Endothelial function in Systemic Lupus Erythematosus and Wegener's granulomatosis: associations with traditional and non-traditional cardiovascular risk factors

Systemic autoimmune diseases, such as systemic lupus erthematosus and Wegener's
granulomatosis, are associated with an increased prevalence of cardiovascular
disease. Atherosclerosis is the major underlying cause of CVD, several studies
have demonstrated the presence of accelerated atherosclerosis in SLE and WG,
using intima-media thickness (IMT) as a surrogate marker for atherosclerosis.
The presence of atherosclerosis could not be explained by the presence of
traditional cardiovascular risk factors. Therefore, additional,
autoimmunity-related non-traditional risk factors, have been suggested to
contribute to the development of atherosclerosis.
Endothelial cell (EC) activation and dysfunction are considered the first steps
in the atherosclerotic process. Indeed, endothelial activation markers like
vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM) and von
Willebrand factor (vWF) are increased in SLE and WG patients, even in inactive
disease.
As a result of EC activation other events occur, like the formation of advanced
glycation endproducts (AGEs). AGEs are a class of compounds resulting from the
glycation and oxidation of proteins, lipids or nucleic acids. The accumulation
of AGEs in the vessel wall has been related to the development of
atherosclerosis.
EC repair is mandatory and endothelial progenitor cells (EPCs) are supposed to
play an important functional role in the repair of damaged endothelium. We
recently found that numbers of EPCs are decreased in SLE patients. Moreover,
EPCs of SLE patients were functionally impaired and we suppose that these
aberrations will contribute to, and even might accelerate, endothelial damage
and atherosclerosis in SLE.
Endothelial function in SLE and WG is still poorly studied. Detection of EC
dysfunction provides the opportunity to intervene in this early stage in order
to prevent cardiovascular disease. EC dysfunction can be detected by several
techniques. Flow-mediated dilation, measuring the response to reactive
hyperemia, is most commonly used. However, this method has a poor
reproducibility and informs about larger vessels. EC dysfunction can also be
detected non-invasively by pulse-wave analysis (PWA), which measures large and
small artery elasticity (LAE and SAE, respectively). Unlike FMD, PWA is more
readily available and well tolerated.
We hypothesise that EC dysfunction, measured by SAE, will be present in our
cohorts of SLE and WG patients. This EC dysfunction is related to EC
activation, AGE formation, the number and function of EPCs and the presence of
atherosclerosis. To analyse the cause of EC dysfunction, we will investigate
all traditional cardiovascular risk factors as well as non-traditional risk
factors. Finally, we want to analyse whether PWA is usable for intervention
studies.

We hypothesise that EC dysfunction is present in SLE and WG patients compared
to controls. In summary, our hypothesis leads to the following questions:

1. Is EC dysfunction, measured by SAE, present in SLE patients?
2. Is EC dysfunction related to EC activation markers, AGEs, levels and
functional capacity of circulation EPCs, and the presence of atherosclerosis?
3. Is EC dysfunction related to traditional cardiovascular risk factors or
non-traditional factors
4. Can PWA be used in intervention studies?

For this cross sectional study we will include 40 SLE patients, 40 WG patients,
40 healthy age and sex matched controls (serve as negative controls) and 40
patients with essential hypertension (serve as positive control).

To be informed about test variation in all participants (except WG patients)
SAE will be detected twice, in one half of the participants immediately after
the first measurement, in the other half of the participants one week after the
first measurement. In addition, in all participants both arms will be tested.

For half of the participant measurements will take about 2 hours and 30
minutes, measurements will take place on two moments. For the other half of the
participants and all WG patients measurement will take about two hours.

We will try to combine a patient's visit to the treating physician with our
research.

In SLE and WG patients 3 tubes of blood (28 ml) will be drawn for further
analysis. In controls and essential hypertension patients 4 tubes of blood (34
ml) will be drawn.

Participants need to fast and have to refrain from tobacco in the 12 hours
before Pulse-Wave Analysis.