Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. The SHEP Cooperative Research Group.

BACKGROUND: There are scant data on the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) on cardiovascular events and death in older patients with hypertension. OBJECTIVE: To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke. PATIENTS: Participants were 3975 men and women (mean age, 71 years) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial, a randomized, double-blind, placebo-controlled clinical trial of lowdose antihypertensive therapy, with follow-up for 5 years. MAIN OUTCOME MEASURES: Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses. RESULTS: There was no statistically significant relation of death or stroke with BMI in the placebo group (P = .47), and there was a U- or J-shaped relation in the treatment group. The J-shaped relation of death with BMI in the treated group (P = .03) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6; the curve was quite flat for women across a wide range of BMIs. For stroke, men and women did not differ, and the BMI nadir for both sexes combined was 29, with risk increasing steeply at BMIs below 24. Those in active treatment, however, had lower death and stroke rates compared with those taking placebo. CONCLUSIONS: Among older patients with hypertension, a wide range of BMIs was associated with a similar risk of death and stroke; a low BMI was associated with increased risk. Lean, older patients with hypertension in treatment should be monitored carefully for additional risk factors.

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.

OBJECTIVE: To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients. DESIGN: Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP). SETTING: Multiple clinical and support centers in the United States. PARTICIPANTS: A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics. INTERVENTION: The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP. MAIN OUTCOME MEASURES: The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality. RESULTS: The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. CONCLUSION: Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.

Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program.

BACKGROUND: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. METHODS: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. RESULTS: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. CONCLUSIONS: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities.

Recruitment of elderly volunteers for a multicenter clinical trial: the SHEP pilot study.

Few large trials have involved the elderly, and little is known about the feasibility of recruiting such participants for study and the validity of inferences drawn from them. This article reviews the recruitment experience of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. That program involved five clinical centers, and contacted approximately 75,000 persons in order to enroll a cohort of 551 individuals over 60 years old isolated systolic hypertension. The enrolled cohort was somewhat older and more highly educated than those screened. Except for deliberate oversampling of blacks and those over 70 years old, the enrolled population resembled the U.S. population, although individuals in the SHEP group were initially healthier, and more likely to have had some college education than those in the general population. There was substantial variation among sites in number of staff hours spent per participant recruited. The SHEP experience indicates that older persons are willing to volunteer for clinical trials research and that problems of inference are probably not any greater for that age group than for any other.

Survival of treated hypertensive patients as a function of compliance and control.

In the 1950s, 223 white patients had varyingly severe hypertension controlled in hospital with ganglioplegic agent and hydralazine. At home, each was instructed to take and record his/her blood pressure (BP) four or five times per day and to bring all BP records to the next treatment visit. Our file of home BP records exactly one year after treatment began was used to divide the patients into: non-compliant; compliant but uncontrolled; controlled. There were 56 non-compliant, 60 compliant but uncontrolled, and 107 controlled patients. Their respective median survival times after beginning therapy were 56.5, 134, and 153 months. Thus, survival was a strong function of compliance and a significant but weaker function of control. The non-compliant quarter of the group survived an average of less than five years, while the controlled half survived an average of more than 12 years.