High von Willebrand Factor Levels Increase the Risk of First Ischemic Stroke

Abstract

Background and Purpose-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 Ϫ1793C/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.

Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke

“…This is in agreement with the study by Catto et al [7], which involved 169 patients with ischemic or hemorrhagic stroke. In contrast, significantly increased VWF levels at the 3-month follow-up were not detected in three other studies [5,6,17]. However, these studies only included a small number of patients at follow-up (26-64 patients) [5,6,17].…”

“…Furthermore, blood sampling was standardized and performed at two time points, whereof one was in the chronic phase. Only a few previous studies [5][6][7]11,17] have examined VWF levels at more than one well-defined time-point. There are also some limitations that should be considered.…”

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

“…The association between ADAMTS13 and ischemic stroke has been investigated previously in small case-control studies. 10,[36][37][38] The association between low ADAMTS13 activity and ischemic stroke risk is likely to be explained by less cleavage of vWF HMWMs, which are the most prothrombotic. 4,35 Freynhofer et al affirm that vWF and its cleaving protease ADAMTS13 might play an important role in the development and perpetuation of vascular disease in patients with AF.…”

“…9 Our results show that increased vWF levels, vWF activity, and modifications in the multimeric structure showing HMWMs all correlate with the incidence of stroke and could indicate a causal role of vWF. 10,25 Several studies have reported an association between high vWF levels and the risk of ischemic stroke. 11,43,44 We found increased vWF levels, vWF activity, and vWF HMWMs in patients with acute stroke .…”

“…2,6 Atrial fibrillation (AF) is the most commonly sustained cardiac arrhythmia and is associated with a high risk of stroke and thromboembolism. 7,8 Elevated vWF concentrations are associated with cardiovascular disease, 9 increased risk of ischemic heart disease, and the occurrence of acute ischemic stroke 10 ; these high levels of vWF are associated with the risk of stroke, even in the general population. 11 The biological function of vWF depends largely on the size of its multimers.…”