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.

Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program.

Interaction of thiazide diuretics and the serum uric acid and creatinine levels was studied in 3693 stepped care participants in the Hypertension Detection and Follow-up Program not receiving treatment at baseline. Among men grouped into quartiles by their level of uric acid at baseline, the upper quartile (average uric acid, 7.7 mg/dL [458 mumol/L]) had an average serum creatinine level of 1.2 mg/dL (106 mumol/L) and the lowest quartile (uric acid, 4.9 mg/dL [291 mumol/L]) had an average serum creatinine level of 1.1 mg/dL (97 mumol/L). Similar findings were present in women. Therapy with chlorthalidone or other thiazide-type diuretics tended to increase levels of uric acid and creatinine, but the increase in both was less in the upper quartile than in the lower quartile. Among individuals who were prescribed uric acid-lowering drugs, the level of serum creatinine increased just as much as in those whose uric acid level was not pharmacologically lowered. Baseline uric acid level was a weak predictor of mortality in men; the introduction of an interaction term for creatinine suggested that this effect was primarily restricted to those with elevated levels of both uric acid and creatinine at baseline. Change in uric acid level at one year after therapy was inversely correlated with mortality in men. There were few episodes of gout (only 15 recorded in five years among 3693 participants at risk). These results suggest that neither the baseline uric acid level nor the change in uric acid level produced by therapy injures the kidney. These results suggest no reason to lower uric acid levels pharmacologically in the treated hypertensive patient who is not gouty. They leave unanswered whether there is a predictive value to baseline uric acid level not explainable by other correlated cardiovascular risk factors.

Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly).

OBJECTIVE: To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality. DESIGN: Cohort analytic study of data from randomized placebo-controlled double-blind clinical trial of antihypertensive therapy. Depressive symptoms were assessed semi-annually with the Center for Epidemiological Studies-Depression (CES-D) scale during an average follow-up of 4.5 years. SETTING: Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program. PATIENTS: Generally healthy men and women aged 60 years or older randomized to active antihypertensive drug therapy or placebo who were 70% white and 53% women and had follow-up CES-D scores and no outcome events during the first 6 months (N=4367). MAIN OUTCOME MEASURES: All-cause mortality, fatal or nonfatal stroke, or myocardial infarction. RESULTS: Baseline depressive symptoms were not related to subsequent events; however, an increase in depression was prognostic. Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable, controlling for multiple covariates, indicated a 25% increased risk of death per 5-unit increase in the CES-D score (relative risk [RR], 1.25;95% confidence interval [CI], 1.15 to 1.36). The RR for stroke or myocardial infarction was 1.18(95%CI,1.08 to 1.30). Increase in CES-D score was an independent predictor in both placebo and active drug groups, and it was strongest as a risk factor for stroke among women (RR,1.29;95%CI,1.07 to 1.34). CONCLUSIONS: Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended.

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.

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group.

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-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 micromol/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 micromol/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.

Clinical trial participant satisfaction: survey of SHEP enrollees. SHEP Cooperative Research Group. Systolic Hypertension in the Elderly Program.

OBJECTIVE: The purpose of this study was to determine older persons' reasons for joining a clinical trial, and to provide data that could be useful in planning and carrying out clinical trials in older and minority populations. DESIGN: A survey. PARTICIPANTS: The sample included 4281 men and women 60 years of age or older who were randomized to the Systolic Hypertension in the Elderly Program (SHEP). MEASUREMENTS: A 10-item satisfaction/attitude questionnaire was designed to evaluate (1) what personal benefits people expect from participation in this trial, (2) motivation for joining, and (3) satisfaction with clinic staff and operations. Each question had a response category asking for a measure of agreement, satisfaction, or importance. RESULTS: The most important reasons for joining the clinical trial were to contribute to science (96%), improve the health of others (96%), and improve their own health (93%). Free medical care and social aspects were less important reasons to join. There were no differences by treatment assignment, but differences in reasons for joining SHEP by age, race, gender, and education were observed. CONCLUSION: Older adults were enthusiastic about clinical trial participation. Recruitment, participant management strategies, and allocation of resources should consider the needs of specific patient groups.

Age, race, and gender variation in the utilization of coronary artery bypass surgery and angioplasty in SHEP. SHEP Cooperative Research Group. Systolic Hypertension in the Elderly Program.

OBJECTIVE: To assess variability in the use of coronary artery bypass grafting (CABG) and percutaneous transluminal angioplasty (PTCA) in the Systolic Hypertension in the Elderly Program (SHEP) cohort with incident coronary heart disease (CHD) by age, sex, and race. DESIGN: Retrospective analysis of a multicenter prospective cohort study. SETTING: Community-based ambulatory population in academic centers. PATIENTS: Among 4736 subjects initially enrolled in SHEP, there were 432 incident cases of CHD, excluding those patients who experienced rapid or sudden cardiac death. MAIN OUTCOME MEASURE: Incident cases of CHD who underwent CABG or PTCA. RESULTS: Of those participants > or = 60 and < 75 years of age, 7.3% underwent PTCA, compared with 3.9% of those > or = 75 years (P = 0.14). 15.4% of those < 75 underwent CABG surgery, compared with 7.8% of those 75 and older (P = 0.018). When both of these endpoints, CABG and PTCA, were combined, 22.4% of those < 75 underwent a procedure, while only 11.7% of the older cohort did (P = 0.005). Twenty-six percent of men underwent either CABG or PTCA, while only 9.1% of women did (P < 0.001). Of those < 75 years of age, 31.1% of men and 12.3% of women underwent CABG or PTCA (P < 0.001). In the 75 and older age category, 19.5% of men underwent these interventions, compared with 5.9% of women (P = 0.005). Active treatment group was significantly associated with decreased use of procedures in participants < 75 year old with CHD. Race, activity limitations, number of comorbid conditions, education level, marital status, employment status, and social support were not significantly associated with CABG or PTCA use. When the variables studied were entered into a logistic regression model, increased age and female sex remained independently associated with decreased CABG and PTCA use. CONCLUSION: In the SHEP trial older patients and women, regardless of comorbid conditions, socioeconomic status, and social support, underwent less intensive cardiovascular interventions than did younger patients and men when they developed CHD.

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Systolic blood pressure as an independent predictor of mortality in the Hypertension Detection and Follow-up Program.

The Hypertension Detection and Follow-up Program (HDFP) findings demonstrate the predictive value of baseline systolic blood pressure (SBP) and of pulse pressure (PB) in five-year mortality from all causes. Grouping participants into four SBP strata revealed an approximately two-fold increase in age-adjusted mortality rate from SBP stratum I to SBP stratum IV. This effect remained after the contributions of other risk factors were controlled by multivariate analysis. In contrast, baseline diastolic blood pressure (DBP) had little demonstrable effect on mortality in this particular population. The predictive power of pulse pressure was similar to that of SBP. The group mean SBP of every stratum fell progressively during the trial, the change being of greater magnitude in the stepped care (SC) group than in the referred care (RC) group. Also, the reduction in all-cause mortality associated with SC treatment was observed at all levels of baseline SBP. An analysis using life table regression with SBP as a time-dependent variable showed that the postrandomization reduction in SBP was a significant factor in reducing mortality. Similarly, reduced DBP was also contributory. Prospective studies are required to answer definitively the question of the efficacy of treatment of systolic hypertension. Nevertheless, the present analysis of the HDFP data, despite design limitations, supports the advisability of reducing elevated systolic blood pressure.

Effect of thiazide-based therapy on serum alkaline phosphatase. Hypertension Detection and Follow-up Group.

This study reports a correlation of alkaline phosphatase (AP) with diastolic blood pressure (DBP), and a reduction of alkaline phosphatase after chlorthalidone therapy that reached a nadir at three years of therapy, then gradually returned toward, but not reaching, baseline values. The data is from the baseline examination and follow-up of 3928 initially untreated stepped-care patients in the Hypertension Detection and Follow-up Program. In multiple regression analysis, both age and DBP were significantly correlated with increased AP in males and females. After initiation of therapy with chlorthalidone, AP levels fell progressively until the third year, when they were reduced by 11 +/- 15 IU in the males and 14 +/- 15 IU in the females. The data are compatible with the interpretation that thiazide-induced reduction in urinary calcium excretion has led to a more positive calcium balance and reduction of bone turnover, and suggests that a beneficial effect of thiazide-based antihypertensive therapy could be decreased osteoporosis.

Effective dietary intervention in hypertensives: sodium restriction and weight reduction.

A Dietary Intervention Study of Hypertension (DISH) was undertaken to determine whether patients whose high blood pressure had been controlled pharmacologically for a period of more than 5 years could maintain that control with sodium restriction or weight reduction instead of drugs. Four hundred ninety-six patients, classified by degree of overweight, were randomly assigned into one of seven groups. Included were those who would be withdrawn from antihypertensive medication and receive intervention for either sodium restriction or weight reduction. After 8 weeks of intervention, an average reduction of 24-hour urinary sodium output from a baseline of 158 mEq to 106 mEq (p less than .001) and from 130 mEq to 96 mEq (p less than .01) was achieved for the overweight and nonoverweight groups, respectively. That decline was still maintained at 56 weeks. Dietary estimates, obtained by analysis of 3-day food records, underestimated urinary output by an average of 12%, with blacks more likely to underestimate than whites, and the overweight more likely to underestimate than the nonoverweight. An average 10-lb weight loss was achieved, with no difference between men and women. Weight declined for 32 weeks, then leveled off and was maintained up to 56 weeks, indicating that sodium intake modification can be accomplished faster than weight reduction. Modest sodium restriction and weight reduction are feasible and achievable in a free-living population and have a positive effect on control of hypertension.

Prediction of response to sodium intervention for blood pressure control.

In the Dietary Intervention Study of Hypertension (DISH) we found that patients formerly treated with drugs and assigned to sodium-reduction intervention were twice as likely to remain off medication for up to 56 weeks as were the controls assigned to no-diet intervention, after adjusting for covariates. Within the sodium-restriction group approximately 60% of 131 people were Intervention Successes (IS) (urinary sodium less than or equal to 100 mmol/day at 8 weeks). The rest were classed as Non-Intervention Successes (NIS). Of the IS group, 54% were responders (drug-free for at least 56 weeks), but about 56% of the NIS group also remained drug-free. Multiple logistics showed that no one factor was able to predict response among the IS. We conclude that the IS likely to respond to sodium reduction are not readily identifiable a priori. Furthermore, since both IS and NIS showed similar blood-pressure effects from the sodium-restriction regimen compared with controls, the questions arise: whether a factor other than sodium reduction affects the blood pressure response for the sodium-restriction group; or whether the measurement of sodium intake and excretion is sufficiently precise to distinguish compliers from non-compliers.

Formation of specialized propagules resistant to desiccation and cryopreservation in the threatened moss Ditrichum plumbicola (Ditrichales, Bryopsida).

BACKGROUND AND AIMS: Successful cryopreservation of bryophytes is linked to intrinsic desiccation tolerance and survival can be enhanced by pre-treatment with abscisic acid (ABA) and sucrose. The pioneer moss Ditrichum plumbicola is naturally subjected to desiccation in the field but showed unexpectedly low survival of cryopreservation, as well as a poor response to pre-treatment. The effects of the cryopreservation protocol on protonemata of D. plumbicola were investigated in order to explore possible relationships between the production in vitro of cryopreservation-tolerant asexual propagules and the reproductive biology of D. plumbicola in nature. METHODS: Protonemata were prepared for cryopreservation using a four-step protocol involving encapsulation in sodium alginate, pre-treatment for 2 weeks with ABA and sucrose, desiccation for 6 h and rapid freezing in liquid nitrogen. After each stage, protonemata were prepared for light and electron microscopy and growth on standard medium was monitored. Further samples were prepared for light and electron microscopy at intervals over a 24-h period following removal from liquid nitrogen and re-hydration. KEY RESULTS: Pre-treatment with ABA and sucrose caused dramatic changes to the protonemata. Growth was arrested and propagules induced with pronounced morphological and cytological changes. Most cells died, but those that survived were characterized by thick, deeply pigmented walls, numerous small vacuoles and lipid droplets in their cytoplasm. Desiccation and cryopreservation elicited no dramatic cytological changes. Cells returned to their pre-dehydration and cryopreservation state within 2 h of re-hydration and/or removal from liquid nitrogen. Regeneration was normal once the ABA/sucrose stimulus was removed. CONCLUSIONS: The ABA/sucrose pre-treatment induced the formation of highly desiccation- and cryopreservation-tolerant propagules from the protonemata of D. plumbicola. This parallels behaviour in the wild, where highly desiccation-tolerant rhizoids function as perennating organs allowing the moss to endure extreme environmental conditions. An involvement of endogenous ABA in the desiccation tolerance of D. plumbicola is suggested.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Ascertainment of vital status through the National Death Index and the Social Security Administration.

Ascertainment of the vital status of individuals is of central importance to epidemiologic studies which monitor mortality as an end point. Utilizing identifying information collected in 1973-1974, the Hypertension Detection and Follow-up Program, a prospective, multicenter study, followed 25,362 individuals to determine eight-year mortality. In the most recent follow-up, there were 617 individuals whose vital status was not known. Available identifying information on these and on all 1,322 participants known to have died in 1979-1981 was submitted to the National Death Index (NDI) for possible confirmation of vital status. A subset of individuals who had Social Security numbers (490 lost to follow-up and 1,154 known deaths) was also submitted to the Social Security Administration (SSA). The NDI correctly identified 87.0% of the known deaths. Of the 1,154 known deaths (those with known Social Security numbers) submitted to both agencies, the NDI identified 93.1% and the SSA 83.6%. Significant variations by race and sex were noted in the identification rates, in part because of Social Security number discrepancies. False matches through the NDI matching process occurred for 10.4% of the known deaths. In the more restrictive SSA search, only 0.5% false matches resulted. For those lost to follow-up, vital status was ascertained in 57.1%. This paper describes the relative efficacy and attributes of the use of these systems to ascertain vital status.

Nosological coding of cause of death.

Death certificates representing 766 decedents who had participated in the Hypertension Detection and Follow-up Program (1973-1979) at one of 14 US centers were given to three nosologists for purposes of coding underlying cause of death. Analyses examined interobserver variability among the three nosologists as well as intraobserver variability for each of the three nosologists. All three nosologists agreed on a three-digit International Classification of Diseases, Adapted (ICDA) code in 90.2% of the cases and at least two out of three agreed in 99.7% of the death certificates examined. Agreement rates improved when disease codes were collapsed into broader categories utilized in the Hypertension Detection and Follow-up Program. When particular disease classifications (e.g., cerebrovascular, ischemic heart disease, myocardial infarction, and neoplasms) were examined, three out of three agreement rates were highest for neoplasms (97.8%) and lowest for myocardial infarction (86.5%). Similarly, two out of three agreement was highest for neoplasms (98.5%) and lowest for myocardial infarction (88.0%). Intranosologist agreement rates were based on a recoded 20% sample of death certificates. Agreement rates for three-digit ICDA codes ranged from 94.8% to 96.1% for the three nosologists. The agreement rates for the general disease categories ranged from 96.7% to 97.4%.

Statistical considerations in monitoring the Systolic Hypertension in the Elderly Program (SHEP).

The Systolic Hypertension in the Elderly Program (SHEP), a randomized, double-masked, placebo-controlled trial of 4736 persons, was designed to assess the efficacy of antihypertensive drug treatment to reduce the risk of fatal and nonfatal strokes among people age 60 and over with isolated systolic hypertension. The statistical method used in interim monitoring of results was conditional power (or stochastic curtailment). The findings did not become conclusive until near the completion of the trial, and therefore SHEP was continued to its scheduled closing date. The trial demonstrated a 36% reduction in the incidence of stroke in the active treatment group (P = .0003). In addition to evaluating overall efficacy of treatment, the monitoring process considered such other issues as nonstroke outcomes, lag time between first report of stroke and final confirmation of stroke diagnosis, consistency of results across subgroups, and completeness of follow-up. The purpose of this article is to review these factors with primary emphasis on the statistical aspects.