Primary Hyperaldosteronism and Ischemia-reperfusion Injury

Primary Hyperaldosteronism and Endothelial Ischemia-reperfusion Injury

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.

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