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Endothelial and Leukocyte-Derived Microvesicles and Cardiovascular Risk After Stroke: PROSCIS-B
Shufan Huo1, Nicolle Kränkel2, Alexander Heinrich Nave2
1From the Center for Stroke Research Berlin CSB (S.H., A.H.N., P.S.S., J.L.R., M.E., B.S., T.G.L.), Klinik für Neurologie (S.H., A.H.N., M.E., T.G.L.), Institute of Public Health (J.L.R.), Institute of Biometry and Clinical Epidemiology (S.K.P.), Campus Benjamin Franklin (N.K., U.L.), Department of Cardiology, and Excellence Cluster Neurocure (M.E.), Charité-Universitätsmedizin Berlin; DZHK (German Centre for Cardiovascular Research), partner site Berlin (S.H., N.K., A.H.N., P.S.S., U.L., M.E., T.G.L.); Berlin Institute of Health (A.H.N., S.K.P.); Institute of Clinical Epidemiology and Biometry (P.H.), University of Würzburg; Clinical Trial Center Würzburg (P.H., U.L.), University Hospital Würzburg; and DZNE (German Center for Neurodegenerative Disease) Partner Site Berlin (M.E.), Germany. shufan.huo@charite.de.
Insights
High levels of endothelial microvesicles (EMV) and leukocyte-derived microvesicles (LMV) are linked to poorer cardiovascular outcomes in stroke survivors. These markers may aid in predicting long-term risks for patients post-stroke.
Area of Science:
- Cardiovascular Research
- Stroke Medicine
- Biomarker Discovery
Background:
- Circulating microvesicles (MV) are implicated in vascular processes.
- Understanding their role in long-term outcomes after stroke is crucial for patient prognosis.
Purpose of the Study:
- To investigate the association between circulating microvesicle levels and long-term cardiovascular outcomes in patients following a first-ever stroke.
Main Methods:
- Prospective cohort study (PROSCIS-B) with 3-year follow-up of 571 first-ever ischemic stroke patients.
- Measured endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) via flow cytometry.
- Analyzed associations with a combined endpoint of recurrent stroke, myocardial infarction, and all-cause mortality using Cox models.
Main Results:
- Elevated levels of EMV (aHR 2.5) and LMV (aHR 3.1) in the highest quartile were significantly associated with adverse cardiovascular events.
- Associations for PMV (aHR 1.7) were less pronounced, and no association was found for MMV (aHR 1.1).
- Class II evidence supports the impact of MV levels on stroke, MI, and mortality in mild stroke survivors.
Conclusions:
- High circulating EMV and LMV levels predict worse cardiovascular outcomes within 3 years post-stroke.
- These findings highlight the roles of endothelial dysfunction and vascular inflammation in long-term stroke prognosis.
- EMV and LMV show potential as predictive biomarkers for stroke patients.
Objective:
To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up.
Methods:
In the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up 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 with 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 NIH Stroke Scale score 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 with the lowest quartile used as the 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.
Clinicaltrialsgov Identifier:
NCT01363856.
Classification Of Evidence:
This study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke.
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