scholarly journals Growth Differentiation Factor 15 (GDF-15): A Novel Biomarker Associated with Poorer Respiratory Function in COVID-19

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1998
Author(s):  
Leticia Alserawan ◽  
Patricia Peñacoba ◽  
Sandra Elizabet Orozco Echevarría ◽  
Diego Castillo ◽  
Esther Ortiz ◽  
...  
Keyword(s):  
Respiratory Function ◽  
Operating Characteristics ◽  
Growth Differentiation Factor 15 ◽  
Reactive Protein ◽  
Pathological Conditions ◽  
Differentiation Factor ◽  
Receiver Operating Characteristics Curve ◽  
Pulmonary Impairment ◽  
New Biomarkers ◽  
Circulating Levels

It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical and laboratory parameters reflecting severity in 84 patients with COVID-19, finding that GDF-15 levels were higher in both patients than in 20 healthy controls and were higher in patients with poorer respiratory function. GDF-15 levels also correlated with interleukin-6, C-reactive protein, ferritin and D-dimer levels and with neutrophilia and lymphopenia. Of all the analysed biomarkers, GDF-15 showed the best area under the receiver operating characteristics curve in identifying patients with poor respiratory function. In conclusion, our data support GDF-15 as a biomarker associated with pulmonary impairment in COVID-19 and so can potentially be useful in stratifying COVID-19 cases by severity.

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 Association between Circulating Growth Differentiation Factor 15 and Cirrhotic Primary Biliary Cholangitis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhanyi Li ◽  
Yu Liu ◽  
Xiangyong Li ◽  
Yuankai Wu ◽  
Fangji Yang ◽  
...  
Keyword(s):  
Serum Levels ◽  
Response To Treatment ◽  
Primary Biliary Cholangitis ◽  
Strongly Correlated ◽  
Weight Changes ◽  
Adequate Treatment ◽  
Growth Differentiation Factor 15 ◽  
Reactive Protein ◽  
Differentiation Factor ◽  
End Stage

Primary biliary cholangitis (PBC) is a common condition that usually shows a progressive course towards cirrhosis without adequate treatment. Growth differentiation factor 15 (GDF15) plays multiple roles in various pathological conditions. The overall role of circulating GDF15 in cirrhotic PBC requires further investigation. Twenty patients with cirrhotic PBC, 26 with non-cirrhotic PBC, and 10 healthy subjects were enrolled between 2014 and 2018, and the serum levels of GDF15 were measured via enzyme immunoassay. The correlations between serum GDF15, weight, biochemical parameters, and the prognosis were analysed. Serum levels of GDF15 were significantly higher in cirrhotic PBC patients than in non-cirrhotic PBC patients or healthy controls ( p = 0.009 and p < 0.001 , respectively). The circulating GDF15 levels strongly correlated with weight changes ( r = − 0.541 , p = 0.0138 ), albumin ( r = − 0.775 , p < 0.0001 ), direct bilirubin ( r = − 0.786 , p < 0.0001 ), total bile acids ( r = 0.585 , p = 0.007 ), and C-reactive protein ( r = 0.718 , p = 0.0005 ). Moreover, circulating GDF15 levels strongly correlated with the Mayo risk score ( r = 0.685 , p = 0.0009 ) and Model for End-stage Liver Disease score ( r = 0.687 , p = 0.0008 ). Determined by the area under the receiver operating characteristic curves, the overall diagnostic accuracies of GDF15 were as follows: cirrhosis = 0.725 (>3646.55 pg/mL, sensitivity: 70.0%, specificity: 69.2%), decompensated   cirrhosis = 0.956 (>4073.30 pg/mL, sensitivity: 84.62%, specificity: 100%), and cirrhotic biochemical non-responders = 0.835 (>3479.20 pg/mL, sensitivity: 71.43%, specificity: 92.31%). GDF15 may be a useful and integrated biochemical marker to evaluate not only the disease severity and prognosis but also the nutrition and response to treatment of cirrhotic PBC patients, and its overall performance is satisfactory. Therapy targeting GDF15 is likely to benefit cirrhotic PBC patients and is worth further research.

scholarly journals Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Alberto Dominguez-Rodriguez ◽  
Pedro Abreu-Gonzalez ◽  
Idaira F. Hernandez-Baldomero ◽  
Pablo Avanzas ◽  
Francisco Bosa-Ojeda
Keyword(s):  
Acute Coronary Syndrome ◽  
Rate Of Change ◽  
C Reactive Protein ◽  
Cardiac Events ◽  
Growth Differentiation Factor 15 ◽  
St Segment Elevation ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
Differentiation Factor ◽  
Elevation Acute Coronary Syndrome

Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase.

scholarly journals Plasma levels of growth differentiation factor 15 are associated with future risk of venous thromboembolism

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1863-1870
Author(s):  
Ellen-Sofie Hansen ◽  
Kristian Hindberg ◽  
Nadezhda Latysheva ◽  
Pål Aukrust ◽  
Thor Ueland ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Growth Differentiation Factor 15 ◽  
Vein Thrombosis ◽  
Reactive Protein ◽  
Differentiation Factor ◽  
Increased Risk ◽  
Future Risk ◽  
Age And Sex

Abstract Growth differentiation factor 15 (GDF-15), a marker of inflammation and oxidative stress, has emerged as a biomarker for arterial cardiovascular disease. However, the association between GDF-15 and venous thromboembolism (VTE) remains uncertain. We therefore investigated the association between plasma GDF-15 levels and future risk of incident VTE and explored the potential of a causal association using Mendelian randomization (MR). We conducted a population-based nested case-control study comprising 416 VTE patients and 848 age- and sex-matched controls derived from the Tromsø Study. Logistic regression was used to calculate odds ratios (ORs) for VTE across GDF-15 quartiles. For the MR, we used data from the International Network on Venous Thrombosis (INVENT) consortium to examine whether single nucleotide polymorphisms (SNPs) associated with GDF-15 levels with genome-wide significance were related to VTE. We found that the ORs for VTE increased across GDF-15 quartiles (Ptrend = .002). Participants with GDF-15 values in the highest quartile (≥358 pg/mL) had an OR for VTE of 2.05 (95% confidence interval, 1.37-3.08) compared with those with GDF-15 in the lowest quartile (&lt;200 pg/mL) in the age- and sex-adjusted model. ORs remained essentially the same after further adjustment for body mass index, smoking, hormone therapy, physical activity, and C-reactive protein. Similar results were obtained for provoked/unprovoked events, deep vein thrombosis, and pulmonary embolism. GDF-15 levels, as predicted by the SNPs, were not associated with VTE in MR. Our results indicate that high GDF-15 levels are associated with increased risk of VTE, but MR suggests that this association is not causal.

scholarly journals Prognostic significance of serum Growth differentiating factor15(GDF) in adult acute myeloid leukemia patients

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H M A Hegab ◽  
A M S Elghammaz ◽  
M K H Elrazzaz ◽  
R A A Helal
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Transforming Growth Factor ◽  
Prognostic Significance ◽  
P Value ◽  
Growth Differentiation Factor 15 ◽  
Pathological Conditions ◽  
Differentiation Factor ◽  
The Mean ◽  
Acute Myeloid

Abstract Background Growth differentiation factor 15 (GDF-15)3 is a stress responsive member of the transforming growth Factor-B(TGF-B) cytokine superfamily. In health GDF-15 is weakly expressed in human tissues. Under pathological conditions, GDF-15 can be produced by many malignant and non-malignant conditions. The aim of the present study is to assess expression of Growth differentiation factor 15 (GDF15) in the serum of adult patients with acute myeloid leukemia and its influence on remission and survival statuses of AML patients. Material and methods The serum level of GDF15 was measured in 30 AML patients in comparison to 15 healthy adult controls. Results and conclusion Higher GDF15 levels were observed in AML patients than in controls with a sensitivity of 93% and a specificity of 93.3% at cut off level of 1530 pg/ml assessed by ROC curve. Comparing the outcome (alive and dead) between patients above and below the mean level of GDF15(5674pg/ml) it was statistically significant (P = 0.028), but there is no statistical difference between the resistant patients and patients in remission (P-value= 0.593) Comparison between the overall survival (OS) in AML patients with GDF15&gt; 5674pg/ml and those with GDF15&lt;5674pg/ml,It was statistically significant.(P-value &lt;0.001).A statistically significant positive correlation is detected between age and the GDF15 level in the patients group (P-value= 0.011).

scholarly journals Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease

2017 ◽  
Vol 63 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Kai C Wollert ◽  
Tibor Kempf ◽  
Lars Wallentin
Keyword(s):  
Bleeding Risk ◽  
Community Dwelling ◽  
Growth Differentiation Factor 15 ◽  
Reduced Ejection Fraction ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
Differentiation Factor ◽  
Artery Disease ◽  
New Treatment ◽  
Cv Disease

Abstract BACKGROUND Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation. Cardiovascular (CV) disease is a major driver of GDF-15 production. GDF-15 has favorable preanalytic characteristics and can be measured in serum and plasma by immunoassay. CONTENT In community-dwelling individuals higher concentrations of GDF-15 are associated with increased risks of developing CV disease, chronic kidney disease, and cancer, independent of traditional CV risk factors, renal function, and other biomarkers (C-reactive protein, B-type natriuretic peptide, cardiac troponin). Low concentrations of GDF-15 are closely associated with longevity. GDF-15 is as an independent marker of all-cause mortality and CV events in patients with coronary artery disease, and may help select patients with non–ST-elevation acute coronary syndrome for early revascularization and more intensive medical therapies. GDF-15 is independently associated with mortality and nonfatal events in atrial fibrillation and heart failure (HF) with preserved or reduced ejection fraction. GDF-15 reflects chronic disease burden and acute perturbations in HF and responds to improvements in hemodynamic status. GDF-15 is independently associated with major bleeding in patients receiving antithrombotic therapies and has been included in a new bleeding risk score, which may become useful for decision support. SUMMARY GDF-15 captures distinct aspects of CV disease development, progression, and prognosis, which are not represented by clinical risk predictors and other biomarkers. The usefulness of GDF-15 to guide management decisions and discover new treatment targets should be further explored.

Sign in / Sign up

Export Citation Format

Share Document