MRI vessel wall characteristics of peripheral arteries and arterial stiffness in hemophilia patients

We previously showed that patients with hemophilia have the same degree of
atherosclerosis compared to control subjects, which predisposes them to
vascular complications at older age. In clinical practice, we indeed see an
increasing amount of patients with myocardial infarction and ischemic stroke.
In our previous studies, formation of atherosclerosis was detected in the
coronary and carotid arteries. We therefore recently analyzed the prevalence of
atherosclerosis in the peripheral arteries in patients with hemophilia, by
measuring the ankle-brachial index (ABI), which assesses perfusion of the large
leg arteries. 69 adult patients with hemophilia were investigated. The mean age
was 52 years, and 39% had a severe type of hemophilia. 7% had a previous
cardiovascular disease and 26% was treated with antihypertensive medication.
48% of the hemophilia patients had an ABI >=1.3, while the other patients had an
ABI of 0.9-1.2. A low ABI (<0.9), which is associated with stenosed vessels,
was not found. In summary, nearly half of the hemophiliacs had a high ABI. In
general, an ABI >= 1.3 is found in about 0.5% of the general population. The
most common conditions that predispose to a high ABI are type II diabetes
mellitus and chronic kidney disease, with a prevalence of 20-40%. A high ABI
points to vascular calcification of the media of the artery (VCm), caused by
deposits of hydroxyapatite with a high degree of crystallization. As a
consequence, elasticity of the peripheral arteries decreases which leads to
arterial stiffness. It is unclear why hemophilia patients have such a high
prevalence of VCm, but it is tempting to speculate that due to recurrent
bleeding in either joints or muscles, vascular calcification occurs, as has
been shown in hemophilic mice.
Furthermore, the most common cardiovascular risk factor in hemophilia patients
is arterial hypertension, which is also more common in this group than in the
general population. Since arterial stiffness is an important contributor to
arterial hypertension, VCm and consequently arterial stiffness may be more
prevalent in hemophiliacs, and this may explain the high rate of systolic
hypertension.
Magnetic resonance imaging (MRI) enables transverse 3-dimensional imaging of
the vessel wall at high resolution with excellent interscan reproducibility.
3-Tesla MRI directly visualizes the artery wall and the constitution of the
artery wall, including the media. The great advantage of MRI compared to
CT-scan is the fact that MRI gives no radiation exposure. In addition, it has
been shown that 3T-MRI can also visualise endothelial shear stress, an
important marker for arterial stiffness and remodelling.
Furthermore, pulse wave velocity (PWV) is the gold standard of measuring
arterial stiffness.

The primary objective is to analyze and compare morphological (media-
thickness) and functional (stiffness) vessel wall parameters of peripheral
arteries between hemophilia patients with an ankle- brachial index >= 1.3 and
hemophilia patients with a normal ankle- brachial index (0.9-1.3)

The secondary objectives are to explore the relation between media- thickness
and arterial stiffness and 1) traditional cardiovascular risk factors, 2)
severity of hemophilia.

Cross-sectional, exploratory, sinlge center study

Apart from the drawing of blood, none of the procedures the subjects will
undergo are invasive and participation will consist of a single visit to our
study centre. Subjects will be asked to come to our study centre in the morning
after an overnight fast. Subjects will remain in our study centre for no longer
than three hours. MRI scanning will be performed, followed by PWV analysis.
Next blood will be drawn and measurement of height, weight and waist/ hip ratio
will be performed. We consider the risk of bleeding complications to be very
small and MRI scanning has no radiation exposure.