title: Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation.
abstract: BACKGROUND
  Atrial fibrillation is associated with increased but variable risk of stroke. Our aim was to validate the recently developed biomarker-based ABC (age, biomarkers [high-sensitivity troponin and N-terminal fragment B-type natriuretic peptide], and clinical history of prior stroke/transient ischemic attack)-stroke risk score and compare its performance with the CHA2DS2VASc and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) risk scores.
  
  
  METHODS
  The ABC-stroke score includes age, biomarkers (N-terminal fragment B-type natriuretic peptide and high-sensitivity cardiac troponin), and clinical history (prior stroke). This validation was based on 8356 patients, 16 137 person-years of follow-up, and 219 adjudicated stroke or systemic embolic events in anticoagulated patients with atrial fibrillation in the RE-LY study (Randomized Evaluation of Long-Term Anticoagulation Therapy). Levels of N-terminal fragment B-type natriuretic peptide, high-sensitivity cardiac troponin T (hs-cTnT), and high-sensitivity cardiac troponin I (hs-cTnI) were determined in plasma samples obtained at study entry.
  
  
  RESULTS
  The ABC-stroke score was well calibrated with 0.76 stroke/systemic embolic events per 100 person-years in the predefined low (<1%/y) risk group, 1.48 in the medium (1%-2%/y) risk group, and 2.60 in the high (>2%/y) risk group for the ABC-stroke score with hs-cTnT. Hazard ratios for stroke/systemic embolic events were 1.95 for medium- versus low-risk groups, and 3.44 for high- versus low-risk groups. ABC-stroke score achieved C indices of 0.65 with both hs-cTnT and hs-cTnI, in comparison with 0.60 for CHA2DS2VASc (P=0.004 for hs-cTnT and P=0.022 hs-cTnI) and 0.61 for ATRIA scores (P=0.005 hs-cTnT and P=0.034 for hs-cTnI).
  
  
  CONCLUSIONS
  The biomarker-based ABC-stroke score was well calibrated and consistently performed better than both the CHA2DS2VASc and ATRIA stroke scores. The ABC score should be considered an improved decision support tool in the care of patients with atrial fibrillation.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifiers: ARISTOTLE, NCT00412984; RE-LY, NCT00262600.
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.). jonas.oldgren@ucr.uu.se.
authors: Jonas
authors: J
authors: Oldgren
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Ziad
authors: Z
authors: Hijazi
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Johan
authors: J
authors: Lindbäck
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: John H
authors: JH
authors: Alexander
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Stuart J
authors: SJ
authors: Connolly
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: John W
authors: JW
authors: Eikelboom
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Michael D
authors: MD
authors: Ezekowitz
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Christopher B
authors: CB
authors: Granger
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Elaine M
authors: EM
authors: Hylek
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Renato D
authors: RD
authors: Lopes
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Agneta
authors: A
authors: Siegbahn
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Salim
authors: S
authors: Yusuf
authors: From Department of Medical Sciences, Cardiology, Uppsala University, Sweden (J.O., Z.H., L.W.); Uppsala Clinical Research Center, Uppsala University, Sweden (J.O., Z.H., J.L., A.S., L.W.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.H.A., C.B.G., R.D.L.); Population Health Research Institute, Hamilton, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); Boston University Medical Center, MA (E.M.H.); and Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden (A.S.).
authors: Lars
authors: L
authors: Wallentin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D014336:Troponin / Q000097:blood*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D010446:Peptide Fragments; D014336:Troponin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: anticoagulation; atrial fibrillation; models, cardiovascular; prevention and control; risk assessment; stroke