Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2007
Publication Date: 3/20/2008
Citation: Lamon-Fava, S., Herrington, D.M., Reboussin, D.M., Sherman, M., Horvath, K.V., Cupples, A.L., White, C., Demissie, S., Schaefer, E.J., Asztalos, B.F. 2008. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically defined disease in post-menopausal women. Arteriosclerosis Thrombosis and Vascular Biology. 28(3):575-579. Interpretive Summary: The risk of coronary heart disease is greater in men who have higher blood levels of “bad cholesterol” and lower blood levels of “good cholesterol”. Since both bad and good cholesterol are carried in the blood by a series of different particles, our objective was to assess which of these subparticles is more important in predicting the risk of heart disease in women. We measured the degree of coronary heart disease via angiography in 256 postmenopausal women and found that women who had higher blood levels of alpha 2, a type of large particle carrying good cholesterol, had less disease occurrence than women with low levels of apha2. Also, women who had higher levels of a small type of good cholesterol particle had more disease. In addition, women were more prone to having extensive coronary disease if they had higher levels of a bad cholesterol particle called remnant lipoprotein. As indicated by its name, this particle is the result of the processing in the blood of a particle containing both bad cholesterol and triglycerides. We conclude that the severity of coronary heart disease in women is in part determined by an altered metabolism of the particles carrying both bad and good cholesterol in blood.
Technical Abstract: The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women. Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis, and plasma remnant-like particle cholesterol (RLP-C) concentrations were measured in 256 postmenopausal women with established CHD and in 126 CHD-free postmenopausal women. Coronary artery disease was assessed in women with CHD by quantitative coronary angiography. Plasma RLP-C and pre_1 HDL concentrations were higher and _1 and _2 HDL concentrations were lower in CHD than in CHD-free women. After adjustment for conventional CHD-risk factors, plasma levels of RLP-C were positively associated with the degree of coronary artery disease. In similar analyses, plasma pre_1 HDL particle concentrations were positively associated and _2 HDL particle concentrations were inversely associated with the extent of coronary atherosclerosis. Plasma TG, low density lipoprotein cholesterol, and HDL cholesterol levels were not associated with the degree of coronary atherosclerosis. The degree of coronary atherosclerosis in postmenopausal women is linked to a dysregulation of the TG/HDL metabolism. Subpopulations of TG-rich and HDL lipoproteins are better predictors of disease than TG and HDL cholesterol concentrations.