Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension
Brigham and Women's Hospital
75 participants
Aug 25, 2023
INTERVENTIONAL
Conditions
Summary
The investigators' goal is to show that in hypertensive men and women with left ventricular hypertrophy (LVH) treatment with a mineralocorticoid receptor (MR) antagonist, versus a thiazide-like diuretic, will improve coronary microvascular function and cardiac efficiency, which will associate with improvements in LV structure and function. The investigators will achieve this through a randomized, controlled, basic experimental study involving humans (BESH).
Eligibility
Inclusion Criteria7
- History of hypertension
- Seated systolic BP \< 180 mmHg and diastolic \< 110 mmHg if on antihypertensives
- Seated systolic BP 141-200 mmHg and/or diastolic BP 90-114 mmHg if not on antihypertensives
- LVH by echocardiogram
- For men: interventricular septum thickness ≥ 12mm
- For women: interventricular septum thickness ≥ 11mm
- We will also allow inclusion of people with treated hypothyroidism, pre-diabetes and diabetes controlled by diet, exercise, and/or metformin.
Exclusion Criteria16
- Use of MR antagonist (eplerenone, spironolactone, or finerenone) or amiloride (amiloride inhibits ENaC, which is a key mediator of MR's actions) within the past year
- Orthostatic hypotension
- Major medical illness, including uncontrolled diabetes mellitus (Hemoglobin A1c \>7.5)
- LV ejection fraction \< 40%
- New York Heart Association class III to IV congestive heart failure or unstable angina
- A history in the prior 6 months of Q-wave myocardial infarction, stroke, transient ischemic attack, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft
- History of secondary hypertension
- Known genetic cardiomyopathy
- Renal disease (seum creatinine \>1.5 mg/dL for men and \>1.3 mg/dL for women)
- Hepatic disease
- Bronchospastic lung disease
- Alcohol or substance abuse
- Hormone replacement therapy
- Abnormal values for electrolytes, liver enzymes or TSH
- Pregnancy or lactation
- All individuals \<18 and \>75 years will be excluded due to safety concerns of administering an angiotensin-II infusion in these patient groups.
Interventions
After the Pre-Treatment Assessment, participants in the eplerenone arm will be given 50 mg eplerenone. At 2 weeks, eplerenone will be increased to 100 mg.
After the Pre-Treatment Assessment, participants in the chlorthalidone arm will be given 12.5 mg chlorthalidone + 10 mEq potassium. At 2 weeks, chlorthalidone will be increased to 25 mg + 20 mEq potassium.
After the Pre-Treatment Assessment, participants in the chlorthalidone arm will be given 12.5 mg chlorthalidone + 10 mEq potassium. At 2 weeks, chlorthalidone will be increased to 25 mg + 20 mEq potassium.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05593055