Value Of Growth Differentiation Factor-15 Research Articles

Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study

Abstract Background Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown. Purpose To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value. Methods Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15. Results A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table). Conclusions In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable

Biomarkers in early and late period after radiofrequency and pulsed field catheter ablation of atrial fibrillation

Abstract Introduction Biomarkers are routinely used parameters for disease diagnosis, treatment control and risk stratification. In connection with atrial fibrillation (AF), the importance of GDF-15 (growth differentiation factor 15), NT-proBNP (N-terminal fragment brain natriuretic factor) and hs-TnT (high sensitivity cardiac troponin T) is discussed. Catheter ablation is an established treatment method in selected population with AF. However, biomarker response to radiofrequency catheter ablation (RFCA) and pulsed field ablation (PFA) of AF has not been precisely described. Purpose Purpose of the study was to describe early and late dynamics of GDF-15, hs-TnT and NT-proBNP in different ablation technologies. Methods We prospectively enrolled 48 patients (median (IQR) age 62 (55; 70) years, 30 males) undergoing RFCA, which we compared with 30 patients (median (IQR) age 64 (56; 71) years, 18 males) undergoing PFA. All patients underwent 6 sequential blood takes: before ablation (baseline), right after ablation (0h), 24 and 48 hours after procedure (24h and 48h), 90 and 180 days after procedure. Levels of GDF-15, hs-TnT and NT-proBNP were analyzed. Results Out of all patients, 19 (40 %) and 20 (67 %) patients had paroxysmal AF in RFCA and PFA group, respectively. Additional ablation lesions over pulmonary vein isolation were done in 26 (54 %) patients in RFCA group and 11 (43 %) patients in PFA group. Median procedural time was significantly longer in RFCA than in PFA group (155 (130; 190) vs. 80 (70; 90) min; p < 0.01). Early dynamics of GDF-15 and cardiac hs-TnT are visualised in Figure 1 and 2. GDF-15 level peak was registered 48 hours after ablation with median (IQR) 1183 (824; 1988) ng/l. Compared to baseline, GDF-15 values sustained elevated up to 90 days after ablation in both groups and decreased to baseline levels after 180 days. No significant differences were found in GDF-15 levels between patients treated with RFCA and PFA. Maximal values of hs-TnT were significantly higher in PFA group than in RFCA group (1001±589 vs. 458±202 ng/l; p < 0.001). We have recognised decrease of NT-proBNP between baseline and 90 days after procedure in both groups: 338 (112; 613) vs. 209 (101; 545) ng/l; p < 0.05. Conclusion Eventhough GDF-15 is considered as a nonspecific biomarker reflecting general condition of patient, the levels are significantly affected by catheter ablation of AF for several months irrespective to ablation technology. PFA is associated with advanced elevation of hs-TnT.Dynamics of GDF-15 (median; IQR)Dynamics of hs-TnT (median; IQR)

Combined Use of GDF-15 and NT-Pro BNP for Outcome Prediction in Patients with Acute Heart Failure

Background: Acute heart failure (AHF) is characterized by a complex pathophysiology. Aims: This study aimed to evaluate the usefulness of combined serial measurements of N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and growth differentiation factor 15 (GDF-15) for predicting long-term outcomes in patients with AHF. Methods: This study included 104 consecutive patients hospitalized due to AHF. The mean (SD) age was 65 (±15) years. Blood samples were collected on admission, at discharge, and at a 30-day follow-up visit. The primary composite endpoint was all-cause mortality or rehospitalization due to heart failure (HF) at 1-year follow-up. Results: During follow-up, the primary endpoint occurred in 31 persons. In the ROC analysis, the optimal cut-off values of GDF-15 for predicting the outcome were 5115.5 pg/mL on admission, 4145 pg/mL at discharge, and 4218.5 pg/mL at the 30-day visit. For NT-pro BNP, the optimal cut-off reached 6011 ng/L, 1250 ng/L, and 1456.5 ng/L, respectively. Patients with both GDF-15 and NT-pro BNP levels above the cut-off value had a higher risk of the primary composite endpoint than patients with only one or none of the biomarkers elevated at three time points. At the 30-day visit, the model combining NT-pro BNP and GDF-15 showed the highest predictive value for the primary composite endpoint (area under the curve, 0.75). Conclusions: Combined serial measurements of NT-pro BNP and GDF-15 outperform single measurements in outcome prediction at 1-year follow-up in patients with AHF. The repetitive combined model may serve as a useful risk assessment tool and facilitate decision-making during long-term observation.

Diagnostic value of serum GDF-15 in patients with pseudomyxoma peritonei

Background and aimsPseudomyxoma peritonei (PMP) is a rare malignancy that lacks a highly sensitive and specific biomarker for its diagnosis. Identifying reliable serum markers is crucial for improving the diagnostic accuracy and management of PMP. This study aims to explore the diagnostic value of serum growth differentiation factor 15 (GDF-15) in patients with PMP. Material and methodsWe carried on a 1:1 matched case-control study. 44 patients with PMP hospitalized in Aerospace Center Hospital were recruited as cases, and 44 sex- and age-matched apparently healthy participants were selected as controls. The serum GDF-15 concentrations were tested using an ELISA method. The diagnostic value of GDF-15 in PMP patients was assessed by receiver operating characteristic (ROC) curve analysis. ResultsThe median serum GDF-15 level in PMP patients was 1192.77 (843.03–1879.06) pg/mL, notably higher than that in healthy controls [533.27 (410.46–641.47) pg/mL] (P<0.001). The area under the curve (AUC) of serum GDF-15 for PMP diagnosis was 0.907, the optimal diagnostic threshold value was 644.58 pg/mL, the sensitivity was 93.18 %, and the specificity was 77.27 %. The AUC of GDF-15 combined with carbohydrate antigen 125 (CA125) was larger than that of GDF-15 alone (P=0.027), and the sensitivity and specificity achieved 86.36 % and 95.45 %. GDF-15 levels showed a significant correlation with age (P=0.042), with younger PMP patients exhibiting notably lower concentrations of GDF-15 compared to older patients. ConclusionSerum GDF-15 could become a new marker for the PMP diagnosis. The combination of GDF-15 and CA125 demonstrated superior diagnostic performance for PMP compared to GDF-15 alone, achieving a sensitivity of 86.36% and a specificity of 95.45%.

Growth differentiation factor-15 as a biomarker of coronary microvascular dysfunction in ST-segment elevation myocardial infarction

BackgroundThe predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. MethodsThis study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. ResultsA total of 134 patients, with an average age of 59.78 ± 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661–3.779, P < 0.001). The area under the curve (AUC) of GDF-15 for CMD was 0.782 (95 % CI: 0.704–0.861), with a sensitivity of 0.795 and specificity of 0.643 in predicting CMD in PPCI. The AUC of the GDF-15 model (Model With GDF-15) was 0.867 (95 % CI: 0.806−0.928), significantly outperforming the clinical baseline model (Model Without GDF-15) (Δ AUC = 0.079, 95 % CI: 0.020–0.138, P = 0.009). Furthermore, the net reclassification improvement (NRI) was 0.854 (95 % CI: 0.543–1.166, P < 0.001), and the integrated discrimination improvement (IDI) was 0.151 (95 % CI: 0.089–0.213, P < 0.001). ConclusionsGDF-15 can serve as a biomarker for predicting the development of CMD in STEMI patients undergoing PPCI.

Growth differentiation factor-15 predicts all-cause death and major adverse cardiovascular events in patients with coronary heart disease: a prospective cohort study.

The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes.

Serum growth differentiation factor 15 as a biomarker for malnutrition in patients with acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that often coexists with malnutrition during acute exacerbation (AECOPD) and significantly affects the prognosis. Previous studies have shown that growth differentiation factor 15 (GDF15) levels promote appetite suppression, weight loss, and muscle weakness, and are markedly high in peripheral blood following inflammatory stimulation. However, it is still unknown whether serum GDF15 levels can be used to predict malnutrition in patients with AECOPD. A total of 142 patients admitted to the Department of Respiratory Medicine at Anshun People's Hospital between December 2022 and August 2023 were selected for this study. The participants were divided into two groups: malnutrition group (n = 44) and non-malnutrition group (n = 98) based on a body mass index (BMI) < 18.5 kg/m2, according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Serum GDF15 levels were measured using the enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Spearman correlation analysis was used to examine the association between serum GDF15 levels, baseline data, and clinical indicators. Binary logistic regression was used to identify the independent risk factors for AECOPD combined with malnutrition. The predictive value of serum GDF15, albumin (ALB), and a combination of these was evaluated to identify malnutrition in patients with AECOPD using a receiver operating characteristic (ROC) curve. Serum GDF15 levels in patients with malnutrition and AECOPD were significantly higher than those in patients without malnutrition, whereas the serum ALB levels were significantly lower than those in patients without malnutrition (p < 0.001). Moreover, serum GDF15 levels were negatively correlated with BMI (r = -0.562, p < 0.001), mid-arm circumference (r = -0.505, p < 0.001), calf circumference (r = -0.490, p < 0.001), total protein (r = -0.486, p < 0.001), ALB (r = -0.445, p < 0.001), and prognostic nutritional index (r = -0.276, p = 0.001), and positively correlated with C-reactive protein (r = 0.318, p < 0.001), COPD assessment test score (r = 0.286, p = 0.001), modified medical research council classification (r = 0.310, p < 0.001), and global initiative for chronic obstructive pulmonary disease grade (r = 0.177, p = 0.035). Furthermore, serum GDF15 levels were an independent risk factor for malnutrition in patients with AECOPD (OR = 1.010, 95% CI, 1.003∼1.016). The optimal cut-off value of serum GDF15 level was 1,092.885 pg/mL, with a sensitivity of 65.90% and a specificity of 89.80%, while the serum ALB level was 36.15 g/L, with a sensitivity of 86.40% and a specificity of 65.00%, as well as a combined sensitivity of 84.10% and a specificity of 73.90%. Serum GDF15 and serum ALB levels had a good predictive ability (AUC = 0.856, AUC = 0.887), and the ROC revealed a greater combined prediction value for the two (AUC = 0.935). Serum GDF15 levels could be used as a potential biomarker in the prediction of malnutrition in patients with AECOPD, offering a guidance for future clinical evaluation of malnutrition.

Correlation of plasma GDF15 with aging, organ disfunction, sarcopenia, and postoperative infectious complication in patients with esophageal cancer.

e16088 Background: The age of cancer incidence is increasing every year. Along with it, cancer patients getting has more comorbidity and decreasing muscle strength which may lead to increase postoperative complications. Especially, since esophageal cancer (EC) patients have heavy drinking and smoking history and high age of morbidity, they usually have multiple comorbidities and so that they particularly have high incidence of cachexia. A novel inflammatory marker known as growth differentiation factor 15 (GDF15) has been recently reported relation with cancer cachexia. This study conducted to evaluate correlation between clinical data which suggested cachexia of EC patients and plasma GDF15. Methods: Eighty-one esophageal cancer patients who first visited our outpatient ward from July 2021 to March 2023 were enrolled in this study. After obtaining consent for the study, plasma samples collected before starting any treatment for the cancer. The quantification of GDF15 was performed by ELISA. Clinical information was collected from clinical record including age, comorbidities, biochemical data, Controlling Nutritional Status (CONUT) score, and Skeletal Mass Index (SMI). GDF15 was then evaluated for clinical impact by comparison with postoperative results. Mann-Whitney U test, student-t test, ANOVA were used appropriately to analyze the relationship between the GDF-15 and patient characteristics and post operative complications. Multivariate analysis ware used logistic regression analysis. P-values &lt; 0.05 were considered statistically significant for all statistical analyses. Results: Mean age was 68.3-year-old and 80.3% of these were male. Malnutrition patients diagnosed by using CONUT were 24 (29.6%) and sarcopenia patients diagnosed by using SMI were 21 (25.9%). The median value of GDF15 was 1165 pg/mL with its range were from 298 to 9100 pg/mL. Plasma GDF15 was statistically correlated with age ( P&lt; 0.001), performance status ( P= 0.046), prevalence of hypertension ( P= 0.045) and/or diabetes ( P= 0.018), serum level of aspartate aminotransferase (AST) ( P&lt; 0.001)/ γ-glutamyltransferase (γ-GTP) ( P&lt; 0.001)/ creatinine ( P= 0.004)/ blood sugar ( P= 0.028), and SMI ( P= 0.003). Seventy-two patients underwent curative surgery, and no perioperative death was observed. The patients who occurred anastomotic leakage and infectious complication observed statistically higher GDF15 than those without (P = 0.030, P = 0.016). Optimal cut-off value was detected as 940 ng/mL for detecting infectious complication by ROC-curve with AUC value of 0.68. Conclusions: This study showed GDF15 is potentially suggesting deterioration of general condition, which came from aging, organ disfunction, and decreasing muscle mass, which may lead to cachexia in EC patients. In addition, higher GDF15 patients have risk of postoperative infectious complication.

GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally and the sixth most common cancer worldwide. Evidence shows that growth differentiation factor 15 (GDF15) contributes to hepatocarcinogenesis through various mechanisms. This paper reviews the latest insights into the role of GDF15 in the development of HCC, its role in the immune microenvironment of HCC, and its molecular mechanisms in metabolic dysfunction associated steatohepatitis (MASH) and metabolic associated fatty liver disease (MAFLD)-related HCC. Additionally, as a serum biomarker for HCC, diagnostic and prognostic value of GDF15 for HCC is summarized. The article elaborates on the immunological effects of GDF15, elucidating its effects on hepatic stellate cells (HSCs), liver fibrosis, as well as its role in HCC metastasis and tumor angiogenesis, and its interactions with anticancer drugs. Based on the impact of GDF15 on the immune response in HCC, future research should identify its signaling pathways, affected immune cells, and tumor microenvironment interactions. Clinical studies correlating GDF15 levels with patient outcomes can aid personalized treatment. Additionally, exploring GDF15-targeted therapies with immunotherapies could improve anti-tumor responses and patient outcomes.

Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients.

Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVIDbiomarkers in non-hospitalized patients. Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers. The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.

Prognostic value of growth differentiation factor-15 in heart failure among whole ejection fraction phenotypes.

The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model. This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P=0.002) and a higher MAGGIC risk score (P<0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR)=1.36, 95% confidence interval (CI): 1.20-1.54; P<0.001] and HF rehospitalization (HR=1.75, 95% CI: 1.57-1.95; P<0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR=1.73, 95% CI: 1.40-2.14; P<0.001; HF rehospitalization: HR=3.37, 95% CI: 2.73-4.15; P<0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index=0.021, 95% CI: 0.002-0.041; IDI=0.011, 95% CI: 0.001-0.025; continuous NRI=0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index=0.034, 95% CI: 0.005-0.063; IDI=0.021, 95% CI: 0.007-0.032; continuous NRI=0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup. GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

Convalescent Growth Differentiation Factor-15 and Long-Term Outcomes after an Acute Coronary Syndrome.

Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. ACTRN12605000431628.

Prognostic significance of growth differentiation factor-15 across age in chronic heart failure.

Growth differentiation factor-15 (GDF15), a cytokine in the transforming growth factor family, is up-regulated in stress and inflammatory conditions and is elevated in patients with heart failure (HF). However, the age-specific attributes and prognostic significance of GDF15 across age remain unknown in chronic HF (CHF). Serum levels of GDF15 were examinedin 942 hypertensive patients (median 68years) with CHF from the SUPPORT trial across the four age groups [under 50 (n=73), 51-59 (n=158), 60-69 (n=296), and 70-79years (n=415)] and in the continuous spectrum. Clinical correlates of GDF15 were explored using the classic stepwise and LASSO (least absolute shrinkage and selection operator) regression approaches. Interaction terms with age were tested in the LASSO regression approach. The associations with the composite outcome of HF hospitalization or all-cause death were investigated across ages. Median GDF15 levels (pg/mL) increased along with aging, from 691 in under 50years to 855 in 51-59years, 1114 in 60-69years, and 1516 in 70-79years (trend P<0.001). Age, sex, systolic blood pressure, history of diabetes, ischaemic heart disease, left ventricular (LV) end-systolic dimension, LV ejection fraction, estimated glomerular filtration rate, haemoglobin, N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin, C-reactive protein, and the use of angiotensin-converting enzyme inhibitors, diuretics, and statins were mutually selected as clinical covariates of GDF15. The LASSO regression analysis identified significant interactions between age and the history of diabetes and NT-proBNP, with particularly robust associations in patients aged between 60 and 70years. During the mean follow-up of 8.6years, 474 composite endpoints of HF hospitalization or death occurred. GDF15 was associated with a higher risk of HF hospitalization or all-cause death [adjusted hazard ratio 1.84 (95% confidence interval 1.45-2.33)], with a particularly heightened risk in patients aged around 70years (Pinteraction=0.0008). The model with GDF15 on top of other established risk factors yielded marginally higher C-statistics compared with the model without GDF15 (0.803 and 0.796, P=0.045). The additive value of GDF15 on top of other established risk factors appeared similar across ages. A universal cut-off value of 1400pg/mL performed well in discriminating between those with and without HF hospitalization or death. Some clinical correlates of GDF15 have an interaction with age. GDF15 is an important determinant of cardiovascular endpoints, particularly in patients aged around 70years. The additive value of GDF15 appeared consistent across ages, suggesting the use of a universal cut-off value.

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea

BackgroundThe objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA).MethodsA total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays.ResultsCompared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea–hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77–0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6.ConclusionsThis study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6.

Low-intensity inflammation as a manifestation of comorbidity and a factor in the unfavorable clinical course of heart failure with preserved ejection fraction

Aim. To analyze the prognostic significance of clinical, anamnestic and paraclinical parameters in patients with heart failure with preserved ejection fraction (HFpEF) and non-obstructive coronary artery disease.Material and methods. The study included 54 patients. Cardiac and lung ultrasound was performed. In addition, the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-1β, interleukin-18, growth differentiation factor 15 (GDF-15), and cryopyrin was determined. The level of quality of life, anxiety and depression, and adherence to treatment were analyzed.Results. The patients were divided into 2 following groups: group 1 (n=22) with an unfavorable course and group 2 (n=32) with a favorable disease course. Basic echocardiographic parameters, as well as the number of B-lines in lungs, were comparable in both groups. An unfavorable HFpEF course was associated with a longer history of hypertension — 17,5 [10;20] and 7 [5;15] years (p=0,03), smoking — 36,4 and 9,4% (p=0,035), impaired carbohydrate metabolism — 54,5 and 15,6% (p=0,003) and lower adherence to treatment (p=0,02). In group 1, GDF-15 levels were higher than in group 2 — 1841 [1237;3552] vs 1709,5 [1158;2492] pg/ml (p=0,026).Conclusion. Low-intensity subclinical inflammation, the predisposing factors of which are smoking, impaired carbohydrate metabolism, and a long history of hypertension, is associated with higher GDF-15 values in patients with HFpEF and, along with low patient adherence to treatment, has an adverse effect on the clinical course of heart failure.

Analysis of growth differentiation factor-15 at the hospital stage of treatment of patients with acute myocardial infarction

Objective: to dynamically study the clinical characteristics, the level of growth differentiation factor 15 (GDF-15) during hospital treatment in patients with acute ST-segment elevation myocardial infarction (STEMI). Materials and methods: an analysis of clinical and laboratory data of STEMI patients during hospital treatment and echocardiography parameters was carried out. Scores were calculated on the GRACE scale to assess the prognosis of in-hospital mortality of patients. The characteristics of patients with STEMI were identified taking into account GDF-15 values. Statistical processing using the statistical software package "Statistica 10.0 for Windows". Results: clinical and laboratory characteristics of STEMI patients on the first day of the disease determined the prognosis. GDF-15 values increased on the first day of STEMI development and depended on the risk of in-hospital mortality on the GRACE scale. GDF-15 values tended to decrease during the inpatient phase of treatment. Patients with STEMI with a GDF-15 concentration equal to or more than 1200 ng/ml did not reach reference values in the dynamics of hospital treatment and had higher values of markers of myocardial necrosis, reflecting the impact on the prognosis. Conclusion: the GDF-15 indicator can be used as a marker for the prognosis of STEMI in combination with the GRACE scale assessment. High GDF-15 values during the hospital phase of patient treatment reflect the prognosis of STEMI patients.

Prognostic value of growth differentiation factor-15 3 months after an acute chest pain admission

ObjectiveGrowth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of...

Abstract 12519: Biomarker Characterisation of Heart Failure Subtypes: A Population-Based Bioresource Linked Study

Background: Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study. Methods: We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany). Results: We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was &gt;0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days. Conclusions: In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.

Determination of systemic inflammatory biomarkers in multiple sclerosis.

Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system. We aimed to investigate serum and cerebrospinal fluid levels of different laboratory inflammatory biomarkers in patients with MS. A total of 120 subjects participated in the study, 60 of whom were diagnosed with MS, 30 with the final diagnosis of non-inflammatory diseases of the central nervous system (CNS), and 30 healthy subjects representing the control group. Regarding the progression of radiological findings after 2 years from the initial diagnosis, the MS group was divided into stationary radiological findings (n=30) and radiologically proven disease progression (n=30). In all patients, we analyzed levels of laboratory inflammatory biomarkers: C reactive protein (CRP), Neutrophil-to-lymphocyte ratio (NLR), Growth differentiation factor 15 (GDF15) in serum samples, and neurofilaments (NFs) in cerebrospinal fluid (CSF). NFs and GDF15 were analyzed initially, while CRP and NLR values were analyzed initially and after two years. We found statistically lower GDF15 values and initial CRP values in the MS group regarding the group with non-inflammatory diseases of the CNS (p<0.0001). On the other side, we determined a significant elevation of laboratory markers CRP and NLR, initially and after a two-year period, in the MS subgroup with the progression of magnetic resonance imaging (MRI) findings (p<0.0001 and p=0.050, respectively). Also, we found a positive correlation between CRP and NFs (r=0.243, p=0.04), as well as a positive correlation between CRP and GDF15 in patients with MS (r=0.769, p<0.0001). We found a significant elevation of laboratory markers of systemic inflammation, CRP, and NLR in MS patients who developed disease progression based on MRI findings. There is a need for further studies to validate current parameters to be considered as useful markers of MS activity and disability.

​Meta-analysis of the applied value of the growth differentiation factor 15 detection in HFpEF diagnosis

Objective To systematically evaluate the diagnostic value of growth differentiation factor-15 (GDF-15) for heart failure with preserved ejection fraction (HFpEF). Methods Chinese and English literature on the diagnosis of HFpEF using GDF-15 were searched in PubMed, Embase, Web of Science (WOS), Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and others. The literature on the diagnostic value of the GDF-15 test for HFpEF was screened from the establishment of the database to April 2023 according to the inclusion and exclusion criteria. The quality of the included studies was then assessed based on the QUADAS-2 list, and the threshold effect was evaluated using the Meta-Disc1.4 software. STATA 17.0 software was used to combine the sensitivity, specificity, and area under the curve (AUC) of the included studies. Moreover, heterogeneity was evaluated by the inconsistency index (I2) and Cochrane Q index, and the source of heterogeneity was explored by subgroup analysis, meta-regression, and sensitivity analysis. Finally, Deek’s quantitative funnel plot was used to assess whether there was publication bias among the included studies. Results A total of ten studies involving 1550 patients were included. The pooled sensitivity was 0.77 (95%CI: 0.70–0.83), the specificity was 0.79 (95%CI: 0.68–0.87), the positive likelihood ratio was 3.9 (95%CI: 2.6–5.9), and the negative likelihood ratio was 0.21 (95%CI:0.12–0.36). The diagnostic odds ratio was 19 (95%CI: 9–37), and the AUC of SROC was 0.88 (95%CI: 0.85–0.9). The results of the heterogeneity test showed significant heterogeneity among the studies (I2 = 96%, p = 0.000 < 0.01). Meta-regression analysis showed that there was a significant difference in diagnostic efficacy between the gold standard group (p = 0.0064 < 0.05), while there was no significant difference in diagnostic efficacy among the three subgroups of age, gender, and comprehensive group (p > 0.05). After excluding the articles that did not include biomarkers for the diagnosis of HFpEF, the average age ≥73 years old, and the proportion of women >55%, the remaining four articles had the pooled sensitivity of 0.80 (I2 = 60.1%, p = 0.06 >​ 0.05) and the pooled specificity of 0.84 (I2 = 0%, p = 0.61 >​0.05), which insisted that there is no significant heterogeneity among them. Conclusion With its high sensitivity and specificity for HFpEF diagnosis, GDF-15 is a novel biomarker for HFpEF diagnosis.