| BackgroundHeart failure(HF)is a severe manifestation or terminal stage of various heart diseases with high prevalence,hospitalization,and mortality.The precision treatment of patients with HF depends on the accurate assessment of the condition,in which HF biomarkers have a very important role.As the most important biomarker of HF,brain natriuretic peptide(BNP)/N-terminal pro brain natriuretic peptide(NT-proBNP)is of great value in the diagnosis,evaluation of the condition and efficacy,and determination of prognosis.However,BNP/NT-proBNP is limited in clinical application due to some factors such as age,gender,weight,disease,renal function,and medications.It is therefore particularly important to explore novel HF biomarkers to compensate for the limitations of BNP/NT-proBNP or assist with the advancement of BNP/NT-proBNP for HF diagnosis and evaluation.HF not only has cardiac dysfunction,but also affects multiple organs,such as the liver,and can lead to liver dysfunction.In patients with HF,the increase of central venous pressure or the decrease of cardiac output may lead to liver damage,which may lead to changes in liver function indexes such as transaminase,albumin,bilirubin,etc.Previous studies have shown that they are related to the prognosis of HF.However,they cannot evaluate liver function in multiple ways.Albumin-bilirubin(ALBI)score combined with albumin and total bilirubin is a simple,evidence-based and objective method to evaluate the liver function.From the study on the correlation between ALBI score and the detection and prognosis of liver function in patients with hepatocellular carcinoma in 2015,the ALBI score was gradually extended to the correlation with the prognosis of other liver diseases and other system diseases,which included HF.In recent years,studies on the relationship between ALBI score and HF mainly focus on critical HF,acute HF,the prediction of mortality of patients with HF during hospitalization,and the prediction of prognosis of patients with HF receiving cardiac resynchronization therapy.There are no studies on the prognosis of overall patients with HF,including chronic HF.And there are no studies on the possible reasons for the correlation between ALBI score and the prognosis of HF,and whether ALBI score is superior to BNP/NT-proBNP in terms of application value.In summary,this study investigated the correlation between ALBI score and prognosis of patients with HF through the following two parts:Part Ⅰ:The predictive value of albumin bilirubin score for long-term mortality in patients with heart failure;Part Ⅱ:Analysis of the correlation between albumin bilirubin score and recovery of cardiac function and cardiac reverse remodeling in patients with chronic HFrEF under standard therapy.Part Ⅰ:The predictive value of albumin bilirubin score for long-term mortality in patients with heart failureObjectives1.To explore the correlation between ALBI score and cardiovascular death in overall patients with HF;2.To explore the correlation between ALBI score and all-cause death in overall patients with HF;3.To explore the predictive value of the ALBI score for cardiovascular death in overall patients with HF.Methods1.Study patients:This study included participants in the The National Health and Nutrition Examination Survey(NHANES)from 2009 to 2018.Patients with HF were defined as who answered "Yes" to "Have doctors or other health professionals told you that you have congestive heart failure?".1.1 Inclusion criteria:(1)Participants in the NHANES from 2009 to 2018;(2)Age≥18 years old;(3)Patients with HF.1.2 Exclusion criteria:(1)Age<18 years old;(2)Absence of HF status or non patients with HF;(3)Absence of albumin or total bilirubin data.2.ALBI score:ALBI score is calculated based on serum albumin and total bilirubin using the formula(log10 total bilirubin[mmol/L]×0.66)+(albumin[g/L]×(-0.085)).Grade 1 is defined by ALBI score≤-2.60,grade 2 is defined by>-2.60 to≤-1.39,and grade 3 is defined by>-1.39.3.Data collection:The gender,age,race,smoking and drinking history,medical history,medication,physical examination data,test results,death and follow-up time of patients with HF were extracted from the official website of NHANES.4.Study outcomes:The primary outcome is cardiovascular death.The secondary outcome is all-cause death.5.Statistical analysis:SPSS 26.0,Graphpad prism 8 and statistical software package R 4.0.1(R Foundation for Statistical Computing,Vienna,Austria)were used to statistically analyze the data.The measurement data subject to normal distribution were expressed as mean±standard deviation(x±s).The measurement data subject to non normal distribution were expressed as median(first quartile,third quartile)[Q2(Q1,Q3)].Independent sample t-test was used for comparison of two groups of data subject to normal distribution,and non parametric test was to non normal distribution.The counting data were expressed by frequency or rate(%),and the chi square test or Fisher’s exact test was used to analyze the comparison between the two groups.Kaplan Meier survival analysis and Cox proportional hazards model were used to analyze the influence of different factors on the change of dichotomous outcome variables over time.Restricted cubic splines were used to analyze the relationship of the dependent variable with the independent variable.The predictive value of variables for outcome events was analyzed using ROC curves.Statistical significance was defined as a 2-tailed P value<0.05.Results1.Baseline characteristics of patients with HF:A total of 845 patients with HF from 2009 to 2018 in NHANES were included in this study,with a mean age of 70(60,79)years and a male proportion of 55.5%.According to the ALBI grade,there were 440 patients with ALBI grade 1 and 405 patients with ALBI grade 2.The patients with ALBI grade 2 had more diabetes and kidney diseases,higher body mass index(BMI),larger waist circumference,lower diastolic blood pressure,lower effective glomerular filtration rate(eGFR),alanine aminotransferase(ALT),aspartate transaminase(AST),albumin(Alb),triglycerides,total cholesterol and high-density lipoprotein cholesterol,and higher total bilirubin(TBIL).And more patients using diuretics.All of which were statistically different.2.Correlation between ALBI score and cardiovascular death and all-cause death in patients with HF:The cardiovascular mortality and all-cause mortality of patients with HF with ALBI grade 2 were significantly higher than those with ALBI grade 1,and there were statistical differences(cardiovascular mortality:8.41%vs 20.00%,P<0.001;all-cause mortality:27.27%vs 42.72%,P<0.001).Kaplan-Meier survival analysis and COX proportional hazards model showed that the higher the ALBI score was,the higher the risk of cardiovascular death and all-cause death were in patients with HF and there was significant statistical difference.The restricted cubic spline curve showed that there was significant positive linear correlation between ALBI score and the risk of cardiovascular and all-cause death.Subgroup analysis showed that there was no statistical difference in the interaction between ALBI score and each subgroup on the risk of cardiovascular death,indicating that the correlation between ALBI score and the risk of cardiovascular death was consistent in each subgroup,and the results were stable.3.Correlation between albumin and total bilirubin and cardiovascular and all-cause death in patients with HF:COX proportional hazards model showed that,as a continuous variable,the higher albumin,the lower the risk of cardiovascular and all-cause death in patients with HF without adjusting or adjusting for related factors.Total bilirubin was not an independent risk factor for cardiovascular and all-cause death in patients with HF.4.The predictive value of ALBI score of patients with HF for cardiovascular death:The area under the curve of ALBI score was 0.643(P<0.001),indicating that ALBI score has statistically significant predictive value for cardiovascular death.Compared with albumin,the predictive value of ALBI score on cardiovascular death was better with statistical difference.Conclusion1.Albumin bilirubin score is an independent risk factor for cardiovascular and all-cause death in overall patients with HF.2.Albumin rather than total bilirubin is an independent risk factor for cardiovascular and all-cause death in overall patients with HF..3.The prognostic value of the albumin bilirubin score for adverse prognosis in overall patients with HF is superior to that of albumin,and can be a simple and reliable index for risk stratification and intervention in prognosis of HF..Part Ⅱ:Analysis of the correlation between albumin bilirubin score and recovery of cardiac function and cardiac reverse remodeling in patients with chronic HFrEF under standard therapyObjectives1.To explore the correlation between albumin bilirubin score and recovery of cardiac function in patients with chronic heart failure with reduced ejection fraction(HFrEF)under standard therapy;2.To explore the correlation between albumin bilirubin score and cardiac reverse remodeling in patients with chronic HFrEF under standard therapy;3.To explore the correlation between albumin bilirubin score and NT-proBNP.Methods1.Study patients:In 2018,based on the national grading diagnosis and treatment mode,Cheeloo Hospital of Shandong University established a "medical circle" with Cheeloo Hospital as the core and conjunction with 62 primary hospitals in Shandong province,which can refer patients with HF between core hospital and primary hospitals.This study included patients with chronic HFrEF who visited "medical circle" from March 2018 to March 2022,including patients who participated in two-way referral and only visited Cheeloo Hospital.1.1 Inclusion criteria:(1)Consistent with the diagnosis of chronic HFrEF(LVEF≤40%);(2)Age≥18 years old.1.2 Exclusion criteria:(1)Age<18 years old;(2)Patients with primary right heart disease;(3)Patients with primary pulmonary hypertension;(4)Complicated with severe liver and kidney disease(eGFR<30ml/min/1.73m2 or aminotransferase is more than 5 times higher than the upper limit of normal),hematopoietic system diseases and tumor;(5)Absence of albumin or total bilirubin data;(6)There are serious adverse reactions and contraindications to HF treatment medications.2.ALBI score:ALBI score is calculated based on serum albumin and total bilirubin using the formula(log 10 total bilirubin[mmol/L]×0.66)+(albumin[g/L]×(-0.085)).Grade 1 is defined by ALBI score≤-2.60,grade 2 is defined by>-2.60 to≤-1.39,and grade 3 is defined by>-1.39.3.Data collection:Collect the information of patients,vital signs,auxiliary examinations,medication and adverse events of initial and follow-up visits.4.Study outcomes:The primary outcome is the changes of cardiac structure and function evaluated by transthoracic echocardiography.And the secondary outcomes are the changes of NT-proBNP and ALBI score.5.Statistical analysis:SPSS 26.0 and Graphpad prism 8 were used to statistically analyze the data.The measurement data subject to normal distribution were expressed as mean±standard deviation(x±s).The measurement data subject to non normal distribution were expressed as median(first quartile,third quartile)[Q2(Q1,Q3)].Independent sample t-test was used for comparison of two groups of data subject to normal distribution,and non parametric test was to non normal distribution.The counting data were expressed by frequency or rate(%),and the chi square test or Fisher’s exact test was used to analyze the comparison between the two groups.Kaplan Meier survival analysis and Cox proportional hazards model were used to analyze the influence of different factors on the change of dichotomous outcome variables over time.Spearman correlation analysis was used for correlation testing.Statistical significance was defined as a 2-tailed P value<0.05.Results1.Baseline characteristics:A total of 229 patients with chronic HFrEF were included in this study,with a mean age of 53(40,63)years,and a male proportion of 72.8%.According to the ALBI grade,there were 177 patients with ALBI grade 1 and 52 patients with ALBI grade 2.More patients with ALBI grade 2 had atrial fibrillation and were NYHA grade Ⅳ.Patients with ALBI grade 2 had lower left ventricular ejection fraction(LVEF),and higher left atrial anteroposterior diameter(LA-ap),right atrial area(RAA),right ventricular anteroposterior diameter(RV-ap)and pulmonary artery systolic pressure(PASP),and higher NT-proBNP,ALT,AST,TBIL,and lower Alb.2.Medication utilization and target dose achievement in patients with chronic HFrEF with different ALBI grades:At baseline and at each follow-up time point,there was no statistical difference in the utilization rate of β-receptor blockers,angiotensin-converting enzyme inhibitor(ACEI)/angiotensin-receptor blocker(ARB)/angiotensin receptor-neprilysin inhibitor(ARNI),mineralocorticoid receptor antagonists(MRA)and sodium-glucose cotransporter 2 inhibitor(SGLT2i).There was statistical difference in the utilization rate of diuretics between the two groups in the 1st month after the first visit.At baseline and at each follow-up time point,there was no statistical difference in the target dose reaching rate of β-receptor blockers and ACEI/ARB/ARNI.Logistic regression results showed that ALBI score was not the influence factor in target dose achievement of β-receptor blockers and ACEI/ARB/ARNI.There was also no statistical difference in the arrival time of target dose achievement of β-receptor blockers and ACEI/ARB/ARNI.3.Changes of ALBI score in patients with chronic HFrEF with different ALBI grades:The ALBI score of patients in both groups significantly reduced from baseline.There was no statistical difference in ALBI score between the two groups at each follow-up time point,except that at baseline and the 1 st month after the first visit.4.Improvement of cardiac function,cardiac remodeling and PASP in patients with chronic HFrEF under standard therapy with different ALBI grades:LA-ap,LVEF and left ventricular end diastolic diameter(LVEDd)of the two groups were significantly improved at 6th and 12th months compared with the baseline,and there was no statistical difference between the two groups at 6th and 12th months.The RAA and PASP of patients with ALBI grade 2 were significantly improved at 6th and 12th months compared with the baseline.And RV-ap was significantly improved at 6th month.There were no significant changes of those in patients with ALBI grade 1.Comparison of the two groups revealed no statistically significant differences in RAA,RV-ap and PASP between the two groups at each follow-up time point except for baseline.5.Correlation between ALBI score and cardiac function,cardiac remodeling and PASP:The correlation test results showed that the ALBI score was significantly negatively correlated with LVEF,and was significantly positively correlated with LA-ap,RAA,RV-ap and PASP,but not with LVEDd.6.Changes of NT-proBNP in patients with chronic HFrEF with different ALBI grades:NT-proBNP in both groups was significantly improved from baseline.Except for the baseline,there was no statistical difference in NT-proBNP between the two groups at each follow-up time point.7.Correlation between ALBI score and NT-proBNP in patients with chronic HFrEF:The results of correlation analysis and linear fitting showed that there was a significant positive correlation between ALBI score and NT-proBNP,and the correlation was higher than Alb and TBIL and has statistical significance.8.Correlation between ALBI score and NT-proBNP and eGFR:NT-proBNP was significantly negatively correlated with eGFR,while ALBI score was not correlated with eGFR,indicating that the level of ALBI score was not influenced by renal function.Conclusion1.Albumin bilirubin score was significantly correlated with LVEF,left atrial diameter,right heart diameter and PASP in patients with chronic HFrEF.2..Baseline albumin bilirubin score does not affect the titration and target dose achievement of medications of guideline-directed medical therapy(GDMT)in patients with chronic HFrEF,and was not associated with recovery of cardiac function or cardiac reverse remodeling.3.Under the standard therapy,the albumin bilirubin score significantly decreased from baseline.It can be used to evaluate the treatment effect.4.Albumin bilirubin score has a significant positive correlation with NT-proBNP and is less affected by renal function.It can be used as an auxiliary evaluation index in patients with heart failure and renal dysfunction,and provide a good supplement to NT-proBNP. |
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