Elevated systolic blood pressure and risk of cardiovascular and renal disease: Overview of evidence from observational epidemiologic studies and randomized controlled trials,☆☆,

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Abstract

The effect of elevated blood pressure on risk of cardiovascular and renal disease has been documented in both observational 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 randomized controlled trials to quantify the risk associated with systolic blood pressure. Prospective studies and randomized controlled 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.)

Section snippets

Observational studies

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 association of systolic blood pressure with these outcomes is stronger than that of diastolic blood pressure. This evidence is summarized in the next three sections.

Randomized controlled trials

Over the past several decades, many antihypertensive drug treatment trials have been conducted to determine whether blood pressure reduction decreases the risk of cardiovascular disease.26 Results from these trials have been pooled in several meta-analyses to obtain a more precise and accurate estimate of the effect of antihypertensive treatment on clinical outcomes.3, 4, 26, 27 However, all of these meta-analyses have emphasized the effect of diastolic blood pressure reduction on the risk of

Characteristics of participants in 10 systolic blood pressure reduction trials

Characteristics of the 18,542 participants who were enrolled in these trials as well as important elements of the study design used in each trial are summarized in Table I.

. Characteristics of participants and study design for 10 randomized trials of antihypertensive drug therapy

Trial, year, and referenceSample sizeEntry SBP (mm Hg)Entry DBP (mm Hg)Mean age (years)Men (%)Mean follow-up (years)BlindingMain drug type(s)*Mean SBP reduction (mm Hg)†Mean DBP reduction (mm Hg)
Veterans Administration,

Effects of systolic blood pressure reduction on CHD and stroke

Overall, 412 CHD events occurred in the participants who were assigned to active treatment and 520 in those who were allocated to control (Table II). When the results from the 10 trials were pooled, a highly significant reduction in the odds of total and fatal CHD (both P < .001) was observed among the participants allocated to active treatment. The reduction in total CHD was 21% (95% confidence intervals [CI] 10% to 31%) and the reduction in fatal CHD was 27% (95% CI 13% to 38%). As shown in

Effects of systolic blood pressure reduction on death from cardiovascular disease and from all causes

Overall, 467 deaths from cardiovascular disease occurred in the participants who were allocated to active treatment and in 617 of their counterparts who were allocated to control (Table II). The overall reduction in cardiovascular disease mortality rates for active treatment compared with control was 25% (95% CI 15% to 34%; P < .001). In 5 of the 10 trials, the reduction in cardiovascular disease mortality rates was statistically significant (Figure 9).

. Odds ratios and 95% CIs for

Subgroup analysis

Reduction in CHD and stroke risk by hypertension status is presented in Table III.

. Risk reduction in coronary heart disease and stroke by hypertension status*

Hypertension status and trial numberActive treatmentControl treatment% Risk reduction (95% CI)P value
Fatal eventsTotal eventsNo. of participantsFatal eventsTotal eventsNo. of participantsFatalTotalFatalTotal
Coronary heart disease
SDH (n = 8)1592754515225333459628 (12-42)17 (2-29).001.03
ISH (n = 2)911374763116187466823 (–1-42)28 (10-43).06

Conclusion

In conclusion, prospective observational studies have repeatedly demonstrated that systolic blood pressure is an independent and strong predictor of risk of CHD, stroke, and ESRD. Pooling of the data available from randomized controlled clinical trials indicates that an average reduction of 12 to 13 mm Hg in systolic pressure over 4 years of follow-up is associated with a 21% reduction in CHD, 37% reduction in stroke, 25% reduction in total cardiovascular mortality rate, and 13% reduction in

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    From the Department of Biostatistics and Epidemiology, Tulane University School of Public Health and Tropical Medicine.

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    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: [email protected]

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