The relationship between depressive symptoms and pro-inflammatory cytokine serum levels in adults with congenital heart disease

Morbidity among patients with a congenital heart disease (CHD) is substantial:
more than 60% of the patients have undergone one or more cardiac operations,
32% of the patients have had one or more complications, such as endocarditis,
stroke, hypertension, or heart failure (HF). Moreover, HF is identified as the
number one risk factor of death in CHD-patients. Besides the above traditional
co-morbidities, preliminary results of the EXACD-study (an ongoing study
investigating the EXperiences of Adults with a Congenital heart Defect) show
that the prevalence of depressive symptoms in CHD-patients is more than three
times higher than that in the general population. Extensive research has shown
that depression is a risk factor for the development and progression of
cardiovascular diseases (CVD*s), including HF. Preliminary results of the
EXACD-study are in line with this conclusion, showing a Spearman rank
correlation of .35 between depressive symptoms and the degree of HF
(NYHA-class). Researchers have suggested an immunological mechanism underlying
the negative effects of depression in patients with HF or other CVD*s. Two
lines of research support this suggestion: 1) the causative role of
pro-inflammatory cytokines, in particular Tumor Necroses Factor-alpha (TNF-*),
interleukin (IL-)1 and IL-6, in the pathogenesis of HF has been extensively
documented, and 2) both experimental and clinical studies in various patient
groups have described a relation between depressive symptoms and increased
serum levels of these three pro-inflammatory cytokines. Thus far, however, the
relation between depressive symptoms and pro-inflammatory cytokine serum levels
has never been studied in CHD-patients. There is reason to believe that the
relation between the level of depressive symptoms and pro-inflammatory
cytokines does not automatically apply to CHD-patients. That is, CHD-patients
show an adaptive response, namely the upregulation of cytokines. CHD-patients
show deviant cytokine levels at early age, which remains during adulthood. In
contrast, patients with acquired hearth diseases develop deviant cytokine
levels as their disease develops. Examining the relation between depressive
symptoms and cytokine levels in CHD-patients is therefore needed. Confirmation
of this relation in this group of patients is a first step in understanding the
associations between depressive symptoms, pro-inflammatory cytokines and HF in
CHD-patients. Subsequently, future longitudinal studies can then be developed
to investigate the possibility of a causal relation between elevated
pro-inflammatory cytokine serum levels accompanying depressive symptoms and the
development/ progression of HF in CHD-patients. Ultimately, these results may
provide useful information for the development of new treatment options for
both depressive symptoms and HF in CHD-patients. Anti-depressants, with their
anti-inflammatory effects might be an option, not only treating the depressive
symptoms, but perhaps also reducing the risk to develop or progress HF.

The current pilot-study will examine the relation between depressive symptoms
and serum levels of pro-inflammatory cytokines in CHD-patients.

We will adopt a cross-sectional design.

Filling out a questionnaire assessing the level of depressive symptoms is
non-invasive and free of risk (completion takes approximately 10 minutes). The
burden for both CHD-patients is the blood sample (10 minutes) in order to
assess pro-inflammatory cytokine serum levels.