title: Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes.
abstract: OBJECTIVE
  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. We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebrand factor (vWF), primarily reflecting activation of endothelial cells, and increased concentrations of soluble P-selectin and platelet-derived microvesicles (PDM), primarily reflecting activation of platelets, compared with healthy controls. We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- 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 205 randomly selected community controls stratified by age, sex, and postal code. Using established criteria, we classified cases of stroke by etiological subtype in a blinded fashion. The prevalence of vascular risk factors and blood concentrations of E-selectin, P-selectin, vWF antigen, and PDM were determined in stroke cases within 7 days and at 3 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 all significantly higher in cases compared with controls. At 3 to 6 months after stroke, the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls, and PDM concentrations remained elevated. There was a strong, graded, and independent (of age, sex, and vascular risk factors) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke, particularly ischemic stroke caused by large-artery atherothrombosis. There was also a significant, graded, and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis.
  
  
  CONCLUSIONS
  We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis. Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke.
authors.affiliation: Department of Medicine, University of Western Australia, Perth, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Cherian
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Jim
authors.initials: J
authors.lastname: Thom
authors.forename: Ross I
authors.initials: RI
authors.lastname: Baker
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillan
authors.forename: Janelle
authors.initials: J
authors.lastname: Staton
authors.forename: Qilong
authors.initials: Q
authors.lastname: Yi
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000453:epidemiology / Q000503:physiopathology*; D016022:Case-Control Studies; D015897:Comorbidity; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000453:epidemiology / Q000503:physiopathology*; D013347:Subcellular Fractions / Q000737:chemistry; D014904:Western Australia / Q000453:epidemiology; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D019007:P-Selectin; D014841:von Willebrand Factor