title: Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts.
abstract: OBJECTIVE
  Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans.
  
  
  RESULTS
  We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001).
  
  
  CONCLUSIONS
  In patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice.
authors: Department of Medicine, University of California, San Francisco, CA, USA.
authors: Kristoff A
authors: KA
authors: Olson
authors: Department of Medicine, University of California, San Francisco, CA, USA Cardiology Section, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Alexis L
authors: AL
authors: Beatty
authors: Department of Medicine, University of California, San Francisco, CA, USA.
authors: Bettina
authors: B
authors: Heidecker
authors: The Veterans Health Research Institute, San Francisco, CA, USA.
authors: Mathilda C
authors: MC
authors: Regan
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Edward N
authors: EN
authors: Brody
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Trudi
authors: T
authors: Foreman
authors: NEC Corporation of America, USA.
authors: Shintaro
authors: S
authors: Kato
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Robert E
authors: RE
authors: Mehler
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Britta S
authors: BS
authors: Singer
authors: Lifandis AS, Norway HUNT Research Center, Department of Public Health, NTNU, Trondheim, Norway.
authors: Kristian
authors: K
authors: Hveem
authors: Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway MI Lab and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Norway.
authors: Havard
authors: H
authors: Dalen
authors: SomaLogic Inc., Boulder, CO, USA.
authors: David G
authors: DG
authors: Sterling
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Richard M
authors: RM
authors: Lawn
authors: Department of Medicine, University of California, San Francisco, CA, USA.
authors: Nelson B
authors: NB
authors: Schiller
authors: SomaLogic Inc., Boulder, CO, USA.
authors: Stephen A
authors: SA
authors: Williams
authors: Department of Medicine, University of California, San Francisco, CA, USA Veterans Affairs Medical Center, San Francisco, CA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, USA.
authors: Mary A
authors: MA
authors: Whooley
authors: Department of Medicine, University of California, San Francisco, CA, USA Division of Cardiology, San Francisco General Hospital, San Francisco, CA, USA peter.ganz@ucsf.edu.
authors: Peter
authors: P
authors: Ganz
mesh_terms: D000367:Age Factors; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood / Q000401:mortality; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000378:metabolism*; D055412:Growth Differentiation Factors / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood / Q000401:mortality; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000401:mortality*; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000401:mortality
chemical_list: D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D055412:Growth Differentiation Factors
keywords: Ageing; Cardiovascular outcomes; Epidemiology; Growth differentiation factor 11 and 8; Hypertrophy