Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.
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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, Mak Henry Ka Fung, 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, 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, Thijs Vincent, Heo Ji Hoe, Mok Vincent, Veltkamp Roland, Ay Hakan, Imaizumi Toshio, Gomez-Anson Beatriz, Lau Kui Kai, Jouvent Eric, Rothwell Peter M, Toyoda Kazunori, Bae Hee-Joon, Marti-Fabregas Joan, Werring David J, Microbleeds International Collaborative Network
Аннотация
METHODS: 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.
FINDINGS: 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).
INTERPRETATION: 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.
FUNDING: British Heart Foundation and UK Stroke Association.