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JACC Heart Fail. 2019 Jul 31. pii: S2213-1779(19)30549-9. doi: 10.1016/j.jchf.2019.07.005. [Epub ahead of print]

Circulating Neprilysin in Patients with Heart Failure with Preserved Ejection Fraction.

Author information

1
The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
2
Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina, USA.
3
Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
5
The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota. Electronic address: Pereira.naveen@mayo.edu.

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 HFpEF patients with normal controls.

METHODS:

A case-control study was performed in 242 symptomatic HFpEF patients previously enrolled in the RELAX and 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 ELISA assay in all subjects.

RESULTS:

Overall, sNEP levels were lower in HFpEF compared to controls (3.5 ng/ml [CI 2.5, 4.8] vs 8.5 ng/ml [CI 7.2, 10.0], p<0.001). After adjusting for age, gender, BMI and smoking history, mean sNEP levels were also lower in HFpEF compared with controls (4.0 ng/ml [CI 2.7,5.4] vs 8.2 ng/ml [CI 6.8, 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 [IQR 0.6, 27.7] vs 4.9 ng/ml [IQR 1.2, 42.2], p=0.02).

CONCLUSIONS:

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

KEYWORDS:

diastolic dysfunction; heart failure; neprilysin

PMID:
31392960
DOI:
10.1016/j.jchf.2019.07.005

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