{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:34:08Z","timestamp":1790678048699,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T00:00:00Z","timestamp":1441238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure &amp;gt;125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF\/RF) readmission at 60 days\/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF\/RF rehospitalizations\/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.331","type":"journal-article","created":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T02:35:46Z","timestamp":1441247746000},"page":"1133-1143","source":"Crossref","is-referenced-by-count":106,"title":["Growth Differentiation Factor 15 (GDF-15) in Patients Admitted for Acute Heart Failure: Results from the RELAX-AHF Study"],"prefix":"10.1093","volume":"17","author":[{"given":"Gad","family":"Cotter","sequence":"first","affiliation":[{"name":"Momentum Research Inc , 3100 Tower Boulevard, Durham, NC, 27707 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"University Medical Centre Groningen , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret F.","family":"Prescott","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation , New Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Michael","family":"Felker","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Athens University Hospital , Attikon, Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry H.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"University of California at San Diego , San Diego, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Pang","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine , Indianapolis, IN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Medical University, Clinical Military Hospital , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Milo","sequence":"additional","affiliation":[{"name":"Momentum Research Inc , 3100 Tower Boulevard, Durham, NC, 27707 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsushung A.","family":"Hua","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation , New Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Qian","sequence":"additional","affiliation":[{"name":"Columbia University , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Severin","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation , New Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Teerlink","sequence":"additional","affiliation":[{"name":"University of California-San Francisco and San Francisco Veterans Affairs Medical Center , San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Davison","sequence":"additional","affiliation":[{"name":"Momentum Research Inc , 3100 Tower Boulevard, Durham, NC, 27707 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,3]]},"reference":[{"key":"2026011921102398700_ejhf331-bib-0001","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1093\/emboj\/19.10.2212","article-title":"The propeptide of macrophage inhibitory cytokine (MIC-1), a TGF-\u03b2 superfamily member, acts as a quality control determinant for correctly folded MIC\u20131","volume":"19","author":"Bauskin","year":"2000","journal-title":"EMBO J"},{"key":"2026011921102398700_ejhf331-bib-0002","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3109\/08977194.2011.607137","article-title":"The TGF-\u03b2 superfamily cytokine, MIC-1\/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism","volume":"29","author":"Breit","year":"2011","journal-title":"Growth Factors"},{"key":"2026011921102398700_ejhf331-bib-0003","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jss.2005.07.036","article-title":"Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms","volume":"130","author":"Zimmers","year":"2006","journal-title":"J Surg Res"},{"key":"2026011921102398700_ejhf331-bib-0004","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm1272","article-title":"The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy","volume":"11","author":"Buitrago","year":"2005","journal-title":"Nat Med"},{"key":"2026011921102398700_ejhf331-bib-0005","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1161\/01.RES.0000202805.73038.48","article-title":"The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia\/reperfusion injury","volume":"98","author":"Kempf","year":"2006","journal-title":"Circ Res"},{"key":"2026011921102398700_ejhf331-bib-0006","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.109.928846","article-title":"Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial","volume":"122","author":"Anand","year":"2010","journal-title":"Circulation"},{"key":"2026011921102398700_ejhf331-bib-0007","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchf.2013.10.005","article-title":"Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure","volume":"2","author":"Gaggin","year":"2014","journal-title":"JACC Heart Fail"},{"key":"2026011921102398700_ejhf331-bib-0008","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3109\/1354750X.2010.510580","article-title":"Growth differentiation factor 15 in different stages of heart failure: potential screening implications","volume":"15","author":"Wang","year":"2010","journal-title":"Biomarkers"},{"key":"2026011921102398700_ejhf331-bib-0009","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.amjcard.2013.05.013","article-title":"Incremental prognostic power of novel biomarkers (growth-differentiation factor-15, high-sensitivity C-reactive protein, galectin-3, and high-sensitivity troponin-T) in patients with advanced chronic heart failure","volume":"112","author":"Lok","year":"2013","journal-title":"Am J Cardiol"},{"key":"2026011921102398700_ejhf331-bib-0010","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(12)61855-8","article-title":"Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial","volume":"381","author":"Teerlink","year":"2013","journal-title":"Lancet"},{"key":"2026011921102398700_ejhf331-bib-0011","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.jacc.2007.04.091","article-title":"Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure","volume":"50","author":"Kempf","year":"2007","journal-title":"JACC"},{"key":"2026011921102398700_ejhf331-bib-0012","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/biomet\/41.1-2.133","article-title":"A distribution-free k-sample test against ordered alternatives","volume":"41","author":"Jonckheere","year":"1954","journal-title":"Biometrika"},{"key":"2026011921102398700_ejhf331-bib-0013","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S1385-7258(52)50043-X","article-title":"The asymptotic normality and consistency of Kendall\u2019s test against trend, when ties are present in one ranking","volume":"14","author":"Terpstra","year":"1952","journal-title":"Indagationes Mathematicae"},{"key":"2026011921102398700_ejhf331-bib-0014","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1037\/0022-3514.51.6.1173","article-title":"The moderator\u2013mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations","volume":"51","author":"Baron","year":"1986","journal-title":"J Pers Soc Psychol"},{"key":"2026011921102398700_ejhf331-bib-0015","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1037\/1082-989X.7.1.83","article-title":"A comparison of methods to test mediation and other intervening variable effects","volume":"7","author":"MacKinnon","year":"2002","journal-title":"Psycholog Methods"},{"key":"2026011921102398700_ejhf331-bib-0016","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1093\/eurjhf\/hfs120","article-title":"Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support","volume":"14","author":"Lok","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"2026011921102398700_ejhf331-bib-0017","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1161\/ATVBAHA.110.213512","article-title":"Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22","volume":"31","author":"Bonaca","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.331","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/11\/1133\/66422244\/eurjhf_17_11_1133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/11\/1133\/66422244\/eurjhf_17_11_1133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:11:01Z","timestamp":1768875061000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/17\/11\/1133\/8426439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,3]]},"references-count":17,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,9,3]]},"published-print":{"date-parts":[[2015,11,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.331","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,11]]},"published":{"date-parts":[[2015,9,3]]}}}