Cardiac Biomarkers are Associated with an Increased Risk of Stroke and Death in Patients with Atrial Fibrillation: A RELY Substudy
Background—Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and NT-proBNP and their association to cardiovascular events in atrial fibrillation (AF) patients in the RELY trial.
Methods and Results—Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS2 and CHA2DS2-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010-0.019 μg/L, n=2006; 0.020-0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentrations quartiles: <387; 387-800; 801-1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio (HR) 1.99 [95% confidence interval (CI) 1.17-3.39], p=0.0040), and to NT-proBNP with 2.30%/year vs. 0.92% in the highest vs. lowest NT-proBNP quartile groups, (HR 2.40 [CI 1.41-4.07], p=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR 4.38 [CI 3.05-6.29] p<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR 6.73 [3.95-11.49] p<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, p<0.0001, for a composite of thromboembolic events.
Conclusions—Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.
Clinical Trial Registration Information—www.clinicaltrials.gov; NCT00262600
- Received April 20, 2011.
- Accepted February 16, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited