Biomarker, Imaging, and Clinical Factors Associated With Overt and Covert Stroke in Patients With Atrial Fibrillation
Gian Marco De Marchis, Philipp Krisai, Laura Werlen, Tim Sinnecker, Stefanie Aeschbacher, Tolga Dittrich, Alexandros A. Polymeris, Michael Coslovksy, Manuel R. Blum, Nicolas Rodondi, Tobias Reichlin, Giorgio Moschovitis, Jens Wuerfel, Philippe Lyrer, Urs Fischer, David Conen, Peter Kastner, André Ziegler, Stefan Osswald, Michael Kühne, Leo H. Bonati, for the Swiss-AF Investigators
Abstract
BACKGROUND: Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA 2 DS 2 -VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up. METHODS: Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA 2 DS 2 -VASc score. RESULTS: We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45–2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20–2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11–2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02–2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00–1.86]), and hFABP (heart-type fatty acid–binding protein; aOR, 0.48 [95% CI, 0.31–0.73]). Overall performance and discrimination of the new model was superior to that of the CHA 2 DS 2 -VASc score (C statistic, 0.82 [95% CI, 0.77–0.87] versus 0.64 [95% CI, 0.58–0.70]). CONCLUSIONS: In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures.