Use of the Centaur TnI-Ultra Assay for Detection of Myocardial Infarction and Adverse Events in Patients Presenting With Symptoms Suggestive of Acute Coronary Syndrome Fred S. Apple, 1* Stephen W. Smith, 2 Lesly A. Pearce, 3 Ranka Ler, 1 and MaryAnn M. Murakami 1 BACKGROUND: We determined the diagnostic accuracy of the Advia Centaur TnI-Ultra assay for detecting myocardial infarction (MI) and assessing risk of ad- verse events in patients presenting with ischemic symp- toms suggestive of acute coronary syndrome. METHODS: We measured cardiac troponin I (cTnI) on admission and 6 –24 h after admission (follow-up) in plasma specimens from 371 consecutive patients. The end point was the first of cardiac event or death within 60 days. We estimated survival curves using the Kaplan-Meier method and compared groups with the log rank statistic. RESULTS: MI was established in 49 patients (13%). Clin- ical sensitivities and specificities for MI based on the 99th percentile (0.04 g/L) were 74% and 84%, respec- tively, on admission and 94% and 81% at follow-up. ROC curves showed significantly higher accuracy for MI in the follow-up specimen compared with admis- sion (P = 0.001). Overall there were 2 cardiac deaths, 1 noncardiac death, 49 MIs, 7 coronary artery bypass grafts, and 36 percutaneous coronary interventions in 59 patients during follow-up. The event rate in those with cTnI 0.006 g/L was significantly lower than in groups with cTnI 0.006 – 0.04 g/L, 0.04 – 0.10 g/L, or 0.10 g/L (2.8% vs 11.1%, 24.1%, 55.1%, respec- tively; P 0.0001). Relative risks for the increasing cTnI cutoff groups were 3.9 (95% CI 1.2–13), 8.9 (2.4 – 34), and 25 (7.3– 82) after adjustment for age, diabetes, history of hypertension, previous MI, and estimated glomerular filtration rate. CONCLUSIONS: The TnI-Ultra assay is a sensitive, early diagnostic biomarker for MI and an independent pre- dictor of adverse events at any measurable cTnI in pa- tients with symptoms of acute coronary syndrome. © 2008 American Association for Clinical Chemistry The presence of circulating cardiac troponin (cTn) 4 is indicative of myocardial injury (1–3). Increased con- centrations of cTn are associated with more frequent thrombus, impaired myocardial tissue perfusion, and higher probability of adverse outcomes following cor- onary intervention (4–6). In addition, the evidence- based literature shows a consistently strong direct rela- tionship between increased cTn concentration and the risk of both short- and long-term cardiac events and mortality in patients who present with symptoms of acute coronary syndrome (ACS) (2, 7 ). The prognostic information obtained from the measurement of cTnI or cTnT has been shown to be independent of clinical risk factors such as age, ECG, renal disease, and diabe- tes (2, 7, 8 ). International associations in cardiology laboratory medicine and emergency medicine have all designated cTn as the preferred biomarker for aiding in the diagnosis of MI and for risk stratification in pa- tients presenting with suspected ACS, and recommend that independent studies validate all cTn assays after FDA clearance before acceptance for risk assessment of adverse outcomes (1–3). The purpose of this study was to determine both the diagnostic accuracy for detection of myocardial infarction (MI) and the prognostic value for assessing risk of short-term adverse events for the second-generation Advia Centaur TnI-Ultra assay in a nonselected, heterogeneous population of patients presenting with ischemic symptoms suggestive of ACS based on cTnI values at the limit of detection (LoD) 1 Departments of Laboratory Medicine and Pathology and 2 Emergency Medicine, Hennepin County Medical Center, University of Minnesota School of Medicine, Minneapolis, MN; 3 Biostatistical Consulting, Minot, ND. * Address correspondence to this author at: Hennepin County Medical Center, Clinical Laboratories P4, 701 Park Ave., Minneapolis, MN 55415. Fax 612-904- 4229; e-mail apple004@umn.edu. Received August 20, 2007; accepted January 15, 2008. Previously published online at DOI: 10.1373/clinchem.2007.097162 4 Nonstandard abbreviations: cTn, cardiac troponin I; ACS, acute coronary syn- drome; MI, myocardial infarction; LoD, limit of detection; eGFR, estimated glomerular filtration rate; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; RR, relative risk. Clinical Chemistry 54:4 723–728 (2008) Proteomics and Protein Markers 723