Prospective Evaluation of the Prognostic Implications of Improved Assay Performance With a Sensitive Assay for Cardiac Troponin I

Objectives The purpose of this study was to investigate the prognostic implications of low-level increases in cardiac troponin I (cTnI) using a current-generation sensitive assay in patients with suspected acute coronary syndrome (ACS). Background Recent enhancements in troponin assays have enabled resolution of the 99th percentile reference limit at progressively lower concentrations. However, the clinical significance of low-level increases with sensitive assays is still debated. Methods We measured cTnI using a sensitive assay (TnI-Ultra, Siemens Healthcare Diagnostics, Deerfield, Illinois) at baseline in 4,513 patients with non-ST-segment elevation ACS randomly assigned to ranolazine or placebo. We applied decision limits at the 99th percentile reference limit (0.04 mu g/l), the cut point of the predecessor assay (0.1 mu g/l), and 1 equivalent to elevation of creatine kinase-myocardial band (1.5 ng/ml). Results Patients with baseline cTnI >= 0.04 mu g/l (n = 2,924) were at higher risk of death/myocardial infarction (MI) at 30 days than were patients with a negative cTnI (6.1% vs. 2.0%, p < 0.001). After adjusting for the TIMI (Thrombolysis In Myocardial Infarction) risk score, cTnI >= 0.04 mu g/l was associated with a 3-fold (95% confidence interval: 2.0 to 4.4, p < 0.001) higher risk of death/MI at 30 days. Moreover, patients with low-level increases (0.04 mu g/l to <0.1 mu g/l), were at significantly higher risk of death/MI at 30 days (5.0% vs. 2.0%, p = 0.001) and death at 12 months (6.4% vs. 2.4%, p = 0.005) than were patients with cTnI <0.04 mu g/l. Conclusions Low-level increases in cTnI using a sensitive assay identify patients at higher risk of death or MI. These findings support current American College of Cardiology/American Heart Association recommendations defining MI, and the incremental value of newer, more sensitive assays in identifying high-risk patients with ACS. (J Am Coll Cardiol 2010;55:2118-24) (C) 2010 by the American College of Cardiology Foundation