High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability.
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.
Bongers
Tamara N
TN
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. t.bongers@erasmusmc.nl
de Maat
Moniek P M
MP
van Goor
Mary-Lou P J
ML
Bhagwanbali
Vinod
V
van Vliet
Huub H D M
HH
Gómez García
Encarna B
EB
Dippel
Diederik W J
DW
Leebeek
Frank W G
FW
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
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human