Journal
JOURNAL OF LIPID RESEARCH
Volume 50, Issue 9, Pages 1927-1935Publisher
ELSEVIER
DOI: 10.1194/jlr.P900039-JLR200
Keywords
lipids; lipoproteins; lathosterol; desmosterol; phytosterols; campesterol; sitosterol; coronary heart disease
Categories
Funding
- National Institutes of Health [HL-074388, NO1-HC-25195]
- US Department of Agriculture
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Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively) in Framingham Offspring Study Cycle-6 participants diagnosed with established CVD and/or >= 50% carotid stenosis not taking lipid lowering medication (cases, N = 155) and matched controls (N = 414). Cases and controls had similar plasma LDL-cholesterol; HDL-cholesterol was significantly lower in males, while triglyceride concentrations were significantly higher in female cases relative to their respective controls. Cholesterol absorption markers were significantly higher (229 +/- 7 vs. 196 +/- 4, 169 +/- 6 vs. 149 +/- 3 and 144 +/- 5 vs. 135 +/- 3 for campesterol, sitosterol, and cholestanol, respectively), whereas cholesterol synthesis markers were significantly lower (116 +/- 4 vs. 138 +/- 3, 73 +/- 3 vs. 75 +/- 2 for lathosterol and desmosterol, respectively) in cases compared with controls, irrespective of sex. After controlling for standard risk factors, campesterol (2.47 [1.71-3.56]; P < 0.0001), sitosterol (1.86 [1.38-2.50]; P < 0.0001), cholestanol (1.57 [1.09-2.27]; P = 0.02), desmosterol (0.59 [0.42-0.84]; P = 0.003), and lathosterol (0.58 [0.43-0.77]; P = 0.0002) were significantly associated with CVD (odds ratio [95% confidence interval]). These data suggest that impaired cholesterol homeostasis, reflected by lower synthesis and higher absorption marker concentrations, are highly significant independent predictors of prevalent CVD in this study population.-Matthan N. R., M. Pencina, J. M. LaRocque, P. F. Jacques, R. B. D'Agostino, E. J. Schaefer, and A. H. Lichtenstein. Alterations in cholesterol absorption/synthesis markers characterize Framingham Offspring Study participants with CHD. J. Lipid Res. 2009. 50: 1927-1935.
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