Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure

BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.     

Intrathoracic impedance monitoring to detect chronic heart failure deterioration: relationship to changes in NT-proBNP

BACKGROUND: An alert algorithm, based on intrathoracic impedance monitoring, has been incorporated into a cardiac resynchronisation device (CRT) to detect pulmonary fluid accumulation, and to audibly alert patients to decompensating chronic heart failure (CHF). AIMS: To evaluate this algorithm, alert events were correlated with changes in NT-proBNP concentration and CHF status. METHODS AND RESULTS: In a prospective observational study of 62 patients (89% male, aged 67+/-1 year), NT-proBNP plasma concentrations, clinical CHF status, and device data were collected at enrolment, during regular follow-up and at device alerts. Over a mean follow-up of 27+/-2 weeks, pooled data indicated a weak, but significant inverse relationship between relative changes in intrathoracic impedance and NT-proBNP (r=-0.3; p<0.001). In 52 device alerts from 35 patients, NT-proBNP increased by 66+/-19% from 2039+/-331 pg/ml (p<0.001). The increase in NT-proBNP was higher in alerts with clinical signs of CHF deterioration (n=30, 89+/-25%; p<0.001) than in alert events without clinical signs (n=22, 25+/-15%; p=n.s.). CONCLUSION: Intrathoracic impedance based alert events are associated with a significant increase in NT-proBNP concentration. These data indicate that intrathoracic impedance monitoring might facilitate the outpatient management of CHF patients with implanted CRT devices.     

NT‐pro‐BNP predicts worsening renal function in patients with chronic systolic heart failure

Background: Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP) and WRF. Methods: A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT‐pro‐BNP with WRF was analysed during a follow up of 18 months. Results: Twenty‐eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063–4765) had significantly higher baseline NT‐pro‐BNP values than patients without WRF (547 pg/mL, IQR 173–1454). The risk for WRF increased by 4.0 (95% CI 2.1–7.5) for each standard deviation of log NT‐pro‐BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT‐pro‐BNP and diabetes were independent predictors of WRF. At a cut‐off level of 696 pg/mL, NT‐pro‐BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF. Conclusion: NT‐pro‐BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno‐protective strategies in patients with elevated NT‐pro‐BNP.     

Tissue Doppler velocities of mitral annulus and NT-proBNP in patients with heart failure

BACKGROUND: It has been shown that pulsed wave tissue Doppler velocities of mitral annulus correlate well with left ventricular (LV) diastolic and systolic functions. It is not yet clear whether these velocities can be used to estimate left ventricular dysfunction in an unselected population of patients with clinical signs and symptoms of heart failure (HF). AIM: To determine whether LV mitral annulus velocities measured by tissue Doppler imaging (TDI) correlate with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF. METHODS AND RESULTS: Early diastolic (E(m)) and systolic (S(m)) TDI velocities of septal and lateral mitral annulus were measured in 50 patients with HF together with other conventional echocardiographic parameters, and compared with plasma NT-proBNP levels. Significant correlations were found between NT-proBNP level and E(m) velocity (r=-0.79), S(m) velocity (r=-0.43), early transmitral to E(m) velocity ratio (r=0.38), LV end diastolic diameter (r=0.29), LV ejection fraction (r=-0.44) and tricuspid regurgitant velocity (r=0.31). In multiple regression model (R(2)=0.733), the E(m) velocity was the most important predictor of NT-proBNP level. CONCLUSIONS: Early diastolic mitral annulus velocity measured by TDI correlates strongly with plasma NT-proBNP levels, and provides a simple, accurate and reproducible echocardiographic index of heart failure.     

Use of NT-proBNP in routine testing and comparison to BNP

OBJECTIVES: B-type natriuretic peptide (BNP) is a strong diagnostic predictor of left-ventricular (LV)-dysfunction. Recently, the aminoterminal portion of pro-BNP (NT-proBNP) has been introduced, which could be even more sensitive because of its longer half-life. The aim of this study was to evaluate the new marker NT-proBNP within a large, heterogeneous population of patients with suspected cardiovascular disease at risk of cardiovascular dysfunction and to compare it with the established diagnostic parameter BNP. SUBJECTS AND METHODS: NT-proBNP and BNP were measured in 339 hospitalised patients undergoing diagnostic angiography (median age 66 years, 244 male vs. 95 female). RESULTS: Median values of NT-proBNP increased with worsening LV-dysfunction and higher NYHA class. The area under the receiver operator characteristics curve (AUC) of NT-proBNP for detecting severe systolic dysfunction or for detecting any systolic LV-dysfunction was 0.83 and 0.77, respectively. The latter improved (AUC=0.81) when patients with clinically relevant heart disease like valvular dysfunction were included, independent of the haemodynamic values. Compared to BNP, NT-proBNP tended to be more accurate in identifying lesser degrees of LV-dysfunction. CONCLUSIONS: Even after optimisation of target criteria, there was still a substantial overlap of NT-proBNP values between patients with and without relevant heart disease. Therefore, NT-proBNP is not suitable as a screening test for LV-dysfunction in the community. Nevertheless, because of its good negative predictive value, NT-proBNP could be an easy and effective tool to rule out severe systolic LV-dysfunction in high risk patients. No clinically significant advantage of BNP testing could be found.     

Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure

BACKGROUND: B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). METHODS: We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. RESULTS: While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. CONCLUSION: Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.     

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.     

Left atrial enlargement and NT-proBNP as predictors of sudden cardiac death in patients with heart failure

AIMS: The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction. METHODS: A cohort of 494 patients with established HF had baseline echocardiographic and NT-proBNP measurements and were followed for 942+/-323 days. RESULTS: Fifty patients suffered SCD. Independent predictors of SCD were indexed LA size>26 mm/m2 (HR 2.8; 95% CI 1.5-5.0; p=0.0007), NT-proBNP>908 ng/L (HR 3.1; 95% CI 1.5-6.7; p=0.003), history of myocardial infarction (HR 2.3; 95% CI 1.3-4.1; p=0.007), peripheral oedema (HR 2.1; 95% CI 1.1-3.9; p=0.02), and diabetes mellitus (HR 1.9; 95% CI 1.1-3.3; p=0.03). NYHA functional class, left ventricular ejection fraction and glomerular filtration rate were not independent predictors of SCD in this cohort. Notably, the combination of both LA size>26 mm/m2 and NT-proBNP>908 ng/L increased the risk of SCD (HR 4.3; 95% CI 2.5-7.6; p<0.0001). At 36 months, risk of SCD in patients with indexed LA size26 mm/m2 and NT-proBNP>908 ng/L reached 25% (p<0.0001). CONCLUSIONS: Among HF patients, indexed LA size and NT-proBNP levels are more useful to stratify risk of SCD than other clinical, echocardiographic or biochemical variables. The combination of these two parameters should be considered for predicting SCD in patients with HF.     

NT-proBNP correlates with right heart haemodynamic parameters and volumes in patients with atrial septal defects

BACKGROUND: To investigate the role of N-terminal pro-BNP (NT-proBNP) for the estimation of right heart failure and pulmonary pressure in patients with atrial septal defects (ASD) before and after percutaneous defect closure. METHODS: We performed correlation analysis for NT-proBNP and right ventricular systolic pressure (RVSP) as well as right ventricular enddiastolic and endsystolic volume (RVEDV, RVESV) determined by cardiac magnetic resonance imaging (MRI) before and up to one year following ASD closure. Additionally NT-proBNP concentrations were correlated with right atrial (RA) and RV enddiastolic pressure (RVEDP), ASD size and interatrial left-to-right shunt. RESULTS: Baseline RVSP was 33+/-8 mmHg, which decreased significantly during follow-up. Initially, NT-proBNP levels were 240+/-93 pg/ml. After closure, a reduction to 116+/-62 pg/ml was obvious (p<0.01). Baseline MRI showed enlarged RV volumes in all individuals. At six and twelve months follow-up a significant reduction of RVEDV and RVESV was apparent. A positive correlation was noted between RV volumes and NT-proBNP (r=0.65, p<0.05). Furthermore RA pressure, RVEDP, RVSP and left-to-right shunt significantly correlated to peptide levels. No correlation was seen between ASD size and NT-proBNP. CONCLUSION: NT-proBNP correlates to right ventricular dilatation, pulmonary pressure and left-to-right shunt in volume load of the right heart caused by an underlying ASD.     

卡维地洛对慢性心力衰竭心功能和ANP及BNP的影响

目的观察卡维地洛(达利全)对慢性心力衰竭(CHF)患者心功能和ANP/BNP的影响。方法60例CHF患者,在常规治疗病情基本稳定的基础上,增加服用卡维地洛,从每次3.125mg开始,2次/d,缓慢递增。治疗前后分别进行心率、血压、心功能分期评估和血清ANP/BNP测定。结果与治疗前相比,治疗5个月后,心率明显下降(P<0.01),心功能分级明显改善,血清ANP/BNP明显下降(P<0.01)。66.7%患者服用卡维地洛剂量可达到目标剂量25mg,2次/d;33.3%患者使用中等剂量12.5mg,2次/d,维持治疗。结论长期服用卡维地洛能改善心功能,降低血清ANP和BNP水平。     

缬沙坦对老年心力衰竭患者N端脑钠肽前体及和肽素的影响

目的观察老年慢性心力衰竭（简称“心衰”）患者缬沙坦治疗前后血浆N端脑钠肽前体（NT-proBNP）及和肽素的变化,探讨缬沙坦抑制心室重构的作用机制。方法纳入2011年6月至2012年9月在湖南株洲凯德心血管病医院心内科就诊的老年慢性心衰患者99例,随机分为治疗组（常规治疗＋缬沙坦,n＝50）和对照组（仅常规治疗,n＝49）,分别检测两组治疗前、治疗1个月、治疗6个月,血浆NT-proBNP、和肽素水平及心室结构功能的变化。结果两组患者治疗1个月与治疗前、治疗6个月与1个月比较,血浆NT-proBNP及和肽素水平均下降,差异均有统计学意义（P＜0.05或P＜0.01）;治疗组患者治疗1个月、6个月的血浆NT-proBNP、和肽素水平与同时间段对照组相比均下降,差异均有统计学意义（P＜0.05或P＜0.01）。治疗1个月,两组患者左室射血分数（LVEF）、左心室收缩末期内径（LVESD）及左心室舒张末期内径（LVEDD）与治疗前比较,以及两组间比较,差异均无统计学意义（P＞0.05）;治疗6个月,治疗组LVEF较对照组明显升高（P＜0.01）,LVESD及LVEDD较对照组明显减小（均P＜0.01）。结论血管紧张素Ⅱ受体拮抗剂缬沙坦能够抑制老年慢性心衰患者血浆NT-proBNP、和肽素的分泌,抑制神经内分泌因子,抑制心室重构,改善心功能。     

Prognostic impact of NT-proBNP and renal function in comparison to contemporary multi-marker risk scores in heart failure patients

BACKGROUND: Multi-marker risk scores accurately predict prognosis in heart failure patients but calculation is complex. AIMS: To compare the prognostic accuracy of the Seattle Heart Failure Survival Score (SHFS) and a model derived from the CHARM programme, with laboratory parameters NT-proBNP and glomerular filtration rate (GFR). METHODS AND RESULTS: In a sample of 290 heart failure patients, 39 patients died, 22 were hospitalised with acute heart failure and 4 underwent urgent cardiac transplantation during a median follow-up of 498 days. NT-proBNP, GFR, CHARM and SHFS showed an AUC for an endpoint during 1-year of 0.80, 0.72, 0.79 and 0.69, respectively. The hazard ratio for an endpoint during follow-up was 2.1, 2.6, 1.9 and 2.1 per 1 SD increase of log NT-proBNP and CHARM and per 1 SD decrease of GFR and SHFS, respectively. In multivariate analysis, log NT-proBNP and GFR added independent prognostic information to CHARM and SHFS, respectively. CONCLUSION: NT-proBNP and GFR independently predicted endpoint-free survival in systolic heart failure patients, with NT-proBNP being superior and equally predictive to the SHFS and CHARM score, respectively. Assessment of both laboratory markers can simplify prognostic stratification, addition to multi-marker scores should be evaluated.     

COPD并肺心病心力衰竭hs-CRP、BNP检测临床意义分析

目的探讨COPD并肺心病心力衰竭患者超敏C反应蛋白（hs—CRP）及脑纳肽（BNP）临床水平变化意义。方法测量COPD并肺心病心力衰竭患者组55例及门诊健康体检组30例血清hs—CRP、BNP水平,按照美国纽约心脏病协会分级方案对COPD并肺心病心力衰竭患者组55例分组。结果COPD并肺心病患者组hs—CRP、BNP水平明显高于对照组（P〈0．05）,心力衰竭分组hs—CRP、BNP水平随心衰分级明显升高,Ⅳ级组明显高于I级组,Pa02水平随心衰分级逐步下降,各组之间两两比较均有统计学意义（P〈0．05）。相关性分析显示慢性阻塞性肺病（COPD）并肺心病心力衰竭患hs—CRP、BNP与心衰分级呈正相关（r=0．384,0．280,P〈005）,Pa02水平与心衰分级呈负相关（r=-0．251,P〈0．05）。结论COPD并肺心病心力衰竭组患者hs—CRP、BNP水平明显升高,监测hs—CRP、BNP水平可作为临床评估肺心病心力衰竭预后指标。     

Cardiac dysfunction and N‐terminal pro‐B‐type natriuretic peptide in exacerbations of chronic obstructive pulmonary disease

Elevated levels of B‐type natriuretic peptides among patients with exacerbations of chronic obstructive pulmonary disease (COPD) are associated with higher mortality. The pathophysiology is unclear. To establish if elevated levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are due to right or left heart dysfunction, we performed echocardiograms in 18 patients admitted to hospital with COPD. Elevated levels of NT‐proBNP were associated with both right and left heart dysfunction and indicate that these patients have biventricular dysfunction rather than isolated right ventricular compromise.     

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.