Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study.
BACKGROUND
Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking.


RESULTS
Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo.


CONCLUSIONS
In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.
Momentum Research Inc, 3100 Tower Boulevard, Durham, NC, 27707, USA.
Gad
G
Cotter
University Medical Centre Groningen, Groningen, the Netherlands.
Adriaan A
AA
Voors
Novartis Pharmaceuticals Corporation, New Hanover, NJ, USA.
Margaret F
MF
Prescott
Duke Clinical Research Institute, Durham, NC, USA.
G Michael
GM
Felker
Athens University Hospital, Attikon, Athens, Greece.
Gerasimos
G
Filippatos
University of California at San Diego, San Diego, CA, USA.
Barry H
BH
Greenberg
Indiana University School of Medicine, Indianapolis, IN, USA.
Peter S
PS
Pang
Medical University, Clinical Military Hospital, Wroclaw, Poland.
Piotr
P
Ponikowski
Momentum Research Inc, 3100 Tower Boulevard, Durham, NC, 27707, USA.
Olga
O
Milo
Novartis Pharmaceuticals Corporation, New Hanover, NJ, USA.
Tsushung A
TA
Hua
Columbia University, New York, NY, USA.
Min
M
Qian
Novartis Pharmaceuticals Corporation, New Hanover, NJ, USA.
Thomas M
TM
Severin
University of California-San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
John R
JR
Teerlink
University of Brescia, Brescia, Italy.
Marco
M
Metra
Momentum Research Inc, 3100 Tower Boulevard, Durham, NC, 27707, USA.
Beth A
BA
Davison
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002317:Cardiovascular Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012065:Relaxin / Q000008:administration & dosage*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D000067251:Symptom Flare Up; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D011994:Recombinant Proteins; C109794:pro-brain natriuretic peptide (1-76); C577649:serelaxin protein, human; D020097:Natriuretic Peptide, Brain; D012065:Relaxin
Acute heart failure; GDF-15; RELAX-AHF study