Affiliation:
1. Department of Internal Medicine II Division of Cardiology Medical University of Vienna Vienna Austria
2. Complexity Research Vienna Austria
Abstract
Background
Neprilysin is a transmembrane endopeptidase involved in the breakdown of a variety of vasoactive peptides and serves as a therapeutic target in heart failure with reduced ejection fraction (
HF
r
EF
). This study aimed to investigate the relationship of circulating neprilysin with neurohumoral activation and the impact of plasma neprilysin activity on prognosis in
HF
r
EF
.
Methods and Results
A total of 369 chronic
HF
r
EF
patients were enrolled prospectively. Plasma neprilysin concentration and activity were determined by a specific
ELISA
and a fluorometric method. The association between plasma neprilysin and heart failure (
HF
) severity, neurohumoral activation, ie norepinephrine and absolute renin concentration, as well as all‐cause mortality was assessed. Median plasma neprilysin concentrations and activity levels were 413 pg/mL (interquartile range 0–4111) and 2.36 nmol/mL per minute (interquartile range 1.16–4.59). No correlation could be shown between plasma neprilysin concentrations and activity (
r
s
=0.09,
P
=0.088). Plasma neprilysin activity correlated with
HF
severity reflected by New York Heart Association stage (
P
=0.003) and tertiles of N‐terminal pro‐B‐type natriuretic peptide (
P
<0.001), whereas neprilysin concentrations did not (
P
=0.220;
P
=0.849). There was no relevant relationship between plasma neprilysin concentrations and activity, with neurohumoral activation reflected by absolute renin concentration (
r
s
=−0.02,
P
=0.648;
r
s
=0.03,
P
=0.574) or norepinephrine levels (
r
s
=−0.06,
P
=0.248;
r
s
=0.20,
P
<0.001). Neither circulating neprilysin concentrations nor activity were associated with outcome.
Conclusions
Plasma neprilysin concentrations and activity are not directly related to neurohumoral activation, indicating that neprilysin regulation is either more complex or not correctly mirrored by circulating neprilysin as a biomarker. Circulating neprilysin concentrations and activity were not associated with overall survival, implicating limited prognostic value of plasma neprilysin measurements in
HF
r
EF
patients.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
6 articles.
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