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。     

Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report

B-type natriuretic peptide (BNP) is a cardiac hormone widely used as a biomarker for heart failure. Here, we present the first report of extremely high levels of immunoreactive BNP caused by formation of macro-proBNP.A 70-year-old woman with left ventricular hypertrophy and normal systolic function presented with extremely high plasma levels of BNP (35,374 pg/ml) and N-terminal proBNP (NT-proBNP; 30,600 pg/ml). Our recently developed proBNP immunoassay showed that nearly 100% of her immunoreactive BNP was proBNP. Polyethylene glycol precipitation tests reported extremely low BNP recovery (1.3%), while protein G addition tests also reported a remarkably low BNP fraction (3.3%). Gel filtration chromatography with normal elution buffer combined with BNP immunoassays showed a BNP peak with a retention time slightly shorter than that of IgG. With acidic elution buffer (pH 3.0), however this peak disappeared and a new BNP peak consistent with glycosylated human proBNP appeared. These results suggest that in this case most BNP immunoreactivity consisted of macro-proBNP, which is an immune complex composed of proBNP and an anti-proBNP autoantibody. Gel filtration chromatography combined with NT-proBNP immunoassays revealed that the NT-proBNP assay cross-reacts with both the proBNP-IgG complex and proBNP. In addition, with acidic buffer, a new large peak appeared with a retention time the same as that of glycosylated NT-proBNP.These results suggest spuriously high levels of BNP and NT-proBNP are caused by macro-proBNP. Macro-NT-proBNP is not detected by the currently available NT-proBNP assay system.     

Analytical performance and diagnostic accuracy of a fully-automated electrochemiluminescent assay for the N-terminal fragment of the pro-peptide of brain natriuretic peptide in patients with cardiomyopathy: comparison with immunoradiometric assay methods for brain natriuretic peptide and atrial natriuretic peptide.

We evaluated the analytical performance of a fully-automated electrochemiluminescence "sandwich" immunoassay method for the N-terminal fragment of the pro-peptide of brain natriuretic peptide (BNP). We then compared the diagnostic accuracy of this method in discriminating between normal subjects and patients with cardiomyopathy with that found with two previously described immunoradiometric assay methods for the assay of atrial natriuretic peptide (ANP) and BNP. We studied 193 consecutive patients (mean age 64.4 +/- 12.3 years, range 20-89 years, including 56 women and 137 men) with chronic cardiomyopathy and a group of 85 healthy subjects (mean age 52.3 +/- 12.0 years, 42 women and 43 men, range 20-79 years). N-terminal fragment of proBNP1-76 (NT-proBNP) was measured with a fully-automated "sandwich" electrochemiluminescence method using an Elecsys 2010 analyzer, while ANP and BNP were measured with immunoradiometric assay methods. The low detection limit of the NT-proBNP assay was 4.2 pg/ml (0.50 pmol/l), while the functional sensitivity was 22 pg/ml (2.60 pmol/l) with a working range (imprecision profile < or = 10% coefficient of variation) extended up to about 30 000 pg/ml (3540 pmol/l). Healthy women (64.3 +/- 41.6 pg/ml, 7.59 +/- 4.91 pmol/l) showed significantly higher values than men (46.9 +/- 30.9 pg/ml, 5.53 +/- 3.64 pmol/l, p = 0.0118). Moreover, age and sex were significantly and independently related to the NT-proBNP values in healthy subjects, as assessed by a multiple linear regression analysis (R = 0.389, F-value = 7.316, P-value = 0.0012). As expected, the NT-proBNP values of patients with cardiomyopathy were significantly higher than those of normal subjects and progressively increased with the severity of heart failure. The respective diagnostic accuracy of the ANP, BNP and NT-proBNP assays in discriminating between the group of normal subjects and that of patients with cardiomyopathy was tested by the response operating characteristic curve analysis. Our data indicated that the NT-proBNP assay is significantly better than either of the ANP or BNP immunoradiometric assays in discriminating affected patients from healthy subjects, especially when only patients with mild disease severity (New York Heart Association class I and II) are considered.     

两台仪器检测NT-proBNP结果比对分析

目的通过Cobas h232和Roche Elecsys E170测定N-末端前脑钠肽(NT-proBNP)的方法比对,探讨两台仪器间测定数据是否具有可比性和一致性。方法依据美国国家临床实验室标准委员会EP9-A2文件要求,对两台仪器检测结果进行比对和偏差评估。结果 Cobas h232与Roche Elecsys E170相比较,r2≥0.95,相对偏倚小于12.5%。结论两台仪器测定具有很好的相关性,结果具有可比性。     

Development and calibration of a new point-of-care test for the determination of NT-proBNP in whole blood

A new point-of-care test for the determination of NT-proBNP in whole blood was developed based on the existing gold-label rapid immunoassay technology of the Roche Cardiac reader system. The novel gold-labelled monoclonal antibody recognizes NT-proBNP at amino acid sequence 27 to 31, the biotinylated polyclonal antibody recognizes sequence 39 to 50. In a model assay based upon the reference method Elecsys proBNP and with an R & D lot of the point-of-care test, this newly selected and developed combination of antibodies showed a very good correlation with the standard Elecsys proBNP assay with correlations of 0.96 or 0.94, respectively. The test was calibrated according to the existing masterlot concept of the Roche CARDIAC tests with Elecsys proBNP as a reference. In a preliminary method comparison with Elecsys proBNP the accuracy of the calibration was confirmed; the bias was between 1 and 6%. Possible reasons of approximately 1% outliers (> +/- 100%) were discussed.     

Plasma N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in assessment of acute dyspnea.

We examined the analytical correlation between non-radioimmunometric plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) and evaluated whether NT-proBNP or BNP was superior in the emergency diagnosis of heart failure and whether this was influenced by age, gender, body mass index (BMI) and renal function. Data were collected prospectively from patients admitted to the emergency department for acute dyspnea. Plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche diagnostic(R)) were measured at admission in addition to other standard biological parameters and clinical variables. Reference diagnosis was adjudicated by two independent cardiologists using the European society of cardiology guidelines. We evaluated the influence of creatinine clearance, age, gender and BMI on plasma BNP and NT-proBNP levels. One hundred and sixty consecutive patients were included: 84 females and 76 males, mean age 80.1 + 13.5 (16-98). The analytical correlation between the automated electro-chemiluminescence immunoassay for NT-proBNP and the single use fluorescence immunoassay for BNP was satisfactory using the equation: NT-proBNP = 1.1 BNP + 0.57 and a correlation r = 0.93. This was established over a wide range of concentration (5-6400 pg/ml for BNP). Areas under receiver operating characteristic (ROC) curve for BNP and NT-proBNP as a diagnostic marker for heart failure were 0.82 and 0.84, respectively and a BNP level of 150 pg/ml has similar sensitivity and specificity that NT-proBNP level of 1000 pg/ml. The correlation was not influenced by age, gender and BMI of patients. Renal dysfunction did not affect significantly this correlation (r = 0.93). We conclude that NT-proBNP, as assayed in the present study, correlates closely with BNP. This correlation is only slightly modulated by creatinine clearance values. The NT-proBNP appears as accurate as BNP according to area under ROC curve. Used in conjunction with other clinical information, rapid measurement of BNP or NT-proBNP is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.     

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). METHODS: We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. RESULTS: The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP=7.23xAxSYM BNP+2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 degrees Celsius or 25 degrees Celsius for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. CONCLUSIONS: Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.     

NT-proBNP定量检测在心力衰竭实验室诊断中的应用

目的评价血清N末端脑钠尿肽前体(NT-proBNP)定量检测对不同程度心力衰竭患者的实验诊断价值,以及血清NT-proBNP水平与心功能间的相关性.方法采用电化学发光检测仪Elecsys 2010定量检测,分析不同心功状态的心力衰竭患者血清NT-proBNP水平.结果①血清NT-proBNP诊断心力衰竭的ROC曲线的曲线下面积(AUC)为0.880(P<0.01),以155 pg/ml作为界值,其敏感性、特异性均为81%,阳性似然比为4.25,而当NT-proBNP水平>350 pg/ml时,阳性似然比可增至14.32;②心衰患者血清NT-proBNP水平明显增高,与心功能正常的心脏病患者比较有显著性差异(P<0.05),血清NT-proBNP含量随着心力衰竭程度加重呈指数增加,NT-proBNP水平和心脏功能状态的秩相关性系数为0.859(P<0.01);③中国汉族人和欧洲人心功分级采用相同标准,但NT-proBNP水平的表达程度不同.结论血清NT-proBNP定量检测是目前评价心力衰竭患者心功能状态较好的实验室指标,能够用于心力衰竭临床诊断.     

The Differential Diagnostic Value of Serum NT‐proBNP in Hospitalized Patients of Heart Failure With Pneumonia

Serum N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is considered as an effective predictor for patients with heart failure (HF), while a strong body of evidence has found its utility in inflammatory diseases. It is difficult to differentiate HF and HF coexisting with other inflammations by measuring NT‐proBNP. The aim of this study was to estimate the differential diagnostic performance of serum NT‐proBNP in hospitalized HF patients with pneumonia. A prospective study was launched. Sixty nine HF patients, 51 HF patients complicated with pneumonia, and 38 patients with pneumonia were enrolled. Serum NT‐proBNP levels were measured on Roche Elecsys. X‐ray and the European Society of Cardiology (ESC) diagnostic principles were adopted to identify patients with pneumonia and HF, respectively. The diagnostic performance of NT‐proBNP was assessed by ROC. Serum NT‐proBNP [7,039(1,008–24,672) pg/ml] in patients of HF complicated with pneumonia was significantly higher than that in those of patients with single HF [3,147(616–24,062) pg/ml] or single pneumonia [911(98–3,812) pg/ml] (P < 0.0001). No correlation was found between the level of NT‐proBNP and hospital stay. The area under ROC curve (AUC) of NT‐proBNP for distinguishing patients of HF with pneumonia was 0.8082. At the level of 4,691 pg/ml, the optimal cutoff value, 74.5% sensitivity and 81.8% specificity of NT‐proBNP were predicted. Evaluation of serum NT‐proBNP is conducive for clinicians to identify patients of HF with pneumonia, but its poor efficacy in monitoring the curative therapy in this entire cohort is not recommended.     

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood.

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.     

盐酸贝那普利对慢性心力衰竭患者的NT-pro BNP影响

目的通过观察慢性心力衰竭患者（CHF）接受盐酸贝那普利（洛汀新）治疗前后血浆氨基末端脑利钠前体（NT-proBNP）水平的变化,探讨洛汀新对CHF治疗的价值。方法选择2007年5月至2008年7月我院心内科收治的按纽约心脏协会（NYHA）分级≥Ⅲ级的慢性心力衰竭患者80例作为研究对象,根据是否接受洛汀新治疗随机分为两组：洛汀新组和对照组。所有患者均接受常规地高辛、利尿剂、β受体阻滞剂治疗,洛汀新组在此基础上加用洛汀新2.5-10.0mg／d。患者入选后立即测定NT-proBNP水平并在同一天内进行超声心动图检查,3个月后复查上述结果。结果CHF患者接受洛汀新治疗后的NT-proBNP水平明显低于治疗前[4531（2160-9127）pg／ml vs.6381（4386-11742）pg/ml,P〈0.05],显著低于对照组[4531（2160-9127）pg／ml vs.9834（5900-18744）pg／ml（P〈0.001）]。而且接受洛汀新治疗患者的左心室舒张末内径（LVEDD）显著缩小（57.74±9.69mm vs. 56.00±10.13mm,P〈0.01）,左心室射血分数（LVEF）显著升高（41.37±0.084％ vs. 48.87±0.11％,P〈0.01）,优于对照组。结论洛汀新作为血管紧张素转换酶抑制剂（ACEI）药物能够明显降低CHF患者的血浆NT-proBNP水平,显著改善心功能,而血浆NT-proBNP变化可以作为评价洛汀新治疗CHF患者疗效有价值的生化指标。     

The changes in NT-proBNP plasma concentrations during dialysis are highly dependent of the dialysis membrane ultrafiltration coefficient

BACKGROUND: NT-proBNP is a powerful marker with diagnostic and pronostic value for heart failure. It is of particular interest in patients with end-stage renal disease who are at high risk for heart failure. The aim of this study was to investigate the effect of hemodialysis on plasma NT-proBNP concentrations. METHODS: NT-proBNP concentration was measured in 67 patients before and after hemodialysis. RESULTS: In the 20 patients dialyzed with a membrane whose ultrafiltration coefficient was below or equal to12, NT-proBNP concentration was comparable after and before dialysis (16611+/-21024 vs. 15216+/-19027 pg/ml, NS). At the opposite, in the 47 patients dialyzed with a membrane whose ultrafiltration coefficient was above or equal to 40, NT proBNP concentration was 35% lower after dialysis compared to before dialysis (11983+/-21819 vs. 18574+/-31862 pg/ml, p<0.0001). CONCLUSIONS: In patients dialyzed with a membrane whose ultrafiltration coefficient is high, dialysis is likely to decrease results by one third. Thus sampling blood before dialysis in hemodialyzed patients appears as the best time to stratify the cardiovascular risk in these patients.     

老年慢性心力衰竭患者NT—proBNP检测及其临床意义

【目的】探讨检测N端脑利钠肽前体（NT-proBNP）水平在老年慢性心力衰竭患者的临床应用价值。【方法】采用电化学发光法测定80例治疗前后老年慢性心力衰竭患者（心衰组）和60例健康对照者血清（对照组）NT-proBNP水平,心力衰竭患者心功能按NYHA心功能分级,以6分钟步行试验评价运动耐量。【结果】心衰组NT-proBNP水平较对照组明显升高E（5052．6土1860．4）pg／mLvs（220．4士99．2）,pg／mL,P〈0．O11;心衰组治疗后NT-proBNP水平较治疗前明显降低[（5052．6±4-1860．4）pg／mLVS（3203±1453．4）pg／mL,Pd0．01）]。NT-proBNP水平与左室射血分数（LVEF）（r=-O．174,Pd0．05）和6分钟步行距离成显著负相关（r=-0．187,Pd0．05）。【结论】老年慢性心力衰竭患者NT—proBNP水平明显增高,其检测水平可反映老年心力衰竭患者心功能状态、运动耐量,并可作为疗效判断指标。     

前体脑钠肽对血液透析患者发生急性心功能不全的临床诊断价值

目的 在维持性血液透析患者中,研究前体脑钠肽(NT-proBNP)对评价急性心功能不全的临床价值.方法 检测113人次以呼吸困难就诊,临床上怀疑存在急性心功能不全的血液透析患者的NT-proBNP水平.根据<急性心力衰竭诊断和治疗指南>定义的临床指标判断急性左心力衰竭.结果 急性心力衰竭组NT-proBNP水平高于非急性心力衰竭组.NT-proBNP和年龄、透析时间以及左心室厚度无关,和右心房大小正相关.对于急性心力衰竭的患者,NT-proBNP水平和心力衰竭临床分级呈正相关性(rs=0.526,P=0.012).多变量分析显示,NT-proBNP水平每升高100 pg/ml,急性心力衰竭的危险性增加2.01倍(OR 3.01,95% CI 2.11～3.85).经ROC曲线分析,NT-proBNP诊断急性心力衰竭的曲线下面积为0.819(95% CI 0.728～0.842).结论 对于血液透析患者,NT-proBNP能作为诊断急性心力衰竭的生物学标志物.     

Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples.

The aim of the present study was to assess the long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in plasma samples stored at -20 degrees C without addition of protease inhibitors (e.g., aprotinin). Stability of BNP and NT-proBNP was tested in 60 EDTA plasma samples with BNP values between 30 and 420 pg/ml. Initial BNP and NT-proBNP plasma concentrations were determined within four hours after blood collection using the AxSYM BNP and the Elecsys NT-proBNP assays. Subsequently, all samples were stored at -20 degrees C and were thawed for the second BNP and NT-proBNP determination on the two instruments after one day, 30 days, 60 days, 90 days and 120 days, respectively. Mean recovery (i.e., residual immunoreactivity) of BNP and NT-proBNP expressed in percent of the initial value for the given time interval of storage was calculated. Mean recovery of BNP was less than 70% after one day of storage at -20 degrees C and decreased to less than 50% after two to four months of storage (e.g., recovery of endogenous BNP after three months of storage at -20 degrees C ranging from 0% to 71%). In contrast, mean recovery of NT-proBNP was generally greater than 90%, irrespective of the duration of storage at -20 degrees C (e.g., recovery of endogenous NT-proBNP after three months of storage at -20 degrees C ranging from 91% to 112%). In conclusion, the determination of endogenous BNP with the AxSYM assay using frozen plasma samples may not be valid under the conditions tested. In contrast, NT-proBNP as measured by the Elecsys assay may be stored at -20 degrees C for at least four months without a relevant loss of the immunoreactive analyte.     

氨基端前脑钠肽在不同年龄心力衰竭中的界值选择

目的 探讨氨基端前腩钠肽(NT-proBNP)在不同年龄段评价心功能的界值选择.方法 48例心功能不全(NYHA Ⅰ-Ⅳ)患者来自复旦大学附属中山医院急诊科.入选标准:有器质性心脏疾病基础;心功能(NYI-IA)Ⅰ-Ⅳ级.所有患者均排除急性冠脉综合征、持续性房颤、肺气肿、肺栓塞、慢性肾功能不全、贫血、甲状腺功能异常以及肿瘤患者.按年龄是否超过75岁分两组,高龄组(n=18)和非高龄组(n=30),并按NYHA标准进行心功能分级.测定患者血NT-proBNP,分析高龄组和非高龄组心功能分级与NT-proBNP之间的关系,分析利用心功能分级参考值作为鉴别急性心源性呼吸困难界值的可行性.计量数据以均数±标准差表示.两组间差异的显著性分析用t检验,多组间差异的显著性分析用方差分析.P＜0.05具有统计学意义.数据分析使用统计软件SPSS11.0.结果 研究对象的NT-proBNP与心功能分级、左心室射血分数(LVEF)关系密切.非高年龄组的NT-proBNP值较高龄组高,在心功能Ⅱ、Ⅳ级水平,两组NT-proBNP相比,差异具有统计学意义[(407±277)vs.(1358±967),P＜0.05;(727±1342)vs.(9031±2363),P＜0.01].在心功能Ⅲ级水平,尽管高龄组的NT-proBNP值更高,但组间没有显著性差异(P=0.067).NT-proBNP检测严重症状性心衰(NYHAⅢ-Ⅳ级)的受试者工作特性曲线下面积为0.958,界值525 pg/ml,敏感性100%,特异性76%;界值1911pg/ml,敏感性73%,特异性96%.高龄患者NT-proBNP检测严重症状性心衰(NYHA Ⅲ-Ⅳ级)的受试者工作特性曲线下面积为0.922,界值849 pg/ml,敏感性100%,特异性57%;界值2990 pg/ml,敏感性81%,特异性100%.结论 心功能分级的NT-proBNP参考值存在年龄组间差异.笔者建议对高龄患者选择更高的NT-proBNP参考值评价心功能状况,选择更高的界值鉴别急性心源性呼吸困难.     

Concentrations of N-terminal pro-brain natriuretic peptide and troponin T in plasma of 75-year-old apparently healthy persons.

Clinical chemical reference values for older persons are sparse and mostly intermixed with those for younger persons. We had a unique opportunity to obtain blood samples from volunteers who were 75 years old and living in two districts of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain reference intervals for 120 apparently healthy 75-year-old participants for pro-brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in patients with heart failure and as a prognostic marker in acute coronary syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids in the prognosis of ventricular systolic dysfunction and helps to differentiate between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men and women in our cohort was calculated as 98 pg/ml, comparing favorably with reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes acutely decompensated heart failure. Our calculated 97.5 percentile was slightly higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons (198 and 222 pg/ml for men and women, respectively) revealing the influence of age on this parameter. Because of its high tissue-specificity, cardiac troponin T is a cardiospecific, highly sensitive marker for myocardial damage. However, the troponin T concentrations in the plasma specimens from this cohort were all below the detection limit of 0.01 ng/ml, preventing any further data handling.     

Impact of atrial fibrillation on NT-proBNP levels in a 75-year-old population

Objective: The objective of this study was to investigate the impact of atrial fibrillation (AF) on serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a 75-year-old population. Methods: All 75-year-old citizens in Asker and Baerum counties in Norway were invited to participate in a prevalence study of AF. Blood samples for measurement of NT-proBNP were collected at rest from 61 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. NT-proBNP was measured in serum using the Elecsys proBNP sandwich immunoassay (Roche Diagnostics, Basel, Switzerland). Results: Subjects with permanent AF had higher levels of NT-proBNP (median 1119pg/mL (interquartile range 701, 1643)) than subjects with paroxysmal AF (257pg/mL (169, 382)) and controls (95pg/mL (60, 171)), p<0.001 for both. The presence of AF was still significantly associated with higher log NT-proBNP (B=0.61, p<0.001) after adjusting for the presence of heart failure, coronary heart disease and hypertension. Conclusion: In this stable, out-of-hospital population of 75-year-old subjects, AF was independently associated with increased levels of NT-proBNP. Permanent AF was associated with higher NT-proBNP levels than paroxysmal AF.     

Prohormone brain natriuretic peptide (proBNP), BNP and N-terminal-proBNP circulating levels in chronic hemodialysis patients. Correlation with ventricular function, fluid removal and effect of hemodiafiltration

BACKGROUND: Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and to a lesser extent prohormone proBNP are recognized as biochemical markers of left ventricular dysfunction. In renal failure, interpretation of natriuretic peptide remains unclear, as natriuretic peptide levels may be not only be dependent on cardiac function and dimensions but also on renal function, fluid volume and removal by dialysis procedure including hemodiafiltration (HDF). The purpose of this study was (i) to assess BNP, NT-proBNP and proBNP levels and their correlation with clinical and echocardiographic data in chronic hemodialysis patients, and (ii) to investigate basal level alteration following HDF. METHODS: Baseline clinical and echocardiographic parameters were collected in 31 dialysis patients without evidence of cardiac failure. Pre- and post-HDF BNP, NT-proBNP and proBNP concentrations were measured. Correlations between echocardiographic measurements and basal circulating peptides, between changes in peptide values and changes in fluid volume after HDF were investigated. RESULTS: Baseline plasmatic levels were elevated (BNP=517+/-840 pg/mL, NT-proBNP=5340+/-6132 pg/mL and proBNP=3569+/-4683 pg/mL) and correlated with left auricular diameter and left ventricular mass index. HDF session induced a significant decrease of 39%, 59% and 36% for BNP, NT-proBNP and proBNP levels, respectively. This decrease was not correlated to post-HDF fluid removal or weight decrease. Correlation between BNP and proBNP was stronger (r(2)=0.88) than between NT-proBNP and proBNP (r(2)=0.54). CONCLUSIONS: Despite their elimination, BNP, NT-proBNP and proBNP could be potential markers of left ventricular remodeling in chronic renal failure patients on hemodialysis. According to these results, their cut-off values, however, need to be re-evaluated.