Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions

B-Type natriuretic peptide (BNP) is elevated in states of increased ventricular wall stress. BNP is most commonly used to rule out congestive heart failure (CHF) in dyspneic patients. BNP levels are influenced by age, gender and, to a surprisingly large extent, by body mass index (BMI). In addition, it can be elevated in a wide variety of clinical settings with or without CHF. BNP is elevated in other cardiac disease states such as the acute coronary syndromes, diastolic dysfunction, atrial fibrillation (AF), amyloidosis, restrictive cardiomyopathy (RCM), and valvular heart disease. BNP is elevated in non-cardiac diseases such as pulmonary hypertension, chronic obstructive pulmonary disease, pulmonary embolism, and renal failure. BNP is also elevated in the setting of critical illness such as in acute decompensated CHF (ADHF) and sepsis. This variation across clinical settings has significant implications given the increasing frequency with which BNP testing is being performed. It is important for clinicians to understand how to appropriately interpret BNP in light of the comorbidities of individual patients to maximize its clinical utility. We will review the molecular biology and physiology of natriuretic peptides as well as the relevant literature on the utilization of BNP in CHF as well as in other important clinical situations, conditions that are commonly associated with CHF and or dyspnea.     

Coronary angiography transiently increases plasma pro-B-type natriuretic peptide.

AIMS: Increased plasma concentrations of B-type natriuretic peptide (BNP) and its precursor (proBNP) provide important prognostic information in patients presenting with acute coronary syndromes. Although a majority of these patients undergo early invasive assessment, the effects of coronary angiography per se on plasma BNP and proBNP concentrations are not known. We therefore sought to determine whether coronary angiography and ventriculography affect the cardiac secretion of these prognostic markers. METHODS AND RESULTS: Blood samples were collected before and two minutes after coronary angiography and ventriculography in patients with or without coronary artery disease (CAD) and normal left ventricular ejection fraction. In patients with suspected CAD and normal left ventricular ejection fraction, the plasma proBNP concentration transiently increased from 11 pmol/l (range 1-67 pmol/l) to 19 pmol/l (range 5-102 pmol/l, n=29,P<0.0001) two minutes after coronary angiography and ventriculography. The increase was similar in patients with or without CAD, although patients with stable CAD displayed higher plasma BNP and proBNP concentrations at baseline. In contrast, plasma BNP concentrations did not change after coronary angiography and ventriculography. CONCLUSION: Coronary angiography induces a transient increase in cardiac proBNP secretion. Blood sampling for plasma proBNP measurements in patient stratification and prognosis estimation should consequently be avoided immediately after coronary angiography.     

脑钠肽对心力衰竭患者发生心房颤动的预测价值

目的通过测定心力衰竭(心衰)患者的血清脑钠肽(BNP)浓度,探讨BNP对心衰患者并发心房颤动(房颤)的预测价值。方法入选2010年7月至2013年12月在河南省安阳地区医院心内二科住院的心衰患者169例,152例完成随访,失访17例,其中男性79例,女性73例,年龄37~71岁,平均年龄(48±11)岁,根据随访结果将患者分为两组,房颤组(n=29)和窦性心律组(n=123)。所有患者在入选前以及随访1年均行Holter检查,同时检测患者血清BNP水平。结果随访1年后,152例患者完成随访,其中有29例患者记录到房颤。房颤组[(312.21±52.78)pg/ml]BNP水平明显高于窦性心律组[(218.24±67.45)pg/ml],差异具有统计学意义(P0.01)。多因素分析结果显示,年龄OR值为4.162,95%CI:1.521-7.132;LVEF OR值为1.027,95%CI:0.939-1.058。年龄和左室射血分数(LVEF)是心衰患者并发房颤的独立危险因素。结论血清BNP水平对心衰患者是否发生房颤有重要的预测价值。     

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading

Background and Aims

Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target.The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading.

Methods and Results

120 patients with heart failure treated with high-dose furosemide + HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load.After treatment with high-dose furosemide + HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5-159.5) pg/ml vs 64 (21-150) pg/ml], BNP [215.5 (80.5-487) pg/ml vs 87 (66-141.5) pg/ml], TNF-α [389.5 (265-615.5) pg/ml vs 231.5 (156-373.5) pg/ml], IL-1β [8 (7-9) pg/ml vs 4 (3-7) pg/ml], IL-6 [5 (3-7.5) pg/ml vs 3 (2-4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1β (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups.

Conclusions

Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.     

B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts

BACKGROUND: Plasma concentrations of B-type natriuretic peptide (BNP-32) and its precursor (proBNP) are increased in chronic heart failure. Accordingly, BNP-32 and proBNP are both being implemented as clinical markers. AIM: To determine the molar relation of BNP-32 and proBNP in different cardiovascular regions. METHODS AND RESULTS: Blood samples were obtained from different cardiovascular regions during right heart catheterization in heart failure patients, and from normal subjects. Plasma BNP-32 and proBNP concentrations were measured using sequence-specific radioimmunoassays. Patients with severe left ventricular dysfunction (n=21) displayed increased peripheral plasma concentrations of both BNP-32 (four-fold, P=0.0008) and proBNP (seven-fold, P=0.0002) compared with normal subjects. Moreover, the peripheral concentrations were highly correlated with the corresponding concentrations in the coronary sinus (BNP-32: r=0.97, P<0.0001; proBNP: r=0.94, P<0.0001). Despite comparable peripheral concentrations of BNP-32 and proBNP, the BNP-32 concentration was higher than the proBNP concentration in the coronary sinus (median 126 pmol/l (21-993) vs. 103 pmol/l (16-691), P=0.035). CONCLUSIONS: The BNP-32 and proBNP concentrations are closely related in venous cardiac blood. The findings suggest an overall constitutive secretion of processed proBNP, i.e. an N-terminal precursor fragment and BNP-32, in chronic heart failure.     

Plasma B-type natriuretic peptide concentration in beta-thalassaemia patients

BACKGROUND: Plasma B-type natriuretic peptide (BNP) concentration has significant diagnostic accuracy and prognostic value in various forms of heart disease. Whether BNP is also useful in the evaluation and management of thalassaemia heart disease remains to be determined. METHODS AND RESULTS: Eighty three thalassaemia major patients; 8 with acutely decompensated heart failure (New York Heart Association [NYHA] class III or IV, group A), 25 with NYHA class II symptoms and impaired systolic left ventricular function (ejection fraction<55% or fractional shortening<30%, group B) and 50 with normal systolic function (group C), as well as 50 healthy controls, were studied. Assessment included history, physical examination, Doppler echocardiography and plasma BNP determination. Mean BNP levels were 431+/-219 pg/mL (range, 283-890 pg/mL) in group A, 158+/-31 pg/mL in group B, 176+/-54 pg/mL in group C and 43+/-24 pg/mL in controls. BNP levels were significantly higher in group A (p<0.001), but did not differ between groups B and C. Moreover, BNP was not correlated with left ventricular end-diastolic diameter, left ventricular mass, right ventricular diameter index, Doppler diastolic indexes (except in group C), the mean 2-year serum ferritin concentration or the peak serum ferritin concentration in any of the three patient groups. CONCLUSION: A potential deficiency of BNP-related neurohormonal mechanisms may impair its clinical usefulness in thalassaemia major.     

The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the detection of major structural heart disease in patients with atrial fibrillation.

AIMS: To assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the diagnosis of major structural heart disease (MSHD) in patients with atrial fibrillation (AF) compared with those with sinus rhythm (SR) using receiver operator characteristic (ROC) analysis. NT-proBNP is elevated in MSHD and heart failure (HF). AF, a common finding in HF and MSHD, is also associated with raised plasma NT-proBNP. As a result, the utility of NT-proBNP for predicting MSHD may be reduced. METHODS AND RESULTS: One thousand four hundred and seventy-six patients underwent assessment at a single centre, performed without the knowledge of NT-proBNP levels. MSHD included left ventricular (LV) systolic and diastolic dysfunctions, left-sided valvular disease, right heart disease (including pulmonary hypertension) and severe LV hypertrophy. One hundred and fifty-five patients were excluded due to renal impairment, atrial flutter, or a pacemaker. Seven hundred and ninety-three patients were diagnosed with MSHD. Median NT-proBNP concentrations for patients with MSHD were 960 (IQR 359-2625) pg/mL and 2491 (1443-4368) pg/mL for SR (n = 591) and AF (n = 202), respectively (P < 0.001). Patients without MSHD had NT-proBNP levels of 179 (90-401) pg/mL and 1000 (659-1760) pg/mL for SR (n = 454) and AF (n = 74), respectively (P < 0.001). The area under the ROC curve for NT-proBNP to detect MSHD was 0.79 for SR (95% CI 0.77-0.82) and 0.78 for AF (95% CI 0.72-0.84). NT-proBNP cut-off levels necessary to achieve a 1 in 100 false negative rate were 27.5 (7.5-30.5) pg/ml and 524 (253-662) pg/ml for SR and AF, respectively. CONCLUSION: NT-proBNP performs as well in patients with SR as in those with AF. However, significantly higher cut-off levels are required for patients with AF to achieve similar levels of diagnostic specificity.     

Prognostic value of B-type natriuretic peptide and its amino-terminal proBNP fragment for cardiovascular events with stratification by renal function

BackgroundBrain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction.Methods and resultsThis retrospective cohort study evaluated patients with cardiovascular diseases (64.9 ± 11.7 years, mean ± SD). The end points were all-cause death and a composite end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for severe heart failure, and initiation of hemodialysis. Baseline plasma BNP and NT-proBNP levels, expressed as log-transformed data, were closely correlated in patients with CKD stages 1–3 (n = 998) (r² = 0.870, p < 0.001), whereas for CKD stages 4–5 (n = 85) there was a significant but weaker correlation (r² = 0.209, p < 0.001). During follow-up periods (51.3 ± 0.4 months), 132 patients died and 202 patients reached the composite end point. The area under the receiver operating characteristic curve (AUROC) for BNP and NT-proBNP were similar for CKD stages 1–3. However, for CKD stages 4–5, the AUC for mortality for BNP was 0.713 and that for NT-proBNP was 0.760, while the AUC for the composite end point for BNP was 0.666 and that for NT-proBNP was 0.720.ConclusionsBoth BNP and NT-proBNP are useful biomarkers for mortality and cardiovascular events, but NT-proBNP may be superior to BNP for CKD stages 4–5.     

B-type natriuretic peptide may predict prognosis in older adults admitted with a diagnosis other than heart failure

Background and Aims

The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF.

Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT-ANP and BNP/NT-proBNP

BACKGROUND: Natriuretic peptides are currently used in the diagnosis and follow-up of patients with Chronic Heart Failure (CHF). However, it is unknown whether there are different influences of age on atrial natriuretic peptide (ANP)/N-terminal-ANP (NT-ANP) or B-type natriuretic peptide (BNP)/N-terminal-proBNP (NT-proBNP). AIMS: To compare the influence of age and gender on plasma levels of ANP/NT-ANP and BNP/NT-proBNP in CHF patients. METHODS AND RESULTS: Natriuretic peptides were measured in 311 CHF patients (68+/-8 years, 76% males, left ventricular ejection fraction (LVEF) 0.23+/-0.08). All natriuretic peptides were significantly related to age (p<0.05) on multivariate regression analysis, with partial correlation coefficients of 0.18, 0.29, 0.28 and 0.25 for ANP, NT-ANP, BNP and NT-proBNP, respectively. The relative increase of both BNP/NT-proBNP were more pronounced than of ANP/NT-ANP (p<0.01). Furthermore, the relative increase of BNP with age was markedly larger than of NT-proBNP (p<0.01). Levels of all natriuretic peptides were also significantly related to cardiothoracic ratio, renal function and LVEF. CONCLUSION: In patients with CHF, BNP/NT-proBNP were more related to age than ANP/NT-ANP, and BNP was more related to age than NT-proBNP. However, in these CHF patients the influence of age on the levels of all natriuretic peptides was modest, and comparable to several other factors.     

脑钠素在心力衰竭诊断中的应用

目的 研究血浆脑钠素（BNP）在诊断心力衰竭尤其是早期心力衰竭中的作用，观察BNP水平与纽约心脏病学会（NYHA）心功能分级及心脏超声指标的相关性；评价血浆BNP水平对心力衰竭患者不良心血管事件发生率的预测价值。方法 把所有受试者分为2组：观察组及对照组。观察组进一步分为慢性心功能不全组，急性心功能不全组，慢性心功能不全急性恶化组。用放射免疫法测定血浆BNP水平，用超声心动图测定左房内径（LA）、左室射血分数（LVEF）、左室舒张末期内径（LVEDD），观察BNP水平与LA、LVEF、LVEDD的相关性。对出院时NYHA心功能分级为Ⅱ～Ⅲ级的患者进行3个月随访，根据出院后的服药情况分为：常规治疗组和卡维地络组，观察其血浆BNP水平变化。结果 （1）观察组的血浆BNP水平显著高于对照组；（2）各心功能不全组间BNP水平存在显著差异，且BNP水平随NYHA分级升高而升高；（3）BNP值与LA、LVEDD呈显著正相关、与LVEF值（％）呈负相关；（4）发生不良心血管事件患者的BNP水平高于无不良心血管事件患者；卡维地络组病人的血浆BNP水平显著低于常规治疗组。结论 BNP测定是辅助诊断心功能不全的有效方法，尤其是在心力衰竭早期，BNP水平还可以反映心功能不全的严重程度。     

Atrial natriuretic peptide in atrial fibrillation before and after electrical cardioversion therapy

In eight patients with atrial fibrillation of less than 3 monthsduration and without congestive heart failure the plasma concentrationof atrial natriuretic peptide was determined one day before,the day after and again 30 days after electrical cardioversiontherapy. The pretreatment plasma concentration of the peptidewas 99 pg mg^–1 (23–480, median and range). The dayafter cardioversion to sinus rhythm the peptide concentrationhad normalized to 36 pg ml^–1 (18–151). The plasmaconcentration of atrial natriuretic peptide remained stablein all but one patient for a period of 30 days (46 pg ml^–1,16–695) (P = 0·03). In conclusion, the plasma concentration of atrial natriureticpeptide in patients with atrial fibrillation was significantlyreduced after electrical cardioversion to sinus rhythm and remainedstable for a period of 30 days.     

Brain natriuretic peptide measurement in pulmonary medicine

Serum levels of natriuretic peptides are well established as important biomarkers in patients with cardiac disease. Less attention has been placed on the role of natriuretic peptides in patients with pulmonary conditions. In several well-defined groups of patients with pulmonary disease natriuretic peptides provide the clinician with clinically valuable information. A limitation of the interpretation of natriuretic peptides in pulmonary disease is the confounding effect of concurrent conditions such as heart failure, hypoxia, sepsis and renal failure. The present paper reviews the role of natriuretic peptides for diagnosis, risk stratification and prognosis of several pulmonary disorders.     

Troponin, B-type natriuretic peptides and outcomes in severe heart failure: differences between ischemic and dilated cardiomyopathies

BACKGROUND: Ischemic (ISCM) and idiopathic dilated (IDCM) cardiomyopathies have different responses to therapy and outcomes. Both may demonstrate elevations in troponin and B-type natriuretic peptides, but biomarker levels have not been reported to differ as a function of the etiology of heart failure (HF). Accordingly, we compared these biomarkers in patients with chronic HF. HYPOTHESIS: Biomarker levels of troponin T, troponin I, B-type natriuretic peptide (BNP), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) are quantitatively different between ischemic and idiopathic dilated etiologies of chronic HF. METHODS: Forty patients (27 male, 68 +/- 2 years; LVEF 25 +/- 1%; NYHA Class III-IV) admitted to hospital for acute HF were studied. Biomarkers were drawn at admission prior to treatment intervention. RESULTS: Of the 40 patients, 27 had ISCM and 13 IDCM. Baseline clinical characteristics were similar with the exception of GFR. cTnT, cTnI, and BNP levels were higher in ISCM patients (cTnT: 0.373 +/- 0.145 vs. 0.064 +/- 0.016 ng/mL, p < 0.05; cTnI: 2.02 +/- 0.76 vs. 0.21 +/- 0.11 ng/mL, p < 0.05; BNP: 776 +/- 91 vs. 532 +/- 85 pg/mL, p < 0.05). Cardiovascular mortality during follow up (10 +/- 1 months) was 48% in patients with ISCM and 23% with IDCM (p < 0.05). CONCLUSIONS: Patients with acutely decompensated chronic HF have elevations in troponin and BNP. These elevations, as well as mortality are significantly higher in patients with ISCM compared to IDCM. The differential levels in biomarkers may be due to differences in disease pathogenesis, and fit with the adverse prognosis in these patients.     

Clinical applications of B-type natriuretic peptide (BNP) testing.

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the 'normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100 pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical context.     

快速测定血浆B型钠尿肽鉴别老年人呼吸困难病因的临床观察

目的　评估快速B型钠尿肽 (BNP)测定在老年人呼吸困难诊断及充血性心力衰竭(CHF)近期预后判断的意义。　方法　根据最后诊断将 2 92例老年呼吸困难患者分为 4组 :CHF组( 14 6例 )、肺病组 ( 75例 )、CHF 肺病组 ( 5 2例 )和非CHF 非肺病组 ( 19例 ) ,采用干式快速免疫荧光法定量测定全部患者的血浆BNP浓度。　结果　CHF组BNP水平为 ( 736± 381)ng/L ;肺病组为 ( 6 2± 37)ng/L ;CHF 肺病组为 ( 5 14± 32 7)ng/L ;非CHF 非肺病组为 ( 6 1± 2 9)ng/L。肺病组的BNP水平与非CHF 非肺病组差异无显著性 (P >0 0 5 ) ,其余各组间差异有显著性 (P <0 0 1)。心功能Ⅱ～Ⅳ级〔纽约心脏学会 (NYHA)分级〕的BNP水平分别为 ( 374± 2 2 1)ng/L、( 6 34± 336 )ng/L、( 96 4± 32 1)ng/L ,组间差异有显著性 (P <0 0 1)。BNP值等于 110ng/L为界值时预测CHF的准确性最强。经短期观察发现 ,CHF组 14 6例中有 2 1例发生心血管事件 ,其BNP水平显著高于无心血管事件患者〔( 110 9± 4 31)ng/L和 ( 6 73± 336 )ng/L ,P <0 0 1)〕。　 结论　快速测定血浆BNP有助于鉴别老年人呼吸困难病因 ,是一种判断CHF预后的客观性指标     

N-terminal pro-brain natriuretic peptide for discriminating between cardiac and non-cardiac dyspnoea

AIM: Evaluation of N-terminal pro-brain natriuretic peptide (NT-proBNP) to confirm or disprove heart failure in community patients complaining of dyspnoea. METHODS AND RESULTS: General practitioners referred 345 consecutive patients complaining of dyspnoea to our hospital-based clinic, where a diagnosis was established based on a combined programme for heart and lung diseases including echocardiography. The level of NT-proBNP in plasma was also measured. The mean (S.D.) concentration of NT-proBNP in patients with heart failure was significantly higher, 189 (270) pmol/l in patients with heart failure (n=81), than in patients with non-cardiac dyspnoea (n=264), 17 (38) pmol/l (P<0.001). In patients > or = 50 years NT-proBNP <11 pmol/l for men and <17 pmol/l for women excluded heart failure with a negative predictive value of 97% while the positive predictive value was 53%, the sensitivity 95% and the specificity 68%. Areas under receiver operator characteristic curves for men and women were 0.93 and 0.90, respectively. CONCLUSION: In a relevant setting of primary care patients complaining of dyspnoea, NT-proBNP seems promising for disproval of heart failure, and this test may reduce the need for echocardiographic screening with 50%. However, the discrimination levels of NT-proBNP found in this study may need prospective confirmation, before the test can be generally recommended.     

B-type natriuretic peptide level in a patient with constrictive pericarditis.

We report the case of a 35-year-old man with constrictive pericarditis who had a B-type natriuretic peptide (BNP) level of 129 pg/dl despite a left ventricular end diastolic pressure of 35 mmHg. We discuss a possible explanation for the relatively low BNP level given this patient's markedly elevated intracavitary pressures in the setting of constrictive pericarditis.