Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease

Nirupa R. Matthan, Michael Pencina, Jane M. LaRocque, Paul F. Jacques, Ralph B. D'Agostino, Ernst J. Schaefer, and Alice H. Lichtenstein

Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

Corresponding Author: nirupa.matthan{at}tufts.edu

Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing CVD relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursors 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 to 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%CI]). 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.

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