Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I.
OBJECTIVE
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 microg/l), the cut point of the predecessor assay (0.1 microg/l), and 1 equivalent to elevation of creatine kinase-myocardial band (1.5 ng/ml).


RESULTS
Patients with baseline cTnI > or =0.04 microg/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 > or =0.04 microg/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 microg/l to <0.1 microg/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 microg/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.
Bonaca
Marc
M
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. mbonaca@partners.org
Scirica
Benjamin
B
Sabatine
Marc
M
Dalby
Anthony
A
Spinar
Jindrich
J
Murphy
Sabina A
SA
Jarolim
Peter
P
Braunwald
Eugene
E
Morrow
David A
DA
D000083:Acetanilides / Q000627:therapeutic use; D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D010879:Piperazines / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D000069458:Ranolazine; D012307:Risk Factors; D019210:Troponin I / Q000097:blood*
D000083:Acetanilides; D015415:Biomarkers; D004791:Enzyme Inhibitors; D010879:Piperazines; D019210:Troponin I; D000069458:Ranolazine