Sex differences in excess risk of cardiovascular disease and mortality among patients with type 2 diabetes: a matched register-based cohort study

Background Individuals with type 2 diabetes have elevated risk of cardiovascular disease (CVD)(1) but how their excess risk compared to people without diabetes varies with sex, across age groups, and type of cardiovascular outcome has not been reliably assessed (2). Methods All men and women with a first diagnosis of type 2 diabetes between 1998 and 2019 were identified through the Swedish National Diabetes Register and compared with population controls without diabetes. For both patients and controls, we assessed the cumulative adult lifetime incidence rates of CVD outcomes (acute myocardial infarction (AMI), ischemic stroke, and heart failure) and mortality. Excess risks were estimated using age- and sex-specific hazard ratios (HRs), adjusted for age, duration of diabetes, immigrant status, marital status, income, education, and comorbidities. Results After excluding individuals with prior CVD, we identified 561,896 patients with type 2 diabetes (44.6% women) and 2,287,180 population controls from the Swedish Total Population Register, matched for age, sex and county. Follow-up continued through December 31, 2019. Among individuals with diabetes, there were 23,756 incident cases of AMI, 17,598 of ischemic stroke and 17,846 with heart failure in men, and 14,862, 15,102, and 15,533, respectively in women. Excess risks for all outcomes were higher in younger compared to older patients, with the largest sex differences observed for AMI. Women aged 18–34 years had a markedly elevated excess risk of AMI, with an adjusted HR of 9.08 (95% confidence intervals [CI]:4.80–17.18) compared to controls, while men in the same age group, had an HR of 5.14 (95% CI:3.16–8.34) (Figure 1). Sex differences in excess risk were less pronounced for ischemic stroke, heart failure and all-cause mortality, but most apparent in midlife. Conclusions Women with type 2 diabetes had a lower absolute risk but markedly higher excess risk of AMI compared to men, while sex differences were less apparent for ischemic stroke, and heart failure. These sex differences in excess risk decreased with increasing age and were minimal among the oldest individuals.