Primary Hyperaldosteronism and Ischemia-reperfusion Injury (PHA-FMD)

Radboud University Medical Center

Status: Completed

Conditions: Primary Hyperaldosteronism

Treatments: Procedure: forearm ischemia and reperfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT01978132

NL45381.091.13

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups, including a placebo group

Primary hyperaldosteronism

Active Comparator group

Description:

patients with primary hyperaldosteronism will be subjected to the intervention forearm ischemia and reperfusion (20 minutes of forearm ischemia and 20 minutes of reperfusion). Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury

Treatment:

Procedure: forearm ischemia and reperfusion

Primary hypertension

Placebo Comparator group

Description:

Patients with primary hypertension (PHA excluded)will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion. Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury

Treatment:

Procedure: forearm ischemia and reperfusion