George Ntaios1, Gregory Y H Lip2, Konstantinos Vemmos2, Eleni Koroboki2, Efstathios Manios2, Anastasia Vemmou2, Ana Rodríguez-Campello2, Elisa Cuadrado-Godia2, Jaume Roquer2, Valentina Arnao2, Valeria Caso2, Maurizio Paciaroni2, Exuperio Diez-Tejedor2, Blanca Fuentes2, Josefa Pérez Lucas2, Antonio Arauz2, Sebastian F Ameriso2, Lucía Pertierra2, Maia Gómez-Schneider2, Maximiliano A Hawkes2, Fabio Bandini2, Beatriz Chavarria Cano2, Ana Maria Iglesias Mohedano2, Andrés García Pastor2, Antonio Gil-Núñez2, Jukka Putaala2, Turgut Tatlisumak2, Miguel A Barboza2, George Athanasakis2, Fotios Gioulekas2, Konstantinos Makaritsis2, Vasileios Papavasileiou2. 1. From the Department of Medicine (G.N., G.A., K.M., V.P.), Larissa University Hospital, School of Medicine, University of Thessaly, Larissa, Greece; University of Birmingham Institute of Cardiovascular Sciences (G.Y.H.L.), City Hospital, UK; Department of Clinical Therapeutics (K.V., E.K., E.M., A.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.P.L.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Department of Neurology (M.A.H.), Division of Critical Care Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Subdirectorate of Informatics (F.G.), Larissa General University Hospital, Greece; and Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK. gntaios@med.uth.gr. 2. From the Department of Medicine (G.N., G.A., K.M., V.P.), Larissa University Hospital, School of Medicine, University of Thessaly, Larissa, Greece; University of Birmingham Institute of Cardiovascular Sciences (G.Y.H.L.), City Hospital, UK; Department of Clinical Therapeutics (K.V., E.K., E.M., A.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.P.L.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Department of Neurology (M.A.H.), Division of Critical Care Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Subdirectorate of Informatics (F.G.), Larissa General University Hospital, Greece; and Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK.
Abstract
OBJECTIVE: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS). METHODS: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death. RESULTS: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively). CONCLUSIONS: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.
OBJECTIVE: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS). METHODS: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death. RESULTS: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively). CONCLUSIONS: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.
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