Effect of hormone replacement therapy on plasma lipoprotein levels and coronary atherosclerosis progression in postmenopausal women according to type 2 diabetes mellitus status

Type 2 diabetes mellitus is associated with dyslipidemia and with an increased risk of coronary heart disease (CHD). Our objective was to compare the effects of hormone replacement therapy (HRT) on plasma lipoproteins and coronary disease progression in postmenopausal women with and without diabetes. Study subjects were participants in the Estrogen Replacement and Atherosclerosis trial, a placebo-controlled, randomized trial of HRT (conjugated equine estrogen 0.625 mg/d with or without medroxyprogesterone acetate 2.5 mg/d) in postmenopausal women with established CHD (mean age, 65 ± 7 years). Plasma remnant lipoprotein levels and high-density lipoprotein (HDL) subpopulation levels were measured at baseline and year 1. Quantitative coronary angiography was assessed at baseline and at follow-up. At baseline, remnant lipoprotein levels were significantly higher and HDL cholesterol (HDL-C) levels were significantly lower in diabetic women than in women without diabetes. Hormone replacement therapy lowered remnant lipoproteins and increased HDL-C and large HDL particle levels in both groups. However, during HRT, levels of these parameters were still significantly worse in diabetic women than in nondiabetic women. A significant interaction between HRT and diabetes status, with greater increases in plasma atheroprotective HDL α1 particles in nondiabetic women than in diabetic women during HRT, was observed. Coronary heart disease progressed significantly more in women with diabetes than in women without diabetes. Our findings indicate that diabetes attenuates the HRT-related increase in atheroprotective HDL α1 particles. Faster progression of coronary atherosclerosis in women with diabetes could be mediated in part by a worse lipoprotein profile in these women than in women without diabetes, both before and during HRT.