Prognostic Role Of Blood Lipids In Heart Failure And Metabolomics Study Of Light-chain Cardiac Amyloidosi

Background:Blood lipid is the general name of cholesterol,triglyceride and lipoid in serum.Although blood lipid has been proved to be closely related to the occurrence and development of cardiovascular disease,its prognostic role in heart failure is still controversial.At present,there is few large-scale and long-term follow-up clinical researches focusing on the correlation between the prognosis of heart failure patients with blood lipids including triglycerides,total cholesterol,high-density lipoprotein cholesterol(HDL-C),or low-density lipoprotein cholesterol(LDL-C)in China.Objective:To reveal the association of all-cause mortality with baseline triglycerides,total cholesterol,HDL-C,and LDL-C in heart failure patients.Methods:This study enrolled heart failure patients admitted to the Heart Failure Care Unit of Fuwai Hospital from 2008 to 2018.Kaplan-Meier analysis,Cox regression,Cstatistic,net reclassification improvement and integrated discrimination improvement were used to evaluate the incremental predictive value of baseline triglycerides,total cholesterol,HDL-C,and LDL-C for all-cause mortality in heart failure.Results:This study enrolled 2838 hospitalized patients with heart failure;71.4%were male and the mean age was 56.82±15.99 years.The median follow-up time was 976 days,and mortality occurred in 1120 patients(39.7%).After adjusting for clinical features,etiologies,complications,laboratory examination and medication,triglyceride,HDL-C,and LDL-C were not significantly associated with all-cause death as continuous variables.For per 1 unit increase in total cholesterol,the adjusted risk of all-cause death decreased by 7%[hazard ratio(HR):0.93,95%confidence interval(CI):0.87-0.99,P=0.03].After dividing triglycerides,total cholesterol,HDL-C,and LDL-C into quartiles,P for trend for the association of all-cause mortality with triglycerides,total cholesterol,HDL-C,and LDL-C was 0.049,0.01,0.35,and 0.09 respectively.However,addition of the quartiles of triglyceride,total cholesterol HDL-C or LDL-C did not increase the prognostic value of the origin model.Conclusion:Low baseline triglyceride level was associated with an increased all-cause mortality in heart failure patients.Background:Lower cholesterol levels are found associated with increased mortality in heart failure patients.The results of the first section of this study found a negative relationship between baseline serum total cholesterol level and all-cause mortality in patients with heart failure.Remnant cholesterol is all cholesterol in serum except LDL-C and HDL-C.Studies have found that remnant cholesterol is related to the occurrence and prognosis of various cardiovascular diseases,but the prognostic role of remnant cholesterol in heart failure remains unclear.Objective:To reveal the relationship between the baseline remnant cholesterol level and all-cause mortality in heart failure patients.Methods:This study enrolled 2823 patients hospitalized for heart failure.Kaplan-Meier analysis,Cox regression,C-statistic,NRI and IDI were used to evaluate prognostic value of remnant cholesterol for all-cause mortality in heart failure.Results:The mortality rate was lowest in the fourth quartile of remnant cholesterol,which had an adjusted HR for death of 0.56(95%CI:0.46,0.68)relative to the first quartile.Per unit increase in the level of remnant cholesterol was associated with a 41%decrease risk of all-cause mortality(HR=0.59,95%CI:0.47-0.73,P<0.01)after adjustment.Compared with the first quartile,HR adjusted for all-cause mortality in the second,third,and fourth quartile of remnant cholesterol was 0.71(95%CI:0.60-0.85,P<0.01),0.64(95%CI:0.53-0.77,P<0.01),and 0.56(95%CI:0.56,P<0.01),respectively(P for trend<0.01).A refinement in risk prediction was observed after adding remnant cholesterol quartile to the original model(ΔC-statistic=0.010,95%CI:0.003-0.017;net reclassification index=0.036,95%CI:0.003-0.070;integrated discrimination improvement=0.025,95%CI:0.018-0.033;all P<0.01).Conclusion:Low remnant cholesterol level was associated with an increased all-cause mortality in heart failure patients.Addition of remnant cholesterol quartile improved the predictive value over traditional risk factors.Background:Malnutrition is common in patients with heart failure and is associated with poor prognosis.The prognostic nutritional index(PNI)is calculated based on serum albumin level and lymphocyte count.Lower PNI indicates worse nutritional status.PNI has been shown to be associated with poor prognosis in a variety of diseases.Lipid level is closely related to nutrition level.However,it is not clear whether the prognostic effect of PNI in heart failure is affected by lipid level.Objective:To access the association between baseline PNI and all-cause death in heart failure patients with different triglyceride,total cholesterol,LDL-C,HDL-C and remnant cholesterol levels.Methods:Hospitalized patients with heart failure were included in this study.KaplanMeier analysis and Cox regression were used to evaluate the prognostic value of PNI in heart failure patients with different serum lipids levels.Results:A total of 2925 patients with heart failure were included in this study,71.5%of whom were male.The mean age of the patients was 56.69±15.95 years.In all patients,the mean value of PNI was 48.24±7.12,the maximum value was 77.25,and the minimum value was 19.50.At a median follow-up of 967 days,all-cause mortality occurred in 1177(41.7%)patients.Kaplan-Meier curves showed that patients in the first quartile of PNI had the highest risk of all-cause mortality and those in the fourth quartile had the lowest risk of all-cause mortality.Multivariate Cox regression analysis showed a negative correlation between PNI and all-cause mortality(HR:0.95,95%CI:0.940.96,P<0.01).After adjusting for other factors,compared with patients in the first quartile of PNI,HR in the second,third,and fourth quartile were 0.63(95%CI:0.540.74,P<0.01),0.51(95%CI:0.43-0.60,P<0.01),and 0.44(95%CI:0.36-0.53,P<0.01).Subgroup analysis found that PNI was negatively associated with all-cause mortality in heart failure patients with different triglyceride,total cholesterol,LDL-C,HDL-C and remnant cholesterol levels.Conclusion:PNI was negatively correlated with all-cause mortality in patients with heart failure,and its prognostic value on all-cause mortality was not affected by serum lipid levels.Background:Insulin plays an important role in the regulation of myocardial energy metabolism.Recent studies have shown that insulin resistance plays a protective role in heart failure.Triglyceride/high-density cholesterol-lipoprotein ratio(TG/HDL-C)and triglyceride-glucose(TyG)index have been proved to be correlated with insulin resistance in a variety of populations,which can be used for clinical evaluation of insulin sensitivity.However,there are few studies focusing on the correlations between TG/HDL-C and TyG index and the prognoses in patients with heart failure,especially in patients with different left ventricular ejection fraction(LVEF).Objective:To reveal the relationship of baseline TG/HDL-C and TyG index with allcause mortality in heart failure patients.Methods:This study enrolled 2823 patients hospitalized for heart failure.Kaplan-Meier analysis and Cox regression were used to evaluate prognostic values of baseline TG/HDL-C and TyG index for all-cause mortality in heart failure.Results:Among heart failure patients with LVEF)40%,compared with the first quartile of TG/HDL-C,the adjusted HR of all-cause death in the second quartile,third quartile and fourth quartile of TG/HDL-C were 0.68(95%CI:0.52-0.90,P<0.01),0.54(95%CI:0.40-0.74,P<0.01)and 0.70(95%CI:0.56-0.87,P<0.01),respectively.Compared with patients with the first quartile of TyG index,the adjusted HR of all-cause death in the second,third,and fourth quartile were 0.68(95%CI:0.52-0.90,P<0.01),0.54(95%CI:0.40-0.74,P<0.01),and 0.70(95%CI:0.56-0.87,P<0.01).However,in patients with LVEF<40%,there was no significant correlation between TG/HDL-C or TyG index and all-cause death.Conclusion:The prognostic values of TG/HDL-C and TyG index for all-cause mortality were different in heart failure patients with different LVEF.Increased TG/HDL-C and TyG index were associated with reduced all-cause mortality risk in heart failure patients with LVEF≥40%,but not in patients with LVEF<40%.Background:Light chain cardiac amyloidosis is the most common type of cardiac amyloidosis.The prognosis of light chain cardiac amyloidosis is very poor,and the pathophysiological mechanism has not been fully elucidated.Untargeted metabolomics allows high-throughput determination of metabolites in samples,and can be used to find the metabolic differences between light chain cardiac amyloidosis and other kinds of heart failure to explore the metabolic pathways and changes related to light chain cardiac amyloidosis.Objective:To explore metabolic differences between heart failure patients with light chain cardiac amyloidosis and patients with other kinds of heart failure without light chain cardiac amyloidosis by untargeted metabolomics.Methods:43 patients with heart failure admitted to the heart failure care unit of Fuwai Hospital who were first diagnosed with light chain cardiac amyloidosis by myocardial biopsy were included.63 heart failure patients who were excluded from cardiac amyloidosis were enrolled as controls.The serum metabolites of patients were detected by high performance liquid chromatography-mass spectrometry,and the differential metabolites between groups were detected by principal component analysis and partial least squares-discriminant analysis(PLS-DA).Finally,KEGG metabolic pathway enrichment analysis was performed on the screened differential metabolites.Results:The mean age of patients with light chain cardiac amyloidosis was 59.30±11.04 years,and 74.6%of them were male.The mean age of patients in the control group was 45.97±15.95 years,and 74.4%of them were male.A total of 355 differential metabolites with the variable important in projection of the first two principal components of PLS-DA model≥1,differential change ratio≥1.2 or≤0.83 and P value<0.05 were detected.Among them,207 metabolites were up-regulated and 148 metabolites were down-regulated in patients with light chain cardiac amyloidosis.Metabolic enrichment analysis showed that different metabolites were related to the cholesterol metabolism,primary bile acid biosynthesis,bile secretion,biosynthesis of unsaturated fatty acids,tyrosine metabolism,dopaminergic synapse,and ubiquinone and other terpenoid-quinone biosynthesis.Conclusion:The serum untargeted metabolomic characteristics differed remarkably between patients with light chain cardiac amyloidosis and other type of heart failure.