title: Prediction of cardiovascular events in statin-treated stable coronary patients of the treating to new targets randomized controlled trial by lipid and non-lipid biomarkers.
abstract: Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P ≤ 0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.
  
  
  BACKGROUND
  ClinicalTrials.gov 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.affiliation: The Heart Research Institute, Sydney, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Barter
authors.affiliation: Pfizer Inc, New York, NY, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: DeMicco
authors.affiliation: Pfizer Inc, New York, NY, United States of America.
authors.forename: Weihang
authors.initials: W
authors.lastname: Bao
authors.affiliation: Pfizer Inc, New York, NY, United States of America.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Preston
authors.affiliation: State University of New York Health Science Center, Brooklyn, NY, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: LaRosa
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Grundy
authors.affiliation: Veterans Affairs Central California Health Care System and University of California San Francisco School of Medicine, San Francisco, CA, United States of America.
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.affiliation: Universitätsklinikum, Eppendorf, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Greten
authors.affiliation: Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Nanette K
authors.initials: NK
authors.lastname: Wenger
authors.affiliation: University of Glasgow, Glasgow, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: San Francisco General Hospital, San Francisco, CA, United States of America.
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids