There have also been systematic

screening studies of living haemophilic subjects for markers of atherosclerosis using ultrasound techniques to detect intima media thickening (IMT) and arterial plaques. Bilora et al. [17] found less evidence of atherosclerosis in their study group compared with controls and concluded that haemophilia offered some protection against ischaemic Proteasome inhibitor heart disease. However, a later study by the same group found no significant difference in IMT between haemophilic subjects and controls and in addition, they reported the presence of endothelial dysfunction, a potential early marker for atherosclerosis in their study group. [18] Another group, Sramek et al. [19] also found no significant difference in intima media thickening in their cohort of subjects with congenital bleeding disorders compared with controls. Of note, these studies were relatively small, did not confine their studies to severe haemophilia and the median age of subjects was relatively young. There have been no studies in a large population of older haemophiliacs, the group most likely to be at risk of symptomatic disease, probably because, to date, there are so few individuals in this age group available for study. Perhaps the most direct evidence of cardiovascular

disease in haemophilia is the reports of clinical cases. There have been regular, small numbers of such reports over time and it appears that the motivation selleckchem for publication was the view that such cases were unexpected.

Small et al. [20] reported two cases of extensive atherosclerosis in severe haemophilia. One individual had a myocardial infarction after intensive replacement therapy and the other showed severe atherosclerosis at postmortem after dying from unrelated causes. Girolami et al. [21]) reviewed all published 42 cases up to 2006 and noted that most occurred in older individuals and after intensive replacement therapy. There have been several reports on the prevalence of risk factors for IHD in pwh, often with conflicting data. The risk factors for IHD in pwh appear to be the same as for the general population [12,22,23]. Hypertension, a recognized risk factor for CVD, has been studied in several Thymidine kinase cohorts and most reported a higher prevalence in pwh [12,13.22-25] and although it is postulated that this may be linked with renal disease in haemophilia, it is not clear whether hypertension caused or was a consequence of renal disease. Hypercholesterolaemia has also been reported to be linked with IHD in haemophiliacs but, by contrast other studies have found that compared with controls, cholesterol levels are lower in pwh. It has been suggested that this latter observation may be a consequence of hepatitis C liver disease but there are insufficient data from which to draw firm conclusions [13,23].