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 influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.展开更多
Background The neutrophil-to-lymphocyte （N/L） ratio has been associated with poor prognosis in patients with heart failure, but it has not been compared with N-terminal pro-brain natriuretic peptide （NT-proBNP） in...Background The neutrophil-to-lymphocyte （N/L） ratio has been associated with poor prognosis in patients with heart failure, but it has not been compared with N-terminal pro-brain natriuretic peptide （NT-proBNP） in elderly patients with chronic heart failure （CHF）. We sought to make this comparison. Methods A total of 1355 elderly patients with CHF were analyzed. A multivariate logistic regression model was used to analyze the variables associated with atrial fibrillation （AF）. Cox regression analysis was used to assess the multivariable rela- tionship between the N/L ratio, NT-proBNP level, and subsequent major cardiovascular events （MCE）. Results In the multiple logistic regression analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly patients with CHF [odds ratio （OR）： 1.079, 95% confi- dence interval （CI）： 1.027-1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable model using tertiles of both variables, the highest tertile of the N/L ratio was significantly associated with MCE [hazard ratio （HR）： 1.407, 95% CI： 1.098-1.802, P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP tertile was also significantly associated with MCE （HR： 1.461, 95% CI： 1.104-1.934, P- 0.008）. Conclusions In elderly patients with CHF, the N/L ratio is one of the important risk factors for AF and it is an inexpensive and readily available marker with similar independent prognostic power to NT-proBNP. The risk of MCE increases 1.407-fold when the N/L ratio is elevated to the highest tertile.展开更多
Background Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtype...Background Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtypes in Chinese subjects remains unclear. This study aimed to compare the differences in inflammation biomarkers among Chinese patients with different subtypes of HF who have been identified to date. Methods We included 413 consecutive patients with HF,including 262 with preserved ejection fraction (HFpEF),55 with middle-ranged ejection fraction (HFmrEF) and 96 with reduced ejection fraction (HFrEF). Ten inflammation biomarkers were analyzed and compared according to the HF subtypes. One hundred contemporary non-HF subjects were also recruited as the control group. Moreover,the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the HF subtypes were assessed. Results The mean age of the HF patients was 65.0 ± 12.0 years,65.8% were male. Distinct subtypes of HF demonstrated different inflammation biomarker panels. IL-6,PTX-3,ANGPTL-4 and TNF-α were correlated with HFrEF;IL-1β and PTX-3 were correlated with HFmrEF;and IL-1β and IL-6 were correlated with HFpEF. The multivariable logistic regression showed that IL-1β[relative ratio (RR)= 1.08,95% CI: 1.02–1.15,P = 0.010],IL-6 (RR = 1.03,95% CI: 1.01–1.06,P = 0.016),PTX-3 (RR = 1.31,95% CI: 1.11–1.55,P = 0.001),and ANGPTL-4 (RR = 1.05,95% CI: 1.02–1.07,P < 0.001) were independently associated with HF,while IL-6 (RR = 1.03,95% CI: 1.01–1.04,P = 0.019),PTX-3 (RR = 1.23,95% CI: 1.06–1.43,P = 0.007),and ANGPTL-4 (RR = 1.03,95% CI: 1.01–1.06,P = 0.005) were independently associated with the HF subtype. Conclusions Diverse inflammation biomarkers have multifaceted presentations according to the subtype of HF,which may illustrate the diverse mechanisms of inflammation in Chinese HF patients. IL-6,PTX-3,and ANGPTL-4 were independent inflammation factors associated with HFrEF and HF.展开更多
Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat car...Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.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 influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.
文摘Background The neutrophil-to-lymphocyte （N/L） ratio has been associated with poor prognosis in patients with heart failure, but it has not been compared with N-terminal pro-brain natriuretic peptide （NT-proBNP） in elderly patients with chronic heart failure （CHF）. We sought to make this comparison. Methods A total of 1355 elderly patients with CHF were analyzed. A multivariate logistic regression model was used to analyze the variables associated with atrial fibrillation （AF）. Cox regression analysis was used to assess the multivariable rela- tionship between the N/L ratio, NT-proBNP level, and subsequent major cardiovascular events （MCE）. Results In the multiple logistic regression analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly patients with CHF [odds ratio （OR）： 1.079, 95% confi- dence interval （CI）： 1.027-1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable model using tertiles of both variables, the highest tertile of the N/L ratio was significantly associated with MCE [hazard ratio （HR）： 1.407, 95% CI： 1.098-1.802, P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP tertile was also significantly associated with MCE （HR： 1.461, 95% CI： 1.104-1.934, P- 0.008）. Conclusions In elderly patients with CHF, the N/L ratio is one of the important risk factors for AF and it is an inexpensive and readily available marker with similar independent prognostic power to NT-proBNP. The risk of MCE increases 1.407-fold when the N/L ratio is elevated to the highest tertile.
基金supported by the National Natural Science Foundation of China (No.31701155)the National Key Research and Development Program of China (2017YFC 0114001)Chinese PLA General Hospital Medical Big Data Research and Development Project (No.2017MBD-007)
文摘Background Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtypes in Chinese subjects remains unclear. This study aimed to compare the differences in inflammation biomarkers among Chinese patients with different subtypes of HF who have been identified to date. Methods We included 413 consecutive patients with HF,including 262 with preserved ejection fraction (HFpEF),55 with middle-ranged ejection fraction (HFmrEF) and 96 with reduced ejection fraction (HFrEF). Ten inflammation biomarkers were analyzed and compared according to the HF subtypes. One hundred contemporary non-HF subjects were also recruited as the control group. Moreover,the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the HF subtypes were assessed. Results The mean age of the HF patients was 65.0 ± 12.0 years,65.8% were male. Distinct subtypes of HF demonstrated different inflammation biomarker panels. IL-6,PTX-3,ANGPTL-4 and TNF-α were correlated with HFrEF;IL-1β and PTX-3 were correlated with HFmrEF;and IL-1β and IL-6 were correlated with HFpEF. The multivariable logistic regression showed that IL-1β[relative ratio (RR)= 1.08,95% CI: 1.02–1.15,P = 0.010],IL-6 (RR = 1.03,95% CI: 1.01–1.06,P = 0.016),PTX-3 (RR = 1.31,95% CI: 1.11–1.55,P = 0.001),and ANGPTL-4 (RR = 1.05,95% CI: 1.02–1.07,P < 0.001) were independently associated with HF,while IL-6 (RR = 1.03,95% CI: 1.01–1.04,P = 0.019),PTX-3 (RR = 1.23,95% CI: 1.06–1.43,P = 0.007),and ANGPTL-4 (RR = 1.03,95% CI: 1.01–1.06,P = 0.005) were independently associated with the HF subtype. Conclusions Diverse inflammation biomarkers have multifaceted presentations according to the subtype of HF,which may illustrate the diverse mechanisms of inflammation in Chinese HF patients. IL-6,PTX-3,and ANGPTL-4 were independent inflammation factors associated with HFrEF and HF.
基金This study was supported by the Ministry Science Foundation of the Chinese People's Liberation Army during the 12th Five-Year Plan Period
文摘Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.
