Primary Hyperaldosteronism and Ischemia-reperfusion Injury

N/ACompletedNCT01978132

Radboud University Medical Center40 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Primary Hyperaldosteronism

Interventions

forearm ischemia and reperfusionPROCEDURE

both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Outcomes

Primary Outcomes

brachial FMD

primary outcome measure is the reduction in brachial artery FMD after 20 minutes of forearm ischemia and 20 minutes of reperfusion in patients with primary hyperaldosteronism (compared to patients with primary hypertension)

Time frame: 1 day morning

Secondary Outcomes

CD73 and adenosine

Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells

Time frame: one day morning (just before FMD experiment)

Data from ClinicalTrials.gov

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