biostudies-literatureUnknown79(5)Perera KS<h4>Importance</h4>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.<h4>Objective</h4>To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.<h4>Design, setting, and participants</h4>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.<h4>Main outcomes and measures</h4>Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO).<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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.JAMA neurology450-458https://www.ebi.ac.uk/biostudies/studies/S-EPMC8922202biostudies-literatureEvaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.PMC8922202D'Anna LWharton CKallmuenzer BYoung ESUS InvestigatorsFrancisco Arenillas JNaqvi ACoutts SBKoehn JRezania FMackey EMalik ABurn MTaylor APikula APujol Lereis VPerera KWijeratne THankey GJMazzon EMarkus HMaamari BSignh RGluszkiewicz MXu JMikulik RSeidel GDetmar KKleinig TBojaryn URodriguez Lucci FRenouf AFabregas JMArauz ADossi DKarlinski MLee SSoledad Rodriguez MWeerathunga JBuckley CElyas SBathula RFerdinand PPretorius MPico FKelly EMaud ABhandari MStotts GJavier Alet MCheng AVeltkamp RCField TRedgrave JRashed KBader JTuetuencue SZiomek MLutsep HGoldlin MOlavarria VMeseguer EPerera KSKozera DJung SCohen DMajid AMeinel TAmeriso SAhmad NVynckier JHart RGHill MObaid MHalse ORosales JToni DCoutts STse DSethi PRoeder SLindert RMarti-Fabregas JNayar SBowring ASen SHarvey Jde Sa Boasquevisque DCzlonkowska ARoffe CArnold MGunathilagan GTeleg EBasson MHarkness KRandus IHaeusler KGNolte CGomis MRao-Melacini PCollas DVeronica Marroquin MDutta DMunoz LAbano NMenon NBrola WAli Sheikh AAli ABirnbaum LVeltkamp RAmeriso SFBanerjee SGomez Schneider MSmith ECortijo Garcia EChembala JPablo Povedano GHorvath TWarburton EMandzia JGuyler PMacha KGeran RField TSArauz Gongora AAfalseEvaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.<h4>Importance</h4>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.<h4>Objective</h4>To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.<h4>Design, setting, and participants</h4>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.<h4>Main outcomes and measures</h4>Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO).<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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.2022-01-01T00:00:00Z2022 May2026-05-09T22:26:40.963Z2025-02-18T22:34:36.812ZS-EPMC89222023528586910.1001/jamaneurol.2022.0048