☆ 4.7 Article

Soluble Neprilysin Is Predictive of Cardiovascular Death and Heart Failure Hospitalization in Heart Failure Patients

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2015)

Journal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Volume 65, Issue 7, Pages 657-665

Publisher

ELSEVIER SCIENCE INC

DOI: 10.1016/j.jacc.2014.11.048

Keywords

B-type natriuretic peptide; prognosis; survival

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Abstract

BACKGROUND Neprilysin is a membrane-bound enzyme that breaks down natriuretic peptides. The PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showed that patients with heart failure (HF) treated with an angiotensin receptor neprilysin inhibitor lived longer without being hospitalized for HF than those receiving standard care with enalapril. OBJECTIVES This study sought to assess the presence of circulating soluble neprilysin in a real-life cohort of HF patients and correlate neprilysin levels with outcomes. METHODS Circulating soluble neprilysin was measured with a modified sandwich immunoassay in consecutive ambulatory patients with HF who were followed up for 4.1 years. Associations between neprilysin level and a composite endpoint that included cardiovascular death or HF hospitalization were explored. RESULTS Median neprilysin concentration in 1,069 patients was 0.642 ng/ml (median quartile 1 to 3: 0.385 to 1.219). Neprilysin weakly but significantly correlated with age (rho = 0.16; p < 0.001). In age-adjusted Cox regression analyses, neprilysin concentrations were significantly associated with the composite endpoint (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.06 to 1.29; p = 0.001) and cardiovascular death (HR: 1.19; 95% CI: 1.06 to 1.32; p = 0.002). In comprehensive multivariable analyses, soluble neprilysin remained significantly associated with both the composite endpoint (HR: 1.18; 95% CI: 1.07 to 1.31; p = 0.001) and cardiovascular death (HR: 1.18; 95% CI: 1.05 to 1.32; p = 0.006). CONCLUSIONS Identification of circulating neprilysin in HF patients and the positive association of neprilysin with cardiovascular mortality and morbidity further support the importance of NEP inhibition for augmenting natriuretic peptides as a therapeutic target. (C) 2015 by the American College of Cardiology Foundation.

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C-Type Natriuretic Peptide in Essential Hypertension Old Ways for a New Time

Tara Perunovic, Jens P. Goetze

Summary: Multiple mechanisms contribute to essential hypertension, and antihypertensive drugs primarily target increased sympathetic nervous system activity, altered production of vasoactive mediators, vascular inflammation, fibrosis, and increased peripheral resistance. C-type natriuretic peptide (CNP) is an endothelium-derived peptide that influences vascular signaling through two receptors, NPR-B and NPR-C. This article summarizes the effects of CNP on the vasculature in relation to essential hypertension and proposes targeting the CNP system as a potential tool for managing long-term essential hypertension.

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