Microvascular Function in Primary Aldosteronism

Study Overview
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Brief Summary
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Patients with primary aldosteronism, which is the most prevalent form of secondary hypertension, have an increased rate of cardiovascular events, compared to patients with essential hypertension, even with equal severity of hypertension. This might be partially attributed to the association of increased aldosterone levels with insulin resistance. How this relation can be explained from a pathophysiological point of view, is insufficiently established. Recently, microvascular dysfunction has been proposed as a link between insulin resistance and hypertension. Loss of NO-mediated vasodilation is an important feature of microvascular dysfunction; in addition, an impaired insulin-mediated microvascular NO production has been suggested to underlie the reduction in insulin-stimulated glucose disposal that is characteristic of insulin-resistant states. Increased aldosterone levels are not only associated with insulin resistance, but also with endothelial dysfunction. In addition, they interfere with the vascular effects of insulin. Therefore, the investigators hypothesize that in patients with primary aldosteronism, increased aldosterone levels induce microvascular dysfunction through reduction of NO-availability, which contributes to the development of insulin resistance, and of hypertension, in addition to the sodium-retaining effects of aldosterone.

Official Title
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Microvascular Function in Patients With Primary Aldosteronism and Essential Hypertension

Conditions
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Primary Aldosteronism, Essential Hypertension

Intervention / Treatment
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* Procedure: Adrenal extirpation
* Drug: Antihypertensive medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary aldosteronism Age 18-70 years Confirmed diagnosis of primary aldosteronism Serum potassium > 3.5 mmol/L with or without supplementation Patients with essential hypertension Age 18-70 years Secondary causes of hypertension excluded Exclusion Criteria: Cardiovascular disease (stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death) Diabetes mellitus Unstable or severe pulmonary disease Inflammatory diseases Alcohol use > 2 U/day (women) / > 3 U/day (men) (Frequent) use of acetylsalicylic acid, NSAID's, dipyridamole and corticosteroids eGFR < 60 mL/min Impairment of hepatic function Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Primary aldosteronism<br>Patients with primary aldosteronism, who undergo surgery or will be started on antihypertensive medication, including mineralocorticoid receptor antagonists | Procedure: Adrenal extirpation<br> <br> Drug: Antihypertensive medication<br> <br> |
| Essential hypertension<br>Patients with essential hypertension who will be started on antihypertensive medication | Drug: Antihypertensive medication<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular recruitment in skeletal muscle during hyperinsulinaemia |  | Baseline | 
| Microvascular recruitment in skeletal muscle during hyperinsulinaemia |  | 3 months after (initiation of) treatment |