Abstract 1342: High Density Lipoprotein Subpopulations and Lipoprotein Remnants: Effects of Hormonal Replacement Therapy and Association with Baseline Coronary Atherosclerosis in the Estrogen Replacement and Atherosclerosis (ERA) Trial
An HDL subpopulation profile characterized by low levels of α1 and α2 and high levels of preβ1 is associated with increased risk for coronary heart disease (CHD) in men. No information is available concerning these relationships in women. The effect of hormone replacement therapy on HDL subpopulations in women is also not well known. The ERA trial is a randomized, double-blind, placebo-controlled study of the effects of conjugated equine estrogen 0.625 mg/d (CEE), or CEE and medroxyprogesterone acetate 2.5 mg/d (CEE+MPA) on coronary atherosclerosis progression in postmenopausal women with CHD. The distribution of HDL subpopulations (expressed as mg/dl of apo A-I) was measured by 2-dimensional gel electrophoresis and remnant lipoproteins were measured as mg/dl cholesterol (RLP-C) at baseline and after one year of treatment in women in the placebo (N=87), CEE (N=82), and CEE+MPA (N=85) arms. Plasma lipoprotein levels did not change in the placebo arm. HDL cholesterol significantly increased both in the CEE and CEE+MPA arms (20% and 12%, respectively, P<0.001). Similar findings were observed for apo A-I levels (17% and 13%, respectively, P<0.0001). Significant increases (P<0.0001) occurred in α-1 (77% and 57%) and α2 (17%, and 20%) on the two treatments, respectively. A significant increase in preβ1 (18%) was observed only in the CEE arm. A significant reduction in the atherogenic RLP-C level was observed in the two treatment arms (−10% and −11%, P<0.001, respectively). Using unadjusted Spearman correlations, at baseline, a significant positive association was observed between the minimal coronary-artery luminal diameter and α1 and α2 (P<0.01), and an inverse correlation with preβ1 and RLP-C (P<0.05). After adjustment for lesion location, prior angioplasty, smoking, diabetes, use of lipid-lowering medications, age and BMI, the association between minimal luminal diameter and α2 (P<0.03) and preβ1 (P<0.01) remained significant. No significant association was observed for HDL-C level. These results in women confirm our previous observations in men that HDL subpopulations are better predictors of CHD than HDL-C. They also provide information about the effects of hormone therapy on HDL subpopulations and remnant lipoproteins in women with CHD.