Cherian Paul, Hankey Graeme J, Eikelboom John W, Thom Jim, Baker Ross I, McQuillan Andrew, Staton Janelle, Yi Qilong
Department of Medicine, University of Western Australia, Perth, Australia.
Stroke. 2003 Sep;34(9):2132-7. doi: 10.1161/01.STR.0000086466.32421.F4. Epub 2003 Aug 7.
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.
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.
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.
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.
内皮细胞和血小板的激活是动脉粥样硬化血栓形成的重要介质。内皮细胞和血小板激活的标志物，如可溶性黏附分子，可以在血浆中检测到。我们假设，与健康对照相比，急性缺血性卒中患者血浆中可溶性E-选择素和血管性血友病因子（vWF）的浓度会升高，主要反映内皮细胞的激活；可溶性P-选择素和血小板衍生微泡（PDM）的浓度会升高，主要反映血小板的激活。我们还假设，与心源性栓塞相比，这些标志物在大动脉和小动脉粥样硬化血栓形成所致缺血性卒中中升高程度会有所不同。
我们进行了一项病例对照研究，纳入200例首次因缺血性卒中住院的患者，并按年龄、性别和邮政编码随机选取205例社区对照。我们采用既定标准，以盲法将卒中病例按病因亚型进行分类。在卒中病例发病7天内、发病后3至6个月以及对照中，确定血管危险因素的患病率以及E-选择素、P-选择素、vWF抗原和PDM的血浓度。
与对照相比，卒中发病7天内可溶性E-选择素、P-选择素和PDM的平均血浓度在病例中均显著更高。卒中后3至6个月，E-选择素和P-选择素的平均血浓度显著低于对照，而PDM浓度仍升高。急性期E-选择素血浓度升高与所有缺血性卒病因亚型，尤其是大动脉粥样硬化血栓形成所致缺血性卒中之间存在强烈、分级且独立（不受年龄、性别和血管危险因素影响）的关联。急性期vWF血浓度升高与大动脉粥样硬化血栓形成所致缺血性卒中之间也存在显著、分级且独立的关联。
我们已证明内皮细胞和血小板激活的血液标志物急性升高与缺血性卒中之间，以及内皮细胞激活的血液标志物急性升高与大动脉粥样硬化血栓形成所致缺血性卒中之间存在显著关联。PDM血浓度持续升高可能是缺血性卒中风险增加的标志物。
