Aldosterone, Microvascular Function and Salt-sensitivity

Hypertension Clinical Trial

Official title:

Aldosterone-induced Microvascular Dysfunction as a Cause of Salt-sensitivity in Obesity?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02068781
• Other study ID #: 47438/IMP10124
• Status: Completed
• Phase: N/A
• First received: February 19, 2014
• Last updated: May 18, 2017
• Start date: July 2014
• Est. completion date: October 2016

Study information

• Verified date: May 2017
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Currently, the incidence of obesity and obesity-related disorders is reaching epidemic proportions, which entails an increasing burden for health care systems. The association of obesity with other risk factors for type 2 diabetes mellitus and cardiovascular disease, such as insulin resistance and hypertension, is often referred to as the metabolic syndrome. During recent years, salt-sensitivity of blood pressure has emerged as an additional cardiovascular risk factor that is related to obesity and other key components of the metabolic syndrome. The underlying pathophysiological mechanisms of these interrelationships are complex and incompletely elucidated. Microvascular dysfunction has been proposed as a link between insulin resistance and hypertension in obese individuals. In addition, impairment of microvascular function was found to be associated with salt-sensitivity of blood pressure. Increased aldosterone levels, as observed in obese individuals, might be a cause of microvascular dysfunction-induced salt-sensitivity and insulin resistance. Aldosterone not only gives rise to sodium-retention in the distal tubule of the kidney, but was also found to impair endothelial function and thus lower NO-availability, which is characteristic of microvascular dysfunction. In addition, elevated aldosterone levels are associated with both hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism, but also in the general population.

The investigators hypothesize that increased aldosterone levels in obese individuals lead to impairment of microvascular function through reduction of NO-availability. This microvascular dysfunction is suggested to play a central role in the pathogenesis of salt-sensitive hypertension and insulin resistance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Obese individuals

• Age 18-65 years

• Caucasian

• Waist circumference > 102 cm (men)/> 88 cm (women)

Lean individuals

• Age 18-65 years

• Caucasian

• Waist circumference < 94 cm (men)/< 80 cm (women)

Exclusion Criteria:

Obese/lean individuals

• 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

• Stage 3 hypertension (blood pressure > 180/110 mm Hg)

• Unstable or severe pulmonary disease

• Unstable or severe thyroid disorders

• Inflammatory diseases

• Smoking

• Alcohol use > 2 U/day (women)/> 3 U/day (men)

• Use of antihypertensive, lipid-lowering or glucose-lowering medications

• Use of corticosteroids and regular use of NSAIDs

• eGFR< 60 mL/min

• Impairment of hepatic function

• Pregnancy or lactation

Related Conditions & MeSH terms

• Abdominal Obesity
• Hypersensitivity
• Hypertension
• Insulin Resistance
• Metabolic Syndrome
• Metabolic Syndrome X
• Obesity
• Obesity, Abdominal
• Sodium-sensitivity

Intervention

Dietary Supplement:
• Low-sodium diet
50 mmol NaCl per 24h
• High-sodium diet
250 mmol NaCl per 24h

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in capillary recruitment between low- and high sodium diets		One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized