Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro)BNP.

AIMS: To study the determinants of natriuretic peptides in advanced chronic heart failure (CHF) patients with and without atrial fibrillation (AF) and to evaluate the prognostic value of natriuretic peptides in AF compared with sinus rhythm patients with advanced CHF. METHODS AND RESULTS: The study group comprised 354 advanced CHF patients [all New York Heart Association (NYHA) III/IV], including 76 AF patients. AF patients were older (70+/-7 vs. 67+/-8; P=0.01), and non-ischaemic CHF was more common (42 vs. 19%; P=0.002) than in sinus rhythm patients, but left-ventricular ejection fraction was comparable (0.23+/-0.08 vs. 0.24+/-0.07; P=ns). At baseline, (NT-)ANP and NT-proBNP levels were significantly higher in AF patients, compared with those in sinus rhythm. By multivariate regression analysis, AF was identified as independent determinant of (NT-)ANP, but not of (NT-pro)BNP levels. After a mean follow-up of 3.2+/-0.9 (range 0.4-5.4) years, cardiovascular mortality was comparable (55 vs. 47%; P=ns). In both groups, AF and sinus rhythm, NT-proBNP [AF: adjusted HR 5.8 (1.3-25.4), P=0.02; sinus rhythm: adjusted HR 3.1 (1.7-5.7), P<0.001] was an independent risk indicator of cardiovascular mortality. CONCLUSION: In advanced CHF patients, AF affects (NT-)ANP levels, but not (NT-pro)BNP levels. NT-proBNP is an independent determinant of prognosis in advanced CHF, irrespective of the rhythm, AF, or sinus rhythm.     

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.     

Prognostic value of Doppler transmitral flow patterns and cardiac natriuretic peptides in patients with chronic congestive heart failure admitted for episodes of acute decompensation

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) <120 ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 ± 145 pg/ml and 865 ± 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = −0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r = −0.50, P = 0.003). The combined index of both shorter DcT (<120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (χ² = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation. Received: December 28, 1999 / Accepted: July 14, 2000     

Low pulse pressure is an independent predictor of mortality and morbidity in non ischaemic, but not in ischaemic advanced heart failure patients

In patients with atherosclerotic disease, a high pulse pressure is an important predictor of cardiovascular events. However, in patients with chronic heart failure (CHF) a low pulse pressure is related to worse outcome, although no distinction was made between ischaemic and non ischaemic heart failure. We therefore aimed to compare the prognostic value of pulse pressure (PP) between those with ischaemic and non ischaemic advanced heart failure. METHOD AND RESULTS: Pulse pressure was analysed for its effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 1901 patients with NYHA class III or IV heart failure (mean age 65 years, mean ejection fraction 26%). In ischaemic heart failure (n=1118), low mean arterial pressure (MAP) was an independent predictor of overall mortality (Hazard Ratio (HR) 0.88 per 10 mm Hg; p=0.04), while pulse pressure was not. In contrast, in non ischaemic heart failure (n=783), a low pulse pressure was an independent predictor of overall mortality (HR 0.84 per 10 mm Hg; p=0.036), while mean arterial pressure was not. In addition, higher NYHA class and lower pulse pressure (HR 0.87 per 10 mm Hg; p=0.002) were the only independent predictors for first heart failure hospitalisation in both ischaemic and non ischaemic patients. CONCLUSION: Low pulse pressure is a readily obtainable risk marker of death in advanced non ischaemic heart failure. Mean arterial pressure remains an important component of blood pressure in predicting mortality, especially in those with heart failure of an ischaemic aetiology. It is postulated that pulse pressure may reflect a deleterious haemodynamic state, in non-atherosclerotic heart failure patients.     

难治性感染性休克患者脉压与预后的关系初探

 目的 初步探讨脉压对难治性感染性休克患者组织灌注及预后的影响。方法 回顾性分析2012年1—12月大连医科大学附属第一医院重症医学科连续收治的68例难治性感染性休克患者的临床资料,包括入科休克复苏24 h血流动力学指标[收缩压、舒张压、平均动脉压(MAP)、心率、中心静脉压(CVP)、脉压、脉压/收缩压、脉压/舒张压、脉压/MAP、脉压/心率、收缩压与MAP差值(SMP)、MAP与舒张压差值(MDP)]、动脉血乳酸水平及28 d生存状况。结果 (1)死亡者复苏24 h时间点心率和乳酸水平高于存活者,24 h乳酸清除率(rLac)低于存活者,差异均有统计学意义(P值均<0.05)。(2)以24 h时间点心率进行分组,心率≥100次/min组病死率(56.25%)高于心率<100次/min组(36.11%),但差异无统计学意义(P=0.096),两组中死亡者24 h时间点乳酸水平高于存活者,rLac低于存活者,差异均有统计学意义(P值均<0.05);心率≥100次/min组中,死亡者脉压、脉压/心率、脉压/MAP、脉压/收缩压、脉压/舒张压、SMP及MDP高于存活者,差异均有统计学意义(P值均<0.05);心率<100次/min组中,死亡者与存活者各血流动力学指标差异均无统计学意义(P＞0.05)。(3)以24 h时间点MAP进行分组,MAP≥85 mmHg(1 mmHg=0.133 kPa)组病死率(42.42%)与MAP<85 mmHg组(48.57%)差异无统计学意义(P=0.611),两组死亡者24 h时间点乳酸水平高于存活者,rLac低于存活者,差异均有统计学意义(P值均<0.05);MAP≥85 mmHg组中,死亡者心率高于存活者,差异有统计学意义(P<0.05);MAP<85 mmHg组中,死亡者脉压、脉压/MAP、脉压/收缩压、脉压/舒张压、SMP及MDP高于存活者,舒张压低于存活者,差异均有统计学意义(P值均<0.05)。结论 对难治性感染性休克患者以特定方案进行复苏,24 h后的脉压在不同心率、MAP时对其预后的影响不同,快心率和低MAP时,其对组织灌注及预后的影响更大。         

Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic peptide to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure.

BACKGROUND--Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B type or brain natriuretic peptide (BNP) are increased in patients with congestive heart failure (CHF). OBJECTIVE--To examine the haemodynamic and hormonal responses, especially of ANP and BNP, to oral administration of an angiotensin-converting enzyme (ACE) inhibitor in patients with CHF and in controls. PATIENTS--12 patients with CHF and 11 controls. METHODS--Haemodynamic variables and plasma concentrations of ANP, BNP, and other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth. RESULTS--Pulmonary capillary wedge pressure and systemic vascular resistance decreased significantly in both groups. The cardiac index increased only in the CHF group. In patients with CHF pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac index were significantly changed from 1 to 12 hours after alacepril administration. Plasma ANP and BNP decreased significantly after alacepril was given to the CHF group: neither concentration changed in the control group. In the CHF group plasma ANP was significantly lower between 1 and 6 hours and was highly significantly correlated with pulmonary capillary wedge pressure. Plasma BNP, however, was significantly lower between 6 and 24 hours after alacepril and was not correlated with pulmonary capillary wedge pressure. CONCLUSIONS--The response of plasma BNP after alacepril administration occurred later and lasted longer than the plasma ANP response. This may indicate that the mechanisms of synthesis, secretion, or degradation of the two peptides are different.     

Plasma cardiac natriuretic peptides as biochemical markers of recurrence of atrial fibrillation in patients with mild congestive heart failure

To determine changes in plasma brain natriuretic peptide (BNP) after direct current cardioversion (DC) and to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and BNP and the recurrence of atrial fibrillation (AF) after DC in patients with mild congestive heart failure (CHF), plasma ANP and BNP were measured before and after DC in 71 patients with mild CHF and then followed. In 65 patients with successful DC, both ANP and BNP decreased 15 min after DC. Cox stepwise multivariate analysis among 14 variables such as age, history of AF, echocardiographic parameters, medication and ANP and BNP revealed that only low ANP (p=0.005) and high BNP before DC (p=0.0002) were independent predictors of recurrent AF. A ratio of ANP to BNP less than 0.44 was a significant risk factor for AF recurrence by Kaplan-Meier analysis (p=0.02). BNP began to decrease immediately after successful DC. High BNP and relatively low ANP compared with BNP were independent risk factors of AF recurrence in patients with mild CHF.     

Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction

OBJECTIVE: Activation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) is considered a hallmark of myocardial remodeling. To determine magnitude and relative proportion of activation during the progression to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rapid ventricular pacing-induced heart failure in rabbits. METHODS: Six animals underwent progressive pacing with incremental rates (330 beats per min (bpm) to 380 bpm over 30 days), resulting in congestive heart failure (CHF). Five animals underwent pacing at 330 bpm for 10 days only (early LV dysfunction, ELVD) and five additional animals served as control group (CTRL). RESULTS: ELVD was characterized by decreased mean arterial pressure (P=0.05 vs. CTRL) as well as significantly impaired LV function (LV fractional shortening (FS) P<0.01 vs. CTRL) and dilatation (P<0.01 vs. CTRL). CHF was characterized by further decreased mean arterial pressure (P<0.01 vs. ELVD), further impaired LV function (FS P<0.03 vs. ELVD) and dilatation (P<0.01 vs. CTRL). In control animals, significant ANP expression was observed only in atrial tissue (P<0.02 vs. BNP) while BNP expression was ubiquitous but marginal (LV P<0.05 vs. ANP). In ELVD, activation of ANP (atria and LV P<0.05 vs. CTRL) and BNP (atria P<0.05 vs. CTRL, LV n.s.) was observed. In CHF, LV-BNP increased further markedly (P<0.01 vs. CTRL, P<0.05 vs. ELVD) while atrial ANP and BNP expression as well as LV ANP expression remained unchanged (all P=n.s. vs. ELVD). CONCLUSION: The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.     

High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure.

AIMS: To determine the potential adjunct of high-sensitivity (hs) C-reactive protein for risk stratification in patients with stable congestive heart failure (CHF). METHODS AND RESULTS: We studied 546 consecutive patients clinically stable with an ejection fraction <45% who were referred to our centre for evaluation of left ventricular dysfunction. hs C-reactive protein levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 972 days) was obtained for 545 patients. Cardiovascular mortality was significantly increased (P=0.001) in patients with hs C-reactive protein >3 mg/L. By multivariable analysis, including clinical, biological, and echocardiographic variables, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality [HR=1.78 (1.17-2.72); P=0.008]; the strongest predictive parameter in this model was B-type natriuretic peptide (BNP) (P=0.005). When peak VO(2) was included into the model, hs C-reactive protein >3 mg/L remained an independent predictor of cardiovascular mortality [HR=1.55 (1.02-2.38); P=0.04]; the strongest predictive parameter in this model was peak VO(2) (P<0.0001). In patients with ischaemic CHF, cardiovascular mortality was significantly increased in patients with hs C-reactive protein >3 mg/L (P=0.001), whereas in patients with non-ischaemic CHF, hs C-reactive protein >3 mg/L was not associated with cardiovascular mortality (P=0.098). By multivariable analysis, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality in ischaemic patients [HR=2.16 (1.23-3.78)] but not in non-ischaemic patients [HR=1.05 (0.52-2.11)]. CONCLUSION: Cardiovascular mortality is increased in CHF patients with hs C-reactive protein >3 mg/L. The impact of hs C-reactive protein is independent of usual prognostic parameters, in particular BNP and peak VO(2). The interest of hs C-reactive protein determination appears to be especially marked in patients with ischaemic cardiomyopathy.     

内源性促红细胞生成素对慢性心力衰竭患者预后的影响

目的了解内源性促红细胞生成素(EPO)对慢性心力衰竭(CHF)患者预后的判定价值。方法选择住院的CHF患者115例,以患者是否存活分为死亡组55例,存活组60例。另选同期住院的年龄、性别相匹配的非CHF患者67例为对照组,以便建立logEPO和血红蛋白(Hb)的回归方程。对CHF患者进行全因死亡和因心力衰竭再次入院的随访观察,测定血EPO,并进行分析。结果与存活组比较,死亡组高龄患者多、心功能(NYHA)Ⅱ级比例低、Hb降低和B型钠尿肽(BNP)水平升高(P<0.01)。Kaplan-Meier生存曲线显示,贫血的CHF患者病死率增高(RR=2.50,95%CI:1.38～4.54,P=0.002)。ROC曲线评估EPO和BNP预测CHF患者死亡的最佳界值分别为44.4 U/L和752 ug/L(P=0.036,=0.000)。年龄、Hb、BNP和NYHA对CHF患者全因死亡有独立预测价值;而男性、BNP和Hb水平对因心力衰竭再次入院有独立预测价值。贫血的CHF患者EPO是独立于Hb的全因死亡的强预测指标(RR=2.86,95%CI:1.18～6.94,P=0.020)。结论贫血是CHF患者不良预后的独立预测因素。EPO是贫血CHF患者全因死亡的独立预测指标。     

Is hormonal activation during exercise useful for risk stratification in patients with moderate congestive heart failure?

Background

We previously demonstrated that A-type natriuretic peptide (ANP) at peak exercise was an independent predictor of cardiac survival. No data are available concerning the predictive value of B-type natriuretic peptide (BNP) at peak exercise.

Methods

One hundred and fifty consecutive stable patients with moderate congestive heart failure (CHF) underwent echocardiography and a cardiopulmonary exercise test. Blood samples were drawn at rest and at peak exercise for the determination of plasma levels of ANP, BNP, and norepinephrine.

Results

Exercise significantly increased plasma values of ANP, BNP, and norepinephrine. After a median follow-up period of 1171 days, there were 35 cardiac related deaths. Mortality rates at 1 and 2 years were 4% and 8%, respectively. Independent predictors of cardiac survival were percent of maximal predicted oxygen consumption (RR = 4.8 [2.1-11], P = .002), BNP at rest (RR = 2.5 [1.2-5.6], P = .01), and left atrial diameter (RR = 2.8 [1.2-6.5], P = .02).

Conclusions

In patients with stable, moderate CHF, plasma levels of ANP, BNP, and norepinephrine measured at peak exercise did not improve risk stratification. However, in addition to percent of maximal predicted oxygen consumption and left atrial diameter, plasma level of BNP at rest was an independent predictor of survival in CHF patients with low risk of cardiac events.     

慢性心力衰竭患者血浆利钠肽水平的变化

目的 :研究慢性心力衰竭 (CHF)患者血浆利钠肽 (ANP、BNP、CNP)水平的变化及其与心功能状态、心脏结构的关系 ,探讨其用于CHF诊断的价值。方法 :4 8例CHF患者为心力衰竭组 ,心功能按HYHA标准分级 :Ⅱ级 15例 ,Ⅲ级 2 4例 ,Ⅳ级 9例 ,基本病因为冠心病、扩张型心肌病、高血压性心脏病 ;对照组 10例 ,为健康体检者。用同位素放射免疫法和免疫放射法测定血浆ANP、BNP、CNP水平 ,心脏彩色多普勒超声诊断仪测量左室结构和功能。结果 :心力衰竭组血浆ANP、BNP水平均较对照组显著增高(P均 <0 0 1) ,并与心功能严重程度有关 ,但不同病因的CHF患者之间血浆ANP、BNP、CNP水平均无明显差异 (P均 >0 0 5 )。其中LVEF <4 5 %的患者 4 1例 ,其血浆BNP水平和LVEF负相关 (r=- 0 37,P <0 0 5 ) ,和左室舒张末期内径 (LVEDD)、左室心肌重量指数 (LVMI)呈正相关 (r均为 0 36 ,P均 <0 0 5 ) ,血浆ANP、BNP水平和肺动脉收缩压正相关 (P <0 0 5或P <0 0 1)。血浆CNP水平在CHF患者无明显升高 (P >0 0 5 )。结论 :血浆ANP、BNP水平可作为反映心功能状态的指标 ,其中血浆BNP水平更为敏感、特异并且和心脏结构相关 ,可作为CHF诊断及鉴别诊断的指标     

Plasma brain natriuretic peptide and atria natriuretic peptide as predictors for diastolic heart failure in patients with type 2 diabetes mellitus

Objective To study the change of diastolic cardiac function in diabetic patients and to determine the diagnostic value of plasma brain natriuretic peptide （BNP） and atria natriuretic peptide （ANP） for diastolic heart failure in patients with type 2 diabetes mellitus. Methods Twelve healthy subjects and seventy-one diabetic patients were included in the study. Plasma BNP and ANP were measured with immtmoradiometic assay. Results Plasma levels of BNP and ANP increased significantly with increased severity of diastolic heart dysfunction. The ratio of E/A had significant negative correlation with the plasma levels ofBNP （r=0.669,P〈0.001） and ANP （r=0.579, P〈0.01）. AUC of ANP and BNP in ROC model was 91.9% and 65.3%, respectively. Conclusions The plasma level of BNP might be a valuable predictor for differential diagnosis of diastolic cardiac function in diabetic patients.     

Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era

OBJECTIVES: This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI). BACKGROUND: Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use. METHODS: A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI). RESULTS: During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD. CONCLUSIONS: Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.     

Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. METHODS AND RESULTS: The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). CONCLUSION: Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.     

Natriuretic Peptides in Sheep with Pressure Overload Left Ventricular Hypertrophy

To examine tissue and plasma atrial (ANP) and brain natriuretic peptide (BNP) responses to left ventricular hypertrophy (LVH) 7 sheep underwent suprarenal aortic banding (20mmHg initial pressure differential). Median survival time was 15 days. Proximal mean aortic pressure (MAP) increased from 65.1±5.0mmHg (baseline) to 111.6±7.5mmHg (day 7, p<0.0001). Distal systolic aortic pressure fell from 85.5±8.7mmHg (baseline) to 55.6±6.4mmHg (day 7, p=0.0002). Maximal plasma ANP (26.9±3.6 vs. 10.1±1.2pmol/L, p=0.005) and BNP (15.3±3.6 vs. 3.5±1.0pmol/L, p=0.006) were recorded at 15±4.0 days. Coarctation induced rapid increases in PRA and plasma aldosterone and a fall in urinary sodium. Post-mortem examination of hearts confirmed LVH. Compared with controls, tissue ANP concentration was reduced in left atrium (p=0.04) and LV (p=0.04). BNP concentration was reduced in left atrium (p=0.02) but tended to be higher in LV In conclusion, suprarenal aortic coarctation leads to progressive hypertension resulting in LVH, progressive increases in plasma ANP and BNP and, in most cases, death from heart failure.     

Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure

The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C₁₈ extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample f-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r=0.94, p < 0.001; ANP: r=0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EE ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r=0.99, ANP: r=0.94, p<0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful noninvasive indices of cardiac performance.     

Effect of exercise on natriuretic peptides in plasma and urine in chronic heart failure

BACKGROUND: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in chronic heart failure (CHF). ANP is known to be increased during exercise in healthy subjects and CHF, while the response in BNP during exercise is less clear and does not exist in C-type natriuretic peptide (CNP) and aquaporin-2 (AQP2) in either healthy subjects or CHF. METHODS: Eleven patients with CHF and eleven healthy subjects performed a maximal aerobic exercise test. ANP and BNP in plasma were determined every 3 min and at maximum exercise by radioimmunoassay (RIA) and CNP and AQP2 in urine were determined before and after the exercise test by RIA. RESULTS: The absolute increase in BNP during exercise was higher in patients with CHF (CHF: 4.1 pmol/l; healthy subjects: 1.3 pmol/l, P<0.05) and was positively correlated to BNP at rest (P<0.05), while the absolute increase in ANP during exercise was the same in the two groups (CHF: 4.2 pmol/l; healthy subjects: 6.8 pmol/l, not significant, NS). In CHF, exercise did not change either u-CNP excretion (rest: 9.8 ng/mmol creatinine; after exercise: 8.8 ng/mmol, NS) or u-AQP2 (rest: 466 ng/mmol creatinine; after exercise: 517 ng/mmol creatinine, NS) as well as in healthy subjects where u-CNP (rest: 9.7 ng/mmol creatinine; after exercise: 9.2 ng/mmol creatinine) and u-AQP2 (rest: 283 ng/mmol creatinine; after exercise: 307 ng/mmol creatinine) were the same at rest and after exercise. CONCLUSION: The absolute increase in BNP during exercise is higher in patients with CHF compared to healthy subjects. It is suggested that this is a compensatory phenomenon to improve the exercise capacity in CHF, and that BNP is a more important factor in cardiovascular homeostasis during exercise in CHF than ANP.     

Impact of oxidative stress on plasma adiponectin in patients with chronic heart failure

BACKGROUND: Adiponectin, which is an adipocyte-specific cytokine that has a beneficial effect in cardiovascular disease, may be downregulated by oxidative stress in patients with chronic heart failure (CHF). Plasma levels of both adiponectin and biomarkers of oxidative stress are increased and have a prognostic impact on CHF patients. METHODS AND RESULTS: The plasma adiponectin level was measured in 116 patients with CHF (left ventricular ejection fraction <45%) who underwent cardiac catheterization, and these findings were compared with the atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) levels, hemodynamic parameters and plasma oxidized low-density lipoprotein (oxLDL) level as a marker of oxidative stress. There was no correlation between the plasma adiponectin level and hemodynamic parameters, but there was a positive correlation with the cardiac natriuretic peptides [ANP (r(s)=0.464, p<0.0001) or BNP (r(s)=0.489, p<0.0001)]. There was a significant negative correlation between plasma adiponectin level and oxLDL (r=-0.245, p=0.0079). In the stepwise multivariate analysis, a high level of natriuretic peptide (log BNP) (p=0.0098), and a low level of oxLDL (p=0.0105) were independent predictors of a high adiponectin level in CHF patients. CONCLUSIONS: The plasma adiponectin level is regulated not only by cardiac natriuretic peptides but also by oxidative stress in patients with CHF.     

Association of double product and pulse pressure with cardiovascular and all‐cause mortality in the LURIC study

Systolic (SBP) and diastolic blood pressure (DBP) and mean arterial pressure (MAP) are risk factors for cardiovascular mortality (CVM). Pulse pressure (PP) is considered as an easily available marker of vascular stiffness and the double product (DP) as a marker of cardiac workload. Therefore, we have examined the predictive value of PP and DP in the Ludwigshafen Risk and Cardiovascular Health study, a monocentric cohort study of 3316 patients referred to coronary angiography. An increase of SBP or PP by 1mmHg increased the risk of CVM with hazard ratios of 1.009 (95% CI, 1.005‐1.012) and 1.016 (1.012‐1.020), respectively. Increasing DP by 100 mm Hg/min was associated with a 1.010 (1.007‐1.013) higher risk of CVM. In patient subgroups with coronary artery disease (CAD) and heart failure (HF), PP and DP predicted CVM better than SBP or MAP. In a multivariate analysis adjusted for sex, BMI, diabetes, eGFR, hazard ratios for CVM for z‐standardized PP, DP, SBP, and HR were 1.20, 1.16, 1.12, and 1.14. After adding age to the multivariate analysis, only DP and HR remained significant. We provide evidence that PP and DP are powerful predictors of CVM and all‐cause mortality in a CV medium‐ to high‐risk population, especially in patients with CAD and HF. While DP proved to be an independent predictor of cardiovascular and all‐cause mortality also in multivariate analysis, PP was no independent predictor in our cohort with widespread antihypertensive treatment (>85%). PP is associated with age, presence of diabetes, obesity, and impaired renal function.