Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events

Aims/hypothesis: A previous pooled analysis suggested that women with diabetes are at substantially increased risk of fatal CHD compared with affected men. Additional findings from several larger and more contemporary studies have since been published on the sex-specific associations between diabetes and incident CHD. We performed an updated systematic review with meta-analysis to provide the most reliable evidence of any sex difference in the effect of diabetes on subsequent risk of CHD. Methods: PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between 1 January 1966 and 13 February 2013. Eligible studies had to have reported sex-specific RR estimates for incident CHD associated with diabetes and its associated variability that had been adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain sex-specific RRs and the RR ratio (RRR) (women:men) for incident CHD associated with diabetes. Results: Data from 64 cohorts, including 858,507 individuals and 28,203 incident CHD events, were included. The RR for incident CHD associated with diabetes compared with no diabetes was 2.82 (95% CI 2.35, 3.38) in women and 2.16 (95% CI 1.82, 2.56) in men. The multiple-adjusted RRR for incident CHD was 44% greater in women with diabetes than in men with diabetes (RRR 1.44 [95% CI 1.27, 1.63]) with no significant heterogeneity between studies (I =20%). Conclusions/interpretation: Women with diabetes have more than a 40% greater risk of incident CHD compared with men with diabetes. Sex disparities in pharmacotherapy are unlikely to explain much of the excess risk in women, but future studies are warranted to more clearly elucidate the mechanisms responsible for the substantial sex difference in diabetes-related risk of CHD