Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes

P. Cherian, Graeme Hankey, J.W. Eikelboom, J. Thom, R.I. Baker, A. Mcquillan, J. Staton, Q. Yi

    Research output: Contribution to journalArticle

    142 Citations (Scopus)

    Abstract

    Background and Purpose—Activation of endothelial cells and platelets is an important mediator of atherothrombosis.Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma. Wehypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectinand von Willebrand factor (vWF), primarily reflecting activation of endothelial cells, and increased concentrations ofsoluble P-selectin and platelet-derived microvesicles (PDM), primarily reflecting activation of platelets, compared withhealthy controls. We also hypothesized that these markers would be differentially elevated in ischemic stroke caused bylarge- and small-artery atherothrombosis compared with cardiogenic embolism.Methods—We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205randomly selected community controls stratified by age, sex, and postal code. Using established criteria, we classifiedcases of stroke by etiological subtype in a blinded fashion. The prevalence of vascular risk factors and bloodconcentrations of E-selectin, P-selectin, vWF antigen, and PDM were determined in stroke cases within 7 days and at3 to 6 months after stroke and in controls.Results—Mean blood concentrations of soluble E-selectin, P-selectin, and PDM within 7 days of stroke onset were allsignificantly higher in cases compared with controls. At 3 to 6 months after stroke, the mean blood concentrations ofE-selectin and P-selectin fell significantly below that of controls, and PDM concentrations remained elevated. There wasa strong, graded, and independent (of age, sex, and vascular risk factors) association between increasing bloodconcentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke, particularly ischemicstroke caused by large-artery atherothrombosis. There was also a significant, graded, and independent associationbetween increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-arteryatherothrombosis.Conclusions—We have demonstrated significant associations between acute elevation of blood markers of endothelial celland platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activationand ischemic stroke caused by large-artery atherothrombosis. Persistent elevated blood concentrations of PDM may bea marker of increased risk of ischemic stroke.
    Original languageEnglish
    Pages (from-to)2132-2137
    JournalStroke
    Volume34
    Issue number9
    DOIs
    Publication statusPublished - 2003

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