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Predicting Outcomes in Acute Coronary Syndrome Using Biochemical Markers

This study aimed to assess the ability of biomarkers like hs-CRP, creatinine, troponin I, and CK-MB to predict outcomes in patients with acute coronary syndrome (ACS) during hospitalization, at 6 weeks, and at 6 months. 108 ACS patients were followed up and biomarkers were measured at admission, 6 weeks, and 6 months. hs-CRP >5 mg/dl and eGFR ≤30 ml/min/1.73 m2 were significant in predicting mortality.
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0% found this document useful (0 votes)
55 views9 pages

Predicting Outcomes in Acute Coronary Syndrome Using Biochemical Markers

This study aimed to assess the ability of biomarkers like hs-CRP, creatinine, troponin I, and CK-MB to predict outcomes in patients with acute coronary syndrome (ACS) during hospitalization, at 6 weeks, and at 6 months. 108 ACS patients were followed up and biomarkers were measured at admission, 6 weeks, and 6 months. hs-CRP >5 mg/dl and eGFR ≤30 ml/min/1.73 m2 were significant in predicting mortality.
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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indian heart journal 67 (2015) 529–537

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.elsevier.com/locate/ihj

Original Article

Predicting outcomes in acute coronary syndrome


using biochemical markers

P. Karki a,*, K.K. Agrawaal b, M. Lamsal c, N.R. Shrestha d


a
Prof & Head, Department of Internal Medicine & Chair, Cardiology Division, B.P. Koirala Institute of Health Sciences,
Dharan, Nepal
b
Senior Resident, Department of Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal
c
Professor, Department of Biochemistry, B.P. Koirala Institute of Health Sciences, Dharan, Nepal
d
Associate Professor, Department of Internal Medicine & Cardiology Division, B.P. Koirala Institute of Health Sciences,
Dharan, Nepal

article info abstract

Article history: Objectives: To assess risk prediction in patients with acute coronary syndrome (ACS) during
Received 7 February 2014 the hospital stay, at 6 weeks and at 6 months period using high sensitivity C-reactive protein
Accepted 29 June 2015 (hs-CRP), serum creatinine, cardiac troponin I, creatine kinase total, and MB levels.
Available online 26 October 2015 Methods: It was a prospective observational study. The primary outcome was taken as all-
cause mortality. Patients with ACS were enrolled and followed up at 6 weeks and 6 months
Keywords: duration from the index event. Mortality and cause of death were recorded. The hs-CRP was
Acute coronary syndrome estimated on admission, at 6 weeks, and at 6 months. The estimated glomerular filtration
Biochemical markers rate (eGFR) was calculated using the abbreviated modification of diet in renal disease (MDRD)
High sensitivity C-reactive protein formula at admission, at 6 weeks, and 6 months.
(hs-CRP) Results: There were a total of 108 cases of ACS in the duration of 6 months who completed
Estimated glomerular filtration rate the follow-up. The hs-CRP level of >5 mg/dl was highly significant for predicting mortality
(eGFR) during hospital stay and at 6 weeks ( p < 0.001). There was 11% of in-hospital mortality
Predicting outcome ( p < 0.001). At 6 months, the overall mortality was 28% ( p < 0.001). There was a statistical
significance with low eGFR (median eGFR 45 ml/min/1.73 m2) levels during the admission.
Conclusion: hs-CRP levels above 5 mg/dl and the eGFR levels ≤30 ml/min/1.73 m2 were signifi-
cant in predicting mortality of the patients with ACS. This may provide simple assessment
tools for predicting outcome in ACS in resource-poor settings if validated further.
# 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

and will become the prevailing overall cause of mortality


1. Introduction
among the inhabitants of South Asia in the next 20 years. The
current epidemic and imminent growth are due to the huge
Cardiovascular disease (CVD) is the prevailing non-communi- burden of CVD risk factors, largely driven by urbanization.1,2
cable cause of death and disability in the Indian subcontinent, Although we do not have any national data on ischemic heart

* Corresponding author.
E-mail address: prahladkarki@hotmail.com (P. Karki).
http://dx.doi.org/10.1016/j.ihj.2015.06.029
0019-4832/# 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
530 indian heart journal 67 (2015) 529–537

disease (IHD), it was found that the prevalence of CVD is 3.2. Setting
increasing and there is a fivefold increase in the incidence of
coronary artery disease (CAD).3 This study was conducted in the Department of Internal
The significance of the contribution of laboratory medi- Medicine at B.P. Koirala Institute of Health Sciences, Dharan,
cine to clinical cardiology has grown in importance over the Nepal for a period of 1 year.
years. This is witnessed by the recent incorporation of
biomarkers into new international guidelines and in the re- 3.3. Primary outcome
definition of myocardial infarction (MI). There are mainly
two classes of indicators: markers of early injury/ischemia All-cause mortality.
and markers of inflammation and coronary plaque instabil-
ity and disruption.4 3.4. Inclusion criteria
There are various biomarkers associated with acute
coronary syndrome (ACS). The clinical application of All the patients meeting the diagnostic criteria of ACS, who
cardiac biomarkers in ACS is no longer limited to establishing were admitted under the Department of Internal Medicine at B.
or refuting the diagnosis of myocardial necrosis. Cardiac P. Koirala Institute of Health Sciences and who gave consent,
biomarkers provide a convenient and noninvasive means to were enrolled for this study.
gain insights into the underlying causes and consequences of
ACS that mediate the risk of recurrent events and may be 3.5. Exclusion criteria
targets for specific treatment.4 Biochemical markers play a
major role for risk assessment in patients with an ongoing Alternate diagnosis of chest pain and/or refusal to give consent
non-ST segment elevation ACS. Although the cardiac troponin for the study.
in particular is generally recognized as an important risk
For the purpose of the study, different components of ACS were
indicator, other markers of left ventricular performance (i.e. N-
defined as following:
terminal pro-brain natriuretic peptide), inflammation (i.e. C-
reactive protein), and renal function (i.e. estimated glomerular
filtration rate (eGFR)] are equally important in providing strong (1) ST elevation Myocardial Infarction (STEMI):
prognostic information.5,6 (a) Characteristic rise and fall of cardiac biomarkers
With the availability of highly specific and sensitive (presence of troponin I, and/or rise of CK NAC and CK
methods for evaluating myocardial tissue damage, such as MB)
the immunoassays for MB isoenzyme of creatine kinase (CK And
MB), myoglobin, and especially, cardiac specific troponin T and (b) Central ischemic chest pain (described as retro-
I (cTnT and cTnI) and their introduction in clinical practice, the sternal pressure, pain, discomfort, or heaviness radiat-
definition of acute myocardial infarction (AMI) has radically ing to neck, jaw, left arm, or shoulder precipitated by
changed.7 exertion more than 20 min)
The information gathered from this study would help us in And/or
various ways. Firstly, it will help us predict the outcomes of the (c) Typical ischemic ECG changes:
patients with ACS using the commonly used biomarkers and  ST elevation in at least two contiguous leads, ≥0.2 mV in
thus the treatment of the patient can be guided. The leads V1–V3 or ≥0.1 mV in all other leads.
demographic information provided by this study shows us  Established MI (in the absence of confounders) is
that ACS is increasing in Nepal, especially in the young indicated by any Q wave in leads V1–V3 or by Q waves
population. This study provides us a complete profile of of ≥1 mm for ≥30 ms in two other contiguous leads.
patients with ACS.  Presumed new left bundle branch block.
(2) Non-ST elevation myocardial infarction (NSTMI): Features
as described for STEMI, but not meeting electrocar-
2. Objective
diographic ST-T criteria.
(3) Unstable angina:
The study was undertaken to assess risk prediction in patients At least one of the following:
with ACS during the hospital stay, at 6 weeks, and at 6 months (a) Chest discomfort occurring at rest or at minimal
period using high sensitivity C-reactive protein (hs-CRP), exertion and lasting for >10 min;
serum creatinine, cTnI, and CK MB fraction. (b) Is new onset and severe (within last 6 weeks);
(c) Occurs with crescendo pattern.

3. Materials and methods


3.6. Variables studied
3.1. Study design
Cardiac troponin I (cTnI), hs-CRP, eGFR using four variable
The study was hospital-based prospective observational modification of diet in renal disease (MDRD) equation, and
study, which was more practical in our setting and ethically serum CK MB levels in patients with ACS during index event, at
acceptable. 6 weeks, and 6 months.
indian heart journal 67 (2015) 529–537 531

3.7. Methods the bivariate analysis for the numerical data in both the groups
(improved or death at 6 months), mean comparison was done
All the consecutive patients with the diagnosis of ACS and who and p value was calculated using the non-parametric test
gave informed consent for the study were enrolled and (Mann–Whitney U test). Percentage, graphical presentation,
followed up at 6 weeks and 6 months duration from the index and other descriptive statistics were calculated. Multiple
event. Mortality and the likely cause of death were recorded variables, which were significantly affecting the outcome,
along with the day since admission. The hs-CRP was estimated were together taken into multivariate logistic regression
on admission, at 6 weeks, and at 6 months. The eGFR was analysis. The significance level of the data, which were taken
calculated using the abbreviated MDRD formula at admission, for the multivariate analysis, was ≤0.05 at the bivariate
at 6 weeks, and 6 months. For estimating cTnI, qualitative analysis.
membrane-based immunoassay was used. For estimating CK,
the serum sample was analyzed using a semi-automatic 3.9. Ethical clearance
analyzer using standard commercially available kits on
admission. The patient socioeconomic status was assessed Ethical clearance was taken as per the guidelines of Institu-
by modified family income groups in Nepalese Rupees of the tional ethical review board (IERB), BPKIHS, Dharan.
Kuppuswamy's socioeconomic status scale modified for 2009.8

4. Results
3.8. Statistical analysis

The sample size was calculated as per the WHO's Software for There were a total of 114 cases of ACS in duration of 6 months.
calculating sample size depending on the prevalence of ACS as As 6 patients did not complete the follow-up, they were
per the previous epidemiological study in the same setting.9 excluded from the study. The total numbers included in the
Data were entered in Microsoft Excel 2000 and converted final analysis were 108, out of which 44 were STEMI, 41
into SPSS version 10 for statistical analysis. Median was were NSTEMI, and 23 were unstable angina (UA) (Fig. 1 and
calculated for the demographic presentation of the sample. In Table 1).

Table 1 – Socio-demographic characteristics of patients with acute coronary syndrome.


Characteristics Categories No. of patients Percentage p-Value
Age groups (in years) <55 27 25.00 0.01
55–75 56 51.90
>75 25 23.10
Median age in years (IQR) 65.00 (54.50–73.75)

Sex Male 58 53.70 0.53


Female 50 46.30

Education Illiterate 40 37.00 0.049


Literate 41 38.00
Formal education 27 25.00

Kuppuswamy's scale Upper 3 2.80 0.968


Middle 34 31.70
Upper lower 66 61.10
Lower 5 4.60

Body mass index (kg/m2) <18.5 9 8.30 0.144


18.5–23 35 32.40
23–27.5 45 41.70
>27.5 19 17.60
Median body mass index in kg/m2 (IQR) 24.12 (21.25–26.87)

Abdominal circumference (males) in cm <90 20 34.44 0.971


≥90 38 65.56
Median abdominal circumference of males in cm (IQR) 88.00 (93.50–98.00)

Waist hip ratio males <0.9 4 6.00 0.817


≥0.9 54 94.00
Median waist hip ratio of males (IQR) 0.97 (0.93–1.02)

Abdominal circumference (females) in cm <80 5 10.00 0.748


≥80 45 90.00
Median abdominal circumference of females in cm (IQR) 88.00 (84.00–92.00)

Waist hip ratio female <0.8 1 2.00 0.926


≥0.8 49 98.00
Median waist hip ratio of females (IQR) 0.94 (0.91–0.98)
532 indian heart journal 67 (2015) 529–537

Total number of patients with ACS were then subjected to blood sugar fasting and/or HbA1c
(n = 114) estimation to confirm the diagnosis of diabetes mellitus if it
was not established (Table 3).
The CK NAC showed a median of 301.50 mg/dl (106–811).
(6 patients didn’t complete follow up) Among the group, it was seen that 86 (80%) patients had a
raised CK NAC levels. The median CK MB level was 40 mg/dl
Total number included in the (20–90.25) and 76 (70%) of the patients had raised CK MB levels.
final analysis (n= 108) The qualitative troponin I estimation showed positive results
only in 44 (41%) of the patients. The median eGFR on admission
was 45.59 ml/min/1.73 m2. The hs-CRP levels on admission
showed a median value of 24.50 mg/dl (8.25–74.75). The urine
routine examination done using multistix on admission
showed albuminuria of range trace/1+ (30 mg/dl) in 32 (30%)
patients and 2+/3+ (100/300 mg/dl) in 15 (14%) patients
STEMI NSTEMI Unstable angina (Table 4).
(n=44) (n=41) (n=23) On follow-up at the 6 weeks and 6 months, the median
eGFRs were 55.27 ml/min/1.73 m2 (40.11–66.18) and 59.02 ml/
min/1.73 m2 (45.35–68.58) and the median hs-CRP values were
Fig. 1 – Patients with ACS enrolled in the study. 8 mg/dl (4–12.50) and 5 mg/dl (3–11), respectively. Among the
patients with ACS, 23 (21%) were diagnosed to have UA, 41
(38%) had NSTEMI and 44 (41%) had STEMI.
The most dominant wall involvement was anterior wall in
Based on the age distribution with the median age of 65 68 (63%) patients, while 23 (21%) had inferior wall. Whereas 15
years, majority of the patients (56/108, 52%) were 55–75 years of (14%) had lateral wall and 2 (2%) had septal wall involvement.
age while almost equal proportions were less than 75 years of In the patients with ACS, 56 (52%) had a Killip class of I.
age. The sex distribution showed a nearly equal male 58 (54%) This study showed that 10.28 (26%) of the patients had
and female 50 (46%) ratio. arrhythmias. The most common arrhythmia was atrial
The patients' socioeconomic status was calculated using fibrillation followed by ventricular arrhythmias and then the
the Kuppuswamy's modification for Nepal.8 There were 66 bundle branch blocks whereas 24 (22%) of the total patients
(61%) patients in the upper lower strata whereas 34 (32%) had cardiogenic shock during the index event, 2 (2%) patients
belonged to middle group, 5 (5%) were in lower group, and 3 had ischemic events, and 9 (8%) had uncontrolled hyperten-
(3%) were in the upper group. The median body mass index sion. The other complications included coagulopathy (1%),
(BMI) was 24.12 kg/m2. The waist to hip ratio for the males was hemoptysis (1%), and intracranial hematoma (1%).
0.97 and that of the females was 0.94. The mean duration of hospital stay was 6 days. There were
Out of the presenting complaints, the most common was 12 patients who died during the hospital stay whose cause of
chest pain 71 (66%) and then shortness of breath 60 (56%), death is known and for 2 patients the cause of death is
epigastric discomfort 38 (35%) followed by palpitations 32 unknown, and 16 died during the follow-up period. The in-
(30%), whereas 22 (20%) patients had syncope. Other symp- hospital mortality rate was 11% whereas overall mortality at 6
toms include cough (1%), fever (6%), headache (1%), altered months follow-up was 28% including all the patients from the
sensorium (1%), loose stools (3%), nausea/vomiting (10%), and index event until final outcome at 6 months.
diaphoresis (30%). Cardiogenic shock was seen in six (6%), sudden cardiac
It was observed that 74 (69%) patients had hypertension death in four (4%), and ventricular tachycardia in two (2%) of
and 32 (30%) patients had a history of diabetes, 24 (22%) had the patients who died during the index event.
CAD in past, and 11 (10%) patients had renal disease The bivariate analysis was performed and the data were
previously. Fifty-seven (53%) patients were smokers, and compared in two groups. G1 represented improved outcome
among the smokers, 50 (46%) had more than 10 pack years whereas G2 included mortality at the end of 6 months follow-
of smoking. Regarding physical activity, 52 (48%) had a up.
sedentary lifestyle. The distribution of age was comparable in both the groups.
On examination, the median pulse rate was 84/min (68–92). Age >75 years showed statistical significance with all-cause
The median systolic blood pressure was 140 mmHg and the mortality ( p = 0.011). There was no significant association with
diastolic being 90 mmHg (Table 2). mortality in sex, occupation of the patient, and Kuppuswamy's
The median leukocyte count was 12,300 cells/mm3. Other scale for socioeconomic status or BMI. Those who were not
baseline investigations were in the normal range. The lipid formally educated had increased all-cause death ( p = 0.049).
profile analysis of the patients showed a normal range. The The abdominal circumference and waist to hip ratio were not
median triglyceride was 132.50 mg/dl (98–177), cholesterol statistically significant.
was 138.50 mg/dl (107.50–178.00), HDL was 38.00 mg/dl (37– The systolic blood pressure <90 mmHg was associated with
40), and the median calculated LDL was 67.20 mg/dl (45.05– increased chances of mortality but was not statistically
110.90). It was seen that 5 (5%) of the patients had significant ( p = 0.058).
hypoglycemia on presentation, whereas 81 (75%) had a There were no significant differences in the mean total
random blood sugar level above 200 mg/dl. These patients leukocyte count and hemoglobin level in between mortality
indian heart journal 67 (2015) 529–537 533

Table 2 – Laboratory findings of patients with acute coronary syndrome on admission.


Investigations Categories No. of patients Percentage p-Value
3
Total leukocyte count/mm <4000 1 0.90 0.088
4000–11,000 45 41.70
>11,000 62 57.40
Median TLC (IQR) 12,300.00 (9050.00–16,425.00)

Differential count neutrophil % <50 4 3.70 0.244


50–70 41 38.00
>70 63 58.30
Median DLC neutrophil count (IQR) 73.50 (64.25–82.00)

Differential count lymphocyte % <20 34 31.48 0.303


20–40 60 55.55
>40 14 12.97
Median DLC lymphocyte count (IQR) 26.00 (17.00–34.75)

Hemoglobin (gm/dl) <12 47 43.51 0.146


12–13 9 8.33
>13 52 48.16
Median hemoglobin (IQR) 12.45 (10.65–14.770)

Urea (mg/dl) <10 0 0.00 0.007


10–40 74 68.50
>40 34 31.50
Median urea (IQR) 29.00 (23.00–51.50)

Sodium (mmol/l) <135 9 8.30 0.028


135–145 76 70.40
>145 23 21.30
Median serum sodium (IQR) 141.00 (138.00–145.00)

Triglyceride (mg/dl) <80 11 10.19 0.160


80–200 83 76.88
>200 14 12.93
Median triglyceride (IQR) 132.50 (98.00–177.00)

Total cholesterol (mg/dl) <200 96 88.88 0.810


200–239 11 10.19
>240 1 0.93
Median total cholesterol (IQR) 138.50 (107.50–178.00)

HDL cholesterol (mg/dl) <40 66 61.11 0.994


40–60 42 38.89
>60 0 0.00
Median HDL cholesterol (IQR) 38.00 (37.00–40.00)

LDL cholesterol (mg/dl) <70 59 54.63 0.850


70–<100 19 17.60
100–129 19 17.60
130–159 9 8.34
>160 2 1.83
Median LDL cholesterol (IQR) 67.20 (45.05–110.90)

Blood sugar level random (mg/dl) <60 5 4.62 0.058


60–200 22 20.38
>200 81 75.00
Median blood sugar level (IQR) 119.00 (90.00–178.00)

and improved group. The mean serum urea mg/dl was 36.81 mortality. Similarly, albuminuria of 30 mg/dl and above was
 29.36 in the improved group but it was significantly higher significant for mortality ( p = 0.002).
(50.03  30.92) in the death group ( p = 0.007). Similarly, the The type of ACS was not statistically significant. The Killip
serum sodium level >145 mmol/l was significant for death class IV was associated with increased mortality ( p = 0.007).
( p = 0.028). Although blood sugar levels >200 mg/dl and In-hospital mortality during the index event was signifi-
<60 mg/dl were associated with overall mortality, it was cant ( p = <0.001). The mean duration of stay in the
statistically not significant ( p = 0.058). The mean eGFR in the death group was 6.89  7.53 days. In the causes of mortality,
mortality group was 36.68  19.74 mg/dl in the death group ventricular tachycardia was the most significant ( p = <0.001)
( p = 0.012). The hs-CRP level at admission was highly signifi- followed by sudden cardiac death and cardiogenic shock
cant ( p = 0.001) with a mean value of 54.37 mg/dl in the (Tables 5 and 6).
534 indian heart journal 67 (2015) 529–537

Table 3 – Cardiac markers of patients with acute coronary syndrome on admission.


Cardiac markers Categories No. of patients Percentage p-Value
CK NAC (mg/dl) <90 22 20.30 0.950
≥90 86 79.70
Median CK NAC (IQR) 301.50 (106.00–811.50)

CK MB (mg/dl) <25 32 29.70 0.612


>25 76 70.30
Median CK MB (IQR) 40.00 (20.00–90.25)

Cardiac troponin I Negative 64 59.30 0.593


Positive 44 40.70
eGFR at admission (ml/min/1.73 m2) <30 34 31.50 0.012
30–59 53 49.10
>60 21 19.40
Median eGFR at admission (IQR) 45.59 (26.11–57.28)

Highly sensitive CRP at admission (mg/dl) <2 0 0.00 0.001


2–5 21 19.40
>5 87 80.60
Median hs-CRP at admission (IQR) 24.50 (8.25–74.75)

Urine albumin Nil 61 56.50 0.002


Trace/1+ 32 29.60
2+/3+ 15 13.90
CK, creatine kinase; hs-CRP, high sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate.

Table 4 – Laboratory findings of patients with acute coronary syndrome at 6 weeks and 6 months.
Investigations Categories 6 weeks p-Value 6 months p-Value

No. of patients Percentage No. of patients Percentage


2
eGFR (ml/min/1.73 m ) <30 11 12.80 0.298 7 8.97 0.384
30–59 44 51.16 34 43.60
>60 31 36.04 37 47.43
Median eGFR (IQR) 55.27 (40.11–66.18) 59.02 (45.35–68.58)

Highly sensitive CRP (mg/dl) <2 0 0.00 0.642 0 0.00


2–5 35 32.40 41 38.00
>5 73 67.60 67 62.00
Median hs-CRP (IQR) 8.0 (4.00–12.50) 5.00 (3.00–11.00)
hs-CRP, high sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate.

The primary outcome was highly significant at 6 weeks and multivariate analysis showed that age, hs-CRP, albuminuria,
6 months period (Table 7). and cardiogenic shock were strongest predictors of mortality
For the multivariate analysis, the variables at a significance when used in relation to each other. In the study, the cause of
level of p = ≤0.05 in the bivariate analysis were taken. The death was not known in two patients who had died during the

Table 5 – Outcome of patients with acute coronary syndrome at 6 weeks.


Outcome Categories No. of patients Percentage p-Value
Death at 6 weeks Yes 9 8.30 <0.001
No 85 78.70

Acute coronary syndrome at 6 weeks Yes 3 2.80 0.230


No 82 75.90

New York Heart Association at 6 weeks in class I 31 28.70 0.097


II 42 38.90
III 12 11.10
IV 0 0.00

PCI/CABG at 6 weeks Yes 7 6.50 0.508


No 79 73.10
indian heart journal 67 (2015) 529–537 535

Table 6 – Outcome of patients with acute coronary syndrome at 6 months.


Outcome Categories No. of patients Percentage p-Value
Death at 6 months Yes 7 6.50 <0.001
No 78 72.20

New York Heart Association at 6 months in class I 40 37.00 0.740


II 34 31.50
III 4 3.70
IV 0 0.00

PCI/CABG at 6 months Yes 4 3.70 0.780


No 74 68.50

Final status of patients at 6 months Improved 78 72.20 <0.001


Death 30 27.80

Table 7 – Outcome in patients with acute coronary syndrome by mortality or no mortality.


Outcome Categories Improved Mortality p-Value
Death at 6 weeks Yes 0 9 <0.001
No 78 7

Death at 6 months Yes 0 7 <0.001


No 78 0

Outcome final Improved 78 0 <0.001


Death 0 30

index event. Autopsy was not done in both the cases, as the culprit lesion with higher white blood count at presentation
facility was available in our setup. The samples of the patients with ACS.15 The level of blood urea above 40 mg/dl was
were collected in the emergency, but as the cause of death was significantly associated with all-cause mortality during the
not known, they were not included in the in-hospital mortality index event and also during the 6 months period. There was a
data analysis. As their discharge status was considered death, statistical significance with low eGFR (median eGFR 45.59 ml/
they were included in the final analysis. The final outcome of min/1.73 m2) levels during the admission. It was also associ-
the study was all-cause mortality. ated with high serum sodium levels. It is arguable on the basis
of these observations that the patients are mainly dehydrated
(high urea, low eGFR, and high sodium levels) in the mortality
5. Discussion
group. These all were statistically significant at the final
outcome. The most important was the creatinine levels at
In this series, 114 consecutive patients were studied. The age admission. The eGFR in VALIANT study, where the four-
of the patients ranged from age 27 to 92 years with the median component MDRD equation was used, found that the
age of 65 years, which is similar with the studies done in the distribution of estimated GFR was wide and normally shaped,
same setting.9,10 The mean age at diagnosis was 64 years in a with a mean (SD) value of 70  21 ml/min/1.73 m2 of body-
study done at western part of Nepal.11,12 Thus, it was seen that surface area, the probable reason of this difference being
the prevalence is higher in older age group and with higher primarily that we used median in our analysis and secondly
mortality rate. It was statistically significant with age >75 ethnicity being one of the variables.16 A more recent analysis
years. Age is a powerful predictor of adverse events after ACS. from the GUSTO (Global Utilization of Strategies To Open
In a study on ACS in Nepal, it is stated that death claims mostly occluded arteries) IV study found that creatinine clearance and
the elderly population; in US, 83% of IHD deaths were in troponin elevation provided the greatest relative contribution
patients of more than 65 years of age as per the GRACE to risk (1-year mortality or 30-day mortality/MI) beyond
registry.12–14 In the study, 27 patients were less than 55 years of traditional risk factors.17
age, which is also similar to the study done previously in the There have been different studies on the risk stratification
same setting.10 There is an increasing trend of young people of CK MB, but in one study done by Alexander et al., it showed a
having ACS. The male to female ratio is 1.16:1 whereas in statistical difference in 30-day mortality even if there was
previous study, it was 1.6:1, but in other studies from Nepal, it increase in the level of CK MB levels 1–2 times the upper
was 1.14:1,9 which varied with sample size and study settings. normal. In this study, the median CK MB level was 40 mg/dl,
The median leukocyte count was 12,300 cells/mm3. The but there was no statistical significance for risk stratification.
leukocytosis was in response to the inflammatory nature of The reasons may be due to smaller sample size when
ACS. In a study, it was seen that there was an epidemiological compared with the other study where it is very large.18
association indicating a worse angiographic appearance of the Secondly, the patients presented with a median duration of
536 indian heart journal 67 (2015) 529–537

2 days after the chest pain and as the levels of CK MB come to Logistic regression analysis of the variables studied was
normal level within 72 h, this delayed presentation gives us a done. Only those variables, which were significant at p ≤ 0.05 in
different picture. It was seen that there is a low triglyceride the bivariate analysis, were taken for multivariate analysis to
levels (<200 mg/dl) in the Caucasian patients with ACS if taken increase the statistical significance. It was found that age >55
within 24 h of admission. The study showed low triglyceride years; albuminuria and cardiogenic shock at the index event
level to be an independent predictor of mortality at 3 years remained as a strong predictor of all-cause mortality in
from the index event. In this study, the mean triglyceride patients with ACS in relation to each other. Similarly, hs-CRP
levels was 161.53  76.55 mg/dl, which is in lower range with levels >5 mg/dl and CK levels at the index event are also a
the given reference limit. This is also similar to the studies strong predictor of mortality.
done on ACS in the same setting.19
In this study, the hs-CRP levels of >5 mg/dl were highly
6. Summary and conclusion
significant for predicting mortality during hospital stay and at
6 weeks. In the GRACE registry, 12% of patients with STEMI,
13% with NSTEMI, and 8% with UA were expected to die in 6 The levels of serum hs-CRP, serum blood urea, serum
months within onset of symptoms.20 There have been a creatinine, and albuminuria (done using a simple uristix/
number of studies done which found the prognostic signifi- multistix test) at admission are statistically significant
cance of hs-CRP. Most of the studies were done in stable CAD. independent predictors of death in patients of ACS at the
The JUPITER trial, which was restricted to participants with index event at 6 weeks and at 6 months.
CRP levels >2 mg/l, found that treating the patients with When the significant biomarkers and the significant
rosuvastatin decreased the hs-CRP and LDL levels and the established risk factors were studied in relation to each other,
cardiovascular outcomes.21 hs-CRP levels were significant along with age in predicting
In this study, microalbuminuria was not taken as a variable, outcomes. Fluid balance is a very important aspect and we
as it was studied earlier but urine sample was sent for routine need to do a bigger study with larger sample size to generalize
analysis, which was done from multistix/uristix kit on every this observation.
patient with ACS. It was found that albuminuria was a
predictor of mortality. The more the level of albumin on
7. Limitations
admission, there was increased mortality. Acuna et al.22 found
microalbuminuria to be an independent risk factor of heart
failure (OR = 1.75; 95% CI = 1.02–3.01; p = 0.04) and of mortality In our setting, we did not have facilities for estimation of
(OR = 2.6; 95% CI = 1.05–6.41). quantitative levels of troponin and novel biomarkers like
In a study done in western Nepal, involvement of ACS was NTproBNP, which are more specific and better tools for
most common in anterior wall and inferior wall than any predicting outcomes in patients with ACS. During the study,
others wall.11 In this study, it was found there was a very there were no facilities for cardiac catheterization at our
similar involvement. This was also similar to the study on ACS setting.
at BPKIHS done previously. In a study, it was seen that
arrhythmias were in 27%, similar to the findings of this study,
Contributors
where 26% of patients had arrhythmias and it was found
statistically significant for predicting mortality. Cardiogenic
shock complicating STEMI resulted in high mortality.11 It was PK performed substantial contribution to conception and
observed that there was 11% in-hospital mortality in this design, revised the content of the draft critically for important
study. From the study, if the total in-hospital mortality intellectual content, and approved the final version to be
irrespective of the cause of death was taken, then it was published. KKA, LM and NRS performed substantial contribu-
found to be 13% (2 cases were excluded as the cause of death tion to conception and design, drafted the article, and
was not known). The high in-hospital mortality (14%) was approved the final version to be published.
observed in other study.10 This can be ascribed to markedly
delayed presentation, lack of resources for the best possible
Patient consent
available care, and major logistic difficulties to organize timely
PCI. During the study period, there were no facilities for PCI at
this setting. Similarly, in other study from Nepal, the in- Obtained.
hospital mortality was 12%.11 Outcomes at 6 weeks period
showed a significant mortality. The duration of hospital course
Ethics approval
was almost similar when compared with other contemporary
international surveys like GRACE registry. At 6 months, the
overall mortality was 28%, which is highly significant. No other Institutional Ethical Review Board (ERB) of B.P. Koirala Institute
study was done in this setting to compare results at 6 months of Health Sciences, Dharan, Nepal.
duration.
We also searched to look for other studies in Nepal which
Conflicts of interest
did a follow-up of the patients. We found a registry of patients
in western Nepal, but data for 6 months period were lacking in
that study. The authors have none to declare.
indian heart journal 67 (2015) 529–537 537

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