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 postmenopausal 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 squalene, Delta(8)-cholestenol, desmosterol, lathosterol (indicators of cholesterol synthesis), cholestanol, campesterol and sitosterol (indicators of cholesterol absorption) were measured in 48 50- to 55-year-old consecutive women with angiographically verified CAD and in 61 age-matched healthy controls. 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) compared with the controls, despite similar serum cholesterol levels. Adjusted for age, body mass index, family history of CAD, smoking, hypertension, serum triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol level and glycosylated hemoglobin A1c% (GHbA1c), the ratios 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 sitosterol (1.01; 1.00 to 1.03) were significantly associated with the risk of CAD. In addition, family history of CAD and GHbA1c% were also independently related to the presence of CAD. CONCLUSIONS The results suggest that women with elevated ratios of serum squalene, campesterol and sitosterol to cholesterol and low respective lathosterol values have enhanced risk for CAD. Thus, enhanced absorption and reduced synthesis of cholesterol may be related to coronary atherosclerosis. (J Am Coll Cardiol 2000,35:1185-91) (C) 2000 by the American College of Cardiology.