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(Circulation. 2004;109:740-744.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

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

Results From a Multicenter Study in 47 Patients

A. rámek, MD; P. Bucciarelli, MD; A.B. Federici, MD; P.M. Mannucci, MD; V. De Rosa, MD; G. Castaman, MD; M. Morfini, MD; M.G. Mazzucconi, MD; A. Rocino, MD; M. Schiavoni, MD; F.A. Scaraggi, MD; J.H.C. Reiber, PhD; F.R. Rosendaal, MD

From the Department of Clinical Epidemiology (A.S., F.R.R.), Department of Radiology (J.H.C.R.), and Hemostasis and Thrombosis Research Center (F.R.R.), Leiden University Medical Center, Leiden, the Netherlands; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (P.B., A.B.F., P.M.M.), IRCCS Maggiore Hospital and University of Milano, Milano, Italy; Department of Angiology and Blood Coagulation (V.D.R.), University Hospital S. Orsola, Bologna, Italy; Department of Haematology and Hemophilia and Thrombosis Center (G.C.), San Bortolo Hospital, Vicenza, Italy; Department of Hematology & Hemophilia Center (M.M.), University of Florence, Florence, Italy; Department of Hematology (M.G.M.), University La Sapienza, Rome, Italy; Hemophilia and Thrombosis Center (A.R.), Hospital San Giovanni Bosco, Naples, Italy; Servizio di Coagulazione (M.S.), Centro Emofilia, Policlinico-Universitá, Bari, Italy; and Hemostasis and Thrombosis Center (F.A.S.), University of Bari, Italy.

Correspondence to Prof Dr F.R. Rosendaal, Department of Clinical Epidemiology, C9-P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail F.R.Rosendaal{at}lumc.nl

Received December 3, 2002; de novo received July 29, 2003; revision received October 29, 2003; accepted October 29, 2003.

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 -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 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 -0.22 mm, 95% CI -0.69 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.

Key Words: atherosclerosis • coagulation • von Willebrand factor • cardiovascular disease • carotid arteries

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