Decreased Coagulability Has No Clinically Relevant Effect on Atherogenesis

Abstract

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).

Prevalence and risk factors for heart disease among males with hemophilia

“…This is because of the dominant role of atherosclerosis in arterial disease. The degree of atherogenesis among PWH has been shown to be similar to that in unaffected males [22,23]. In a recent review of the role of elevated FVIII levels and the risk of thrombosis, Kamphuisen et al [24] concluded that high levels of FVIII are indeed a risk factor for thrombosis, levels of FVIII 150% accounted for 16% of all venous thrombosis and levels of 123% explained 4% of arterial thrombosis.…”

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

“…28 In a recent study, we found no substantial protection against atherosclerosis among individuals with hemophilia. 22 That result suggests that the protection that was found in pigs and mice with severe vWD is caused by an impaired adhesion and aggregation of platelets to the vessel wall. Postmortem studies of individuals who had severe vWD, however, showed that patients with a complete deficiency of vWF developed advanced atherosclerotic lesions.…”

“…Furthermore, we showed in a previous study that intima-media thickness measurements in the carotid and especially in the femoral artery are a good indicator of advanced atherosclerotic lesions in the coronary arteries. 22 Because the major role of vWF is to promote thrombus formation in stenosed vessels, 2 we can speculate that type 3 vWD patients, who lack vWF in plasma, platelet, and subendothelium, might be protected against arterial occlusion even in the presence of atherosclerotic lesions. The data suggest a slightly higher prevalence and severity of hypertension among patients with severe vWD.…”

Noninvasive Assessment of Coronary Arteries in Patients with Hematologic Disorders

“…These patients are less prone to develop acute thrombosis in the coronary arteries, however, they might not be protected from atherosclerosis. 19,20 Arterial thrombosis and myocardial infarction (MI) is not exceptional in patients with thrombophilia. 21 Girolami et al studied 42 patients with hemophilia and atherosclerotic disease, majority of these patients (36 cases) presenting with MI.…”