Metabolomics of statin efficacy and cardiovascular disease risk
Statins, or HMG CoA reductase (HMGCR) inhibitors, are widely prescribed for prevention and management of cardiovascular disease (CVD). Reduced CVD risk as a result of statin treatment is primarily attributed to decreases in plasma LDL, but recent evidence has demonstrated an additional benefit of statin-induced reductions in the inflammatory marker, C-reactive protein (CRP). Despite the general efficacy of statins in clinical trials, a substantial number of CVD events occur under active treatment in patients that have achieved adequate LDL and CRP reductions, indicating the persistence of underlying pathophysiology. The central premise of this project is that metabolomic analyses in samples derived from clinical and cellular studies of statin treatment will identify signatures for pathways that underlie inter-individual variation in statin efficacy. These samples are available by close linkage of this project with the NIH funded project "Pharmacogenomics and Risk of Cardiovascular Disease" (PARC, U01-HL69757), a component of the NIH Pharmacogenomics Research Network (PGRN).