Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack : a pooled analysis of individual patient data from cohort studies
Wilson, Duncan (New Zealand Brain Research Institute, Christchurch, New Zealand)
Ambler, Gareth (Department of Statistical Science, University College London, London, UK)
Lee, Keon-Joo (Department of Neurology, Seoul National University Bundang Hospital, Seoul National University School of Medicine, Seongnam, South Korea)
Lim, Jae-Sung (Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea)
Shiozawa, Masayuki (Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan)
Koga, Masatoshi (Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan)
Li, Linxin (University of Oxford. Centre for Prevention of Stroke and Dementia)
Lovelock, Caroline (University of Oxford. Centre for Prevention of Stroke and Dementia)
Chabriat, Hugues (Département Hospitalo-Universtaire NeuroVasc, University Paris Diderot, and INSERM U1141, Paris, France)
Hennerici, Michael (Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany)
Wong, Yuen Kwun (Division of Neurology, Department of Medicine, The University of Hong Kong, Hong Kong)
Mak, Henry Ka Fung (Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong)
Prats-Sánchez, Luis (Institut d'Investigació Biomèdica Sant Pau)
Martínez-Domeño, Alejandro (Institut d'Investigació Biomèdica Sant Pau)
Inamura, Shigeru (Department of Neurosurgery, Kushiro City General Hospital, Kushiro, Japan)
Yoshifuji, Kazuhisa (Department of Neurosurgery, Kushiro City General Hospital, Kushiro, Japan)
Arsava, Ethem Murat (Harvard Medical School)
Horstmann, Solveig (Heidelberg University Hospital (Alemanya))
Purrucker, Jan (Heidelberg University Hospital (Alemanya))
Lam, Bonnie Yin Ka (Therese Pei Fong Chow Research Centre for Prevention of Dementia)
Wong, Adrian (Therese Pei Fong Chow Research Centre for Prevention of Dementia, Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong)
Kim, Young Dae (Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea)
Song, Tae-Jin (Department of Neurology, Ewha Womans University College of Medicine, Seoul, South Korea)
Schrooten, Maarten (Center for Brain and Disease Research, VIB, Leuven, Belgium)
Lemmens, Robin (Experimental Neurology and Leuven Institute for Neuroscience and Disease, Katholieke Universiteit Leuven, University of Leuven, Laboratory of Neurobiology, Leuven, Belgium)
Eppinger, Sebastian (Department of Neurology, Medical University of Graz, Graz, Austria)
Gattringer, Thomas (Department of Neurology, Medical University of Graz, Graz, Austria)
Uysal, Ender (Department of Neurology, Demiroglu Bilim University, Istanbul, Turkey)
Tanriverdi, Zeynep (Department of Neurology, Demiroglu Bilim University, Istanbul, Turkey)
Bornstein, Natan M. (Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel)
Assayag, Einor Ben (Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel)
Hallevi, Hen (Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel)
Tanaka, Jun (Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Nabeshima, Saga, Japan)
Hara, Hideo (Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Nabeshima, Saga, Japan)
Coutts, Shelagh B. (Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada)
Hert, Lisa (Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland)
Polymeris, Alexandros (Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland)
Seiffge, David J. (Bern University Hospital)
Lyrer, Philippe (Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland)
Algra, Ale (Department of Neurology and Neurosurgery, Utrecht Stroke Centre, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands)
Kappelle, Jaap (Department of Neurology and Neurosurgery, Utrecht Stroke Centre, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands)
Al-Shahi Salman, Rustam (Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK)
Jäger, Hans Rolf (Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK)
Lip, Gregory Y H. (Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark)
Mattle, Heinrich P. (Bern University Hospital)
Panos, Leonidas D. (Bern University Hospital)
Mas, Jean-Louis (Department of Neurology, Sainte-Anne Hospital, Paris Descartes University, INSERM U1266, Paris, France)
Legrand, Laurence (Sainte-Anne Hospital, Paris Descartes University, INSERM U1266, Paris, France)
Karayiannis, Christopher (Peninsula Clinical School, Peninsula Health, Monash University, Melbourne, VIC, Australia)
Phan, Thanh (Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia)
Gunkel, Sarah (Department of Neurology, University Hospital of Würzburg, Josef-Schneider Strasse 11, Würzburg, Germany)
Christ, Nicolas (Department of Neurology, University Hospital of Würzburg, Josef-Schneider Strasse 11, Würzburg, Germany)
Abrigo, Jill (Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong)
Leung, Thomas (Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong)
Chu, Winnie (Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong)
Chappell, Francesca (UK Dementia Institute at the University of Edinburgh, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK)
Makin, Stephen (Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK)
Hayden, Derek (The Neurovascular Research Unit and Health Research Board, Stroke Clinical Trials Network Ireland, University College Dublin, Dublin, Ireland)
Williams, David J. (Beaumont Hospital (Dublín, Irlanda))
Kooi, M. Eline (Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, Netherlands)
van Dam-Nolen, Dianne H. K. (University Medical Centre (Rotterdam, Netherlands))
Barbato, Carmen (University College London Hospitals NHS Trust)
Browning, Simone (University College London Hospitals NHS Trust)
Wiegertjes, Kim (Radboud University Medical Centre. Department of Neurology)
Tuladhar, Anil M. (Radboud University Medical Center (Nijmegen, Països Baixos))
Maaijwee, Noortje (Lucerne State Hospital (Suïssa))
Guevarra, Christine (National Neuroscience Institute (Singapore))
Yatawara, Chathuri (National Neuroscience Institute (Singapore))
Mendyk, Anne-Marie (University of Lille)
Delmaire, Christine (University of Lille)
Köhler, Sebastian (Maastricht University. Department of Psychiatry and Neuropsychology)
van Oostenbrugge, Robert (Maastricht University Medical Centre)
Zhou, Ying (Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China)
Xu, Chao (Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China)
Hilal, Saima (National University Health System (Singapore))
Gyanwali, Bibek (National University Health System (Singapore))
Chen, Christopher (National University Health System (Singapore))
Lou, Min (Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China)
Staals, Julie (Department of Neurology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, Netherlands)
Bordet, Régis (University of Lille, Inserm, CHU de Lille, Degenerative and vascular cognitive disorders U1171, Lille, France)
Kandiah, Nagaendran (Department of Neurology, National Neuroscience Institute, Singapore, Singapore)
de Leeuw, Frank-Erik (Radboud University Medical Centre. Department of Neurology)
Simister, Robert (University College London Hospitals NHS Trust)
van der Lugt, Aad (Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, University Medical Centre, Rotterdam, Netherlands)
Kelly, Peter J. (The Neurovascular Research Unit and Health Research Board, Stroke Clinical Trials Network Ireland, University College Dublin, Dublin, Ireland)
Wardlaw, Joanna (University of Edinburgh. UK Dementia Institute)
Soo, Yannie (Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong)
Fluri, Felix (University Hospital of Würzburg (Würzburg, Alemanya))
Srikanth, Velandai (Peninsula Clinical School, Peninsula Health, Monash University, Melbourne, VIC, Australia)
Calvet, David (Department of Neurology, Sainte-Anne Hospital, Paris Descartes University, INSERM U1266, Paris, France)
Jung, Simon (Bern University Hospital)
Kwa, Vincent I H. (Department of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands)
Engelter, Stefan T. (Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland)
Peters, Nils (Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland)
Smith, Eric E. (Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada)
Yakushiji, Yusuke (Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Nabeshima, Saga, Japan)
Orken, Dilek Necioglu (Department of Neurology, Demiroglu Bilim University, Istanbul, Turkey)
Fazekas, Franz (Department of Neurology, Medical University of Graz, Graz, Austria)
Thijs, Vincent (University Hospitals Leuven (Bèlgica))
Heo, Ji Hoe (Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea)
Mok, Vincent (Therese Pei Fong Chow Research Centre for Prevention of Dementia, Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong)
Veltkamp, Roland (Heidelberg University Hospital (Alemanya))
Ay, Hakan (Harvard Medical School)
Imaizumi, Toshio (Department of Neurosurgery, Kushiro City General Hospital, Kushiro, Japan)
Gómez-Ansón, Beatriz (Institut d'Investigació Biomèdica Sant Pau)
Lau, Kui Kai (Division of Neurology, Department of Medicine, The University of Hong Kong, Hong Kong)
Jouvent, Eric (Département Hospitalo-Universtaire NeuroVasc, University Paris Diderot, and INSERM U1141, Paris, France)
Rothwell, Peter M. (University of Oxford. Centre for Prevention of Stroke and Dementia)
Toyoda, Kazunori (Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan)
Bae, Hee-Joon (Department of Neurology, Seoul National University Bundang Hospital, Seoul National University School of Medicine, Seongnam, South Korea)
Martí-Fàbregas, Joan (Institut d'Investigació Biomèdica Sant Pau)
Werring, David J. (Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, UK)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. British Heart Foundation and UK Stroke Association.
Note:	Altres ajuts: British Heart Foundation and UK Stroke Association.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	The Lancet neurology, Vol. 18 (july 2019) , p. 653-665, ISSN 1474-4465

DOI: 10.1016/S1474-4422(19)30197-8
PMID: 31130428

13 p, 818.2 KB

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