Aldosterone, Microvascular Function and Salt-sensitivity

Not Applicable

Completed

• Conditions: Abdominal Obesity; Sodium-sensitivity; Metabolic Syndrome; Hypertension; Insulin Resistance
• Interventions: Dietary Supplement: Low-sodium diet; Dietary Supplement: High-sodium diet

• Registration Number: NCT02068781
• Lead Sponsor: Maastricht University Medical Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-02-19
• Study First Submitted QC: 2014-02-19
• Study First Posted: 2014-02-21
• Study Start: 2014-07
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-18
• Last Update Posted: 2017-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Start with low-sodium diet	Low-sodium diet	One week of low-sodium diet, followed by a two-week wash-out period and subsequently, another week of high-sodium diet
Start with low-sodium diet	High-sodium diet	One week of low-sodium diet, followed by a two-week wash-out period and subsequently, another week of high-sodium diet
Start with high-sodium diet	Low-sodium diet	One week of high-sodium diet, followed by a two-week wash-out period and subsequently, another week of low-sodium diet
Start with high-sodium diet	High-sodium diet	One week of high-sodium diet, followed by a two-week wash-out period and subsequently, another week of low-sodium diet

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Maastricht University; 🇳🇱 Maastricht, Limburg, Netherlands