Microvascular Function in Primary Aldosteronism

Microvascular Function in Patients With Primary Aldosteronism and Essential Hypertension

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.

Study Overview

• Status: Withdrawn
• Conditions: Essential Hypertension; Primary Aldosteronism
• Intervention / Treatment: Procedure: Adrenal extirpation; Drug: Antihypertensive medication

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Twenty patients with primary aldosteronism and twenty patients with essential hypertension

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary aldosteronism; Patients with primary aldosteronism, who undergo surgery or will be started on antihypertensive medication, including mineralocorticoid receptor antagonists	Procedure: Adrenal extirpation; Drug: Antihypertensive medication
Essential hypertension; Patients with essential hypertension who will be started on antihypertensive medication	Drug: Antihypertensive medication

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Prof. C.D.A. Stehouwer, MD, PhD, Maastricht University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): April 1, 2016
• Study Completion (Anticipated): April 1, 2016

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Estimate): August 25, 2015
• Last Update Submitted That Met QC Criteria: August 24, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hypertension; Essential Hypertension; Hyperaldosteronism; Antihypertensive Agents
• Other Study ID Numbers: 48364

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No