Elsevier

JACC: Heart Failure

Volume 9, Issue 2, February 2021, Pages 85-95
JACC: Heart Failure

Focus Issue: Mechanistic Insights and Drug Therapy
Original Research
Soluble Neprilysin and Corin Concentrations in Relation to Clinical Outcome in Chronic Heart Failure

https://doi.org/10.1016/j.jchf.2020.08.015Get rights and content
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Abstract

Objectives

This study investigated whether patients with chronic heart failure (HF) can be stratified according to the combination of soluble neprilysin and corin concentrations and whether this is related to clinical outcome.

Background

Natriuretic peptide processing by the enzymes corin and neprilysin plays a pivotal role in conversion of pro–natriuretic peptides to active natriuretic peptides, as well as their degradation, respectively.

Methods

A prospective cohort of patients with chronic HF (n = 1,009) was stratified into 4 equal groups based on high or low neprilysin/corin concentration relative to the median: 1) low neprilysin/low corin; 2) low neprilysin/high corin; 3) high neprilysin/low corin; and 4) high neprilysin/high corin. Cox regression survival analysis was performed for the composite primary endpoint of cardiovascular death and HF hospitalization.

Results

Median neprilysin and corin concentrations were not correlated (rho: −0.04; p = 0.21). Although in univariate analysis there was no association with outcome, after correction for baseline differences in age and sex, a significant association with survival was demonstrated: with highest survival in group 1 (low neprilysin/low corin) and lowest in group 4 (high neprilysin/high corin) (adjusted hazard ratio: 1.56; p = 0.003), which remained statistically significant after comprehensive multivariable analysis (adjusted hazard ratio: 1.41; p = 0.03).

Conclusions

Stratification of patients with chronic HF based on circulating neprilysin and corin concentrations is associated with clinical outcomes. These results suggest that regulation of these enzymes is of importance in chronic HF and may offer an interesting approach for classification of patients with HF in a step toward individualized HF patient management.

Key Words

clinical outcome
corin
heart failure
natriuretic peptide
neprilysin

Abbreviations and Acronyms

aHR
adjusted hazard ratio
ANP
atrial natriuretic peptide
ARNI
Angiotensin-receptor-neprilysin inhibitor
BNP
B-type natriuretic peptide
CI
confidence interval
CV
cardiovascular
ELISA
enzyme-linked immunosorbent assay
HF
heart failure
HFpEF
heart failure with preserved ejection fraction
HFrEF
heart failure with reduced ejection fraction
IQR
interquartile range
NEP
neprilysin
NP
natriuretic peptide
NT-proBNP
N-terminal pro–B-type natriuretic peptide
proANP
pro-atrial natriuretic peptide
proBNP
pro-B-type natriuretic peptide
sCOR
soluble corin
sNEP
soluble neprilysin

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs. Bayés-Genis and R.J. van Kimmenade contributed equally and are joint senior authors.