Emil Hagström1,2, Claes Held3,2, Ralph A H Stewart4, Philip E Aylward5, Andrzej Budaj6, Christopher P Cannon7, Wolfgang Koenig8,9,10, Sue Krug-Gourley11, Emile R Mohler12, Philippe Gabriel Steg13,14,15,16, Elizabeth Tarka17, Ollie Östlund2, Harvey D White4, Agneta Siegbahn2,18, Lars Wallentin3,2. 1. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; emil.hagstrom@ucr.uu.se. 2. Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden. 3. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. 4. Green Lane Cardiovascular Service, Auckland City Hospital, and University of Auckland, Auckland, New Zealand. 5. South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, Australia. 6. Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland. 7. Cardiovascular Division, Brigham and Women's Hospital, and Harvard Clinical Research Institute, Boston, MA, USA. 8. Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany. 9. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. 10. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. 11. Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA, USA. 12. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. 13. Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Paris, France. 14. Paris Diderot University, Sorbonne Paris Cité, Paris, France. 15. NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK. 16. FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, INSERM U1148, Paris, France. 17. former employee of Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA, USA. 18. Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND:Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited. METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed. RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI. CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
RCT Entities:
BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited. METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed. RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI. CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
Authors: Daniel Lindholm; Stefan K James; Katja Gabrysch; Robert F Storey; Anders Himmelmann; Christopher P Cannon; Kenneth W Mahaffey; Philippe Gabriel Steg; Claes Held; Agneta Siegbahn; Lars Wallentin Journal: JAMA Cardiol Date: 2018-12-01 Impact factor: 14.676
Authors: Paul Welsh; Dorien M Kimenai; Riccardo E Marioni; Caroline Hayward; Archie Campbell; David Porteous; Nicholas L Mills; Stephen O'Rahilly; Naveed Sattar Journal: Clin Chem Lab Med Date: 2022-08-18 Impact factor: 8.490
Authors: Daniel Lindholm; Emil Hagström; Stefan K James; Richard C Becker; Christopher P Cannon; Anders Himmelmann; Hugo A Katus; Gerald Maurer; José Luis López-Sendón; Philippe Gabriel Steg; Robert F Storey; Agneta Siegbahn; Lars Wallentin Journal: J Am Heart Assoc Date: 2017-04-14 Impact factor: 5.501
Authors: Claes Held; Nermin Hadziosmanovic; Philip E Aylward; Emil Hagström; Judith S Hochman; Ralph A H Stewart; Harvey D White; Lars Wallentin Journal: J Am Heart Assoc Date: 2022-01-21 Impact factor: 6.106
Authors: Ralph A H Stewart; Emil Hagström; Claes Held; Tom Kai Ming Wang; Paul W Armstrong; Philip E Aylward; Christopher P Cannon; Wolfgang Koenig; José Luis López-Sendón; Emile R Mohler; Nermin Hadziosmanovic; Susan Krug-Gourley; Marco Antonio Ramos Corrales; Saulat Siddique; Philippe Gabriel Steg; Harvey D White; Lars Wallentin Journal: J Am Heart Assoc Date: 2017-08-22 Impact factor: 5.501