N末端B型钠尿肽原在妇产科心源性与非心源性呼吸困难的临床鉴别价值

目的：通过检测妇产科呼吸困难患者血清N末端B型钠尿肽原（NT—proBNP）水平,探讨NT—proBNP在心源性和非心源性呼吸困难的临床鉴别价值。方法：在对妇产科病房69例急性呼吸困难患者临床干预前抽取静脉血。检测血清NT—proBNP,采用电化学发光免疫分析（ECLIA）法。结果：心源性呼吸困难组患者血清NT—proBNP水平显著高于非心源性呼吸困难组患者（P〈0．01）,其阳性率也显著高于后者（P〈0．01）。以血清NT—proBNP〉100pg／ml为标准诊断心源性呼吸困难时,敏感度、特异度、阳性预测值及阴性预测值分别为：100％、92．9％、95．4％和100％;据血清NT-proBNP〉130pg／ml为标准诊断心源性呼吸困难时,敏感度、特异度、阳性预测值及阴性预测值均为100％。结论：妇产科心源性呼吸困难患者血清NT—proBNP水平显著高于非心源性呼吸困难患者,血清NT-proBNP可作为鉴别心源性与非心源性呼吸困难的一项观察指标,具有敏感性和特异性高的特点。     

N末端脑型钠尿肽定量检测在心力衰竭诊断中的价值

目的评价血清N末端脑型钠尿肽（NT-proBNP）定量检测对不同程度心力衰竭患者的实验室诊断应用价值和血清NT—proBNP水平与心功能问的相关性分析。方法采用电化学发光检测仪Elecsys2010定量检测不同心功状态的心力衰竭患者血清NT—proBNP水平。结果血清NT—proBNP的诊断性实验受试者工作特征曲线的曲线下面积为0．880（P〈0．01），155pg／ml为界值时，其敏感性，特异性均为81％，阳性似然比为4．25，当NT—proBNP水平〉350pg／ml时，阳性似然比可增至14．32。心衰患者血清NT．proBNP水平明显增高，与心功能正常的疾病对照组比较其差异有统计学意义（P〈0．05），血清NT-proBNP水平随着心力衰竭程度加重呈指数增加，其秩相关性系数为0．859（P〈0．01）。采用相同的心功分级标准，但中国汉族和欧洲心力衰竭患者不同心功分级时血清NT-proBNP水平的变化趋势不同。结论血清NT-proBNP定量检测是目前用于评价心衰患者心功能状态最佳实验室指标。NT—proBNP实验室诊断标准的确立必须以本地区本实验室为基础。     

N末端B型钠尿肽原和大内皮素-1对严重心力衰竭患者的预后作用及其与心血管病关系的研究

目的探讨两检测指标血浆N末端B型钠尿肽原（NT—proBNP）和大内皮素-1（big ET-1）之间，两指标与心力衰竭（心衰）伴心房颤动（Af）、心衰伴肺动脉高压（PAH）等心血管病的关系，以及两指标对严重心衰患者半年期预后的预测价值。方法阜外医院严重心衰患者132人，测定他们入院时的血浆LgNT—proBNP和big ET-1浓度（酶联免疫法）以及纽约心脏病协会心功能分级（NYHA分级）、左室射血分数（LVEF）等指标。随访观察患者出院后半年内心血管事件的再发生。结果严重心衰患者132人（NYHAⅢ-Ⅳ级，年龄24～80岁，男83人，女49人，LVEF13％～66％），其血浆LgNT—proBNP与big ET-1呈正相关（r=0．414，P=0．000）。有、无Af的两组间big ET-1水平比较差异有统计学意义（P=0．022）；有、无PAH的两组间LgNT-proBNP和big ET-1浓度差异均有统计学意义（P=0．019，P=0．000）。以big ET-1诊断严重心衰患者伴PAH的ROC曲线下面积为0．74（95％CI：0．65～0．83，P=0．000），以4．09fmol／ml为big ET-1诊断心衰伴PAH的cutoff值时，灵敏度为71．4％，特异度67．8％。经过6个月的随访，132例严重心衰患者中，有20例发生心源性死亡（15．2％），有25例因心脏原因再住院（18．9％）。Cox比例风险模型分析显示，包括了年龄、性别、NYHA分级、LVEF、LgNT-proBNP、big ET-1等指标后，只有NT-proBNP是独立的心脏事件再发生的预后因素，RR为5．30（95％CI：2．07～13．55，P=0．001）。Logistic回归显示也只有NT—proBNP是独立的心源性死亡发生的危险因素，OR为13．67（95％CI：2．59～72．25，P=0．002）。big ET-1、LVEF、NYHA分级等指标对严重心衰患者心血管事件再发生没有预后价值。结论NT—proBNP与big ET-1间可能存在相互作用；严重心衰伴舡的患者可能有内皮细胞损伤和功能异常；big ET-1可辅助诊断严重心衰患者伴发PAH；NT—proBNP可用于严重心衰患者半年期预后的评估，而big ET-1没有此预测价值。     

血浆B型钠尿肽和心钠素在小儿慢性充血性心力衰竭诊断中的价值

目的探讨血浆B型钠尿肽（BNP）、心钠素（ANP）在小儿慢性充血性心力衰竭（CHF）中的诊断价值。方法分别采用酶联免疫吸附试验（ELISA）和放射免疫法检测41例CHF患儿及35名健康体检儿童的血浆BNP和ANP浓度。结果CHF组的血浆BNP、ANP水平均较对照组显著升高（P〈0．01）。纽约心脏学会（NY．HA）Ⅲ、Ⅳ级的CHF患儿血浆BNP、ANP水平显著高于NYHAⅡ级患儿（P〈0．05）,NYHAⅣ级患儿的BNP也显著高于Ⅲ级患儿（P〈0．05）。CHF组血浆BNP、ANP均与左心室舒张末期内径（LVEDD）呈正相关,与左心室射血分数（LVEF）呈负相关,且血浆BNP与LVEDD、LVEF的相关性显著优于ANP（P〈0．01）。结论CHF患儿的血浆BNP及ANP水平升高显著,且与心力衰竭程度关系密切,可以作为临床诊断和心力衰竭分级的一个有效指标。     

B型钠尿肽水平对心力衰竭诊断价值的探讨

目的探讨B型钠尿肽（BNP）在心力衰竭（简称心衰）患者中的检测意义和应用价值。方法选取32例心衰患者、34例非心衰的心脏病患者、32名正常对照组,用酶联免疫方法定量检测血清BNP水平。结果心衰组BNP水平与非心衰组、正常对照组相比差异有统计学意义（P〈0．05）;随着心功能分级级数的增高,BNP水平逐渐升高,Ⅳ级组与Ⅰ～Ⅱ级组、Ⅲ级组比较,差异有统计学意义（P〈0．01）。心衰组治疗后BNP水平与治疗前比较,差异有统计学意义（P〈0．05）。结论测定血清BNP水平有助于心衰患者诊断、病情严重程度和预后的判断。     

血清N末端B型钠尿肽原在心功能评价及慢性充血性心力衰竭诊断中的初步应用

目的　通过观察血清N末端B型钠尿肽原 (NT proBNP)浓度与心功能分级 (NYHA分级 )、左室射血分数 (LVEF)等临床指标之间的关系 ,研究NT proBNP对心功能的评价作用及其在诊断慢性充血性心力衰竭中的初步应用。方法　选择我院 2 0 0 3年 10月至 2 0 0 4年 4月门诊及住院慢性心衰患者 111例 ,正常对照组 39名。采用电化学发光法测定血清NT proBNP浓度 ,超声心动测定受试者LVEF等指标。依据美国纽约心脏病协会 (NYHA)分级方案对心衰患者进行心功能分级。心衰诊断以临床医生依据病史、症状、体征、客观检查等作出的综合判断为金标准。结果　心衰组NT proBNP中位数 (316 5 pg/ml)显著高于对照组 (5 6 2 1pg/ml) (P <0 0 1)。NYHA分级与NT proBNP呈显著正相关 (r =0 818,P <0 0 1) ,LVEF与NT proBNP呈显著负相关 (r =- 0 6 36 ,P<0 0 1)。受试者工作特征 (receiveroperatingcharacteristics,ROC)曲线分析 ,NT proBNP诊断心衰和左室收缩功能不全的诊断界值 (cutoff值 )分别为 12 7 2 pg/ml和 6 6 7pg/ml,此时诊断心衰和左室收缩功能不全的灵敏度和特异度分别为 73%、10 0 %和 91 7%、85 7% ;诊断心衰的阳性预测值为 10 0% ,阴性预测值为 5 7%。结论　NT proBNP可以客观准确评价心功能 ,对心衰及左室收缩     

急诊呼吸困难患者测定B型尿钠肽的诊断价值

目的 评价BNP水平对急诊呼吸困难病因鉴别诊断的意义。方法 呼吸困难患者共85例，比较心源性和肺源性呼吸困难患者的BNP水平、左室射血分数（LVEF）等。将肺源性组分为四个亚组：肺部炎症（A）组、单纯慢性阻塞性肺病（B）组、慢性阻塞性肺病伴右心衰（C）组、肺动脉栓塞（D）组，比较各组的BNP水平。结果 心源性呼吸困难组BNP较肺源性组明显升高（P〈0．001），而LVEF明显低于后者（P〈0．001）。心源性呼吸困难患者LVEF与BNP呈高度负相关（r=-0．663，P〈0．001）。右心功能受累的C、D组BNP值分别都比有心功能未受累的A、B组高（P〈0．05）。结论 对急性呼吸困难患者测定BNP可判别心源性和肿源性病因。在肺源性疾病中，BNP对是否合并右心功能受累有鉴别诊断意义。     

B型钠尿肽对急性呼吸困难病因诊断的临床意义

目的 探讨B型钠尿肽(BNP)对鉴别急性呼吸困难病因的临床意义.方法 213例急性呼吸困难患者行BNP检测,将患者分为心源性急性呼吸困难组(112例)和肺源性急性呼吸困难组(101例),分别比较心源性和肺源性呼吸困难组不同心功能分级(NYHA)之间BNP水平、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)及超敏C反应蛋白(hs-CRP)水平,计算BNP诊断心源性呼吸困难的受试者工作特征(ROC)曲线下面积及最佳界值.结果 心源性呼吸困难组BNP较肺源性组明显升高(P＜0.001),LVEDD也明显高于肺源性组＜0.001),但LVEF明显低于肺源性组(P＜0.001);不同心功能分级亚组之间BNP比较差异有统计学意义(P＜0.01);BNP及hs-CRP与LVEDD呈正相关;心源性呼吸困难患者BNP与LVEF呈高度负相关(r=-0.838,P＜0.001);BNP诊断心源性呼吸困难的ROC曲线下面积为0.926,95%可信区间为0.892～0.960(P＜0.01).BNP鉴别诊断的最佳界值为250 pg/mL,准确性为86%.结论 急性呼吸困难患者BNP的测定有助于心源性或肺源性病因的判定.     

N末端B型脑钠肽前体在心力衰竭中的诊断和预后价值

【目的】探讨N末端B型脑钠肽前体（NT-proBNP）对心力衰竭（简称心衰）的诊断意义以及对心衰的预后价值。【方法】设心衰组65例,对照组92例,测定血浆NT—ProBNP、左室射血分数（LVEF）,左室舒张末内径（LVDd）及评价NYHA心功能分级。出院复查一次,随访病人3个月内的再入院率。【结果】①心衰组NYHAⅡ、Ⅲ、Ⅳ级与对照组的血浆lnNT-proBNP水平两两比较有统计学差异（P〈0．01）,心功能越差血浆lnNT—proBNP水平显著升高。②lnNT—proBNP（取自然对数ln）与LVDd呈正相关（r=0．423,P〈0．01）,lnNT—proBNP与LVEF呈负相关（r=-0．407,P〈0．01）。③NT—proBNP诊断心衰的ROC曲线显示,当cut—Off值定为459pg／mL时,正确诊断指数最高（0．578）,此时敏感度76．7％,特异度100％。④心衰患者出院时NT—proBNP升高组45例,正常组20例。升高组3个月内因心衰再住院者20例（44．4％）,正常组2例（10％）。【结论】NT—proBNP是诊断心衰的可靠指标,与心衰的严重程度密切相关,动态观察NT—proBNP变化水平可有效地判断心衰患者的预后。     

不同类型冠心病患者血浆B型钠尿肽水平的变化及其临床意义

目的 观察不同类型冠心病患者血浆B型钠尿肽（BNP）浓度的改变及其与左心室射血分数（LNEF）的相关性,并探讨其临床意义。方法 把经冠状动脉造影证实为冠心病的患者112例作为观察对象,按临床类型分为：急性心肌梗死（AMI）组（38例）,不稳定型心绞痛（UAP）组（50例）,稳定型心绞痛（SAP）组（24例）;对照组为非冠心病患者22例。采用双抗夹心免疫荧光法测定血浆B型钠尿肽（BNP）浓度,并行超声心动图检查评价心功能。比较不同组BNP浓度的差异以及各组BNP水平与LVEF的相关性,并观察AMI组心血管事件发生者与未发生者血浆BNP浓度的差异。结果 AMI组BNP水平明显高于UAP、SAP和对照组（P＜0．01）,UAP组BNP水平明显高于SAP组和对照组（P＜0．01）,SAP和对照组BNP水平无明显差异（P〉0．05）。AMI组和UAP组LVEF与血浆BNP水平均呈明显负相关,AMI组发生心血管事件的患者血浆BNP浓度明显高于未发生者（P〈O．05）。结论 不同类型冠心病患者血浆BNP浓度存在差异,血浆BNP浓度与LVEF有明显的负相关,血浆BNP浓度可预测AMI近期预后。     

Pediatric brain natriuretic peptide and N-terminal pro-brain natriuretic peptide reference intervals

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown to be useful biomarkers for the diagnosis of heart failure. Pediatric reference intervals for these analytes have been reported in part. Previous studies lack large numbers in each group, have not covered all age ranges and have not compared results for BNP with NT-proBNP in simultaneously drawn samples. METHODS: We measured BNP in whole blood using the Biosite Triage point-of-care method and plasma NT-proBNP using the Dade RxL Dimension. We assessed between and within-day precision of both methods and after removing outliers employed the Hoffmann approach to calculate pediatric reference intervals over the age range of 0-21 y. We also compared the 2 methods on simultaneously drawn samples. RESULTS: Reference intervals revealed approximately 20-fold higher 97.5th percentiles for neonates than for children >3 y of age. 97.5th percentiles decreased significantly over the first 3 years of life. As shown by others, the CVs for the automated Dade RxL platform were somewhat lower than those for the POCT method. BNP and NT-proBNP correlated well in simultaneously drawn samples (r=0.947). DISCUSSION: Reference intervals for BNP and NT-proBNP are far higher in neonates and infants than in children older than three years of age. The reasons for this are unknown but resemble the elevated CK-MBs and troponins also found in neonates, although the 97.5th percentiles for these latter 2 cardiac markers decrease more rapidly to values found in older children by 6 months of age.     

Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.     

Atrial natriuretic peptide stability

ObjectiveAtrial natriuretic peptide (ANP) is a key regulator in the homeostasis of water excretion and has emerged as an important prognostic marker for symptomatic chronic heart failure (CHF). The stability of ANP represents a crucial factor in assessing its use as a cardiac biomarker. Accordingly, we assessed the stability of ANP in blood samples collected from healthy controls and CHF subjects for a 12 month period.MethodsBlood samples from 10 healthy controls and 12 symptomatic CHF subjects with left ventricular systolic dysfunction were drawn. Determination of plasma ANP was performed by a standardized radioimmunoassay protocol.ResultsThe ANP levels of healthy subjects were 68.5 ± 11.6 pg/mL at baseline and 69.9 ± 17.2 pg/mL at 12 months (p = 0.71). The ANP concentrations of CHF subjects were 199.25 ± 44.8 pg/mL at baseline and 197.83 ± 47.4 pg/mL at 12 months (p = 0.70) respectively.ConclusionANP is a stable molecule with no evidence of degradation when stored at ? 80 °C.     

Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75±0.06. However, NT-proBNP (AUC: 0.67±0.07) and NT-proANP (AUC: 0.69±0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83±0.06. NT-proBNP showed only a slightly smaller AUC (0.79±0.07). The AUC for NT-proANP was significantly smaller (0.65±0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: −0.472, p<0.001; NT-proBNP: −0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.     

脑钠肽前体及氨基末端脑钠肽前体基因的克隆与表达

目的在大肠杆菌中表达脑钠肽前体(proBNP)及氨基末端前体蛋白(NT-proBNP)。方法采用分子生物学技术构建重组质粒PGEX-20T-proBNP和PGEX-20T-NT-proBNP,分别对其进行PCR、双酶切和测序鉴定,然后将已测序鉴定的包含两种重组质粒的工程菌,转化至大肠杆菌BL21菌中表达脑钠肽前体及氨基末端前体蛋白,并用Western-blot鉴定纯化的重组蛋白。结果在大肠杆菌中成功的表达脑钠肽前体及氨基末端前体蛋白,两种蛋白均以可溶性形式表达,更有利于保存其生物学活性。结论两种蛋白的成功表达将有利于后续的单抗制备及检测试剂盒的开发奠定基础。     

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF ( n =12) and controls ( n =12) were investigated. Plasma ANP and BNP levels were determined every 2 min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76 pmol/l; controls, 0.75 pmol/l; P <0.01. BNP: CHF, 3.24 pmol/l; controls, 0.23 pmol/l; P <0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.