Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation: A RELY Substudy

Study Questions:

Are plasma levels of troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) predictive of stroke and vascular mortality in patients with atrial fibrillation?


Biomarkers were analyzed in 6,189 patients at randomization in the RELY study. Outcomes were evaluated after adjusting for established cardiovascular risk factors and the CHADS2 and CHA2DS2-VASc risk scores. Patients were stratified based on troponin I concentration quartiles: <0.010; 0.010-0.019; 0.020-0.039; ≥0.040 μg/L; and on NT-proBNP concentration 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; p = 0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups (HR, 2.40; 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; p < 0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73; p < 0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, p < 0.0001, for a composite of thromboembolic events.


The authors concluded that elevations of troponin I and NT-proBNP are common in patients with atrial fibrillation and are independently related to increased risks of stroke and mortality.


This study supports previous findings that elevated cardiac biomarkers predict adverse cardiac events. The finding that these biomarkers also predict stroke in the setting of atrial fibrillation is novel and important since they improve risk stratification when added to commonly used clinical scoring methods. Thus, these findings may have important implications in guiding antithrombotic and other therapies, especially in atrial fibrillation subgroups who are otherwise deemed low risk. Since all patients in this study had at least one stroke risk factor and all were treated with oral anticoagulants, this approach will need to be tested in other atrial fibrillation populations.

Clinical Topics: Anticoagulation Management

Keywords: Stroke, Biological Markers, Troponin I, Cardiology, Peptide Fragments, Risk Factors, Troponin, Natriuretic Peptide, Brain

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