Hypertension
Introduction
1-Hypertension is defined as persistently elevated
arterial blood pressure (BP).
2-Isolated systolic hypertension is diastolic
blood pressure (DBP) <80 mm Hg and
systolic blood pressure (SBP) 130 mm Hg.
3-Hypertensive crisis (BP >180/120 mm Hg)
is categorized as hypertensive emergency
(extreme BP elevation with acute or
progressing end-organ damage) or
hypertensive urgency (extreme BP elevation
without acute or progressing end-organ
injury).
End-organ damage
Pathophysiology
1-Hypertension may result from an
unknown etiology (primary or essential
hypertension) or from a specific cause
(secondary hypertension).
2-Secondary hypertension (<10% of
cases) is usually caused by chronic kidney
disease (CKD) or renovascular disease.
3-Examples of drugs that may increase BP
include corticosteroids, estrogens, NSAIDs,
cyclosporine, erythropoietin, and venlafaxine.
4-Major causes of death include
cerebrovascular events, cardiovascular (CV)
events, and renal failure.
Clinical presentation
1-Patients with uncomplicated primary
hypertension are usually asymptomatic
initially.
2-Patients with secondary hypertension
may have symptoms of the underlying
disorder.
Diagnosis
1-Elevated BP may be the only sign of primary
hypertension on physical examination.
2-Diagnosis should be based on the average
of two or more readings taken at each of two
or more clinical encounters.
3-Signs of end-organ damage occur primarily
in the eyes, brain, heart, kidneys, and
peripheral vasculature.
Treatment
1-Goals of Treatment: The overall goal is
to reduce morbidity and mortality from
CV events.
The 2017 ACC/AHA guideline
recommends a goal BP of <130/80 mm
Hg for most patients.
2-For institutionalized older patients and
those with a high disease burden or
limited life expectancy, consider a
relaxed SBP goal of <150 mm Hg (or <140
mm Hg if tolerated).
Nonpharmacologic Therapy
A-Implement lifestyle modifications in all
patients with elevated BP or stage 1 or 2
hypertension.
B-Lifestyle modifications shown to lower BP
include:
(1) weight loss if overweight or obese, (2) the
Dietary Approaches to Stop Hypertension (DASH)
eating plan, (3) reduced salt intake, ideally to 1.5
g/day sodium (3.8 g/day sodium chloride), (4)
physical activity (90 150 min/week of aerobic or
dynamic resistance training), and (5) moderation of
alcohol intake. Although smoking cessation does
not control BP, it reduces CV disease risk and should
be encouraged.
Pharmacologic Therapy
General Approach to Treatment
1-Initial drug selection depends on the degree
of BP elevation and presence of compelling
indications for certain drugs.
2-Use a single first-line drug as initial therapy
in most patients with newly diagnosed stage 1
hypertension.
3-Start combination drug
therapy (preferably with two
first-line drugs) as the initial
regimen in patients with
newly diagnosed stage 2
hypertension.
4-The four first-line options
are angiotensin-converting
enzyme (ACE) inhibitors,
angiotensin II receptor
blockers (ARBs), calcium
channel blockers (CCBs), and
thiazide diuretics.
5- -Blockers should be reserved to treat a
specific compelling indication or in
combination with a first-line antihypertensive
agent for patients without a compelling
indication.
6-Other antihypertensive drug classes 1-
blockers, direct renin inhibitors, central 2-
agonists, and direct arterial vasodilators) may
be used for select patients after
implementing first-line agents.
Compelling Indications
Compelling indications are specific
comorbid conditions for which clinical
trial data support using specific
antihypertensive drug classes to treat
both hypertension and the compelling
indication.
Notes:
1- -Blockers (without ISA) are first-line
therapy in Stable Ischemic Heart Disease
(SIHD).
2-For acute coronary syndromes, first-line
therapy includes a -blocker and ACE
inhibitor (or ARB).
3-Any first-line agent can be used to
control hypertension in patients with
diabetes in the absence of albuminuria.
4-In addition to lowering BP, ACE
inhibitors and ARBs reduce
intraglomerular pressure, which may
further slow chronic kidney disease
progression.
5-The threshold for starting
antihypertensive drug therapy in
patients with a history of stroke is when
BP is >140/90 mm Hg (goal of <130/80
mm Hg).
Angiotensin-Converting Enzyme Inhibitors
(captopril, enalapril, fosinopril, imidapril, lisinopril,
perindopril, quinapril, ramipril, and trandolapril)
1-ACE inhibitors block conversion of angiotensin I to
angiotensin II, a potent vasoconstrictor and
stimulator of aldosterone secretion.
2-Starting doses should be low with slow dose
titration. Acute hypotension may occur at the onset
of therapy.
3-ACE inhibitors decrease aldosterone
and can increase serum potassium
concentrations.
Hyperkalemia occurs primarily in
patients with CKD or those also taking
potassium supplements, potassium-
sparing diuretics, mineralocorticoid
receptor antagonists, ARBs, or direct
renin inhibitors.
4-AKI is an uncommon but serious side
effect; preexisting kidney disease
increases risk.
Patients with bilateral renal artery
stenosis or unilateral stenosis are
particularly susceptible to AKI.
5-Serum creatinine concentrations often
increase, but modest elevations (eg, absolute
increases <1 mg/dL) do not warrant
treatment changes. Discontinue therapy or
reduce dose if larger increases occur.
6-Angioedema occurs in <1% of patients.
Drug withdrawal is necessary, and some
patients may require drug treatment and/or
emergent intubation to support respiration.
Angioedema
7-An ARB can generally be used in patients
with a history of ACE inhibitor-induced
angioedema, with careful monitoring.
8-A persistent dry cough occurs in up to 20%
of patients and is thought to be due to
inhibition of bradykinin breakdown.
10-ACE inhibitors (as well as ARBs and direct
renin inhibitors) are contraindicated in
pregnancy.
Angiotensin II Receptor Blockers (candesartan,
eprosartan, irbesartan, losartan, olmesartan,
telmisartan, and valsartan)
1-The ARBs directly block the angiotensin II type 1
receptor that mediates the effects of angiotensin
II.
2-Unlike ACE inhibitors, ARBs do not block
bradykinin breakdown and this accounts for the
lack of cough as a side effect.
3-ARBs have a low incidence of side
effects. Like ACE inhibitors, they may
cause renal insufficiency, hyperkalemia,
and orthostatic hypotension.
Calcium Channel Blockers
1-Dihydropyridine and nondihydropyridine CCBs are
first-line antihypertensive therapies and are also
used in addition to or instead of other first-line
agents for the compelling indication of ischemic
heart disease.
2-Dihydropyridine CCBs may cause reflex
sympathetic activation, and all agents (except
amlodipine and felodipine) may have negative
inotropic effects.
3-Verapamil produces a negative inotropic effect
that may precipitate HF in patients with borderline
cardiac reserve. Diltiazem decreases heart rate to a
lesser extent than verapamil.
4-Both diltiazem and verapamil can cause
peripheral edema and hypotension. Verapamil
causes constipation in about 7% of patients.
5-Dihydropyridines cause a
baroreceptor-mediated reflex increase in
heart rate because of potent peripheral
vasodilating effects.
Other side effects of dihydropyridines
are dizziness, flushing, headache, gingival
hyperplasia, and peripheral edema.
Diuretics
1-Thiazides are the preferred type of diuretic
and are a first-line option for most patients
with hypertension. Chlorthalidone (thiazide-
like) is preferred over hydrochlorothiazide,
especially in resistant hypertension, because it
is more potent on a milligram-per-milligram
basis.
2-Loop diuretics (Furosemide, Bumetanide
and Torasemide) are more potent for
inducing diuresis but are not ideal
antihypertensives unless edema treatment is
also needed.
Loop diuretics are sometimes required over
thiazides in patients with severe CKD when
eGFR is <30 mL/min/1.73 m2, especially when
edema is present.
3-Potassium-sparing diuretics are weak
antihypertensives when used alone.
Their primary use is in combination with
another diuretic to counteract potassium-
wasting properties.
4-Mineralocorticoid receptor antagonists
(spironolactone and eplerenone) are also
potassium-sparing diuretics that are usually
used to treat resistant hypertension because
elevated aldosterone concentrations are
prevalent in this setting. They are also used
as add-on agents in patients with HFrEF with
or without concomitant hypertension.
5-Acutely, diuretics lower BP by
causing diuresis. With chronic
therapy, reduced peripheral vascular
resistance is responsible for
persistent hypotensive effects.
6-Side effects of thiazides include hypokalemia,
hypomagnesemia, hypercalcemia, hyperuricemia,
hyperglycemia, dyslipidemia, and sexual
dysfunction.
7-Loop diuretics have less effect on serum lipids and
glucose, but hypokalemia is more pronounced, and
hypocalcemia may occur.
8-Hypokalemia and hypomagnesemia may cause
muscle fatigue or cramps, and severe electrolyte
abnormalities may result in serious cardiac
arrhythmias.
9-Potassium-sparing diuretics may cause
hyperkalemia, especially in patients with CKD or
diabetes and in patients receiving concurrent
treatment with a mineralocorticoid receptor
antagonist, ACE inhibitor, ARB, direct renin inhibitor,
or potassium supplement.
10-Spironolactone may cause gynecomastia in up
to 10% of patients; this effect occurs rarely with
eplerenone.
-Blockers
1-Evidence suggests that -blockers may not
reduce CV events as well as ACE inhibitors, ARBs,
CCBs, or thiazides when used as the initial drug in
patients who do not have a compelling indication
for a -blocker.
2- -Blockers are appropriate first-line agents when
used to treat specific compelling indications or
when an ACE inhibitor, ARB, CCB, or thiazide cannot
be used.
3-Atenolol, betaxolol, bisoprolol, metoprolol,
and nebivolol are 1-cardioselective at low
dose. As a result, they are less likely to
provoke bronchospasm and vasoconstriction
and are safer than nonselective -blockers in
patients with asthma or diabetes.
Cardioselectivity is a dose-dependent
phenomenon, and the effect is lost at higher
doses.
5-Acebutolol, carteolol, and pindolol possess
intrinsic sympathomimetic activity (ISA) or
partial -receptor agonist activity.
Theoretically, these drugs may have
advantages in select patients with HF or sinus
bradycardia. Unfortunately, they do not
reduce CV events as well as other -blockers
and may increase CV risk in patients with
SIHD. Thus, agents with ISA are rarely
needed and have no role in hypertension
management.
6-Atenolol and nadolol have relatively long
half-lives and are excreted renally; the
dosage may need to be reduced in patients
with renal insufficiency.
7-Even though the half-lives of other -
blockers are shorter, once-daily
administration still may be effective.
8-Cardiac side effects include bradycardia, AV
conduction abnormalities, and acute HF.
Blocking 2-receptors in arteriolar smooth
muscle may cause cold extremities and
aggravate intermittent claudication or
Raynaud phenomenon because of decreased
peripheral blood flow.
9-Increases in serum lipids and glucose
appear to be transient and of little clinical
significance.
10-Abrupt cessation of -blockers
should be avoided.
The dose should always be tapered
gradually over 1 2 weeks before
discontinuation.
1-Receptor Blockers
1-Prazosin, terazosin, and doxazosin are selective
1-receptor blockers that inhibit catecholamine
uptake in smooth muscle cells of peripheral
vasculature, resulting in vasodilation and BP
lowering.
2-Although they can provide symptomatic benefit in
men with benign prostatic hyperplasia, they should
be used to lower BP only in combination with first-
line antihypertensive agents.
Direct Renin Inhibitor
Aliskiren blocks the RAAS at its point of
activation, resulting in reduced plasma renin
activity and BP. It is approved for
monotherapy or in combination therapy. Its
role in the management of hypertension is
limited.
Central 2-Agonists
1-Clonidine, guanfacine, and methyldopa
lower BP primarily by stimulating 2-
adrenergic receptors in the brain, which
reduces sympathetic outflow from the
vasomotor center.
2-Clonidine is often used in resistant
hypertension, and methyldopa is frequently
used for pregnancy-induced hypertension.
Direct Arterial Vasodilators
1-Hydralazine and minoxidil directly relax
arteriolar smooth muscle, resulting in
vasodilation and BP lowering.
Special Populations
Older Persons
1-Older patients may present with either isolated
systolic hypertension or elevation in both SBP and
DBP. CV morbidity and mortality are more directly
correlated to SBP than to DBP in patients aged 50
and older.
2-First-line antihypertensives provide significant
benefits and can be used safely in older patients,
but smaller-than-usual initial doses must be used
for initial therapy.
Children and Adolescents
1-Because secondary hypertension is
more common in children and
adolescents than in adults, an
appropriate workup is required if
elevated BP is identified.
2-Nonpharmacologic treatment is the
cornerstone of therapy for primary
hypertension.
3-ACE inhibitors, ARBs, -blockers, CCBs, and
thiazide diuretics are all acceptable drug
therapy choices.
Pregnancy
1-Preeclampsia can lead to life-threatening
complications for both mother and fetus.
2-Eclampsia is the onset of convulsions in
preeclampsia and is a medical emergency.
3-Definitive treatment of preeclampsia is
delivery, and labor induction is indicated if
eclampsia is imminent or present. Otherwise,
management consists of restricting activity,
bed rest, and close monitoring. Salt
restriction or other measures that contract
blood volume should be avoided.
4-Antihypertensives are used before induction of
labor if DBP is >105 mm Hg, with a target DBP of
95 105 mm Hg. Intravenous (IV) hydralazine is most
commonly used; IV labetalol is also effective.
5-Chronic hypertension is hypertension that
predates pregnancy. Labetalol, long-acting
nifedipine, or methyldopa is recommended as
first-line therapy due to favorable safety profiles. -
Blockers (except atenolol) and CCBs are also
reasonable alternatives.
Black Patients
1-CCBs and thiazides are most effective in
African Americans and should be first-line in
the absence of a compelling indication.
Pulmonary Disease and Peripheral Arterial
Disease (PAD)
1-Although -blockers (especially nonselective
agents) have generally been avoided in
hypertensive patients with asthma and COPD
because of fear of inducing bronchospasm,
cardioselective -blockers can be used safely.
2- -Blockers can theoretically be problematic
in patients with PAD because of possible
decreased peripheral blood flow secondary to
unopposed stimulation of 1-receptors that
results in vasoconstriction. However, available
data indicate that -blockers do not worsen
claudication symptoms or cause functional
impairment. Therefore, antihypertensive
treatment for patients with PAD should
follow the same general principles as
patients without PAD.
Hypertensive Urgencies and
Emergencies
1-Acute administration of a short-acting oral
drug (captopril, clonidine, or labetalol) is an
option.
2-Hypertensive emergencies require
immediate BP reduction with a parenteral
agent to limit new or progressing end-organ
damage.
Evaluation of therapeutic outcomes
1-Evaluate BP response in the clinic 4 weeks
after initiating or making changes in
therapy and compare the results to home BP
readings.
2-Once goal BP is obtained, monitor BP
every 3 6 months, assuming no signs or
symptoms of acute end-organ damage.
3-Assess patient adherence with the
regimen regularly.
Thank You
