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.

Background-Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. Methods and Results-A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography.To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, Ϫ0.078 mm; 95% CI, Ϫ0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, Ϫ0.10 mm; 95% CI, Ϫ0.27 to 0.061 mm).

SummaryPlasma clotting factor VII and plasma fibrraogen have been claimed äs mdependent nsk factors for occlusive caidiovasculai disease The aim of this study was to mvestigate whethei these coagulation paiameters affect early atheioscleiosis, additional to their possible effect on aitenal throrabosisWe used high-iesolution quantitative ultrasonography to measme carotid mtiraa-media thickness in 121 healthy volunteers, aged 18 to 56 years It has pieviously been demonstiated that an incieased aitery wall thickness is seen in advanced atheioscleiosis To validate our method ology foi relatively young individuals, we assessed the association of intima-media thickness with the nsk-factor Status of out subjects, by tncluding classical cardiovascular nsk factors, e g age, sex, serum cholesterol, smoking habits and blood pressure Theieaftei, we studied the effect of factor VII and fibrmogen plasma levels on carotid intimamedia thickness, äs well äs that of polymoiphisms of the factoi VII and fibrmogen genes All classical nsk factois except smoking and family histoiy were associated with intima media thickness When adjusted for by multivanate linear regiesston analysis, age, blood piessure and cholestetol appeaied to be mdependent deteirmnants of mtima-media Ihickness Factor VII and fibrmogen levels showed no association m multivanate analysis with intima-media thickness We conclude that aiteiy wall thickness measurement by ultrasound is a useful tool to mvestigate the lole of clotting factois in eaily atheioscleiosis Factoi VII and fibimö-gen levels m young and middle-aged volunteeis have no association with eaily ai therosclerotic vessel wall changes

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Summary. Recent studies suggest that high lipoprotein(a) [Lp(a)] plasma levels are associated with symptomatic ischemic cardiovascular disease. We examined whether Lp(a) plasma levels are associated with early atherosclerotic vessel wall changes in a group of asymptomatic subjects. In a group of 142 asymptomatic men, the intima-media thickness (IMT) in the common carotid artery, the carotid bifurcation and the common femoral artery was determined by B-mode ultrasonography. In addition to Lp(a) Several hypotheses have been put forward concerning the etiological role of Lp(a) in cardiovascular disease, based on the specific structure of Lp(a). Lipoprotein(a) consists of an LDLlike particle that is disulfide-linked to an apolipoprotein(a). LDL levels are major independent risk factors for atherosclerosis, and DNA sequence analysis has shown that a part of apolipoprotein(a) resembles plasminogen [9]. It has been hypothesized that because of this, high levels of Lp(a) might interfere with the fibrinolytic process, leading to a prothrombotic state [10]. This could be enhanced by the ability of Lp(a) to activate PAI-1 (plasminogen activator inhibitor-1) and inactivate t-PA (tissue-type plasminogen activator) and TFPI (tissue factor pathway inhibitor) [11][12][13]. Furthermore, Lp(a) might directly contribute to the atherogenic process by decreasing the break-up of mural thrombi which subsequently may be incorporated in atherosclerotic plaques. Finally, according to recent studies, high Lp(a) levels decrease tissue growth factor-b activation, resulting in proliferation and migration of smooth muscle cells into the intimal layer of the arterial wall [14,15]. This process is considered to be one of the earliest stages in the atherosclerotic process.To study the role of Lp(a) in the atherosclerotic process, a number of research groups have investigated whether high Lp(a) levels are associated with symptomatic and premature atherosclerosis in the carotid artery as assessed by ultrasound [16][17][18][19][20][21][22][23][24][25]. The results of these studies are, however, contradictory.In this study, we examined the effect of Lp(a) on premature atherosclerotic vessel wall changes by ultrasound measurement. Contrary to previous studies, we also included the femoral artery, as risk factors may differ in their effects on various arteries. We measured Lp(a) levels and intima-media thickness in a group of asymptomatic population controls. Major cardiovascular risk factors were assessed to examine the atherogenic effect of Lp(a) in addition to the conventional risk factors. Materials and methods Study designWe included 142 asymptomatic male volunteers who were randomly selected from the archives of the Leiden Anticoagulation Clinic (108 individuals) and asymptomatic friends (34 individuals) of patients who received anticoagulant treatment. All the individuals from the Leiden Anticoagulation Clinic received temporarily prophylactic anticoagulant treatment because of an orthopedic condition such as orthopedic surgery and fractures.