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Cited by 402Atrial Fibrillation Management and OutcomesHeart Failure Treatment and ManagementAcute Myocardial Infarction Research

Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation: A Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Substudy

Hijazi, Ziad, Oldgren, Jonas, Andersson, Ulrika, Connolly, Stuart J., Ezekowitz, Michael D., Hohnloser, Stefan H., Reilly, Paul A., Vinereanu, Dragos +3 more·2012·Circulation
DOI 10.1161/circulationaha.111.038729
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Abstract

BACKGROUND: Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) 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 CHADS(2) and CHA(2)DS(2)-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 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% CI, 1.17-3.39]; 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 [95% 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 [95% 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.

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  • Measurement of cardiac troponin (high-sensitivity troponin T or I) and N-terminal pro-B-type natriuretic peptide may provide additional prognostic information in selected AF patients.

    “Measurement of cardiac troponin (high-sensitivity troponin T or I) and N-terminal pro-B-type natriuretic peptide may provide additional prognostic information in selected AF patients.[380][381][382]”

    From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [380]

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Authors
Hijazi, Z., Oldgren, J., Andersson, U., Connolly, S. J., Ezekowitz, M. D., Hohnloser, S. H., Reilly, P. A., Vinereanu, D., Siegbahn, A., Yusuf, S., & Wallentin, L.
Affiliations
  • Goethe University Frankfurt (DE)
  • From the Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden (Z.H., J.O., L.W.); Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (U.A.); Population Health Research Institute, Hamilton, Canada (S.J.C., S.Y.); Lankenau Institute for Medical Research and the Heart Center, Wynnewood, PA (M.D.E.); Department of Cardiology, J.W. Goethe University, Frankfurt, Germany (S.H.H.); Boehringer Ingelheim Pharmaceuticals,...
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-04-03
Volume
125
Issue
13
Pages
1605-1616
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.111.038729
OpenAlex
W1972837977
Cited by
402
References
48
Citations by year
2026: 11 · 2025: 23 · 2024: 19 · 2023: 20 · 2022: 17 · 2021: 19 · 2020: 31 · 2019: 31 · 2018: 26 · 2017: 31 · 2016: 43 · 2015: 29 · 2014: 31 · 2013: 60 · 2012: 11
FWCI
26.96
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
atrial fibrillation, cardiac biomarkers, troponin I, NT-proBNP, stroke risk, vascular death, RE-LY trial, anticoagulation, CHA2DS2-VASc score, CHADS2 score, cardiovascular risk stratification, biomarker thresholds, risk prediction model, bleeding risk, warfarin, direct oral anticoagulants
MeSH terms
Aged, Anticoagulants, Atrial Fibrillation, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Male, Peptide Fragments, Prospective Studies, Risk Factors, Cohort Studies, Biomarkers, Treatment Outcome, Troponin I, Natriuretic Peptide, Brain, Stroke

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