Elevated Plasma B-type Natriuretic Peptide Research Articles

Predictive Factors of Cardiac Mortality Following TEER in Patients with Secondary Mitral Regurgitation

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has emerged as a viable approach to addressing substantial secondary mitral regurgitation. In the contemporary landscape where ultimate heart failure-specific therapies, such as cardiac replacement modalities, are available, prognosticating a high-risk cohort susceptible to early cardiac mortality post-TEER is pivotal for formulating an effective therapeutic regimen. Methods: Our study encompassed individuals with secondary mitral regurgitation and chronic heart failure enlisted in the multi-center (Optimized CathEter vAlvular iNtervention (OCEAN)-Mitral registry. We conducted an assessment of baseline variables associated with cardiac death within one year following TEER. Results: Amongst the 1517 patients (median age: 78 years, 899 males), 101 experienced cardiac mortality during the 1-year observation period after undergoing TEER. Notably, a history of heart failure-related admissions within the preceding year, utilization of intravenous inotropes, and elevated plasma B-type natriuretic peptide levels emerged as independent prognosticators for the primary outcome (p < 0.05 for all). Subsequently, we devised a novel risk-scoring system encompassing these variables, which significantly stratified the cumulative incidence of the 1-year primary outcome (16%, 8%, and 4%, p < 0.001). Conclusions: Our study culminated in the development of a new risk-scoring system aimed at predicting 1-year cardiac mortality post-TEER.

Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis.

Rheumatoid arthritis is a prototypic inflammatory condition with affected patients being at greater risk of incident heart failure (HF). Targeting innate immune cell function in the pathogenesis of HF bears the potential to guide the development of future therapies. A collagen-induced arthritis (CIA) model in DBA/1 J mice was used to generate arthritis. Mice with CIA developed concentric hypertrophic myocardial remodeling, left ventricular (LV) diastolic dysfunction, and HF with elevated plasma B-type natriuretic peptide levels but preserved LV ejection fraction. Key features of HF in CIA were increased infiltration of activated neutrophils, deposition of neutrophil extracellular traps in the myocardium, and increased tissue levels of the proinflammatory cytokine IL-1β. Specific inhibition of protein arginine deiminase 4 (PAD4) by an orally available inhibitor (JBI-589), administered after the onset of clinical arthritis, prevented HF with reduced neutrophil infiltration. We identify PAD4-mediated neutrophil activation and recruitment as the key thromboinflammatory pathway driving HF development in arthritis. Targeting PAD4 may be a viable therapeutic approach for the prevention of HF secondary to chronic inflammation.

Sleep-disordered breathing is independently associated with elevated natriuretic peptide levels in patients with cardiovascular diseases

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66years (55-74years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9pg/ml (23.5-146.4pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17-10.88; moderate: OR, 3.62; 95% CI 2.17-6.02; mild: OR, 2.22: 95% CI 1.42-3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

Association of BNP with Frailty in Elderly Population: Rugao Longevity and Ageing Study

To explore the associations of B-type natriuretic peptide (BNP) with physical frailty status as well as each domain of frailty in a general elderly population. Cross-sectional analysis of prospective cohort study. All of 31 communities in Jiang'an township. Overall 1338 participants (aged 70-89 years, mean 77.42±4.08 years) without a history of cardiovascular diseases in the third-wave of the aging arm of the Rugao Longevity and Aging Study (RuLAS). Frailty was defined as the presence of ≥3 domains among five modified Fried's criteria (unintentional weight loss, low physical activity level, weakness (low grip strength), exhaustion, and slowness (slow gait speed)) and pre-frailty as the presence of 1-2 domains. The prevalence of frailty and pre-frailty was 10.4% and 53.3%, respectively, in this elderly population. Elevated BNP (≥100 pg/mL) was significantly associated with pre-frailty (OR: 1.61, 95% CI: 1.13-2.29) and frailty (OR: 2.63, 95% CI: 1.61-4.32) after adjustment for covariates. In addition, elevated BNP was associated with low grip strength (OR: 2.00, 95% CI: 1.41-2.82) and low gait speed (OR: 1.62, 95% CI: 1.15-2.28) after adjustment for multiple covariates. Log BNP was inversely associated with grip strength (r= -0.265, p<0.001) and gait speed (r= -0.189, p<0.001). Elevated plasma BNP was associated with increased risks of frailty, pre-frailty, and low levels of grip strength and gait speed in the elderly community people.

Elevated Plasma B-Type Natriuretic Peptide Concentrations Directly Inhibit Circulating Neprilysin Activity in Heart Failure

ObjectivesThis study sought to hypothesize that elevated B-type natriuretic peptide (BNP) could act as an endogenous neprilysin inhibitor. BackgroundA hallmark of acute decompensated heart failure (ADHF) is the overproduction of natriuretic peptides (NPs) by stretched cardiomyocytes. Various strategies have been developed to potentiate the beneficial effect of the NPs, including the recent use of neprilysin angiotensin receptor inhibitors. Contrary to rodents, human BNP is poorly sensitive to neprilysin degradation while retaining affinity to neprilysin. MethodsWe enrolled 638 patients presenting to the emergency department with acute dyspnea of which 468 had ADHF and 169 had dyspnea of noncardiac origin. We also included 46 patients with stable chronic heart failure (HF) and 10 age-matched healthy subjects. Plasma samples were collected within 4 h after emergency department admission. BNP, neprilysin concentration and activity, and the neprilysin substrate substance P concentration were measured. ResultsWe found that when plasma BNP rose above 916 pg/ml, neprilysin activity was markedly reduced (p < 0.0001) and stratified 95% of the population into 2 groups: BNP <916 pg/ml/neprilysin activity ≥ 0.21 nmol/ml/min and BNP ≥916 pg/ml/neprilysin activity <0.21 nmol/ml/min with very different prognoses. In vitro, BNP was responsible for neprilysin inhibition. Neprilysin activity was inversely correlated with the concentration of substance P (ρ = −0.80; p < 0.0001). ConclusionsBesides being an effector of the cardiac response to cardiomyocyte stretching in ADHF, elevated plasma BNP is also an endogenous neprilysin inhibitor. A biologically relevant BNP threshold discriminates 2 populations of HF patients with different vasoactive peptide profiles and outcome. If confirmed, this may identify an important threshold for managing HF patients.

Elevated plasma B-type natriuretic peptide concentration and resistive index, but not decreased aortic distensibility, associate with impaired blood flow at popliteal artery in type 2 diabetic patients.

Blood flow in lower extremity arteries is frequently impaired in diabetic patients even though they have a normal ankle-brachial index (ABI 1.0-1.4). Risk factors contributing to this lower extremity arterial disease have not been fully elucidated. We enrolled 52 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Plasma B-type natriuretic peptide (BNP) concentrations were measured. Distensibility in ascending thoracic and abdominal aortas as well as total flow volume and resistive index at popliteal artery were evaluated by gated magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV). Diabetic patients showed lower distensibility in ascending thoracic aorta (p<0.001) and total flow volume (p<0.001) and higher baPWV (p<0.001) and resistive index (p=0.005) and similar BNP and distensibility in abdominal aorta compared to nondiabetic subjects. Simple linear regression analyses revealed that distensibility in ascending thoracic (p=0.019) and abdominal (p=0.030) aortas positively as well as baPWV (p=0.020), resistive index (p<0.001) and BNP (p<0.001) negatively correlated with total flow volume. Stepwise multiple regression analysis demonstrated that increased BNP and resistive index were independent risk factors for total flow volume in diabetic patients (r(2)=0.639, p<0.001). These results indicate that increased plasma BNP levels and peripheral vascular resistance, but not decreased aortic distensibility, associate with impaired blood flow in lower extremity arteries in diabetic patients.

Prognostic Significance of B Type Natriuretic Peptide in Acute Coronary Syndrome

Acute Coronary syndrome (ACS) is the most common cause of admission to the coronary care unit with highest risk of death and adverse outcomes. ACS accounts for 60–70% of all admissions in the hospital. Patients with ACS encompass a heterogeneous group that varies widely regarding severity of the underlying coronary artery disease, prognosis and response to treatment. Patients with the highest risk of subsequent events usually have the largest benefit of an intensified pharmacological treatment and early mechanical intervention. The prognosis for low-risk patients, on the other hand, is often difficult to improve further and these patients usually benefit more from a conservative management with a lower risk of side effects. Therefore, risk stratification is essential and should be initiated early and updated continuously throughout the hospital stay. Early risk stratification is usually performed by the use of clinical background factors, clinical presentation, electrocardiography and biochemical markers of myocardial damage. Levels of natriuretic peptides have been shown to reflect cardiac performance. The aim of this study was to review elaborately on B type Natriuretic Peptide (BNP) and its prognostic value in patient with ACS. This review focuses on the emerging role of these peptides in the early risk stratification of ACS patients. Elevation of BNP levels in acute MI and UA is predictive of a greater risk of death, post infarction heart failure, or reinfarction. Post infarction studies demonstrate that elevated plasma BNP levels are associated with larger infarct size, increased probability of ventricular remodeling, lower ejection fraction, higher risk of heart failure, and increased mortality. This cardiac marker is a potent predictor of mortality in patients with all forms ACS. BNP measurements serve as an index of severity of the ischemic injury, as well as the degree of impairment in left ventricular function.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i2.21079

Factors responsible for elevated plasma B-type natriuretic peptide levels in severe aortic stenosis: Comparison between elderly and younger patients

BackgroundElevated plasma B-type natriuretic peptide (BNP) is a predictor of outcome and helpful for risk stratification in aortic stenosis (AS). However, left ventricular (LV) diastolic dysfunction progresses with aging and may also influence plasma BNP levels in elderly patients. We hypothesized that plasma BNP levels may be influenced by age in severe AS, and that factors that affect the elevation of plasma BNP levels may be different between elderly and younger patients with AS. MethodsWe performed echocardiography in 341 patients with severe AS [aortic valve area (AVA)<1.0cm2] and classified them into two groups by age (elderly ≥75 years old, n=201; younger patients <75 years old, n=140). We used multivariate linear regression analysis to assess the factors that determine plasma BNP levels in both groups. ResultsAge was found to be one of the independent determinants of plasma BNP levels in all patients (β=0.135, p=0.005). Although AVA was similar in the two groups, plasma BNP levels and E/e′ were significantly higher in elderly than younger patients [133.0 (IQR, 73.3–329.7)pg/dl vs 92.8 (IQR, 40.6–171.8)pg/dl, p<0.01; 20±8 vs 16±6, p<0.01, respectively). In multivariate stepwise linear regression analysis, AVA index, LV ejection fraction, mass index, E/e′, estimated systolic pulmonary artery pressure (eSPAS), and the presence of atrial fibrillation were independent determinants of plasma BNP levels in younger patients. In contrast, the independent determinants of plasma BNP levels in elderly patients were LV ejection fraction, mass index, E/e′, eSPAS, the presence of atrial fibrillation, age, and hemoglobin levels, but not AVA index. ConclusionsThere may be differences in the factors that influence plasma BNP levels between elderly and younger patients with severe AS. In elderly patients, plasma BNP levels may be influenced more by these factors than AS severity compared with younger patients.

Elevated Plasma B-type Natriuretic Peptide and C-reactive Protein Levels in Children with Restrictive Right Ventricular Physiology Following Tetralogy of Fallot Repair

This study aimed to compare the levels of plasma B-type natriuretic peptide (BNP) and C-reactive protein (CRP) in relation to oxygen transport between patients with restrictive right ventricle (rRV) and those without (non-rRV) early after tetralogy of Fallot (TOF) repair. Eighty patients (30 in the rRV group) underwent TOF repair in 2011 and 2012. BNP and CRP were repeatedly measured during postoperative day (POD) 7, along with oxygen transport variables including arterial and superior vena cava oxygen saturation (SaO2 and SvO2 ), oxygen extraction ratio (ERO2 ), and lactate. Demographic data included age and durations of cardiopulmonary bypass (CPB), aortic cross-clamping (ACC), mechanical ventilation, and ICU and hospital stays. During POD 7, BNP did not change in either of the two groups but was consistently higher in the rRV group (P < .0001). CRP increased from POD 1 to POD 2 and decreased thereafter. The decrease was slower in the rRV group (P = .04). The increase in SvO2 and the decrease in ERO2 were slower in the rRV group (P < .05). Lactate decreased in both groups (P < .05) but was consistently higher in the rRV group (P = .03). BNP was negatively correlated with SvO2 and preoperative SaO2 and positively correlated with ERO2 and lactate (P < .05). No correlation was found between CRP and oxygen transport variables. The rRV group was older and required longer CPB, ACC, mechanical ventilation, and ICU and hospital stays compared with the non-rRV group (P < .05 for all). rRV physiology is associated with significantly higher BNP and CRP levels with poorer balance of systemic oxygen transport. Information about these pathophysiological changes may help to identify appropriate treatment strategies in this difficult group of patients.

Abstract 18336: Does the Interaction of B-Type Natriuretic Peptide and Depressive Symptom Status Predict Cardiac Mortality and Re-Hospitalization in Rural-Dwelling Heart Failure Patients?

BACKGROUND: Identification of reduced and preserved left ventricular ejection fraction (LVEF) is a stratification used in heart failure (HF) management and prognosis. Elevated B-type natriuretic peptide (BNP) levels and depressive symptoms are independently associated with poor prognosis; however, their combined risk on cardiac death and re-hospitalization for HF is less clear. OBJECTIVE: To assess the combined effect of BNP and depressive symptoms on clinical outcomes in rural-dwelling HF patients with both reduced and preserved LVEF. METHODS: Baseline data were collected on 576 patients in the Rural Education to Improve Outcome in Heart Failure (REMOTE) trial. Measures included BNP levels and depressive symptoms (Patient Health Questionnaire [PHQ]-9). Patients were stratified into 4 groups by elevated and normal plasma BNP (&gt;100 pg/ml and ≤100 pg/ml) and with and without depressive symptoms (PHQ-9 ≥ 10 and &lt; 10). Outcomes were defined as composite 2-year endpoint of cardiac death or first HF re-hospitalization. RESULTS: There were 199 patients (35%) who had a cardiac event. Kaplan-Meier with log rank test showed the probability of event-free survival differed significantly depending on BNP and depressive symptom status (Figure). In multivariable Cox regression analysis, the risk of the composite endpoint for those with depressive symptoms alone was 0.8 (p = 0.85); with elevated BNP alone, 16.8 (p &lt; 0.001); and combined, 13.1 (p = 0.003) compared to non-depressed patients with normal BNP, independent of other covariates. Composite risk was similar between elevated BNP groups with or without depressive symptoms (p = 0.56). However, LVEF significantly modified the effect (p interaction = 0.03); higher LVEF reduced composite risk in patients with elevated BNP alone (hazard ratio 0.96, p = 0.01). CONCLUSION: Combined effect of BNP and depressive symptoms on cardiac event risk may provide useful clinical data in the risk stratification and management of HF outcomes.

Elevated plasma B-type natriuretic peptide level predicts 30-day and 1-year mortality after transapical but not transfemoral transcatheter aortic valve implantation

Purpose: Evaluate the predictive value of B-type natriuretic peptide (BNP) levels for 30-day and 1-year mortality after transfemoral (TF-) and transapical (TA-) transcatheter aortic valve implantation (TAVI) Methods: Plasma BNP was measured in 419 consecutive patients who underwent TAVI in our center either through TF- or TA- access at least one day before procedure. Results: 419 consecutive patients underwent TAVI in our center. TF- access was used in 308 patients and TA- access in 111 patients. 39 (9%) patients died at 30-day after procedure and 74 (18%) patients died at 1-year after procedure. Baseline BNP was 540±837 pg/ml in whole group with a trend towards higher baseline BNP in TF- patients (561±846 pg/ml) compared to TA- patients (484±814 pg/ml), p= 0.07. Baseline Ln-BNP was lower in 30-day survivors (5.6 vs. 6.0, p= 0.04) as well as 1-year survivors (5.6 vs. 5.9, p= 0.02) versus non survivors in the whole patients population and in TA- subgroup (5.4 vs. 6.3, p= 0.009 for 30-day mortality and 5.3 vs. 6.1, p= 0.001 for 1-year mortality), while TF- subgroup showed no significant difference in Ln-BNP between survivors and non survivors (5.7 vs. 5.9, p= 0.4 for 30-day mortality and 5.7 vs. 5.8, p= 0.4 for 1-year mortality). Kaplan Meier survival analysis showed increased 30-day mortality (13% vs. 3%, p= 0.001) and 1-year mortality (23% vs. 9%, p 195 pg/ml in the whole population and in TA- subgroup (19% vs. 0%, p= 0.002 for 30-day mortality and 37% vs. 4%, p 195 pg/ml had significantly higher 1-year mortality compared to TF- subgroup (37% vs. 18%, p= 0.003). Conclusion: Baseline plasma BNP is a useful outcome predictor in TA- but not in TF-TAVI. TF-TAVI may provide a better outcome than TA-TAVI in patients with baseline BNP> 195 pg/ml.

Fetal Rat Hearts Do Not Display Acute Cardiotoxicity in Response to Maternal Doxorubicin Treatment

Anthracyclines are used to treat cancers during the second and third trimester of pregnancy. The chemotherapeutic effect of anthracyclines is associated with a dose- and time-dependent cardiotoxicity that is well described for infants and adults. However, data regarding fetal anthracycline-related cardiotoxicity after administration of chemotherapeutics during pregnancy are limited. In this study, we analyzed the acute effect of doxorubicin, an anthracycline derivative, on fetal and maternal rat myocardium. We injected 10 or 20 mg/kg i.v. doxorubicin to pregnant Wistar rats at day 18 of pregnancy; age-matched pregnant rats injected with physiologic saline served as controls. Maternal echocardiography and fetal Doppler scanning were performed before the injection and before sacrifice. Cesarean operation was performed at day 19 or 20, and maternal and fetal blood samples and heart biopsies were collected to measure apoptosis, the impact on cell proliferation, and structural cardiac damage. Acute maternal cardiotoxicity is associated with loss of body weight, moderately deteriorated left ventricular function, induction of apoptosis, and a decrease in cell turnover. Despite a 30% lower fetal body weight and elevated plasma B-type natriuretic peptide concentrations after doxorubicin administration, the fetal hearts had intact microstructure, an unaltered number of apoptotic cells, and preserved cell proliferation compared with controls. Our study suggests that acute treatment using anthracyclines during pregnancy impairs maternal cardiac function, whereas fetal hearts are protected.

Defining and Refining Heart Failure Risk Stratification to Optimize Patient Selection for Cardiac Transplantation

VO2, BNP, GFR, RAP, CI, LVEDP, EF, Na, BUN, MR, LVEDD, PCWP, PVCs, VT, QRS, LBBB, COPD, DM, TpnI, alb, CAD, OSA, Hct, RDW, CRT, ICD, HRV—the complex alphabet soup of heart failure risk assessment used to inform clinical decision making, select patient cohorts for trials, and ensure that expensive and supply-limited treatments are utilized in the most effective and equitable manner. Despite the seeming complexity of this task, heart failure clinicians have become facile at integrating multiple distinct variables into a cohesive understanding of risk using baseline patient characteristics, measures of cardiac structure and function, biomarkers, and assessment of functional capacity. The prognostic significance of many risk-associated parameters, such as ejection fraction, ventricular size, and the pathogenesis of heart failure are firmly established. However, recognition of the importance of common comorbidities and the rapidly evolving field of novel biomarkers that represent perturbation of normal biological pathways or markers of early organ damage have reshaped and refined contemporary risk assessment. More recently, larger datasets have facilitated the derivation and validation of multivariable risk-prediction models, such as the Heart Failure Survival Score, the Seattle Heart Failure Model, and the ESCAPE Risk Score.1–3 Article see p 6 In this issue of Circulation: Heart Failure , Kato et al4 re-examine the pivotal role of cardiopulmonary exercise testing in heart failure risk assessment and extend the sentinel work by Mancini that validated VO2 as a potent predictor of short- and intermediate-term mortality.5 Mancini’s original observation that a peak VO2 <14 mL/kg per min was associated with excessive morality led to its …

Abstract 9451: Determinant Factors of Elevated Plasma B-type Natriuretic Peptide Level in Severe Aortic Stenosis

Background: Elevated plasma B-type natriuretic peptide (BNP) level reflects left ventricular (LV) dysfunction and is associated with poor outcome in aortic stenosis (AS). We aimed to determine the echocardiographic and clinical factors that are associated with elevated plasma BNP level in patients with severe AS. Methods: We performed echocardiography in 142 patients (age 72±10 years) with severe AS (aortic valve area (AVA) &lt; 1.0cm 2 ). We excluded patients with chronic renal failure and other significant valvular disease. We used multivariate linear regression analysis to evaluate factors that are associated with the plasma BNP levels in these patients. Results: Mean AVA was 0.77±0.16cm 2 . The factors associated with plasma BNP levels were left ventricular (LV) ejection fraction, E/A, E/e’, left atrial diameter, estimated systolic pulmonary artery pressure (SPAP), AVA, LV mass index, e’, systolic systemic blood pressure and the presence of atrial fibrillation (Table). In multivariate stepwise linear regression analysis, LV ejection fraction was the strongest independent determinants of plasma BNP level. In addition, estimated SPAP, and E/e’, and AVA were also found to be independently associated with plasma BNP level. Conclusions: In patients with severe AS, plasma BNP levels mainly correlates with LV systolic dysfunction. However, LV diastolic dysfunction, elevated pulmonary hypertension, and AS severity are also independently associated with elevated plasma BNP levels in severe AS.

Abstract 17770: Utility of Plasma B-Type Natriuretic Peptide Levels for Cardiovascular Risk Assessment in Subjects with Albuminuria

Background: The subjects with albuminuria is a high risk group for cardiovascular disease (CVD). Also, increased plasma B-type natriuretic peptide (BNP) levels have been reported to be associated with CVD risk in several clinical and population-based settings. However, it remains unknown whether CVD risk in subjects with albuminuria could be stratified by plasma BNP levels. METHODS: At baseline, we measured spot urinary albumin/creatinine concentrations (UACR) and plasma BNP concentration in the general population (n = 15,344). Albuminuria was defined by UACR more than 30 mg/g creatinine (Cr). Data from 3,214 subjects aged 40 to 80 (mean age = 65 years) with no cardiovascular history were analyzed. The cohort was divided into quartiles according to plasma BNP, and the CVD event free rate within each BNP quartile was estimated using the Kaplan-Meier method. In addition, Cox regression analysis was performed to examine the relative risk of onset of CVD events among the quartiles. RESULTS: The mean follow-up duration was 5.7 years. Cases admitted for CVD events (heart failure, stroke, myocardial infarction) in the cohort were surveyed prospectively. The event free rate of the highest BNP quartile showed the lowest event free ratio (p &lt; 0.001). After adjustment for established CVD risk factors including glycosylated hemoglobin (HbA1c) values and estimated glomerular filtration rate (eGFR), the hazard ratio (HR) for CVD events increased significantly according to BNP quartile (p for trend &lt; 0.001), and the HR for the highest BNP quartile was significantly elevated compared to that for the lowest quartile (HR = 2.43, 95% CI; 1.44 - 4.09: Figure). When subjects with diabetes or reduced eGFR (&lt;60) were excluded, the association remained to be robust (Figure). CONCLUSION: Elevated plasma BNP levels are a useful biomarker for CVD risk stratification in subjects with albuminuria independent of classical risk factors including diabetes or renal dysfunction.

Sex-Specific Threshold Levels of Plasma B-Type Natriuretic Peptide for Prediction of Cardiovascular Event Risk in a Japanese Population Initially Free of Cardiovascular Disease

Elevated plasma B-type natriuretic peptide (BNP) levels have been reported to be related to a high risk for cardiovascular (CV) disease in the general population. However, there has been no accurate determination of the threshold levels of plasma BNP that indicate an increased potential for the development of general CV events (i.e., heart failure, stroke, and myocardial infarction) and the validity of these levels for predicting CV events compared to classic risk markers. To establish gender-specific thresholds of plasma BNP levels associated with increased risk for CV disease in the general population, baseline BNP levels were determined in community-dwelling adults (n = 13,209, mean age 62 ± 10 years,) and CV events in the cohort were captured prospectively. The cohort was divided by deciles of plasma BNP level in each gender. A Cox proportional-hazards model was used to determine the relative hazard ratios among the deciles. In addition, to compare the utility of plasma BNP to the Framingham 10-year risk score for predicting general CV events, receiver-operating characteristic analysis was performed. During follow-up, CV events were identified in 429 patients in the cohort. Compared to the reference decile level (first to fourth), the hazard ratio was significantly increased from the ninth decile in men (greater than approximately 37 pg/ml) and the highest decile in women (greater than approximately 55 pg/ml). The area under the curve generated on receiver-operating characteristic analysis of plasma BNP testing was comparable to that for the Framingham risk scoring system (0.67 vs 0.68 in men, 0.63 vs 0.68 in women; p = NS for both). In conclusion, within a community-based general population with no CV history, plasma BNP levels higher than defined thresholds show increased risk for general CV events, and the predictive ability for CV events occurring within several years may be comparable to that of an established long-standing risk score.

B-type natriuretic peptide at the early stage of univentricular circulation reflects inadequate adaptation to volume overload

BackgroundRecent studies showed that children with univentricular heart have elevated plasma B-type natriuretic peptide (BNP) levels prior to bidirectional cavopulmonary anastomosis (BDCPA). However, it remains to be established whether BNP levels reflect the degree of hemodynamic overload and relate to long-term outcome in univentricular circulation. MethodsFifty one consecutive children with functionally univentricular heart prior to BDCPA were studied. All patients underwent cardiac catheterization and BNP measurement. Ventricular end-systolic wall stress (ESWS) and end-diastolic wall stress (EDWS) were calculated from cardiac catheterization data. ResultsMedian age was 1.1years and 34% were female. Median BNP concentration was 90.4pg/ml. Patients with high BNP (≥100pg/ml) had higher pulmonary to systemic flow ratio (p=0.014), a greater end-diastolic volume (p=0.009), more severe atrioventricular valve regurgitation (p=0.02) and lower ventricular mass to end-diastolic volume ratio (p=0.006). BNP levels strongly related to EDWS (r=0.75, p<0.0001) and ESWS (r=0.63, p<0.0001). During median follow-up period of 3.2years, 15 patients died and one underwent heart transplantation for refractory heart failure. On multivariate Cox regression analysis, high BNP concentration was an independent predictor of death or transplantation (HR 3.05, CI: 1.06–8.83, p=0.04). ConclusionsHigh BNP concentration at the first palliative stage towards Fontan circulation reflects high wall stress due to high volume load and insufficient ventricular hypertrophy. Moreover, high BNP levels at this stage were independently related to long-term outcome. BNP may be used as a guide to identify patients with high workload due to inadequate adaptation to hemodynamic load, who are at high risk.

High Plasma Levels of the B-type Natriuretic Peptide in Patients Without Heart Failure: Is There Clinical Significance?

We report a case of a 19-year-old female with an elevated plasma B-type natriuretic peptide (BNP) level, but without evidence of heart failure (HF). She presented with non-specific chest pain and a high level of the B-type natriuretic peptide, despite having unremarkable findings on physical examination, laboratory analysis, electrocardiogram, echocardiogram, chest X-ray, chest computed tomography, whole body scan, and coronary angiography. We attribute this finding to a genetic variation in the synthesis and cleavage of the natriuretic peptides.

The Impact of B‐type Natriuretic Peptide, New York Heart Association Classification and Depression on Quality of Life in Nonhospitalized Heart Failure Patients

Healthcare providers should be concerned with improving the quality of life (QOL) of patients with heart failure (HF) because disease-specific QOL is linked to disease progression. The present study investigated the significance of elevated b-type natriuretic peptide (BNP), NYHA classification and depression to HF-related QOL to develop better management strategies. Outpatient subjects with left ventricular systolic dysfunction (n=108; mean age=64.9+/-12) completed the self-administered Minnesota Living with Heart Failure questionnaire and the Center for Epidemiologic Studies Depression Scale. Functional status was measured using the New York Heart Association Classification (NYHA) and BNP concentrations were measured in plasma samples. Multiregression analysis determined that plasma BNP levels did not contribute significantly to the total QOL score while depression (r=0.63, t ratio=7.43, P<.0001) and NHYA class (r=0.47, t ratio=3.31, P<.001) were significant contributors. NYHA III subjects exhibited worse depression scores (II 15+/-7 and III: 22+/-10, P<.001) and elevated plasma BNP (II: 2.0+/-0.5 and III: 2.4+/-0.6, P<.001). Low-cost psychological assessments are recommended to evaluate depression and suggest that those HF patients with NYHA III be closely monitored for depression and reduced QOL.

Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

B-type natriuretic peptide (BNP) is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH). Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease.