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

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Summary

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.

Funding

None.

Introduction

Excess bodyweight is believed to be one of the most important modifiable risk factors for chronic diseases.1, 2, 3, 4 Indeed, a strong and continuous association between BMI and coronary heart disease has been reported for values of BMI higher than 20 kg/m2.1 Reliable estimates of both the prevalence of overweight and obesity and the relative risks associated with these conditions have become the cornerstones for epidemiological modelling of the existing and projected burden of obesity-related disease. In 2013, an estimated 36·9% of men and 38·0% of women worldwide were overweight or obese (BMI >25 kg/m2),5 with attributable fractions for coronary heart disease as high as 25% in the USA and 58% in the Asia-Pacific region.6, 7

Such estimates are based on the assumption that the association between BMI and coronary heart disease is similar between the sexes, and therefore only one estimate of the association is used to predict the burden of overweight-related disease. However, this assumption might be incorrect, since it is becoming increasingly recognised that important and clinically meaningful sex differences exist in the associations 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 shown to confer significantly greater vascular hazards in women than in men,8, 9, 10 whereas the effect of blood pressure on cardiovascular risk is similar between the sexes.11 However, the fact that sexual dimorphism in the distribution of underlying fat composition is well established,12, 13 and because women have a predominance of subcutaneous fat—which confers less cardiometabolic risk than does visceral fat—might imply a higher relative risk of coronary heart disease for men than women with a similar BMI.

Although previous reviews have mostly reported no sex difference in the relative risk between BMI and coronary heart disease, these reports did not specifically compare women and men from within the same study.1, 3, 14 These estimates might be confounded by differences in source population and variations in background risk, which might have hidden a true sex difference in the association. Therefore, we did a systematic review and meta-analysis of only those prospective cohort studies that reported sex-specific estimates of the association between BMI and coronary heart disease in general populations. We postulated that higher BMI would be associated with an increased risk of coronary heart disease, with a stronger association for men than for women.

Section snippets

Search strategy and selection criteria

We systematically searched PubMed and Embase for records relating to the longitudinal association between BMI and coronary heart disease in women and men in general populations worldwide, published up to Feb 20, 2015. The full search criteria used for both sources is available in appendix p 1. We excluded studies for the following reasons: if they contained duplicate data from the same study; they reported estimates only for Z scores or percentiles of BMI; they did not report an estimate of

Results

Of the 8561 individual articles that were identified through the systematic search, 395 qualified for full-text evaluation (figure 1). Of these, 32 articles and four studies with individual participant data were included (table), comprising 95 studies, 1 219 187 participants, and 37 488 cases of coronary heart disease. The study names and abbreviations are listed in appendix p 20.

Figure 2, Figure 3 show the age-adjusted association between BMI and risk of coronary heart disease in women and

Discussion

This meta-analysis incorporating data for 1 219 187 individuals and 37 488 incident cases of coronary heart disease shows definitively that the association between BMI and coronary heart disease is the same in women and men. Women and men who are overweight or obese have a similar increase in risk of incident coronary heart disease, whether measured on a continuous or categorical scale, compared with individuals of a normal weight. These associations were robust in a wide range of subgroup

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