Systemic damage and quality of life in patients with ANCA-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a
rare disease. This necrotizing vasculitis, predominantly affects small vessels
and is often associated with ANCA specific for myeloperoxidase (MPO) or
proteinase 3 (PR3). Three main variants of AAV are microscopic polyangiitis
(MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis
with polyangiitis (EGPA). Over the last decades, survival of AAV patients has
improved dramatically, but long-term sequelae from vasculitis or treatment are
a major problem for most patients. Therefore quantification of this damage and
the association with disease activity have become an important focus in
research.

An important long-term complication of disease activity in AAV is
cardiovascular disease. The current burden of cardiovascular disease in chronic
AAV patients is largely unknown. Furthermore, impaired quality of life (QOL) is
of high relevance to those living with chronic diseases. Thus far, only one
study has addressed QOL and depression in AAV patients, showing an increased
prevalence. However the prevalence of depression and impaired QOL in AAV
patients in The Netherlands and the relation with disease activity have not
been studied so far.

The aim of the present study is to evaluate cardiovascular damage and risk in
chronic AAV patients. We will do this by measuring the burden of
cardiovascular disease in AAV. Furthermore we will focus on mental health of
AAV patients by assessing health related QOL, pain scores and depression
scores. We will assess if these findings are related with disease activity and
duration. Finally, we will perform a prospective survival analysis, in order to
relate damage to survival.

The aim of this study is a better understanding of the burden of AAV related
damage in chronic AAV, which will lead to a better recognition and eventually a
better treatment.

Primary Objectives:
1. To assess the prevalence of AAV related damage in AAV, i.e. cardiovascular
damage and impaired QOL.

Secondary objectives
2. To assess whether there exists an association between cardiovascular
disease, QOL and disease activity in AAV.
3. To investigate the association between damage and long term cardiovascular
disease and survival.

We will perform a multi-center cross sectional study and a longitudinal cohort
study in the Noordwest Ziekenhuisgroep, the VU University Medical Center and
the Mount Sinai Hospital in Toronto. Patients with a clinical diagnosis AAV in
accordance with the CHCC guidelines will be enrolled. In September 2016
patients will be sent an information letter, after which they will be contacted
by the investigator for further information about the study. Permission will be
asked for participation in this study.

Informed consent forms and questionnaires about QOL, depression and pain will
be sent to patients home addresses. Filling out the questionnaires will take
approximately 20-30 minutes. Following a routine appointment with a patients
treating nephrologist, an appointment will be scheduled with the investigator.
During this visit skin autofluorescence for Advanced Glycation Endproducts
(AGE*s)(11) will be measured (both are described in more detail below). The
vascular damage index (VDI)(9) and the Birmingham Vasculitis Activity Score
(BVAS)(11) will be calculated in all patients based on interviewing the
patient, physical examination and reviewing medical records. Skin
autofluorescence is a non-invasive measurement for vascular damage that take a
few minutes. The entire visit will take approximately 20-30 minutes. The AGE
measurement will only be performed in the Noordwest Ziekenhuisgroep.

In 2016 all MPA and GPA patients will be screened routinely by an
internist-nephrologist. Data of these routine visits will be withdrawn
retrospectively from medical records, including: routine laboratory results,
imaging results (if available), an electrocardiogram (if available) medical
history and medication. Patients will be asked permission for the collection of
one extra blood sample of 4 milliliters during a routine laboratory
investigation within 3 months of the hospital visit with the investigator. This
serum sample will be stored at -70 °C in the laboratory and will be kept for
future research. This sample will only be taken during a routine venipuncture.
No additional venipunctures are required. The extra blood samples will only be

After 1,2, 3, 4 and 5 years medical records will be consulted for information
about prognosis, i.e. mortality, relapses,hospital admissions and
cardiovascular events. If there exist any doubt on mortality or cause of death,
family doctors will be contacted for further information. If a patient is still
alive, he or she will be contacted by a phone call. In this phone call
questions will be asked on cardiovascular events in the past year (see yearly
questionnaire in the appendix). If a cardiovascular event happened outside the
Noordwest Ziekenhuisgroep, permission will be asked from a patient or his/her
representative (if applicable) to collect source documents, such as a hospital
discharge letter.

There are no risks for included subjects in this study, since we will not
intervene with routine medical treatment. The questionnaires and AGEs
measurements are without risks. The patients that are enrolled in the study are
unlikely to directly benefit from the study results. However future patients
might benefit if chronic physicial and mental damage is better recognized and
treated in an earlier stage.