Brain Natriuretic Peptide Response Research Articles

Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?

Copeptin, the C-terminal part of arginine-vasopressin, is increased in hypertensive adolescents and closely associated with metabolic syndrome (MS). We aimed to investigate whether serum copeptin can be used to differentiate masked hypertension (MHT) and MS, and the role of sodium intake, natriuretic peptide response and renin-angiotensin-aldosterone system in MHT and MS in obese youth. Obese children aged 10-18 years with normal office blood pressure measurements were included. Patients with MHT and normotension and those with MS and non-MS were evaluated separately. Biochemical parameters, copeptin, brain natriuretic peptide (BNP), aldosterone, renin, urine sodium, and protein were evaluated. Echocardiography, fundoscopic examination, and ambulatory blood pressure monitoring were performed. There were 80 (M/F=39/41) obese patients with a mean age of 13.78±1.93 years. The cases with MHT, MS, and concomitant MHT and MS were 53,24, and 13%, respectively. Copeptin levels were similar among patients with and without MHT or MS (p>0.05). However, multivariate analysis revealed that copeptin significantly increased the probability of MHT (OR 1.01, 95% CI=1.001-1.018, p=0.033). Copeptin was positively correlated with daytime systolic and diastolic load, aldosterone, BNP, and urine microalbumin/creatinine levels (p<0.05). Linear regression analyses revealed that copeptin was significantly correlated with BNP regardless of having MHT or MS in obese youth. In the MHT group, 24-h sodium excretion was not significantly correlated with BNP. Copeptin may be a beneficial biomarker to discriminate MHT, but not MS in obese children and adolescents. An insufficient BNP response to sodium intake might be one of the underlying causes of MHT in obese cases.

Six-Minute Walk Test As a Measure of Functional Change after Chemotherapy in Cardiac AL Amyloidosis

Background: Light chain amyloidosis (AL) is characterized by tissue deposition of misfolded proteins that cause multisystem organ dysfunction. Current treatments, including chemotherapy and autologous hematopoietic cell transplantation (AHCT), target plasma cells producing pathogenic amyloid proteins. The development of amyloid protein targeted monoclonal antibody therapy has led to an increased need for objective measurements of clinical response. The 6-minute walk test (6MWT) has been used for years as the primary outcome measure to monitor disease severity in clinical trials of heart failure (HF). For example, HF trials with cardiac devices MIRACLE (Abraham, 2002) and MUSTIC (Cazeau, 2001) demonstrated important therapeutic effects based on an improved 6MWT distance of 39 meters and a change of 23%, respectively. These findings, in conjunction with improvement in other markers of disease activity, lead to approval of cardiac resynchronization for the management of HF. Our primary objective was to determine the impact of chemotherapy on changes in 6MWT in patients with AL cardiac amyloid and correlate these changes with cardiac biomarkers.Patients and Methods: We retrospectively analyzed outcomes of 22 AL amyloid patients with cardiac involvement. Subjects performed 6MWT at diagnosis and at the end of planned initial chemotherapy. All patients received bortezomib (B)-based chemotherapy. About half received chemotherapy alone (45%) and the others received B-based induction chemotherapy followed by AHCT (55%). To identify factors associated with changes in 6MWT, we analyzed cardiac response and changes in New York Heart Association (NYHA) class, troponin I, brain natriuretic peptide (BNP) and left ventricular ejection fraction (LV EF). Cardiac response was defined as BNP decrease of 30% or NYHA class decrease ≥ 2 in subjects with baseline NYHA class 3 or 4 (adapted from Comenzo, 2012).Results: At baseline, 59% (n=13) of patients were modified AL amyloid cardiac stage I/II and 41% (n=9) stage III. The median percent change in 6MWT was an increase in 26.5% with a median change of 90 meters (range, -120 to 365), p < 0.001. Overall, 81% (n=18) had improvement in 6MWT distance, 9% (n=2) declined and 9% (n=2) were unchanged. Patients had reassessment of 6MWT a median of 13.5 months from diagnosis. Hematological responses (HR) included CR (36%), VGPR (36%), PR (23%) and SD (5%). HR was not associated with change in 6MWT. Fifty percent (n=11) experienced a cardiac response. By Wilcoxon rank sum test, variables that were associated with improvement in 6MWT included improved BNP, LV EF, troponin I, NYHA class and cardiac response (all p<0.001). The median follow-up of patients was 2.15 years (range, 1.10 - 7.20).By multivariate analysis, patients with a cardiac response had significantly better improvement in 6MWT disease compared with patients without cardiac response (p=0.02). A cardiac response was associated with a median increase of 170 meters of distance traveled by 6MWT when compared with patients having no cardiac response. All other variables tested were not statistically significant.Conclusion: In AL amyloid patients with cardiac involvement, the 6MWT can be used as an objective marker of functional improvement complementing biochemical and imaging parameters of response. Furthermore, treatment of cardiac amyloidosis with contemporary standard regimens has a major impact on the disease process by a number of objective parameters. Patients experiencing a cardiac response had substantial improvements in 6MWT. The 6MWT should be incorporated in trials of patients with cardiac amyloid. [Display omitted] DisclosuresCornell:Prothena: Research Funding.

Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude

BackgroundHigh altitude (HA) pulmonary edema (PE) results from complex and misunderstood interactions between adaptation mechanisms. We assessed the occurrence of subclinical PE and brain natriuretic peptide (BNP) levels among nonacclimatized individuals during an expedition on Mount Elbrus (5642 m). MethodsSeven subjects underwent assessment of vital signs, Lake Louise Score, ultrasound lung comets using handheld echography and circulating BNP using capillary testing at different stages of ascension, in addition to baseline echocardiography. Friedman tests were used to compare serial measurements. ResultsHeart rate, Lake Louise Score (P < 0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P < 0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P < 0.01) after the summit, as did ultrasound lung comet count throughout ascension (P < 0.0001), but both parameters were not correlated (r = 0.36; P = 0.42). Post-summit peak BNP correlated with baseline left ventricular mass index (r = −0.79; P = 0.033). ConclusionThis study confirms the high incidence of subclinical PE during subacute exposure to hypobaric hypoxia and enhancement of this phenomenon after exertion. Although not correlated with the degree of PE, BNP levels increased after sustained effort at HA, but not at rest. Further investigation is needed to determine the mechanisms underlying the BNP response at HA and its usefulness as a monitoring tool during expeditions.

Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients.

BackgroundBrain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls.MethodsCutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response.ResultsNon-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester (L-NAME), blocked the BNP response (in controls). Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls (increase in flow: 251% in CHF vs. 908% in controls; P < 0.001). In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not affected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response.ConclusionsThe findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.

154: Prognostic Importance of Exercise Brain Natriuretic Peptide in Asymptomatic Degenerative Mitral Regurgitation

Exercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary MR. The resting BNP level is a good surrogate marker of MR consequences and is a powerful predictor of outcome. The incremental prognostic value of BNP response during exercise is unknown. We aimed to identify the determinants of exercise brain natriuretic peptide (BNP) level and to evaluate its prognostic value in asymptomatic patients with primary mitral regurgitation (MR). Comprehensive resting and exercise transthoracic Dopplerechocardiography was performed in 113 consecutive asymptomatic patients with moderate to severe degenerative MR and preserved LV function. Blood samples were collected both at rest and exercise. The BNP level significantly increased from rest to exercise (p<0.0001). The independent determinants of exercise BNP were resting E/Ea ratio (p=0.043), indexed left atrial volume (p=0.022) and exercise LV global longitudinal strain (p=0.001). There was a significant graded relationship between increasing BNP level at exercise (according to tertiles) and increased incidence of cardiac events (death, heart failure, mitral valve surgery driven by symptoms or LV dilatation/dysfunction onset) (2-year: 21±7 vs. 40±8 vs. 67±9%; in tertiles 1, 2 and 3, respectively). On multivariable analysis, after adjustment for demographic and echocardiographic data and for resting BNP level, exercise BNP remained significantly associated with increased risk of cardiac events during the follow-up (hazard ratio= 2.8 and 3.4, p=0.041 and 0.023, for tertiles 2 and 3, as compared to tertile 1). In asymptomatic patients with primary regurgitation, exercise BNP level provides important incremental prognostic value beyond what is achieved by demographic and echocardiographic data and resting BNP level. Patients with elevated exercise BNP should be considered at high risk of reduced cardiac event-free survival.

Prognostic importance of exercise brain natriuretic peptide in asymptomatic degenerative mitral regurgitation

The exercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary mitral regurgitation (MR). The resting brain natriuretic peptide (BNP) level is a good surrogate marker of the consequences of MR and is a powerful predictor of outcome. The incremental prognostic value of BNP response during exercise is unknown. We aimed to identify the determinants of exercise BNP level and to evaluate its prognostic value in asymptomatic patients with primary MR. Comprehensive resting and exercise transthoracic Doppler echocardiography was performed in 113 consecutive asymptomatic patients with moderate to severe degenerative MR and preserved left ventricular (LV) function. Blood samples were collected both at rest and during exercise. The BNP level significantly increased from rest to exercise (P < 0.0001). The independent determinants of exercise BNP were resting E/Ea ratio (P = 0.043), indexed left atrial volume (P = 0.022), and exercise LV global longitudinal strain (P = 0.001). There was a significant graded relationship between increasing BNP level at exercise (according to tertiles) and increased incidence of cardiac events (death, heart failure, mitral valve surgery driven by symptoms, or LV dilatation/dysfunction onset) (1 year, 11 ± 5% vs. 14 ± 6% vs. 43.5 ± 9%; 2 years, 21 ± 7% vs. 40 ± 8% vs. 67 ± 9%; in tertiles 1, 2 and 3, respectively). On multivariable analysis, after adjustment for demographic and echocardiographic data and for resting BNP level, exercise BNP remained significantly associated with increased risk of cardiac events during the follow-up (hazard ratio 2.8 and 3.4, P = 0.041 and 0.023, for tertiles 2 and 3, as compared with tertile 1). In asymptomatic patients with primary MR, exercise BNP level provides incremental prognostic value beyond what is achieved by demographic and echocardiographic data and resting BNP level. Patients with elevated exercise BNP should be considered at high risk of reduced cardiac event-free survival.

Severe acute mountain sickness, brain natriuretic peptide and NT‐proBNP in humans

To examine the response of brain natriuretic peptide (BNP) and NT-proBNP to high altitude (HA) both at rest and following exercise. We measured NT-proBNP and BNP and Lake Louise (LL) acute mountain sickness (AMS) scores in 20 subjects at rest in Kathmandu (Kat; 1300 m), following exercise and at rest at 4270 and 5150 m. BNP and NT-proBNP (pg ml(-1) , mean ± SEM) rose significantly from Kat (9.2 ± 2 and 36.9 ± 6.6, respectively) to arrival at 4270 m after exercise (16.6 ± 4 and 152 ± 56.1, P=0.008 and P<0.001, respectively) and remained elevated the next morning at rest (28.9 ± 9 and 207.4 ± 65.1, P = 0.004 and P<0.001 respectively). At 5150, immediately following ascent/descent to 5643 m, BNP and NT-proBNP were 32.3 ± 8.8 and 301.1 ± 96.3 (P=0.003 and P<0.001 vs. Kat, respectively) and at rest the following morning were 33.3 ± 9.7 and 258.9 ± 89.5 (P=0.008 and P=0.001 vs. Kat respectively). NT-proBNP and BNP correlated strongly at 5150 m (ρ 0.905, P<0.001 and ρ 0.914, P<0.001 for resting and post-exercise samples respectively). At 5150 m, BNP levels were significantly higher among the four subjects with severe (LL score>6) AMS (58.4 ± 18.7) compared with those without (BNP 22.7 ± 8.6, P=0.048). There were significant correlations between change in body water from baseline to 5150 m with both BNP and NT-proBNP (ρ 0.77, P=0.001, ρ 0.745, P=0.002 respectively). In conclusion, these data suggest that BNP and NT-proBNP increase with ascent to HA both after exercise and at rest. We also report the novel finding that BNP is significantly greater in those with severe AMS at 5150 m.

Brain natriuretic peptide and acute hypobaric hypoxia in humans

In animal models, the secretion of the cardiac hormone, brain natriuretic peptide (BNP), and its closely related peptide, atrial natriuretic peptide (ANP), are stimulated by acute hypoxia. There is extensive human evidence for a rise in ANP under acute hypoxic conditions but very little evidence regarding the BNP response to acute hypoxia in humans. We therefore subjected seven healthy subjects to an acute hypobaric hypoxic stimulus to examine if BNP secretion increases rapidly. Significant hypoxaemia (mean nadir oxygen saturation 62.3%) was induced but no significant rise in BNP occurred. This suggests that either such acute hypoxaemia is well tolerated by the healthy human heart or it is not a stimulus for BNP secretion.

Effects of altitude exposure on brain natriuretic peptide in humans

Acute mountain sickness (AMS) is common at high altitude (HA) and associated with a relative failure of the natriuresis and diuresis that occurs at HA. The role of Brain Natriuretic Peptide (BNP) in this context has not been thoroughly investigated. We aimed to clarify if BNP rises in response to exercise at HA and if so whether this is related to AMS. 32 healthy subjects had assessments of BNP, aldosterone and AMS scores [as assessed by the AMS-C score of the Environmental Symptom Questionnaire (ESQ) and Lake Louise questionnaire] made following exertion at sea-level (SL), 3,400, 4,300 and 5,150m. Data were analysed in the 23 subjects who did not consume drugs known to affect acclimatization. BNP (pg/ml, mean±SEM) was significantly higher at 5,150m versus the lower altitudes (p<0.001 for all): 7.1±1; 6.1±0.3; 6.8±0.9 and 17.7±5.1 at sea-level; 3,400, 4,300 and 5,150m. In those that showed a BNP response at 5,150m (n=19) versus those that did not demonstrate a BNP response (n=4) there was a significant difference in Lake Louise (LL) AMS scores at 5,150m on day 10 of the expedition (mean LL score 3.3 vs. 0.75, p=0.034) and day 11 (mean LL score 3.3 vs. 0, p=0.003). This is the first report to demonstrate a significant rise in BNP at HA. A BNP response at 5,150m may be associated with a greater likelihood of suffering AMS.

Diagnostic, prognostic and therapeutic relevance of B-type natriuretic hormone and related peptides in children with congenital heart diseases

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with congenital cardiac diseases (CHD). A computerized literature search in the National Library of Medicine using the keywords "BNP assay" and "NT-proBNP assay"+neonate/s and newborn/s was performed. Next, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP measurements in children with CHD. Several authors suggested that BNP/NT-proBNP is clinically helpful as a diagnostic and prognostic marker for children with suspected CHD. BNP values are age dependent, even in paediatric populations. Unfortunately, accurate reference values for BNP and NT-proBNP for neonatal ages have only recently become available. As a result, the lack of homogenous and accurate decisional levels in the neonatal period greatly limits the clinical impact of the BNP assay, and also contributed to the production of conflicting results. Regardless of age, there is great variability in BNP/NT-proBNP values among CHD characterized by different hemodynamic and clinical conditions. In particular, cardiac defects characterized by left ventricular volume and pressure overload usually show a higher BNP response than CHD which is characterized by right ventricular volume or pressure overload. BNP and NT-proBNP may be considered helpful markers in the integral clinical approach for patients with CHD. Measurement of BNP cannot replace cardiac imaging (including echocardiography, angiography and magnetic resonance), but provide independent, low cost and complementary information for the evaluation of cardiac function and clinical status.

NT-proBNP Does Not Rise on Acute Ascent to High Altitude

The response of brain natriuretic peptide (BNP) to acute ascent to altitude is of interest as a surrogate for ventricular function and because BNP is involved in the normal homeostasis of the pulmonary vasculature. The structurally related hormone atrial natriuretic pressure (ANP) has been demonstrated to be elevated at altitude and implicated in natriuresis. We measured plasma concentrations of ANP and NT-proBNP (a more stable BNP precursor) in 10 healthy non-HAPE-susceptible lowlanders during acute exposure to 5200 m on the Apex 2 expedition to Bolivia. Systolic pulmonary artery pressure (PASP) was measured using tricuspid regurgitant jet estimation by echocardiography. Despite a significant rise in the PASP, NT-proBNP did not rise. A small decrease in NT-pro BNP occurred after 7 days at high altitude. There was no significant change in ANP levels. The lack of any increase in NT-proBNP in healthy resting subjects supports the view that ventricular function is well preserved and suggests that BNP is not playing a significant role in altered pulmonary artery pressure.

Relation of Brain Natriuretic Peptide Level to Extent of Left Ventricular Scarring in Patients With Chronic Heart Failure Secondary to Ischemic Cardiomyopathy

Multiple factors influence brain natriuretic peptide (BNP) release in patients with heart failure. We hypothesized that extensive myocardial scarring could result in an attenuated BNP response. A total of 115 patients with New York Heart Association class III chronic heart failure and ischemic cardiomyopathy were evaluated for ischemia, hibernation, and myocardial scarring by dipyridamole-rubidium-positron emission tomographic scanning with fluorine-18, 2-fluoro-2-deoxyyglucose. Plasma BNP levels were determined within 2 weeks of the study. Left ventricular dimension and function were evaluated by echocardiography. Patients were categorized as having <33% myocardial scar (n=67) or>or=33% myocardial scar (n=48). BNP measurements were correlated with amount of myocardial scarring. Compared with patients with less scar, those with >or=33% scar had lower BNP levels (mean 317+/-364 vs 635+/-852 pg/ml, median 212 vs 357, p=0.016). Using multiple regression analysis, presence of scarring was associated with decreased BNP response (p=0.022). Further, patients with <33% scar in whom a higher BNP level was noted had more ischemia (51% vs 27%, p=0.01) and greater myocardial hibernation (22+/-14% vs 12+/-7%, p=0.02) compared with patients with >or=33% scar. In conclusion, in patients with chronic heart failure, a decreased BNP response indicated extensive myocardial scarring.

Melphalan and Dexamethasone Is an Effective Therapy for Primary Systemic Amyloidosis.

Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder with a poor survival, especially in patients (pts) with multiple organ involvement. For pts with limited organ involvement, high dose chemotherapy with autologous stem cell (SCT) support is an effective approach. However, the toxicity of SCT limits its widespread use. Melphalan and dexamethasone has been previously shown to be effective in pts ineligible for SCT.Methods: We reviewed our experience with melphalan and dexamethasone for treatment of AL. Eighty one pts were treated between 2001 and 2003; median age at start of therapy was 63 years (range, 38–80) and 56 pts (69%) were males. Among these, 46 pts (57%) had 2 or more major organs (cardiac, renal, hepatic) involved. Intravenous melphalan (IV) was used in 45 pts (56%), 32 (40%) received oral melphalan (PO) and the rest received cycles of both. The most common doses were 16 mg/m2 for IV administration (every 4–6 weeks) and 0.22 mg/kg for PO administration (every 4 weeks). Dexamethasone was usually given at a dose of 40 mg for the first 4 days of each cycle.Results: Patients received a median of 5 cycles (range; 1–17). At the time of analysis, 53 (65%) pts were alive with a median follow up of 10.8 months (range, 1.4–47.1).The estimated median overall survival (OS) was 25.6 months for the entire group, with the number or type of organs involved not impacting survival. Hematological response (HR) was defined by a 50% reduction in either serum M-spike, urine M-spike, or the absolute difference between the involved and uninvolved immunoglobulin free light chains. A HR was observed in 43 pts (67%) of the 64 pts measurable for HR by conventional criteria. Achievement of HR was associated with a superior OS with a median post-therapy OS that was not reached, while non-responders had a median OS of 11.1 months (p<0.0001) (Figure 1). Among these pts, an organ response as defined by conventional criteria, was seen in 14 pts (22%), which was significantly correlated with obtaining a hematological response (33% vs. 5%, p=0.01). A 25% reduction in the difference between the involved and uninvolved FLC strongly predicted prolonged OS, with a median post-therapy OS that was not reached for responders vs. 11.3 months for non-responders (p<0.0001) (Figure 2). A decrease in post-therapy brain natriuretic peptide (BNP) also predicted for a survival improvement, with the median OS not reached for responders vs. a median OS of 17 months for non-responders (p<0.016).Conclusion: Treatment with melphalan and dexamethasone is effective and a significant survival advantage is achieved in patients with a hematological response. FLC and BNP response can help identify patients that are likely to benefit from this therapy. [Display omitted] [Display omitted]

Blood volume and brain natriuretic peptide in congestive heart failure: A pilot study

Brain natriuretic peptide (BNP) levels rise in response to stretch of ventricular myocytes or increases in wall tension, as in congestive heart failure (CHF). Brain natriuretic peptide can be released in bursts, but nonetheless, BNP levels may lag behind clinical changes. We postulated that concomitant measurement of blood volume (BV), BNP, and hemodynamics during treatment of CHF may elucidate interrelationships among changes in these parameters. We studied 10 male patients, aged 60 +/- 8 years, who were admitted for pulmonary catheter-guided treatment of CHF. Hemodynamics, venous BNP, and blood and plasma volumes were measured at baseline before treatment and again on the following morning after 12 to 24 hours of acute treatment for CHF. At baseline, all 10 patients exhibited marked expansion of BV at 29% +/- 19%. At baseline, increased systolic pulmonary artery pressure correlated with BV (r = 0.615) and diastolic pulmonary artery pressure (PAD) with BV (r = 0.609). After treatment, there was an inverse correlation between change (decline) in expanded BV and change (improvement) in mixed venous oxygenation (r = -0.775) and a positive correlation with central venous pressure (CVP) (r = 0.710). Poor correlation was found between BNP and any hemodynamic parameter. Little correlation was found between absolute BNP and BV before or after treatment (r = -0.127 and -0.126, respectively). In this pilot study, changes in BV with treatment correlate better with hemodynamics than do changes in BNP, likely reflecting the lag in BNP response to treatment and its tendency to reflect long-term rather than instantaneous volume status. These preliminary data suggest that BV may be a more accurate guide in optimizing CHF treatment than BNP.

Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation

Background In patients with atrial fibrillation (AF) information regarding exercise release of atrial natriuretic peptide (ANP) is sparse and data on plasma brain natriuretic peptide (BNP) response to exercise is lacking. The aim of this study was to investigate plasma ANP and BNP response to exercise in patients with permanent AF and to assess if the response was different from the response in healthy age- and sex-matched control subjects. Methods Plasma venous concentrations of ANP and BNP were determined at rest, at peak exercise and 30 min from the end of exercise in 38 patients with permanent AF and in 43 age- and sex-matched healthy control subjects. Results Plasma concentrations of ANP and BNP were significantly higher in AF patients compared with the healthy control group at rest, peak exercise and after 30 min of recovery ( p<0.0001). ANP and BNP increased significantly during exercise in both patients with AF and in the healthy control subjects ( p<0.05). The increase in plasma concentration of ANP and BNP during exercise was significantly higher in AF patients compared with healthy controls ( p=0.0002 for ANP; p<0.0001 for BNP). In the recovery period plasma BNP decreased significantly ( p<0.0001) where as the decrease in plasma ANP was insignificant ( p=0.4). Conclusions Patients with permanent AF have elevated levels of ANP and BNP at rest and exhibit much higher exercise release compared to healthy control subjects. This enhanced secretion of potent vasodilating and natriuretic agents may represent an important compensatory mechanism to improve exercise capacity in patients with AF.

Brain natriuretic peptide response is heterogeneous during β-blocker therapy for congestive heart failure

Background Plasma brain natriuretic peptide (BNP) levels are useful marker to guide medical treatment in patients with congestive heart failure (CHF). We tested the hypothesis that the plasma BNP concentration would be a useful marker of β-blocker therapy for CHF. Methods and Results Eighty-four patients with New York Heart Association class II-IV CHF and a left ventricular ejection fraction (LVEF) <40% were treated with β-blockers, including metoprolol and carvedilol, for at least 16 weeks. End-diastolic and end-systolic dimensions decreased, and radionuclide LVEF increased 4 weeks after introduction of β-blockers (early phase). LV end-diastolic and end-systolic dimensions both decreased, and LVEF increased 16 to 48 weeks after the therapy (late phase). However, the BNP concentration did not change during the observation period. Overall LV function improved in all 4 subgroups divided according to the baseline BNP levels. Conclusions Plasma BNP concentration is not a sensitive marker of successful β-blocker therapy for CHF.

Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic peptide and brain natriuretic peptide in healthy men

Background Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP. Methods Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage. Results Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men. Conclusions Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race. (Am Heart J 2001;141:751-8.)

Differential Expression of Natriuretic Peptides and their Receptors in Volume Overload Cardiac Hypertrophy in the Rat

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregulation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and blood pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynamic stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2, 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastolic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34±0.04 vs 3.07±0.10 mg/g, P<0.05) while RV weight did not change over the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP and BNP were increased >2-fold by day 2 and this increase was sustained throughout 7 days. NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before the onset of LV hypertrophy and RV BNP mRNA levels increased in the absence of RV hypertrophy. The disparate response of BNP and the NP clearance receptor transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in response to acute haemodynamic stress.

Ovine brain natriuretic peptide in cardiac tissues and plasma: effects of cardiac hypertrophy and heart failure on tissue concentration and molecular forms

Whereas numerous studies have examined the cardiac tissue content and secretion of atrial natriuretic peptide (ANP), the response of brain natriuretic peptide (BNP) in states of experimental cardiac overload is less well documented. Our recent partial cloning of the ovine BNP gene has enabled us to study changes in cardiac tissue concentration, together with tissue and circulating molecular forms of ANP and BNP, in response to cardiac overload induced by rapid ventricular pacing (n = 7) and aortic coarctation (n = 6). In normal sheep, although highest levels of BNP were found in atrial tissue (15-fold those of the ventricle), the BNP/ANP concentration ratio in the ventricles was 10- to 20-fold higher than the ratio calculated for atrial tissue. Compared with normal sheep, significant depletion of both ANP and BNP concentrations within the left ventricle occurred after rapid ventricular pacing. Size exclusion and reverse phase HPLC analysis of atrial and ventricular tissue extracts from normal and overloaded sheep showed a single peak of high molecular weight BNP consistent with the proBNP hormone. In contrast, immunoreactive BNP extracted from plasma drawn from the coronary sinus was all low molecular weight material. Further analysis of plasma BNP using ion exchange HPLC disclosed at least 3 distinct immunoreactive peaks consistent with ovine BNP forms 26-29 amino acid residues in length. These findings show that BNP is stored as the prohormone in sheep cardiac tissues and that complete processing to mature forms occurs at the time of secretion. The capacity to process the prohormone at secretion is not impaired by chronic heart failure.

Responses of atrial natriuretic peptide and brain natriuretic peptide to exercise in patients with chronic heart failure and normal control subjects.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.