Importance Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, Setting, and Participants This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Main Outcomes and Measures Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

中文翻译：

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评估未确定来源的栓塞性中风的年轻成人中复发性缺血性中风的发生率：青年 ESUS 纵向队列研究。

重要性 隐源性卒中约占年轻人缺血性卒中的 40%，并且大多数符合不明原因栓塞性卒中 (ESUS) 的标准。两项随机临床试验 NAVIGATE ESUS 和 RESPECT ESUS 显示，患有 ESUS 的老年人中风复发率很高，但患有 ESUS 的年轻个体的预后和预后因素尚不确定。目的 确定年轻人中复发性缺血性卒中和死亡以及新发心房颤动 (AF) 的发生率和相关因素。设计、设置和参与者 这项多中心纵向队列研究的入组时间为 2017 年 10 月至 2019 年 10 月，平均随访期为 12 个月，截至 2020 年 10 月，包括 13 个国家/地区的 41 个中风研究中心。连续纳入诊断为 ESUS 的 50 岁及以下患者。在筛选的 576 人中，535 人在 1 人撤回同意后入组，41 人被发现不符合条件，2 人因其他原因被排除。最终随访由 520 名患者完成。主要结果和措施 复发性缺血性卒中和/或死亡、复发性缺血性卒中和卵圆孔未闭 (PFO) 的患病率。结果 参与者的平均 (SD) 年龄为 40.4 (7.3) 岁，297 (56%) 名参与者为男性。最常见的血管危险因素是吸烟（240 名患者 [45%]）、高血压（118 名患者 [22%]）和血脂异常（109 名患者 [20%]）。在 177 名参与者 (50%) 中检测到 PFO，他们进行了经胸超声心动图和气泡研究。在最初的 ESUS 之后，468 名参与者 (88%) 正在接受抗血小板治疗，52 名 (10%) 接受抗凝治疗。复发性缺血性卒中和死亡率为每 100 患者年 2.19 例，缺血性卒中复发率为每 100 患者年 1.9 例。在复发性卒中中，9 例 (64%) 为 ESUS，2 例 (14%) 为心源性栓塞，3 例 (21%) 为其他明确原因。15 名参与者检测到 AF（2.8%；95% CI，1.6-4.6）。在多变量分析中，以下因素与复发性缺血性卒中相关：卒中或短暂性脑缺血发作史（风险比，5.3；95% CI，1.8-15），存在糖尿病（风险比，4.4；95% CI，1.5- 13)，以及冠状动脉疾病史（风险比，10；95% CI，4.8-22）。结论和相关性 在这一大型 ESUS 年轻成年患者队列中，随后的缺血性卒中发生率相对较低，新发房颤的发生率也较低。大多数复发性中风也符合 ESUS 的标准，这表明需要进一步的研究来提高我们对该人群潜在中风机制的理解。