Markers of cholesterol absorption and synthesis predict the low-density lipoprotein cholesterol response to atorvastatin

Journal of Cardiovascular Pharmacology
Michel R HoenigLeslie Johnson

Abstract

Genetic loci predict <5% of variation in low-density lipoprotein cholesterol (LDL-C) response to statins. Cholestanol and desmosterol are plasma markers of cholesterol absorption and synthesis, respectively. Because statins lower LDL-C by inhibiting cholesterol synthesis, we studied the relationship between cholestanol and desmosterol and LDL-C response to atorvastatin. High-risk patients were treated with 80 mg of atorvastatin for 6 weeks. LDL-C response to atorvastatin was related to baseline cholestanol to cholesterol ratio (CCR) and desmosterol. The following comparisons were used: (1) correlates of percentage LDL-C response, (2) baseline characteristics of hyperresponders versus hyporesponders, and (3) binary logistic regression analysis for predictors of achieved LDL-C <70 mg/dL. One hundred fifty-four patients were enrolled of which 118 completed the study with adequate adherence. Average LDL-C reduction was 57% ± 13% (mean ± SD). On univariate analysis, desmosterol and CCR correlated with percentage LDL-C reduction and multivariate modeling explained approximately 16% of the variation in response. Atorvastatin hyperresponders had higher mean desmosterol (P = 0.046) and lower CCR (P = 0.035) than hyporesponders. On logis...Continue Reading

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Citations

Aug 12, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Niek C A van de PasAlbert A de Graaf
Dec 22, 2015·Journal of Clinical Lipidology·Thomas D DayspringJoseph P McConnell
Mar 3, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Cheng-Xian GuoHong-Hao Zhou
Aug 1, 2015·Journal of Clinical Lipidology·Daniela M T MalinaMaria C Izar

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