{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:53:51Z","timestamp":1791388431621,"version":"4.3.3"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human epididymis protein 4 (HE4) has emerged as a biomarker linked to fibrosis and cardiovascular disease. However, its prognostic relevance in peripheral artery disease (PAD) remains unclear. We therefore investigated the association of circulating HE4 with long\u2010term outcomes in patients with PAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective cohort study, 291 patients with symptomatic PAD were enrolled and followed for 10\u2009years. Serum HE4 concentrations were measured by ELISA at baseline. Primary endpoints were all\u2010cause mortality and major adverse cardiovascular events (MACE); secondary endpoints were cardiovascular and non\u2010cardiovascular mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During follow\u2010up, 44.7% of patients died and 41.2% experienced MACE. In univariable models, higher HE4 levels were associated with all\u2010cause mortality and MACE. These associations remained significant after adjustment for established cardiovascular risk factors and renal function: HR 1.35 (95% CI 1.14\u20131.58;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) for all\u2010cause mortality and HR 1.24 (95% CI 1.05\u20131.46;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010) for MACE per doubling of HE4. In secondary analyses, HE4 was independently associated with both cardiovascular and non\u2010cardiovascular mortality. Addition of HE4 to established risk factors significantly improved risk discrimination and reclassification for all\u2010cause mortality (NRI\u2009=\u20090.412,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; IDI\u2009=\u20090.028,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004), whereas incremental prognostic value for MACE was not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating HE4 is a robust and independent predictor of long\u2010term mortality and MACE in patients with PAD, with incremental prognostic value for mortality, primarily in terms of risk reclassification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70236","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:51:49Z","timestamp":1780401109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Human Epididymis Protein 4 Predicts 10\u2010Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-4125","authenticated-orcid":false,"given":"Axel","family":"Muendlein","sequence":"first","affiliation":[{"name":"Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT)  Feldkirch Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Heinzle","sequence":"additional","affiliation":[{"name":"Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT)  Feldkirch Austria"},{"name":"Central Medical 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