中性粒细胞明胶酶相关脂质运载蛋白和N-末端B型脑钠肽前体水平与慢性心力衰竭关系的研究

目的:观察97例慢性充血性心力衰竭(CHF)患者,血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和N-末端B型脑钠肽前体(NT-proBNP)等指标水平变化,并探讨两者间的相关关系。方法:收集97例CHF患者的临床资料,进行回顾性分析。同期年龄相同体检为健康者50例作为对照组。比较分析疾病组与健康组血浆中NGAL、NT-proBNP,尿素氮(BUN)、肌酐(Cr)、肾小球滤过率(e GFR)以及左心功能指标左心室射血分数(LVEF)。结果:CHF患者血NGAL、血NT-proBNP、BUN和Cr水平明显高于健康对照组(均为P<0.05),而LVEF、e GFR低于对照组(P<0.05),血NGAL、NT-proBNP在各组中水平依次是NYHA-Ⅳ级>NYHA-Ⅲ级>NYHA-Ⅱ级>NYHA-Ⅰ级,各级间差异均有统计学意义(P<0.05)。CHF患者血清NGAL与NT-proBNP呈正相关(r=0.79,P<0.05),LVEF与血浆NGAL、NT-proBNP水平呈负相关(r=-0.36,P<0.05;r=-0.39,P<0.05)。结论:CHF患者血浆NGAL和NT-proBNP水平升高可能与心力衰竭、肾损伤的发展进程有关。     

Admission plasma neutrophil gelatinase associated lipocalin (NGAL) predicts worsening renal function during hospitalization and post discharge outcome in patients with acute heart failure

Abstract

Background: The role of neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF), however less data are available in patients admitted for acute HF.

Methods: We evaluated the role of NGAL in predicting in-hospital worsening renal function (WRF) and post-discharge follow-up during six months period in patients with acute HF. All patients were submitted to creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and B-type natriuretic peptide (BNP) measurement during hospitalization and before discharge.

Results: Patients with chronic kidney dysfunction (CKD) demonstrated higher NGAL respect to subject with preserved renal function (241 ± 218 and 130 ± 80 ng/ml; P = 0.0001). In subgroup that developed WRF during hospitalization, NGAL levels were significantly increased respect to patients without WRF (272 ± 205 versus 136 ± 127 ng/ml; P = 0.0001). A cut off of 134 ng/ml has been related to WRF with good sensibility and specificity (92% and 71% AUC 0.83; P = 0.001). Multivariable Cox regression analysis showed that cut-off of 134 ng/ml was the only marker related to death (HR: 1.75; 95% CI: 1.24–2.45; P < 0.001). Follow-up analysis confirmed that NGAL > 130 ng/ml was associated with adverse events during a six-month period.

Conclusion: Admission NGAL measurement appears a sensible tool for in-hospital WRF prediction as well as an early marker for adverse outcome during post discharge vulnerable phase.     

Estimating the prevalence of elevated plasma neutrophil gelatinase associated lipocalin level in patients with acute coronary syndromes and its association with outcomes

ObjectivesThe principal objective of this study was to estimate the plasma levels of neutrophil gelatinase associated lipocalin (NGAL) in a cohort of patients with acute coronary syndromes (ACS) across their entire spectrum, and to correlate them with outcomes.Methods87 patients with acute coronary syndromes were included in the study. Apart from the routine work up and management, all patients underwent determination of plasma NGAL and serum high sensitivity C reactive protein (HSCRP) levels at admission. The patients were followed up through the hospital stay as well as for one month after discharge for clinical outcomes, and echocardiographic parameters of left ventricular function. Plasma NGAL was studied for its predictive power for various defined outcomes.ResultsPlasma NGAL levels were detectably elevated in 67% of patients with ACS without any significant proportion with renal dysfunction, sepsis or overt infection. Plasma NGAL was the strongest independent predictor of all cause hospital mortality in Cox regression multivariate analysis with an odds ratio of 8.353, p = 0.0237. Plasma NGAL did not correlate with HSCRP, or severity of coronary artery disease (CAD).ConclusionThis is a small study that shows that plasma NGAL in patients admitted with ACS can predict hospital mortality and forms the basis for consideration of this molecule as a possible new risk marker in ACS meriting further and more extensive investigation.     

The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: results from CORONA*

OBJECTIVE: To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. BACKGROUND: Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. METHODS: We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all-cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow-up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points.     

慢性肾脏疾病增加慢性心力衰竭患者死亡率

目的探讨慢性肾脏疾病(CKD)对慢性心力衰竭(CHF)患者死亡率的影响。方法对2007年1月1日至2009年12月31日在北京协和医院心内科住院,年龄≥21岁,临床诊断为心力衰竭,且左心室射血分数(LVEF)≤45%的缺血性(心肌梗死后至少40 d以上)或非缺血性心肌病患者进行回顾性研究,根据肾小球滤过率(eGFR)情况分为两组,一组为eGFR<60 ml.min-1.1.73 m-2(CKD组),另一组为eGFR≥60 ml.min-1.1.73 m-2(对照组),并进行电话随访。结果共筛选242例患者,除外41例不符合入选标准者,对201例进行随访,14例(7%)失访,经过2～41个月[平均(20±9)个月]的随访,共36例(19%)发生全因死亡,包括CKD组21例(30%)和对照组15例(13%)(P=0.003)。结论 CKD增加CHF患者死亡率。合并CKD的CHF患者,积极处理CHF的同时应高度重视CKD处理。     

血清NGAL和Cys C对慢加急性肝衰竭患者并发肝肾综合征早期诊断价值研究

目的 研究血清中性粒细胞明胶酶相关载脂蛋白（NGAL）和光抑素C（Cys-C）诊断慢加急性肝衰竭（ACLF）患者并发肝肾综合征（HRS）的价值。方法 2010年1月~2017年1月收治的204例ACLF患者,并发HRS 58例。采用固相夹心酶联免疫吸附法检测血清NGAL,常规检测血清Cys-C、β2-微球蛋白（β2-MG）。绘制受试者工作特征曲线（ROC）评估血清指标诊断ACLF患者并发HRS的价值。结果 HRS与非HRS患者在性别、病程、BMI、糖尿病、血小板计数、血K⁺、平均动脉压方面比较无显著性差异（P>0.05）,两组在年龄、高血压、冠心病、白细胞计数、白蛋白、蛋白尿、血尿素氮、血Na⁺和Child-Pugh评分方面存在明显差异（P<0.05）;HRS患者NGAL、Cys-C、sCr、β2-MG、BUN水平分别为（64.1±18.4） ng/mL、（3.1±1.1） mg/L、（165.8±25.7） mol/L、（6.3±2.1） mg/L、（12.6±4.3） mmol/L,显著高于无HRS组【（11.5±2.3） ng/mL、（1.2±0.4） mg/L、（62.6±11.4） mol/L、（2.7±1.2） mg/L、（4.1±1.5） mmol/L,P<0.05】;HRS组患者肝损伤程度显著重于无HRS组（P<0.05）;血清 NGAL和Cys-C诊断ACLF并发HRS的敏感度和准确度分别为（89.6%）和（92.1%）,和85.9%和95.4%,显著高于血清sCr、β2-MG或BUN,而NGAL联合Cys-C检测诊断的敏感度和准确度分别为92.1%和96.2%,明显优于血清NGAL或Cys-C单独检测。结论 在ACLF患者中年龄越大,并发HRS的机会越大,病情重的患者血清NGAL和Cys-C水平升高,应用它们联合诊断ACLF患者并发HRS的效能较好,值得进一步研究。     

瑞舒伐他汀对慢性心力衰竭合并肾功能不全患者的疗效观察

目的 观察瑞舒伐他汀治疗慢性心力衰竭合并肾功能不全的临床疗效.方法 回顾性分析2010年2月至2013年2月我院住院治疗的72例慢性心力衰竭合并肾功能不全患者的临床记录资料,所有患者均给予心力衰竭基础治疗,给予瑞舒伐他汀的患者作为治疗组,未给予的患者作为对照组.比较治疗6月后两组患者心功能和肾功能的变化.结果 治疗6个月后,治疗组心功能改善的总有效率显著高于对照组（P＜0.05）;左室射血分数较治疗前明显增高（P＜0.05）,左室舒张末期内径、左室收缩末期内径较治疗前缩小（P＜0.05）,且均优于对照组（P＜0.05）;血尿素氮、肌酐、β2-微球蛋白较对照组明显降低（P＜0.05）.结论 在常规抗心衰治疗的基础上联合使用瑞舒伐他汀,可以改善慢性心力衰竭患者的心功能及肾功能.     

老年脑梗死患者血清中性粒细胞明胶酶脂质运载蛋白及凝集素样氧化型低密度脂蛋白受体-1水平的表达及临床意义

目的分析老年颈内动脉粥样硬化脑梗死患者血清中性粒细胞明胶酶脂质运载蛋白(NGAL)、凝集素样氧化型低密度脂蛋白受体-1(sLox-1)表达及颈动脉内膜改变,探讨其临床意义。方法收集2012年3月至2013年9月在湖南省老年医院神经内科确诊为动脉粥样硬化脑梗死患者70例为A组,颈内动脉粥样硬化患者72例为B组,两组按随机分组法再分为常规治疗组和强化治疗组两个亚组,分别在0周、12周、24周时采用酶联免疫吸附法测定患者血清NGAL、sLox-1水平,并同时测定患者的颈动脉内膜中层厚度和斑块面积,数据结果采用SPSS 17.0软件进行统计分析。结果脑梗死组患者血清中NGAL和sLox-1的表达水平、颈动脉内膜中层厚度及斑块面积均高于动脉硬化组(P0.05),阿托伐他汀治疗24周后强化亚组下降明显(P0.05),且颈动脉内膜中层厚度及斑块面积较前降低(P0.05)。结论血清NGAL及sLox-1参与动脉粥样硬化性脑梗死的发生机制,强化调脂治疗后其表达水平下调。     

Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2 diabetic patients with nephropathy: one year observational follow-up study

We initiated the present work to explore whether neutrophil gelatinase-associated lipocalin (NGAL) could be used to predict the progression of diabetic nephropathy in type-2 diabetic patients. Seventy-four type-2 diabetic patients were divided into normo-, micro- and macro-albuminuria groups according to their 24 h-urinary albumin excreting rate. Serum and urine NGAL, and other clinical parameters were detected. Patients were followed and measurements were repeated 1 year later. An increased tendency of urine NGAL and a decreased tendency of serum NGAL were detected, from normo-albuminuria group to macro-albuminuria group. Serum NGAL was found to rise after follow-up. Moreover, urine NGAL was found to be correlated positively with cystatin C, urea nitrogen, and serum creatinine (SCr), and inversely with glomerular filtration rate (GFR), while serum NGAL correlated negatively with cystatin C and urea nitrogen, at both baseline and follow-up levels. The results indicate that NGAL correlates closely with renal function. Both serum and urine NGAL are sensitive for predicting the progression of type-2 diabetic nephropathy but they may change differently. Serum NGAL may be more useful in early detection and urine NGAL may be more meaningful in renal function assessment. Yi-Hua Yang and Xiao-Jie He contributed equally to the work. Shen-Ren Chen, En-Min Li and Li-Yan Xu are co-corresponding authors.     

Improvement of increased cQTd is associated with heart function in patients with ischemic heart failure

Background Chronic heart failure (CHF) is life-threatening without timely or effective intervention. In this study, we investigated the association between QT dispersion corrected for heart rate (cQTd) and heart function in patients with CHF. Methods From January 2013 to December 2015, we continuously enrolled 240 patients categorized as New York Heart Association functional class (NYHA) III?IV with a left ventricular ejection fraction (LVEF) < 40%. Based on the etiology, the patients were divided into a dilated cardiomyopathy (DCM) group (n = 120) and an ischemic cardiomyopathy (ICM) group (n = 120). Then, based on the cQTd width, the ICM group was divided into two subgroups: a QS group (cQTd ≤ 60 ms, n = 70) and a QL group (cQTd > 60 ms, n = 50). All patients were examined by echocardiography and 12-lead electrocardiography (ECG) at 1, 3, 6, and 12 months after enrollment. Results After one year of optimized medical treatment, patients in both groups showed significant improvement in LVEF and NYHA classification from baseline. However, the cQTd in the ICM group, especially the QL, was significantly shorter than that in the DCM group at each time point. In addition, the cQTd was negatively correlated with LVEF and 6-min walking test and positively correlated with NYHA class in the ICM group. Conclusions The present findings clearly demonstrate that cQTd is a meaningful parameter for assessing heart function in the follow-up of ICM patients.     

慢性心力衰竭合并肾损害患者血清白细胞介素1、白细胞介素6水平的变化及临床意义

目的探讨慢性心力衰竭合并肾损害患者血清白细胞介素1(IL-1)和白细胞介素6(IL-6)水平的变化及其临床意义。方法选取纽约心脏病学会(NYHA)心功能分级在Ⅱ~Ⅳ级的慢性心力衰竭患者220例,测定其血清尿素氮(BUN)、血肌酐(SCr)、N末端B型利钠肽原(NT-pro BNP)及IL-1、IL-6水平,计算肾小球滤过率(e GFR),随机尿检测尿微量白蛋白(MAU),心脏超声测定左室射血分数(LVEF),比较不同心功能患者的IL-1、IL-6、NT-pro BNP、e GFR和MAU,不同肾功能患者的IL-1、IL-6,分析IL-1、IL-6与NYHA心功能分级、NT-pro BNP、LVEF、e GFR及MAU的关系。结果与NYHAⅡ级心功能患者相比,NYHAⅢ~Ⅳ级心功能患者血清IL-1、IL-6、NT-pro BNP水平及MAU升高,e GFR降低(P0.05),NYHAⅣ级心功能患者IL-1、IL-6、NT-pro BNP水平及MAU高于NYHAⅢ级(P0.05)。NYHAⅢ~Ⅳ级心功能患者中,30%≤EF≤50%患者血清IL-1、IL-6、NT-pro BNP水平及MAU高于EF50%患者(P0.05),e GFR低于EF50%患者(P0.05),EF30%患者IL-1、IL-6、NT-pro BNP水平及MAU高于30%≤EF≤50%患者(P0.05)。NYHAⅢ~Ⅳ级心功能患者中,肾功能不全组[e GFR60 m L/(min·1.73 m2)]血清IL-1、IL-6水平高于肾功能正常组[e GFR≥60 m L/(min·1.73 m2)](P0.05)。不同基础疾病的心力衰竭患者之间IL-1、IL-6水平及e GFR比较,差异无统计学意义(P0.05)。血清IL-1、IL-6水平与NYHA心功能分级、NT-pro BNP及MAU呈正相关(P0.05),与e GFR、LVEF呈负相关(P0.05)。结论慢性心力衰竭患者血清炎症因子IL-1、IL-6水平升高,与心力衰竭的严重程度和肾功能受损相关,测定血清IL-1、IL-6水平可能有助于临床心衰病情的评估。     

Association of renal tubular damage with cardio-renal anemia syndrome in patients with heart failure

Background

Cardio-renal anemia syndrome (CRAS) has begun to gather attention as a vicious circle since chronic heart failure (CHF), chronic kidney disease (CKD), and anemia are all able to be caused and exacerbated by each other. However, it remains unclear whether renal tubular damage (RTD), another type of kidney dysfunction, is associated with this vicious circle. The aim of the present study was to assess the association of RTD with CRAS in patients with CHF.

Methods and results

We included 300 consecutive patients with CHF. RTD was defined as a urinary β₂-microglobulin to creatinine ratio ≥ 300 μg/g. Patients with RTD had lower serum iron and higher levels of high sensitivity C-reactive protein than those without it. Multivariate logistic analysis showed that RTD was closely associated with anemia in patients with CHF, after adjustment for confounding factors. During a median period of 1098 days, there were 86 cardiac events, including 14 cardiac deaths and 72 re-hospitalizations for worsening heart failure. Net reclassification improvement was significantly improved by addition of RTD to the model including age, New York Heart Association functional class, brain natriuretic peptide, anemia, and CKD. All patients were divided into 3 groups: CRAS + RTD group, CRAS group, and control group. Kaplan–Meier analysis demonstrated that CRAS + RTD had the greatest risk in patients with CHF.

Conclusions

RTD was associated with normocytic anemia, accompanying iron deficiency and inflammation. RTD added prognostic information to conventional CRAS, suggesting the importance of RTD in cardio-renal anemia interaction.     

血清NGAL联合肌酐早期判断乙型肝炎肝硬化患者并发肝肾综合征的临床价值分析

目的 研究血清中性粒细胞明胶酶相关载脂蛋白（NGAL）联合血清肌酐（sCr）在早期诊断肝炎肝硬化患者并发肝肾综合征（HRS）的临床价值,旨在为提高早期诊断肝炎肝硬化并发肝肾综合征提供有效的诊断依据。方法 2014年3月~2017年3月我院收治的108例乙型肝炎肝硬化患者,回顾性分析其临床资料。发现并发HRS患者45例,非HRS患者63例,另选同期在我院进行健康体检的正常人66例作为对照组。采用固相夹心酶联免疫吸附法检测血清NGAL,采用肌氨酸氧化酶法检测sCr,计算24 h内肌酐清除率（24-Ccr）。采用受试者工作特征曲线（ROC）下面积评价血清NGAL和sCr诊断存在HRS的效能。结果 HRS患者血清NGAL和sCr水平分别为（64.1±18.4） ng/ml和（109.6±24.5） μmol/L,显著高于非HRS组【（10.6±3.1） ng/ml和（88.2±15.7） μmol/L,P<0.05】或正常人【（8.3±2.2） ng/ml和（82.6±14.3） μmol/L,P<0.05】,而非HRS患者血清NGAL和sCr水平与对照组比较无显著差异（P>0.05）;经Spearman相关性分析显示,血清NGAL和sCr水平与24-Ccr呈负相关（r=-0.768,P<0.01;r=-0.721,P<0.01）;应用NGAL和sCr诊断HRS的ROC曲线下的面积为0.895（0.860~0.912）,其灵敏度为82.5%,特异度为83.4%,正确性为75.84%,明显高于血清NGAL或sCr单项检测【ROC_NGAL曲线下面积为0.751（0.708~0.794）,灵敏度为75.3%,特异度为84.5%,正确性为63.84%;ROC_sCr曲线下面积为0.743（0.714~0.772）,灵敏度为73.2%,特异度为66.8%,正确性为56.38%】。结论 应用血清NGAL比sCr能更准确地早期诊断肝炎肝硬化患者并发肝肾综合征,而两者联合检测的灵敏度和特异度更高,可提高早期诊断率。