Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/20841
Title: Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.
Authors: Wilson, Duncan;Ambler, Gareth;Lee, Keon-Joo;Lim, Jae-Sung;Shiozawa, Masayuki;Koga, Masatoshi;Li, Linxin;Lovelock, Caroline;Chabriat, Hugues;Hennerici, Michael;Wong, Yuen Kwun;Srikanth, Velandai;Calvet, David;Jung, Simon;Kwa, Vincent I H;Engelter, Stefan T;Peters, Nils;Smith, Eric E;Yakushiji, Yusuke;Orken, Dilek Necioglu;Fazekas, Franz;Mok, Vincent;Thijs, Vincent N;Heo, Ji Hoe;Veltkamp, Roland;Ay, Hakan;Imaizumi, Toshio;Gomez-Anson, Beatriz;Lau, Kui Kai;Jouvent, Eric;Rothwell, Peter M;Toyoda, Kazunori;Bae, Hee-Joon;Mak, Henry Ka Fung;Marti-Fabregas, Joan;Werring, David J;Prats-Sánchez, Luis;Martínez-Domeño, Alejandro;Inamura, Shigeru;Yoshifuji, Kazuhisa;Arsava, Ethem Murat;Horstmann, Solveig;Purrucker, Jan;Lam, Bonnie Yin Ka;Wong, Adrian;Kim, Young Dae;Song, Tae-Jin;Schrooten, Maarten;Lemmens, Robin;Eppinger, Sebastian;Gattringer, Thomas;Uysal, Ender;Tanriverdi, Zeynep;Bornstein, Natan M;Assayag, Einor Ben;Hallevi, Hen;Tanaka, Jun;Hara, Hideo;Coutts, Shelagh B;Hert, Lisa;Polymeris, Alexandros;Seiffge, David J;Lyrer, Philippe;Algra, Ale;Kappelle, Jaap;Al-Shahi Salman, Rustam;Jäger, Hans R;Lip, Gregory Y H;Mattle, Heinrich P;Panos, Leonidas D;Mas, Jean-Louis;Legrand, Laurence;Karayiannis, Christopher;Phan, Thanh;Gunkel, Sarah;Christ, Nicolas;Abrigo, Jill;Leung, Thomas;Chu, Winnie;Chappell, Francesca;Makin, Stephen;Hayden, Derek;Williams, David J;Kooi, M Eline;van Dam-Nolen, Dianne H K;Barbato, Carmen;Browning, Simone;Wiegertjes, Kim;Tuladhar, Anil M;Maaijwee, Noortje;Guevarra, Christine;Yatawara, Chathuri;Mendyk, Anne-Marie;Delmaire, Christine;Köhler, Sebastian;van Oostenbrugge, Robert;Zhou, Ying;Xu, Chao;Hilal, Saima;Gyanwali, Bibek;Chen, Christopher;Lou, Min;Staals, Julie;Bordet, Régis;Kandiah, Nagaendran;de Leeuw, Frank-Erik;Simister, Robert;van der Lugt, Aad;Kelly, Peter J;Wardlaw, Joanna M;Soo, Yannie;Fluri, Felix
Affiliation: Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK
Unit of Neuroradiology, Hospital Santa Creu i Sant Pau, Universitat Autonoma, Barcelona, Spain
Centre for Prevention of Stroke and Dementia, University of Oxford, Oxford, UK
Department of Neuroradiology, Sainte-Anne Hospital, Paris Descartes University, INSERM U1266, Paris, France
Department of Neurology, University Hospital of Würzburg, Josef-Schneider Strasse 11, Würzburg, Germany
Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
The Neurovascular Research Unit and Health Research Board, Stroke Clinical Trials Network Ireland, University College Dublin, Dublin, Ireland
Department of Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; Beaumont Hospital Dublin, Ireland
Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, Netherlands
Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, University Medical Centre, Rotterdam, Netherlands
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Medical Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
Lucerne State Hospital; Switzerland Center for Neurology and Neurorehabilitation, Luzern, Switzerland
Department of Neurology, National Neuroscience Institute, Singapore, Singapore
University of Lille, Inserm, CHU de Lille, Degenerative and vascular cognitive disorders U1171, Lille, France
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
Department of Neurology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, Netherlands
Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
Department of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland; Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland
Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Diagnostic and Interventional Neuroradiology and Department of Neurology Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
New Zealand Brain Research Institute, Christchurch, New Zealand
Department of Neurology, Seoul National University Bundang Hospital, Seoul National University School of Medicine, Seongnam, South Korea
Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, Department of Neurology, Paris, France; Département Hospitalo-Universtaire NeuroVasc, University Paris Diderot, and INSERM U1141, Paris, France
Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany
Division of Neurology, Department of Medicine, The University of Hong Kong, Hong Kong
Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute, Barcelona, Spain
Department of Neurosurgery, Kushiro City General Hospital, Kushiro, Japan
Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA
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
Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
Department of Neurology, Ewha Womans University College of Medicine, Seoul, South Korea
Center for Brain and Disease Research, VIB, Leuven, Belgium
Experimental Neurology and Leuven Institute for Neuroscience and Disease, Katholieke Universiteit Leuven, University of Leuven, Laboratory of Neurobiology, Leuven, Belgium
Department of Neurology, Medical University of Graz, Graz, Austria
Department of Neurology, Demiroglu Bilim University, Istanbul, Turkey
Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Nabeshima, Saga, Japan
Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Department of Neurology and Stroke Centre, University Hospital Basel and University of Basel, Basel, Switzerland
Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands; Department of Neurology and Neurosurgery, Utrecht Stroke Centre, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands
Department of Neurology and Neurosurgery, Utrecht Stroke Centre, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands
Department of Diagnostic and Interventional Neuroradiology and Department of Neurology Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
Department of Neurology, Sainte-Anne Hospital, Paris Descartes University, INSERM U1266, Paris, France
Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
Department of Neurosciences, University Hospitals Leuven, Belgium
Department of Neurology, Austin Health, Heidelberg, Victoria, Australia
Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
Peninsula Clinical School, Peninsula Health, Monash University, Melbourne, VIC, Australia
Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK
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
Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK
Department of Statistical Science, University College London, London, UK
UK Dementia Institute at the University of Edinburgh, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK
Edinburgh Imaging, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK
Department of Stroke Medicine, Imperial College London, London, UK
Comprehensive Stroke Service, University College London Hospitals NHS Trust, London, UK
National Hospital for Neurology and Neurosurgery, London UK
Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, UK
Issue Date: 22-May-2019
EDate: 2019-07
Citation: The Lancet. Neurology 2019; 18(7): 653-665
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 [1·23-1·82]). 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20841
DOI: 10.1016/S1474-4422(19)30197-8
ORCID: 0000-0002-6614-8417
PubMed URL: 31130428
Type: Journal Article
Appears in Collections:Journal articles

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