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

Huo, Shufan; Kränkel, Nicolle; Nave, Alexander Heinrich; Sperber, Pia Sophie; Rohmann, Jessica Lee; Piper, Sophie Käthe; Heuschmann, Peter; Landmesser, Ulf; Endres, Matthias; Siegerink, Bob; Liman, Thomas Günter Gerhard

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.