Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies
Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies
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DOI：
10.1016/s1474-4422(19)30197-8
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发表时间：
2019-07-01
期刊：
影响因子：
48
通讯作者：
Werring, David J.
中科院分区：
文献类型：
--
作者：
Wilson, Duncan;Ambler, Gareth;Werring, David J.
背景：脑微出血是卒中风险的神经影像学生物标志物。一个关键的临床问题是，脑微出血是否表明近期发生缺血性卒中或短暂性脑缺血发作的患者，在接受抗血栓药物治疗时，未来颅内出血的发生率可能超过复发性缺血性卒中的发生率。因此，我们的目的是建立一个大的负担，脑微出血或脑微出血的特定解剖模式，可以确定缺血性中风或短暂性脑缺血发作患者颅内出血的绝对风险高于ischaemicstroke.Methods，我们做了一个汇总分析，从队列研究中的个别患者的数据，在最近的缺血性中风或短暂性脑缺血发作的成年人。如果队列前瞻性招募了缺血性卒中或短暂性脑缺血发作的成年受试者;至少纳入50名受试者;收集了至少3个月随访期间的卒中事件数据;使用了对磁化率敏感的适当MRI序列;并使用共识标准和经验证的量表可靠地记录了脑微出血的数量和解剖分布，则队列有资格入选。我们预先设定的主要结局是任何症状性颅内出血或缺血性卒中、症状性颅内出血和症状性缺血性卒中的复合结局。我们在PROSPERO国际前瞻性系统评价注册中心注册了这项研究，编号CRD 42016036602。结果在1996年1月1日至2018年12月1日期间，我们识别了344项研究。在排除不合格或拒绝入选请求后，来自38个队列的20322例患者（随访超过35225患者年;中位数1.34年[IQR 0-19-2.44]）被纳入我们的分析。颅内出血和缺血性卒中的复合结局中，发生脑微出血患者与未发生脑微出血患者的校正风险比[aHR]为1.35（95% CI 1- 20-1- 50）;颅内出血为2.45（1.82 3.29），而缺血性卒中为1.45（95% CI 1 - 20 -1- 50）。缺血性卒中23例（1.08 ± 1.40）。颅内出血的aHR随着脑微出血负荷的增加而增加，但这种影响在缺血性卒中中不太明显（对于5次或5次以上脑微出血，颅内出血的aHR为4.55 [95% CI 3.08-6.72]，缺血性卒中为1.47 [149-1.80];对于10个或更多脑微出血，aHR 5.52 [3.36-9.05] vs 1.43 [1.07 1.91];对于≥ 20个脑微出血，aHR 8.61 [4.69 15.81] vs 1.86 [1.23 1.82]）。然而，无论脑微出血的解剖分布或负荷如何，缺血性卒中的发生率均超过颅内出血（对于10例或10例以上脑微出血，每1000患者年64例缺血性卒中[95% CI 48-84] vs 27例颅内出血[17-41];对于>= 20例脑微出血，每1000患者-年73例缺血性卒中[46-108]对每1000患者-年39例颅内出血[21-67]）。与缺血性卒中相比，脑微出血与后续颅内出血的相对危险度（aHR）相关，但无论脑微出血的存在、解剖学分布或负荷如何，缺血性卒中的绝对风险均高于颅内出血。版权所有（C）2019作者。由爱思唯尔有限公司发布
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 [149-1.80] 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. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.