{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:48:13Z","timestamp":1792234093902,"version":"4.4.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["[#01GD9820\/0]"],"award-info":[{"award-number":["[#01GD9820\/0]"]}]},{"name":"Pitzer Foundation"},{"name":"Department of Internal Medicine II-Cardiology"},{"name":"University of Ulm Medical Center"},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>This study considered whether baseline concentrations and 12-month changes of growth differentiation factor 15 (GDF-15) are associated with subsequent cardiovascular events (CVEs) and total mortality in patients with stable coronary heart disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Baseline GDF-15 serum concentrations were measured in 1073 participants in a cardiac rehabilitation program (median follow-up 10 years). GDF-15 associations with subsequent CVE and total mortality were evaluated by Cox-proportional hazards models adjusting for well-established cardiovascular risk factors (Model 2), plus N-terminal probrain natriuretic peptide, high-sensitivity (hs) CRP, and hs cardiac troponin T (Model 3).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>In our study population [84.7% men, mean age 59 years, median baseline GDF-15 1232 ng\/L (interquartile range, 916, 1674)] we observed 190 CVE and 162 deaths. Compared to participants with GDF-15 &amp;lt;1200 ng\/L, increased risk for death was found in participants with GDF-15 \u22651200 and \u22641800 ng\/L [hazard ratio (HR) 1.68 (95% CI, 1.08\u20132.62)] and with GDF-15 &amp;gt;1800 ng\/L [HR 1.73 (1.02\u20132.94)], even in Model 3. The 12-month relative median change was \u221216.7%. As compared to participants with 12-month relative changes between \u221220% and 20%, GDF-15 increments &amp;gt;20% were associated with: a) an HR of 1.84 (1.04\u20133.26) for CVE in Model 2, but found nonsignificant in Model 3; (b) an HR of 2.26 (1.32\u20133.86) for death even in Model 3.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>GDF-15 at baseline is independently associated with subsequent CVE and 10-year total mortality. Twelve-month relative changes remained associated with subsequent CVE when adjusting for well-established cardiovascular risk factors, and with total mortality even after further adjustment for established cardiac biomarkers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2016.254755","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T06:06:11Z","timestamp":1463724371000},"page":"982-992","source":"Crossref","is-referenced-by-count":31,"title":["Growth Differentiation Factor 15, Its 12-Month Relative Change, and Risk of Cardiovascular Events and Total Mortality in Patients with Stable Coronary Heart Disease: 10-Year Follow-up of the KAROLA Study"],"prefix":"10.1093","volume":"62","author":[{"given":"Dhayana","family":"Dallmeier","sequence":"first","affiliation":[{"name":"Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany"},{"name":"Agaplesion Bethesda Hospital, Geriatric Research Unit, Ulm University and Geriatric Center Ulm\/Alb-Donau, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Mons","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Rottbauer","sequence":"first","affiliation":[{"name":"Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Koenig","sequence":"first","affiliation":[{"name":"Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany"},{"name":"Deutsches Herzzentrum M\u00fcnchen, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Rothenbacher","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany"},{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,1]]},"reference":[{"key":"2020022605340267700_B1","unstructured":"WHO. 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