ANCA-associated Vasculitis and the Metabolic Syndrom

Atherosclerosis and vasculitis are systemic inflammatory diseases (1). Immune
processes caused by activity of T cells and antibodies play an important role
in this matter (1,2).
A high incidence of clinical manifestations of vascular disease like premature
atherosclerosis, has been demonstrated in patients with auto-immune diseases
like systemic lupus erythematosus (SLE), rheumatoid arthritis en
ANCA-associated vasculitis (AAV) (1). Cardiovascular diseases are a major cause
of mortality in patients with small vessel vasculitis. (1). During an active
period of disease, these patient experience an acceleration of the
atherosclerotic process (1). Important risk factors like diabetes mellitus,
hypertension, impaired renal function, persistent proteinuria and increased
levels of C-reactive protein (CRP) are more often present within this patient
group compared to healthy controls (1). Nevertheless, there is still much
unknown about the pathophysiology of accelerated atherosclerosis in these
patients (1), mainly regarding its relationship to the development of the
metabolic syndrome.

The incidence and prevalence of the metabolic syndrome is very high in The
Netherlands and worldwide (3,4). In the Hoorn Study a prevalence of 17 tot 32%
was found (3). In another Dutch study which combined the results of the studies
'PREVEND' and 'MORGEN' a prevalence of 14% was measured (4). There are clear
indications that immune processes are involved in the pathophysiology of the
metabolic syndrome (5). To our knowledge, studies of the relation between the
metabolic syndrome and ANCA associated vasculitis have never been reported
until now.

In the current study proposal the presence of the metabolic syndrome will be
investigated in as ANCA-associated patient cohort group. The main focus lies
within the possibly disturbed immune regulation as the underlying mechanism of
the development of the metabolic syndrome. The study will be performed in a
known ANCA-associated vasculitis patient group at the MUMC. Partners of the
patients will be approached and asked to take part of the study as healthy
controls.

The occurrence of the metabolic syndrome within ANCA-associated vasculitis
patient and healthy controls will be studied in a cross-sectional study
design. Parameters for inflammation will be analyzed and correlated to the
presence of the metabolic syndrome within the ANCA-associated vasculitis group.

This study concerns a research that is aimed to investigate the prevalence of
the metabolic syndrome in a group of patients known with ANCA-associated
vaculitis. Hereby we will compare the presence of the metabolic syndrome
between an ANCA-associated vasculitis cohort group and a group of healthy
controls .
There are indications that immune processes are the underlying conditions
needed for the pathophysiology of the metabolic syndrome; on the other hand we
postulate that the presence or absence of the metabolic syndrome, can influence
the course of the vasculitis. Throught this study we want to have more insights
over this relationship.

This study concerns a cross-sectional study that will be performed in the
course of 1 year at the MUMC.
The research can be divided into 3 steps:

1) Inclusion of patients and healthy controls:
- measurement of blood pressure + abdominal circumference + weight + length
- measurement of blood fasting-levels of glucose, triglycerides, cholesterol
- questions about smoking history and medical history.

2) Included patients:
- look up measurement of albumin levels in urine + CRP + neopterine + relapses
+ ANCA (en subtypes) in the patient files.

3) Included healthy controls:
- measurement of blood pressure + abdominal circumference + weight + length
- measurement of blood fasting-levels of glucose, triglycerides, cholesterol
- questions about smoking history and medical history.

Patients and healthy controls will be examined during outpatient controls where
their blood pressure, weight, length and abdominal circumference will be
measured. Within the patient group, the fasting-state blood levels that may
indicate the presence or absence of the metabolic syndrome (cholesterol,
HDL-cholesterol, LDL-cholesterol, triglycerides, glucose) and parameters that
indicate disease activity (CRP, PR3-ANCA, MPO- ANCA, neopterine) will be
determined during the regularly taken bloodtests. Furthermore, healthy controls
will be examined as well via a sole blood test regarding the parameters that
may indicate the presence or absence of the metabolic syndrome as mentioned
above.

The possible adverse events for patients and healthy controls in this study are
limited to the eventual development of a hematoma after venipuncture. This
requires no further interventions.

Our experience is that patients and their partners are very approachable with
regard to research. In our opinion a sole blood test for the healthy controls
is a reasonable strain. Considering the small amount of strain asked form both
the patients and the healthy controls, and the advantage of gaining more
knowledge about the relationship between ANCA associated vasculitis and the
metabolic syndrome, we regard the execution of this research as justifiable.