Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women

Background: Lp(a), implicated in both atherogenesis and thrombosis pathways, varies significantly by demographic and metabolic factors, providing challenges for its use in Coronary Heart Disease (CHD) risk. The purpose of this study was to investigate whether type-2 diabetic subjects, relative to non-diabetics, might benefit more from Lp(a) measurement in the prediction of CHD risk, as measured by coronary artery calcium (CAC). Methods: We performed cross sectional analyses in two community-based studies: the Penn Diabetes Heart Study [N = 1299 with type-2 diabetes] and the Study of Inherited Risk of Coronary Atherosclerosis [N = 860 without diabetes]. Results: Blacks had 2-3 fold higher Lp(a) levels than whites in diabetic and non-diabetic samples. There was significant difference by gender (interaction p < 0.001), but not race, in the association of Lp(a) with CAC in type-2 diabetic subjects. In age and race adjusted analysis of diabetic women, Lp(a) was associated with CAC [Tobit regression ratio 2.76 (95% CI 1.73-4.40), p < 0.001]. Adjustment for exercise, medications, Framingham risk score, metabolic syndrome, BMI, CRP and hemoglobin A1c attenuated this effect, but the association of Lp(a) with CAC remained significant [2.25, (1.34-3.79), p = 0.002]. This relationship was further maintained in women stratified by race, or by the use of HRT or lipid lowering drugs. In contrast, Lp(a) was not associated with CAC in diabetic men, nor in non-diabetic men and women. Conclusions: Lp(a) is a strong independent predictor of CAC in type-2 diabetic women, regardless of race, but not in men. Lp(a) does not relate to CAC in men or women without type-2 diabetes.