Elsevier

The Lancet

Volume 355, Issue 9207, 11 March 2000, Pages 865-872
The Lancet

Articles
Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

https://doi.org/10.1016/S0140-6736(99)07330-4Get rights and content

Summary

Background

Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension

Methods

Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 X 2 contingency tables after application of Zelen's test of heterogeneity.

Findings

In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor.

Active treatment reduced total mortality by 13% (95% Cl 2–22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37).

Interpretation

Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Introduction

The prevalence of isolated systolic hypertension rises curvilinearly with age, averaging 8% in sexagenarians and exceeding 25% beyond 80 years.1 Isolated systolic hypertension is a distinct pathophysiological entity, in which the rise in systolic blood pressure is mainly due to a decreased elasticity of the large arteries and is not necessaily accompanied by a rise in maen arterial blood pressure or in preipheral resistance.1

Among the cardiovascular risk factors amenable to prevention in the elderly, systolic hypertension is of major importance.1 The past decade witnessed the publication of three outcome trials,2, 3, 4 which specifically addressed the question whether in the elderly the cardiovascular risk conferred by isolated systolic hypertension is reversible by antihypertensive drug treatment. Earlier published trials also included groups of older patients with isolated systolic hypertension.5, 6, 7, 8, 9 Previous meta-analyses of outcome trials in hypertension10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 did not provide specific estimates of the risks in treated and untreated older patients with isolated systolic hypertension or explained treatment benefit mainly in function of the achieved diastolic blood pressure. We therefore reanalysed the evidence from the published trials. In untreated control patients we first evaluated the risk conferred by systolic and diastolic blood pressure at baseline both before and after correction for regression dilution bias.22, 23 We then calculated pooled estimates of relative and absolute benefit of antihypertensive drug treatment with and without stratification for the risk at baseline.

Section snippets

Acquisition and selection

We defined isolated systolic hypertension as it was in two published trials.3, 4 Systolic blood pressure below 95 mm Hg. As in other studies,2, 5 we set the lower boundary of old age at 60 years without an upper limit. We screened published overviews10, 13, 16, 21 and reports on collaborations between trialists14, 15 for outcome studies in hypertension, in which older patients with isolated systolic hypertension had been enrolled. Among the trials with eligible patients, we excluded seven: the

Characteristics of trials

The main characteristics of the trials appear in table 1. In SHEP, Syst-Eur, Syst-China, EWPHE, and MRC1, the stratification criteria included centre,2, 3, 4, 9 sex,3, 4, 5, 9 age,9 previous cardiovascular complications,3, 4, 5 or anti-hypertensive drug treatment at initial contact.2 No stratification was applied in HEP, STOP, and MRC2. The SHEP, Syst-Eur, EWPHE, HEP, and STOP trials relied on balanced randomisation to active medication or a control group. In MRC1 and MRC2 the patients were

Discussion

Previous meta-analyses focused on the role of diastolic blood pressure as cardiovascular risk factor17, 22, 31 and studied the benefit of antihypertensive drug treatment relative to the achieved reduction in diastolic blood pressure.10, 19 In our overview we found that in untreated patients systolic blood pressure was a more accurate predictor of mortality and cardiovascular complications than diastolic blood pressure. After correction for regression dilution bias,22, 23 a 10 mm Hg increase in

References (48)

  • Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP)

    JAMA

    (1991)
  • L Liu et al.

    Systolic Hypertension in China (Syst-China) Collaborative Group: comparison of active treatment and placebo for older patients with isolated systolic hypertension

    J Hypertens

    (1998)
  • J Coope et al.

    Randomised trial of treatment of hypertension in elderly patients in primary care

    BMJ

    (1986)
  • Medical Research Council trial of treatment of hypertension in older adults: principal results

    BMJ

    (1992)
  • MRC trial of treatment of mild hypertension: principal results

    BMJ

    (1985)
  • AF Lever et al.

    Treatment of hypertension in the elderly

    J Hypertens

    (1995)
  • BM Psaty et al.

    Health outcomes associated with antihypertensive therapies used as first-line agents: a systemic review and meta-analysis

    JAMA

    (1997)
  • F Gueyffier et al.

    INDANA: a meta-analysis on individual patient data in hypertension—Protocol and preliminary results

    Thérapie

    (1995)
  • Protocol for prospective collaborative overviews of major randomized trials of blood-pressure-lowering treatments

    J Hypertens

    (1998)
  • CD Mulrow et al.

    Hypertension in the elderly: implications and generalizability of randomized trials

    JAMA

    (1994)
  • Blood pressure lowering for the secondary prevention of stroke: rationale and design for PROGRESS

    J Hypertens

    (1996)
  • JT Insua et al.

    Drug treatment of hypertension in the elderly: a meta-analysis

    Ann Intern Med

    (1994)
  • R Collins et al.

    Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease

    Br Med Bull

    (1994)
  • J Staessen et al.

    Epidemiology of treated, compared to untreated hypertension

  • Cited by (0)

    View full text