The incidence of endothelial dysfunction and atherogenesis in hemophilia patients with obesity: the Idaho-study

Results of studies concerning the role of haemostasis in ischemic
cardiovascular disease (CVD) indicate that hypercoagulability increases the
risk of CVD, whereas hypocoagulability decreases that risk. Patients with a
hereditary deficiency of clotting factor VIII (Haemophilia A) have considerable
protection against myocardial infarction. In 2001, a Dutch group reported no
effect of haemophilia A on intima media thickness (IMT) in the carotid and
femoral artery. Subgroup analysis, however, revealed that patients with
moderate or severe haemophilia had a tendency towards a thinner IMT. The group
of patients with severe haemophilia was too small (n=20) to adequately address
this question. However, considering the increasing life expectancy, if
haemophilia patients are not protected against atherogenesis, atherosclerotic
risk factors will have to be treated. Another question that arises, is whether
there is an inverse association between the severity of haemophilia and
atherosclerosis? A larger study population is necessary to further analyse the
matter. As is the case in the general population, in haemophiliac patients
there is an increasing prevalence of overweight (BMI>25 kg/m2) and obesity
(BMI>30 kg/m2), which may predispose to atherosclerotic cardiovascular disease.
As obesity is associated with an increased procoagulant activity, this can lead
to atherosclerosis-related morbidity, like hypertension and peripheral vascular
disease. A potential advantage for an overweight or obese haemophiliac patient
may be a less severe bleeding phenotype.

Are overweight or obese patients protected against atherosclerosis when
suffering from haemophilia A? Is this association influenced by the severity of
haemophilia? When the coagulation activity increases due to obesity (and
inflammation), will this lead to a decreased bleeding tendency?

This multicenterd, case-control study will include patients with severe,
moderate and mild types of haemophilia A, that either have obesity or a normal
bodymass. Healthy sex-, age- and BMI- matched individuals will serve as
controls. All subjects will receive a standardized questionnaire and will,
after an overnight fast, be invited to come to the department of Vascular
Medicine of the study centres for the drawing of blood, waist to hip ratio, BMI
and bloodpressure measurements. Additionally they will undergo non-invasive
ultrasonography.

None of the procedures the subjects will undergo are invasive and the
participation will consist of a one day visit to our study centre. Subjects
will receive a standardized questionnaire at home prior to their visit to our
study centre and they will be asked to come after an overnight fast. We will
measure BMI, waist to hip ratio and blood pressure (three times). We will also
draw blood samples. In addition, we will perform non-invasive carotid IMT and
brachial FMD ultrasound measurements.