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A diagnosis of hypertension is based on the mean of two or more
properly measured seated blood pressure (BP) measurements taken on
Most patients with hypertension have a recommended BP goal of less
than 140/90 mm Hg (including those with diabetes or chronic kidney
disease [CKD] under age 70 years). Elderly patients (age > 60 years)
have a higher BP goal of less than 150/90 mm Hg (see core principle
Lifestyle modifications are the foundation for preventing hypertension,
and they are an important component of first-line therapy in all patients
treated with antihypertensive drug therapy.
Evidence supports the use of an angiotensin-converting enzyme inhibitor
(ACEI), angiotensin receptor blocker (ARB), calcium-channel blocker
(CCB), or thiazide diuretic as first-line therapy to prevent cardiovascular
(CV) events for most patients.
In black population, including those with diabetes, evidence supports the
use of thiazide diuretics and CCB.
Pharmacotherapy recommendations for patients with hypertension and
other comorbidities are specifically based on evidence demonstrating
Elderly patients with hypertension should be managed using the same
general treatment principles that apply to all patients with hypertension.
However, their BP goal is higher (less than 150/90 mm Hg) unless they
also have CKD and age younger than 70 years. In such case, their BP
goal is less than 140/90 mm Hg.
In the population aged ≥18 years with CKD and age under 70 years,
evidence supports initial (or add-on) antihypertensive treatment to
include an ACEI or ARB to improve renal outcomes. This applies to all
CKD patients with hypertension regardless of race or diabetes status.
If goal BP is not attained within a month of treatment, increase the dose
of the initial drug or add a second drug (ACEI, ARB, CCB, or thiazide
diuretic). If goal BP cannot be reached with two drugs, add and titrate a
third drug. If goal BP cannot be reached using only the drugs
recommended as first line, because of a contraindication or the need to
use more than three drugs to reach goal BP, antihypertensive drugs
from other classes can be used. Referral to a hypertension specialist
Approximately 80 million Americans have hypertension, also called high blood
It is estimated that approximately 33% of adult Americans have
hypertension, making it the most frequently encountered chronic medical condition.
About 77% of those are using antihypertensive medication, but only 54% of those are
controlled (defined as both systolic BP [SBP] <140 mm Hg and diastolic BP [DBP]
<90 mm Hg). It is also one of the most significant risk factors for cardiovascular
(CV) morbidity and mortality resulting from target-organ damage to blood vessels in
the heart, brain, kidney, and eyes. These complications can manifest as either
atherosclerotic vascular disease or other forms of CV disease. The exact etiology of
essential hypertension is unknown; however, lifelong management with lifestyle
modifications and pharmacotherapy are usually needed.
During systole, the left ventricle contracts, ejecting blood systemically into the
arteries causing a sharp rise in arterial BP. This is the systolic BP. The left ventricle
then relaxes during diastole, and arterial BP decreases to a trough value as blood
returns to the heart from the venous system. This is the diastolic BP. When recording
BP (e.g., 120/76 mm Hg), the numerator is the SBP and the denominator is the DBP.
BP has a predictable diurnal rhythm, with fluctuations throughout the day. Values are
lowest during the nighttime, sharply rise starting in the early morning, and peak in the
late morning to early afternoon.
Mean arterial pressure (MAP) is sometimes used to represent BP, especially in
patients with hypertensive emergency. MAP collectively reflects both SBP and DBP,
with one-third of the pressure from SBP and two-thirds from DBP. It is calculated
using the following equation (Eq. 9-1):
Hypertension is defined as an elevated SBP, DBP, or both. A clinical diagnosis of
hypertension is based on the mean of two or more properly measured seated BP
measurements taken on two or more occasions. Since 1976, the National Heart Lung
and Blood Institute has collaborated with researchers and practitioners to develop
clinical practice guidelines focused on the management of hypertension (The Joint
National Commission [JNC]). In late 2013, the eighth edition of the JNC guidelines
2 Unlike previous editions of the JNC guidelines, definitions and
staging of BP were not addressed, but thresholds for pharmacologic treatment were
defined, which will be discussed here.
PATHOPHYSIOLOGY OF BLOOD PRESSURE REGULATION
Various neural and humoral factors are known to influence and regulate BP.
include the adrenergic nervous system (controls α- and β-adrenergic receptors), the
renin–angiotensin–aldosterone system (RAAS) (regulates systemic and renal blood
flow), renal function and renal blood flow (influences fluid and electrolyte balance),
several hormonal factors (adrenal cortical hormones, vasopressin, thyroid hormone,
and insulin), and the vascular endothelium (regulates release of nitric oxide [NO],
bradykinin, prostacyclin, and endothelin). Knowledge of these mechanisms is
important in understanding antihypertensive drug therapy. BP is normally regulated
by compensatory mechanisms that respond to changes in cardiac demand. An
increase in cardiac output (CO) normally results in a compensatory decrease in total
peripheral resistance (TPR); likewise, an increase in TPR results in a decrease in
CO. These events regulate MAP, as is represented in the following equation (Eq. 9-
Adverse changes in BP can occur when these compensatory mechanisms are not
functioning properly. It has been suggested that in hypertension an initial increase in
fluid volume increases CO and arterial pressure. Eventually, with long-standing
hypertension, it is believed that TPR increases so that CO returns to normal.
The kidney plays an important role in the regulation of arterial pressure, especially
through the RAAS. Decreases in BP and renal blood flow, volume depletion or
decreased sodium concentration, and an activation of the sympathetic nervous system
can all trigger an increased secretion of the enzyme renin from the cells of the
juxtaglomerular apparatus in the kidney. Renin acts on angiotensinogen to catalyze the
formation of angiotensin I. Angiotensin-converting enzyme (ACE) converts
angiotensin I to angiotensin II (see Figs. 14-2 and 14-6 in Chapter 14, Heart Failure).
Angiotensin II is a potent vasoconstrictor that acts directly on arteriolar smooth
muscle and also stimulates the production of aldosterone by the adrenal glands.
Aldosterone causes sodium and water retention and the excretion of potassium.
Several factors influence renin release, especially those that alter renal perfusion.
The resultant increase in BP results in suppression of renin release through negative
concentrations that are higher than normal. Those with normal to high PRA (e.g.,
young and whites) should theoretically be more responsive to drug therapies that
target the RAAS (e.g., ACE inhibitors and angiotensin receptor blockers [ARBs]).
Patients with low PRA may be more responsive to diuretic therapy. However,
routinely measuring PRA as a strategy to guide empiric drug selection has limited
clinical utility and does not generally result in an outcome superior to careful
selection of antihypertensive drug therapy.
Arterial BP is also regulated by the adrenergic nervous system, which causes
contraction and relaxation of vascular smooth muscle. Stimulation of α-adrenergic
receptors in the central nervous system (CNS) results in a reflex decrease in
sympathetic outflow, causing a decrease in BP. Stimulation of postsynaptic α1
receptors in the periphery causes vasoconstriction. The α-receptors are regulated by
a negative feedback system; as norepinephrine is released into the synaptic cleft and
-receptors, further norepinephrine release is inhibited. This
negative feedback results in a balance between vasoconstriction and vasodilatation.
Stimulation of postsynaptic β1
-receptors located in the myocardium causes an
increase in heart rate and contractility, whereas stimulation of postsynaptic β2
receptors in blood vessels results in vasodilation.
A direct association exists between sodium and BP. Although there is a
considerably high degree of patient variability in BP sensitivity to sodium (likely
affected by heredity and interactions with other environmental exposures), patients
with a high dietary sodium intake generally have a greater prevalence of hypertension
than those with a low sodium intake. The mechanism by which excess sodium intake
contributes to hypertension is uncertain, but it is believed to involve an undetermined
natriuretic hormone (not the A- and B-type natriuretic peptides associated with heart
failure) that may be induced as a consequence of impaired renal sodium excretion.
This natriuretic hormone might also cause an increase in intracellular sodium and
calcium, resulting in increased vascular tone and hypertension. The consequences of
impaired sodium excretion may have an underlying evolutionary basis. Human
physiology evolved in a “hunter-gatherer” society with diets characterized by low
sodium and high potassium. The
relatively recent shifts in diet patterns brought about by the advent of modern food
processing, coupled with increased survival beyond reproductive years, may not
have made it possible for modern humans to adapt successfully to high sodium
Epidemiologic evidence and clinical trials have demonstrated an inverse
relationship between calcium and BP. One proposed mechanism for this relationship
involves an alteration in the balance between intracellular and extracellular calcium.
Increased intracellular calcium concentrations can increase peripheral vascular
resistance (PVR), resulting in increased BP.
A decrease in dietary potassium has been associated with an increase in PVR. In
theory, diuretic-induced hypokalemia could counteract some of the antihypertensive
effects of diuretic therapy, but this has not been seen in clinical trials. It is important,
however, that potassium concentrations be maintained within the normal range
because hypokalemia increases the risk of CV events, such as sudden death.
Insulin resistance and hyperinsulinemia also have been associated with
3 suggests that insulin resistance is responsible for the frequent
coexistence of hyperglycemia, dyslipidemia, hypertension, and abdominal obesity
(also called the metabolic syndrome).
4 The exact role of insulin resistance in the
development of hypertension is still evolving.
The vascular epithelium is a dynamic system in which vascular tone is regulated
by numerous substances. As noted previously, angiotensin II promotes
vasoconstriction of the vascular epithelium. However, several other substances
regulate vascular tone. NO is produced in the endothelium and is a potent
vasodilatory chemical that relaxes the vascular smooth muscle. Hypothetically, some
patients with hypertension have an intrinsic deficiency in NO release and inadequate
vasodilation, which could contribute to hypertension and its vascular complications.
Factors that regulate BP are well understood and continue to evolve, but the cause
of essential hypertension is still unknown. It is impossible to target therapy to
specific abnormalities. Therefore, antihypertensive therapy should be selected based
CARDIOVASCULAR RISK AND BLOOD PRESSURE
Direct correlations between BP values and risk of CV disease have been established
based primarily on epidemiologic data. Beginning at a benchmark BP of 115/75 mm
Hg, the risk of CV disease doubles with every increment of 20/10 mm Hg.
Clinically, it is important to note that incremental elevations in SBP are more
predictive of CV disease than elevations in DBP, especially for patients older than
50 years of age. Therefore, SBP is the target of evaluation and intervention for most
patients with hypertension. In younger patients with hypertension, elevated DBP may
be the only BP abnormality present.
The measurement of BP should be standardized to minimize variability in readings.
The American Heart Association (AHA) technique for auscultatory BP measurement
5 should be used in most patients.
For a video demonstrating methods for measuring BP in adults (courtesy of the University of Colorado
School of Pharmacy), go to http://www.youtube.com/watch?
v=Blqei6_s6J0&list=UUPLXxewjAvEBrO9DuLERbbQ.
Correct BP measurements require that the clinician listen through a stethoscope
that is placed over the brachial artery for the appearance of the five phases of the
Korotkoff sounds. Each sound has distinct features, which are depicted in Figure 9-
6 Examples of Korotkoff sounds can be found in the Thinklabs Medical Sound
(http://www.thinklabsmedical.com/stethoscope_community/Sound_Library)
under Blood Pressure—Korotkoff Sounds 1 and Blood Pressure—Korotkoff Sounds
Auscultatory Method for Blood Pressure Measurement in Adults as
Recommended by the American Heart Association
40% of the bladder length and cover at least 80% of the upper arm circumference. The cuff should be
wrapped snugly around the arm with the center of the bladder over the brachial artery
MONITOR: Measurements should be taken with a correctly calibrated mercury sphygmomanometer, an
aneroid manometer, or a validated electronic device
PALPATORY METHOD: SBP should be estimated using the palpatory method. The cuff is rapidly inflated
SBP. The cuff is then deflated rapidly
KOROTKOFF SOUNDS: The head of the stethoscope, ideally using the bell, should be placed over the
10 to 20 mm Hg below phase 5, the cuff can be rapidly deflated
DOCUMENTATION: BP values should always be recorded. The BP values (SBP/DBP) should be
recorded using even numbers (rounded up from an odd number)
a along with the patient’s position (seated,
standing, or supine), arm used, cuff size, time, and date
in the arm with the higher reading at subsequent visits
aTerminal digit preference (i.e., tendency to report readings that end in 0 or 5) should be avoided.
BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.
Out-of-Office Blood Pressure Monitoring
Home BP measurements can provide information on response to therapy and may
help improve adherence to therapy and goal BP achievement in some patients.
Devices for home measurement should be validated for accuracy according to
established protocols from either the British Hypertension Society or the Association
for Advancement of Medical Instrumentation. When placed in service, they should be
routinely checked against office-based readings for accuracy, especially when
readings between office and home are widely discrepant. Patients with average home
BP values greater than 135/85 mm Hg are considered hypertensive.
devices that measure BP are generally not accurate and should not be routinely used.
Figure 9-1 Phases of the Korotkoff sounds heard when indirectly measuring blood pressure.
Ambulatory blood pressure monitoring (ABPM) typically measures BP every 15
to 30 minutes throughout the day and nighttime using a portable, noninvasive
oscillometric device typically worn for 24 hours.
monitoring is indicated for patients with suspected white-coat hypertension and may
also be helpful in patients with apparent drug resistance, hypotensive symptoms
while receiving antihypertensive therapy, episodic hypertension, and autonomic
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