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 D Dittrich; Alexandros A Polymeris; Michael Coslovksy; Manuel R Blum; Nicolas Rodondi; Tobias Reichlin; Giorgio Moschovitis; Jens Wuerfel; Philippe A Lyrer; Urs Fischer; David Conen; Peter Kastner; André Ziegler; Stefan Osswald; Michael Kühne; Leo H Bonati; Swiss-AF Investigators

doi:10.1161/STROKEAHA.123.043302

Biomarker, Imaging, and Clinical Factors Associated With Overt and Covert Stroke in Patients With Atrial Fibrillation

Stroke. 2023 Oct;54(10):2542-2551. doi: 10.1161/STROKEAHA.123.043302. Epub 2023 Aug 7.

Authors

Gian Marco De Marchis^#^{1

2

3}, Philipp Krisai^#⁴, Laura Werlen², Tim Sinnecker^{1

5}, Stefanie Aeschbacher², Tolga D Dittrich^{1

2

3}, Alexandros A Polymeris¹, Michael Coslovksy^{2

4}, Manuel R Blum^{6

7}, Nicolas Rodondi^{6

7}, Tobias Reichlin⁸, Giorgio Moschovitis⁹, Jens Wuerfel⁵, Philippe A Lyrer^{1

2}, Urs Fischer^{1

2

10}, David Conen¹¹, Peter Kastner¹², André Ziegler¹², Stefan Osswald⁴, Michael Kühne^#¹³, Leo H Bonati^#^{1

2

14}; Swiss-AF Investigators

Affiliations

¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Switzerland (G.M.D.M., T.S., T.D.D., A.A.P., P.A.L., U.F., L.H.B.).
² Department of Clinical Research (G.M.D.M., L.W., S.A., T.D.D., M.C., P.A.L., U.F., L.H.B.), University of Basel, Switzerland.
³ Department of Neurology and Stroke Center, Kantonsspital St.Gallen, Switzerland (G.M.D.M., T.D.D.).
⁴ Cardiology Division, Department of Medicine, University Hospital Basel, Switzerland (P.K., M.C., S.O., M.K.).
⁵ Department of Biomedical Engineering, Medical Image Analysis Center AG and Qbig (T.S., J.W.), University of Basel, Switzerland.
⁶ Institute of Primary Health Care (BIHAM) (M.R.B., N.R.), University of Bern, Switzerland.
⁷ Department of General Internal Medicine, Inselspital, Bern University Hospital (M.R.B., N.R.), University of Bern, Switzerland.
⁸ Department of Cardiology, Inselspital, Bern University Hospital (T.R.), University of Bern, Switzerland.
⁹ Cardiology Division, Ente Ospedaliero Cantonale, Istituto Cardiocentro Ticino, Regional Hospital of Lugano, Switzerland (G.M.).
¹⁰ Department of Neurology, University Hospital Bern, Switzerland (U.F.).
¹¹ Population Health Research Institute, McMaster University, Hamilton, Canada (D.C.).
¹² Roche Diagnostics GmbH, Penzberg, Germany (P.K., A.Z.).
¹³ Cardiovascular Research Institute Basel, Switzerland (P.K., S.A., S.O., M.K.).
¹⁴ Rheinfelden Rehabilitation Clinic, Switzerland (L.H.B.).

^# Contributed equally.

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 CHA₂DS₂-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 CHA₂DS₂-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 CHA₂DS₂-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.

Keywords: brain; creatinine; humans; infarction; risk factors.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Anticoagulants / therapeutic use
Atrial Fibrillation* / complications
Atrial Fibrillation* / diagnostic imaging
Biomarkers
Cohort Studies
Humans
Prospective Studies
Risk Assessment
Risk Factors
Stroke* / diagnostic imaging
Stroke* / epidemiology
Stroke* / etiology

Substances

Biomarkers
Anticoagulants