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Published in: BMC Cardiovascular Disorders 1/2020

Open Access 01-12-2020 | Heart Failure | Research article

Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study

Authors: Ik Jun Choi, Sungmin Lim, Youngdeok Hwang, Dongjae Lee, Won Jik Lee, Kwan Yong Lee, Mi-Jeong Kim, Doo Soo Jeon

Published in: BMC Cardiovascular Disorders | Issue 1/2020

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Abstract

Background

Neprilysin has an essential role in regulating fluid balance and vascular resistance, and neprilysin inhibitors have shown beneficial effects in patients with heart failure. However, the potential predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear. The aim of this study was to assess the prognostic value of soluble neprilysin (sNEP) levels in patients with ischemic heart disease.

Methods

Neprilysin levels were measured in 694 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). These patients were classified into two groups according to their serum levels of neprilysin and categorized into the lower neprilysin group (n = 348) and the higher neprilysin group (n = 346). The primary clinical endpoint was all-cause mortality, and the secondary endpoint was a composite of major adverse cardiac events (MACE).

Results

The median sNEP level was 76.0 pg/ml. The median sNEP levels were higher in patients with left ventricular ejection fraction (LVEF) ≥40% (77.6 pg/ml, interquartile range 46.6–141.3) than in those with LVEF < 40% (70.0 pg/ml, interquartile range 47.1–100.6; P = 0.032). Among all patients, each clinical outcome and MACE did not differ significantly according to the groups divided into median, tertile, or quartile of sNEP levels during a median follow-up of 28.4 months. We did not find a significant relationship between sNEP levels and clinical outcomes in multivariate Cox regression analysis. Among patients with LVEF < 40%, an increased sNEP level was associated with a higher rate of all-cause death (adjusted hazard ratio 2.630, 95% confidence interval 1.049–6.595, P = 0.039).

Conclusion

Serum sNEP levels are not associated with long-term mortality or cardiovascular outcomes after PCI in patients with CAD. In the LVEF < 40% group, increased sNEP levels may be associated with a higher risk of all-cause death.
Literature
1.
go back to reference Bayes-Genis A, Barallat J, Richards AM. A test in context: Neprilysin: function, inhibition, and biomarker. J Am Coll Cardiol. 2016;68:639–53.CrossRef Bayes-Genis A, Barallat J, Richards AM. A test in context: Neprilysin: function, inhibition, and biomarker. J Am Coll Cardiol. 2016;68:639–53.CrossRef
2.
go back to reference Seronde MF, Mebazaa A. Neprilysin: biotarget and biomarker in heart failure. JACC Hear Fail. 2015;3:645–6.CrossRef Seronde MF, Mebazaa A. Neprilysin: biotarget and biomarker in heart failure. JACC Hear Fail. 2015;3:645–6.CrossRef
3.
go back to reference Bayés-Genís A. Neprilysin in heart failure: from oblivion to center stage. JACC Hear Fail. 2015;3:637–40.CrossRef Bayés-Genís A. Neprilysin in heart failure: from oblivion to center stage. JACC Hear Fail. 2015;3:637–40.CrossRef
4.
go back to reference Janssen WM, de Jong PE, van der Hem GK, de Zeeuw D. Effect of human atrial natriuretic peptide on blood pressure after sodium depletion in essential hypertension. Br Med J (Clin Res Ed). 1986;293:351–3.CrossRef Janssen WM, de Jong PE, van der Hem GK, de Zeeuw D. Effect of human atrial natriuretic peptide on blood pressure after sodium depletion in essential hypertension. Br Med J (Clin Res Ed). 1986;293:351–3.CrossRef
5.
go back to reference Dillingham MA, Anderson RJ. Inhibition of vasopressin action by atrial natriuretic factor. Science. 1986;231:1572–3.CrossRef Dillingham MA, Anderson RJ. Inhibition of vasopressin action by atrial natriuretic factor. Science. 1986;231:1572–3.CrossRef
6.
go back to reference Lyle MA, Iyer SR, Redfield MM, Reddy YNV, Felker GM, Cappola TP, et al. Circulating Neprilysin in patients with heart failure and preserved ejection fraction. JACC Hear Fail. 2020;8:70–80.CrossRef Lyle MA, Iyer SR, Redfield MM, Reddy YNV, Felker GM, Cappola TP, et al. Circulating Neprilysin in patients with heart failure and preserved ejection fraction. JACC Hear Fail. 2020;8:70–80.CrossRef
7.
go back to reference Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48.CrossRef Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48.CrossRef
8.
go back to reference McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRef McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRef
10.
go back to reference Bayés-Genís A, Barallat J, Galán A, De Antonio M, Domingo M, Zamora E, et al. Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients. J Am Coll Cardiol. 2015;65:657–65.CrossRef Bayés-Genís A, Barallat J, Galán A, De Antonio M, Domingo M, Zamora E, et al. Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients. J Am Coll Cardiol. 2015;65:657–65.CrossRef
11.
go back to reference Bayés-Genís A, Barallat J, Pascual D, Nuñez J, Miñana G, Sánchez-Mas J, et al. Prognostic value and kinetics of soluble Neprilysin in acute heart failure. A pilot study. JACC Hear Fail. 2015;3:641–4.CrossRef Bayés-Genís A, Barallat J, Pascual D, Nuñez J, Miñana G, Sánchez-Mas J, et al. Prognostic value and kinetics of soluble Neprilysin in acute heart failure. A pilot study. JACC Hear Fail. 2015;3:641–4.CrossRef
13.
go back to reference Bernelin H, Mewton N, Si-Mohamed S, Croisille P, Rioufol G, Bonnefoy-Cudraz E, et al. Neprilysin levels at the acute phase of ST-elevation myocardial infarction. Clin Cardiol. 2019;42:32–8.CrossRef Bernelin H, Mewton N, Si-Mohamed S, Croisille P, Rioufol G, Bonnefoy-Cudraz E, et al. Neprilysin levels at the acute phase of ST-elevation myocardial infarction. Clin Cardiol. 2019;42:32–8.CrossRef
14.
go back to reference Goliasch G, Pavo N, Zotter-Tufaro C, Kammerlander A, Duca F, Mascherbauer J, et al. Soluble neprilysin does not correlate with outcome in heart failure with preserved ejection fraction. Eur J Heart Fail. 2016;18:89–93.CrossRef Goliasch G, Pavo N, Zotter-Tufaro C, Kammerlander A, Duca F, Mascherbauer J, et al. Soluble neprilysin does not correlate with outcome in heart failure with preserved ejection fraction. Eur J Heart Fail. 2016;18:89–93.CrossRef
15.
go back to reference Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574–651.PubMed Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574–651.PubMed
16.
go back to reference O’Gara PT, Kushner FG, Ascheim DD, Casey DEJ, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;127:e362–425.CrossRef O’Gara PT, Kushner FG, Ascheim DD, Casey DEJ, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;127:e362–425.CrossRef
17.
go back to reference Amsterdam EA, Wenger NK, Brindis RG, Casey DEJ, Ganiats TG, Holmes DRJ, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;130:2354–94.CrossRef Amsterdam EA, Wenger NK, Brindis RG, Casey DEJ, Ganiats TG, Holmes DRJ, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;130:2354–94.CrossRef
18.
go back to reference Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40:87–165.CrossRef Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40:87–165.CrossRef
19.
go back to reference de Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science. 1985;230:767–70.CrossRef de Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science. 1985;230:767–70.CrossRef
20.
go back to reference Sudoh T, Minamino N, Kangawa K, Matsuo H. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990;168:863–70.CrossRef Sudoh T, Minamino N, Kangawa K, Matsuo H. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990;168:863–70.CrossRef
21.
go back to reference Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988;332:78–81.CrossRef Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988;332:78–81.CrossRef
22.
go back to reference Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol. 2007;50:2357–68.CrossRef Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol. 2007;50:2357–68.CrossRef
23.
go back to reference Bavishi C, Messerli FH, Kadosh B, Ruilope LM, Kario K. Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials. Eur Heart J. 2015;36:1967–73.CrossRef Bavishi C, Messerli FH, Kadosh B, Ruilope LM, Kario K. Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials. Eur Heart J. 2015;36:1967–73.CrossRef
24.
go back to reference Dewan P, Docherty KF, McMurray JJV. Sacubitril/valsartan in Asian patients with heart failure with reduced ejection fraction. Korean Circ J. 2019;49:669–84.CrossRef Dewan P, Docherty KF, McMurray JJV. Sacubitril/valsartan in Asian patients with heart failure with reduced ejection fraction. Korean Circ J. 2019;49:669–84.CrossRef
25.
go back to reference Potter LR. Natriuretic peptide metabolism, clearance and degradation. FEBS J. 2011;278:1808–17.CrossRef Potter LR. Natriuretic peptide metabolism, clearance and degradation. FEBS J. 2011;278:1808–17.CrossRef
26.
go back to reference George SG, Kenny AJ. Studies on the enzymology of purified preparations of brush border from rabbit kidney. Biochem J. 1973;134:43–57.CrossRef George SG, Kenny AJ. Studies on the enzymology of purified preparations of brush border from rabbit kidney. Biochem J. 1973;134:43–57.CrossRef
27.
go back to reference Kerr MA, Kenny AJ. The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. Biochem J. 1974;137:477–88.CrossRef Kerr MA, Kenny AJ. The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. Biochem J. 1974;137:477–88.CrossRef
29.
go back to reference Richards AM, Wittert GA, Espiner EA, Yandle TG, Ikram H, Frampton C. Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers. Circ Res. 1992;71:1501–7.CrossRef Richards AM, Wittert GA, Espiner EA, Yandle TG, Ikram H, Frampton C. Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers. Circ Res. 1992;71:1501–7.CrossRef
30.
go back to reference Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383:45–51.CrossRef Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383:45–51.CrossRef
31.
go back to reference Stephenson SL, Kenny AJ. The hydrolysis of α-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11. Biochem J. 1987;243:183–7.CrossRef Stephenson SL, Kenny AJ. The hydrolysis of α-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11. Biochem J. 1987;243:183–7.CrossRef
33.
go back to reference Yandle T, Richards M, Smith M, Charles C, Livesey J, Espiner E. Assay of endopeptidase-24.11 activity in plasma applied to in vivo studies of endopeptidase inhibitors. Clin Chem. 1992;38:1785–91.CrossRef Yandle T, Richards M, Smith M, Charles C, Livesey J, Espiner E. Assay of endopeptidase-24.11 activity in plasma applied to in vivo studies of endopeptidase inhibitors. Clin Chem. 1992;38:1785–91.CrossRef
34.
go back to reference Núñez J, Núñez E, Barallat J, Bodí V, Miñana G, Cruz Pastor M, et al. Serum neprilysin and recurrent admissions in patients with heart failure. J Am Heart Assoc. 2017;6:1–9.CrossRef Núñez J, Núñez E, Barallat J, Bodí V, Miñana G, Cruz Pastor M, et al. Serum neprilysin and recurrent admissions in patients with heart failure. J Am Heart Assoc. 2017;6:1–9.CrossRef
35.
go back to reference Reddy YNV, Iyer SR, Scott CG, Rodeheffer RJ, Bailey K, Jenkins G, et al. Soluble Neprilysin in the general population: clinical determinants and its relationship to cardiovascular disease. J Am Heart Assoc. 2019;8:e012943.PubMedPubMedCentral Reddy YNV, Iyer SR, Scott CG, Rodeheffer RJ, Bailey K, Jenkins G, et al. Soluble Neprilysin in the general population: clinical determinants and its relationship to cardiovascular disease. J Am Heart Assoc. 2019;8:e012943.PubMedPubMedCentral
36.
go back to reference Vodovar N, Séronde MF, Laribi S, Gayat E, Lassus J, Januzzi JL, et al. Elevated plasma B-type natriuretic peptide concentrations directly inhibit circulating Neprilysin activity in heart failure. JACC Hear Fail. 2015;3:629–36.CrossRef Vodovar N, Séronde MF, Laribi S, Gayat E, Lassus J, Januzzi JL, et al. Elevated plasma B-type natriuretic peptide concentrations directly inhibit circulating Neprilysin activity in heart failure. JACC Hear Fail. 2015;3:629–36.CrossRef
Metadata
Title
Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study
Authors
Ik Jun Choi
Sungmin Lim
Youngdeok Hwang
Dongjae Lee
Won Jik Lee
Kwan Yong Lee
Mi-Jeong Kim
Doo Soo Jeon
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2020
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01636-5

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