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The Systolic Hypertension in the Elderly Program

Peter J. Savage, MD; Sara L. Pressel, MS; J. David Curb, MD; Eleanor B. Schron, RN, MS; William B. Applegate, MD; Henry R. Black, MD; Jerome Cohen, MD; Barry R. Davis, MD, PhD; Philip Frost, MD; W. Smith, MD; Nelly Gonzalez, MD; Gordon P. Guthrie, MD; Albert Oberman, MD; Gale Rutan, MD; Jeffrey L. Probstfield, MD; Jeremiah Stamler, MD; for the SHEP Cooperative Research Group

Arch Intern Med. 1998;158:741-751.

Background  Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and -blockers adversely alters levels of other cardiovascular disease risk factors.

Methods  The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo.

Results  After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 µmol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 µmol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment.

Conclusions  Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.

From the Division of Clinical Applications, the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (Dr Savage and Ms Schron); the University of Texas School of Public Health, Houston (Ms Pressel and Dr Davis); John A. Burns School of Medicine, Honolulu, Hawaii (Dr Curb); University of Tennessee (Dr Applegate) and the Veterans Affairs Medical Center (Dr Rutan) Memphis; Rush-Presbyterian-St Luke's Medical Center (Dr Black); and Northwestern University Medical School (Dr Stamler) Chicago, Ill; Washington University School of Medicine, St Louis, Mo (Dr Cohen); University of California, San Francisco (Drs Frost and Smith); University of Minnesota, Minneapolis (Dr Gonzalez); University of Kentucky, Lexington (Dr Guthrie); University of Alabama, Birmingham (Dr Oberman); and University of Washington, Seattle (Dr Probstfield). A complete listing of SHEP group members was published previously (JAMA. 1991;265:3255-3264).

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