Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Best, Jonathan G.; Ambler, Gareth; Wilson, Duncan; Lee, Keon‐Joo; Lim, Jae Sung; Shiozawa, Masayuki; Koga, Masatoshi; Li, Linxin; Lovelock, Caroline; Chabriat, Hugues; Hennerici, Michael G.; Wong, Yuen Kwun; Mak, Henry Ka Fung; Prats‐Sánchez, Luís; 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; Lemmens, Robin; Eppinger, Sebastian; Gattringer, Thomas; Uysal, Ender; Tanrıverdi, Zeynep; Bornstein, Natan M.; Assayag, Einor Ben; Hallevi, Hen; Molad, Jeremy; Nishihara, Masashi; Tanaka, Jun; Coutts, Shelagh B.; Polymeris, Alexandros; Wagner, Benjamin; Seiffge, David J; Lyrer, Philippe; Algra, Ale; Kappelle, L. Jaap; Salman, Rustam Al-Shahi; Jäger, Hans Rolf; Lip, Gregory Y. H.; Fischer, Urs; El-Koussy, Marwan; Mas, Jean‐Louis; Legrand, Laurence; Karayiannis, Christopher; Phan, Thanh G.; Gunkel, Sarah; Christ, Nicolas; Abrigo, Jill; Leung, Thomas Wai Hong; Chu, Winnie Cw; Chappell, Francesca M; Makin, Stephen; Hayden, Derek; Williams, David; Mess, Werner H.; Nederkoorn, Paul J.; Barbato, Carmen; Browning, Simone; Wiegertjes, Kim; Tuladhar, Anil M.; Maaijwee, Noortje A.M.; Guevarra, Anne Cristine Deocariza; Yatawara, Chathuri; Mendyk, Anne‐Marie; Delmaire, Christine; Köhler, Sebastian; Oostenbrugge, Robert J. van; Zhou, Ying; Xu, Chao; Hilal, Saima; Gyanwali, Bibek; Chen, Christopher; Lou, Min; Staals, Julie; Bordet, Régis; Kandiah, Nagaendran; Leeuw, Frank‐Erik de; Simister, Robert; Hendrikse, Jeroen; Kelly, Peter; Wardlaw, Joanna M.; Soo, Yannie; Fluri, Felix; Srikanth, Velandai; Calvet, D.; Jung, Simon; Kwa, Vincent I H; Engelter, Stefan T.; Peters, Nils; Smith, Eric E.; Hara, Hideo; Yakushiji, Yusuke; Örken, Dilek Neci̇oğlu; Fazekas, Franz; Thijs, Vincent; Heo, Ji Hoe; Mok, Vincent; Veltkamp, Roland; Ay, Hakan; Imaizumi, Toshio; Gómez‐Anson, Beatriz; Lau, Kui Kai; Jouvent, Éric; Rothwell, Peter M.; Toyoda, Kazunori; Bae, Hee‐Joon; Martí‐Fàbregas, Joan; Werring, David J.; Harkness, Kirsty; Shaw, Louise; Sword, Jane; Nor, Azlisham Mohd; Sharma, Pankaj; Kelly, Deborah F.; Harrington, Frances; Randall, Marc; Smith, Matthew; Mahawish, Karim; Elmarim, Abduelbaset; Esisi, Bernard; Cullen, Claire; Nallasivam, Arumug; Price, Chris; Barry, Adrian; Roffe, Christine; Coyle, John; Hassan, Ahamad; Birns, Jonathan; Cohen, David E.; 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, M. J.; 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 A.; 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 M.; Charidimou, Andreas; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark; Yousry, Tarek; Floßmann, Enrico; Muir, Keith W.; Gratz, Pascal P.; Mattle, Heinrich; Panos, Leonidas; Korczyn, Amos D.; Kliper, Efrat; Maeder, Philippe; Gass, Achim; Pachaï, Chahin; Bracoub, Luc; Douste-Blazy, M Y; Fratacci, Marie Dominique; Vicaut, Éric; Sato, Shoichiro; Miwa, Kaori; Fujita, Kyohei; Ide, Toshihiro; Ma, Henry; Ly, John; Singhal, Shaloo; Chandra, Ronil V.; Slater, Lee-Anne; Soufan, Cathy; Moran, Christopher J.; Traenka, Christopher; Thilemann, Sebastian; Fladt, Joachim; Gensicke, Henrik; Bonati, Leo H.; Kim, Beom Joon; Han, Min Hyun; Kang, Jihoon; Ko, Eunbin; Yang, Mi; Jang, Myung Suk; Murphy, Sean; Carty, Fiona; Akijian, Layan; Thornton, John; Schembri, Mark A.; Douven, Elles; Delgado‐Mederos, Raquel; Marín, Rebeca; Camps‐Renom, Pol; Guisado‐Alonso, Daniel; Núñez, Fidel Ángel; Medrano-Martorell, Santiago; Martín-Merino, Elisa; Iida, Kotaro; Ikeda, Syuhei; Irie, Hiroyuki; Demirelli, Derya Selçuk; Medanta, Jayesh Modi; Zerna, Charlotte; Hernández, Maria Valdés; Armitage, Paul A.; Heye, Anna K.; Muñoz‐Maniega, Susana; Sakka, Eleni; Thrippleton, Michael J.; Dennis, Martin; Beigneux, Ysoline; Silva, Mauro Ramalho; Venketasubramanian, Narayanaswamy; Ho, Shu Leung; Cheung, Raymond Tak Fai; Chan, Koon Ho; Teo, Kay Cheong; Hui, Edward S.; Kwan, Joseph; Chang, Richard Shek‐kwan; Tse, Man Yu; Hoi, Chu Peng; Chan, Chung Yan; Chan, Oi Ling; Cheung, Ryan; Wong, Edmund Ka Ming; Leung, Kam Tat; Tsang, Suk Fung; Ip, Hing Lung; Ho, Sze; Ma, Karen; Fong, Wing Chi; Li, Siu Hung; Li, Richard; Ng, Ping Wing; Wong, Kwok Kui; Liu, Wenyan; Wong, Lawrence K. S.; Ramos, L. M. P.; Schryver, Els De; Jöbsis, Joost; Sande, Jaap van der; Brouwers, P. J. A. M.; Roos, Yvo; Stam, Jan; Bakker, S. L. M.; Verbiest, H; Schoonewille, Wouter; Linn, Cisca; Hertzberger, Leopold; Gemert, Maarten van; Berntsen, Paul; Dam-Nolen, Dianne H.K. van; Kooi, M. Eline; Lugt, Aad van der; Koudstaal, Peter J.; Leff, Alexander; Ward, Nicholas; Nachev, Parashkev; Perry, Richard; Özkan, Hatice; Mitchell, John

doi:10.1016/s1474-4422(21)00024-7

Cited by 46 publications

(34 citation statements)

References 35 publications

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“…Recently, the Microbleeds International Collaborative Network initiative allowed to build and validate a score to predict the risk of ischemic and hemorrhagic stroke in patients with previous ischemic stroke or transient ischemic attack. In line with the abovementioned, somehow counter-intuitive results, the risk of ischemic stroke in these patients is higher in those with larger numbers of CMs [25].…”

Section: Cerebral Microbleeds a Novel Mri Marker Of Hemorrhagic And I...supporting

confidence: 82%

Cerebral Small-Vessel Diseases: A Look Back from 1991 to Today

Grosset

Jouvent

2022

Cerebrovasc Dis

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Background: Cerebral small-vessel diseases (cSVDs) encompass a number of causes involving, but not limited to, alterations in the intracranial microvasculature, leading to the accumulation of brain tissue damage and the development of various degrees of cognitive impairment, behavioral alterations, gait instability, and localization signs, often associated with the occurrence of ischemic or hemorrhagic strokes. Summary: In 2021, although key questions remain unanswered, there is general agreement on the construct, its main pathophysiological bases, and the terms used to describe its main clinical and radiological features. However, this has not always been the case, and the 30th anniversary of Cerebrovascular Diseases is an opportunity to look back from 1991 to the present to understand how a number of features, sometimes considered independent, have been progressively brought together by successive scientific breakthroughs, gradually leading to the definition of the now widely accepted concept of cSVDs. Key Messages: In the course of this journey, we will detail with particular attention the role of what we consider 2 crucial events: the advent of cerebral MRI and the building of large cohorts with monogenic forms of small-vessel disease of the brain.

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Section: Cerebral Microbleeds a Novel Mri Marker Of Hemorrhagic And I...supporting

confidence: 82%

Cerebral Small-Vessel Diseases: A Look Back from 1991 to Today

Grosset

Jouvent

2022

Cerebrovasc Dis

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“… 29 Recently, risk scores for ischemic or hemorrhagic stroke using a component of SVD like CMBs have been given attention. 4 Nonetheless, both albuminuria and reduced eGFR would also increase the risks for ischemic and hemorrhagic stroke. 30 , 31 Our results suggest that, in determining the antithrombotic‐associated bleeding risk in association with the cerebral SVD burden, these CKD measures should be included in the risk models.…”

Section: Discussionmentioning

confidence: 99%

“…Among the magnetic resonance imaging (MRI) biomarkers for cerebral small vessel disease (SVD), cerebral microbleeds (CMBs) are known predictors of intracranial hemorrhage especially in patients on antithrombotic therapy post stroke. 1 , 2 , 3 , 4 Cerebral SVD is also associated with noncerebral problems as a marker of systemic SVD including chronic kidney disease (CKD), which also seems to increase risks for bleeding events. 5 , 6 A total SVD score combining individual MRI features of SVD offers potential for more accurate stratification of the cerebral SVD burden than the use of individual features separately, 7 , 8 and the association of total SVD score increment with reduced estimated glomerular filtration rate (eGFR) was reported in an analysis of 1080 patients with ischemic stroke or transient ischemic attack from the Oxford Vascular Study, with the associations attenuating at older ages.…”

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confidence: 99%

Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2

Tanaka

Miwa

Takagi

et al. 2022

JAHA

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Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0–4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m 2 ), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11–2.39) at category G4 (eGFR 15–<30 mL/min per 1.73 m 2 ) and 2.05 (95% CI, 1.33–3.16) at G5 (eGFR <15 mL/min per 1.73 m 2 ). Corresponding odds ratios relative to urinary albumin‐to‐creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12–1.49) for category A2 (ACR 30–<300 mg/g) and 1.37 (95% CI, 1.05–1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased. Conclusions Both reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000023669.

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“…71 White matter hyperintensities can be assessed quantitatively by lesion segmentation or semi-quantitatively by rating scales that can be used routinely in clinical practice. The impact of other MRI manifestations of SVD, 157 such as cerebral microbleeds, 158 on stroke outcome is currently being investigated. Also, there is increasing recognition of diffusion MRI markers as precise and reliable metrics of SVD burden.…”

Section: Neuroimagingmentioning

confidence: 99%

Post-Stroke Cognitive Impairment and Dementia

Rost

Brodtmann

Pase

et al. 2022

Circulation Research

354

194

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Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbid neurodegenerative pathology, which is common in elderly individuals and can contribute to the clinical expression of PSCID. Manifestations of cerebral small vessel disease, such as covert brain infarcts, white matter lesions, microbleeds, and cortical microinfarcts, are also common in patients with stroke and likewise contribute to cognitive outcomes. Although studies of PSCID historically varied in the approach to timing and methods of diagnosis, most of them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid cognitive or functional decline, life-course exposure to vascular risk factors, and a history of prior stroke increase risk of PSCID. Stroke characteristics, in particular stroke severity, lesion volume, lesion location, multiplicity and recurrence, also influence PSCID risk. Understanding the complex interaction between an acute stroke event and preexisting brain pathology remains a priority and will be critical for developing strategies for personalized prediction, prevention, targeted interventions, and rehabilitation. Current challenges in the field relate to a lack of harmonization of definition and classification of PSCID, timing of diagnosis, approaches to neurocognitive assessment, and duration of follow-up after stroke. However, evolving knowledge on pathophysiology, neuroimaging, and biomarkers offers potential for clinical applications and may inform clinical trials. Preventing stroke and PSCID remains a cornerstone of any strategy to achieve optimal brain health. We summarize recent developments in the field and discuss future directions closing with a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome.

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Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Cited by 46 publications

References 35 publications

Cerebral Small-Vessel Diseases: A Look Back from 1991 to Today

Cerebral Small-Vessel Diseases: A Look Back from 1991 to Today

Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2

Post-Stroke Cognitive Impairment and Dementia

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