Sex differences in the diabetes-related risk of incident myocardial infarction and relationship to established CHD risk factors. The Tromsø Study (1979-2016)

Aim To examine whether the adverse effect of diabetes on the risk of incident myocardial infarction (MI) differs between sexes and assess to what extent established coronary heart disease (CHD) risk factors contribute to the elevated risk. Methods Prospective study of 42,907 Tromsø Study participants (51.5% women) with 3942 incident MI (357 with diabetes) at ages 35–104 years. Relative risks (IRR) were estimated in Poisson regression analyses. Impact of CHD risk factors was quantified as percentage change in the regression coefficient for diabetes. Results A contrast in risk of MI by diabetes status was seen from age 45 in men and 55 in women. Adjusted for age and birth-cohort, the IRR was 2.26 in women and 1.84 in men (p = 0.12, test for interaction). In a mutually adjusted model, adjustment for the triglyceride to HDL-cholesterol ratio weakened the association with diabetes similarly in women (-19.0%) and men (−17.0%), systolic blood pressure had larger impact in women (-10.3% vs. + 2.2%), whereas smoking strengthened the association more in men (+23.1% vs. + 7.1%). Body mass index had minor impact. A larger joint impact of adjustment factors in women (-33.6% vs. -15.9%) narrowed the initial gender gap (adjusted IRR of 1.72 and 1.67 respectively). Adverse lipid levels and increasing systolic blood pressure emerged already during the pre-diabetic phase. Conclusions Traditional CHD risk factors contributed substantially to the diabetes-related risk of incident MI. A larger joint impact of these factors in women reduced the initial observed sex difference in the adverse effect of diabetes.