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

Suman Srinivasa, Christopher deFilippi, Kathleen V Fitch, Sanjna Iyengar, Grace Shen, Tricia H Burdo, Allie R Walpert, Teressa S Thomas, Gail K Adler, Steven K Grinspoon, Suman Srinivasa, Christopher deFilippi, Kathleen V Fitch, Sanjna Iyengar, Grace Shen, Tricia H Burdo, Allie R Walpert, Teressa S Thomas, Gail K Adler, Steven K Grinspoon

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.

Keywords: HIV; NT-proBNP; eplerenone; renin-angiotensin-aldosterone system.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Comparison of the change in NT-proBNP after 6 months of treatment among persons with HIV randomized to eplerenone vs placebo. Box plots represent the 25th and 75th percentiles, and lines within the boxes represent the median.

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