{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:18:39Z","timestamp":1793726319216,"version":"4.6.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg\/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78\u20132.57) unadjusted, 1.96 (1.49\u20132.53) after adjustment for clinical confounders and 1.44 (1.05\u20131.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78\u20133.33) and 1.52 (1.15\u20132.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.trialregister.nl\/trial\/1783\">https:\/\/www.trialregister.nl\/trial\/1783<\/jats:ext-link>\n              ; Unique Identifier: NTR1893. (The trial can be found temporarily at\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=NTR1893\">https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=NTR1893<\/jats:ext-link>\n              .)\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.122.009526","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T10:00:36Z","timestamp":1669024836000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-3841","authenticated-orcid":true,"given":"Muhammed T.","family":"G\u00fcrg\u00f6ze","sequence":"first","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"van Vark","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-901X","authenticated-orcid":true,"given":"Sara J.","family":"Baart","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, the Netherlands (S.J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Kardys","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Martijn","family":"Akkerhuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2202-7314","authenticated-orcid":true,"given":"Olivier C.","family":"Manintveld","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douwe","family":"Postmus","sequence":"additional","affiliation":[{"name":"Department of Epidemiology (D.P., H.L.H.), University Medical Center Groningen, University of Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[{"name":"Department of Epidemiology (D.P., H.L.H.), University Medical Center Groningen, University of Groningen, the Netherlands"},{"name":"Department of Cardiology (H.L.H.), University Medical Center Groningen, University of Groningen, the Netherlands"},{"name":"University Medical Center Groningen, University of Groningen, the Netherlands (H.L.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1715-0385","authenticated-orcid":true,"given":"Ivonne","family":"Lesman-Leegte","sequence":"additional","affiliation":[{"name":"Department of General Practice and Elderly Care Medicine (I.L.-L.), University Medical Center Groningen, University of Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-8669","authenticated-orcid":true,"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, the Netherlands (F.W.A.)."},{"name":"Institute of Cardiovascular Science, Faculty of Population Health Sciences (F.W.A.), University College London, United Kingdom."},{"name":"Health Data Research UK and Institute of Health Informatics (F.W.A.), University College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4356-8566","authenticated-orcid":true,"given":"Hans-Peter","family":"Brunner-la-Rocca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center, the Netherlands (H.-P.B.-l.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewout J.","family":"van den Bos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Albert Schweitzer Hospital, 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