Cheung Yuen, Foley Marianne, Bradley David, Cassidy Tim, Collins Ronan, Cronin Simon, Dolan Eamon, Gorey Sarah, Khadjooi Kayvan, Induruwa Isuru, Katan Mira, O'Connor Margaret, O'Donnell Martin J, Synnott Pádraig, Williams David, Zietz Annaelle, Kelly Peter J, McCabe John Joseph
From the Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (Y.C., M.F., D.B., T.C., R.C., S.C., E.D., S.G., M.O.C., M.J.O.D., P.S., D.W., P.J.K., J.J.M.); Neurovascular Unit for Applied Translational and Therapeutics Research (Y.C., M.F., S.G., P.S., P.J.K., J.J.M.), Catherine McAuley Centre; School of Medicine (Y.C., M.F., T.C., S.G., P.S., P.J.K., J.J.M.), University College Dublin; Stroke Service (Y.C., M.F., S.G., P.S., J.J.M.), Department of Geriatric Medicine, Mater Misericordiae University Hospital; School of Medicine (D.B., R.C.), Trinity College Dublin; Department of Neurology (D.B.), St James Hospital; Department of Geriatric Medicine (T.C.), St Vincent's University Hospital; Stroke Service (R.C.), Department of Geriatric Medicine, Tallaght University Hospital, Dublin; Department of Neurology (S.C.), Cork University Hospital; Clinical Neurosciences (S.C.), School of Medicine, University College Cork; Stroke Service (E.D.), Department of Geriatric Medicine, James Connolly Memorial Hospital, Dublin, Ireland; Department of Clinical Neurosciences (K.K., I.I.), University of Cambridge, Addenbrooke's Hospital, United Kingdom; Department of Neurology & Stroke Centre (M.K., A.Z.), University Hospital Basel, Switzerland; Department of Geriatric Medicine (M.O.C.), Limerick University Hospital; College of Medicine (M.J.O.D.), Nursing and Health Sciences, University of Galway and University Hospital Galway; Department of Geriatric and Stroke Medicine (D.W.), RCSI University of Medicine and Health Sciences; Department of Geriatric Medicine (D.W.), and Department of Geriatric and Stroke Medicine (D.W.), Beaumont Hospital; and Stroke Service (P.J.K.), Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland.
Neurology. 2025 Jan 14;104(1):e210061. doi: 10.1212/WNL.0000000000210061. Epub 2024 Dec 18.
Despite effective secondary prevention, including oral anticoagulant (OAC) therapy, the risk of recurrent stroke (RS) in patients with atrial fibrillation (AF) remains substantial with an annualized risk of 3.2%-6.5% per year. The reasons for this high residual risk are unclear. There is growing need for improved risk prediction tools to identify patients at greatest risk of RS in AF and to find new therapeutic targets for secondary prevention. Our objective was to perform a systematic review to investigate the association of clinical factors and echocardiographic, blood, and neuroimaging biomarkers, with stroke recurrence after AF-related stroke.
We searched Embase/Ovid Medline until August 2023. Studies were included irrespective of OAC use. Risk ratios (RRs) were pooled using random effects. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
Of 5,427 records searched, 42 reports from 28 studies including 52,798 patients (5,046 RS events during follow-up) were identified. In addition to the CHADS-Vasc score (RR 1.22, 95% CI 1.15-1.30, per point) and its individual components, the clinical factors associated with recurrence were a qualifying stroke despite OAC (RR 1.55, 1.23-1.94 [vs OAC-naïve]), sustained AF (RR 1.44, 1.19-1.75 [vs paroxysmal]), hyperlipidemia (RR 1.27, 1.05-1.53), chronic kidney disease (RR 1.86, 1.19-2.92), and malignancy (RR 4.36, 1.85-10.78). NIH Stroke Scale scores (RR 0.97, 0.95-0.99) and Asian ethnicity (RR 0.59, 0.36-0.97) were associated with a reduced risk of recurrence. Known AF was not associated with a higher risk of stroke compared with AF detected after stroke (RR 1.20, 0.93-1.55). Neuroimaging markers associated with RS included chronic lacunar (RR 1.91, 1.29-2.84) or embolic-appearing (RR 2.76, 1.32-5.77) infarcts and cerebral microbleeds (RR 1.29, 1.04-1.59). Echocardiographic markers included atrial size (RR 1.40, 1.12-1.75 per cm/m), intracardiac thrombus (RR 1.99, 1.38-2.87), spontaneous left atrial appendage (LAA) echocardiographic contrast (RR 2.91, 1.21-6.17), or low LAA intensity variation (RR 2.81, 1.48-5.32). Data were limited for blood biomarkers.
We identified several clinical factors associated with recurrence after AF-related stroke, with AF burden and stroke despite OAC of particular clinical relevance. Biomarkers of atrial cardiopathy, small vessel disease, or previous infarction were also associated with RS. Collaborative efforts are needed to identify and validate new risk factors and biomarkers of RS in AF.
尽管有包括口服抗凝剂（OAC）治疗在内的有效二级预防措施，但心房颤动（AF）患者的复发性卒中（RS）风险仍然很高，年化风险为每年3.2%-6.5%。这种高残留风险的原因尚不清楚。越来越需要改进风险预测工具，以识别AF中RS风险最高的患者，并找到二级预防的新治疗靶点。我们的目的是进行一项系统评价，以研究临床因素、超声心动图、血液和神经影像学生物标志物与AF相关性卒中后卒中复发的关联。
我们检索了截至2023年8月的Embase/Ovid Medline。纳入的研究不考虑是否使用OAC。使用随机效应汇总风险比（RRs）。遵循系统评价和Meta分析的首选报告项目指南。
在检索的5427条记录中，确定了来自28项研究的42份报告，包括52798例患者（随访期间5046例RS事件）。除CHADS-Vasc评分（RR 1.22，95%CI 1.15-1.30，每增加1分）及其各个组成部分外，与复发相关的临床因素包括尽管使用了OAC仍发生的合格卒中（RR 1.55，1.23-1.94[与未使用OAC者相比]）、持续性AF（RR 1.44，1.19-1.75[与阵发性相比]）、高脂血症（RR 1.27，1.05-1.53）、慢性肾病（RR 1.86，1.19-2.92）和恶性肿瘤（RR 4.36，1.85-10.78）。美国国立卫生研究院卒中量表评分（RR 0.97，0.95-0.99）和亚洲种族（RR 0.59，0.36-0.97）与复发风险降低相关。与卒中后检测到的AF相比，已知AF与更高的卒中风险无关（RR 1.20，0.93-1.55）。与RS相关的神经影像学生物标志物包括慢性腔隙性梗死（RR 1.91，1.29-2.84）或栓塞样梗死（RR 2.76，1.32-5.77）以及脑微出血（RR 1.29，1.04-1.59）。超声心动图生物标志物包括心房大小（RR 1.40，每增加1 cm/m为1.12-1.75）、心内血栓（RR 1.99，1.38-2.87）、自发性左心耳（LAA）超声心动图造影（RR 2.91，1.21-6.17）或低LAA强度变化（RR 2.81，1.48-5.32）。血液生物标志物的数据有限。
我们确定了几个与AF相关性卒中后复发相关的临床因素，AF负担和尽管使用OAC仍发生卒中具有特别的临床相关性。心房心肌病、小血管疾病或既往梗死的生物标志物也与RS相关。需要共同努力来识别和验证AF中RS的新风险因素和生物标志物。
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