title: Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.
abstract: OBJECTIVE
  The aim of this study is to simultaneously evaluate the incremental prognostic value of multiple cardiac biomarkers reflecting different underlying pathophysiological processes in a well-characterized population of patients with non-ST-segment acute coronary syndrome (NSTE-ACS).
  
  
  RESULTS
  We measured cardiac troponin I (cTnI), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein, and myeloperodixase (MPO) among 4352 patients with NSTE-ACS in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischaemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. When added individually to a multivariable model adjusted for clinical characteristics, the risk of cardiovascular (CV) death rose in a stepwise fashion with increasing quartiles of each biomarker, and when using their pre-defined cut-points [HR(adj) 2.71 (P < 0.001) for cTnI ≥0.03 ng/mL; HR(adj) 3.01 (P < 0.001) for NT-proBNP ≥400 pg/mL; HR(adj) 1.45 (P = 0.019) for high-sensitivity (hs) C-reactive protein ≥15 mg/L; and HR(adj) 1.49 (P = 0.006) for MPO ≥670 pmol/L]. After including all biomarkers, only NT-proBNP and cTnI were independently associated with CV death, and only cTnI with myocardial infarction (MI). The addition of NT-proBNP to a model adjusted for TIMI risk score incorporating cTnI significantly improved both the discrimination and re-classification of the model for CV death and heart failure (HF) while there was no such improvement after the addition of either MPO or hs-C-reactive protein.
  
  
  CONCLUSIONS
  In this study of over 4300 patients presenting with NSTEACS, we found that both cTnI and NT-proBNP offer prognostic information beyond that achieved with clinical risk variables for CV death, MI, and HF. Myeloperoxidase and hs-C-reactive protein, while independently associated with some adverse CV outcomes, did not provide substantial incremental prognostic information when evaluated together with cTnI and NT-proBNP.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. bscirica@partners.org
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: James L
authors.initials: JL
authors.lastname: de Lemos
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000401:mortality*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D019210:Troponin I / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000401:mortality
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D009195:Peroxidase