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J Am Coll Cardiol, 2000; 35:1185-1191
© 2000 by the American College of Cardiology Foundation
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ARTICLE

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

Radhakrishnan A. Rajaratnam, MDa, Helena Gylling, MD, PhDa and Tatu A. Miettinen, MD, PhDa

a Division of Internal Medicine, Department of Medicine, University of Helsinki, Helsinki, Finland

Manuscript received July 1, 1999; revised manuscript received October 27, 1999, accepted December 15, 1999.

Reprint requests and correspondence: Prof. Tatu A. Miettinen, Division of Internal Medicine, Department of Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HYKS, Helsinki, Finland
tatu.a.miettinen{at}helsinki.fi

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.

Abbreviations and Acronyms
  BMDP = Biomedical Data Program
  CAD = coronary artery disease
  ECG = electrocardiogram
  FSH = follicle-stimulating hormone
  GHbA1c = glycosylated hemoglobin A1c
  GLC = gas–liquid chromatography
  HDL = high-density lipoprotein
  LDL = low-density lipoprotein
  Q = quartiles
  ROC = receiver operating characteristic
  SHBG = sex hormone binding globulin




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