4879

NPPB

BNP;natriuretic peptide B;NPPB;natriuretic peptide B

brain type natriuretic peptide|gamma-brain natriuretic peptide|natriuretic peptide precursor B|natriuretic peptides B|natriuretic protein

1p36.2

protein-coding

Count: NPPB; 4879

STUDY OBJECTIVES: pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH. STUDY DESIGN: We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH. RESULTS: In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics. CONCLUSION: We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.

BACKGROUND: Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI). METHODS: Thirty-eight patients with CTEPH (55 +/- 15 years), and ten healthy controls (46 +/- 15 years) were studied. The BNP was determined by an immunoradiometric assay. RESULTS: The CTEPH patients had a mean pulmonary artery pressure of 49 +/- 13 mm Hg, cardiac index 2.1 +/- 0.7 l x min(-1) x m(-2), and pulmonary vascular resistance of 867 +/- 432 dynes x s x cm(-5). In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = -0.80) and ejection fraction (EF; r = -0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients. CONCLUSIONS: In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify "high risk" CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality.

OBJECTIVE: In congenital diaphragmatic hernia (CDH) the severity of pulmonary hypertension (PH) is considered, by several authors, determinant of clinical outcome. Plasmatic N-terminal-pro-B type natriuretic peptide (NT-proBNP) might be useful in diagnosis and management of PH in newborns, although its interest in CDH infants remains to be defined. Early NT-proBNP levels were assessed in CDH infants and correlated with cardiovascular echocardiographic parameters. PATIENTS AND METHODS: 28 newborns, CDH and age-matched controls were enrolled in a prospective study. Clinical condition, NT-proBNP plasmatic levels, echo parameters of PH and biventricular function were assessed at 24 h after delivery as well as survival outcome. RESULTS: Estimated mean pulmonary pressure and NT-proBNP were significantly higher in CDH than control infants. NT-proBNP significantly correlated with estimated pulmonary artery pressure, right ventricular Tei index, and tricuspid E/A ratio. Additionally, we found that CDH infants with NT-proBNP >11,500 pg/ml experienced a worse prognosis. CONCLUSIONS: We demonstrated that PH is associated with NT-proBNP elevation and diastolic impairment in CDH infants. Early elevations in NT-proBNP levels seem to alert for a subset of CDH infants with worse prognosis.CI - (c) 2007 S. Karger AG, Basel.

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

BACKGROUND: Cardiac involvement and pulmonary hypertension (PH) are life-threatening complications in sarcoidosis. OBJECTIVE: This study aimed to investigate the utility of plasma NT-proBNP in the assessment of these conditions in sarcoidosis patients. STUDY DESIGN AND METHODS: A prospective, observational study was performed on 150 consecutive Japanese sarcoidosis patients. Doppler echocardiography was performed in all subjects, and those who were successfully evaluated for PH status were included in the analysis. Cardiac sarcoidosis was diagnosed based on Japanese guidelines, and PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 35 mmHg. The diagnostic accuracy of NT-proBNP according to the presence of cardiac sarcoidosis and PH was assessed based on receiver-operator characteristic (ROC) curves. RESULTS: 130 subjects were successfully evaluated for PH status. Of these, 29 met the diagnostic criteria of cardiac sarcoidosis, and 21 were diagnosed with PH. Plasma NT-proBNP levels were significantly higher in patients with cardiac sarcoidosis (p < 0.0001). Stepwise regression analysis showed that presence of cardiac sarcoidosis, decreased ejection fraction and increased sPAP were all independently associated with higher plasma NT-proBNP levels. Plasma NT-proBNP showed good accuracy in identifying patients with cardiac sarcoidosis (area under the ROC curve; AURC = 0.913). However, even when patients with cardiac sarcoidosis were excluded, plasma NT-proBNP levels could not be used reliably to identify patients with PH (AURC = 0.681). CONCLUSION: In patients with sarcoidosis, plasma NT-proBNP levels are a useful biomarker to identify cardiac involvement, but not to identify PH.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-beta-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH). METHODS: GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein. RESULTS: GDF-15 expression was found to be increased in lung specimens from PAH patients, compared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein. CONCLUSIONS: GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients.

OBJECTIVES: B-type natriuretic peptide (BNP) and the amino-terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. DESIGN: We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years old. Two hundred sixty-three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. RESULTS: There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean systemic arterial pressure ratio (r= 0.40, P < .01; r= 0.45, P < .01; respectively), mean right atrial pressure (r= 0.48, P < .01; r= 0.48, P < .01), and tricuspid regurgitant velocity (r= 0.36, P < .01; r= 0.41, P < .01). BNP and NTproBNP are associated with 6-minute walk distance, mean pulmonary arterial pressure, mean pulmonary arterial pressure/mean systemic arterial pressure ratio, mean right atrial pressure, pulmonary vascular resistance index, and tricuspid regurgitant velocity when investigated longitudinally. On the average, a 1-unit increase in log BNP or NTproBNP was associated with 4.5 units x m(2) or 3.4 units x m(2) increase in pulmonary vascular resistance index, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r= 0.87, P < .01). CONCLUSION: In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross-sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time; therefore, NTproBNP can add additional information toward predicting these clinical measurements.CI - (c) 2012 Wiley Periodicals, Inc.