血清肝功能指标与心力衰竭患者预后的相关性研究
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摘要
目的：评价血清蛋白浓度与心力衰竭患者预后相关性,同时评价血清白蛋白浓度是否可以提供独立于NT-proBNP以外的预后信息。
方法：顺序入选2009年1月全2010年11月于阜外医院住院的心力衰竭患者,左室射血分数(LVEF)<45%,纽约心功能分级(New York Heart Association class)Ⅱ-Ⅳ级。排除标准：急性冠脉综合征；急性心肌炎；肝脏及胆道疾病；肾功不全,血清肌酐265μJmol/L及以上；合并其他非心源性疾病,预期生存期限少于两年,如恶性肿瘤等；药物引起的肝功能障碍；严重感染,如感染性心内膜炎、肺感染等；其他严重的全身性疾病。收集并记录临床资料,如患者症状和体征,胸部X线检查、心脏超声检查,同时给与血常规、生化系列、NT-proBNP等血液学检验,记录患糟住院期间用药情况。患者出院后,由专人对患者本人或家属进行电话或见面随访,记录患者出院后的用药情况、生存情况、以及再住院。本研究的终点事件为患者出院后因心力衰竭加重再住院、死亡和安置CRT/CRT-D、心脏移植术。
结果：共顺序入选心力衰竭患者385名。在单变量分析当中中,有意义的临床变量分别为血清总胆红素(T-Bil)、血清直接胆红素(D-Bil)、血清白蛋白浓度、心率(HR)、NYHA分级、血浆NT-proBNP浓度、血清肌酐浓度、血常规淋巴细胞计数、血常规中性粒细胞计数、血清钠离子浓度、血清氯离子浓度、血清尿酸浓度、左室射血分数(LVEF)、右室内径(RV)和左房内径(LA)。而接下来的多变量分析表明,与试验人群出院后心脏性事件发生有独立相关性的临床变量为血清白蛋白浓度(HR0.96,C10.94-0.99,P=0.02)、血清肌酐(HR1.01,CI1.00-1.01,P<0.01)、血清钠离子浓度(HR0.92,C10.88-0.97,P<0.01)、血清总胆红素(HR1.01,CI1.00-1.02, P<0.01)、NT-proBNP(HR1.01,C11.00-1.02,P=0.01)。在Kaplan-Meier分析中,将人群以血清白蛋白中位数和NT-proBNP中位数将人群分为2组,发现无心脏事件生存率在低NT-proBNP、高血清白蛋白浓度的组显著高于各自相对的浓度高于中位数或低于中位数的另外1组。将试验人群以血清白蛋白中位数和血浆NT-proBNP中位数为分界线,将实验人群分为4组,以检验血清白蛋白浓度是否可以提供NT-proBNP以外的预后信息。结果是,NT-proBNP高于中位数而血清白蛋白浓度低于中位数的组别(n=128)发生心脏事件的风险比为4组中最高(HR2.89,CI1.90-4.40,P<0.001),NT-proBNP高于中位数而血清白蛋白也高于中位数的组别(n=74)发生心脏事件的风险比(HR2.50,CI1.55-4.04,P<0.001)仅次于NT-proBNP高于中位数而血清白蛋白浓度低于中位数的组,接下来是NT-proBNP低于中位数,而血清白蛋白也低于中位数的组别(n=68),风险比为2.12(CI1.30-3.45,P<0.01),且各组结果均具有统计学意义。
结论：血清白蛋白浓度是心力衰竭患者预后的有效预测因素,同时可以提供NT-proBNP以外的独立预测信息。
目的：评价血清胆红素浓度与心力哀竭患者预后相关性,同时评价血清胆红素浓度是否可以提供独立于NT-proBNP以外的预后信息。
方法：顺序入选2009年1月至2010年12月于阜外医院住院的心力衰竭患者,左室射血分数(LVEF)<45%,纽约心功能分级(New York Heart Association class) Ⅱ-Ⅳ级。排除标准：急性冠脉综合征；急性心肌炎；肝朋及胆道疾病；肾功不全,血清肌酐265μmol/L及以上；合并其他非心源性疾病,预期生存期限少于两年,如恶性肿瘤等；药物引起的肝功能障碍；严重感染,如感染性心内膜炎、肺感染等；其他严重的全身性疾病。收集并记录临床资料,如患者症状和体征,胸部x线检查、心脏超声检查,同时给与血常规、生化系列、NT-proBNP等血液学检验,记录患者住院期间用药情况。患者出院后,由专人对患者本人或家属进行电话或见面随访,记录患者出院后的用药情况、生存情况、以及再住院。本研究的终点事件为患者出院后因心力哀竭加重再住院、死亡和安置CRT/CRT-D、心脏移植术。
结果：共顺序入选心力衰竭患者392名。在单变量分析当中,有意义的临床变量分别为血清总胆红素(T-Bil)、血清直接胆红素(D-Bil)、血清白蛋白浓度、心率(HR)、NYHA分级、血浆NT-proBNP、血清肌酐浓度、血常规淋巴细胞计数、血常规中性粒细胞计数、血清钠离了浓度、血清氯离子浓度、血清尿酸浓度、左室射血分数(LVEF).右室内径(RV)和左房内径(LA)。多变量分析得出对心脏性事件有独立相关性的变量是血清肌酐浓度(P=0.001,HR1.009,C11.004-1.014)、血清钠离子浓度(P=0.001,HR0.912, C10.863-0.964)、血清总胆红素(P=0.017,HR1.009,C11.002-1.017)、血清直接胆红素(P=0.011,HR1.021,CI1.005-1.037)、NT-proBNP(P=0.001,HR1.014,C11.006-1.022)。分别选取血清总胆红素浓度中位数与血浆NT-proBNP的中位数为界限,将试验人群分为4个亚组；同样的方法用于和血清直接胆红素浓度和NT-proBNP分层,再次将人群分为4个亚组。结果得到,NT-proBNP和血清总胆红素均高于中位数的亚组(HR1.668,p=0.004,C11.180-2.414)、NT-proBNP和血清直接胆红素浓度均高于中位数的亚组风险比(HR2.748,P<0.001,C11.859-4.060)分别为4个亚组中最高。
结论：血清胆红素浓度是心力衰竭患者预后的有效预测因素,同时可以提供NT-proBNP以外的独立预测信息。
Objective
To evaluate the effect of serum albumin on prognosis and the power of albumin adding information to NT-proBNP in a Chinese cohort of heart failure.
Methods
385consecutive patients (male vs. female:292vs.93; mean age:54.89±14.41years; NYHA class Ⅱ-Ⅴ) admitted for heart failure exacerbation with LVEF≤45%were enrolled. Excluded criteria:acute coronary syndrome, acute myocarditis, hepatobiliary diseases, creatinine265μmol/L or more, life expectancy less than2years caused by non-cardiac disease (e.g. malignancy), drug-induced liver dysfunction, severe infection(such as infective endocarditis, severe pneumonia, etc.), and other serious systemic diseases. Biochemical data were measured at baseline. The endpoint was defined as cardiac death or rehospitalization for aggravated heart failure. Follow-up period was25±7months.
Results
In the univariate analysis, the significant clinical variables were total bilirubin (T-Bil), direct bilirubin (D-Bil), heart rate, NYHA functional class, NT-proBNP, creatinine, lymphocytes count, neutrophil count, serum sodium concentration, serum chloride concentration, uric acid concentration (UA), LVEF, size of right ventricle (RV) and size of left atrium (LA). Multivariate analysis in a Cox proportional hazard model revealed serum albumin was an independent predictor for adverse prognosis (HR0.96,CI0.94-0.99, P=0.02), and other independent risk factors were serum creatinine (HR1.01,CI1.00-1.01,P<0.01), serum sodium (HR0.92, CI0.88-0.97, P<0.01), NT-proBNP (HR1.01,CI1.00-1.02,P=0.01), and serum T-bil (HR1.01,CI1.00-1.02, P<0.01). In the process we testified the additional role of albumin on prognosis of heart failure patients, we stratified the whole population into4groups according to the median of serum albumin (40.20g/L) and NT-proBNP (2125.50fmol/ml), using cox-proportion hazard model to calculate the hazard risk of each group respectively. Then we found that patients with higher NT-proBNP and lower albumin than median (n=128) had the highest risk for cardiac events (HR2.890, CI1.90-4.40, P<0.001), Meanwhile, the hazard ratio of the group (n=74) with NT-proBNP>2125.50fmol/ml and albumin>40.20g/L was2.497(CI1.55-4.04, P<0.01). The hazard ratio of the group (n=68) with NT-proBNP<2125.50fmol/ml and albumin<40.20g/L was2.119(CI1.30-3.45, P<0.01).
Conclusion
Serum albumin is a useful prognosis indicator for heart failure and it adds important information to NT-proBNP.
Objective
To evaluate the effect of serum T-bil and D-bil on prognosis of heart failure in Chinese population and testify the power of serum T-bil and D-bil adding information to NT-proBNP in a Chinese cohort of heart failure.
Methods
392consecutive patients with heart failure exacerbation admitted to Fuwai Hospital were enrolled. Plasma concentrations of NT-proBNP, serum T-bil, D-bil and other biochemical categories were measured at baseline. The endpoint was defined as cardiac death and rehospitalization for aggravated heart failure.
Results
In the univariate analysis, the significant clinical variables were T-Bil, D-Bil, heart rate, NYHA class, NT-proBNP, creatinine, lymphocytes count, neutrophil count, serum sodium, serum chloride, uric acid (UA), left ventricular ejection fraction (LVEF), the size of right ventricular and size of left atrium. Cox proportional hazard analysis revealed that serum T-Bil (HR1.009, p=0.017, CI1.002-1.017) and D-bil (HR1.021, p=0.011, CI1.005-1.037) were independent predictors of subsequent cardiac events after hospital discharge. When the cohort was stratified according to median T-bil and NT-proBNP concentrations, and to median D-bil and NT-proBNP concentrations, respectively, Cox proportional-hazards regression analyses showed the highest risk for cardiac events in patients with both increased T-bil and NT-proBNP (HR1.668,p=0.004,CI1.180-2.414), and increased D-bil and NT-proBNP (HR2.748,P<0.001,CI1.859-4.060).
Conclusion
Our study demonstrates that serum T-bil and D-bil are independent prognosis indicator and increased serum T-bil and D-bil concentrations provide prognosis information in addition to NT-proBNP measurement for patients with heart failure.
方法：顺序入选2009年1月全2010年11月于阜外医院住院的心力衰竭患者,左室射血分数(LVEF)<45%,纽约心功能分级(New York Heart Association class)Ⅱ-Ⅳ级。排除标准：急性冠脉综合征；急性心肌炎；肝脏及胆道疾病；肾功不全,血清肌酐265μJmol/L及以上；合并其他非心源性疾病,预期生存期限少于两年,如恶性肿瘤等；药物引起的肝功能障碍；严重感染,如感染性心内膜炎、肺感染等；其他严重的全身性疾病。收集并记录临床资料,如患者症状和体征,胸部X线检查、心脏超声检查,同时给与血常规、生化系列、NT-proBNP等血液学检验,记录患糟住院期间用药情况。患者出院后,由专人对患者本人或家属进行电话或见面随访,记录患者出院后的用药情况、生存情况、以及再住院。本研究的终点事件为患者出院后因心力衰竭加重再住院、死亡和安置CRT/CRT-D、心脏移植术。
结果：共顺序入选心力衰竭患者385名。在单变量分析当中中,有意义的临床变量分别为血清总胆红素(T-Bil)、血清直接胆红素(D-Bil)、血清白蛋白浓度、心率(HR)、NYHA分级、血浆NT-proBNP浓度、血清肌酐浓度、血常规淋巴细胞计数、血常规中性粒细胞计数、血清钠离子浓度、血清氯离子浓度、血清尿酸浓度、左室射血分数(LVEF)、右室内径(RV)和左房内径(LA)。而接下来的多变量分析表明,与试验人群出院后心脏性事件发生有独立相关性的临床变量为血清白蛋白浓度(HR0.96,C10.94-0.99,P=0.02)、血清肌酐(HR1.01,CI1.00-1.01,P<0.01)、血清钠离子浓度(HR0.92,C10.88-0.97,P<0.01)、血清总胆红素(HR1.01,CI1.00-1.02, P<0.01)、NT-proBNP(HR1.01,C11.00-1.02,P=0.01)。在Kaplan-Meier分析中,将人群以血清白蛋白中位数和NT-proBNP中位数将人群分为2组,发现无心脏事件生存率在低NT-proBNP、高血清白蛋白浓度的组显著高于各自相对的浓度高于中位数或低于中位数的另外1组。将试验人群以血清白蛋白中位数和血浆NT-proBNP中位数为分界线,将实验人群分为4组,以检验血清白蛋白浓度是否可以提供NT-proBNP以外的预后信息。结果是,NT-proBNP高于中位数而血清白蛋白浓度低于中位数的组别(n=128)发生心脏事件的风险比为4组中最高(HR2.89,CI1.90-4.40,P<0.001),NT-proBNP高于中位数而血清白蛋白也高于中位数的组别(n=74)发生心脏事件的风险比(HR2.50,CI1.55-4.04,P<0.001)仅次于NT-proBNP高于中位数而血清白蛋白浓度低于中位数的组,接下来是NT-proBNP低于中位数,而血清白蛋白也低于中位数的组别(n=68),风险比为2.12(CI1.30-3.45,P<0.01),且各组结果均具有统计学意义。
结论：血清白蛋白浓度是心力衰竭患者预后的有效预测因素,同时可以提供NT-proBNP以外的独立预测信息。
目的：评价血清胆红素浓度与心力哀竭患者预后相关性,同时评价血清胆红素浓度是否可以提供独立于NT-proBNP以外的预后信息。
方法：顺序入选2009年1月至2010年12月于阜外医院住院的心力衰竭患者,左室射血分数(LVEF)<45%,纽约心功能分级(New York Heart Association class) Ⅱ-Ⅳ级。排除标准：急性冠脉综合征；急性心肌炎；肝朋及胆道疾病；肾功不全,血清肌酐265μmol/L及以上；合并其他非心源性疾病,预期生存期限少于两年,如恶性肿瘤等；药物引起的肝功能障碍；严重感染,如感染性心内膜炎、肺感染等；其他严重的全身性疾病。收集并记录临床资料,如患者症状和体征,胸部x线检查、心脏超声检查,同时给与血常规、生化系列、NT-proBNP等血液学检验,记录患者住院期间用药情况。患者出院后,由专人对患者本人或家属进行电话或见面随访,记录患者出院后的用药情况、生存情况、以及再住院。本研究的终点事件为患者出院后因心力哀竭加重再住院、死亡和安置CRT/CRT-D、心脏移植术。
结果：共顺序入选心力衰竭患者392名。在单变量分析当中,有意义的临床变量分别为血清总胆红素(T-Bil)、血清直接胆红素(D-Bil)、血清白蛋白浓度、心率(HR)、NYHA分级、血浆NT-proBNP、血清肌酐浓度、血常规淋巴细胞计数、血常规中性粒细胞计数、血清钠离了浓度、血清氯离子浓度、血清尿酸浓度、左室射血分数(LVEF).右室内径(RV)和左房内径(LA)。多变量分析得出对心脏性事件有独立相关性的变量是血清肌酐浓度(P=0.001,HR1.009,C11.004-1.014)、血清钠离子浓度(P=0.001,HR0.912, C10.863-0.964)、血清总胆红素(P=0.017,HR1.009,C11.002-1.017)、血清直接胆红素(P=0.011,HR1.021,CI1.005-1.037)、NT-proBNP(P=0.001,HR1.014,C11.006-1.022)。分别选取血清总胆红素浓度中位数与血浆NT-proBNP的中位数为界限,将试验人群分为4个亚组；同样的方法用于和血清直接胆红素浓度和NT-proBNP分层,再次将人群分为4个亚组。结果得到,NT-proBNP和血清总胆红素均高于中位数的亚组(HR1.668,p=0.004,C11.180-2.414)、NT-proBNP和血清直接胆红素浓度均高于中位数的亚组风险比(HR2.748,P<0.001,C11.859-4.060)分别为4个亚组中最高。
结论：血清胆红素浓度是心力衰竭患者预后的有效预测因素,同时可以提供NT-proBNP以外的独立预测信息。
Objective
To evaluate the effect of serum albumin on prognosis and the power of albumin adding information to NT-proBNP in a Chinese cohort of heart failure.
Methods
385consecutive patients (male vs. female:292vs.93; mean age:54.89±14.41years; NYHA class Ⅱ-Ⅴ) admitted for heart failure exacerbation with LVEF≤45%were enrolled. Excluded criteria:acute coronary syndrome, acute myocarditis, hepatobiliary diseases, creatinine265μmol/L or more, life expectancy less than2years caused by non-cardiac disease (e.g. malignancy), drug-induced liver dysfunction, severe infection(such as infective endocarditis, severe pneumonia, etc.), and other serious systemic diseases. Biochemical data were measured at baseline. The endpoint was defined as cardiac death or rehospitalization for aggravated heart failure. Follow-up period was25±7months.
Results
In the univariate analysis, the significant clinical variables were total bilirubin (T-Bil), direct bilirubin (D-Bil), heart rate, NYHA functional class, NT-proBNP, creatinine, lymphocytes count, neutrophil count, serum sodium concentration, serum chloride concentration, uric acid concentration (UA), LVEF, size of right ventricle (RV) and size of left atrium (LA). Multivariate analysis in a Cox proportional hazard model revealed serum albumin was an independent predictor for adverse prognosis (HR0.96,CI0.94-0.99, P=0.02), and other independent risk factors were serum creatinine (HR1.01,CI1.00-1.01,P<0.01), serum sodium (HR0.92, CI0.88-0.97, P<0.01), NT-proBNP (HR1.01,CI1.00-1.02,P=0.01), and serum T-bil (HR1.01,CI1.00-1.02, P<0.01). In the process we testified the additional role of albumin on prognosis of heart failure patients, we stratified the whole population into4groups according to the median of serum albumin (40.20g/L) and NT-proBNP (2125.50fmol/ml), using cox-proportion hazard model to calculate the hazard risk of each group respectively. Then we found that patients with higher NT-proBNP and lower albumin than median (n=128) had the highest risk for cardiac events (HR2.890, CI1.90-4.40, P<0.001), Meanwhile, the hazard ratio of the group (n=74) with NT-proBNP>2125.50fmol/ml and albumin>40.20g/L was2.497(CI1.55-4.04, P<0.01). The hazard ratio of the group (n=68) with NT-proBNP<2125.50fmol/ml and albumin<40.20g/L was2.119(CI1.30-3.45, P<0.01).
Conclusion
Serum albumin is a useful prognosis indicator for heart failure and it adds important information to NT-proBNP.
Objective
To evaluate the effect of serum T-bil and D-bil on prognosis of heart failure in Chinese population and testify the power of serum T-bil and D-bil adding information to NT-proBNP in a Chinese cohort of heart failure.
Methods
392consecutive patients with heart failure exacerbation admitted to Fuwai Hospital were enrolled. Plasma concentrations of NT-proBNP, serum T-bil, D-bil and other biochemical categories were measured at baseline. The endpoint was defined as cardiac death and rehospitalization for aggravated heart failure.
Results
In the univariate analysis, the significant clinical variables were T-Bil, D-Bil, heart rate, NYHA class, NT-proBNP, creatinine, lymphocytes count, neutrophil count, serum sodium, serum chloride, uric acid (UA), left ventricular ejection fraction (LVEF), the size of right ventricular and size of left atrium. Cox proportional hazard analysis revealed that serum T-Bil (HR1.009, p=0.017, CI1.002-1.017) and D-bil (HR1.021, p=0.011, CI1.005-1.037) were independent predictors of subsequent cardiac events after hospital discharge. When the cohort was stratified according to median T-bil and NT-proBNP concentrations, and to median D-bil and NT-proBNP concentrations, respectively, Cox proportional-hazards regression analyses showed the highest risk for cardiac events in patients with both increased T-bil and NT-proBNP (HR1.668,p=0.004,CI1.180-2.414), and increased D-bil and NT-proBNP (HR2.748,P<0.001,CI1.859-4.060).
Conclusion
Our study demonstrates that serum T-bil and D-bil are independent prognosis indicator and increased serum T-bil and D-bil concentrations provide prognosis information in addition to NT-proBNP measurement for patients with heart failure.
引文
1. Jessup M, Albert NM, Lanfear DE, et al. ACCF/AHA/HFSA 2011 survey results: current staffing profile of heart failure programs, including programs that perform heart transplant and mechanical circulatory support device implantation:a report of the ACCF Heart Failure and Transplant Committee, AHA Heart Failure and Transplantation Committee, and Heart Failure Society of America. J Am Coll Cardiol. May 17 2011;57(20):2115-2124.
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