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Improving stroke risk prediction in atrial fibrillation with circulating biomarkers: the CHA2DS2-VASc-Biomarkers

Samuel A P Short1, Katherine Wilkinson2, Erin Hald3

  • 1Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.

Journal of Thrombosis and Haemostasis : JTH
|August 7, 2025
PubMed

Insights

Biomarkers can improve stroke risk prediction in atrial fibrillation (AF). Five biomarkers were linked to higher stroke risk, with two significantly enhancing the CHA₂DS₂-VASc score for better anticoagulation decisions.

Area of Science:

  • Cardiology
  • Neurology
  • Biomarker Research

Background:

  • Anticoagulation is crucial for preventing ischemic stroke in atrial fibrillation (AF) but carries a bleeding risk.
  • Current risk calculators for AF have limitations in accurately guiding anticoagulation therapy.

Purpose of the Study:

  • To investigate if general population stroke risk biomarkers are associated with stroke risk in AF patients.
  • To assess if these biomarkers improve the predictive performance of the CHA₂DS₂-VASc score.

Main Methods:

  • Analysis of the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study data.
  • Inclusion of 2411 AF participants without prior stroke or anticoagulation.
  • Measurement of nine circulating biomarkers and assessment of their association with incident stroke using Cox models, comparing CHA₂DS₂-VASc score alone versus with added biomarkers.

Main Results:

  • Among 2411 AF participants, 163 experienced ischemic stroke over 13 years.
  • N-terminal pro-B-type natriuretic peptide, growth differentiation factor 15, cystatin C, interleukin 6, and lipoprotein (a) were independently associated with increased stroke risk.
  • Biomarkers significantly improved CHA₂DS₂-VASc model fit and predictive ability (5-year NRI>0 of 0.42), with NT-proBNP and GDF-15 showing optimal results.

Conclusions:

  • Five circulating biomarkers are associated with ischemic stroke risk in AF patients.
  • Two biomarkers, N-terminal pro-B-type natriuretic peptide and growth differentiation factor 15, enhanced the predictive performance of the CHA₂DS₂-VASc score.
  • An improved CHA₂DS₂-VASc-Biomarkers score can aid in selecting AF patients who would benefit most from anticoagulation therapy to reduce stroke incidence.
Abstract

Keywords:
atrial fibrillationbiomarkerscohort studyischemic strokerisk assessment

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