{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:37:04Z","timestamp":1778589424646,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004937","name":"Bundesministerium f\u00fcr Forschung und Technologie","doi-asserted-by":"publisher","award":["BMFT No. 01 EF940\/6"],"award-info":[{"award-number":["BMFT No. 01 EF940\/6"]}],"id":[{"id":"10.13039\/501100004937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016545","name":"Roche Diagnostics","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100016545","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Arthrosehilfe","award":["P306-A707"],"award-info":[{"award-number":["P306-A707"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Subjects with osteoarthritis (OA) are at increased risk for cardiovascular (CV) and all-cause mortality. Whether biomarkers improve outcome prediction in these patients remains to be elucidated. We investigated the association between growth differentiation factor 15 (GDF-15), a novel stress-responsive cytokine, and long-term all-cause mortality among OA patients. Methods: Within the Ulm Osteoarthritis Study, GDF-15 has been measured in the serum of 636 subjects, who underwent hip or knee arthroplasty between 1995 and 1996 (median age 65 years). Results: During a median follow-up of 19.7 years, a total of 402 deaths occurred. GDF-15 was inversely associated with walking distance. Compared to the bottom quartile (Q), subjects within the top quartile of GDF-15 demonstrated a 2.69-fold increased risk of dying (hazard ratio (HR) (95% confidence interval (CI)) 2.69 (1.82\u20133.96) adjusted for age, sex, BMI, smoking status, localization of OA, diabetes, maximum walking distance, total cholesterol, and cystatin C. Further adjustment for NT-proBNP, troponin I, and hs-C-reactive protein did not change the results appreciably (HR (95%CI) 1.56 (1.07\u20132.28); 1.75 (1.21\u20132.55); 2.32 (1.55\u20133.47) for Q2, Q3, and Q4 respectively, p for trend &lt; 0.001). Conclusions: In subjects with OA, GDF-15 represents a potent predictor of decreased survival over &gt;20 years, independently of conventional CV risk factors, renal, cardiac, and inflammatory biomarkers as well as walking disability, previously associated with increased mortality and lower extremity OA.<\/jats:p>","DOI":"10.3390\/jcm9103107","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T08:02:58Z","timestamp":1601280178000},"page":"3107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Growth Differentiation Factor-15 as a Potent Predictor of Long-Term Mortality among Subjects with Osteoarthritis"],"prefix":"10.3390","volume":"9","author":[{"given":"Natalie","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Centre Hamburg, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), partner site Hamburg\/Kiel\/Luebeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Rehm","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela","family":"B\u00fcchele","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-9500","authenticated-orcid":false,"given":"Raphael Simon","family":"Peter","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf Erwin","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus-Peter","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Technical University of Dresden, University Center of Orthopedic and Trauma Surgery, 01069 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":false,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Koenig","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany"},{"name":"Deutsches Herzzentrum M\u00fcnchen, Technische Universit\u00e4t M\u00fcnchen, 80636 Munich, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80333 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-2791","authenticated-orcid":false,"given":"Dietrich","family":"Rothenbacher","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"d1165","DOI":"10.1136\/bmj.d1165","article-title":"All cause and disease specific mortality in patients with knee or hip osteoarthritis: Population based cohort study","volume":"342","author":"Dieppe","year":"2011","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/ard.2009.113696","article-title":"EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis","volume":"69","author":"Peters","year":"2010","journal-title":"Ann. 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