Circulating Neprilysin in Patients With Heart Failure and Preserved Ejection Fraction.

Abstract

BACKGROUND:

In heart failure with reduced ejection fraction (HFrEF), elevated soluble neprilysin (sNEP) levels are associated with an increased risk of cardiovascular death, and its inhibition with sacubitril/valsartan has improved survival.

OBJECTIVES:

This study sought to determine the relevance of sNEP as a biomarker in heart failure with preserved ejection fraction (HFpEF) and to compare circulating sNEP levels in patients with HFpEF with normal controls.

METHODS:

A case-control study was performed in 242 symptomatic patients with HFpEF previously enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) and Nitrates's Effect on Activity Tolerance in Heart Failure With Preserved Ejection (NEAT-HFpEF) clinical trials and 891 asymptomatic subjects without HF or diastolic dysfunction (confirmed by NT-proBNP levels <200 pg/ml and echocardiography) who were enrolled in the Prevalence of Asymptomatic Left Ventricular Dysfunction study. sNEP was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects.

RESULTS:

Overall, sNEP levels were lower in HFpEF compared with controls (3.5 ng/ml; confidence interval [CI]: 2.5 to 4.8 vs. 8.5 ng/ml; CI: 7.2 to 10.0; p < 0.001). After adjusting for age, gender, body mass index (BMI), and smoking history, mean sNEP levels were also lower in HFpEF compared with controls (4.0 ng/ml [CI: 2.7 to 5.4] vs. 8.2 ng/ml [CI: 6.8 to 9.7]; p = 0.002). The cohorts were propensity matched based on age, BMI, diabetes, hypertension, smoking history, and renal function, and sNEP levels remained lower in HFpEF compared with controls (median 2.4 ng/ml [interquartile range: 0.6 to 27.7] vs. 4.9 ng/ml [interquartile range: 1.2 to 42.2]; p = 0.02).

CONCLUSIONS:

Patients with HFpEF on average have significantly lower circulating sNEP levels compared with controls. These findings challenge our current understanding of the complex biology of circulating sNEP in HFpEF.

• Authors: Melissa A Lyle, Seethalakshmi R Iyer, Margaret M Redfield, Yogesh N V Reddy, G Michael Felker, Thomas P Cappola, Adrian F Hernandez, Christopher G Scott, John C Burnett Jr, Naveen L Pereira
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 8 Issue 1 Pg. 70-80 (01 2020) ISSN: 2213-1787 [Electronic] United States
• PMID: 31392960 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Biomarkers
• Biphenyl Compounds
• Drug Combinations
• Tetrazoles
• Valsartan
• Neprilysin
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aged
• Aminobutyrates (therapeutic use)
• Angiotensin Receptor Antagonists (therapeutic use)
• Biomarkers (blood)
• Biphenyl Compounds
• Case-Control Studies
• Drug Combinations
• Echocardiography
• Female
• Heart Failure (blood, diagnosis, drug therapy, physiopathology)
• Heart Ventricles (diagnostic imaging, physiopathology)
• Humans
• Male
• Middle Aged
• Neprilysin (antagonists & inhibitors, blood)
• Stroke Volume (physiology)
• Tetrazoles (therapeutic use)
• Valsartan
• Ventricular Function, Left (physiology)