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

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

Aldosterone-blocking agents may reduce arterial inflammation in people with HIV

“…''The exact mechanism remains unclear, but preclinical data suggest that excess aldosterone may drive inflammatory cytokine production, vascular inflammation and fibrosis, oxidative stress, and endothelial dysfunction.'' Srinivasa and colleagues at Massachusetts General Hospital designed a double-blind, placebo-controlled study to evaluate the effects of eplerenone, a selective aldosterone receptor antagonist, on the progression of inflammation and cardiovascular disease in PWH [5]. The initial data, collected from 26 adequately treated PWH without known ASCVD, showed that treatment with eplerenone for 12 months significantly reduced arterial inflammation.…”

“…Srinivasa and colleagues at Massachusetts General Hospital designed a double-blind, placebo-controlled study to evaluate the effects of eplerenone, a selective aldosterone receptor antagonist, on the progression of inflammation and cardiovascular disease in PWH [5]. The initial data, collected from 26 adequately treated PWH without known ASCVD, showed that treatment with eplerenone for 12 months significantly reduced arterial inflammation.…”