title: High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. t.bongers@erasmusmc.nl
authors.forename: Tamara N
authors.initials: TN
authors.lastname: Bongers
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Mary-Lou P J
authors.initials: ML
authors.lastname: van Goor
authors.forename: Vinod
authors.initials: V
authors.lastname: Bhagwanbali
authors.forename: Huub H D M
authors.initials: HH
authors.lastname: van Vliet
authors.forename: Encarna B
authors.initials: EB
authors.lastname: Gómez García
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology*; D014841:von Willebrand Factor / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human