Author + information
- Received May 15, 2019
- Revision received June 21, 2019
- Accepted July 15, 2019
- Published online August 7, 2019.
- Melissa A. Lyle, MD1,∗,
- Seethalakshmi R. Iyer, MS1,∗,
- Margaret M. Redfield, MD1,
- Yogesh N.V. Reddy, MD, MSc1,
- G Michael Felker, MD, MHS2,
- Thomas P. Cappola, MD3,
- Adrian F. Hernandez, MD2,
- Christopher G. Scott, MS4,
- John C. Burnett Jr., MD1 and
- Naveen L. Pereira, MD1,5,∗ (, )@nl_pereira
- 1The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
- 2Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina, USA
- 3Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- 4Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
- 5Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence: Naveen L Pereira, MD Mayo Clinic and Foundation 200 First Street SW Rochester, MN 55905 Phone: 507-284-8260.
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.
↵∗ These authors contributed equally to this work
-Dr. Naveen Pereira is supported by National Institute on Aging Grant R21AG53512
-Dr. Michael Felker has received research grants from NHLBI, American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; he has acted as a consultant to Novartis, Amgen, BMS, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, and SC Pharma
-The remaining authors have nothing to disclose
- Received May 15, 2019.
- Revision received June 21, 2019.
- Accepted July 15, 2019.