Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with C...Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may展开更多
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 facto...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.展开更多
BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation fact...BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-展开更多
BACKGROUND:To investigate the eff ects of early standardized enteral nutrition(EN)on the crosssectional area of erector spine muscle(ESMcsa),plasma growth diff erentiation factor-15(GDF-15),and 28-day mortality of acu...BACKGROUND:To investigate the eff ects of early standardized enteral nutrition(EN)on the crosssectional area of erector spine muscle(ESMcsa),plasma growth diff erentiation 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 cm^(2) vs.25.205±6.127 cm^(2);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.展开更多
Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future is...Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.展开更多
Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive s...Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.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.展开更多
文摘Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may
文摘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.
文摘BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-
基金funded by the Social Development Project of Jiangsu Provincial Department of Science and Technology(BE2020670)the Social Development Project of Lianyungang Science and Technology(SF2117).
文摘BACKGROUND:To investigate the eff ects of early standardized enteral nutrition(EN)on the crosssectional area of erector spine muscle(ESMcsa),plasma growth diff erentiation 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 cm^(2) vs.25.205±6.127 cm^(2);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.
基金supported by the Beijing Municipal Science and Technology Committee(D0906006000091)the Ministry of Science and Technology of the People’s Republic of China,State Science and Technology Support Program(No.2011BAI11B05).
文摘Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.
基金This work was supported by the National Natural Science Foundation of China(82021002,31771164,and 31930042)the National Key R&D Program of China(2017YFB0403803)+1 种基金the Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Zhang Jiang Laboratory.
文摘Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.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.
