# Aldosterone, the Mineralocorticoid Receptor, and Cardiovascular Disease in Obesity

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $877,015

## Abstract

PROJECT ABSTRACT
Obesity is a rapidly expanding epidemic that is arguably the leading cause of cardiovascular disease. Obese
individuals have increased autonomous aldosterone production resulting in excessive activation of the
mineralocorticoid receptor that increases the risk for myocardial fibrosis and ischemia, hypertension, and stroke.
Since mineralocorticoid receptor antagonists are widely available and safe medications, autonomous
aldosterone production represents a modifiable mechanism to prevent cardiovascular disease in obesity. We
hypothesize that mineralocorticoid receptor antagonists can improve myocardial perfusion and fibrosis in obese
individuals. We propose a mechanistic clinical trial that involves deep phenotyping of aldosterone physiology
and cardiac MRI imaging to evaluate this hypothesis. Participants with high-risk obesity, defined as obesity with
untreated hypertension and/or one or more features of the metabolic syndrome, will be enrolled. Participants will
undergo a deep-phenotyping protocol to characterize aldosterone physiology, and cardiac MRI to measure
myocardial perfusion reserve (to assess coronary microvascular function) and extracellular volume fraction (to
assess myocardial fibrosis), before double-blinded randomization to eplerenone (a mineralocorticoid receptor
antagonist and potassium-sparing diuretic) or chlorthalidone (a conventional blood pressure medication and
potassium-wasting diuretic) along with potassium chloride for one year. During this year, blood pressure and
potassium will be maintained in a target range to ensure outcomes are independent of these variables. Cardiac
MRI-derived outcomes will be measured again after one year of the randomized intervention. It is anticipated
that eplerenone therapy will improve measures of coronary microvascular function and fibrosis, independent of
blood pressure, when compared to chlorthalidone with potassium. This mechanistic study is designed to
investigate a targeted treatment for the prevention of cardiovascular disease in high-risk obesity using innovative
hormonal phenotyping and sophisticated imaging outcomes. If our hypothesis is correct, this study may justify
the early use of mineralocorticoid receptor antagonists in patients with obesity to prevent or delay the onset of
cardiovascular disease, and establish a foundation for future trials to evaluate incident clinical cardiovascular
outcomes.

## Key facts

- **NIH application ID:** 10254306
- **Project number:** 5R01HL153004-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Anand Vaidya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $877,015
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254306

## Citation

> US National Institutes of Health, RePORTER application 10254306, Aldosterone, the Mineralocorticoid Receptor, and Cardiovascular Disease in Obesity (5R01HL153004-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254306. Licensed CC0.

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