Serial measurement of growth-differentiation factor-15 in heart failure

Relation to disease severity and prognosis in the valsartan heart failure trial

Inder Anand, Tibor Kempf, Thomas S. Rector, Heike Tapken, Tim Allhoff, Franziska Jantzen, Michael A Kuskowski, Jay N Cohn, Helmut Drexler, Kai C. Wollert

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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.

Original languageEnglish (US)
Pages (from-to)1387-1395
Number of pages9
JournalCirculation
Volume122
Issue number14
DOIs
StatePublished - Oct 5 2010

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Valsartan
Growth Differentiation Factor 15
Heart Failure
Troponin T
Biomarkers
Brain Natriuretic Peptide
Confidence Intervals
C-Reactive Protein
Mortality

Keywords

  • GDF-15
  • biomarkers
  • heart failure
  • pathophysiology
  • prognosis

Cite this

Serial measurement of growth-differentiation factor-15 in heart failure : Relation to disease severity and prognosis in the valsartan heart failure trial. / Anand, Inder; Kempf, Tibor; Rector, Thomas S.; Tapken, Heike; Allhoff, Tim; Jantzen, Franziska; Kuskowski, Michael A; Cohn, Jay N; Drexler, Helmut; Wollert, Kai C.

In: Circulation, Vol. 122, No. 14, 05.10.2010, p. 1387-1395.

Research output: Contribution to journalArticle

Anand, Inder ; Kempf, Tibor ; Rector, Thomas S. ; Tapken, Heike ; Allhoff, Tim ; Jantzen, Franziska ; Kuskowski, Michael A ; Cohn, Jay N ; Drexler, Helmut ; Wollert, Kai C. / Serial measurement of growth-differentiation factor-15 in heart failure : Relation to disease severity and prognosis in the valsartan heart failure trial. In: Circulation. 2010 ; Vol. 122, No. 14. pp. 1387-1395.
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T2 - Relation to disease severity and prognosis in the valsartan heart failure trial

AU - Anand, Inder

AU - Kempf, Tibor

AU - Rector, Thomas S.

AU - Tapken, Heike

AU - Allhoff, Tim

AU - Jantzen, Franziska

AU - Kuskowski, Michael A

AU - Cohn, Jay N

AU - Drexler, Helmut

AU - Wollert, Kai C.

PY - 2010/10/5

Y1 - 2010/10/5

N2 - 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.

AB - 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.

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