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. 2020 Feb 4;72(1):14–19. doi: 10.1016/j.ihj.2020.01.006

Table 1.

Summarized studies included in the review.

Reference Study population Biomarkers analyzed Analytical method used for neprilysin estimation Brief conclusion of the study Type of study
A. Bayes-Genis et al, 2015 797 patients with HF Plasma sNEP, NT-pro BNP, hscTnT, ST2 Modified sandwich immunoassay sNEP independently associated with HF-related death than NT-pro BNP Cohort
Thomas A Zelniker et al, 2018 144 patients of cardiac arrest of nontraumatic origin out-of-hospital Plasma sNEP, hsTnT, hsCRP, NT-pro BNP Human neprilysin DuoSet ELISA research kit sNEP independently associated with all-cause mortality in patients with out-of-hospital cardiac arrest of nontraumatic origin Cohort
Pajenda et al, 2017 90 critically ill patients Urine NEP Human NEP ELISA Elevated urinary NEP is indicative of proximal tubular cell stress or injury. Cohort
Sridevi Gutta et al, 2018 60 patients with type 2 DM with a history of microalbuminuria and macroalbuminuria ACE2 and NEP Human ELISA kit ACE2 and NEP as noninvasive biomarkers to assess kidney damage in patients with diabetes at an early stage. Cross-sectional
Mattia Arrigo et al, 2018 50 patients (28 patients with acute HF and 22 acute noncardiac dyspnea) sNEP Modified sandwich immunoassay Short-term clinical improvement after acute dyspnea or mid-term improvement after total artificial heart transplantation are associated with an increase rather than a decrease in sNEP Cohort
Antoni Bayes-Genis et al, 2016 98 patients with chronic HF sNEP Fluorometric assay Circulating sNEP as a biotarget in heart failure Cohort
Antoni Bayés-Genís et al, 2015 1069 patients with HF sNEP Modified sandwich immunoassay High levels of neprilysin are found in the circulation of patients with HF and that neprilysin concentrations are indicators of adverse outcomes for both cardiovascular
mortality and morbidity.
Cohort
Julio Nu ~ nez et al, J 2017 1021 consecutive ambulatory patients with heart failure sNEP, NT-pro BNP Modified sandwich immunoassay Elevated sNEP levels predicted an increased risk of recurrent all-cause, cardiovascular, and AHF admissions in ambulatory patients with heart failure. Cohort
Elena Guillén-Gómez et al, 2018 21 patients with type 2 diabetic [12 without DN (control patients) and 9 with incipient DN (DN basal)] Urine NEP, VCAM-1 Specific enzyme-linked immunosorbent assay Neprilysin and VCAM-1 as potential new tools as DN progression biomarkers Case control
Kristina F. Standeven et al, 2011 318 clinically healthy white men of European origin, characterized for the presence of the MetS sNEP, tissue plasminogen activator, insulin, plasminogen activator
inhibitor-1
Modified fluorescence Obesity and the development of insulin resistance is associated with increased plasma NEP levels Cross-sectional
Julio Núñez et al, 2016 210 patients consecutively admitted for AHF NT-pro BNP, hscTnT, sNEP Modified sandwich immunoassay sNEP was associated with the
risk of long-term recurrent all-cause and AHF rehospitalizations
Prospective cohort
Reddy et al, 2019 1536 patients in the general population sNEP, ANP, BNP, NT-pro ANP, NT-pro BNP Sandwich ELISA sNEP and natriuretic peptide did not correlate. Large community-based cohort study

HF = heart failure; sNEP = soluble neprilysin; NT-pro BNP = N-terminal brain natriuretic peptide; hscTnT = high sensitive cardiac troponin T; ST2 = suppression of tumorigenicity 2; NEP = neprilysin; ACE2 = angiotensin-converting enzyme 2; IL6 = interleukin; VCAM-1 = human vascular cell adhesion molecule-1; STEMI = ST-segment elevation myocardial infarction; DM = diabetes mellitus; DN = diabetic nephropathy; MetS = metabolic syndrome; AHF = acute heart failure; ANP = A-type natriuretic peptide; BNP = brain natriuretic peptide; NT-pro ANP = N-terminal pro-ANP; NT-pro BNP = N-terminal pro-BNP.