title: The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia.
abstract: 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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065-0900, USA. fabian_chen@merck.com
authors.forename: Fabian
authors.initials: F
authors.lastname: Chen
authors.forename: Vic
authors.initials: V
authors.lastname: Maridakis
authors.forename: Edward A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: Brian K
authors.initials: BK
authors.lastname: Hubbard
authors.forename: Alison
authors.initials: A
authors.lastname: Strack
authors.forename: Chan
authors.initials: C
authors.lastname: Beals
authors.forename: Gary A
authors.initials: GA
authors.lastname: Herman
authors.forename: Peggy
authors.initials: P
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000097:blood; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases