Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women

OBJECTIVES The purpose of the study was to investigate whether cholesterol metabolism is associated with coronary artery disease (CAD) in postmenopaus al women. BACKGROUND Although hypercholesterolemia, a predominant risk factor of CAD, is related to cholesterol metabolism, the association between cholesterol metabolism and CAD is not well known. METHODS In addition to conventional coronary risk factors, fasting serum sq ualene, Delta(8)-cholestenol, desmosterol, lathosterol (indicators of chole sterol synthesis), cholestanol, campesterol and sitosterol (indicators of c holesterol absorption) were measured in 48 50- to 55-year-old consecutive w omen with angiographically verified CAD and in 61 age-matched healthy contr ols. RESULTS The coronary patients had elevated ratios of squalene (p < 0.001), desmosterol (p = 0.005), campesterol (p = 0.028) and sitosterol (p = 0.022) to cholesterol, but had lower respective lathosterol value (p = 0.041) com pared with the controls, despite similar serum cholesterol levels. Adjusted for age, body mass index, family history of CAD, smoking, hypertension, se rum triglycerides, low-density lipoprotein (LDL) and high-density lipoprote in (HDL) cholesterol level and glycosylated hemoglobin A1c% (GHbA1c), the r atios of squalene (odds ratio, 1.36; 95% confidence interval, 1.17 to 1.57) , lathosterol (0.98; 0.97 to 0.99), campesterol (1.01; 1.00 to 1.01) and si tosterol (1.01; 1.00 to 1.03) were significantly associated with the risk o f CAD. In addition, family history of CAD and GHbA1c% were also independent ly related to the presence of CAD. CONCLUSIONS The results suggest that women with elevated ratios of serum sq ualene, campesterol and sitosterol to cholesterol and low respective lathos terol values have enhanced risk for CAD. Thus, enhanced absorption and redu ced synthesis of cholesterol may be related to coronary atherosclerosis. (J Am Coll Cardiol 2000,35:1185-91) (C) 2000 by the American College of Cardi ology.