The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation

Ziad Hijazi, Johan Lindbäck, John H Alexander, Michael Hanna, Claes Held, Elaine M Hylek, Renato D Lopes, Jonas Oldgren, Agneta Siegbahn, Ralph A H Stewart, Harvey D White, Christopher B Granger, Lars Wallentin, ARISTOTLE and STABILITY Investigators, Ziad Hijazi, Johan Lindbäck, John H Alexander, Michael Hanna, Claes Held, Elaine M Hylek, Renato D Lopes, Jonas Oldgren, Agneta Siegbahn, Ralph A H Stewart, Harvey D White, Christopher B Granger, Lars Wallentin, ARISTOTLE and STABILITY Investigators

Abstract

Aims: Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF.

Methods and results: A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.

Conclusion: A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF.

Clinicaltrials gov identifier: NCT00412984, NCT00799903.

Keywords: Atrial fibrillation; Biomarkers; Natriuretic peptides; Risk score; Stroke; Troponin.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Nomogram for the new biomarker-based risk score. For each predictor, read the points assigned on the 0–10 scale at the top and then sum these points. Find the number on the ‘Total Points’ scale and then read the corresponding predictions of 1- and 3-year risk of stroke or systemic embolism below it. Continuous variables are represented from the 1st to the 99th percentiles. The prediction model is preferably used as a web-based calculator or app. Application of the nomogram is exemplified in Supplementary material online,Figures EandF.
Figure 2
Figure 2
(A) Kaplan–Meier estimated cumulative event rate by four ABC-stroke risk classes for the CHA 2 DS 2 -VASc score (panel): 0–1, 2, 3, 4, and ≥5 points. (B) Kaplan–Meier estimated cumulative event rate by the CHA 2 DS 2 -VASc score: 0–1, 2, 3, 4, and ≥5 points for the three ABC-stroke risk classes (panel): 0–0.3%, 0.3–1%, 1–2, and >2%.
Figure 3
Figure 3
Kaplan–Meier estimated cumulative event rate by randomized treatment (colour) for the three ABC-stroke risk classes (panel): low (2%).
Figure 4
Figure 4
Cumulative risk of stroke by predicted 1-year ABC-stroke risk group (green 2%) for the derivation (solid lines,n= 14 701) and the external validation (dashed lines,n= 1400) data.

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