BNP Concentrations Research Articles

Renal Dysfunction, Hemodialysis, and the NT-proBNP/BNP RatioThe Authors’ Reply

With great interest we read the article by Srisawasdi et al.1 They found that the ratio between N-terminal (NT)-pro-B-natriuretic peptide (BNP) and BNP increases exponentially with the stage of renal disease. van Kimmenade et al,2 however, suggested the NT-proBNP/BNP ratio increases only slightly and shows a linear trend. Their findings are used to support the hypothesis that BNP and NT-proBNP concentrations rely equally on the glomerular filtration rate and predominantly on cardiac diseases, rather than on renal clearance.2,3 The findings by Srisawasdi et al1 suggest otherwise, and they rightly advocate that renal dysfunction should be taken into account when interpreting the diagnostic and prognostic potential of NT-proBNP and BNP. Missing in the data from Srisawasdi et al1 are the ratios in the patients with end-stage renal disease who were treated with hemodialysis. On reading the article by Srisawasdi et al,1 we decided to take a look at the NT-proBNP/BNP ratios in a population of patients receiving long-term hemodialysis for whom we recently described cardiac biomarker concentrations4 and their relationship …

Natriuretic pro-peptides in idiopathic intracranial hypertension

Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 ± 23 vs 231 ± 22 pmol/L, proBNP: < 2 pmol/L in all, proCNP: 1079 ± 318 vs 1138 ± 323 pmol/L). In plasma, proCNP was lower in IIH compared with controls (35.3 ± 4.8 pmol/L vs 43.8 ± 5.9 pmol/L, p < 0.0001). Moreover, plasma proBNP was significantly lower in patients compared with controls (47.1 ± 21.4 pmol/L vs 59.2 ± 22.0 pmol/L, p = 0.045). There were no associations between peptide concentrations and ICP and BMI, respectively. Plasma proANP and proCNP increased during 3 months follow-up ( p = 0.01 and p = 0.006), n = 12. We suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. Further studies of proCNP and endothelial function are needed to establish such role.

BNP concentrations and cardiovascular adaptation in preterm and fullterm newborn infants

To evaluate and compare cardiovascular adaptation of 36 preterm and 34 fullterm newborns, we analyzed BNP concentration and echocardiographic parameters at day 3 of life and at day 28 (± 2). On day 3 BNP concentrations (pg/ml) resulted higher in PDA preterm group ( n = 11; 125, IQR 56.1–301) than preterm without PDA ( n = 25; 25.5 IQR 10.9–49; p < 0.001) than fullterms ( n = 34; 55.1 IQR 23.6–82.7; p = 0.013). No difference resulted in all groups at 28 days (respectively: 12.7 IQR 4.9–23.8; 15.6 IQR 10–22; 8.9 IQR 5.6–20.6). Because of the newborns' growth, all echocardiographic parameters increased with linear relationship with body weight. On day 3 BNP concentration and echocardiographic parameters were not correlated besides LA/AO in preterms with PDA ( p = 0.0015). On day 28, BNP was significantly correlated with mVTI ( p = 0.019), M ( p = 0.007) and LA ( p = 0.005) in fullterms and only with LA ( p = 0.007) in preterms. In conclusion, BNP concentrations and echocardiographic measures confirm that preterm, and fullterm newborns conduct themselves in a similar manner during the transition from foetal to post-natal circulation, reaching low levels at a month of life. The presence of PDA during first days of life has no significant impact in this adaptation. LA is the echocardiographic parameter mostly related to BNP concentration in the newborns.

Application of BNP and NT-proBNP in diagnosis of diastolic heart failure

Objective To investigate the plasma levels of BNP and NT-proBNP in patients with chronic heart failure(CHF),and to evaluate the capabilities of them to discriminate diastolic heart failure(DHF)from systolic heart failure(SHF).Methods One hundred and twenty nine patients with DHF and109 patients with SHF were subjected to plasma BNP and NT-proBNP determination in Beijing PLA general hospital from the year of 2004 to 2006.The factors influencing the levels of BNP and NT-proBNP were analyzed through the comparison with results from 77 age and gender-matched healthy volunteers.ROC was used to evaluate the mles of BNP and NT-proBNP in the diagnosis of Diastolic heart failure.Results Compared with the controls.plasma BNP and NT-proBNP concentrations were upregulated significantly in DHF and SHF patients,with the median of 254.16 ng/L and 899 ng/L in DHF and 923.08 ng/L and 3 695 ng/L in SHF respectively.The increase extent of BNP and NT-proBNP was exclusively related to NYHA classification of heart function(β=0.201 and 0.323 respectively,P<0.001).BNP and NT-proBNP showed AUCs of 0.906(95% CI: 0.865-0.946)and 0.956(95% CI:0.932-0.980)respectively for diagnosis of CHF.BNP and NT-proBNP showed AUCs of 0.781(95% CI: 0.710-0.815)and 0.757(95% CI: 0.686-0.828)respectively for diagnosis of DHF and SHF.Conclusions BNP and NT-proBNP are upregnlated significantly in CHF patients and associated with the NYHA classification significantly and exclusively.BNP and NT-proBNP can be used to identify CHF rather than DHF. Key words: Heart failure,diastolic; Natriuretic peptide,brain; Peptide fragments; Stroke volume

B-Type Natriuretic Peptide as a Marker of Heart Failure: New Insights From Biochemistry and Clinical Implications

The mature, biologically active 32-amino acid long B-type natriuretic peptide (BNP(1-32)), is cleaved by corin from the BNP prohormone. Recent data demonstrated that BNP(1-32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase (DPP) IV. DPP IV removes the two amino-terminal amino acids (Ser and Pro) from BNP(1-32) to produce BNP(3-32), which has been detected in plasma of patients with heart failure. In a canine model, intravenous BNP(3-32) infusion resulted in less natriuresis, diuresis and vasodilation compared to intravenous infusion of BNP(1-32). The clinical relevance of these observations may be important for patients with high plasma BNP concentrations, which can be measured by commercially available immunoassays. Further studies are needed to explore whether DPP IV inhibitors increase the bioavailability of BNP(1-32), delay the progression of heart failure and increase the efficacy of exogenously administered BNP(1-32) in decompensated heart failure.

Relations of Biomarkers of Distinct Pathophysiological Pathways and Atrial Fibrillation Incidence in the Community

Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial. In 3120 Framingham cohort participants (mean age 58.4+/-9.7 years, 54% women), we related 10 biomarkers that represented inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B-type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide), oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen activator inhibitor type 1), and microvascular damage (urinary albumin excretion; n=2673) to incident AF (n=209, 40% women) over a median follow-up of 9.7 years (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker panel was associated with incident AF (P<0.0001). In stepwise-selection models (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62, 95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard ratio 1.25, 95% confidence interval 1.07 to 1.45, P=0.004) were chosen. The addition of BNP to variables recently combined in a risk score for AF increased the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95% confidence interval 0.78 to 0.83) and showed an integrated discrimination improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9% relative improvement in reclassification analysis. The combined analysis of BNP and C-reactive protein did not appreciably improve risk prediction over the model that incorporated BNP in addition to the risk factors. BNP is a predictor of incident AF and improves risk stratification based on well-established clinical risk factors. Whether knowledge of BNP concentrations may be used to target individuals at risk of AF for more intensive monitoring or primary prevention requires further investigation.

Utility of Echocardiography Versus BNP Level for the Prediction of Pulmonary Arterial Pressure in Patients With Pulmonary Arterial Hypertension

Recent advances in the treatment of pulmonary arterial hypertension provide a rational basis for earlier, noninvasive diagnosis of pulmonary arterial hypertension. However, the reliability of transthoracic echocardiography, plasma BNP levels, and other parameters for the diagnosis of pulmonary arterial hypertension remains unclear. Thus, the purpose of this study was to determine the utility of these modes of investigation for the prediction of pulmonary arterial pressure as compared with the current gold standard, Swan-Ganz catheterization. Among 46 PAH patients, 37 had connective tissue diseases, while the remainder had primary pulmonary arterial hypertension, chronic pulmonary thromboembolism, and interstitial pneumonitis. Systolic pulmonary arterial pressure calculated by transthoracic echocardiography was significantly correlated with systolic pulmonary arterial pressure measured using a Swan-Ganz catheter (r = 0.51, P < 0.01). Plasma BNP concentration did not correlate with systolic pulmonary arterial pressure (r = 0.10, NS) in the overall patient population. However, when we excluded left ventricular heart failure and left ventricular hypertrophy, BNP concentration was correlated with systolic pulmonary arterial pressure (r = 0.508, P < 0.05). Among other variables tested, ECG electrical axis was correlated with pulmonary arterial pressure (r = 0.46, P < 0.05) but uric acid, lactate dehydrogenase, %DLCO, enhanced IIp sound, and pulmonary artery enlargement on chest x-ray did not correlate with pulmonary arterial pressure. These data suggest that echocardiography is the noninvasive modality of choice for the assessment of pulmonary arterial hypertension. Plasma BNP level also predicts pulmonary arterial pressure, when left ventricular heart failure and cardiac hypertrophy are excluded.

264 Effects of Angiotensin-1 Converting Enzyme inhibition on oxidative stress and bradykinin receptor expression during doxorubic in-induced cardiomyopathy in rats

To evaluate the mechanisms and the impact of the ACE-inhibitor perindopril (P) in a model of doxorubicin (D)- induced cardiotoxicity, male Wistar rats received D (1mg/kg/d, i.p. for 10 days), P (2 mg/kg/d by gavage from day 1 to day 18), D (for 10 days) + P (for 18 days) or saline. D decreased systolic blood pressure, body and heart weights. Left ventricular diastolic diameter was increased by D (p<0.01) but it was not attenuated by P. D decreased plasma vitamin C (p<0.05) and increased the ascorbyl radical/vitamin C ratio (p<0.01). This ratio was attenuated by P. No difference was found among groups in cTnI, BNP concentrations and tissue oxidative stress (OS). Myocardial MCP-1 expression was higher in the D group. Cardiac kinin receptor (B1R and B2R) expression was not affected by D yet binding sites for B2R and B1R were increased in D+P and P groups, respectively (p<0.05). In conclusion, D induced cardiac functional alterations, inflammation and plasma OS whereas tissue OS, and cardiac kinin receptors expression were not modified. P did not improve cardiac performance, but modulated kinin receptor expression and enhanced antioxidant defense.

THE EFFECTS OF COMBINED EXERCISE ON CARDIAC FUNCTION AND ADIPOCYTOKINE CONCENTRATION ACCORDING TO ACE GENOTYPE IN ABDOMINAL OBESE MIDDLE AGED MEN

The purpose of this study was to investigate the effects of combined exercise on visceral fat, cardiac function, adipocytokine, and NT-pro BNP concentration according to angiotensin-converting enzyme(ACE) genotype in obese middle aged men. Fifty three obese men (II type: 18, ID type: 20, DD type: 15), ratio of visceral and subcutaneous were over 0.4, were enrolled in the study. The combined exercise program included stretching, resistance training, aerobic exercise, and yoga. The exercise was conducted for 60 minutes, 4 times a week for 12 week period. ACE genotype was determined using a polymerase chain reaction (PCR), and the genetic subtype was classified in three patterns e.g. II, ID, DD. As a results, body weight, BMI, and WHR significantly decreased after 12 weeks of combined exercise in ID type and DD type. Body fat(%), visceral fat and V/S significantly decreased after 12 weeks in DD type. HDL-C and LDL-C significantly improved in II, ID and DD type. Cardiac structure decreased in all genotype and cardiac function increased in DD type. IL-6 and NT-pro BNP, the risk factors of cardiovascular disease, were significantly decreased in DD type, after 12 weeks. Therefore, exercises have shown to be most effective in type DD which is also considered as the risk of cardiovascular diseases. Among all the ACE genotype, DD type requires the most exercise.

Predictive value of NT-pro BNP after acute myocardial infarction: Relation with acute and chronic infarct size and myocardial function

We sought to assess the relation of N-terminal brain natriuretic peptide (NT-pro BNP) determined on day 3 after onset of acute myocardial infarction (AMI) symptoms with acute and chronic infarct size and functional parameters assessed by cardiac magnetic resonance (CMR) imaging. Furthermore, we wanted to investigate its predictive value for recovery of myocardial function. CMR was performed in 49 consecutive patients within 6 days and in a subgroup 4 (n = 27) and 12 (n = 22) months after first acute ST-elevation AMI and successful primary angioplasty. NT-pro BNP was measured in the subacute phase at 66 ± 8 h after onset of symptoms. Log-transformed NT-pro BNP (lgNT-pro BNP) significantly correlated with infarct size in % of left ventricular myocardial mass (r = 0.59 to 0.64; p < 0.004), with ejection fraction (EF) (r = -0.49 to -0.55; p < 0.004) as well as with segmental wall thickening (SWT, mm) (r = 0.41 to -0.52; p < 0.04) at any time of assessment. Multiple linear regression analysis revealed baseline EF and lgNT-pro BNP to predict global functional recovery. Patients with NT-pro BNP concentrations <the mean level of 1115 pg/ml significantly improved in EF and SWT (all p < 0.02) during the study period, whereas patients with NT-pro BNP >1115 pg/ml did not show significant functional recovery (all p = NS). NT-pro BNP on day 3 after admission correlates with acute and chronic infarct size and myocardial function after AMI. Global and regional myocardial function did not recover in patients with higher NT-pro BNP (>1115 pg/ml) during subacute phase of AMI.

Plasma ACE2 Activity is an Independent Prognostic Marker in Chagas' Disease and Equally Potent as BNP

BackgroundAngiotensin-converting enzyme (ACE) 2 is a novel homologue of ACE. It metabolizes angiotensin (Ang)II to Ang-(1-7). This study aims to investigate the diagnostic and prognostic potency of circulating ACE2 activity in patients with heart failure (HF) from Chagas' disease (CD). Methods and ResultsBlood samples were obtained from 111 CD patients and 40 age- and gender-matched healthy subjects. The CD patients were further subdivided according to their New York Heart Association classification. ACE2 activity was significantly increased in CD patients with HF, but not in patients without systolic dysfunction. Moreover, plasma ACE2 activity was significantly correlated with their clinical severity and echocardiographic parameters. Importantly, the potency of circulating ACE2 activity in CD patients was equally potent as that of B-type natriuretic peptide to predict cardiac death and heart transplant. Most importantly, patients with both parameters elevated were on a 5-fold higher risk to reach an endpoint than patients with increase in only 1 of the 2 parameters. ConclusionsDetermination of ACE2 activity may provide a new and important diagnostic and prognostic marker for patients with CD. ACE2 activity and BNP concentration have additive predictive value and may be used in combination to offer a new dimension of prediction in HF.

Brain natriuretic peptide a predictive marker in cardiac surgery

BNP which stands for B-type natriuretic peptide is a cardiac neurohormone and is secreted in response to myocardial stress and causes natriuresis and vasodilatation. Studies have reported close correlation between a high concentration of BNP in blood and worse short-term and long-term prognosis following myocardial infarction and heart failure. In this study, we have tested its usefulness and predictive value in the outcome post cardiac surgery. Between March 2006 and June 2007, 141 patients, undergoing cardiac surgery, were enrolled in this study. Their BNP concentration was measured prior to the operation and their comorbidities were examined against their BNP levels. Postoperatively their outcome was closely monitored. Main clinical endpoints were atrial fibrillation (AF), inotrope use, renal impairment, early deaths and hospital stay. Some preoperative comorbidities, such as renal impairment, peripheral vascular disease (PVD) and low ejection fraction (EF) were associated with higher BNP level. Statistically, EuroSCORE and Parsonnet score showed significant correlation with preoperative BNP concentration (P<0.0001). Postoperatively, high-BNP concentration predicted inotropic use, higher than baseline creatinine level, longer ventilation time, longer hospital stay and early mortality (P<0.05) but our study did not reveal any predictive value for BNP in identifying those developing AF or infection postoperatively. BNP is a valuable biochemical marker, which is easy to measure and can be beneficial in predicting the operative outcome.

Cardiopulmonary test in elderly: feasible, safe and useful

We thank Dr. Donadini and Colleagues for the comments [1] to our paper entitled ‘‘Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure.’’ [2] In this paper, we demonstrated the additive value of CPx in the prognostic stratification of HF in a ‘‘young elderly’’ population (mean age 68 years) of 156 consecutive patients. In a recently published paper [3], we demonstrated the safety and feasibility of CPx in the elderly. Our conclusions in that work were that this population normally excluded from CPx can benefit in terms of improved prognostic stratification from this test. Even in the present report, we confirm that a large proportion of elderly patients can undergo CPx: about one-fourth of patients (48 subjects, 24%) were in fact excluded from the study for clinical contraindications, the main reasons for exclusion being orthopaedic problems (38 subjects, 79%), cardiac conditions in six patients (severe aortic stenosis 3, mitral stenosis 1, recent onset atrial fibrillation 2 and severe chronic lung disease in 3). Furthermore, we excluded four subjects with severe kidney dysfunction that might impact on BNP concentrations, while six patients refused to undergo the procedure. Moreover, Dr. Donadini invites to consider with caution the results of BNP assessment in this population due to the possible high prevalence of pulmonary hypertension (from thromboembolism or chronic pulmonary disease) or chronic renal impairment. Both situations were reasons for exclusion [2] so that we believe that BNP assessment could be considered a reliable parameter in the studied population. On the other side, the demonstration of high BNP in a screening strategy in the elderly must be followed by an echocardiogram, which is discriminating for a possible false positive. The small HR of VE/VCO2 slope 1.07 (95% CI 1.01– 1.13) results from the inclusion of the continuous slope value in the model: each one-point slope increase determines a 7% increase in mortality. Conversely, when EVR (VE/VCO2 slope C35) is included as a discrete value in the model, we observe a fourfold increase in the risk of death (HR 4.02, 95% CI 1.17–10.3), as shown in Fig. 2 of Ref. [2].

Role for precursor Pro-B type natriuretic peptide in assessing response to therapy and prognosis in patients with decompensated heart failure treated with nesiritide

Background ProBNP, the precursor peptide to BNP and NT-proBNP (NP), circulates in patients with chronic heart failure (HF) and appears to be the predominant form of NP. This heterogeneity may confound interpretation of NP concentrations. The aim of this study was to evaluate the response to therapy and prognostic influence of proBNP in a cohort of patients admitted to hospital for decompensated HF. Methods We prospectively evaluated 40 Class III–IV patients who received clinically-indicated nesiritide infusions as part of their care. Blood was drawn before, during, and post-infusion, and assayed for proBNP, BNP, and NT-proBNP. Results All biomarkers were increased at baseline consistent with HF. ProBNP and NT-proBNP demonstrated significant reductions in response to therapy (42% and 18% post-infusion, respectively). In the patients who experienced post-hospital mortality (40% at 6 months), baseline proBNP and BNP concentrations were significantly lower than in survivors. This paradoxical finding may be explained by the end-stage nature of this patient cohort possibly experiencing exhaustion of their NP systems. Conclusions Circulating concentrations of proBNP are increased in decompensated HF and similar to NT-proBNP are reduced in response to acute therapy. Paradoxically and similar to BNP, baseline proBNP concentrations were lower in post-hospital non-survivors. While hypothesis generating, the results of this study support a role for proBNP in monitoring therapy and predicting short-term outcome. These findings need to be confirmed in a patient cohort without nesiritide therapy and more moderate HF.

Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath

Objective:The evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure (HF).Design:Prospectively conducted study on diagnostic accuracy.Setting:Emergency department of a tertiary care hospital.Patients:251 consecutive patients presenting to the...

Plasma levels of B-type natriuretic peptide in patients with tetralogy of Fallot after surgical repair

Objective To evaluate the utility of plasma BNP measurement in the long term follow-up of patients with surgically repaired tetralogy of Fallot (TOF). Methods From 2002 to 2008, plasma BNP concentration was measured in 130 patients with TOF at the age of mean 16.1 ± 7.1 years and mean 13.0 ± 6.5 years after surgically repair. BNP levels were compared to age and gender-specific normal values, results of exercise testing, clinical, electrocardiographic, and echocardiographic data. Results BNP was < 200 pg/ml in all and elevated in 60% of patients. Higher values were found in females ( p = 0.001), in patients waiting for pulmonary valve replacement ( p < 0.001), and in NYHA class II compared to NYHA I patients ( p = 0.012) with an inverse correlation between BNP and exercise time ( r = − 0.59, p < 0.001). BNP was correlated with right ventricular dilatation ( r = 0.29, p = 0.005) and severity of both tricuspid ( r = 0.22, p = 0.015) and pulmonary regurgitation ( r = 0.20, p = 0.029). Longitudinal data revealed increasing BNP levels before ( p = 0.04) and a BNP decrease after pulmonary valve replacement ( p = 0.03), but no change in patients without surgery. Conclusions In patients with surgically repaired TOF, plasma BNP is significantly correlated with right ventricular volume load. In clinical practice a considerable overlap limits the estimation of right ventricular volume load by BNP, but longitudinal evaluation helps to appoint the appropriate timing of pulmonary valve replacement.

The BNP concentrations and exercise capacity assessment with cardiopulmonary stress test in cyanotic adult patients with congenital heart diseases

Cyanosis is observed in patients with complex congenital heart disease (CHD) and pulmonary hypertension, heart failure represents an important clinical problem in such patients. The aim of this study was to evaluate the exercise capacity in patients with cyanotic CHDs using cardiopulmonary exercise test, measuring serum BNP levels as well as to seek correlation between BNP levels and cardiopulmonary exercise test parameters and identify the effects of blood oxygen desaturation and pulmonary hypertension on these indices.The study group consisted of 53 patients (21 males) at the mean age of 39.4±14.3 years, of whom 19 were operated on at the mean age of 9.6±8.6 years. Mean blood oxygen saturation (SO2) in patients was 81.2±6.2%. Twenty four patients presented with Eisenmenger syndrome, 16 — univentricular hearts, 4 — transposition of the great arteries, 6 — Fallot's tetralogy, and 3 — Ebstein anomaly. The control group comprised 32 healthy individuals (16 males) at the mean age of 40.7±9.9 years. Cardiopulmonary stress test showed significantly lower exercise capacity in patients with cyanosis than in controls: maximal oxygen uptake (VO2max) 15.5±4.9 vs. 31.6±7.1 ml/kg/min (p=0.00001), maximum heart rate at peak exercise (HR max): 139.5±22.5 bpm vs. 176.6±12.1 (p=0.0001), VE/VCO2 slope: 46.4±10.1 vs. 27.3±2.9 (p=0.00001), forced vital capacity FVC: 3.1±1.1 l vs. 4.4±0.8 l (p=0.00001). Subjects with the evidence of pulmonary hypertension (PH+) had lower exercise capacity than those without (PH-): VO2max: 17.2±4.2 vs. 12.8±4.8 ml/kg/min (p=0.002), VE/VCO2: 43.7±11.1 vs. 50.9±6.4 (p=0.01), FVC: 3.46±1.05 l vs. 2.37±0.91 l (p=0.0002). Plasma BNP levels in the study group were higher than in controls: 122.4±106.7 vs. 21.1±20.2 pg/ml p=0.00001 and did not differ between PH+ and PH− groups (115.7±99.0 vs. 127.9±114.1 pg/ml p=0.78). Negative correlations between BNP levels and VO2max (r=−0.389, p=0.006), FVC (r=−0.395 p=0.005), FEV1 (r=−0.386 p=0.006), SO2 (r=−0.445 p=0.00001), and positive correlation between BNP level and VE/VCO2 (r=0.369 p=0.009) were found.

Abstract 2423: B-type Natriuretic Peptide Upregulates Erythropoietin Receptor Gene Expression via Protein Kinase G in Heart Failure

Backgroud: Recent studies demonstrated non-hematopoietical effects of Erythropoietin (Epo) and its receptor (EpoR) in a variety of tissues including cardiovascular system. Epo treatment improves cardiac function in patients with heart failure and reduces infarct size after ischemia/reperfusion injury in the heart. However, little attention has been paid for the endogenous regulatory mechanisms regulating EpoR expression. In this study, we hypothesize that B-type natriuretic peptide upregulates EpoR gene expression in failing heart. Methods and Results: Wister rats underwent transverse aortic constriction surgery to induce hypertrophy. RT-PCR analyses of those rats showed that EpoR mRNA levels were increased in the left ventricle and positively correlated with the levels of BNP mRNA (n=10, r=0.67, p&lt;0.05). Next we examined the expression of EpoR in human failing heart by using autopsy specimens and found that EpoR mRNA levels were significantly elevated in patients with dilated cardiomyopathy compared with those in normal heart. Immunohistochemistry of endomyocardial biopsy specimens of failing heart (n=54) showed that EpoR mRNA levels were correlated with severity of cardiac dysfunction estimated by diameter of cardiac chambers, pathomorphology, serum BNP concentration and functional class of New York Heart Association. Interestingly, stimulation of cultured neonatal rat cardiac myocytes with BNP, but not with hypertrophic reagents including endothelin I, angiotensin II and norepinephrine, significantly increased the EpoR mRNA levels in a time-dependent manner. Overexpression of cGMP-dependent protein kinase (PKG) increased EpoR transcript in cultured cardiac myocytes. BNP-induced EpoR expression was abrogated in the presence of KT5823, a specific inhibitor for PKG. Conclusion: These results suggest a role for BNP in mediating an induction of EpoR expression in failing myocardium and indicate that the cardiac EpoR gene is a target of cGMP/PKG signaling.

Clinical characteristics of patients with acute heart failure associated with elevated systolic blood pressure on admission.

Objectives: Systolic blood pressure (sBP) is often elevated in acute heart failure (AHF) that may precipitate the increase in left ventricular end-diastolic pressure especially in the presence of diastolic dysfunction. To elucidate whether elevated sBP is the cause or the result of AHF, we studied the clinical characteristics of patients with AHF who showed elevated sBP on admission. Methods: Consecutive 60 patients with AHF were enrolled. LV fractional shortening (LVFS) and plasma BNP concentration were measured on admission and at recovery phase.

Evaluation of NT‐Pro BNP and CT‐ANP as Markers of Concentric Hypertrophy in Dogs with a Model of Compensated Aortic Stenosis

Serum C-terminal atrial natriuretic peptide (CT-ANP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) concentrations have not been measured serially in dogs with chronic pressure overload of the heart. We investigated whether serial evaluation of CT-ANP and NT-pro BNP concentrations is a useful guide to the risk of cardiac remodeling in dogs with a model of aortic stenosis. Six male Beagles. After anesthesia, the aorta was constricted with a polyester band and mean left ventricular systolic pressure (LVPs) was 50 mmHg above baseline. Echocardiographic and intracardiac catheter examinations and blood sampling were performed before surgery and 3 and 6 months after surgery. LVP and left ventricular end-diastolic pressure (LVEDP) were significantly higher at 6 months. Compared with baseline, end-diastolic intraventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), and relative wall thickness (RWT) were significantly increased 3 and 6 months after aortic constriction. Serum CT-ANP concentrations were increased significantly at 3 months and serum NT-pro BNP concentrations were significantly higher 3 and 6 months after aortic constriction. Serum NT-pro BNP concentration was significantly correlated with LVEDP and IVSd whereas serum CT-ANP concentration was not correlated with any measurement. Stepwise regression analysis showed that LVEDP, IVSd, and RWT could predict serum NT-pro BNP. This study indicated the differential regulation of NT-pro BNP and CT-ANP concentrations during pressure overload. NT-pro BNP assay may be used as an additional screening method to stratify early-stage ventricular remodeling because of aortic constriction.