Clinical Cardiology: New Frontiers
Essential Hypertension
Part I: Definition and Etiology
Oscar A. Carretero, MD; Suzanne Oparil, MD
E ssential hypertension remains a major modifiable risk
factor for cardiovascular disease (CVD) despite impor-
tant advances in our understanding of its pathophysiology and
the availability of effective treatment strategies. High blood
pressure (BP) increases the risk of CVD for millions of
people worldwide, and there is evidence that the problem is
only getting worse. In the past decade, age-adjusted rates of
stroke incidence have risen, and the slope of the age-adjusted
rate of decline in coronary disease has leveled off. The
incidence of end-stage renal disease and the prevalence of
heart failure have also increased. A major contributor to these
trends is inadequate control of BP in the hypertensive
population. This review of current concepts regarding the
definition, etiology, and treatment of essential hypertension is
intended to aid the clinician in identifying those individuals at
high risk who need to undergo evaluation and treatment, as
well as in selecting optimal treatment strategies for hyperten-
sive patients with comorbid conditions and/or target organ
damage. The part of the review that deals with the genetic
basis of hypertension and the gene/environment interaction
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that may lead to elevated BP is still a work in progress.
Information gained from the Human Genome Project and
from ongoing studies of the genetic basis of hypertension
both in animal models and human populations may revolu-
tionize the treatment of hypertension by replacing current
empirical therapy with more effective, targeted treatments
based on the genotype of the patient. Concepts introduced in
this review form the basis for such “pharmacogenomic”
approaches to antihypertensive therapy.
Definition of Essential or
Primary Hypertension
BP is a quantitative trait that is highly variable1; in population
studies, BP has a normal distribution that is slightly skewed to
the right. There is a strong positive and continuous correlation
between BP and the risk of CVD (stroke, myocardial infarc-
tion, heart failure), renal disease, and mortality, even in the
normotensive range. This correlation is more robust with
systolic than with diastolic BP.2 There is no specific level of
BP where cardiovascular and renal complications start to
occur; thus the definition of hypertension is arbitrary but
This is Part I of a 2-part article. Part II of this article will be published in the February 1, 2000 issue of Circulation.
From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division
of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.).
Correspondence to Oscar A. Carretero, MD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI
48202. E-mail ocarret1@hfhs.org
(Circulation. 2000;101:329-335.)
© 2000 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
329
needed for practical reasons in patient assessment and
treatment.
The Sixth Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC VI) defined and classified hypertension
in adults, as shown in Table 1.3 The diagnosis of hypertension
is made when the average of 2 or more diastolic BP
measurements on at least 2 subsequent visits is ⱖ90 mm Hg
or when the average of multiple systolic BP readings on 2 or
more subsequent visits is consistently ⱖ140 mm Hg. Isolated
systolic hypertension is defined as systolic BP ⱖ140 mm Hg
and diastolic BP ⬍90 mm Hg. Individuals with high normal
BP tend to maintain pressures that are above average for the
general population and are at greater risk for development of
definite hypertension and cardiovascular events than the
general population. With the use of these definitions, it is
estimated that 43 million people in the United States have
hypertension or are taking antihypertensive medication,
which is ⬇24% of the adult population. This proportion
changes with (1) race, being higher in blacks (32.4%) and
lower in whites (23.3%) and Mexican Americans (22.6%);
(2) age, because in industrialized countries systolic BP rises
throughout life, whereas diastolic BP rises until age 55 to 60
years and thus the greater increase in prevalence of hyper-
tension among the elderly is mainly due to systolic hyperten-
sion; (3) geographic patterns, because hypertension is more
prevalent in the southeastern United States; (4) gender,
because hypertension is more prevalent in men (though
menopause tends to abolish this difference); and (5) socio-
economic status, which is an indicator of lifestyle attributes
and is inversely related to the prevalence, morbidity, and
mortality rates of hypertension.
Essential, primary, or idiopathic hypertension is defined as
high BP in which secondary causes such as renovascular
disease, renal failure, pheochromocytoma, aldosteronism, or
other causes of secondary hypertension or mendelian forms
(monogenic) are not present. Essential hypertension accounts
for 95% of all cases of hypertension. Essential hypertension is
a heterogeneous disorder, with different patients having
different causal factors that lead to high BP. Essential
hypertension needs to be separated into various
 330 Circulation January 25, 2000
TABLE 1. Definitions and Classification of Blood
Pressure Levels
Category Systolic, mm Hg Diastolic, mm Hg
Optimal ⬍120 and
Normal ⬍130 and
High normal 130–139 or
Hypertension
Stage 1 (mild) 140–159 or
Subgroup: borderline 140–149 or
Stage 2 (moderate) 160–179 or
Stage 3 (severe) ⱖ180 or
Isolated systolic hypertension ⱖ140 and
Subgroup: borderline 140–149 and
When a patient’s systolic and diastolic blood pressures fall into different
categories, the higher category should apply.
From JNC VI.3
syndromes because the causes of high BP in most patients
presently classified as having essential hypertension can be
recognized.
Known Etiological Factors in
Essential Hypertension
Although it has frequently been indicated that the causes of
essential hypertension are not known, this is only partially
true because we have little information on genetic variations
or genes that are overexpressed or underexpressed as well as
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the intermediary phenotypes that they regulate to cause high
BP.4 A number of factors increase BP, including (1) obesity,
(2) insulin resistance, (3) high alcohol intake, (4) high salt
intake (in salt-sensitive patients), (5) aging and perhaps (6)
sedentary lifestyle, (7) stress, (8) low potassium intake, and
(9) low calcium intake.5,6 Furthermore, many of these factors
are additive, such as obesity and alcohol intake.
In this review, variations in BP that are genetically deter-
mined will be called “inherited BP,” although we do not
know which genes cause BP to vary; we know from family
studies that inherited BP can range from low normal BP to
severe hypertension. Factors that increase BP, such as obesity
and high alcohol and salt intake, will be called “hyperten-
sinogenic factors.” Some of these factors have inherited,
behavioral, and environmental components. Inherited BP
could be considered core BP, whereas hypertensinogenic
factors cause BP to increase above the range of inherited BPs,
thus creating 4 main possibilities: (1) patients who have
inherited BP in the optimal category (⬍120/⬍80 mm Hg); if
1 or more hypertensinogenic factors are added, BP would
probably increase but remain in the normal range (⬍135/
⬍85 mm Hg) (Figure 1, first 2 columns); (2) patients who
have inherited BP in the normal category (ⱕ130/
ⱕ85 mm Hg); if 1 or more hypertensinogenic factors are
added, BP will probably increase to the high normal range
(130 to 139/85 to 89 mm Hg) or to stage 1 of the hypertensive
category (140 to 159/90 to 99 mm Hg) (Figure 1, second 2
columns); (3) patients who have inherited BP in the high
normal category (130 to 139/85 to 89 mm Hg); if 1 or more
hypertensinogenic factors are added, BP will increase to the
⬍80
⬍85
85–89
90–99
90–94
100–109
ⱖ110
⬍90
⬍90
Figure 1. Additive effect of hypertensinogenic factors (hatched
areas) such as obesity and alcohol intake on hereditary systolic
(white areas) and diastolic BP (black areas). Abscissa indicates
the stage of inherited BP according to JNC VI without adding
the effect of the hypertensinogenic factors. Patients with normal
or high normal inherited BP become hypertensive stage 1 when
BP is increased by a hypertensinogenic factor. In patients with
inherited hypertension in stages 1 to 3, their hypertension
becomes more severe when hypertensinogenic factors are
added.
hypertensive range (ⱖ140/ⱖ90 mm Hg) (Figure 1, third 2
columns); and (4) patients who have inherited BP in the
hypertensive range; addition of 1 or more hypertensinogenic
factors will make hypertension more severe, changing it from
stage 1 to stage 2 or 3 (Figure 1, fourth to sixth 2 columns).
Theoretically, in a population unaffected by hypertensino-
genic factors, BP will have a normal distribution; it will be
skewed to the right and will have a narrow base or less
variance (Figure 2, continuous line). When 1 hypertensino-
genic factor is added to this population, such as increased
body mass, one would expect the normal distribution curve to
be further skewed to the right; consequently the base will be
wider (more variance) and the curve will be flatter (Figure 2,
broken line). If a second hypertensinogenic factor such as
alcohol intake is added to increased body mass, the curve will
be skewed more to the right and the variance will increase
further, with more subjects classified as hypertensive (Figure
2, dotted line).
Discovering which genetic variations place BP on the left
or right side of the distribution curve is of both theoretical and
practical importance because it could help the physician to
better treat or cure hypertension.7 Recognition of the hyper-
tensinogenic factors may allow nonpharmacological preven-
tion, treatment, or cure of hypertension. Hypertensinogenic
factors such as obesity, insulin resistance, or high alcohol
intake also have an important genetic component. Further-
more, there are interactions between genetic and environmen-
tal factors (Figure 2) that influence intermediary phenotypes
such as sympathetic nerve activity, the renin-angiotensin-
aldosterone and renal kallikrein-kinin systems, and endothe-
lial factors, which in turn influence other intermediary phe-
notypes such as sodium excretion, vascular reactivity, and
cardiac contractility. These and many other intermediary
phenotypes determine total vascular resistance and cardiac
output and, consequently, BP. Recognition of the hypertensi-
 Carretero and Oparil
distribution curves are shifted to the right (high BP) and the number of hypertensive individuals is significantly increased when
hypertensinogenic factors are added.
nogenic factor(s) and establishing that the patient’s hyperten-
sion is the result of obesity (either alone or combined with
other factors such as insulin resistance or high alcohol intake)
or old age instead of essential hypertension may help the
physician as well as the patient and his or her family to
modify or eliminate these hypertensinogenic and CVD risk
factors when possible, which may cure the hypertension or at
least facilitate control of BP. When the hypertensinogenic
factor cannot be reduced or eliminated, as with systolic
hypertension induced by aging (arteriosclerosis), recognition
of the underlying cause of high BP will emphasize the need
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for (1) further studies to determine whether the patient has
arteriosclerosis and/or atherosclerosis, the magnitude of the
disease, and whether there are occlusive lesions; (2) treatment
of the atherosclerosis with lifestyle and dietary changes and
lipid-lowering agents if necessary; and (3) pharmacological
treatment of systolic hypertension to decrease passive stiff-
ness (arteriosclerosis) of the major central elastic arteries and
decrease morbidity and mortality rates. Thus recognition of
factors that induce hypertension is not only of theoretical but
also of practical importance. In conclusion, as stated by
Beilin,8 “it is no longer appropriate to define essential
hypertension as a rise in blood pressure without cause,” since
a number of causes can be clearly identified in most cases of
so-called “essential hypertension.” As discussed later in more
detail, there is clear evidence that changes in lifestyle,
including dietary changes that reduce body weight, fat, and
alcohol intake and increase potassium and calcium intake,9 as
well as exercise,10,11 reduce or normalize BP in many
patients.
Inherited BP
The identification of variant (allelic) genes that contribute to
the development of hypertension is complicated by the fact
that the 2 phenotypes that determine BP, cardiac output and
total peripheral resistance, are controlled by intermediary
phenotypes, including the autonomic nervous system, vaso-
pressor/vasodepressor hormones, the structure of the cardio-
vascular system, body fluid volume and renal function, and
many others. Furthermore, these intermediary phenotypes are
also controlled by complex mechanisms including BP itself.12
Essential Hypertension 331
Figure 2. Interaction among genetic
and environmental factors in the devel-
opment of hypertension. Left side of
figure shows how environmental fac-
tors and multiple genes responsible for
high BP interact and affect intermedi-
ary phenotypes. The result of these
intermediary phenotypes is blood pres-
sure with a normal distribution skewed
to the right. Continuous line indicates
the theoretical BP of the population
that is not affected by hypertensino-
genic factors; shaded area indicates
systolic BP in the hypertensive range.
Broken and dotted lines indicate popu-
lations in which 1 (obesity) or 2 hyper-
tensinogenic factors (obesity plus high
alcohol intake) have been added.
Notice that in these 2 populations the
Thus there are many genes that could participate in the
development of hypertension.
The influence of genes on BP has been suggested by family
studies demonstrating associations of BP among siblings and
between parents and children. There is a better association
among BP values in biological children than in adopted
children and in identical as opposed to nonidentical twins. BP
variability attributed to all genetic factors varies from 25% in
pedigree studies to 65% in twin studies. Furthermore, genetic
factors also influence behavioral patterns, which might lead
to BP elevation. For example, a tendency toward obesity or
alcoholism will be influenced by both genetic and environ-
mental factors; thus the proportion of BP variability caused
by inheritance is difficult to determine and may vary in
different populations.
Mutations in at least 10 genes have been shown to raise or
lower BP through a common pathway by increasing or
decreasing salt and water reabsorption by the nephron.13,14
The genetic mutations responsible for 3 rare forms of men-
delian (monogenic) hypertensive syndromes⫺glucocorticoid-
remediable aldosteronism (GRA), Liddle’s syndrome, and
apparent mineralocorticoid excess⫺have been identified,
whereas in a fourth, autosomal dominant hypertension with
brachydactyly, the gene is not yet identified but has been
mapped to chromosome 12 (12p). Subtle variations in one of
these genes may also cause some forms of “essential”
hypertension. For a review of the mutations that cause a
decrease in BP, see Lifton.13
Glucocorticoid-Remediable Aldosteronism
This is an autosomal dominant form of monogenic hyperten-
sion in which aldosterone secretion is regulated by adreno-
corticotropic hormone. Glucocorticoid treatment causes BP to
decrease and gives the syndrome its name. The genetic
mutation that causes GRA has been identified by Lifton14 as
a chimeric gene fusing nucleotide sequences of the promoter-
regulatory region of 11␤-hydroxylase (controlled by adreno-
corticotropic hormone) and the structural portion of the
aldosterone synthase gene. The chimeric gene results from a
meiotic mismatch and unequal crossing over. The patients are
usually thought to have primary aldosteronism because they
 332 Circulation January 25, 2000
exhibit volume expansion, metabolic alkalosis with hypoka-
lemia, low plasma renin, and high aldosterone. Most of the
patients first described as having GRA showed severe hyper-
tension and died prematurely from stroke. However, with the
development of direct genetic testing, the BP of patients with
this syndrome was found to cover a wide range, including
normotensive levels.15,16 In patients with GRA and normal
BP, expression of the chimeric gene may be variable, but
because steroid levels are similar in patients with severe and
mild hypertension, this seems unlikely. It is also possible that
the genetic background of the trait (other than the chimeric
mutation), such as high renal kallikrein, places the inherited
BP of these subjects in the low or ideal normal range and the
mutation causes BP to increase to high normal or hyperten-
sive stage 1. Thus the final BP would be the combined result
of the inherited BP (including the genetic mutation) and the
increase in BP caused by hypertensinogenic factors such as
salt.
Liddle’s Syndrome
This is an autosomal dominant form of monogenic hyperten-
sion that results from mutations in the amiloride-sensitive
epithelial sodium channel, leading to increased channel ac-
tivity.17 The mutations reported to date result in the elimina-
tion of 45 to 75 amino acids from the cytoplasmic carboxyl
terminus of ␤- or ␥-subunits of the channel; thus Liddle’s
syndrome is genetically heterogeneous. It is characterized by
the early onset of hypertension with hypokalemia and sup-
pression of both plasma renin activity and aldosterone, the
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latter differentiating this syndrome from primary aldosteron-
ism. Both the hypertension and the hypokalemia vary in
severity, raising the possibility that some patients classified as
having salt-sensitive essential hypertension actually have
Liddle’s syndrome.18 It is also possible that high BP in
blacks, who are frequently salt-sensitive, is due to a poly-
morphism in one of the sodium channel genes or in one of the
genes of systems that regulate it, causing its activity to
increase.
Apparent Mineralocorticoid Excess
This is an autosomal recessive form of monogenic juvenile
hypertension that results from a mutation in the renal-specific
isoform 11␤-hydroxysteroid dehydrogenase gene.19 Nor-
mally this enzyme converts cortisol to the inactive metabolite
cortisone. In the distal nephron this is important because
cortisol and aldosterone have a similar affinity for the
mineralocorticoid receptor. The enzymatic deficiency allows
the mineralocorticoid receptors in the nephron to be occupied
and activated by cortisol, causing sodium and water retention,
volume expansion, low renin, low aldosterone, and more
importantly, a salt-sensitive form of hypertension. Thus this
gene may be a locus for salt-sensitive essential hypertension.
Autosomal Dominant Hypertension
With Brachydactyly
In this monogenic syndrome, hypertension and brachydactyly
are always inherited together (100% cosegregation).4 Af-
fected persons are shorter than nonaffected relatives. The
gene for hypertension has been mapped to the short arm of
chromosome 12 (12p) in a large Turkish kindred. Two other
families with this syndrome have been reported, 1 in Canada
and 1 in the United States. In addition, the study of a Japanese
child with hypertension and type E brachydactyly has al-
lowed the area on 12p containing the gene mutation to be
pinpointed further, although the gene responsible for this
syndrome has not yet been cloned. Unlike the other 3
autosomal forms of hypertension, BP is not affected by
volume expansion and the underlying mechanism is not
known. Thus identification of the gene responsible may help
clarify some of the genetic alterations in essential
hypertension.
Essential or Primary Hypertension
The genetic alterations responsible for inherited “essential”
hypertension remain largely unknown.4 Results from family
studies suggest several possible intermediary phenotypes
(genetic traits) that may be related to inherited high BP, such
as high sodium-lithium countertransport, low urinary kal-
likrein excretion, high fasting plasma insulin concentrations,
high-density LDL subfractions, fat pattern index, and body
mass index (BMI).12 Jeunemaitre et al20,21 first reported a
polymorphism in the angiotensinogen gene linked with es-
sential hypertension in hypertensive siblings from Utah and
France. This polymorphism consists of a substitution of
thymidine for cytosine in nucleotide 704, which causes
substitution of methionine for threonine at position 235
(M235T) and is associated with increased concentrations of
plasma angiotensinogen. This variant appears to be in tight
linkage disequilibrium with a promoter mutation in which
adenine replaces guanine (-6A) upstream from the initiation
side of transcription.22 Tests of promoter activity suggest that
this nucleotide substitution increases the rate of gene tran-
scription, which may explain the higher angiotensinogen
concentration found in subjects with the variant M235T.22
Many studies have been published on various racial groups
with regard to the association between allelic variations in
angiotensinogen and hypertension.23 However, these varia-
tions explain only a small part of the BP variation (⬇6%).
Furthermore, plasma angiotensinogen concentrations, though
higher in patients with the polymorphism, clearly overlap
with normotensive patients.
Polymorphisms and mutations in other genes such as
angiotensin-converting enzyme, ␤2-adrenergic receptor,
␣ -adducin, angiotensinase C, renin-binding protein,
G-protein ␤3-subunit, atrial natriuretic factor, and the insulin
receptor have also been linked to the development of essential
hypertension; however, most of them show a weak associa-
tion if any, and most of these studies need further confirma-
tion. Thus these gene alterations will not be discussed here
because they go beyond the scope of this review (see Luft4).
Hypertensinogenic Factors
There is evidence that obesity, insulin resistance, high alcohol
intake, high salt intake, a sedentary lifestyle, stress, dyslipid-
emia, and low potassium or calcium intake increase BP in
susceptible subjects. Here we will briefly discuss obesity and
insulin resistance; other hypertensinogenic factors will be
discussed in the section “Lifestyle Modification.”
 Carretero and Oparil
Obesity and Insulin Resistance
Obesity, and especially abdominal obesity, is the main
hypertensinogenic factor. It was estimated in the Framingham
study that each 10% weight gain is associated with a
6.5 mm Hg increase in systolic BP.24 Obesity is also the cause
of insulin resistance, adult-onset diabetes mellitus, left ven-
tricular hypertrophy, hyperlipidemia, and atherosclerotic dis-
ease. Thus obesity is an important cardiovascular health
problem; its incidence and prevalence are rising in most
industrialized societies and in the United States has reached
epidemic proportions. The relationship between BP and body
fat is not restricted to the morbidly obese but is continuous
throughout the entire range of body weight. A direct associ-
ation between hypertension and BMI (weight in kilograms
divided by the square height in meters) has been observed in
cross-sectional and longitudinal population studies from early
childhood to old age.25 A BMI of ⬍25 is considered normal
or healthy, whereas a BMI of 26 to 28 (as compared with
BMI ⬍23) increases the risk of high BP by 180% and the risk
of insulin resistance by ⬎1000%. Thus insulin resistance is
present in many patients with obesity and hypertension.
The mechanism by which obesity raises BP is not fully
understood, but increased BMI is associated with an increase
in plasma volume and cardiac output; both these alterations
and BP can be decreased by weight loss in both normotensive
and hypertensive subjects,26 even when sodium intake is kept
relatively constant.27 BP in obese adolescents is sodium-
sensitive, and fasting insulin is the best predictor of this
sensitivity.26 In these adolescents, mean BP dropped by
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10 mm Hg after changing from 2 weeks on a high-sodium
diet (⬎250 mmol sodium/d) to a low-sodium diet
(⬍30 mmol/d). When some of these subjects lost weight by
dieting, BP decreased by 10 mm Hg and salt sensitivity was
no longer present. The variables that best predicted sodium
sensitivity were fasting plasma insulin, plasma aldosterone,
and plasma norepinephrine, supporting the hypothesis that BP
is sensitive to dietary sodium and that this sensitivity may be
due to the combined effect of hyperinsulinemia, hyperaldo-
steronism, and increased activity of the sympathetic nervous
system. It is not clear whether body fat by itself is a factor
because in overweight women, exercise for 1 hour per day, 3
times per week lowered BP, and this decrease was observed
mainly in those who initially had high fasting insulin and
whose insulin levels fell in response to exercise. In this study
weight loss was not a factor because the subjects were on a
free diet and actually gained an average of 2.6 pounds during
the 6-month exercise trial,10 which suggests that exercise
decreases plasma insulin by a different mechanism than loss
of body weight. These studies can be interpreted as showing
that high plasma insulin causes salt sensitivity and that
decreasing insulin resistance by losing weight or exercising
reduces BP. Furthermore, nonobese hypertensive subjects are
much more likely to exhibit insulin resistance than normo-
tensive individuals.28 On the other hand, insulin by itself has
a vasodilator effect. In obese subjects with hypertension there
is resistance to the effects of insulin on glucose uptake.
However, in addition to this metabolic effect, insulin in-
creases both sympathetic nerve activity and sodium and water
retention, and it could be that the hypertension is due to the
Essential Hypertension 333
TABLE 2. Blood Pressure Management
Patients should be seated with back supported and arm bared and
supported.
Patients should refrain from smoking or ingesting caffeine for 30 minutes
before measurement.
Measurement should begin after at least 5 minutes of rest.
Appropriate cuff size and calibrated equipment should be used.
Both systolic BP and diastolic BP should be recorded.
Two or more readings should be averaged.
From JNC VI.3
lack of resistance to these secondary effects of insulin.29 More
recently, insulin-like growth factor I30 and leptin,31 a neu-
ropeptide that regulates appetite, have also been implicated in
the pathogenesis of obesity-induced hypertension. Thus, al-
though the mechanisms by which obesity and insulin resis-
tance increase BP remain undefined, it is clear that these
increases in BP are overlain on the inherited BP.
Diagnosis of Hypertension
Initial Evaluation
The goals of the initial evaluation are to determine baseline
BP; assess the presence and extent of target organ damage
and concomitant CVD; screen for potentially curable specific
causes of hypertension (secondary hypertension); identify
hypertensinogenic factors and other CVD risk factors; and
characterize the patient to facilitate the choice of therapy
(especially drug selection) and define prognosis.
BP Measurement
The accurate and reproducible measurement of BP by the cuff
technique is the most important part of the diagnostic evalu-
ation and follow-up of the patient and should be carried out in
a standardized fashion (Table 2) with the use of properly
calibrated and certified equipment.3,32,33 A mercury sphyg-
momanometer is preferred; acceptable alternatives include a
recently calibrated aneroid manometer or a validated elec-
tronic device attached to an arm cuff. Two or 3 measurements
should be taken at each visit, and at least 2 minutes should be
allowed between readings. The diastolic reading is taken at
the level when sounds disappear (Korotkoff phase V).
Measurement of BP by patients or family members and/or
automated ambulatory BP monitoring often helps verify the
diagnosis and assess the severity of hypertension. BP values
obtained outside the clinical setting are lower and correlate
better with target organ damage than BP measurements by
healthcare personnel. Self-measurement of BP has several
potential advantages, including distinguishing sustained hy-
pertension from hypertension that occurs only in the health-
care setting (“white coat” hypertension); assessing the re-
sponse to antihypertensive treatment; improving adherence to
treatment by making the patient a “partner” in his or her own
care; and lowering costs by reducing the need for frequent
office BP checks. Accordingly, ambulatory or self-
monitoring of BP is recommended for many patients with
high BP, particularly those who appear to be resistant to
antihypertensive treatment. A limitation of home or work-
place BP measurements is that accurate and calibrated BP
 334 Circulation January 25, 2000
TABLE 3. Medical History and Physical Examination
Medical history
● Duration and classification of hypertension
● Patient history of CVD
● Family history
● Symptoms suggesting causes of hypertension
● Lifestyle factors
● Current and previous medications
Physical examination
● Blood pressure readings (2 or more), including the standing position
● Verification in contralateral arm
● Height, weight, and waist circumference
● Funduscopic examination for hypertensive retinopathy
● Examination of the neck, heart, lungs, abdomen, and extremities for
evidence of target organ damage
From JNC VI.3
monitors must be used and that careful and repeated instruc-
tion in how to measure BP must be given.
Medical History and Physical Examination
A careful, complete history should be obtained and a physical
examination performed in all patients before beginning treat-
ment. The assessment should include the elements described
in Table 3. It should help to identify known, remediable
causes of high BP; establish the presence or absence of target
organ damage and CVD; and identify other CVD or comorbid
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conditions that might affect prognosis or treatment.
Laboratory Tests and Other
Diagnostic Procedures
Routine tests include only urinalysis, complete blood count,
blood chemistry (potassium, sodium, creatinine, fasting glu-
cose, total and high-density lipoprotein or HDL cholesterol),
and a 12-lead ECG. Optional tests indicated in selected
patients for the diagnosis of secondary hypertension and/or
comorbid conditions include creatinine clearance, 24-hour
urinary protein, measurement of microalbuminuria, uric acid,
calcium, glycosylated hemoglobin, fasting triglycerides, lim-
ited echocardiography,34 and plasma renin activity/aldoster-
one measurements.
Acknowledgments
This work was supported by National Institutes of Health
grant HL-28982.
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KEY WORDS: hypertension 䡲 pathology 䡲 diagnosis