Evaluation of Mineralocorticoid Receptor Antagonism on Changes in NT-proBNP Among Persons With HIV

Author:

Srinivasa Suman1ORCID,deFilippi Christopher2,Fitch Kathleen V1,Iyengar Sanjna1,Shen Grace1ORCID,Burdo Tricia H3,Walpert Allie R1,Thomas Teressa S1,Adler Gail K4,Grinspoon Steven K1ORCID

Affiliation:

1. Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

2. INOVA Heart and Vascular Institute, Falls Church, VA 22042, USA

3. Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA

4. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA

Abstract

Abstract Subclinical myocardial dysfunction is prevalent among well-treated persons with HIV (PWH). We have previously demonstrated unique renin-angiotensin-aldosterone system physiology among PWH with metabolic dysregulation. Mineralocorticoid receptor blockade may be a targeted treatment strategy for subclinical heart disease in PWH. Forty-six PWH were randomized to receive either eplerenone 50 mg daily or placebo in a 6-month randomized, double-blinded, placebo-controlled trial. We assessed changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker of cardiac stretch, under controlled posture and dietary conditions. The eplerenone- and placebo-treated groups demonstrated a long duration of HIV with good immunological control. NT-proBNP levels were similar between the groups at baseline (41.1 [20.2, 97.9] vs 48.9 [29.2, 65.4] ng/L, P = .80) and decreased significantly more in the eplerenone- vs placebo-treated groups after 6 months (change NT-proBNP -9.6 [-46.8, 0.3] vs -3.0 [-17.0, 39.9] ng/L, P = .02 for comparison of change between groups). Decreases in NT-proBNP were independent of changes in systolic and diastolic blood pressure, and related to decreases in high-sensitivity C-reactive protein (ρ = 0.32, P = .05) and inversely to increases in serum aldosterone (ρ = -0.33, P = .04) among all participants. Treatment with eplerenone for 6 months vs placebo significantly decreases NT-proBNP levels among PWH, independent of eplerenone’s known blood pressure-lowering effects. Further studies should elucidate whether lowering NT-proBNP in this at-risk metabolic population with subclinical heart disease will offer cardioprotection. Clinical Trial Registration NCT01405456

Funder

National Institutes of Health

Harvard Catalyst

National Center for Research Resources

National Center for Advancing Translational Sciences

Publisher

The Endocrine Society

Subject

Endocrinology, Diabetes and Metabolism

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