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The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9\u2009\u00b1\u20092.2 vs 4.4\u2009\u00b1\u20090.9\u2009ng\/ml,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (<jats:italic>r<\/jats:italic>\u2009=\u20090.331,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and right atrial pressure (<jats:italic>r<\/jats:italic>\u2009=\u20090.30,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.03). After a mean follow-up of 20\u2009\u00b1\u200910\u2009months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels &gt;\u20096.5\u2009ng\/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC]\u2009=\u20090.81). Multivariate Cox regression analysis demonstrated that HE4 (\u03c7<jats:sup>2<\/jats:sup>: 5.10; hazard ratio [HR]\u2009=\u20091.26; 95% confidence interval: 1.03 to 1.55,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.02) and pulmonary vascular resistance (\u03c7<jats:sup>2<\/jats:sup>: 4.19; HR\u2009=\u20091.14; 95% confidence interval: 1.00\u20131.29,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.04) were independently predictive of clinical worsening. Patients with HE4\u2009&gt;\u20096.5\u2009ng\/ml had a worse 2-year survival rate than those with HE4\u00a0\u2264\u00a06.5\u2009ng\/ml (58.9% vs 96.2%,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Serum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12872-020-01461-w","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T18:03:51Z","timestamp":1586973831000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study"],"prefix":"10.1186","volume":"20","author":[{"given":"Qi","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhai","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinkun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"1461_CR1","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1378\/chest.11-1460","volume":"142","author":"RL Benza","year":"2012","unstructured":"Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. 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