Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease.

In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. OBJECTIVES: The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. BACKGROUND: Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. METHODS: In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay. RESULTS: Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. CONCLUSIONS: In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.     

B-type natriuretic peptide in ischemic heart disease

B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-proBNP) are released from the heart in response to increased wall stress. Assays for these peptides are now commercially available, and measurement of BNP and N-proBNP is becoming commonplace in patients with suspected heart failure. BNP and N-proBNP facilitate diagnosis and risk stratification in patients with heart failure, and may help guide response to therapy. This review focuses on the emerging role of BNP and NproBNP measurement in patients with acute coronary syndromes (ACS). Although experimental studies demonstrate rapid BNP release in response to cardiac ischemia, it is unlikely that BNP will be used to diagnose cardiac ischemia, because many other conditions are also associated with modest BNP elevation. In contrast, BNP holds tremendous promise as a prognostic marker in patients with ACS. Studies to date have shown consistently that higher BNP levels are associated with worse clinical outcomes, and that BNP provides unique information to clinical variables, other biomarkers, and left ventricular ejection fraction. Future studies are needed to identify the therapeutic implications of BNP elevation in patients with ACS.     

血浆BNP水平与老年慢性充血性心衰患者心功能状态及预后的关系

目的探讨血浆B型利钠肽（BNP）水平与老年慢性充血性心衰（CHF）患者心功能状态及预后的关系。方法选择62例心功能NYHA分级Ⅱ～Ⅳ级的老年CHF患者,均行血浆BNP、肾功、血脂指标及心脏功能检查。比较不同BNP水平患者的上述指标变化。结果根据血浆BNP水平分为两组,A组BNP≤400 pg/ml,B组BNP〉400 pg/ml。与A组比较,B组房颤、陈旧性心肌梗死及死亡患者比例增加,尿素氮、肌酐、胆固醇、低密度脂蛋白升高,左室舒张末期内径、左室射血分数降低（P〈0.05或〈0.01）。心功能NYHA分级Ⅳ级患者的血浆BNP水平〉Ⅲ级〉Ⅱ级,两两比较均有统计学差异（P均〈0.01）。结论血浆BNP水平是判定老年CHF患者心功能的良好指标。     

BNP对稳定型冠状动脉疾病预后的判断价值

目的:探讨BNP对稳定型冠状动脉疾病患者的预后判断价值. 方法:对186例稳定型冠状动脉疾病患者入院时测定其BNP值,并行冠状动脉及左室造影,平均随访16个月,观察其死亡率,对BNP与死亡率相关性进行统计学分析. 结果:随访期间15例(8.0%)死亡.存活者的BNP均值显著低于死亡者(120 pg/ml对386pg/ml,P＜0.01).BNP水平位于最高的四分位数的患者与低四分位数的患者相比,具有高龄、低左室射血分数(LVEF)等特点,更可能患有心肌梗死及糖尿病等病史.在多变量COX回归模型中,BNP水平位于第四个四分位数的患者与第一个四分位数相比,其死亡的危险比为2.4(95% CI:1.5～4.0,P＜0.001). 结论:BNP是稳定型冠状动脉疾病患者预后不良的指标,其预后判断价值可能大于常规的危险因素.     

BNP对稳定型冠状动脉疾病预后的判断价值

目的：探讨BNP对稳定型冠状动脉疾病患者的预后判断价值。方法：对186例稳定型冠状动脉疾病患者入院时测定其BNP值,并行冠状动脉及左室造影,平均随访16个月,观察其死亡率,对BNP与死亡率相关性进行统计学分析。结果：随访期间15例(8．0%)死亡。存活者的BNP均值显著低于死亡者(120pg/ml对386 pg/ml,P＜0．01)。BNP水平位于最高的四分位数的患者与低四分位数的患者相比,具有高龄、低左室射血分数(LVEF)等特点,更可能患有心肌梗死及糖尿病等病史。在多变量COX回归模型中,BNP水平位于第四个四分位数的患者与第一个四分位数相比,其死亡的危险比为2．4(95%CI：1．5～4．0,P＜0．001)。结论：BNP是稳定型冠状动脉疾病患者预后不良的指标,其预后判断价值可能大于常规的危险因素。     

阿托伐他汀对冠心病心力衰竭患者血浆钠尿肽水平及心功能的影响

目的:观察阿托伐他汀对冠心病心力衰竭(心衰)患者血浆钠尿肽(BNP)水平和心功能的影响。方法:将128例冠心病心衰(心功能Ⅱ～Ⅲ级)患者随机分为10mg阿托伐他汀组(A组)、20mg阿托伐他汀组(B组)和对照组(C组),3组均给予抗心衰基础治疗,A组加服阿托伐他汀10mg/d,B组加服阿托伐他汀20mg/d。治疗前及治疗后12周时测定血浆BNP、血清高敏C反应蛋白(hs-CRP)水平、6min步行试验,并采用超声心动图测量左心室射血分数(LVEF)。结果:3组患者治疗12周时心功能指标、血浆BNP水平及血清hs-CRP水平均较治疗前明显改善,2种剂量治疗组血浆BNP、血清hs-CRP水平均降低,LVEF均升高,与对照组比较差异有统计学意义(P<0.01)。A、B治疗组的6min步行距离明显增加,与对照组比较,差异有统计学意义(P<0.05);而A、B治疗组间血浆BNP水平、血清hs-CRP水平、LVEF及6min步行距离无差异。结论:冠心病心衰患者在基础治疗上加用小剂量阿托伐他汀即可以降低BNP水平及血清hs-CRP水平,进一步改善心功能,抑制心肌微炎症可能是该药机制之一。     

B-type natriuretic peptides. A diagnostic breakthrough in heart failure

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles, which is released as N-terminal pro-brain natriuretic peptide (NT-proBNP) and then enzymatically cleaved in to the NT fragment and the immunoreactive BNP. Both tests have been used to identify patients with congestive heart failure (CHF). Important considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, and the interpretation of their units of measure. In general, a BNP level below 100 pg/mL has strong negative predictive value in the assessment of patients with dyspnea caused by a disorder other than CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated heart failure, and the peptide has been shown to be a reliable independent predictor of sudden cardiac death. In the absence of renal dysfunction NT-proBNP has also been shown to be an independent predictor of sudden death in CHF patients. Because both a large area of myonecrosis or concomitant left ventricular failure are related to prognosis in acute coronary syndromes, B-type natriuretic peptides have also been linked to outcomes in this condition. This article describes the physiology and timing of release of B-type natriuretic peptides and the rationale for their use in the following settings: 1) evaluation of decompensated CHF, 2) screening for chronic CHF, 3) prognosis of CHF and sudden death, and 4) prognosis in acute coronary syndromes with inferred left ventricular dysfunction.     

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.     

Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical diagnosis of chronic obstructive pulmonary disease

AIMS: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: 200 patients aged >or=65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by a panel using the diagnostic principles of the European Society of Cardiology. All available diagnostic results, including echocardiography, but not BNP or NT-proBNP measurements, were used. The ability of different B-type natriuretic peptide assays to identify heart failure was estimated using the area under the receiver operating characteristic curves (ROC-area). RESULTS: The ROC-areas did not differ significantly between the various assays of NT-proBNP and BNP, and ranged from 0.68 (95%CI 0.60-0.73) to 0.73 (95%CI 0.64-0.81). For NT-proBNP the age- and gender-independent 'optimal' cut-point was 15 pmol/l (125 pg/ml) and for BNP 10 pmol/l (35 pg/ml). All assays were much better at excluding than detecting heart failure. CONCLUSIONS: All assays of B-type natriuretic peptide showed reasonable and comparable accuracy in recognising heart failure. At 'optimal' cut-points, all assays performed better at excluding than detecting new cases of heart failure in this population.     

Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18

OBJECTIVES: This study was designed to evaluate B-type natriuretic peptide (BNP) for risk assessment and clinical decision making over a range of cut points, alone and with cardiac troponin I (cTnI), in patients with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: B-type natriuretic peptide holds promise for risk stratification. Additional evidence regarding optimal decision limits, use in combination with troponin, and use in targeting therapy is needed before acceptance into clinical use for ACS. METHODS: We evaluated BNP at baseline in 1,676 patients with non-ST-elevation ACS randomized to early invasive versus conservative management. RESULTS: Patients with elevated BNP (>80 pg/ml; n = 320) were at higher risk of death at seven days (2.5% vs. 0.7%, p = 0.006) and six months (8.4% vs. 1.8%, p < 0.0001). The association between BNP and mortality at six months (adjusted odds ratio [OR] 3.3; 95% confidence interval [CI] 1.7 to 6.3) was independent of important clinical predictors, including cTnI and congestive heart failure (CHF). Patients with elevated BNP had a fivefold higher risk of developing new CHF by 30 days (5.9% vs. 1.0%, p < 0.0001). B-type natriuretic peptide added prognostic information to cTnI, discriminating patients at higher mortality risk among those with negative (OR 6.9; 95% CI 1.9 to 25.8) and positive (OR 4.1; 95% CI 1.9 to 9.0) baseline cTnI results. No difference was observed in the effect of invasive versus conservative management when stratified by baseline levels of BNP (p(interaction) > or = 0.6). CONCLUSIONS: Elevated BNP (>80 pg/ml) at presentation identifies patients with non-ST-elevation ACS who are at higher risk of death and CHF and adds incremental information to cTnI. Additional work is needed to identify therapies that may reduce the risk associated with increased BNP.     

Urinary B-type natriuretic peptide levels in the diagnosis and prognosis of heart failure

BackgroundPlasma B-type natriuretic peptide (BNP) is a useful biomarker for diagnosis and prognosis of heart failure (HF); however, urine BNP has never been calculated. We sought to compare urinary and plasma BNP levels and to investigate the potential diagnostic and prognostic value of this peptide in HF.Methods and ResultsUrine and plasma BNP levels were measured in 92 HF patients and 30 control subjects. Urinary BNP levels were higher in HF patients than in control subjects (P < .0001), correlating with plasma BNP levels (r = 0.64, P < .0001). Urine BNP was a good tool for the diagnosis of HF, the area under the curve (AUC) being 0.91 ± 0.06 (P < .0001). Urinary BNP levels had prognostic power for cardiac events (cardiac admissions + mortality) with an odds ratio of 6.6 (P < .05). To determine the prognostic power of urinary BNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.76 ± 0.6 (P = .014).ConclusionsThe data suggest that urine BNP is a new candidate marker for diagnosis and prognosis of HF mortality and cardiac events. This raises the possibility of using this relatively simple noninvasive test in primary care settings or in specific conditions where the collection of blood samples could be difficult.     

The biologic variability of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in stable heart failure patients

BackgroundThere are conflicting data on the usefulness of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the optimization of therapy for heart failure (HF). Discordant results may be explained by the intra-individual variability of these peptides. This study evaluates the intraindividual variability of BNP and NT-proBNP and the impact of the covariates of age, sex, and renal function.Methods and ResultsStable HF patients attending our unit were included. Blood samples were drawn 1 hour apart on 2 occasions 1 week apart. Forty-five patients were enrolled (69.6 ± 12.1 years, 64% male, 84% systolic HF). Within-hour and within-week intraindividual variability were: 6.9% and 21.1% for NT-proBNP; 14.6% and 28.4% for BNP (P < .01 for within-hour comparison of BNP and NT-proBNP). Reference change values over 1 week for NT-proBNP and BNP were 49.2% and 66.2%, respectively. There were no significant relationships identified between variability and age, gender, or glomerular filtration rate.ConclusionThere is considerable intraindividual variability in these peptides in stable HF patients. Changes of approximately 50% and 66% for NT-proBNP and BNP from week to week are needed to indicate an altered clinical status and caution should be exercised in interpreting serial changes in these peptide levels when monitoring patient responses to treatment or clinical status.