Activation of the innate immune system in patients with primary hyperaldosteronism

Primary hyperaldosteronism (PA) is the main cause of secondary hypertension.
Patients with hypertension due to PA are at a much higher risk of stroke or
myocardial infarction than patients with similar blood pressure levels due to
essential hypertension. Cardiovascular events, such as stroke and myocardial
infarction are caused by atherosclerosis, which is characterized by a low-grade
inflammation of the vascular wall. Monocyte-derived macrophages are the most
abundant inflammatory cells within atherosclerotic plaques. Preclinical studies
suggest that aldosterone can induce vascular wall inflammation by activation of
the mineralocorticoid receptor (MR) on monocytes and macrophages. In this
study, we aim to test the hypothesis that hyperaldosteronism is an independent
determinant of vascular wall inflammation and that this is at least in part
mediated through activation of the innate immune system by aldosterone.

The primary objective of the study is to determine whether patients with PA
have a higher level of arterial wall inflammation than patients with essential
hypertension.

Secondary Objectives:
To determine whether circulating monocytes of patients with PA are
characterized by a more pro-inflammatory phenotype compared to patients with
essential hypertension.
To investigate whether ex vivo incubation of healthy donor monocytes with the
pooled plasma of patients with PA induces a pro-inflammatory phenotype compared
to the plasma of patients with essential hypertension. If so, to investigate is
this can be prevented by co-incubation with MR antagonists.
To study whether patients with PA have increased FDG-uptake in the bone marrow
and spleen.
To explore whether treatment with MR antagonists or adrenalectomy reduces
arterial wall inflammation in patients with PA, if these patients indeed appear
to have an increased vascular inflammation.

Observational study in patients with PA and patients with essential
hypertension.

The risks associated with participation in this study are low. In total, 50 ml
blood will be obtained, which will not have relevant effects. In addition, all
patients will undergo a 18FDG-PET/CT. This diagnostic procedure will be
performed according to standard state-of-the-art clinical procedures as define
by the European association of Nuclear Medicine. Duration of the procedure: 3
hours. Procedure-related exposure to radioactivity: 4,8 mSv. Patients will not
have a direct benefit from participation in the study.

If baseline measurements reveal differences in vascular inflammation between PA
patients and controls with essential hypertension, Follow-up measurements will
be performed. These consist of one additional venous blood sampling (50 ml of
venous blood) and a second PET-CT scan using the same scanning protocol after
treatment with adrenalectomy or mineralocorticoid receptor antagonists,
respectively. Total procedure-related exposure to radioactivity will then be
9,6mSv, which is considered proportional to the potential future benefit that
knowledge on the mechanism of the increased cardiovascular risk of patients
with PA will yield.