of CHD and stroke have been assessed in several ran-
domized controlled trials.
The objectives of this overview are 2-fold. The first is
to provide a review of the available evidence from
prospective studies for an association between systolic
pressure and risk of CHD, stroke, and end-stage renal
disease (ESRD). The second is to provide the results of a
systematic review of randomized controlled trials of sys-
tolic blood pressure reduction.
Results from several prospective studies indicate that
the association between systolic blood pressure and risk
of CHD, stroke, and ESRD is continuous, graded and
independent. Furthermore, they suggest that the associ-
ation of systolic blood pressure with these outcomes is
stronger than that of diastolic blood pressure. This evi-
dence is summarized in the next three sections.
Coronary heart disease
CHD is the most common blood pressure–related
major clinical complication in the United States and
most other industrialized countries.
only a small number of prospective studies had assessed
the independent effect of systolic blood pressure on risk
Data from a 30-year follow-up of the origi-
The association between blood pressure and risk of
coronary heart disease (CHD) and stroke has been inves-
tigated in many prospective observational studies.
Results from these prospective studies have been com-
bined in several major pooling projects that have
demonstrated that blood pressure is positively, continu-
ously, and independently associated with an increased
risk of CHD and stroke.
In these pooling projects,
however, only diastolic blood pressure was used to
characterize the blood pressure level of an individual.
Likewise, randomized controlled trials have traditionally
concentrated on examining the effects of diastolic
blood pressure lowering on risk of CHD and stroke.
During the past 10 years, several major prospective
studies have indicated that systolic blood pressure is a
more powerful predictor of the risk of cardiovascular
and renal disease than diastolic pressure.
the effects of systolic blood pressure reduction on risk
From the Department of Biostatistics and Epidemiology, Tulane University School of
Public Health and Tropical Medicine.
Reprint requests: Jiang He, MD, PhD, Department of Biostatistics and Epidemiology,
Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Ave,
SL 18, New Orleans, LA 70112-2699. E-mail: firstname.lastname@example.org
Copyright © 1999 by Mosby, Inc.
0002-8703/99/$8.00 + 0 4/0/100201
Elevated systolic blood pressure and risk of
cardiovascular and renal disease: Overview of
evidence from observational epidemiologic studies
and randomized controlled trials
Jiang He, MD, PhD, and Paul K. Whelton, MD, MSc New Orleans, La
The effect of elevated blood pressure on risk of cardiovascular and renal disease has been documented in both observa-
tional epidemiologic studies and clinical trials. However, these studies have traditionally concentrated on diastolic blood
pressure to characterize the risk associated with hypertension. We reviewed evidence from prospective studies and random-
ized controlled trials to quantify the risk associated with systolic blood pressure. Prospective studies and randomized con-
trolled clinical trials that were published in English-language journals were retrieved using MEDLINE, bibliographies, and the
authors’ reference files. All retrieved publications were reviewed and information on sample size, duration, study design,
antihypertensive medication, participant characteristics, and outcomes was abstracted for randomized controlled trials that
reported systolic blood pressure reduction during intervention. Several prospective studies indicate that the association
between systolic blood pressure and risk of coronary heart disease, stroke, and end-stage renal disease is continuous,
graded, and independent. Furthermore, they suggest that the association of systolic blood pressure with these outcomes is
stronger than that of diastolic blood pressure. Pooling of the data available from randomized controlled trials indicates that
an average reduction of 12 to 13 mm Hg in systolic blood pressure over 4 years of follow-up is associated with a 21%
reduction in coronary heart disease, 37% reduction in stroke, 25% reduction in total cardiovascular mortality, and 13%
reduction in all-cause mortality rates. These data indicate that systolic blood pressure is an independent and strong predictor
for risk of cardiovascular and renal disease. (Am Heart J 1999;138:S211-S219.)