Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial.
BACKGROUND
Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure.


RESULTS
The circulating concentration of GDF-15 was measured at baseline (n=1734) and at 12 months (n=1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT). GDF-15 levels at baseline ranged from 259 to 25 637 ng/L and were abnormally high (>1200 ng/L) in 85% of patients. Higher levels were associated with features of worse heart failure and biomarkers of neurohormonal activation, inflammation, myocyte injury, and renal dysfunction. Baseline GDF-15 levels (per 100 ng/L) were associated with the risks of mortality (hazard ratio, 1.017; 95% confidence interval, 1.014 to 1.019; P<0.001) and first morbid event (hazard ratio, 1.020; 95% confidence interval, 1.017 to 1.023; P<0.001). In a comprehensive multiple-variable Cox regression model that included clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T, GDF-15 remained independently associated with mortality (hazard ratio, 1.007; 95% confidence interval, 1.001 to 1.014; P=0.02) but not first morbid event. At 12 months, the GDF-15 levels had increased by a similar amount in the placebo and valsartan groups (P=0.94). Increases in GDF-15 over 12 months were independently associated with the risks of future mortality and first morbid event also after adjustment for clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T and their changes.


CONCLUSIONS
GDF-15 reflects information from several pathological pathways and provides independent prognostic information in heart failure. GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT.
Anand
Inder S
IS
Cardiology 111-C, VA Medical Center, 1 Veterans Drive, Minneapolis, MN 55417, USA. anand001@umn.edu
Kempf
Tibor
T
Rector
Thomas S
TS
Tapken
Heike
H
Allhoff
Tim
T
Jantzen
Franziska
F
Kuskowski
Michael
M
Cohn
Jay N
JN
Drexler
Helmut
H
Wollert
Kai C
KC
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications; D015415:Biomarkers / Q000097:blood; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011379:Prognosis; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D055436:Growth Differentiation Factor 15; D010919:Placebos; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine