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Objective:To investigate relationships between serum growth differentiation factor 15 (GDF15) and glycolipid metabolism in patients with metabolic associated fatty liver disease (MAFLD).Methods:The current investigation was a cross-sectional study. A total of 333 patients from the Fengxian District Central Hospital were recruited into the study after physical examination from February 2020 to February 2021. There were 107 patients with MAFLD and type 2 diabetes mellitus (T2DM), including 54 males and 53 females with a mean age of (57±11) years. There were 65 patients with simple MAFLD only, including 32 men and 33 women with a mean age of (49±5) years. There were 105 patients with T2DM only, including 53 men and 52 women, with a mean age of (56±10) years. A control group of 56 people without MAFLD or diabetes,28 male, 28 female, mean age (48±6) years, was also included in the study. Serum GDF15 was measured via enzyme-linked immunosorbent assays. IBM SPSS 26.0 was used for statistical analysis. Logistic regression was used to evaluate relationships between GDF15 and metabolic abnormalities in MAFLD patients.Results:GDF15 progressively increased in the control [385 (296, 484) ng/L], nonobese MAFLD [388 (319, 435) ng/L], obese MAFLD [426 (354, 527) ng/L], T2DM [664 (483, 900) ng/L], and MAFLD+T2DM groups [770 (560, 1 074) ng/L]( H=113.82, P=0.001). There was no significant difference in serum GDF15 between the simple MAFLD [406 (339, 524) ng/L] and control group ( U=1 505.50, P=0.132). GDF15 was significantly higher in the MAFLD+T2DM group than in the T2DM-only group ( U=4 573.50, P=0.019). In logistic regression analysis increased GDF15 was associated with increased risks of simple MAFLD [odds ratio ( OR)=2.202], T2DM ( OR=29.656), and MAFLD+T2DM( OR=58.197). In patients with MAFLD, serum GDF15 was higher in the FIB4 index>1.45 group [773 (534, 1 162) ng/L] than in the FIB4 index<1.45 group [527 (389, 787) ng/L] ( U=1 709.50, P<0.001). Increased GDF15 was associated with an increased risk of advanced liver fibrosis ( OR=2.388). Conclusion:In patients with simple MAFLD, GDF15 level was not significantly higher than in the control group. In the T2DM-only group and the MAFLD+T2DM group GDF15 was significantly higher than in the control group. Increased serum GDF15 was associated with increased risk and severity of MAFLD complicated with abnormal glucose and lipid metabolism. High GDF15 increased the risk of advanced fibrosis in MAFLD patients.
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@#BACKGROUND: To investigate the effects of early standardized enteral nutrition (EN) on the cross-sectional area of erector spine muscle (ESMcsa), plasma growth differentiation factor-15 (GDF-15), and 28-day mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with invasive mechanical ventilation (MV). METHODS: A total of 97 AECOPD patients with invasive MV were screened in the ICUs of the First People's Hospital of Lianyungang. The conventional EN group (stage I) and early standardized EN group (stage II) included 46 and 51 patients, respectively. ESMcsa loss and GDF-15 levels on days 1 and 7 of ICU admission and 28-day survival rates were analyzed. RESULTS: On day 7, the ESMcsa of the early standardized EN group was significantly higher than that of the conventional EN group, while the plasma GDF-15 levels were significantly lower than those in the conventional EN group (ESMcsa: 28.426±6.130 cm2 vs. 25.205±6.127 cm2; GDF-15: 1661.608±558.820 pg/mL vs. 2541.000±634.845 pg/mL; all P<0.001]. The 28-day survival rates of the patients in the early standardized EN group and conventional EN group were 80.40% and 73.90%, respectively (P=0.406). CONCLUSION: ESMcsa loss in AECOPD patients with MV was correlated with GDF-15 levels, both of which indicated acute muscular atrophy and skeletal muscle dysfunction. Early standardized EN may prevent acute muscle loss and intensive care unit-acquired weakness (ICU-AW) in AECOPD patients.
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Resumo Nos 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.
Abstract In the last years, several diagnostic and prognostic biomarkers have been studied in cardiovascular disease. Growth differentiation factor-15 (GDF-15), a cytokine belonging to the transforming growth factor- (TGF-) family, is highly up-regulated in stress and inflammatory conditions and has been correlated to myocardial injury and pressure cardiac overload in animal models. This new biomarker has been positively correlated with increased risk of cardiovascular events in population studies and shown an independent predictor of mortality in patients with coronary artery disease and heart failure. This review aimed to summarize the current evidence on the diagnostic and prognostic value of GDF-15 in different settings in cardiology.
Subject(s)
Humans , Tachycardia, Ventricular/diagnosis , Algorithms , Diagnosis, Differential , ElectrocardiographyABSTRACT
Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
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Objective:To investigate the diagnostic and prognostic value of the growth differentiation factor 15 (GDF15) and the procalcitonin (PCT) in sepsis.Methods:A total number of 137 patients with sepsis (considered as the sepsis group) and 59 patients with inflammatory infection but not diagnosed as sepsis (the non-sepsis group) received treatment in intensive care unit of Renming Hospital of Wuhan University were collected from July 2020 to January 2021, and 62 cases of healthy physical examination (control group) were simultaneously chosen as control. Sepsis patients were divided into two groups (death group [ n=48] and survival group [ n=89]) according to their 28-day′s survival. The serum levels of GDF15, PCT, C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) were examined, and the levels of each index, was dynamically monitored on the 1st, 3rd and 7th day after admission. The differences of the two indicators between different groups were compared by non-parametric test. The correlation between GDF15 and PCT was analyzed by Spearman correlation test. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of the two indicators for sepsis. Results:The levels of GDF15 in the sepsis group, non-sepsis group and control group were 3.22 (1.39, 6.31) μg/L, 0.84 (0.21, 1.66) μg/L and 0.11 (0.09, 0.13) μg/L, respectively. The levels of PCT were 13.10 (1.99, 50.25) μg/L, 0.24 (0.13, 0.68) μg/L and 0.05 (0.03, 0.10) μg/L, respectively. The levels of CRP were 115.80 (26.40, 184.07) mg/L, 24.20 (11.30, 53.20) mg/L and 0.50 (0.50, 2.76) mg/L, respectively. The levels of IL-6 were 68.26 (21.59, 255.46) ng/L, 33.20 (10.81, 89.27) ng/L and 8.82 (7.33, 11.23) ng/L, respectively. The levels of IL-10 were 11.30 (5.88, 25.50) ng/L, 9.34 (5.65, 16.90) ng/L and 4.94 (4.31, 5.31) ng/L, respectively. The GDF15, PCT, CRP and IL-6 of the sepsis group were significantly higher than those of the non-sepsis group (The U values were 67.681, 86.034, 44.164 and 38.934, respectively, with P values less than 0.05) and the control group (The U values were 136.475, 138.667, 120.701 and 100.886, respectively, with P values less than 0.001). There was no significant difference in IL-10 between sepsis group and nonsepsis group, but it was higher than that of control group ( U=80.221, P<0.001). There was a positive correlation between GDF15 and PCT in patients with sepsis, and the spearman correlation coefficient was 0.234 ( P=0.006). The GDF15 of the death group and the survival group were 5.49 (3.60, 8.25) μg/L and 2.03 (1.06, 3.69) μg/L, and the PCT levels were 26.45 (11.23, 94.25) μg/L and 9.08 (1.33, 22.75) μg/L, respectively. GDF15 and PCT in the death group were significantly higher than those in the survival group ( U values were 3 305.500 and 3 060.000, respectively, and P values were both less than 0.001). The GDF15 and PCT levels in the death group were higher than those in the survival group on the 1st, 3rd and 7th day of dynamic monitoring ( P<0.05), however, the level of CRP and IL-10 were not significantly different ( P>0.05). The level of IL-6 in the death group was not significantly different from that of the death group on 1st day, but was higher than that of the survival group on the 3rd and 7th day ( P<0.05). The area under the curve (AUC) of GDF15, PCT, CRP, IL-6 and IL-10 alone and in the combined diagnosis of sepsis were 0.899, 0.938, 0.874, 0.789, 0.698 and 0.962, respectively. The combined detection of AUC was better than a single index; the GDF15, PCT, CRP, IL-6 and IL-10 alone and combined detection of sepsis prognosis AUC were 0.774, 0.716, 0.522, 0.623, 0.520 and 0.839, respectively, the combined detection of AUC is also better than single index. Conclusions:GDF15 and PCT have good clinical reference value in the differential diagnosis and prognosis of sepsis. The combination of indicators has a higher clinical value. GDF15 may become a biomarker for the diagnosis and prognosis of sepsis.
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Objective:To explore the value of growth differentiation factor 15 (GDF15) in the early diagnosis of acute chest pain.Methods:A total of 96 patients with acute chest pain admitted to the Emergency Department of Hainan Hospital of PLA General Hospital from January to November 2020 were retrospectively collected. The sex, age, troponin T, creatine kinase, creatine kinase isoenzyme, GDF15 and B-type natriuretic peptide of patients within 30 min after admission were recorded, and the differences of each index in different groups were compared. ROC curve was drawn to evaluate the diagnostic value of GDF15 and TNT/BNP in acute coronary syndrome (ACS). The Gensini score, left ventricular ejection fraction, length of stay in hospital and the number of stents were calculated, and the correlation between these indexes and GDF15 concentration was evaluated.Results:The general trend of acute chest pain was more male than female (72.92% vs. 27.08%) , the oldest group was the UA group (64.67 ± 13.87) years old , the youngest group was cardiac arrest group (47.29 ± 9.99) years old . There were higher rates of hypertension in the STEMI group, NSTEMI group and UA group, and none of the groups showed significant advantage in diabetes. The GDF15 concentration was higher in ACS related chest pain group [(2.360 ± 1.710) ng/mL vs. (1.380 ± 1.040) ng/mL, P<0.01]. The area under the Receiver Operating Characteristic Curve (AUC) of GDF15 combined with TNT was up to 0.863. GDF15 concentration was negatively correlated with ejection fraction, positively correlated with Gensini score, positively correlated with the number of stents implanted, and positively correlated with the length of hospital stay. Conclusions:GDF15 is valuable in the diagnosis and prognosis of acute chest pain. The combination of GDF15 and TNT can improve the diagnostic rate of ACS.
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Objective:To explore the early warning and prediction value of GDF15 for sudden death patients.Methods:From January to December 2018, 49 patients with sudden death who were treated in the Emergency Department of the First Clinical Center of PLA General Hospital were included in the case group, and 46 healthy physical examiners in the Physical Examination Center of the Hospital were randomly selected as the control group. The general situation, comparison of myocardial markers and analysis of the basic data of the case group were carried out, so as to evaluate the early warning value of each myocardial marker in sudden death.Results:Patients aged 40-49 years old accounted the highest proportion among sudden death cases, reaching 26.54%. Sudden death under 60 years old accounted for 59.19%, and the ratio of male to female was 3.83:1. There were significant differences between the case group and the control group in CK-MB [(41.35±98.38) vs. (3.13±2.17), P=0.009], CK [(2652.82±6845.66) vs. (102.73±47.93), P=0.012], and GDF15 [(549.80±809.79) vs. (115.70±167.42), P=0.001]. At the same time, the AUC value of GDF15 was 0.816, which has the highest diagnostic value for sudden death. And CK-MB, CK and GDF15 had no correlation with age. Conclusions:GDF15, as a biological marker, has a good early warning function in sudden death.
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Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
Subject(s)
Animals , Rats , Analgesia , Ganglia, Spinal , Growth Differentiation Factor 15 , Sensory Receptor Cells , Sodium Channels , Tetrodotoxin/pharmacologyABSTRACT
Objective: To investigate the|protective effect of Shuxuening Injection on the brain tissue of the rats with acute cerebral infarction, and to elucidate its mechanism. Methods: Fifty rats were randomly divided into control group, sham operation group, model group, nimodipine group and Shuxuening Injection group ( n=10). The rat models of acute cerebral infarction were made by internal carotid artery suture method in model group, nimodipine group and Shuxuening Injection group. The common carotid arteries, the external carotid arteries and the internal carotid arteries of the rats in sham operation group were separated∗ and only the external carotid arteries were ligated; the rats in control group were not treated with operation; the rats in Shuxuening Injection group were given Shuxuening Injection, the rats in nimodipine group were given nimodipine∗ and the rats in control group, model group and sham operation group were given normal saline at the same volume. The score of neurological impairment, water contents in brain tissue and relative cerebral infarction areas of the rats in various groups were measured. HE staining was used to observe the morphology of brain tissue of the rats in various groups, and immumohistochemical staining was used to detect the expression levels of growth differentiation factor-15 (GDF-15) and C-reactive protein (CRP) in brain tissue of the rats in various groups. EL ISA method was used to detect the levels of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) and interleukin-1(3 (1L-1|3) in brain tissue of the rats in various groups. Results: The cortical structures of cortex of the rats in control group and sham operation group were complete and the cells were arranged neatly; the cytoplasm and nucleus of the nerve cells of the rats in model group were wrinkled, and the interstitium between nerve cells and capillaries were loose; the swelling degrees of cerebral cortical nerve cells and glial cells and the loose degrees of stroma of the rats in Shuxuening Injection group were reduced, and the histopathological manifestations were similar to those in nimodipine group. Compared with control group and sham operation group∗ the water content in brain tissue of the rats in model group was significantly increased ( P 0.05). Conclusion: Shuxuening Injection can protect the acute cerebral infarction by up-regulating the expression of GDF-15 and inhibiting the expression of CRP in brain tissue of the rats with acute cerebral infarction, reducing the levels of inflammatory cytokines and improving the neurological function.
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Objective: To investigate the effect of nerve growth factor (NGF) on the expression level of growth differentiation factor-15 (GDF-15) in the brain tissue of the rats with cerebral infarction, and to elucidate the mechanism of NGF in the rats with cerebral infarction. Methods: The middle cerebral artery occlusion (MCAO) models were established by the Longa' s method. A total of 54 SD rats were randomly divided into sham operation group, model group and NGF group, and there were 18 rats in each group. The rats in NGF group were given NGF (50 μg middot; kg-1) by intraperitoneal injection, and equal volume of normal saline was given to the rats in sham operation (the artery was isolated without ligation) group and model group. The neurological function scores of the rats in various groups were measured 1, 3 and 7 d after operation; HE staining was used to observe the pathomorphology of nerves in brain tissue and immunohistochemical staining was used to detect the number of GDF-15 positive cells; the expression levels of GDF-15 in brain tissue of the rats in various groups were detected by ELISA method. Results: The results of HE staining showed that the degrees nerve cell necrosis, interstitial edema and glial cell proliferation were relatively low in NGF group 7 d after operation. Compared with sham operation group, the neurological function scores, the number of GDF-15 positive cells, and the expression levels of GDF-15 in brain tissue of the rats in model group and NGF group were significantly increased (P<0. 05). Compared with model group, the neurological function scores of the rats in NGF group were significantly decreased 3 and 7 d after operation (P<0. 05), and the number of GDF-15 positive cells and the expression levels of GDF-15 in brain tissue of the rats in NGF group were significantly increased at different time points after operation (P<0. 05). Conclusion: NGF can protect the brain nerve by up-regulating the expression level of GDF-15 in brain tissue and improving the nerve function.
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Objective@#To investigate the relationship between plasma activin A(ACTA), B-type natriuretic peptide(BNP), growth differentiation factor-15 (GDF-15) and interleukin-6 (IL-6) levels and heart failure.@*Methods@#From January 2017 to December 2018, 80 patients with acute heart failure admitted to Lishui Central Hospital were selected as observation group.According to NYHA cardiac function classification, 23 patients were classified as grade II, 30 patients were classified as grade Ⅲ and 27 patients were classified as grade Ⅳ.Another 60 healthy people were selected as control group from January 2017 to December 2018.The left ventricular end-diastolic diameter(LVEDD) and left ventricular ejection fraction(LVEF) were measured by Doppler echocardiography, and the levels of ACTA, BNP, GDF-15 and IL-6 were measured by ELISA.@*Results@#The plasma ACTA[(2.43±0.54)ng/mL], BNP[(219.31±34.25)ng/L], GDF-15[(854.31±46.57)ng/L], IL-6[(183.25±39.89)ng/L]in the observation group were significantly higher than those in the control group[(0.32±0.10)ng/mL, (16.74±3.89)ng/L, (467.52±60.91)ng/L, (40.31±6.57)ng/L](t=29.859, 45.553, 42.591, 27.455, all P<0.05). The LVEDD[(65.73±5.38)mm] in the observation group was higher than that in the control group[(47.83±4.31)mm], while the LVEF[(39.82±3.56)%]was lower than that in the control group[(64.32±4.16)%](t=21.170, 37.475, all P<0.05). The ACTA[(3.98±0.58)ng/mL], BNP[(304.21±41.30)ng/L], GDF-15[(989.83±50.38)ng/L], IL-6[(249.81±45.61)ng/L] in grad Ⅳ group were lower than those in grade Ⅱ group[(1.17±0.21)ng/mL, (135.42±23.98)ng/L, (735.24±41.87)ng/L, (120.74±33.45)ng/L] and grade Ⅲ group[(2.41±0.52)ng/mL, (217.27±35.46)ng/L, (861.32±53.46)ng/L, (185.42±42.31)ng/L](F=8.391, 23.154, 17.849, 14.568, all P<0.05). The plasma levels of ACTA, BNP, GDF-15 and IL-6 in gradeⅢgroup were lower than those in grade Ⅱ group (t=10.764, 9.517, 9.322, 6.025, all P<0.05). The LVEDD[(72.31±5.91)mm]in grade Ⅳ group was higher than that in grade Ⅱ group[(58.98±4.64)mm]and grade Ⅲ group[(66.01±5.48)mm], and the LVEF[(29.97±3.36)%]was lower than that in grade Ⅱ group[(51.54±3.27)%]and grade Ⅲ group[(40.35±3.81)%], the differences were statistically significant (F=12.415, 9.829, all P<0.05). The LVEDD in grade Ⅲ group was higher than that in grade Ⅱ group, and the LVEF was lower than that in gradeⅡgroup, the differences were statistically significant(t=4.176, 10.856, all P<0.05).@*Conclusion@#The levels of ACTA, BNP, GDF-15 and IL-6 in plasma are increased in patients with acute heart failure, and are closely related to the progress of the disease.They can be used as diagnostic and prognostic indicators of acute heart failure.
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Background@#Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF).@*Methods@#In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.@*Results@#Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648–0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622–0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685–0.795, P < 0.001).@*Conclusions@#GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.@*Clinical trial registration@#ChiCTR-ONC-12001944, http://www.chictr.org.cn.
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Objective To investigate the relationship between plasma activin A (ACTA),B－type natriuretic peptide(BNP),growth differentiation factor －15 (GDF－15) and interleukin－6 ( IL－6) levels and heart failure. Methods From January 2017 to December 2018,80 patients with acute heart failure admitted to Lishui Central Hospitalwere selected as observation group.According to NYHA cardiac function classification , 23 patients were classified as grade II,30 patients were classified as grade Ⅲand 27 patients were classified as grade Ⅳ.Another 60 healthy people were selected as control group from January 2017 to December 2018.The left ventricular end －diastolic diameter(LVEDD) and left ventricular ejection fraction (LVEF) were measured by Doppler echocardiography ,and the levels of ACTA, BNP, GDF －15 and IL －6 were measured by ELISA.Results The plasma ACTA [(2.43 ± 0.54)ng／mL],BNP[(219.31 ±34.25)ng／L],GDF－15[(854.31 ±46.57)ng／L],IL－6[(183.25 ±39.89)ng／L] in the observation group were significantly higher than those in the control group [(0.32 ±0.10) ng／mL,(16.74 ± 3.89)ng／L,(467.52 ±60.91)ng／L,(40.31 ±6.57) ng／L]( t＝29.859,45.553,42.591,27.455,all P＜0.05). The LVEDD[(65.73 ±5.38) mm] in the observation group was higher than that in the control group [(47.83 ± 4.31)mm],while the LVEF[(39.82 ±3.56)%]was lower than that in the control group [(64.32 ±4.16)%]( t＝21.170,37.475,all P＜0.05).The ACTA [(3.98 ±0.58) ng／mL],BNP[(304.21 ±41.30) ng／L],GDF－15 [(989.83 ±50.38) ng／L],IL－6[(249.81 ±45.61) ng／L] in grad Ⅳ group were lower than those in grade Ⅱgroup[(1.17 ±0.21)ng／mL,(135.42 ±23.98)ng／L,(735.24 ±41.87)ng／L,(120.74 ±33.45)ng／L] and gradeⅢgroup[(2.41 ±0.52)ng／mL,(217.27 ±35.46)ng／L,(861.32 ±53.46) ng／L,(185.42 ±42.31) ng／L] ( F＝8.391,23.154,17.849,14.568,all P＜0.05).The plasma levels of ACTA,BNP,GDF－15 and IL－6 in gradeⅢgroup were lower than those in gradeⅡgroup (t＝10.764,9.517,9.322,6.025,all P＜0.05).The LVEDD[(72.31 ± 5.91) mm] in grade Ⅳ group was higher than that in grade Ⅱ group [(58.98 ±4.64) mm] and grade Ⅲ group [(66.01 ±5.48) mm], and the LVEF [( 29.97 ±3.36)%] was lower than that in grade Ⅱ group [(51.54 ± 3.27)%]and gradeⅢgroup[(40.35 ±3.81)%],the differences were statistically significant (F＝12.415,9.829, all P＜0.05).The LVEDD in grade Ⅲgroup was higher than that in grade Ⅱgroup,and the LVEF was lower than that in gradeⅡgroup,the differences were statistically significant ( t ＝4.176,10.856,all P＜0.05).Conclusion The levels of ACTA,BNP,GDF－15 and IL－6 in plasma are increased in patients with acute heart failure ,and are closely related to the progress of the disease.They can be used as diagnostic and prognostic indicators of acute heart failure.
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Objective: To study therapeutic effect and influence of fluvastatin combined arotinolol on serum levels of growth differentiation factor 15 (GDF-15) and neutrophil gelatinase associated lipocalin (NGAL) in patients with coronary heart disease (CHD) complicated heart failure (HF). Methods: A total of 140 CHD + HF patients, who were treated in our department of cardiology from May 2013 to May 2015, were selected. According to random number table, patients were randomly and equally divided into arotinolol group and combined treatment group (received fluvastatin based on arotinolol group), both groups were treated for three months. Therapeutic effect, left ventricular end-diastolic dimension (LVEDd), end-diastolic interventricular septal thickness (IVSTd), left ventricular ejection fraction (LVEF), mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), stroke volume (SV), serum levels of GDF-15 and NGAL before and after treatment were compared between two groups. Results: Compared with arotinolol group after treatment, there were significant rise in LVEF [(45. 31±6. 73) ％ vs. (72. 64±7. 29) ％], MAP [(59. 34±6. 93) mmHg vs. (75. 61±7. 24) mmHg], CI [(2. 66±1. 31) L/min2 vs. (3. 12± 1. 37) L/min2], SI [(27. 15±4. 37) ml/m2 vs. (49. 81±5. 79) ml/m2]and SV [(60. 99±5. 13) ml vs. (71. 24± 5. 94) ml], and significant reductions in IVSTd [(13. 51±3. 17) mm vs. (11. 27±7. 26) mm], serum levels of GDF-15 [(1153. 4±153. 7) ng/L vs. (923. 8±81. 4) ng/L]and NGAL [(112. 52±61. 49) μg/L vs. (78. 14± 35. 74) μg/L]in combined treatment group (P＜0. 05 or＜0. 01). Total effective rate of combined treatment group was significantly higher than that of arotinolol group (87. 14％ vs. 74. 29％), P=0. 007. Conclusion: Fluvastatin combined arotinolol can effectively improve heart function, significantly reduce serum GDF-15 and NGAL levels, and improve prognosis in CHD + HF patients, which is worth extending.
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Objective To explore the relationship between single nucleotide polymorphism (SNP) locus rs1058587,rs1059519 and rs1059369 polymorphisms of growth differentiation factor-15 (GDF-15)gene and susceptibility to chronic Keshan disease in Gansu Province.Methods Using the case-control study method,56 individuals with chronic Keshan disease were taken as case group,and 53 individuals without chronic Keshan disease from the same villages were selected as control group in Gansu Keshan disease areas,venous blood samples were collected,and ethylenediamine tetraacetic acid disodium salt (EDTA) was used for anticoagulation,and the samples were sent for gene sequencing.Univariate and multivariate logistic regression analyses were conducted to analyze the influence of genotypes of rs1058587,rs1059519 and rs1059369 on the prevalence of chronic Keshan disease,and the risk factors for disease were expressed as odds ratio (OR).Results The age of the 56 patients in the case group was (60.93 + 21.99) years old,15 males and 41 females;the age of the 53 residents in control group was (47.49-+ 33.61) years old,26 males and 27 females.There was no significant difference in age between the two groups (t =46.16,P ＞ 0.05);the difference in gender was statistically significant (x2=5.76,P ＜ 0.05).The differences of allele frequencies of case group and control group rs1058587 (C:36.6％,32.1％,G:63.4％,67.9％),rs1059369 (A:61.6％,72.6％,T:38.4％,27.4％) between the two groups were not significantly different (x2 =0.50,3.00,P ＞ 0.05);the differences of allele frequencies of GDF-15 rs1059319 (C:25.0％,40.6％,G:75.0％,59.4％) between the two groups were significantly different (x2 =6.01,P ＜ 0.05).The genotype frequency distribution of GDF-15 gene rs1058587,rs1059519 and rs1059369 in the case group and the control group was not significantly different between the groups (P ＞ 0.05).However,in the case group,the mutant GG frequency of rs1059519 locus was higher than wild type CC (x2 =5.33,P ＜ 0.05).In multivariate logistic regression analysis,women were 3.81 times more likely to suffer from chronic Keshan disease than men,and people aged 45 or older were 5.30 times more likely to suffer from chronic Keshan disease than those younger than 45.The heterozygous and mutant types of GDF-15 gene rs1058587 and rs1059369 were compared with wild type,and the difference was not statistically significant (ORrs1058587 =0.46,0.50,ORrs1059369 =1.30,2.59,P ＞ 0.05);there was no significant difference between the heterozygous type of GDF-15 gene rs1059519 and wild type (OR =3.34,P ＞ 0.05),and the difference between the mutant and wild type was statistically significant (OR =8.58,P ＜ 0.05).Conclusions In this study,we find women of the study population are more likely to have chronic Keshan disease than men,and aged≥45 is a risk factor for chronic Keshan disease.Genetic polymorphisms of GDF-15 gene rs1058587,rs1059369 are not associated with susceptibility to chronic Keshan disease,and a certain correlation between genetic polymorphism of rs1059519 locus and susceptibility to chronic Keshan disease.
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Objective To analyze the correlation between acute coronary syndrome (ACS) and stress differentiation factors (GDF-15), catecholamines, and heat shock proteins (HSP-70). Methods A total of 40 patients with ACS were selected from the Emergency Department of the PLA General Hospital from September 10, 2016 to October 10, 2016. 40 healthy volunteers were selected as the control group. The information of age, gender, history of smoking, drinking, hyperlipidemia, hypertension and diabetes. Inspection indicators of blood biochemistry (Creation kinase Isoenzyme, Total cholesterol, Triglyceride, High-density lipoprotein, Blood glucose, Total bilirubin, Direct bilirubin), serum level of GDF-15, catecholamine (Adrenaline,norepinephrine,dopamine)and HSP-70 were collected. Evaluation of Coronary Stenosis used with Coronary Artery Lesions and Gensini Score. Statistical analysis using SPSS 17.0 statistical software, measurement data are expressed as mean ± standard deviation (x±s),count data to the number of cases and percentage, measurement using t test, count data using chisquare test. Results Serum levels of GDF-15[(21.94±14.23) vs. (7.06±5.53), P=0.007],catecholami ne[(46592.15±30931.27) vs. (5507.14±2083.28), P<0.01], HSP-70 [(369.56±300.44) vs. (07.76±54.23),P<0.001],all higher than the control group. GDF-15 serum levels of Gensini scores> 40 compare with <20group was significantly higher [(324.27 ± 198.81) vs. (77.43 ± 699.22), P=0.035], serum catecholaminelevels of > 40 group compare with <20 group significantly increased [(18.71 ± 7.32) vs. (18.6±46.1),P=0.017], GDF-15 levels were significantly higher in the multi-vessel stenosis group than in the doublevessel stenosis group[ (618.40±434.42) vs. (292.07±219.65), P=0.033]. Conclusions GDF-15,catecholamine and HSP-70 are correlated with ACS, as well as the severity of coronary artery lesions.
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Summary Objective: To explore the correlation between growth differentiation factor 15 (GDF-15) -3148C/G polymorphism and the formation of collateral circulation in acute ST-elevation myocardial infarction (STEMI) in Han population of Taiyuan area. Method: The present study included 92 STEMI patients and 56 normal controls based on coronary angiography; STEMI group was divided into collateral group and non-collateral group according to Rentrop's grading method. Polymerase chain reaction (PCR) and DNA sequencing methods were used to detect and analyze the GDF-15 -3148C/G polymorphism in all participants. Results: There was significant difference in GDF-15 -3148C/G CC and GC distribution between STEMI group and control group (p=0.009); the allele frequencies between these two groups were also significant different (p=0.016); and the risk genotype for STEMI was CC with increased OR=2.660. For STEMI group, GDF-15 -3148C/G CC and GC distribution was also significantly different between patients with and without collateral (p=0.048), and CC genotype significantly promote the formation of collateral circulation. However, there were no significant differences in allele frequencies between these two subgroups of STEMI. Conclusion: There was correlation between GDF-15-3148C/G polymorphism and the formation of collateral circulation in patients with acute STEMI.
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Humans , Male , Female , Polymorphism, Genetic , Collateral Circulation/physiology , Growth Differentiation Factor 15/genetics , ST Elevation Myocardial Infarction/genetics , Case-Control Studies , Polymerase Chain Reaction , Risk Factors , Coronary Angiography , ST Elevation Myocardial Infarction/diagnostic imaging , Gene Frequency , Genotype , Middle AgedABSTRACT
Objective To explore the correlation among ST-2,adiponectin(APN),positive growth dif-ferentiation factor -15(GDF-15)and senile heart failure,and to investigate the diagnostic values of these indica-tors. Methods Totally 129 patients(15 patients of NYHA Ⅰ,60 of NYHA Ⅱ,28 of NYHA Ⅲ and 26 of NYHAⅣin study group)with heart failure and 30 control subjects(control group)were enrolled in the study.Se-rum levels of ST-2,APN and GDF-15 were determined by ELISA,and their correlation with senile heart failure was analyzed.Results Compared with those in control group,serum levels of ST-2,APN and GDF-15 in study group were significantly increased(P<0.05).There were significant differences in serum levels of ST-2,APN and GDF-15 among patients of different classifications in study group(P<0.05)and the higher level of cardiac func-tion,the higher serum ST-2,APN and GDF-15. There was a positive correlation among serum ST-2,APN and GDF-1. Conclusions The serum levels of ST-2,APN and GDF-1 are positively related to the severity of senile heart failure,thus it could be served as the index of diagnosis,curative effect monitoring and prognosis of patients with heart failure.
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BACKGROUND/AIMS: Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. METHODS: The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. RESULTS: Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). CONCLUSIONS: This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease.
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Humans , Biomarkers , Fibrosis , Growth Differentiation Factor 15 , Hepatitis, Chronic , Immunoenzyme Techniques , Liver Cirrhosis , Liver Diseases , Liver , ROC Curve , Sensitivity and SpecificityABSTRACT
Objective To explore the correlation between serum growth differentiation factor‐15(GDF‐15) level and acute myocardial infarction(AMI) to provide a basis for the prognostic evaluation of AMI .Methods Totally 192 Han patients with AMI (AMI group) and non‐coronary heart disease (NCHD ,NCHD group) diagnosed in Chengde Municipal Central Hospital from Sep‐tember 2013 to January 2015 ,were selected and their clinical data were collected .The biochemical markers and serum GDF‐15 level were detected .Results Comparing the AMI group with the NCHD group ,differences in the patients′age ,smoking ,blood glucose (Glu) ,TC ,TG ,LDL‐C levels had statistical significance (P<0 .05);the serum GDF‐15 level in the AMI group was significantly higher than that in the NCHD ;serum GDF‐15 level was positively correlated with TC ,LDL‐C ,hs‐CRP and Glu in the AMI group . Conclusion The increase of serum GDF‐15 level is obviously correlated AMI ,therefore GDF‐15 can serve as an indicator for moni‐toring myocardial infarction .