The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia

Background: Lipidomic biomarkers will facilitate the development of novel anti-atherosclerotic therapies. Objective: To evaluate the responses of circulating biomarkers to simvastatin treatment. Methods: A randomized, cross-over study in men with mixed dyslipidaemia was used to compare effects of simvastatin 40 mg/day with placebo. Results: Plasma concentrations of nine fatty acids (FA; of 33 evaluated) were reduced significantly by simvastatin. No changes in the rates of FA synthesis or in hepatic lipase or lipoprotein lipase activities were apparent. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased. Conclusion: We identified lipidomic biomarkers of simvastatin treatment effect that are consistent with statin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase (ClinicalTrials. gov:NCT00935259).