Clinical relevance of measurement of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide in pediatric cardiology

BACKGROUND: The aim of this review is to understand the clinical usefulness of Brain Natriuretic Peptide (BNP) and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in pediatric cardiology. METHODS: A computerized literature search on National Library of Medicine using the keywords "BNP assay" and "NT-proBNP assay" was performed. Then, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP assays in patients with congenital heart disease. RESULTS: BNP and NT-proBNP are useful marker for diagnosis of heart failure, for the assessment of clinical severity and for the follow-up of congenital and pediatric heart diseases. However, results from different studies are often partial and not always univocal. Moreover, reference intervals in pediatric population have not yet been extensively evaluated. CONCLUSIONS: BNP and NT-proBNP may be considered helpful markers for the integrated diagnosis and management of pediatric patients, though further studies are needed to support their routine use.     

Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease

BACKGROUND: B-type natriuretic peptide (BNP) and the amino-terminal fragment of the BNP prohormone (NT-proBNP) are markers for functional cardiac impairment and are elevated in heart failure (HF). Aim of the present study was to perform a head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease. METHODS: We prospectively classified 180 consecutive subjects according to ACC/AHA guidelines. Blood concentrations of BNP and NT-proBNP were determined by two fully automated chemiluminescent assays (Bayer and Roche method). Diagnostic utilities were tested by ROC analyses and logistic regression. RESULTS: ROC curves of BNP and NT-proBNP in patients with symptomatic HF (n=43) and asymptomatic subjects (n=137) did not differ significantly (AUC 0.930 vs. 0.918, p=0.650), but comparison of patients with asymptomatic structural heart disease (n=56) and subjects without structural disorder of the heart (n=81) revealed different AUCs for the respective assays (0.735 vs. 0.839, p=0.009). In the population studied, age, sex and renal function had no impact on the diagnostic performance of both tests when compared by logistic regression models. CONCLUSIONS: Both assays facilitate diagnosis of symptomatic and asymptomatic structural heart disease. BNP and NT-proBNP may be equally useful as an aid in the differential diagnosis of probable signs or symptoms of HF. In contrast, NT-proBNP might be a more discerning marker of early cardiac dysfunction than BNP.     

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.     

Capability of B-type natriuretic peptide (BNP) and amino-terminal proBNP as indicators of cardiac structural disease in asymptomatic patients with systemic arterial hypertension

BACKGROUND: The aim of the present study was to prospectively evaluate the diagnostic utility of B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) measurements for the detection of cardiac structural disease in asymptomatic patients with systemic arterial hypertension and to test the hypothesis that the 2 analytes are equally useful in this clinical setting. METHODS: We studied a consecutive series of 149 asymptomatic patients referred for echocardiographic evaluation of the cardiac effects of systemic arterial hypertension. Diagnosis of cardiac structural disease was based on the presence of systolic or diastolic dysfunction, left atrial dilatation, left ventricular dilatation or hypertrophy, pulmonary hypertension, and wall motion or valvular abnormalities. Blood concentrations of BNP and NT-proBNP were measured by 2 commercially available assays (Abbott AxSYM and Roche Elecsys, respectively). Diagnostic accuracies of BNP and NT-proBNP were assessed by ROC curve analysis. Areas under the curves were compared by analysis of equivalency. RESULTS: In distinguishing between hypertensive patients with cardiac structural disease (n = 118) and hypertensive patients without (n = 31), areas under the curves were 0.740 (95% confidence interval, 0.662-0.808) for BNP and 0.762 (0.685-0.828) for NT-proBNP and were significantly equivalent (P = 0.015). Cutoff values with a 90% sensitivity for cardiac structural disease were 17 ng/L for BNP and 39 ng/L for NT-proBNP, with 29% and 32% specificity, respectively. CONCLUSIONS: BNP and NT-proBNP have similar capabilities for detecting cardiac structural disease in asymptomatic patients with systemic arterial hypertension. However, in the setting evaluated, a screening strategy relying on measurement of BNP or NT-proBNP may be of limited value because of the low specificity at the selected cutoff values.     

B-type natriuretic peptide: issues for the intensivist and pulmonologist

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), although promising as biomarkers for heart failure, are affected by multiple confounders. The purpose of this article is to review the literature on the utility of BNP and NT-proBNP as biomarkers, with a focus on their role in critical illness and pulmonary diseases. DATA SOURCE: Published articles on BNP and NT-proBNP. DATA ANALYSIS: Multiple disorders in the intensive care unit cause elevated BNP and NT-proBNP levels, including cardiac diseases, shock, pulmonary hypertension, acute respiratory distress syndrome, acute pulmonary embolism, chronic obstructive pulmonary disease, renal failure, and other conditions. CONCLUSIONS: Intensivists and pulmonologists should understand that BNP and NT-proBNP levels might be raised to different degrees not only in heart failure but also in critical illness and various pulmonary diseases; in these situations, BNP and NT-proBNP may also serve as markers of severity and prognosis.     

What is the value of B-type natriuretic peptide testing for diagnosis, prognosis or monitoring of critically ill adult patients in intensive care?

BACKGROUND: B-natriuretic peptide (BNP) and aminoterminal proBNP (NT-proBNP) are clinically useful for the diagnosis of decompensated heart failure and for prognosis in heart failure and acute coronary syndromes. Clinical use of these biomarkers in critically ill patients being treated in intensive care is not well established. METHODS: This is a narrative review of evidence identified searching MEDLINE with the strategy [(BNP OR NT-proBNP) AND (critical illness AND intensive care)]. Seven primary reports and two narrative reviews were retrieved. For completeness, literature from each of the following searches was reviewed: [(BNP OR NT-proBNP) AND (critical illness)] and [(BNP OR NT-proBNP) AND (intensive care)]. RESULTS: Primary literature used BNP and NT-proBNP for diagnosis, prognosis and monitoring. For diagnosis of acute lung injury in unselected intensive care patients and for diagnosis of heart failure in trauma patients, the biomarkers had low sensitivity and are of modest use. BNP and NT-proBNP were found to have a significant ability to prognosticate adverse outcomes in critically ill patients. A single paper examined the use of BNP as a non-invasive replacement for pulmonary capillary wedge pressure, finding little value. The impact of renal insufficiency on the markers was noted as a confounder in most studies. In the secondary searches, some preliminary data suggested a possible role for the natriuretic peptides in exclusion of a cardiac cause for certain conditions among intensive care unit (ICU) patients. However, the general findings were that the performance of BNP and NT-proBNP is unimpressive among ICU patients. CONCLUSIONS: Currently, utilization of BNP and NT-proBNP does not appear to provide much useful information or have a substantial role in the care of critically ill patients in intensive care.     

B-type natriuretic peptides: prognostic markers in stable coronary artery disease

Circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment (NT) of its prohormone (proBNP) are related to cardiac function and have emerged as clinically useful tools for the diagnosis of heart failure and for the estimation of prognosis in patients with heart failure and acute coronary syndromes. Recent studies have also convincingly documented that both BNP and NT-proBNP are powerful, independent prognostic indicators in patients with stable coronary artery disease. The associations are strongest for the end-points of death and heart failure, whereas the association with cardiac ischemic events is weaker or nonexistent, after adjustment for confounding factors. Importantly, BNP and NT-proBNP appear to provide incremental prognostic information to conventional risk factors, including markers of ventricular function and ischemia. Data documenting that BNP or NT-proBNP measurements can be used to guide treatment decisions in patients with stable coronary artery disease are still lacking.     

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.     

Updating the role of natriuretic peptide levels in cardiovascular disease

Heart disease affects 1 in 3 individuals in the United States, and the prevalence of heart failure (HF) is increasing exponentially. Although our understanding of the disease progression of congestive HF (CHF) has advanced, refining the areas of diagnosis, risk stratification, prognosis, and treatment is still needed. The natriuretic peptides, specifically B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have shown promise in clinical practice. Brain natriuretic peptide is released from cardiac ventricular myocytes in response to volume or pressure overload. Rapid measurement of plasma BNP or NT-proBNP has been shown to increase the diagnostic accuracy of HF exacerbations. A cutoff value of 100 pg/mL has a sensitivity and specificity of 90% and 73%, respectively, according to the Breathing Not Properly Study. In addition, BNP and NT-proBNP have been considered independent predictors of adverse outcome. One study calculated a 35% increase in risk of death due to HF for every 100-pg/mL increase in BNP level. Lastly, natriuretic peptides have been known to decrease following medical therapy of HF, suggesting the role of their measurement in monitoring inpatient disease progression and outpatient medical programs. The future of natriuretic peptides lies in risk stratification in other cardiac diseases, such as acute coronary syndrome, and possibly determining severity of valvular disease. Although there is substantial work done in elucidating the power of natriuretic peptides in clinical practice, more research is necessary to reach a consensus regarding how to appropriately utilize them in treatment regimens.     

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.     

N-terminal B-type natriuretic peptide concentrations are similarly increased by 30 minutes of moderate and brisk walking in patients with coronary artery disease

Elevated concentrations of B-type natriuretic peptide (BNP) and N-terminal pro- BNP (NT-proBNP) reflect elevated myocardial wall stress due to volume or pressure overload in cardiac disease. Recently, exercise-induced elevations of (NT-pro)BNP in coronary artery disease (CAD) patients have been reported to result from exercise-induced ischemia associated regional wall abnormalities. Therefore, the study aimed to examine NT-proBNP concentrations in patients with CAD after moderate and brisk walking (MW, BW). We hypothesized that BW induces higher increases than MW. Methods and results In randomized order 14 patients with stable CAD (12♂/2♀; 63 ± 9 years; LV ejection fraction: 59±9%) of a out-patient rehabilitation group performed MW with 4.5 ± 0.6 km/h (mean heart rate: 80 ± 11/min) or BWat their allowed upper exercise heart rate of 102±9/min with a speed of 6.2 ± 0.6 km/h for 30 min on a tartan track on two separate days. Blood samples were taken before, immediately, 1 h, 3 h and 1 day after exercise to determine NT-proBNP and cardiac troponin T (cTnT). Echocardiographic LV function was determined before and 1 h after exercise. Median concentrations of NT-proBNP significantly increased from 222 to 295 ng/l (MW) and from 222 to 296 ng/l (BW) without a difference between both modalities. cTnT remained below the detection limit of 0.01 μg/l. LV functions remained unchanged. A cutoff level of 250 ng/l distinguished CAD patients with elevated exercise-induced increases in NT-proBNP and a diminished LV ejection fraction at rest. Conclusion BW and MW induce similar increases in NT-proBNP in CAD patients without myocardial damage, which have to be considered when NT-proBNP is determined. Derived from the exercise- induced increase in NTproBNP, the myocardial strain in BW is not elevated in comparison to MW.     

Physiological, pathological, pharmacological, biochemical and hematological factors affecting BNP and NT-proBNP

OBJECTIVES: To gain a better understanding of the scope and breadth of factors associated with the B-type natriuretic peptides. DESIGN AND METHODS: Databases were searched from 1989 to February 2005 for primary studies that measured BNP or NT-proBNP for the purpose of diagnosis, prognosis and monitoring treatment. RESULTS: There were 103 factors identified in 72 studies. Most of the cardiac diseases were positively associated with BNP and NT-proBNP concentrations and of the non-cardiac conditions, dyspnea, diabetic nephropathy, and stroke were all associated with higher concentrations. Most biochemical and hematological markers showed positive associations. Factors that assessed heart function showed both positive and negative associations and drug therapy was either negatively associated or had no effect on BNP or BNT-proBNP concentrations. Few studies reported independent associations and of those that did age, female gender, and creatinine concentrations were positively associated with BNP and NT-proBNP. CONCLUSIONS: Various factors were found to be associated with BNP and NT-proBNP.     

High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure

BACKGROUND: Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CV(i)) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CV(i) values in stable heart failure patients. METHODS: We recruited 43 patients with stable chronic heart failure living in Curacao (22 males, 21 females; median age, 63 years; range, 20-86 years; New York Heart Association classes I-III). Samples were collected for within-day CV(i) (n = 6; every 2 h starting at 0800), day-to-day CV(i) (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CV(i) (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay. RESULTS: Median (range) concentrations were 134 (0-1630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CV(i), and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CV(i)s were inversely related to median BNP concentrations. Week-to week CV(i)s for BNP were 44% (BNP < or =350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations. CONCLUSIONS: The high CV(i)s hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CV(i) have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established.     

The brain natriuretic peptide (BNP) precursor is the major immunoreactive form of BNP in patients with heart failure

BACKGROUND: Peptides derived from brain natriuretic peptide (BNP) precursor (proBNP), BNP, and the N-terminal fragment of proBNP (NT-proBNP) are used as biomarkers of heart failure. It remains unclear which forms of these peptides circulate in blood and which forms are measured by assays for these natriuretic peptides. METHODS: To design assays for immunodetection of proBNP, NT-proBNP, and BNP, we used a panel of BNP- and NT-proBNP-specific monoclonal antibodies (MAbs). All MAbs were tested in 2-site combinations in time-resolved fluoroimmunoassays with recombinant or synthetic antigens and plasma from heart failure (HF) patients. ProBNP and related molecules were assayed in HF plasma samples and plasma extracts by means of gel filtration fast protein liquid chromatography (FPLC) before and after protein fractionation on Sep-Pak C18 cartridges. RESULTS: The limits of detection for BNP, proBNP, and NT-proBNP assays were 0.4, 3, and 10 ng/L, respectively. Gel filtration-FPLC studies revealed 1 peak of NT-proBNP (approximately 25 kDa), 1 peak of proBNP (approximately 37 kDa), and 2 peaks of BNP immunoreactivity, a major peak (approximately 37 kDa) for proBNP, and a minor peak (approximately 4 kDa) for BNP. In patient plasma, the molar concentration of NT-proBNP was almost 10 times that of proBNP. The mean proBNP:BNP ratio in patient plasma was 6.3, ranging from 1.8 to 10.8. CONCLUSIONS: ProBNP is the major BNP-immunoreactive form in human blood. The proBNP:BNP ratio in plasma samples is dependent on the methods used for sample handling and for the measurement of the peptides.     

Quality specifications for B-type natriuretic peptide assays

BACKGROUND: The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. METHODS: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.     

Comparison of BNP and NT-proBNP assays in the approach to the emergency diagnosis of acute dyspnea

N-terminal pro-brain natriuretic peptide (NT-proBNP) and BNP measurement could have a significant role in differentiating dyspnea between cardiac or pulmonary origin in the emergency room. The development of new and different commercial assays for these B-type natriuretic peptides offers the possibility of improving and simplifying their measurements but this could be defaulted due to the differences in methodology and the lack of assay standardization. We compared four available methods of measuring NT-proBNP and BNP and evaluated their usefulness in diagnosing the causes of breathlessness in the emergency room. The correlation of BNP with different assays was strong with r>0.98 (P<0.0001). Comparison studies between NT-proBNP and BNP procedures were in good agreement with r>0.87. The area under the receiver-operating characteristic curve (ROC) for BNP or NT-proBNP for detecting any cardiac dysfunction was higher than 0.96 (95% CI). A BNP value of 116 pg/mL measurement with the Access BNP assay (Beckman Coulter Inc., Fullerton, CA), a BNP value of 79 pg/mL with Advia Centaur BNP assay (Bayer Diagnostics, Tarrytown, NY), and an NT-proBNP level of 817 pg/mL in Elecsys NT-proBNP assay (Roche Diagnostic, Mannheim, Germany), showed both high sensitivity (>92%) and high specificity (>93%). We have found that NT-proBNP and BNP present similar diagnostic accuracies for the differential diagnosis of dyspnea.     

Monitoring the response to pharmacologic therapy in patients with stable chronic heart failure: Is BNP or NT-proBNP a useful assessment tool?

OBJECTIVES: B-type natriuretic peptides are biomarkers of heart failure (HF) that can decrease following treatment. We sought to determine whether B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) concentration changes occurred in parallel to changes in other measures of heart failure following treatment. METHODS: We conducted a systematic review of the literature for studies that assessed B-type natriuretic peptide measurements in treatment monitoring of patients with stable chronic heart failure. Selected studies had to include at least three consecutive measurements of BNP or NT-proBNP. RESULTS: Of 4338 citations screened, only 12 met all of the selection criteria. The selected studies included populations with a wide range of heart failure severity and therapy. BNP and NT-proBNP decreased following treatment in nine studies and was associated with improvement in clinical measures of HF. CONCLUSIONS: There was limited data to support using BNP or NT-proBNP to monitor therapy in patients with HF.     

BNP和NT-proBNP在鉴别舒张性心力衰竭中的应用研究

目的 研究慢性心力衰竭患者血浆BNP及NT-proBNP浓度的变化,评价BNP及NT-proBNP对鉴别舒张性心力衰竭的作用.方法 对2004-2006年在解放军总医院临床诊断为舒张性心力衰竭129例患者和收缩性心力衰竭109例患者进行血浆BNP和NT-proBNP浓度测定,通过与对照组(77名)的比较,分析血浆BNP和NT-proBNP升高的相关因素,并用ROC曲线评价BNP和NT-proBNP对鉴别舒张性心力衰竭的作用.结果 和对照组(血浆BNP和NT-proBNP浓度中位数分别为58.51 ng/L和69.80 ng/L)比较,慢性心力衰竭患者血浆BNP和NT-proBNP浓度明显升高,其中舒张性心力衰竭和收缩性心力衰竭组患者血浆BNP浓度中位数分别为254.16 ng/L和923.08 ng/L,NT-proBNP浓度中位数分别为899 ng/L和3 695 ng/L,血浆BNP和NT-proBNP升高的程度与NYHA心功能分级显著相关(β值分别为0.201和0.323,P值均<0.001).BNP和NT-proBNP诊断慢性心力衰竭的曲线下面积分别为0.906(95%可信区间:0.865～0.946)和0.956(95%可信区间:0.932～0.980),BNP鉴别舒张性心力衰竭和收缩性心力衰竭的曲线下面积为0.781(95%可信区间:0.710～0.852),NT-proBNP鉴别舒张性心力衰竭和收缩性心力衰竭的曲线下面积为0.757(95%可信区间:0.686～0.828).结论 慢性心力衰竭患者的血浆BNP和NT-proBNP水平均明显升高,升高的程度和NYHA心功能分级相关,两者是诊断慢性心力衰竭的良好指标,但对鉴别舒张性心力衰竭的作用不大.     

Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay

BACKGROUND: Brain natriuretic peptides (BNPs) are useful in the assessment of heart failure, left ventricular dysfunction, and acute coronary syndromes. METHODS: We performed a multicenter evaluation of the automated Roche NT-proBNP assay and compared its performance to the Biosite Triage BNP assay. RESULTS: The N-terminal (1-76) pro brain natriuretic peptide (NT-proBNP) method is precise (CV2-fold higher CV, and plasma samples are more labile when stored at room temperature and 4 degrees C. Comparison studies showed a reasonable correlation between NT-proBNP and BNP assays, with a substantially higher slope bias of 6-20 for the NT-proBNP assay. CONCLUSIONS: The automated Roche NT-proBNP assay has good analytical performance and better precision than the Biosite BNP assay. Unlike BNP, NT-proBNP is stable in EDTA plasma for 3 days at room temperature or longer at 4 degrees C. The Roche NT-proBNP is fully automated and will accommodate the testing of large numbers of clinical samples for assessing cardiac dysfunction.     

Pathophysiology and significance of natriuretic peptides in patients with end-stage kidney disease

Natriuretic peptides (NP), especially B type (BNP) and its N-terminal pro-B type natriuretic peptide (NT-proBNP), have long been regarded as biomarkers of volume overload and tools to exclude heart failure in the general population. However, their role in end-stage kidney disease (ESKD) is less certain given that BNP and NT-proBNP are excreted by the kidney and so serum concentrations of NPs are nearly universally elevated compared to controls. Nevertheless, the accumulated evidence suggests that serum concentrations of NPs in patients with ESKD show moderate or strong positive relationships with underlying heart disease, abnormal cardiac structure or function and mortality. Limited evidence also supports the role of BNP including NT-proBNP, ANP in some studies, rather than CNP or DNP in risk stratification among ESKD patients as well as the utility of BNP samplings pre- and post- hemodialysis. However, studies of the cut-off values of NPs have yielded inconsistent results, such that further large-scale studies are needed to clarify these issues. This review summarizes the pathophysiology and significance of NPs in ESKD patients, especially their potential role as risk stratification biomarkers in clinical management.