Bongers Tamara N, de Maat Moniek P M, van Goor Mary-Lou P J, Bhagwanbali Vinod, van Vliet Huub H D M, Gómez García Encarna B, Dippel Diederik W J, Leebeek Frank W G
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Stroke. 2006 Nov;37(11):2672-7. doi: 10.1161/01.STR.0000244767.39962.f7. Epub 2006 Sep 21.
Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism.
In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G polymorphism in the vWF gene, and C-reactive protein.
vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association.
vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.
血管性血友病因子（vWF）浓度升高与缺血性心脏病风险增加相关。多种因素会影响vWF抗原水平及活性，包括血型、基因变异性、急性期反应以及具有血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTS13）介导的蛋白水解作用，ADAMTS13是vWF蛋白水解切割的一个决定因素。我们评估了这些因素如何影响vWF与中风发生之间的关系，以了解潜在机制。
在一项病例对照研究中，纳入124例首次发生缺血性中风的患者和125例年龄及性别匹配的对照，我们研究了vWF抗原（vWF:Ag）、vWF瑞斯托霉素辅因子活性（vWF:RCo）、ADAMTS13活性、vWF基因中的-1793C/G多态性以及C反应蛋白。
病例组的vWF抗原和活性水平显著高于对照组。与vWF:Ag和vWF:RCo最低四分位数的个体相比，处于vWF:Ag上四分位数的个体发生缺血性中风的相对风险最高（比值比，3.2；95%可信区间，1.4至7.5），处于vWF:RCo上四分位数的个体相对风险为2.1（95%可信区间，0.9至4.8）。与ADAMTS13最高四分位数的个体相比，处于最低四分位数的个体中风相对风险为1.7（95%可信区间，0.7至3.9）。C反应蛋白、ADAMTS13和基因变异并未影响vWF与中风相对风险之间的关联，而血型确实影响该关联。
vWF抗原和活性与急性缺血性中风的发生相关。这种关系不受急性期反应严重程度、基因变异或降解的影响。
