elkind MS, D’Agostino R Sr, Dhamoon MS, Goff DC Jr, 33. Gerber Y, Weston SA, Enriquez-Sarano M, Berardi C, Chamberlain AM,

CLINICAL STATEMENTS
Higashida RT, McClure LA, Mitchell PH, Sacco RL, Sila CA, Smith SC Jr, Manemann SM, Jiang R, Dunlay SM, Roger VL. Mortality associated with heart

AND GUIDELINES
Tanne D, Tirschwell DL, Touzé E, Wechsler LR; on behalf of the American failure after myocardial infarction: a contemporary community perspective. Circ
Heart Association Stroke Council; Council on Epidemiology and Prevention; Heart Fail. 2016;9:e002460. doi: 10.1161/CIRCHEARTFAILURE.115.002460
Council on Cardiovascular Radiology and Intervention; Council on 34. Pearson-Stuttard J, Guzman-Castillo M, Penalvo JL, Rehm CD, Afshin
Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council A, Danaei G, Kypridemos C, Gaziano T, Mozaffarian D, Capewell S,
on Quality of Care and Outcomes Research. Inclusion of stroke in cardio- O’Flaherty M. Modeling future cardiovascular disease mortality in the
vascular risk prediction instruments: a statement for healthcare profes- United States: national trends and racial and ethnic disparities. Circulation.
sionals from the American Heart Association/American Stroke Association. 2016;133:967–978. doi: 10.1161/CIRCULATIONAHA.115.019904
Stroke. 2012;43:1998–2027. doi: 10.1161/STR.0b013e31825bcdac 35. Lloyd-Jones DM. Slowing progress in cardiovascular mortality rates:
18. Shillinglaw B, Viera AJ, Edwards T, Simpson R, Sheridan SL. Use of global you reap what you sow. JAMA Cardiol. 2016;1:599–600. doi:
coronary heart disease risk assessment in practice: a cross-sectional survey 10.1001/jamacardio.2016.1348
of a sample of U.S. physicians. BMC Health Serv Res. 2012;12:20. doi: 36. Case A, Deaton A. Mortality and Morbidity in the 21st Century. https://
10.1186/1472-6963-12-20 www.brookings.edu/wp-content/uploads/2017/03/case-deaton-postcon-
19. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, ference-april-10-2017-with-appendix-figs.pdf. Accessed April 20, 2017.
Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, 37. Mosca L, Hammond G, Mochari-Greenberger H, Towfighi A, Albert MA;
Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/ on behalf of the American Heart Association Cardiovascular Disease and
AHA guideline on the treatment of blood cholesterol to reduce athero- Stroke in Women and Special Populations Committee of the Council on
sclerotic cardiovascular risk in adults: a report of the American College of Clinical Cardiology, Council on Cardiovascular Nursing, Council on High
Cardiology/American Heart Association Task Force on Practice Guidelines Blood Pressure Research, and Council on Nutrition, Physical Activity and
[published corrections appear in Circulation. 2014;129(suppl 2):S46–S48 Metabolism. Fifteen-year trends in awareness of heart disease in women:
and Circulation. 2015;132:e396]. Circulation. 2014;129(suppl 2):S1–S45. results of a 2012 American Heart Association national survey. Circulation.
doi: 10.1161/01.cir.0000437738.63853.7a 2013;127:1254–1263, e1–e29. doi: 10.1161/CIR.0b013e318287cf2f
20. Cook NR, Ridker PM. Calibration of the pooled cohort equations for 38. Leifheit-Limson EC, D’Onofrio G, Daneshvar M, Geda M, Bueno H, Spertus
atherosclerotic cardiovascular disease: an update. Ann Intern Med. JA, Krumholz HM, Lichtman JH. Sex differences in cardiac risk factors, per-
2016;165:786–794. doi: 10.7326/M16-1739 ceived risk, and health care provider discussion of risk and risk modification
21. National Center for Health Statistics. Centers for Disease Control and Prevention among young patients with acute myocardial infarction: the VIRGO study.
website. National Vital Statistics System: public use data file documentation: J Am Coll Cardiol. 2015;66:1949–1957. doi: 10.1016/j.jacc.2015.08.859
mortality multiple cause-of-death micro-data files, 2016. https://www.cdc.gov/ 39. Makam RP, Erskine N, Yarzebski J, Lessard D, Lau J, Allison J, Gore JM,
nchs/nvss/mortality_public_use_data.htm. Accessed May 21, 2018. Gurwitz J, McManus DD, Goldberg RJ. Decade long trends (2001–2011)
22. Bucholz EM, Butala NM, Ma S, Normand ST, Krumholz HM. Life expec- in duration of pre-hospital delay among elderly patients hospitalized for
tancy after myocardial infarction, according to hospital performance. N an acute myocardial infarction. J Am Heart Assoc. 2016;5:e002664. doi:
Engl J Med. 2016;375:1332–1342. doi: 10.1056/NEJMoa1513223 10.1161/JAHA.115.002664
23. Rodriguez F, Foody JM, Wang Y, López L. Young Hispanic women experi- 40. Khoshchehreh M, Groves EM, Tehrani D, Amin A, Patel PM, Malik S.
ence higher in-hospital mortality following an acute myocardial infarction. Changes in mortality on weekend versus weekday admissions for acute
J Am Heart Assoc. 2015;4:e002089. doi: 10.1161/JAHA.115.002089 coronary syndrome in the United States over the past decade. Int J Cardiol.
24. Bucholz EM, Ma S, Normand SL, Krumholz HM. Race, socioeconomic 2016;210:164–172. doi: 10.1016/j.ijcard.2016.02.087
status, and life expectancy after acute myocardial infarction. Circulation. 41. Alrwisan A, Eworuke E. Are discrepancies in waiting time for chest
Downloaded from http://ahajournals.org by on February 7, 2019

2015;132:1338–1346. doi: 10.1161/CIRCULATIONAHA.115.017009 pain at emergency departments between African Americans and
25. Conrad Z, Rehm CD, Wilde P, Mozaffarian D. Cardiometabolic mortal- whites improving over time? J Emerg Med. 2016;50:349–355. doi:
ity by Supplemental Nutrition Assistance Program participation and eli- 10.1016/j.jemermed.2015.07.033
gibility in the United States. Am J Public Health. 2017;107:466–474. doi: 42. Agrawal S, Garg L, Sharma A, Mohananey D, Bhatia N, Singh A, Shirani
10.2105/AJPH.2016.303608 J, Dixon S. Comparison of inhospital mortality and frequency of coronary
26. Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population trends angiography on weekend versus weekday admissions in patients with
in the incidence and outcomes of acute myocardial infarction. N Engl J non-ST-segment elevation acute myocardial infarction. Am J Cardiol.
Med. 2010;362:2155–2165. doi: 10.1056/NEJMoa0908610 2016;118:632–634. doi: 10.1016/j.amjcard.2016.06.022
27. Roger VL, Weston SA, Gerber Y, Killian JM, Dunlay SM, Jaffe AS, Bell MR, 43. Pilgrim T, Vranckx P, Valgimigli M, Stefanini GG, Piccolo R, Rat J,
Kors J, Yawn BP, Jacobsen SJ. Trends in incidence, severity, and outcome of Rothenbühler M, Stortecky S, Räber L, Blöchlinger S, Hunziker L, Silber
hospitalized myocardial infarction. Circulation. 2010;121:863–869. doi: S, Jüni P, Serruys PW, Windecker S. Risk and timing of recurrent ischemic
10.1161/CIRCULATIONAHA.109.897249 events among patients with stable ischemic heart disease, non-ST-segment
28. Krumholz HM, Normand SL, Wang Y. Trends in hospitalizations and out- elevation acute coronary syndrome, and ST-segment elevation myocardial
comes for acute cardiovascular disease and stroke, 1999-2011. Circulation. infarction. Am Heart J. 2016;175:56–65. doi: 10.1016/j.ahj.2016.01.021
2014;130:966–975. doi: 10.1161/CIRCULATIONAHA.113.007787 44. Masoudi FA, Ponirakis A, de Lemos JA, Jollis JG, Kremers M, Messenger
29. Goldberg RJ, Makam RC, Yarzebski J, McManus DD, Lessard D, Gore JM. JC, Moore JW, Moussa I, Oetgen WJ, Varosy PD, Vincent RN, Wei J, Curtis
Decade-long trends (2001-2011) in the incidence and hospital death rates JP, Roe MT, Spertus JA. Trends in U.S. cardiovascular care: 2016 report
associated with the in-hospital development of cardiogenic shock after from 4 ACC National Cardiovascular Data Registries. J Am Coll Cardiol.
acute myocardial infarction. Circ Cardiovasc Qual Outcomes. 2016;9:117– 2017;69:1427–1450. doi: 10.1016/j.jacc.2016.12.005
125. doi: 10.1161/CIRCOUTCOMES.115.002359 45. Masoudi FA, Ponirakis A, de Lemos JA, Jollis JG, Kremers M, Messenger
30. Sugiyama T, Hasegawa K, Kobayashi Y, Takahashi O, Fukui T, Tsugawa Y. JC, Moore JW, Moussa I, Oetgen WJ, Varosy PD, Vincent RN, Wei J, Curtis
Differential time trends of outcomes and costs of care for acute myocar- JP, Roe MT, Spertus JA. Executive summary: trends in U.S. cardiovascular
dial infarction hospitalizations by ST elevation and type of intervention in care: 2016 report from 4 ACC national cardiovascular data registries. J Am
the United States, 2001-2011. J Am Heart Assoc. 2015;4:e001445. doi: Coll Cardiol. 2017;69:1424–1426. doi: 10.1016/j.jacc.2016.12.004
10.1161/JAHA.114.001445 46. Mahmoud AN, Taduru SS, Mentias A, Mahtta D, Barakat AF, Saad M, Elgendy
31. Wilmot KA, O’Flaherty M, Capewell S, Ford ES, Vaccarino V. Coronary heart AY, Mojadidi MK, Omer M, Abuzaid A, Agarwal N, Elgendy IY, Anderson RD,
disease mortality declines in the United States from 1979 through 2011: Saw J. Trends of incidence, clinical presentation, and in-hospital mortality
evidence for stagnation in young adults, especially women. Circulation. among women with acute myocardial infarction with or without spontane-
2015;132:997–1002. doi: 10.1161/CIRCULATIONAHA.115.015293 ous coronary artery dissection: a population-based analysis. JACC Cardiovasc
32. Desta L, Jernberg T, Löfman I, Hofman-Bang C, Hagerman I, Spaak J, Persson Interv. 2018;11:80–90. doi: 10.1016/j.jcin.2017.08.016
H. Incidence, temporal trends, and prognostic impact of heart failure com- 47. Smilowitz NR, Mahajan AM, Roe MT, Hellkamp AS, Chiswell K, Gulati M,
plicating acute myocardial infarction: the SWEDEHEART Registry (Swedish Reynolds HR. Mortality of myocardial infarction by sex, age, and obstruc-
Web-System for Enhancement and Development of Evidence-Based Care in tive coronary artery disease status in the ACTION Registry-GWTG (Acute
Heart Disease Evaluated According to Recommended Therapies): a study of Coronary Treatment and Intervention Outcomes Network Registry-Get
199,851 patients admitted with index acute myocardial infarctions, 1996 to With the Guidelines). Circ Cardiovasc Qual Outcomes. 2017;10:e003443.
2008. JACC Heart Fail. 2015;3:234–242. doi: 10.1016/j.jchf.2014.10.007 doi: 10.1161/CIRCOUTCOMES.116.003443

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e379

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

48. Levitan EB, Muntner P, Chen L, Deng L, Kilgore ML, Becker D, Glasser 65. Cavalcante R, Sotomi Y, Zeng Y, Lee CW, Ahn JM, Collet C, Tenekecioglu
CLINICAL STATEMENTS

SP, Safford MM, Howard G, Kilpatrick R, Rosenson RS. Burden of coro- E, Suwannasom P, Onuma Y, Park SJ, Serruys PW. Coronary bypass sur-
AND GUIDELINES

nary heart disease rehospitalizations following acute myocardial infarc- gery versus stenting in multivessel disease involving the proximal left
tion in older adults. Cardiovasc Drugs Ther. 2016;30:323–331. doi: anterior descending coronary artery. Heart. 2017;103:428–433. doi:
10.1007/s10557-016-6653-6 10.1136/heartjnl-2016-309720
49. McNeely C, Markwell S, Vassileva CM. Readmission after inpatient percu- 66. Kim LK, Looser P, Swaminathan RV, Minutello RM, Wong SC, Girardi
taneous coronary intervention in the Medicare population from 2000 to L, Feldman DN. Outcomes in patients undergoing coronary artery
2012. Am Heart J. 2016;179:195–203. doi: 10.1016/j.ahj.2016.07.002 bypass graft surgery in the United States based on hospital volume,
50. McManus DD, Saczynski JS, Lessard D, Waring ME, Allison J, Parish DC, 2007 to 2011. J Thorac Cardiovasc Surg. 2016;151:1686–1692. doi:
Goldberg RJ, Ash A, Kiefe CI; TRACE-CORE Investigators. Reliability of 10.1016/j.jtcvs.2016.01.050
predicting early hospital readmission after discharge for an acute coronary 67. Bangalore S, Gupta N, Généreux P, Guo Y, Pancholy S, Feit F. Trend in
syndrome using claims-based data. Am J Cardiol. 2016;117:501–507. doi: percutaneous coronary intervention volume following the COURAGE and
10.1016/j.amjcard.2015.11.034 BARI-2D trials: insight from over 8.1 million percutaneous coronary inter-
51. Chen HY, Tisminetzky M, Lapane KL, Yarzebski J, Person SD, Kiefe CI, Gore ventions. Int J Cardiol. 2015;183:6–10. doi: 10.1016/j.ijcard.2015.01.053
JM, Goldberg RJ. Decade-long trends in 30-day rehospitalization rates 68. Bradley SM, Bohn CM, Malenka DJ, Graham MM, Bryson CL, McCabe
after acute myocardial infarction. J Am Heart Assoc. 2015;4:e002291. JM, Curtis JP, Lambert-Kerzner A, Maynard C. Temporal trends in percu-
doi: 10.1161/JAHA.115.002291 taneous coronary intervention appropriateness: insights from the Clinical
52. Chen HY, Tisminetzky M, Yarzebski J, Gore JM, Goldberg RJ. Decade-long Outcomes Assessment Program. Circulation. 2015;132:20–26. doi:
trends in the frequency of 90-day rehospitalizations after hospital dis- 10.1161/CIRCULATIONAHA.114.015156
charge for acute myocardial infarction. Am J Cardiol. 2016;117:743–748. 69. Culler SD, Kugelmass AD, Brown PP, Reynolds MR, Simon AW. Trends
doi: 10.1016/j.amjcard.2015.12.006 in coronary revascularization procedures among Medicare beneficia-
53. Beatty AL, Li S, Thomas L, Amsterdam EA, Alexander KP, Whooley MA. ries between 2008 and 2012. Circulation. 2015;131:362–370. doi:
Trends in referral to cardiac rehabilitation after myocardial infarction: data 10.1161/CIRCULATIONAHA.114.012485
from the National Cardiovascular Data Registry 2007 to 2012. J Am Coll 70. Alnasser SM, Bagai A, Jolly SS, Cantor WJ, Dehghani P, Rao SV, Cheema
Cardiol. 2014;63:2582–2583. doi: 10.1016/j.jacc.2014.03.030 AN. Transradial approach for coronary angiography and intervention in the
54. Aragam KG, Dai D, Neely ML, Bhatt DL, Roe MT, Rumsfeld JS, Gurm HS. elderly: a meta-analysis of 777,841 patients. Int J Cardiol. 2017;228:45–
Gaps in referral to cardiac rehabilitation of patients undergoing percu- 51. doi: 10.1016/j.ijcard.2016.11.207
taneous coronary intervention in the United States. J Am Coll Cardiol. 71. Kurlansky P, Herbert M, Prince S, Mack M. Coronary artery bypass graft
2015;65:2079–2088. doi: 10.1016/j.jacc.2015.02.063 versus percutaneous coronary intervention: meds matter: impact of
55. Dunlay SM, Pack QR, Thomas RJ, Killian JM, Roger VL. Participation in car- adherence to medical therapy on comparative outcomes. Circulation.
diac rehabilitation, readmissions, and death after acute myocardial infarc- 2016;134:1238–1246. doi: 10.1161/CIRCULATIONAHA.115.021183
tion. Am J Med. 2014;127:538–546. doi: 10.1016/j.amjmed.2014.02.008 72. Torio CM, Moore BJ. National Inpatient Hospital Costs: The Most Expensive
56. Hammill BG, Curtis LH, Schulman KA, Whellan DJ. Relationship between Conditions by Payer, 2013. HCUP Statistical Brief #204. Rockville, MD:
cardiac rehabilitation and long-term risks of death and myocardial infarc- Agency for Healthcare Research and Quality; May 2016. http://www.
tion among elderly Medicare beneficiaries. Circulation. 2010;121:63–70. hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hospital-Con-
doi: 10.1161/CIRCULATIONAHA.109.876383 ditions.pdf. Accessed April 1, 2017.
57. Peters AE, Keeley EC. Trends and predictors of participation in cardiac reha- 73. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD,
bilitation following acute myocardial infarction: data from the Behavioral Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA,
Downloaded from http://ahajournals.org by on February 7, 2019

Risk Factor Surveillance System. J Am Heart Assoc. 2017;7:e007664. doi: Nichol G, Orenstein D, Wilson PW, Woo YJ; on behalf of the American Heart
10.1161/JAHA.117.007664 Association Advocacy Coordinating Committee; Stroke Council; Council on
58. Centers for Disease Control and Prevention website. National Ambulatory Cardiovascular Radiology and Intervention; Council on Clinical Cardiology;
Medical Care Survey: 2015 State and National Summary Tables. https:// Council on Epidemiology and Prevention; Council on Arteriosclerosis;
www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_ Thrombosis and Vascular Biology; Council on Cardiopulmonary; Critical
tables.pdf. Accessed June 14, 2018. Care; Perioperative and Resuscitation; Council on Cardiovascular Nursing;
59. Centers for Disease Control and Prevention website. National Hospital Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular
Ambulatory Medical Care Survey: 2015 Emergency Department Summary Surgery and Anesthesia, and Interdisciplinary Council on Quality of Care
Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_ and Outcomes Research. Forecasting the future of cardiovascular disease in
web_tables.pdf. Accessed June 14, 2018. the United States: a policy statement from the American Heart Association.
60. Will JC, Loustalot F, Hong Y. National trends in visits to physician offices Circulation. 2011;123:933–944. doi: 10.1161/CIR.0b013e31820a55f5
and outpatient clinics for angina 1995 to 2010. Circ Cardiovasc Qual 74. Ben-Yehuda O, Kazi DS, Bonafede M, Wade SW, Machacz SF, Stephens
Outcomes. 2014;7:110–117. doi: 10.1161/CIRCOUTCOMES.113.000450 LA, Hlatky MA, Hernandez JB. Angina and associated healthcare costs
61. Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, Zeng following percutaneous coronary intervention: a real-world analysis from
Y, Park DW, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. a multi-payer database. Catheter Cardiovasc Interv. 2016;88:1017–1024.
Coronary artery bypass grafting versus drug-eluting stents implantation doi: 10.1002/ccd.26365
for previous myocardial infarction. Am J Cardiol. 2016;118:17–22. doi: 75. Amin AP, Patterson M, House JA, Giersiefen H, Spertus JA, Baklanov
10.1016/j.amjcard.2016.04.009 DV, Chhatriwalla AK, Safley DM, Cohen DJ, Rao SV, Marso SP. Costs
62. Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, Park DW, associated with access site and same-day discharge among Medicare
Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Impact of mul- beneficiaries undergoing percutaneous coronary intervention: an evalu-
tivessel coronary artery disease with versus without left main coronary ation of the current percutaneous coronary intervention care pathways
artery disease on long-term mortality after coronary bypass grafting ver- in the United States. JACC Cardiovasc Interv. 2017;10:342–351. doi:
sus drug-eluting stent implantation. Am J Cardiol. 2017;119:225–230. 10.1016/j.jcin.2016.11.049
doi: 10.1016/j.amjcard.2016.09.048 76. LaMori JC, Shoheiber O, Dudash K, Crivera C, Mody SH. The economic
63. Palmerini T, Serruys P, Kappetein AP, Genereux P, Riva DD, Reggiani LB, impact of acute coronary syndrome on length of stay: an analysis using
Christiansen EH, Holm NR, Thuesen L, Makikallio T, Morice MC, Ahn JM, the Healthcare Cost and Utilization Project (HCUP) databases. J Med Econ.
Park SJ, Thiele H, Boudriot E, Sabatino M, Romanello M, Biondi-Zoccai G, 2014;17:191–197. doi: 10.3111/13696998.2014.885907
Cavalcante R, Sabik JF, Stone GW. Clinical outcomes with percutaneous 77. Page RL 2nd, Ghushchyan V, Gifford B, Read RA, Raut M, Crivera C,
coronary revascularization vs coronary artery bypass grafting surgery in Naim AB, Damaraju CV, Nair KV. The economic burden of acute coro-
patients with unprotected left main coronary artery disease: a meta-anal- nary syndromes for employees and their dependents: medical and
ysis of 6 randomized trials and 4,686 patients. Am Heart J. 2017;190:54– productivity costs. J Occup Environ Med. 2013;55:761–767. doi:
63. doi: 10.1016/j.ahj.2017.05.005 10.1097/JOM.0b013e318297323a
64. Milojevic M, Head SJ, Parasca CA, Serruys PW, Mohr FW, Morice MC, 78. Goldberg RJ, Saczynski JS, McManus DD, Waring ME, McManus R,
Mack MJ, Ståhle E, Feldman TE, Dawkins KD, Colombo A, Kappetein AP, Allison J, Parish DC, Lessard D, Person S, Gore JM, Kiefe CI; TRACE-
Holmes DR Jr. Causes of death following PCI versus CABG in complex CORE Investigators. Characteristics of contemporary patients dis-
CAD: 5-year follow-up of SYNTAX. J Am Coll Cardiol. 2016;67:42–55. charged from the hospital after an acute coronary syndrome. Am J Med.
doi: 10.1016/j.jacc.2015.10.043 2015;128:1087–1093. doi: 10.1016/j.amjmed.2015.05.002

e380 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

79. Elgendy IY, Mahmoud AN, Mansoor H, Bavry AA. Early invasive versus ini- 94. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T,

CLINICAL STATEMENTS
tial conservative strategies for women with non-ST-elevation acute coro- Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson

AND GUIDELINES
nary syndromes: a nationwide analysis. Am J Med. 2017;130:1059–1067. G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM,
doi: 10.1016/j.amjmed.2017.01.049 Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir
80. Elgendy IY, Mahmoud AN, Wen X, Bavry AA. Meta-analysis of ran- S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB,
domized trials of long-term all-cause mortality in patients with non- Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson
ST-elevation acute coronary syndrome managed with routine invasive G, Thorsteinsdottir U, Kong A, Stefansson K. A common variant on
versus selective invasive strategies. Am J Cardiol. 2017;119:560–564. doi: chromosome 9p21 affects the risk of myocardial infarction. Science.
10.1016/j.amjcard.2016.11.005 2007;316:1491–1493. doi: 10.1126/science.1142842
81. Yoon SS, Dillon CF, Illoh K, Carroll M. Trends in the prevalence of 95. Palomaki GE, Melillo S, Bradley LA. Association between 9p21 genomic
coronary heart disease in the U.S.: National Health and Nutrition markers and heart disease: a meta-analysis. JAMA. 2010;303:648–656.
Examination Survey, 2001–2012. Am J Prev Med. 2016;51:437–445. doi: doi: 10.1001/jama.2010.118
10.1016/j.amepre.2016.02.023 96. Franceschini N, Carty C, Bůzková P, Reiner AP, Garrett T, Lin Y, Vöckler
82. Kureshi F, Shafiq A, Arnold SV, Gosch K, Breeding T, Kumar AS, Jones PG, JS, Hindorff LA, Cole SA, Boerwinkle E, Lin DY, Bookman E, Best LG,
Spertus JA. The prevalence and management of angina among patients with Bella JN, Eaton C, Greenland P, Jenny N, North KE, Taverna D, Young
chronic coronary artery disease across US outpatient cardiology practices: AM, Deelman E, Kooperberg C, Psaty B, Heiss G. Association of ge-
insights from the Angina Prevalence and Provider Evaluation of Angina Relief netic variants and incident coronary heart disease in multiethnic co-
(APPEAR) study. Clin Cardiol. 2017;40:6–10. doi: 10.1002/clc.22628 horts: the PAGE study. Circ Cardiovasc Genet. 2011;4:661–672. doi:
83. Sheiham A. Closing the gap in a generation: health equity through action 10.1161/CIRCGENETICS.111.960096
on the social determinants of health: a report of the WHO Commission 97. Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia
on Social Determinants of Health (CSDH) 2008. Community Dent Health. Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and
2009;26:2–3. the risk of coronary disease [published correction appears in N Engl J
84. Kilpi F, Konttinen H, Silventoinen K, Martikainen P. Living arrangements as Med. 2016;374:1898]. N Engl J Med. 2016;374:1134–1144. doi:
determinants of myocardial infarction incidence and survival: a prospec- 10.1056/NEJMoa1507652
tive register study of over 300,000 Finnish men and women. Soc Sci Med. 98. Webb TR, Erdmann J, Stirrups KE, Stitziel NO, Masca NG, Jansen H,
2015;133:93–100. doi: 10.1016/j.socscimed.2015.03.054 Kanoni S, Nelson CP, Ferrario PG, König IR, Eicher JD, Johnson AD,
85. Kilpi F, Silventoinen K, Konttinen H, Martikainen P. Early-life and adult socio- Hamby SE, Betsholtz C, Ruusalepp A, Franzén O, Schadt EE, Björkegren
economic determinants of myocardial infarction incidence and fatality. JL, Weeke PE, Auer PL, Schick UM, Lu Y, Zhang H, Dube MP, Goel A,
Soc Sci Med. 2017;177:100–109. doi: 10.1016/j.socscimed.2017.01.055 Farrall M, Peloso GM, Won HH, Do R, van Iperen E, Kruppa J, Mahajan
86. Patel SA, Ali MK, Narayan KM, Mehta NK. County-level variation in cardio- A, Scott RA, Willenborg C, Braund PS, van Capelleveen JC, Doney
vascular disease mortality in the United States in 2009-2013: comparative AS, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano N, Denny
assessment of contributing factors. Am J Epidemiol. 2016;184:933–942. JC, Shaffer C, El-Mokhtari NE, Franke A, Heilmann S, Hengstenberg
doi: 10.1093/aje/kww081 C, Hoffmann P, Holmen OL, Hveem K, Jansson JH, Jöckel KH, Kessler
87. Koren A, Steinberg DM, Drory Y, Gerber Y; Israel Study Group on First T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, McCarthy MI, Van
Acute Myocardial Infarction. Socioeconomic environment and recur- Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher SA, Alver M, Moebus
rent coronary events after initial myocardial infarction. Ann Epidemiol. S, Morris AD, Virtamo J, Nikpay M, Olivieri O, Provost S, AlQarawi A,
2012;22:541–546. doi: 10.1016/j.annepidem.2012.04.023 Robertson NR, Akinsansya KO, Reilly DF, Vogt TF, Yin W, Asselbergs
88. Bachmann JM, Willis BL, Ayers CR, Khera A, Berry JD. Association FW, Kooperberg C, Jackson RD, Stahl E, Müller-Nurasyid M, Strauch K,
Downloaded from http://ahajournals.org by on February 7, 2019

between family history and coronary heart disease death across long-term Varga TV, Waldenberger M; Wellcome Trust Case Control Consortium,
follow-up in men: the Cooper Center Longitudinal Study. Circulation. Zeng L, Chowdhury R, Salomaa V, Ford I, Jukema JW, Amouyel P,
2012;125:3092–3098. doi: 10.1161/CIRCULATIONAHA.111.065490 Kontto J; MORGAM Investigators, Nordestgaard BG, Ferrières J,
89. Lloyd-Jones DM, Nam BH, D’Agostino RB Sr, Levy D, Murabito JM, Saleheen D, Sattar N, Surendran P, Wagner A, Young R, Howson JM,
Wang TJ, Wilson PW, O’Donnell CJ. Parental cardiovascular disease as a Butterworth AS, Danesh J, Ardissino D, Bottinger EP, Erbel R, Franks
risk factor for cardiovascular disease in middle-aged adults: a prospec- PW, Girelli D, Hall AS, Hovingh GK, Kastrati A, Lieb W, Meitinger T,
tive study of parents and offspring. JAMA. 2004;291:2204–2211. doi: Kraus WE, Shah SH, McPherson R, Orho-Melander M, Melander O,
10.1001/jama.291.18.2204 Metspalu A, Palmer CN, Peters A, Rader DJ, Reilly MP, Loos RJ, Reiner
90. Patel J, Al Rifai M, Blaha MJ, Budoff MJ, Post WS, Polak JF, Bluemke AP, Roden DM, Tardif JC, Thompson JR, Wareham NJ, Watkins H, Willer
DA, Scheuner MT, Kronmal RA, Blumenthal RS, Nasir K, McEvoy JW. CJ, Samani NJ, Schunkert H, Deloukas P, Kathiresan S; Myocardial
Coronary artery calcium improves risk assessment in adults with a fam- Infarction Genetics and CARDIoGRAM Exome Consortia Investigators.
ily history of premature coronary heart disease: results from Multiethnic Systematic evaluation of pleiotropy identifies 6 further loci associated
Study of Atherosclerosis. Circ Cardiovasc Imaging. 2015;8:e003186. doi: with coronary artery disease. J Am Coll Cardiol. 2017;69:823–836. doi:
10.1161/CIRCIMAGING.115.003186 10.1016/j.jacc.2016.11.056
91. Choi J, Daskalopoulou SS, Thanassoulis G, Karp I, Pelletier R, Behlouli H, 99. Dewey FE, Gusarova V, Dunbar RL, O’Dushlaine C, Schurmann C,
Pilote L; GENESIS-PRAXY Investigators. Sex- and gender-related risk fac- Gottesman O, McCarthy S, Van Hout CV, Bruse S, Dansky HM, Leader
tor burden in patients with premature acute coronary syndrome. Can J JB, Murray MF, Ritchie MD, Kirchner HL, Habegger L, Lopez A, Penn J,
Cardiol. 2014;30:109–117. doi: 10.1016/j.cjca.2013.07.674 Zhao A, Shao W, Stahl N, Murphy AJ, Hamon S, Bouzelmat A, Zhang R,
92. Agarwal MA, Garg L, Lavie CJ, Reed GL, Khouzam RN. Impact of fam- Shumel B, Pordy R, Gipe D, Herman GA, Sheu WHH, Lee IT, Liang KW,
ily history of coronary artery disease on in-hospital clinical outcomes Guo X, Rotter JI, Chen YI, Kraus WE, Shah SH, Damrauer S, Small A,
in ST-segment myocardial infarction. Ann Transl Med. 2018;6:3. doi: Rader DJ, Wulff AB, Nordestgaard BG, Tybjærg-Hansen A, van den Hoek
10.21037/atm.2017.09.27 AM, Princen HMG, Ledbetter DH, Carey DJ, Overton JD, Reid JG, Sasiela
93. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, Waite LL, WJ, Banerjee P, Shuldiner AR, Borecki IB, Teslovich TM, Yancopoulos GD,
Freitag DF, Fauman EB, Salfati EL, Sun BB, Eicher JD, Johnson AD, Sheu Mellis SJ, Gromada J, Baras A. Genetic and pharmacologic inactivation of
WHH, Nielsen SF, Lin WY, Surendran P, Malarstig A, Wilk JB, Tybjærg- ANGPTL3 and cardiovascular disease. N Engl J Med. 2017;377:211–221.
Hansen A, Rasmussen KL, Kamstrup PR, Deloukas P, Erdmann J, Kathiresan doi: 10.1056/NEJMoa1612790
S, Samani NJ, Schunkert H, Watkins H, Do R, Rader DJ, Johnson JA, Hazen 100. Nomura A, Won HH, Khera AV, Takeuchi F, Ito K, McCarthy S, Emdin
SL, Quyyumi AA, Spertus JA, Pepine CJ, Franceschini N, Justice A, Reiner CA, Klarin D, Natarajan P, Zekavat SM, Gupta N, Peloso GM, Borecki IB,
AP, Buyske S, Hindorff LA, Carty CL, North KE, Kooperberg C, Boerwinkle Teslovich TM, Asselta R, Duga S, Merlini PA, Correa A, Kessler T, Wilson
E, Young K, Graff M, Peters U, Absher D, Hsiung CA, Lee WJ, Taylor JG, Bown MJ, Hall AS, Braund PS, Carey DJ, Murray MF, Kirchner HL,
KD, Chen YH, Lee IT, Guo X, Chung RH, Hung YJ, Rotter JI, Juang JJ, Leader JB, Lavage DR, Manus JN, Hartze DN, Samani NJ, Schunkert
Quertermous T, Wang TD, Rasheed A, Frossard P, Alam DS, Majumder AAS, H, Marrugat J, Elosua R, McPherson R, Farrall M, Watkins H, Juang JJ,
Di Angelantonio E, Chowdhury R, Chen YI, Nordestgaard BG, Assimes TL, Hsiung CA, Lin SY, Wang JS, Tada H, Kawashiri MA, Inazu A, Yamagishi
Danesh J, Butterworth AS, Saleheen D; CARDIoGRAMplusC4D; EPIC-CVD. M, Katsuya T, Nakashima E, Nakatochi M, Yamamoto K, Yokota M,
Fifteen new risk loci for coronary artery disease highlight arterial-wall-spe- Momozawa Y, Rotter JI, Lander ES, Rader DJ, Danesh J, Ardissino D,
cific mechanisms. Nat Genet. 2017;49:1113–1119. doi: 10.1038/ng.3874 Gabriel S, Willer CJ, Abecasis GR, Saleheen D, Kubo M, Kato N, Ida Chen

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e381

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 19

YD, Dewey FE, Kathiresan S. Protein-truncating variants at the cholesteryl coronary heart disease. Eur Heart J. 2016;37:3267–3278. doi: 10.1093/
CLINICAL STATEMENTS

ester transfer protein gene and risk for coronary heart disease. Circ Res. eurheartj/ehw450
AND GUIDELINES

2017;121:81–88. doi: 10.1161/CIRCRESAHA.117.311145 106. Kullo IJ, Jouni H, Austin EE, Brown SA, Kruisselbrink TM, Isseh IN, Haddad
101. Zhan Y, Karlsson IK, Karlsson R, Tillander A, Reynolds CA, Pedersen RA, Marroush TS, Shameer K, Olson JE, Broeckel U, Green RC, Schaid DJ,
NL, Hägg S. Exploring the causal pathway from telomere length Montori VM, Bailey KR. Incorporating a genetic risk score into coronary
to coronary heart disease: a network mendelian randomization heart disease risk estimates: effect on low-density lipoprotein cholesterol
study. Circ Res. 2017;121:214–219. doi: 10.1161/CIRCRESAHA. levels (the MI-GENES clinical trial). Circulation. 2016;133:1181–1188.
116.310517 doi: 10.1161/CIRCULATIONAHA.115.020109
102. Helgadottir A, Gretarsdottir S, Thorleifsson G, Hjartarson E, Sigurdsson 107. Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman
A, Magnusdottir A, Jonasdottir A, Kristjansson H, Sulem P, Oddsson A, DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O,
Sveinbjornsson G, Steinthorsdottir V, Rafnar T, Masson G, Jonsdottir I, Orho-Melander M, Ridker PM, Kathiresan S. Genetic risk, adherence to
Olafsson I, Eyjolfsson GI, Sigurdardottir O, Daneshpour MS, Khalili D, a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375:2349–
Azizi F, Swinkels DW, Kiemeney L, Quyyumi AA, Levey AI, Patel RS, Hayek 2358. doi: 10.1056/NEJMoa1605086
SS, Gudmundsdottir IJ, Thorgeirsson G, Thorsteinsdottir U, Gudbjartsson 108. Global Burden of Disease Study 2016. Global Burden of Disease Study
DF, Holm H, Stefansson K. Variants with large effects on blood lipids and 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
the role of cholesterol and triglycerides in coronary disease. Nat Genet. Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
2016;48:634–639. doi: 10.1038/ng.3561 data.org/gbd-results-tool. Accessed May 1, 2018.
103. Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield M, Devlin JJ, Nordio 109. Labarthe DR, Lloyd-Jones DM. 50×50×50: cardiovascular health and the
F, Hyde C, Cannon CP, Sacks F, Poulter N, Sever P, Ridker PM, Braunwald cardiovascular disease endgame. Circulation. 2018;138:968–970. doi:
E, Melander O, Kathiresan S, Sabatine MS. Genetic risk, coronary heart 10.1161/CIRCULATIONAHA.118.035985
disease events, and the clinical benefit of statin therapy: an analysis of 110. Kypridemos C, Collins B, McHale P, Bromley H, Parvulescu P, Capewell
primary and secondary prevention trials. Lancet. 2015;385:2264–2271. S, O’Flaherty M. Future cost-effectiveness and equity of the NHS Health
doi: 10.1016/S0140-6736(14)61730-X Check cardiovascular disease prevention programme: microsimulation
104. Tada H, Melander O, Louie JZ, Catanese JJ, Rowland CM, Devlin JJ, modelling using data from Liverpool, UK. PLoS Med. 2018;15:e1002573.
Kathiresan S, Shiffman D. Risk prediction by genetic risk scores for cor- doi: 10.1371/journal.pmed.1002573
onary heart disease is independent of self-reported family history. Eur 111. Huang Y, Pomeranz J, Wilde P, Capewell S, Gaziano T, O’Flaherty
Heart J. 2016;37:561–567. doi: 10.1093/eurheartj/ehv462 M, Kersh R, Whitsel L, Mozaffarian D, Micha R. Adoption and
105. Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, design of emerging dietary policies to improve cardiometabolic
Yetukuri L, Tikkanen E, Perola M, Schunkert H, Sijbrands EJ, Palotie health in the US. Curr Atheroscler Rep. 2018;20:25. doi: 10.1007/
A, Samani NJ, Salomaa V, Ripatti S, Inouye M. Genomic prediction of s11883-018-0726-x
Downloaded from http://ahajournals.org by on February 7, 2019

e382 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

20. CARDIOMYOPATHY AND HEART Abbreviations Used in Chapter 20 Continued

CLINICAL STATEMENTS
FAILURE MRI magnetic resonance imaging

AND GUIDELINES
NAMCS National Ambulatory Medical Care Survey
See Tables 20-1 and 20-2 and Charts 20-1 NCHS National Center for Health Statistics
through 20-7 NH non-Hispanic
NHAMCS National Hospital Ambulatory Medical Care Survey
Click here to return to the Table of Contents NHANES National Health and Nutrition Examination Survey
NHLBI National Heart, Lung, and Blood Institute
NIS National (Nationwide) Inpatient Sample
Cardiomyopathy OR odds ratio
ICD-9 425; ICD-10 I42. PA physical activity
PAR population attributable risk
2016: Mortality—22 114. Any-mention mortality— PPCM peripartum cardiomyopathy
43 707. PVC premature ventricular contraction
Using HCUP data for cardiomyopathy in 2014, there QALY quality-adjusted life-year
were 16 000 inpatient hospitalizations for which car- RR relative risk
diomyopathy was the principal diagnosis and 966 000 SBP systolic blood pressure
SCD sudden cardiac death
where it was included among all-listed diagnoses
SES socioeconomic status
(NHLBI unpublished tabulation).

Abbreviations Used in Chapter 20 Hypertrophic Cardiomyopathy

• Approximately 1 in 500 individuals have unex-
ACEI angiotensin-converting enzyme inhibitor
ACR albumin-to-creatinine ratio
plained LVH, of whom 20% to 30% are likely to
AF atrial fibrillation have a sarcomere mutation that suggests clinically
AHA American Heart Association expressed HCM; however, not all people with sar-
ARIC Atherosclerosis Risk in Communities Study comere mutations manifest clinical HCM because
BMI body mass index of incomplete penetrance, even among mem-
BNP B-type natriuretic peptide
bers of the same family (see Family History and
BP blood pressure
CAD coronary artery disease Genetics for more details).1
CARDIA Coronary Artery Risk Development in Young Adults Study • The Sarcomeric Human Cardiomyopathy Registry
CHD coronary heart disease studied 4591 HCM patients, contributing >24 000
Downloaded from http://ahajournals.org by on February 7, 2019

CHS Cardiovascular Health Study person-years of follow-up, and found that the
CI confidence interval
mortality risk of patients with HCM is ≈3-fold
CKD chronic kidney disease
CRP C-reactive protein
higher than that of similarly aged individuals in
CVD cardiovascular disease the US general population. Risk for adverse events
DCM dilated cardiomyopathy (ie, any ventricular arrhythmia, HF, AF, stroke, or
DM diabetes mellitus death) was highest in patients diagnosed before
ED emergency department age 40 years versus after age 60 years (77% [95%
EF ejection fraction
CI, 72%–80%] versus 32% [95% CI, 29%–36%]
FHS Framingham Heart Study
GBD Global Burden of Disease
cumulative incidence). Adverse events were also
GWAS genome-wide association study 2-fold higher in patients with versus without
GWTG Get With The Guidelines sarcomere mutations. AF and HF accounted for
HbA1c hemoglobin A1c (glycosylated hemoglobin) a substantial proportion of the adverse events,
HCM hypertrophic cardiomyopathy despite not typically manifesting until years after
HCUP Healthcare Cost and Utilization Project
initial diagnosis.2
HD heart disease
Health ABC Health, Aging, and Body Composition Dilated Cardiomyopathy
HF heart failure
• Commonly recognized causes of chronic DCM
HR hazard ratio
ICD-9 International Classification of Diseases, 9th Revision
are mutations in a diverse group of genes that
ICD-10 International Classification of Diseases, 10th Revision are inherited in an autosomal dominant fash-
IHD ischemic heart disease ion with age-dependent penetrance and vari-
INTERMACS Interagency Registry for Mechanically Assisted Circulatory able clinical expression (see Family History and
Support
Genetics for more details). Other causes of DCM
LV left ventricular
LVAD left ventricular assist device
of variable chronicity and reversibility include car-
LVEF left ventricular ejection fraction diomyopathies that can develop after an identi-
LVH left ventricular hypertrophy fiable exposure such as tachyarrhythmia, stress,
MESA Multi-Ethnic Study of Atherosclerosis neurohormonal disorder, alcoholism, chemo-
MI myocardial infarction therapy, infection, or pregnancy (see Peripartum
(Continued ) Cardiomyopathy).3

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e383

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

• The annual incidence of chronic idiopathic that 9% progress to HF and 12% to SCD.9 See
CLINICAL STATEMENTS

DCM has been reported as between 5 and 8 Chapter 16 (Disorders of Heart Rhythm) for statis-
AND GUIDELINES

cases per 100 000, although these estimates tics regarding sudden death in HCM.
could be low because of underrecognition, • The estimated annual incidence of DCM in chil-
especially in light of prevalent asymptomatic LV dren <18 years of age is 0.57 per 100 000 over-
dysfunction observed in community studies (see all, with higher incidence in boys than girls (0.66
LV Function).4 versus 0.47 cases per 100 000, respectively) and
blacks than whites (0.98 versus 0.46 cases per
Peripartum Cardiomyopathy
100 000, respectively). The most commonly rec-
• Data from the NIS databases indicate that the
ognized causes of DCM were myocarditis (46%)
incidence of PPCM increased between 2004
and neuromuscular disease (26%).10 The 5-year
and 2011 from 8.5 to 11.8 per 10 000 live births
incidence rate of SCD among children with DCM
(Ptrend<0.001), likely related to rising average
is 3%.11
maternal age and prevalence of PPCM risk factors
• Data from the Childhood Cancer Survivor Study
such as obesity, hypertension, pregnancy-related
cohort of 14 358 survivors of childhood or ado-
hypertension, and DM.5
lescent cancers show that these individuals are at
• The NIS data also show that maternal age has
6-fold increased risk for future HF,12 usually pre-
increased in all racial/ethnic groups, except
ceded by asymptomatic cardiomyopathy. This risk
Hispanics and Asians/Pacific Islanders, and
is especially pronounced for individuals who were
across all census regions in the United States.
treated with chest radiation or anthracycline che-
When stratifying by race/ethnicity, incidence of
motherapy and persists up to 30 years after the
PPCM was lowest in Hispanics and highest in
original cancer diagnosis.
African Americans. When stratifying by region,
incidence was lowest in the West (6.5 [95% CI, Global Burden of Cardiomyopathy
6.3–6.7]) and highest in the South (13.1 [95% (See Table 20-1 and Charts 20-1 through 20-3)
CI, 12.9–13.1]).5 • Chart 20-1 shows the incidence of PPCM
• In females diagnosed with PPCM, data from a globally.13
prospective cohort indicate that 13% of females • Between 1990 and 2016, the global number of
had major events (death, cardiac transplanta- deaths attributable to cardiomyopathy and myo-
Downloaded from http://ahajournals.org by on February 7, 2019

tion, or implantation of an LVAD) or persistent carditis decreased 27.3%, and the age-adjusted
severe cardiomyopathy at 12 months. Black death rate is 5.2 per 100 00014 (Table 20-1).
females had worse LV dysfunction at presenta- • The GBD 2016 Study used statistical models and
tion and at 6 and 12 months postpartum than data on incidence, prevalence, case fatality, excess
nonblack females.6 mortality, and cause-specific mortality to estimate
disease burden for 315 diseases and injuries in
Youth 195 countries and territories.14
• Since 1996, the NHLBI-sponsored Pediatric — The highest mortality rates attributed to car-
Cardiomyopathy Registry has collected data on diomyopathy and myocarditis were in Central
children with newly diagnosed cardiomyopathy in and Eastern Europe (Chart 20-2).
New England and the central Southwest (Texas, — The prevalence of cardiomyopathy and myo-
Oklahoma, and Arkansas).7 carditis was highest in Central and Eastern
— The overall incidence of cardiomyopathy is Europe (Chart 20-3).
1.13 cases per 100 000 among children <18
years of age.
— Among children <1 year of age, the inci- Heart Failure
dence is 8.34, and among children 1 to 18 ICD-9 428; ICD-10 I50.
years of age, it is 0.70 per 100 000.
2016: Mortality—78 356. Any-mention mortality—
— The annual incidence is higher in black chil-
336 732. 2014: Hospital discharges—900 000.
dren than in white children, in boys than in
girls, and in New England (1.44 per 100 000) Prevalence
than in the central Southwest (0.98 per (See Table 20-2 and Chart 20-4)
100 000). • On the basis of data from NHANES 2013 to 2016,
• The estimated annual incidence of HCM in chil- an estimated 6.2 million Americans ≥20 years
dren was 4.7 per 1 million children, with higher of age had HF (Chart 20-4). This represents an
incidence in New England than in the central increase from an estimated 5.7 million US adults
Southwest region and in boys than in girls.8 Long- with HF based on NHANES 2009 to 2012 (NHLBI
term outcomes of children with HCM suggest unpublished tabulation).

e384 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

• Projections show that the prevalence of HF will the NHLBI-sponsored Chicago Heart Association

CLINICAL STATEMENTS
increase 46% from 2012 to 2030, resulting Detection Project in Industry, ARIC, and CHS

AND GUIDELINES
in >8 million people ≥18 years of age with HF. cohorts indicated the following16:
Additionally, the total percentage of the popula- — Overall, at age 45 years through age 95 years,
tion with HF is predicted to increase from 2.42% lifetime risks for HF were high (20%–45%).
in 2012 to 2.97% in 2030.15 — Lifetime risks for HF were 30% to 42% in
white males, 20% to 29% in black males,
Incidence
32% to 39% in white females, and 24% to
(See Table 20-2 and Chart 20-5)
46% in black females. The lower lifetime risk
• Data from the NHLBI-sponsored Chicago Heart
in black males appears likely to be attribut-
Association Detection Project in Industry, ARIC,
able to competing risks.
and CHS cohorts indicate that HF incidence
— Lifetime risk for HF was higher with higher
approaches 21 per 1000 population after 65
BP and BMI at all ages.
years of age.16
• Data from Kaiser Permanente indicated an — The lifetime risk of HF occurring for people
increase in the incidence of HF among the elderly with BMI ≥30 kg/m2 was approximately dou-
and improved HF survival, resulting in increased ble that of those with BMI <25 kg/m2.
HF prevalence, with both trends being more pro- — The lifetime risk of HF occurring for people
nounced in males.17 with BP >160/90 mm Hg was 1.6 times that
• Data from Olmsted County, MN, indicate that the of those with BP <120/90 mm Hg.
age- and sex-adjusted incidence of HF declined Risk Factors
substantially, from 315.8 per 100 000 in 2000 • Traditional risk factors for HF are common in the
to 219.3 per 100 000 in 2010, with a greater US adult population. Data from NHANES indicate
rate reduction for HF with reduced EF (−45.1% that at least 1 HF risk factor is present in up to
[95% CI, −33.0% to −55.0%]) than for HF with one-third of the US adult population.22
preserved EF (−27.9% [95% CI, −12.9% to • Traditional factors account for a considerable pro-
−40.3%]).18 portion of HF risk. Data from Olmstead County,
• In the CARDIA study, HF before 50 years of age MN, indicate that CHD, hypertension, DM, obe-
was more common among blacks than whites. sity, and smoking are responsible for 52% of
Downloaded from http://ahajournals.org by on February 7, 2019

Hypertension, obesity, and systolic dysfunction incident HF cases in the population, with ORs or
were important risk factors that may be targets RRs and their PARs as follows23: CHD OR, 3.1 and
for prevention.19 overall PAR, 20% (highest in males, 23% versus
• Data from the 2005 to 2014 community surveil- 16% in females); cigarette smoking RR, 1.4 and
lance component of the ARIC study indicate that PAR, 14%; hypertension RR, 1.4 and PAR, 20%
rates of hospitalizations for HF are increasing (highest in females, 28% versus 13% in males);
over time, apparently driven by rises in HF with obesity RR, 2.0 and PAR, 12%; DM OR, 2.7 and
preserved EF. Overall events included 50% HF PAR, 12%.
with reduced EF and 39% HF with preserved EF, • Racial disparities in risks for HF persist, as shown
where the former was more common in black in the Health ABC Study, a US cohort of 2934
males and white males and the latter was most adults aged 70 to 79 years followed up for 7
common in white females. Age-adjusted rates years.24 Among blacks, a greater proportion of
of HF hospitalization were highest in blacks HF risk (68% versus 49% among whites) was
(38 per 1000 black males, 31 per 1000 black attributable to modifiable risk factors, includ-
females).20
ing elevated SBP, elevated fasting glucose level,
• In MESA, African Americans had the highest risk
CHD, LVH, and smoking. LVH was 3-fold more
of developing HF, followed by Hispanic, white,
prevalent in blacks than in whites. CHD (PAR,
and Chinese Americans (4.6, 3.5, 2.4, and 1.0 per
23.9% for white participants, 29.5% for black
1000 person-years, respectively). This higher risk
participants) and uncontrolled BP (PAR, 21.3%
reflected differences in the prevalence of hyper-
for white participants, 30.1% for black par-
tension, DM, and low SES.21 African Americans
ticipants) had the highest PARs in both races.24
had the highest proportion of incident HF not
Hispanics carry a predominance of HF risk fac-
preceded by clinical MI (75%).21
tors and healthcare disparities, which suggests
Lifetime Risk a relatively elevated HF risk in this population
• Because most forms of HF tend to present in as well.25
older age, and the population is aging, lifetime • Risk factors appear to differ by HF subtype.
risk for HF in the community is high. Data from As a group, patients with HF with preserved

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e385

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

EF are older, are more likely to be female, LV Function

CLINICAL STATEMENTS

and have greater prevalence of hypertension, • Measures of impaired systolic or diastolic LV func-
AND GUIDELINES

obesity, and anemia than those with HF with tion are common precursors to clinical HF.
reduced EF.26 — In the FHS, the prevalence of asymptom-
• Dietary and lifestyle factors also impact HF risk. atic LV systolic dysfunction was 5% and
• Among 20 900 male physicians in the Physicians’ diastolic dysfunction was 36%. LV sys-
Health Study, the lifetime risk of HF was higher tolic and diastolic dysfunction were asso-
in males with hypertension, whereas healthy ciated with increased risk of incident HF.
lifestyle factors (normal weight, not smoking, Measures of major organ system dysfunc-
regular PA, moderate alcohol intake, consump- tion (higher serum creatinine, lower ratios
tion of breakfast cereals, and consumption of of forced expiratory volume in 1 second to
fruits and vegetables) were related to lower risk forced vital capacity, and lower hemoglo-
of HF.26a bin concentrations) were also associated
• In the ARIC study, greater adherence to the with an adjusted increased risk of new-
AHA’s Life’s Simple 7 guidelines (better profiles onset HF.45
in smoking, BMI, PA, diet, cholesterol, BP, and — In Olmsted County, MN, diastolic dysfunc-
glucose) was associated with a lower lifetime tion (HR, 1.81 [95% CI, 1.01–3.48]) was
risk of HF, as well as more optimal echocardio- observed to progress with advancing age
graphic parameters of cardiac structure and and was associated with an increased risk
function.27 of incident clinical HF during 6 years of sub-
• Multiple nontraditional risk factors for HF have sequent follow-up after adjustment for age,
been identified. hypertension, DM, and CAD.46
— In the NHLBI-sponsored FHS, circulat- — With respect to variation by race/ethnic-
ing BNP, urinary ACR, elevated serum
ity, presence of asymptomatic LV sys-
γ-glutamyl transferase, and higher levels of
tolic dysfunction in MESA was higher in
hematocrit were identified as risk factors
African Americans than in whites, Chinese,
for incident HF.28–30 Circulating concentra-
and Hispanics (1.7% overall and 2.7% in
tions of resistin were also associated with
blacks). After 9 years of follow-up, asymp-
incident HF independent of prevalent coro-
Downloaded from http://ahajournals.org by on February 7, 2019

tomaic LV dysfunction was associated with

nary disease, obesity, insulin resistance,
increased risk of overt HF (HR, 8.69 [95% CI,
and inflammation.31 Circulating adiponec-
4.89–15.45]), as well as CVD and all-cause
tin concentrations were also related to
mortality.47
incident HF, with a J-shaped relationship.32
Inflammatory markers (interleukin-6 and — In the Echocardiographic Study of Hispanic/
tumor necrosis factor-α), serum albumin Latinos, more than half (49.7%) of middle-
levels, and cigarette smoking exposure aged or older Hispanics had some form of
additionally were associated with increased cardiac dysfunction (systolic, diastolic, or
HF risk.33–35 both), although fewer than 1 in 20 Hispanic/
— In the CHS, baseline cardiac high-sensitivity Latinos had symptomatic or clinically recog-
troponin and changes in high-sensitivity tro- nized HF.48
ponin levels were significantly associated • LV function is variably abnormal in the setting of
with incident HF.36 Conversely, circulating clinically overt HF.
individual and total omega-3 fatty acid con- — GWTG–HF data from 2005 to 2010 indicate
centrations were associated with lower inci- that of 110 621 patients hospitalized with
dence of HF.37 HF, half had a reduced EF (<40%), 14% had
— In the ARIC study, white blood cell count, an EF that was ≥40% and <50%, and 36%
CRP, albuminuria, HbA1c among individu- had an EF of ≥50%.26
als without DM, cardiac troponin, PVCs, — Data collected between 1985 and 2014
and socioeconomic position over the life from 12  857 person-observations in the
course were all identified as risk factors FHS showed that the frequency of HF
for HF.38–43 with reduced EF (EF <40%) decreased
— In MESA, plasma N-terminal pro-BNP pro- over time, whereas HF with mid-range EF
vided incremental prognostic information (40% to <50%) remained stable, and HF
beyond the traditional risk factors and the with preserved EF (EF ≥50%) increased over
MRI-determined LV mass index for incident time. These findings appeared attribut-
symptomatic HF.44 able to trends in risk factors, especially a

e386 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

decrease in prevalent CHD among people people per year; incidence of recurrent

CLINICAL STATEMENTS
with HF.49 hospitalized HF was 6.6 per 1000 people

AND GUIDELINES
per year.
Hospital Discharges/Ambulatory Care Visits — Age-adjusted annual hospitalized HF inci-
(See Table 20-2 and Chart 20-6) dence was highest for black males (15.7 per
• Hospital discharges for HF (including discharged 1000), followed by black females (13.3 per
alive, dead, and status unknown) are shown for 1000), white males (12.3 per 1000), and
the United States (1997–2014) by sex in Chart white females (9.9 per 1000).
20-6. Discharges for HF decreased from 2004 — Of incident hospitalized HF events, 53%
to 2014, with principal diagnosis discharges had HF with reduced EF and 47% had pre-
of 1 042 000 and 900 000, respectively (NCHS, served EF. Black males had the highest pro-
NHLBI unpublished tabulation).50 portion of hospitalized HF with reduced EF
• In 2015, there were 2 671 000 physician office vis- (70%); white females had the highest pro-
its with a primary diagnosis of HF (NAMCS, NHLBI portion of hospitalized HF with preserved
unpublished tabulation).51 In 2015, there were EF (59%).
481 000 ED visits for HF (NHAMCS, NHLBI unpub- — Age-adjusted 28-day and 1-year case fatal-
lished tabulation).52 ity after hospitalized HF was 10.4% and
• Among 1077 patients with HF in Olmsted County, 29.5%, respectively, and did not differ by
MN, hospitalizations were common after HF diag- race or sex.
nosis, with 83% patients hospitalized at least • Data from the Health and Retirement Study from
once and 43% hospitalized at least 4 times. More 1998 to 2014 show racial/ethnic differences
than one-half of all hospitalizations were related in hospitalization trajectories over 24 months
to noncardiovascular causes.53 after HF diagnosis.60 Compared with NH males,
• Among Medicare beneficiaries, the overall HF Hispanic males have declines in hospitalization
hospitalization rate declined substantially from after initial diagnosis but then increases in hos-
1998 to 2008 but at a lower rate for black pitalizations in later stages of disease. Among
males,54 and the temporal trend findings were females, compared with whites, blacks had sig-
uneven across states. nificantly more hospitalizations throughout the
• In the GWTG–HF Registry, only one-tenth of
Downloaded from http://ahajournals.org by on February 7, 2019

follow-up period.
eligible HF patients received cardiac rehabilita- • Data from Olmsted County, MN, indicate that
tion referral at discharge after hospitalization among those with HF, hospitalizations were
for HF.55 particularly common among males and did not
• Among Medicare part D coverage beneficiaries, differ by HF with reduced EF versus preserved
HF medication adherence (ACEI/angiotensin EF, with 63% of hospitalizations for noncardio-
receptor blocker, β-blockers, and diuretic agents) vascular causes. Among those with HF, hospi-
after HF hospitalization discharge decreased over talization rates for cardiovascular causes did
2 to 4 months after discharge, followed by a pla- not change over time, whereas those for non-
teau over the subsequent year for all 3 medica- cardiovascular causes increased from 2000 to
tion classes.56 2010.18
• Rates of HF rehospitalization or cardiovascular
death were greatest for those previously hospital- Mortality
ized for HF.57 (See Table 20-2)
• Although Hispanic patients hospitalized with • Survival after the onset of HF in older adults
HF were significantly younger than NH whites, has improved, as indicated by data from Kaiser
the prevalence of DM, hypertension, and over- Permanente17; however, improvements in HF
weight/obesity was higher among them. In survival have not been even across all demo-
multivariate analysis, a 45% lower in-hospital graphics. Among Medicare beneficiaries,
mortality risk was observed among Hispanics the overall 1-year HF mortality rate declined
with HF with preserved EF compared with NH slightly from 1998 to 2008 but remained high
whites but not among those with HF with at 29.6%, and rates of decline were uneven
reduced EF.58 across states.61,61a In the NHLBI’s ARIC study,
• On the basis of data from the community sur- the 30-day, 1-year, and 5-year case fatality
veillance component of the ARIC study of the rates after hospitalization for HF were 10.4%,
NHLBI59: 22%, and 42.3%, respectively, and blacks had
— The average incidence of hospitalized HF for a greater 5-year case fatality rate than whites
those aged ≥55 years was 11.6 per 1000 (P<0.05).62

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e387

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

• Observed mortality declines have been primarily blacks, 33.3 for NH Asians or Pacific Islanders,
CLINICAL STATEMENTS

attributed to evidence-based approaches to treat 75.0 for NH American Indians or Alaska Natives,
AND GUIDELINES

HF risk factors and the implementation of ACEIs, and 48.8 for Hispanics.68
β-blockers, coronary revascularization, implant-
Cost
able cardioverter-defibrillators, and cardiac resyn-
chronization therapies.63 Contemporary evidence The overall cost of HF continues to rise. See Chapter 26
from the GWTG–HF registry suggests that ≈47% (Economic Cost of Cardiovascular Disease) for further
of individuals admitted to the hospital with HF statistics.
should have had initiation of ≥1 new medica- • In 2012, total cost for HF was estimated to
tion on discharge; ≈24% need to start ≥1 new be $30.7 billion (2010$), of which over two-
medication and ≈14% need to start ≥3 new thirds was attributable to direct medical costs.15
medications to be in compliance with current Projections suggest that by 2030, the total cost
guidelines.64 of HF will increase by 127%, to $69.8 billion,
• In a large Swedish registry of patients with HF amounting to ≈$244 for every US adult.15
with preserved EF, statins improved 1-year cardio- • Implantable cardioverter-defibrillators could be
vascular hospitalization, mortality, and cardiovas- cost-effective in the guideline-recommended
cular mortality.65 Accordingly, 5-year survival of HF groups of individuals with HF with reduced EF;
diagnosis after an MI in Olmstead County, MN, however, the benefit might not be as great in
improved in 2001 to 2010 versus 1990 to 2000, those with high overall mortality risk (eg, age
from 54% to 61%.66 ≥75 years, New York Heart Association func-
• Some data suggest that improvements in sur- tional class III, LVEF ≤20%, BNP ≥700 pg/mL, SBP
vival could be leveling off over time. Data from ≤120 mm Hg, AF, DM, chronic lung disease, and
the Rochester Epidemiology Project in Olmsted CKD).69,70
County, MN, showed improved survival after • The costs associated with treating HF comorbidi-
HF diagnosis between 1979 and 200067; how- ties and HF exacerbations in youths are signifi-
ever, 5-year mortality did not decline from 2000 cant, totaling nearly $1 billion in inpatient costs,
to 2010 and remained high at ≈50% (52.6% and may be rising. The associated cost burden of
overall; 24.4% for 60-year-olds and 54.4% for HF is anticipated to constitute a large portion of
80-year-olds), Importantly, mortality was more total pediatric healthcare costs.71
Downloaded from http://ahajournals.org by on February 7, 2019

frequently ascribed to noncardiovascular causes

(54.3%), and the risk of noncardiovascular death Open Heart Transplantation and Assist Device
was greater in HF with preserved EF than in HF Placement in the United States
with reduced EF.18 (See Chart 20-7)
• Given improvements in HF survival overall, the From September 1987 to December 2012, 40 253
number of individuals carrying a diagnosis of HF people were waiting for heart transplants, with a
at death has increased. Mortality associated with median survival of 2.3 years; 26 943 received trans-
HF is substantial, such that 1 in 8 deaths has HF plants, with median survival of 9.5 years. Life-years
mentioned on the death certificate (NCHS, NHLBI saved were 465  296; life-years saved per patient
unpublished tabulation).68 were 5.0.
• In 2016, HF was the underlying cause in • The 7th INTERMACS report of >15 000 LVAD
78  356 deaths (35  424 males and 42  932 implantations from June 2006 to December 2014
females).68 Table  20-2 shows the numbers of revealed 80% survival at 1 year and 70% at 2
these deaths that were coded for HF as the years.72
underlying cause. • The number of patients receiving LVADs increased
• The number of underlying cause of deaths attrib- from 98 in 2006 to 2423 in 2014.
utable to HF was 27.7% higher in 2015 (75 251) • The proportion of LVADs as destination therapy
than it was in 2005 (58 933) (NCHS, NHLBI unpub- increased from 14.7% in 2006 to 2007 to 19.6%
lished tabulation). in 2008 to 2010, 41.6% in 2011 to 2013, and
• In 2015, the overall any-mention age-adjusted 45.7% in 201472 (Chart 20-7).
death rate for HF was 87.9 per 100 000, with • The NIS reported 2038 LVAD implantations from
variation across racial/ethnic groups: in males, 2005 to 2011, with 127 in 2005 and increasing to
the rates were 107.4 for NH whites, 112.6 for 506 procedures in 2011.73
NH blacks, 47.0 for NH Asians or Pacific Islanders, • In-hospital mortality with LVAD implantation
100.9 for NH American Indians or Alaska Natives, decreased significantly from 47.2% in 2005
and 67.5 for Hispanics; in females, the respec- to 12.7% in 2011. An inflection point was
tive rates were 79.6 for NH whites, 83.9 for NH seen with a sharp rise in LVAD implantation

e388 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

and decrease in the in-hospital mortality transplantation performed at 102 centers, blacks

CLINICAL STATEMENTS
rate in 2008. Average hospital length of stay had a higher adjusted 1-year mortality, particu-

AND GUIDELINES
decreased from the pulsatile LVAD (pre-2008) to larly at poor-performing centers (observed-to-
the continuous-flow LVAD (2008–2011) eras.74 expected mortality ratio >1.2; OR, 1.37 [95% CI,
The mean cost of LVAD-related hospitalization 1.12–1.69]; P=0.002).79 Compared with whites
increased from $194 380 in 2005 to $234 808 and Hispanics, a higher proportion of blacks were
in 2011.75 treated at centers with higher than expected mor-
• In a meta-analysis of 8 studies (7957 patients tality, which persisted after adjustment for insur-
total) comparing mortality rates in patients ance type and education level.
treated with heart transplantation versus bridge-
to-transplantation LVAD or LVAD as destina-
Family History and Genetics
tion therapy, there was no difference in late (>6
months) all-cause mortality between heart trans- • HCM and familial DCM are the most common
plantation and LVAD (pooled OR, 0.91 [95% CI, mendelian cardiomyopathies, with autosomal
0.62–1.32] for transplantation versus bridge-to- dominant or recessive transmission, in addition to
transplantation LVAD; pooled OR, 1.49 [95% CI, X-linked and mitochondrial inheritance.
0.48–4.66] for transplantation versus destination • Familial DCM accounts for up to 50% of cases of
therapy LVAD).76 DCM, with a prevalence of 1 in 2500, but is likely
• In a Markov model analysis, compared with underestimated.80 Familial DCM often displays an
nonbridged heart transplant recipients (who did age-dependent penetrance.81 Up to 40% of cases
not receive an LVAD bridge), receiving a bridge- have an identifiable genetic cause.80
to-transplantation LVAD increased survival, with • Given the heterogeneous nature of the under-
greater associated cost (range, $84 964 per lying genetics, manifestation of the disease is
life-year to $119 574 per life-year for high-risk highly variable, even in cases for which the causal
and low-risk patients, respectively). Open heart mutation has been identified.82 Variants in the
transplantation increased life expectancy and β-myosin heavy chain gene (MYH7) were some
was cost-effective (8.5 years with <$100 000 of the earliest to be associated with familial
per QALY relative to medical therapy), but LVAD HCM,83,84 with >30 other genes implicated since,
each accounting for <5% of cases, as reviewed
Downloaded from http://ahajournals.org by on February 7, 2019

either for bridge to transplantation (12.3 years

at $226 000 per QALY) or as destination ther- elsewhere.81,85,86 The considerable variability in the
apy (4.4 years at $202 000 per QALY) was not penetrance and pathogenicity of specific muta-
cost-effective.77 tions makes clinical interpretation of sequence
• Elevated LVAD index admission costs could data particularly challenging.
be related to procurement costs and length • Missense and truncating variants in the Titin gene
of stay. Hospital readmissions also contribute have been linked to autosomal dominant cardio-
significantly to overall cost of LVAD therapy: myopathy,87 as well as to DCM, with incomplete
with continuous-flow LVAD, 44% of patients penetrance in the general population.87 Analysis
were readmitted within 30 days of discharge, of sequence data in 7855 cardiomyopathy case
with a median cost of $7546. The most com- subjects and >60 000 control subjects revealed
mon causes of readmission were gastrointesti- the variance in penetrance of putative disease
nal bleeding, infection, and stroke, with device variants, which further highlights the challenges
malfunction and arrhythmias the most costly in clinical interpretation of variation in mendelian
causes of readmission. There was no difference disease genes.88
in survival between patients who were and were • Several GWASs have been conducted to
not readmitted, although median follow-up was identify common variations associated with
only 11 months.78 cardiomyopathy and HF in the general popula-
tion, albeit with modest results,81,84 highlight-
LVAD and Open Heart Transplantation ing a small number of putative loci, including
Disparities HSPB789–91 and CACNB4.92 Given the hetero-
• The 7th INTERMACS report did not specifically geneous multifactorial nature of common HF,
address the influence of race or ethnicity on mor- identification of causal genetic loci remains a
tality after LVAD procedures but did report that a challenge.
higher mortality was seen in females (HR, 1.16; • Genetic variation within subjects with HF may
P=0.005).72 determine outcomes, with a locus on chromosome
• In the United Network for Organ Sharing 5q22 associated with mortality in HF patients.93 A
Database of 18 085 patients who had open heart large meta-analysis of >73 000 subjects identified

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e389

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

52 loci associated with myocardial mass.94 The contributor to HF in certain parts of South Asia,
CLINICAL STATEMENTS

clinical utility of genetic testing for variants asso- such as India, but recently, trends toward an isch-
AND GUIDELINES

ciated with common HF and related phenotypes emic cause for HF have been observed in Asia,
remains unclear. such as in China and Japan.99
• HCM is a monogenic disorder with primarily auto- • Ischemic HF prevalence in 2010 was highest
somal dominant inheritance and is caused by one (>5 per 1000) in high-income North America,
of hundreds of mutations in up to 18 genes that Oceania, and Eastern Europe. In particular, HF
primarily encode components of the sarcomere, prevalence in 2010 was highest in Oceania (4.53
with mutations in MYH7 and cardiac myosin- [95% CI, 3.19–6.29] per 1000 in females; 5.22
binding protein C (MYBPC3) being the most com- [95% CI, 3.84–7.08] per 1000 in males), followed
mon, with each having 40 HCM cases attributed by high-income North America and North Africa/
to it.95 A mutation is identifiable in 50% to 75% Middle East. HF prevalence was lowest in west
of familial HCM cases. sub-Saharan Africa (0.74 [95% CI, 0.58–0.98] per
• Clinical genetic testing is recommended for 1000 in males and 0.57 [96% CI, 0.44–0.76] per
patients with DCM with significant conduction 1000 in females).100 HF made the largest contribu-
system disease or a family history of SCD, as well tion to age-standardized years lived with disabil-
as in patients with a strong clinical index of suspi- ity among males in high-income North America,
cion for HCM. It can be considered in other forms
Oceania, Eastern and Western Europe, southern
of DCM and restrictive cardiomyopathy and in LV
Latin America, and Central Asia.100
noncompaction.96
• HF risk factors vary substantially across world
• Genetic testing is also recommended in family
regions, with hypertension being highly associ-
members of patients with DCM, HCM, restrictive
ated with HF in all regions but most commonly
cardiomyopathy, and LV noncompaction.96
in Latin America, the Caribbean, Eastern Europe,
and sub-Saharan Africa, and with a minimal asso-
Global Burden of HF ciation of IHD with HF in sub-Saharan Africa.101
• HF is common throughout sub-Saharan Africa. IHD prevalence among HF patients is highest
Forty-four percent of patients with newly diag- in Europe and North America but rare in sub-
Saharan Africa, whereas hypertension prevalence
Downloaded from http://ahajournals.org by on February 7, 2019

nosed CVD have HF, whereas only 10% have

CAD.97 Common causes include nonischemic among HF patients was highest in Eastern Europe
cardiomyopathies, rheumatic HD, congeni- and sub-Saharan Africa; valvular and rheumatic
tal HD, hypertensive HD, and endomyocardial HD prevalence among HF patients was highest in
fibrosis; IHD remains relatively uncommon. HF East Asia and Asia-Pacific countries.101 Follow-up
strikes individuals in sub-Saharan Africa at a from a multiethnic cohort composed of indi-
much younger age than in the United States and viduals from low- to middle-income countries in
Europe.98 Africa, Asia, the Middle East, and South America
• The prevalence estimates for HF across Asia range will provide additional data regarding the global
from 1.26% to 6.7%. Rheumatic HD is a major burden of HF.102

e390 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

Table 20-1.  Global Prevalence and Mortality of Cardiomyopathy and Myocarditis52

CLINICAL STATEMENTS
Both Sexes Combined Males Females

AND GUIDELINES
Death Prevalence Death Prevalence Death Prevalence
(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)
Total number (millions) 0.3 6.1 0.2 2.8 0.1 3.4
(0.3 to 0.4) (5.6 to 6.7) (0.2 to 0.2) (2.5 to 3.0) (0.1 to 0.2) (3.1 to 3.7)
Percent change total number 2006 13.1 19.8 12.0 21.4 14.7 18.6
to 2016 (5.1 to 23.9) (18.0 to 21.6) (1.3 to 25.3) (19.1 to 23.7) (5.2 to 27.1) (16.5 to 20.7)
Percent change total number 1990 46.1 36.5 52.5 37.6 38.6 35.5
to 2016 (32.1 to 69.7) (33.5 to 39.4) (35.1 to 78.2) (33.7 to 41.2) (22.1 to 70.7) (32.2 to 38.7)
Rate per 100 000 5.2 88.9 6.3 84.9 4.1 92.2
(4.3 to 5.7) (81.2 to 98.1) (5.1 to 7.0) (77.2 to 94.3) (3.2 to 4.6) (84.6 to 101.2)
Percent change rate 1990 to 2016 −27.3 −24.1 −24.1 −24.4 −31.4 −23.1
(−34.8 to −10.9) (−25.8 to −22.3) (−32.9 to −5.8) (−26.5 to −22.3) (−40.2 to −12.0) (−24.9 to −21.1)
Percent change rate 2006 to 2016 −13.0 −4.7 −12.5 −3.8 −13.5 −4.8
(−19.0 to −4.7) (−5.9 to −3.4) (−20.0 to −3.0) (−5.6 to −2.1) (−20.6 to −4.0) (−6.2 to −3.2)

Table 20-2.  Heart Failure

Prevalence, 2013– Incidence, 2014, Mortality, 2016, Hospital Discharge,

Population Group 2016, Age ≥20 y Age ≥55 y All Ages* 2014, All Ages Cost, 2012†
Both sexes 6 200 000 (2.2%) 1 000 000 78 356 900 000 $30.7 billion
Males 3 000 000 (2.4%) 495 000 35 424 (45.2%)‡ 462 000 …
Females 3 200 000 (2.1%) 505 000 42 932 (54.8%)‡ 438 000 …
NH white males 2.2% 430 000§ 29 155 … …
NH white females 1.9% 425 000§ 35 526 … …
NH black males 3.5% 65 000§ 3777 … …
NH black females 3.9% 80 000§ 4584 … …
Downloaded from http://ahajournals.org by on February 7, 2019

Hispanic males 2.5% … 1721 … …

Hispanic females 2.1% … 1905 … …
NH Asian males 1.7% … 561‖ … …

NH Asian females 0.7% … 715‖ … …

NH American Indian or Alaska Native … … 262 … …

Heart failure includes people who answered “yes” to the question of ever having congestive heart failure. Ellipses (…) indicate data not available; and NH,
non-Hispanic.
*Mortality data for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because
of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown
underreporting on death certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these
groups in censuses.
†Cost data are from Heidenreich et al.15
‡These percentages represent the portion of total mortality attributable to heart failure that is for males vs females.
§Estimates for whites include other nonblack races.
‖Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2013 to 2016 (National Center for Health Statistics [NCHS]) and National Heart,
Lung, and Blood Institute (NHLBI). Percentages are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2016 US
population estimates. These data are based on self-reports. Incidence: Atherosclerosis Risk in Communities Study Community Surveillance, 2005 to 2014
from the NHLBI. Mortality: Centers for Disease Control and Prevention/NCHS, 2016 Mortality Multiple Cause-of-Death–United States. Mortality for NH Asians
includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, Hospital Discharges, 2014 (data include those inpatients discharged
alive, dead, or status unknown).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e391

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20
CLINICAL STATEMENTS
AND GUIDELINES
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 20-1. Incidence of peripartum cardiomyopathy.

Adapted from Blauwet et al103 with permission from BMJ Publishing Group Ltd. Copyright © 2011, BMJ Publishing Group Ltd and the British Cardiovascular
Society.

e392 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

CLINICAL STATEMENTS
AND GUIDELINES
Chart 20-2. Age-standardized global mortality rates of cardiomyopathy and myocarditis per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.14 Printed with permission. Copyright ©
2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 20-3. Age-standardized global prevalence rates of cardiomyopathy and myocarditis per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.14 Printed with permission. Copyright ©
2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e393

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20
CLINICAL STATEMENTS
AND GUIDELINES

Chart 20-4. Prevalence of heart failure for adults ≥20 years by sex and age (NHANES, 2013–2016).
NHANES indicates National Health and Nutrition Examination Survey.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 20-5. First acute decompensated heart failure annual event rates per 1000 from ARIC Community Surveillance (2005–2014).
ARIC indicates Atherosclerosis Risk in Communities Study.
Source: ARIC and National Heart, Lung, and Blood Institute.

e394 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

CLINICAL STATEMENTS
AND GUIDELINES
Chart 20-6. Hospital discharges for heart failure by sex (United States, 1997–2014).
Hospital discharges include people discharged alive, dead, and status unknown.
Source: National Hospital Discharge Survey/National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 20-7. Number of patients receiving left ventricular assist devices in the United States, 2006 to 2014.
Adapted from Kirklin et al.72 with permission from the International Society for Heart and Lung Transplantation. Copyright © 2015, International Society for Heart
and Lung Transplantation.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e395

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

REFERENCES Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett

CLINICAL STATEMENTS

S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H,

1. Bick AG, Flannick J, Ito K, Cheng S, Vasan RS, Parfenov MG, Herman
AND GUIDELINES

Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine
DS, DePalma SR, Gupta N, Gabriel SB, Funke BH, Rehm HL, Benjamin EJ, H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson
Aragam J, Taylor HA Jr, Fox ER, Newton-Cheh C, Kathiresan S, O’Donnell DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L,
CJ, Wilson JG, Altshuler DM, Hirschhorn JN, Seidman JG, Seidman Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman
C. Burden of rare sarcomere gene variants in the Framingham and MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari
Jackson Heart Study cohorts. Am J Hum Genet. 2012;91:513–519. doi:
F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F,
10.1016/j.ajhg.2012.07.017
Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D,
2. Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino
Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B,
AL, Fox JC, Lakdawala NK, Ware JS, Caleshu CA, Helms AS, Colan
Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James
SD, Girolami F, Cecchi F, Seidman CE, Sajeev G, Signorovitch J, Green
SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan
EM, Olivotto I. Genotype and lifetime burden of disease in hyper-
G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton
trophic cardiomyopathy: insights from the Sarcomeric Human
LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL,
Cardiomyopathy Registry (SHaRe). Circulation. 2018;138:1387–1398.
Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M,
doi: 10.1161/CIRCULATIONAHA.117.003200
Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J,
3. Givertz MM, Mann DL. Epidemiology and natural history of recovery of
MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W,
left ventricular function in recent onset dilated cardiomyopathies. Curr
March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R,
Heart Fail Rep. 2013;10:321–330. doi: 10.1007/s11897-013-0157-5
Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-
4. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med.
Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli
1994;331:1564–1575. doi: 10.1056/NEJM199412083312307
V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad
5. Kolte D, Khera S, Aronow WS, Palaniswamy C, Mujib M, Ahn C, Jain D,
AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L,
Gass A, Ahmed A, Panza JA, Fonarow GC. Temporal trends in incidence
Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan
and outcomes of peripartum cardiomyopathy in the United States: a
KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman
nationwide population-based study. J Am Heart Assoc. 2014;3:e001056.
P, Norman R, O’Donnell M, O’Hanlon S, Olives C, Omer SB, Ortblad K,
doi: 10.1161/JAHA.114.001056
Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB,
6. McNamara DM, Elkayam U, Alharethi R, Damp J, Hsich E, Ewald G, Modi
Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips
K, Alexis JD, Ramani GV, Semigran MJ, Haythe J, Markham DW, Marek
MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S,
J, Gorcsan J 3rd, Wu WC, Lin Y, Halder I, Pisarcik J, Cooper LT, Fett JD;
Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D,
IPAC Investigators. Clinical outcomes for peripartum cardiomyopathy in
Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara
North America: results of the IPAC study (Investigations of Pregnancy-
FP, Roberts T, Robinson C, De Leòn FR, Ronfani L, Room R, Rosenfeld LC,
Associated Cardiomyopathy). J Am Coll Cardiol. 2015;66:905–914. doi:
10.1016/j.jacc.2015.06.1309 Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E,
7. Wilkinson JD, Landy DC, Colan SD, Towbin JA, Sleeper LA, Orav EJ, Cox Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H,
GF, Canter CE, Hsu DT, Webber SA, Lipshultz SE. The pediatric cardiomy- Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K,
opathy registry and heart failure: key results from the first 15 years. Heart Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ,
Fail Clin. 2010;6:401–13, vii. doi: 10.1016/j.hfc.2010.05.002 Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor
8. Colan SD, Lipshultz SE, Lowe AM, Sleeper LA, Messere J, Cox GF, WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin
JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ,
Downloaded from http://ahajournals.org by on February 7, 2019

Lurie PR, Orav EJ, Towbin JA. Epidemiology and cause-specific out-
come of hypertrophic cardiomyopathy in children: findings from the van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt
Pediatric Cardiomyopathy Registry. Circulation. 2007;115:773–781. doi: K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman
10.1161/CIRCULATIONAHA.106.621185 MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC,
9. Ziółkowska L, Turska-Kmieć A, Petryka J, Kawalec W. Predictors of long- Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng
term outcome in children with hypertrophic cardiomyopathy. Pediatr ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Years
Cardiol. 2016;37:448–458. doi: 10.1007/s00246-015-1298-y lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries
10. Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, 1990-2010: a systematic analysis for the Global Burden of Disease Study
Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE. Incidence, 2010 [published correction appears in Lancet. 2013;381:628]. Lancet.
causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2012;380:2163–2196. doi: 10.1016/S0140-6736(12)61729-2
2006;296:1867–1876. doi: 10.1001/jama.296.15.1867 14. Global Burden of Disease Study 2016. Global Burden of Disease Study
11. Pahl E, Sleeper LA, Canter CE, Hsu DT, Lu M, Webber SA, Colan SD, 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
Kantor PF, Everitt MD, Towbin JA, Jefferies JL, Kaufman BD, Wilkinson JD, Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
Lipshultz SE; Pediatric Cardiomyopathy Registry Investigators. Incidence of data.org/gbd-results-tool. Accessed May 1, 2018.
and risk factors for sudden cardiac death in children with dilated cardio- 15. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC,
myopathy: a report from the Pediatric Cardiomyopathy Registry. J Am Coll Ikonomidis JS, Khavjou O, Konstam MA, Maddox TM, Nichol G, Pham M,
Cardiol. 2012;59:607–615. doi: 10.1016/j.jacc.2011.10.878 Piña IL, Trogdon JG; on behalf of the American Heart Association Advocacy
12. Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Coordinating Committee; Council on Arteriosclerosis, Thrombosis and
Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM. Cardiac Vascular Biology; Council on Cardiovascular Radiology and Intervention;
outcomes in a cohort of adult survivors of childhood and adolescent can- Council on Clinical Cardiology; Council on Epidemiology and Prevention;
cer: retrospective analysis of the Childhood Cancer Survivor Study cohort. Stroke Council. Forecasting the impact of heart failure in the United
BMJ. 2009;339:b4606. doi: 10.1136/bmj.b4606 States: a policy statement from the American Heart Association. Circ
13. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya Heart Fail. 2013;6:606–619. doi: 10.1161/HHF.0b013e318291329a
K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal 16. Huffman MD, Berry JD, Ning H, Dyer AR, Garside DB, Cai X, Daviglus ML,
R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews Lloyd-Jones DM. Lifetime risk for heart failure among white and black
KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Americans: cardiovascular lifetime risk pooling project. J Am Coll Cardiol.
Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, 2013;61:1510–1517. doi: 10.1016/j.jacc.2013.01.022
Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, 17. Barker WH, Mullooly JP, Getchell W. Changing incidence and survival
Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous for heart failure in a well-defined older population, 1970-1974 and 1990-
S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, 1994. Circulation. 2006;113:799–805. doi: 10.1161/CIRCULATIONAHA.
Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle 104.492033
G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, 18. Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM,
Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen Jiang R, Killian JM, Roger VL. A contemporary appraisal of the heart fail-
H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, ure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern
Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, Med. 2015;175:996–1004. doi: 10.1001/jamainternmed.2015.0924
de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar 19. Bibbins-Domingo K, Pletcher MJ, Lin F, Vittinghoff E, Gardin JM, Arynchyn
KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De A, Lewis CE, Williams OD, Hulley SB. Racial differences in incident heart

e396 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

failure among young adults. N Engl J Med. 2009;360:1179–1190. doi: Aging, and Body Composition) study. J Am Coll Cardiol. 2010;55:2129–

CLINICAL STATEMENTS
10.1056/NEJMoa0807265 2137. doi: 10.1016/j.jacc.2009.12.045

AND GUIDELINES
20. Chang PP, Wruck LM, Shahar E, Rossi JS, Loehr LR, Russell SD, Agarwal 36. deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan
SK, Konety SH, Rodriguez CJ, Rosamond WD. Trends in hospitaliza- M, Seliger SL. Association of serial measures of cardiac troponin T using a
tions and survival of acute decompensated heart failure in four US sensitive assay with incident heart failure and cardiovascular mortality in
communities (2005–2014): the Atherosclerosis Risk in Communities older adults. JAMA. 2010;304:2494–2502. doi: 10.1001/jama.2010.1708
(ARIC) study community surveillance. Circulation. 2018;138:12–24. doi: 37. Mozaffarian D, Lemaitre RN, King IB, Song X, Spiegelman D, Sacks
10.1161/CIRCULATIONAHA.117.027551 FM, Rimm EB, Siscovick DS. Circulating long-chain ω-3 fatty acids and
21. Bahrami H, Kronmal R, Bluemke DA, Olson J, Shea S, Liu K, Burke GL, incidence of congestive heart failure in older adults: the cardiovascular
Lima JA. Differences in the incidence of congestive heart failure by health study: a cohort study. Ann Intern Med. 2011;155:160–170. doi:
ethnicity: the Multi-Ethnic Study of Atherosclerosis. Arch Intern Med. 10.7326/0003-4819-155-3-201108020-00006
2008;168:2138–2145. doi: 10.1001/archinte.168.19.2138 38. Agarwal SK, Simpson RJ Jr, Rautaharju P, Alonso A, Shahar E, Massing
22. Kovell LC, Juraschek SP, Russell SD. Stage A heart failure is not adequately M, Saba S, Heiss G. Relation of ventricular premature complexes to heart
recognized in US adults: analysis of the National Health and Nutrition failure (from the Atherosclerosis Risk In Communities [ARIC] Study). Am J
Examination Surveys, 2007-2010. PLoS One. 2015;10:e0132228. doi: Cardiol. 2012;109:105–109. doi: 10.1016/j.amjcard.2011.08.009
10.1371/journal.pone.0132228 39. Bekwelem W, Lutsey PL, Loehr LR, Agarwal SK, Astor BC, Guild C, Ballantyne
23. Dunlay SM, Weston SA, Jacobsen SJ, Roger VL. Risk factors for heart fail- CM, Folsom AR. White blood cell count, C-reactive protein, and incident
ure: a population-based case-control study. Am J Med. 2009;122:1023– heart failure in the Atherosclerosis Risk in Communities (ARIC) Study. Ann
1028. doi: 10.1016/j.amjmed.2009.04.022 Epidemiol. 2011;21:739–748. doi: 10.1016/j.annepidem.2011.06.005
24. Kalogeropoulos A, Georgiopoulou V, Kritchevsky SB, Psaty BM, Smith NL, 40. Blecker S, Matsushita K, Köttgen A, Loehr LR, Bertoni AG, Boulware LE,
Newman AB, Rodondi N, Satterfield S, Bauer DC, Bibbins-Domingo K, Coresh J. High-normal albuminuria and risk of heart failure in the commu-
Smith AL, Wilson PW, Vasan RS, Harris TB, Butler J. Epidemiology of inci- nity. Am J Kidney Dis. 2011;58:47–55. doi: 10.1053/j.ajkd.2011.02.391
dent heart failure in a contemporary elderly cohort: the Health, Aging, 41. Matsushita K, Blecker S, Pazin-Filho A, Bertoni A, Chang PP, Coresh J,
and Body Composition Study. Arch Intern Med. 2009;169:708–715. doi: Selvin E. The association of hemoglobin A1C with incident heart failure
10.1001/archinternmed.2009.40 among people without diabetes: the Atherosclerosis Risk in Communities
25. Vivo RP, Krim SR, Cevik C, Witteles RM. Heart failure in Hispanics. J Am study. Diabetes. 2010;59:2020–2026. doi: 10.2337/db10-0165
Coll Cardiol. 2009;53:1167–1175. doi: 10.1016/j.jacc.2008.12.037 42. Roberts CB, Couper DJ, Chang PP, James SA, Rosamond WD, Heiss G.
26. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon Influence of life-course socioeconomic position on incident heart failure
CP, Hernandez AF, Fonarow GC; for the Get With the Guidelines Scientific in blacks and whites: the Atherosclerosis Risk in Communities Study. Am J
Advisory Committee and Investigators. Trends in patients hospitalized Epidemiol. 2010;172:717–727. doi: 10.1093/aje/kwq193
with heart failure and preserved left ventricular ejection fraction: prev- 43. Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle
alence, therapies, and outcomes. Circulation. 2012;126:65–75. doi: E, Hoogeveen RC, Liu X, Astor BC, Mosley TH, Folsom AR, Heiss G, Coresh
10.1161/CIRCULATIONAHA.111.080770 J, Ballantyne CM. Cardiac troponin T measured by a highly sensitive
26a. Djousse L, Driver JA, Gaziano JM. Relation between modifiable lifestyle assay predicts coronary heart disease, heart failure, and mortality in the
factors and lifetime risk of heart failure: The Physicians’ Health Study I. Atherosclerosis Risk in Communities Study. Circulation. 2011;123:1367–
JAMA. 2009;302:394–400. doi: 10.1001/jama.2009.1062 1376. doi: 10.1161/CIRCULATIONAHA.110.005264
27. Folsom AR, Shah AM, Lutsey PL, Roetker NS, Alonso A, Avery CL, Miedema 44. Choi EY, Bahrami H, Wu CO, Greenland P, Cushman M, Daniels LB,
MD, Konety S, Chang PP, Solomon SD. American Heart Association’s Almeida AL, Yoneyama K, Opdahl A, Jain A, Criqui MH, Siscovick D,
Downloaded from http://ahajournals.org by on February 7, 2019

Life’s Simple 7: avoiding heart failure and preserving cardiac structure Darwin C, Maisel A, Bluemke DA, Lima JA. N-terminal pro-B-type natri-
and function. Am J Med. 2015;128:970–6.e2. doi: 10.1016/j.amjmed. uretic peptide, left ventricular mass, and incident heart failure: Multi-
2015.03.027 Ethnic Study of Atherosclerosis. Circ Heart Fail. 2012;5:727–734. doi:
28. Dhingra R, Gona P, Wang TJ, Fox CS, D’Agostino RB Sr, Vasan RS. 10.1161/CIRCHEARTFAILURE.112.968701
Serum gamma-glutamyl transferase and risk of heart failure in the 45. Lam CS, Lyass A, Kraigher-Krainer E, Massaro JM, Lee DS, Ho JE, Levy D,
community. Arterioscler Thromb Vasc Biol. 2010;30:1855–1860. doi: Redfield MM, Pieske BM, Benjamin EJ, Vasan RS. Cardiac dysfunction and
10.1161/ATVBAHA.110.207340 noncardiac dysfunction as precursors of heart failure with reduced and
29. Coglianese EE, Qureshi MM, Vasan RS, Wang TJ, Moore LL. preserved ejection fraction in the community. Circulation. 2011;124:24–
Usefulness of the blood hematocrit level to predict development of 30. doi: 10.1161/CIRCULATIONAHA.110.979203
heart failure in a community. Am J Cardiol. 2012;109:241–245. doi: 46. Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett JC
10.1016/j.amjcard.2011.08.037 Jr, Jacobsen SJ, Rodeheffer RJ. Progression of left ventricular diastolic
30. Velagaleti RS, Gona P, Larson MG, Wang TJ, Levy D, Benjamin EJ, Selhub dysfunction and risk of heart failure. JAMA. 2011;306:856–863. doi:
J, Jacques PF, Meigs JB, Tofler GH, Vasan RS. Multimarker approach for 10.1001/jama.2011.1201
the prediction of heart failure incidence in the community. Circulation. 47. Yeboah J, Rodriguez CJ, Stacey B, Lima JA, Liu S, Carr JJ, Hundley
2010;122:1700–1706. doi: 10.1161/CIRCULATIONAHA.109.929661 WG, Herrington DM. Prognosis of individuals with asymptom-
31. Frankel DS, Vasan RS, D’Agostino RB Sr, Benjamin EJ, Levy D, Wang atic left ventricular systolic dysfunction in the Multi-Ethnic Study
TJ, Meigs JB. Resistin, adiponectin, and risk of heart failure the of Atherosclerosis (MESA). Circulation. 2012;126:2713–2719. doi:
Framingham offspring study. J Am Coll Cardiol. 2009;53:754–762. doi: 10.1161/CIRCULATIONAHA.112.112201
10.1016/j.jacc.2008.07.073 48. Mehta H, Armstrong A, Swett K, Shah SJ, Allison MA, Hurwitz B,
32. Djoussé L, Wilk JB, Hanson NQ, Glynn RJ, Tsai MY, Gaziano JM. Association Bangdiwala S, Dadhania R, Kitzman DW, Arguelles W, Lima J, Youngblood
between adiponectin and heart failure risk in the Physicians’ Health Study. M, Schneiderman N, Daviglus ML, Spevack D, Talavera GA, Raisinghani
Obesity (Silver Spring). 2013;21:831–834. doi: 10.1002/oby.20260 A, Kaplan R, Rodriguez CJ. Burden of systolic and diastolic left ventricu-
33. Gopal DM, Kalogeropoulos AP, Georgiopoulou VV, Tang WW, Methvin lar dysfunction among Hispanics in the United States: insights from the
A, Smith AL, Bauer DC, Newman AB, Kim L, Harris TB, Kritchevsky SB, Echocardiographic Study of Latinos. Circ Heart Fail. 2016;9:e002733. doi:
Butler J; Health ABC Study. Serum albumin concentration and heart fail- 10.1161/CIRCHEARTFAILURE.115.002733
ure risk: the Health, Aging, and Body Composition Study. Am Heart J. 49. Vasan RS, Xanthakis V, Lyass A, Andersson C, Tsao C, Cheng S, Aragam J,
2010;160:279–285. doi: 10.1016/j.ahj.2010.05.022 Benjamin EJ, Larson MG. Epidemiology of left ventricular systolic dysfunc-
34. Gopal DM, Kalogeropoulos AP, Georgiopoulou VV, Smith AL, Bauer DC, tion and heart failure in the Framingham Study: an echocardiographic
Newman AB, Kim L, Bibbins-Domingo K, Tindle H, Harris TB, Tang WW, study over 3 decades. JACC Cardiovasc Imaging. 2018;11:1–11. doi:
Kritchevsky SB, Butler J. Cigarette smoking exposure and heart failure risk 10.1016/j.jcmg.2017.08.007
in older adults: the Health, Aging, and Body Composition Study. Am Heart 50. Centers for Disease Control and Prevention, National Center for Health
J. 2012;164:236–242. doi: 10.1016/j.ahj.2012.05.013 Statistics website. 2010 National Ambulatory Medical Care Survey and
35. Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, 2010 National Hospital Ambulatory Medical Care Survey. For meth-
Harrison DG, Liu Y, Hoffmann U, Bauer DC, Newman AB, Kritchevsky SB, odology, see National Center for Health Statistics, Public Use Data File
Harris TB, Butler J; Health ABC Study Investigators. Inflammatory markers Documentation: 2010 National Ambulatory Medical Care Survey and
and incident heart failure risk in older adults: the Health ABC (Health, Public Use Data File Documentation: 2010 National Hospital Ambulatory

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e397

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

Medical Care Survey. http://www.cdc.gov/nchs/ahcd/ahcd_question- associated with heart failure after myocardial infarction: a contem-
CLINICAL STATEMENTS

naires.htm. Accessed July 17, 2013. porary community perspective. Circ Heart Fail. 2016;9:e002460. doi:
AND GUIDELINES

51. Centers for Disease Control and Prevention website. National Ambulatory 10.1161/CIRCHEARTFAILURE.115.002460
Medical Care Survey: 2015 State and National Summary Tables. https:// 67. Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J,
www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_ Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival
tables.pdf. Accessed June 14, 2018. in a community-based population. JAMA. 2004;292:344–350. doi:
52. Centers for Disease Control and Prevention website. National Hospital 10.1001/jama.292.3.344
Ambulatory Medical Care Survey: 2015 Emergency Department Summary 68. National Center for Health Statistics. Centers for Disease Control and
Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_ Prevention website. National Vital Statistics System: public use data file
web_tables.pdf. Accessed June 14, 2018. documentation: mortality multiple cause-of-death micro-data files, 2016.
53. Dunlay SM, Redfield MM, Weston SA, Therneau TM, Hall Long K, https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed
Shah ND, Roger VL. Hospitalizations after heart failure diagnosis: a May 21, 2018.
community perspective. J Am Coll Cardiol. 2009;54:1695–1702. doi: 69. Bilchick KC, Stukenborg GJ, Kamath S, Cheng A. Prediction of mortality in
10.1016/j.jacc.2009.08.019 clinical practice for Medicare patients undergoing defibrillator implanta-
54. van den Broek KC, Defilippi CR, Christenson RH, Seliger SL, Gottdiener tion for primary prevention of sudden cardiac death. J Am Coll Cardiol.
JS, Kop WJ. Predictive value of depressive symptoms and B-type natri- 2012;60:1647–1655. doi: 10.1016/j.jacc.2012.07.028
uretic peptide for new-onset heart failure and mortality. Am J Cardiol. 70. Heidenreich PA, Tsai V, Curtis J, Wang Y, Turakhia MP, Masoudi FA,
2011;107:723–729. doi: 10.1016/j.amjcard.2010.10.055 Varosy PD, Goldstein MK. A validated risk model for 1-year mortal-
55. Golwala H, Pandey A, Ju C, Butler J, Yancy C, Bhatt DL, Hernandez AF, ity after primary prevention implantable cardioverter defibrillator
Fonarow GC. Temporal trends and factors associated with cardiac reha- placement. Am Heart J. 2015;170:281–289.e2. doi: 10.1016/j.ahj.
bilitation referral among patients hospitalized with heart failure: findings 2014.12.013
from Get With The Guidelines-Heart Failure Registry. J Am Coll Cardiol. 71. Nandi D, Rossano JW. Epidemiology and cost of heart failure
2015;66:917–926. doi: 10.1016/j.jacc.2015.06.1089 in children. Cardiol Young. 2015;25:1460–1468. doi: 10.1017/
56. Sueta CA, Rodgers JE, Chang PP, Zhou L, Thudium EM, Kucharska-Newton S1047951115002280
AM, Stearns SC. Medication adherence based on part D claims for 72. Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume
patients with heart failure after hospitalization (from the Atherosclerosis ED, Myers SL, Miller MA, Baldwin JT, Young JB. Seventh INTERMACS
Risk in Communities Study). Am J Cardiol. 2015;116:413–419. doi: annual report: 15,000 patients and counting. J Heart Lung Transplant.
10.1016/j.amjcard.2015.04.058 2015;34:1495–1504. doi: 10.1016/j.healun.2015.10.003
57. Bello NA, Claggett B, Desai AS, McMurray JJ, Granger CB, Yusuf S, 73. Shah N, Agarwal V, Patel N, Deshmukh A, Chothani A, Garg J, Badheka
Swedberg K, Pfeffer MA, Solomon SD. Influence of previous heart fail- A, Martinez M, Islam N, Freudenberger R. National trends in utilization,
ure hospitalization on cardiovascular events in patients with reduced mortality, complications, and cost of care after left ventricular assist device
and preserved ejection fraction. Circ Heart Fail. 2014;7:590–595. doi: implantation from 2005 to 2011. Ann Thorac Surg. 2016;101:1477–
10.1161/CIRCHEARTFAILURE.113.001281 1484. doi: 10.1016/j.athoracsur.2015.09.013
58. Vivo RP, Krim SR, Krim NR, Zhao X, Hernandez AF, Peterson ED, Piña IL, 74. Khazanie P, Hammill BG, Patel CB, Eapen ZJ, Peterson ED, Rogers JG, Milano
Bhatt DL, Schwamm LH, Fonarow GC. Care and outcomes of Hispanic CA, Curtis LH, Hernandez AF. Trends in the use and outcomes of ventricu-
patients admitted with heart failure with preserved or reduced ejection lar assist devices among Medicare beneficiaries, 2006 through 2011. J Am
fraction: findings from Get With The Guidelines-Heart Failure. Circ Heart Coll Cardiol. 2014;63:1395–1404. doi: 10.1016/j.jacc.2013.12.020
Fail. 2012;5:167–175. doi: 10.1161/CIRCHEARTFAILURE.111.963546 75. Miller LW, Guglin M, Rogers J. Cost of ventricular assist devices: can
Downloaded from http://ahajournals.org by on February 7, 2019

59. Chang PP, Chambless LE, Shahar E, Bertoni AG, Russell SD, Ni H, He M, we afford the progress? Circulation. 2013;127:743–748. doi: 10.1161/
Mosley TH, Wagenknecht LE, Samdarshi TE, Wruck LM, Rosamond WD. CIRCULATIONAHA.112.139824
Incidence and survival of hospitalized acute decompensated heart failure in 76. Theochari CA, Michalopoulos G, Oikonomou EK, Giannopoulos S,
four US communities (from the Atherosclerosis Risk in Communities Study). Doulamis IP, Villela MA, Kokkinidis DG. Heart transplantation versus left
Am J Cardiol. 2014;113:504–510. doi: 10.1016/j.amjcard.2013.10.032 ventricular assist devices as destination therapy or bridge to transplan-
60. Dupre ME, Curtis LH, Peterson ED. Racial and ethnic differences in trajec- tation for 1-year mortality: a systematic review and meta-analysis. Ann
tories of hospitalizations in US men and women with heart failure. J Am Cardiothorac Surg. 2018;7:3–11. doi: 10.21037/acs.2017.09.18
Heart Assoc. 6e006290:1–11. doi: 10.1161/jaha.117.006290 77. Alba AC, Alba LF, Delgado DH, Rao V, Ross HJ, Goeree R. Cost-effectiveness
61. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez- of ventricular assist device therapy as a bridge to transplantation com-
Sarano M. Burden of valvular heart diseases: a population-based study. pared with nonbridged cardiac recipients. Circulation. 2013;127:2424–
Lancet. 2006;368:1005–1011. doi: 10.1016/S0140-6736(06)69208-8 2435. doi: 10.1161/CIRCULATIONAHA.112.000194
61a. Chen J, Normand S-LT, Wang Y, Krumholz HM. National and regional trends 78. Marasco SF, Summerhayes R, Quayle M, McGiffin D, Luthe M. Cost com-
in heart failure hospitalization and mortality rates for Medicare beneficiaries, parison of heart transplant vs. left ventricular assist device therapy at one
1998–2008. JAMA. 2011;306:1669–1678. doi: 10.1001/jama.2011.1474 year. Clin Transplant. 2016;30:598–605. doi: 10.1111/ctr.12725
62. Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. 79. Kilic A, Higgins RS, Whitson BA, Kilic A. Racial disparities in outcomes
Heart failure incidence and survival (from the Atherosclerosis Risk in of adult heart transplantation. Circulation. 2015;131:882–889. doi:
Communities study). Am J Cardiol. 2008;101:1016–1022. doi: 10.1016/j. 10.1161/CIRCULATIONAHA.114.011676
amjcard.2007.11.061 80. Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the com-
63. Merlo M, Pivetta A, Pinamonti B, Stolfo D, Zecchin M, Barbati G, Di plexity of a diverse genetic architecture. Nat Rev Cardiol. 2013;10:531–
Lenarda A, Sinagra G. Long-term prognostic impact of therapeutic 547. doi: 10.1038/nrcardio.2013.105
strategies in patients with idiopathic dilated cardiomyopathy: changing 81. Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in
mortality over the last 30 years. Eur J Heart Fail. 2014;16:317–324. doi: familial dilated cardiomyopathy. J Am Coll Cardiol. 2011;57:1641–1649.
10.1002/ejhf.16 doi: 10.1016/j.jacc.2011.01.015
64. Allen LA, Fonarow GC, Liang L, Schulte PJ, Masoudi FA, Rumsfeld JS, 82. Page SP, Kounas S, Syrris P, Christiansen M, Frank-Hansen R, Andersen
Ho PM, Eapen ZJ, Hernandez AF, Heidenreich PA, Bhatt DL, Peterson ED, PS, Elliott PM, McKenna WJ. Cardiac myosin binding protein-C muta-
Krumholz HM; on behalf of the American Heart Association’s Get With tions in families with hypertrophic cardiomyopathy: disease expression in
The Guidelines Heart Failure (GWTG-HF) Investigators. Medication initia- relation to age, gender, and long term outcome. Circ Cardiovasc Genet.
tion burden required to comply with heart failure guideline recommenda- 2012;5:156–166. doi: 10.1161/CIRCGENETICS.111.960831
tions and hospital quality measures. Circulation. 2015;132:1347–1353. 83. Marian AJ, Yu QT, Mares A Jr, Hill R, Roberts R, Perryman MB. Detection
doi: 10.1161/CIRCULATIONAHA.115.014281 of a new mutation in the beta-myosin heavy chain gene in an individual
65. Alehagen U, Benson L, Edner M, Dahlström U, Lund LH. Association with hypertrophic cardiomyopathy. J Clin Invest. 1992;90:2156–2165.
between use of statins and mortality in patients with heart failure doi: 10.1172/JCI116101
and ejection fraction of ≥50. Circ Heart Fail. 2015;8:862–870. doi: 84. Perryman MB, Yu QT, Marian AJ, Mares A Jr, Czernuszewicz G, Ifegwu J,
10.1161/CIRCHEARTFAILURE.115.002143 Hill R, Roberts R. Expression of a missense mutation in the messenger RNA
66. Gerber Y, Weston SA, Enriquez-Sarano M, Berardi C, Chamberlain for beta-myosin heavy chain in myocardial tissue in hypertrophic cardio-
AM, Manemann SM, Jiang R, Dunlay SM, Roger VL. Mortality myopathy. J Clin Invest. 1992;90:271–277. doi: 10.1172/JCI115848

e398 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 20

85. Cahill TJ, Ashrafian H, Watkins H. Genetic cardiomyopathies causing Ferrucci L, Ford I, Gieger C, Harris TB, Haugen E, Heinig M, Hernandez

CLINICAL STATEMENTS
heart failure. Circ Res. 2013;113:660–675. doi: 10.1161/CIRCRESAHA. DG, Hillege HL, Hirschhorn JN, Hofman A, Hubner N, Hwang SJ, Iorio A,

AND GUIDELINES
113.300282 Kähönen M, Kellis M, Kolcic I, Kooner IK, Kooner JS, Kors JA, Lakatta EG,
86. Tayal U, Prasad S, Cook SA. Genetics and genomics of dilated cardio- Lage K, Launer LJ, Levy D, Lundby A, Macfarlane PW, May D, Meitinger
myopathy and systolic heart failure. Genome Med. 2017;9:20. doi: T, Metspalu A, Nappo S, Naitza S, Neph S, Nord AS, Nutile T, Okin PM,
10.1186/s13073-017-0410-8 Olsen JV, Oostra BA, Penninger JM, Pennacchio LA, Pers TH, Perz S,
87. Hastings R, de Villiers CP, Hooper C, Ormondroyd L, Pagnamenta A, Lise Peters A, Pinto YM, Pfeufer A, Pilia MG, Pramstaller PP, Prins BP, Raitakari
S, Salatino S, Knight SJ, Taylor JC, Thomson KL, Arnold L, Chatziefthimiou OT, Raychaudhuri S, Rice KM, Rossin EJ, Rotter JI, Schafer S, Schlessinger
SD, Konarev PV, Wilmanns M, Ehler E, Ghisleni A, Gautel M, Blair E, D, Schmidt CO, Sehmi J, Silljé HHW, Sinagra G, Sinner MF, Slowikowski
Watkins H, Gehmlich K. Combination of whole genome sequencing, K, Soliman EZ, Spector TD, Spiering W, Stamatoyannopoulos JA, Stolk
linkage, and functional studies implicates a missense mutation in titin RP, Strauch K, Tan ST, Tarasov KV, Trinh B, Uitterlinden AG, van den
as a cause of autosomal dominant cardiomyopathy with features of left Boogaard M, van Duijn CM, van Gilst WH, Viikari JS, Visscher PM, Vitart
ventricular noncompaction. Circ Cardiovasc Genet. 2016;9:426–435. V, Völker U, Waldenberger M, Weichenberger CX, Westra HJ, Wijmenga
doi: 10.1161/CIRCGENETICS.116.001431 C, Wolffenbuttel BH, Yang J, Bezzina CR, Munroe PB, Snieder H, Wright
88. Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, AF, Rudan I, Boyer LA, Asselbergs FW, van Veldhuisen DJ, Stricker BH,
Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Psaty BM, Ciullo M, Sanna S, Lehtimäki T, Wilson JF, Bandinelli S, Alonso
Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H. Reassessment A, Gasparini P, Jukema JW, Kääb S, Gudnason V, Felix SB, Heckbert SR,
of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases de Boer RA, Newton-Cheh C, Hicks AA, Chambers JC, Jamshidi Y, Visel
and 60,706 reference samples. Genet Med. 2017;19:192–203. doi: A, Christoffels VM, Isaacs A, Samani NJ, de Bakker PIW. 52 genetic loci
10.1038/gim.2016.90 influencing myocardial mass. J Am Coll Cardiol. 2016;68:1435–1448.
89. Cappola TP, Li M, He J, Ky B, Gilmore J, Qu L, Keating B, Reilly M, Kim CE, doi: 10.1016/j.jacc.2016.07.729
Glessner J, Frackelton E, Hakonarson H, Syed F, Hindes A, Matkovich SJ, 95. Watkins H, Ashrafian H, Redwood C. Inherited cardiomyopathies. N Engl
Cresci S, Dorn GW 2nd. Common variants in HSPB7 and FRMD4B associ- J Med. 2011;364:1643–1656. doi: 10.1056/NEJMra0902923
ated with advanced heart failure. Circ Cardiovasc Genet. 2010;3:147– 96. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm
154. doi: 10.1161/CIRCGENETICS.109.898395 AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec
90. Matkovich SJ, Van Booven DJ, Hindes A, Kang MY, Druley TE, Vallania H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H,
FL, Mitra RD, Reilly MP, Cappola TP, Dorn GW 2nd. Cardiac signaling Wilde A, Wolpert C, Zipes DP; Heart Rhythm Society (HRS); European
genes exhibit unexpected sequence diversity in sporadic cardiomyopathy, Heart Rhythm Association (EHRA). HRS/EHRA expert consensus state-
revealing HSPB7 polymorphisms associated with disease. J Clin Invest. ment on the state of genetic testing for the channelopathies and cardio-
2010;120:280–289. doi: 10.1172/JCI39085 myopathies: this document was developed as a partnership between the
91. Stark K, Esslinger UB, Reinhard W, Petrov G, Winkler T, Komajda M, Heart Rhythm Society (HRS) and the European Heart Rhythm Association
Isnard R, Charron P, Villard E, Cambien F, Tiret L, Aumont MC, Dubourg (EHRA) [published correction appears in Europace. 2012;14:277].
O, Trochu JN, Fauchier L, Degroote P, Richter A, Maisch B, Wichter T, Europace. 2011;13:1077–1109. doi: 10.1093/europace/eur245
Zollbrecht C, Grassl M, Schunkert H, Linsel-Nitschke P, Erdmann J, 97. Sliwa K, Wilkinson D, Hansen C, Ntyintyane L, Tibazarwa K, Becker A,
Baumert J, Illig T, Klopp N, Wichmann HE, Meisinger C, Koenig W, Stewart S. Spectrum of heart disease and risk factors in a black urban
Lichtner P, Meitinger T, Schillert A, König IR, Hetzer R, Heid IM, Regitz- population in South Africa (the Heart of Soweto Study): a cohort study.
Zagrosek V, Hengstenberg C. Genetic association study identifies HSPB7 Lancet. 2008;371:915–922. doi: 10.1016/S0140-6736(08)60417-1
as a risk gene for idiopathic dilated cardiomyopathy. PLoS Genet. 98. Damasceno A, Mayosi BM, Sani M, Ogah OS, Mondo C, Ojji D,
Downloaded from http://ahajournals.org by on February 7, 2019

2010;6:e1001167. doi: 10.1371/journal.pgen.1001167 Dzudie A, Kouam CK, Suliman A, Schrueder N, Yonga G, Ba SA,
92. Xu H, Dorn Ii GW, Shetty A, Parihar A, Dave T, Robinson SW, Gottlieb Maru F, Alemayehu B, Edwards C, Davison BA, Cotter G, Sliwa K.
SS, Donahue MP, Tomaselli GF, Kraus WE, Mitchell BD, Liggett SB. A The causes, treatment, and outcome of acute heart failure in 1006
genome-wide association study of idiopathic dilated cardiomyopathy in Africans from 9 countries. Arch Intern Med. 2012;172:1386–1394. doi:
African Americans. J Pers Med. 2018;8:E11. doi: 10.3390/jpm8010011 10.1001/archinternmed.2012.3310
93. Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Cupples 99. Sakata Y, Shimokawa H. Epidemiology of heart failure in Asia. Circ J.
LA, Dehghan A, Lumley T, Rosamond WD, Lieb W, Rivadeneira F, Bis 2013;77:2209–2217.
JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, 100. Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Flaxman
Murabito J, Wang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, A, Murray CJ, Naghavi M. The global burden of ischemic heart disease
Rice KM, Hofman A, Heckbert SR, Fox ER, O’Donnell CJ, Uitterlinden AG, in 1990 and 2010: the Global Burden of Disease 2010 study. Circulation.
Rotter JI, Willerson JT, Levy D, van Duijn CM, Psaty BM, Witteman JC, 2014;129:1493–1501. doi: 10.1161/CIRCULATIONAHA.113.004046
Boerwinkle E, Vasan RS. Association of genome-wide variation with the 101. Khatibzadeh S, Farzadfar F, Oliver J, Ezzati M, Moran A. Worldwide risk
risk of incident heart failure in adults of European and African ancestry: a factors for heart failure: a systematic review and pooled analysis. Int J
prospective meta-analysis from the Cohorts for Heart and Aging Research Cardiol. 2013;168:1186–1194. doi: 10.1016/j.ijcard.2012.11.065
in Genomic Epidemiology (CHARGE) Consortium. Circ Cardiovasc Genet. 102. Dokainish H, Teo K, Zhu J, Roy A, Al-Habib K, ElSayed A, Palileo L,
2010;3:256–266. doi: 10.1161/CIRCGENETICS.109.895763 Jaramillo PL, Karaye K, Yusoff K, Orlandini A, Sliwa K, Mondo C, Lanas
94. van der Harst P, van Setten J, Verweij N, Vogler G, Franke L, Maurano F, Dorairaj P, Huffman M, Badr A, Elmaghawry M, Damasceno A, Belley-
MT, Wang X, Mateo Leach I, Eijgelsheim M, Sotoodehnia N, Hayward Cote E, Harkness K, Grinvalds A, McKelvie R, Yusuf S. Heart failure in
C, Sorice R, Meirelles O, Lyytikäinen LP, Polašek O, Tanaka T, Arking low- and middle-income countries: background, rationale, and design of
DE, Ulivi S, Trompet S, Müller-Nurasyid M, Smith AV, Dörr M, Kerr KF, the INTERnational Congestive Heart Failure Study (INTER-CHF). Am Heart
Magnani JW, Del Greco M F, Zhang W, Nolte IM, Silva CT, Padmanabhan J. 2015;170:627–634.e1. doi: 10.1016/j.ahj.2015.07.008
S, Tragante V, Esko T, Abecasis GR, Adriaens ME, Andersen K, Barnett 103. Blauwet LA, Cooper LT. Diagnosis and management of peripar-
P, Bis JC, Bodmer R, Buckley BM, Campbell H, Cannon MV, Chakravarti tum cardiomyopathy. Heart. 2011;97:1970–1981. doi: 10.1136/
A, Chen LY, Delitala A, Devereux RB, Doevendans PA, Dominiczak AF, heartjnl-2011-300349

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e399

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

21. VALVULAR DISEASES Abbreviations Used in Chapter 21 Continued

CLINICAL STATEMENTS

NH non-Hispanic
See Tables 21-1 through 21-3 and Charts 21-1
AND GUIDELINES

NHLBI National Heart, Lung, and Blood Institute

through 21-5 NIS National (Nationwide) Inpatient Sample
OR odds ratio
Click here to return to the Table of Contents PARTNER Placement of Aortic Transcatheter Valve
QALY quality-adjusted life-year
REMEDY Global Rheumatic Heart Disease Registry
Mortality and any-mention mortality in this section
RR relative risk
are for 2016. “Mortality” is the number of deaths in RV right ventricular
2016 for the given underlying cause based on ICD-10. SAVR surgical aortic valve replacement
Prevalence data are for 2006 for US cohorts and 2016 SD standard deviation
and 2017 for European cohorts. Hospital discharge SNP single-nucleotide polymorphism
data are from HCUP, NIS, 2014; data included are for STS Society of Thoracic Surgeons
SURTAVI Surgical Replacement and Transcatheter Aortic Valve
inpatients discharged alive, dead, or status unknown. Implantation
Hospital discharge data for 2014 are based on TA transapical
ICD-9 codes. TAVR transcatheter aortic valve replacement
TF transfemoral
TIA transient ischemic attack
Abbreviations Used in Chapter 21
TOF tetralogy of Fallot
ACC American College of Cardiology TVT Transcatheter Valve Therapy
AF atrial fibrillation
AGES Age, Gene/Environment Susceptibility
AHA American Heart Association
APAC Asia-Pacific
Valvular Heart Disease
ARIC Atherosclerosis Risk in Communities Study (See Table 21-1)
BMI body mass index ICD-9 424; ICD-10 I34 to I38.
CABG coronary artery bypass graft
CAD coronary artery disease 2016: Mortality—24 902. Any-mention mortality—
CALA Caribbean and Latin America 51 608.
CARDIA Coronary Artery Risk Development in Young Adults 2014: Hospital discharges—105 000.
CER cost-effectiveness ratio
Prevalence
Downloaded from http://ahajournals.org by on February 7, 2019

CHS Cardiovascular Health Study

CI confidence interval • A large, population-based epidemiological study
DALY disability-adjusted life-year with systematic use of echocardiography on
DCM dilated cardiomyopathy
16 501 participants from Olmsted County, MN,
DM diabetes mellitus
EF ejection fraction showed an overall age-adjusted prevalence of
EVEREST Efficacy of Vasopressin Antagonism in Heart Failure clinically diagnosed (moderate or greater) valvular
Outcome Study With Tolvaptan HD of 1.8%.1
EVEREST II HRS Endovascular Valve Edge-to-Edge Repair High-Risk • Prevalence of any valve disease increased with
Study
FHS Framingham Heart Study
age (Ptrend<0.0001)1:
GBD Global Burden of Disease — 18 to 44 years: 0.3% (95% CI, 0.2%–0.3%)
GWAS genome-wide association study — 45 to 54 years: 0.7% (95% CI, 0.6%–0.9%)
HCUP Healthcare Cost and Utilization Project — 55 to 64 years: 1.6% (95% CI, 1.4%–1.9%)
HD heart disease — 65 to 74 years: 4.4% (95% CI, 3.9%–4.9%)
HF heart failure
— ≥75 years: 11.7% (95% CI, 11.0%–12.5%)
HR hazard ratio
ICD International Classification of Diseases
• Pooled echocardiographic data from 11 911 par-
ICD-9 International Classification of Diseases, 9th Revision ticipants from CARDIA (4351), ARIC (2435), and
ICD-10 International Classification of Diseases, 10th Revision CHS (5125) demonstrated a similar increase in
ICE-PCS International Collaboration on Endocarditis–Prospective prevalence with advancing age (Ptrend<0.0001;
Cohort Study
Table 21-1)1:
ICE-PLUS International Collaboration on Endocarditis–PLUS
IE infective endocarditis
— 18 to 44 years: 0.7% (95% CI, 0.5%–1.0%)
IHD ischemic heart disease — 45 to 54 years: 0.4% (95% CI, 0.1%–1.3%)
IQR interquartile range — 55 to 64 years: 1.9% (95% CI, 1.2%–2.8%)
LDL-C low-density lipoprotein cholesterol — 65 to 74 years: 8.5% (95% CI, 7.6%–9.4%)
LV left ventricular — ≥75 years: 13.2% (95% CI, 11.7%–15.0%)
LVEF left ventricular ejection fraction
• Adjusted to the entire 2000 US adult popula-
MI myocardial infarction
MR mitral regurgitation
tion, these data suggest that the prevalence of
NCHS National Center for Health Statistics any valve disease is 2.5% (95% CI, 2.2%–2.7%),
(Continued ) with no difference between males (2.4% [95%

e400 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

CI, 2.1%–2.8%]) and females (2.5% [95% CI, • Nationally representative data from Sweden dem-

CLINICAL STATEMENTS
2.1%–2.9%]).1 onstrate a lower age-adjusted incidence of aortic

AND GUIDELINES
• In a recent report using the Swedish nationwide stenosis, from 15.0 to 11.4 per 100 000 males and
register to identify all patients with a first diagno- from 9.8 to 7.1 per 100 000 females, between
sis of valvular HD at Swedish hospitals between the years 1989 to 1991 and 2007 to 2009.6
2003 and 2010 (N=10 164 211), the incidence of • The prevalence of moderate or severe aortic
valvular HD was 63.9 per 100 000 person-years, regurgitation in patients ≥75 years is 2.0% (95%
with aortic stenosis (47.2%), MR (24.2%), and CI, 1.4%–2.7%) based on pooled CARDIA, ARIC,
aortic regurgitation (18.0%) contributing most and CHS data (Table 21-1).1
of the valvular diagnoses. The majority of valvu-
Lifetime Risk and Cumulative Risk
lopathies were diagnosed in the elderly (68.9%
• The number of elderly patients with calcific aortic
in subjects aged ≥65 years). Incidences of aor-
stenosis is projected to more than double by 2050
tic regurgitation, aortic stenosis, and MR were
in both the United States and Europe based on a
higher in males, who were also more frequently
simulation model in 7 decision analysis studies.
diagnosed at an earlier age. Mitral stenosis inci-
In the Icelandic AGES-Reykjavik study alone, pro-
dence was higher in females.2
jections suggest a doubling in prevalence among
• Previously undiagnosed, predominantly mild val-
those with severe aortic stenosis aged ≥70 years
vular HD was found in 51% of 2500 individuals
by 2040 and a tripling by 2060.7
aged ≥65 years from a primary care population
screened using transthoracic echocardiography. Mortality
The prevalence of undiagnosed moderate or • On the basis of ICD-10 (with data coded from
severe valvular HD was 6.4%.3 1999 to 2009), there were 146 304 deaths in the
aortic valve disease category in the United States.
Of these, 82.7% were attributed to aortic ste-
Aortic Valve Disorders nosis, 4.0% to aortic insufficiency, and 0.6% to
(See Table 21-1 and Chart 21-1) aortic stenosis with insufficiency, whereas 11.9%
ICD-9 424.1; ICD-10 I35. were unspecified or coded as attributed to other
2016: Mortality—17  046. Any-mention mortality aortic valve disease and 0.7% to congenital aor-
Downloaded from http://ahajournals.org by on February 7, 2019

34 769. tic valve disease (assumed to be predominantly

2014: Hospital discharges—77 000. bicuspid aortic valve). The change in annual age-
and sex-adjusted mortality rate over time was
Prevalence and Incidence 1.016 (95% CI, 1.015–1.016; P<0.001) for non-
• On the basis of the CARDIA, ARIC, and CHS rheumatic aortic valve disease.8
studies, the authors estimated an age- and sex- • A retrospective analysis of 3 different cohorts
adjusted (2000 US adult population) prevalence of consecutive patients with echocardiographic
of 0.4% (95% CI, 0.3%–0.5%) for aortic steno- diagnosis of bicuspid aortic valve included
sis and 0.5% (95% CI, 0.3%–0.6%) for aortic the following: (1) a community cohort of 416
regurgitation.1 patients with bicuspid aortic valve diagnosed
• The prevalence of moderate or severe calcific for the first time (aged 35±21 years, follow-up
aortic stenosis in patients ≥75 years old is 2.8% 16±7 years); (2) a tertiary care cohort of 2824
(95% CI, 2.1%–3.7%) based on pooled echo- adults with bicuspid aortic valve (aged 51±16
cardiographic data from US cohorts including years, follow-up 9±6 years); and (3) a cohort of
CARDIA, ARIC, and CHS (Table 21-1).1 2242 adults with bicuspid aortic valve referred
• Prevalence of aortic stenosis by echocardiogra- for aortic valve replacement (aged 62±14 years,
phy is higher (4.3%) among individuals aged ≥70 follow-up 6±5 years).9 In the community, mor-
years in the Icelandic AGES-Reykjavik cohort. In bidity related to bicuspid aortic valve was higher
the Norwegian Tromsø study, the incidence of in males than in females, with a total combined
new aortic stenosis was 5 per 1000 per year, risk of aortic regurgitation, surgery, and IE of
with the initial mean age of participants being 52±4% versus 35±6% in females (P=0.01).9
60 years.4 Nevertheless, females had a significantly higher
• In younger age groups, the most prevalent cause RR of death in tertiary and surgical referral
of aortic stenosis is bicuspid aortic valve, the most cohorts, with an age-adjusted relative death risk
common form of congenital HD. In an Italian of 1.63 (95% CI, 1.40–1.89) for females versus
study of 817 primary school students, the preva- 1.34 (95% CI, 1.22–1.47) for males (P=0.026).9
lence of bicuspid aortic valve was 0.5% (95% CI, The risk of death was independently associated
0.13%–1.2%).5 with aortic regurgitation (P≤0.04).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e401

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

Complications • GWAS of aortic valve stenosis have identified sev-

CLINICAL STATEMENTS

• In a cohort of 416 community-based participants eral loci, including LPA, PALMD, and TEX41.20,26
AND GUIDELINES

from Olmsted County, MN with bicuspid aortic • In a nationwide Swedish study comprising
valve followed up for a mean (SD) of 16 (7) years, 6 117 263 siblings (13 442 with aortic stenosis),
the incidence of aortic dissection in individuals ≥50 having at least 1 sibling with aortic stenosis was
years of age at baseline was 17.4 (95% CI, 2.9– associated with an HR of 3.41 (95% CI, 2.23–
53.6) cases per 10 000 patient-years. For patients 5.21) to be diagnosed with aortic stenosis. These
aged ≥50 years with a bicuspid valve and a base- findings indicate an overall familial aggregation of
line aortic aneurysm, the incidence of aortic dis- this disease beyond bicuspid aortic valve alone.27
section was 44.9 (95% CI, 7.5–138.5) cases per
10 000 patient-years. In the remaining participants Awareness, Treatment, and Control
without baseline aortic aneurysm, the incidence of • Before US Food and Drug Administration approval
aneurysm was 84.9 (95% CI, 63.3–110.9) cases of TAVR for patients with severe aortic stenosis at
per 10 000 patient-years, for an age-adjusted RR high surgical risk in 2011, ≈50% of patients with
of 86.2 (95% CI, 65.1–114) compared with the severe aortic stenosis were referred for cardiotho-
general population.10 racic surgery and ≈40% underwent aortic valve
replacement, according to data from 10 US cen-
Risk Factors ters of various sizes and geographic distribution.
• Several prospective and retrospective series have Reasons for not undergoing aortic valve replace-
attempted to identify risk factors for progression ment included high perioperative risk, age, lack of
of aortic stenosis.11–15 Among the highlighted symptoms, and patient or family refusal.28
factors were baseline valve area, degree of valve • Two trials using 2 different devices (PARTNER 1A
calcification, CAD, older age, male sex, bicuspid and US CoreValve High Risk) have shown that
versus tricuspid involvement, mitral annular calci- TAVR is able to compete in terms of mortality with
fication, hypercholesterolemia, higher BMI, renal SAVR in high-risk patients at 1, 2, and 5 years.29–31
insufficiency, hypercalcemia, smoking, metabolic • From 2011 through 2014, the STS/ACC TVT
syndrome, and DM.16–18 Registry recorded 26 414 TAVR procedures per-
• In a retrospective analysis of predictors of cardiac formed at 348 centers in 48 US states.32 Sixty-
outcomes in 227 ambulatory adults with bicuspid eight percent of patients were ≥80 years of age,
Downloaded from http://ahajournals.org by on February 7, 2019

aortic valve, independent predictors of the com- and preoperative risk was high; in 2014, median
posite end point (need for surgery, death, aortic STS risk was 6.7%, and 95% of patients were
dissection, endocarditis, HF, arrhythmias, or IHD) deemed to be at extreme or high risk. The num-
were baseline moderate to severe aortic valve dys- ber of patients receiving commercially approved
function (HR, 3.19 [95% CI, 1.35–7.54]; P<0.01) devices from 2012 through 2015 increased to
and aortic valve leaflet calcification (HR, 4.72 54 782 in a recent report from the same registry.33
[95% CI, 1.91–11.64]; P<0.005).19 • In Germany, the number of TAVR procedures
Genetics and Family History increased from 144 in 2007 to 9147 in 2013. In
• A GWAS in 6942 individuals identified an SNP the same study, the number of SAVR procedures
located in an intron of the lipoprotein(a) gene decreased from 8622 to 7048 (Chart 21-1).34
that was significantly associated with the pres- • A recent meta-analysis identified 50 studies
ence of aortic calcification (OR per allele, 2.05), enrolling 44 247 patients with a mean follow-up
circulating lipoprotein(a) levels, and the develop- of 21.4 months that compared TAVR to SAVR
ment of aortic stenosis.20 for patients at high surgical risk. No difference
• Multiple SNPs that encode for LDL-C have been was found in intermediate-term (mean follow-
combined to form a genetic risk score that has up 21.4 months) all-cause mortality (3980 of
been associated with prevalent aortic valve calcifi- 11 728 deaths [33.9%] in the TAVR group com-
cation (OR, 1.38 [95% CI, 1.09–1.74] per genetic pared with 5811 of 32 366 deaths [17.9%] in
risk score increment) and incident aortic valve ste- the SAVR group; RR, 1.06 [95% CI, 0.91–1.22]).
nosis (HR, 2.78 [95% CI, 1.22–6.37] per genetic There was a significant difference favoring TAVR
risk score increment) by use of a mendelian ran- in the incidence of stroke (348 of 7079 [4.9%]
domization design.21 compared with 389 of 6974 [5.5%] in the SAVR
• The heritability of bicuspid aortic valve has been group; RR, 0.82 [95% CI, 0.71–0.94]), AF (371
estimated at 89% (0.89±0.06; P<0.001), which of 3509 [10.5%] versus 1017 of 3589 [28.3%]
suggests that most cases are familial.22 Bicuspid in patients treated with SAVR; RR, 0.43 [95% CI,
aortic valve has been linked to mutations of 0.33–0.54]), acute kidney injury (404 of 6065
NOTCH1, GATA5, and more recently GATA4.23–25 [6.6%] versus 544 of 6103 [8.9%] in the SAVR

e402 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

group; RR, 0.70 [95% CI, 0.53–0.92]), and major per life-year gained. On the basis of sensitivity

CLINICAL STATEMENTS
bleeding (607 of 4863 [12.4%] versus 1454 of analyses, a reduction in the initial cost of TAVR by

AND GUIDELINES
5078 [28.6%] in the SAVR group; RR, 0.57 [95% ≈$1650 was expected to lead to an incremental
CI, 0.40–0.81]). TAVR resulted in a significantly CER of <$50 000 per QALY gained.38
higher incidence of vascular complications (392
of 4995 [7.8%] compared with 143 of 5084
[2.8%] in the SAVR group; RR, 2.90 [95% CI,
Mitral Valve Disorders
1.87–4.49]), moderate to severe aortic regurgi- ICD-9 424.0; ICD-10 I34.
tation (377 of 5548 [6.7%] versus 47 of 5531 2016: Mortality—2596. Any-mention mortality—5885.
[0.8%] in patients treated with SAVR; RR, 7.00 2014: Hospital discharges—26 000.
[95% CI, 5.27–9.30]), and pacemaker implanta-
tion (872 of 6157 [14.1%] compared with 456 of Prevalence
(See Table 21-1)
6257 [7.2%] in the SAVR group; RR, 2.02 [95%
• In pooled data from CARDIA, ARIC, and CHS,
CI, 1.51–2.68]).35
mitral valve disease was the most common val-
• The 54  782 patients with TAVR who entered
vular lesion. At least moderate MR occurred at a
the STS/ACC TVT Registry between 2012 and
frequency of 1.7% as adjusted to the US adult
2015 demonstrated decreases in expected risk
population in 2000, increasing from 0.5% in par-
of 30-day operative mortality (STS Predicted
ticipants aged 18 to 44 years to 9.3% in partici-
Risk of Mortality score) from 7% to 6% and in
pants aged ≥75 years.1 In the same pooled sample,
TVT Registry predicted risk of mortality from 4%
mitral stenosis (commonly related to rheumatic
to 3% (both P<0.0001) from 2012 to 2015.
involvement) was rare, with a frequency of 0.1%
Observed in-hospital mortality decreased from
(Table 21-1).
5.7% to 2.9%, and 1-year mortality decreased
• A systematic review by de Marchena and col-
from 25.8% to 21.6%. However, 30-day postpro-
leagues39 found that in the US population, the
cedure pacemaker insertion increased from 8.8%
prevalence of MR according to the Carpentier
in 2013 to 12.0% in 2015.33
functional classification system was as follows:
• In a cohort of 1746 patients with severe aortic ste-
— Type I (congenital MR [<10 per million] and
nosis at intermediate surgical risk in the SURTAVI
endocarditis [3–7 per million]): <20 per 1
Downloaded from http://ahajournals.org by on February 7, 2019

trial, the estimated incidence of the primary end

million
point (death attributable to any cause or debili-
— Type II (myxomatous MR): 15 170.5 per 1
tating stroke) was 12.6% in the TAVR group and
million
14.0% in the SAVR group (95% credible interval
— Type IIIa (rheumatic HD, systemic lupus ery-
[bayesian analysis] for difference, −5.2 to 2.3%;
thematosus, antiphospholipid syndrome,
posterior probability of noninferiority, >0.999) at
and rare diseases): 10 520 per 1 million
24 months. In the PARTNER 2 trial, the Kaplan-
— Type IIIb (ischemic MR, LV dysfunction, DCM):
Meier event rates of the same end point were
16 250 per 1 million
19.3% in the TAVR group and 21.1% in the sur-
— Unclassified: 9530 per 1 million
gery group (HR in the TAVR group, 0.89 [95% CI,
• In a retrospective investigation of 134 874 indi-
0.73–1.09]; P=0.25) at 2-year follow-up. These
viduals in China, 42.44%, 1.63%, and 1.44%
findings demonstrate that TAVR is a noninferior
had mild, moderate, and severe MR, respec-
alternative to SAVR in patients with severe aortic
tively.40 The prevalence of MR increased with
stenosis at intermediate surgical risk.36,37
advancing age. In individuals with severely
Cost reduced systolic function (LVEF <30%), the
• Initial length of stay was an average of 4.4 days prevalence of severe MR was 22.14%, whereas
shorter for patients treated with TAVR than for in individuals with LVEF that was moderately
those who underwent surgical valve replace- depressed (LVEF 30%–44%), the prevalence
ment. TAVR also reduced the need for rehabilita- was 13.0%. Similarly, the prevalence of severe
tion services at discharge and was associated with MR was higher with higher mean LV end-systolic
improved 1-month quality of life. TAVR had higher diameter: 15.74% at 50 to 59 mm and 27.28%
index admission and projected lifetime costs than at ≥60 mm. The authors reported the cause of
SAVR (differences of $11 260 and $17 849 per severe MR in 1948 individuals. About half had
patient, respectively). However, TAVR was esti- secondary MR (N=976) and half had primary
mated to provide a lifetime gain of 0.32 QALYs causes, including 55 with rheumatic HD, 96 with
(0.41) with 3% discounting. Lifetime incremental IE, 141 with papillary muscle dysfunction, and
CERs were $55 090 per QALY gained and $43 114 608 with mitral valve prolapse.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e403

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

Lifetime Risk and Cumulative Risk [1.1%]; adjusted OR, 4.51 [95% CI, 2.13–9.54];
CLINICAL STATEMENTS

• Because of the associations between MR and P<0.0001).47 A number of genetic variants have
AND GUIDELINES

advancing age and between functional MR and been identified for the rare X-linked valvular dys-
HF, an increase in prevalence of MR is expected trophy and the most common form of autosomal
over the coming decades, although no population- dominant mitral valve prolapse through pedigree
based lifetime risk estimations of MR are available investigations and GWASs. Genes implicated
in the literature.41 in mitral valve prolapse include FLNA (encoding
for the filamin A protein), DCHS1, TNS1, and
Complications
LMCD1.48–50
• In the Olmsted County, MN, population, charac-
• Familial clustering exists across different MR
terized by a mixed spectrum of community-dwell-
subtypes including both primary (ie, related to
ing and referred patients, females were diagnosed
with mitral valve prolapse more often than males mitral valve prolapse) and nonprimary MR. In a
and at a younger age42; however, females had recent study, heritability of MR in the FHS was
fewer complications (flail leaflet occurred in 2% estimated at 0.15% (95% CI, 7%–23%), 12%
versus 8% in males and severe regurgitation in (95% CI, 4%–20%) excluding mitral valve pro-
10% versus 23%; all P<0.001). At 15 years of lapse, and 44% (95% CI, 15%–73%) for mod-
follow-up, females with no or mild MR had bet- erate or greater MR only (all P<0.05). In Sweden,
ter survival than males (87% versus 77%; adjusted sibling MR was associated with an HR of 3.57
RR, 0.82 [95% CI, 0.76–0.89]). In contrast, in indi- (95% CI, 2.21–5.76; P<0.001) for development
viduals with severe MR, females had worse survival of MR.51
than males (60% versus 68%; adjusted RR, 1.13 Awareness, Treatment, and Control
[95% CI, 1.01–1.26]). Survival 10 years after sur- (See Chart 21-2)
gery was similar in females and males (77% versus • The treatment of mitral valve prolapse remains
79%; P=0.14).43 largely surgical and based on valve repair.
Risk Factors Nevertheless, percutaneous mitral valve repair
• In a community-based study of 833 individuals techniques are becoming a common treatment
diagnosed with asymptomatic mitral valve pro- option for high-risk patients not deemed can-
lapse and followed up longitudinally in Olmsted didates for surgical repair. Data from the STS/
Downloaded from http://ahajournals.org by on February 7, 2019

County, MN, cardiac mortality was best predicted ACC TVT Registry on patients commercially
by the presence of MR and LV systolic dysfunction treated with the MitraClip percutaneous mitral
at the time of diagnosis. Risk factors for cardio- valve repair device showed the following: of 564
vascular morbidity (defined as the occurrence of patients (56% male, median age 83 years), 473
HF, thromboembolic events, endocarditis, AF, or (86%) were severely symptomatic. The median
need for cardiac surgery) included age ≥50 years, STS predicted risk of mortality scores for mitral
left atrial enlargement, MR, presence of a flail leaf- valve repair and replacement were 7.9% (IQR,
let, and prevalent AF at the time of the baseline 4.7%−12.2%) and 10% (IQR, 6.3%−14.5%),
echocardiogram.43 respectively.52 Most of the transcatheter mitral
valve repair patients (90.8%) had degenerative
Subclinical Disease disease, and the procedure was successful in
• Milder, nondiagnostic forms of mitral valve pro- reducing the MR to moderate levels in 93% of
lapse, first described in the familial context, are cases. In-hospital mortality was 2.3%, and 30-day
also present in the community and are associ- mortality was 5.8%. Events occurring in the first
ated with higher likelihood of mitral valve pro- 30 days included stroke (1.8%), bleeding (2.6%),
lapse in offspring (OR, 2.52 [95% CI, 1.25–5.10]; and device-related complications (1.4%). Most
P=0.01). Up to 80% of nondiagnostic morphol-
patients (84%) were discharged to home after
ogies can progress to diagnostic mitral valve
a 3-day median hospital length (IQR, 1−6 days).
prolapse.44–46
The authors reported a procedural success rate
Genetics and Family History of 91%. However, based on the EVEREST II trial,
• Among 3679 generation 3 participants in the mitral valve dysfunction is more common with
FHS (53% female; mean age 40±9 years) with percutaneous mitral valve repair than with surgi-
available parental data, 49 (1%) had mitral valve cal repair (20% versus 2%).53
prolapse. Parental mitral valve prolapse was asso- • Worldwide, the number of MitraClip procedures
ciated with a higher prevalence of mitral valve has increased progressively since 2008, especially
prolapse in offspring (10/186 [5.4%]) compared in Western Europe. In the United States, the com-
with no parental mitral valve prolapse (39/3493 mercial use of the MitraClip started in 2014, with

e404 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

a steadily growing number of procedures per- repair.62,63 Percutaneous pulmonic valve implanta-

CLINICAL STATEMENTS
formed (Chart 21-2).54 tion of either a Melody or a SAPIEN valve is an

AND GUIDELINES
• In patients with severe chronic MR secondary option in patients with prosthetic pulmonic valve
to ischemic cardiomyopathy undergoing CABG regurgitation, including those with a pulmonary
surgery, survival rates were not significantly dif- artery conduit with regurgitant prosthetic valve.64
ferent after bypass alone compared with bypass Surgical pulmonary valve replacement is preferred
combined with mitral valve repair (1-, 5-, and for native pulmonic valve regurgitation (caused by
10-year survival of 88%, 75%, and 47% versus endocarditis, carcinoid, etc) and is associated with
92%, 74%, and 39%, respectively; P=0.6).55 In <1% periprocedural mortality and excellent long-
patients with moderate secondary MR, the rate of term outcome, with >60% freedom from reop-
death was 6.7% in the combined-surgery group eration at 10 years.65
and 7.3% in the CABG-alone group (HR with
mitral valve repair, 0.90 [95% CI, 0.38 to 2.12];
Tricuspid Valve Disorders
P=0.81).56
ICD-9 424.2; ICD-10 I36.
Cost
2016: Mortality—36. Any-mention mortality—152.
• Lifetime costs, life-years, QALYs, and incremental Tricuspid valve stenosis is an uncommon valvular
cost per life-year and QALY gained were estimated abnormality usually seen in patients with rheumatic
for patients receiving MitraClip therapy compared HD.66
with standard of care.57 The EVEREST II HRS pro- • Abnormal degrees of tricuspid regurgitation in
vided data on treatment-specific overall survival, adults are largely functional (ie, related to tri-
risk of clinical events, quality of life, and resource cuspid annular dilation or leaflet tethering in the
utilization. The published literature was reviewed setting of RV pressure or volume overload) and
to obtain health utility and unit costs (Canadian much less often caused by primary disorders of
2013 dollars). The incremental cost per QALY the valve apparatus (endocarditis, Ebstein anom-
gained was $23 433. On the basis of sensitivity aly, rheumatic, carcinoid, prolapse, or direct valve
analysis, MitraClip therapy had a 92% chance injury from a permanent pacemaker or implant-
of being cost-effective compared with standard able cardioverter-defibrillator lead placement).66
of care at a $50 000 per QALY willingness-to-pay
Downloaded from http://ahajournals.org by on February 7, 2019

• The frequency of tricuspid regurgitation and val-

threshold. vular pathology was evaluated in a study of 5223
adults (predominantly males, with a mean age of
Pulmonary Valve Disorders 67 years) who underwent echocardiography at
3 Veterans Affairs medical centers.67 Moderate
ICD-9 424.3; ICD-10 I37.
to severe tricuspid regurgitation was present in
2016: Mortality—16. Any-mention mortality—54. 819 (16%), but only 8% had primary tricuspid
• Pulmonic valve stenosis is a relatively common valve pathology. In the same study, moderate
congenital defect, occurring in ≈10% of children or greater tricuspid regurgitation was associated
with congenital HD.58 It is slightly more preva- with increased mortality regardless of pulmonary
lent in females, and familial occurrence has been artery systolic pressure (HR, 1.31 [95% CI, 1.16–
reported in 2% of cases.59 Pulmonic stenosis is 1.49] for pulmonary artery systolic pressure >40
usually associated with a benign clinical course. mm Hg; HR, 1.32 [95% CI, 1.05–1.62] for pulmo-
In a 2-center consecutive series of 85 children and nary artery systolic pressure ≤40 mm Hg) and LVEF
adolescents followed up for up to 10 years, rein- (HR, 1.49 [95% CI, 1.34–1.66] for EF <50%; HR,
tervention occurred in 11% who received repeat 1.54 [95% CI, 1.37–1.71] for EF ≥50%).67
balloon dilation and 5% who required surgical • Tricuspid valve surgery is recommended for
intervention for subvalvular or supravalvular ste- patients with severe tricuspid regurgitation
nosis.60 Although residual pulmonary regurgita- undergoing surgery for left-sided valve disease. A
tion was noted in the majority of patients, it was weaker recommendation for tricuspid valve sur-
predominantly mild. gery exists for patients with severe primary tricus-
• Trivial or mild pulmonic valve regurgitation is pid regurgitation with symptoms unresponsive to
commonly found in normal hearts on color medical therapy.68
Doppler echocardiography.61 The most common • An analysis of the NIS demonstrated an increase
cause of severe pulmonic regurgitation is iatro- in the number of isolated tricuspid valve surger-
genic, caused by surgical valvotomy/valvectomy ies performed over a 10-year period, from 290 in
or balloon pulmonary valvuloplasty performed 2004 to 780 in 2013. In-hospital mortality was
for RV outflow tract obstruction as part of TOF consistent over this time period at 8.8%.69

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e405

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

• In a cohort of 64 consecutive patients (mean • Prognosis after development of complications is

CLINICAL STATEMENTS

age 76.6±10 years) at excessive surgical risk also worse for people living with rheumatic HD.
AND GUIDELINES

who underwent compassionate MitraClip treat- In Thailand, patients with rheumatic mitral valve
ment of chronic, severe tricuspid regurgitation, disease who had ischemic stroke had a higher
tricuspid regurgitation was reduced by at least 1 risk of cardiac arrest (OR, 2.1), shock (OR, 2.1),
grade in 91% of the patients at a mean of 14±18 arrhythmias (OR, 1.7), respiratory failure (OR,
days. There were no intraprocedural deaths, 2.1), pneumonia (OR, 2.0), and sepsis (OR, 1.4)
cardiac tamponade, emergency surgery, stroke, after controlling for age, sex, and other comorbid
MI, or major vascular complications. There was chronic diseases.76
a significant improvement of New York Heart Subclinical Disease
Association class (P<0.001) and 6-minute walking • The prevalence of subclinical or latent rheumatic
distance (177.4±103.0 m versus 193.5±115.9 m; HD among children has been estimated by echo-
P=0.007).70 cardiography using published guidelines77 and
can be classified as definite or borderline. The
prevalence of combined definite and borderline
Rheumatic Fever/Rheumatic HD
disease ranges between 10 and 45 per 1000 in
(See Table 21-2 and Charts 21-3 recent studies from endemic countries (eg, Nepal,
through 21-5) Brazil, and Uganda) compared with <8 per 1000
ICD-9 390 to 398; ICD-10 I00 to I09. in low-risk populations.78–81
2016: Mortality—3553. Any-mention mortality—6622. • The natural history of latent rheumatic HD
2014: Hospital discharges—26 000. detected by echocardiography is not clear.
Emerging data suggest that up to 20% of chil-
Prevalence dren with definite rheumatic HD may progress to
• Rheumatic HD is uncommon in high-income coun- severe disease that requires valve surgery over a
tries such as the United States but remains endemic median follow-up of 7.5 years82; however, many
in some low- and middle-income countries.71 with borderline disease will remain stable, and
30% to 50% will regress to normal over 2 to 5
Mortality
years of follow-up.83,84
Downloaded from http://ahajournals.org by on February 7, 2019

• In the United States in 2016, mortality attributable

• In the largest prospective registry of latent rheu-
to rheumatic fever/rheumatic HD was 3553 for all
matic HD published to date, 26% of children with
ages (2345 females and 1208 males; Table 21-2).
definite rheumatic HD progressed over a median
• Mortality attributable to rheumatic HD varies follow-up of 2.6 years. Younger age at diagnosis
widely across the United States, with the highest and presence of morphologic mitral valve changes
rates clustered in Alaska, Mississippi, Alabama, were independent predictors of progression.85
Kentucky, and Utah, where age-standardized
mortality rates were estimated to be 5 to 10 per Awareness, Treatment, and Control
100 000 population in 2014.72 • The REMEDY study highlighted consistently poor
• In 1950, ≈15 000 Americans (adjusted for changes access to recommended therapies among peo-
in ICD codes) died of rheumatic fever/rheumatic ple living with rheumatic HD: only 55% were
HD compared with ≈3400 annually in the present taking penicillin prophylaxis, and only 3.6% of
era (NCHS/NHLBI) (Table 21-2). Recent declines in females of childbearing age were using contra-
mortality have been slowest in the South com- ception. Although 70% of those with indications
pared with other regions.72 (mechanical valve, AF, or severe mitral steno-
sis) were appropriately prescribed anticoagulant
Complications drugs, only a quarter of these had therapeutic
• People living with rheumatic HD experience high international normalized ratios.73
rates of morbid complications. In REMEDY, 33% • Underrecognition of acute rheumatic fever can
had HF, 22% had AF, 7% had prior stroke, and contribute to delayed presentation of disease and
4% had prior endocarditis at baseline.73 After 2 poor outcomes. Of the REMEDY participants from
years of follow-up, the incidence of new events low-income countries, only 22% reported a his-
was 38 per 1000 patient-years for HF, 8.5 per tory of prior acute rheumatic fever.73
1000 patient-years for stroke or TIA, and 3.7 per • In Uganda, retention in care over time is poor
1000 patient-years for endocarditis.74 Rates may (56.9% [95% CI, 54.1–59.7%] seen in clinic in
be even higher in lower-income countries of sub- the past 12 months), but among those retained in
Saharan Africa such as Uganda, where patients care, optimal adherence to benzathine penicillin
tend to present with advanced disease.75 G is high (91.4% [95% CI, 88.7–93.5%]).86

e406 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

Global Burden of Rheumatic HD Prevalence and Incidence

CLINICAL STATEMENTS
(See Charts 21-3 and 21-5) • In 2011, there were 47 134 cases of IE and valve

AND GUIDELINES
• In 2015, 33.4 million people were estimated to replacement in the United States (Table 21-3).89
be living with rheumatic HD around the world, • According to the 2015 GBD study, the age-stan-
with sub-Saharan Africa and Oceania having the dardized death rate attributable to IE in 2015 was
highest concentration of DALYs attributable to 1.3 per 100 000.90
rheumatic HD.71 • Although the absolute risk for acquiring IE from
• Unfortunately, estimates of the global burden of a dental procedure is impossible to measure pre-
rheumatic HD are hampered by a lack of data cisely, the best available estimates are as follows:
from endemic areas, which increases uncertainty If dental treatment causes 1% of all cases of viri-
of the estimates.71 dans group streptococcal IE annually in the United
• Globally, age-standardized mortality from rheu- States, the overall risk in the general population
matic HD was estimated to have declined 47.8% is estimated to be as low as 1 case of IE per 14
from 1990 to 2015; however, the prevalence of million dental procedures. The estimated absolute
HF attributable to rheumatic HD increased by risk rates for acquiring IE from a dental procedure
88% in the same time period.71 in patients with underlying cardiac conditions are
• The REMEDY study is a prospective registry of as follows91:
3343 patients with rheumatic HD from 25 hos- — Mitral valve prolapse: 1 per 1.1 million
pitals in 12 African countries, India, and Yemen procedures
(Chart 21-3). The age and sex distribution of the — Congenital HD: 1 per 475 000
subjects is shown in Chart 21-3.74 Rheumatic HD — Rheumatic HD: 1 per 142 000
was twice as common among females, a finding — Presence of a prosthetic cardiac valve: 1 per
consistent with prior studies across a variety of 114 000
populations.73 — Previous IE: 1 per 95 000 dental procedures
• Mortality attributable to rheumatic HD remains • Data collected between 2004 and 2010 from the
exceptionally high in endemic settings. In a study Pediatric Health Information System database
from Fiji of 2619 people followed up during 2008 from 37 centers that included 1033 cases of IE
to 2012, the age-standardized death rate was 9.9 demonstrated a mortality rate of 6.7% (N=45)
and 3.5% (N=13) among children (0–19 years old)
Downloaded from http://ahajournals.org by on February 7, 2019

(95% CI, 9.8–10.0) per 100 000, or more than

with and without congenital HD, respectively.92
twice the GBD estimates.87 Prognosis is exception-
• Data from the NIS (2000–2011)89 suggested no
ally poor in sub-Saharan Africa, as highlighted by
change in temporal trends in the incidence of IE
a follow-up study of REMEDY, which had a mor-
before and after publication of the 2007 AHA
tality rate of 116 per 1000 patient-years in the
guideline for antibiotic prophylaxis before dental
first year and 65 per 1000 patient-years in the
procedures.91 These findings from referral centers
second year.74
were corroborated by a community-based review
• The GBD 2016 Study used statistical models and
of adults in Olmsted County, MN.93 In the Olmsted
data on incidence, prevalence, case fatality, excess
County study, age- and sex-adjusted incidence of
mortality, and cause-specific mortality to estimate
IE was 7.4 (95% CI, 5.3–9.4) cases per 100 000
disease burden for 315 diseases and injuries in
person-years. In addition, these guideline changes
195 countries and territories.88
do not appear to have altered rates of pediat-
— Age-standardized mortality attributable to
ric endocarditis. Using 2003 to 2010 data from
rheumatic HD is highest in Southeast and 37 centers in the Pediatric Health Information
South Asia, sub-Saharan Africa, and the Systems Database, Pasquali and colleagues94 did
Pacific Islands (Chart 21-4). not demonstrate a significant difference in the
— Rheumatic HD prevalence is highest in cen- number of IE hospitalizations after the guidelines
tral sub-Saharan Africa, South Asia, and the were implemented in 2007 (1.6% difference after
Pacific Island Countries (Chart 21-5). versus before guideline implementation [95% CI,
−6.4% to 10.3%]; P=0.7).
Infective Endocarditis • A systematic review that included 160 studies
and 27 083 patients from 1960 to 2011 dem-
(See Table 21-3)
onstrated that in hospital-based studies (142
ICD-9 421.0; ICD-10 I33.0. studies; 23 606 patients), staphylococcal endo-
2016: Mortality—1414. Any-mention mortality—3060. carditis has increased over time (coagulase-nega-
2014: Hospital discharges—11 000, primary plus tive Staphylococcus 2% to 10%, P<0.001), with
secondary diagnoses. recent increases in S aureus IE (21% to 30%,

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e407

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

P<0.05) and enterococcal IE (6.8% to 10.5%, the opioid drug crisis. The prevalence of docu-
CLINICAL STATEMENTS

P<0.001) over the past decade and a correspond- mented intravenous drug use among patients
AND GUIDELINES

ing decrease in streptococcal endocarditis (32% admitted for endocarditis in the NIS rose from
to 17%) over the same time period.95 4.3% in 2008 to 10% in 2014. This trend was
accentuated among the young (<30 years old)
Complications
and among whites (compared with blacks and
• Among 162 cases of left-sided native-valve S
other races).98
aureus IE retrospectively identified among 1254
• Cardiac device IE appears to be present in 6.4%
patients hospitalized between 1990 and 2010 for
(95% CI, 5.5%–7.4%) of patients with definite
IE, Staphylococcus represented 18% of all IE cases
IE, according to data from ICE-PCS (2000–2006).
and 23% of native-valve IE cases. HF occurred in
45% of IE cases, acute renal failure in 23%, sep- Nearly half (45.8% [95% CI, 38.3%–53.4%])
sis in 29%, neurological events in 36%, systemic of such cases were related to healthcare-associ-
embolic events in 55%, and in-hospital mortal- ated infection. In-hospital and 1-year mortality
ity in 25%. The risk of in-hospital mortality was rates for these patients were 14.7% (26 of 177
higher in patients with HF (OR, 2.5; P=0.04) and [95% CI, 9.8%–20.8%]) and 23.2% (41 of 177
sepsis (OR, 5.3; P=0.001). Long-term 5-year sur- [95% CI, 17.2%–30.1%]), respectively. Although
vival was 49.6±4.9%. There was higher long-term not based on randomized data, compared with
risk of death among individuals with HF (OR, 1.7; individuals without initial hospitalization device
P=0.03), sepsis (OR, 3.0; P=0.0001), and delayed removal, there appeared to be a 1-year survival
surgery (OR, 0.43; P=0.003). When the authors benefit in individuals undergoing device explan-
compared 2 study periods, 1990 to 2000 and tation during the index hospitalization (HR, 0.42
2001 to 2010, there was a significant increase in [95% CI, 0.22–0.82]).99
bivalvular involvement, valvular insufficiency, and • Prosthetic valve IE continues to be associated with
acute renal failure from 2001 to 2010. In-hospital high in-hospital and 1-year mortality, although
mortality rates and long-term 5-year survival were early surgery is associated with improved out-
not significantly different between the 2 study comes compared with medical therapy alone
periods (28.1% versus 23.5%; P=0.58).96 (1-year mortality 22% versus 27%; HR, 0.68
[95% CI, 0.53–0.87]), even in propensity-adjusted
Risk Factors
Downloaded from http://ahajournals.org by on February 7, 2019

analyses (HR, 0.57 [95% CI, 0.49–0.67]).51

• The 15-year cohort risk (through 2006) of IE after
diagnosis of mitral valve prolapse (between 1989 Awareness, Treatment, and Control
to 1998) among Olmsted County, MN, residents • Surgery was performed in 47% of cases of defi-
was 1.1±0.4% (incidence, 86.6 cases per 100 000 nite left-sided, non–cardiac device-related IE in
person-years [95% CI, 43.3–173.2 cases per the ICE-PLUS registry of 1296 patients from 16
100 000 person-years]); there was a higher age- countries.100
and sex-adjusted risk of IE in patients with mitral
valve prolapse (RR, 8.1 [95% CI, 3.6–18.0]) com-
Heart Valve Procedure Costs
pared with the general population of Olmsted
County (P<0.001). No IE cases were identified • In 2013, for heart valve procedures101:
among patients without previously diagnosed — The mean inflation-adjusted cost per hospi-
MR. Conversely, there was a higher incidence of IE talization in 2013 dollars was $51 415, com-
in patients with mitral valve prolapse and moder- pared with $53 711 in 2005 and $43 829 in
ate, moderate-severe, or severe MR (289.5 cases 2000.
per 100 000 person-years [95% CI, 108.7–771.2 — The number of discharges for which heart
cases per 100 000 person-years]; P=0.02 com- valve surgery was the principal operating
pared with trivial, mild, or mild-moderate MR) room procedure was 102 425, which was an
and in patients with a flail mitral leaflet (715.5 increase from 93 802 in 2005 and 79 719 in
cases per 100 000 person-years [95% CI, 178.9– 2000.
2861.0 cases per 100 000 person-years]; P=0.02 • Total inflation-adjusted national cost in 2013 dol-
compared with no flail mitral leaflet).97 lars (in millions) was $5264, which was an increase
• Admissions for endocarditis related to injection from the mean cost (in millions) of $5058 in 2005
drug use have risen in recent years in parallel with and $3488 in 2000.101

e408 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

Table 21-1.  Pooled Prevalence of Valvular Heart Disease From CARDIA, ARIC, and CHS Cohorts

CLINICAL STATEMENTS
Age, y

AND GUIDELINES
P Value for Frequency Adjusted to
18–44 45–54 55–64 65–74 ≥75 Trend 2000 US Adult Population
Participants, N 4351 696 1240 3879 1745 … 209 128 094
Male 1959 (45) 258 (37) 415 (33) 1586 (41) 826 (47) … 100 994 367 (48)
Mitral regurgitation (n=449) 23 (0.5) 1 (0.1) 12 (1.0) 250 (6.4) 163 (9.3) <0.0001 1.7% (95% CI, 1.5%–1.9%)
Mitral stenosis (n=15) 0 (0) 1 (0.1) 3 (0.2) 7 (0.2) 4 (0.2) 0.006 0.1% (95% CI, 0.02%–0.2%)
Aortic regurgitation (n=90) 10 (0.2) 1 (0.1) 8 (0.7) 37 (1.0) 34 (2.0) <0.0001 0.5% (95% CI, 0.3%–0.6%)
Aortic stenosis (n=102) 1 (0.02) 1 (0.1) 2 (0.2) 50 (1.3) 48 (2.8) <0.0001 0.4% (95% CI, 0.3%–0.5%)
Any valve disease … … … … … … …
Overall (N=615) 31 (0.7) 3 (0.4) 23 (1.9) 328 (8.5) 230 (13.2) <0.0001 2.5% (95% CI, 2.2%–2.7%)
Female (n=356) 19 (0.8) 1 (0.2) 13 (1.6) 208 (9.1) 115 (12.6) <0.0001 2.4% (95% CI, 2.1%–2.8%)
Male (n=259) 12 (0.6) 2 (0.8) 10 (2.4) 120 (7.6) 115 (14.0) <0.0001 2.5% (95% CI, 2.1%–2.9%)

Values are n (%) unless otherwise indicated. ARIC indicates Atherosclerosis Risk in Communities study; CARDIA, Coronary Artery Risk
Development in Young Adults; CHS, Cardiovascular Health Study; and ellipses (…), not applicable.
Reprinted from The Lancet (Nkomo et al1), with permission from Elsevier. Copyright © 2006, Elsevier Ltd.

Table 21-2.  Rheumatic Fever/Rheumatic Heart Disease

Hospital
Mortality,2016: Discharges, 2014:
Population Group All Ages* All Ages
Both sexes 3553 26 000
Males 1208 (33.2%)† 12 000
Females 2345 (66.8%)† 14 000
NH white males 985 …
Downloaded from http://ahajournals.org by on February 7, 2019

NH white females 1916 …

NH black males 100 …
NH black females 185 …
Hispanic males 77 …
Hispanic females 138 …
NH Asian or Pacific Islander 37‡ …
males
NH Asian or Pacific Islander 82‡ …
females
NH American Indian or Alaska 23 …
Native

Ellipses (…) indicate data not available; and NH, non-Hispanic.

*Mortality for American Indian or Alaska Native and Asian and Pacific
Islander people should be interpreted with caution because of inconsistencies
in reporting race on the death certificate compared with censuses, surveys,
and birth certificates. Studies have shown underreporting on death certificates
of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic
decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total mortality that is for males
vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific
Islander.
Sources: Mortality: Centers for Disease Control and Prevention/National
Center for Health Statistics, 2016 Mortality Multiple Cause-of-Death–United
States; data represent underlying cause of death only. Hospital discharges:
Healthcare Cost and Utilization Project, Hospital Discharges, 2014; data include
those inpatients discharged alive, dead, or of unknown status.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e409

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

Table 21-3.  Incidence of IE and Valve Replacement From 2000 to 2011

CLINICAL STATEMENTS

Total IE IE Incidence Valve Replacement

AND GUIDELINES

Year Cases per 100 000 per 1000 IE Cases

2000 29 820 11 14
2001 31 526 11 16
2002 32 229 11 19
2003 35 190 12 18
2004 36 660 13 19
2005 37 508 13 23
2006 40 573 14 23
2007 38 207 12 30
2008 41 143 14 19
2009 43 502 14 27
2010 43 560 14 27
2011 47 134 15 26

IE indicates infective endocarditis.

Reprinted from Pant et al89 with permission from The American College
of Cardiology Foundation. Copyright © 2015, The American College of
Cardiology Foundation.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 21-1. Number of TAVR and SAVR procedures performed according to type of procedure and age group, 2007 to 2013.
SAVR indicates surgical aortic valve replacement; TA, transapical; TAVR, transcatheter aortic valve replacement; and TF, transfemoral.
Reprinted from Reinöhl et al34 with permission from the Massachusetts Medical Society. Copyright © 2015, Massachusetts Medical Society.

e410 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

CLINICAL STATEMENTS
AND GUIDELINES
Chart 21-2. Worldwide experience with the MitraClip procedure from September 2008 until April 2015.
APAC indicates Asia-Pacific; and CALA, Caribbean and Latin America.
Reprinted from Deuschl et al54 with permission. Figure courtesy of Abbott Laboratories.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 21-3. Age and sex distribution of 3343 subjects with rheumatic heart disease participating in the REMEDY study.
REMEDY indicates Global Rheumatic Heart Disease Registry.
Reprinted from Zühlke et al74 by permission of Oxford University Press. Copyright © 2014, The Authors.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e411

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21
CLINICAL STATEMENTS
AND GUIDELINES

Chart 21-4. Age-standardized global mortality rates of rheumatic heart disease per 100 000, both sexes, 2016..
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.88 Printed with permission. Copyright ©
2017, University of Washington.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 21-5. Age-standardized global prevalence rates of rheumatic heart disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.88 Printed with permission. Copyright ©
2017, University of Washington.

e412 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

REFERENCES 19. Rodrigues I, Agapito AF, de Sousa L, Oliveira JA, Branco LM, Galrinho A,

CLINICAL STATEMENTS
Abreu J, Timóteo AT, Rosa SA, Ferreira RC. Bicuspid aortic valve outcomes.
1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-

AND GUIDELINES
Cardiol Young. 2017;27:518–529. doi: 10.1017/S1047951116002560
Sarano M. Burden of valvular heart diseases: a population-based study. 20. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso
Lancet. 2006;368:1005–1011. doi: 10.1016/S0140-6736(06)69208-8 GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O’Brien
2. Andell P, Li X, Martinsson A, Andersson C, Stagmo M, Zöller B, Sundquist KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA,
K, Smith JG. Epidemiology of valvular heart disease in a Swedish nation- Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van
wide hospital-based register study. Heart. 2017;103:1696–1703. doi: der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M,
10.1136/heartjnl-2016-310894 Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R,
3. d’Arcy JL, Coffey S, Loudon MA, Kennedy A, Pearson-Stuttard J, Birks Kathiresan S, Melander O, Gudnason V, O’Donnell CJ, Post WS; CHARGE
J, Frangou E, Farmer AJ, Mant D, Wilson J, Myerson SG, Prendergast Extracoronary Calcium Working Group. Genetic associations with valvular
BD. Large-scale community echocardiographic screening reveals a calcification and aortic stenosis. N Engl J Med. 2013;368:503–512. doi:
major burden of undiagnosed valvular heart disease in older people: the 10.1056/NEJMoa1109034
OxVALVE Population Cohort Study. Eur Heart J. 2016;37:3515–3522. doi: 21. Smith JG, Luk K, Schulz CA, Engert JC, Do R, Hindy G, Rukh G, Dufresne
10.1093/eurheartj/ehw229 L, Almgren P, Owens DS, Harris TB, Peloso GM, Kerr KF, Wong Q, Smith
4. Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolv- AV, Budoff MJ, Rotter JI, Cupples LA, Rich S, Kathiresan S, Orho-Melander
ing epidemiology of valvular aortic stenosis: the Tromsø study. Heart. M, Gudnason V, O’Donnell CJ, Post WS, Thanassoulis G; Cohorts for Heart
2013;99:396–400. doi: 10.1136/heartjnl-2012-302265 and Aging Research in Genetic Epidemiology (CHARGE) Extracoronary
5. Basso C, Boschello M, Perrone C, Mecenero A, Cera A, Bicego D, Thiene Calcium Working Group. Association of low-density lipoprotein choles-
G, De Dominicis E. An echocardiographic survey of primary school chil- terol-related genetic variants with aortic valve calcium and incident aortic
dren for bicuspid aortic valve. Am J Cardiol. 2004;93:661–663. doi: stenosis. JAMA. 2014;312:1764–1771. doi: 10.1001/jama.2014.13959
10.1016/j.amjcard.2003.11.031 22. Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid
6. Martinsson A, Li X, Andersson C, Nilsson J, Smith JG, Sundquist K. aortic valve is heritable. J Am Coll Cardiol. 2004;44:138–143. doi:
Temporal trends in the incidence and prognosis of aortic stenosis: a 10.1016/j.jacc.2004.03.050
nationwide study of the Swedish population. Circulation. 2015;131:988– 23. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN,
994. doi: 10.1161/CIRCULATIONAHA.114.012906 Grossfeld PD, Srivastava D. Mutations in NOTCH1 cause aortic valve dis-
7. Danielsen R, Aspelund T, Harris TB, Gudnason V. The prevalence of ease. Nature. 2005;437:270–274. doi: 10.1038/nature03940
aortic stenosis in the elderly in Iceland and predictions for the coming 24. Padang R, Bagnall RD, Richmond DR, Bannon PG, Semsarian C. Rare non-
decades: the AGES-Reykjavík study. Int J Cardiol. 2014;176:916–922. doi: synonymous variations in the transcriptional activation domains of GATA5
10.1016/j.ijcard.2014.08.053 in bicuspid aortic valve disease. J Mol Cell Cardiol. 2012;53:277–281. doi:
8. Coffey S, Cox B, Williams MJ. Lack of progress in valvular heart disease in 10.1016/j.yjmcc.2012.05.009
the pre-transcatheter aortic valve replacement era: increasing deaths and 25. Yang B, Zhou W, Jiao J, Nielsen JB, Mathis MR, Heydarpour M, Lettre
minimal change in mortality rate over the past three decades. Am Heart J. G, Folkersen L, Prakash S, Schurmann C, Fritsche L, Farnum GA, Lin
2014;167:562–567.e2. doi: 10.1016/j.ahj.2013.12.030 M, Othman M, Hornsby W, Driscoll A, Levasseur A, Thomas M, Farhat
9. Michelena HI, Suri RM, Katan O, Eleid MF, Clavel MA, Maurer MJ, L, Dubé MP, Isselbacher EM, Franco-Cereceda A, Guo DC, Bottinger EP,
Pellikka PA, Mahoney D, Enriquez-Sarano M. Sex differences and sur- Deeb GM, Booher A, Kheterpal S, Chen YE, Kang HM, Kitzman J, Cordell
vival in adults with bicuspid aortic valves: verification in 3 contemporary HJ, Keavney BD, Goodship JA, Ganesh SK, Abecasis G, Eagle KA, Boyle
echocardiographic cohorts. J Am Heart Assoc. 2016;5:e004211. doi:
Downloaded from http://ahajournals.org by on February 7, 2019

AP, Loos RJF, Eriksson P, Tardif JC, Brummett CM, Milewicz DM, Body SC,
10.1161/jaha.116.004211 Willer CJ. Protein-altering and regulatory genetic variants near GATA4
10. Michelena HI, Khanna AD, Mahoney D, Margaryan E, Topilsky Y, Suri implicated in bicuspid aortic valve. Nat Commun. 2017;8:15481. doi:
RM, Eidem B, Edwards WD, Sundt TM 3rd, Enriquez-Sarano M. Incidence 10.1038/ncomms15481
of aortic complications in patients with bicuspid aortic valves. JAMA. 26. Helgadottir A, Thorleifsson G, Gretarsdottir S, Stefansson OA, Tragante V,
2011;306:1104–1112. doi: 10.1001/jama.2011.1286 Thorolfsdottir RB, Jonsdottir I, Bjornsson T, Steinthorsdottir V, Verweij N,
11. Aronow WS, Schwartz KS, Koenigsberg M. Correlation of serum lipids, Nielsen JB, Zhou W, Folkersen L, Martinsson A, Heydarpour M, Prakash
calcium, and phosphorus, diabetes mellitus and history of systemic hyper- S, Oskarsson G, Gudbjartsson T, Geirsson A, Olafsson I, Sigurdsson EL,
tension with presence or absence of calcified or thickened aortic cusps or Almgren P, Melander O, Franco-Cereceda A, Hamsten A, Fritsche L, Lin
root in elderly patients. Am J Cardiol. 1987;59:998–999. M, Yang B, Hornsby W, Guo D, Brummett CM, Abecasis G, Mathis M,
12. Mohler ER, Sheridan MJ, Nichols R, Harvey WP, Waller BF. Development Milewicz D, Body SC, Eriksson P, Willer CJ, Hveem K, Newton-Cheh C,
and progression of aortic valve stenosis: atherosclerosis risk fac- Smith JG, Danielsen R, Thorgeirsson G, Thorsteinsdottir U, Gudbjartsson
tors: a causal relationship? A clinical morphologic study. Clin Cardiol. DF, Holm H, Stefansson K. Genome-wide analysis yields new loci asso-
1991;14:995–999. ciating with aortic valve stenosis. Nat Commun. 2018;9:987. doi:
13. Lindroos M, Kupari M, Valvanne J, Strandberg T, Heikkilä J, Tilvis R. Factors 10.1038/s41467-018-03252-6
associated with calcific aortic valve degeneration in the elderly. Eur Heart 27. Martinsson A, Li X, Zoller B, Andell P, Andersson C, Sundquist K,
J. 1994;15:865–870. Smith JG. Familial aggregation of aortic valvular stenosis: a nationwide
14. Boon A, Cheriex E, Lodder J, Kessels F. Cardiac valve calcification: charac- study of sibling risk. Circ Cardiovasc Genet. 2017;10:e001742. doi:
teristics of patients with calcification of the mitral annulus or aortic valve. 10.1161/circgenetics.117.001742
Heart. 1997;78:472–474. 28. Bach DS. Prevalence and characteristics of unoperated patients with
15. Peltier M, Trojette F, Sarano ME, Grigioni F, Slama MA, Tribouilloy CM. severe aortic stenosis. J Heart Valve Dis. 2011;20:284–291.
Relation between cardiovascular risk factors and nonrheumatic severe cal- 29. Mack MJ, Leon MB, Smith CR, Miller DC, Moses JW, Tuzcu EM, Webb JG,
cific aortic stenosis among patients with a three-cuspid aortic valve. Am J Douglas PS, Anderson WN, Blackstone EH, Kodali SK, Makkar RR, Fontana
Cardiol. 2003;91:97–99. GP, Kapadia S, Bavaria J, Hahn RT, Thourani VH, Babaliaros V, Pichard A,
16. Yan AT, Koh M, Chan KK, Guo H, Alter DA, Austin PC, Tu JV, Wijeysundera Herrmann HC, Brown DL, Williams M, Akin J, Davidson MJ, Svensson LG;
HC, Ko DT. Association between cardiovascular risk factors and aor- PARTNER 1 Trial Investigators. 5-Year outcomes of transcatheter aortic
tic stenosis: the CANHEART Aortic Stenosis study. J Am Coll Cardiol. valve replacement or surgical aortic valve replacement for high surgical risk
2017;69:1523–1532. doi: 10.1016/j.jacc.2017.01.025 patients with aortic stenosis (PARTNER 1): a randomised controlled trial.
17. Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: Lancet. 2015;385:2477–2484. doi: 10.1016/S0140-6736(15)60308-7
pathogenesis, disease progression, and treatment strategies. 30. Kapadia SR, Leon MB, Makkar RR, Tuzcu EM, Svensson LG, Kodali S,
Circulation. 2005;111:3316–3326. doi: 10.1161/CIRCULATIONAHA. Webb JG, Mack MJ, Douglas PS, Thourani VH, Babaliaros VC, Herrmann
104.486738 HC, Szeto WY, Pichard AD, Williams MR, Fontana GP, Miller DC, Anderson
18. Capoulade R, Clavel MA, Dumesnil JG, Chan KL, Teo KK, Tam JW, Côté WN, Akin JJ, Davidson MJ, Smith CR; PARTNER Trial Investigators. 5-Year
N, Mathieu P, Després JP, Pibarot P; ASTRONOMER Investigators. Impact outcomes of transcatheter aortic valve replacement compared with stan-
of metabolic syndrome on progression of aortic stenosis: influence dard treatment for patients with inoperable aortic stenosis (PARTNER
of age and statin therapy. J Am Coll Cardiol. 2012;60:216–223. doi: 1): a randomised controlled trial. Lancet. 2015;385:2485–2491. doi:
10.1016/j.jacc.2012.03.052 10.1016/S0140-6736(15)60290-2

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e413

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

31. Adams DH, Popma JJ, Reardon MJ. Transcatheter aortic-valve replacement mitral valve prolapse: insights from the Framingham Heart Study. Circulation.
CLINICAL STATEMENTS

with a self-expanding prosthesis. N Engl J Med. 2014;371:967–968. doi: 2016;133:1688–1695. doi: 10.1161/circulationaha.115.020621
AND GUIDELINES

10.1056/NEJMc1408396 46. Nesta F, Leyne M, Yosefy C, Simpson C, Dai D, Marshall JE, Hung
32. Holmes DR Jr, Nishimura RA, Grover FL, Brindis RG, Carroll JD, Edwards J, Slaugenhaupt SA, Levine RA. New locus for autosomal domi-
FH, Peterson ED, Rumsfeld JS, Shahian DM, Thourani VH, Tuzcu EM, nant mitral valve prolapse on chromosome 13: clinical insights
Vemulapalli S, Hewitt K, Michaels J, Fitzgerald S, Mack MJ; STS/ACC from genetic studies. Circulation. 2005;112:2022–2030. doi:
TVT Registry. Annual outcomes with transcatheter valve therapy: from 10.1161/circulationaha.104.516930
the STS/ACC TVT Registry. J Am Coll Cardiol. 2015;66:2813–2823. doi: 47. Delling FN, Rong J, Larson MG, Lehman B, Osypiuk E, Stantchev P,
10.1016/j.jacc.2015.10.021 Slaugenhaupt SA, Benjamin EJ, Levine RA, Vasan RS. Familial clustering of
33. Grover FL, Vemulapalli S, Carroll JD, Edwards FH, Mack MJ, Thourani mitral valve prolapse in the community. Circulation. 2015;131:263–268.
VH, Brindis RG, Shahian DM, Ruiz CE, Jacobs JP, Hanzel G, Bavaria JE, doi: 10.1161/circulationaha.114.012594
Tuzcu EM, Peterson ED, Fitzgerald S, Kourtis M, Michaels J, Christensen 48. Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A, Le Bouffant F, Toquet
B, Seward WF, Hewitt K, Holmes DR Jr; STS/ACC TVT Registry. 2016 C, Roy E, McGregor L, Lynch SA, Newbury-Ecob R, Tran V, Young I, Trochu
annual report of the Society of Thoracic Surgeons/American College JN, Le Marec H, Schott JJ. Mutations in the gene encoding filamin A as a
of Cardiology Transcatheter Valve Therapy Registry. J Am Coll Cardiol. cause for familial cardiac valvular dystrophy. Circulation. 2007;115:40–49.
2017;69:1215–1230. doi: 10.1016/j.jacc.2016.11.033 doi: 10.1161/circulationaha.106.622621
34. Reinöhl J, Kaier K, Reinecke H, Schmoor C, Frankenstein L, Vach W, 49. Dina C, Bouatia-Naji N, Tucker N, Delling FN, Toomer K, Durst R, Perrocheau
Cribier A, Beyersdorf F, Bode C, Zehender M. Effect of availability of M, Fernandez-Friera L, Solis J, Le Tourneau T, Chen MH, Probst V, Bosse
transcatheter aortic-valve replacement on clinical practice. N Engl J Med. Y, Pibarot P, Zelenika D, Lathrop M, Hercberg S, Roussel R, Benjamin EJ,
2015;373:2438–2447. doi: 10.1056/NEJMoa1500893 Bonnet F, Lo SH, Dolmatova E, Simonet F, Lecointe S, Kyndt F, Redon R,
35. Villablanca PA, Mathew V, Thourani VH, Rodés-Cabau J, Bangalore S, Le Marec H, Froguel P, Ellinor PT, Vasan RS, Bruneval P, Markwald RR,
Makkiya M, Vlismas P, Briceno DF, Slovut DP, Taub CC, McCarthy PM, Norris RA, Milan DJ, Slaugenhaupt SA, Levine RA, Schott JJ, Hagege AA,
Augoustides JG, Ramakrishna H. A meta-analysis and meta-regression of Jeunemaitre X; PROMESA investigators; MVP-France; Leducq Transatlantic
long-term outcomes of transcatheter versus surgical aortic valve replace- MITRAL Network. Genetic association analyses highlight biological path-
ment for severe aortic stenosis. Int J Cardiol. 2016;225:234–243. doi: ways underlying mitral valve prolapse. Nat Genet. 2015;47:1206–1211.
10.1016/j.ijcard.2016.10.003 doi: 10.1038/ng.3383
36. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, 50. Durst R, Sauls K, Peal DS, deVlaming A, Toomer K, Leyne M, Salani M,
Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H, Chetcuti S, Gleason Talkowski ME, Brand H, Perrocheau M, Simpson C, Jett C, Stone MR,
T, Heiser J, Lange R, Merhi W, Oh JK, Olsen PS, Piazza N, Williams M, Charles F, Chiang C, Lynch SN, Bouatia-Naji N, Delling FN, Freed LA,
Windecker S, Yakubov SJ, Grube E, Makkar R, Lee JS, Conte J, Vang E, Tribouilloy C, Le Tourneau T, LeMarec H, Fernandez-Friera L, Solis J,
Nguyen H, Chang Y, Mugglin AS, Serruys PW, Kappetein AP; SURTAVI Trujillano D, Ossowski S, Estivill X, Dina C, Bruneval P, Chester A, Schott
Investigators. Surgical or transcatheter aortic-valve replacement in JJ, Irvine KD, Mao Y, Wessels A, Motiwala T, Puceat M, Tsukasaki Y,
intermediate-risk patients. N Engl J Med. 2017;376:1321–1331. doi: Menick DR, Kasiganesan H, Nie X, Broome AM, Williams K, Johnson
10.1056/NEJMoa1700456 A, Markwald RR, Jeunemaitre X, Hagege A, Levine RA, Milan DJ, Norris
37. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, RA, Slaugenhaupt SA. Mutations in DCHS1 cause mitral valve prolapse.
Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, Doshi D, Cohen DJ, Nature. 2015;525:109–113. doi: 10.1038/nature14670
Pichard AD, Kapadia S, Dewey T, Babaliaros V, Szeto WY, Williams MR, 51. Lalani T, Chu VH, Park LP, Cecchi E, Corey GR, Durante-Mangoni E,
Downloaded from http://ahajournals.org by on February 7, 2019

Kereiakes D, Zajarias A, Greason KL, Whisenant BK, Hodson RW, Moses Fowler VG Jr, Gordon D, Grossi P, Hannan M, Hoen B, Muñoz P, Rizk
JW, Trento A, Brown DL, Fearon WF, Pibarot P, Hahn RT, Jaber WA, H, Kanj SS, Selton-Suty C, Sexton DJ, Spelman D, Ravasio V, Tripodi MF,
Anderson WN, Alu MC, Webb JG; PARTNER 2 Investigators. Transcatheter Wang A; International Collaboration on Endocarditis–Prospective Cohort
or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Study Investigators. In-hospital and 1-year mortality in patients under-
Med. 2016;374:1609–1620. doi: 10.1056/NEJMoa1514616 going early surgery for prosthetic valve endocarditis. JAMA Intern Med.
38. Reynolds MR, Lei Y, Wang K, Chinnakondepalli K, Vilain KA, Magnuson 2013;173:1495–1504. doi: 10.1001/jamainternmed.2013.8203
EA, Galper BZ, Meduri CU, Arnold SV, Baron SJ, Reardon MJ, Adams DH, 52. Sorajja P, Mack M, Vemulapalli S, Holmes DR Jr, Stebbins A, Kar S, Lim
Popma JJ, Cohen DJ; CoreValve US High Risk Pivotal Trial Investigators. DS, Thourani V, McCarthy P, Kapadia S, Grayburn P, Pedersen WA,
Cost-effectiveness of transcatheter aortic valve replacement with a self- Ailawadi G. Initial experience with commercial transcatheter mitral valve
expanding prosthesis versus surgical aortic valve replacement. J Am Coll repair in the United States. J Am Coll Cardiol. 2016;67:1129–1140. doi:
Cardiol. 2016;67:29–38. doi: 10.1016/j.jacc.2015.10.046 10.1016/j.jacc.2015.12.054
39. de Marchena E, Badiye A, Robalino G, Junttila J, Atapattu S, Nakamura 53. Feldman T, Foster E, Glower DD, Glower DG, Kar S, Rinaldi MJ, Fail PS,
M, De Canniere D, Salerno T. Respective prevalence of the different Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper
Carpentier classes of mitral regurgitation: a stepping stone for future ER, Fudge T, Letsou GV, Massaro JM, Mauri L; EVEREST II Investigators.
therapeutic research and development. J Card Surg. 2011;26:385–392. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med.
doi: 10.1111/j.1540-8191.2011.01274.x 2011;364:1395–1406. doi: 10.1056/NEJMoa1009355
40. Li J, Pan W, Yin Y, Cheng L, Shu X. Prevalence and correlates of 54. Deuschl F, Schofer N, Lubos E, Blankenberg S, Schäfer U. Critical evalua-
mitral regurgitation in the current era: an echocardiography study tion of the MitraClip system in the management of mitral regurgitation.
of a Chinese patient population. Acta Cardiol. 2016;71:55–60. doi: Vasc Health Risk Manag. 2016;12:1–8. doi: 10.2147/VHRM.S65185
10.2143/AC.71.1.3132098 55. Mihaljevic T, Lam BK, Rajeswaran J, Takagaki M, Lauer MS, Gillinov AM,
41. Singh JP, Evans JC, Levy D, Larson MG, Freed LA, Fuller DL, Lehman B, Blackstone EH, Lytle BW. Impact of mitral valve annuloplasty combined with
Benjamin EJ. Prevalence and clinical determinants of mitral, tricuspid, revascularization in patients with functional ischemic mitral regurgitation.
and aortic regurgitation (the Framingham Heart Study). Am J Cardiol. J Am Coll Cardiol. 2007;49:2191–2201. doi: 10.1016/j.jacc.2007.02.043
1999;83:897–902. 56. Smith PK, Puskas JD, Ascheim DD, Voisine P, Gelijns AC, Moskowitz AJ,
42. Avierinos JF, Inamo J, Grigioni F, Gersh B, Shub C, Enriquez-Sarano M. Sex Hung JW, Parides MK, Ailawadi G, Perrault LP, Acker MA, Argenziano
differences in morphology and outcomes of mitral valve prolapse. Ann M, Thourani V, Gammie JS, Miller MA, Pagé P, Overbey JR, Bagiella E,
Intern Med. 2008;149:787–795. Dagenais F, Blackstone EH, Kron IL, Goldstein DJ, Rose EA, Moquete EG,
43. Avierinos JF, Gersh BJ, Melton LJ 3rd, Bailey KR, Shub C, Nishimura RA, Jeffries N, Gardner TJ, O’Gara PT, Alexander JH, Michler RE; Cardiothoracic
Tajik AJ, Enriquez-Sarano M. Natural history of asymptomatic mitral valve Surgical Trials Network Investigators. Surgical treatment of moderate
prolapse in the community. Circulation. 2002;106:1355–1361. ischemic mitral regurgitation. N Engl J Med. 2014;371:2178–2188. doi:
44. Delling FN, Gona P, Larson MG, Lehman B, Manning WJ, Levine RA, 10.1056/NEJMoa1410490
Benjamin EJ, Vasan RS. Mild expression of mitral valve prolapse in the 57. Cameron HL, Bernard LM, Garmo VS, Hernandez JB, Asgar AW. A
Framingham offspring: expanding the phenotypic spectrum. J Am Soc Canadian cost-effectiveness analysis of transcatheter mitral valve
Echocardiogr. 2014;27:17–23. doi: 10.1016/j.echo.2013.09.015 repair with the MitraClip system in high surgical risk patients with sig-
45. Delling FN, Rong J, Larson MG, Lehman B, Fuller D, Osypiuk E, Stantchev P, nificant mitral regurgitation. J Med Econ. 2014;17:599–615. doi:
Hackman B, Manning WJ, Benjamin EJ, Levine RA, Vasan RS. Evolution of 10.3111/13696998.2014.923892

e414 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

58. Allen HD,Shaddy RE, Penny DJ, Feltes TF, Cetta F. Moss & Adams’ Heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

CLINICAL STATEMENTS
Disease in Infants, Children, and Adolescents, Including the Fetus and Eur Heart J. 2015;36:1115–122a. doi: 10.1093/eurheartj/ehu449

AND GUIDELINES
Young Adult. Vol 1. 9th ed. Baltimore, MD: Lippincott Williams & Wilkins; 74. Zühlke L, Karthikeyan G, Engel ME, Rangarajan S, Mackie P, Cupido-Katya
2016. Mauff B, Islam S, Daniels R, Francis V, Ogendo S, Gitura B, Mondo C,
59. Mutlak D, Lessick J, Reisner SA, Aronson D, Dabbah S, Agmon Y. Okello E, Lwabi P, Al-Kebsi MM, Hugo-Hamman C, Sheta SS, Haileamlak
Echocardiography-based spectrum of severe tricuspid regurgitation: the A, Daniel W, Goshu DY, Abdissa SG, Desta AG, Shasho BA, Begna DM,
frequency of apparently idiopathic tricuspid regurgitation. J Am Soc ElSayed A, Ibrahim AS, Musuku J, Bode-Thomas F, Yilgwan CC, Amusa
Echocardiogr. 2007;20:405–408. doi: 10.1016/j.echo.2006.09.013 GA, Ige O, Okeahialam B, Sutton C, Misra R, Abul Fadl A, Kennedy N,
60. Rao PS, Galal O, Patnana M, Buck SH, Wilson AD. Results of three to Damasceno A, Sani MU, Ogah OS, Elhassan TO, Mocumbi AO, Adeoye
10 year follow up of balloon dilatation of the pulmonary valve. Heart. AM, Mntla P, Ojji D, Mucumbitsi J, Teo K, Yusuf S, Mayosi BM. Clinical
1998;80:591–595. outcomes in 3343 children and adults with rheumatic heart disease
61. Klein AL, Burstow DJ, Tajik AJ, Zachariah PK, Taliercio CP, Taylor CL, Bailey from 14 low- and middle-income countries: two-year follow-up of the
KR, Seward JB. Age-related prevalence of valvular regurgitation in normal Global Rheumatic Heart Disease Registry (the REMEDY Study). Circulation.
subjects: a comprehensive color flow examination of 118 volunteers. J Am 2016;134:1456–1466. doi: 10.1161/CIRCULATIONAHA.116.024769
Soc Echocardiogr. 1990;3:54–63. 75. Okello E, Longenecker CT, Beaton A, Kamya MR, Lwabi P. Rheumatic
62. O’Connor BK, Beekman RH, Lindauer A, Rocchini A. Intermediate-term heart disease in Uganda: predictors of morbidity and mortality one
outcome after pulmonary balloon valvuloplasty: comparison with a year after presentation. BMC Cardiovasc Disord. 2017;17:20. doi:
matched surgical control group. J Am Coll Cardiol. 1992;20:169–173. 10.1186/s12872-016-0451-8
63. Hayes CJ, Gersony WM, Driscoll DJ, Keane JF, Kidd L, O’Fallon WM, Pieroni 76. Wood AD, Mannu GS, Clark AB, Tiamkao S, Kongbunkiat K, Bettencourt-
DR, Wolfe RR, Weidman WH. Second natural history study of congenital Silva JH, Sawanyawisuth K, Kasemsap N, Barlas RS, Mamas M, Myint
heart defects: results of treatment of patients with pulmonary valvar ste- PK. Rheumatic mitral valve disease is associated with worse outcomes in
nosis. Circulation. 1993;87(suppl):I28–I37. stroke: a Thailand National Database study. Stroke. 2016;47:2695–2701.
64. Gillespie MJ, Rome JJ, Levi DS, Williams RJ, Rhodes JF, Cheatham JP, doi: 10.1161/STROKEAHA.116.014512
Hellenbrand WE, Jones TK, Vincent JA, Zahn EM, McElhinney DB. Melody 77. Reményi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K, Lawrenson
valve implant within failed bioprosthetic valves in the pulmonary position: J, Maguire G, Marijon E, Mirabel M, Mocumbi AO, Mota C, Paar J,
a multicenter experience. Circ Cardiovasc Interv. 2012;5:862–870. doi: Saxena A, Scheel J, Stirling J, Viali S, Balekundri VI, Wheaton G, Zühlke L,
10.1161/CIRCINTERVENTIONS.112.972216 Carapetis J. World Heart Federation criteria for echocardiographic diag-
65. Lee C, Kim YM, Lee CH, Kwak JG, Park CS, Song JY, Shim WS, Choi nosis of rheumatic heart disease: an evidence-based guideline. Nat Rev
EY, Lee SY, Baek JS. Outcomes of pulmonary valve replacement in 170 Cardiol. 2012;9:297–309. doi: 10.1038/nrcardio.2012.7
patients with chronic pulmonary regurgitation after relief of right ven- 78. Nascimento BR, Beaton AZ, Nunes MC, Diamantino AC, Carmo GA,
tricular outflow tract obstruction: implications for optimal timing of pul- Oliveira KK, Oliveira CM, Meira ZM, Castilho SR, Lopes EL, Castro IM,
monary valve replacement. J Am Coll Cardiol. 2012;60:1005–1014. doi: Rezende VM, Chequer G, Landay T, Tompsett A, Ribeiro AL, Sable C;
10.1016/j.jacc.2012.03.077 PROVAR (Programa de RastreamentO da VAlvopatia Reumática) investiga-
66. Hauck AJ, Freeman DP, Ackermann DM, Danielson GK, Edwards WD. tors. Echocardiographic prevalence of rheumatic heart disease in Brazilian
Surgical pathology of the tricuspid valve: a study of 363 cases spanning schoolchildren: data from the PROVAR study. Int J Cardiol. 2016;219:439–
25 years. Mayo Clin Proc. 1988;63:851–863. 445. doi: 10.1016/j.ijcard.2016.06.088
67. Nath J, Foster E, Heidenreich PA. Impact of tricuspid regurgitation 79. Ploutz M, Lu JC, Scheel J, Webb C, Ensing GJ, Aliku T, Lwabi P, Sable C,
on long-term survival. J Am Coll Cardiol. 2004;43:405–409. doi: Beaton A. Handheld echocardiographic screening for rheumatic heart disease
Downloaded from http://ahajournals.org by on February 7, 2019

10.1016/j.jacc.2003.09.036 by non-experts. Heart. 2016;102:35–39. doi: 10.1136/heartjnl-2015-308236

68. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton 80. Shrestha NR, Karki P, Mahto R, Gurung K, Pandey N, Agrawal K,
RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas Rothenbühler M, Urban P, Jüni P, Pilgrim T. Prevalence of subclinical rheu-
JD. 2014 AHA/ACC guideline for the management of patients with matic heart disease in eastern Nepal: a school-based cross-sectional study.
valvular heart disease: a report of the American College of Cardiology/ JAMA Cardiol. 2016;1:89–96. doi: 10.1001/jamacardio.2015.0292
American Heart Association Task Force on Practice Guidelines. Circulation. 81. Clark BC, Krishnan A, McCarter R, Scheel J, Sable C, Beaton A. Using
2014;129:e521–e643. doi: 10.1161/CIR.0000000000000031 a low-risk population to estimate the specificity of the World Heart
69. Zack CJ, Fender EA, Chandrashekar P, Reddy YNV, Bennett CE, Stulak Federation criteria for the diagnosis of rheumatic heart disease. J Am Soc
JM, Miller VM, Nishimura RA. National trends and outcomes in isolated Echocardiogr. 2016;29:253–258. doi: 10.1016/j.echo.2015.11.013
tricuspid valve surgery. J Am Coll Cardiol. 2017;70:2953–2960. doi: 82. Engelman D, Wheaton GR, Mataika RL, Kado JH, Colquhoun SM,
10.1016/j.jacc.2017.10.039 Remenyi B, Steer AC. Screening-detected rheumatic heart dis-
70. Nickenig G, Kowalski M, Hausleiter J, Braun D, Schofer J, Yzeiraj E, ease can progress to severe disease. Heart Asia. 2016;8:67–73. doi:
Rudolph V, Friedrichs K, Maisano F, Taramasso M, Fam N, Bianchi G, 10.1136/heartasia-2016-010847
Bedogni F, Denti P, Alfieri O, Latib A, Colombo A, Hammerstingl C, 83. Bertaina G, Rouchon B, Huon B, Guillot N, Robillard C, Noël B, Nadra
Schueler R. Transcatheter treatment of severe tricuspid regurgitation M, Tribouilloy C, Marijon E, Jouven X, Mirabel M. Outcomes of border-
with the edge-to-edge MitraClip technique. Circulation. 2017;135:1802– line rheumatic heart disease: a prospective cohort study. Int J Cardiol.
1814. doi: 10.1161/CIRCULATIONAHA.116.024848 2017;228:661–665. doi: 10.1016/j.ijcard.2016.11.234
71. Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, 84. Zühlke L, Engel ME, Lemmer CE, van de Wall M, Nkepu S, Meiring A,
Bukhman G, Forouzanfar MH, Longenecker CT, Mayosi BM, Mensah GA, Bestawros M, Mayosi BM. The natural history of latent rheumatic heart
Nascimento BR, Ribeiro ALP, Sable CA, Steer AC, Naghavi M, Mokdad disease in a 5 year follow-up study: a prospective observational study.
AH, Murray CJL, Vos T, Carapetis JR, Roth GA. Global, regional, and BMC Cardiovasc Disord. 2016;16:46. doi: 10.1186/s12872-016-0225-3
national burden of rheumatic heart disease, 1990-2015. N Engl J Med. 85. Beaton A, Aliku T, Dewyer A, Jacobs M, Jiang J, Longenecker CT, Lubega
2017;377:713–722. doi: 10.1056/NEJMoa1603693 S, McCarter R, Mirabel M, Mirembe G, Namuyonga J, Okello E, Scheel
72. Roth GA, Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, Morozoff C, A, Tenywa E, Sable C, Lwabi P. Latent rheumatic heart disease: identi-
Naghavi M, Mokdad AH, Murray CJL. Trends and patterns of geographic fying the children at highest risk of unfavorable outcome. Circulation.
variation in cardiovascular mortality among US counties, 1980-2014. 2017;136:2233–2244. doi: 10.1161/CIRCULATIONAHA.117.029936
JAMA. 2017;317:1976–1992. doi: 10.1001/jama.2017.4150 86. Longenecker CT, Morris SR, Aliku TO, Beaton A,Costa MA, Kamya MR,
73. Zühlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, Kityo C, Lwabi P Mirembe G, Nampijja D, Rwebembera J, Sable C,
Mauff K, Islam S, Joachim A, Daniels R, Francis V, Ogendo S, Gitura B, Salata RA, Scheel A, Simon DI, Ssinabulya I, Okello E. Rheumatic heart
Mondo C, Okello E, Lwabi P, Al-Kebsi MM, Hugo-Hamman C, Sheta SS, disease treatment cascade in Uganda. Circ Cardiovasc Qual Outcomes.
Haileamlak A, Daniel W, Goshu DY, Abdissa SG, Desta AG, Shasho BA, 2017;10:e004037. doi: 10.1161/CIRCOUTCOMES.117.004037
Begna DM, ElSayed A, Ibrahim AS, Musuku J, Bode-Thomas F, Okeahialam 87. Parks T, Kado J, Miller AE, Ward B, Heenan R, Colquhoun SM,
BN, Ige O, Sutton C, Misra R, Abul Fadl A, Kennedy N, Damasceno A, Sani Bärnighausen TW, Mirabel M, Bloom DE, Bailey RL, Tukana IN, Steer AC.
M, Ogah OS, Olunuga T, Elhassan HH, Mocumbi AO, Adeoye AM, Mntla Rheumatic heart disease-attributable mortality at ages 5-69 years in Fiji:
P, Ojji D, Mucumbitsi J, Teo K, Yusuf S, Mayosi BM. Characteristics, com- a five-year, national, population-based record-linkage cohort study. PLoS
plications, and gaps in evidence-based interventions in rheumatic heart Negl Trop Dis. 2015;9:e0004033. doi: 10.1371/journal.pntd.0004033

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e415

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 21

88. Global Burden of Disease Study 2016. Global Burden of Disease Study 95. Slipczuk L, Codolosa N, Carlos D, Romero-Corral A, Pressman G,
CLINICAL STATEMENTS

2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and Figueredo V. Systematic review & meta-analysis of infective endocarditis
AND GUIDELINES

Evaluation (IHME), University of Washington; 2016. http://ghdx.health- microbiology over 5 decades. Circulation. 2012;126(suppl 21):A15138.
data.org/gbd-results-tool. Accessed May 1, 2018. Abstract 15138.
89. Pant S, Patel NJ, Deshmukh A, Golwala H, Patel N, Badheka A, Hirsch 96. Abdallah L, Remadi JP, Habib G, Salaun E, Casalta JP, Tribouilloy C.
GA, Mehta JL. Trends in infective endocarditis incidence, microbiology, Long-term prognosis of left-sided native-valve Staphylococcus au-
and valve replacement in the United States from 2000 to 2011. J Am Coll reus endocarditis. Arch Cardiovasc Dis. 2016;109:260–267. doi:
Cardiol. 2015;65:2070–2076. doi: 10.1016/j.jacc.2015.03.518 10.1016/j.acvd.2015.11.012
90. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, 97. Katan O, Michelena HI, Avierinos JF, Mahoney DW, DeSimone DC,
and national life expectancy, all-cause mortality, and cause-specific mor- Baddour LM, Suri RM, Enriquez-Sarano M. Incidence and predictors of
tality for 249 causes of death, 1980–2015: a systematic analysis for the infective endocarditis in mitral valve prolapse: a population-based study.
Global Burden of Disease Study 2015. Lancet. 2016;388:1459–1544. doi: Mayo Clin Proc. 2016;91:336–342. doi: 10.1016/j.mayocp.2015.12.006
10.1016/S0140-6736(16)31012-1 98. Deo SV, Raza S, Kalra A, Deo VS, Altarabsheh SE, Zia A, Khan MS,
91. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger Markowitz AH, Sabik JF 3rd, Park SJ. Admissions for infective endocar-
A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, ditis in intravenous drug users. J Am Coll Cardiol. 2018;71:1596–1597.
Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, doi: 10.1016/j.jacc.2018.02.011
Gardner T, Goff D, Durack DT. Prevention of infective endocarditis: guidelines 99. Athan E, Chu VH, Tattevin P, Selton-Suty C, Jones P, Naber C, Miró
from the American Heart Association: a guideline from the American Heart JM, Ninot S, Fernández-Hidalgo N, Durante-Mangoni E, Spelman D,
Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Hoen B, Lejko-Zupanc T, Cecchi E, Thuny F, Hannan MM, Pappas P,
Council on Cardiovascular Disease in the Young, and the Council on Clinical Henry M, Fowler VG Jr, Crowley AL, Wang A; ICE-PCS Investigators.
Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Clinical characteristics and outcome of infective endocarditis involv-
Quality of Care and Outcomes Research Interdisciplinary Working Group [pub- ing implantable cardiac devices. JAMA. 2012;307:1727–1735. doi:
lished correction appears in Circulation. 2007;116:e376–e377]. Circulation. 10.1001/jama.2012.497
2007;116:1736–1754. doi: 10.1161/CIRCULATIONAHA.106.183095 100. Chu VH, Park LP, Athan E, Delahaye F, Freiberger T, Lamas C, Miro JM,
92. Ware AL, Tani LY, Weng HY, Wilkes J, Menon SC. Resource utilization and Mudrick DW, Strahilevitz J, Tribouilloy C, Durante-Mangoni E, Pericas
outcomes of infective endocarditis in children. J Pediatr. 2014;165:807– JM, Fernández-Hidalgo N, Nacinovich F, Rizk H, Krajinovic V, Giannitsioti
812.e1. doi: 10.1016/j.jpeds.2014.06.026 E, Hurley JP, Hannan MM, Wang A; for the International Collaboration
93. DeSimone DC, Tleyjeh IM, Correa de Sa DD, Anavekar NS, Lahr BD, Sohail on Endocarditis (ICE) Investigators. Association between surgical indica-
MR, Steckelberg JM, Wilson WR, Baddour LM. Temporal trends in infec- tions, operative risk, and clinical outcome in infective endocarditis: a
tive endocarditis epidemiology from 2007 to 2013 in Olmsted County, prospective study from the International Collaboration on Endocarditis.
MN. Am Heart J. 2015;170:830–836. doi: 10.1016/j.ahj.2015.07.007 Circulation. 2015;131:131–140. doi: 10.1161/CIRCULATIONAHA.
94. Pasquali SK, He X, Mohamad Z, McCrindle BW, Newburger JW, Li JS, Shah 114.012461
SS. Trends in endocarditis hospitalizations at US children’s hospitals: impact 101. National Center for Health Statistics. Health, United States, 2015: With
of the 2007 American Heart Association antibiotic prophylaxis guidelines. Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD:
Am Heart J. 2012;163:894–899. doi: 10.1016/j.ahj.2012.03.002 National Center for Health Statistics; 2016.
Downloaded from http://ahajournals.org by on February 7, 2019

e416 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

22. VENOUS THROMBOEMBOLISM (principal diagnosis), 473 

000 (all-listed diagnoses)

CLINICAL STATEMENTS
(2014 HCUP).
(DEEP VEIN THROMBOSIS AND

AND GUIDELINES
PULMONARY EMBOLISM), CHRONIC
VENOUS INSUFFICIENCY, PULMONARY Venous Thromboembolism
HYPERTENSION Incidence
(Charts 22-1 and 22-2)
See Charts 22-1 and 22-2 • VTE includes both DVT and PE. Information on
VTE incidence in the United States is limited
Click here to return to the Table of Contents because there is no national surveillance system.
The HCUP NIS (Charts 22-1 and 22-2) shows
Pulmonary Embolism increasing rates of hospitalization cases for both
ICD-9 415.1; ICD-10 I26. PE from 1996 to 2014 and DVT from 2005 to
Mortality—8502. Any-mention mortality—33  987 2014, with DVT trending down since 2012.
(2016 NHLBI tabulation). Hospital discharges—178 000 Extrapolating from these data, if we assume
(principal diagnosis), 339 000 (all-listed diagnoses) 30% of DVTs were treated in the outpatient
(2014 HCUP). setting, we estimate that in 2014 there were
≈676 000 DVTs, ≈340 000 PEs and ≈1 016 000
total VTE events in the United States (US popula-
Deep Vein Thrombosis tion was 319 million in 2014).1
ICD-9 451.1, 451.2, 451.81, 451.9, 453.0, • Interpretation of the HCUP NIS, and most other
453.1 453.2, 453.3, 453.4, 453.5, 453.9; sources of VTE incidence data, should be viewed
in light of secular trends and data characteristics
ICD-10 I80.1, I80.2, I80.3, I80.9, I82.0,
that could have resulted in an increase in VTE
I82.1, I82.2, I82.3, I82.4, I82.5, I82.9. diagnosis that might overstate changes in VTE
Mortality—3187. Any-mention mortality—16  479 incidence (eg, advances in PE imaging, which
(2016 NHLBI tabulation). Hospital discharges—114 000 enable the detection of smaller PEs2 increased
use of full leg ultrasound, which detects distal
DVT; the co-occurrence of codes for DVT and PE
Downloaded from http://ahajournals.org by on February 7, 2019

Abbreviations Used in Chapter 22

BMI body mass index

in the same patient) and other factors that could
CI confidence interval lead to underestimation of VTE incidence (eg,
CT computed tomography outpatient management of ≈35% of DVT cases3
CTEPH chronic thromboembolic pulmonary hypertension and a smaller portion of PE cases,4,5 misdiagnosis
CVI chronic venous insufficiency of VTE events, and failure to ascertain fatal PEs
DM diabetes mellitus
because of low autopsy rates).
DVT deep vein thrombosis
FHS Framingham Heart Study
• A modeling study estimated VTE incidence in 6
GWAS genome-wide association study countries in Europe (total population 310.4 mil-
HCUP Healthcare Cost and Utilization Project lion), accounting for missed diagnoses related
HD heart disease to factors such as lack of routine autopsy, mis-
HF heart failure diagnosis, or underdiagnosis because of lack of
HIV human immunodeficiency virus
symptom recognition.6 The authors estimated
HR hazard ratio
ICD-9 International Classification of Diseases, 9th Revision there were 465 715 (404 664–538 189) cases of
ICD-10 International Classification of Diseases, 10th Revision DVT, 295 982 (242 450–360 363) cases of PE, and
ICU intensive care unit 370 012 (300 193–483 108) VTE-related deaths
NHLBI National Heart, Lung, and Blood Institute annually. Of these deaths, only 7% were diag-
NIS National (Nationwide) Inpatient Sample
nosed antemortem; 34% were sudden fatal PE,
OR odds ratio
PAH pulmonary arterial hypertension
and 59% followed undiagnosed PE.
PE pulmonary embolism • Using administrative data in the United States, the
PH pulmonary hypertension estimated admissions for PE increased from 23
PTS postthrombotic syndrome per 100 000 in 1993 to 65 per 100 000 in 2012.7
REVEAL Registry to Evaluate Early and Long-term PAH Disease Trends in DVT incidence were not reported. The
Management
RCT randomized controlled trial
Danish National Cohort also reported that PE inci-
RR relative risk dence increased from 45 to 83 per 100 000 from
RV right ventricular 2004 to 2014.8
VTE venous thromboembolism • Regarding trends in total VTE incidence, the
WHO World Health Organization Tromsø Study in Norway reported that the VTE

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e417

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

incidence rate increased from 158 per 100 000 for VTE primary treatment could further reduce
CLINICAL STATEMENTS

in 1996 to 1997 to 201 per 100 000 in 2010 to bleeding risk.24

AND GUIDELINES

2011.9 This trend was driven by increasing inci- • Postthrombotic syndrome/venous stasis syndrome
dence of PE. and venous stasis ulcers are important complica-
• VTE incidence varies by race/ethnicity.10–13 Blacks tions of proximal lower-extremity DVT, which are
appear to be at greatest risk, followed by discussed in greater depth in the Chronic Venous
Caucasians, Hispanics, and Asians, respectively. Insufficiency section of this chapter. After proximal
• Incidence rates for PE and DVT increase expo- lower-extremity DVT, the 20-year cumulative inci-
nentially with advancing age for both males and dences of PTS/venous stasis syndrome and venous
females.11,14,15 stasis ulcers are 30% and 3.7%, respectively.25
• CTEPH affects ≈4% of patients with PE within 2
Lifetime Risk years of their initial PE event.26
• In 2 US cohorts including 19  599 males and
females aged 45 to 99 years at baseline and fol- Costs
lowed up for 288 535 person-years, the remain- • A literature review estimated incremental direct
ing lifetime risk of VTE at age 45 years was 8.1% medical costs (2014 US dollars) per case among
(95% CI, 7.1%–8.7%) overall, 11.5% in African 1-year survivors of acute VTE at $12  000 to
Americans, 10.9% in those with obesity, 17.1% in $15 000 and the cost of complications, including
individuals with the factor V Leiden genetic muta- recurrent VTE, PTS, CTEPH, and anticoagulation-
tion, and 18.2% in people with sickle cell trait or related adverse events, at $18 000 to $23 000 per
disease.16 case. This review assumed 375 000 to 425 000
new cases in the United States annually and esti-
Mortality mated the annual overall cost at $7 to 10 billion.27
• Using administrative data for first-time VTE in
Risk Factors
Quebec, Canada, from 2000 to 2009, 30-day
• Approximately 50% of VTEs are provoked
case fatality was 10.6% and 1-year mortality was
because of immobilization, trauma, surgery,
23.0%. The 1-year survival rate was 47% (95%
or hospitalization in the antecedent 3 months;
CI, 46%–48%) for cases with VTE and cancer,
20% are associated with cancer; and 30% are
93% (95% CI, 93%–94%) for cases with unpro-
Downloaded from http://ahajournals.org by on February 7, 2019

unprovoked.28–31
voked VTE, and 84% (95% CI, 83%–84%) for
• Independent VTE risk factors include increasing
those with provoked VTE.17
age, obesity, family history or personal history
• Data from a Worcester, MA, surveillance study
of thrombosis, recent surgery, trauma/fracture,
from 1999 to 2009 suggested a decline in 3-year
hospitalization, prolonged immobility, nursing
mortality after VTE (from 41% to 26%).18 Declines
home residence, active cancer, indwelling central
in VTE mortality rates have also been reported in
venous catheter or transvenous pacemaker, prior
the National Danish Cohort for the period from
superficial vein thrombosis, infection, inherited or
2004 to 2014.8 A decrease in mortality rates
acquired thrombophilia, kidney disease, neurolog-
associated with VTE could be the result of several
ical disease with leg paresis, sickle cell anemia and
factors, including recognition of smaller PEs2 and
sickle cell trait, long-distance travel, and among
recent changes in treatment options.19
females, the use of estrogen-based contraceptives
Recurrence or hormone therapy, pregnancy, and the postpar-
• VTE is a chronic disease with episodic recurrence; tum period.20,32–34 Recently, autoimmune diseases,
in the absence of long-term anticoagulation, such as lupus and Sjögren syndrome, and acute
≈30% of patients develop recurrence within the infection have also been associated with elevated
next 10 years.20–22 VTE risk.35–38
• Independent predictors of recurrence within 180 • Traditional atherosclerotic risk factors, including
days include active cancer and inadequate anti- hypertension, hyperlipidemia, and DM, were not
coagulation. Two-week case-fatality rates are 2% associated with VTE risk in a 2017 individual-level
for recurrent DVT alone and 11% for recurrent PE meta-analysis of >240 000 participants from 9
with or without DVT.23 cohorts.39 Cigarette smoking was associated with
provoked but not with unprovoked VTE events.
Complications • Among patients hospitalized for acute medical
• Because of the use of anticoagulant therapy to illness, independent risk factors for VTE include
treat VTE, bleeding is a major potential complica- prior VTE, thrombophilia, cancer, age >60 years,
tion. Data from phase III RCTs suggest that use leg paralysis, immobilization for 7 days, and
of direct oral anticoagulants, instead of warfarin, admission to an ICU or coronary care unit.40

e418 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

• Pregnancy-associated VTE has an incidence of 1 of these trials suggested that direct oral antico-

CLINICAL STATEMENTS
to 2 per 1000 person-years; compared with non- agulant drugs have a lower risk of most bleeding

AND GUIDELINES
pregnant females of childbearing age, the RR for complications than warfarin.
VTE is increased 4-fold.41–43 VTE risk is higher for
pregnancies after in vitro fertilization than for nat-
ural pregnancies,44 and with multiple gestation, Chronic Venous Insufficiency
cesarean delivery, or other pregnancy complica- ICD-10 I87.2.
tions.45 Risk factors associated with VTE in the Mortality—46. Any-mention mortality—490 (2016
general population (eg, obesity) are also associ- NHLBI tabulation).
ated with pregnancy-associated VTE.
• VTE risk during the postpartum period is ≈5-fold Prevalence
higher than during pregnancy. Among females • Varicose veins are a common manifestation of
who are pregnant or postpartum, approximately CVI, affecting 25 million US adults. More severe
one-third of the DVT events and one-half of the venous disease affects 6 million adults.58
PE events occur after delivery,46 with the RR being • By way of international comparators, Zolotukhin
21- to 84-fold increased within 6 weeks postpar- and colleagues59 described the prevalence of CVI
tum compared with females who are not preg- (8.2%) and venous ulcers (1.1%) in a cohort of
nant or postpartum.47 703 people from central Russia.
• Functional chronic venous disease was recently
Family History and Genetics reviewed by Serra and colleagues,60 who described
• VTE is highly heritable.48,49 it as a complex syndrome that is as of now poorly
• Factor V Leiden is a genetic variant responsible for understood.
≈90% of cases of VTE caused by activated pro-
tein C resistance and is the most common genetic Incidence
cause of VTE. Factor V Leiden increases risk of • The FHS reported an annual incidence of varicose
VTE 3- to 18-fold depending on the number of veins of 2.6% in females and 1.9% in males.61
variants carried, and its presence can influence Complications
management.50 • More severe venous disease often includes mani-
• More common genetic variants associated with festations such as hyperpigmentation, venous
Downloaded from http://ahajournals.org by on February 7, 2019

VTE have a lesser risk of VTE than rare mutations eczema, lipodermatosclerosis, atrophie blanche,
and include non-O blood group, prothrom- and healed or active venous ulcers.62
bin 20210A, and sickle cell disease and trait.51 • Analysis of NIS data for black and white Americans
GWASs have identified additional common demonstrated declines in ulcer debridement, vein
genetic variants associated with VTE risk, includ- stripping, and sclerotherapy procedures from
ing variants in F5, F2, F11, FGG, and ZFPM2.52 1998 to 2011. Blacks presented at younger ages
These common variants individually increase and more often had ulcer debridement and his-
the risk of VTE to a small extent, but genetic tory of DVT than whites.63
risk scores composed of a combination of these • A recent publication that used a database of 300
variants can increase the OR of VTE risk to patients treated for advanced CVI with radiofre-
up to 7.5.53 quency ablation procedures showed that African-
Treatment Americans presented with higher severity CVI and
• VTE is generally treated for 3 to 6 months with had less improvement with ablation.64
anticoagulation (primary treatment), at which • A 2017 study reviewed the risk factors for PTS as
point the risks and benefits of continued anti- well, finding age, sex, and prior DVT to be pre-
coagulation should be assessed (secondary dictors, though nonmodifiable. Oral anticoagula-
prevention).19 When oral anticoagulation is con- tion with warfarin or newer factor Xa inhibitors,
traindicated or ineffective, inferior vena cava fil- along with catheter-directed thrombolysis, are
ters can be used. suggested as potential therapeutic options.65
• Current treatment guidelines consider anticoagu-
Cost
lation with either warfarin or direct oral anticoag-
• Estimated cost in the United States to treat venous
ulant drugs (ie, apixaban, rivaroxaban, dabigatran,
ulcers is $1 billion annually.62
edoxaban) as the standard of care.19 In phase III
RCTs of VTE primary treatment,54–57 the direct oral Risk Factors
anticoagulant drugs were each shown to be as • The prevalence of moderate CVI increases with
effective as warfarin in the prevention of recur- advancing age, family history, hernia surgery, obe-
rent VTE and VTE-related death. A meta-analysis24 sity, number of births, and presence of flat feet

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e419

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

in females and is less likely in those with hyper- 3: 9%), WHO group 1, underlying causes com-
CLINICAL STATEMENTS

tension; risk factors for more severe CVI include bined (3%), and CTEPH (WHO group 4: 2%);
AND GUIDELINES

smoking in males and leg injury in females.66 15% were unclassifiable.75

Blood coagulation disorders and inflammatory • The prevalence of WHO group 1 PH (idiopathic,
biomarkers that are related to DVT risk are also heritable, drug/toxin induced, or associated with
associated with an increased risk of CVI, consis- other factors including connective tissue disease,
tent with the hypothesis that DVT predisposes to infections [HIV, schistosomiasis], portal hyperten-
CVI.67 sion, and congenital HD) is estimated at 6.6 to
• PTS, a subset of CVI, has specific risk factors that 26.0 per million adults and the incidence at 1.1 to
can be identified at the time of or after DVT: 7.6 per million adults annually.76
recurrent ipsilateral DVT, obesity, more extensive • WHO group 2 PH is attributable to left-sided HD.
DVT, poor quality of initial anticoagulation, ongo- Estimates of the incidence and prevalence are dif-
ing symptoms or signs of DVT 1 month after diag- ficult to ascertain but most likely would track with
nosis, and elevated D-dimer at 1 month.68–70 HF prevalence rates.76
• Galanaud and colleagues70 described the 2 most • The prevalence and incidence of WHO group 3
important predictors of PTS as an extensive proxi- PH (attributable to lung disease or hypoxia) is dif-
mal DVT and prior DVT in the same limb. PTS ficult to estimate but likely would track with lung
was reviewed by Rabinovich and Kahn,71 who disease prevalence.76
described prevention of DVT and appropriate • The prevalence of WHO group 4 PH (CTEPH and
anticoagulation of DVT once it occurs as the best other pulmonary obstructions) ranges from 1.0%
means to prevent PTS. to 8.8% among those with PE.76 CTEPH inci-
• Varicose veins are more likely to occur in the set- dence, however, may be underestimated based
ting of a positive family history, consistent with on general population data; in a 2017 model-
a heritable component. Although a number of ing study, only 7% to 29% of CTEPH cases were
genes are implicated, the genetic factors72 predis- diagnosed.77
posing to varicose veins have not been definitively • WHO group 5 PH has multifactorial mechanisms.
identified.73 When it accompanies sickle cell disease, the prev-
• Similarly, in the study by Zolotukhin et al,59 family alence is 6% to 10% and increases with advanc-
Downloaded from http://ahajournals.org by on February 7, 2019

history was independently associated with chronic ing age. When it accompanies thalassemia, the
venous disease. prevalence is 2.1%.76,78
Mortality
Pulmonary Hypertension Mortality of PH depends on the cause and treatment.
ICD-10 I27.0, I27.2. • In the US-based REVEAL registry of patients with
group 1 PH enrolled from 2006 to 2009, 5-year
Mortality—7313. Any-mention mortality—23 
067
survival was 61.2% to 65.4%. Lower 5-year sur-
(2016 NHLBI tabulation).
vival was strongly and directly associated with
Prevalence and Incidence worse functional class at presentation.79 In an
• In the United States, between 2001 and 2010, earlier study from this registry, 6-minute walk
hospitalization rates for PH increased significantly, distance was also shown to be a strong predic-
and among those aged ≥85 years, hospitalization tor, with 97%, 90%, and 68% 1-year survival for
rates nearly doubled.74 In 2010, the age-adjusted patients with >440, 165 to 440, and <165 meter
rate of hospitalization associated with PH was walk distances, respectively. A decline of >15%
131 per 100 000 discharges overall and 1527 over time also predicted a significantly worse
per 100 000 for those aged ≥85 years. There is outcome compared with a stable or improving
also evidence of increasing mortality rates in both 6-minute walk distance.80
males and females; in 2010, the death rate for PH • A German single-center registry study reported
as any contributing cause of death was 6.5 per 5-year survival rates of 65.3% for patients with
100 000.74 idiopathic PH, 50.9% for those with PH associ-
• The WHO classifies PH into 5 groups (described ated with connective tissue disease, 74.5% for
below) according to underlying pathogenesis. those with PH caused by congenital HD, and
Limited information is available on prevalence of 18.7% for those with pulmonary venous occlu-
PH subtypes in nonreferral settings. In one study sive disease, respectively.81
conducted in Armadale, Australia, the most com- • In a multicenter study of patients with PH caused
monly identified PH subtypes were left-sided HD by congenital HD with Eisenmenger syndrome,
(WHO group 2: 68%), lung disease (WHO group mortality was associated with age, pretricuspid

e420 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

lesion, and the presence of a pericardial effusion and lung disease, but schistosomiasis, rheumatic

CLINICAL STATEMENTS
and inversely associated with sinus rhythm and HD, HIV, and sickle cell disease remain promi-

AND GUIDELINES
resting oxygen saturation.82 nent compared with developed countries. In
• In a French Registry study of 981 patients with these countries, younger people are more often
idiopathic, heritable, or drug-induced PAH affected (average age of onset <40 years).76
enrolled between 2006 and 2016, survival at 1 • In high-income countries, rates of CTEPH are
and 3 years was 90% and 73%, respectively.83 believed to be lower in Japan than in the United
• In sickle cell disease–related PH, the 5-year sur- States and Europe.77
vival rate in one study was 63% with and 83%
Treatment
without PH.84
• Galiè and colleagues88 performed a double-blind
• An international prospective registry that included
RCT of 500 treatment-naïve patients with WHO
679 patients with CTEPH estimated that the
group 2 or 3 PH, randomizing them to ambrisen-
3-year survival was 89% with and 70% without
tan, tadalafil, or both in combination. The com-
pulmonary thromboendarterectomy.85 Among the
bination group (versus the pooled monotherapy
patients with CTEPH, treatments for PH did not
groups) was at lower risk for the composite pri-
affect survival. High New York Heart Association
mary end point of death, PAH hospitalization, or
functional class, increased right atrial pressure,
clinical disease progression (HR, 0.50 [95% CI,
and history of cancer were associated with mor-
0.35–0.72]).
tality regardless of surgery.
• In a large, placebo-controlled, double-blind RCT of
Risk Factors 1156 patients with PAH randomized to selexipag,
• Risk factors are implicit in the WHO disease clas- an oral selective IP prostacyclin receptor agonist,
sification of the 5 mechanistic subtypes of PH versus placebo, Sitbon and colleagues89 found
described above. The most common risk factors a significant reduction in the primary compos-
are left-sided HD and lung disease. ite end point of death attributable to any cause
• In a study of 772 consecutive PE patients with- or PAH-related complication (HR, 0.60 [99% CI,
out major comorbidities such as cancer, the risk 0.46–0.78]). This observed benefit was driven by
factors for CTEPH were unprovoked PE, hypothy- differences in disease progression and hospital-
roidism, symptom onset >2 weeks before PE diag- ization; no significant difference in mortality was
Downloaded from http://ahajournals.org by on February 7, 2019

nosis, RV dysfunction on CT or echocardiography, seen between selexipag and placebo.

DM, and thrombolytic therapy or embolectomy; • Pulido and colleagues90 performed a 250-patient
a risk prediction score that included these factors RCT of 3 mg or 10 mg of macitentan, a dual
was able to predict a group with a CTEPH inci- endothelin receptor antagonist, versus placebo,
dence of 10% (95% CI, 6.5%–15%).86 It is not with a primary end point composite of death,
clear to what extent these factors may be affected atrial septostomy, lung transplantation, initiation
by the possibility that the index presentation was of treatment with intravenous or subcutaneous
caused by worsening RV failure in the setting of prostanoids, or worsening of PAH. Macitentan
CTEPH rather than acute PE. Higher BMI also has was shown to have statistically and clinically sig-
been associated with CTEPH risk after PE.87 nificant benefit at either tested dose; the HR for
3 mg of macitentan versus placebo was 0.70
Global Burden
(97.5% CI, 0.52–0.96), and for 10 mg of maci-
• 80% of patients with PH live in developing coun-
tentan versus placebo, the HR was 0.55 (97.5%
tries, and the cause of their PH is primarily HD
CI, 0.39–0.76).90‍‍

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e421

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22
CLINICAL STATEMENTS
AND GUIDELINES

Chart 22-1. Trends in hospitalized pulmonary embolism, 1996 to 2014.

Source: Weighted national estimates from Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample, Agency for Healthcare Research and
Quality, based on data collected by individual states.1
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 22-2. Trends in hospitalized deep vein thrombosis, 2005 to 2014.

Source: Weighted national estimates from Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample, Agency for Healthcare Research and
Quality, based on data collected by individual states.1

e422 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

REFERENCES P, Woller SC, Moores L. Antithrombotic therapy for VTE disease: CHEST

CLINICAL STATEMENTS
Guideline and Expert Panel Report. Chest. 2016;149:315–352. doi:
1. Weighted national estimates from HCUP National (Nationwide) Inpatient

AND GUIDELINES
10.1016/j.chest.2015.11.026
Sample (NIS), AHRQ, based on data collected by individual states. http:// 20. Heit JA. The epidemiology of venous thromboembolism in the com-
www.HCUP-US.AHRQ.gov. Accessed May 20, 2017. munity. Arterioscler Thromb Vasc Biol. 2008;28:370–372. doi:
2. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embo- 10.1161/ATVBAHA.108.162545
lism in the United States: evidence of overdiagnosis. Arch Intern Med. 21. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R,
2011;171:831–837. doi: 10.1001/archinternmed.2011.178
Iotti M, Tormene D, Simioni P, Pagnan A. The risk of recurrent venous
3. Stein PD, Matta F, Hughes MJ. Home treatment of deep venous thrombo-
thromboembolism after discontinuing anticoagulation in patients with
sis according to comorbid conditions. Am J Med. 2016;129:392–397. doi:
acute proximal deep vein thrombosis or pulmonary embolism: a pro-
10.1016/j.amjmed.2015.10.022
spective cohort study in 1,626 patients. Haematologica. 2007;92:
4. Stein PD, Matta F, Hughes PG, Hourmouzis ZN, Hourmouzis NP, White RM,
199–205.
Ghiardi MM, Schwartz MA, Moore HL, Bach JA, Schweiss RE, Kazan VM,
22. Lutsey PL, Virnig BA, Durham SB, Steffen LM, Hirsch AT, Jacobs DR Jr,
Kakish EJ, Keyes DC, Hughes MJ. Home treatment of pulmonary embo-
Folsom AR. Correlates and consequences of venous thromboembolism:
lism in the era of novel oral anticoagulants. Am J Med. 2016;129:974–
the Iowa Women’s Health Study. Am J Public Health. 2010;100:1506–
977. doi: 10.1016/j.amjmed.2016.03.035
1513. doi: 10.2105/AJPH.2008.157776
5. Klil-Drori AJ, Coulombe J, Suissa S, Hirsch A, Tagalakis V. Temporal
23. Heit JA, Lahr BD, Petterson TM, Bailey KR, Ashrani AA, Melton LJ
trends in outpatient management of incident pulmonary embo-
3rd. Heparin and warfarin anticoagulation intensity as predictors of
lism and associated mortality. Thromb Res. 2018;161:111–116. doi:
recurrence after deep vein thrombosis or pulmonary embolism: a
10.1016/j.thromres.2017.10.026
population-based cohort study. Blood. 2011;118:4992–4999. doi:
6. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG,
10.1182/blood-2011-05-357343
Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama
24. van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman
MM, Spannagl M; VTE Impact Assessment Group in Europe (VITAE).
MV. Effectiveness and safety of novel oral anticoagulants as compared
Venous thromboembolism (VTE) in Europe: the number of VTE events and
with vitamin K antagonists in the treatment of acute symptomatic venous
associated morbidity and mortality. Thromb Haemost. 2007;98:756–764.
thromboembolism: a systematic review and meta-analysis. J Thromb
7. Smith SB, Geske JB, Kathuria P, Cuttica M, Schimmel DR, Courtney
Haemost. 2014;12:320–328. doi: 10.1111/jth.12485
DM, Waterer GW, Wunderink RG. Analysis of national trends in
25. Mohr DN, Silverstein MD, Heit JA, Petterson TM, O’Fallon WM,
admissions for pulmonary embolism. Chest. 2016;150:35–45. doi:
Melton LJ. The venous stasis syndrome after deep venous thrombo-
10.1016/j.chest.2016.02.638
sis or pulmonary embolism: a population-based study. Mayo Clin Proc.
8. Lehnert P, Lange T, Møller CH, Olsen PS, Carlsen J. Acute pulmonary
2000;75:1249–1256.
embolism in a national Danish cohort: increasing incidence and decreas-
26. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F,
ing mortality. Thromb Haemost. 2018;118:539–546. doi: 10.1160/
TH17-08-0531 Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P; Thromboembolic
9. Arshad N, Isaksen T, Hansen JB, Brækkan SK. Time trends in incidence Pulmonary Hypertension Study Group. Incidence of chronic thromboem-
rates of venous thromboembolism in a large cohort recruited from the bolic pulmonary hypertension after pulmonary embolism. N Engl J Med.
general population. Eur J Epidemiol. 2017;32:299–305. doi: 10.1007/ 2004;350:2257–2264. doi: 10.1056/NEJMoa032274
s10654-017-0238-y 27. Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE. The
10. White RH, Zhou H, Murin S, Harvey D. Effect of ethnicity and gender economic burden of incident venous thromboembolism in the United
States: a review of estimated attributable healthcare costs. Thromb Res.
Downloaded from http://ahajournals.org by on February 7, 2019

on the incidence of venous thromboembolism in a diverse popula-

tion in California in 1996. Thromb Haemost. 2005;93:298–305. doi: 2016;137:3–10. doi: 10.1016/j.thromres.2015.11.033
10.1160/TH04-08-0506 28. Connolly GC, Francis CW. Cancer-associated thrombosis. Hematology
11. Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright Am Soc Hematol Educ Program. 2013;2013:684–691. doi:
P, Folsom AR. Deep vein thrombosis and pulmonary embolism in two 10.1182/asheducation-2013.1.684
cohorts: the Longitudinal Investigation of Thromboembolism Etiology. Am 29. Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of
J Med. 2004;117:19–25. doi: 10.1016/j.amjmed.2004.01.018 cancer-associated venous thrombosis. Blood. 2013;122:1712–1723. doi:
12. Klatsky AL, Armstrong MA, Poggi J. Risk of pulmonary embolism 10.1182/blood-2013-04-460121
and/or deep venous thrombosis in Asian-Americans. Am J Cardiol. 30. Khorana AA, Connolly GC. Assessing risk of venous thromboembo-
2000;85:1334–1337. lism in the patient with cancer. J Clin Oncol. 2009;27:4839–4847. doi:
13. Stein PD, Kayali F, Olson RE, Milford CE. Pulmonary thromboem- 10.1200/JCO.2009.22.3271
bolism in Asians/Pacific Islanders in the United States: analysis of 31. Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboem-
data from the National Hospital Discharge Survey and the United bolism: burden, mechanisms, and management. Thromb Haemost.
States Bureau of the Census. Am J Med. 2004;116:435–442. doi: 2017;117:219–230. doi: 10.1160/TH16-08-0615
10.1016/j.amjmed.2003.11.020 32. Folsom AR, Tang W, Roetker NS, Kshirsagar AV, Derebail VK, Lutsey PL,
14. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton Naik R, Pankow JS, Grove ML, Basu S, Key NS, Cushman M. Prospective
LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmo- study of sickle cell trait and venous thromboembolism incidence. J Thromb
nary embolism: a 25-year population-based study. Arch Intern Med. Haemost. 2015;13:2–9. doi: 10.1111/jth.12787
1998;158:585–593. 33. Mahmoodi BK, Gansevoort RT, Næss IA, Lutsey PL, Brækkan SK, Veeger
15. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal NJ, Brodin EE, Meijer K, Sang Y, Matsushita K, Hallan SI, Hammerstrøm
FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: J, Cannegieter SC, Astor BC, Coresh J, Folsom AR, Hansen JB,
a population-based study. J Thromb Haemost. 2007;5:692–699. doi: Cushman M. Association of mild to moderate chronic kidney disease
10.1111/j.1538-7836.2007.02450.x with venous thromboembolism: pooled analysis of five prospective
16. Bell EJ, Lutsey PL, Basu S, Cushman M, Heckbert SR, Lloyd-Jones DM, Folsom general population cohorts. Circulation. 2012;126:1964–1971. doi:
AR. Lifetime risk of venous thromboembolism in two cohort studies. Am J 10.1161/CIRCULATIONAHA.112.113944
Med. 2016;129:339.e19–339.e26. doi: 10.1016/j.amjmed.2015.10.014 34. Parkin L, Sweetland S, Balkwill A, Green J, Reeves G, Beral V; for the Million
17. Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortal- Women Study Collaborators. Body mass index, surgery, and risk of venous
ity from venous thromboembolism in a real-world population: the thromboembolism in middle-aged women: a cohort study. Circulation.
Q-VTE Study Cohort. Am J Med. 2013;126:832.e13–832.e21. doi: 2012;125:1897–1904. doi: 10.1161/CIRCULATIONAHA.111.063354
10.1016/j.amjmed.2013.02.024 35. Ahlehoff O, Wu JJ, Raunsø J, Kristensen SL, Khalid U, Kofoed K, Gislason
18. Huang W, Goldberg RJ, Cohen AT, Anderson FA, Kiefe CI, Gore JM, G. Cutaneous lupus erythematosus and the risk of deep venous throm-
Spencer FA. Declining long-term risk of adverse events after first-time bosis and pulmonary embolism: a Danish nationwide cohort study. Lupus.
community-presenting venous thromboembolism: the population-based 2017;26:1435–1439. doi: 10.1177/0961203317716306
Worcester VTE study (1999 to 2009). Thromb Res. 2015;135:1100–1106. 36. Annangi S, Dammalapati TR, Nutalapati S, Henriques King MN. Prevalence
doi: 10.1016/j.thromres.2015.04.007 of pulmonary embolism among systemic lupus erythematosus discharges:
19. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, a decade of analysis of the National Hospital Discharge Survey. J Clin
Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells Rheumatol. 2017;23:200–206. doi: 10.1097/RHU.0000000000000521

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e423

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

37. Aviña-Zubieta JA, Jansz M, Sayre EC, Choi HK. The risk of deep venous 56. Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of
CLINICAL STATEMENTS

thrombosis and pulmonary embolism in primary Sjögren syndrome: a symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–
AND GUIDELINES

general population-based study. J Rheumatol. 2017;44:1184–1189. doi: 1415. doi: 10.1056/NEJMoa1306638

10.3899/jrheum.160185 57. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M,
38. Cohoon KP, Ashrani AA, Crusan DJ, Petterson TM, Bailey KR, Heit JA. Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; for the
Is infection an independent risk factor for venous thromboembolism? A AMPLIFY Investigators. Oral apixaban for the treatment of acute
population-based, case-control study. Am J Med. 2018;131:307–316.e2. venous thromboembolism. N Engl J Med. 2013;369:799–808. doi:
doi: 10.1016/j.amjmed.2017.09.015 10.1056/NEJMoa1302507
39. Mahmoodi BK, Cushman M, Anne Næss I, Allison MA, Bos WJ, Brækkan 58. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiol-
SK, Cannegieter SC, Gansevoort RT, Gona PN, Hammerstrøm J, Hansen ogy of chronic venous insufficiency and varicose veins. Ann Epidemiol.
JB, Heckbert S, Holst AG, Lakoski SG, Lutsey PL, Manson JE, Martin LW, 2005;15:175–184. doi: 10.1016/j.annepidem.2004.05.015
Matsushita K, Meijer K, Overvad K, Prescott E, Puurunen M, Rossouw JE, 59. Zolotukhin IA, Seliverstov EI, Shevtsov YN, Avakiants IP, Nikishkov AS,
Sang Y, Severinsen MT, Ten Berg J, Folsom AR, Zakai NA. Association of tra- Tatarintsev AM, Kirienko AI. Prevalence and risk factors for chronic venous
ditional cardiovascular risk factors with venous thromboembolism: an indi- disease in the general Russian population. Eur J Vasc Endovasc Surg.
vidual participant data meta-analysis of prospective studies. Circulation. 2017;54:752–758. doi: 10.1016/j.ejvs.2017.08.033
2017;135:7–16. doi: 10.1161/CIRCULATIONAHA.116.024507 60. Serra R, Andreucci M, De Caridi G, Massara M, Mastroroberto P, de
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, Decousus H, Pini M, Chong Franciscis S. Functional chronic venous disease: a systematic review.
BH, Zotz RB, Bergmann JF, Tapson V, Froehlich JB, Monreal M, Merli GJ, Phlebology. 2017;32:588–592. doi: 10.1177/0268355516686451
Pavanello R, Turpie AGG, Nakamura M, Piovella F, Kakkar AK, Spencer 61. Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of
FA; IMPROVE Investigators. Predictive and associative models to identify varicose veins: the Framingham Study. Am J Prev Med. 1988;4:96–101.
hospitalized medical patients at risk for VTE. Chest. 2011;140:706–714. 62. Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation.
doi: 10.1378/chest.10-1944 2014;130:333–346. doi: 10.1161/CIRCULATIONAHA.113.006898
41. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboem- 63. Dua A, Desai SS, Heller JA. The impact of race on advanced chronic
bolism during pregnancy and the postpartum period: incidence, risk fac- venous insufficiency. Ann Vasc Surg. 2016;34:152–156. doi:
tors, and mortality. Am J Obstet Gynecol. 2006;194:1311–1315. doi: 10.1016/j.avsg.2016.01.020
10.1016/j.ajog.2005.11.008 64. Dua A, Heller JA. Advanced chronic venous insufficiency. Vasc Endovascular
42. Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance Surg. 2017;51:12–16. doi: 10.1177/1538574416682175
for the treatment and prevention of obstetric-associated venous 65. Strijkers RH, de Wolf MA, Wittens CH. Risk factors of postthrombotic syn-
thromboembolism. J Thromb Thrombolysis. 2016;41:92–128. doi: drome before and after deep venous thrombosis treatment. Phlebology.
10.1007/s11239-015-1309-0 2017;32:384–389. doi: 10.1177/0268355516652010
43. Greer IA. Thrombosis in pregnancy: updates in diagnosis and manage- 66. Criqui MH, Denenberg JO, Bergan J, Langer RD, Fronek A. Risk factors
ment. Hematology Am Soc Hematol Educ Program. 2012;2012:203–207. for chronic venous disease: the San Diego Population Study. J Vasc Surg.
doi: 10.1182/asheducation-2012.1.203 2007;46:331–337. doi: 10.1016/j.jvs.2007.03.052
44. Henriksson P, Westerlund E, Wallén H, Brandt L, Hovatta O, Ekbom A. 67. Cushman M, Callas PW, Denenberg JO, Bovill EG, Criqui MH. Risk factors
Incidence of pulmonary and venous thromboembolism in pregnancies for peripheral venous disease resemble those for venous thrombosis: the
after in vitro fertilisation: cross sectional study. BMJ. 2013;346:e8632. doi: San Diego Population Study. J Thromb Haemost. 2010;8:1730–1735. doi:
10.1136/bmj.e8632 10.1111/j.1538-7836.2010.03924.x
45. McLean K, Cushman M. Venous thromboembolism and stroke in preg- 68. Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg
Downloaded from http://ahajournals.org by on February 7, 2019

nancy. Hematology Am Soc Hematol Educ Program. 2016;2016:243–250. NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; on behalf
doi: 10.1182/asheducation-2016.1.243 of the American Heart Association Council on Peripheral Vascular
46. James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Disease, Council on Clinical Cardiology, and Council on Cardiovascular
Vasc Biol. 2009;29:326–331. doi: 10.1161/ATVBAHA.109.184127 and Stroke Nursing. The postthrombotic syndrome: evidence-based pre-
47. Jackson E, Curtis KM, Gaffield ME. Risk of venous thromboembolism vention, diagnosis, and treatment strategies: a scientific statement from
during the postpartum period: a systematic review. Obstet Gynecol. the American Heart Association. Circulation. 2014;130:1636–1661. doi:
2011;117:691–703. doi: 10.1097/AOG.0b013e31820ce2db 10.1161/CIR.0000000000000130
48. Zöller B, Li X, Sundquist J, Sundquist K. A nationwide family study of pul- 69. Busuttil A, Lim CS, Davies AH. Post thrombotic syndrome. Adv Exp Med
monary embolism: identification of high risk families with increased risk of Biol. 2017;906:363–375. doi: 10.1007/5584_2016_126
hospitalized and fatal pulmonary embolism. Thromb Res. 2012;130:178– 70. Galanaud JP, Monreal M, Kahn SR. Epidemiology of the post-
182. doi: 10.1016/j.thromres.2012.02.002 thrombotic syndrome. Thromb Res. 2018;164:100–109. doi:
49. Zöller B, Ohlsson H, Sundquist J, Sundquist K. Familial risk of venous 10.1016/j.thromres.2017.07.026
thromboembolism in first-, second- and third-degree relatives: a nation- 71. Rabinovich A, Kahn SR. The postthrombotic syndrome: current evidence
wide family study in Sweden. Thromb Haemost. 2013;109:458–463. doi: and future challenges. J Thromb Haemost. 2017;15:230–241. doi:
10.1160/TH12-10-0743 10.1111/jth.13569
50. Kujovich JL. Factor V Leiden thrombophilia. In: Adam MP, Ardinger 72. Slonková V, Slonková V Jr, Vašků A, Vašků V. Genetic predisposition for
HH, Pagon RA, Wallace SE, eds. GeneReviews [Internet]. Seattle, WA: chronic venous insufficiency in several genes for matrix metalloprotein-
University of Washington; 1993. ases (MMP-2, MMP-9, MMP-12) and their inhibitor TIMP-2. J Eur Acad
51. Morange PE, Suchon P, Trégouët DA. Genetics of venous throm- Dermatol Venereol. 2017;31:1746–1752. doi: 10.1111/jdv.14447
bosis: update in 2015. Thromb Haemost. 2015;114:910–919. doi: 73. Anwar MA, Georgiadis KA, Shalhoub J, Lim CS, Gohel MS, Davies
10.1160/TH15-05-0410 AH. A review of familial, genetic, and congenital aspects of primary
52. Klarin D, Emdin CA, Natarajan P, Conrad MF; and the INVENT varicose vein disease. Circ Cardiovasc Genet. 2012;5:460–466. doi:
Consortium, Kathiresan S. Genetic analysis of venous thromboembo- 10.1161/CIRCGENETICS.112.963439
lism in UK Biobank identifies the ZFPM2 locus and implicates obesity 74. George MG, Schieb LJ, Ayala C, Talwalkar A, Levant S. Pulmonary hyper-
as a causal risk factor. Circ Cardiovasc Genet. 2017;10:e001643. doi: tension surveillance: United States, 2001 to 2010. Chest. 2014;146:476–
10.1161/CIRCGENETICS.116.001643 495. doi: 10.1378/chest.14-0527
53. de Haan HG, Bezemer ID, Doggen CJ, Le Cessie S, Reitsma PH, Arellano 75. Strange G, Playford D, Stewart S, Deague JA, Nelson H, Kent A,
AR, Tong CH, Devlin JJ, Bare LA, Rosendaal FR, Vossen CY. Multiple Gabbay E. Pulmonary hypertension: prevalence and mortality in the
SNP testing improves risk prediction of first venous thrombosis. Blood. Armadale echocardiography cohort. Heart. 2012;98:1805–1811. doi:
2012;120:656–663. doi: 10.1182/blood-2011-12-397752 10.1136/heartjnl-2012-301992
54. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, 76. Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K,
Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran Jing ZC, Gibbs JS. A global view of pulmonary hypertension. Lancet Respir
versus warfarin in the treatment of acute venous thromboembolism. N Med. 2016;4:306–322. doi: 10.1016/S2213-2600(15)00543-3
Engl J Med. 2009;361:2342–2352. doi: 10.1056/NEJMoa0906598 77. Gall H, Hoeper MM, Richter MJ, Cacheris W, Hinzmann B, Mayer E. An
55. EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous epidemiological analysis of the burden of chronic thromboembolic pul-
thromboembolism. N Engl J Med. 2010;363:2499–2510. doi: monary hypertension in the USA, Europe and Japan. Eur Respir Rev.
10.1056/NEJMoa1007903 2017;26:160121. doi: 10.1183/16000617.0121-2016

e424 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 22

78. Derchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, Quarta sickle cell disease. Am J Respir Crit Care Med. 2013;187:840–847. doi:

CLINICAL STATEMENTS
A, Casu G, Perrotta S, Pinto V, Musallam KM, Forni GL; on behalf 10.1164/rccm.201207-1222OC

AND GUIDELINES
of the Webthal Pulmonary Arterial Hypertension Group. Prevalence 85. Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D’Armini AM, Snijder R,
and risk factors for pulmonary arterial hypertension in a large Bresser P, Torbicki A, Mellemkjaer S, Lewczuk J, Simkova I, Barberà JA,
group of β-thalassemia patients using right heart catheterization: de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA,
a Webthal study. Circulation. 2014;129:338–345. doi: 10.1161/ Kovacs G, Jaïs X, Ambroz D, Treacy C, Morsolini M, Jenkins D, Lindner
CIRCULATIONAHA.113.002124 J, Dartevelle P, Mayer E, Simonneau G. Long-term outcome of patients
79. Farber HW, Miller DP, Poms AD, Badesch DB, Frost AE, Muros-Le Rouzic E, with chronic thromboembolic pulmonary hypertension: results from an
Romero AJ, Benton WW, Elliott CG, McGoon MD, Benza RL. Five-year out- international prospective registry. Circulation. 2016;133:859–871. doi:
comes of patients enrolled in the REVEAL Registry. Chest. 2015;148:1043– 10.1161/CIRCULATIONAHA.115.016522
1054. doi: 10.1378/chest.15-0300 86. Klok FA, Dzikowska-Diduch O, Kostrubiec M, Vliegen HW, Pruszczyk P,
80. Farber HW, Miller DP, McGoon MD, Frost AE, Benton WW, Benza RL. Hasenfuß G, Huisman MV, Konstantinides S, Lankeit M. Derivation of a
Predicting outcomes in pulmonary arterial hypertension based on the clinical prediction score for chronic thromboembolic pulmonary hyperten-
6-minute walk distance. J Heart Lung Transplant. 2015;34:362–368. doi: sion after acute pulmonary embolism. J Thromb Haemost. 2016;14:121–
10.1016/j.healun.2014.08.020 128. doi: 10.1111/jth.13175
81. Gall H, Felix JF, Schneck FK, Milger K, Sommer N, Voswinckel R, Franco 87. Barros A, Baptista R, Nogueira A, Jorge E, Teixeira R, Castro G, Monteiro P,
OH, Hofman A, Schermuly RT, Weissmann N, Grimminger F, Seeger Providência LA. Predictors of pulmonary hypertension after intermediate-
W, Ghofrani HA. The Giessen Pulmonary Hypertension Registry: sur- to-high risk pulmonary embolism. Rev Port Cardiol. 2013;32:857–864.
vival in pulmonary hypertension subgroups. J Heart Lung Transplant. doi: 10.1016/j.repc.2013.02.008
2017;36:957–967. doi: 10.1016/j.healun.2017.02.016 88. Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin
82. Kempny A, Hjortshøj CS, Gu H, Li W, Opotowsky AR, Landzberg MJ, VV, Peacock AJ, Simonneau G, Vachiery JL, Grünig E, Oudiz RJ, Vonk-
Jensen AS, Søndergaard L, Estensen ME, Thilén U, Budts W, Mulder Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J,
BJ, Blok I, Tomkiewicz-Pająk L, Szostek K, D’Alto M, Scognamiglio G, Rubin LJ; AMBITION Investigators. Initial use of ambrisentan plus tadalafil
Prokšelj K, Diller GP, Dimopoulos K, Wort SJ, Gatzoulis MA. Predictors in pulmonary arterial hypertension. N Engl J Med. 2015;373:834–844.
of death in contemporary adult patients with Eisenmenger syn- doi: 10.1056/NEJMoa1413687
drome: a multicenter study. Circulation. 2017;135:1432–1440. doi: 89. Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galiè N, Ghofrani HA,
10.1161/CIRCULATIONAHA.116.023033 Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho
83. Weatherald J, Boucly A, Chemla D, Savale L, Peng M, Jevnikar M, Jaïs I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV; GRIPHON
X, Taniguchi Y, O’Connell C, Parent F, Sattler C, Hervé P, Simonneau Investigators. Selexipag for the treatment of pulmonary arterial hyperten-
G, Montani D, Humbert M, Adir Y, Sitbon O. Prognostic value of sion. N Engl J Med. 2015;373:2522–2533. doi: 10.1056/NEJMoa1503184
follow-up hemodynamic variables after initial management in pul- 90. Pulido T, Adzerikho I, Channick RN, Delcroix M, Galiè N, Ghofrani HA,
monary arterial hypertension. Circulation. 2018;137:693–704. doi: Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L,
10.1161/CIRCULATIONAHA.117.029254 Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau
84. Mehari A, Alam S, Tian X, Cuttica MJ, Barnett CF, Miles G, Xu D, Seamon G; SERAPHIN Investigators. Macitentan and morbidity and mortality in
C, Adams-Graves P, Castro OL, Minniti CP, Sachdev V, Taylor JG 6th, Kato pulmonary arterial hypertension. N Engl J Med. 2013;369:809–818. doi:
GJ, Machado RF. Hemodynamic predictors of mortality in adults with 10.1056/NEJMoa1213917
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e425

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

23. PERIPHERAL ARTERY DISEASE AND results with ABI), in 2000, PAD was estimated
CLINICAL STATEMENTS

to affect ≈8.5 million Americans aged ≥40 years

AORTIC DISEASES
AND GUIDELINES

(7.2%).2
ICD-9 440.20 to 440.24, 440.30 to 440.32, 440.4, • Estimates of PAD prevalence in males and females
440.9, 443.9, 445.02; ICD-10 I70.2, I70.9, I73.9, by age and ethnicity are shown in Charts 23-1
I74.3, I74.4. See Tables 23-1 through 23-3 and and 23-2.2
Charts 23-1 through 23-9 • The highest prevalence of low ABI (<0.9) has been
observed among older adults (22.7% among
Click here to return to the Table of Contents individuals aged ≥80 years versus 1.6% among
those aged 40–49 years) and NH blacks (≈11.6%
Peripheral Artery Disease in NH blacks versus ≈5.5% in whites).2 The preva-
Prevalence and Incidence lence of low ABI (<0.9) is similar between females
(See Table 23-1 and Charts 23-1 and 23-2) (5.9%) and males (5.0%).
• On the basis of data from several US cohorts dur- • Only ≈10% of people with PAD have the clas-
ing the 1970s to 2000s and the 2000 US Census, sic symptom of intermittent claudication.
6.5 million Americans aged ≥40 years (5.5%) are Approximately 40% do not complain of leg pain,
estimated to have low ABI (<0.9).1 Of these, one- whereas the remaining 50% have a variety of
fourth have severe PAD (ABI <0.7).1 leg symptoms different from classic claudication
• Further accounting for PAD cases with ABI (ie, exertional pain that either did not stop the
>0.9 (after revascularization or false-negative individual from walking or did stop the individual
from walking but did not involve the calves or did
Abbreviations Used in Chapter 23 not resolve within 10 minutes of rest).3,4
AAA abdominal aortic aneurysm • On the basis of ICD codes in nationwide claims
ABI ankle-brachial index data from large employers’ health plans and
ACC American College of Cardiology from Medicare and Medicaid programs between
AHA American Heart Association 2003 and 2008, among adults aged >40 years,
Amer. American
the annual incidence and prevalence of PAD
CHD coronary heart disease
CI confidence interval were 2.69% and 12.02%, respectively.5 The cor-
Downloaded from http://ahajournals.org by on February 7, 2019

CKD chronic kidney disease responding estimates for critical limb ischemia,
CORAL Cardiovascular Outcomes in Renal Atherosclerotic Lesions the most severe form of PAD, were 0.35% and
CVD cardiovascular disease 1.33%, respectively.
DM diabetes mellitus
• Data from the NIS demonstrate that admission
ED emergency department
GBD Global Burden of Disease
rates because of critical limb ischemia remained
GWAS genome-wide association study constant from 2003 to 2011.6
HCUP Healthcare Cost and Utilization Project
HF heart failure
Mortality
HR hazard ratio (See Table 23-1 and Chart 23-3)
ICD International Classification of Diseases • In 2016, the overall any-mention age-adjusted
ICD-9 International Classification of Diseases, 9th Revision death rate for PAD was 14.8 per 100 000. Any-
ICD-10 International Classification of Diseases, 10th Revision mention death rates in males were 18.2 for NH
IRAD International Registry of Acute Aortic Dissection
whites, 22.8 for NH blacks, 7.6 for NH Asians or
JHS Jackson Heart Study
KD Kawasaki disease Pacific Islanders, 17.5 for NH American Indians or
LDL low-density lipoprotein Alaska Natives, and 14.1 for Hispanic males. In
MACE major adverse cardiovascular event females, rates were 12.5 for NH whites, 15.7 for
MI myocardial infarction NH blacks, 5.9 for NH Asians or Pacific Islanders,
NAMCS National Ambulatory Medical Care Survey
14.6 for NH American Indians or Alaska Natives,
NH non-Hispanic
NHAMCS National Hospital Ambulatory Medical Care Survey
and 10.0 for Hispanic females.7
NHLBI National Heart, Lung, and Blood Institute • In 2016, PAD was the underlying cause in 13 048
NIS Nationwide Inpatient Sample deaths. The number of any-mention deaths
OR odds ratio attributable to PAD was 56 923 in 2016 (NHLBI
OVER Open Versus Endovascular Repair
tabulation).7
PA physical activity
PAD peripheral artery disease
• A 2008 meta-analysis of 24 955 males and 23 339
RR relative risk females from 16 cohorts demonstrated a reverse-
SBP systolic blood pressure J-shaped association between ABI and mortality
SES socioeconomic status in which participants with an ABI of 1.11 to 1.40
SNP single-nucleotide polymorphism were at lowest risk for mortality (Chart 23-3). In

e426 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

males, low ABI (≤0.9) carried a 3-fold (RR, 3.33 was significant geographic variation in the rate

CLINICAL STATEMENTS
[95% CI, 2.74–4.06]) risk of all-cause death com- of lower-extremity amputation, from 8400 ampu-

AND GUIDELINES
pared with a normal ABI (1.11–1.40), and a simi- tations per 100 000 patients with PAD in the
lar risk was observed in females (RR, 2.71 [95% East South Central region to 5500 amputations
CI, 2.03–3.62]).8 A similar reverse-J-shaped asso- per 100 000 patients with PAD in the Mountain
ciation between ABI was observed for cardiovas- region. After adjustment for clustering at the
cular mortality. US Census Bureau level, geographic variation in
• In-hospital mortality was higher in females than lower-extremity amputations remained. Lower-
males, regardless of disease severity or procedure extremity amputation was performed more often
performed, even after adjustment for age and in the East South Central region (adjusted OR,
baseline comorbidities: 0.5% versus 0.2% after 1.152 [95% CI, 1.131–1.174]; P<0.001) and
percutaneous transluminal angioplasty or stent- West South Central region (adjusted OR, 1.115
ing for intermittent claudication; 1.0% versus [95% CI, 1.097–1.133]; P<0.001) and less often
0.7% after open surgery for intermittent clau- in the Middle Atlantic region (OR, 0.833 [95% CI,
dication; 2.3% versus 1.6% after percutaneous 0.820–0.847]; P<0.001) versus the South Atlantic
transluminal angioplasty or stenting for critical reference region.17
limb ischemia; and 2.7% versus 2.2% after open • Among 186  338 older Medicare PAD patients
surgery for critical limb ischemia (P<0.01 for all undergoing major lower-extremity amputation,
comparisons).9 mortality was found to be 48.3% at 1 year.18
• Progression of PAD as measured by a decline • A study of Medicare beneficiaries reported that
in ABI also carries prognostic value beyond sin- between 2006 and 2011, 39 339 required revas-
gle measurements.10 Among 508 patients (449 cularization for PAD, and the annual rate of
males) identified from 2 vascular laboratories in peripheral vascular intervention increased slightly
San Diego, CA, a decline in ABI of >0.15 within a from 401.4 to 419.6 per 100 000 people.19
10-year period was associated with a subsequent • People with PAD have impaired function and
increased risk of all-cause mortality (RR, 2.4 [95% quality of life, regardless of whether or not they
CI, 1.2–4.8]) and CVD mortality (RR, 2.8 [95% CI, report leg symptoms. Furthermore, patients with
1.3–6.0]) at 3 years’ follow-up.10 PAD, including those who are asymptomatic,
Downloaded from http://ahajournals.org by on February 7, 2019

• Among 400 patients with PAD confirmed with experience a significant decline in lower-extremity
digital subtraction angiography, aortoiliac (proxi- function over time.20–22 A few recent studies have
mal) disease was associated with an increased risk demonstrated that even individuals with low-nor-
of mortality or cardiovascular events compared mal ABI (0.91–0.99) have reduced physical func-
with infrailiac (distal) disease (adjusted HR, 3.28 tion compared with those with normal ABI.23
[95% CI, 1.87–5.75]).11 Compared with infrailiac • Among patients with established PAD, higher PA
PAD, aortoiliac PAD was associated with younger levels during daily life are associated with better
age, male sex, and smoking. overall survival rate, a lower risk of death because
of CVD, and slower rates of functional decline.24,25
Complications
In addition, better 6-minute walk performance
• PAD is a marker for systemic atherosclerotic dis-
and faster walking speed are associated with
ease, and thus, people with PAD are more likely
lower rates of all-cause mortality, cardiovascular
to have atherosclerosis in other vascular beds (eg,
mortality, and mobility loss.26,27
coronary, carotid, and renal arteries and abdomi-
nal aorta).12–15 Interventions
• Pooled data from 11 studies in 6 countries found • A 2011 systematic review evaluated lower-
that the pooled age-, sex-, risk factor–, and CVD- extremity aerobic exercise against usual care and
adjusted RRs in people with PAD (defined by ABI demonstrated a range of benefits, including the
<0.9) versus those without were 1.45 (95% CI, following28:
1.08–1.93) for CHD and 1.35 (95% CI, 1.10– — Increased time to claudication by 71 seconds
1.65) for stroke.16 (79%) to 918 seconds (422%)
• From 2000 to 2008, the overall rate of lower- — Increased distance before claudication by 15
extremity amputation decreased significantly, m (5.6%) to 232 m (200%)
from 7258 to 5790 per 100 000 Medicare ben- — Increased walking distance/time by 67% to
eficiaries with PAD. Patients with PAD who under- 101% after 40 minutes of walking 2 to 3
went major lower-extremity amputation were times per week
more likely to have DM (60.3% versus 35.7% • Observational studies have found that the risk of
with PAD without amputation; P<0.001). There death,29 MI,30 and amputation29 are substantially

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e427

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

greater in individuals with PAD who continue to stronger risk factor for PAD than for CHD.40 Age-
CLINICAL STATEMENTS

smoke than in those who have stopped smoking. and sex-adjusted OR for heavy smoking was 3.94
AND GUIDELINES

• The “2016 AHA/ACC Guideline on the for symptomatic PAD and 1.66 for CHD.40
Management of Patients With Lower Extremity • Among males in the Health Professionals
Peripheral Artery Disease” noted that several ran- Follow-up Study, smoking, type 2 DM, hyperten-
domized and observational studies demonstrated sion, and hypercholesterolemia accounted for
that statins reduced the risk of MACE and ampu- 75% (95% CI, 64%–87%) of risk associated with
tation among people with PAD.31 development of clinical PAD.41
• A meta-analysis of 42 trials demonstrated that • In a meta-analysis of 34 studies from high-
antiplatelet therapy reduces the odds of vascular income countries and low- to middle-income
events by 26% among patients with PAD.32,33 countries, respectively, important risk factors for
• A recent Danish trial in males aged 65 to 74 years PAD included cigarette smoking (OR, 2.72 versus
reported that screening of PAD (with ABI), AAA 1.42), DM (OR, 1.88 versus 1.47), hypertension
(with abdominal ultrasound), and hypertension (OR, 1.55 versus 1.36), and hypercholesterolemia
followed by optimal care resulted in 7% lower risk (OR, 1.19 versus 1.14).42
of 5-year mortality compared with no screening.34 • A study of 3.3 million people 40 to 99 years of
• Data from the US Department of Veterans Affairs age primarily self-referring for vascular screening
during 2013 to 2014 demonstrate that patients tests in the United States showed that risk fac-
with PAD alone receive optimal medical therapy tor burden was associated with increased preva-
less frequently than patients with CHD (including lence of PAD, and there was a graded association
those with concomitant PAD; statin use 59% ver- between the number of traditional risk factors
sus 72% and antiplatelet use 66% versus 84%, and the prevalence of PAD.43
respectively).35 • Other risk factors for PAD include sedentary life-
• In a study that randomized patients with PAD to 3 style, elevated inflammation markers, hyperten-
groups (optimal medical care, supervised exercise sion in pregnancy, and CKD.43–46
training, and iliac artery stent placement), super- • African Americans have a 37% higher amputa-
vised exercise resulted in superior treadmill walk- tion risk than whites (HR, 1.37 [95% CI, 1.30–
ing distance compared with stenting. Results in 1.45]). Lower SES is an independent predictor for
the exercise group and stent group were superior amputation (HR, 1.12 [95% CI, 1.06–1.17]).47
Downloaded from http://ahajournals.org by on February 7, 2019

to optimal medical care alone.36 • A secondary analysis of a randomized feeding

• In 2017, the Centers for Medicare & Medicaid trial showed reduced risk of incident PAD with
Services decided to cover supervised exercise the Mediterranean diet compared with a control
therapy (up to 36 sessions over 12 weeks) for eli- diet.48
gible symptomatic PAD patients with intermittent
Social Determinants
claudication.37
• In the JHS, the prevalence of PAD was higher
• Endovascular therapies for critical limb ischemia
among participants who did not graduate from
are being used with greater frequency in the
high school than among participants with an asso-
United States. From 2003 to 2011, there was a
ciate’s degree or higher.49
significant increase in endovascular treatment
of critical limb ischemia (from 5.1% to 11.0%), Awareness
which was accompanied by lower rates of in-hos- • A cross-sectional, population-based telephone
pital mortality and major amputation, as well as survey of >2500 adults ≥50 years of age, with
shorter length of stay.6 oversampling of blacks and Hispanics, found that
26% expressed familiarity with PAD in contrast
Hospital Discharges and Ambulatory Care Visits
to >65% for CHD, stroke, and HF. Of these, half
(See Table 23-1)
were not aware that DM and smoking increase
• Principal diagnosis discharges for PAD slightly
the risk of PAD. One in 4 knew that PAD is asso-
decreased from 2004 to 2014, with first-listed
ciated with increased risk of MI and stroke, and
discharges of 140 000 and 115 000, respectively
only 14% were aware that PAD could lead to
(NHLBI tabulation).
amputation. All knowledge domains were lower
• In 2015, there were 1 070 000 physician office vis-
in individuals with lower income and education
its and 22 000 ED visits with a primary diagnosis
levels.3
of PAD (NAMCS/NHAMCS, NHLBI tabulation).38,39
• In data concerning people aged ≥70 years or
Risk Factors those aged 50 to 69 years with a history of DM
• The risk factors for PAD are similar but not iden- or smoking, as well as their physicians, 83% of
tical to those for CHD. Cigarette smoking is a patients with a prior diagnosis of PAD were aware

e428 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

of the diagnosis, but only half of their physicians — PAD prevalence is high in Southern and sub-

CLINICAL STATEMENTS
had recognized the diagnosis.3 Saharan Africa, North America, and Western

AND GUIDELINES
and Northern Europe (Chart 23-6).
Genetics of PAD
• Atherosclerotic PAD is heritable, even indepen-
dent of risk factors for PAD which themselves are Aortic Diseases
heritable. ICD-9 440, 441, 444, and 447; ICD-10 I70,
• In the ethnically diverse San Diego Population I71, I74, I77, and I79.
Study, a family history of PAD was independently
associated with a 1.83-fold higher odds of PAD.50 Aortic Aneurysm and Acute Aortic Dissection
In the Swedish Twin Registry, the OR of PAD in a (See Charts 23-7 and 23-8)
monozygotic twin was 17.7 and 5.7 in dizygotic ICD-9 441; ICD-10 I71.
twins; estimated genetic effects accounted for Prevalence and Incidence
58% and nonshared environmental effects for • The prevalence of AAAs that are 2.9 to 4.9 cm
42% of the phenotypic variance between twins.51 in diameter ranges from 1.3% in males 45 to 54
The NHLBI Twin Study found that 48% of the years of age to 12.5% in males 75 to 84 years
variability in ABI with similar environmental risk of age. For females, the prevalence ranges from
factors could be attributed to additive genetic 0% in the youngest to 5.2% in the oldest age
effects.52 groups.58
• There are monogenic (mendelian) diseases that • A meta-analysis of 15 475 individuals from 18
result in PAD, including familial lipoprotein disor- studies on small AAAs (3.0–5.4 cm) demonstrated
ders such as chylomicronemia and familial hyper- that mean aneurysm growth rate was 2.21 mm
cholesterolemia, hyperhomocysteinemia, and per year and did not significantly vary by age and
pseudoxanthoma elasticum.53 sex. Growth rates were higher in smokers ver-
• GWASs have identified genetic loci associated sus former or never smokers (by 0.35 mm/y) and
with atherosclerotic PAD, including the CHD- lower in people with DM than in those without
associated chromosome 9p21 genetic locus, DM (by 0.51 mm/y).59
which has been shown to be associated with • A study from Olmsted County, MN,60 dem-
PAD, AAA, and intracranial aneurysm.54 Other onstrated annual age- and sex-adjusted inci-
Downloaded from http://ahajournals.org by on February 7, 2019

PAD-associated genetic loci found through dences per 100 000 people of 3.5 (95% CI,
2.2–4.9) for thoracic aortic aneurysm rupture
GWASs include SNPs in the cholinergic receptor
and 3.5 (95% CI, 2.4–4.6) for acute aortic
nicotinic α3 (CHRNA3), DAB2 interaction protein
dissection.
(DAB21P), and cytochrome B-245 α-chain (CYBA)
genes.55 Mortality
• GWASs have also identified genetic variants 2016: Mortality—9758. Any-mention mortality—
associated with inflammatory forms of PAD such 16 458.
as KD.56
Complications
Global Burden of PAD • Rates of rupture of small AAAs (3.0–5.4 cm in
(See Table 23-2 and Charts 23-4 through 23-6) diameter) range from 0.71 to 11.03 per 1000
• A systematic study of 34 studies reported that person-years, with higher rupture rates in smok-
globally, 202 million people were living with PAD, ers (pooled HR, 2.02 [95% CI, 1.33–3.06]) and
and during the preceding decade, the number of females (pooled HR, 3.76 [95% CI, 2.58–5.47];
people with PAD increased by 28.7% in low- to P<0.001).59
middle-income countries and by 13.1% in high- • There is a dose-response association between the
income countries (Chart 23-4).42 diameter and the minimum and maximum risk of
• Global mortality attributable to PAD and global AAA rupture per year (Chart 23-7).61
prevalence of PAD by sex from the GBD 2016 • A 2015 systematic review that included 4 random-
Study are shown in Table 23-2.57 ized trials of ultrasound screening demonstrated
• The GBD 2016 Study used statistical models and lower AAA-associated mortality, emergency
data on incidence, prevalence, case fatality, excess operations, and rupture with screening, but with
mortality, and cause-specific mortality to estimate higher AAA-associated elective repair rates; how-
disease burden for 315 diseases and injuries in ever, there was no effect on all-cause mortality
195 countries and territories.57 (Chart 23-8).62 Similar results were reported in
— PAD mortality is high in Russia and in Central a systematic review report prepared for the US
and Eastern Europe (Chart 23-5). Preventive Services Task Force63 and in a 2016

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e429

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

Swedish study evaluating a nationwide screening complications at 1 year than patients who under-
CLINICAL STATEMENTS

program targeting 65-year-old males.64 went endovascular repair.70 However, after 8 years
AND GUIDELINES

• Data from IRAD demonstrated that the rate of of follow-up, survival in the open repair group was
mesenteric malperfusion in 1809 patients with similar to that in the endovascular repair group. Of
type A acute dissections was 3.7%, with a higher note, individuals in the endovascular repair group
mortality rate than for patients without malperfu- had a higher rate of eventual aneurysm rupture
sion (63.2% versus 23.8%; P<0.001).65 (5.4%) than patients who underwent open repair
• Data from IRAD demonstrated that patients with (1.4%).71 Similar findings were observed in the
acute type B aortic dissection have heterogeneous OVER Veterans Affairs Cooperative trial, which
in-hospital outcomes. In-hospital mortality in compared open AAA repair to endovascular
patients with and without complications (such as repair in 881 patients and demonstrated reduc-
mesenteric ischemia, renal failure, limb ischemia, tions in mortality from endovascular repair at 2
or refractory pain) was 20.0% and 6.1%, respec- years (HR, 0.63 [95% CI, 0.40–0.98]) and 3 years
tively. In patients with complications, in-hospital (HR, 0.72 [95% CI, 0.51–1.00]).72 However, there
mortality associated with surgical and endovas- was no survival difference between open and
cular repair was 28.6% and 10.1% (P=0.006), endovascular repair in individuals followed up for
respectively.66 up to 9 years (mean, 5 years; HR, 0.97 [95% CI,
0.77–1.22]).72
Hospital Discharges
• In comparisons of the United States and the
• In 2014, there were 69 000 hospital discharges
United Kingdom, the United States demonstrated
with aortic aneurysm as principal diagnoses, of
a higher rate of AAA repair, smaller AAA diameter
which 50 000 were males and 19 000 were females
at the time of repair, and lower rates of AAA rup-
(HCUP, NHLBI tabulation).
ture and AAA-related death.73
Interventions • In ruptured AAAs, implementation of a contem-
• Results from 4 trials (N=3314 participants) evalu- porary endovascular-first protocol was associated
ating the effect of open or endovascular repair of with decreased perioperative morbidity and mor-
small AAAs (4.0–5.5 cm) did not demonstrate an tality, a higher likelihood of discharge to home,
advantage to earlier intervention compared with and improved long-term survival in a retrospective
analysis of 88 consecutive patients seen at an aca-
Downloaded from http://ahajournals.org by on February 7, 2019

routine ultrasound surveillance.67

• Data from 23 838 patients with ruptured AAAs demic medical center.74
collected through the NIS (2005–2010) demon- • Perioperative mortality of endovascular aneurysm
strated in-hospital mortality of 53.1% (95% CI, repair was not related to surgeon case volume
51.3%–54.9%), with 80.4% (95% CI, 79.0%– but was lower in hospitals with higher volume
81.9%) undergoing intervention for repair. Of (eg, 1.9% in hospitals with <10 cases a year ver-
individuals who underwent repair, 20.9% (95% sus 1.4% in those with 49–198 cases; P<0.01).
CI, 18.6%–23.2%) underwent endovascular Perioperative mortality after open repair was
repair, with a 26.8% (95% CI, 23.7%–30.0%) inversely related to both surgeon case volume
postintervention mortality rate, and 79.1% (95% (6.4% in ≤3 cases versus 3.8% in 14–62 cases;
CI, 76.8%–81.4%) underwent open repair, with P<0.01) and hospital case volume (6.3% in ≤5
a 45.6% (95% CI, 43.6%–47.5%) postinterven- cases vs 3.8% in 14–62 cases; P<0.01).75
tion mortality rate.68 • The data for surgery in thoracic aortic aneurysms
• Data from the NIS suggest that the use of endo- are more mixed between open and endovascular
vascular repair of AAAs rose substantially between repair. A sample of 12 573 and 2732 Medicare
2000 and 2010 (5% versus 74% of all AAA patients who underwent open thoracic aortic
repairs, respectively), whereas the overall num- aneurysm and endovascular repair from 1998 to
ber of AAAs (≈45 000 per year) remained stable. 2007 demonstrated higher perioperative mortality
In-hospital mortality and length of stay declined for open repair in both intact (7.1% versus 6.1%;
during this period, but costs rose.69 P=0.07) and ruptured (46% versus 28%; P<0.01)
• At least for the first 3 years after elective repair thoracic aortic aneurysms but higher 1-year (87%
of an AAA, individuals who have endovascular versus 82%; P=0.001) and 5-year (72% versus
repair may have better outcomes than those who 62%; P=0.001) survival rates.76 Perioperative
undergo open repair. After multivariable adjust- mortality rates for open thoracic aortic aneurysms
ment, Medicare patients who underwent open were higher for NH black Medicare patients than
AAA repair had a higher risk of all-cause mortal- for white Medicare patients (18% versus 10%;
ity (HR, 1.24 [95% CI, 1.05–1.47]), AAA-related P<0.001), but rates were similar for endovascu-
mortality (HR, 4.37 [95% CI, 2.51–7.66]), and lar repair (8% versus 9%; P=0.56).63 On the basis

e430 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

of data from the NIS (N=1400), weekend repair on chromosome 3p12.3 and SNPs in DAB2IP,

CLINICAL STATEMENTS
for thoracic aortic aneurysm rupture (N=322) was LDLR, LRP1, MMP3, TGFβR2, and SORT1.87,88

AND GUIDELINES
associated with higher mortality than weekday • A GWAS has also identified common genetic vari-
repair (N=1078; OR, 2.55 [95% CI, 1.77–3.68]), ants for intracranial aneurysms.89 In addition, rare
likely because of delays in surgical intervention.77 variants in ANGPTL6 are associated with increased
• Seventeen-year trends in the IRAD database risk of intracranial aneurysms.90
(1996–2013) demonstrate an increase in surgical • Despite the co-occurrence of different types of
repair of type A thoracic dissections (79%–90%) aneurysms, a meta-analysis has found no shared
and a significant decrease in in-hospital and sur- genetic variants for intracranial, thoracic, and aor-
gical mortality for type A dissections (31%–22% tic aneurysms.85
[P<0.001] and 25%–18% [P=0.003], respec- • Nonatherosclerotic forms of arterial disease such
tively). Type B dissections were more likely to be as fibromuscular dysplasia and spontaneous coro-
treated with endovascular therapies, but no sig- nary artery dissection are more difficult to evaluate
nificant changes in mortality were observed.78 for genetic components given their lesser preva-
lence and heterogeneous nature, but studies of
Risk Factors
these diseases are ongoing. A recent study has
• Many risk factors for atherosclerosis are also asso-
identified a noncoding SNP in the phosphatase
ciated with increased risk for AAAs.79 Of these,
and actin regulator 1 (PHACTR1) gene as being
smoking is the most important modifiable risk
associated with fibromuscular dysplasia.91
factor for AAAs.80
• A 2014 systematic review of 17 community-based Global Burden of Aortic Aneurysm
observational studies demonstrated a consistent, (See Table 23-3 and Chart 23-9)
inverse association between DM and prevalent • Global mortality attributable to and prevalence of
AAAs (OR, 0.80 [95% CI, 0.70–0.90]).81 aortic aneurysm by sex are shown in Table 23-3.57
• On the basis of nationally representative data • The GBD 2016 Study used statistical models and
from the United Kingdom, giant cell arteritis has data on incidence, prevalence, case fatality, excess
been demonstrated to be associated with a 2-fold mortality, and cause-specific mortality to estimate
higher risk (sub-HR, 1.92 [95% CI, 1.52–2.41]) disease burden for 315 diseases and injuries in
after adjustment for competing risks for devel- 195 countries and territories. The highest age-
Downloaded from http://ahajournals.org by on February 7, 2019

oping an AAA. These data also demonstrate an standardized mortality rates attributable to aortic
inverse association between DM and AAAs.82 aneurysm are estimated for Northern and Eastern
Europe, southern and tropical Latin America, and
Genetics Oceania (Chart 23-9).57
• Monogenic diseases that cause thoracic aortic dis-
ease include Marfan syndrome, Loeys-Dietz syn-
drome, vascular Ehlers-Danlos syndrome, arterial Atherosclerotic Renal Artery Stenosis
tortuosity syndrome, and familial thoracic aortic ICD-9 440.1; ICD-10 I70.1.
aneurysm disease. Mutations in the genes caus-
Prevalence and Incidence
ing these disorders significantly increase the risk
• A US community-based cohort of older adults
of developing vascular aneurysms. If these disor-
(≥65 years old) reported the prevalence of renal
ders are suspected, referral to a specialty clinic for
artery disease as 6.8%.92 Among those with renal
genetic testing can be useful for diagnosis, treat-
artery stenosis, 88% were unilateral and 12%
ment, and cascade screening in family members.
were bilateral.
• GWASs have identified genetic variants associ-
• A US study using Medicare data reported that
ated with nonfamilial forms of thoracic aortic
the incidence rate of renal artery stenosis was
aneurysm/dissection, including common variants
3.1 per 1000 patient-years.93 The incidence of
in the fibrillin gene (FBN1; rare mutations in this
renal artery stenosis increased by ≈5 fold from
gene cause Marfan syndrome) and variants in the
1992 to 2004.
LDL receptor protein–related 1 (LRP1) and unc-
51–like kinase 4 (ULK4) genes.83,84 Complications
• AAA is heritable; a family history of AAA is a • Atherosclerotic renal artery stenosis is often a
risk factor for AAA, particularly in male siblings cause of drug-resistant hypertension.94
of male patients, for whom the RR for AAA is as • An Irish study reported that among a total of
high as 18.85,86 3987 patients undergoing coronary angiography,
• GWASs and other studies have identified genetic the presence of renal artery stenosis conferred 2
variants associated with AAA, including a locus times higher mortality risk.95

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e431

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

Interventions there was no difference in the primary end point

CLINICAL STATEMENTS

• The CORAL study compared medical therapy alone of major cardiovascular or kidney event.96
AND GUIDELINES

versus medical therapy plus renal artery stenting

Risk Factors
in patients with atherosclerotic renal artery steno-
• Traditional atherosclerotic risk factors such as
sis and hypertension. Although there was a sig-
advanced age, DM, smoking, and hypertension
nificant difference in SBP favoring the stent group
are associated with higher prevalence of athero-
(−2.3 mm Hg [95% CI, −4.4 to −0.2 mm Hg]),
sclerotic renal artery stenosis.94

Table 23-1.  Peripheral Artery Disease

Mortality, 2016, All Hospital Discharges,

Population Group Prevalence, Age ≥40 y Ages* 2014, All Ages
Both sexes ≥6.8 Million 13 048 115 000

Males … 5888 (45.1%)† 69 000

Females … 7160 (54.9%)† 46 000
NH white males … 4689 …
NH white females … 5677 …
NH black males … 719 …
NH black females … 938 …
Hispanic males … 331 …
Hispanic females … 377 …
NH Asian or Pacific Islander males … 110‡ …
NH Asian or Pacific Islander females … 110‡ …
NH American Indian/Alaska Native … 70 …

Ellipses (…) indicate data not available; and NH, non-Hispanic.

Downloaded from http://ahajournals.org by on February 7, 2019

*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted
with caution because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses,
surveys, and birth certificates. Studies have shown underreporting on death certificates of American Indian or Alaska Native,
Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total mortality attributable to peripheral artery disease that is for males vs
females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific Islander.
Sources: Prevalence: Data derived from Allison et al.2 Prevalence of peripheral artery disease is based on an ankle-brachial
index <0.9 or a previous revascularization for peripheral artery disease. Mortality: Centers for Disease Control and Prevention/
National Center for Health Statistics, 2015 Mortality Multiple Cause-of-Death–United States.

Table 23-2.   Global Mortality From and Prevalence of PAD by Sex

Both Sexes Combined Males Females

Death Prevalence Death Prevalence Death Prevalence
Total number (millions) 0.1 120.1 0.02 50.6 0.03 69.5
(0.0 to 0.1) (105.6 to 137.7) (0.02 to 0.04) (44.4 to 58.3) (0.02 to 0.06) (61.3 to 79.7)
Percent change total 128.6 82.2 109.3 91.2 148.5 76.2
number, 1990 to 2016 (92.1 to 173.3) (80.3 to 84.2) (84.5 to 167.4) (88.8 to 93.7) (61.9 to 199.6) (74.2 to 78.3)
Percent change total 37.4 30.0 33.9 31.8 40.5 28.8
number, 2006 to 2016 (26.0 to 51.3) (29.0 to 31.0) (21.7 to 49.5) (30.6 to 33.0) (22.7 to 59.0) (27.7 to 29.9)
Rate per 100 000 1.0 1805.2 1.1 1,657.6 0.9 1,929.8
(0.8 to 1.5) (1588.5 to 2063.9) (0.9 to 1.6) (1456.5 to 1899.6) (0.5 to 1.6) (1702.0 to 2202.2)
Percent change rate, 1990 2.0 −8.0 −7.2 −6.5 8.9 −8.4
to 2016 (−16.0 to 19.6) (−8.8 to −7.2) (−18.6 to 16.0) (−7.5 to −5.6) (−29.7 to 30.4) (−9.3 to −7.5)
Percent change rate, 2006 −2.6 −1.6 −4.7 −1.3 −0.8 −1.6
to 2016 (−10.5 to 6.9) (−2.3 to −0.9) (−12.7 to 5.4) (−2.2 to −0.5) (−13.6 to 12.0) (−2.3 to −0.9)

PAD indicates peripheral artery disease.

e432 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

Table 23-3.  Global Mortality From and Prevalence of Aortic Aneurysm by Sex

CLINICAL STATEMENTS
Both sexes Males Females

AND GUIDELINES
Total number (millions) 0.2 (0.2 to 0.2) 0.1 (0.1 to 0.1) 0.1 (0.1 to 0.1)
Percent change total number, 1990 to 2016 61.7 (54.5 to 70.1) 55.3 (46.9 to 66.4) 73.4 (60.6 to 82.6)
Percent change total number, 2006 to 2016 20.5 (17.0 to 24.9) 18.3 (13.3 to 24.8) 24.4 (18.3 to 30.2)
Rate per 100 000 2.6 (2.6 to 2.7) 3.8 (3.6 to 3.9) 1.7 (1.7 to 1.8)
Percent change rate, 1990 to 2016 −20.5 (−23.7 to −16.7) −26.2 (−29.9 to −21.6) −15.0 (−20.9 to −10.7)
Percent change rate, 2006 to 2016 −10.1 (−12.6 to −7.0) −13.0 (−16.4 to −8.4) −7.4 (−11.9 to −3.2)
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 23-1. Estimates of prevalence of peripheral artery disease in males by age and ethnicity.
Amer. indicates American; and NH, non-Hispanic.
Data derived from Allison et al.2

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e433

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23
CLINICAL STATEMENTS
AND GUIDELINES

Chart 23-2. Estimates of prevalence of peripheral artery disease in females by age and ethnicity.
Amer. indicates American; and NH, non-Hispanic.
Data derived from Allison et al.2
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 23-3. Hazard ratios of cardiovascular mortality with 95% CI by ankle-brachial index categories.
Data derived from Fowkes et al.8

e434 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

CLINICAL STATEMENTS
AND GUIDELINES
Chart 23-4. Prevalence of peripheral artery disease by age in males and females in high-income countries and low-income or middle-income
countries.
Adapted from The Lancet (Fowkes et al42), with permission from Elsevier. Copyright © 2013, Elsevier Ltd.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 23-5. Age-standardized mortality rates of peripheral artery disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.57 Printed with permission. Copyright ©
2017 University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e435

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23
CLINICAL STATEMENTS
AND GUIDELINES

Chart 23-6. Age-standardized prevalence of peripheral artery disease per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.57 Printed with permission. Copyright ©
Downloaded from http://ahajournals.org by on February 7, 2019

2017, University of Washington.

Chart 23-7. Association between diameter and minimum and maximum risk of abdominal aortic aneurysm rupture per year.
Data derived from Brewster et al.61

e436 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

CLINICAL STATEMENTS
AND GUIDELINES
Chart 23-8. Numbers needed to screen to avoid an AAA-associated death and a ruptured AAA.
AAA indicates abdominal aortic aneurysm.
Data derived from Eckstein et al.62
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 23-9. Age-standardized mortality rates of aortic aneurysm per 100 000, both sexes, 2016.
Country codes: ATG, Antigua and Barbuda; BRB, Barbados; COM, Comoros; DMA, Dominica; E Med., Eastern Mediterranean; FJI, Fiji; FSM, Micronesia, Federated
States of; GRD, Grenada; KIR, Kiribati; LCA, Saint Lucia; MDV, Maldives; MHL, Marshall Islands; MLT, Malta; MUS, Mauritius; SGP, Singapore; SLB, Solomon Islands; SYC,
Seychelles; TLS, Timor-Leste; TON, Tonga; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines; VUT, Vanuatu; W Africa, West Africa; and WSM, Samoa.
Data derived from Global Burden of Disease Study 2016, Institute for Health Metrics and Evaluation, University of Washington.57 Printed with permission. Copyright ©
2017, University of Washington.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e437

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

REFERENCES 19. Jones WS, Mi X, Qualls LG, Vemulapalli S, Peterson ED, Patel MR, Curtis
CLINICAL STATEMENTS

LH. Trends in settings for peripheral vascular intervention and the effect of
1. Centers for Disease Control and Prevention (CDC). Lower extremity dis-
AND GUIDELINES

changes in the outpatient prospective payment system. J Am Coll Cardiol.

ease among persons aged ≥40 years with and without diabetes: United 2015;65:920–927. doi: 10.1016/j.jacc.2014.12.048
States, 1999−2002. MMWR Morb Mortal Wkly Rep. 2005;54:1158–1160. 20. McDermott MM, Greenland P, Liu K, Guralnik JM, Celic L, Criqui MH,
2. Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz Chan C, Martin GJ, Schneider J, Pearce WH, Taylor LM, Clark E. The ankle
RR, Criqui MH. Ethnic-specific prevalence of peripheral arterial dis- brachial index is associated with leg function and physical activity: the
ease in the United States. Am J Prev Med. 2007;32:328–333. doi: Walking and Leg Circulation Study. Ann Intern Med. 2002;136:873–883.
10.1016/j.amepre.2006.12.010 21. McDermott MM, Liu K, Greenland P, Guralnik JM, Criqui MH, Chan C,
3. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Pearce WH, Schneider JR, Ferrucci L, Celic L, Taylor LM, Vonesh E, Martin
Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott GJ, Clark E. Functional decline in peripheral arterial disease: associations
MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treat- with the ankle brachial index and leg symptoms. JAMA. 2004;292:453–
ment in primary care. JAMA. 2001;286:1317–1324. 461. doi: 10.1001/jama.292.4.453
4. McDermott MM, Greenland P, Liu K, Guralnik JM, Criqui MH, Dolan NC, 22. McDermott MM, Guralnik JM, Tian L, Liu K, Ferrucci L, Liao Y, Sharma L,
Chan C, Celic L, Pearce WH, Schneider JR, Sharma L, Clark E, Gibson D, Criqui MH. Associations of borderline and low normal ankle-brachial index
Martin GJ. Leg symptoms in peripheral arterial disease: associated clinical values with functional decline at 5-year follow-up: the WALCS (Walking
characteristics and functional impairment. JAMA. 2001;286:1599–1606. and Leg Circulation Study). J Am Coll Cardiol. 2009;53:1056–1062. doi:
5. Nehler MR, Duval S, Diao L, Annex BH, Hiatt WR, Rogers K, Zakharyan A, 10.1016/j.jacc.2008.09.063
Hirsch AT. Epidemiology of peripheral arterial disease and critical limb isch- 23. McDermott MM, Applegate WB, Bonds DE, Buford TW, Church T, Espeland
emia in an insured national population. J Vasc Surg. 2014;60:686–695.e2. MA, Gill TM, Guralnik JM, Haskell W, Lovato LC, Pahor M, Pepine CJ, Reid
doi: 10.1016/j.jvs.2014.03.290 KF, Newman A. Ankle brachial index values, leg symptoms, and functional
6. Agarwal S, Sud K, Shishehbor MH. Nationwide trends of hospital admis- performance among community-dwelling older men and women in the
sion and outcomes among critical limb ischemia patients: from 2003-2011. lifestyle interventions and independence for elders study. J Am Heart
J Am Coll Cardiol. 2016;67:1901–1913. doi: 10.1016/j.jacc.2016.02.040 Assoc. 2013;2:e000257. doi: 10.1161/JAHA.113.000257
7. National Center for Health Statistics. Centers for Disease Control and 24. Garg PK, Liu K, Tian L, Guralnik JM, Ferrucci L, Criqui MH, Tan J,
Prevention website. National Vital Statistics System: public use data file McDermott MM. Physical activity during daily life and functional decline
documentation: mortality multiple cause-of-death micro-data files, 2016. in peripheral arterial disease. Circulation. 2009;119:251–260. doi:
https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed 10.1161/CIRCULATIONAHA.108.791491
May 21, 2018. 25. Garg PK, Tian L, Criqui MH, Liu K, Ferrucci L, Guralnik JM, Tan J,
8. Ankle Brachial Index Collaboration. Ankle brachial index combined with McDermott MM. Physical activity during daily life and mortality in patients
Framingham Risk Score to predict cardiovascular events and mortality: a with peripheral arterial disease. Circulation. 2006;114:242–248. doi:
meta-analysis. JAMA. 2008;300:197–208. doi: 10.1001/jama.300.2.197 10.1161/CIRCULATIONAHA.105.605246
9. Lo RC, Bensley RP, Dahlberg SE, Matyal R, Hamdan AD, Wyers M, Chaikof 26. McDermott MM, Guralnik JM, Tian L, Ferrucci L, Liu K, Liao Y, Criqui MH.
EL, Schermerhorn ML. Presentation, treatment, and outcome differences Baseline functional performance predicts the rate of mobility loss in per-
between men and women undergoing revascularization or amputation sons with peripheral arterial disease. J Am Coll Cardiol. 2007;50:974–982.
for lower extremity peripheral arterial disease. J Vasc Surg. 2014;59:409– doi: 10.1016/j.jacc.2007.05.030
418.e3. doi: 10.1016/j.jvs.2013.07.114 27. McDermott MM, Tian L, Liu K, Guralnik JM, Ferrucci L, Tan J, Pearce WH,
10. Criqui MH, Ninomiya JK, Wingard DL, Ji M, Fronek A. Progression of periph-
Downloaded from http://ahajournals.org by on February 7, 2019

Schneider JR, Criqui MH. Prognostic value of functional performance for

eral arterial disease predicts cardiovascular disease morbidity and mortality. mortality in patients with peripheral artery disease. J Am Coll Cardiol.
J Am Coll Cardiol. 2008;52:1736–1742. doi: 10.1016/j.jacc.2008.07.060 2008;51:1482–1489. doi: 10.1016/j.jacc.2007.12.034
11. Aboyans V, Desormais I, Lacroix P, Salazar J, Criqui MH, Laskar M. The gen- 28. Parmenter BJ, Raymond J, Dinnen P, Singh MA. A systematic review of
eral prognosis of patients with peripheral arterial disease differs accord- randomized controlled trials: walking versus alternative exercise pre-
ing to the disease localization. J Am Coll Cardiol. 2010;55:898–903. doi: scription as treatment for intermittent claudication. Atherosclerosis.
10.1016/j.jacc.2009.09.055 2011;218:1–12. doi: 10.1016/j.atherosclerosis.2011.04.024
12. Barba A, Estallo L, Rodríguez L, Baquer M, Vega de Céniga M. Detection of 29. Armstrong EJ, Wu J, Singh GD, Dawson DL, Pevec WC, Amsterdam
abdominal aortic aneurysm in patients with peripheral artery disease. Eur J EA, Laird JR. Smoking cessation is associated with decreased mortality
Vasc Endovasc Surg. 2005;30:504–508. doi: 10.1016/j.ejvs.2005.05.011 and improved amputation-free survival among patients with symptom-
13. Kurvers HA, van der Graaf Y, Blankensteijn JD, Visseren FL, Eikelboom atic peripheral artery disease. J Vasc Surg. 2014;60:1565–1571. doi:
B; SMART Study Group. Screening for asymptomatic internal carotid 10.1016/j.jvs.2014.08.064
artery stenosis and aneurysm of the abdominal aorta: comparing the yield 30. Jonason T, Bergström R. Cessation of smoking in patients with intermit-
between patients with manifest atherosclerosis and patients with risk fac- tent claudication: effects on the risk of peripheral vascular complica-
tors for atherosclerosis only. J Vasc Surg. 2003;37:1226–1233. tions, myocardial infarction and mortality. Acta Med Scand. 1987;221:
14. Lee JY, Lee SW, Lee WS, Han S, Park YK, Kwon CH, Jang JY, Cho YR, 253–260.
Park GM, Ahn JM, Kim WJ, Park DW, Kang SJ, Kim YH, Lee CW, Park 31. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA,
SW, Park SJ. Prevalence and clinical implications of newly revealed, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein
asymptomatic abnormal ankle-brachial index in patients with significant R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A,
coronary artery disease. JACC Cardiovasc Interv. 2013;6:1303–1313. doi: Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC
10.1016/j.jcin.2013.08.008 guideline on the management of patients with lower extremity peripheral
15. Leertouwer TC, Pattynama PM, van den Berg-Huysmans A. Incidental renal artery disease: a report of the American College of Cardiology/American
artery stenosis in peripheral vascular disease: a case for treatment? Kidney Heart Association Task Force on Clinical Practice Guidelines. Circulation.
Int. 2001;59:1480–1483. doi: 10.1046/j.1523-1755.2001.0590041480.x 2017;135:e726–e779. doi: 10.1161/CIR.0000000000000471
16. Heald CL, Fowkes FG, Murray GD, Price JF; Ankle Brachial Index 32. Ramos R, García-Gil M, Comas-Cufí M, Quesada M, Marrugat J, Elosua R,
Collaboration. Risk of mortality and cardiovascular disease associ- Sala J, Grau M, Martí R, Ponjoan A, Alves-Cabratosa L, Blanch J, Bolíbar
ated with the ankle-brachial index: systematic review. Atherosclerosis. B. Statins for prevention of cardiovascular events in a low-risk population
2006;189:61–69. doi: 10.1016/j.atherosclerosis.2006.03.011 with low ankle brachial index. J Am Coll Cardiol. 2016;67:630–640. doi:
17. Jones WS, Patel MR, Dai D, Subherwal S, Stafford J, Calhoun S, Peterson 10.1016/j.jacc.2015.11.052
ED. Temporal trends and geographic variation of lower-extremity 33. Westin GG, Armstrong EJ, Bang H, Yeo KK, Anderson D, Dawson DL,
amputation in patients with peripheral artery disease: results from U.S. Pevec WC, Amsterdam EA, Laird JR. Association between statin medica-
Medicare 2000-2008. J Am Coll Cardiol. 2012;60:2230–2236. doi: tions and mortality, major adverse cardiovascular event, and amputation-
10.1016/j.jacc.2012.08.983 free survival in patients with critical limb ischemia. J Am Coll Cardiol.
18. Jones WS, Patel MR, Dai D, Vemulapalli S, Subherwal S, Stafford J, 2014;63:682–690. doi: 10.1016/j.jacc.2013.09.073
Peterson ED. High mortality risks after major lower extremity amputa- 34. Lindholt JS, Søgaard R. Population screening and intervention for vascu-
tion in Medicare patients with peripheral artery disease. Am Heart J. lar disease in Danish men (VIVA): a randomised controlled trial. Lancet.
2013;165:809–815, 815.e1. doi: 10.1016/j.ahj.2012.12.002 2017;390:2256–2265. doi: 10.1016/S0140-6736(17)32250-X

e438 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

35. Hira RS, Cowart JB, Akeroyd JM, Ramsey DJ, Pokharel Y, Nambi V, Jneid 51. Wahlgren CM, Magnusson PK. Genetic influences on peripheral arterial

CLINICAL STATEMENTS
H, Deswal A, Denktas A, Taylor A, Nasir K, Ballantyne CM, Petersen LA, disease in a twin population. Arterioscler Thromb Vasc Biol. 2011;31:678–

AND GUIDELINES
Virani SS. Risk factor optimization and guideline-directed medical therapy 682. doi: 10.1161/ATVBAHA.110.210385
in US veterans with peripheral arterial and ischemic cerebrovascular dis- 52. Carmelli D, Fabsitz RR, Swan GE, Reed T, Miller B, Wolf PA. Contribution
ease compared to veterans with coronary heart disease. Am J Cardiol. of genetic and environmental influences to ankle-brachial blood pressure
2016;118:1144–1149. doi: 10.1016/j.amjcard.2016.07.027 index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute.
36. Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds Am J Epidemiol. 2000;151:452–458.
MR, Massaro JM, Lewis BA, Cerezo J, Oldenburg NC, Thum CC, Goldberg 53. Kullo IJ, Leeper NJ. The genetic basis of peripheral arterial disease: current
S, Jaff MR, Steffes MW, Comerota AJ, Ehrman J, Treat-Jacobson D, knowledge, challenges, and future directions. Circ Res. 2015;116:1551–
Walsh ME, Collins T, Badenhop DT, Bronas U, Hirsch AT; for the CLEVER 1560. doi: 10.1161/CIRCRESAHA.116.303518
Study Investigators. Supervised exercise versus primary stenting for 54. Helgadottir A, Thorleifsson G, Magnusson KP, Grétarsdottir S,
claudication resulting from aortoiliac peripheral artery disease: six- Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD,
month outcomes from the Claudication: Exercise Versus Endoluminal Ronkainen A, Jääskeläinen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas
Revascularization (CLEVER) study. Circulation. 2012;125:130–139. doi: K, Gottsäter A, Flex A, Stefansson H, Hansen T, Andersen G, Weinsheimer
10.1161/CIRCULATIONAHA.111.075770 S, Borch-Johnsen K, Jorgensen T, Shah SH, Quyyumi AA, Granger CB,
37. Decision memo for supervised exercise therapy (SET) for symptomatic Reilly MP, Austin H, Levey AI, Vaccarino V, Palsdottir E, Walters GB,
peripheral artery disease. May 25, 2017. Centers for Disease Control and Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell
Prevention website. https://www.cms.gov/medicare-coverage-database/ RE, Sveinbjornsdottir S, Hernesniemi J, Niemelä M, Limet R, Andersen
details/nca-decision-memo.aspx?NCAId=287. Accessed September 10, K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE,
2018 Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson
38. Centers for Disease Control and Prevention website. National Ambulatory EM, Magnadottir HB, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van
Medical Care Survey: 2015 State and National Summary Tables. https:// Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson
www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_ G, Kong A, Thorsteinsdottir U, Stefansson K. The same sequence vari-
tables.pdf. Accessed June 14, 2018. ant on 9p21 associates with myocardial infarction, abdominal aortic
39. Centers for Disease Control and Prevention website. National Hospital aneurysm and intracranial aneurysm. Nat Genet. 2008;40:217–224. doi:
Ambulatory Medical Care Survey: 2015 Emergency Department Summary 10.1038/ng.72
Tables. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2015_ed_ 55. Murabito JM, White CC, Kavousi M, Sun YV, Feitosa MF, Nambi V, Lamina
web_tables.pdf. Accessed June 14, 2018. C, Schillert A, Coassin S, Bis JC, Broer L, Crawford DC, Franceschini N,
40. Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GD, Fowkes FG. Relationship Frikke-Schmidt R, Haun M, Holewijn S, Huffman JE, Hwang SJ, Kiechl
between smoking and cardiovascular risk factors in the development of S, Kollerits B, Montasser ME, Nolte IM, Rudock ME, Senft A, Teumer A,
peripheral arterial disease and coronary artery disease: Edinburgh Artery van der Harst P, Vitart V, Waite LL, Wood AR, Wassel CL, Absher DM,
Study. Eur Heart J. 1999;20:344–353. Allison MA, Amin N, Arnold A, Asselbergs FW, Aulchenko Y, Bandinelli S,
41. Joosten MM, Pai JK, Bertoia ML, Rimm EB, Spiegelman D, Mittleman MA, Barbalic M, Boban M, Brown-Gentry K, Couper DJ, Criqui MH, Dehghan
Mukamal KJ. Associations between conventional cardiovascular risk fac- A, den Heijer M, Dieplinger B, Ding J, Dörr M, Espinola-Klein C, Felix
tors and risk of peripheral artery disease in men. JAMA. 2012;308:1660– SB, Ferrucci L, Folsom AR, Fraedrich G, Gibson Q, Goodloe R, Gunjaca
1667. doi: 10.1001/jama.2012.13415 G, Haltmayer M, Heiss G, Hofman A, Kieback A, Kiemeney LA, Kolcic I,
42. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott Kullo IJ, Kritchevsky SB, Lackner KJ, Li X, Lieb W, Lohman K, Meisinger C,
MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Melzer D, Mohler ER 3rd, Mudnic I, Mueller T, Navis G, Oberhollenzer F,
Downloaded from http://ahajournals.org by on February 7, 2019

Comparison of global estimates of prevalence and risk factors for periph- Olin JW, O’Connell J, O’Donnell CJ, Palmas W, Penninx BW, Petersmann
eral artery disease in 2000 and 2010: a systematic review and analysis. A, Polasek O, Psaty BM, Rantner B, Rice K, Rivadeneira F, Rotter JI,
Lancet. 2013;382:1329–1340. doi: 10.1016/S0140-6736(13)61249-0 Seldenrijk A, Stadler M, Summerer M, Tanaka T, Tybjaerg-Hansen A,
43. Berger JS, Hochman J, Lobach I, Adelman MA, Riles TS, Rockman CB. Uitterlinden AG, van Gilst WH, Vermeulen SH, Wild SH, Wild PS, Willeit
Modifiable risk factor burden and the prevalence of peripheral artery dis- J, Zeller T, Zemunik T, Zgaga L, Assimes TL, Blankenberg S, Boerwinkle
ease in different vascular territories. J Vasc Surg. 2013;58:673–81.e1. doi: E, Campbell H, Cooke JP, de Graaf J, Herrington D, Kardia SL, Mitchell
10.1016/j.jvs.2013.01.053 BD, Murray A, Münzel T, Newman AB, Oostra BA, Rudan I, Shuldiner AR,
44. Garg PK, Biggs ML, Carnethon M, Ix JH, Criqui MH, Britton KA, Snieder H, van Duijn CM, Völker U, Wright AF, Wichmann HE, Wilson JF,
Djoussé L, Sutton-Tyrrell K, Newman AB, Cushman M, Mukamal KJ. Witteman JC, Liu Y, Hayward C, Borecki IB, Ziegler A, North KE, Cupples
Metabolic syndrome and risk of incident peripheral artery disease: the LA, Kronenberg F. Association between chromosome 9p21 variants and
Cardiovascular Health Study. Hypertension. 2014;63:413–419. doi: the ankle-brachial index identified by a meta-analysis of 21 genome-
10.1161/HYPERTENSIONAHA.113.01925 wide association studies. Circ Cardiovasc Genet. 2012;5:100–112. doi:
45. Wattanakit K, Folsom AR, Selvin E, Coresh J, Hirsch AT, Weatherley BD. 10.1161/CIRCGENETICS.111.961292
Kidney function and risk of peripheral arterial disease: results from the 56. Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, Yeung RS,
Atherosclerosis Risk in Communities (ARIC) Study. J Am Soc Nephrol. Tan DE, Sim KS, Wang JJ, Wong TY, Pang J, Mitchell P, Cimaz R, Dahdah
2007;18:629–636. doi: 10.1681/ASN.2005111204 N, Cheung YF, Huang GY, Yang W, Park IS, Lee JK, Wu JY, Levin M, Burns
46. Weissgerber TL, Turner ST, Bailey KR, Mosley TH Jr, Kardia SL, Wiste HJ, JC, Burgner D, Kuijpers TW, Hibberd ML; Hong Kong–Shanghai Kawasaki
Miller VM, Kullo IJ, Garovic VD. Hypertension in pregnancy is a risk factor Disease Genetics Consortium; Korean Kawasaki Disease Genetics
for peripheral arterial disease decades after pregnancy. Atherosclerosis. Consortium; Taiwan Kawasaki Disease Genetics Consortium; International
2013;229:212–216. doi: 10.1016/j.atherosclerosis.2013.04.012 Kawasaki Disease Genetics Consortium; US Kawasaki Disease Genetics
47. Arya S, Binney Z, Khakharia A, Brewster LP, Goodney P, Patzer R, Consortium; Blue Mountains Eye Study. Genome-wide association study
Hockenberry J, Wilson PWF. Race and socioeconomic status indepen- identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat
dently affect risk of major amputation in peripheral artery disease. J Am Genet. 2011;43:1241–1246. doi: 10.1038/ng.981
Heart Assoc. 2018;7:e007425. doi: 10.1161/JAHA.117.007425 57. Global Burden of Disease Study 2016. Global Burden of Disease Study
48. Ruiz-Canela M, Estruch R, Corella D, Salas-Salvadó J, Martínez-González 2016 (GBD 2016) results. Seattle, WA: Institute for Health Metrics and
MA. Association of Mediterranean diet with peripheral artery dis- Evaluation (IHME), University of Washington; 2016. http://ghdx.health-
ease: the PREDIMED randomized trial. JAMA. 2014;311:415–417. doi: data.org/gbd-results-tool. Accessed May 1, 2018.
10.1001/jama.2013.280618 58. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL,
49. Collins TC, Slovut DP, Newton R Jr, Johnson WD, Larrivee S, Patterson J, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks
Johnston JA, Correa A. Ideal cardiovascular health and peripheral artery D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA. ACC/AHA
disease in African Americans: results from the Jackson Heart Study. Prev 2005 practice guidelines for the management of patients with periph-
Med Rep. 2017;7:20–25. doi: 10.1016/j.pmedr.2017.05.005 eral arterial disease (lower extremity, renal, mesenteric, and abdomi-
50. Wassel CL, Loomba R, Ix JH, Allison MA, Denenberg JO, Criqui MH. Family nal aortic): a collaborative report from the American Association for
history of peripheral artery disease is associated with prevalence and Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular
severity of peripheral artery disease: the San Diego Population Study. J Am Angiography and Interventions, Society for Vascular Medicine and
Coll Cardiol. 2011;58:1386–1392. doi: 10.1016/j.jacc.2011.06.023 Biology, Society of Interventional Radiology, and the ACC/AHA Task Force

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e439

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

on Practice Guidelines (Writing Committee to Develop Guidelines for the 75. Zettervall SL, Schermerhorn ML, Soden PA, McCallum JC, Shean KE, Deery
CLINICAL STATEMENTS

Management of Patients With Peripheral Arterial Disease). Circulation. SE, O’Malley AJ, Landon B. The effect of surgeon and hospital volume on
AND GUIDELINES

2006;113:e463–e654. doi: 10.1161/CIRCULATIONAHA.106.174526 mortality after open and endovascular repair of abdominal aortic aneu-
59. Sweeting MJ, Thompson SG, Brown LC, Powell JT; RESCAN Collaborators. rysms. J Vasc Surg. 2017;65:626–634. doi: 10.1016/j.jvs.2016.09.036
Meta-analysis of individual patient data to examine factors affecting 76. Goodney PP, Brooke BS, Wallaert J, Travis L, Lucas FL, Goodman DC,
growth and rupture of small abdominal aortic aneurysms. Br J Surg. Cronenwett JL, Stone DH. Thoracic endovascular aneurysm repair, race,
2012;99:655–665. doi: 10.1002/bjs.8707 and volume in thoracic aneurysm repair. J Vasc Surg. 2013;57:56–63,
60. Clouse WD, Hallett JW Jr, Schaff HV, Spittell PC, Rowland CM, Ilstrup 63.e1. doi: 10.1016/j.jvs.2012.07.036
DM, Melton LJ 3rd. Acute aortic dissection: population-based incidence 77. Groves EM, Khoshchehreh M, Le C, Malik S. Effects of weekend admission
compared with degenerative aortic aneurysm rupture. Mayo Clin Proc. on the outcomes and management of ruptured aortic aneurysms. J Vasc
2004;79:176–180. Surg. 2014;60:318–324. doi: 10.1016/j.jvs.2014.02.052
61. Brewster DC, Cronenwett JL, Hallett JW Jr, Johnston KW, Krupski WC, 78. Pape LA, Awais M, Woznicki EM, Suzuki T, Trimarchi S, Evangelista A,
Matsumura JS; Joint Council of the American Association for Vascular Myrmel T, Larsen M, Harris KM, Greason K, Di Eusanio M, Bossone E,
Surgery and Society for Vascular Surgery. Guidelines for the treatment of Montgomery DG, Eagle KA, Nienaber CA, Isselbacher EM, O’Gara P.
abdominal aortic aneurysms: report of a subcommittee of the Joint Council Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year
of the American Association for Vascular Surgery and Society for Vascular trends from the International Registry of Acute Aortic Dissection. J Am
Surgery. J Vasc Surg. 2003;37:1106–1117. doi: 10.1067/mva.2003.363 Coll Cardiol. 2015;66:350–358. doi: 10.1016/j.jacc.2015.05.029
62. Eckstein H-H, Reeps C, Zimmermann A, Söllner H. Ultrasound screening 79. Singh K, Bønaa KH, Jacobsen BK, Bjørk L, Solberg S. Prevalence of and risk
for abdominal aortic aneurysms. Gefässchirurgie. 2015;20(suppl 1):1–12. factors for abdominal aortic aneurysms in a population-based study: the
doi: 10.1007/s00772-014-1398-7 Tromsø Study. Am J Epidemiol. 2001;154:236–244.
63. Guirguis-Blake JM, Beil TL, Sun X, Senger CA, Whitlock EP. Primary Care 80. Lederle FA. In the clinic: abdominal aortic aneurysm. Ann Intern Med. 2009;
Screening for Abdominal Aortic Aneurysm: A Systematic Evidence Review 150:ITC5-1–ITC5-15. doi: 10.7326/0003-4819-150-9-200905050-01005
for the U.S. Preventive Services Task Force. Rockville, MD: Agency for 81. De Rango P, Farchioni L, Fiorucci B, Lenti M. Diabetes and abdominal
Healthcare Research and Quality; 2014. Evidence Synthesis No. 109. aortic aneurysms. Eur J Vasc Endovasc Surg. 2014;47:243–261. doi:
AHRQ publication No. 14-05202-EF-1. 10.1016/j.ejvs.2013.12.007
64. Wanhainen A, Hultgren R, Linné A, Holst J, Gottsäter A, Langenskiöld 82. Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B,
M, Smidfelt K, Björck M, Svensjö S; on behalf of the Swedish Aneurysm Hamilton W, Emin A, Culliford D, Luqmani RA. The relative risk of aor-
Screening Study Group (SASS). Outcome of the Swedish Nationwide tic aneurysm in patients with giant cell arteritis compared with the
Abdominal Aortic Aneurysm Screening Program. Circulation. general population of the UK. Ann Rheum Dis. 2015;74:129–135. doi:
2016;134:1141–1148. doi: 10.1161/CIRCULATIONAHA.116.022305 10.1136/annrheumdis-2013-204113
65. Di Eusanio M, Trimarchi S, Patel HJ, Hutchison S, Suzuki T, Peterson MD, 83. Guo DC, Grove ML, Prakash SK, Eriksson P, Hostetler EM, LeMaire SA, Body
Di Bartolomeo R, Folesani G, Pyeritz RE, Braverman AC, Montgomery DG, SC, Shalhub S, Estrera AL, Safi HJ, Regalado ES, Zhou W, Mathis MR, Eagle
Isselbacher EM, Nienaber CA, Eagle KA, Fattori R. Clinical presentation, KA, Yang B, Willer CJ, Boerwinkle E, Milewicz DM; GenTAC Investigators;
management, and short-term outcome of patients with type A acute dis- BAVCon Investigators. Genetic variants in LRP1 and ULK4 are associated
section complicated by mesenteric malperfusion: observations from the with acute aortic dissections. Am J Hum Genet. 2016;99:762–769. doi:
International Registry of Acute Aortic Dissection. J Thorac Cardiovasc 10.1016/j.ajhg.2016.06.034
Surg. 2013;145:385–390.e1. doi: 10.1016/j.jtcvs.2012.01.042 84. LeMaire SA, McDonald ML, Guo DC, Russell L, Miller CC 3rd, Johnson
66. Trimarchi S, Tolenaar JL, Tsai TT, Froehlich J, Pegorer M, Upchurch GR, RJ, Bekheirnia MR, Franco LM, Nguyen M, Pyeritz RE, Bavaria JE,
Downloaded from http://ahajournals.org by on February 7, 2019

Fattori R, Sundt TM 3rd, Isselbacher EM, Nienaber CA, Rampoldi V, Devereux R, Maslen C, Holmes KW, Eagle K, Body SC, Seidman C,
Eagle KA. Influence of clinical presentation on the outcome of acute Seidman JG, Isselbacher EM, Bray M, Coselli JS, Estrera AL, Safi HJ,
B aortic dissection: evidences from IRAD. J Cardiovasc Surg (Torino). Belmont JW, Leal SM, Milewicz DM. Genome-wide association study
2012;53:161–168. identifies a susceptibility locus for thoracic aortic aneurysms and aortic
67. Filardo G, Powell JT, Martinez MAM, Ballard DJ. Surgery for small asymp- dissections spanning FBN1 at 15q21.1. Nat Genet. 2011;43:996–1000.
tomatic abdominal aortic aneurysms. Cochrane Database Syst Rev. doi: 10.1038/ng.934
2015;(2):CD001835. doi: 10.1002/14651858.CD001835.pub4 85. van ‘t Hof FN, Ruigrok YM, Lee CH, Ripke S, Anderson G, de Andrade M,
68. Karthikesalingam A, Holt PJ, Vidal-Diez A, Ozdemir BA, Poloniecki Baas AF, Blankensteijn JD, Böttinger EP, Bown MJ, Broderick J, Bijlenga P,
JD, Hinchliffe RJ, Thompson MM. Mortality from ruptured abdomi- Carrell DS, Crawford DC, Crosslin DR, Ebeling C, Eriksson JG, Fornage M,
nal aortic aneurysms: clinical lessons from a comparison of out- Foroud T, von Und Zu Fraunberg M, Friedrich CM, Gaál EI, Gottesman O,
comes in England and the USA. Lancet. 2014;383:963–969. doi: Guo DC, Harrison SC, Hernesniemi J, Hofman A, Inoue I, Jääskeläinen JE,
10.1016/S0140-6736(14)60109-4 Jones GT, Kiemeney LA, Kivisaari R, Ko N, Koskinen S, Kubo M, Kullo IJ,
69. Dua A, Kuy S, Lee CJ, Upchurch GR Jr, Desai SS. Epidemiology of aortic Kuivaniemi H, Kurki MI, Laakso A, Lai D, Leal SM, Lehto H, LeMaire SA,
aneurysm repair in the United States from 2000 to 2010. J Vasc Surg. Low SK, Malinowski J, McCarty CA, Milewicz DM, Mosley TH, Nakamura
2014;59:1512–1517. doi: 10.1016/j.jvs.2014.01.007 Y, Nakaoka H, Niemelä M, Pacheco J, Peissig PL, Pera J, Rasmussen-Torvik
70. Jackson RS, Chang DC, Freischlag JA. Comparison of long-term sur- L, Ritchie MD, Rivadeneira F, van Rij AM, Santos-Cortez RL, Saratzis A,
vival after open vs endovascular repair of intact abdominal aortic aneu- Slowik A, Takahashi A, Tromp G, Uitterlinden AG, Verma SS, Vermeulen
rysm among Medicare beneficiaries. JAMA. 2012;307:1621–1628. doi: SH, Wang GT; Aneurysm Consortium; Vascular Research Consortium of
10.1001/jama.2012.453 New Zealand; Han B, Rinkel GJ, de Bakker PI. Shared genetic risk factors
71. Schermerhorn ML, Buck DB, O’Malley AJ, Curran T, McCallum JC, of intracranial, abdominal, and thoracic aneurysms. J Am Heart Assoc.
Darling J, Landon BE. Long-term outcomes of abdominal aortic aneu- 2016;5:e002603. doi: 10.1161/JAHA.115.002603
rysm in the Medicare population. N Engl J Med. 2015;373:328–338. doi: 86. Verloes A, Sakalihasan N, Koulischer L, Limet R. Aneurysms of the abdomi-
10.1056/NEJMoa1405778 nal aorta: familial and genetic aspects in three hundred thirteen pedi-
72. Lederle FA, Freischlag JA, Kyriakides TC, Matsumura JS, Padberg FT Jr, grees. J Vasc Surg. 1995;21:646–655.
Kohler TR, Kougias P, Jean-Claude JM, Cikrit DF, Swanson KM; OVER 87. Davis FM, Rateri DL, Daugherty A. Abdominal aortic aneurysm: novel
Veterans Affairs Cooperative Study Group. Long-term comparison of mechanisms and therapies. Curr Opin Cardiol. 2015;30:566–573. doi:
endovascular and open repair of abdominal aortic aneurysm. N Engl J 10.1097/HCO.0000000000000216
Med. 2012;367:1988–1997. doi: 10.1056/NEJMoa1207481 88. Gretarsdottir S, Baas AF, Thorleifsson G, Holm H, den Heijer M, de Vries
73. Karthikesalingam A, Vidal-Diez A, Holt PJ, Loftus IM, Schermerhorn JP, Kranendonk SE, Zeebregts CJ, van Sterkenburg SM, Geelkerken RH,
ML, Soden PA, Landon BE, Thompson MM. Thresholds for abdominal van Rij AM, Williams MJ, Boll AP, Kostic JP, Jonasdottir A, Jonasdottir A,
aortic aneurysm repair in England and the United States. N Engl J Med. Walters GB, Masson G, Sulem P, Saemundsdottir J, Mouy M, Magnusson
2016;375:2051–2059. doi: 10.1056/NEJMoa1600931 KP, Tromp G, Elmore JR, Sakalihasan N, Limet R, Defraigne JO, Ferrell RE,
74. Ullery BW, Tran K, Chandra V, Mell MW, Harris EJ, Dalman RL, Lee JT. Ronkainen A, Ruigrok YM, Wijmenga C, Grobbee DE, Shah SH, Granger
Association of an endovascular-first protocol for ruptured abdominal CB, Quyyumi AA, Vaccarino V, Patel RS, Zafari AM, Levey AI, Austin H,
aortic aneurysms with survival and discharge disposition. JAMA Surg. Girelli D, Pignatti PF, Olivieri O, Martinelli N, Malerba G, Trabetti E, Becker
2015;150:1058–1065. doi: 10.1001/jamasurg.2015.1861 LC, Becker DM, Reilly MP, Rader DJ, Mueller T, Dieplinger B, Haltmayer

e440 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 23

M, Urbonavicius S, Lindblad B, Gottsäter A, Gaetani E, Pola R, Wells H, ICAN Study Group; Loirand G, Desal H, Redon R. Rare coding variants

CLINICAL STATEMENTS
P, Rodger M, Forgie M, Langlois N, Corral J, Vicente V, Fontcuberta J, in ANGPTL6 are associated with familial forms of intracranial aneurysm.

AND GUIDELINES
España F, Grarup N, Jørgensen T, Witte DR, Hansen T, Pedersen O, Aben Am J Hum Genet. 2018;102:133–141. doi: 10.1016/j.ajhg.2017.12.006
KK, de Graaf J, Holewijn S, Folkersen L, Franco-Cereceda A, Eriksson 91. Kiando SR, Tucker NR, Castro-Vega LJ, Katz A, D’Escamard V, Tréard C,
P, Collier DA, Stefansson H, Steinthorsdottir V, Rafnar T, Valdimarsson Fraher D, Albuisson J, Kadian-Dodov D, Ye Z, Austin E, Yang ML, Hunker
EM, Magnadottir HB, Sveinbjornsdottir S, Olafsson I, Magnusson MK, K, Barlassina C, Cusi D, Galan P, Empana JP, Jouven X, Gimenez-Roqueplo
Palmason R, Haraldsdottir V, Andersen K, Onundarson PT, Thorgeirsson AP, Bruneval P, Hyun Kim ES, Olin JW, Gornik HL, Azizi M, Plouin PF, Ellinor
G, Kiemeney LA, Powell JT, Carey DJ, Kuivaniemi H, Lindholt JS, Jones GT, PT, Kullo IJ, Milan DJ, Ganesh SK, Boutouyrie P, Kovacic JC, Jeunemaitre X,
Kong A, Blankensteijn JD, Matthiasson SE, Thorsteinsdottir U, Stefansson Bouatia-Naji N. PHACTR1 is a genetic susceptibility locus for fibromuscu-
K. Genome-wide association study identifies a sequence variant within lar dysplasia supporting its complex genetic pattern of inheritance. PLoS
the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. Genet. 2016;12:e1006367. doi: 10.1371/journal.pgen.1006367
Nat Genet. 2010;42:692–697. doi: 10.1038/ng.622 92. Hansen KJ, Edwards MS, Craven TE, Cherr GS, Jackson SA, Appel RG,
89. Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, Simon Burke GL, Dean RH. Prevalence of renovascular disease in the elderly: a
M, Krex D, Arlier Z, Nayak N, Ruigrok YM, Niemelä M, Tajima A, von und population-based study. J Vasc Surg. 2002;36:443–451.
zu Fraunberg M, Dóczi T, Wirjatijasa F, Hata A, Blasco J, Oszvald A, Kasuya 93. Kalra PA, Guo H, Gilbertson DT, Liu J, Chen SC, Ishani A, Collins AJ, Foley
H, Zilani G, Schoch B, Singh P, Stüer C, Risselada R, Beck J, Sola T, Ricciardi RN. Atherosclerotic renovascular disease in the United States. Kidney Int.
F, Aromaa A, Illig T, Schreiber S, van Duijn CM, van den Berg LH, Perret 2010;77:37–43. doi: 10.1038/ki.2009.406
C, Proust C, Roder C, Ozturk AK, Gaál E, Berg D, Geisen C, Friedrich CM, 94. Shafique S, Peixoto AJ. Renal artery stenosis and cardiovascular risk. J Clin
Summers P, Frangi AF, State MW, Wichmann HE, Breteler MM, Wijmenga Hypertens (Greenwich). 2007;9:201–208.
C, Mane S, Peltonen L, Elio V, Sturkenboom MC, Lawford P, Byrne J, 95. Conlon PJ, Little MA, Pieper K, Mark DB. Severity of renal vascular disease
Macho J, Sandalcioglu EI, Meyer B, Raabe A, Steinmetz H, Rüfenacht D, predicts mortality in patients undergoing coronary angiography. Kidney
Jääskeläinen JE, Hernesniemi J, Rinkel GJ, Zembutsu H, Inoue I, Palotie A, Int. 2001;60:1490–1497. doi: 10.1046/j.1523-1755.2001.00953.x
Cambien F, Nakamura Y, Lifton RP, Günel M. Genome-wide association 96. Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM,
study of intracranial aneurysm identifies three new risk loci. Nat Genet. Cohen DJ, Matsumoto AH, Steffes M, Jaff MR, Prince MR, Lewis EF,
2010;42:420–425. doi: 10.1038/ng.563 Tuttle KR, Shapiro JI, Rundback JH, Massaro JM, D’Agostino RB Sr,
90. Bourcier R, Le Scouarnec S, Bonnaud S, Karakachoff M, Bourcereau E, Dworkin LD; CORAL Investigators. Stenting and medical therapy for ath-
Heurtebise-Chrétien S, Menguy C, Dina C, Simonet F, Moles A, Lenoble C, erosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13–22. doi:
Lindenbaum P, Chatel S, Isidor B, Génin E, Deleuze JF, Schott JJ, Le Marec 10.1056/NEJMoa1310753
Downloaded from http://ahajournals.org by on February 7, 2019

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e441

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

24. QUALITY OF CARE Abbreviations Used in Chapter 24 Continued

CLINICAL STATEMENTS

IQR interquartile range

See Tables 24-1 through 24-11 and Chart 24-1
AND GUIDELINES

IV intravenous
LDL-C low-density lipoprotein cholesterol
Click here to return to the Table of Contents LV left ventricular
LVEF left ventricular ejection fraction
The Institute of Medicine has defined quality of care LVSD left ventricular systolic dysfunction
MD medical doctor
as “the degree to which health services for individu-
MEPS Medical Expenditure Panel Survey
als and populations increase the likelihood of desired MESA Multi-Ethnic Study of Atherosclerosis
health outcomes and are consistent with current pro- MI myocardial infarction
fessional knowledge,”1 and further defined 6 specific N/A not available or not applicable
domains for improving health care: safety, effective- NCDR National Cardiovascular Data Registry
ness, patient or people-centeredness, timeliness, effi- NSTEMI non–ST-segment–elevation myocardial infarction
OHCA out-of-hospital cardiac arrest
ciency, and equity.
OR odds ratio
PCI percutaneous coronary intervention
Abbreviations Used in Chapter 24 PINNACLE Practice Innovation and Clinical Excellence
ACC American College of Cardiology PPO preferred provider organization
ACEI angiotensin-converting enzyme inhibitor QALY quality-adjusted life-year
ACS acute coronary syndrome ROC Resuscitation Outcomes Consortium
ACTION Acute Coronary Treatment and Intervention RR relative risk
Outcomes Network RSMR risk-standardized mortality rate
AED automated external defibrillator rtPA recombinant tissue-type plasminogen activator
AF atrial fibrillation SD standard deviation
AHA American Heart Association STEMI ST-segment–elevation myocardial infarction
AMI acute myocardial infarction TIA transient ischemic stroke
ARB angiotensin receptor blocker TOPCAT Treatment of Preserved Cardiac Function Heart
ASCVD atherosclerotic cardiovascular disease Failure With an Aldosterone Antagonist
AVAIL Adherence Evaluation After Ischemic Stroke tPA tissue-type plasminogen activator
Longitudinal UFH unfractionated heparin
BMI body mass index VF ventricular fibrillation
BP blood pressure VT ventricular tachycardia
Downloaded from http://ahajournals.org by on February 7, 2019

CAD coronary artery disease

CHA2DS2-VASc Clinical prediction rule for estimating the risk
of stroke based on congestive heart failure, Assessing care quality requires the development
hypertension, diabetes mellitus, and sex (1 point and implementation of performance measures, explicit
each); age ≥75 y and stroke/transient ischemic
attack/thromboembolism (2 points each); plus standards or metrics of care against which actual clini-
history of vascular disease, age 65–74 y, and cal care delivered can be judged.2 Performance mea-
(female) sex category sures are standards that, if not followed, represent
CHD coronary heart disease
clinician error. This differs from guidelines, which are
CHS Cardiovascular Health Study
CI confidence interval
clinical recommendations applicable to most clinical
CPR cardiopulmonary resuscitation scenarios but ultimately left to reasonable clinician
CVD cardiovascular disease discretion. Measuring performance requires a robust
DM diabetes mellitus process for data collection across care facilities and
DNR do not resuscitate
clinicians, data transfer, analysis, and dissemination.
DVT deep vein thrombosis
ECG electrocardiogram
Over the past 15 years, there has been a proliferation
ED emergency department of clinical registries in the United States and worldwide
EF ejection fraction designed to help us better understand and improve
EMS emergency medical services quality, performance, and outcomes. Early registries
ERR excess readmission ratio have focused primarily on the inpatient setting (MI,
ETco2 end-tidal CO2
HF, stroke) or discrete procedures (PCI, defibrillator
GLORIA-AF Global Registry on Long-term Oral Antithrombotic
Treatment in Patients with Atrial Fibrillation implantation, peripheral vascular interventions, car-
GWTG Get With The Guidelines diothoracic surgery). In the United States, these have
HbA1c hemoglobin A1c (glycosylated hemoglobin) been principally run by the ACC’s NCDR3 and the AHA’s
HF heart failure GWTG Program.4 More recently, a variety of elective
HF-ACTION Heart Failure: A Controlled Trial Investigating
Outcomes of Exercise Training
procedural registries have also been developed by the
HMO health maintenance organization AHA and ACC, such as for AF ablation and left atrial
HR hazard ratio appendage occlusion. New outpatient registries such
IHCA in-hospital cardiac arrest as the ACC’s PINNACLE Registry use electronic health
(Continued ) record data transfer rather than case report form data

e442 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

entry to examine performance measures across a wide 2015 [−0.74% per year; P<0.001] versus 15.7%

CLINICAL STATEMENTS
range of cardiovascular conditions. Increasingly, out- in 2009 to 14.0% in 2015 [−0.26% per year;

AND GUIDELINES
patient postmarketing registries have been sponsored P<0.001]; Pinteraction<0.001).
by pharmaceutical or device companies and managed • In a study examining the association between
by contract research organizations, such as for anti- higher-than-expected risk-adjusted 30-day
coagulation in AF. Finally, medical claims data from readmission rates (ERR >1) after AMI and MI
payers (Medicare, commercial claims) or integrated care processes and outcomes, Pandey and col-
healthcare systems (Veterans Affairs) have also exam- leagues7 showed participating hospitals’ risk-
ined quality. adjusted 30-day readmission rates after MI were
In the following sections, data on quality of care will not associated with in-hospital quality of MI care
be presented across these 6 domains to highlight cur- (adjusted OR, 0.94 [95% CI, 0.81–1.08] per
rent care and to stimulate efforts to improve the qual- 0.1-unit increase in MI ERR for overall defect-
ity of cardiovascular care nationally. Rather than group free care). Among the 51  453 patients with
findings by domains as we have in prior years, we now 1-year outcomes data available, higher MI ERR
group findings by disease or therapeutic area. Where was associated with higher all-cause readmis-
possible, data are reported from recently published sion within 1 year of discharge; however, this
literature or as standardized quality indicators drawn association was largely driven by readmissions
from quality-improvement registries whose methods early after discharge and was not significant in
are consistent with performance measures endorsed by landmark analyses beginning 30 days after dis-
the ACC and the AHA.2,5,6 charge. The MI ERR was not associated with risk
Additional data on adherence to ACC/AHA clinical for mortality within 1 year of discharge.
practice guidelines are also included to supplement • Bucholz and colleagues8 showed that patients
performance measures data where appropriate. The admitted to high-performing hospitals after AMI
select data presented are meant to provide illustrative had longer life expectancies than patients treated
examples of quality of care and are not meant to be at low-performing hospitals. This survival benefit
comprehensive given the sheer volume of quality data appeared in the first 30 days and persisted over
published each year. 17 years of follow-up. The study sample included
119 735 patients with AMI who were admitted
to 1824 hospitals. On average, patients treated
Downloaded from http://ahajournals.org by on February 7, 2019

Acute Myocardial Infarction at high-performing hospitals lived between 0.74

(See Tables 24-1 through 24-5) and 1.14 years longer than patients treated at
• The ACTION Registry–GWTG is currently the larg- low-performing hospitals.
est US-based hospital registry of inpatient AMI • Makam and Nguyen9 showed cardiac biomarker
care and is the current best source for national- testing in the ED is common even among those
level quality data (Tables 24-1 through 24-5). without symptoms suggestive of ACS. Biomarker
• Wadhera and colleagues5 examined a large testing occurred in 8.2% of visits in the absence
cohort of Medicare beneficiaries with 642 105 of symptoms related to ACS, representing 8.5
index hospitalizations for AMI and showed million visits. Among individuals who were sub-
that higher 30-day payments were associated sequently hospitalized, cardiac biomarkers were
with lower 30-day mortality after adjustment tested in 47% of all visits. Biomarkers were
for patient characteristics and comorbidities tested in 35.4% of visits in this group despite the
(adjusted OR for additional $1000 payments, absence of ACS-related symptoms.
0.986 [95% CI, 0.979–0.992]; P<0.001). This • Using data from the ACTION Registry–GWTG,
could have implications for payment programs among 202 213 patients discharged after AMI
that incent reduction in payments without con- from 526 US participating sites between January
sidering value. 2007 and March 2011, Rao and colleagues10
• Chatterjee and Joynt-Maddox6 examined patterns showed that only 14.5% of the eligible patients
in 30-day mortality from AMI as they relate to without a documented contraindication received
public reporting of these outcomes. In data from aldosterone antagonists. Fewer than 2% of the
2009 to 2015 from 2751 hospitals with publicly participating sites used aldosterone antagonists in
reported mortality data for AMI, they showed ≥50% of eligible patients.
30-day mortality among baseline poor performers • According to national Medicare data from July
(worst quartile in 2009 and 2010 in public report- 2015 through June 2016, the median (IQR) hos-
ing, before value-based payment) was higher at pital RSMR for MI was 13.1% (12.6%, 13.5%),
baseline but improved more over time compared and the median (IQR) risk-standardized 30-day
with other hospitals (18.6% in 2009 to 14.6% in readmission rate was 15.8% (15.5%, 16.2%).11

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e443

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

• Mathews and colleagues12 examined post-MI 13.0%; −0.12% per year; P<0.001), but mean
CLINICAL STATEMENTS

medication adherence as a hospital-level variable mortality among all other HF hospitals increased
AND GUIDELINES

using data from 347 US hospitals participating in during the study period. (from 10.9% to 12.0%;
the ACTION Registry–GWTG. They observed that 0.17% per year; P<0.001, Pinteraction<0.001). In a
postdischarge use of secondary prevention medi- secondary analysis of the TOPCAT and HF-ACTION
cations varied significantly across US hospitals and trials focused on patient-reported outcomes,
was inversely associated with 2-year outcomes at Pokharel and colleagues15 observed that the most
the hospital level. recent of a series of Kansas City Cardiomyopathy
Questionnaire scores was most strongly associ-
ated with subsequent death and cardiovascular
Heart Failure hospitalization.
(See Tables 24-6 and 24-7) • Using pooled participant-level data from the
• Current US HF quality data are best captured by CHS and MESA, Pandey and colleagues16 stud-
the widespread but voluntary GWTG–HF Program ied sex differences in the lifetime risk of HF. At an
(Tables 24-6 and 24-7). index age of 45 years, the lifetime risk for any HF
• Elucidating the validity of use of hospital volume through age 90 years was higher in males than
as a structural metric for assessing quality of HF females (27.4% versus 23.8%). Among partici-
care, Kumbhani and colleagues13 examined the pants with antecedent MI before HF diagnosis,
relationship between admission volume, process- the remaining lifetime risks for HF with preserved
of-care metrics, and short- and long-term out- EF and HF with reduced EF were 2.5-fold and
comes in patients admitted with acute HF in the 4-fold higher, respectively, than for participants
GWTG–HF registry with linked Medicare inpatient without antecedent MI.
data. In their cohort of 125 595 patients at 342 • Using NIS data, Ziaeian and colleagues17 showed
hospitals, they found that hospital volume as a HF hospitalization rates decreased 30.8%
structural metric correlated with process mea- between 2002 and 2013. The ratio of males to
sures but not with 30-day outcomes and only females increased from 20% greater to 39%
marginally with outcomes up to 6 months of fol- greater (Ptrend=0.002) over that time. Black males
low-up. Lower-volume hospitals were significantly and black females had rates that were 229%
(Ptrend=0.141) and 240% (Ptrend=0.725) those of
Downloaded from http://ahajournals.org by on February 7, 2019

less likely to be adherent to HF process measures

than higher-volume hospitals. On multivariable whites in 2013. Hispanic males had a rate that
modeling, higher hospital volume was not associ- was 32% greater in 2002, and the difference
ated with a difference in the in-hospital mortality narrowed to 4% greater (Ptrend=0.047) in 2013
(OR, 0.99 [95% CI, 0.94–1.05]; P=0.78), 30-day relative to whites. For Hispanic females, the rate
mortality (HR, 0.99 [95% CI, 0.97–1.01]; P=0.26), was 55% greater in 2002 and narrowed to 8%
or 30-day readmissions (HR, 0.99 [95% CI, 0.97– greater (Ptrend=0.004) in 2013 relative to whites.
1.00]; P=0.10). Gupta and colleagues14 exam- Asian/Pacific Islander males had a 27% lower
ined the association of the Hospital Readmissions rate in 2002, which improved to 43% lower
Reduction Program with readmission and mortal- (Ptrend=0.040) in 2013 relative to whites. For Asian/
ity outcomes among patients hospitalized with Pacific Islander females, the hospitalization rate
HF. Among a cohort of 115 245 fee-for-service was 24% lower in 2002 and improved to 43%
Medicare beneficiaries discharged after HF hos- lower (Ptrend=0.021) in 2013 relative to whites.
pitalizations, the 1-year risk-adjusted readmis- • Among 106 304 patients hospitalized with HF
sion rate declined from 57.2% to 56.3% (HR, at 317 centers in the AHA GWTG–HF registry,
0.92 [95% CI, 0.89–0.96]), and the 1-year risk- there was a graded inverse association between
adjusted mortality rate increased from 31.3% 30-day RSMR and long-term mortality (quartile
to 36.3% (HR, 1.10 [95% CI, 1.06–1.14]) after 1 versus quartile 4: 5-year mortality, 73.7% ver-
the Hospital Readmissions Reduction Program sus 76.8%). Lower hospital-level 30-day RSMR
implementation. was associated with greater 1-, 3-, and 5-year
• Chatterjee and Joynt-Maddox6 examined pat- survival for patients with HF. These differences
terns in 30-day mortality from HF as they relate to in 30-day survival continued to accrue beyond
public reporting of these outcomes. In data from 30 days and persisted long term, which suggests
2009 to 2015 from 3796 hospitals with pub- that 30-day RSMR could be a useful HF perfor-
licly reported mortality data for HF, they showed mance metric.18
baseline poor performers (worst quartile in 2009 • Pandey et al19 reported results from the
and 2010 in public reporting, before value-based GWTG−HF registry evaluating the association
payment) improved over time (from 13.5% to between HF ERR and performance measures, as

e444 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

well as in-hospital and 1-year clinical outcomes. rates and changes in mortality rates. They observed

CLINICAL STATEMENTS
They stratified participating centers into groups that among Medicare fee-for-service beneficiaries

AND GUIDELINES
with low (HF ERR ≤1) versus high (HF ERR >1) risk- hospitalized for HF and AMI, reductions in hos-
adjusted readmission rates. There were no differ- pital 30-day readmission rates were weakly but
ences between the low and high risk-adjusted significantly correlated with reductions in hospital
30-day readmission groups in median adherence 30-day mortality rates after discharge.
rate to all performance measures (95.7% versus
96.5%, P=0.37) or median percentage of defect-
free care (90.0% versus 91.1%, P=0.47). The
Prevention and Risk Factor Modification
composite 1-year outcome of death or all-cause (See Table 24-8)
readmission rates was also not different between • The National Committee for Quality Assurance
the 2 groups (median 62.9% versus 65.3%; Health Plan Employer Data and Information Set
P=0.10). The high HF ERR group had higher consists of established measures of quality of care
1-year all-cause readmission rates (median 59.1% related to CVD prevention in the United States
versus 54.7%; P=0.01); however, 1-year mortal- (Table 24-8).
ity rates were lower among the high versus low • Pokharel and colleagues23 examined practice-level
group, with a trend toward statistical significance variation in statin therapy among 40- to 75-year-
(median 28.2% versus 31.7%; P=0.07). The old patients with DM and no CVD between
authors concluded that the quality of care and May 2008 and October 2013 from the ACC’s
clinical outcomes were comparable among hospi- PINNACLE Registry. Among 215  193 patients
tals with high versus low risk-adjusted 30-day HF (582 048 encounters) from 204 cardiology prac-
readmission rates. tices, statins were prescribed in 61.6% of patients
• In a longitudinal cohort study of 48 million hos- with DM. Among 182 practices with ≥30 patients
pitalizations among 20 million Medicare fee-for- with DM, the median practice statin prescription
service patients across 3497 hospitals, Desai and rate was 62.3%, with no noticeable change over
colleagues20 showed that patients at hospitals sub- time. There was a 57% practice-level variation
ject to penalties under the Hospital Readmissions in statin use for 2 similar patients that was not
Reduction Program had greater reductions in affected by adjustment for patient-related vari-
readmission rates than those at nonpenalized
Downloaded from http://ahajournals.org by on February 7, 2019

ables, which suggests that practice- or provider-

hospitals. Reductions in readmission rates were related factors primarily determined variation in
greater for target versus nontarget conditions for statin use.
patients at the penalized hospitals but not at non- • Using data from the PINNACLE Registry, Hira and
penalized hospitals. colleagues24 showed that among 27 533 patients
• According to national Medicare data from July receiving prasugrel, 13.9% (N=3824) had a con-
2015 through June 2016, the median (IQR) hos- traindication to prasugrel use (ie, history of TIA
pital RSMR for HF was 11.6% (10.8%, 12.4%), or stroke). This was considered inappropriate pra-
and the median (IQR) risk-standardized 30-day sugrel use. A further 4.4% of patients (N=1210)
readmission rate was 21.4% (20.8%, 22.1%).11 were receiving it for a nonrecommended indi-
• Krumholz and colleagues21 examined readmis- cation (age >75 years without history of DM or
sion outcomes among patients who had mul- MI or weight <60 kg). Both inappropriate and
tiple admissions at >1 hospital within a given nonrecommended prasugrel use showed wide
year to attempt to separate hospital from patient practice-level variation (median rate ratio of 2.89
effects. They found the observed readmission [95% CI, 2.75–3.03] and 2.29 [95% CI, 2.05–
rate to be consistently higher among patients 2.51], respectively).
admitted to hospitals in a worse-performing • In an analysis from the PINNACLE Registry, Hira
quartile than among those admitted to hospi- and colleagues25 showed that among 68  808
tals in a better-performing quartile, but the only patients receiving aspirin therapy for primary pre-
statistically significant difference was observed vention, roughly 11.6% (7972 of 68 808) were
when one was in the best-performing quartile receiving inappropriate aspirin therapy (10-year
and the other was in the worst (absolute differ- risk of CVD <6%). There was significant practice-
ence in readmission rate 2.0 percentage points level variation in inappropriate aspirin use (range,
[95% CI, 0.4–3.5]). 0%–71.8%; median, 10.1%; IQR, 6.4%) for
• In a Medicare cohort comprising almost 3 mil- practices with an adjusted median rate ratio of
lion admissions for HF and 1.2 million for MI, 1.63 (95% CI, 1.47–1.77).
Dharmarajan and colleagues22 studied the asso- • Using aspirin dosing data from 221 199 patients
ciation between changes in hospital readmission with MI enrolled in the ACTION Registry–GWTG,

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e445

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Hall and colleagues26 showed a 25-fold variation among those with established ASCVD, but use
CLINICAL STATEMENTS

in the use of high-dose aspirin (325 mg/d) across in higher-risk groups was suboptimal. Statin
AND GUIDELINES

participating centers. Overall, 60.9% of patients use was significantly lower in females (OR, 0.81
were discharged on high-dose aspirin. High- [95% CI, 0.79–0.85]) and racial/ethnic minorities
dose aspirin was prescribed to 73% of patients (OR, 0.65 [95% CI, 0.61–0.70]). Gross domestic
treated with PCI and 44.6% of patients managed product–adjusted total cost for statins decreased
medically; 56.7% of patients with an in-hospital from $17.2 billion (out-of-pocket cost, $7.6 bil-
bleeding event were also discharged on high- lion) in 2002 to 2003 to $16.9 billion (out-of-
dose aspirin. Among 9075 patients discharged pocket cost, $3.9 billion) in 2012 to 2013, and
on aspirin, thienopyridine, and warfarin, 44.0% the mean annual out-of-pocket costs for patients
were prescribed high-dose aspirin therapy. decreased from $348 to $94.
• Data from the PINNACLE Registry showed
that among 156 145 patients with CAD in 58
practices, just over two-thirds (N=103 830, or Atrial Fibrillation
66.5%) of patients were prescribed the optimal • Of all CVD, AF may have the largest quantity of
combination of medications (β-blockers, ACEIs registries, with at least 10 non–industry-funded
or angiotensin receptor blockers, statins) for and 6 industry-funded registries.30 Almost all of
which they were eligible. After adjustment for these emerged after the introduction of direct
patient factors, the practice median rate ratio oral anticoagulants to the market, and perfor-
for prescription was 1.25 (95% CI, 1.20–1.32), mance measures and utilization of anticoagula-
which indicates a 25% likelihood that any 2 tion has remained a major focus.
practices would differ in treating identical CAD • In 2016, the ACC and AHA revised the clinical per-
patients.10 formance and quality measures for AF and atrial
• A study of 35 191 CHD patients from the US flutter.31 The 3 pairs of inpatient and outpatient
Department of Veterans Affairs healthcare system performance measures include documentation
showed that among 27 947 patients with LDL-C of CHA2DS2-VASc score, oral anticoagulant pre-
levels <100 mg/dL, 9200 (32.9%) received addi- scription, and planned or monthly international
tional lipid assessments without any treatment normalized ratio testing for warfarin. The 18
intensification during the 11 months from the quality measures reflect metrics for appropriate
Downloaded from http://ahajournals.org by on February 7, 2019

index lipid panel. Even among 13 114 patients medications for comorbidities (HF), inappropriate
with LDL-C <70 mg/dL, repeat lipid testing was prescription of specific anticoagulant drugs and
performed in 8177 patients (62.4%) during 11 antiarrhythmic drugs in specific clinical scenarios,
months of follow-up. These results show that and documentation of shared decision making.
redundant lipid testing is common in patients Overuse of oral anticoagulants in AF patients with
with CHD.27 very low stroke risk has been observed but has
• Heller and colleagues28 determined the cost- not yet been formalized into quality or perfor-
effectiveness of statins after the expanded rec- mance measures.
ommendations in the “2013 ACC/AHA Guideline • There is considerable variation across registries
on the Treatment of Blood Cholesterol to Reduce in estimated use of anticoagulation. In general,
Atherosclerotic Cardiovascular Risk in Adults.”28a administrative claims data and electronic health
They determined the ACC/AHA guideline would record data from healthcare systems tend to show
potentially result in up to 12.3 million more statin lower oral anticoagulant prescription than site-
users than the Adult Treatment Panel III guideline, based informed-consent studies.
with a marginal number needed to treat for 10 • Over the past decade, the proportion of AF
years per QALY gained of 68. Moderate-intensity patients with AF receiving oral anticoagulants has
statin use in all males 45 to 74 years of age and increased from ≈67% to >80%.30
females 55 to 74 years of age would result in • The highest uptake is reported in European reg-
28.9 million more statin users than the ACC/AHA istries (90%) and the lowest in Asia (58%).30
guideline, with a marginal number needed to However, methodological factors are likely a
treat for 10 years per QALY gained of 108. In all major source of difference in estimates, including
cases, they estimated benefits would be greater in selection bias of both numerator and denomina-
males than females.28 tor (patient, clinician, site, and in some registries,
• Using data from MEPS, Salami and colleagues29 requirement of informed consent), patient char-
described trends in statin use and related out- acteristics, and oral anticoagulant ascertainment
of-pocket expense from 2002 to 2013. They methodology. For example, in the outpatient,
found that statin use increased overall and electronic health record–based PINNACLE-AF US

e446 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

registry, oral anticoagulant prescription for those improvement program. The US-based program is

CLINICAL STATEMENTS
with CHA2DS2-VASc score ≥2 in 2014 was 48%. an ongoing, voluntary hospital registry and per-

AND GUIDELINES
In the industry-funded, informed-consent, post- formance improvement initiative for acute stroke
marketing GLORIA-AF international registry, oral and supplies most quality data for acute stroke
anticoagulant prescription between 2011 and care.
2014 was 80%.32 • Care processes that would lead to best functional
• Healthcare insurance coverage may influence outcomes after acute stroke are poorly under-
oral anticoagulant and novel oral anticoagulant stood. A study of 2083 ischemic stroke patients
use. An analysis of 363 309 prevalent AF patients from 82 hospitals with data in both the AVAIL
from the PINNACLE-AF outpatient registry found registry and GWTG–Stroke found that one-third
considerable variation in oral anticoagulant use of acute stroke patients were functionally depen-
across insurance plans.33 Relative to Medicare, dent or dead at 3 months after stroke. Functional
Medicaid insurance was associated with a lower rates varied considerably across hospitals, which
odds of oral anticoagulant prescription and of indicates the need to understand which process
novel oral anticoagulant use. measures could be targeted to minimize hospi-
• Potential overuse in low-risk patients remains tal variation and improve poststroke functional
a concern, with oral anticoagulants adminis- outcomes.37
tered to AF patients with no stroke risk factors.30 • Door-to-needle time for tPA administration
Methodological limitations of comorbidity ascer- decreased on average by 10 minutes, from 77
tainment could lead to overestimation of overuse. minutes (IQR 60–98 minutes) to 67 minutes (IQR
• Inappropriate use of aspirin for patients at mod- 51–87 minutes), after implementation of Target:
erate to high risk of stroke remains a concern. Stroke Phase I, the first stage of AHA’s GWTG–
In PINNACLE-AF, which examined the use of Stroke quality improvement program. During this
aspirin rather than guideline-recommended oral period, in-hospital all-cause mortality declined
anticoagulants for patients with CHA2DS2-VASc (from 9.93% to 8.25%), and discharge to home
score ≥2, 40% of patients were treated with became more frequent (37.6% versus 42.7%).38
aspirin alone, and this was influenced by CHD • Target: Stroke Phase II was launched in April 2014
comorbidities.34 to promote further reduction in door-to-needle
time. There was significant site variation in door-
Downloaded from http://ahajournals.org by on February 7, 2019

• Treating specialty can influence likelihood of

therapy and resultant outcomes. In the Veterans to-needle time; 16 strategies were identified
Health Administration, the largest integrated that were significantly associated with reduced
healthcare system in the United States, cardiol- door-to-needle time. It was estimated that door-
ogy outpatient care within 90 days of newly diag- to-needle time could be reduced on average by
nosed AF was associated with a reduced adjusted an additional 20 minutes if all strategies were
risk of stroke (HR, 0.91 [95% CI, 0.86–0.96]) and implemented.39
death (HR, 0.89 [95% CI, 0.88–0.91]), although • A study of 204 591 patients with ischemic and
with an increased risk of arrhythmia-related hos- hemorrhagic strokes admitted to 1563 GWTG–
pitalization (HR, 1.48 [95% CI, 1.35–1.42]).35 This Stroke participating hospitals between April 1,
finding was statistically mediated by an increase 2003, and June 30, 2010, showed that 63.7% of
in 90-day oral anticoagulant prescription. the patients arrived at the hospital by EMS. Older
patients, those with Medicaid and Medicare, and
Other Treatments those with severe strokes were more likely to
The AHA GWTG–AF program has been designed to activate EMS. Conversely, minority race/ethnicity
track the 2016 performance measures, but there are (black, Hispanic, Asian) and living in rural com-
no published data yet.36 Data on use of rate versus munities were associated with a lower likelihood
rhythm control, appropriate and inappropriate use of of EMS use. EMS transport was independently
antiarrhythmic drugs, and procedural factors related to associated with an onset-to-door time ≤3 hours,
catheter ablation are expected to be forthcoming. The a higher proportion of patients meeting door-
NCDR AF ablation and left atrial appendage occlusion to-imaging time of ≤25 minutes, more patients
registries have also not yet published data. meeting a door-to-needle time of ≤60 minutes,
and more eligible patients being treated with
tPA if onset of symptoms was ≤2 hours. The
Stroke
authors concluded that although EMS use was
(See Tables 24-4 and 24-9) associated with rapid evaluation and treatment
• The AHA GWTG–Stroke program (Tables  24- of stroke, more than one-third of stroke patients
4 and 24-9) remains the largest stroke quality fail to use EMS.40

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e447

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Implantable Defibrillators risk-standardized survival. Whether reduction in

CLINICAL STATEMENTS

this process measure could improve outcomes has

• In a comparative effectiveness study of single-
AND GUIDELINES

versus dual-chamber implantable cardioverter- not yet been demonstrated.44

defibrillators using data from the Implantable • A composite performance score for in-hospital
Cardioverter Defibrillator Registry, Peterson and arrest varied significantly across hospitals (89.7%
colleagues41 found that among patients receiv- [IQR 85.4%–93.1%]). Hospital process com-
ing an implantable cardioverter-defibrillator for posite quality performance was associated with
primary prevention without indications for pac- risk-standardized discharge rates and favorable
ing, the use of a dual-chamber device compared neurological status at discharge.45
with a single-chamber device was associated with • Chan et al46 demonstrated that rates of survival to
a higher risk of device-related complications and discharge were lower for black patients (25.2%)
similar 1-year mortality and hospitalization out- than for white patients (37.4%) after IHCA.
comes. In a propensity-matched cohort, rates of Lower rates of survival to discharge for blacks
complications were lower for single-chamber reflected lower rates of both successful resusci-
devices (3.51% versus 4.72%; P<0.001; risk differ- tation (55.8% versus 67.4%) and postresuscita-
ence, −1.20 [95% CI, −1.72 to −0.69]), but device tion survival (45.2% versus 55.5%). Adjustment
type was not significantly associated with 1-year for the hospital site at which patients received
mortality (unadjusted rate, 9.85% versus 9.77%; care explained a substantial portion of the racial
HR, 0.99 [95% CI, 0.91–1.07]; P=0.79), 1-year all- differences in successful resuscitation (adjusted
cause hospitalization (unadjusted rate, 43.86% RR, 0.92 [95% CI, 0.88–0.96]; P<0.001) and
versus 44.83%; HR, 1.00 [95% CI, 0.97–1.04]; eliminated the racial differences in postresus-
P=0.82), or hospitalization for HF (unadjusted rate, citation survival (adjusted RR, 0.99 [95% CI,
14.73% versus 15.38%; HR, 1.05 [95% CI, 0.99– 0.92–1.06]; P=0.68). The authors concluded
1.12]; P=0.19). that much of the racial difference was associated
with the hospital center in which black patients
Resuscitation received care.
(See Tables 24-10 and 24-11 and • Stub et al47 reported a post hoc secondary anal-
ysis of a large, partial factorial trial of interven-
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 24-1)
tions for patients with OHCA. The quality of
• Quality measures in resuscitation have targeted hospital-based postresuscitation care given to
inpatient care settings. Started in 1999, the AHA each patient was assigned an evidence-based
GWTG–Resuscitation Registry remains the domi- quality score that considered (1) initiation of
nant source of US quality improvement data temperature management; (2) achievement
(Tables  24-10 and 24-11; Chart 24-1). GWTG– of target temperature 32°C to 34°C; (3) con-
Resuscitation is a voluntary hospital registry and tinuation of temperature management for >12
performance improvement initiative for in-hospi-
hours; (4) performance of coronary angiogra-
tal cardiac arrest.
phy within 24 hours; and (5) no withdrawal of
• Process measures for in-hospital resuscitation are
life-sustaining treatment before day 3. These
generally based on time to correct administration
were aggregated as hospital-level compos-
of specific resuscitation and postresuscitation pro-
ite performance scores, which varied widely
cedures, drugs, or therapies. Recent findings are
(median [IQR] scores from lowest to highest
discussed here.
• Among Medicare beneficiaries participating in hospital quartiles, 21% [20%–25%] versus
GWTG–Resuscitation, 1-year survival after in- 59% [55%–64%]). Adjusted survival to dis-
hospital cardiac arrest has increased modestly charge increased with each quartile of compos-
over the past decade for both shockable and ite performance score (from lowest to highest:
nonshockable presenting arrest rhythms (Chart 16.2%, 20.8%, 28.5%, and 34.8%; P<0.01).
24-1).42 However, despite an overall improvement Adjusted rates of favorable neurological out-
in survival, there remains lower survival in IHCA come also increased (from lowest quartile to
during off-hours (nights and weekends) com- highest: 8.3%, 13.8%, 22.2%, and 25.9%;
pared with on-hours events.43 P<0.01). Hospital score was significantly asso-
• In 103 932 in-hospital cardiac arrests between ciated with outcome after risk adjustment for
2000 and 2014, 12.7% had delays to epineph- established baseline factors (highest versus low-
rine administration, with marked variation across est adherence quartile: adjusted OR of survival,
hospitals. The delay was inversely correlated to 1.64 [95% CI, 1.13–2.38]).47

e448 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Table 24-1.  AMI Quality-of-Care Measures, 2016

CLINICAL STATEMENTS
ACTION Registry– ACTION Registry–

AND GUIDELINES
Quality-of-Care Measure GWTG STEMI* GWTG NSTEMI*
Aspirin within 24 h of admission† 98.4 97.8
Aspirin at discharge‡ 99.2 98.4

β-Blockers at discharge 98.2 97.0

Lipid-lowering medication at discharge§ 99.6 99.2

ARB/ACEI at discharge for patients with LVEF <40% 92.5 89.8
ACEI at discharge for AMI patients 64.8 52.0
ARB at discharge for AMI patients 12.9 17.0
Adult smoking cessation advice/counseling 98.1 98.1
Cardiac rehabilitation referral for AMI patients 83.4 75.2

Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; ACTION Registry–
GWTG, Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines;
AMI, acute myocardial infarction; ARB, angiotensin receptor blocker; LVEF, left ventricular ejection fraction;
NSTEMI, non–ST-segment–elevation myocardial infarction; and STEMI, ST-segment–elevation myocardial
infarction.
*ACTION Registry–GWTG: STEMI and NSTEMI patients are reported separately. Patients must be
admitted with acute ischemic symptoms within the previous 24 hours, typically reflected by a primary
diagnosis of STEMI or NSTEMI. Patients who are admitted for any other clinical condition are not eligible.
Data reported include data from the first quarter of 2016 to the fourth quarter of 2016.
†Effective January 1, 2015, this measure was updated in the ACTION Registry–GWTG to exclude patients
who are taking dabigatran, rivaroxaban, or apixaban (novel oral anticoagulant medications) at home.
‡Effective January 1, 2015, this measure was updated in the ACTION Registry–GWTG to exclude
patients who were prescribed dabigatran, rivaroxaban, or apixaban (novel oral anticoagulant medications)
at discharge.
§Denotes statin use at discharge. Use of nonstatin lipid-lowering agent was 3.9% for STEMI patients and
6.2% for NSTEMI patients in the ACTION Registry–GWTG.

Table 24-2.  Time Trends in ACTION Registry–GWTG CAD Quality-of-Care Measures, 2010 to 2016
Downloaded from http://ahajournals.org by on February 7, 2019

Quality-of-Care Measure 2010 2011 2012 2013 2014 2015 2016

Aspirin within 24 h of admission* 97 97.6 97.8 95.4 98.1 98.6 98.5
Aspirin at discharge† 98 98.3 98.4 98.4 98.7 98.7 98.7

β-Blockers at discharge 96 96.7 97.1 97.1 97.6 97.5 97.5

Statin use at discharge 92 98.4 98.8 98.8 99.1 99.2 99.4

ARB/ACEI at discharge for patients with LVEF <40% 86 87.8 89.7 90.0 91.2 90.2 91.0
Adult smoking cessation advice/counseling 98 98.4 98.4 98.4 98.6 98.0 98.1
Cardiac rehabilitation referral for AMI patients 75 76.5 77.3 77.2 79.4 77.8 78.6

Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; ACTION Registry–GWTG, Acute Coronary Treatment and Intervention
Outcomes Network Registry–Get With The Guidelines; AMI, acute myocardial infarction; ARB, angiotensin receptor blocker; CAD, coronary artery disease;
and LVEF, left ventricular ejection fraction.
*Effective January 1, 2015, this measure was updated in the ACTION Registry–GWTG to exclude patients taking dabigatran, rivaroxaban, or apixaban
(novel oral anticoagulant medications) at home.
†Effective January 1, 2015, this measure was updated in the ACTION Registry–GWTG to exclude patients who were prescribed dabigatran, rivaroxaban,
or apixaban (novel oral anticoagulant medications) at discharge.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e449

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Table 24-3.  Additional ACTION Registry–GWTG Quality-of-Care Metrics for AMI Care, 2016
CLINICAL STATEMENTS

Quality Metrics Overall STEMI NSTEMI

AND GUIDELINES

ECG within 10 min of arrival 68.1 77.0 64.2

Aspirin within 24 h of arrival 98.5 98.4 97.8
Any anticoagulant use* 95.0 96.7 93.8
Dosing errors
 UFH dose 49.4 46.9 49.6
 Enoxaparin dose 9.0 6.3 9.1
 Glycoprotein IIb/IIIa inhibitor dose 5.0 5.2 4.5
Aspirin at discharge 98.7 99.2 98.4
Prescribed statins on discharge 99.4 99.6 99.2
Adult smoking cessation advice/counseling 98.1 98.1 98.1
Cardiac rehabilitation referral 78.6 83.4 75.2
In-hospital mortality† (95% CI) 4.17 (4.01–4.41) 6.17 (5.90–6.64) 2.92 (2.79–3.17)

Values are percentages. Data reported include data from the first quarter of 2015 to the fourth quarter
of 2015. ACTION Registry–GWTG indicates Acute Coronary Treatment and Intervention Outcomes Network
Registry–Get With The Guidelines; AMI, acute myocardial infarction; NSTEMI, non–ST-segment–elevation
myocardial infarction; STEMI, ST-segment–elevation myocardial infarction; and UFH, unfractionated heparin.
*Includes UFH, low-molecular-weight heparin, or direct thrombin inhibitor use.
†Includes all patients.

Table 24-4.  Timely Reperfusion for AMI and Stroke

GWTG–Stroke ACTION Registry–

Quality-of-Care Measure (for Stroke) GWTG STEMI
STEMI
 Thrombolytic agents within N/A 52.0
Downloaded from http://ahajournals.org by on February 7, 2019

30 min
 PCI within 90 min* N/A 95.9
Stroke
 IV tPA in patients who arrived 87.74† N/A
<2 h after symptom onset,
treated ≤3 h
 IV tPA in patients who arrived 81.03†‡ N/A
<3.5 h after symptom onset,
treated ≤4.5 h
 IV tPA door-to-needle time 83.54† N/A
≤60 min

Values are percentages. AMI data from the ACTION registry, 2016. Stroke
data from the GWTG–Stroke registry June 2017 to May 2018. ACTION
Registry–GWTG indicates Acute Coronary Treatment and Intervention
Outcomes Network Registry–Get With The Guidelines; AMI, acute myocardial
infarction; IV, intravenous; N/A, not applicable; PCI, percutaneous coronary
intervention; STEMI, ST-segment–elevation myocardial infarction; and tPA,
tissue plasminogen activator.
*Excludes transfers.
†Reflects analysis performed for 2018 update.
‡IV tPA in patients who arrived <3.5 hours after symptom onset, treated
≤4.5 hours measure was changed in 2016 to include in-hospital strokes in the
denominator.

e450 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Table 24-5.  Quality of Care by Race/Ethnicity and Sex in the ACTION Registry, 2014

CLINICAL STATEMENTS
Race/Ethnicity Sex

AND GUIDELINES
Quality-of-Care Measure White Black Other Males Females
Aspirin at admission 98.1 98.2 98.3 98.4 97.7
Aspirin at discharge 98.8 98.0 98.8 98.9 98.2

β-Blockers at discharge 97.6 97.2 97.5 97.9 97.0

Time to PCI ≤90 min for STEMI patients 96.1 94.3 96.0 96.2 95.2

ARB/ACEI at discharge for patients with LVEF <40% 91.2 91.7 88.5 91.5 90.5
Statins at discharge 99.1 98.9 99.4 99.3 98.8

Values are percentages. Data reported include data from first quarter of 2015 to fourth quarter of 2015. ACEI indicates
angiotensin-converting enzyme inhibitor; ACTION, Acute Coronary Treatment and Intervention Outcomes Network; ARB,
angiotensin receptor blocker; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; and STEMI, ST-
segment–elevation myocardial infarction.

Table 24-6.  HF Quality-of-Care Measures, 2016

Quality-of-Care Measure AHA GWTG–HF

LVEF assessment 98.94
ARB/ACEI at discharge for patients with LVSD 93.66
Complete discharge instructions 94.06

β-Blockers at discharge for patients with LVSD, no 97.81

contraindications
Anticoagulation for AF or atrial flutter, no 85.48
contraindications

Values are percentages. ACEI indicates angiotensin-converting enzyme

inhibitor; AF, atrial fibrillation; AHA, American Heart Association; ARB,
angiotensin receptor blocker; GWTG–HF, Get With The Guidelines–Heart
Failure; HF, heart failure; LVEF, left ventricular ejection fraction; and LVSD, left
Downloaded from http://ahajournals.org by on February 7, 2019

ventricular systolic dysfunction.

Table 24-7.  Quality of Care by Race/Ethnicity and Sex in the GWTG–HF Program, 2016

Race/Ethnicity Sex
Quality-of-Care Measure White Black Hispanic Males Females
Postdischarge appointment* 78.35 79.18 70.65 77.64 77.62
Complete set of discharge instructions 93.60 95.21 95.17 94.63 93.37
Measure of LV function* 99.07 99.29 97.01 99.06 98.81
ACEI or ARB at discharge for patients with LVSD, no contraindications* 93.45 94.83 92.14 93.68 93.83
Smoking cessation counseling, current smokers 92.10 93.96 93.79 93.15 92.49

Evidence-based specific β-blockers* 91.88 94.69 91.52 92.88 92.25

β-Blockers at discharge for patients with LVSD, no contraindications 97.82 98.16 96.93 97.95 97.59

Hydralazine/nitrates at discharge for patients with LVSD, no … 31.53 20.00 33.30 28.07
contraindications†
Anticoagulation for AF or atrial flutter, no contraindications 86.11 84.23 83.14 86.10 84.73
Composite quality-of-care measure (using discharge instructions and β- 96.46 96.99 95.79 96.65 96.35
blocker at discharge)

Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; ellipses,
data not available; GWTG–HF, Get With The Guidelines−Heart Failure; LV, left ventricular; and LVSD, left ventricular systolic dysfunction.
*Indicates the 4 key achievement measures targeted in GWTG–HF.
†For black patients only.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e451

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Table 24-8.  National Committee for Quality Assurance Health Plan Employer Data and Information Set Measures of Care, 2016
CLINICAL STATEMENTS

Commercial Medicare Medicaid

AND GUIDELINES

HMO PPO HMO PPO HMO

Cardiovascular disease

 β-Blocker persistence after MI* 84.4 83.8 90.1 89.9 79.9

 BP control† 62.4 54.5 69.6 69.7 56.5

 Statin therapy for patients with CVD 79.2 79.9 77.3 76.8 74.7
DM
 HbA1c testing 90.6 89.3 93.5 93.6 86.7
 HbA1c >9.0% 33.0 42.5 26.3 23.3 43.3
 Eye examination performed 53.6 47.5 70.4 69.6 54.9
 Monitoring nephropathy 90.2 88.1 95.6 95.3 89.9
 BP <140/90 mm  Hg 61.6 50.5 63.9 60.6 59.7
 Statin therapy for patients with DM 60.2 58.9 70.7 67.8 60.2
Tobacco, nutrition, and lifestyle
 Advising smokers and tobacco users to quit 75.1 72.3 85.6 83.8 76.2
 BMI percentile assessment in children and adolescents (3–17 y of age) 65.2 52.0 N/A N/A 69.1
 Nutrition counseling (children and adolescents [3–17 y of age]) 60.8 50.0 N/A N/A 65.3
 Counseling for physical activity (children and adolescents [3–17 y of age]) 55.5 44.9 N/A N/A 57.6
 BMI assessment for adults 18–74 y of age 76.6 62.9 94.2 91.8 80.7

 Physical activity discussion in older adults (≥65 y of age) (2015 data) N/A 53.5 55.3 N/A

 Physical activity advice in older adults (≥65 y of age) (2015 data) N/A 50.5 49.9 N/A

Values are percentages. BMI indicates body mass index; BP, blood pressure; CVD, cardiovascular disease; DM, diabetes mellitus; HbA1c, hemoglobin
A1c; HMO, health maintenance organization; MI, myocardial infarction; N/A, not available or not applicable; and PPO, preferred provider organization.
*β-Blocker persistence: received persistent β-blocker treatment for 6 months after acute myocardial infarction hospital discharge.
†Adults 18 to 59 years of age with BP <140/90 mm Hg, adults aged 60 to 85 years with a diagnosis of DM and BP <140/90 mm Hg, and adults aged
Downloaded from http://ahajournals.org by on February 7, 2019

60 to 85 years without a diagnosis of DM and BP <150/90 mm Hg.

Table 24-9.  Quality of Care by Race/Ethnicity and Sex in the GWTG–Stroke Program, 2016

Race/Ethnicity Sex
Quality-of-Care Measure White Black Hispanic Males Females

IV tPA in patients who arrived ≤2 h after symptom onset, treated ≤3 h* 86.37 87.38 87.03 87.25 86.23

IV tPA in patients who arrived <3.5 h after symptom onset, treated ≤4.5 h† 45.83 49.24 50.97 47.54 46.58

IV tPA door-to-needle time ≤60 min 79.51 80.11 80.79 81.31 78.37

Thrombolytic complications: IV tPA and life-threatening, serious systemic hemorrhage 10.62 10.77 7.46 10.70 11.00
Antithrombotic agents <48 h after admission* 97.40 97.08 96.53 97.41 97.10
DVT prophylaxis by second hospital day* 99.24 99.19 99.04 99.21 99.23
Antithrombotic agents at discharge* 98.82 98.40 97.95 98.72 98.46
Anticoagulation for atrial fibrillation at discharge* 96.16 95.63 96.09 96.33 95.94
Therapy at discharge if LDL-C >100 mg/dL or LDL-C not measured or on therapy at 98.01 98.33 97.51 98.43 97.68
admission*
Counseling for smoking cessation* 97.48 97.40 97.11 97.49 97.39
Lifestyle changes recommended for BMI >25 kg/m 2
52.86 54.45 54.37 53.20 53.29
Composite quality-of-care measure 97.89 97.76 97.37 97.95 97.61

Values are percentages. BMI indicates body mass index; DVT, deep vein thrombosis; GWTG, Get With The Guidelines; IV, intravenous; LDL-C, low-density
lipoprotein cholesterol; and tPA, tissue-type plasminogen activator.
*Indicates the 7 key achievement measures targeted in GWTG–Stroke.
†This measure was changed in 2016 to include in-hospital strokes in the denominator.

e452 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

Table 24-10.  Quality of Care for Patients With Out-of-Hospital Cardiac Arrest at US ROC Sites (January 1, 2014 to December 31,

CLINICAL STATEMENTS
2014)

AND GUIDELINES
Overall Adults Children
Bystander and EMS care*
 Bystander CPR, % 46.1 (45.0–47.3) 45.7 (44.6–46.9) 61.4 (54.9–67.9)
 Shocked by AED before EMS, % 2.0 (1.7–2.4) 2.1 (1.7–2.4) 1.4 (0.0–3.0)
 Chest compression fraction during first 5 min of CPR, % 0.85 (0.12) 0.85 (0.12) 0.83 (0.13)
 Compression depth, mm 48.1 (10.7) 48.1 (10.7) 47.2 (9.5)
 Preshock pause duration, s 10.8 (11.0) 10.8 (10.9) 16.2 (16.4)
 Time to first EMS defibrillator applied, min 8.8 (4.5) 8.8 (4.5) 8.7 (4.2)
Hospital-based metrics†
 Hypothermia induced after initial VT/VF, %‡ 66.3 (62.3–70.3) 66.2 (62.1–70.2) 100 (100–100)
 No order for withdrawal/DNR during first 72 h, %§ 45.0 (42.1–48.0) 44.8 (41.9–47.8) 100 (100–100)
 Implantable cardioverter-defibrillator assessment, initial VT/ 30.3 (24.8–35.8) 30.0 (24.5–35.6) 100 (100–100)
VF, no AMI per MD notes or final ECG interpretation, %‖

Values are mean (95% confidence interval) or mean (SD). Because age is missing for some cases, these cases are not included in either adults
or children, thus explaining why overall rates equal the adult rates when rates for children are not available. AED indicates automated external
defibrillator; AMI, acute myocardial infarction; CPR, cardiopulmonary resuscitation; DNR, do not resuscitate; EMS, emergency medical services;
MD, medical doctor; ROC, Resuscitation Outcomes Consortium; VF; ventricular fibrillation; and VT, ventricular tachycardia.
*Data are from EMS-treated cases.
†During 2014, there was 1 pediatric case with initial rhythm VT/VF admitted to the hospital.
‡Denominator is all cases with initial rhythm VT/VF and admitted to the hospital.
§Denominator is all cases admitted to the hospital.
‖Denominator is all cases with initial rhythm VT/VF, no indication of AMI, no percutaneous coronary intervention, no bypass, and admitted to
the hospital.

Table 24-11.  Quality of Care of Patients With In-Hospital Cardiac

Arrest Among GWTG–Resuscitation Hospitals, 2016
Downloaded from http://ahajournals.org by on February 7, 2019

Adults Children
Event outside critical care setting 46.3 12.5
All objective CPR data collected 98.7 99.1
ETco2 used during arrest 6.9 33.2
Induced hypothermia after resuscitation 7.6 10.7
from shockable rhythm

Values are mean percentages. CPR indicates cardiopulmonary resuscitation;

ETco2, end-tidal CO2; and GWTG, Get With The Guidelines.
Source: GWTG–Resuscitation Investigators, June 2017.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e453

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24
CLINICAL STATEMENTS
AND GUIDELINES

Chart 24-1. Survival rates after out-of-hospital cardiac arrest in US sites of the Resuscitation Outcomes Consortium, 2006 to 2014.
AED indicates automated external defibrillator; CPR, cardiopulmonary resuscitation; and EMS, emergency medical services.

11. Medicare Hospital Quality 2017 Chartbook: Performance Report on

REFERENCES Outcome Measures. Centers for Medicare & Medicaid Services website.
https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-
1. Committee on Quality of Health Care in America, Institute of Medicine.
Instruments/HospitalQualityInits/OutcomeMeasures.html. Accessed April
Crossing the Quality Chasm: A New Health System for the 21st Century.
Washington, DC: National Academy Press; 2001. 20, 2017.
2. Quality of Care and Outcomes Research in CVD and Stroke Working 12. Mathews R, Wang W, Kaltenbach LA, Thomas L, Shah RU, Ali M,
Peterson ED, Wang TY. Hospital variation in adherence rates to second-
Downloaded from http://ahajournals.org by on February 7, 2019

Groups. Measuring and improving quality of care: a report from the

American Heart Association/American College of Cardiology First ary prevention medications and the implications on quality. Circulation.
Scientific Forum on Assessment of Healthcare Quality in Cardiovascular 2018;137:2128–2138. doi: 10.1161/CIRCULATIONAHA.117.029160
Disease and Stroke. Circulation. 2000;101:1483–1493. 13. Kumbhani DJ, Fonarow GC, Heidenreich PA, Schulte PJ, Lu D, Hernandez
3. American College of Cardiology Quality Improvement for Institutions A, Yancy C, Bhatt DL. Association between hospital volume, processes
Registries. https://cvquality.acc.org/NCDR-Home/Registries. Accessed March 6, of care, and outcomes in patients admitted with heart failure: insights
2018. from Get With The Guidelines-Heart Failure. Circulation. 2018;137:1661–
4. American Heart Association Focus on Quality. American Heart Association 1670. doi: 10.1161/CIRCULATIONAHA.117.028077
website. http://www.heart.org/en/professional/quality-improvement. Accessed 14. Gupta A, Allen LA, Bhatt DL, Cox M, DeVore AD, Heidenreich PA,
August 31, 2018. Hernandez AF, Peterson ED, Matsouaka RA, Yancy CW, Fonarow GC.
5. Wadhera RK, Joynt Maddox KE, Wang Y, Shen C, Bhatt DL, Yeh RW. Association of the Hospital Readmissions Reduction Program implemen-
Association between 30-day episode payments and acute myocardial tation with readmission and mortality outcomes in heart failure. JAMA
infarction outcomes among Medicare beneficiaries. Circ Cardiovasc Qual Cardiol. 2018;3:44–53. doi: 10.1001/jamacardio.2017.4265
Outcomes. 2018;11:e004397. doi: 10.1161/CIRCOUTCOMES.117.004397 15. Pokharel Y, Khariton Y, Tang Y, Nassif ME, Chan PS, Arnold SV, Jones
6. Chatterjee P, Joynt Maddox KE. US national trends in mortality from acute PG, Spertus JA. Association of serial Kansas City Cardiomyopathy
myocardial infarction and heart failure: policy success or failure? JAMA Questionnaire assessments with death and hospitalization in patients with
Cardiol. 2018;3:336–340. doi: 10.1001/jamacardio.2018.0218 heart failure with preserved and reduced ejection fraction: a secondary
7. Pandey A, Golwala H, Hall HM, Wang TY, Lu D, Xian Y, Chiswell K, Joynt analysis of 2 randomized clinical trials. JAMA Cardiol. 2017;2:1315–1321.
KE, Goyal A, Das SR, Kumbhani D, Julien H, Fonarow GC, de Lemos doi: 10.1001/jamacardio.2017.3983
JA. Association of US Centers for Medicare and Medicaid Services hos- 16. Pandey A, Omar W, Ayers C, LaMonte M, Klein L, Allen NB, Kuller LH,
pital 30-day risk-standardized readmission metric with care quality and Greenland P, Eaton CB, Gottdiener JS, Lloyd-Jones DM, Berry JD. Sex and
outcomes after acute myocardial infarction: findings from the National race differences in lifetime risk of heart failure with preserved ejection
Cardiovascular Data Registry/Acute Coronary Treatment and Intervention fraction and heart failure with reduced ejection fraction. Circulation.
Outcomes Network Registry-Get With the Guidelines. JAMA Cardiol. 2018;137:1814–1823. doi: 10.1161/CIRCULATIONAHA.117.031622
2017;2:723–731. doi: 10.1001/jamacardio.2017.1143 17. Ziaeian B, Kominski GF, Ong MK, Mays VM, Brook RH, Fonarow GC.
8. Bucholz EM, Butala NM, Ma S, Normand ST, Krumholz HM. Life expec- National differences in trends for heart failure hospitalizations by sex and
tancy after myocardial infarction, according to hospital performance. N race/ethnicity. Circ Cardiovasc Qual Outcomes. 2017;10:e003552. doi:
Engl J Med. 2016;375:1332–1342. doi: 10.1056/NEJMoa1513223 10.1161/CIRCOUTCOMES.116.003552
9. Makam AN, Nguyen OK. Use of cardiac biomarker testing in the 18. Pandey A, Patel KV, Liang L, DeVore AD, Matsouaka R, Bhatt DL,
emergency department. JAMA Intern Med. 2015;175:67–75. doi: Yancy CW, Hernandez AF, Heidenreich PA, de Lemos JA, Fonarow GC.
10.1001/jamainternmed.2014.5830 Association of hospital performance based on 30-day risk-standardized
10. Rao KK, Enriquez JR, de Lemos JA, Alexander KP, Chen AY, McGuire mortality rate with long-term survival after heart failure hospitalization:
DK, Fonarow GC, Das SR. Use of aldosterone antagonists at discharge an analysis of the Get With The Guidelines-Heart Failure Registry. JAMA
after myocardial infarction: results from the National Cardiovascular Cardiol. 2018;3:489–497. doi: 10.1001/jamacardio.2018.0579
Data Registry Acute Coronary Treatment and Intervention Outcomes 19. Pandey A, Golwala H, Xu H, DeVore AD, Matsouaka R, Pencina M,
Network (ACTION) Registry-Get With The Guidelines (GWTG). Am Heart Kumbhani DJ, Hernandez AF, Bhatt DL, Heidenreich PA, Yancy CW, de
J. 2013;166:709–715. doi: 10.1016/j.ahj.2013.06.020 Lemos JA, Fonarow GC. Association of 30-day readmission metric for

e454 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 24

heart failure under the Hospital Readmissions Reduction Program with 33. Yong CM, Liu Y, Apruzzese P, Doros G, Cannon CP, Maddox TM, Gehi A,

CLINICAL STATEMENTS
quality of care and outcomes. JACC Heart Fail. 2016;4:935–946. doi: Hsu JC, Lubitz SA, Virani S, Turakhia MP; ACC PINNACLE Investigators.

AND GUIDELINES
10.1016/j.jchf.2016.07.003 Association of insurance type with receipt of oral anticoagulation in
20. Desai NR, Ross JS, Kwon JY, Herrin J, Dharmarajan K, Bernheim SM, insured patients with atrial fibrillation: a report from the American College
Krumholz HM, Horwitz LI. Association between hospital penalty status of Cardiology NCDR PINNACLE registry. Am Heart J. 2018;195:50–59.
under the Hospital Readmission Reduction Program and readmission rates doi: 10.1016/j.ahj.2017.08.010
for target and nontarget conditions. JAMA. 2016;316:2647–2656. doi: 34. Hsu JC, Maddox TM, Kennedy K, Katz DF, Marzec LN, Lubitz SA, Gehi
10.1001/jama.2016.18533 AK, Turakhia MP, Marcus GM. Aspirin instead of oral anticoagulant pre-
21. Krumholz HM, Wang K, Lin Z, Dharmarajan K, Horwitz LI, Ross JS, Drye EE, scription in atrial fibrillation patients at risk for stroke. J Am Coll Cardiol.
Bernheim SM, Normand ST. Hospital-readmission risk: isolating hospital 2016;67:2913–2923. doi: 10.1016/j.jacc.2016.03.581
effects from patient effects. N Engl J Med. 2017;377:1055–1064. doi: 35. Perino AC, Fan J, Schmitt SK, Askari M, Kaiser DW, Deshmukh
10.1056/NEJMsa1702321 A, Heidenreich PA, Swan C, Narayan SM, Wang PJ, Turakhia MP.
22. Dharmarajan K, Wang Y, Lin Z, Normand ST, Ross JS, Horwitz LI, Desai NR, Treating specialty and outcomes in newly diagnosed atrial fibrilla-
Suter LG, Drye EE, Bernheim SM, Krumholz HM. Association of changing tion: from the TREAT-AF Study. J Am Coll Cardiol. 2017;70:78–86. doi:
hospital readmission rates with mortality rates after hospital discharge. 10.1016/j.jacc.2017.04.054
JAMA. 2017;318:270–278. doi: 10.1001/jama.2017.8444 36. Lewis WR, Piccini JP, Turakhia MP, Curtis AB, Fang M, Suter RE, Page RL 2nd,
23. Pokharel Y, Gosch K, Nambi V, Chan PS, Kosiborod M, Oetgen WJ, Spertus Fonarow GC. Get With The Guidelines AFIB: novel quality improvement
JA, Ballantyne CM, Petersen LA, Virani SS. Practice-level variation in statin registry for hospitalized patients with atrial fibrillation. Circ Cardiovasc Qual
use among patients with diabetes: insights from the PINNACLE registry. J Outcomes. 2014;7:770–777. doi: 10.1161/CIRCOUTCOMES.114.001263
Am Coll Cardiol. 2016;68:1368–1369. doi: 10.1016/j.jacc.2016.06.048 37. Bettger JP, Thomas L, Liang L, Xian Y, Bushnell CD, Saver JL, Fonarow
24. Hira RS, Kennedy K, Jneid H, Alam M, Basra SS, Petersen LA, Ballantyne GC, Peterson ED. Hospital variation in functional recovery after stroke.
CM, Nambi V, Chan PS, Virani SS. Frequency and practice-level variation in Circ Cardiovasc Qual Outcomes. 2017;10:e002391. doi: 10.1161/
inappropriate and nonrecommended prasugrel prescribing: insights from CIRCOUTCOMES.115.002391
the NCDR PINNACLE registry. J Am Coll Cardiol. 2014;63(pt A):2876– 38. Fonarow GC, Zhao X, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Xian Y,
2877. doi: 10.1016/j.jacc.2014.04.011 Hernandez AF, Peterson ED, Schwamm LH. Door-to-needle times for tis-
25. Hira RS, Kennedy K, Nambi V, Jneid H, Alam M, Basra SS, Ho PM, Deswal sue plasminogen activator administration and clinical outcomes in acute
A, Ballantyne CM, Petersen LA, Virani SS. Frequency and practice-level ischemic stroke before and after a quality improvement initiative. JAMA.
variation in inappropriate aspirin use for the primary prevention of car- 2014;311:1632–1640. doi: 10.1001/jama.2014.3203
diovascular disease: insights from the National Cardiovascular Disease 39. Xian Y, Xu H, Lytle B, Blevins J, Peterson ED, Hernandez AF, Smith EE,
Registry’s Practice Innovation and Clinical Excellence registry. J Am Coll Saver JL, Messé SR, Paulsen M, Suter RE, Reeves MJ, Jauch EC, Schwamm
Cardiol. 2015;65:111–121. doi: 10.1016/j.jacc.2014.10.035 LH, Fonarow GC. Use of strategies to improve door-to-needle times with
26. Hall HM, de Lemos JA, Enriquez JR, McGuire DK, Peng SA, Alexander tissue-type plasminogen activator in acute ischemic stroke in clinical
KP, Roe MT, Desai N, Wiviott SD, Das SR. Contemporary patterns practice: findings from Target: Stroke. Circ Cardiovasc Qual Outcomes.
of discharge aspirin dosing after acute myocardial infarction in the 2017;10:e003227. doi: 10.1161/CIRCOUTCOMES.116.003227
United States: results from the National Cardiovascular Data Registry 40. Ekundayo OJ, Saver JL, Fonarow GC, Schwamm LH, Xian Y, Zhao X,
(NCDR). Circ Cardiovasc Qual Outcomes. 2014;7:701–707. doi: Hernandez AF, Peterson ED, Cheng EM. Patterns of emergency medical
10.1161/CIRCOUTCOMES.113.000822 services use and its association with timely stroke treatment: findings
27. Virani SS, Woodard LD, Wang D, Chitwood SS, Landrum CR, Urech TH, Pietz from Get With the Guidelines-Stroke. Circ Cardiovasc Qual Outcomes.
Downloaded from http://ahajournals.org by on February 7, 2019

K, Chen GJ, Hertz B, Murawsky J, Ballantyne CM, Petersen LA. Correlates 2013;6:262–269. doi: 10.1161/CIRCOUTCOMES.113.000089
of repeat lipid testing in patients with coronary heart disease. JAMA Intern 41. Peterson PN, Varosy PD, Heidenreich PA, Wang Y, Dewland TA, Curtis JP,
Med. 2013;173:1439–1444. doi: 10.1001/jamainternmed.2013.8198 Go AS, Greenlee RT, Magid DJ, Normand SL, Masoudi FA. Association of
28. Heller DJ, Coxson PG, Penko J, Pletcher MJ, Goldman L, Odden MC, single- vs dual-chamber ICDs with mortality, readmissions, and compli-
Kazi DS, Bibbins-Domingo K. Evaluating the impact and cost-effec- cations among patients receiving an ICD for primary prevention. JAMA.
tiveness of statin use guidelines for primary prevention of coronary 2013;309:2025–2034. doi: 10.1001/jama.2013.4982
heart disease and stroke. Circulation. 2017;136:1087–1098. doi: 42. Thompson LE, Chan PS, Tang F, Nallamothu BK, Girotra S, Perman SM,
10.1161/CIRCULATIONAHA.117.027067 Bose S, Daugherty SL, Bradley SM; American Heart Association’s Get
28a. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel With the Guidelines-Resuscitation Investigators. Long-term survival trends
RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz of Medicare patients after in-hospital cardiac arrest: insights from Get
JS, Shero ST, Smith SC Jr, Watson K, Wilson PW. 2013 ACC/AHA guideline With The Guidelines-Resuscitation. Resuscitation. 2018;123:58–64. doi:
on the treatment of blood cholesterol to reduce atherosclerotic cardio- 10.1016/j.resuscitation.2017.10.023
vascular risk in adults: a report of the American College of Cardiology/ 43. Ofoma UR, Basnet S, Berger A, Kirchner HL, Girotra S; American Heart
American Heart Association Task Force on Practice Guidelines [pub- Association Get With The Guidelines–Resuscitation Investigators. Trends
lished corrections appear in Circulation. 2015;132:e396 and Circulation. in survival after in-hospital cardiac arrest during nights and weekends. J
2014;129(Suppl 2):S46-S48]. Circulation. 2014;129(Suppl 2):S1–S45. Am Coll Cardiol. 2018;71:402–411. doi: 10.1016/j.jacc.2017.11.043
29. Salami JA, Warraich HJ, Valero-Elizondo J, Spatz ES, Desai NR, Rana JS, 44. Khera R, Chan PS, Donnino M, Girotra S; for the American Heart
Virani SS, Blankstein R, Khera A, Blaha MJ, Blumenthal RS, Katzen BT, Association’s Get With The Guidelines-Resuscitation Investigators.
Lloyd-Jones D, Krumholz HM, Nasir K. National trends in nonstatin use Hospital variation in time to epinephrine for nonshockable in-
and expenditures among the US adult population from 2002 to 2013: hospital cardiac arrest. Circulation. 2016;134:2105–2114. doi:
insights from Medical Expenditure Panel Survey. J Am Heart Assoc. 10.1161/CIRCULATIONAHA.116.025459
2018;7:e007132. doi: 10.1161/JAHA.117.007132 45. Anderson ML, Nichol G, Dai D, Chan PS, Thomas L, Al-Khatib SM,
30. Mazurek M, Huisman MV, Lip GYH. Registries in atrial fibrillation: from Berg RA, Bradley SM, Peterson ED; American Heart Association’s Get
trials to real-life clinical practice. Am J Med. 2017;130:135–145. doi: With The Guidelines–Resuscitation Investigators. Association between
10.1016/j.amjmed.2016.09.012 hospital process composite performance and patient outcomes after
31. Heidenreich PA, Solis P, Mark Estes NA 3rd, Fonarow GC, Jurgens in-hospital cardiac arrest care. JAMA Cardiol. 2016;1:37–45. doi:
CY, Marine JE, McManus DD, McNamara RL. 2016 ACC/AHA clini- 10.1001/jamacardio.2015.0275
cal performance and quality measures for adults with atrial fibrilla- 46. Chan PS, Nichol G, Krumholz HM, Spertus JA, Jones PG, Peterson ED,
tion or atrial flutter: a report of the American College of Cardiology/ Rathore SS, Nallamothu BK; American Heart Association National Registry
American Heart Association Task Force on Performance Measures. of Cardiopulmonary Resuscitation (NRCPR) Investigators. Racial differ-
Circ Cardiovasc Qual Outcomes. 2016;9:443–488. doi: 10.1161/HCQ. ences in survival after in-hospital cardiac arrest. JAMA. 2009;302:1195–
0000000000000018 1201. doi: 10.1001/jama.2009.1340
32. Huisman MV, Rothman KJ, Paquette M, Teutsch C, Diener HC, Dubner 47. Stub D, Schmicker RH, Anderson ML, Callaway CW, Daya MR, Sayre MR,
SJ, Halperin JL, Ma CS, Zint K, Elsaesser A, Bartels DB, Lip GY; GLORIA-AF Elmer J, Grunau BE, Aufderheide TP, Lin S, Buick JE, Zive D, Peterson ED,
Investigators. The changing landscape for stroke prevention in AF: findings Nichol G; ROC Investigators. Association between hospital post-resuscita-
from the GLORIA-AF Registry phase 2. J Am Coll Cardiol. 2017;69:777– tive performance and clinical outcomes after out-of-hospital cardiac arrest.
785. doi: 10.1016/j.jacc.2016.11.061 Resuscitation. 2015;92:45–52. doi: 10.1016/j.resuscitation.2015.04.015

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e455

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 25

25. MEDICAL PROCEDURES Inpatient Cardiac Catheterization and PCI

CLINICAL STATEMENTS

See Tables 25-1 and 25-2 and Charts 25-1 (See Tables 25-1 and 25-2)
AND GUIDELINES

through 25-4 • Inpatient PCI discharges decreased from 359 000

for males and 190 000 for females in 1997 to
Click here to return to the Table of Contents 325  000 and 155  000, respectively, by 2014
(Chart 25-1).
Trends in Operations and Procedures • Data on Medicare beneficiaries undergoing a cor-
(See Tables 25-1 and 25-2 and Charts 25-1 onary revascularization procedure between 2008
and 25-2) and 2012 indicate that the rapid growth in non-
• The mean hospital charges for cardiovascular pro- admission PCIs (from 60 405 to 106 495) has been
cedures in 2014 ranged from $43 484 for carotid more than offset by the decrease in PCI admis-
endarterectomy to $808 770 for heart transplan- sions (from 363 384 to 295 434).2
tations (Table 25-1). • In 2014, the mean inpatient hospital charge for
• The trends in the numbers of 5 common cardio- PCI was $84 813 (Table 25-1).
vascular procedures in the United States from • From 2004 to 2014, the number of inpatient car-
1993 to 2014 are presented in Chart 25-1. Of diac catheterizations decreased from 1 486 000
the 5 procedures, cardiac catheterization was the to 1 016 000 annually (HCUP, NHLBI tabulation;
most common procedure for all years presented Chart 25-1).
(Chart 25-1). • In 2014, an estimated 480 000 inpatient PCI (pre-
• Of the 10 leading diagnostic groups in the United viously referred to as percutaneous transluminal
States, the greatest number of surgical proce- coronary angioplasty, or PTCA) procedures were
dures were cardiovascular and obstetrical proce- performed in the United States (HCUP, NHLBI tab-
dures (Chart 25-2). ulation; Chart 25-1).
• The total number of inpatient cardiovascular • In 2014, ≈68% of PCI procedures were per-
operations and procedures decreased 6%, from formed on males, and ≈50% were performed on
8 461 000 in 2004 to 7 971 000 in 2014 (NHLBI people ≥65 years of age (HCUP, NHLBI tabulation;
tabulation of HCUP data; Table 25-2). Table 25-2).
• Data from the HCUP were examined for trends • Inpatient hospital deaths for PCI increased from
Downloaded from http://ahajournals.org by on February 7, 2019

from 1997 to 2014 for use of PCI and CABG.1 0.8% in 2004 to 2.1% in 2014 (HCUP, NHLBI tab-
ulation). In 2014, ≈82% of stents implanted dur-
ing PCI were drug-eluting stents compared with
Coronary Artery Bypass Grafting 18% that were bare-metal stents (HCUP, NHLBI
• The number of inpatient discharges for CABG tabulation).
decreased from 683 000 in 1997 to 371 000 in • The rate of any cardiac stent procedure per
2014 (Chart 25-1). 10 000 population rose by 61% from 1999 to
• In 1997, the number of inpatient discharges for 2006, then declined by 27% between 2006 and
CABG was 484 000 for males and 199 000 for 2009.3
females; these declined to 277 000 and 94 000,
respectively, in 2014. Cardiac Open Heart Surgery
Abbreviations Used in Chapter 25
• Data from the STS Adult Cardiac Surgery
Database, which voluntarily collects data from
ASD atrial septal defect
AV atrioventricular
≈80% of all hospitals that perform CABG in the
CABG coronary artery bypass graft United States, indicate that a total of 159 869
HCUP Healthcare Cost and Utilization Project procedures involved isolated CABG in 2016.4
HLHS hypoplastic left heart syndrome • Among other major procedures, there were
ICD-9-CM International Classification of Diseases, 9th Revision, 28 493 isolated aortic valve replacements and
Clinical Modification
NHLBI National Heart, Lung, and Blood Institute
7706 isolated mitral valve replacements; 17 507
PCI percutaneous coronary intervention procedures involved both aortic valve replace-
PTCA percutaneous transluminal coronary angioplasty ment and CABG, whereas 2935 procedures
STS Society of Thoracic Surgeons involved both mitral valve replacement and
VSD ventricular septal defect CABG.4

e456 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 25

Congenital Heart Surgery, 2013 to 2016 are 254 transplantation hospitals in the United

CLINICAL STATEMENTS
States, 139 of which performed heart transplan-
According to data from the STS Congenital Heart

AND GUIDELINES
tations in 2017.
Surgery Database5:
• Of the recipients in 2017, 71.6% were male, and
• There were 122 193 procedures performed from
61.6% were white; 23.3% were black, whereas
January 2013 to December 2016. The in-hospital
10.0% were Hispanic. Heart transplantations by
mortality rate was 3.0% during that time period.
recipient age are shown in Chart 25-4.
The 5 most common diagnoses were type 2 VSD
• For transplantations that occurred between 2012
(6.2%), HLHS (6.0%), patent ductus arteriosus
and 2015, the 1-year survival rate was 90.5% for
(4.8%), open sternum with open skin (4.1%),
males and 91.1% for females; the 5-year survival
and secundum ASD (4.0%).5
rates based on 2008 to 2011 transplantations
• The 5 most common primary procedures were
were 78.3% for males and 77.7% for females.
delayed sternal closure (8.0%), patch VSD repair
The 1- and 5-year survival rates for white cardiac
(6.3%), mediastinal exploration (3.6%), patch
transplantation patients were 90.7% and 79.0%,
ASD repair (3.2%), and complete AV canal (AV
respectively. For black patients, they were 90.7%
septal defect) repair (2.8%).5
and 74.1%, respectively. For Hispanic patients,
they were 90.1% and 79.9%, respectively. For
Heart Transplantations Asian patients, they were 91.3% and 80.0%,
(See Charts 25-3 and 25-4) respectively.
• As of April 27, 2018, 3994 patients were on
According to data from the Organ Procurement and
the transplant waiting list for a heart transplant,
Transplantation Network (as of April 27, 2018)6
and 55 patients were on the list for a heart/lung
• In 2017, 3244 heart transplantations were per-
transplant.‍
formed in the United States (Chart 25-3). There

Table 25-1.  2014 National HCUP Statistics: Mean Hospital Charges, In-Hospital Death Rates, and Mean Length of Stay for
Various Cardiovascular Procedures
Downloaded from http://ahajournals.org by on February 7, 2019

Mean Hospital In-Hospital Mean Length

Procedure Charges, $ Death Rate, % of Stay, d ICD-9-CM Procedure Codes
Total vascular and cardiac surgery 90 215 3.34 6.3 35–39, 00.50–00.51,
and procedures 00.53–00.55, 00.61–00.66
Cardiac revascularization (bypass) 168 541 1.78 9.3 36.1–36.3
PCI 84 813 2.07 3.5 00.66, 17.55, 36.01, 36.02, 36.05
Cardiac catheterization 57 494 1.42 4.2 37.21–37.23
Pacemakers 83 521 1.46 5.1 37.7–37.8, 00.50, 00.53
Implantable defibrillators 171 476 0.69 6.3 37.94–37.99, 00.51, 00.54
Carotid endarterectomy 43 484 0.27 2.6 38.12
Heart valves 201 557 3.36 9.7 35.00–35.14, 35.20–35.28, 35.96,
35.97, 35.99
Heart transplantations 808 770 7.84 45.4 37.51

Principal procedure only. HCUP indicates Healthcare Cost and Utilization Project; ICD-9-CM, International Classification of Diseases,
Clinical Modification, 9th Revision; and PCI, percutaneous coronary intervention.
Data derived from the Agency for Healthcare Research and Quality.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e457

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 25

Table 25-2.  Estimated* Inpatient Cardiovascular Operations, Procedures, and Patient Data by Sex and Age: United States, 2014 (in Thousands)
CLINICAL STATEMENTS

Sex Age, y
AND GUIDELINES

Operation/Procedure/
Patients ICD-9-CM Procedure Codes All Male Female 18–44 45–64 64–84 ≥85
Heart valves 35.00–35.14, 35.20–35.28, 35.96, 156 92 63 11 40 83 16
35.97, 35.99
PCI 00.66, 17.55, 36.01, 36.02, 36.05 480 325 155 26 213 212 28
PCI with stents 36.06, 36.07 434 294 140 24 194 191 25
Coronary artery bypass graft 36.1–36.3 371 276 94 10 148 204 9
Cardiac catheterization 37.21–37.23 1016 625 391 68 432 455 54
Pacemakers 37.7, 37.8, 00.50, 00.53 351 185 166 9 57 197 85
  Pacemaker devices 37.8, 00.53 141 72 69 3 19 80 38
  Pacemaker leads 37.7, 00.50 210 114 97 7 38 117 47
Implantable defibrillators 37.94–37.99, 00.51, 00.54 60 43 17 4 21 30 3
Carotid endarterectomy 38.12 86 51 35 0 20 60 6
Total vascular and cardiac 35–39, 00.50–00.51, 7971 4602 3368 777 2860 3402 558
surgery and procedures†‡ 00.53– 00.55, 00.61–00.66

These data do not reflect any procedures performed on an outpatient basis. Many more procedures are being performed on an outpatient basis. Some of the lower
numbers in this table compared with 2006 probably reflect this trend. Data include procedures performed on newborn infants. Some of the ICD-9-CM procedure
codes may have changed over the years. ICD-9-CM indicates International Classification of Diseases, Clinical Modification, 9th Revision; and PCI, percutaneous
coronary intervention.
*Breakdowns are not available for some procedures, so entries for some categories do not add to totals. These data include codes for which the estimated number
of procedures is <5000. Categories with such small numbers are considered unreliable by the National Center for Health Statistics and in some cases may have been
omitted.
†Totals include procedures not shown here.
‡This estimate includes angioplasty and stent insertions for noncoronary arteries.
Data derived from Healthcare Cost and Utilization Project National Inpatient Sample, 2014, Agency for Healthcare Research and Quality.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 25-1. Trends in cardiovascular procedures, United States, 1993 to 2014; inpatient procedures only.
Data derived from Healthcare Cost and Utilization Project, National (Nationwide) Inpatient Sample, Agency for Healthcare Research.1

e458 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 25

CLINICAL STATEMENTS
AND GUIDELINES
Chart 25-2. Number of surgical procedures in the 10 leading diagnostic groups, United States, 2014.
Data derived from Healthcare Cost and Utilization Project, National (Nationwide) Inpatient Sample, Agency for Healthcare Research.1
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 25-3. Trends in heart transplantations, 1975 to 2017.

Data derived from Organ Procurement and Transplantation Network as of April 27, 2018.6

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e459

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 25
CLINICAL STATEMENTS
AND GUIDELINES

Chart 25-4. Heart transplantations in the United States by recipient age, 2017.
Data derived from Organ Procurement and Transplantation Network as of April 27, 2018.6

4. Adult Cardiac Surgery Database: Executive Summary: 10 Years: STS

‍REFERENCES Period Ending 06/30/2017. Society of Thoracic Surgeons website.
https://www.sts.org/sites/default/files/documents/ACSD2017Harvest3_
1. HCUPnet: Healthcare Cost and Utilization Project. Agency for Healthcare
Downloaded from http://ahajournals.org by on February 7, 2019

ExecutiveSummary.pdf. Accessed March 14, 2018.

Research and Quality website. https://hcupnet-archive.ahrq.gov/. Accessed
5. STS Congenital Heart Surgery Database. All Patients. STS Period Ending
May 1, 2017.
12/31/2016. Society of Thoracic Surgeons website. https://www.sts.
2. Culler SD, Kugelmass AD, Brown PP, Reynolds MR, Simon AW. Trends
org/sites/default/files/documents/CHSD_ExecutiveSummary_AllPatients_
in coronary revascularization procedures among Medicare beneficia-
Spring2017.pdf. Accessed March 14, 2018.
ries between 2008 and 2012. Circulation. 2015;131:362–370. doi:
6. Organ Procurement and Transplantation Network website. https://optn.
10.1161/CIRCULATIONAHA.114.012485
transplant.hrsa.gov/data/. Accessed April 27, 2018.
3. Auerbach DI, Maeda JL, Steiner C. Hospital stays with cardiac stents,
2009. HCUP Statistical Brief #128. Rockville, MD: Agency for Healthcare
Research and Quality; April 2012.

e460 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26

26. ECONOMIC COST OF workers, people keeping house, people in institutions,

CLINICAL STATEMENTS
and people unable to work. Those morbidity costs
CARDIOVASCULAR DISEASE

AND GUIDELINES
were substantial in very old studies, but because of the
See Tables 26-1 and 26-2 and Charts 26-1 lack of contemporary data, an adequate update could
through 26-6 not be made.

Click here to return to the Table of Contents

Most Costly Diseases
Using data from MEPS, the annual direct and indirect (See Tables 26-1 and 26-2 and Chart 26-2)
cost of CVD in the United States is an estimated $351.2 CVD and stroke accounted for 14% of total US health
billion (Table 26-1 and Chart 26-1). This figure includes expenditures in 2014 to 2015, more than any major
$213.8 billion in expenditures (direct costs, which diagnostic group.1 By way of comparison, CVD total
include the cost of physicians and other profession- direct costs shown in Table 26-1 are higher than the
als, hospital services, prescribed medication, and home 2014 to 2015 Agency for Healthcare Research and
health care, but not the cost of nursing home care) and Quality estimates for cancer, which were $84.0 bil-
$137.4 billion in lost future productivity attributed to lion (55% for outpatient or doctor office visits,
premature CVD and stroke mortality in 2014 to 2015 32% for inpatient care, and 9% for prescription
(indirect costs). drugs).1
The direct costs for CVD and stroke for 2014 to Table  26-2 shows direct and indirect costs for
2015 (average annual) are available on the website of CVD by sex and by 2 broad age groups. Chart 26-2
the nationally representative MEPS of the Agency for shows total direct costs for the 21 leading chronic
Healthcare Research and Quality.1 Details on the advan- diseases on the MEPS list. HD is the most costly
tages or disadvantages of using MEPS data are pro- condition.1
vided in the “Heart Disease and Stroke Statistics–2011 The estimated direct costs of CVD and stroke in
Update.”2 Indirect mortality costs are estimated for the United States increased from $103.5 billion in
2014 to 2015 (average annual) by multiplying the 1996 to 1997 to $213.8 billion in 2014 to 2015
number of deaths for those years attributable to CVD (Chart 26-3).
and strokes, in age and sex groups, by estimates of the
present value of lifetime earnings for those age and sex
Downloaded from http://ahajournals.org by on February 7, 2019

groups as of 2014 to 2015. Mortality data are from the Projections

National Vital Statistics System of the NCHS.3 The pres- (See Charts 26-3 through 26-6)
ent values of lifetime earnings are unpublished esti- • The AHA developed methodology to project future
mates furnished by the Institute for Health and Aging, costs of care for HBP, CHD, HF, stroke, and all other
University of California, San Francisco, by Wendy Max, CVD.6
PhD, on April 4, 2018. Those estimates incorporate a • By 2035, 45.1% of the US population is projected
3% discount rate, which is the recommended percent- to have some form of CVD.6
age.4 The discount rate removes the effect of inflation • Between 2015 and 2035, total direct medical costs
in income over the lifetime of earnings. The estimate of CVD are projected to increase from $318 billion
is for 2014, inflated to 2015 to account for the 2014 to $749 billion (2015$ in billions). Of this total in
to 2015 change in hourly worker compensation in the 2035, 55.5% will be attributable to hospital costs,
business sector reported by the US Bureau of Labor 15.3% to medications, 15.0% to physicians, 7.2%
Statistics.5 The indirect costs exclude lost productiv- to nursing home care, 5.5% to home health care,
ity costs attributable to chronic, prevalent nonfatal and 1.5% to other costs.6
CVD and stroke illness during 2014 to 2015 among • Indirect costs (attributable to lost productivity)
Abbreviations Used in Chapter 26 for all fatal and nonfatal CVDs are estimated to
AHA American Heart Association
increase from $237 billion in 2015 to $368 bil-
CHD coronary heart disease lion in 2035 (2015$ in billions), an increase of
CHF congestive heart failure 55%.6
COPD chronic obstructive pulmonary disease • Between 2015 and 2035, the total costs are
CVD cardiovascular disease expected to increase for total CVD, HBP and HBP
ED emergency department
as a risk factor, CHD, CHF, stroke, and other CVDs
GI gastrointestinal (tract)
HBP high blood pressure
(Chart 26-4).
HD heart disease • Between 2015 and 2035, the projected total
HF heart failure (direct and indirect) costs of total CVD are esti-
MEPS Medical Expenditure Panel Survey mated to remain relatively stable for 18- to 44-year-
NCHS National Center for Health Statistics olds, increase slightly for 45- to 64-year-olds, and

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e461

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26

increase sharply for 65- to 79-year-olds and adults to more than double in this same time frame
CLINICAL STATEMENTS

aged ≥80 years (Chart 26-5). (Chart 26-6).

AND GUIDELINES

• Whereas the direct costs of CVD for home health • These data indicate that CVD prevalence and costs
care, nursing homes, physicians, and medica- are projected to increase substantially unless CVD
tions are estimated to rise steadily between 2015 incidence is reduced or short-term and long-term
and 2035, projected hospital costs are estimated CVD care costs are better controlled.

Table 26-1.  Estimated Direct and Indirect Costs (in Billions of Dollars) of CVD and Stroke: United States, Average Annual, 2014 to
2015

Heart Hypertensive Other Circulatory

Disease* Stroke Disease† Conditions‡ Total CVD
Direct costs§
  Hospital inpatient stays 59.4 17.4 7.9 12.8 97.5
  Hospital ED visits 6.3 0.8 1.3 1.0 9.4
  Hospital outpatient or office-based provider visits 22.6 2.4 13.7 7.9 46.6
  Home health care 11.1 6.6 8.2 1.6 27.5
  Prescribed medicines 10.0 0.8 20.2 1.8 32.8
  Total expenditures 109.4 28.0 51.3 25.1 213.8

Indirect costsǁ
  Lost productivity/mortality 109.3 17.5 4.6 6.1 137.4
Grand totals 218.7 45.5 55.9 31.2 351.2

Numbers do not add to total because of rounding. CVD indicates cardiovascular disease; and ED, emergency department.
*This category includes coronary heart disease, heart failure, part of hypertensive disease, cardiac dysrhythmias, rheumatic heart disease,
cardiomyopathy, pulmonary heart disease, and other or ill-defined heart diseases.
†Costs attributable to hypertensive disease are limited to hypertension without heart disease.
‡Other circulatory conditions include arteries, veins, and lymphatics.
§Medical Expenditure Panel Survey (MEPS) healthcare expenditures are estimates of direct payments for care of a patient with the given disease
provided during the year, including out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources. Payments
Downloaded from http://ahajournals.org by on February 7, 2019

for over-the-counter drugs are not included. These estimates of direct costs do not include payments attributed to comorbidities. Total CVD costs
are the sum of costs for the 4 diseases but with some duplication.
ǁThe Statistics Committee agreed to suspend presenting estimates of lost productivity attributable to morbidity until a better estimating method
can be developed. Lost future earnings of people who died in 2014 to 2015, discounted at 3%.
Sources: Estimates from the Household Component of the MEPS of the Agency for Healthcare Research and Quality for direct costs (average
annual 2014 to 2015).1 Indirect mortality costs are based on 2014 to 2015 counts of deaths by the National Center for Health Statistics and
an estimated present value of lifetime earnings furnished for 2014 by Wendy Max (Institute for Health and Aging, University of California, San
Francisco, April 4,2018) and inflated to 2015 from change in worker compensation reported by the US Bureau of Labor Statistics. All estimates
prepared by Michael Mussolino, National Heart, Lung, and Blood Institute.

Table 26-2.  Costs of Total CVD and Stroke in Billions of Dollars by Age
and Sex: United States, Average Annual, 2014 to 2015

Total Males Females Age <65 y Age ≥65 y

Direct 213.8 122.4 91.4 85.5 128.3
Indirect mortality 137.4 102.3 35.1 115.5 21.9
Total 351.2 224.7 126.5 201.0 150.2

Numbers may not add to total because of rounding. CVD indicates

cardiovascular disease.
Source: Medical Expenditure Panel Survey, average annual 2014 to 2015
(direct costs) and mortality data from the National Center for Health Statistics
and present value of lifetime earnings from the Institute for Health and Aging,
University of California, San Francisco (indirect costs).1
All estimates prepared by Michael Mussolino, National Heart, Lung, and
Blood Institute.

e462 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26

CLINICAL STATEMENTS
AND GUIDELINES
Chart 26-1. Direct and indirect costs of CVD and stroke (in billions of dollars), United States, average annual 2014 to 2015.
CVD indicates cardiovascular disease.
Source: Prepared by the National Heart, Lung, and Blood Institute.1,3
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 26-2. The 21 leading diagnoses for direct health expenditures, United States, average annual 2014 to 2015 (in billions of dollars).
COPD indicates chronic obstructive pulmonary disease; and GI, gastrointestinal (tract).
Source: National Heart, Lung, and Blood Institute; estimates are from the Medical Expenditure Panel Survey, Agency for Healthcare Research and Quality, and
exclude nursing home costs.1

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e463

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26
CLINICAL STATEMENTS
AND GUIDELINES

Chart 26-3. Estimated direct cost (in billions of dollars) of cardiovascular disease and stroke, United States, average annual (1996–1997 to 2014–
2015).
Sources: Estimates from the Household Component of the Medical Expenditure Panel Survey of the Agency for Healthcare Research and Quality for direct costs
(average annual 1996–1997 to 2014–2015).1
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 26-4. Projected total costs of CVD, United States, 2015 to 2035 (2015 dollars in billions).
CHD indicates coronary heart disease; CHF, congestive heart failure; CVD, cardiovascular disease; and HBP, high blood pressure.
Data from RTI International.6 Copyright © 2016, American Heart Association, Inc.

e464 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26

CLINICAL STATEMENTS
AND GUIDELINES
Chart 26-5. Projected total (direct and indirect) costs of total cardiovascular disease by age from 2015 to 2035 (2015 dollars in billions).
Data from RTI International.6 Copyright © 2016, American Heart Association, Inc.
Downloaded from http://ahajournals.org by on February 7, 2019

Chart 26-6. Projected direct costs of total cardiovascular disease by type of cost from 2015 to 2035 (2015 dollars in billions).
Data from RTI International.6 Copyright © 2016, American Heart Association, Inc.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e465

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 26

REFERENCES 3. National Center for Health Statistics. Centers for Disease Control and
CLINICAL STATEMENTS

Prevention website. National Vital Statistics System: public use data file
1. Medical Expenditure Panel Survey: household component summary
AND GUIDELINES

documentation: mortality multiple cause-of-death micro-data files, 2016.

tables. Total expenditures in millions by condition, United States, 2014– https://www.cdc.gov/nchs/nvss/mortality_public_use_data.htm. Accessed
2015. Agency for Healthcare Research and Quality website. https://meps. March 15, 2018.
ahrq.gov/mepstrends/hc_cond/. Accessed March 15, 2018. 4. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in Health
2. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, and Medicine. New York, NY: Oxford University Press; 1996.
Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, 5. US Bureau of Labor Statistics, Office of Compensation Levels and Trends.
Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Employment Cost Index, Historical Listing – Volume V: Continuous
Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc Occupational and Industry Series: September 1975-December 2017. Table
DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs 4: employment cost index for total compensation, for civilian workers,
JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, by occupation and industry: continuous occupational and industry series.
Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong https://www.bls.gov/web/eci/ecicois.pdf. Accessed March 15, 2018.
ND, Wylie-Rosett J; on behalf of the American Heart Association 6. RTI International. Projections of Cardiovascular Disease Prevalence and
Statistics Committee and Stroke Statistics Subcommittee. Heart disease Costs: 2015–2035: Technical Report [report prepared for the American
and stroke statistics–2011 update: a report from the American Heart Heart Association]. Research Triangle Park, NC: RTI International; November
Association [published corrections appear in Circulation. 2011;124:e426 2016. RTI project number 021480.003.001.001. http://www.heart.
and Circulation. 2011;123:e240]. Circulation. 2011;123:e18–e209. doi: org/idc/groups/heart-public/@wcm/@adv/documents/downloadable/
10.1161/CIR.0b013e3182009701 ucm_491513.pdf. Accessed March 15, 2018.
Downloaded from http://ahajournals.org by on February 7, 2019

e466 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 27

27. AT-A-GLANCE SUMMARY TABLES • High Blood Pressure in the United States—

CLINICAL STATEMENTS
See Tables 27-1 through 27-3 Table 8-1

AND GUIDELINES
• Diabetes Mellitus—Table 9-1
Click here to return to the Table of Contents • Cardiovascular Diseases—Table 13-1
• Stroke—Table 14-1
Sources: See the following summary tables for com- • Congenital Cardiovascular Defects—Table 15-1
plete details: • Coronary Heart Disease—Table 19-1; Angina
• Overweight and Obesity—Table 6-1 Pectoris—Table 19-2
• High TC and LDL-C and Low HDL-C—Table 7-1 • Heart Failure—Table 20-2‍‍‍

Table 27-1.  Males and CVD: At-a-Glance Table

NH American
NH White NH Black Hispanic NH Asian Indian/
Diseases and Risk Factors Both Sexes Total Males Males Males Males Males Alaska Native*
Overweight and obesity
 Prevalence, 2011–2014

  Overweight and obesity, BMI ≥25.0 kg/m2† 157.2 M (69.4%) 78.8 M (72.5%) 73.0% 69.1% 79.6% 46.6% …

  Obesity, BMI ≥30.0 kg/m †

2
82.2 M (36.3%) 37.3 M (34.3%) 33.6% 37.5% 39.0% 11.2% …

Blood cholesterol
 Prevalence, 2013–2016

  Total cholesterol ≥200 mg/dL‡ 92.8 M (38.2%) 41.2 M (35.4%) 35.4% 29.8% 39.9% 38.7% …

  Total cholesterol ≥240 mg/dL‡ 28.5 M (11.7%) 12.4 M (10.7%) 10.5% 8.9% 13.0% 11.7% …

  LDL-C ≥130 mg/dL, 2011–2014‡ 71.3 M (30.3%) 34.0 M (30.0%) 29.3% 29.9% 36.6% 29.2% …

  HDL-C <40 mg/dL, 2013–2016‡ 45.6 M (19.2%) 33.7 M (29.0%) 29.7% 19.8% 32.6% 25.9% …
HBP
Downloaded from http://ahajournals.org by on February 7, 2019

 Prevalence, 2013–2016† 116.4 M (46.0%) 58.7 M (49.0%) 48.2% 58.6% 47.4% 46.4% …

 Mortality, 2016§‖ 82 735 39 577 (47.8%)¶ 26 402 8429 3063 1153# 520

DM
 Prevalence, 2013–2016  
  Diagnosed DM† 26.0 M (9.8%) 13.7 M (10.9%) 9.4% 14.7% 15.1% 12.8% …
  Undiagnosed DM† 9.4 M (3.7%) 5.5 M (4.6%) 4.7% 1.7% 6.3% 6.1% …
  Prediabetes† 91.8 M (37.6%) 51.7 M (44.0%) 43.7% 31.9% 48.1% 47.1% …

 Incidence, diagnosed DM, 2015⁎⁎ 1.5 M … … … … … …

 Mortality, 2016§‖ 80 058 43 763 (54.7%)¶ 30 010 6976 4603 1414# 1078

Total CVD
 Prevalence, 2013–2016† 121.5 M (48.0%) 61.5 M (51.2%) 50.6% 60.1% 49.0% 47.4% …

 Mortality, 2016§‖ 840 678 428 434 (51.0%)¶ 332 556 52 874 27 801 11 023# 4313

Stroke
 Prevalence, 2013–2016† 7.0 M (2.5%) 3.2 M (2.5%) 2.4% 3.1% 2.0% 1.1% …
 New and recurrent strokes§ 795.0 K 370.0 K (46.5%)¶ 325.0 K†† 45.0 K†† … … …
 Mortality, 2016§ 142 142 59 355 (41.8%)¶ 43 713 8115 4798 2268# 632‡‡
CHD
 Prevalence, CHD, 2013–2016† 18.2 M (6.7%) 9.4 M (7.4%) 7.7% 7.2% 6.0% 4.8% …
 Prevalence, MI, 2013–2016† 8.4 M (3.0%) 5.1 M (4.0%) 4.0% 4.0% 3.4% 2.4% …
 Prevalence, AP, 2013–2016† 9.4 M (3.6%) 4.3 M (3.5%) 3.8% 3.6% 2.6% 2.0% …
 New and recurrent MI and fatal CHD§§ 1.05 M 610.0 K 520.0 K†† 90.0K†† … … …
 New and recurrent MI§§ 805.0 K 470.0 K … … … … …

 Incidence, stable AP‖‖ 565.0 K 370.0 K … … … … …

(Continued )

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e467

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 27

Table 27-1. Continued
CLINICAL STATEMENTS

NH American
AND GUIDELINES

NH White NH Black Hispanic NH Asian Indian/

Diseases and Risk Factors Both Sexes Total Males Males Males Males Males Alaska Native*
 Mortality, 2016, CHD§‖ 363 452 210 156 (57.8%)¶ 167 036 21 900 13 696 5262 2069

 Mortality, 2016, MI§‖ 111 777 64 713 (57.9%)¶ 51 594 6587 4331 1601# 606

HF
 Prevalence, 2013–2016† 6.2 M (2.2%) 3.0 M (2.4%) 2.2% 3.5% 2.5% 1.7% …
 Incidence, 2014¶¶ 1.0 M 495.0 K 430.0 K†† 65.0 K†† … … …
 Mortality, 2016§‖ 78 356 35 424 (45.2%)¶ 29 155 3777 1721 561# 262

AP indicates angina pectoris (chest pain); BMI, body mass index; CHD, coronary heart disease (includes MI, AP, or both); CVD, cardiovascular disease; DM, diabetes
mellitus; ellipses (…), data not available; HBP, high blood pressure; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; K, thousands; LDL-C, low-density
lipoprotein cholesterol; M, millions; MI, myocardial infarction (heart attack); and NH, non-Hispanic.
*Both sexes.
†Age ≥20 years.
‡Total data for total cholesterol are for Americans ≥20 years of age. Data for LDL-C, HDL-C, and all racial/ethnic groups are age adjusted for age ≥20 years.
§All ages.
‖Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting.
¶These percentages represent the portion of total incidence or mortality that is for males vs females.
#Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
⁎⁎Age ≥18 years.
††Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
‡‡Estimate considered unreliable or does not meet standards of reliability or precision.
§§Age ≥35 years.
‖‖Age ≥45 years.
¶¶Age ≥55 years.

Table 27-2.  Females and CVD: At-a-Glance Table

NH American
Downloaded from http://ahajournals.org by on February 7, 2019

Total NH White NH Black Hispanic NH Asian Indian/Alaska

Diseases and Risk Factors Both Sexes Females Females Females Females Females Native*
Overweight and obesity
 Prevalence, 2011–2014

  Overweight and obesity, 157.2 M (69.4%) 78.2 M (66.4%) 63.7% 82.2% 77.1% 34.6% …
BMI ≥25.0 kg/m2†

  Obesity, BMI ≥30.0 kg/m2† 82.2 M (36.3%) 45.1 M (38.3%) 35.5% 56.9% 45.7% 11.9% …

Blood cholesterol

 Prevalence, 2013–2016

  Total cholesterol ≥200 mg/dL‡ 92.8 M (38.2%) 51.6 M (40.4%) 41.8% 33.1% 38.9% 39.6% …

  Total cholesterol ≥240 mg/dL‡ 28.5 M (11.7%) 16.1 M (12.4%) 13.6% 9.0% 10.1% 10.8% …

  LDL-C ≥130 mg/dL, 2011–2014‡ 71.3 M (30.3%) 37.3 M (30.4%) 32.1% 27.9% 28.7% 25.0% …

  HDL-C <40 mg/dL, 2013–2016‡ 45.6 M (19.2%) 11.9 M (9.9%) 9.3% 8.1% 13.1% 7.9% …

HBP

 Prevalence, 2013–2016† 116.4 M (46.0%) 57.7 M (42.8%) 41.3% 56.0% 40.8% 36.4% …

 Mortality, 2016§‖ 82 735 43 158 (52.2%)¶ 30 638 7897 2856 1362# 520

DM

 Prevalence, 2013–2016

  Diagnosed DM† 26.0 M (9.8%) 12.3 M (8.9%) 7.3% 13.4% 14.1% 9.9% …

  Undiagnosed DM† 9.4 M (3.7%) 3.9 M (2.8%) 2.6% 3.3% 4.0% 2.1% …

  Prediabetes† 91.8 M (37.6%) 40.1M (31.3%) 32.2% 24.0% 31.7% 29.4% …

 Incidence, diagnosed DM, 2015⁎⁎ 1.5 M … … … … … …

 Mortality, 2016§‖ 80 058 36 295 (45.3%)¶ 23 389 7077 3943 1283# 1078

(Continued )

e468 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 27

Table 27-2. Continued

CLINICAL STATEMENTS
NH American

AND GUIDELINES
Total NH White NH Black Hispanic NH Asian Indian/Alaska
Diseases and Risk Factors Both Sexes Females Females Females Females Females Native*
Total CVD

 Prevalence, 2013–2016† 121.5 M (48.0%) 60.0 M (44.7%) 43.4% 57.1% 42.6% 37.2% …

 Mortality, 2016§‖ 840 678 412 244 (49.0%)¶ 322 328 51 767 24 428 10 672# 4313

Stroke

 Prevalence, 2013–2016† 7.0 M (2.5%) 3.8 M (2.6%) 2.5% 3.8% 2.2% 1.6% …

 New and recurrent strokes§ 795.0 K 425.0 K (53.5%)¶ 365.0 K** 60.0 K** … … …

 Mortality, 2016§ 142 142 82 787 (58.2%)¶ 63 778 10 074 5485 2949# 632††

CHD

 Prevalence, CHD, 2013–2016† 18.2 M (6.7%) 8.8 M (6.2%) 6.1% 6.5% 6.0% 3.2% …

 Prevalence, MI, 2013–2016† 8.4 M (3.0%) 3.3 M (2.3%) 2.2% 2.2% 2.0% 1.0% …

 Prevalence, AP, 2013–2016† 9.4 M (3.6%) 5.1 M (3.7%) 3.8% 3.8% 3.6% 1.6% …

 New and recurrent MI and fatal CHD‡‡ 1.05 M 445.0 K 370.0 K** 75.0 K** … … …

 New and recurrent MI‡‡ 805.0 K 335.0 K … … … … …

 Incidence, stable AP§§ 565.0 K 195.0 K … … … … …

 Mortality, 2016, CHD§‖ 363 452 153 296 (42.2%)¶ 119 996 18 256 9878 3827 2069

 Mortality, 2016, MI§‖ 111 777 47 064 (42.1%)¶ 36 664 5750 3086 1197# 606

HF

 Prevalence, 2013–2016† 6.2 M (2.2%) 3.2 M (2.1%) 1.9% 3.9% 2.1% 0.7% …

 Incidence, 2014‖‖ 1.0 M 505.0K 425.0 K†† 80.0 K†† … … …

 Mortality, 2016§‖ 78 356 42 932 (54.8%)¶ 35 526 4584 1905 715# 262

AP indicates angina pectoris (chest pain); BMI, body mass index; CHD, coronary heart disease (includes MI, AP, or both); CVD, cardiovascular disease; DM, diabetes
Downloaded from http://ahajournals.org by on February 7, 2019

mellitus; ellipses (…), data not available; HBP, high blood pressure; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; K, thousands; LDL-C, low-density
lipoprotein cholesterol; M, millions; MI, myocardial infarction (heart attack); and NH, non-Hispanic.
*Both sexes.
†Age ≥20 years.
‡Total data for total cholesterol are for Americans ≥20 years of age. Data for LDL-C, HDL-C, and all racial/ethnic groups are age adjusted for age ≥20 years.
§All ages.
‖Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting.
¶These percentages represent the portion of total incidence or mortality that is for males vs females.
#Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
**Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
††Estimate considered unreliable or does not meet standards of reliability or precision.
‡‡Age ≥35 years.
§§ Age ≥45 years.
‖‖Age ≥55 years.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e469

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 27

Table 27-3.  Children, Youth, and CVD: At-a-Glance Table

CLINICAL STATEMENTS

NH Whites NH Blacks Hispanic NH Asian

AND GUIDELINES

Diseases and Risk

Factors Both Sexes Total Males Total Females Males Females Males Females Males Females Males Females
Overweight and obesity
 Prevalence, 2011–2014
  Overweight and 24.0 M (32.1%) 12.3 M (32.3%) 11.7 M (32.0%) 29.3% 28.0% 32.8% 37.6% 40.4% 39.8% 24.9% 15.0%
obesity, ages 2–19 y*
  Obesity, ages 2–19 y* 12.3 M (16.5%) 6.2 M (16.3%) 6.1 M (16.7%) 14.0% 14.7% 17.5% 20.0% 21.7% 21.0% 11.4% 5.3%
Blood cholesterol, mg/dL, 2013–2016
 Mean total cholesterol, mg/dL
  Ages 6–11 y 157.8 157.9 157.7 157.1 159.1 158.8 158.2 158.7 153.9 160.1 161.5
  Ages 12–19 y 154.4 151.6 157.5 150.6 157.2 150.8 156.0 152.7 156.0 155.4 170.2
 Mean HDL-C, mg/dL
  Ages 6–11 y 56.0 57.4 54.5 56.6 54.7 62.5 58.1 55.9 52.2 58.1 54.4
  Ages 12–19 y 51.8 49.9 53.8 49.2 53.5 54.4 56.9 49.6 52.2 52.8 56.6
 Mean LDL-C, 2011–2014, mg/dL
  Ages 12–19 y 87.7 85.7 89.8 86.5 89.9 86.6 90.9 85.9 87.8 84.5 96.9
Congenital cardiovascular defects (all age groups: children and adults)
 Mortality, 2016†‡§‖ 3063 1670 (54.5%)§ 1393 (45.5%)§ 973 821 284 248 322 245 66 54

CVD indicates cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; M, millions; and NH, non-Hispanic.
*In children, overweight and obesity are based on body mass index (BMI)-for-age values at or above the 85th percentile of the 2000 Centers for Disease Control
and Prevention (CDC) growth charts. Obesity is based on BMI-for-age values at or above the 95th percentile of the CDC growth charts.
†All ages.
‡Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies in
reporting.
§These percentages represent the portion of total congenital cardiovascular mortality that is for males vs females.
‖NH American Indian/Alaska Native, Mortality: 38.
Downloaded from http://ahajournals.org by on February 7, 2019

e470 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 28

28. GLOSSARY — National Health and Nutrition Examination

CLINICAL STATEMENTS
Survey II (NHANES II; 1976–1980)

AND GUIDELINES
— National Health and Nutrition Examination
Click here to return to the Table of Contents
Survey III (NHANES III; 1988–1994)
— National Health and Nutrition Examination
• Age-adjusted rates—Used mainly to compare the
Survey (NHANES; 1999 to …) (ongoing)
rates of ≥2 communities or population groups or
— National Health Interview Survey (NHIS;
the nation as a whole over time. The American
ongoing)
Heart Association (AHA) uses a standard popu-
— National Hospital Discharge Survey (NHDS;
lation (2000), so these rates are not affected by
1965–2010)
changes or differences in the age composition of
— National Ambulatory Medical Care Survey
the population. Unless otherwise noted, all death
(NAMCS; ongoing)
rates in this publication are age adjusted per
— National Hospital Ambulatory Medical Care
100 000 population and are based on underlying
Survey (NHAMCS; ongoing)
cause of death.
— National Nursing Home Survey (periodic)
• Agency for Healthcare Research and Quality
— National Home and Hospice Care Survey
(AHRQ)—A part of the US Department of Health
(periodic)
and Human Services, this is the lead agency — National Vital Statistics System (ongoing)
charged with supporting research designed to • Centers for Medicare & Medicaid Services—The
improve the quality of health care, reduce the cost federal agency that administers the Medicare,
of health care, improve patient safety, decrease Medicaid, and Child Health Insurance programs.
the number of medical errors, and broaden • Comparability ratio—Provided by the NCHS to
access to essential services. The AHRQ sponsors allow time-trend analysis from one International
and conducts research that provides evidence- Classification of Diseases (ICD) revision to another.
based information on healthcare outcomes, qual- It compensates for the “shifting” of deaths from
ity, cost, use, and access. The information helps one causal code number to another. Its applica-
healthcare decision makers (patients, clinicians, tion to mortality based on one ICD revision means
health system leaders, and policy makers) make that mortality is “comparability modified” to be
Downloaded from http://ahajournals.org by on February 7, 2019

more informed decisions and improve the qual- more comparable to mortality coded to the other
ity of healthcare services. The AHRQ conducts ICD revision.
the Medical Expenditure Panel Survey (MEPS; • Coronary heart disease (CHD) (ICD-10 codes I20–
ongoing). I25)—This category includes acute myocardial
• Bacterial endocarditis—An infection of the infarction (I21–I22); other acute ischemic (coro-
heart’s inner lining (endocardium) or of the nary) heart disease (I24); angina pectoris (I20);
heart valves. The bacteria that most often cause atherosclerotic cardiovascular disease (I25.0); and
endocarditis are streptococci, staphylococci, and all other forms of chronic ischemic (coronary)
enterococci. heart disease (I25.1–I25.9).
• Body mass index (BMI)—A mathematical formula • Death rate—The relative frequency with which
to assess body weight relative to height. The mea- death occurs within some specified interval of
sure correlates highly with body fat. It is calcu- time in a population. National death rates are
lated as weight in kilograms divided by the square computed per 100 000 population. Dividing
of the height in meters (kg/m2). the total number of deaths by the total pop-
• Centers for Disease Control and Prevention/ ulation gives a crude death rate for the total
National Center for Health Statistics (CDC/NCHS)— population. Rates calculated within specific
CDC is an agency within the US Department of subgroups, such as age-specific or sex-specific
Health and Human Services. The CDC conducts rates, are often more meaningful and infor-
the Behavioral Risk Factor Surveillance System mative. They allow well-defined subgroups of
(BRFSS), an ongoing survey. The CDC/NCHS con- the total population to be examined. Unless
ducts or has conducted these surveys (among otherwise stated, all death rates in this pub-
others): lication are age adjusted and are per 100 000
— National Health Examination Survey (NHES I, population.
1960–1962; NHES II, 1963–1965; NHES III, • Diseases of the circulatory system (ICD-10 codes
1966–1970) I00–I99)—Included as part of what the AHA calls
— National Health and Nutrition Examination “cardiovascular disease” (“Total cardiovascular
Survey I (NHANES I; 1971–1975) disease” in this Glossary).

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e471

<zjs;AHA Statistical Update> • <zjss;10163> • <zdoi;10.1161/CIR.0000000000000659>

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 28

• Diseases of the heart (ICD-10 codes I00–I09, 111, new data are available; they are not computed
CLINICAL STATEMENTS

113, 120-151)—Classification the NCHS uses in annually.

AND GUIDELINES

compiling the leading causes of death. Includes • Major cardiovascular diseases—Disease classifica-
acute rheumatic fever/chronic rheumatic heart tion commonly reported by the NCHS; represents
diseases (I00–I09); hypertensive heart disease ICD-10 codes I00 to I78. The AHA does not use
(I11); hypertensive heart and renal disease (I13); “major cardiovascular diseases” for any calcula-
CHD (I20–I25); pulmonary heart disease and dis- tions. See “Total cardiovascular disease” in this
eases of pulmonary circulation (I26–I28); heart Glossary.
failure (I50); and other forms of heart disease • Metabolic syndrome—Metabolic syndrome is
(I29–I49, I50.1–I51). “Diseases of the heart” are defined* as the presence of any 3 of the fol-
not equivalent to “total cardiovascular disease,” lowing 5 diagnostic measures: Elevated waist
which the AHA prefers to use to describe the circumference (≥102 cm in males or ≥88 cm in
leading causes of death. females), elevated triglycerides (≥150 mg/dL [1.7
• Hispanic origin—In US government statistics, mmol/L] or drug treatment for elevated triglyc-
“Hispanic” includes people who trace their erides), reduced high-density lipoprotein choles-
ancestry to Mexico, Puerto Rico, Cuba, Spain, terol (<40 mg/dL [0.9 mmol/L] in males, <50 mg/
the Spanish-speaking countries of Central or dL [1.1 mmol/L] in females, or drug treatment for
South America, the Dominican Republic, or reduced high-density lipoprotein cholesterol), ele-
other Spanish cultures, regardless of race. It vated blood pressure (≥130 mm Hg systolic blood
does not include people from Brazil, Guyana, pressure, ≥85 mm Hg diastolic blood pressure, or
Suriname, Trinidad, Belize, or Portugal, because drug treatment for hypertension), and elevated
Spanish is not the first language in those coun- fasting glucose (≥100 mg/dL or drug treatment
tries. Most of the data in this update are for for elevated glucose).
Mexican Americans or Mexicans, as reported • Morbidity—Incidence and prevalence rates are
by government agencies or specific studies. In both measures of morbidity (ie, measures of vari-
many cases, data for all Hispanics are more dif- ous effects of disease on a population).
ficult to obtain. • Mortality—Mortality data for states can be
• Hospital discharges—The number of inpatients obtained from the NCHS website (http://cdc.
(including newborn infants) discharged from gov/nchs/), by direct communication with the
Downloaded from http://ahajournals.org by on February 7, 2019

short-stay hospitals for whom some type of dis- CDC/NCHS, or from the AHA on request. The
ease was the first-listed diagnosis. Discharges total number of deaths attributable to a given
include those discharged alive, dead, or “status disease in a population during a specific interval
unknown.” of time, usually 1 year, are reported. These data
• International Classification of Diseases (ICD) are compiled from death certificates and sent
codes—A classification system in standard use by state health agencies to the NCHS. The pro-
in the United States. The ICD is published by the cess of verifying and tabulating the data takes
World Health Organization. This system is reviewed ≈2 years.
and revised approximately every 10 to 20 years to • National Heart, Lung, and Blood Institute
ensure its continued flexibility and feasibility. The (NHLBI)—An institute in the National Institutes
10th revision (ICD-10) began with the release of of Health in the US Department of Health and
1999 final mortality data. The ICD revisions can Human Services. The NHLBI conducts such studies
cause considerable change in the number of as the following:
deaths reported for a given disease. The NCHS — Framingham Heart Study (FHS; 1948 to …)
provides “comparability ratios” to compensate (ongoing)
for the “shifting” of deaths from one ICD code to — Honolulu Heart Program (HHP; 1965–1997)
another. To compare the number or rate of deaths — Cardiovascular Health Study (CHS; 1988
with that of an earlier year, the “comparability- to …) (ongoing)
modified” number or rate is used. — Atherosclerosis Risk in Communities (ARIC)
• Incidence—An estimate of the number of new Study (1985 to …) (ongoing)
cases of a disease that develop in a population, — Strong Heart Study (SHS; 1989–1992,
usually in a 1-year period. For some statistics, new 1991–1998)
and recurrent attacks, or cases, are combined. — Multi-Ethnic Study of Atherosclerosis (MESA;
The incidence of a specific disease is estimated by 2000–2012)
multiplying the incidence rates reported in com-
munity- or hospital-based studies by the US popu- *According to criteria established by the AHA/NHLBI and published in
lation. The rates in this report change only when Circulation (Circulation. 2005;112:2735–2752).

e472 March 5, 2019 Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659

 Benjamin et al Heart Disease and Stroke Statistics—2019 Update: Chapter 28

— The NHLBI also published reports of the • Race and Hispanic origin—Race and Hispanic ori-

CLINICAL STATEMENTS
Joint National Committee on Prevention, gin are reported separately on death certificates.

AND GUIDELINES
Detection, Evaluation, and Treatment of In this publication, unless otherwise specified,
High Blood Pressure and the Third Report of deaths of people of Hispanic origin are included
the Expert Panel on Detection, Evaluation, in the totals for whites, blacks, American Indians
and Treatment of High Blood Cholesterol in or Alaska Natives, and Asian or Pacific Islanders
Adults (Adult Treatment Panel III). according to the race listed on the decedent’s
• National Institute of Neurological Disorders and death certificate. Data for Hispanic people include
Stroke (NINDS)—An institute in the National all people of Hispanic origin of any race. See
Institutes of Health of the US Department of “Hispanic origin” in this Glossary.
Health and Human Services. The NINDS sponsors • Stroke (ICD-10 codes I60–I69)—This category
and conducts research studies such as these: includes subarachnoid hemorrhage (I60); intra-
— Greater Cincinnati/Northern Kentucky Stroke cerebral hemorrhage (I61); other nontraumatic
Study (GCNKSS) intracranial hemorrhage (I62); cerebral infarc-
— Rochester (Minnesota) Stroke Epidemiology tion (I63); stroke, not specified as hemorrhage or
Project infarction (I64); occlusion and stenosis of prece-
— Northern Manhattan Study (NOMAS) rebral arteries not resulting in cerebral infarction
— Brain Attack Surveillance in Corpus Christi (I65); occlusion and stenosis of cerebral arteries
(BASIC) Project not resulting in cerebral infarction (I66); other
• Physical activity—Any bodily movement pro- cerebrovascular diseases (I67); cerebrovascular
duced by the contraction of skeletal muscle disorders in diseases classified elsewhere (I68);
that increases energy expenditure above a basal and sequelae of cerebrovascular disease (I69).
level. • Total cardiovascular disease (ICD-10 codes I00–
• Physical fitness—The ability to perform daily tasks I99, Q20–Q28)—This category includes rheumatic
with vigor and alertness, without undue fatigue, fever/rheumatic heart disease (I00–I09); hyperten-
and with ample energy to enjoy leisure-time sive diseases (I10–I15); ischemic (coronary) heart
pursuits and respond to emergencies. Physical disease (I20–I25); pulmonary heart disease and
fitness includes a number of components con- diseases of pulmonary circulation (I26–I28); other
sisting of cardiorespiratory endurance (aerobic forms of heart disease (I30–I52); cerebrovascular
Downloaded from http://ahajournals.org by on February 7, 2019

power), skeletal muscle endurance, skeletal mus- disease (stroke) (I60–I69); atherosclerosis (I70);
cle strength, skeletal muscle power, flexibility, other diseases of arteries, arterioles, and capillar-
balance, speed of movement, reaction time, and ies (I71–I79); diseases of veins, lymphatics, and
body composition. lymph nodes not classified elsewhere (I80–I89);
• Prevalence—An estimate of the total number of and other and unspecified disorders of the circu-
cases of a disease existing in a population dur- latory system (I95–I99). When data are available,
ing a specified period. Prevalence is sometimes we include congenital cardiovascular defects
expressed as a percentage of population. Rates (Q20–Q28).
for specific diseases are calculated from periodic • Underlying cause of death or any-mention cause
health examination surveys that government of death—These terms are used by the NCHS
agencies conduct. Annual changes in preva- when defining mortality. Underlying cause of
lence as reported in this Statistical Update reflect death is defined by the World Health Organization
changes in the population size. Changes in rates as “the disease or injury which initiated the chain
can be evaluated only by comparing prevalence of events leading directly to death, or the circum-
rates estimated from surveys conducted in dif- stances of the accident or violence which pro-
ferent years. Note: In the data tables, which duced the fatal injury.” Any-mention cause of
are located in the different disease and risk fac- death includes the underlying cause of death and
tor chapters, if the percentages shown are age up to 20 additional multiple causes listed on the
adjusted, they will not add to the total. death certificate.

Circulation. 2019;139:00–00. DOI: 10.1161/CIR.0000000000000659 March 5, 2019 e473