Value Of Growth Differentiation Factor-15 Research Articles

The Prognostic Values of GDF-15 in Comparison with NT-proBNP in Patients with Normotensive Acute Pulmonary Embolism

An early prediction of prognosis in pulmonary embolism (PE) is a crucial clinical entity. The aim of the study is to investigate whether growth differentiation factor-15 (GDF-15) or N-terminal pro-brain natriuretic peptide levels (NT-proBNP) can better predict the 30 day overall mortality in patients with normotensive acute PE. Patients with a high clinical probability of PE, or with low/intermediate probability and a positive D-dimer test, underwent contrast-enhanced computed tomography and ventilation/perfusion lung scan. Simplified pulmonary embolism severity index, the presence of echocardiographic right ventricular dysfunction, and ROC curve analysis by calculated cut-off value of serum GDF-15 and NT-proBNP levels were evaluated for each individual of study population. The serum levels of GDF-15 and NT-proBNP were found to be significantly higher in patients with PE compared with controls (p < 0.0001). In this study, GDF-15 provided better results compared to NT-proBNP in predicting the short-term or 30 day mortality (p = 0.046 and p = 0.418, respectively). Serum GDF-15 with a cut-off value of > 2943 pg/mL yielded a 75% sensitivity, 68.7% specificity, 91.6% negative predictive value, and 90% accuracy for predicting 30 day overall mortality. The results of these tests were found as 62.5%, 40.6%, 81.2%, and 40% for NT-proBNP (with the cut-off value of > 1409 pg/mL), respectively. High serum GDF-15 levels may provide better information than NT-proBNP for early death in the subjects with normotensive PE and these patients should be closely followed up.

Iron overload in transfusion-dependent β-thalassemia patients: defining parameters of comorbidities

Background Iron overload represents a consistent and almost inevitable complication in patients with transfusion-dependent β-thalassemia. The frequently needed erythrocyte transfusions are known to be the leading source of body iron. Increased iron deposition in tissues was strongly suggested to underlie poor growth and development in transfusion-dependent β-thalassemia. This study aimed to investigate the pattern of increase in iron-overload parameters in relation to the therapeutic measures used and explore its effect on the physical growth of patients with transfusion-dependent β-thalassemia. Patients and methods The study included 60 transfusion-dependent β-thalassemia patients (median age 12.5 years, interquartile range 8-17 years) and 20 age-matched and sex-matched controls; each group was further subcategorized into less than 12-year-old and more than 12-year-old subgroups. The studied clinical parameters comprised weight and height, which were used to calculate the body mass index (BMI). Laboratory assays included complete blood counts for the assessment of pretransfusion hemoglobin, serum iron, total iron-binding capacity, ferritin, and growth differentiation factor 15 (GDF15), and the calculation of the transferrin iron saturation percentage (TISP). Results Less than one-third (30%) of the patients had a low BMI; no patient was overweight or obese. The median pretransfusion hemoglobin was 7.1 g/dl (interquartile range 6.8-7.2 g/dl). Fifty-two (86.7%) patients were inadequately chelated, showing serum ferritin levels more than 1000 ng/ml. In patients older than 12 years of age, the BMI was significantly lower in comparison with controls of the same age subgroup as well as patients less than 12 years old. Patients with a low BMI had significantly higher median values of TISP, ferritin, and GDF15 than those with a normal BMI. GDF15 values of the more than 12-year-old patients showed significant positive correlations with TISP and ferritin levels. Setting optimal cutoffs at 63% for TISP and 1210 ng/ml for serum ferritin (area under the curve 0.965 and 0.957, respectively) had indicated low BMI with higher certainties compared with GDF15 at a level of 10 000 pg/ml (area under the curve 0.783) in the more than 12-year-old patients.Conclusion Avoiding iron overload should be warranted for transfusion-dependent β-thalassemia patients to have normal BMI. Although a high GDF15 level is helpful in pointing toward the development of a low BMI, it added no value to TISP or ferritin as indictors of patients' growth retardation.

GDF15 Is a Novel Biomarker for Impaired Fasting Glucose

BackgroundGrowth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG.MethodsThe participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level.ResultsAge, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females.ConclusionGDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients.

Growth differentiation factor 15 can distinguish between hypertrophic cardiomyopathy and hypertensive hearts

To distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on a morphological examination is often challenging. Growth differentiation factor 15 (GDF-15) is a novel diagnostic and prognostic biomarker for several cardiovascular diseases. In patients with LVH, GDF-15 promises to be a useful biomarker to distinguish between HCM and H-LVH. We evaluated 93 patients with H-LVH, 28 with HCM, and 28 disease control individuals. Serum GDF-15 concentrations were measured with an enzyme-linked immunosorbent assay. Circulating GDF-15 levels were significantly higher in patients with H-LVH than with HCM (P=0.003). On the other hand, values for plasma B-type natriuretic peptide (BNP) levels were significantly lower in patients with H-LVH than with HCM (P = 0.004). Serum GDF-15 and plasma BNP levels positively correlated in patients with H-LVH but not with HCM. Multivariate logistic regression analysis revealed GDF-15 (odds ratio 12.06, confidence interval 1.85-78.77, P < 0.01) as an independent predictor of H-LVH among patients with LVH. In receiver-operating characteristic analysis, GDF-15 achieved an area under the curve of 0.70 for the identification of H-LVH. We found that GDF-15 might be a useful biomarker for discriminating HCM from H-LVH. Understanding serum GDF-15 values may have clinical utility for patients with LVH because the therapeutic strategies for treating HCM and H-LVH differ.

Clinical value of growth differentiation factor-15 on myocardial injury in pediatric critical illness

Objective To study the clinical value of growth differentiation factor-15 (GDF-15) in judgment of the degree of myocardial injury in children with critical illness. Methods Fifty cases of children [pediatric critical illness score(PCIS)≤80]without primary cardiac disease in Pediatric Intensive Care Unit (PICU) of Changzhou Children's Hospital Affiliated to Nantong University were selected after hospitalization, and 20 healthy children were taken as normal control group (n=20). The level of GDF-15 in peripheral blood serum were detected by enzyme-linked immunosorbent assay and biochemical indicators like troponin I (cTnI), creatine kinase isoenzyme (CK-MB) and so on were recorded.Fifty cases of critically ill children were divided into myocardial injury group (n=23), and without myocardial injury group(n=27), according to the myocardial injury standard which was cTnI > 0.2 μg/L.The relationship between the level of GDF-15 and myocardial injury in critically ill children was observed, and the correlation analysis of GDF-15 and cTnI was performed. Results 1.The rate of the myocardial injury in critically ill children was 46%(23/50 cases).2.Compared with the without myocardial injury group [25.93%(7/27 cases)] and the normal control group [5.00%(1/20 cases)], GDF-15 positive rate in myocardial injury group [60.87%(14/23 cases)] was significantly higher, and there were significant differences (P=0.027, 0.000); there was no significant difference between the without myocardial injury group and the normal control group (P=0.056).3.The levels of GDF-15 had significant difference between myocardial injury group and the without myocardial injury group (P=0.000).4.GDF-15 was positively correlated with cTnI(r=0.9704, P<0.05). Conclusions The level of GDF-15 with myocardial injury in critically ill children is higher than that of without myocardial injury children.GDF-15 and cTnI have an important value in judging the degree of myocardial injury of critically ill children. Key words: Critical illness; Growth differentiation factor-15; Troponin I; Myocardial injury

Prognostic value of growth differentiation factor-15 in Chinese patients with heart failure: A prospective observational study.

Growth differentiation factor-15 (GDF-15), a biomarker associated with remodeling, oxidative stress and inflammation, has been used to stratify heart failure (HF) patients. However, its prognostic value in Chinese HF patients is still unknown. GDF-15 levels were examined on admission in 272 consecutive HF patients in Beijing Hospital (a Chinese tertiary medical center) by a commercial enzyme-linked immunosorbent assay. We recorded the incidence of all-cause mortality and/or readmission for HF during a median follow-up period of 558 days. Patients were stratified according to the tertiles of GDF-15. Fifty-three (19.5%) patients died and 103 (37.9%) patients had major adverse cardiac events (MACE) which included the composite outcome of all-cause mortality or readmission for HF at the end of follow-up. Kaplan-Meier survival curves showed that the third tertile of GDF-15 was associated with increased rate of all-cause mortality (compared with the first and second tertiles, log rank p = 0.001 and 0.001, respectively) or MACE (compared with the first and second tertiles, log rank p = 0.002 and p < 0.001, respectively). In addition, multivariate Cox regression model showed that the highest tertile of GDF-15 was independently associated with increased risk of all-cause death (hazard ratio = 5.95, 95% confidence interval 1.88-18.78, p = 0.002) compared with the lowest tertile after adjustment for related clinical variables such as age, renal function or N-terminal pro-B-type natriuretic peptide. Plasma GDF-15 is an independent predictor of all-cause mortality in Chinese patients with HF. It may potentially be used to stratify and prognosticate HF patients.

Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer

Background:Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).Methods:Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.Results:Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).Conclusion:Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

Iron Metabolism and Erythropoietic Stress in Myelodysplastic Syndromes.

Abstract 1752Poster Board I-778Iron overload (IO) occurs in a large proportion of patients affected by myelodysplastic syndromes; however data on the mechanisms responsible for IO and on the consequences on organ damages are scanty. IO in MDS may result both from ineffective erythropoiesis and from reiterative transfusions. The role of iron chelation therapy in MDS is deduced from thalassemia experience. We evaluated parameters of iron metabolism and erythropoiesis in 171 consecutive chelation naïve MDS patients. Patients were classified according WHO criteria, and prognostic scores evaluated according IPSS and WPSS criteria. CMML patients (n= 7) were also included in the analysis. Serum ferritin, iron, transferrin, transferrin saturation and non-transferrin-bound iron (NTBI) were measured. Growth-differentiation factor-15 (GDF-15) and hepcidin-25 were also determined, parallel to hemoglobin, endogenous erythropoietin (EPO) and LDH. All the parameters studied were highly variable within the analyzed cohort, as expected due to the great heterogeneity of MDS. As already observed, ferritin levels were higher than normal range in MDS patients (1091 ± 1135 ng/ml) and significantly increased in transfused ones (1890,55 ± 1833 ng/ml). EPO production was stimulated in all MDS patients (215, 40; range 85-1011 U/L), respect to normal range, and physiologically inversely correlated with hemoglobin levels (p<0.001). Serum EPO was lower in IPSS low risk patients than in IPSS high risk ones. Analysis of variance among different WHO subtypes indicated that RAEB-2 patients had the highest levels of EPO, 5q- patients had significantly increased levels of EPO (313; 67,7-836 U/L), while RARS and RA patients did not show significantly higher EPO than other WHO MDS subtypes. NTBI was found elevated in all MDS patients (0,35 ± 1,73 microM) respect to normal subjects (-0,72 ± 0,39 microM). NTBI levels did not correlate with disease duration, nor with patient age. NTBI was significantly elevated in RARS patients (2,37; -0,8-9,3 microM) compared to other WHO subtypes (0,123; -2,3 - 4,5 microM). An increasing trend was observed in MDS patients with high and very high WPSS score. Consistently, toxic iron was significantly increased in transfused MDS patients (1,214; -1,38-9,26 microM) vs non transfused ones (-0,052; -2,23 - 5,84 microM). GDF-15, a marker of erythropoietic stress, was significantly increased in MDS patients (9429; 302-87758 pg/ml) compared to normal subjects (450 ± 50 pg/ml). Transfused patients had higher GDF-15 values vs non-transfused patients (12458,0; 838-74717 pg/ml vs 6623,15; 302-43816 pg/ml respectively). GDF-15 levels did not correlate with disease duration, age, WHO subtypes, or IPSS and WPSS prognostic scores. A correlation between NTBI and: ferritin (p< 0.001), GDF-15 (p= 0.048) and transferrin saturation (p<0.001) was observed. Serum hepcidin-25, measured by mass spectrometry, was significantly elevated in IPSS low risk MDS patients (9,48; 1,06-38,35 nM) respect to normal (4,62 3.01–7.02 nM), with the exception of RARS patients, where hepcidin-25 was significantly lower (3,71 ± 1,33 nM) than normal, with high GDF-15 (8027,82 ± 7086,32 pg/ml). Hepcidin was found significantly increased in CMML, RAEB-1 and unclassifiable MDS patients (19,1 nM), while patients with RCMD had less high levels (8,27 ± 6,63 nM). Hepcidin levels did not show linear correlation with GDF-15, NTBI, and ferritin. LDH was not correlated with NTBI, GDF-15, hepcidin, EPO and ferritin. These observations indicate that in MDS patients iron homeostasis is altered although the clear relationship among the different players (hepcidin, GDF-15, EPO) is not yet fully understood. Many factors may be involved, including the intervention of pro-inflammatory cytokines as stimulators of hepcidin production in MDS, counterbalancing GDF-15 effect. The “ferrostat“ mechanism seemed to be maintained only in RARS patients who had the highest levels of NTBI and elevated GDF-15, with consequent repression of hepcidin production. Our results suggest that the regulation of iron absorption in MDS may be altered by the concomitant effect of several parameters acting at different rates in the various subtypes of dysplasia: GDF-15, induced by the expanded erythroid dysplastic compartment, but also EPO, hypoxia, generation of ROS and production of cytokines. The significance of each of these molecules needs to be further investigated. DisclosuresNo relevant conflicts of interest to declare.

Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction

Our aim was to assess the long-term prognostic value of growth differentiation factor-15 (GDF-15) in patients post-acute myocardial infarction (AMI). Growth differentiation factor-15 is a member of the transforming growth factor beta family. Growth differentiation factor-15 is expressed in the myocardium and upregulated due to 'stress' and has been shown to have antiapoptotic actions. Its role in the cardiovascular system however is not well defined. We were interested to see if GDF-15 could provide long-term prognostic value in post-AMI patients. We compared GDF-15 with N-terminal pro-B-type natriuretic peptide (NT-proBNP). We recruited 1142 consecutive post-AMI patients [820 men, median (range) age 67 (24-97) years] in a prospective study with a follow-up period of 505 (range 1-2837) days. Growth differentiation factor-15 levels increased with increasing Killip class (P < 0.001) and were correlated with NT-proBNP (r = 0.47, P < 0.001). Using a multivariable Cox proportional hazards model, log GDF-15 (HR 1.77), log NT-proBNP (HR 2.06), age (HR 1.03) Killip class above 1, (HR 1.62), use of beta-blockers (HR 0.54) and past history of MI (HR 1.44) were significant independent predictors of death or heart failure (HF). Predictors of death were log NT-proBNP, log GDF-15, age, eGFR, past history of MI, use of beta-blockers, and use of ACE inhibitors or angiotensin receptor blockers. The C-statistic for GDF-15 for predicting death or HF at 1 year was 0.73 (95% CI: 0.70-0.76, P < 0.001) and was 0.76 (95% CI: 0.70-0.80, P < 0.001) for NT-proBNP. Combining these markers yielded an AUC of 0.81 (95% CI: 0.77-0.85), which exceeded that of GDF-15 (P < 0.001) and NT-proBNP (P = 0.004) alone. The Kaplan-Meier analysis revealed that those patients with above median GDF-15 and NT-proBNP had the highest event rate for death and HF (log rank 50.22, P < 0.001). Growth differentiation factor-15 is a new marker for predicting death and HF in post-AMI patients. GDF-15 provides prognostic information over and above clinical factors and the established biomarker NT-proBNP. Combined levels of GDF-15 with NT-proBNP can identify a high-risk group of patients.

Growth-differentiation factor-15 for risk stratification in patients with acute chest pain

We read with interest the article by Eggers et al. 1 reporting the value of growth-differentiation factor-15 (GDF-15) for risk stratification in patients with acute chest pain. The authors found that GDF-15 was an independent predictor of a combined endpoint of death or myocardial infarction at 6 months. Their findings suggest that GDF-15 levels might be useful for early risk assessment of patients presenting to the emergency department with acute chest pain. Eggers et al. reported that GDF-15 added incremental prognostic …

Abstract 5016: Growth-Differentiation Factor-15 is an Independent Predictor of Cardiovascular Events and Mortality in Patients with Stable Coronary Artery Disease

Circulating levels of the TGF β-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with unstable coronary artery disease (CAD). To explore the prognostic utility of GDF-15 in patients with stable CAD, we analyzed the relation of GDF-15 to mortality and cardiovascular (CV) events in the AtheroGene registry which enrolled consecutive patients with stable angina and at least one stenosis &gt;30% in a larger coronary artery. Patients were followed for a median of 3.6 years. Serum samples for measurement of GDF-15 along with other biomarkers were available from 1352 patients. Two pre-specified cutoff points (1200 and 1800 ng/L) were used to identify different risk groups. 55.9%, 26.4%, and 17.7% of the patients presented with GDF-15 values &lt;1200 ng/L, between 1200 and 1800 ng/L, and &gt;1800 ng/L, respectively. Increasing levels of GDF-15 were related to age (P&lt;0.001), hypertension (P=0.01), diabetes mellitus (P&lt;0.001), low HDL cholesterol (P&lt;0.001), and the extent of CAD (P=0.001). Moreover, significant relations to hsCRP, troponin T, NT-proBNP, and reduced renal function (GFR) were observed (all P&lt;0.001). Increasing levels of GDF-15 were associated with an increased risk of all-cause mortality (P&lt;0.001, log-rank test), CV mortality (P&lt;0.001), and CV events (P&lt;0.001). Receiver operating curve analyses confirmed GDF-15 as a strong marker of 2-year adverse outcomes (area under the curve for all-cause mortality, 0.79; CV mortality, 0.81; CV events, 0.70). By multiple Cox regression analysis, GDF-15 emerged as an independent predictor of all-cause mortality (HR 2.1 per one standard deviation of lnGDF-15 [95% CI 1.6 –2.8], P&lt;0.001), CV mortality (HR 2.2 [95% CI 1.5–3.3], P&lt;0.001), and CV events (HR 1.7 [95% CI 1.3–2.4], P=0.001) after adjustment for baseline characteristics, clinical variables, LDL/HDL ratio, hsCRP, troponin T, NT-proBNP, and GFR. Patients with a GDF-15 level above 1800 ng/L had a highly elevated risk of CV mortality even in the fully adjusted model (HR 5.2 [95% CI 1.6 –16.1], P=0.005). These data identify GDF-15 as a powerful and independent biomarker of mortality and CV events in patients with stable CAD.