title: Importance of persistent elevation of cardiac biomarkers in atrial fibrillation: a RE-LY substudy.
abstract: OBJECTIVE
  To evaluate the prognostic importance of transient or persistent elevations of cardiac troponin-I (cTnI) and N-terminal-B-type natriuretic peptide (NT-proBNP) in atrial fibrillation (AF).
  
  
  METHODS
  Plasma samples were obtained at randomisation and after 3 months in 2514 patients with AF in the RE-LY trial; median follow-up was 2.0 years. Patients were grouped based on levels at the two time points according to detectable cTnI levels (≥0.01 µg/L) or NT-proBNP levels above median (≥778 ng/L). These groups were related to occurrence of stroke or cardiovascular events evaluated with Cox models adjusting for established risk factors.
  
  
  RESULTS
  The proportion of patients with detectable cTnI levels at both time points was 48.5%, at one time point 28.5% and at neither time point 21.0%. Patients with detectable cTnI at both time points had substantially higher rates of stroke compared with those with transient elevations and those with no elevation at either time point (p<0.005, effect of cTnI). Persistent elevation of either or both cardiac biomarkers at baseline and 3 months was associated with a higher risk for cardiovascular events and mortality (p<0.0001). Prognostic prediction improved most with the use of repeated measurements of both cardiac biomarkers simultaneously (p<0.05) and achieved C-statistic 0.644 for stroke compared with 0.611 for CHADS2-score.
  
  
  CONCLUSIONS
  Persistent elevation of troponin and NT-proBNP indicates a worse prognosis than transient elevations or no elevations of either marker. Prognostication of stroke, death and thromboembolic events is improved by the use of repeated determinations of cardiac biomarkers.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov, NCT00262600.
authors.affiliation: Department of Cardiology, Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Hijazi
authors.affiliation: Department of Cardiology, Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Population Health Research Institute, Hamilton, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.affiliation: Thomas Jefferson Medical College and the Heart Center, Wynnewood, Pennsylvania, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.affiliation: Department of Cardiology, J. W. Goethe University, Frankfurt, Germany.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Ridgefield, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.affiliation: Population Health Research Institute, Hamilton, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Department of Cardiology, Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D015996:Survival Rate / Q000639:trends; D013548:Sweden / Q000453:epidemiology; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain