Affiliation:
1. From the VA Medical Center (I.S.A., T.S.R., M.K.) and University of Minnesota (I.S.A., T.S.R., M.K., J.N.C.), Minneapolis, and Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (T.K., H.T., T.A., F.J., H.D., K.C.W.).
Abstract
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.
Methods and 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
258 articles.
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