Sex-specific Associations Between Cardiovascular Risk Factors and Myocardial Infarction in Patients With Type 2 Diabetes: The ADVANCE-ON Study

Aims: Sex differences in associations between several risk factors and myocardial infarction (MI), including diabetes, have been found in general populations. Whether similar differences are observed in patients with diabetes is unknown.

Materials and methods: 11,065 (42% women) participants with type 2 diabetes in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non-fatal) by sex, and the women-to-men ratio of HRs (RHR).

Results: Over a median of 9.6 years of follow-up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c , total and LDL cholesterol, duration of diabetes, triglycerides and BMI and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05-2.91) for current smoking, 1.53 (1.00-2.32) for former smoking, 1.18 (1.02-1.37) for SBP, and 1.13 (95% CI, 1.003-1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1,000 person-years) compared with women (5.8 per 1,000 person-years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI.

Conclusions: In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex-specific approaches and early interventions in women with diabetes.