Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source
Authors: Kanjana S. Perera, Danielle de Sa Boasquevisque, Purnima Rao-Melacini, Amanda Taylor, Anna Cheng, Graeme J. Hankey, Sarah Lee, Joan Marti Fabregas, Sebastian F. Ameriso, Thalia S. Field, Antonio Arauz, Shelagh B. Coutts, Marcel Arnold, Robert Mikulik, Danilo Toni, Jennifer Mandzia, Roland C. Veltkamp, Elena Meseguer, Karl Georg Haeusler, Robert G. Hart, Sebastian Ameriso, Daiana Dossi, Federico Rodriguez Lucci, Julieta Rosales, Maia Gomez Schneider, Maria Soledad Rodriguez, Matias Javier Alet, Virginia Pujol Lereis, Guillermo Pablo Povedano, Maria Veronica Marroquin, Tissa Wijeratne, Elizabeth Mackey, Elyce Warburton, Fatemeh Rezania, Timothy Kleinig, Erin Kelly, Jackson Harvey, Sumiti Nayar, Kanjana Perera, Thalia Field, Shelagh Coutts, Dominic Tse, Eric Smith, Ericka Teleg, Michael Hill, Ravinder Signh, Jennifer Mandzia, Aleksandra Pikula, GRANT Stotts, Veronica Olavarria, Enrico Mazzon, Elena Meseguer, Fernando Pico, Bernd Kallmuenzer, Julia Koehn, Kosmas Macha, Sebastian Roeder, Christian Nolte, Ida Randus, Jonas Bader, Rohat Geran, Serdar Tuetuencue, Gunter Seidel, Kuecken Detmar, Angel Antonio Arauz Gongora, Anna Czlonkowska, Dorota Kozera, Marcin Gluszkiewicz, Michal Karlinski, Waldemar Brola, Malgorzata Ziomek, Matthys Basson, Maria Pretorius, Juan Francisco Arenillas, Elisa Cortijo Garcia, Joan Marti-Fabregas, MERITXELL GOMIS, Lucia Munoz, Marcel Arnold, Basel Maamari, Jan Vynckier, Martina Goldlin, Simon Jung, Thomas Horvath, Thomas Meinel, Hugh Markus, Jayan Chembala, Christine Roffe, Janaka Weerathunga, Nenette Abano, Phillip Ferdinand, Roland Veltkamp, Abid Malik, Ambreen Ali Sheikh, Lucio D'Anna, Omid Halse, Soma Banerjee, Urszula Bojaryn, Ali Ali, Aaizza Naqvi, Arshad Majid, Jessica Redgrave, Kirsty Harkness, Ralf Lindert, David Collas, Mohit Bhandari, Khalid Rashed, Clare Buckley, Paul Guyler, Nisha Menon, Matthew Burn, Nasar Ahmad, Chris Wharton, David Cohen, Raj Bathula, Dipankar Dutta, Mudhar Obaid, Gunaratnam Gunathilagan, Salim Elyas, Adrian Renouf, Angela Bowring, Sarah Lee, Pramodkumar Sethi, Jindong Xu, Alberto Maud, Lee Birnbaum, Souvik Sen, Helmi Lutsep
Journal: JAMA Neurology (2022)

<h3>Importance</h3> 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. <h3>Objective</h3> To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. <h3>Design, Setting, and Participants</h3> 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. <h3>Main Outcomes and Measures</h3> Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). <h3>Results</h3> 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). <h3>Conclusions and Relevance</h3> 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.