SummaryBackgroundBody-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors.MethodsWe pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators.FindingsThe HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23–1·31) for coronary heart disease and 1·18 (1·14–1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12–1·18) for coronary heart disease and 1·04 (1·01–1·08) for stroke, suggesting that 46% (95% CI 42–50) of the excess risk of BMI for coronary heart disease and 76% (65–91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28–35) of the excess risk for coronary heart disease and 65% (56–75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44–58) of the excess risk of overweight and 44% (41–48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69–155) for overweight and 69% (64–77) for obesity.InterpretationInterventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits.FundingUS National Institute of Health, UK Medical Research Council, National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, Lown Scholars in Residence Program on cardiovascular disease prevention, and Harvard Global Health Institute Doctoral Research Grant.

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Moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction.

OBJECTIVE: Since the prevalence of adult obesity is increasing in the United States, we examined the effect of changing common habits (exercise, TV viewing, smoking and eating habits) on four year change in body weight. DESIGN: A prospective cohort study of US male health professionals with follow-up from 1988±1992. Participants were 19 478 men aged 40±75 in 1986, who were free of cancer, coronary heart disease, stroke and diabetes. METHODS: Multiple regression was used to determine the association between four year change in body weight (from 1988±1992) and common habits, after adjusting for baseline age, hypertension and hypercholesterolemia. RESULTS: For middle aged men, vigorous activity was associated with weight reduction and TVaVCR viewing and eating between meals with weight gain. Quitting smoking and a history of voluntary weight loss prior to the study period were consistently related to weight increase. Recently being on a diet was more strongly associated with weight loss among older men. Over the four year follow-up period, middle-aged men who increased their exercise, decreased TV viewing and stopped eating between meals, lost an average weight of 71.4 kg (95% con®dence interval (CI)71.6 ± 71.1 kg), compared to a weight gain of 1.4 kg among the overall population. The prevalence of obesity among middle-aged men was lowest among those who maintained a relatively high level of vigorous physical activity, compared to those who were relatively sedentary. CONCLUSION: These data suggest that improvement in the mix of health habits, particularly increasing vigorous activity, as well as decreasing TV use and changing eating habits, results in weight maintenance or a modest weight loss over four years.