Hypertension

Learning objectives
Upon completion of the chapter, the reader will be able to:
1. Classify blood pressure levels and treatment goals.
2. Recognize the underlying causes and contributing factors
in the development of hypertension.
3. Describe the appropriate measurement of blood pressure.
4. Recommend appropriate lifestyle modifications and
pharmacotherapy for patients with hypertension.
5. Identify populations requiring special consideration when
designing a treatment plan.
6. Construct an appropriate monitoring plan to assess
hypertension treatment.
• Hypertension is a common disease that is simply defined
as persistently elevated arterial blood pressure (BP).
• Arterial BP is the pressure in the arterial wall measured in
millimeters of mercury (mm Hg).
• The two typical arterial BP values are
– systolic BP (SBP)

– diastolic BP (DBP)

• SBP is achieved during cardiac contraction

• DBP is achieved after contraction when the cardiac
chambers are filling.
Etiology
• In most patients, hypertension results from an unknown
pathophysiologic etiology
– essential or primary hypertension

– This form of hypertension cannot be cured, but it can be

controlled.

• A small percentage of patients have a specific cause of

their hypertension
– secondary hypertension
Types of Hypertension and Their Frequency
• There are many potential secondary causes
– that are either concurrent medical conditions or are
endogenously induced.

• If the cause can be identified, hypertension in these

patients has the potential to be cured.
Classification of Blood Pressure in Adults (Age ≥18 Years)
Pathophysiology
• Multiple factors that control BP are potential contributing
components in the development of essential hypertension.
• These include
– malfunctions in humoral (i.e., the renin–angiotensin–
aldosterone system [RAAS])
– vasodepressor mechanisms, abnormal neuronal
mechanisms, defects in peripheral autoregulation, and
disturbances in sodium, calcium, and natriuretic
hormones.
Humoral Mechanisms
• Several humoral abnormalities may be involved in the
development of essential hypertension.
• These abnormalities may involve the RAAS

Renin–Angiotensin–Aldosterone System
• The RAAS is a complex endogenous system that is
involved with most regulatory components of arterial BP.
• Activation and regulation are primarily governed by the
kidney.
• The RAAS regulates sodium, potassium, and fluid
balance.
• Consequently, this system significantly influences vascular
tone and sympathetic nervous system activity
– is the most influential contributor to the homeostatic
regulation of BP.

• Renin is an enzyme that is stored in the juxtaglomerular

cells
– which are located in the afferent arterioles of the kidney
• Juxtaglomerular cells function as a baroreceptor-sensing
device.
• Decreased renal artery pressure and kidney blood flow
– are sensed by these cells and stimulate secretion of renin.

• The juxtaglomerular apparatus also includes a group of

specialized distal tubule cells
– referred to collectively as the macula densa

• A decrease in sodium and chloride delivered to the distal

tubule stimulates renin release.
• Renin catalyzes the conversion of angiotensinogen to
angiotensin I in the blood.
• Angiotensin I is then converted to angiotensin II by
angiotensin-converting enzyme (ACE).

• Circulating angiotensin II can elevate BP through pressor

and volume effects.
• Pressor effects include direct vasoconstriction.

• Angiotensin II also stimulates aldosterone synthesis from

the adrenal cortex.
– This leads to sodium and water reabsorption that increases
plasma volume, total peripheral resistance, and ultimately BP.
Treatment of Hypertension

Desired Outcomes
Overall Goal of Therapy

• The overall goal of treating hypertension is to reduce

hypertension associated morbidity and mortality.
General Approach to Treatment

• After a definitive diagnosis of hypertension is made

– most patients should be placed on both lifestyle
modifications and drug therapy concurrently.
• Lifestyle modification alone is considered appropriate
therapy for patients with prehypertension.
• Most patients with stage 1 hypertension should be
initially treated with
– thiazide-type diuretic, ACE inhibitor, ARB, or CCB.

• For patients with more severe BP elevation (stage 2

hypertension)
– combination drug therapy, with one of the agents being
preferably a thiazide type-diuretic, is recommended.
Algorithm for treatment of hypertension.

Initial Drug Therapy

Choices

No Compelling Compelling
Indications Indications

Stage 1 Hypertension Stage 2 Hypertension

(SBP 140–159 or DBP 90– (SBP >160 or DBP >100
99 mm Hg) mm Hg)

Two-drug combination for most

Thiazide-type diuretics ,
Usually a thiazide-type diuretic
ACE inhibitor, ARB, CCB, or
with an ACE inhibitor, or ARB, or
combination CCB
Nonpharmacologic Therapy
• All patients with prehypertension and hypertension should
be prescribed lifestyle modifications.
• A sensible dietary program is one that is designed to
reduce weight gradually
– for overweight and obese patients

• Restricts sodium intake with only moderate alcohol

consumption.
• Patients may better understand the rationale for dietary
intervention in hypertension
1. Hypertension is two to three times more likely in
overweight than in lean persons.
2. More than 60% of patients with hypertension are
overweight.
3. As little as 10 pounds of weight loss can decrease BP
significantly in overweight patients.
4. Abdominal obesity is associated with the metabolic
syndrome, which is a precursor to diabetes, dyslipidemia,
and, ultimately, CV disease.
Lifestyle Modifications to Prevent and Manage Hypertension
5. Diets rich in fruits and vegetables and low in saturated fat
lower BP in patients with hypertension.

6. Most people experience some degree of SBP reduction with

sodium restriction.
Pharmacotherapy
• A diuretic (primarily a thiazide-type)
• ACE inhibitor(ACEI)

• Angiotensin IIreceptor blocker (ARB)

• Calcium channel blocker (CCB)

– Are considered primary antihypertensive agents that are

acceptable firstline options
• These agents should be used to treat the majority of patients
with hypertension
– because evidence from outcomes data have demonstrated CV
risk reduction benefits with these classes.

• β-Blockers are effective antihypertensive agents that

previously were considered primary agents.
• They are now preferred
– to treat a specific compelling indication

– in combination with one of the aforementioned primary

antihypertensive agents for patients without a compelling
indication.
• Other antihypertensive drug classes are considered
– alternative drug classes that may be used in select
patients after primary agents
Individual Antihypertensive Agents

Diuretics
• Thiazide, are first-line agents for hypertension
• When combination therapy is needed in hypertension
– diuretic is recommended to be one of the agents used

• There are four subclasses of diuretics that are used in the

treatment of hypertension:
– thiazides, loops, potassium-sparing agents, and
aldosterone antagonists
• Potassium-sparing diuretics are weak antihypertensive agents
– but provide an additive effect when used in combination with a
thiazide or loop diuretic.

– They counteract the potassium- and magnesium-losing properties

of the other diuretic agents and possible glucose intolerance.

• Thiazides are the preferred type of diuretic for treating

hypertension.

• In patients requiring diuresis to treat concurrent edema, such as

in heart failure, a loop diuretic should be considered.
ACE Inhibitors
• Are a first-line agents for hypertension
• Angiotensin II
– is a potent vasoconstrictor

– also stimulates aldosterone secretion

• causing an increase in sodium and water reabsorption
with accompanying potassium loss.

• Blocking the ACE

– vasodilation and a decrease in aldosterone occur
• ACE inhibitors
– block degradation of bradykinin

– stimulate the synthesis of other vasodilating substances

(prostaglandin E2 and prostacyclin)

• Increased bradykinin
– enhances the BP-lowering effects of ACE inhibitors

– responsible for the side effect of dry cough

Angiotensin Receptor Blockers/ARBs
• Are first-line agents for hypertension.
• Angiotensin II is generated by two enzymatic pathways:
– RAAS, which involves ACE, and an alternative pathway
that uses other enzymes such as chymases.

• ACE inhibitors inhibit only the effects of angiotensin II

produced through the RAAS
• ARBs inhibit angiotensin II from all pathways.
• ARBs directly block the angiotensin II receptor subtype 1
receptor that mediates
– the known effects of angiotensin II in humans:
• vasoconstriction, aldosterone release, sympathetic
activation, antidiuretic hormone release, and constriction of
the efferent arterioles of the glomerulus.

• ARBs do not block the angiotensin II receptor subtype 2

receptor
– the beneficial effects of angiotensin II receptor subtype 2
stimulation (vasodilation, tissue repair, and inhibition of
cell growth) remain intact when ARBs are used.
• Unlike ACE inhibitors, ARBs do not block the breakdown
of bradykinin.
• Therefore, some of the beneficial effects of bradykinin,
such as vasodilation are not present with ARB therapy
• ARBs have the lowest incidence of side effects compared
to other antihypertensive agents.
• Because they do not affect bradykinin, they do not have
the potential to illicit a dry cough like ACE inhibitors.
Calcium Channel Blockers/ CCBs
• Both dihydropyridine CCBs and nondihydropyridine CCBs
– are first-line agents for hypertension.

• Dihydropyridine CCBs are very effective in older patients

with isolated systolic hypertension.
• Nondihydropyridines decrease heart rate
β-Blockers
• Cardioselective β-blockers (e.g., atenolol, metoprolol)
have clinically significant advantages over nonselective β-
blockers (e.g., propranolol, nadolol), and are generally
preferred to treat hypertension.
• Cardioselective agents are safer than nonselective agents
in patients with asthma or diabetes.
Compelling indications for individual drug classes
Special Populations
Pregnancy
• Hypertension during pregnancy is a major cause of maternal and
neonatal morbidity and mortality.
• Hypertension during pregnancy is categorized as preeclampsia,
eclampsia, gestational, chronic
• Preeclampsia, defined as a elevated BP greater than or equal to
140/90 mm Hg that appears after 20 weeks gestation
– accompanied by new-onset proteinuria (≥300 mg/24 hours)

– can lead to life-threatening complications for both mother

and fetus.
• Eclampsia, the onset of convulsions in preeclampsia, is a
medical emergency.
• Gestational hypertension is defined as new-onset
hypertension arising after midpregnancy in the absence of
proteinuria
• Chronic hypertension is elevated BP that is noted before
the pregnancy began.
Treatment of Chronic Hypertension in Pregnancy
Hypertensive Urgencies and Emergencies
• Both hypertensive urgencies and emergencies are
– characterized by the presence of very elevated BP—
greater than 180/120 mm Hg.

Hypertensive Urgency
• Hypertensive urgencies are ideally managed by adjusting
maintenance therapy
– by adding a new antihypertensive and/or increasing the
dose of a present medication.
• This is the preferred approach to these patients as it
provides a more gradual reduction in BP.
• Very rapid reductions in BP to goal values should be
discouraged because of potential risks.
• Because autoregulation of blood flow in patients with
hypertension occurs at a much higher range of pressure
than in normotensive persons
– the inherent risks of reducing BP too precipitously include
cerebrovascular accidents, MI, and acute kidney failure.
• Hypertensive urgency requires BP reductions with oral
antihypertensive agents to stage 1 values over a period of
several hours to several days.
• All patients with hypertensive urgency should be
reevaluated within 7 days (preferably after 1 to 3 days).
• Acute administration of a short-acting oral antihypertensive
(captopril, clonidine or labetalol) followed by careful
observation for several hours
– to assure a gradual reduction in BP is an option for
hypertensive urgency.
• Oral captopril is one of the agents of choice and can be
used in doses of 25 to 50 mg at 1- to 2- hour intervals.
• The onset of action of oral captopril is 15 to 30 minutes
Hypertensive Emergency
• Hypertensive emergencies are those rare situations
– that require immediate BP reduction to limit new or
progressing target-organ damage

• Hypertensive emergencies require parenteral therapy

• The goal in hypertensive emergencies is not to lower BP to
less than 140/90 mm Hg
• Nitroprusside is widely considered the agent of choice for
most cases
– but can be problematic in patients with chronic kidney
disease.

• It is a direct-acting vasodilator that decreases peripheral

vascular resistance
• Intravenous nitroglycerin dilates both arterioles and
venous capacitance vessels
– thereby reducing both cardiac afterload and preload which
can decrease myocardial oxygen demand.
• Fenoldopam and nicardipine are newer and more
expensive alternative agents.
• It can improve renal blood flow and may be especially
useful in patients with kidney insufficiency.
Parenteral Antihypertensive Agents for Hypertensive Emergency