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

Jonas Oldgren; Ziad Hijazi; Johan Lindbäck; John H Alexander; Stuart J Connolly; John W Eikelboom; Michael D Ezekowitz; Christopher B Granger; Elaine M Hylek; Renato D Lopes; Agneta Siegbahn; Salim Yusuf; Lars Wallentin; RE-LY and ARISTOTLE Investigators

doi:10.1161/CIRCULATIONAHA.116.022802

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.

Affiliations

¹ 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.
² 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.).

PMID: 27569438
DOI: 10.1161/CIRCULATIONAHA.116.022802

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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. 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

Substances

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

Associated data

ClinicalTrials.gov/NCT00412984
ClinicalTrials.gov/NCT00262600