Shufan Huo1,2,3, Nicolle Kränkel3,4, Alexander Heinrich Nave5,2,3,6, Pia Sophie Sperber5,3, Jessica Lee Rohmann5,7, Sophie Käthe Piper6,8, Peter Heuschmann9,10, Ulf Landmesser3,4,10, Matthias Endres5,2,3,11,12, Bob Siegerink5, Thomas Günter Gerhard Liman5,2,3. 1. Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany. shufan.huo@charite.de. 2. Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. 3. German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany. 4. Campus Benjamin Franklin - Department of Cardiology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 5. Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany. 6. Berlin Institute of Health (BIH), Berlin, Germany. 7. Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany. 8. Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 9. Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. 10. Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany. 11. German Center for Neurodegenerative Disease (DZNE), Partner Site Berlin, Berlin, Germany. 12. Excellence Cluster Neurocure, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract
OBJECTIVE: To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in first-ever stroke patients with a three-year follow-up. METHODS: In the PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured using flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. RESULTS: Five hundred seventy-one patients were recruited (median age 69 years; 39% female; median NIHSS 2, interquartile range 1-4) and 95 endpoints occurred. Patients with levels of EMV [adjusted hazard ratio (HR) = 2.5, 95% confidence interval (CI) 1.2-4.9] or LMV (HR = 3.1, 95% CI 1.4-6.8) in the highest quartile were more likely to experience an event than participants with lower levels using the lowest quartile as reference category. The association was less pronounced for PMV (HR = 1.7, 95% CI 0.9-3.2) and absent for MMV (HR = 1.1, 95% CI 0.6-1.8). CONCLUSION: High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients. STUDY REGISTRATION: clinicaltrials.gov/ct2/show/NCT01363856. UID: NCT01363856. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of the impact of MV levels on subsequent stroke, myocardial infarction or all-cause mortality in survivors of mild stroke.
OBJECTIVE: To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in first-ever strokepatients with a three-year follow-up. METHODS: In the PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured using flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. RESULTS: Five hundred seventy-one patients were recruited (median age 69 years; 39% female; median NIHSS 2, interquartile range 1-4) and 95 endpoints occurred. Patients with levels of EMV [adjusted hazard ratio (HR) = 2.5, 95% confidence interval (CI) 1.2-4.9] or LMV (HR = 3.1, 95% CI 1.4-6.8) in the highest quartile were more likely to experience an event than participants with lower levels using the lowest quartile as reference category. The association was less pronounced for PMV (HR = 1.7, 95% CI 0.9-3.2) and absent for MMV (HR = 1.1, 95% CI 0.6-1.8). CONCLUSION: High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for strokepatients. STUDY REGISTRATION: clinicaltrials.gov/ct2/show/NCT01363856. UID: NCT01363856. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of the impact of MV levels on subsequent stroke, myocardial infarction or all-cause mortality in survivors of mild stroke.
Authors: Ceren Eyileten; Daniel Jakubik; Andleeb Shahzadi; Aleksandra Gasecka; Edwin van der Pol; Salvatore De Rosa; Dominika Siwik; Magdalena Gajewska; Dagmara Mirowska-Guzel; Iwona Kurkowska-Jastrzebska; Anna Czlonkowska; Marek Postula Journal: Int J Mol Sci Date: 2022-04-20 Impact factor: 6.208