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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1650.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cholesterol Absorption, Synthesis, and Fecal Output in Postmenopausal Women With and Without Coronary Artery Disease

Radhakrishnan A. Rajaratnam; Helena Gylling; Tatu A. Miettinen

From the Division of Internal Medicine, Department of Medicine, University of Helsinki, Helsinki, Finland.

Correspondence to Prof Tatu A. Miettinen, Division of Internal Medicine, Department of Medicine, University of Helsinki, PO Box 340, FIN-00029 HUS, Helsinki, Finland. E-mail tatu.a.miettinen{at}helsinki.fi

Abstract—Hypercholesterolemia is a prominent risk factor for coronary artery disease (CAD), yet cholesterol metabolism has not been evaluated in women with CAD. The objective of this study was to determine the interrelations of CAD, serum squalene and sterols, and cholesterol metabolism with each other in postmenopausal women. For this purpose, we measured serum squalene and sterols and fecal steroids (cholesterol and bile acids) and squalene by gas-liquid chromatography and evaluated cholesterol absorption and synthesis in postmenopausal women with CAD (n=29) and age-matched controls (n=20). On similar dietary lipid intake, the cholesterol absorption efficiency and mean serum cholesterol level were comparable, but the squalene-to-cholesterol ratio was higher in cases than in controls. The presence of CAD was inversely associated with fecal total steroids (logistic regression coefficient ß/SE=-2.11, P=0.04) and cholesterol synthesis (ß/SE=-2.14, P=0.04) and turnover (ß/SE=-2.19, P=0.03) after adjustment for dietary cholesterol, family history of CAD, smoking, low and high density lipoprotein cholesterol, and serum triglyceride levels. A high serum squalene ratio was not related to cholesterol synthesis but was inversely related to fecal squalene excretion, which was lower in cases than in controls. In conclusion, the presence of CAD in postmenopausal women is independently associated with altered cholesterol metabolism, as reflected by low synthesis and inefficient elimination of cholesterol.

Key Words: cholesterol synthesis • bile acids • squalene • atherosclerosis • women

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