title: Prognostic performance of a high-sensitivity assay for cardiac troponin I after non-ST elevation acute coronary syndrome: Analysis from MERLIN-TIMI 36.
abstract: BACKGROUND
  Newer troponin assays offer the ability to quantify circulating troponin levels at an order of magnitude lower than contemporary assays, fueling continued debate over the prognostic implications of very low-level increases in concentration. We evaluated the prognostic implications of low-level increases in cardiac troponin I (cTnI) using an investigational single-molecule high-sensitivity assay in patients with acute coronary syndrome (ACS).
  
  
  METHODS
  We measured cTnI using both a high-sensitivity troponin I (hsTnI) assay (Erenna, Singulex, 99(th) percentile 9 pg/ml) and a current generation sensitive assay (TnI-Ultra, Siemens, 99(th) percentile 40 pg/ml) at baseline in 1807 patients with non-ST elevation ACS and compared their prognostic ability for adverse cardiovascular events at 30 days and one year.
  
  
  RESULTS
  Among patients with TnI-Ultra<99(th) percentile, patients with elevated hsTnI (≥ 9 pg/ml) had a significantly higher risk than patients with hsTnI<9 pg/ml: cardiovascular death (CVD) or myocardial infarction (MI) at one year (7.0% vs 3.8%; p<0.001, hazard ratio (HR) 2.05, confidence interval (CI) 1.23-3.41); including a higher risk of CVD (3.5% vs 1.5%, p<0.001) and MI (5.0% vs 2.8%, p<0.001) individually. This higher risk of CVD/MI was independent of clinical risk stratification using the TIMI Risk Score (adj. HR 1.76, CI 1.05-2.90). Moreover, hsTnI showed a trend toward a gradient of risk even below the hsTnI 99 percentile.
  
  
  CONCLUSIONS
  Low-level cardiac troponin detected using a single-molecule technique, below the cutpoint of a contemporary sensitive assay, identified a significant gradient of risk. These findings support the prognostic relevance of low-level cardiac troponin elevation with increasingly sensitive assays in patients with ACS.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA mbonaca@partners.org.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: O'Malley
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, USA.
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Conrad
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002317:Cardiovascular Agents / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000069458:Ranolazine / Q000008:administration & dosage; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D019210:Troponin I; D000069458:Ranolazine
keywords: Cardiac troponin; acute coronary syndrome; prognosis; troponin