Prognostic Utility of Growth Differentiation Factor-15 in Patients With Chronic Heart Failure
Tibor Kempf, MD*,1,
Stephan von Haehling, MD , ,
Timo Peter, MS*,
Tim Allhoff, MS*,
Mariantonietta Cicoira, MD, PhD ,
Wolfram Doehner, MD, PhD,
Piotr Ponikowski, MD||,
Gerasimos S. Filippatos, MD#,
Piotr Rozentryt, MD**,
Helmut Drexler, MD*,1,
Stefan D. Anker, MD, PhD, and
Kai C. Wollert, MD*,1,*
* Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
Division of Applied Cachexia Research, Department of Cardiology, Charité, Berlin, Germany
Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
Section of Cardiology, University of Verona, Verona, Italy
|| Department of Cardiology, Military Hospital, Wroclaw, Poland
# Department of Cardiology, University Hospital, Athens, Greece
** Department of Cardiology, Silesian Center for Heart Disease, Zabrze, Poland.
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Figure 1 GDF-15 Levels in 455 Patients With Chronic Heart Failure Stratified According to NYHA Functional Class or NT-proBNP Levels at Study Entry
Patients were stratified according to New York Heart Association (NYHA) functional class (A) or NT-proBNP quartiles (B). The GDF-15 levels are presented as box (25th percentile, median, 75th percentile) and whisker (10th and 90th percentiles) plots. Patient numbers are indicated. The NT-proBNP levels in the first quartile ranged from 20 to 305 ng/l, in the second quartile from 306 to 800 ng/l, in the third quartile from 801 to 2,307 ng/l, and in the fourth quartile from 2,308 to 88,300 ng/l. p < 0.001 by Kruskal-Wallis test in both panels. GDF-15 = growth differentiation factor 15; NT-proBNP = amino-terminal pro–B-type natriuretic peptide.
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Figure 2 Cumulative Survival in 455 Patients With CHF According to Quartiles of GDF-15 at Study Entry
The number of patients at risk and mortality rates are shown below the graph. p < 0.001 by simple Cox regression analysis. GDF = growth differentiation factor.
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Figure 3 Risk of Death During Follow-Up Associated With a GDF-15 Level >2,729 ng/l at Study Entry
Patient numbers are shown in parentheses. For analyses according to age, body mass index (BMI), creatinine, and creatinine clearance (Crea Cl), median values of the study population were used to create subgroups of comparable size. Patients were also stratified according to presence or absence of anemia (hemoglobin  13 g/dl in men, 12 g/dl in women), hyperuricemia (uric acid >400 µmol/l), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy, and beta-blocker therapy at study entry. The hazard ratio (HR) could not be calculated in patients not receiving ACEI/ARB therapy (there were 0 deaths in 12 patients with growth differentiation factor (GDF)-15 levels 2,729 ng/l, and 8 deaths in 21 patients with GDF-15 levels >2,729 ng/l). The p values were obtained by simple Cox regression analysis. CI = confidence interval.
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Figure 4 One-Year Mortality Rates According to NYHA Functional Class, LVEF, NT-proBNP, and Levels of GDF-15
The number of deaths per number of patients is shown above each bar. For analyses according to LVEF and NT-proBNP, the median values of the study population were used to create subgroups of comparable size. The p values were obtained by simple Cox regression analysis. LVEF = left ventricular ejection fraction; other abbreviations as in Figures 1 and 3.
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