Clinical Advisory Statement:
Importance of Systolic Blood Pressure in Older Americans
Joseph L. Izzo Jr., Daniel Levy, Henry R. Black
This clinical advisory statement from the Coordinating Committee of the National High Blood Pressure Education Program is intended to advance and clarify the recommendations of the Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI, 1997).1 The advisory addresses several interrelated issues about blood pressure (BP) that affect people approaching the later decades of life. On the basis of the wealth of
currently available evidence, the committee now recommends a major paradigm
shift in urging that systolic BP become the major criterion for diagnosis,
staging, and therapeutic management of hypertension, particularly in
middle-aged and older Americans.
Several lines of strong evidence support the
initiative to emphasize systolic BP. Pathophysiologically, there are strong
associations among aging, increased stiffness of large arteries, increased
systolic BP, increased pulse pressure, and the prevalence of cardiac and
vascular disease. Epidemiologically, isolated systolic hypertension is the most
common form of hypertension and is present in approximately two thirds of
hypertensive individuals >60 years of age. Diagnostically, classification
and staging of hypertension are more precise when systolic rather than
diastolic BP is used as the principal criterion. Risk stratification for major
complications of hypertension (stroke, myocardial infarction, heart failure,
and kidney failure) is actually confounded by the use of diastolic BP; in older
people with systolic hypertension, diastolic BP is inversely related to
cardiovascular risk. Clinical benefits of treatment of isolated systolic
hypertension include reductions in stroke, myocardial infarction, heart
failure, kidney failure, and overall cardiovascular disease morbidity and
Currently, only 1 in 4 Americans with hypertension
falls below JNC VI-recommended values of 140/90 mm Hg in uncomplicated
hypertension or 130/85 mm Hg in individuals with kidney disease or diabetes.
Hypertension control rates are poorest in older people, primarily as a result
of inadequate systolic BP control. The Coordinating Committee believes that
achievement of optimal cardiovascular health in the United States requires a
new nationwide initiative to improve our current low rates of systolic BP
control. In addition to the recognition of the preeminent role of systolic BP
in the management of hypertension, the strategic value of risk stratification
and the clinical benefit of vigorous BP management at all ages are
reemphasized. The use of age-adjusted BP targets is discouraged.
Current Perspectives in BP Control and
Cardiovascular Risk Management
Of the 50 million Americans with hypertension in the
United States, only about half are currently treated with antihypertensive
drugs and only about a quarter have BP values below the targets of 140 systolic
and 90 mm Hg diastolic.2 Achievement of BP goals is
even poorer in older Americans. In hypertensives >70 years of age, 25% of
African Americans and 18% of white Americans have achieved the BP goals
recommended by JNC VI. 3 These data reveal that
clinicians may be willing to treat hypertension but still do not achieve
desired goals. Systolic BP is almost always less well controlled than diastolic
BP, even in clinical trials, in which aggressive management is required. In the
Multiple Risk Factor Intervention Trial (MRFIT) and the Hypertension Optimal
Treatment (HOT) trial, diastolic control rates exceeded 90%, whereas systolic
control rates were less than 60%.4,5
As the US population ages, the burden of uncontrolled
systolic hypertension will take an increasing toll on the health and well-being
of our society and will contribute to unnecessarily high healthcare costs.
Inadequate reduction of systolic BP and dismal systolic BP control rates are
causally related to a variety of adverse outcomes. For example, systolic
hypertension is the most prevalent risk factor in heart
failure,6 and clinical trials have demonstrated
unequivocally that control of systolic hypertension prevents the development of
heart failure.7 Other major cardiovascular disease
end points such as stroke and kidney failure also track closely with systolic
BP, and in kidney disease, it is clear that lower pressures are associated with
better outcomes.8 Systolic hypertension interacts
with other major risk factors such as hypercholesterolemia and diabetes, which
also increase in prevalence with age, to amplify the age-related risk of
All high-risk populations benefit markedly from
vigorous BP control. 10 The importance of vigorous BP
control in diabetics is the subject of a companion Clinical Advisory
Statement.11 In all high-risk groups, the number
needed to treat to demonstrate benefit (which is reflective of the absolute
benefit of treatment) is substantially lower than that in lower-risk groups. In
addition to better BP control, aggressive management of other common risk
factors such as hypercholesterolemia and glucose intolerance are required to
achieve optimal cardiovascular benefit at any age.
Age and Pathogenesis of Systolic
Systolic BP increases steadily with age in
industrialized Western societies, whereas diastolic BP increases until about
age 55 and then declines 2 (Figure 1). Pulse pressure
(systolic-diastolic BP difference) therefore widens with
age.12,13 Age-related changes in BP are
manifestations of a generalized process of increasing arterial stiffness (or
decreasing compliance) that results from the progressive replacement of elastin
by collagen in the walls of large arteries. 14 This
process of diffuse arteriosclerosis leads to dilatation and lengthening of the
aorta and its immediate branches via fibrosis and hypertrophy of the arterial
muscularis. Arteriosclerosis inevitably accompanies aging in Western societies,
but its development is clearly accelerated by the presence of hypertension and
the age at which it is expressed varies with the degree of BP elevation.
Arteriosclerosis can be differentiated
pathophysiologically from atherosclerosis, which is primarily related to the
effects of abnormal cholesterol oxidation and deposition in the inner layers of
large arteries. Atherosclerosis begins as endothelial dysfunction and
macrophage uptake of oxidized lipids into the vessel walls and is accelerated
by the coexistence of hypertension. It evolves into a patchy, chronic
inflammatory process that includes varying degrees of complexity and rupture of
cholesterol-laden plaques and eventually, local vascular occlusion or distal
Because of their close relation to arteriosclerosis,
both systolic BP and pulse pressure are reliable markers of age-related
vascular target organ damage. Pulse pressure, although slightly more robust
than systolic BP as a risk indicator, is considerably less straightforward to
use clinically than systolic BP, and it has not yet been validated as a
surrogate end point for morbidity or mortality in a prospective randomized
clinical trial. Accordingly, this statement focuses on systolic BP rather than
Systolic Hypertension: Prevalence, Diagnostic
Value, and Risk Stratification
The prevalence of hypertension increases with age,
with systolic hypertension becoming far more common than diastolic
hypertension. In the National Health and Nutrition Examination Survey (NHANES)
study, isolated systolic hypertension (systolic
140 with diastolic <90 mm Hg) was present in 65% of all
hypertensives >60 years of age, whether male or female.16
The accuracy of diagnosis and staging of hypertension according to JNC
VI guidelines is markedly improved by using systolic rather than diastolic BP.
Applying JNC VI definitions of hypertension (stage 1 hypertension: BP
140 systolic or
90 diastolic, stage 2 hypertension: 160 systolic or
100 diastolic, stage 3 hypertension:
180 systolic or
110 mm Hg diastolic) to the Framingham cohort, those with high
normal BP or hypertension, who were potential candidates for antihypertensive
therapy, were correctly classified by systolic BP alone 91% of the time. In
contrast, correct BP classification occurred in only 22% of these individuals
when diastolic BP was used alone.17
Systolic BP and pulse pressure are closely related
independent cardiovascular disease risk factors13,18
that yield similar diagnostic and prognostic information. It has been known
since the early reports from Kannel and colleagues19
at the Framingham Heart Study that systolic BP is more robust than diastolic BP
as a cardiovascular disease risk factor, a phenomenon recently emphasized by
Dustan. 20 More recent data from Framingham clearly
reinforce the prognostic significance of elevated systolic BP and wide pulse
pressure as independent risk factors.13 In people
>60 years of age, when systolic BP is >120 mm Hg, diastolic BP is
inversely related to cardiovascular disease risk.13
Thus, an individual whose BP is 160/70 is at greater risk than an individual
whose BP is 160/100 mm Hg.
The preeminent value of systolic BP in risk prediction
is even more convincingly demonstrated in 12-year data from >316,000 men
screened for MRFIT.4 As demonstrated in this large
cohort (Figure 2), coronary heart disease death rates were almost linearly
related to systolic BP at all levels of blood pressure. In MRFIT, increased
cardiovascular disease risk in those with systolic BP <140 mm Hg was found
only when diastolic BP exceeded 100 mm Hg.4 With
respect to the risk of renal failure, the MRFIT database revealed that although
both systolic and diastolic BP were important, systolic BP was the more precise
risk indicator. 21
Clinical Trial Benefits of Systolic BP
Compelling data from 2 large clinical trials directly
demonstrate the benefits of treating isolated systolic hypertension (Table).
The SHEP (Systolic Hypertension in the Elderly Program)
study,22 a placebo-controlled, double-blind,
randomized trial, investigated the value of thiazide diuretic-based treatment
in 4736 individuals > 60 years of age with isolated systolic hypertension
(initial BP values
160 mm Hg systolic and <90 mm Hg diastolic). After 5 years of
therapy, active treatment with diuretic, with or without beta-blockers, reduced
average systolic BP values »14 mm Hg more than
placebo, with an overall systolic BP reduction from 171 to 142 mm Hg. Compared
with placebo, those randomized to diuretic treatment had marked reductions in
the rates of myocardial infarction (27%), heart failure (55%), and
stroke (37%), as well as exhibiting trends toward improvement in
depression and dementia scores. A large randomized European trial of isolated
systolic hypertension (Syst-EUR) used dihydropyridine calcium antagonist-based
therapy and found reductions in systolic BP and cardiovascular outcomes similar
to those in SHEP. 23
Optimal Control Strategies: BP Targets and Drug
Epidemiological data demonstrate that cardiovascular
disease morbidity and mortality is roughly proportional to systolic BP across a
very wide range of BP values. Thus, from the perspective of early treatment and
disease prevention, the systolic BP target of 140 mm Hg that has been
established from observational data remains fully justifiable. From the
perspective of treatment of those with established hypertension, however, the
question of how low to go remains open. If therapeutic benefit in systolic
hypertension follows the observational data, the greater the decrease in BP,
the less the risk. SHEP and Syst-EUR demonstrated that lowering systolic BP
<160 mm Hg is markedly beneficial,7,22 but no
trial has directly measured the degree of additional benefit that would occur
at a systolic BP target <140 mm Hg.
Also currently unanswered is the question of whether
all antihypertensive drug classes confer equal benefit or whether some agents
offer therapeutic benefits beyond BP control. In isolated systolic
hypertension, JNC VI recommended diuretics and calcium antagonists for isolated
systolic hypertension, with diuretics preferred because of the convincing
clinical trial data indicating protection against myocardial infarction, heart
failure, and stroke. A recent study, the second Swedish Trial in Old People
with Hypertension (STOP Hypertension-2), was conducted in individuals with
stage 3 hypertension whose pretreatment and posttreatment BP values were
190/100 and 160/80 mm Hg, respectively. 24
No additional benefits were claimed for "newer" drugs (low dose
angiotensin-converting enzyme [ACE] inhibitors or calcium antagonists) compared
with a standard diuretic-beta-blocker regimen, but the data showed ACE
inhibitors to be superior to calcium antagonists (23% better against myocardial
infarction and 22% better against heart failure). The Heart Outcomes Prevention
Evaluation (HOPE) trial, carried out over a period of 4 years in >9000
high-risk individuals >60 years of age, reported that ACE inhibition reduced
the combined incidence of myocardial infarction, stroke, and death by
22%.25 The authors found that ACE
inhibition conferred equal benefit in both hypertensive and normotensive
individuals when compared with placebo and suggested that the small BP
decreases that were observed (3/2 mm Hg) could not fully account for the
cardiovascular benefits of ACE inhibition. In HOPE, however, BP measurements
were sporadic and unstandardized. The attractive possibility of enhanced
benefits with certain antihypertensive drug classes therefore remains open.
In any form of hypertension, the primary goal is to
lower BP by using any approved antihypertensive agent that is effective, well
tolerated, and appropriate for the spectrum of clinical conditions present in
the individual under treatment. JNC VI clearly stated that individualized
therapeutic strategies were most desirable and that the skill and judgment of
individual clinicians were essential in achieving optimal outcomes. JNC VI was
predicated on the idea of integrated management based on risk stratification.
It highlighted the roles of comorbidities in the decision-making process and
identified high-risk conditions in which clinical trial evidence has provided
"compelling indications" for the use of certain drug classes. In isolated
systolic hypertension, thiazide diuretics (with or without beta-blockers) and
long-acting calcium antagonists are recommended on the basis of the results of
SHEP and Syst-EUR. Lifestyle changes remain useful adjuncts in helping older
patients achieve BP goals.
On the basis of the foregoing arguments, the Committee
has specifically recommended: (1) Systolic BP should become the principal
clinical end point for the detection, evaluation, and treatment of
hypertension, especially in middle-aged and older Americans. (2) The importance
of lifelong maintenance of BP <140/90 mm Hg is reaffirmed on the basis of
the known favorable risk-benefit balance at this level. Foremost in this
assertion is the need for early therapy as primary protection against target
organ damage. It should also be recognized that BP control (especially
systolic) remains valuable at any age, initial BP level, or duration of
hypertension. (3) More stringent BP control is necessary to achieve optimal
benefit in high-risk conditions. In hypertensives with diabetes, BP should be
maintained <130/85 mm Hg and in hypertensives with kidney failure or heart
failure, BP should be reduced to the lowest levels possible. (4) Age-adjusted
BP targets are inappropriate, including the unsubstantiated but persistent
clinical folklore that it is acceptable for systolic BP to be "100 + your age."
(5) ACE inhibitors are recommended as agents that lower morbidity and mortality
rates in older people, in whom systolic hypertension is most prevalent.
The vast majority of hypertensive individuals can
achieve recommended BP targets without significant difficulty. It is
acknowledged, however, that clinicians should proceed with caution in treating
certain elderly individuals with long-standing severe systolic hypertension, in
whom rapid lowering of BP may be difficult or possibly harmful. In brittle or
truly resistant patients, it may be wise to allow longer periods of time to
reach goal BP. Although it is reasonable to assume that partial BP control is
preferable to none at all, it is also clear that "lower is better" in the vast
majority of patients.
The authors wish to thank Stanley Franklin MD, Michael
Alderman, MD, Edward Frohlich, MD, and the members of the Coordinating
Committee for their expert scientific and editorial criticisms and Edward J.
Roccella, PhD, MPH, for his invaluable administrative support.
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Table 1. Major Trials in Isolated Systolic
||Relative Risk Reduction (%)
SHEP indicates Systolic Hypertension in the
Elderly Program22 ; Syst-EUR, European Trial in
Systolic Hypertension7 ; CAD, coronary artery
disease; CHF, congestive heart failure; and CVD, cardiovascular disease.
Figure 1. Systolic and diastolic BP by
age and race or ethnicity for men and women over
18 years of age in the US
population. Data from NHANES III, 1988 to 1991.
Text alternative for Figure 1 representing the data
points of the line charts.
Figure 2. Relation of systolic and
diastolic BP to death from coronary heart disease in the
Factor Intervention Trial. Data compiled from more than 316,000 male
followed for 12 years. Adapted from Neaton et
Text alternative for Figure 2 representing the data
points of the bar charts.