Endothelial and Leukocyte-Derived Microvesicles and Cardiovascular Risk After Stroke
PROSCIS-B
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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 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.
ClinicalTrials.gov 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.
Glossary
- AV=
- annexin V;
- CAD=
- coronary artery disease;
- CI=
- confidence interval;
- ED=
- endothelial dysfunction;
- EMV=
- endothelial MV;
- HR=
- hazard ratio;
- IQR=
- interquartile range;
- LAA=
- large artery atherosclerotic;
- LMV=
- leukocyte-derived MV;
- MI=
- myocardial infarction;
- MMV=
- monocytic MV;
- MV=
- microvesicles;
- NIHSS=
- NIH Stroke Scale;
- PMV=
- platelet-derived MV;
- PROCIS-B=
- Prospective Cohort with Incident Stroke Berlin;
- py=
- person-years;
- rcf=
- relative centrifugal force;
- TOAST=
- Trial of ORG 10172 in Acute Stroke Treatment
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received January 22, 2020.
- Accepted in final form October 5, 2020.
- © 2020 American Academy of Neurology
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