Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation

Circulation. 2016 Nov 29;134(22):1697-1707. doi: 10.1161/CIRCULATIONAHA.116.022802. Epub 2016 Aug 28.


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.

Clinical trial registration: URL: Unique identifiers: ARISTOTLE, NCT00412984; RE-LY, NCT00262600.

Keywords: anticoagulation; atrial fibrillation; models, cardiovascular; prevention and control; risk assessment; stroke.

Publication types

  • Randomized Controlled Trial
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Reproducibility of Results
  • Severity of Illness Index
  • Stroke / blood*
  • Stroke / diagnosis
  • Stroke / drug therapy
  • Troponin / blood*
  • Young Adult


  • Anticoagulants
  • Biomarkers
  • Peptide Fragments
  • Troponin
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data