Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease.
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.
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; emil.hagstrom@ucr.uu.se.|Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.
Emil
E
Hagström
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.|Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.
Claes
C
Held
Green Lane Cardiovascular Service, Auckland City Hospital, and University of Auckland, Auckland, New Zealand.
Ralph A H
RA
Stewart
South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, Australia.
Philip E
PE
Aylward
Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
Andrzej
A
Budaj
Cardiovascular Division, Brigham and Women's Hospital, and Harvard Clinical Research Institute, Boston, MA, USA.
Christopher P
CP
Cannon
Department 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.
Wolfgang
W
Koenig
Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA, USA.
Sue
S
Krug-Gourley
University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Emile R
ER
Mohler
Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Paris, France.|Paris Diderot University, Sorbonne Paris Cité, Paris, France.|NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK.|FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, INSERM U1148, Paris, France.
Philippe Gabriel
PG
Steg
former employee of Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA, USA.
Elizabeth
E
Tarka
Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.
Ollie
O
Östlund
Green Lane Cardiovascular Service, Auckland City Hospital, and University of Auckland, Auckland, New Zealand.
Harvey D
HD
White
Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Agneta
A
Siegbahn
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.|Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15