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November 12, 2020Article

Endothelial and leukocyte-derived microvesicles and cardiovascular risk after stroke—PROSCIS-B

View ORCID ProfileShufan Huo, Nicolle Kränkel, Alexander Heinrich Nave, View ORCID ProfilePia Sophie Sperber, View ORCID ProfileJessica Lee Rohmann, View ORCID ProfileSophie Käthe Piper, Peter Heuschmann, View ORCID ProfileUlf Landmesser, Matthias Endres, View ORCID ProfileBob Siegerink, Thomas Günter Gerhard Liman
First published November 12, 2020, DOI: https://doi.org/10.1212/WNL.0000000000011223
Shufan Huo
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
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  • ORCID record for Shufan Huo
Nicolle Kränkel
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
4Campus Benjamin Franklin - Department of Cardiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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  • For correspondence: nicolle.kraenkel@charite.de
Alexander Heinrich Nave
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
5Berlin Institute of Health (BIH), Berlin, Germany
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  • For correspondence: alexander-heinrich.nave@charite.de
Pia Sophie Sperber
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
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  • ORCID record for Pia Sophie Sperber
  • For correspondence: pia.sperber@charite.de
Jessica Lee Rohmann
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
6Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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  • For correspondence: jessica.rohmann@charite.de
Sophie Käthe Piper
5Berlin Institute of Health (BIH), Berlin, Germany
7Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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  • For correspondence: sophie.piper@charite.de
Peter Heuschmann
8Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
9Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
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  • For correspondence: peter.heuschmann@uni-wuerzburg.de
Ulf Landmesser
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
4Campus Benjamin Franklin - Department of Cardiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
9Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
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Matthias Endres
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
11German Center for Neurodegenerative Disease (DZNE), Partner Site Berlin, Berlin, Germany.
12Excellence Cluster Neurocure, Charité—Universitätsmedizin Berlin, Berlin, Germany.
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  • For correspondence: matthias.endres@charite.de
Bob Siegerink
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Thomas Günter Gerhard Liman
1Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
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  • For correspondence: thomas.liman@charite.de
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Citation
Endothelial and leukocyte-derived microvesicles and cardiovascular risk after stroke—PROSCIS-B
Shufan Huo, Nicolle Kränkel, Alexander Heinrich Nave, Pia Sophie Sperber, Jessica Lee Rohmann, Sophie Käthe Piper, Peter Heuschmann, Ulf Landmesser, Matthias Endres, Bob Siegerink, Thomas Günter Gerhard Liman
Neurology Nov 2020, 10.1212/WNL.0000000000011223; DOI: 10.1212/WNL.0000000000011223

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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.

  • Received January 22, 2020.
  • Accepted in final form October 5, 2020.
  • © 2020 American Academy of Neurology

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