title: 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.
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.
  
  
  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.
authors.affiliation: Uppsala Clinical Research Center, Dag Hammarskjölds väg 14B, Uppsala, Sweden. Ziad.hijazi@ucr.uu.se
authors.forename: Ziad
authors.initials: Z
authors.lastname: Hijazi
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain