Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 56, Issue 4, Pages 396-401Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e3181f09bcb
Keywords
statin; cholesterol metabolism; lipids; cholesterol; personalized medicine
Funding
- Pfizer Australia [AUS-ATO-06-002]
- Royal Brisbane and Women's Hospital Foundation
- National Health and Medical Research Council of Australia [409936]
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Objective: 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. Methods: 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. Results: 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 logistic regression analysis for the outcome of achieved LDL-C of <70 mg/dL, baseline LDL-C and CCR were significant predictors; odds ratios were 0.932 and 0.979, respectively. Conclusions: CCR and desmosterol explain more variation in LDL-C response to statin than that reported with pharmacogenomics. CCR and desmosterol may guide lipid-lowering therapy.
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