Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source

George Ntaios; Konstantinos Vemmos; Gregory Y H Lip; Eleni Koroboki; Efstathios Manios; Anastasia Vemmou; Ana Rodríguez-Campello; Elisa Cuadrado-Godia; Eva Giralt-Steinhauer; Valentina Arnao; Valeria Caso; Maurizio Paciaroni; Exuperio Diez-Tejedor; Blanca Fuentes; Josefa Pérez Lucas; Antonio Arauz; Sebastian F Ameriso; Maximiliano A Hawkes; Lucía Pertierra; Maia Gómez-Schneider; Fabio Bandini; Beatriz Chavarria Cano; Ana Maria Iglesias Mohedano; Andrés García Pastor; Antonio Gil-Núñez; Jukka Putaala; Turgut Tatlisumak; Miguel A Barboza; George Athanasakis; Konstantinos Makaritsis; Vasileios Papavasileiou

doi:10.1161/STROKEAHA.116.013713

Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source

Stroke. 2016 Sep;47(9):2278-85. doi: 10.1161/STROKEAHA.116.013713. Epub 2016 Aug 9.

Authors

George Ntaios¹, Konstantinos Vemmos², Gregory Y H Lip², Eleni Koroboki², Efstathios Manios², Anastasia Vemmou², Ana Rodríguez-Campello², Elisa Cuadrado-Godia², Eva Giralt-Steinhauer², Valentina Arnao², Valeria Caso², Maurizio Paciaroni², Exuperio Diez-Tejedor², Blanca Fuentes², Josefa Pérez Lucas², Antonio Arauz², Sebastian F Ameriso², Maximiliano A Hawkes², Lucía Pertierra², Maia Gómez-Schneider², Fabio Bandini², Beatriz Chavarria Cano², Ana Maria Iglesias Mohedano², Andrés García Pastor², Antonio Gil-Núñez², Jukka Putaala², Turgut Tatlisumak², Miguel A Barboza², George Athanasakis², Konstantinos Makaritsis², Vasileios Papavasileiou²

Affiliations

¹ From the Department of Medicine, Larissa University Hospital, School of Medicine, University of Thessaly, Greece (G.N., G.A., K.M., V.P.); Department of Clinical Therapeutics, Medical School of Athens, Alexandra Hospital, Greece (K.V., E.K., E.M., A.V.); University of Birmingham Institute of Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.); Stroke Unit, 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 (A.R.-C., E.C.-G., E.G.-S.); Stroke Unit, University of Perugia, Italy (V.A., V.C., M.P.); Department of Neurology and Stroke Center, La Paz University Hospital - Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain (E.D.-T., B.F., J.P.L.); Stroke Clinic, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico (A.A.); Department of Neurology, Institute for Neurological Research, FLENI, Buenos Aires, Argentina (S.F.A., M.A.H., L.P., M.G.-S.); Department of Neurology, San Paolo Hospital, Savona, Italy (F.B.); Vascular Neurology Section, Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain (B.C.C., A.M.I.M; A.G.P., A.G.-N.); Department of Neurology, Helsinki university Central Hospital and University of Helsinki, Finland (J.P., T.T.); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Department of Neurosciences, Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica (M.A.B.); and Stroke Service, Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, United Kingdom (V.P.). [email protected].
² From the Department of Medicine, Larissa University Hospital, School of Medicine, University of Thessaly, Greece (G.N., G.A., K.M., V.P.); Department of Clinical Therapeutics, Medical School of Athens, Alexandra Hospital, Greece (K.V., E.K., E.M., A.V.); University of Birmingham Institute of Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.); Stroke Unit, 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 (A.R.-C., E.C.-G., E.G.-S.); Stroke Unit, University of Perugia, Italy (V.A., V.C., M.P.); Department of Neurology and Stroke Center, La Paz University Hospital - Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain (E.D.-T., B.F., J.P.L.); Stroke Clinic, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico (A.A.); Department of Neurology, Institute for Neurological Research, FLENI, Buenos Aires, Argentina (S.F.A., M.A.H., L.P., M.G.-S.); Department of Neurology, San Paolo Hospital, Savona, Italy (F.B.); Vascular Neurology Section, Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain (B.C.C., A.M.I.M; A.G.P., A.G.-N.); Department of Neurology, Helsinki university Central Hospital and University of Helsinki, Finland (J.P., T.T.); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Department of Neurosciences, Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica (M.A.B.); and Stroke Service, Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, United Kingdom (V.P.).

PMID: 27507859
DOI: 10.1161/STROKEAHA.116.013713

Abstract

Background and purpose: The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS2) and CHA2DS2-VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS.

Methods: We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS2 and CHA2DS2-VASc scores.

Results: One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS2 score 0, patients with CHADS2 score 1 and CHADS2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86-10.40, respectively). Compared with low-risk CHA2DS2-VASc score, patients with high-risk CHA2DS2-VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4).

Conclusions: The risk of recurrent ischemic stroke/TIA and death in ESUS is reliably stratified by CHADS2 and CHA2DS2-VASc scores. Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc group have much higher risk of ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold, respectively.

Keywords: ischemic attack, transient; mortality; recurrence; stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aged
Brain Ischemia / etiology
Brain Ischemia / mortality*
Embolism / complications
Embolism / mortality*
Female
Humans
Hypertension / complications*
Hypertension / mortality
Ischemic Attack, Transient / etiology
Ischemic Attack, Transient / mortality*
Male
Middle Aged
Recurrence
Registries
Risk Assessment
Risk Factors
Sex Factors
Stroke / etiology
Stroke / mortality*
Survival Rate