Limits...
The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction.

Stahrenberg R, Edelmann F, Mende M, Kockskämper A, Düngen HD, Lüers C, Binder L, Herrmann-Lingen C, Gelbrich G, Hasenfuss G, Pieske B, Wachter R - Eur. J. Heart Fail. (2010)

Bottom Line: In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF.When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy.It is independently associated with impairment in exercise capacity and in physical components of quality of life.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Pneumology, University of Goettingen, 37075 Goettingen, Germany.

ABSTRACT

Aims: Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF.

Methods and results: A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n=86) or HFnEF (n=142) and compared with healthy elderly controls (n=188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy.

Conclusion: Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.

Show MeSH

Related in: MedlinePlus

Growth differentiation factor 15 levels across grades of diastolic dysfunction. Grades 2 and 3 were grouped, as only very few subjects had Grade 3 diastolic dysfunction, P < 0.001 for trend by Jonckheere–Terpstra. Broken line denotes recommended cut-off of 1.20 ng/mL.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2990410&req=5

HFQ151F2: Growth differentiation factor 15 levels across grades of diastolic dysfunction. Grades 2 and 3 were grouped, as only very few subjects had Grade 3 diastolic dysfunction, P < 0.001 for trend by Jonckheere–Terpstra. Broken line denotes recommended cut-off of 1.20 ng/mL.

Mentions: In the whole study sample, higher log(GDF-15) levels were strongly associated with higher age, lower estimated glomerular filtration rate (eGFR), higher NT-proBNP, shorter 6 min walk distance and lower SF-36 physical score, but also moderately with several echocardiographic parameters indicative of systolic and diastolic function (see Supplementary material online, Table S1). Prominent among correlations with echocardiographic parameters of diastolic function were those with increased LAVI, LVMI, E/é, decreased é and é/á. Jonckheere–Terpstra test unravelled significantly increasing GDF-15 levels across grades of diastolic dysfunction (P < 0.001, Figure 2). As differing algorithms for grading the severity of diastolic dysfunction have been used over the past years and guidelines published in the meantime stress the relevance of E/é values (with cut-offs that deviate from the one we used for our grading scheme), Figure 3 additionally shows significantly increasing GDF-15 levels across three strata of E/é. Finally, we observed a strong association with estimated right ventricular systolic pressure.Figure 2


The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction.

Stahrenberg R, Edelmann F, Mende M, Kockskämper A, Düngen HD, Lüers C, Binder L, Herrmann-Lingen C, Gelbrich G, Hasenfuss G, Pieske B, Wachter R - Eur. J. Heart Fail. (2010)

Growth differentiation factor 15 levels across grades of diastolic dysfunction. Grades 2 and 3 were grouped, as only very few subjects had Grade 3 diastolic dysfunction, P < 0.001 for trend by Jonckheere–Terpstra. Broken line denotes recommended cut-off of 1.20 ng/mL.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2990410&req=5

HFQ151F2: Growth differentiation factor 15 levels across grades of diastolic dysfunction. Grades 2 and 3 were grouped, as only very few subjects had Grade 3 diastolic dysfunction, P < 0.001 for trend by Jonckheere–Terpstra. Broken line denotes recommended cut-off of 1.20 ng/mL.
Mentions: In the whole study sample, higher log(GDF-15) levels were strongly associated with higher age, lower estimated glomerular filtration rate (eGFR), higher NT-proBNP, shorter 6 min walk distance and lower SF-36 physical score, but also moderately with several echocardiographic parameters indicative of systolic and diastolic function (see Supplementary material online, Table S1). Prominent among correlations with echocardiographic parameters of diastolic function were those with increased LAVI, LVMI, E/é, decreased é and é/á. Jonckheere–Terpstra test unravelled significantly increasing GDF-15 levels across grades of diastolic dysfunction (P < 0.001, Figure 2). As differing algorithms for grading the severity of diastolic dysfunction have been used over the past years and guidelines published in the meantime stress the relevance of E/é values (with cut-offs that deviate from the one we used for our grading scheme), Figure 3 additionally shows significantly increasing GDF-15 levels across three strata of E/é. Finally, we observed a strong association with estimated right ventricular systolic pressure.Figure 2

Bottom Line: In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF.When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy.It is independently associated with impairment in exercise capacity and in physical components of quality of life.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Pneumology, University of Goettingen, 37075 Goettingen, Germany.

ABSTRACT

Aims: Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF.

Methods and results: A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n=86) or HFnEF (n=142) and compared with healthy elderly controls (n=188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy.

Conclusion: Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.

Show MeSH
Related in: MedlinePlus