Value Of Growth Differentiation Factor-15 Research Articles

Prognostic Value of GDF-15 in Predicting Prolonged Intensive Care Stay following Cardiac Surgery: A Pilot Study.

Introduction Predicting intensive care unit length of stay and outcome following cardiac surgery is currently based on clinical parameters. Novel biomarkers could be employed to improve the prediction models. Materials and Methods We performed a qualitative cytokine screening array to identify highly expressed biomarkers in preoperative blood samples of cardiac surgery patients. After identification of one highly expressed biomarker, growth differentiation factor 15 (GDF-15), a quantitative ELISA was undertaken. Preoperative levels of GDF-15 were compared in regard to duration of intensive care stay, cardiopulmonary bypass time, and indicators of organ dysfunction. Results Preoperatively, GDF-15 was highly expressed in addition to several less highly expressed other biomarkers. After qualitative analysis, we could show that preoperatively raised levels of GDF-15 were positively associated with prolonged ICU stay exceeding 48 h (median 713 versus 1041 pg/ml, p = 0.003). It was also associated with prolonged mechanical ventilation and rates of severe sepsis but not with dialysis rates or cardiopulmonary bypass time. In univariate regression, raised GDF-15 levels were predictive of a prolonged ICU stay (OR 1.01, 95% confidence interval 1–1.02, and p = 0.029). On ROC curves, GDF-15 was found to predict prolonged ICU stay (AUC = 0.86, 95% confidence interval 0.71–0.99, and p = 0.003). Conclusion GDF-15 showed potential as predictor of prolonged intensive care stay following cardiac surgery, which might be valuable for risk stratification models.

Circulating growth differentiation factor-15 as a novel biomarker in heart transplant.

AimsThis study aimed to examine (i) whether circulating growth differentiation factor‐15 (GDF‐15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF‐15 after heart transplantation; and (iii) the prognostic value of GDF‐15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post‐transplant.Methods and resultsSerum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post‐heart transplantation in de novo transplant patients. A total of 60 post‐transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF‐15 levels in patients with ACR were not different from those in the non‐rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF‐15 concentration gradually decreased from 8757 pg/mL pre‐transplant to 5203 pg/mL at 4 weeks post‐transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post‐operative GDF‐15 (odds ratio: 40; 95% confidence interval: 2.01–794.27; P = 0.005) and high inotrope score post‐transplant (odds ratio: 18; 95% confidence interval: 1.22–250.35; P = 0.01).ConclusionsCirculating GDF‐15 concentration was markedly elevated in patients with end‐stage heart failure and decreased after heart transplantation. GDF‐15 was significantly associated with post‐transplant PGD and mortality. A lack of association between ACR and GDF‐15 did not support routine use of GDF‐15 as a biomarker to detect ACR. However, GDF‐15 may be potentially useful to determine heart transplant recipients at high risk for adverse post‐transplant outcomes. We suggest that GDF‐15 levels in recipient serum can provide risk stratification for severe PGD including death during post‐operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF‐15 in heart transplantation are required.

Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease.

Growth Differentiation Factor-15 (GDF15) is a member of the TGF-β superfamily. Increased serum GDF15 has been associated with increased risk of chronic kidney disease (CKD) progression. However, no prior studies have addressed the significance of urinary GDF15 in adult CKD. We measured serum and urinary GDF15 in a prospective cohort of 84 patients who underwent kidney biopsy and assessed their association with outcomes (survival, kidney replacement therapy) during a follow-up of 29 ± 17months. There was a statistically significant correlation between serum and urine GDF15 values. However, while serum GDF15 values increased with decreasing glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located kidney GDF15 expression mainly in tubular cells, and kidney GDF15 staining correlated with urinary GDF15 values. Urine GDF15 was significantly higher in patients with a histologic diagnosis of diabetic nephropathy than in diabetic patients without diabetic nephropathy. This was not the case for serum GDF15. Both serum and urine GDF15 were negatively associated with patient survival in multivariate models. However, when both urine and serum GDF15 were present in the model, lower urine GDF15 predicted patient survival [B coefficient (SEM) - 0.395 (0.182) p 0.03], and higher urine GDF15 predicted a composite of mortality or kidney replacement therapy [0.191 (0.06) p 0.002], while serum GDF15 was not predictive. Decision tree analysis yielded similar results. The area under the curve (AUC) of the receiver operating curve (ROC) for urine GDF15 as a predictor of mortality was 0.95 (95% CI 0.89-1.00, p < 0.001). In conclusion, urinary GDF15 is associated with kidney histology patterns, mortality and the need for renal replacement therapy (RRT) in CKD patients who underwent akidney biopsy.

GROWTH DIFFERENTIATION FACTOR-15 IS AN INDEPENDENT PREDICTOR OF CARDIOVASCULAR DISEASE IN JAPANESE PATIENTS WITH CARDIOVASCULAR RISK FACTORS: THE J-HOP STUDY

Objective: Growth differentiation factor-15 (GDF-15) is emerged as a novel biomarker to predict adverse outcomes in community-dwelling individuals and patients with cardiovascular (CV) disease. However, there is a paucity of information on the association between blood GDF-15 levels and adverse outcomes in outpatients with CV risk factors. In this study, we evaluated the prognostic value of GDF-15 in outpatients with CV risk factors and compared with those of other prognostic biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT). Design and method: We collected blood samples from 3,562 patients with CV risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study. Blood GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we recorded the incidence of adverse outcomes as follows: 1) cardiac events defined as ischemic heart disease and heart failure, 2) stroke events defined as ischemic stroke and cerebral hemorrhage, 3) all-cause death, and 4) cancer death. Patients were stratified according to tertiles of GDF-15. The association between GDF-15 and each outcome was evaluated by Cox-proportional hazard models adjusting for established risk factors and other biomarkers (hs-TnT and NT-proBNP). Results: We observed 141 (4.0%) cardiac events, 81 (2.3%) stroke events, and 155 (4.4%) death including 63 (1.8%) cancer death. Multivariate Cox regression model showed that patients in highest tertile of GDF-15 were independently and significantly associated with increased risk of stroke and death except for cardiac events [stroke events, hazard ratio (HR) 2.87, p = 0.008; all-cause death, HR 2.38, p = 0.007; cancer death, HR 2.48, p = 0.049; cardiac events; HR 1.07, p = 0.805, respectively] compared with lowest tertile after adjustment for established risk factors and other biomarkers. Furthermore, adding GDF-15 to the predictive models for stroke and death improved discrimination and reclassification more than adding other biomarkers to the models. Conclusions: In this study, GDF-15 predicts death and stroke except for cardiac events. Information of GDF-15 might be helpful when assessing the risk of death and stroke events in Japanese patients with CV risk factors.

Predictive value of growth differentiation factor-15 in patients with myocardial infarction

Aim. To evaluate the prognostic value of growth differentiation factor-15 (GDF-15) in patients with acute myocardial infarction (MI).Material and methods. The study included 118 patients under the age of 70 with STand non-ST segment elevation myocardial infarction, who, in addition to routine examination, were tested for GDF-15 by enzyme-linked immunosorbent assay in the first 48 hours from the onset. The statistical significance of the differences in quantitative indicators was assessed by the Student’s t-test for a normal distribution and by the nonparametric U Mann-Whitney test for a non-normal distribution, while in qualitative indicators — by Pearson’s chisquared test. Pearson’s correlation coefficient and Spearman’s rank correlation coefficient were used as an indicator of strength of relationship between quantitative indicators.Results. The average GDF-15 level in patients with MI was 2,25±1,0 ng/ml. For 6 months of follow-up, 15,25% of patients were rehospitalized for unstable angina or recurrent myocardial infarction. The GDF-15 level in 82,6% of cases was in the third and fourth quartiles (≥2,07 ng/ml). All patients with recurrent MI had GDF-15 levels in the upper quartile (≥2б73 ng/ml). Patients with GDF-15 levels in the upper quartile had a significantly higher risk of rehospitalization (hazard ratio, 3,3 (95% CI, 1,65-6,76), p&lt;0,05) compared with patients with GDF-15 levels in other quartiles. The potential for the combined use of GDF-15 and N-terminal probrain natriuretic peptide (NT-proBNP) levels to assess the risk of readmission has been evaluated. Patients who had both GDF-15 and NT-proBNP levels in the upper quartiles (GDF-15&gt;2,73 ng/ml, NT-proBNP&gt;1418 pg/ml) had 4,8 times higher risk of rehospitalizations for unstable angina or recurrent myocardial infarction.Conclusion. In patients with MI, the determination of the GDF-15 level has prognostic value and may serve as an additional marker of the risk of recurrent cardiovascular events.

GDF-15 as a Biomarker in Cardiovascular Disease.

ResumoNos últimos anos, vários biomarcadores estão ganhando importância clínica na avaliação diagnóstica e prognóstica de pacientes com doenças cardiovasculares. O fator de crescimento e diferenciação celular-15 (GDF-15) é uma citocina induzida por estresse e inflamação, membro da família do TGF-, cuja produção no miocárdio foi demonstrada experimentalmente em resposta à injúria isquêmica ou sobrecarga cardíaca. Este novo marcador foi positivamente correlacionado com aumento do risco de eventos cardiovasculares em estudos populacionais e configurou-se preditor independente de mortalidade e prognóstico adverso em pacientes com doença arterial coronariana e insuficiência cardíaca. Este trabalho tem como objetivo revisar o valor diagnóstico e prognóstico do GDF-15 em diferentes cenários na cardiologia.

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study.

AimsThis study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor‐15 (GDF‐15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock.Methods and resultsPatients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP‐SHOCK II score to predict in‐hospital mortality and the additional value of GDF‐15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co‐morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in‐hospital mortality (46% vs. 33%; P = 0.08), but 1 year post‐discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP‐SHOCK II score. Incorporating GDF‐15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84.ConclusionsElderly patients with cardiogenic shock have higher in‐hospital mortality compared with the younger, but post‐discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF‐15 or sST2.

The value of maternal serum levels of growth differentiation factor-15 as a predictor of preeclampsia

Back ground Preeclampsia is a leading cause of maternal morbidity and mortality worldwide. Growth differentiation factor-15 (GDF-15) is a stress-induced cytokine and related to the prognosis of cardiovascular diseases. It was expressed in the placentae of both normal and preeclamptic pregnancies. Objective To evaluate the value of GDF-15 as a predictor of preeclampsia and its correlation with the severity of the disease. Patients and methods This was a prospective study in which we enrolled a number of primigravidae at gestational age between 19 and 20 weeks. After complete and thorough history taking and examination in addition to basal ultrasound, serum blood samples were taken from all women and were frozen at −20°C for later assay. After Institutional Ethics Committee approval, antenatal care for all women till delivery was done. Women who developed preeclampsia, 40 of them, were chosen as the study group (group B), and 40 women who were passed the antenatal period without complications were included as the control group (group A). Results We found that serum levels of GDF-15 were higher in preeclamptic group than control group, and this reached a highly significant level. The mean±SD level of GDF-15 in the preeclamptic group was 383.42±130.67 versus 118.73±28.88 pg/ml in the control group (P=0.000). The more the severity of preeclampsia, the higher GDF-15 level, with the highest level being detected in severe–early preeclampsia. Conclusion GDF-15 is increased in preeclampsia than normal physiological pregnancy, with the highest level detected in severe–early preeclampsia.

Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris.

Background: Growth differentiation factor-15 (GDF-15), a member of transforming growth factors, is a stress-responsive marker whose levels may significantly increase in response to pathological stresses associated with inflammatory tissue injuries such as unstable angina pectoris (USAP). This study evaluated the diagnostic value of GDF-15 in patients with USAP. Methods: The present cross-sectional study recruited 39 patients with USAP criteria and 30 patients with stable angina pectoris (SAP), referred to Shahid Beheshti Hospital, Kashan, Iran. All the patients with USAP had at least 1 coronary artery stenosis (>50%) in angiography. The control group comprised 42 healthy individuals. The serum levels of GDF-15 were measured in all the participants by ELISA. Also analyzed were the relationship between GDF-15 levels and thrombolysis in myocardial infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores in the patients with USAP to determine the severity of the disease. Result: The study population consisted of 111 subjects, 62 women and 49 men, divided into 3 groups of USAP (n=39, mean age=60.07±14.10 y), SAP (n=30, mean age=67.56±9.88 y), and control (n=42, mean age=61.21±7.76 y). The mean serum level of GDF-15 in the USAP group was significantly different from the other 2 groups (P<0.001), while no significant difference was observed in this regard between the SAP and control groups (P=0.797). No correlation was found between the mean GDF-15 serum level and the GRACE (P=0.816) and TIMI (P=0.359) risk scores in the USAP group. Conclusion: The mean serum level of GDF-15 exhibited a rise in our patients with USAP. GDF-15 may be a diagnostic biomarker of USAP and its severity.

Evaluation of Growth Differentiation Factor-15 in Patients with or without Coronary Artery Disease.

Background:Growth-differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-beta cytokine superfamily expressed in human atherosclerotic plaque macrophages. In this study, we sought to compare GDF-15 between patients with coronary artery disease and control group.Methods:In this cross-sectional study, 176 subjects were enrolled, consisted of 88 coronary artery disease patients (CAD group) and 88 non-CAD participants (control group. Clinical and demographic data, comprising of family history of CAD, history, and lifestyle factors, hypertension, diabetes, and some blood parameters (e.g. glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)), triglyceride, high-sensitivity C-reactive protein (hs-CRP)).Results:Mean age of the patients was 55.5±11.1 years (age range: 28–80 years). Of all the participants, 91 (51.7%) were male and 85 (48.3%) female. Hs-CRP, LDL-C, and GDF-15 levels were significantly higher in the CAD patients (P=0.091, P=0.008, and P<0.001, respectively). Total cholesterol, hematocrit, and hemoglobin were significantly higher in the controls (P=0.002, P=0.011, and P=0.055, respectively). The area under the receiver operating characteristic curve yielded the satisfactory result of 0.9 (95% CI, 0.8-0.9; P<0.001). The optimum cut-off value of GDF-15 was 1233 ng/L with 71% specificity and 71% sensitivity for CAD diagnosis.Conclusion:These data suggest that serum GDF-15 might be useful in prediction of CAD. (www.actabiomedica)

Abstract 13448: Impact of Diabetes on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study

Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range], 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P &lt;0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, DM, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P &lt;0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with DM (HR, 1.52; 95% CI, 1.30-1.79) and in those without DM (HR, 1.57; 95% CI, 1.25-1.96). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with DM, but not in those without DM. Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.

Abstract 13423: Impact of Anemia on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study

Background: Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine of the transforming growth factor superfamily. Circulating levels of GDF-15 are elevated in various conditions including anemia and stable coronary artery disease (CAD), and associated with the risk of mortality in patients with stable CAD. However, whether anemia modifies the relationship between GDF-15 and mortality in patients with stable CAD is unknown. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between anemic status and GDF-15 and the impact of anemia on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 564 anemic and 896 non-anemic patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with anemia exhibited significantly higher levels of GDF-15 compared to those without anemia (median [interquartile range], 1953 [1302-3110] vs. 1175 [838-1579] pg/mL, respectively; P &lt;0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, diabetes, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P &lt;0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with anemia (HR, 1.71; 95% CI, 1.44-2.05) and in those without anemia (HR, 1.44; 95% CI, 1.21-1.71). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with anemia, but not in those without anemia. Conclusions: Higher levels of GDF-15 were independently associated with anemia in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with anemia.

Growth differentiation factor-15 is a predictive biomarker in primary ventricular fibrillation: The RUTI-STEMI-PVF study.

Primary ventricular fibrillation is an ominous complication of ST-segment elevation myocardial infarction, and proper biomarkers for risk prediction are lacking. Growth differentiation factor-15 is a marker of inflammation, oxidative stress and hypoxia with well-established prognostic value in ST-segment elevation myocardial infarction patients. We explored the predictive value of growth differentiation factor-15 in a subgroup of ST-segment elevation myocardial infarction patients with primary ventricular fibrillation. Prospective registry of ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention from February 2011-August 2015. Growth differentiation factor-15 concentrations were measured on admission. Logistic regression and Cox proportional regression analyses were used. A total of 1165 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (men 78.5%, age 62.3±13.1 years) and 72 patients with primary ventricular fibrillation (6.2%) were included. Compared to patients without primary ventricular fibrillation, median growth differentiation factor-15 concentration was two-fold higher in ST-segment elevation myocardial infarction patients with primary ventricular fibrillation (2655 vs 1367 pg/ml, p<0.001). At 30 days, mortality was 13.9% and 3.6% in patients with and without primary ventricular fibrillation, respectively (p<0.001), and median growth differentiation factor-15 concentration in patients with primary ventricular fibrillation was five-fold higher among those who died vs survivors (13,098 vs 2415 pg/ml, p<0.001). In a comprehensive multivariable analysis including age, sex, clinical variables, reperfusion time, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, growth differentiation factor-15 remained an independent predictor of 30-day mortality, with odds ratios of 3.92 (95% confidence interval 1.35-11.39) in patients with primary ventricular fibrillation (p=0.012) and 1.72 (95% confidence interval 1.23-2.40) in patients without primary ventricular fibrillation (p=0.001). Growth differentiation factor-15 is a robust independent predictor of 30-day mortality in ST-segment elevation myocardial infarction patients with primary ventricular fibrillation.

Growth Differentiation Factor 15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized With COVID-19.

Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic value of GDF-15 in coronavirus disease 2019 (COVID-19) is unknown. Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID Mechanisms Study. Biobank samples were collected at baseline, day 3 and day 9. The primary end point was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers. Of the 123 patients enrolled, 35 (28%) reached the primary end point; these patients were older, more often had diabetes, and had lower oxygen saturations and higher National Early Warning Scores on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both P<0.001). Patients reaching the primary end point had higher concentrations of GDF-15 (median, 4225 [IQR, 3197-5972] pg/mL versus median, 2187 [IQR, 1344-3620] pg/mL, P<0.001). The area under the receiver operating curve was 0.78 (95% CI, 0.70-0.86). The association between GDF-15 and the primary end point persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate, previous myocardial infarction, heart failure, and atrial fibrillation (P<0.001) and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary end point (median, 1208 [IQR, 0-4305] pg/mL versus median, -86 [IQR, -322 to 491] pg/mL, P<0.001). GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia, and worse outcome. The prognostic value of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04314232.

The value of growth differentiation factor-15 and extravascular lung water index in severity grading of acute respiratory distress syndrome patients and their prognosis prediction

To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS). Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point. A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.

PDB29 Diagnostic and Prognostic VALUE of Galectin-3 and GDF-15 in Diabetic Nephropathy Patients

Evidence from published studies raised doubt on microalbuminuria as a predictive marker for the development and progression of kidney disease in type 2 diabetes mellitus (T2DM) patients. So, this study aimed to assess the predictive potential of galectin-3 and growth differentiation factor-15 (GDF-15) for the early detection of DKD. This was an observational study conducted at Hakeem Abdul Hameed Centenary Hospital (HAHC), New Delhi, India. Study period was of 1.2 years. The study protocol was approved by the Institutional Ethics Committee. Patients were classified on the basis of estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio. Receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potential of the marker, sensitivity and specificity was also calculated. All the analysis was performed using SAS v9.4. A total of 90 patients completed the study. Patients were grouped as normoalbuminuria (30 patients), microalbuminuria (30 patients), and macroalbuminuria (30 patients). Mean age of the patients were 58.5 ± 11.20 years. Galectin-3 and GDF-15 levels were significantly elevated in T2DM patients with macroalbuminuria (p = <0.05). Higher levels of galectin-3 and GDF-15 were found in patients with poor kidney function (Stage IV-V CKD). Negative correlation was observed between galectin- 3 (r = -0.472) and eGFR (p= 0.000), GDF-15 (r = -0.917) and eGFR (p = 0.000). The ROC analysis yielded an area under curve (AUC) of 0.776 (95% CI: 0.677 to 0.875; p = <0.0001) for galectin-3 and an AUC of 0.963 (95% CI: 0.929 to 0.997; p = <0.0001) for GDF-15. In DKD patients the galectin-3 and GDF-15 levels were inversely related to the eGFR which was further confirmed by the ROC curve demonstrating the potential of galectin-3 and GDF-15 as a biomarker.

The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation.

The mechanisms underlying the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) are not well concerned. The study sought to explore the association between growth differentiation factor-15 (GDF-15) and the incidence of recurrent events among AF patients after the ablation procedure. We prospectively included 150 consecutive AF patients who underwent RFCA. Clinical information about the patients was collected. Blood samples on the second morning of hospital admission and three months after RFCA were collected, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of GDF-15. All participants were followed up at specific times (1st/3rd/6th/12th/18th/24th months) after RFCA to record recurrences events. During a median follow-up of 14.0 months, AF recurrence occurred in 37(24.7%) patients. Baseline serum GDF-15 level in the persistent AF group was significantly higher than the paroxysmal AF group [1140(854~1701)ng/L vs. 1062(651~1374)ng/L, P = 0.039]. Baseline serum GDF-15 level in the recurrence group was significantly higher than the nonrecurrence group [1287(889~1768) ng/L vs. 1062(694~1373)ng/L, P = 0.022]. Serum GDF-15 level at three months after RFCA was significantly lower than the baseline [870 (579~1270) ng/L vs. 1155 (735~1632)ng/L, P < 0.001]. The baseline GDF-15 correlated significantly with LAP (r = 0.296, P < 0.001) and LAAV(r = −0.235, P = 0.003). Kaplan-Meier analysis showed a significantly lower event-free survival time in the high baseline GDF-15 (≥1287.3 ng/L) group than the low baseline GDF-15 (<1287.3 ng/L) group (17.1 months vs. 20.4 months, Log Rank P = 0.017). In the multivariate Cox regression, baseline GDF-15(HR 1.053, 95% CI 1.007-1.100, P = 0.022) and LAD (HR 1.124, 95% CI 1.011-1.250, P = 0.030) were independent predictors of AF recurrence after RFCA. Our study indicated increased preprocedural GDF-15 is associated with left atrial remodeling and acts as a predictor of AF recurrence after ablation.

Diagnostic value of growth differentiation factor-15 and β2-microglobulin in children with congenital heart disease combined with chronic heart failure and its relationship with cardiac function.

This study aimed to investigate the diagnostic value of growth differentiation factor-15 (GDF-15) and β2-microglobulin (β2-MG) in infants with congenital heart disease (CHD) combined with chronic heart failure and its relationship with cardiac function. A total of 100 cases of infants diagnosed with CHD combined with chronic heart failure in our hospital from July 2015 to July 2018 were selected as the experimental group, and 80 cases of healthy subjects underwent health examination in our hospital during the same period were selected as the control group. The levels of serum GDF-15 and β2-MG and LVEF index of the two groups were compared. The correlation analysis of GDF-15 and β2-MG levels and cardiac function classification was conducted. The diagnostic value of GDF-15 and β2-MG was analyzed by ROC curve. The levels of GDF-15 and β2-MG were significantly higher in severe and moderate heart failure groups than those in mild heart failure group, and the levels were significantly higher in severe heart failure group than those in moderate heart failure group (p<0.001). Levels of GDF-15 and β2-MG in the experimental group were significantly higher than those in the control group (p<0.001) and the LVEF index in the experimental group was significantly lower than that in the control group (p<0.001). There was a positive correlation between levels of GDF-15 and β2-MG and the severity of heart failure. The sensitivity, specificity, and AUC of GDF-15 alone in diagnosis of CHD combined with chronic heart failure were respectively 91.25%, 74.00% and 0.821, those of β2-MG alone were 82.50%, 62.00% and 0.819, and those of GDF-15 combined with β2-MG were 82.50%, 82.00% and 0.888. In the prognosis, the sensitivity of GDF-15 and β2-MG was respectively 91.30%, 56.52%, specificity was 62.96%, 94.44%, and AUC was 0.806, 0.817. Levels of GDF-15 and β2-MG are positively correlated with the severity of cardiac function, which can be used as an ideal indicator for early diagnosis of CHD combined with chronic heart failure, as well as a clinical indicator to judge the condition.

Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure.

AimsInflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor‐15 (GDF‐15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated.Methods and resultsHere, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short‐term and long‐term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs‐cTnT, C‐reactive protein) alone or using meta‐analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3–90.0). Proportional hazard assumption does not hold for sST2 and C‐reactive protein, and follow‐up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C‐reactive protein and sST2 were predictive of short‐term mortality but not of middle term and long term whereas GDF‐15 was predictive of short and mid‐term but not of long‐term mortality. In a multivariate model after adjustment for meta‐analysis global group in chronic HF score including the three markers, only sST2 was predictive of short‐term mortality (P = 0.0225), and only GDF‐15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long‐term mortality.ConclusionsOur results demonstrate that both sST2 and GDF‐15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF‐15 is more sustained overtime and could predict middle term events.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study.

BACKGROUNDMultiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIMTo determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease (PD) patients and healthy controls.METHODSA case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTSSerum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively).CONCLUSIONSerum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.