Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Duncan Wilson, Gareth Ambler, Keon Joo Lee, Jae Sung Lim, Masayuki Shiozawa, Masatoshi Koga, Linxin Li, Caroline Lovelock, Hugues Chabriat, Michael Hennerici, Yuen Kwun Wong, Henry Ka Fung Mak, Luis Prats-Sánchez, Alejandro Martínez-Domeño, Shigeru Inamura, Kazuhisa Yoshifuji, Ethem Murat Arsava, Solveig Horstmann, Jan Purrucker, Bonnie Yin Ka LamAdrian Wong, Young Dae Kim, Tae Jin Song, Maarten Schrooten, Robin Lemmens, Sebastian Eppinger, Thomas Gattringer, Ender Uysal, Zeynep Tanriverdi, Natan M. Bornstein, Einor Ben Assayag, Hen Hallevi, Jun Tanaka, Hideo Hara, Shelagh B. Coutts, Lisa Hert, Alexandros Polymeris, David J. Seiffge, Philippe Lyrer, Ale Algra, Jaap Kappelle, Rustam Al-Shahi Salman, Hans R. Jäger, Gregory Y.H. Lip, Heinrich P. Mattle, Leonidas D. Panos, Jean Louis Mas, Laurence Legrand, Christopher Karayiannis, Thanh Phan, Sarah Gunkel, Nicolas Christ, Jill Abrigo, Thomas Leung, Winnie Chu, Francesca Chappell, Stephen Makin, Derek Hayden, David J. Williams, M. Eline Kooi, Dianne H.K. van Dam-Nolen, Carmen Barbato, Simone Browning, Kim Wiegertjes, Anil M. Tuladhar, Noortje Maaijwee, Christine Guevarra, Chathuri Yatawara, Anne Marie Mendyk, Christine Delmaire, Sebastian Köhler, Robert van Oostenbrugge, Ying Zhou, Chao Xu, Saima Hilal, Bibek Gyanwali, Christopher Chen, Min Lou, Julie Staals, Régis Bordet, Nagaendran Kandiah, Frank Erik de Leeuw, Robert Simister, Aad van der Lugt, Peter J. Kelly, Joanna M. Wardlaw, Yannie Soo, Felix Fluri, Velandai Srikanth, David Calvet, Simon Jung, Vincent I.H. Kwa, Stefan T. Engelter, Nils Peters, Eric E. Smith, Yusuke Yakushiji, Dilek Necioglu Orken, Franz Fazekas, Vincent Thijs, Ji Hoe Heo, Vincent Mok, Roland Veltkamp, Hakan Ay, Toshio Imaizumi, Beatriz Gomez-Anson, Kui Kai Lau, Eric Jouvent, Peter M. Rothwell, Kazunori Toyoda, Hee Joon Bae, Joan Marti-Fabregas, David J. Werring, Kirsty Harkness, Louise Shaw, Jane Sword, Azlisham Mohd Nor, Pankaj Sharma, Deborah Kelly, Frances Harrington, Marc Randall, Matthew Smith, Karim Mahawish, Abduelbaset Elmarim, Bernard Esisi, Claire Cullen, Arumug Nallasivam, Christopher Price, Adrian Barry, Christine Roffe, John Coyle, Ahamad Hassan, Jonathan Birns, David Cohen, Lakshmanan Sekaran, Adrian Parry-Jones, Anthea Parry, David Hargroves, Harald Proschel, Prabel Datta, Khaled Darawil, Aravindakshan Manoj, Mathew Burn, Chris Patterson, Elio Giallombardo, Nigel Smyth, Syed Mansoor, Ijaz Anwar, Rachel Marsh, Sissi Ispoglou, Dinesh Chadha, Mathuri Prabhakaran, Sanjeevikumar Meenakishundaram, Janice O'Connell, Jon Scott, Vinodh Krishnamurthy, Prasanna Aghoram, Michael McCormick, Nikola Sprigg, Paul O'Mahony, Martin Cooper, Lillian Choy, Peter Wilkinson, Simon Leach, Sarah Caine, Ilse Burger, Gunaratam Gunathilagan, Paul Guyler, Hedley Emsley, Michelle Davis, Dulka Manawadu, Kath Pasco, Maam Mamun, Robert Luder, Mahmud Sajid, James Okwera, Elizabeth Warburton, Kari Saastamoinen, Timothy England, Janet Putterill, Enrico Flossman, Michael Power, Krishna Dani, David Mangion, Appu Suman, John Corrigan, Enas Lawrence, Djamil Vahidassr, Clare Shakeshaft, Martin Brown, Andreas Charidimou, Hannah Cohen, Gargi Banerjee, Henry Houlden, Mark White, Tarek Yousry, Enrico Flossmann, Keith Muir, Marwan El-Koussy, Pascal Gratz, Jeremy Molad, Amos Korczyn, Efrat Kliper, Philippe Maeder, Achim Gass, Chahin Pachai, Luc Bracoub, Marie Yvonne Douste-Blazy, Marie Dominique Fratacci, Eric Vicaut, Shoichiro Sato, Kaori Miwa, Kyohei Fujita, Toshihiro Ide, Henry Ma, John Ly, Shahoo Singhal, Ronil Chandra, Lee Anne Slater, Cathy Soufan, Christopher Moran, Christopher Traenka, Sebastian Thilemann, Joachim Fladt, Henrik Gensicke, Leo Bonati, Beom Joon Kim, Moon Ku Han, Jihoon Kang, Eunbin Ko, Mi Hwa Yang, Myung Suk Jang, Sean Murphy, Fiona Carty, Layan Akijian, John Thornton, Mark Schembri, Elles Douven, Raquel Delgado-Mederos;, Rebeca Marín, Pol Camps-Renom, Daniel Guisado-Alonso, Fidel Nuñez, Santiago Medrano-Martorell, Elisa Merino, Kotaro Iida, Syuhei Ikeda, Masashi Nishihara, Hiroyuki Irie, Derya Selcuk Demirelli, Jayesh Modi Medanta, Charlotte Zerna, Maria Valdés Hernández, Paul Armitage, Anna Heye, Susana Muñoz-Maniega, Eleni Sakka, Michael Thrippleton, Martin Dennis, Ysoline Beigneux, Mauro Silva, Narayanaswamy Venketasubramanian, Shu Leung Ho, Raymond Tak Fai Cheung, Koon Ho Chan, Kay Cheong Teo, Edward Hui, Joseph Shiu Kwong Kwan, Richard Chang, Man Yu Tse, Chu Peng Hoi, Chung Yan Chan, Oi Ling Chan, Ryan Hoi Kit Cheung, Edmund Ka Ming Wong, Kam Tat Leung, Suk Fung Tsang, Hing Lung Ip, Sze Ho Ma, Karen Ma, Wing Chi Fong, Siu Hung Li, Richard Li, Ping Wing Ng, Kwok Kui Wong, Wenyan Liu, Lawrence Wong, Lino Ramos, Els De Schryver, Joost Jöbsis, Jaap van der Sande, Paul Brouwers, Yvo Roos, Jan Stam, Stef Bakker, Henk Verbiest, Wouter Schoonewille, Cisca Linn, Leopold Hertzberger, Maarten van Gemert, Paul Berntsen, Jeroen Hendrikse, Paul Nederkoorn, Werner Mess, Peter Koudstaal, Alexander Leff, Nicholas Ward, Parashkev Nachev, Richard Perry, Hatice Ozkan, John Mitchell

Research output: Contribution to journalArticle

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Abstract

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 [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.

Original languageEnglish
Pages (from-to)653-665
Number of pages13
JournalThe Lancet Neurology
Volume18
Issue number7
DOIs
Publication statusPublished - 2019 Jul

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Transient Ischemic Attack
Cohort Studies
Stroke
Intracranial Hemorrhages

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

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. ; Harkness, Kirsty ; Shaw, Louise ; Sword, Jane ; Mohd Nor, Azlisham ; Sharma, Pankaj ; Kelly, Deborah ; Harrington, Frances ; Randall, Marc ; Smith, Matthew ; Mahawish, Karim ; Elmarim, Abduelbaset ; Esisi, Bernard ; Cullen, Claire ; Nallasivam, Arumug ; Price, Christopher ; Barry, Adrian ; Roffe, Christine ; Coyle, John ; Hassan, Ahamad ; Birns, Jonathan ; Cohen, David ; Sekaran, Lakshmanan ; Parry-Jones, Adrian ; Parry, Anthea ; Hargroves, David ; Proschel, Harald ; Datta, Prabel ; Darawil, Khaled ; Manoj, Aravindakshan ; Burn, Mathew ; Patterson, Chris ; Giallombardo, Elio ; Smyth, Nigel ; Mansoor, Syed ; Anwar, Ijaz ; Marsh, Rachel ; Ispoglou, Sissi ; Chadha, Dinesh ; Prabhakaran, Mathuri ; Meenakishundaram, Sanjeevikumar ; O'Connell, Janice ; Scott, Jon ; Krishnamurthy, Vinodh ; Aghoram, Prasanna ; McCormick, Michael ; Sprigg, Nikola ; O'Mahony, Paul ; Cooper, Martin ; Choy, Lillian ; Wilkinson, Peter ; Leach, Simon ; Caine, Sarah ; Burger, Ilse ; Gunathilagan, Gunaratam ; Guyler, Paul ; Emsley, Hedley ; Davis, Michelle ; Manawadu, Dulka ; Pasco, Kath ; Mamun, Maam ; Luder, Robert ; Sajid, Mahmud ; Okwera, James ; Warburton, Elizabeth ; Saastamoinen, Kari ; England, Timothy ; Putterill, Janet ; Flossman, Enrico ; Power, Michael ; Dani, Krishna ; Mangion, David ; Suman, Appu ; Corrigan, John ; Lawrence, Enas ; Vahidassr, Djamil ; Shakeshaft, Clare ; Brown, Martin ; Charidimou, Andreas ; Cohen, Hannah ; Banerjee, Gargi ; Houlden, Henry ; White, Mark ; Yousry, Tarek ; Flossmann, Enrico ; Muir, Keith ; El-Koussy, Marwan ; Gratz, Pascal ; Molad, Jeremy ; Korczyn, Amos ; Kliper, Efrat ; Maeder, Philippe ; Gass, Achim ; Pachai, Chahin ; Bracoub, Luc ; Douste-Blazy, Marie Yvonne ; Fratacci, Marie Dominique ; Vicaut, Eric ; Sato, Shoichiro ; Miwa, Kaori ; Fujita, Kyohei ; Ide, Toshihiro ; Ma, Henry ; Ly, John ; Singhal, Shahoo ; Chandra, Ronil ; Slater, Lee Anne ; Soufan, Cathy ; Moran, Christopher ; Traenka, Christopher ; Thilemann, Sebastian ; Fladt, Joachim ; Gensicke, Henrik ; Bonati, Leo ; Kim, Beom Joon ; Han, Moon Ku ; Kang, Jihoon ; Ko, Eunbin ; Yang, Mi Hwa ; Jang, Myung Suk ; Murphy, Sean ; Carty, Fiona ; Akijian, Layan ; Thornton, John ; Schembri, Mark ; Douven, Elles ; Delgado-Mederos;, Raquel ; Marín, Rebeca ; Camps-Renom, Pol ; Guisado-Alonso, Daniel ; Nuñez, Fidel ; Medrano-Martorell, Santiago ; Merino, Elisa ; Iida, Kotaro ; Ikeda, Syuhei ; Nishihara, Masashi ; Irie, Hiroyuki ; Demirelli, Derya Selcuk ; Medanta, Jayesh Modi ; Zerna, Charlotte ; Hernández, Maria Valdés ; Armitage, Paul ; Heye, Anna ; Muñoz-Maniega, Susana ; Sakka, Eleni ; Thrippleton, Michael ; Dennis, Martin ; Beigneux, Ysoline ; Silva, Mauro ; Venketasubramanian, Narayanaswamy ; Ho, Shu Leung ; Cheung, Raymond Tak Fai ; Chan, Koon Ho ; Teo, Kay Cheong ; Hui, Edward ; Kwan, Joseph Shiu Kwong ; Chang, Richard ; Tse, Man Yu ; Hoi, Chu Peng ; Chan, Chung Yan ; Chan, Oi Ling ; Cheung, Ryan Hoi Kit ; Wong, Edmund Ka Ming ; Leung, Kam Tat ; Tsang, Suk Fung ; Ip, Hing Lung ; Ma, Sze Ho ; Ma, Karen ; Fong, Wing Chi ; Li, Siu Hung ; Li, Richard ; Ng, Ping Wing ; Wong, Kwok Kui ; Liu, Wenyan ; Wong, Lawrence ; Ramos, Lino ; De Schryver, Els ; Jöbsis, Joost ; van der Sande, Jaap ; Brouwers, Paul ; Roos, Yvo ; Stam, Jan ; Bakker, Stef ; Verbiest, Henk ; Schoonewille, Wouter ; Linn, Cisca ; Hertzberger, Leopold ; van Gemert, Maarten ; Berntsen, Paul ; Hendrikse, Jeroen ; Nederkoorn, Paul ; Mess, Werner ; Koudstaal, Peter ; Leff, Alexander ; Ward, Nicholas ; Nachev, Parashkev ; Perry, Richard ; Ozkan, Hatice ; Mitchell, John. / Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack : a pooled analysis of individual patient data from cohort studies. In: The Lancet Neurology. 2019 ; Vol. 18, No. 7. pp. 653-665.
@article{9069017bc8504a0785be86ae6ddd6775,
title = "Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies",
abstract = "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 [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.",
author = "Duncan Wilson and Gareth Ambler and Lee, {Keon Joo} and Lim, {Jae Sung} and Masayuki Shiozawa and Masatoshi Koga and Linxin Li and Caroline Lovelock and Hugues Chabriat and Michael Hennerici and Wong, {Yuen Kwun} and Mak, {Henry Ka Fung} and Luis Prats-S{\'a}nchez and Alejandro Mart{\'i}nez-Dome{\~n}o and Shigeru Inamura and Kazuhisa Yoshifuji and Arsava, {Ethem Murat} and Solveig Horstmann and Jan Purrucker and Lam, {Bonnie Yin Ka} and Adrian Wong and Kim, {Young Dae} and Song, {Tae Jin} and Maarten Schrooten and Robin Lemmens and Sebastian Eppinger and Thomas Gattringer and Ender Uysal and Zeynep Tanriverdi and Bornstein, {Natan M.} and Assayag, {Einor Ben} and Hen Hallevi and Jun Tanaka and Hideo Hara and Coutts, {Shelagh B.} and Lisa Hert and Alexandros Polymeris and Seiffge, {David J.} and Philippe Lyrer and Ale Algra and Jaap Kappelle and {Al-Shahi Salman}, Rustam and J{\"a}ger, {Hans R.} and Lip, {Gregory Y.H.} and Mattle, {Heinrich P.} and Panos, {Leonidas D.} and Mas, {Jean Louis} and Laurence Legrand and Christopher Karayiannis and Thanh Phan and Sarah Gunkel and Nicolas Christ and Jill Abrigo and Thomas Leung and Winnie Chu and Francesca Chappell and Stephen Makin and Derek Hayden and Williams, {David J.} and Kooi, {M. Eline} and {van Dam-Nolen}, {Dianne H.K.} and Carmen Barbato and Simone Browning and Kim Wiegertjes and Tuladhar, {Anil M.} and Noortje Maaijwee and Christine Guevarra and Chathuri Yatawara and Mendyk, {Anne Marie} and Christine Delmaire and Sebastian K{\"o}hler and {van Oostenbrugge}, Robert and Ying Zhou and Chao Xu and Saima Hilal and Bibek Gyanwali and Christopher Chen and Min Lou and Julie Staals and R{\'e}gis Bordet and Nagaendran Kandiah and {de Leeuw}, {Frank Erik} and Robert Simister and {van der Lugt}, Aad and Kelly, {Peter J.} and Wardlaw, {Joanna M.} and Yannie Soo and Felix Fluri and Velandai Srikanth and David Calvet and Simon Jung and Kwa, {Vincent I.H.} and Engelter, {Stefan T.} and Nils Peters and Smith, {Eric E.} and Yusuke Yakushiji and Orken, {Dilek Necioglu} and Franz Fazekas and Vincent Thijs and Heo, {Ji Hoe} and Vincent Mok and Roland Veltkamp and Hakan Ay and Toshio Imaizumi and Beatriz Gomez-Anson and Lau, {Kui Kai} and Eric Jouvent and Rothwell, {Peter M.} and Kazunori Toyoda and Bae, {Hee Joon} and Joan Marti-Fabregas and Werring, {David J.} and Kirsty Harkness and Louise Shaw and Jane Sword and {Mohd Nor}, Azlisham and Pankaj Sharma and Deborah Kelly and Frances Harrington and Marc Randall and Matthew Smith and Karim Mahawish and Abduelbaset Elmarim and Bernard Esisi and Claire Cullen and Arumug Nallasivam and Christopher Price and Adrian Barry and Christine Roffe and John Coyle and Ahamad Hassan and Jonathan Birns and David Cohen and Lakshmanan Sekaran and Adrian Parry-Jones and Anthea Parry and David Hargroves and Harald Proschel and Prabel Datta and Khaled Darawil and Aravindakshan Manoj and Mathew Burn and Chris Patterson and Elio Giallombardo and Nigel Smyth and Syed Mansoor and Ijaz Anwar and Rachel Marsh and Sissi Ispoglou and Dinesh Chadha and Mathuri Prabhakaran and Sanjeevikumar Meenakishundaram and Janice O'Connell and Jon Scott and Vinodh Krishnamurthy and Prasanna Aghoram and Michael McCormick and Nikola Sprigg and Paul O'Mahony and Martin Cooper and Lillian Choy and Peter Wilkinson and Simon Leach and Sarah Caine and Ilse Burger and Gunaratam Gunathilagan and Paul Guyler and Hedley Emsley and Michelle Davis and Dulka Manawadu and Kath Pasco and Maam Mamun and Robert Luder and Mahmud Sajid and James Okwera and Elizabeth Warburton and Kari Saastamoinen and Timothy England and Janet Putterill and Enrico Flossman and Michael Power and Krishna Dani and David Mangion and Appu Suman and John Corrigan and Enas Lawrence and Djamil Vahidassr and Clare Shakeshaft and Martin Brown and Andreas Charidimou and Hannah Cohen and Gargi Banerjee and Henry Houlden and Mark White and Tarek Yousry and Enrico Flossmann and Keith Muir and Marwan El-Koussy and Pascal Gratz and Jeremy Molad and Amos Korczyn and Efrat Kliper and Philippe Maeder and Achim Gass and Chahin Pachai and Luc Bracoub and Douste-Blazy, {Marie Yvonne} and Fratacci, {Marie Dominique} and Eric Vicaut and Shoichiro Sato and Kaori Miwa and Kyohei Fujita and Toshihiro Ide and Henry Ma and John Ly and Shahoo Singhal and Ronil Chandra and Slater, {Lee Anne} and Cathy Soufan and Christopher Moran and Christopher Traenka and Sebastian Thilemann and Joachim Fladt and Henrik Gensicke and Leo Bonati and Kim, {Beom Joon} and Han, {Moon Ku} and Jihoon Kang and Eunbin Ko and Yang, {Mi Hwa} and Jang, {Myung Suk} and Sean Murphy and Fiona Carty and Layan Akijian and John Thornton and Mark Schembri and Elles Douven and Raquel Delgado-Mederos; and Rebeca Mar{\'i}n and Pol Camps-Renom and Daniel Guisado-Alonso and Fidel Nu{\~n}ez and Santiago Medrano-Martorell and Elisa Merino and Kotaro Iida and Syuhei Ikeda and Masashi Nishihara and Hiroyuki Irie and Demirelli, {Derya Selcuk} and Medanta, {Jayesh Modi} and Charlotte Zerna and Hern{\'a}ndez, {Maria Vald{\'e}s} and Paul Armitage and Anna Heye and Susana Mu{\~n}oz-Maniega and Eleni Sakka and Michael Thrippleton and Martin Dennis and Ysoline Beigneux and Mauro Silva and Narayanaswamy Venketasubramanian and Ho, {Shu Leung} and Cheung, {Raymond Tak Fai} and Chan, {Koon Ho} and Teo, {Kay Cheong} and Edward Hui and Kwan, {Joseph Shiu Kwong} and Richard Chang and Tse, {Man Yu} and Hoi, {Chu Peng} and Chan, {Chung Yan} and Chan, {Oi Ling} and Cheung, {Ryan Hoi Kit} and Wong, {Edmund Ka Ming} and Leung, {Kam Tat} and Tsang, {Suk Fung} and Ip, {Hing Lung} and Ma, {Sze Ho} and Karen Ma and Fong, {Wing Chi} and Li, {Siu Hung} and Richard Li and Ng, {Ping Wing} and Wong, {Kwok Kui} and Wenyan Liu and Lawrence Wong and Lino Ramos and {De Schryver}, Els and Joost J{\"o}bsis and {van der Sande}, Jaap and Paul Brouwers and Yvo Roos and Jan Stam and Stef Bakker and Henk Verbiest and Wouter Schoonewille and Cisca Linn and Leopold Hertzberger and {van Gemert}, Maarten and Paul Berntsen and Jeroen Hendrikse and Paul Nederkoorn and Werner Mess and Peter Koudstaal and Alexander Leff and Nicholas Ward and Parashkev Nachev and Richard Perry and Hatice Ozkan and John Mitchell",
year = "2019",
month = "7",
doi = "10.1016/S1474-4422(19)30197-8",
language = "English",
volume = "18",
pages = "653--665",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "7",

}

Wilson, D, Ambler, G, Lee, KJ, Lim, JS, Shiozawa, M, Koga, M, Li, L, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sánchez, L, Martínez-Domeño, 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, Assayag, EB, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Al-Shahi Salman, R, Jäger, 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, Köhler, 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, Harkness, K, Shaw, L, Sword, J, Mohd Nor, A, Sharma, P, Kelly, D, Harrington, F, Randall, M, Smith, M, Mahawish, K, Elmarim, A, Esisi, B, Cullen, C, Nallasivam, A, Price, C, Barry, A, Roffe, C, Coyle, J, Hassan, A, Birns, J, Cohen, D, Sekaran, L, Parry-Jones, A, Parry, A, Hargroves, D, Proschel, H, Datta, P, Darawil, K, Manoj, A, Burn, M, Patterson, C, Giallombardo, E, Smyth, N, Mansoor, S, Anwar, I, Marsh, R, Ispoglou, S, Chadha, D, Prabhakaran, M, Meenakishundaram, S, O'Connell, J, Scott, J, Krishnamurthy, V, Aghoram, P, McCormick, M, Sprigg, N, O'Mahony, P, Cooper, M, Choy, L, Wilkinson, P, Leach, S, Caine, S, Burger, I, Gunathilagan, G, Guyler, P, Emsley, H, Davis, M, Manawadu, D, Pasco, K, Mamun, M, Luder, R, Sajid, M, Okwera, J, Warburton, E, Saastamoinen, K, England, T, Putterill, J, Flossman, E, Power, M, Dani, K, Mangion, D, Suman, A, Corrigan, J, Lawrence, E, Vahidassr, D, Shakeshaft, C, Brown, M, Charidimou, A, Cohen, H, Banerjee, G, Houlden, H, White, M, Yousry, T, Flossmann, E, Muir, K, El-Koussy, M, Gratz, P, Molad, J, Korczyn, A, Kliper, E, Maeder, P, Gass, A, Pachai, C, Bracoub, L, Douste-Blazy, MY, Fratacci, MD, Vicaut, E, Sato, S, Miwa, K, Fujita, K, Ide, T, Ma, H, Ly, J, Singhal, S, Chandra, R, Slater, LA, Soufan, C, Moran, C, Traenka, C, Thilemann, S, Fladt, J, Gensicke, H, Bonati, L, Kim, BJ, Han, MK, Kang, J, Ko, E, Yang, MH, Jang, MS, Murphy, S, Carty, F, Akijian, L, Thornton, J, Schembri, M, Douven, E, Delgado-Mederos;, R, Marín, R, Camps-Renom, P, Guisado-Alonso, D, Nuñez, F, Medrano-Martorell, S, Merino, E, Iida, K, Ikeda, S, Nishihara, M, Irie, H, Demirelli, DS, Medanta, JM, Zerna, C, Hernández, MV, Armitage, P, Heye, A, Muñoz-Maniega, S, Sakka, E, Thrippleton, M, Dennis, M, Beigneux, Y, Silva, M, Venketasubramanian, N, Ho, SL, Cheung, RTF, Chan, KH, Teo, KC, Hui, E, Kwan, JSK, Chang, R, Tse, MY, Hoi, CP, Chan, CY, Chan, OL, Cheung, RHK, Wong, EKM, Leung, KT, Tsang, SF, Ip, HL, Ma, SH, Ma, K, Fong, WC, Li, SH, Li, R, Ng, PW, Wong, KK, Liu, W, Wong, L, Ramos, L, De Schryver, E, Jöbsis, J, van der Sande, J, Brouwers, P, Roos, Y, Stam, J, Bakker, S, Verbiest, H, Schoonewille, W, Linn, C, Hertzberger, L, van Gemert, M, Berntsen, P, Hendrikse, J, Nederkoorn, P, Mess, W, Koudstaal, P, Leff, A, Ward, N, Nachev, P, Perry, R, Ozkan, H & Mitchell, J 2019, 'Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies', The Lancet Neurology, vol. 18, no. 7, pp. 653-665. https://doi.org/10.1016/S1474-4422(19)30197-8

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack : a pooled analysis of individual patient data from cohort studies. / 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.; Harkness, Kirsty; Shaw, Louise; Sword, Jane; Mohd Nor, Azlisham; Sharma, Pankaj; Kelly, Deborah; Harrington, Frances; Randall, Marc; Smith, Matthew; Mahawish, Karim; Elmarim, Abduelbaset; Esisi, Bernard; Cullen, Claire; Nallasivam, Arumug; Price, Christopher; Barry, Adrian; Roffe, Christine; Coyle, John; Hassan, Ahamad; Birns, Jonathan; Cohen, David; Sekaran, Lakshmanan; Parry-Jones, Adrian; Parry, Anthea; Hargroves, David; Proschel, Harald; Datta, Prabel; Darawil, Khaled; Manoj, Aravindakshan; Burn, Mathew; Patterson, Chris; Giallombardo, Elio; Smyth, Nigel; Mansoor, Syed; Anwar, Ijaz; Marsh, Rachel; Ispoglou, Sissi; Chadha, Dinesh; Prabhakaran, Mathuri; Meenakishundaram, Sanjeevikumar; O'Connell, Janice; Scott, Jon; Krishnamurthy, Vinodh; Aghoram, Prasanna; McCormick, Michael; Sprigg, Nikola; O'Mahony, Paul; Cooper, Martin; Choy, Lillian; Wilkinson, Peter; Leach, Simon; Caine, Sarah; Burger, Ilse; Gunathilagan, Gunaratam; Guyler, Paul; Emsley, Hedley; Davis, Michelle; Manawadu, Dulka; Pasco, Kath; Mamun, Maam; Luder, Robert; Sajid, Mahmud; Okwera, James; Warburton, Elizabeth; Saastamoinen, Kari; England, Timothy; Putterill, Janet; Flossman, Enrico; Power, Michael; Dani, Krishna; Mangion, David; Suman, Appu; Corrigan, John; Lawrence, Enas; Vahidassr, Djamil; Shakeshaft, Clare; Brown, Martin; Charidimou, Andreas; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark; Yousry, Tarek; Flossmann, Enrico; Muir, Keith; El-Koussy, Marwan; Gratz, Pascal; Molad, Jeremy; Korczyn, Amos; Kliper, Efrat; Maeder, Philippe; Gass, Achim; Pachai, Chahin; Bracoub, Luc; Douste-Blazy, Marie Yvonne; Fratacci, Marie Dominique; Vicaut, Eric; Sato, Shoichiro; Miwa, Kaori; Fujita, Kyohei; Ide, Toshihiro; Ma, Henry; Ly, John; Singhal, Shahoo; Chandra, Ronil; Slater, Lee Anne; Soufan, Cathy; Moran, Christopher; Traenka, Christopher; Thilemann, Sebastian; Fladt, Joachim; Gensicke, Henrik; Bonati, Leo; Kim, Beom Joon; Han, Moon Ku; Kang, Jihoon; Ko, Eunbin; Yang, Mi Hwa; Jang, Myung Suk; Murphy, Sean; Carty, Fiona; Akijian, Layan; Thornton, John; Schembri, Mark; Douven, Elles; Delgado-Mederos;, Raquel; Marín, Rebeca; Camps-Renom, Pol; Guisado-Alonso, Daniel; Nuñez, Fidel; Medrano-Martorell, Santiago; Merino, Elisa; Iida, Kotaro; Ikeda, Syuhei; Nishihara, Masashi; Irie, Hiroyuki; Demirelli, Derya Selcuk; Medanta, Jayesh Modi; Zerna, Charlotte; Hernández, Maria Valdés; Armitage, Paul; Heye, Anna; Muñoz-Maniega, Susana; Sakka, Eleni; Thrippleton, Michael; Dennis, Martin; Beigneux, Ysoline; Silva, Mauro; Venketasubramanian, Narayanaswamy; Ho, Shu Leung; Cheung, Raymond Tak Fai; Chan, Koon Ho; Teo, Kay Cheong; Hui, Edward; Kwan, Joseph Shiu Kwong; Chang, Richard; Tse, Man Yu; Hoi, Chu Peng; Chan, Chung Yan; Chan, Oi Ling; Cheung, Ryan Hoi Kit; Wong, Edmund Ka Ming; Leung, Kam Tat; Tsang, Suk Fung; Ip, Hing Lung; Ma, Sze Ho; Ma, Karen; Fong, Wing Chi; Li, Siu Hung; Li, Richard; Ng, Ping Wing; Wong, Kwok Kui; Liu, Wenyan; Wong, Lawrence; Ramos, Lino; De Schryver, Els; Jöbsis, Joost; van der Sande, Jaap; Brouwers, Paul; Roos, Yvo; Stam, Jan; Bakker, Stef; Verbiest, Henk; Schoonewille, Wouter; Linn, Cisca; Hertzberger, Leopold; van Gemert, Maarten; Berntsen, Paul; Hendrikse, Jeroen; Nederkoorn, Paul; Mess, Werner; Koudstaal, Peter; Leff, Alexander; Ward, Nicholas; Nachev, Parashkev; Perry, Richard; Ozkan, Hatice; Mitchell, John.

In: The Lancet Neurology, Vol. 18, No. 7, 07.2019, p. 653-665.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack

T2 - a pooled analysis of individual patient data from cohort studies

AU - Wilson, Duncan

AU - Ambler, Gareth

AU - Lee, Keon Joo

AU - Lim, Jae Sung

AU - Shiozawa, Masayuki

AU - Koga, Masatoshi

AU - Li, Linxin

AU - Lovelock, Caroline

AU - Chabriat, Hugues

AU - Hennerici, Michael

AU - Wong, Yuen Kwun

AU - Mak, Henry Ka Fung

AU - Prats-Sánchez, Luis

AU - Martínez-Domeño, Alejandro

AU - Inamura, Shigeru

AU - Yoshifuji, Kazuhisa

AU - Arsava, Ethem Murat

AU - Horstmann, Solveig

AU - Purrucker, Jan

AU - Lam, Bonnie Yin Ka

AU - Wong, Adrian

AU - Kim, Young Dae

AU - Song, Tae Jin

AU - Schrooten, Maarten

AU - Lemmens, Robin

AU - Eppinger, Sebastian

AU - Gattringer, Thomas

AU - Uysal, Ender

AU - Tanriverdi, Zeynep

AU - Bornstein, Natan M.

AU - Assayag, Einor Ben

AU - Hallevi, Hen

AU - Tanaka, Jun

AU - Hara, Hideo

AU - Coutts, Shelagh B.

AU - Hert, Lisa

AU - Polymeris, Alexandros

AU - Seiffge, David J.

AU - Lyrer, Philippe

AU - Algra, Ale

AU - Kappelle, Jaap

AU - Al-Shahi Salman, Rustam

AU - Jäger, Hans R.

AU - Lip, Gregory Y.H.

AU - Mattle, Heinrich P.

AU - Panos, Leonidas D.

AU - Mas, Jean Louis

AU - Legrand, Laurence

AU - Karayiannis, Christopher

AU - Phan, Thanh

AU - Gunkel, Sarah

AU - Christ, Nicolas

AU - Abrigo, Jill

AU - Leung, Thomas

AU - Chu, Winnie

AU - Chappell, Francesca

AU - Makin, Stephen

AU - Hayden, Derek

AU - Williams, David J.

AU - Kooi, M. Eline

AU - van Dam-Nolen, Dianne H.K.

AU - Barbato, Carmen

AU - Browning, Simone

AU - Wiegertjes, Kim

AU - Tuladhar, Anil M.

AU - Maaijwee, Noortje

AU - Guevarra, Christine

AU - Yatawara, Chathuri

AU - Mendyk, Anne Marie

AU - Delmaire, Christine

AU - Köhler, Sebastian

AU - van Oostenbrugge, Robert

AU - Zhou, Ying

AU - Xu, Chao

AU - Hilal, Saima

AU - Gyanwali, Bibek

AU - Chen, Christopher

AU - Lou, Min

AU - Staals, Julie

AU - Bordet, Régis

AU - Kandiah, Nagaendran

AU - de Leeuw, Frank Erik

AU - Simister, Robert

AU - van der Lugt, Aad

AU - Kelly, Peter J.

AU - Wardlaw, Joanna M.

AU - Soo, Yannie

AU - Fluri, Felix

AU - Srikanth, Velandai

AU - Calvet, David

AU - Jung, Simon

AU - Kwa, Vincent I.H.

AU - Engelter, Stefan T.

AU - Peters, Nils

AU - Smith, Eric E.

AU - Yakushiji, Yusuke

AU - Orken, Dilek Necioglu

AU - Fazekas, Franz

AU - Thijs, Vincent

AU - Heo, Ji Hoe

AU - Mok, Vincent

AU - Veltkamp, Roland

AU - Ay, Hakan

AU - Imaizumi, Toshio

AU - Gomez-Anson, Beatriz

AU - Lau, Kui Kai

AU - Jouvent, Eric

AU - Rothwell, Peter M.

AU - Toyoda, Kazunori

AU - Bae, Hee Joon

AU - Marti-Fabregas, Joan

AU - Werring, David J.

AU - Harkness, Kirsty

AU - Shaw, Louise

AU - Sword, Jane

AU - Mohd Nor, Azlisham

AU - Sharma, Pankaj

AU - Kelly, Deborah

AU - Harrington, Frances

AU - Randall, Marc

AU - Smith, Matthew

AU - Mahawish, Karim

AU - Elmarim, Abduelbaset

AU - Esisi, Bernard

AU - Cullen, Claire

AU - Nallasivam, Arumug

AU - Price, Christopher

AU - Barry, Adrian

AU - Roffe, Christine

AU - Coyle, John

AU - Hassan, Ahamad

AU - Birns, Jonathan

AU - Cohen, David

AU - Sekaran, Lakshmanan

AU - Parry-Jones, Adrian

AU - Parry, Anthea

AU - Hargroves, David

AU - Proschel, Harald

AU - Datta, Prabel

AU - Darawil, Khaled

AU - Manoj, Aravindakshan

AU - Burn, Mathew

AU - Patterson, Chris

AU - Giallombardo, Elio

AU - Smyth, Nigel

AU - Mansoor, Syed

AU - Anwar, Ijaz

AU - Marsh, Rachel

AU - Ispoglou, Sissi

AU - Chadha, Dinesh

AU - Prabhakaran, Mathuri

AU - Meenakishundaram, Sanjeevikumar

AU - O'Connell, Janice

AU - Scott, Jon

AU - Krishnamurthy, Vinodh

AU - Aghoram, Prasanna

AU - McCormick, Michael

AU - Sprigg, Nikola

AU - O'Mahony, Paul

AU - Cooper, Martin

AU - Choy, Lillian

AU - Wilkinson, Peter

AU - Leach, Simon

AU - Caine, Sarah

AU - Burger, Ilse

AU - Gunathilagan, Gunaratam

AU - Guyler, Paul

AU - Emsley, Hedley

AU - Davis, Michelle

AU - Manawadu, Dulka

AU - Pasco, Kath

AU - Mamun, Maam

AU - Luder, Robert

AU - Sajid, Mahmud

AU - Okwera, James

AU - Warburton, Elizabeth

AU - Saastamoinen, Kari

AU - England, Timothy

AU - Putterill, Janet

AU - Flossman, Enrico

AU - Power, Michael

AU - Dani, Krishna

AU - Mangion, David

AU - Suman, Appu

AU - Corrigan, John

AU - Lawrence, Enas

AU - Vahidassr, Djamil

AU - Shakeshaft, Clare

AU - Brown, Martin

AU - Charidimou, Andreas

AU - Cohen, Hannah

AU - Banerjee, Gargi

AU - Houlden, Henry

AU - White, Mark

AU - Yousry, Tarek

AU - Flossmann, Enrico

AU - Muir, Keith

AU - El-Koussy, Marwan

AU - Gratz, Pascal

AU - Molad, Jeremy

AU - Korczyn, Amos

AU - Kliper, Efrat

AU - Maeder, Philippe

AU - Gass, Achim

AU - Pachai, Chahin

AU - Bracoub, Luc

AU - Douste-Blazy, Marie Yvonne

AU - Fratacci, Marie Dominique

AU - Vicaut, Eric

AU - Sato, Shoichiro

AU - Miwa, Kaori

AU - Fujita, Kyohei

AU - Ide, Toshihiro

AU - Ma, Henry

AU - Ly, John

AU - Singhal, Shahoo

AU - Chandra, Ronil

AU - Slater, Lee Anne

AU - Soufan, Cathy

AU - Moran, Christopher

AU - Traenka, Christopher

AU - Thilemann, Sebastian

AU - Fladt, Joachim

AU - Gensicke, Henrik

AU - Bonati, Leo

AU - Kim, Beom Joon

AU - Han, Moon Ku

AU - Kang, Jihoon

AU - Ko, Eunbin

AU - Yang, Mi Hwa

AU - Jang, Myung Suk

AU - Murphy, Sean

AU - Carty, Fiona

AU - Akijian, Layan

AU - Thornton, John

AU - Schembri, Mark

AU - Douven, Elles

AU - Delgado-Mederos;, Raquel

AU - Marín, Rebeca

AU - Camps-Renom, Pol

AU - Guisado-Alonso, Daniel

AU - Nuñez, Fidel

AU - Medrano-Martorell, Santiago

AU - Merino, Elisa

AU - Iida, Kotaro

AU - Ikeda, Syuhei

AU - Nishihara, Masashi

AU - Irie, Hiroyuki

AU - Demirelli, Derya Selcuk

AU - Medanta, Jayesh Modi

AU - Zerna, Charlotte

AU - Hernández, Maria Valdés

AU - Armitage, Paul

AU - Heye, Anna

AU - Muñoz-Maniega, Susana

AU - Sakka, Eleni

AU - Thrippleton, Michael

AU - Dennis, Martin

AU - Beigneux, Ysoline

AU - Silva, Mauro

AU - Venketasubramanian, Narayanaswamy

AU - Ho, Shu Leung

AU - Cheung, Raymond Tak Fai

AU - Chan, Koon Ho

AU - Teo, Kay Cheong

AU - Hui, Edward

AU - Kwan, Joseph Shiu Kwong

AU - Chang, Richard

AU - Tse, Man Yu

AU - Hoi, Chu Peng

AU - Chan, Chung Yan

AU - Chan, Oi Ling

AU - Cheung, Ryan Hoi Kit

AU - Wong, Edmund Ka Ming

AU - Leung, Kam Tat

AU - Tsang, Suk Fung

AU - Ip, Hing Lung

AU - Ma, Sze Ho

AU - Ma, Karen

AU - Fong, Wing Chi

AU - Li, Siu Hung

AU - Li, Richard

AU - Ng, Ping Wing

AU - Wong, Kwok Kui

AU - Liu, Wenyan

AU - Wong, Lawrence

AU - Ramos, Lino

AU - De Schryver, Els

AU - Jöbsis, Joost

AU - van der Sande, Jaap

AU - Brouwers, Paul

AU - Roos, Yvo

AU - Stam, Jan

AU - Bakker, Stef

AU - Verbiest, Henk

AU - Schoonewille, Wouter

AU - Linn, Cisca

AU - Hertzberger, Leopold

AU - van Gemert, Maarten

AU - Berntsen, Paul

AU - Hendrikse, Jeroen

AU - Nederkoorn, Paul

AU - Mess, Werner

AU - Koudstaal, Peter

AU - Leff, Alexander

AU - Ward, Nicholas

AU - Nachev, Parashkev

AU - Perry, Richard

AU - Ozkan, Hatice

AU - Mitchell, John

PY - 2019/7

Y1 - 2019/7

N2 - 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 [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.

AB - 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 [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.

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U2 - 10.1016/S1474-4422(19)30197-8

DO - 10.1016/S1474-4422(19)30197-8

M3 - Article

C2 - 31130428

AN - SCOPUS:85067010802

VL - 18

SP - 653

EP - 665

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 7

ER -