Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure.
OBJECTIVE
We explored the prognostic utility of growth differentiation factor (GDF)-15 in patients with chronic heart failure (CHF).


BACKGROUND
Growth differentiation factor-15 is a stress-responsive member of the transforming growth factor-beta cytokine superfamily. It has recently been observed that patients with CHF have increased circulating levels of GDF-15. The relations of GDF-15 to other biomarkers and to mortality in CHF have never been studied.


METHODS
Circulating levels of GDF-15 were determined by immunoradiometric assay in 455 patients with CHF with a median left ventricular ejection fraction (LVEF) of 32% (interquartile range 25% to 39%).


RESULTS
The median GDF-15 level was 1,949 ng/l (interquartile range 1,194 to 3,577); 74.9% of the patients presented with GDF-15 levels >1,200 ng/l, the upper limit of normal in healthy elderly individuals. The GDF-15 levels were closely related to New York Heart Association (NYHA) functional class and to amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The risk of death during follow-up increased with increasing quartiles of GDF-15. Mortality rates at 48 months were 10.0%, 9.4%, 33.4%, and 56.2% in the respective quartiles (p < 0.001). After adjustment for clinical variables and established biomarkers of adverse prognosis, including NT-proBNP, renal dysfunction, anemia, and hyperuricemia, GDF-15 remained an independent predictor of mortality (adjusted hazard ratio for 1 U in the Ln scale 2.26; 95% confidence interval 1.52 to 3.37; p < 0.001). Growth differentiation factor 15 provided prognostic information in clinically relevant patient subgroups (defined according to age, body mass index, heart failure etiology, concomitant medical therapy, renal function, and the levels of hemoglobin and uric acid) and added prognostic information to NYHA functional class, LVEF, and NT-proBNP.


CONCLUSIONS
Growth differentiation factor 15 is a new biomarker of the risk of death in patients with CHF that provides prognostic information beyond established clinical and biochemical markers.
Kempf
Tibor
T
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
von Haehling
Stephan
S
Peter
Timo
T
Allhoff
Tim
T
Cicoira
Mariantonietta
M
Doehner
Wolfram
W
Ponikowski
Piotr
P
Filippatos
Gerasimos S
GS
Rozentryt
Piotr
P
Drexler
Helmut
H
Anker
Stefan D
SD
Wollert
Kai C
KC
D000368:Aged; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D055436:Growth Differentiation Factor 15; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate