Fasting insulin is a stronger cardiovascular risk factor in women than in men

Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than in men. It is not known whether there is also a sex difference in the association between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively recorded after the baseline survey. Cox-regression models were used to investigate the association of fasting insulin with subsequent development of MACE. Fasting insulin was 54 [38–77] pmol/l in women (age 48 ± 12 yrs) and 57 [40–88] pmol/l in men (age 49 ± 13 yrs). During follow-up for 7.5 [6.9–7.8] yrs, 98 cardiovascular events were recorded in 3626 women and 242 events in 3290 men. There was a significant (P < 0.001) interaction between sex and fasting insulin for MACE, with the strongest association in women. In women, there was a logarithmic association for insulin with MACE, independent of age, alcohol consumption, and smoking (HR = 1.50 [95% CI 1.17–1.91] per doubling of insulin, P = 0.001). In men, for a similar multivariate model, there was a logarithmic association (HR = 1.13 [95% CI [0.97–1.32] per doubling of insulin, P = 0.1). Further adjustment for components of the insulin resistance syndrome weakened the association more in men than in women. With HOMA instead of insulin, results were essentially similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin resistance in non-diabetic subjects is associated with an increased risk for cardiovascular disease, which is more pronounced in women than in men.