Author
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Lamon-Fava, Stefania |
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HERRINGTON, DAVID - WAKE FOREST UNIVERSITY |
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REBOUSSIN, DAVID - WAKE FOREST UNIVERSITY |
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SHERMAN, MICHELLE - TUFTS UNIVERSITY |
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HORVATH, KATALIN - TUFTS UNIVERSITY |
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Schaefer, Ernst |
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Asztalos, Bela |
Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/9/2008 Publication Date: 7/1/2009 Citation: Lamon-Fava, S., Herrington, D.M., Reboussin, D.M., Sherman, M., Horvath, K., Schaefer, E., Asztalos, B. 2009. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women. Atherosclerosis. 205(1):325-330. Interpretive Summary: Recent studies have suggested that hormonal replacement therapy (HT) may increase the risk of coronary heart disease in postmenopausal women. We assessed the effect of HT on plasma levels of two types of lipoproteins: high-density lipoproteins (HDL, also called "good cholesterol"), and remnants of triglyceride-carrying lipoproteins, or RLP, which are considered atherogenic. HT lowered RLP and increased HDL levels. However, the reduction in RLP was greatest in subjects who had more coronary disease progression during HT. Therefore, we conclude that the lipoprotein response to HT may be an indirect marker of susceptibility to the harmful effect of HT. Technical Abstract: The effect of hormone therapy (HT) on the plasma concentration of remnant lipoprotein cholesterol (RLP-C) and high density lipoprotein (HDL) subpopulations and the contribution of HT-related changes in these lipoproteins to the progression of coronary heart disease (CHD) were examined in 256 postmenopausal women. Subjects were participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, a placebo-controlled, randomized trial that examined the effects of 3.2 years of conjugated equine estrogen (CEE, 0.625 mg/day) or CEE (0.625 mg/day) plus medroxyprogesterone acetate (MPA, 2.5 mg/day) on post-menopausal women with established coronary atherosclerosis. Quantitative coronary angiography and plasma RLP-C and HDL subpopulations were assessed at baseline and at follow-up. Relative to placebo, both CEE and CEE+MPA caused a significant reduction in plasma RLP-C concentrations and a significant increase in large HDL subpopulations. However, in the HT-treated subjects, faster progression of coronary atherosclerosis was observed in women who experienced the greatest reductions in RLP-C and in small HDL subpopulations. Our data suggest that individual variability in RLP-C and HDL subpopulation response to HT is a predictor of CHD progression. Lipoprotein response to HT may be an indirect marker of susceptibility to other harmful effect of HT in postmenopausal women with established CHD or an indication of formation of dysfunctional lipoproteins. |