Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study

Charidimou, Andreas; Inamura, Shigeru; Nomura, Tatsufumi; Kanno, Aya; Kim, Sang Nyon; Imaizumi, Toshio

doi:10.1016/j.jns.2016.08.050

Cited by 29 publications

(12 citation statements)

References 23 publications

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“…By contrast with cerebral microbleeds, white matter hyperintensities were not associated with symptomatic intracranial haemorrhage in our study, in keeping with data from two previous smaller similar cohort studies. 25 , 29 …”

Section: Discussionmentioning

confidence: 99%

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

Wilson

Ambler

Shakeshaft

et al. 2018

The Lancet Neurology

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SummaryBackgroundCerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.MethodsOur observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.FindingsBetween Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively).InterpretationIn patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from ora...

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Section: Discussionmentioning

confidence: 99%

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

Wilson

Ambler

Shakeshaft

et al. 2018

The Lancet Neurology

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207

135

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“…The risk of an intracranial bleeding may be too high with the administration of OAs in a patient with ischemic stroke and with an underlying cerebral hemorrhagic-prone angiopathy. [16][17][18][19][20] One study 21 of patients with an acute cardioembolic stroke treated with OAs reported that MBs were independently associated with ICH risk (hazard ratio [HR] = 3.67). Additional cohorts are needed to investigate whether the risk associated with OA therapy is greater than the benefit in patients with MBs, WMH, or SS.…”

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confidence: 99%

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation

et al. 2019

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ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.

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“…Some cohorts reported different outcomes in separate papers, while some studies contained data on more than one outcome in a single publication. In summary, we included 20 studies of ischemic stroke/TIA patients (19 cohorts, n = 7672), 11,21–39 4 studies of memory clinic patients (4 cohorts, n = 1957), 40–43 4 studies in high-risk elderly populations (3 cohorts, n = 1458) 44–47 and 8 population-based studies of healthy elderly participants (5 cohorts, n = 11,722). 12,48–54 Table 1 highlights key baseline and methodological characteristics and outcomes available in the included studies.…”

Section: Resultsmentioning

confidence: 99%

“…Nineteen studies of ischemic stroke/TIA patients (n ¼ 7672), 11,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] one memory clinic cohort (n ¼ 333), 40 and five population-based studies (n ¼ 13,864) [48][49][50]52 examined the relation between CMBs presence and risk of ICH and ischemic stroke. In the pooled analyses of patients with ischemic stroke/TIA, CMBs presence (vs. no CMBs) was associated with an increased crude risk of ICH (OR: 3.71; 95% CI: 2.13-6.45, p < 0.0001) (Figure 2(a)) and recurrent ischemic stroke (OR: 1.84; 95% CI: 1.39-2.42, p < 0.0001) ( Figure 3(a)) during follow-up.…”

Section: Cmbs and Risk Of Ich And Ischemic Strokementioning

confidence: 99%

Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)

Charidimou

Shams

Romero

et al. 2018

International Journal of Stroke

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Background: Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. Methods: Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥ 3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results: We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI:2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions: Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

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Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study

Cited by 29 publications

References 23 publications

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation

Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)

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