History Risk for coronary heart disease (CHD) differs by sex and

History Risk for coronary heart disease (CHD) differs by sex and accumulating evidence suggests sex differences in the effect of coronary risk factors on vascular risk. significantly associated with age-adjusted incident CHD: hazard ratios (95% confidence interval) in women and men were 1.04 (1.03-1.05) and 1.05 (1.04-1.07) for one unit BMI 1.25 1.09 for underweight 1.2 (1.12-1.29) 1.22 (1.12-1.32) for overweight 1.61 (1.42-1.82) and 1.60 (1.43-1.79) for obesity respectively). Overall there was no sex difference in these associations. The women-to-men ratio of the hazard ratios were 0.99 (0.98-1.00) for one unit BMI; 1.08 (0.89-1.31) for underweight; 1.00(0.92-1.07) for overweight; and 1.05 for obesity. Similar results were obtained after multiple-adjustment and in a range of sensitivity analyses. Interpretation Higher BMI measured continuously and categorically has the same deleterious effects on risk of incident CHD in women and men across diverse populations. INTRODUCTION Excess body weight is considered to be one of the most important modifiable risk factors for chronic disease.1-4 Indeed a strong and continuous association between body mass index (BMI) and coronary heart disease (CHD) has been reported for values of BMI above 20 kg/m2.1 Reliable estimates of both the prevalence of overweight and obesity and the relative risks associated with the condition have become the cornerstones for epidemiologic modelling of the current and projected burden of obesity-related disease. In 2013 an estimated 36.9% of men and 38.0% of women were overweight (BMI >25 kg/m2) worldwide 5 with attributable fractions for CHD as high as 25% in the United States and 58% in the Asia-Pacific Region.6-7 Such estimates are predicated on the assumption that the relationship between YM90K hydrochloride BMI and CHD is similar between the sexes YM90K hydrochloride and as such only a single estimate of the YM90K hydrochloride relationship is used in predicting the burden of overweight-related disease. However this may be incorrect as it is becoming increasingly recognised that there are important and clinically meaningful sex differences in the relationships between risk factors and cardiovascular disease – most often to the detriment of women. For example type 1 diabetes type 2 diabetes and cigarette smoking have recently been demonstrated to confer significantly greater vascular hazards in women than in men 8 whereas the YM90K hydrochloride effect of blood pressure on cardiovascular risk is comparable between the sexes.11 Given that sexual dimorphism in the distribution of underlying fat composition is well established 12 and that there is a predominance of subcutaneous fat in women – which confers less cardiometabolic risk relative to visceral fat – this may imply a higher relative risk of CHD for men with the same level of BMI. Although previous reviews have largely reported no sex difference in the relative risk between BMI and CHD these YM90K hydrochloride studies did not specifically compare women and men from within the same study.1-3-14 These estimates may be confounded due to differences in source population and variation in background risk which may have masked a true sex difference in the association. Therefore we conducted a systematic review with meta-analysis of only those Rcan1 prospective cohort studies that reported sex-specific estimates of the relationship between BMI and CHD in the general population. We hypothesize that higher BMI will be associated with increased risk of CHD with a stronger association for men than for women. METHODS Search Strategy and Selection Criteria We systematically searched Pubmed and EMBASE for records relating to the longitudinal association between BMI and CHD in women and men in the general population up to February 20th 2015 The full search criteria used for both sources is available in the Supplemental Methods S1. We excluded studies based on the following criteria: duplicate data from the same study; estimates reported only for z-scores or percentiles of BMI; no report of estimate uncertainty; no report of sex-specific estimates; studies which recruited predominantly from individuals with a prior history of cardiovascular disease or from with selected populations such as those with kidney disease diabetes or hypertension; and articles where the full text was not available in English (Figure 1 and Supplemental Methods S2). All studies included.