Abstract: Objective  To analyze the differences of clinical characteristics and prognosis in patients with multiple nonlacunar cerebral infarctions with or without atrial fibrillation (AF).
Methods  This study was based on data from the third China national stroke registry (CNSR-Ⅲ), a national multicenter prospective study conducted from August 2015 to March 2018. Patients with multiple (2 or more infarctions) acute nonlacunar cerebral infarctions confirmed by head MRI were included. The baseline information, medical history, medication history during hospitalization, TOAST classification and other clinical data were collected. Follow-ups at 3 months and 1 year were conducted to assess outcomes, including stroke recurrence (ischemic stroke and hemorrhagic stroke), composite vascular events (stroke, myocardial infarction, and vascular death), cerebrovascular disease-related death, and unfavorable functional outcomes (mRS score>2). Patients were divided into the AF group and the non-AF group based on whether they had a history of AF. The demographic information and clinical characteristics were compared between the two groups. Analyzing the effects of AF on the outcomes of patients at 3 months and 1 year, and further analyzing the relationship between AF and the 1-year outcomes of patients with infarctions in different vascular distribution subgroups (multiple unilateral anterior circulation infarctions, multiple posterior circulation infarctions, and multiple vascular infarctions). 
Results  A total of 5711 patients with multiple nonlacunar cerebral infarctions were included, with a mean age of (62.8±11.4) years, and 1702 (29.8%) were female. Among these, 611 patients (10.7%) had AF, while 5100 patients (89.3%) did not. Compared with the non-AF group, the age of the AF group was higher, and the proportion of female, coronary artery heart disease, and tumor history was higher. BMI, the proportion of hypertension, diabetes mellitus, TIA, and the proportion of prior smoking and alcohol use were lower. The differences were statistically significant. The distribution differences of TOAST classification between the two groups were also statistically significant. Among them, the proportion of cardioembolic stroke and stroke of undetermined causes in the AF group was higher than that in the non-AF group. Laboratory results showed that the levels of HDL-C, D-dimer, and fibrinogen in the AF group were higher than those in the non-AF group. Multivariate analysis showed that the proportion of unfavorable functional outcomes at 1 year in the AF group was higher than that in the non-AF group, and the difference was statistically significant (adjusted OR 1.35, 95%CI 1.10-1.67, P=0.005). In the multiple unilateral anterior circulation infarctions subgroup, the rates of composite vascular events (adjusted HR 1.31, 95%CI 1.00-1.70, P=0.047), cerebrovascular disease-related death (adjusted HR 3.17, 95%CI 1.63-6.18, P<0.001), and unfavorable functional outcomes (adjusted OR 1.39, 95%CI 1.09-1.77, P=0.007) in patients with AF at 1 year were higher than those without AF.
Conclusions  Significant differences were observed in clinical characteristics between patients with multiple nonlacunar cerebral infarctions with and without AF. Patients with AF had a higher incidence of unfavorable functional outcomes at 1 year, especially in those with multiple unilateral anterior circulation infarctions. AF was a risk factor for composite vascular events, cerebrovascular disease-related death, and unfavorable functional outcomes at 1 year. 

Key words: Ischemic stroke; Atrial fibrillation; Stroke outcome; Multiple cerebral infarction; Stroke risk factor

摘要： 目的 分析伴或不伴心房颤动的多发性非腔隙性脑梗死患者的临床特征和预后差异。
方法 本研究基于全国多中心前瞻性研究——中国国家卒中登记Ⅲ（the third China national stroke registry，CNSR-Ⅲ）数据库（2015年8月—2018年3月），纳入经头颅MRI证实为多发性（≥2个梗死灶）急性非腔隙性脑梗死患者。收集患者的基线信息、既往史、住院期间用药史、TOAST分型等临床资料，进行3个月和1年随访，结局包括卒中复发（缺血性卒中和出血性卒中）、联合血管事件（卒中、心肌梗死及血管性死亡事件）、脑血管源性死亡及不良功能结局（mRS评分＞2分）。根据患者是否有既往心房颤动病史分为心房颤动组和无心房颤动组，比较两组的人口学信息和临床特征的差异。分析心房颤动对患者3个月和1年的结局影响，并进一步分析不同血管分布区梗死亚组（多发单侧前循环梗死、多发后循环梗死、多血管分布区梗死）中心房颤动与患者1年结局的关系。
结果 研究共纳入5711例多发性非腔隙性脑梗死患者，平均年龄为（62.8±11.4）岁，其中女性1702例（29.8%）；心房颤动组611例（10.7%），无心房颤动组5100例（89.3%）。与无心房颤动组相比，心房颤动组的年龄较高，女性、冠心病、肿瘤病史的比例较高；BMI，高血压、糖尿病、TIA的比例，以及既往吸烟和饮酒的比例较低，差异均有统计学意义。两组的TOAST分型分布差异也有统计学意义，其中，心房颤动组中心源性栓塞和不明原因型卒中的比例高于无心房颤动组。实验室检查结果提示，心房颤动组的HDL-C、D-二聚体和纤维蛋白原水平高于无心房颤动组。多因素分析显示，心房颤动组1年不良功能结局比例高于无心房颤动组，差异有统计学意义（校正OR 1.35，95%CI 1.10～1.67，P=0.005）。在多发单侧前循环梗死亚组中，心房颤动患者1年联合血管事件（校正HR 1.31，95%CI 1.00～1.70，P=0.047）、脑血管源性死亡（校正HR 3.17，95%CI 1.63～6.18，P＜0.001）和不良功能结局（校正OR 1.39，95%CI 1.09～1.77，P=0.007）发生率均高于无心房颤动患者。
结论 伴或不伴心房颤动的多发性非腔隙性脑梗死患者的临床特征有较大差异，伴有心房颤动的患者1年不良功能结局发生率更高，特别是在多发单侧前循环梗死亚组人群中，心房颤动是患者1年联合血管事件、脑血管源性死亡和不良功能结局的危险因素。

关键词: 缺血性卒中; 心房颤动; 卒中结局; 多发性脑梗死; 卒中危险因素