Trial reportJACC. Heart failure2020
Circulating Neprilysin in Patients With Heart Failure and Preserved Ejection Fraction.
Trial report in JACC. Heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Heart Failure Biomarkers-Pathophysiology, Diagnosis, Prognosis and Clinical Relevance.International journal of molecular sciences · 2025Review
- Increased neprilysin expression is linked to atrial fibrotic remodeling in cardiovascular surgery patients.International journal of cardiology. Heart & vasculature · 2025Article
- Inhibiting atrial natriuretic peptide clearance reduces myocardial fibrosis and improves cardiac function in diabetic rats.European heart journal open · 2025Article
- Elevated serum neprilysin levels in patients with chronic hepatitis C and metabolic dysfunction-associated steatotic liver disease: hepatic oxidative stress as an underlying mechanism.Molecular biology reports · 2024Article
- Multiple circulating forms of neprilysin detected with novel epitope-directed monoclonal antibodies.Cellular and molecular life sciences : CMLS · 2024Article
- Loop diuretic management after sacubitril/valsartan initiation in heart failure with preserved ejection fraction: deceptively simple or more than meets the eye?European journal of heart failure · 2023Article
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Biomarkers in Heart Failure with Preserved Ejection Fraction.Cardiac failure review · 2022Review
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- Circulating Neprilysin Level Predicts the Risk of Cardiovascular Events in Hemodialysis Patients.Frontiers in cardiovascular medicine · 2021Article
- Characterization of the inflammatory-metabolic phenotype of heart failure with a preserved ejection fraction: a hypothesis to explain influence of sex on the evolution and potential treatment of the disease.European journal of heart failure · 2020Review
- Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study.BMC cardiovascular disorders · 2020Article
- Plasma Neprilysin Displays No Relevant Association With Neurohumoral Activation in Chronic HFrEF.Journal of the American Heart Association · 2020Article
- Angiotensin receptor-neprilysin inhibitor for the treatment of heart failure: a review of recent evidence.The Korean journal of internal medicine · 2020Review
- Neprilysin as a Biomarker: Challenges and Opportunities.Cardiac failure review · 2020Review
- Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin in db/db diabetic mice.Physiological reports · 2020Article
- The vasculature in HFpEF vs HFrEF: differences in contractile protein expression produce distinct phenotypes.Heliyon · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIn 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.
objectivesThis 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.
methodsA 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.
resultsOverall, 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).
conclusionsPatients 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.