Dataset Information

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.

SUBMITTER: Wilson D

PROVIDER: S-EPMC6562236 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wilson Duncan D Ambler Gareth G Lee Keon-Joo KJ Lim Jae-Sung JS Shiozawa Masayuki M Koga Masatoshi M Li Linxin L Lovelock Caroline C Chabriat Hugues H Hennerici Michael M Wong Yuen Kwun YK Mak Henry Ka Fung HKF Prats-Sánchez Luis L Martínez-Domeño Alejandro A Inamura Shigeru S Yoshifuji Kazuhisa K Arsava Ethem Murat EM Horstmann Solveig S Purrucker Jan J Lam Bonnie Yin Ka BYK Wong Adrian A Kim Young Dae YD Song Tae-Jin TJ Schrooten Maarten M Lemmens Robin R Eppinger Sebastian S Gattringer Thomas T Uysal Ender E Tanriverdi Zeynep Z Bornstein Natan M NM Assayag Einor Ben EB Hallevi Hen H Tanaka Jun J Hara Hideo H Coutts Shelagh B SB Hert Lisa L Polymeris Alexandros A Seiffge David J DJ Lyrer Philippe P Algra Ale A Kappelle Jaap J Al-Shahi Salman Rustam R Jäger Hans R HR Lip Gregory Y H GYH Mattle Heinrich P HP Panos Leonidas D LD Mas Jean-Louis JL Legrand Laurence L Karayiannis Christopher C Phan Thanh T Gunkel Sarah S Christ Nicolas N Abrigo Jill J Leung Thomas T Chu Winnie W Chappell Francesca F Makin Stephen S Hayden Derek D Williams David J DJ Kooi M Eline ME van Dam-Nolen Dianne H K DHK Barbato Carmen C Browning Simone S Wiegertjes Kim K Tuladhar Anil M AM Maaijwee Noortje N Guevarra Christine C Yatawara Chathuri C Mendyk Anne-Marie AM Delmaire Christine C Köhler Sebastian S van Oostenbrugge Robert R Zhou Ying Y Xu Chao C Hilal Saima S Gyanwali Bibek B Chen Christopher C Lou Min M Staals Julie J Bordet Régis R Kandiah Nagaendran N de Leeuw Frank-Erik FE Simister Robert R van der Lugt Aad A Kelly Peter J PJ Wardlaw Joanna M JM Soo Yannie Y Fluri Felix F Srikanth Velandai V Calvet David D Jung Simon S Kwa Vincent I H VIH Engelter Stefan T ST Peters Nils N Smith Eric E EE Yakushiji Yusuke Y Orken Dilek Necioglu DN Fazekas Franz F Thijs Vincent V Heo Ji Hoe JH Mok Vincent V Veltkamp Roland R Ay Hakan H Imaizumi Toshio T Gomez-Anson Beatriz B Lau Kui Kai KK Jouvent Eric E Rothwell Peter M PM Toyoda Kazunori K Bae Hee-Joon HJ Marti-Fabregas Joan J Werring David J DJ

The Lancet. Neurology 20190523 7

<h4>Background</h4>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 microb ...[more]

PMID: 31130428

Similar Datasets

Project description:BackgroundCerebral 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 oral anticoagulation.FundingThe Stroke Association and the British Heart Foundation.

Project description:BackgroundAn increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages.ObjectivesTo assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA).Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting.Selection criteriaWe considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA.Data collection and analysisTwo review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method.Main resultsWe identified no studies that met the inclusion criteria.Authors' conclusionsThere is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.

Project description:IntroductionThere is limited knowledge of the effects of blood pressure (BP) lowering on cerebral haemodynamics after transient ischaemic attack (TIA) and non-disabling stroke, particularly at older ages. We aimed to evaluate changes in transcranial Doppler (TCD) haemodynamic indices in patients undergoing early blood pressure lowering after TIA/non-disabling stroke, irrespective of age.Patients and methodsAmong consecutive eligible patients attending a rapid-access clinic with suspected TIA/non-disabling stroke and no evidence of extra/intracranial stenosis, hypertensive ones underwent intensive BP-lowering guided by daily home telemetric blood pressure monitoring (HBPM). Clinic-based BP, HBPM, End-tidal CO2 and bilateral middle cerebral artery (MCA) velocity on TCD were compared in the acute setting versus one-month follow-up; changes were stratified by baseline hypertension (clinic-BP≥140/90) and by age (<65, 65-79 and ≥80).ResultsIn 697 patients with repeated TCD measures, mean/SD baseline systolic-BP (145.0/21.3 mmHg) was reduced by an average of 11.3/19.9 mmHg (p < 0.0001) at one-month (133.7/17.4 mmHg), driven by patients hypertensive at baseline (systolic-BP change = -19.0/19.2 mmHg, p < 0.001; vs -0.5/15.4, p = 0.62 in normotensives). Compared with baseline, a significant change was observed at one-month only in mean/SD MCA end diastolic velocity (EDV) (0.77/7.26 cm/s, p = 0.005) and in resistance index (RI) (-0.005/0.051, p = 0.016), driven by hypertensive patients (mean/SD EDV change: 1.145/6.96 cm/s p = 0.001, RI change -0.007/0.06, p = 0.014). Findings were similar at all ages (EDV change - ptrend=0.357; RI change - ptrend=0.225), including 117 patients aged ≥80. EDV and RI changes were largest in 100 patients with clinic systolic-BP decrease ≥30 mmHg (mean/SD EDV change = 2.49/7.47 cm/s, p = 0.001; RI change -0.024/0.063, p < 0.0001).ConclusionThere was no evidence of worsening of TCD haemodynamic indices associated with BP-lowering soon after TIA/non-disabling stroke, irrespective of age and degree of BP reduction. In fact, EDV increase and RI decrease observed after treatment of hypertensive patients suggest a decrease in distal vascular resistance.

Project description:The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

Project description:ObjectivesThe aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).DesignOur study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).SettingWe derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measuresThe primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months.ResultsAmong the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months.ConclusionsThe LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.

Project description:ObjectiveCerebral autoregulation (CA) is critical to maintenance of cerebral perfusion but its relevance to the risk of stroke and dementia has been under-studied due to small study sizes and a lack of consensus as to the optimal method of measurement. We determined the reliability and reproducibility of multiple CA indices and the effect of intensive data-processing in a large population with transient ischaemic attack or minor stroke.ApproachConsecutive, consenting patients in the population-based Oxford Vascular Study (OXVASC) Phenotyped cohort underwent up to 10-min supine continuous blood pressure monitoring (Finometer) with bilateral middle cerebral artery (MCA) transcranial ultrasound (DWL-Dopplerbox). Un-processed waveforms (Un-A) were median-filtered, systematically reviewed, artefacts corrected and their quality blindly graded (optimal (A) to worst (E)). CA metrics were derived in time-domain (autoregulatory index (ARI), Pearson's Mx, Sx, Dx) and in very-low (VLF) and low-frequency (LF) domains (WPS-SI: wavelet phase synchronisation, transfer function analysis), stratified by recording quality. Reliability and reproducibility (Cronbach's alpha) were determined comparing MCA sides and the first vs. second 5-min of monitoring.Main resultsIn 453 patients, following manual data-cleaning, there was good reliability of indices when comparing MCA sides (Mx: 0.77; WPS-SI-VLF: 0.85; WPS-SI-LF 0.84), or repeated five minute epochs (Mx: 0.57; WPS-SI-VLF: 0.69; WPS-SI-LF 0.90), with persistently good reliability between sides even in lower quality Groups (Group D: Mx: 0.79; WPS-SI-VLF: 0.92; WPS-SI-LF: 0.91). Reliability was greatest for Pearson's Mx and wavelet synchronisation index, with reasonable reliability of transfer function analyses, but ARI was prone to occasional, potentially defective, extreme estimates (left vs right MCA: 0.68).SignificanceResting-state measures of CA were valid, reproducible and robust to moderate noise, but require careful data-processing. Mx and wavelet synchronisation index were the most reliable indices for determining the prognostic value of CA in large epidemiological cohorts and its potential as a treatment target.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets