
Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.
Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0207-x) contains supplementary material, which is available to authorized users.
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- Analytical Chemistry
- 3401 Analytical chemistry
- 3205 Medical biochemistry and metabolomics
- 3101 Biochemistry and cell biology
- 1103 Clinical Sciences
- 0601 Biochemistry and Cell Biology
- 0301 Analytical Chemistry
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Analytical Chemistry
- 3401 Analytical chemistry
- 3205 Medical biochemistry and metabolomics
- 3101 Biochemistry and cell biology
- 1103 Clinical Sciences
- 0601 Biochemistry and Cell Biology
- 0301 Analytical Chemistry