The sex-specific association between BMI and coronary heart disease: A systematic review and meta-analysis of 95 cohorts with 1·2 million participants

Background: The risk of developing coronary heart disease differs by sex, and accumulating evidence suggests that sex differences exist in the effect of coronary risk factors on vascular risk. So far, the existence of a sex difference in the association between BMI and coronary heart disease has not been systematically studied. Since sexual dimorphisms in body composition exist, we postulated that the association between BMI and coronary heart disease would differ between women and men. Methods: We did systematic searches of PubMed and Embase up to Feb 20, 2015, for studies of the longitudinal association between BMI and coronary heart disease in women and men from population-based cohorts. We excluded studies if they contained duplicate data from the same study, reported estimates only for Z scores or percentiles of BMI, did not report estimate uncertainty, did not report sex-specific estimates, recruited mainly individuals with a previous history of cardiovascular disease or from within selected populations, and those for which the full text was not available in English. We also included individual participant data from four large studies. Study results were pooled using random-effect models with inverse variance weighting. Our predefined primary endpoint was the pooled women-to-men ratio of the age-adjusted hazard ratios (HRs), or equivalent, relating (continuous and categorical) BMI to coronary heart disease. Findings: We reviewed a total of 8561 original entries twice for inclusion in the analysis, of which 32 published studies were eligible for inclusion. Data from 95 cohorts, 1 219 187 participants, and 37 488 incident cases of coronary heart disease were included. Higher BMI was significantly associated with age-adjusted coronary heart disease: for a one-unit (kg/m²) increment in BMI; the HR was 1·04 (95% CI 1·03-1·05) in women and 1·05 (1·04-1·07) in men. Compared with people of a normal weight, the age-adjusted HR of coronary heart disease for the underweight group was 1·25 (1·05-1·49) in women and 1·09 (0·91-1·23) in men; for the overweight group 1·20 (1·12-1·29) in women and 1·22 (1·12-1·32) in men; and for the obese group 1·61 (1·42-1·82) in women and 1·60 (1·43-1·79) in men. Overall, these associations did not differ between the sexes. The women-to-men ratios of the HRs were 0·99 (95% CI 0·98-1·00) for a one-unit increment in BMI, 1·10 (0·91-1·32) for the underweight group, 0·99 (0·92-1·07) for the overweight group, and 1·06 (0·95-1·17) for the obese group, relative to the normal weight group. Similar results were obtained after multiple adjustment and in a range of sensitivity analyses. Interpretation: Increased BMI, measured either continuously or categorically, has the same deleterious effects on the risk of coronary heart disease in women and men across diverse populations.