Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies
Por:
Wilson, D, Ambler, G, Lee, KJ, Lim, JS, Shiozawa, M, Koga, M, Li, LX, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, TJ, Schrooten, M, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Salman, RAS, Jager, HR, Lip, GYH, Mattle, HP, Panos, LD, Mas, JL, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Kooi, ME, van Dam-Nolen, DHK, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, C, Yatawara, C, Mendyk, AM, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, FE, Simister, R, van der Lugt, A, Kelly, PJ, Wardlaw, JM, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, HJ, Marti-Fabregas, J, Werring, DJ, Microbleeds Int Collaborative Net
Publicada:
1 jul 2019
Resumen:
Background 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.
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 [149-1.80] 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. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
Filiaciones:
Wilson, D:
Natl Hosp Neurol & Neurosurg, London, England
New Zealand Brain Res Inst, Christchurch, New Zealand
Ambler, G:
UCL, Dept Stat Sci, London, England
Lee, KJ:
Seoul Natl Univ, Bundang Hosp, Dept Neurol, Sch Med, Seongnam, South Korea
Lim, JS:
Hallym Univ, Sacred Heart Hosp, Dept Neurol, Anyang, South Korea
Shiozawa, M:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Koga, M:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Li, LX:
Univ Oxford, Str Prevent Stroke & Dementia, Oxford, England
Lovelock, C:
Lariboisiere Hosp, AP HP, Dept Neurol, Paris, France
Chabriat, H:
Lariboisiere Hosp, AP HP, Dept Neurol, Paris, France
Univ Paris Diderot, Dept Hosp Univ NeuroVasc, Paris, France
INSERM U1141, Paris, France
Hennerici, M:
Univ Mannheim, Univ Heidelberg, Dept Neurol, Mannheim, Germany
Wong, YK:
Univ Hong Kong, Div Neurol, Dept Med, Hong Kong, Peoples R China
Mak, HKF:
Univ Hong Kong, Dept Diagnost Radiol, Hong Kong, Peoples R China
Prats-Sanchez, L:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Martinez-Domeno, A:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Inamura, S:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Japan
Yoshifuji, K:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Japan
Arsava, EM:
Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA
Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA
Horstmann, S:
Univ Heidelberg Hosp, Dept Neurol, Heidelberg, Germany
Purrucker, J:
Univ Heidelberg Hosp, Dept Neurol, Heidelberg, Germany
Lam, BYK:
Chinese Univ Hong Kong, Dept Med & Therapeut, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Therese Pei Fong Cho, Hong Kong, Peoples R China
Wong, A:
Chinese Univ Hong Kong, Dept Med & Therapeut, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Therese Pei Fong Cho, Hong Kong, Peoples R China
Kim, YD:
Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea
Song, TJ:
Ewha Womans Univ, Coll Med, Dept Neurol, Seoul, South Korea
Schrooten, M:
VIB, Ctr Brain & Dis Res, Leuven, Belgium
Lemmens, R:
Katholieke Univ Leuven, Univ Leuven, Lab Neurobiol, Leuven, Belgium
Eppinger, S:
Med Univ Graz, Dept Neurol, Graz, Austria
Gattringer, T:
Med Univ Graz, Dept Neurol, Graz, Austria
Uysal, E:
Demiroglu Bilim Univ, Dept Neurol, Istanbul, Turkey
Tanriverdi, Z:
Demiroglu Bilim Univ, Dept Neurol, Istanbul, Turkey
Bornstein, NM:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Ben Assayag, E:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Hallevi, H:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Tanaka, J:
Saga Univ, Fac Med, Div Neurol, Dept Internal Med, Saga, Japan
Hara, H:
Saga Univ, Fac Med, Div Neurol, Dept Internal Med, Saga, Japan
Coutts, SB:
Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci Radiol & Community Hlth Sci, Calgary Stroke Program, Calgary, AB, Canada
Hert, L:
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Polymeris, A:
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Seiffge, DJ:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Natl Hosp Neurol & Neurosurg, London, England
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Bern, Univ Hosp Bern, Dept Diagnost & Intervent Neuroradiol, Bern, Switzerland
Univ Bern, Univ Hosp Bern, Dept Neurol, Inselspital, Bern, Switzerland
Lyrer, P:
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Algra, A:
Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Utrecht Stroke Ctr, Utrecht, Netherlands
Univ Utrecht, Utrecht, Netherlands
Kappelle, J:
Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Utrecht Stroke Ctr, Utrecht, Netherlands
Univ Utrecht, Utrecht, Netherlands
Salman, RAS:
Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland
Jager, HR:
Natl Hosp Neurol & Neurosurg, London, England
UCL Inst Neurol, Dept Brain Repair & Rehabil, Lysholm Dept Neuroradiol, London, England
UCL Inst Neurol, Neuroradiol Acad Unit, London, England
Lip, GYH:
Univ Liverpool, Cardiovasc Sci, Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England
Aalborg Univ, Aalborg Thrombosis Res Unit, Dept Clin Med, Aalborg, Denmark
Mattle, HP:
Univ Bern, Univ Hosp Bern, Dept Diagnost & Intervent Neuroradiol, Bern, Switzerland
Univ Bern, Univ Hosp Bern, Dept Neurol, Inselspital, Bern, Switzerland
Panos, LD:
Univ Bern, Univ Hosp Bern, Dept Diagnost & Intervent Neuroradiol, Bern, Switzerland
Univ Bern, Univ Hosp Bern, Dept Neurol, Inselspital, Bern, Switzerland
Mas, JL:
Paris Descartes Univ, INSERM U1266, St Anne Hosp, Dept Neurol, Paris, France
Legrand, L:
Paris Descartes Univ, INSERM U1266, St Anne Hosp, Dept Neuroradiol, Paris, France
Karayiannis, C:
Peninsula Hlth, Peninsula Clin Sch, Melbourne, Vic, Australia
Phan, T:
Monash Univ, Stroke & Ageing Res Grp, Sch Clin Sci, Monash Hlth, Melbourne, Vic, Australia
Gunkel, S:
Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, Wurzburg, Germany
Christ, N:
Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, Wurzburg, Germany
Abrigo, J:
Chinese Univ Hong Kong, Dept Imaging & Intervent Radiol, Prince Wales Hosp, Hong Kong, Peoples R China
Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Peoples R China
Leung, T:
Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Peoples R China
Chu, W:
Chinese Univ Hong Kong, Dept Imaging & Intervent Radiol, Prince Wales Hosp, Hong Kong, Peoples R China
Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Peoples R China
Chappell, F:
Univ Edinburgh, Edinburgh Imaging, Edinburgh, Midlothian, Scotland
Univ Edinburgh, Sch Clin Sci, Edinburgh, Midlothian, Scotland
Makin, S:
Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
Hayden, D:
Univ Coll Dublin, Neurovasc Res Unit & Hlth Res Board, Stroke Clin Trials Network Ireland, Dublin, Ireland
Williams, DJ:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Royal Coll Surgeons Ireland, Dept Geriatr & Stroke Med, Dublin, Ireland
Beaumont Hosp, Dublin, Ireland
Kooi, ME:
Maastricht Univ, Med Ctr, Dept Radiol & Nucl Med, Maastricht, Netherlands
Maastricht Univ, Med Ctr, Dept Neurol, CARIM Sch Cardiovasc Dis, Maastricht, Netherlands
van Dam-Nolen, DHK:
Univ Med Ctr, Erasmus Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands
Barbato, C:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Natl Hosp Neurol & Neurosurg, London, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
Browning, S:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Natl Hosp Neurol & Neurosurg, London, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
Wiegertjes, K:
Radboud Univ Nijmegen, Donders Ctr Med Neurosci, Med Ctr, Dept Neurol,Donders Inst Brain Cognit & Behav,Don, Nijmegen, Netherlands
Tuladhar, AM:
Radboud Univ Nijmegen, Donders Ctr Med Neurosci, Med Ctr, Dept Neurol,Donders Inst Brain Cognit & Behav,Don, Nijmegen, Netherlands
Maaijwee, N:
Lucerne State Hosp, Luzern, Switzerland
Ctr Neurol & Neurorehabil, Luzern, Switzerland
Guevarra, C:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
Yatawara, C:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
Mendyk, AM:
Univ Lille, INSERM, CHU Lille, Degenerat & Vasc Cognit Disorders U1171, Lille, France
Delmaire, C:
Univ Lille, INSERM, CHU Lille, Degenerat & Vasc Cognit Disorders U1171, Lille, France
Kohler, S:
Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, Maastricht, Netherlands
van Oostenbrugge, R:
Maastricht Univ, Med Ctr, Dept Neurol, CARIM Sch Cardiovasc Dis, Maastricht, Netherlands
Zhou, Y:
Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou, Zhejiang, Peoples R China
Xu, C:
Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou, Zhejiang, Peoples R China
Hilal, S:
Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore, Singapore
Gyanwali, B:
Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore, Singapore
Chen, C:
Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore, Singapore
Lou, M:
Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou, Zhejiang, Peoples R China
Staals, J:
Maastricht Univ, Med Ctr, Dept Neurol, CARIM Sch Cardiovasc Dis, Maastricht, Netherlands
Bordet, R:
Univ Lille, INSERM, CHU Lille, Degenerat & Vasc Cognit Disorders U1171, Lille, France
Kandiah, N:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
de Leeuw, FE:
Radboud Univ Nijmegen, Donders Ctr Med Neurosci, Med Ctr, Dept Neurol,Donders Inst Brain Cognit & Behav,Don, Nijmegen, Netherlands
Simister, R:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Natl Hosp Neurol & Neurosurg, London, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
van der Lugt, A:
Univ Med Ctr, Erasmus Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands
Kelly, PJ:
Univ Coll Dublin, Neurovasc Res Unit & Hlth Res Board, Stroke Clin Trials Network Ireland, Dublin, Ireland
Wardlaw, JM:
Univ Edinburgh, Sch Clin Sci, Edinburgh, Midlothian, Scotland
Soo, Y:
Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Peoples R China
Fluri, F:
Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, Wurzburg, Germany
Srikanth, V:
Peninsula Hlth, Peninsula Clin Sch, Melbourne, Vic, Australia
Calvet, D:
Paris Descartes Univ, INSERM U1266, St Anne Hosp, Dept Neurol, Paris, France
Jung, S:
Univ Bern, Univ Hosp Bern, Dept Diagnost & Intervent Neuroradiol, Bern, Switzerland
Univ Bern, Univ Hosp Bern, Dept Neurol, Inselspital, Bern, Switzerland
Kwa, VIH:
Onze Lieve Vrouw Hosp, Dept Neurol, Amsterdam, Netherlands
Engelter, ST:
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Basel, Univ Dept Geriatr Med FELIX PLATTER, Neurol & Neurorehabil, Basel, Switzerland
Peters, N:
Univ Basel Hosp, Dept Neurol, Basel, Switzerland
Univ Basel Hosp, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Basel, Univ Dept Geriatr Med FELIX PLATTER, Neurol & Neurorehabil, Basel, Switzerland
Smith, EE:
Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci Radiol & Community Hlth Sci, Calgary Stroke Program, Calgary, AB, Canada
Yakushiji, Y:
Saga Univ, Fac Med, Div Neurol, Dept Internal Med, Saga, Japan
Orken, DN:
Demiroglu Bilim Univ, Dept Neurol, Istanbul, Turkey
Fazekas, F:
Med Univ Graz, Dept Neurol, Graz, Austria
Thijs, V:
Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Melbourne, Vic, Australia
Austin Hlth, Dept Neurol, Melbourne, Vic, Australia
Univ Hosp Leuven, Dept Neurosci, Leuven, Belgium
Heo, JH:
Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea
Mok, V:
Chinese Univ Hong Kong, Dept Med & Therapeut, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Therese Pei Fong Cho, Hong Kong, Peoples R China
Veltkamp, R:
Univ Heidelberg Hosp, Dept Neurol, Heidelberg, Germany
Imperial Coll London, Dept Stroke Med, London, England
Ay, H:
Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA
Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA
Imaizumi, T:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Japan
Gomez-Anson, B:
Univ Autonoma Barcelona, Unit Neuroradiol, Hosp Santa Creu & St Pau, Barcelona, Spain
Lau, KK:
Univ Hong Kong, Div Neurol, Dept Med, Hong Kong, Peoples R China
Jouvent, E:
Univ Paris Diderot, Dept Hosp Univ NeuroVasc, Paris, France
INSERM U1141, Paris, France
Rothwell, PM:
Univ Oxford, Str Prevent Stroke & Dementia, Oxford, England
Toyoda, K:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Bae, HJ:
Seoul Natl Univ, Bundang Hosp, Dept Neurol, Sch Med, Seongnam, South Korea
Marti-Fabregas, J:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Werring, DJ:
UCL Queen Sq Inst Neurol, Stroke Res Ctr, Dept Brain Repair & Rehabil, London WC1B 5EH, England
Green Published, Green Accepted, hybrid
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