Patients With Type 3 Severe von Willebrand Disease Are Not Protected Against Atherosclerosis

Abstract

Background-The results of a number of studies in pigs and mice suggest that absence of von Willebrand factor (vWF) protects against the development of atherosclerosis. We studied whether patients with a complete deficiency of vWF (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall changes than healthy controls. Methods and Results-This study included 47 individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic changes were assessed by measuring the thickness of the intima-media in the carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic changes were quantified by summing the maximal thickness of atherosclerotic plaques in the carotid and femoral arteries and were expressed as a plaque score. Established risk factors were determined to adjust for possible differences between the groups. We found no substantial difference in intima-media thickness between vWD patients and controls (adjusted difference for carotid artery 0.007 mm, 95% CI Ϫ0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI Ϫ0.056 to 0.19 mm). Similar proportions of patients and controls had atherosclerotic plaques (19% and 17%, respectively). No difference was found in the plaque score between groups (adjusted difference Ϫ0.22 mm, 95% CI Ϫ0.69 to 0.26). Among vWD patients, we found no effect of treatment with vWF concentrates on intima-media thickness or plaque score. Conclusions-The results of this study indicate that vWF does not play a substantial role in human atherogenesis.

Cardiovascular risk in patients with hemophilia

“…25 In humans, several earlier studies analyzed the presence of subclinical atherosclerosis by measuring the carotid and femoral intima media thickness (IMT) in patients with hemophilia or von Willebrand disease. [26][27][28][29] Overall, there was no difference in the mean IMT of either the carotid artery (0.75 mm vs 0.74 mm) or femoral artery (0.75 mm vs 0.79 mm) in patients and age-matched healthy controls. 8 Recently, 2 studies investigated whether hypocoagulability is associated with decreased atherogenesis by evaluating subclinical atherosclerosis and endothelial function in hemophilia patients and in matched unaffected controls.…”

Dynamics and Plasticity of Weibel-Palade Bodies in Endothelial Cells

“…67 In contrast to animal models, a clinical study has failed to show protection from atherosclerosis in patients with type 3 VWD who presumably lack WPBs. 68 Interestingly, the 3-hydroxy-3-methylglutaryl coenzyme A (CoA) (3-hydroxy-3-methylglutaryl [HMG]-CoA) reductase inhibitor simvastatin has been shown to decrease regulated exocytosis of WPBs. 69 This mechanism of action of HMG-CoA reductase inhibitors may therefore contribute to the beneficial effects of these reagents in treatment of patients with cardiovascular disease.…”

Intrinsic Pathway of Coagulation and Arterial Thrombosis

“…A role for intrinsic pathway factors in arterial disease in humans is not as clear as for venous events. Severe congenital coagulopathies such as hemophilia, 40 type III von Willebrand disease, 41 or Glanzmann thrombasthenia 42 (absence or abnormality of the platelet ␣IIb/␤III integrin) do not appear to affect development of atherosclerosis, although there are suggestions that hemophilia retards arterial plaque formation somewhat in humans 43 and mice. 44 However, longitudinal studies in the Netherlands of patients with factor VIII or factor IX deficiency demonstrated a lower incidence of myocardial infarction than in controls, and an 80% reduction in mortality from coronary artery disease, suggesting factor VIII or IX deficiency may inhibit formation of thrombi at sites of plaque rupture.…”