Systolic Hypertension in the Elderly

Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel IP et al. Risks of untreated and treated isolated systolic hypertension in the elderly meta-analysis of outcome trials. Lancet 2000 355(9207) 865-72. 

The relative effect of treatment reflects the proportional difference between treatment groups in the incidence of disease events. In the Systolic Hypertension in the Elderly (SHEP) trial, the incidence of major CHD events over 4.5 years in patients assigned active treatment was 4.4% while in those assigned placebo it was 5.9%. This represents a relative risk of 0.73 or a relative risk reduction of 27%. 

SHEP Co-operative Research Group Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension final results of the Systolic Hypertension in the Elderly Programme (SHEP). JAMA 1991 265 3255-64. 

Black DM, Brand RI, Greenlick M, et al Compliance to treatment for hypertension in elderly patients The SHEP pilot study. Systolic Hypertension in the Elderly Program. J Gerontol 1987 42 552-557. 

The issues of whether hyperuricemia is an independent risk factor for cardiovascular disease and the clinical relevance of the rise in serum uric acid caused by diuretic treatment are controversial (SED-14, 660 351). In the Systolic Hypertension in the Elderly Program (SHEP), diuretic-based treatment in 4327 men and women, aged 60 years or more, with isolated systolic hypertension was associated with significant reduction in cardiovascular events (SED-14, 657). Serum uric acid independently... 

Cangiano JL, Martinez-Maldonado M. Isolated systolic hypertension in the elderly. In M. Martinez-Maldonado, editor. Hypertension and renal disease in the elderly. Oxford Blackwell Scientific Publications 1992. p. 79-94. 

A series of trials in elderly hypertensive subjects has shown a very pronounced reduction in cardiac events as a result of treatment based on thiazide diuretics. In the European Working Party on Hypertension in the Elderly (EWPHE) trial (13), total cardiovascular deaths were reduced by 38%, all cardiac deaths by 43%, and deaths due to myocardial infarction by 60%. Benefits in the Systolic Hypertension in the Elderly Program (SHEP) included a reduction in fatal and non-fatal myocardial infarction of 25% and major cardiovascular events of 32% (14) and were seen in those with and without electrocardiographic abnormalities at entry. The risk of heart failure was also reduced in patients taking chlortalidone-based therapy (15). Relative risk was similar in patients with and without non-insulin dependent diabetes meUitus absolute risk reduction was twice as great in the diabetic subjects (16). The Swedish Trial of Old Patients with Hypertension (STOP-Hypertension) reported a significant reduction in myocardial infarction and all-cause mortahty (17). In the MRC Trial in elderly adults (18), diuretic treatment reduced coronary events by 44% and fatal cardiovascular events by 35%. 

Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, Camel G, Davis BR, Frost PH, Gonzalez N, Guthrie G, Oberman A, Rutan GH, Stamler J. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA 1996 276(23) 1886-92. 

Franse LV, Pahor M, Di Bari M, Shorr RI, Wan JY, Somes GW, Applegate WB. Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP). J Hypertens 2000 18(8) 1149-54. 

Even the large resources of the NIH can be strained. The Systolic Hypertension in the Elderly Person (SHEP) investigation recruited 4736 patients aged 60-96 years (average 72). The patient screening and selection was organized from 16 sites but took 31 months to complete, which had initially been projected to be 24 months. 

Three landmark placebo-controlled clinical trials have established the benefits of both hypertension treatment and diuretic therapy. The Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and the Medical Research Council (MRC) trial " showed significant reductions in stroke, myocardial infarction, and aU-cause cardiovascular disease and mortality with thiazide diuretic-based therapy versus placebo. These trials allowed for /3-blockers as add-on therapy for BP control. Newer agents (i.e., ACE inhibitors, angiotensin II receptor blockers [ARBs], and calcium channel blockers [CCBs]) were not available at the time of these studies. However, subsequent clinical trials have compared these newer antihypertensive agents (ACE inhibitors, ARBs, and CCBs) to diuretics." These data show similar effects, but most trials used a prospective, open-label, blinded end point (PROBE) study methodology that is... 

Hypertension often presents as isolated systolic hypertension in the elderly. Epidemiologic data indicate that cardiovascular morbidity and mortality are more closely related to SBP than to DBP in patients aged 50 years and older, so this population is at high risk for hypertension-related target-organ damage. Although several placebo-controlled trials have specifically demonstrated risk reduction in this form of hypertension, many older people with hypertension are either not treated or treated yet not controlled. ... 

Wang JG, Staessen JA, Gong L, Liu L. Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group. Arch Intern Med 2000 160 211—220. 

The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group (1988) Rationale and design of a randomized clinical trial on prevention of stroke in isolated systolic hypertension. J Clin Epidemiol 41 1197-1208... 

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