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United States Department of Agriculture

Agricultural Research Service

Research Project: DIET AND BIOMARKERS OF CARDIOVASCULAR HEALTH

Location: Human Nutrition Research Center on Aging

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

Authors
item Matthan, Nirupa -
item Pencina, Michael -
item Larocque, Jane -
item D'Agostino, Ralph -
item Jacques, Paul -
item Ordovas, Jose -
item Schaefer, Ernst -
item Lichtenstein, Alice -

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 2009
Publication Date: September 1, 2009
Citation: Matthan, N., Pencina, M., Larocque, J., D'Agostino, R.B., Jacques, P.F., Ordovas, J.M., Schaefer, E.J., Lichtenstein, A.H. 2009. Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease. Journal of Lipid Research. 50:1927-1935.

Interpretive Summary: Data is limited on factors influencing cholesterol homeostasis, (balance between cholesterol absorbed and synthesized in the body) in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we measured the concentration of certain compounds in the blood that have been validated as surrogate measures of cholesterol absorption and synthesis respectively. The study population included a subset of subjects enrolled in the Framingham Offspring Study, specifically 155 cases and 414 matched control subjects. 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 signifiantly higher whereas cholesterol synthesis markers were significantly lower in cases compared with controls, irrespective of sex. 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.

Technical Abstract: 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 >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.

Last Modified: 7/30/2014
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