Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD

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.

Fig. 1.

Multivariable-adjusted odd ratios for cholesterol homeostasis markers and CVD risk based on conditional logistic regression. Error bars represent 95% CI.

Fig. 2.

Multivariable-adjusted odd ratios for cholesterol homeostasis markers and CVD risk based on conditional logistic regression. Error bars represent 95% CI per middle tertile (A) and highest tertile 2 (B) relative to the lowest tertile used as referent.