Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoë; Grégoire, Stéphanie; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiroyuki; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I H; Thijs, Vincent; Lee, Yong Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf; Werring, David J.

doi:10.1212/wnl.0000000000003183

Cited by 129 publications

(129 citation statements)

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“…Microbleeds were defined as rounded, hypodense foci up to 10 mm in size and were differentiated from microbleed mimics 10. The locations and numbers of microbleeds were scored according to the Microbleed Anatomical Rating Scale,11 and microbleed burden was graded as 0, 1, 2 to 4, and ≥5, as per recent systematic reviews 4. The severity of white matter hyperintensity (WMH) was determined according to the Fazekas scale 12.…”

Section: Methodsmentioning

confidence: 99%

“…The majority of these studies did not stratify results by antithrombotic use,4 potentially resulting in heterogeneity. Furthermore, significant ethnic differences in microbleed location exist 4. Asians with transient ischemic attack or ischemic stroke have a high prevalence of microbleeds of mixed location (8–40% versus 5–15% in white cohorts), whereas white patients with transient ischemic attack or ischemic stroke have a high prevalence of strictly lobar microbleeds (29–58% versus 6–27% in Asian cohorts), suggesting potential ethnic differences in underlying SVD etiology 4.…”

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confidence: 99%

“…Furthermore, significant ethnic differences in microbleed location exist 4. Asians with transient ischemic attack or ischemic stroke have a high prevalence of microbleeds of mixed location (8–40% versus 5–15% in white cohorts), whereas white patients with transient ischemic attack or ischemic stroke have a high prevalence of strictly lobar microbleeds (29–58% versus 6–27% in Asian cohorts), suggesting potential ethnic differences in underlying SVD etiology 4. It appears that patients with microbleeds of mixed location have the highest risk of recurrent ischemic stroke or ICH,4 but the underlying risk factors leading to this particularly severe subgroup of SVD remains uncertain.…”

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confidence: 99%

“…Asians with transient ischemic attack or ischemic stroke have a high prevalence of microbleeds of mixed location (8–40% versus 5–15% in white cohorts), whereas white patients with transient ischemic attack or ischemic stroke have a high prevalence of strictly lobar microbleeds (29–58% versus 6–27% in Asian cohorts), suggesting potential ethnic differences in underlying SVD etiology 4. It appears that patients with microbleeds of mixed location have the highest risk of recurrent ischemic stroke or ICH,4 but the underlying risk factors leading to this particularly severe subgroup of SVD remains uncertain. Finally, although recent small studies have shown that susceptibility‐weighted imaging has superior reliability and sensitivity for microbleed detection compared with T2* gradient echo,5, 6 studies using susceptibility‐weighted imaging in determining the prevalence and prognostic implications of microbleeds are scarce 4…”

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confidence: 99%

“…It appears that patients with microbleeds of mixed location have the highest risk of recurrent ischemic stroke or ICH,4 but the underlying risk factors leading to this particularly severe subgroup of SVD remains uncertain. Finally, although recent small studies have shown that susceptibility‐weighted imaging has superior reliability and sensitivity for microbleed detection compared with T2* gradient echo,5, 6 studies using susceptibility‐weighted imaging in determining the prevalence and prognostic implications of microbleeds are scarce 4…”

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confidence: 99%

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Long‐Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke

Lau

Wong

Teo

et al. 2017

JAHA

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BackgroundThis study was performed to determine the clinical correlates and long‐term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke.Methods and ResultsWe recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long‐term risks (3126 patient‐years of follow‐up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2–4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all P<0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07–5.05]; 2–4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50–9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25–27.81]; P trend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (P trend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: P trend<0.0001; ischemic stroke P trend=0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11–33.21]; P=0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk.ConclusionsIn Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Long‐Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke

Lau

Wong

Teo

et al. 2017

JAHA

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Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury

et al. 2019

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IMPORTANCE Covert vascular brain injury (VBI) is highly prevalent in community-dwelling older persons, but its clinical and therapeutic implications are debated. OBJECTIVE To better understand the clinical significance of VBI to optimize prevention strategies for the most common age-related neurological diseases, stroke and dementia. DATA SOURCE We searched for articles in PubMed between 1966 and December 22, 2017, studying the association of 4 magnetic resonance imaging (MRI) markers of covert VBI (white matter hyperintensities [WMHs] of presumed vascular origin, MRI-defined covert brain infarcts [BIs], cerebral microbleeds [CMBs], and perivascular spaces [PVSs]) with incident stroke, dementia, or death. STUDY SELECTION Data were taken from prospective, longitudinal cohort studies including 50 or more adults. DATA EXTRACTION AND SYNTHESIS We performed inverse variance-weighted meta-analyses with random effects and z score-based meta-analyses for WMH burden. The significance threshold was P < .003 (17 independent tests). We complied with the Meta-analyses of Observational Studies in Epidemiology guidelines. MAIN OUTCOMES AND MEASURES Stroke (hemorrhagic and ischemic), dementia (all and Alzheimer disease), and death. RESULTS Of 2846 articles identified, 94 studies were eligible, with up to 14 529 participants for WMH, 16 012 participants for BI, 15 693 participants for CMB, and 4587 participants for PVS. Extensive WMH burden was associated with higher risk of incident stroke (hazard ratio [

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Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source

et al. 2021

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The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging.OBJECTIVE To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy.DESIGN, SETTING, AND PARTICIPANTS Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial.INTERVENTIONS Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. MAIN OUTCOMES AND MEASURESThe primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality.RESULTS Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI,, multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P = .97). CONCLUSIONS AND RELEVANCEMicrobleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical out...

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Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

Cited by 129 publications

References 36 publications

Long‐Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke

Long‐Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke

Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source

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