scholarly journals Circulating Concentrations of Growth-Differentiation Factor 15 in Apparently Healthy Elderly Individuals and Patients with Chronic Heart Failure as Assessed by a New Immunoradiometric Sandwich Assay

2007 ◽  
Vol 53 (2) ◽  
pp. 284-291 ◽  
Author(s):  
Tibor Kempf ◽  
Rüdiger Horn-Wichmann ◽  
Georg Brabant ◽  
Timo Peter ◽  
Tim Allhoff ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Transforming Growth Factor ◽  
Size Exclusion ◽  
Igg Antibody ◽  
Elderly Individuals ◽  
Growth Differentiation Factor 15 ◽  
Healthy Elderly ◽  
Differentiation Factor ◽  
Apparently Healthy

Abstract Background: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor β (TGF-β) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. Methods: We developed an IRMA that uses a polyclonal, affinity chromatography–purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). Results: The assay had a detection limit of 20 ng/L, an intraassay imprecision of ≤10.6%, and an interassay imprecision of ≤12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-β. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th–75th percentiles, 600–959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. Conclusion: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.

5949Interleukin-6 and growth differentiation factor-15 in hypertensive heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Fernandez ◽  
J Rysa ◽  
J Nilsson ◽  
G Engstrom ◽  
M Orho-Melander ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transforming Growth Factor ◽  
Mechanical Stretch ◽  
Neonatal Rat ◽  
Chronic Hypertension ◽  
Mrna Levels ◽  
Growth Differentiation Factor 15 ◽  
Hypertrophic Growth ◽  
Differentiation Factor ◽  
Circulating Levels

Abstract Background Hypertension is the leading cause for the development of heart failure (HF). Increased hemodynamic load, including mechanical stretch and neurohumoral factors, is able to trigger hypertrophic growth of cardiac myocytes. Although hypertensive HF is prevalent, there is no useful biomarker to identify HF due to chronic hypertension. Aims To identify plasma markers associated with incidence of hypertensive HF. Methods Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4469 individuals from the Malmö Diet and Cancer study. Protein levels were compared to stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVM) in response to 1, 4, 12, 24 or 48 hours of cyclic mechanical stretch. Association between plasma proteins level and HF incidence and hypertension was studied using respectively Cox proportional hazards model and binary logistic regressions. Results After Bonferroni correction, 44 circulating proteins were significantly differentially expressed in individuals who developed HF during follow-up versus controls (P<3.4E-4). Out of these, 5 proteins (Interleukin-6 (IL-6), Growth Differentiation Factor-15 (GDF15), Interleukin-1 Receptor-Like-1 (ST2), Plasminogen Activator Urokinase Receptor (U-PAR), Transforming Growth Factor-α (TGF-α)), corresponding mRNA levels were upregulated by mechanical stretch in NRVM at all time points (P<0.05). Similar upregulation for the 5 proteins was shown in hypertensive versus normotensive individuals (P≤8.05E-4). In a model with all 5 proteins entered simultaneously, GDF15 and IL-6 were predictive of incident HF after adjustment for age, sex and NT-BNP levels (205 events; hazard ratio [HR] per SD increment of protein: HR=1.29, CI=1.05–1.58, P=0.013 and HR=1.16, CI=1.02–1.33, P=0.028). Using the same model, IL-6 but not GDF15 associated with hypertension (Odds ratio [OR] per SD increment of IL-6: OR=1.18, CI=1.09–1.27, P=3.3E-5). In hypertensive individuals GDF15 and IL-6 were individually predictive of future HF after adjustment for age, sex, NT-BNP levels, smoking, BMI and diabetes (183 events; HR=1.36, CI=1.16–1.60, P=1.64E-4 and HR=1.21, CI=1.05–1.40, P=0.008). Furthermore, in these hypertensive individuals, GDF15 and IL-6 were predictive of HF in a model with IL-6, GDF15, ST2 and TGF-α entered simultaneously after adjustment for age, sex and NT-BNP levels (176 events; HR=1.36, CI=1.13–1.64, P=0.001 and HR=1.16, CI=1.01–1.34, P=0.041). Conclusions Circulating levels of IL-6 and GDF15 might be used as NT-BNP independent biomarkers for HF development in hypertensive patients. Acknowledgement/Funding Påhlsson, Crafoord, Lundström, Åke Wiberg, Royal Physiographic Society and the Swedish Foundation for Strategic Research for IRC15-0067

scholarly journals Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure

2017 ◽  
Vol 5 (10) ◽  
pp. 724-734 ◽  
Author(s):  
Abhinav Sharma ◽  
Susanna R. Stevens ◽  
Joseph Lucas ◽  
Mona Fiuzat ◽  
Kirkwood F. Adams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

scholarly journals Prognostic Utility of Growth Differentiation Factor-15 in Patients With Chronic Heart Failure

2007 ◽  
Vol 50 (11) ◽  
pp. 1054-1060 ◽  
Author(s):  
Tibor Kempf ◽  
Stephan von Haehling ◽  
Timo Peter ◽  
Tim Allhoff ◽  
Mariantonietta Cicoira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Prognostic Utility

Growth Differential Factor 15 (GDF%15), Possible Biomarker in Heart Failure

2017 ◽  
Vol 68 (3) ◽  
pp. 631-634
Author(s):  
Valeriu Gabi Dinca ◽  
Gheorghe Manole ◽  
Daniel Cochior ◽  
Alexandra Ligia Dinca
Keyword(s):  
Heart Failure ◽  
Serum Concentration ◽  
The Other ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Other Hand ◽  
The One ◽  
Growth Differential

The present study aims at determining on the one hand the growth differentiation factor 15 significance as possible risk biomarker for this condition and, on the other hand, the degree of correlation between its serum concentration and the class of inotropism deficit.The value of the current research stems from the very selected theme, the activity of GDF-15, member of the superfamily of cytokines TGF-b recognized as having implication in atherosclerosis, but almost unexplored as role in the myocardiumremodeling processes, more precisely in fibrosis.

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