title: Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: The LIPID biomarker study.
abstract: OBJECTIVE
  In patients with stable coronary heart disease (CHD), we aimed to assess 1. the prognostic power of biomarkers reflecting haemodynamics, micronecrosis, inflammation, coagulation, lipids, neurohumoral activity, and renal function; 2. whether changes in concentrations of these biomarkers over 12 months affected subsequent CHD risk; and 3. whether pravastatin modified the change in biomarker concentrations and this influenced the risk of future events.
  
  
  METHODS
  In the LIPID study, 9014 patients were randomised to pravastatin 40 mg or placebo 3-36 months after an acute coronary syndrome. Eight biomarkers were measured at baseline (n=7863) and 12 months later (n=6434).
  
  
  RESULTS
  During a median of 6.0 (IQR 5.5-6.5) years follow-up, 1100 CHD-related deaths and nonfatal myocardial infarctions occurred, 694 after biomarker measurement at 12 months. Baseline BNP, CRP, cystatin C, D-dimer, midregional pro-adrenomedullin, and sensitive troponin I predicted recurrent CHD events. In a multivariable model, sensitive troponin I, BNP, and cystatin C had the strongest associations with outcome (P<0.001 for trend). The strongest improvement in risk prediction was achieved by including sensitive troponin I (net reclassification improvement (NRI) 5.5%; P=0.003), BNP (4.3%; P=0.02), history of MI (NRI 7.0%; P<0.001). In landmark analyses, among biomarkers, changes to 12 months in sensitive troponin I (HR 1.32 (1.03-1.70) for T3/T1), BNP (HR 1.37 (1.10-1.69) for Q4/Q1) and Lp-PLA2 (HR 1.52 (1.16-1.97)) improved CHD risk prediction.
  
  
  CONCLUSIONS
  Baseline levels and changes in sensitive troponin I, and BNP may have the potential to guide the intensity of secondary prevention therapy.
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address: Andrew.Tonkin@monash.edu.
authors: Andrew M
authors: AM
authors: Tonkin
authors: University Heart Centre Hamburg, Hamburg, Germany.
authors: Stefan
authors: S
authors: Blankenberg
authors: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors: Adrienne
authors: A
authors: Kirby
authors: University Heart Centre Hamburg, Hamburg, Germany.
authors: Tanja
authors: T
authors: Zeller
authors: Wesley Medical Centre and Greenslopes Hospital, Brisbane, Australia.
authors: David M
authors: DM
authors: Colquhoun
authors: University Heart Centre Hamburg, Hamburg, Germany.
authors: Anne
authors: A
authors: Funke-Kaiser
authors: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors: Wendy
authors: W
authors: Hague
authors: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: David
authors: D
authors: Hunt
authors: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors: Anthony C
authors: AC
authors: Keech
authors: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors: Paul
authors: P
authors: Nestel
authors: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors: Ralph
authors: R
authors: Stewart
authors: Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia.
authors: David R
authors: DR
authors: Sullivan
authors: School of Population Health, University of WA, Perth, Australia.
authors: Peter L
authors: PL
authors: Thompson
authors: Department of Medicine, University of QLD, Brisbane, Australia.
authors: Malcolm
authors: M
authors: West
authors: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors: Harvey D
authors: HD
authors: White
authors: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors: John
authors: J
authors: Simes
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D055316:Cystatin C / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D017035:Pravastatin / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D019210:Troponin I / Q000097:blood / Q000378:metabolism; D020107:Troponin T / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D005338:Fibrin Fibrinogen Degradation Products; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D019210:Troponin I; D020107:Troponin T; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D017035:Pravastatin
keywords: Biomarkers; Coronary heart disease; Risk estimation; Statin therapy