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.
abstract: 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.
  
  
  
  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).
  
  
  
  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 <1200 ng/L, increased risk for death was found in participants with GDF-15 ≥1200 and ≤1800 ng/L [hazard ratio (HR) 1.68 (95% CI, 1.08-2.62)] and with GDF-15 >1800 ng/L [HR 1.73 (1.02-2.94)], even in Model 3. The 12-month relative median change was -16.7%. As compared to participants with 12-month relative changes between -20% and 20%, GDF-15 increments >20% were associated with: a) an HR of 1.84 (1.04-3.26) for CVE in Model 2, but found nonsignificant in Model 3; (b) an HR of 2.26 (1.32-3.86) for death even in Model 3.
  
  
  
  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.
authors.affiliation: Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany; Agaplesion Bethesda Hospital, Geriatric Research Unit, Ulm University and Geriatric Center Ulm/Alb-Donau, Ulm, Germany;
authors.forename: Dhayana
authors.initials: D
authors.lastname: Dallmeier
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany;
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany;
authors.forename: Ute
authors.initials: U
authors.lastname: Mons
authors.affiliation: Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.affiliation: Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany; Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; koenig@dhm.mhn.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rothenbacher
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15