Abstract 3787: Nontraditional Risk Factors and Cardiovascular Disease Incidence in Type 2 Diabetes: Prospective Data from the Women’s Health Study
Background: Cardiovascular risk assessment in type 2 diabetes has generally focused on traditional risk factors such as hypertension, dyslipidemia, and glycemic control. Prospective data pertaining to nontraditional risk factors are sparse and few data comparing novel biomarkers, apolipoproteins, standard lipid levels and hemoglobin A1c (HbA1c) are available.
Methods and Results: We conducted a prospective cohort study of 781 otherwise healthy middle-aged diabetic women without prior cardiovascular disease. Baseline levels of high-sensitivity C-reactive protein (hsCRP), fibrinogen, soluble intercellular adhesion molecule-1, homocysteine (sICAM-1), lipoprotein(a), HbA1c, apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and standard lipid levels were measured and subjects were followed for first myocardial infarction, ischemic stroke, cardiovascular death, and coronary revascularization (total n=160; median follow-up 11 years). Hazard ratios (HRs) were estimated from Cox proportional hazards models. In the total population, HbA1c (adjusted HR extreme quartiles 1.8; p-trend=0.006), non-HDL (2.2; p-trend=0.02), HDL (0.5; p-trend=0.003) and the total-to-HDL cholesterol ratio (2.2; p-trend=0.001) were the strongest predictors of risk with borderline non-significant findings for hsCRP (1.6; p-trend=0.07), fibrinogen (1.6; p-trend=0.07), and apoB (1.5; p-trend=0.06). No significant associations were detected for homocysteine, sICAM-1, lipoprotein(a), or apoA. As menopausal hormone therapy (HT) itself may alter levels of lipid and non-lipid biomarkers, analyses were repeated among non-users. In this group, significant effects were noted for hsCRP (HR 1.9; p-trend 0.03), HbA1c (2.4; p-trend 0.003), HDL (0.5; p-trend=0.02), and total-to-HDL cholesterol ratio (2.2; p-trend=0.001). Among groups defined by high or low levels of HbA1c or HDL, hsCRP appeared to identify those at greatest risk for future CVD.
Conclusions: Markers of inflammation independently predict first cardiovascular events in middle-aged diabetic women and may aid identification of high-risk patients beyond HbA1c and traditional lipid levels. HT may weaken this association, however, a risk gradient is evident among non-users.