Markers of cholesterol absorption and synthesis predict the low-density lipoprotein cholesterol response to atorvastatin.
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.
Hoenig
Michel R
MR
Royal Brisbane and Women's Hospital, University of Queensland Centre for Clinical Research, Queensland, Australia. drmhoenig@yahoo.com.au
Walker
Philip J
PJ
Gurnsey
Christine
C
Beadle
Karen
K
Johnson
Leslie
L
D000042:Absorption; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D004083:Cholestanol / Q000097:blood; D002784:Cholesterol / Q000096:biosynthesis*; D008078:Cholesterol, LDL / Q000097:blood*; D003897:Desmosterol / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis* / Q000517:prevention & control; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*
D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D003897:Desmosterol; D004083:Cholestanol; D002784:Cholesterol; D000069059:Atorvastatin