Clinical trial NCT01978132: Primary Hyperaldosteronism and Ischemia-reperfusion Injury
Official title: Primary Hyperaldosteronism and Endothelial Ischemia-reperfusion Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Primary Hyperaldosteronism
Keywords: primary hyperaldosteronism
primary hypertension
forearm ischemia-reperfusion
(reduction) in brachial artery FMD
endothelial ischemia-reperfusion injury
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2013-11-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Patients with primary hyperaldosteronism experience more cardiovascular events compared to patients with primary hypertension, independent of the blood pressure level.

In this research we hypothesize that patients with primary hyperaldosteronism are more susceptible to ischemia-reperfusion injury.

Detailed description: Patients with PHA have an increased risk of cardiovascular events, independent of blood pressure level. Also in patients suffering a myocardial infarction, circulating aldosterone levels are associated with increased mortality. In animal models of myocardial infarction, the administration of exogenous aldosterone increased infarct size, although other studies did not report this effect. In similar models, antagonists of the mineralocorticoid receptor (MR) reduced infarct size, which was completely abolished in ecto-5'-nucleotidase (CD73, the enzyme that catalyses extracellular formation of the endogenous nucleoside adenosine) and adenosine receptor knock-out mice. Therefore, we hypothesize that patients with PHA have an increased susceptibility for ischemia-reperfusion (IR)-injury due to down-regulation of the enzyme CD73. We will use the reduction in brachial flow-mediated dilation (FMD) by forearm IR as a well-validated endpoint for (endothelial) IR-injury.

Eligibility criteria: Inclusion Criteria patients with primary hyperaldosteronism:

* Age 18-75 years
* Confirmed primary hyperaldosteronism (aldosterone \>0.28 nmol/l after salt loading)
* Serum potassium ≥ 3.5 mmol/L (with or without potassium supplementation)
* Written informed consent

Inclusion Criteria patients with primary hypertension:

* Age 18-75 years
* Primary hypertension
* Baseline aldosterone \<0.30 nmol/l and aldosterone-renin-ratio\<0.09
* Serum potassium ≥ 3.5 mmol/L
* Written informed consent

Exclusion Criteria for both arms (patients with primary hyperaldosteronism and patients with primary hypertension:

* Smoking
* History of atherosclerotic disease (myocardial infarction (MI), stroke, or peripheral vascular disease)
* Not possible to change the antihypertensive medication into only diltiazem with or without hydralazine, according to the treating physician.
* Not possible to temporarily interrupt statin treatment, if the patient use statins, according to the treating physician.
* Severe renal dysfunction (MDRD \< 30 ml/min)
* Second/third degree AV-block on electrocardiography
* Cardiac failure
* Diabetes Mellitus
* Use of acetylsalicylic acid and NSAID's theophylline, and dipyridamole

Primary outcomes:
measure: brachial FMD
timeFrame: 1 day morning
Secondary outcomes:
measure: CD73 and adenosine
timeFrame: one day morning (just before FMD experiment)
Other outcomes:
measure: aldosterone and renin
timeFrame: 1 day
measure: leukocyte telomere length (LTL)
timeFrame: 1 day
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
Study officials:
References: