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.     

Vasoactive intestinal peptide--release from the heart and response in heart failure due to left ventricular pressure overload

BACKGROUND: Vasoactive intestinal peptide (VIP) is a peptidergic neurotransmitter and a vasodilator with positive inotropic and chronotropic properties. Whether and how VIP contributes to the neuroendocrine response in heart failure (HF) is disputed, and there are no data on VIP in pressure overload-induced HF. METHODS: We studied 129 adults with isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 48 patients, also from the coronary sinus for determination of VIP by radioimmunoassay. HF was diagnosed according to the European Society of Cardiology criteria. RESULTS: Plasma VIP (mean+/-S.E.M.) was slightly higher in patients with HF (22.6+/-0.9 pmol/l, n=41) than in patients free of HF (21.1+/-0.5 pmol/l, n=88) or in 11 control patients without structural heart disease (20.0+/-1.3 pmol/l, n=11) (p=0.030 across the groups). VIP did not correlate with any measurement of cardiac structure or function in AS. The change in plasma VIP from aortic root to coronary sinus averaged +1.2+/-0.4 pmol/l in the 11 control patients (p=0.021), +1.2+/-0.2 pmol/l in 33 AS patients free of HF (p<0.001) and +0.8+/-0.3 pmol/l in 15 AS patients with HF (p=0.037). CONCLUSIONS: Both structurally normal and diseased hearts release VIP into the coronary sinus. Although marginally elevated in the systemic circulation, VIP is unlikely to contribute significantly to the neuroendocrine activation in HF due to pressure overload.     

N末端B型利钠肽原在陈旧性心肌梗死患者中诊断心力衰竭的价值

目的 评价血浆N末端B型利钠肽原(NT-proBNP)在陈旧性心肌梗死(OMI)患者中诊断失代偿性心力衰竭(心衰)的价值.方法 连续检测586例OMI患者入院时的血浆NT-proBNP浓度.依据NYHA心功能分级标准评价患者的心功能.心衰组为NYHA心功能Ⅱ级、Ⅲ级和Ⅳ级的患者,非心衰组为NYHA心功能I级的患者.通过ROC曲线下面积评价血浆NT-proBNP浓度诊断失代偿性心衰、左心室收缩功能不全和左心室扩大的价值,并找出其诊断失代偿性心衰的切点.结果586例 OMI患者中,男性占80％,年龄25～83岁,平均(58±11)岁.NYHA Ⅰ级374例、Ⅱ级99例、Ⅲ级82例、Ⅳ级31例,其血浆NT-proBNP浓度[中位数(第25百分位数,第75百分位数)]分别为[484.7(381.6,647.8)pmol/L、907.6(516.6,1290.3)pmol/L、1420.2(879.5,2336.2)pmol/L2442.6(1695.4,3670.7)pmol/L,P＜0.01].心衰组(212例)血浆NT-proBNP浓度显著高于非心衰组(374例)[分别为1148.2(707.9,2145.3)pmol/L和484.7(381.6,647.8)pmol/L,P＜0.01].60岁以上的OMI患者的血浆NT-proBNP显著高于＜60岁的患者[分别为702.3(472.4,1208.5)pmol/L和526.6(392.1,855.6)pmol/L,P＜0.01].男女性别间比较差异无统计学意义.血浆NT-proBNP诊断失代偿性心衰的ROC曲线下面积是0.844(95％ CI:0.809～0.880,P＜0.01).根据ROC曲线,将NT-proBNP诊断失代偿性心衰的切点值定为700 pmol/L,大于或等于此值时诊断心衰的敏感性、特异性和准确性分别是75.9％、79.9％和78.3％,阳性预测值和阴性预测值分别为67.9％和85.3％.对于＜60岁患者,该切点值以600 pmol/L最佳,对于≥60岁患者,该切点值以800pmol/L为最佳.结论 血浆NT-proBNP是OMI患者中诊断失代偿性心衰的可靠指标.对≥60岁和＜60岁的患者应采取不同的诊断切点.     

Alternate circulating pro-B-type natriuretic peptide and B-type natriuretic peptide forms in the general population.

OBJECTIVES: This study was designed to determine whether alternate pro-B-type natriuretic peptide (proBNP) and BNP forms circulate in the general population. BACKGROUND: Bioactive BNP(1-32) and NT-proBNP(1-76) are derived from a precursor molecule, proBNP(1-108). Recent data suggest that aminodipeptidase-processed forms of BNP(1-32) (BNP(3-32)) and of proBNP(1-108) itself (proBNP(3-108)) may circulate and have additional diagnostic potential. METHODS: Residents (age > or =45 years) of Olmsted County, Minnesota, underwent medical review, echocardiography, and phlebotomy for 2 novel assays specific for proBNP(3-108) and BNP(3-32) and 2 commercial assays (Triage BNP and Roche NT-proBNP). Groups included normal subjects (n = 613), cardiovascular disease with normal ventricular function (n = 1,043), preclinical ventricular dysfunction (ALVD, n = 130), and chronic heart failure (HF, n = 52). RESULTS: ProBNP(3-108) levels were above assay detection limits in 68% of normal subjects (50th; 25th to 75th percentiles: 7.85; 3.00 to 22.45 pmol/l) and correlated with age, gender, body size, and renal function and with results of commercial assays. ProBNP(3-108) levels were higher in ALVD (17.88; 6.07 to 42.76 pmol/l) or HF (42.75; 20.51 to 65.73 pmol/l), where they correlated more strongly with commercial assays. BNP(3-32) was above assay detection limits in 22% of normal subjects; levels were not correlated with age, body size, or renal function but were higher in HF. Neither novel assay was superior to commercial assays for the detection of ALVD or HF. CONCLUSIONS: The presence of alternate circulating proBNP and BNP forms provides evidence for diverse proBNP and BNP processing in the general population. The physiologic consequences of these observations, both in terms of assay performance and endogenous BNP bioactivity, deserve further study.     

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.     

重组人脑钠肽对射血分数正常心力衰竭患者脑钠肽前体的影响

目的探讨经重组人脑钠肽(recombinant human brain natriuretic peptide,rhBNP)治疗后,射血分数正常心力衰竭(heart failure with normal ejection fraction,HFNEF)患者的血浆脑钠肽前体(pro-brain natriuretic peptide,proBNP)浓度及临床症状的变化。方法入选51例HFNEF患者(纽约心脏协会心功能Ⅲ、Ⅳ级),其中21例在常规治疗的基础上加用rhBNP治疗4～7 d,治疗前、后分别检测血浆proBNP浓度,并与仅用常规治疗的对照组(30例)比较。分析治疗前、后血浆proBNP浓度及临床症状变化。结果治疗组与对照组总有效率分别为95.2%和93.3%,差异无统计学意义(P>0.05)。两组治疗后血浆proBNP浓度与治疗前比较都有下降,差异有统计学意义(P<0.05);且治疗组治疗后血浆proBNP浓度显著低于与对照组,差异有统计学意义[1 297.5 pg/mL vs.2 037.8 pg/mL,P<0.05]。结论rhBNP可降低HFNEF患者血浆proBNP浓度,有效改善患者症状。     

Plasma amino‐terminal pro‐brain natriuretic peptide levels in subjects presenting to the Emergency Department with suspected acute coronary syndrome: possible role in selecting patients for follow up?

Background: Plasma amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) level is a sensitive and specific indicator of cardiac dysfunction. Aim: To determine whether plasma NT‐proBNP level is elevated at the time of presentation with acute coronary syndrome (ACS) and whether it may assist in the diagnosis of heart failure and myocardial ischaemia in the Emergency Department. Methods: Plasma NT‐proBNP levels were measured prospectively in 201 unselected presentations to the Emergency Department with suspected ACS where cardiac injury markers were requested by clinicians as part of routine assessment. NT‐proBNP levels were correlated with clinical, electrocardiogram (ECG), biochemical and radiological findings. Results: Elevated NT‐proBNP level detected heart failure with high sensitivity (95–96%). Among patients without heart failure, NT‐proBNP levels were increased more frequently in patients with previously diagnosed ischaemic heart disease. Elevated NT‐proBNP level predicted cardiomegaly and a cardiac cause of presentation. However, the NT‐proBNP level was not associated with ECG or biochemical markers of myocardial ischaemia, and only one‐third of patients with ACS showed an increase of 40% or more in NT‐proBNP level at repeat measurement of cardiac injury markers 5 h after presentation. Conclusions: Although elevated NT‐proBNP level detected heart failure with high sensitivity, NT‐proBNP level did not assist in the diagnosis of acute myocardial ischaemia. These findings indicate that the major determinant of elevated NT‐proBNP level on presentation with suspected ACS was underlying cardiac dysfunction rather than acute myocardial ischaemia. This suggests that NT‐proBNP measurement in patients with a suspected cardiac reason for presentation to the Emergency Department may identify a previously unrecognized group of patients without acute ischaemia who may nevertheless benefit from further investigation of cardiac function. (Intern Med J 2001; 31: 211–219)     

Plasma N-terminal pro-brain natriuretic peptide in Type 1 diabetic patients with and without diabetic nephropathy.

AIMS: Plasma N-terminal pro-brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy. METHODS: We developed a non-competitive immunoluminometric assay with in-house antibodies to the N- and C-terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3). RESULTS: There were significant differences in 24-h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL-cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75-68), 22 (0.75-82) and 23 (0.75-374) fmol/ml for groups 1-3, respectively. Log-transformed data of NT proBNP were used to compare all three groups (P=0.016). The Pearson correlation between NT proBNP and albuminuria (R=0.27; P=0.02) was positive; HbA1c (R=0.25; P=0.03) and age (R=0.33; P=0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups. CONCLUSIONS: This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down-regulation of A-type guanylate cyclase-coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co-morbidities as cardiovascular disease.     

心力衰竭患者血总胆红素与有创血液动力学及B型利钠肽相关研究

目的 评价心力衰竭(心衰)患者血胆红素与有创血液动力学监测指标、血浆N末端B型利钠肽原(NT-proBNP)和C反应蛋白(CRP)的相关性.方法 对130例心衰患者在入院12 h内行漂浮导管监测和血总胆红素、血浆NT-proBNP和CRP等检测.结果 肺毛细血管楔压[PCWP,(26.09比16.00)mm Hg(1mm Hg=0.133 kPa)]、NT-proBNP[(3.36比2.91)pmol/L]和左室射血分数[(34.12比28.92)%]在高总胆红素血症组均较正常血总胆红素组显著增高(P值均<0.05).血总胆红素水平在高水平PCWP、右房压和NT-proBNP组较低水平组显著增高[(32.22比24.17)、(37.52比24.19)、(32.14比16.74)pmol/L,P值均<0.05].血总胆红素分别与NT-proBNP和右房压独立相关(β=0.39;β=0.29,P值均<0.01).结论 心衰患者血总胆红素水平与右房压、PCWP和血浆NT-proBNP密切相关,是有助于心衰患者准确临床评价的重要生化指标.     

Brain natriuretic peptide as a cardiac hormone in essential hypertension.

PURPOSE: A natriuretic peptide, brain natriuretic peptide (BNP), has been isolated from porcine hearts. We performed this study to determine if BNP is secreted from the heart and to identify changes, if any, in the plasma BNP concentration in essential hypertension. PATIENTS AND METHODS: We measured the immunoreactive (ir) BNP concentration at intracardiac sites including the coronary sinus of five patients with heart disease during cardiac catheterization. We examined plasma ir-BNP in 48 hypertensive patients, 15 borderline hypertensive patients, and 25 normotensive subjects. RESULTS: Plasma ir-BNP in the coronary sinus was greater than at other cardiac sites. The concentration was significantly higher in hypertensive subjects than in borderline hypertensive or normotensive subjects. Hypertensive patients with left ventricular hypertrophy (LVH) established by echocardiography had higher plasma ir-BNP levels than those without LVH. In the hypertensive group, plasma ir-BNP was closely correlated with the LV mass index. In these patients, BNP levels were correlated with mean arterial pressure and inversely correlated with the LV ejection fraction, although these correlations were weak. Reverse-phase high-pressure liquid chromatography showed that the major component of circulating ir-BNP in the hypertensive and normotensive subjects corresponded to authentic human BNP-32. CONCLUSIONS: Human BNP-32 was secreted through the coronary sinus from the heart and may act as a cardiac hormone. Plasma BNP was increased in many of the hypertensive subjects with LVH. The increase in BNP seemed to be related to LVH or the cardiac overload associated with LVH.     

B-type natriuretic peptide and its molecular precursor in myocardial infarction complicated by cardiogenic shock

BackgroundPlasma measurement of cardiac natriuretic peptides and their biosynthetic precursors is helpful in chronic heart failure patients. In contrast, information on circulating B-type natriuretic peptide (BNP) and its molecular precursor (proBNP) in patients with cardiogenic shock is scarce. We therefore examined proBNP-derived peptides in plasma from patients with myocardial infarction complicated by cardiogenic shock.Methods and ResultsPatients were referred for early, invasive therapy because of myocardial infarction complicated by cardiogenic shock (n = 13). Plasma proBNP was measured with an automated assay (NT-proBNP) and an in-house radioimmunoassay (proBNP); BNP concentrations were quantitated with an immunoradiometric assay. The median NT-proBNP concentration was 8.2-fold higher than the corresponding BNP concentration (873 pmol/L [range 41–12,486] versus 107 pmol/L [1–1041], P < .001). Moreover, the NT-proBNP concentration was 3.3-fold higher compared with proBNP (268 pmol/L [19–12,220], P < .01). Despite the molar differences, there was a strong correlation between NT-proBNP and proBNP (r = 0.84, P < .0001) and BNP (r = 0.82, P < .0001) concentrations. Gel filtration chromatography suggested that the proBNP immunoreactivity reflect a molecular form larger than the N-terminal 1-76 fragment.ConclusionsThe study reveals the plasma profile of proBNP-derived peptides during myocardial infarction complicated by cardiogenic shock. Peripheral concentrations of NT-proBNP, proBNP, and BNP were highly correlated despite marked differences between assays. The results also suggest an increase in cardiac proBNP processing after myocardial infarction and cardiogenic shock.     

Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis

BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants. METHODS: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050). CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.     

Coronary sinus and ascending aortic levels of aldosterone, angiotensin II, and B-type natriuretic peptide in patients with aortic stenosis and in patients with coronary heart disease

Demonstration that aldosterone synthesis occurs in the myocardium would suggest that the clinical benefits of aldosterone receptor antagonists may extend to patients with normal circulating plasma levels of aldosterone. Previous studies have reported myocardial aldosterone synthesis in patients with heart failure. This study determined whether myocardial aldosterone and angiotensin II release occurs in patients with aortic stenosis (AS) and/or coronary heart disease (CHD) with normal left ventricular ejection fractions and no clinical heart failure. In 19 patients with severe AS and 18 patients with stable CHD, plasma levels of aldosterone, angiotensin II, B-type natriuretic peptide (BNP), and procollagen type III amino terminal peptide (PIIINP) were measured in blood samples taken from the coronary sinus and aortic root before diagnostic coronary angiography. Plasma aldosterone was approximately 20% greater in the coronary sinus than the aorta, respectively, in the 2 patient groups (AS: 120 vs 102 pmol/L, p <0.001; CHD: 94 vs 77 pmol/L, p <0.001). Plasma angiotensin II was also greater in the coronary sinus (AS: 16 vs 11 pmol/L, p <0.001; CHD: 12 vs 9 pmol/L, p <0.001). Plasma levels of BNP in the coronary sinus were approximately double those in the aorta in the 2 groups of patients (p <0.001). In contrast, there was no transmyocardial gradient in the plasma level of PIIINP for either AS or CHD. In conclusion, these results indicate that aldosterone, angiotensin II, and BNP are released into the coronary sinus in severe AS and in stable CHD, even when the left ventricular ejection fraction is normal and there is no clinical heart failure.     

Hormonal and renal differences between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure.

OBJECTIVE: To assess the differential effects of low dose (5 mg) and high dose (20 mg) lisinopril treatment on cardiovascular hormones, renal function, and blood pressure over 24 hours in patients with heart failure. DESIGN: Double-blind crossover study. SETTING: Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee. PATIENTS: 19 patients with chronic heart failure and left ventricular ejection fraction < or = 45%. RESULTS: Plasma concentrations of aldosterone and endothelin were lower on the 20 mg dose (plasma aldosterone mean at peak drug effect: 90.7 v 152.0 pg/ml, P < 0.001; mean at trough effect: 124.7 v 174.4 pg/ml, P < 0.01; plasma endothelin at trough effect 4.70 v 6.04 pmol/l, P = 0.03). Creatinine clearance was lower on 20 mg lisinopril (68.7 v 82.1 ml/min, P < 0.05). The area under the curve for diastolic blood pressure over 24 hours was significantly lower on 20 mg (mean difference 3.0 mm Hg, P = 0.04); for systolic blood pressure there was a similar trend (mean difference 5.7 mmHg, P = 0.05). Plasma concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide were similar for both doses; urinary excretion of ANP was lower on 20 mg (12.2 v 13.6 pmol, P < 0.05). CONCLUSIONS: These results indicate that within the usual therapeutic range, high doses of lisinopril cause greater suppression of selected cardiovascular hormones than low doses in heart failure, but are associated with lower creatinine clearance in some patients.     

Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists.

BACKGROUND: Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist. METHODS: Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed. RESULTS: N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality. CONCLUSIONS: Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.     

Influence of hypertension, left ventricular hypertrophy, and left ventricular systolic dysfunction on plasma N terminal proBNP

OBJECTIVES: To examine the relation between plasma concentration of the N terminal of the precursor of brain natriuretic peptide (NT proBNP), left ventricular hypertrophy (LVH), and left ventricular systolic dysfunction (LVSD) in patients with a history of hypertension. DESIGN: Prospective study. SETTING: Teaching hospital based study. PATIENTS: NT proBNP concentrations were determined in five groups of individuals. Group 1: 15 echocardiographic normal controls; group 2: 22 patients with hypertension, normal left ventricular systolic function, and no LVH; group 3: 24 patients with hypertension, normal left ventricular systolic function, and LVH; group 4: 13 patients with history of hypertension, no history of ischaemic heart disease, and left ventricular wall motion index (WMI) between 1.9-1.3; and group 5:17 patients with a history of hypertension, no history of ischaemic heart disease, and WMI < 1.2. RESULTS: Median (range) NT proBNP concentrations (in fmol/ml) for groups 1-5, respectively, were: 129.4 (53.6-159.7), 147.4 (54.3-730. 5), 137.1 (35.8-403.9), 356.7 (124.4-934.4), and 493.5 (248.9-909). Mean log NT proBNP differed among all five groups (p < 0.0001), and between groups 4 and 5 versus groups 1-3 (p < 0.0001), and group 4 versus group 5 (p = 0.02) only. CONCLUSIONS: The results suggest that the presence of hypertension with or without LVH (and normal left ventricular systolic function) does not affect NT proBNP concentrations. Moreover, there is a significant rise in NT proBNP only when LVSD develops in hypertension. Thus, NT proBNP remains a useful diagnostic aid for LVSD, even in hypertensive patients.     

N-terminal pro-B-type natriuretic peptide in risk stratification after acute myocardial infarction in patients on long-term beta-adrenergic receptor blocker therapy

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) appears to be a strong risk marker of mortality in patients with acute coronary syndrome. However, little information is available on NT-proBNP as a predictor of long-term serious cardiovascular events beyond that of left ventricular ejection fraction in patients with acute myocardial infarction (AMI), most of them treated with an early invasive strategy and on a uniform optimal secondary preventive medication including long-term beta-adrenergic receptor blockade. OBJECTIVE: To assess the prognostic impact of plasma NT-proBNP in patients with AMI who received optimal medical treatment including long-term beta-adrenergic receptor blockade. METHODS: Plasma NT-proBNP was measured in 219 patients (age range 31-80 years) with AMI at baseline, and then followed for a median duration of 1.63 years. The first occurrences of a serious cardiovascular event including cardiac mortality, nonfatal MI, and congestive heart failure were registered. RESULTS: Ninety serious cardiovascular events occurred. Left ventricular ejection fraction and reperfusion therapy with thrombolysis or percutaneous coronary intervention were identified as confounders. When adjusting for these factors in multivariate analysis, NT-proBNP was a strong predictor of serious cardiovascular events in patients with a plasma NT-proBNP of >162.2 pmol/l and aged <60 years (p = 0.001). The incidence rate was related to increasing NT-proBNP (p = 0.0017). The risk of serious cardiovascular events was higher in patients with NT-proBNP levels in the highest quartile (> or =162.2 pmol/l) than in those with levels in the three lowest quartiles (rate ratio = 2.5, 95% confidence interval = 1.6-3.9, p = 0.0001). CONCLUSION: AMI patients with high plasma NT-proBNP seem to be at an increased risk of serious cardiovascular events, but only those < or =60 years of age.     

Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. CONCLUSION: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.     

Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population

Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. METHODS: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. CONCLUSION: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations.