Focus Issue: Biomarkers in Cardiovascular Disease
Clinical Research: Biomarkers in ACS
Prospective Evaluation of the Prognostic Implications of Improved Assay Performance With a Sensitive Assay for Cardiac Troponin I

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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 μg/l), the cut point of the predecessor assay (0.1 μg/l), and 1 equivalent to elevation of creatine kinase–myocardial band (1.5 ng/ml).

Results

Patients with baseline cTnI ≥0.04 μg/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 μg/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 μg/l to <0.1 μg/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 μg/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.

Key Words

troponin
prognosis
sensitive
acute coronary syndrome
ACS

Abbreviations and Acronyms

ACS
acute coronary syndrome
CI
confidence interval
CK-MB
creatine kinase-myocardial band
cTn
cardiac troponin
HR
hazard ratio
MI
myocardial infarction
NSTE-ACS
non–ST-segment elevation acute coronary syndrome

Cited by (0)

Dr. Scirica has received research support from Merck, Novartis, AstraZeneca, Daiichi-Sankyo, and Bristol-Myers Squibb; honoraria for educational presentations from CV Therapeutics, Novartis, Merck, Schering-Plough, Sanofi-Aventis, Lilly, and Daiichi-Sankyo; has served as a consultant for AstraZeneca, Novartis, Congentus, and Gilead; and is the recipient of an unrestricted grant from the Michael Lerner Foundation. Dr. Sabatine has received research grants from BRAHMS, diaDexus, and Ortho-Clinical Diagnostics, and is a consultant for Singulex. Dr. Jarolim has received research support from Amgen, Beckman-Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics, and honoraria for educational presentations from Ortho Clinical Diagnostics. Dr. Braunwald is the chairman of the TIMI Study Group, who receives grant support from Beckman-Coulter, CV Therapeutics (now Gilead Sciences), and Roche Diagnostics. Dr. Morrow has received research/educational grant support through the TIMI Study Group from Accumetrics, AstraZeneca, Bayer Healthcare, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly and Co., Genentech, Johnson & Johnson, Merck and Company, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Siemens, Singulex, and Schering-Plough; has received honoraria for educational presentations from CV Therapeutics and Eli Lilly and Co.; and is a consultant/on the advisory board of AstraZeneca, Beckman-Coulter, Cardiokinetix, Gilead, Ikaria, Menarini, Molecular Insight, OrthoClinical Diagnostics, Sanofi-Aventis, Schering-Plough Research Institute, Siemens, and Roche Diagnostics.