title: Prediction of cardiovascular events in statin-treated stable coronary patients by lipid and nonlipid biomarkers.
abstract: OBJECTIVE
  The aim of this study was to investigate the relationship between lipid and nonlipid biomarker levels achieved during statin therapy and the incidence of major cardiovascular events (MCVEs) in patients with stable coronary heart disease (CHD).
  
  
  BACKGROUND
  Several plasma nonlipid biomarkers have been shown to predict MCVEs in population studies.
  
  
  METHODS
  This is a nested case-control study in the TNT (Treating to New Targets) study population, a randomized trial that compared the efficacy of high- (80 mg) versus low-dose (10 mg) atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 nonlipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg and again 1 year after being randomized to 10 or 80 mg atorvastatin in 507 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1,020 control subjects. An MCVE was defined as CHD death; nonfatal, non-procedure-related myocardial infarction; resuscitated cardiac arrest; or fatal or nonfatal stroke.
  
  
  RESULTS
  Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were all predictive of recurrent MCVEs (p ≤ 0.009). Concentrations of many of the 18 nonlipid biomarkers were lowered by atorvastatin therapy (independent of dose). However, almost none of the nonlipid biomarker levels, whether measured after the 8-week run-in period or after 1 year of treatment with 10 or 80 mg atorvastatin, were predictive of recurrent MCVEs.
  
  
  CONCLUSIONS
  In patients with stable CHD, atorvastatin improved plasma levels of an expanded panel of nonlipid biomarkers. However, independently of atorvastatin dose, the achieved levels of the vast majority of nonlipid biomarkers did not predict MCVEs. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.forename: Philip
authors.initials: P
authors.lastname: Barter
authors.forename: David A
authors.initials: DA
authors.lastname: DeMicco
authors.forename: Weihang
authors.initials: W
authors.lastname: Bao
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Preston
authors.forename: John C
authors.initials: JC
authors.lastname: LaRosa
authors.forename: Scott M
authors.initials: SM
authors.lastname: Grundy
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.forename: Heiner
authors.initials: H
authors.lastname: Greten
authors.forename: Nanette K
authors.initials: NK
authors.lastname: Wenger
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin