{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:25:38Z","timestamp":1769117138077,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":2551,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T00:00:00Z","timestamp":1548374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K09447"],"award-info":[{"award-number":["16K09447"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K09447"],"award-info":[{"award-number":["16K09447"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia-induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure \u2265 25 mmHg and pulmonary artery wedge pressure \u2264 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all-cause mortality. Laboratory data revealed no significant correlations between sNEP and B-type natriuretic peptide (R = 0.022, P = 0.872), N-terminal proBNP (R = \u22120.018, P = 0.872), and high-sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = \u22120.036, P = 0.764), right ventricular fractional area change (R = \u22120.259, P = 0.064), tricuspid valve pressure gradient (R = \u22120.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan\u2013Meier analysis (mean follow-up, 1284 days, log-rank P = 0.531), all-cause mortality rates were comparable between the higher NEP group (sNEP \u2265 median levels of 1.45 ng\/mL, n = 39) and the lower NEP group (sNEP &amp;lt; 1.45 ng\/mL, n = 40). In the Cox proportional hazard analysis, sNEP was not a predictor of all-cause mortality (hazard ratio 0.902, 95% CI 0.674\u20131.207, P = 0.487) in PH patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating sNEP does not correlate with natriuretic peptide, haemodynamic parameters, or prognosis in patients with PH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12404","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T06:28:21Z","timestamp":1548397701000},"page":"291-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Soluble Neprilysin Does Not Correlate with Prognosis in Pulmonary Hypertension"],"prefix":"10.1093","volume":"6","author":[{"given":"Akiomi","family":"Yoshihisa","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]},{"name":"Department of Advanced Cardiac Therapeutics, Fukushima Medical University , Fukushima ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuro","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]},{"name":"Department of Pulmonary Hypertension, Fukushima Medical University , Fukushima ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomofumi","family":"Misaka","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]},{"name":"Department of Advanced Cardiac Therapeutics, Fukushima Medical University , Fukushima ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Yamaki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]},{"name":"Department of Pulmonary Hypertension, Fukushima Medical University , Fukushima ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kunii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Nakazato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuchika","family":"Takeishi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University , 1 Hikarigaoka, Fukushima, 960-1295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,25]]},"reference":[{"key":"2026012115095821900_ehf212404-bib-0001","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/ejhf.603","article-title":"Combined neprilysin and renin\u2013angiotensin system inhibition in heart failure with reduced ejection fraction: a meta-analysis","volume":"18","author":"Solomon","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026012115095821900_ehf212404-bib-0002","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012115095821900_ehf212404-bib-0003","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/ejhf.799","article-title":"Neprilysin inhibition in heart failure: mechanisms and 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