Gender-specific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits.

BACKGROUND: The purpose of this study was to examine the correlations between plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) and cardiovascular disease-related traits in a general population and whether these correlations differed between females and males. METHODS: Plasma PAI-1 and t-PA antigen levels and C-reactive protein (CRP), HDL-cholesterol, triglycerides, total cholesterol, systolic blood pressure, diastolic blood pressure, urinary albumin excretion, and glucose were measured in the population-based PREVEND study in Groningen, the Netherlands (n = 2527). RESULTS: Except for CRP and total cholesterol levels, all traits were significantly different between gender (P < 0.001). PAI-1 levels were correlated with all measured cardiovascular disease-related traits (P < 0.01) in both females and males. Except for urinary albumin excretion, similar results, albeit less significant, were found for t-PA levels. Age-adjusted correlations between PAI-1 and CRP, triglycerides, total cholesterol, systolic blood pressure, and diastolic blood pressure differed significantly between females and males (P < 0.01). Many of the gender differences were predominantly present between premenopausal females and males. CONCLUSION: PAI-1 and t-PA levels were correlated with cardiovascular disease-related traits in subjects obtained from the general population and several of these correlations differed across gender. The correlations found in the present study suggest the presence of coordinated patterns of cardiovascular risk factors and indicate which traits might influence PAI-1 and t-PA levels and thereby provide a framework and potential tool for therapeutic intervention to reduce thromboembolic events in the general population.

Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II.

Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P<0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P<0.001), 2.0 (P<0.001), and 1.3 (P=0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P=0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes.

Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke.

Recurrent stroke is a major public health concern and new treatment strategies are needed. While modulation of the renin angiotensin aldosterone system (RAAS) has proven effective in reducing recurrent cardiac events, its role in preventing recurrent cerebrovascular events remains unclear. RAAS is both a circulating and tissue based hormonal system that regulates homeostasis and tissue responses to injury in both the CNS and the periphery, via the activity of angiotensin II (Ang II). Vascular and hematologic effects induced by Ang II including endothelial dysfunction, vascular structural changes, inflammation, hemostasis, and fibrinolysis are increasingly linked to the occurrence of cerebrovascular events. Animal models have shown that RAAS modulation may be protective in cerebrovascular disease. The HOPE and LIFE trials support the role of blood pressure independent mechanisms of RAAS modulation for improving outcomes in a broad range of patients with cardiovascular disease but do not specifically address recurrent stroke prevention. PROGRESS, a trial of secondary stroke prevention, demonstrates that blood pressure reduction with a combination strategy including the routine use of ACE inhibitors prevents recurrent stroke. Current evidence suggests that the RAAS plays an important role in the development and progression of cerebrovascular disease. Modulation of the RAAS holds promise for the secondary prevention of stroke, however, ongoing clinical trials will better define the exact role of ACE inhibitor and angiotensin II Type 1 receptor blocker therapy in stroke survivors.

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease.

BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.

Self-selected posttrial aspirin use and subsequent cardiovascular disease and mortality in the physicians' health study.

BACKGROUND: The randomized aspirin component of the Physicians' Health Study (PHS) was terminated early, after 5 years, primarily because of the emergence of a statistically extreme (P<.00001) 44% reduction of first myocardial infarction (MI) among those assigned to aspirin. As a result, there were insufficient numbers of strokes or cardiovascular disease (CVD)-related deaths to evaluate these end points definitively. METHODS: Data on self-selected aspirin use were collected until the beta carotene component ended as scheduled after 12 years. Posttrial use of aspirin was assessed at the 7-year follow-up among 18 496 participants with no previous reported CVD. Randomized and posttrial observational results in the PHS were compared, and differences between those self-selecting aspirin and those not were examined. RESULTS: At 7 years, 59.5% of participants without CVD reported self-selected aspirin use for at least 180 d/y, and 20.8% for 0 to 13 d/y. Use was significantly associated with family history of MI, hypertension, elevated cholesterol levels, body mass index, alcohol consumption, exercise, and use of vitamin E supplements. In multivariate analyses, self-selected aspirin use for at least 180 vs 0 to 13 d/y was associated with lower risk for subsequent MI (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55-0.95), no relation with stroke (RR, 1.02; 95% CI, 0.74-1.39), and significant reductions in CVD-related (RR, 0.65; CI, 0.47-0.89) and total mortality (RR, 0.64; CI, 0.54-0.77). CONCLUSION: These associations between self-selected aspirin use and CVD risk factors increase the likelihood of residual confounding and emphasize the need for large-scale randomized trials, such as the ongoing Women's Health Study, to detect reliably the most plausible small to moderate effects of aspirin in the primary prevention of stroke and CVD-related death.

Serious maternal morbidity after childbirth: prolonged hospital stays and readmissions.

OBJECTIVE: To determine the frequency of and risk factors for serious morbidity resulting in a prolonged hospital stay or readmission among women enrolled in Tennessee's Medicaid program who delivered live or dead infants in 1991. METHODS: This retrospective cohort study included 33,251 women of white or black ethnicity. Main outcome measures included childbirth-related medical conditions serious enough to result in death, prolonged delivery hospitalization, or readmission within 60 days of delivery. RESULTS: Among 25,810 women with vaginal (78%) and 7441 (22%) women with cesarean deliveries, 2.6% and 8.9%, respectively, had at least one childbirth-related medical condition requiring prolonged delivery hospitalization or readmission, including infection (1.8% and 7.9%), hypertension-related complications (0.7% and 2.0%), or hemorrhage (0.5% and 2.4%). After controlling for other risk factors, maternal age over 32 years was independently associated with increased rate of serious morbidity among women who had vaginal (relative risk [RR] 1.9, 95% confidence interval [CI] 1.4, 2.7) or cesarean deliveries (RR 1.6, 95% CI 1.1, 2.2). Black women had approximately twice the rate of maternal morbidity with vaginal (RR 1.9, 95% CI 1.5, 2.4) or cesarean deliveries (RR 2.3, 95% CI 1.9, 2.9). Primiparous women who had vaginal or cesarean deliveries had a 60% (RR 1.6, 95% CI 1.3, 2.0) and 70% (RR 1.7, 95% CI 1.4, 2.0), respectively, greater risk of serious maternal morbidity than women with 1-3 prior births. CONCLUSION: Predictors of serious maternal morbidity included age over 32 years, black ethnicity, and primiparity.

Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials.

OBJECTIVE: To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. DATA SOURCES: We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. TRIAL SELECTION: Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. DATA EXTRACTION: Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. DATA SYNTHESIS: A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large-22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). CONCLUSION: This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.

Adult height and incidence of cancer in male physicians (United States).

Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers. The Physicians' Health Study (PHS), a randomized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men, provided an opportunity to examine the association between height and total malignant neoplasms (excluding non-melanoma skin cancer), as well as site-specific cancers including prostate, colorectal, and lung cancer. The PHS is comprised of 22,071 US male physicians in the United States, a population homogeneous for adult socioeconomic status, aged 40 to 84 years in 1982. Participants were classified into five height categories at study entry. After an average follow-up of over 12 years, there were 2,566 cases of incident total malignant neoplasms, including 1,047 prostate, 341 colorectal, and 170 lung cancer cases. Height was associated positively with both total malignant neoplasms and prostate cancer. Compared with men in the shortest category (<67 inches), relative risks and 95 percent confidence intervals (CI) for total malignant neoplasms for men whose height (in inches) was 68-69, 70-71, 72, and 73+ were, respectively: 1.13 (CI = 0.99-1.28), 1.15 (CI = 1.02-1.30), 1.29 (CI = 1.12-1.49), and 1.21 (CI = 1.05-1.39), P trend 0.001, adjusted for age, randomized treatment assignments, body mass index (wt/ht2), cigarette smoking, alcohol use, and exercise frequency. For prostate cancer, the corresponding RR values were 1.23 (CI = 1.00-1.51), 1.26 (CI = 1.04-1.54), 1.59 (CI = 1.27-1.98), and 1.26 (CI = 1.00-1.59), P trend 0.005. For colorectal cancer, in some but not all height categories compared with the shortest, there were elevated RRs without a significant linear trend: RR = 1.51 (CI = 1.06-2.14), 1.14 (CI = 0.80-1.62), 1.19 (CI = 0.79-1.80), and 1.53 (CI = 1.04-2.25), P trend 0.23. In contrast, there was no evidence of an association of height with lung cancer. These data indicate a positive association between height and risk of total malignant neoplasms, as well as of prostate cancer and, possibly, colorectal cancer.

Cholesterol reduction: weighing the benefits and risks.

The National Cholesterol Education Program recommends reducing total and low-density lipoprotein cholesterol levels to decrease the risk for coronary heart disease. The available evidence clearly indicates that higher cholesterol levels increase the risk for coronary heart disease and that cholesterol reduction results in corresponding decreases in risk. In contrast, existing data do not strongly support the idea that cholesterol reduction causes increases in any specific nonvascular cause of death. The outcomes of ongoing, large-scale trials will enable existing guidelines to be refined. However, current recommendations, which encourage nonpharmacologic interventions for about 30% of U.S. adults and cholesterol-reducing drugs for about 7% of U.S. adults, seem both justified and warranted.

Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials.

OBJECTIVES: This work was done to determine the role of hypertension treatment in the prevention of disease progression, left ventricular hypertrophy and congestive heart failure. BACKGROUND: Lowering of blood pressure in hypertensive patients has been reported to reduce morbidity and mortality from strokes and myocardial infarction. Data on primary prevention of disease progression, left ventricular hypertrophy and congestive heart failure have not previously been carefully quantified. METHODS: All the major long-term hypertension treatment trials over the past 20 years were reviewed. RESULTS: One thousand four hundred ninety-three of 13,342 subjects in the control groups compared with only 95 of 13,389 in the treated groups progressed from less severe to severe hypertension. The incidence of left ventricular hypertrophy in treated compared with control or placebo subjects was 140 of 6,150 and 216 of 6,098 subjects, respectively; congestive heart failure occurred in 240 of 6,923 subjects in the control group compared with only 112 of 6,914 treated subjects. CONCLUSIONS: The lowering of blood pressure over a 3- to 5-year period of time is effective in preventing severe disease, left ventricular hypertrophy and congestive heart failure in addition to strokes and myocardial infarction. In an era when expensive and often complicated methods are being used to prevent recurrence of congestive heart failure or myocardial infarction, it is important to highlight the role of antihypertensive therapy in primary prevention.

Self-reported breast implants and connective-tissue diseases in female health professionals. A retrospective cohort study.

OBJECTIVE: To evaluate the association of breast implants with connective-tissue diseases. DESIGN AND PARTICIPANTS: Retrospective cohort study of 395,543 female health professionals who completed mailed questionnaires for potential participation in the Women's Health Study. A total of 10,830 women reported breast implants and 11,805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analyses. MAIN OUTCOME MEASURE: Self-reported connective-tissue diseases. RESULTS: Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants was 1.24 (95% confidence interval, 1.08 to 1.41, P = .0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P = .017), the findings for rheumatoid arthritis, Sjogren's syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05 < P < .10), and the finding for systemic lupus erythematosus was not statistically significant (P = .44). There were no clear trends in RR with increasing duration of breast implants. CONCLUSION: These self-reported data from female health professionals are compatible with prior reports from other cohort studies that exclude a large hazard, but do suggest small increased risks of connective-tissue diseases among women with breast implants. The very large sample size makes chance an unlikely explanation for the results, but bias due to differential overreporting of connective-tissue diseases or selective participation by affected women with breast implants remains a plausible alternative explanation. The major contribution of this and other observational analytic studies has been to exclude large risks of connective-tissue diseases following breast implants.

Validity of 24-hour dietary recall interviews conducted among volunteers in an adult working community.

There is considerable uncertainty regarding the validity of dietary data collected from free-living populations. Nevertheless, few attempts have been made to validate dietary assessment instruments. To address this issue, we compared average daily protein intake estimated from 24-hour dietary recall interviews to protein intake estimated from urinary nitrogen excretion in 24-hour samples. Among 244 community-dwelling adults who volunteered for a hypertension study, men (n = 139) overreported dietary protein intake by 12 to 19%. In contrast, women (n = 105) reported a dietary protein intake almost exactly in agreement with estimates based on urinary nitrogen levels. Thin men reported about one-third more protein intake than was reflected in their urinary nitrogen measurements. Our results suggest that the accuracy of dietary recall estimates may vary across subgroups of the population. Additional information from sufficiently large validation studies would be helpful in determining the role of dietary assessment instruments which are already in wide use in epidemiologic research. Until such information is obtained, doubts will remain regarding the validity of inferences drawn from nutritional epidemiologic studies.

Antithrombotic therapy for acute myocardial infarction.

Antithrombotic therapy is clearly beneficial in the treatment of acute myocardial infarction, but the optimal regimen is controversial. Treatment with aspirin leads to substantial and significant reductions in rates of mortality, reinfarction and stroke in patients with acute myocardial infarction, and the benefits are additive with those of thrombolytic therapy. It is unclear whether heparin confers additional net benefits over aspirin alone. In patients receiving aspirin and thrombolytic therapy, there is no mortality benefit from adding delayed subcutaneous heparin, no consistent patency benefit from adding immediate intravenous heparin and no reduction in mortality from adding immediate intravenous heparin, at least for patients treated with streptokinase. However, heparin is consistently associated with increased rates of intracranial and other serious bleeding events when used with both aspirin and thrombolytic therapy. Existing data support the need for further large-scale trials of current and newer antithrombotic regimens in acute myocardial infarction to assess the balance of benefits and risks of these regimens compared with that for aspirin alone. In patients not receiving thrombolytic therapy, randomized trial data are currently insufficient to adequately compare the benefits and risks of adding heparin to aspirin alone. The First American Study of Infarct Survival (ASIS-1) will directly compare the balance of risks and benefits of aspirin alone, aspirin plus intravenous heparin and aspirin plus intravenous hirudin in patients with acute myocardial infarction not receiving thrombolytic therapy.

Evidence for a positive linear relation between blood pressure and mortality in elderly people.

Many studies of blood pressure in the elderly have found higher death rates in groups with the lowest blood pressure than in those with intermediate values. In a large community study, we examined whether these findings are real or artifacts of short follow-up, co-morbidity, or low blood pressure in people near death. In 1982-83, we assessed drug use, medical history, disability, physical function, and blood pressure in 3657 residents of East Boston, Massachusetts, aged 65 and older. We identified all deaths (1709) up to 1992 and followed up survivors for an average of 10.5 (range 9.5-11.0) years. After adjustment for confounding variables (including frailty and disorders such as congestive heart failure and myocardial infarction) and exclusion of deaths within the first 3 years of follow-up, higher systolic pressure predicted linear increases in cardiovascular (p < 0.0001) and total (p < 0.0007) mortality. Higher diastolic pressure predicted increases in cardiovascular (p = 0.006) but not total (p = 0.48) mortality. These results differed from those for the first 3 years, during which groups with the lowest systolic and diastolic pressures had the highest death rates. In the long term, lower blood pressure in old age, as in middle age, is associated with better survival. Short-term findings may differ because of associations of co-morbidity and frailty with blood pressure near death. Overall, the findings support recommendations to treat high blood pressure in elderly people.

Implications of small reductions in diastolic blood pressure for primary prevention.

OBJECTIVES: To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke. DESIGN: Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects. SETTING/PARTICIPANTS: White men and women aged 35 to 64 years in the United States. MAIN OUTCOME MEASURES: Incidence of CHD and stroke, including transient ischemic attacks (TIAs). RESULTS: Data from overviews of observational studies and randomized trials suggest that a 2-mm Hg reduction in DBP would result in a 17% decrease in the prevalence of hypertension as well as a 6% reduction in the risk of CHD and a 15% reduction in risk of stroke and TIAs. From an application of these results to US white men and women aged 35 to 64 years, it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher. It could prevent 84% of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher. For stroke (including TIAs), a population-wide 2-mm Hg reduction could prevent 93% of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69% of events for treatment for those with a DBP of 90 mm Hg or higher. A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone. Adding a population-based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events (6%) and 34,000 stroke and TIA events (13%) annually among all those aged 35 to 64 years in the United States. CONCLUSIONS: A small reduction of 2 mm Hg in DBP in the mean of the population distribution, in addition to medical treatment, could have a great public health impact on the number of CHD and stroke events prevented. Whether such DBP reductions can be achieved in the population through lifestyle interventions, in particular through sodium reduction, depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry, government agencies, and health education professionals.

Design of a multicenter trial to evaluate long-term life-style intervention in adults with high-normal blood pressure levels. Trials of Hypertension Prevention (phase II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention (TOHP) is a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute designed to test whether weight loss alone, sodium reduction alone, or the combination of weight loss and sodium reduction will decrease diastolic (DBP) and systolic blood pressure (SBP) as well as the incidence of hypertension (DBP > or = 90 mm Hg, SBP > or = 140 mm Hg, and/or use of antihypertensive medications) in subjects with high-normal DBP (83 to 89 mm Hg) and SBP less than 140 mm Hg at entry. These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure (BP) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP. The phase II study population is comprised of 2382 participants (1566 men and 816 women) who are 110 to 165% of desirable body weight, allocated at random to the four treatment arms using a 2 x 2 factorial design. The trial has 80% power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups. BP observers are blinded to participant treatment assignments. Participants will be followed for 3 to 4 years. This trial may have important public policy implications concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term, thereby avoiding the need for drug therapy which while effective is costly and may have side effects.

Baseline characteristics of participants in phase II of the Trials of Hypertension Prevention (TOHP II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention (TOHP II) is a multicenter, controlled clinical trial designed to test whether weight loss, a reduced sodium intake, or a combination of weight loss and a reduced sodium intake will lower blood pressure (BP) and prevent the occurrence of hypertension. The study population consists of middle-aged, moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg. Of the 2382 randomized participants, 816 (34%) are female and 494 (21%) are from a racial or ethnic minority background. At baseline, mean dietary intakes of sodium, based on measurements of 24-hour urinary excretion, were 199 mmol/d in men and 154 mmol/d in women. The average body mass index was 30.9 kg/m2. Across the four randomized groups, there was no substantial imbalance in the distribution of baseline variables; however, the mean age in the four groups was slightly but significantly different (range: 43.2 to 44.2 years, P = 0.02). A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study. Data reported in this article indicate that any subsequent differences in BP among the randomized groups are unlikely to result from maldistribution of known confounding variables at baseline. Finally, because of the high prevalence of overweight and excessive sodium intake in the United States, results from TOHP II should be broadly applicable to the general population.

An overview of trials of cholesterol lowering and risk of stroke.

BACKGROUND: While blood cholesterol level predicts coronary heart disease, whether there is any association with the risk of stroke is unclear. Some, but not all, observational studies suggest that cholesterol level predicts risk of stroke, particularly ischemic stroke. This hypothesis is attractive because ischemic events constitute the vast majority of all strokes and, like coronary heart disease, involve atherogenic processes. METHODS: To investigate whether lipid lowering reduces the risk of stroke, we performed an overview of randomized trials that included more than 36,000 individuals. RESULTS: The mean reduction in cholesterol level in the treated as compared with the control subjects ranged from 6% to 23%. Those assigned to treatment experienced no significant reduction in all (fatal plus nonfatal) stroke (relative risk, 1.0; 95% confidence interval, 0.8 to 1.2) or fatal stroke (1.1; 0.8 to 1.6). CONCLUSIONS: The confidence interval for fatal stroke is wide, and alternative hypotheses, including either a small protective or harmful effect, cannot be excluded; however, the point estimates are compatible with no benefit of cholesterol lowering on the risk of stroke. Additional large-scale randomized trials assessing total mortality would more definitively address any benefits on stroke, as well as any excess nonvascular causes of mortality, for which risks of cholesterol lowering also remain uncertain.

Height, lung function, and mortality from cardiovascular disease among the elderly.

The relation between height and death from cardiovascular disease was studied in a cohort of 3,809 persons aged 65 years or older (85% of eligible individuals) enrolled in a population survey in 1982-1983 in East Boston, Massachusetts. Self-reported height and weight were obtained, and peak expiratory flow rate (PEFR) was measured using a mini-Wright peak flow meter (Armstrong Industries, North Brook, Illinois). Vital status and cause of death were obtained through 1988. The median height was 62 inches in women and 66 inches in men. After adjustment for age, body mass index, and cigarette smoking, the risk of cardiovascular death decreased with quintile of height in women, with relative risks of 1.65, 1.16, 1.15, 0.76, and 1.00 over successive quintiles, with the tallest as the referent (p trend = 0.015). The trend in men was not as strong, with relative risks of 1.22, 0.77, 0.90, 0.98, and 1.00 from the shortest to the tallest quintiles (not significant). In both men and women, the strongest association was found with height and height squared, indicating a curvilinear relation. Height remained a predictor in women after adjustment for PEFR and other risk factors. These data suggest that a relation between height and cardiovascular death that is not mediated by lung function exists in the elderly, at least among women.

Feasibility and efficacy of sodium reduction in the Trials of Hypertension Prevention, phase I. Trials of Hypertension Prevention Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention was a multicenter, randomized trial of the feasibility and efficacy of seven nonpharmacologic interventions, including sodium reduction, in lowering blood pressure in 30- to 54-year-old individuals with a diastolic blood pressure of 80 to 89 mm Hg. Six centers tested an intervention designed to reduce dietary sodium to 80 mmol (1800 mg)/24 h with a total of 327 active intervention and 417 control subjects. The intervention consisted of eight group and two one-to-one meetings during the first 3 months, followed by less-intensive counseling and support for the duration of the study. The mean net decrease in sodium excretion was 43.9 mmol/24 h at 18 months. Women had lower sodium intake at baseline and were therefore more likely to decrease to less than 80 mmol/24 h. Black subjects were less likely to decrease to less than 80 mmol/d, independent of sex or baseline sodium excretion. The mean (95% confidence interval) net decrease associated with treatment was -2.1 (-3.3, -0.8) mm Hg for systolic blood pressure and -1.2 (-2.0, -0.3) mm Hg for diastolic blood pressure at 18 months (both P < .01). Multivariate analyses indicated a larger systolic blood pressure effect in women (-4.44 versus -1.23 mm Hg in men), adjusted for age, race, baseline blood pressure, and baseline 24-hour urinary sodium excretion (P = .02). Dose-response analyses indicated an adjusted decrease of -1.4 mm Hg for systolic blood pressure and -0.9 mm Hg for diastolic blood pressure for a decrease of 100 mmol/24 h in 18-month sodium excretion. These results support the utility of sodium reduction as a population strategy for hypertension prevention and raise questions about possible differences in dose response associated with gender and initial level of sodium intake.