Aldosterone Antagonism and Microvascular Function

Maastricht University Medical Centre (MUMC)

Status and phase

Terminated

Phase 4

Conditions

Hypertension

Abdominal Obesity Metabolic Syndrome

Insulin Resistance

Treatments

Drug: Eplerenone

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT01887119

133031

Details and patient eligibility

About

The prevalence of obesity and obesity-related complications is currently taking epidemic proportions. These complications increase the risk of type 2 diabetes and cardiovascular disease, which are important causes of morbidity and mortality worldwide.

It is important to gain insight in the mechanisms underlying obesity-related complications, because this may lead to the development of directed therapeutic strategies.

Currently, there is significant evidence that the cause of both insulin resistance and hypertension must be sought at the level of the microcirculation.

Over activity of the renin-angiotensin-aldosterone system is a potential cause of microvascular dysfunction. Angiotensin II was indeed found to be implicated in the pathogenesis of obesity-associated hypertension and insulin resistance, possibly through interference with the vascular effects of insulin.

Increased aldosterone levels have also been associated with resistant hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism. Furthermore, aldosterone is known to exert several detrimental effects on the vasculature, some of which are offset by mineralocorticoid receptor antagonists.

In obese individuals, plasma aldosterone concentrations are increased as well. We hypothesize that increased aldosterone levels in adipose persons induce microvascular dysfunction, which contributes to the development of insulin resistance and hypertension, and mineralocorticoid receptor antagonism results in improved insulin sensitivity and decreased blood pressure by counteracting the adverse effects of aldosterone on the microvasculature.

Enrollment

25 patients

Sex

All

Ages

40 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age 40-65 years
Caucasian
Waist circumference > 102 cm (men)/> 88 cm (women)
Triglycerides > 1.7 mmol/L
High-normal blood pressure (office blood pressure: 130/85 - 139/89 mm Hg) or stage I hypertension (office blood pressure: 140/90 mm Hg - 159/99 mm Hg; 24h ABPM: 125/80 - 149/89 mm Hg)

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/impaired glucose metabolism (fasting glucose values > 5.6 mmol/L)
Grade 2 or 3 hypertension (office blood pressure: > 160/100 mm Hg; ABPM > 150/90 mm Hg)
Unstable or severe pulmonary disease
Unstable or severe thyroid disorders
Inflammatory diseases
Alcohol use > 2 U/day (women)/> 3 U/day (men)
Use of antihypertensive, lipid-lowering or glucose-lowering medications,
Use of corticosteroids, medication known to inhibit or induce CYP3A4, lithium, and tricyclic antidepressants or antipsychotic medication, and regular use (weekly or several times a week) of NSAIDs
Plasma potassium levels < 3.2 mmol/L or > 5 mmol/L
eGFR < 60 mL/min
Impairment of hepatic function
Pregnancy or lactation