BackgroundThe role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse. MethodsWe prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events. ResultsAn increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk. ConclusionsThese prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.

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PURPOSE To determine whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of colorectal cancer. METHODS The population included 159,219 postmenopausal women enrolled in the Women’s Health Initiative in which 2000 pathologically confirmed cases of colorectal cancer were identified during an average of 10.7 (S.D. 2.9) years. Information on statins was collected at baseline and years 1, 3, 6, and 9. Self- and interviewer-administered questionnaires were used to collect information on other risk factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the use of Cox proportional hazards regression to evaluate the relationship between statin use and risk. Statistical tests were two-sided. RESULTS Statins were used by 12,030 (7.6%) women at baseline. The annualized colorectal cancer rate was 0.13% among users and 0.12% among nonusers. The multivariable adjusted HR for users versus nonusers was 0.99 (95% confidence interval [CI], 0.83–1.20, p=.95), and 0.79 (95% CI, 0.56–1.11) for users of ≥3 years. In the multivariable adjusted time-dependent model, the HR for lovastatin was 0.62 (95% CI, 0.39–0.99). There was no effect of tumor location, stage or grade. CONCLUSIONS There was a reduction in colorectal cancer risk associated with lovastatin and a non-significant association with longer duration of use.

Background Although observational evidence has suggested that the measurement of CAC may improve risk stratification for cardiovascular events and thus help guide the use of lipid-lowering therapy, this contention has not been evaluated within the context of a randomized trial. The Value of Imaging in Enhancing the Wellness of Your Heart (VIEW) trial is proposed as a randomized study in participants at low intermediate risk of future coronary heart disease (CHD) events to evaluate whether coronary artery calcium (CAC) testing leads to improved patient outcomes. Purpose To describe the challenges encountered in designing a prototypical screening trial and to examine the impact of uncertainty on power. Methods The VIEW trial was designed as an effectiveness clinical trial to examine the benefit of CAC testing to guide therapy on a primary outcome consisting of a composite of non-fatal myocardial infarction, probable or definite angina with revascularization, resuscitated cardiac arrest, non-fatal stroke (not transient ischemic attack (TIA)), CHD death, stroke death, other atherosclerotic death, or other cardiovascular disease (CVD) death. Many critical choices were faced in designing the trial, including: (1) the choice of primary outcome, (2) the choice of therapy, (3) the target population with corresponding ethical issues, (4) specifications of assumptions for sample size calculations, and (5) impact of uncertainty in these assumptions on power/sample size determination. Results We have proposed a sample size of 30,000 (800 events) which provides 92.7% power. Alternatively, sample sizes of 20,228 (539 events), 23,138 (617 events) and 27,078 (722 events) provide 80, 85, and 90% power. We have also allowed for uncertainty in our assumptions by computing average power integrated over specified prior distributions. This relaxation of specificity indicates a reduction in power, dropping to 89.9% (95% confidence interval (CI): 89.8 to 89.9) for a sample size of 30,000. Samples sizes of 20,228, 23,138, and 27,078 provide power of 78.0% (77.9 to 78.0), 82.5% (82.5 to 82.6), and 87.2% (87.2 to 87.3), respectively. Limitations These power estimates are dependent on form and parameters of the prior distributions. Conclusions Despite the pressing need for a randomized trial to evaluate the utility of CAC testing, conduct of such a trial requires recruiting a large patient population, making efficiency of critical importance. The large sample size is primarily due to targeting a study population at relatively low risk of a CVD event. Our calculations also illustrate the importance of formally considering uncertainty in power calculations of large trials as standard power calculations may tend to overestimate power.