Houwei Du1,2, Duncan Wilson2,3, Gareth Ambler4, Gargi Banerjee2, Clare Shakeshaft2, Hannah Cohen5, Tarek Yousry6, Rustam Al-Shahi Salman7, Gregory Y H Lip8,9, Henry Houlden10, Martin M Brown2, Keith W Muir11, Hans Rolf Jäger6, David J Werring2. 1. Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China (H.D.). 2. Department of Brain Repair and Rehabilitation, UCL Stroke Research Center (H.D., D.W., G.B., C.S., M.M.B., D.J.W.), UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London. 3. New Zealand Brain Research Institute, Christchurch (D.W.). 4. Department of Statistical Science (G.A.), University College London, United Kingdom. 5. Haemostasis Research Unit, Department of Haematology (H.C.), University College London, United Kingdom. 6. Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (T.Y., H.R.J.). 7. Center for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, United Kingdom (R.A.-S.S.). 8. Liverpool Center for Cardiovascular Science, University of Liverpool, Liverpool Heart and Chest Hospital, United Kingdom (G.Y.H.L.). 9. Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.). 10. Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, United Kingdom (H.H.). 11. Department of Molecular Neuroscience (K.W.M.), UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London.
Abstract
BACKGROUND AND PURPOSE: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. METHODS: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score. RESULTS: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60-3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59-1.62) in those without SVD (P=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01-3.53]; P=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04-1.70]; P=0.023). CONCLUSIONS: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.
BACKGROUND AND PURPOSE: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. METHODS: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score. RESULTS: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60-3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59-1.62) in those without SVD (P=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01-3.53]; P=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04-1.70]; P=0.023). CONCLUSIONS: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.
Entities:
Keywords:
anticoagulation; atrial fibrillation; brain; ischemic attack, transient; white matter
Authors: Alexandros A Polymeris; Thomas R Meinel; Jan C Purrucker; David J Seiffge; Hannah Oehler; Kyra Hölscher; Annaelle Zietz; Jan F Scheitz; Christian H Nolte; Christoph Stretz; Shadi Yaghi; Svenja Stoll; Ruihao Wang; Karl Georg Häusler; Simon Hellwig; Markus G Klammer; Simon Litmeier; Christopher R Leon Guerrero; Iman Moeini-Naghani; Patrik Michel; Davide Strambo; Alexander Salerno; Giovanni Bianco; Carlo Cereda; Timo Uphaus; Klaus Gröschel; Mira Katan; Susanne Wegener; Nils Peters; Stefan T Engelter; Philippe A Lyrer; Leo H Bonati; Lorenz Grunder; Peter Arthur Ringleb; Urs Fischer; Bernd Kallmünzer Journal: J Neurol Neurosurg Psychiatry Date: 2022-04-08 Impact factor: 13.654
Authors: Alexandros A Polymeris; Kosmas Macha; Maurizio Paciaroni; Duncan Wilson; Masatoshi Koga; Manuel Cappellari; Sabine Schaedelin; Annaelle Zietz; Nils Peters; David J Seiffge; David Haupenthal; Luise Gassmann; Gian Marco De Marchis; Ruihao Wang; Henrik Gensicke; Svenja Stoll; Sebastian Thilemann; Nikolaos S Avramiotis; Bruno Bonetti; Georgios Tsivgoulis; Gareth Ambler; Andrea Alberti; Sohei Yoshimura; Martin M Brown; Masayuki Shiozawa; Gregory Y H Lip; Michele Venti; Monica Acciarresi; Kanta Tanaka; Maria Giulia Mosconi; Masahito Takagi; Rolf H Jäger; Keith Muir; Manabu Inoue; Stefan Schwab; Leo H Bonati; Philippe A Lyrer; Kazunori Toyoda; Valeria Caso; David J Werring; Bernd Kallmünzer; Stefan T Engelter Journal: Ann Neurol Date: 2021-11-29 Impact factor: 11.274