The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis.

PubMed

Rodseth, Reitze N; Biccard, Bruce M; Le Manach, Yannick; Sessler, Daniel I; Lurati Buse, Giovana A; Thabane, Lehana; Schutt, Robert C; Bolliger, Daniel; Cagini, Lucio; Cardinale, Daniela; Chong, Carol P W; Chu, Rong; Cnotliwy, Miłosław; Di Somma, Salvatore; Fahrner, René; Lim, Wen Kwang; Mahla, Elisabeth; Manikandan, Ramaswamy; Puma, Francesco; Pyun, Wook B; Radović, Milan; Rajagopalan, Sriram; Suttie, Stuart; Vanniyasingam, Thuvaraha; van Gaal, William J; Waliszek, Marek; Devereaux, P J

2014-01-21

The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone. Copyright © 2014 American College of Cardiology

Head-to-head comparison of B-type natriuretic peptide (BNP) and NT-proBNP in daily clinical practice.

PubMed

Mair, Johannes; Gerda, Falkensammer; Renate, Hiemetzberger; Ulmer, Hanno; Andrea, Griesmacher; Pachinger, Otmar

2008-02-29

B-type natriuretic peptide (BNP; Abbott Diagnostics) and N-terminal proBNP (NT-proBNP, Roche Diagnostics) were compared in consecutive samples of 458 patients (mean age 60 years+/-16 years; 159 female, 299 male) sent for NT-proBNP measurement to investigate influences on both markers. BNP and NT-proBNP showed a close correlation with each other (r=0.89, p<0.0001). Using age- and gender-adjusted upper reference values the inter-rater agreement of both parameters was satisfactory (83%, Cohen's kappa coefficient=0.7). The combination of normal BNP and elevated NT-proBNP was significantly more frequent than vice versa (61 vs. 16 patients), and a calculated glomerular filtration rate<60 ml/min/1.73 m(2) was found in 39% of these patients. Multiple linear regression analysis revealed a significant influence of a reduced ejection fraction (<50%), renal dysfunction (calculated glomerular filtration rate<60 ml/min/1.73 m(2)), anemia, hypertension, age, and gender on both BNP and NT-proBNP. In conclusion, despite a close correlation and a satisfactory agreement between both markers in classification, frequent discrepancies in individual patients demonstrate that both markers are clinically not completely equivalent.

Interpretation of B-type natriuretic peptides in the era of angiotensin receptor-neprilysin inhibitors.

PubMed

Bettencourt, Paulo; Fonseca, Cândida; Franco, Fátima; Andrade, Aurora; Brito, Dulce

2017-12-01

Assessment of serum levels of natriuretic peptides, especially the amino-terminal portion (NT-proBNP) and the carboxy-terminal portion (BNP) of pro-B-type natriuretic peptide, has had a highly significant clinical impact on the diagnosis and prognostic stratification of patients with heart failure (HF). They are now an instrument with recognized value in this context and several studies have demonstrated their value in tailoring therapy for these patients. Following the recent advent of angiotensin receptor-neprilysin inhibitors (ARNIs), there is a need to review how these two biomarkers are interpreted in HF. The use of ARNIs is associated with a reduction in NT-proBNP but an increase in BNP levels. The authors of this concise article review the interpretation of natriuretic peptide levels in the light of the most recent evidence. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients.

PubMed

Meyer, Brigitte; Huelsmann, Martin; Wexberg, Paul; Delle Karth, Georg; Berger, Rudolf; Moertl, Deddo; Szekeres, Thomas; Pacher, Richard; Heinz, Gottfried

2007-10-01

Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. Prospective, observational study. A tertiary intensive care unit in a university hospital. A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). None. Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not

Release kinetics of N-terminal pro-B-type natriuretic peptide in a clinical model of acute myocardial infarction.

PubMed

Liebetrau, Christoph; Gaede, Luise; Dörr, Oliver; Troidl, Christian; Voss, Sandra; Hoffmann, Jedrzej; Paszko, Agata; Weber, Michael; Rolf, Andreas; Hamm, Christian; Nef, Holger; Möllmann, Helge

2014-02-15

N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP) is elevated in patients with acute myocardial infarction (AMI) thus providing both diagnostic information and prognostic information. The aim of the present study was to determine the time course of NT-proBNP release in patients undergoing transcoronary ablation of septal hypertrophy (TASH) a procedure mimicking AMI. We analyzed the release kinetics of NT-proBNP in 18 consecutive patients with hypertrophic obstructive cardiomyopathy undergoing TASH. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24h after TASH. NT-proBNP concentrations showed a continuous increase during the first 75 min with a significant percent change compared to baseline value already 15 min after TASH (105.6% [IQR 102.2-112.7]; P<0.001). All patients had a significant increase of NT-proBNP at 45 min (range of percent increase [min-max]: 103.5-137.2%; range of absolute increase [min-max]: 23.5-304.0 ng/L). NT-proBNP concentrations decreased below the baseline value until the 8th h after initiation of myocardial infarction. NT-proBNP concentration increases immediately after induction of myocardial infarction proving early evidence of myocardial injury despite the decrease of the left ventricular wall stress due to the TASH related reduction of the left ventricular outflow gradient. Copyright © 2013 Elsevier B.V. All rights reserved.

B-type natriuretic peptide and echocardiography reflect volume changes during pregnancy

PubMed Central

Burlingame, Janet M.; Yamasato, Kelly; Ahn, Hyeong Jun; Seto, Todd; Tang, W. H. Wilson

2017-01-01

Objective To evaluate B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac structure and function in normal women through pregnancy and the postpartum. Methods In this prospective observational study, we obtained serial transthoracic echocardiograms, BNP, and NT-proBNP at seven intervals from 6 weeks’ gestation through 12 months postpartum. Women with hypertension or cardiac disease were excluded. Using 6–12 months postpartum as reference for non-pregnant levels, echocardiogram measurements and BNP/NT-proBNP were compared over time using linear mixed models with Tukey-Kramer adjustment for multiple comparisons. Results Of 116 patients, data was available for 78–114 healthy pregnant or postpartum women within each time interval, and 102 patients provided data for ≥ 4 intervals. Compared to 6–12 months postpartum, BNP and NT-proBNP remained stable through pregnancy and delivery, increased within 48 h postpartum (P < 0.0001), then returned to baseline. Left ventricular volume increased within 48 h postpartum (P = 0.021) while left atrial volume increased at 18–24 weeks (P = 0.0002), 30–36 weeks (P < 0.0001) and within 48 h postpartum (P = 0.002). The transmittal early/late diastolic velocity (E/A) ratio, transmittal early/peak mitral annulus diastolic velocity (E/E′) ratio, isovolumic relaxation times, and mitral valve deceleration times were similar within 48 h and 6–12 months postpartum. Conclusion In normal women, BNP/NT-proBNP, left atrial, and left ventricular volumes increase within 48 h postpartum without indications of altered diastolic function. PMID:28195551

N-Terminal Pro-B-Type Natriuretic Peptide Is Related to Retinal Microvascular Damage: The Rotterdam Study.

PubMed

Mutlu, Unal; Ikram, M Arfan; Hofman, Albert; de Jong, Paulus T V M; Klaver, Caroline C W; Ikram, M Kamran

2016-08-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage. From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio [95% confidence interval] per SD increase in natural log-transformed NT-proBNP: 1.14 [1.03-1.27]). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP: -0.89 µm [-1.54 to -0.24]). This association remained unchanged after excluding participants with retinopathy signs. In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease. © 2016 American Heart Association, Inc.

Impact of Modifiable Risk Factors on B-type Natriuretic Peptide and Cardiac Troponin T Concentrations

PubMed Central

Srivastava, Pratyaksh K.; Pradhan, Aruna D.; Cook, Nancy R.; Ridker, Paul M.; Everett, Brendan M.

2015-01-01

Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the amino-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with detectable hsTnT (>3 ng/L) or with NT-proBNP in the highest quartile (≥127.3 ng/L). The median (Q1-Q3) NT-proBNP of the cohort was 68.8 (40.3–127.3), and 30.8% (160/519) of the cohort had detectable circulating hsTnT. In adjusted models, women who drank 1–6 drinks per week had lower odds of having a detectable hsTnT (0.58, 95% CI: 0.34–0.96) and lower odds of having an elevated NT-proBNP (OR 0.55, 95% CI 0.32–0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, two cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium. PMID:26739393

N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population.

PubMed

Zonneveld, Hazel I; Ikram, M Arfan; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Krestin, Gabriel P; Franco, Oscar H; Vernooij, Meike W

2017-04-01

Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter

Pathophysiology, prognostic significance and clinical utility of B-type natriuretic peptide in acute coronary syndromes.

PubMed

Wiviott, Stephen D; de Lemos, James A; Morrow, David A

2004-08-16

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

N-terminal pro B-type natriuretic peptide in the early evaluation of suspected acute myocardial infarction.

PubMed

Haaf, Philip; Balmelli, Cathrin; Reichlin, Tobias; Twerenbold, Raphael; Reiter, Miriam; Meissner, Julia; Schaub, Nora; Stelzig, Claudia; Freese, Michael; Paniz, Patricia; Meune, Christophe; Drexler, Beatrice; Freidank, Heike; Winkler, Katrin; Hochholzer, Willibald; Mueller, Christian

2011-08-01

Myocardial ischemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release. As ischemia precedes necrosis in acute myocardial infarction, we hypothesized that NT-proBNP might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction. In a prospective multicenter study, NT-proBNP was measured at presentation in 658 consecutive patients with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long term regarding mortality. Acute myocardial infarction was the adjudicated final diagnosis in 117 patients (18%). NT-proBNP levels at presentation were significantly higher in acute myocardial infarction as compared with patients with other final diagnoses (median 886 pg/mL vs 135 pg/mL, P <.001). The diagnostic accuracy of NT-proBNP for acute myocardial infarction as quantified by the area under the receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval [CI], 0.75-0.83). When added to cardiac troponin T, NT-proBNP significantly increased the AUC from 0.89 (95% CI, 0.84-0.93) to 0.91 (95% CI, 0.88-0.94; P=.033). Cumulative 24-month mortality rates were 0% in the first, 1.3% in the second, 8.3% in the third, and 23.3% in the fourth quartile of NT-proBNP (P <.001). NT-proBNP (AUC 0.85, 95% CI, 0.81-0.89) predicted all-cause mortality independently of and more accurately than both cardiac troponin T (AUC 0.66, 95% CI, 0.58-0.74; P <.001) and the Thrombolysis in Myocardial Infarction risk score (AUC 0.79, 95% CI, 0.74-0.84; P <.001). Net reclassification improvement (Thrombolysis in Myocardial Infarction vs additionally NT-proBNP) was 0.188 (P <.009), and integrated discrimination improvement was 0.100 (P <.001). Use of NT-proBNP improves the early diagnosis and risk stratification of patients with suspected acute myocardial infarction. Copyright © 2011 Elsevier Inc. All rights reserved.

Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).

PubMed

Koller, K J; Lowe, D G; Bennett, G L; Minamino, N; Kangawa, K; Matsuo, H; Goeddel, D V

1991-04-05

The natriuretic peptides are hormones that can stimulate natriuretic, diuretic, and vasorelaxant activity in vivo, presumably through the activation of two known cell surface receptor guanylyl cyclases (ANPR-A and ANPR-B). Although atrial natriuretic peptide (ANP) and, to a lesser extent, brain natriuretic peptide (BNP) are efficient activators of the ANPR-A guanylyl cyclase, neither hormone can significantly stimulate ANPR-B. A member of this hormone family, C-type natriuretic peptide (CNP), potently and selectively activated the human ANPR-B guanylyl cyclase. CNP does not increase guanosine 3',5'-monophosphate accumulation in cells expressing human ANPR-A. The affinity of CNP for ANPR-B is 50- or 500-fold higher than ANP or BNP, respectively. This ligand-receptor pair may be involved in the regulation of fluid homeostasis by the central nervous system.

Evidence for functional heterogeneity of circulating B-type natriuretic peptide.

PubMed

Liang, Faquan; O'Rear, Jessica; Schellenberger, Ute; Tai, Lungkuo; Lasecki, Michael; Schreiner, George F; Apple, Fred S; Maisel, Alan S; Pollitt, N Stephen; Protter, Andrew A

2007-03-13

These studies describe molecular forms of circulating B-type natriuretic peptide (BNP) as well as their biological activity. Increased circulating levels of immunoreactive BNP correlate with the severity of heart failure and are considered a sensitive biomarker. However, little is known about the molecular forms of circulating BNP and their biological activity. Western blot analysis was used to characterize immunoreactive BNP species in heart failure plasma. Recombinant proBNP was assessed for reactivity in commercially available BNP assays and cell activity by cyclic guanosine monophosphate production in vascular cells. Heart failure plasma contained both low- (LMW-BNP) and high-molecular-weight (HMW-BNP) forms. The LMW-BNP migrated similarly to a 32-amino acid BNP standard, whereas HMW-BNP, when deglycosylated, was similar to deglycosylated recombinant proBNP. Recombinant proBNP and BNP were equally recognized by the Triage BNP assay (Biosite, San Diego, California). Furthermore, recombinant proBNP and BNP were both recognized by the Advia Centaur BNP test (Bayer Diagnostics, Tarrytown, New York), but only recombinant proBNP was recognized by the Elecsys NTproBNP assay (Roche Diagnostics, Indianapolis, Indiana). Recombinant proBNP exerted significantly less biological activity than BNP on human endothelial and vascular smooth muscle cells. Comparison of effective concentration (50%) values indicates that proBNP is 6- to 8-fold less potent than BNP in these human cells. This study demonstrates that proBNP, constituting a substantial portion of immunoreactive BNP in heart failure plasma, possesses significantly lower biological activity than the processed 32-amino acid hormone. These results implicate a discordance in heart failure between the high circulating levels of immunoreactive BNP and hormone activity, suggesting that some patients may be in a state of natriuretic peptide deficiency.

N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

PubMed

Dionne, Audrey; Meloche-Dumas, Léamarie; Desjardins, Laurent; Turgeon, Jean; Saint-Cyr, Claire; Autmizguine, Julie; Spigelblatt, Linda; Fournier, Anne; Dahdah, Nagib

2017-03-01

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm. © 2016 Japan Pediatric Society.

Cocoa flavanols reduce N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure.

PubMed

De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G; Khan, Noorafza Q; Butler, Jane; Johnston, Atholl; Rothman, Martin T; Corder, Roger

2016-06-01

Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an index of improved cardiac function. Thirty-two patients with chronic HF, stable on guideline-directed medical therapy, were randomized to consume 50 g/day of high-flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low-flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty-four patients completed the study. After 4 weeks of HFDC, NT-proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (-44 ± 69%), LFDC (-33 ± 72%), and follow-up (-41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (-6.7 ± 10.1 mmHg). Reductions in blood pressure and NT-proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF.

B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis.

PubMed

Llombart, Víctor; Antolin-Fontes, Albert; Bustamante, Alejandro; Giralt, Dolors; Rost, Natalia S; Furie, Karen; Shibazaki, Kensaku; Biteker, Murat; Castillo, José; Rodríguez-Yáñez, Manuel; Fonseca, Ana Catarina; Watanabe, Tetsu; Purroy, Francisco; Zhixin, Wu; Etgen, Thorleif; Hosomi, Naohisa; Jafarian Kerman, Scott Reza; Sharma, Jagdish C; Knauer, Carolin; Santamarina, Estevo; Giannakoulas, George; García-Berrocoso, Teresa; Montaner, Joan

2015-05-01

Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis. We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index. From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up. Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification. © 2015 American Heart Association, Inc.

N-Terminal Pro-B Type Natriuretic Peptide is Associated with Mild Cognitive Impairment in the General Population.

PubMed

Kara, Kaffer; Mahabadi, Amir Abbas; Weimar, Christian; Winkler, Angela; Neumann, Till; Kälsch, Hagen; Dragano, Nico; Moebus, Susanne; Erbel, Raimund; Jöckel, Karl-Heinz; Jokisch, Martha

2017-01-01

N-terminal pro-B type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and is linked with silent cardiac diseases. While associations of cognitive impairment with manifest cardiovascular diseases are established, data on whether subclinical elevation of NT-proBNP levels below clinically established threshold of heart failure is related with cognitive functioning, especially mild cognitive impairment (MCI), is rare. Aim of the present study was to investigate the cross-sectional association of NT-proBNP levels and MCI in a population-based study sample without heart failure. We used data from the second examination of the population based Heinz-Nixdorf-Recall-Study. Subjects with overt coronary heart disease and subjects with NT-proBNP levels indicating potential heart failure (NT-proBNP≥300 pg/ml) were excluded from this analysis. Participants performed a validated brief cognitive assessment and were classified either as MCI [subtypes: amnestic-MCI (aMCI), non-amnestic-MCI (naMCI)], or cognitively-normal. We included 419 participants with MCI (63.1±7.4 y; 47% men; aMCI n = 209; naMCI n = 210) and 1,206 cognitively normal participants (62.42±7.1 y; 48% men). NT-proBNP-levels≥125 pg/ml compared to <125 pg/ml were associated with MCI in fully adjusted models (OR 1.65 (1.23;2.23) in the total sample, 1.73 (1.09;2.74) in men and 1.63(1.10;2.41) in women). For aMCI, the fully adjusted OR was 1.53 (1.04;2.25) and for naMCI, the fully adjusted OR was 1.34 (1.09; 166) in the total sample. Within normal ranges and without manifest heart failure, higher NT-proBNPlevels are associated with MCI and both MCI subtypes independent of traditional cardiovascular risk factors and sociodemographic parameters.

Prognostic value of B-Type natriuretic peptides in patients with stable coronary artery disease: the PEACE Trial.

PubMed

Omland, Torbjørn; Sabatine, Marc S; Jablonski, Kathleen A; Rice, Madeline Murguia; Hsia, Judith; Wergeland, Ragnhild; Landaas, Sverre; Rouleau, Jean L; Domanski, Michael J; Hall, Christian; Pfeffer, Marc A; Braunwald, Eugene

2007-07-17

The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition. The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear. Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke. The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations. In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic

The additive value of N-terminal pro-B-type natriuretic peptide testing at the emergency department in patients with acute dyspnoea.

PubMed

van der Burg-de Graauw, N; Cobbaert, C M; Middelhoff, C J F M; Bantje, T A; van Guldener, C

2009-05-01

B-type natriuretic peptide (BNP) and its inactive counterpart NT-proBNP can help to identify or rule out heart failure in patients presenting with acute dyspnoea. It is not well known whether measurement of these peptides can be omitted in certain patient groups. We conducted a prospective observational study of 221 patients presenting with acute dyspnoea at the emergency department. The attending physicians estimated the probability of heart failure by clinical judgement. NT-proBNP was measured, but not reported. An independent panel made a final diagnosis of all available data including NT-proBNP level and judged whether and how NT-proBNP would have altered patient management. NT-proBNP levels were highest in patients with heart failure, alone or in combination with pulmonary failure. Additive value of NT-proBNP was present in 40 of 221 (18%) of the patients, and it mostly indicated that a more intensive treatment for heart failure would have been needed. Clinical judgement was an independent predictor of additive value of NT-proBNP with a maximum at a clinical probability of heart failure of 36%. NT-proBNP measurement has additive value in a substantial number of patients presenting with acute dyspnoea, but can possibly be omitted in patients with a clinical probability of heart failure of >70%.

N-Terminal Pro-B-type Natriuretic Peptide Is Useful to Predict Cardiac Complications Following Lung Resection Surgery

PubMed Central

Lee, Chang Young; Bae, Mi Kyung; Lee, Jin Gu; Kim, Kwan-Wook; Park, In Kyu

2011-01-01

Background Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion An elevated preoperative NT-proBNP level is identified as an

High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated with Reduced Heart Rate Variability in Acute Myocardial Infarction

PubMed Central

Lorgis, Luc; Moreau, Daniel; Mock, Laurent; Daumas, Bernadette; Potard, Daniel; Touzery, Claude; Cottin, Yves; Zeller, Marianne

2012-01-01

Aim We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI). Methods and Results The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders. Conclusions In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI. PMID:23071500

In-hospital and long-term outcomes of congestive heart failure: Predictive value of B-type and amino-terminal pro-B-type natriuretic peptides and their ratio.

PubMed

Dai, Yuxiang; Yang, Jun; Takagi, Atsutoshi; Konishi, Hakuoh; Miyazaki, Tetsuro; Masuda, Hiroshi; Shimada, Kazunori; Miyauchi, Katsumi; Daida, Hiroyuki

2017-08-01

Relative changes in B-type natriuretic peptide (BNP) and amino terminal pro-BNP (NT-proBNP) levels may help to assess the risk of congestive heart failure (CHF). However, whether these levels at the time of admission enable the prediction of outcomes with acute exacerbation remains unknown. The current study determined the abilities of BNP, NT-proBNP and their ratio to predict in-hospital and long-term outcomes of patients with CHF. Patients who were admitted to the cardiac care unit of Juntendo University Hospital (Tokyo, Japan) with acute CHF onset were consecutively enrolled into the present observational study. Serum levels of BNP and NT-proBNP were immediately measured on admission, and other biomarkers and clinical data were also investigated. Of 195 enrolled patients, 16 (8.2%) succumbed to CHF in hospital and 124 (69.3%) reached the endpoint of mortality or readmission following a median follow-up of 14 months. Multiple linear regression analysis revealed body mass index, low density lipoprotein cholesterol, hemoglobin, estimated glomerular filtration rate and C-reactive protein as independent predictors of the NT-proBNP/BNP ratio. BNP, NT-proBNP and their ratio were significantly higher among those who succumbed to CHF than in those who remained alive in hospital (P<0.05). Logistic regression analysis indicated that the ratio was an independent predictor for in-hospital mortality and long-term outcomes. In conclusion, the ratio of NT-proBNP to BNP more effectively predicts in-hospital outcomes than either factor alone and it may also help to predict outcomes among patients with acute exacerbation of HF.

A glycosylated form of the human cardiac hormone pro B-type natriuretic peptide is an intrinsically unstructured monomeric protein.

PubMed

Crimmins, Dan L; Kao, Jeffrey L-F

2008-07-01

The N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) and proBNP are used as gold standard clinical markers of myocardial dysfunction such as cardiac hypertrophy and left ventricle heart failure. The actual circulating molecular forms of these peptides have been the subject of intense investigation particularly since these analytes are measured in clinical assays. Conflicting data has been reported and no firm consensus on the exact nature of the molecular species exists. Because these clinical assays are immunoassay-based, specific epitopes are detected. It is conceivable then that certain epitopes may be masked and therefore unavailable for antibody binding, thus the importance of determining the nature of the circulating molecular forms of these analytes. This situation is an unavoidable Achilles' heel of immunoassays in general. A recombinant O-linked glycosylated form of proBNP has been show to mimic some of the properties of extracted plasma from a heart failure patient. In particular the recombinant and native material co-migrated as diffuse Western-immunostained bands on SDS-PAGE and each band collapsed to an apparent homogeneous band following deglycosylation. Thus, glycosylated-proBNP may be one such circulating form. Here we provide extensive physiochemical characterization for this O-linked protein and compare these results to other described circulating species, non-glycosylated-proBNP and NT-proBNP. It will be shown that glycosylation has no influence on the secondary and quaternary structure of proBNP. In fact, at moderate concentration in benign physiological neutral pH buffer, all three likely circulating species are essentially devoid of major secondary structure, i.e., are intrinsically unstructured proteins (IUPs). Furthermore, all three proteins exist as monomers in solution. These results may have important implications in the design of NT-proBNP/BNP immunoassays.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

PubMed

McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

2012-10-01

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus.

PubMed

Wolsk, Emil; Claggett, Brian; Pfeffer, Marc A; Diaz, Rafael; Dickstein, Kenneth; Gerstein, Hertzel C; Lawson, Francesca C; Lewis, Eldrin F; Maggioni, Aldo P; McMurray, John J V; Probstfield, Jeffrey L; Riddle, Matthew C; Solomon, Scott D; Tardif, Jean-Claude; Køber, Lars

2017-05-29

Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus. Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow-up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT-proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT-proBNP to best risk models. Overall, BNP and NT-proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77-0.82, P <0.001), cardiovascular death (0.77-0.83, P <0.001), and heart failure (0.84-0.87, P <0.001). BNP or NT-proBNP alone predicted death as well as all other variables combined (0.77 versus 0.77). In patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT-proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cardiac Troponin I and Amino-Terminal Pro B-Type Natriuretic Peptide in Dogs With Stable Chronic Kidney Disease.

PubMed

Pelander, L; Häggström, J; Ley, C J; Ljungvall, I

2017-05-01

Increased concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results. The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT-proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs. Fifty student-, staff-, and client-owned dogs were included. Twenty-three of the dogs were healthy and 27 were diagnosed with CKD. In this cross-sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR. Plasma volume factor and PCV were independently associated with NT-proBNP (Radj2 = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI (Radj2 = 0.50; P < .0001). Neither NT-proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT-proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot.

PubMed

Eindhoven, Jannet A; Menting, Myrthe E; van den Bosch, Annemien E; Cuypers, Judith A A E; Ruys, Titia P E; Witsenburg, Maarten; McGhie, Jackie S; Boersma, Eric; Roos-Hesselink, Jolien W

2014-07-01

Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity. NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7-33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = -0.195, p = 0.022), but more strongly with LV systolic dysfunction (r=-0.367, p<0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found. NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Sanchez, O.A.; Duprez, D.A.; Bahrami, H.; Peralta, C.A.; Daniels, L.B.; Lima, J.A.; Maisel, A.; Folsom, A.R.; Jacobs, D.R.

2016-01-01

Aims This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. Methods lasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA).ΔNT-proBNP was calculated as NT-proBNPvisit3 − NT-proBNPbaseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n = 3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1) <54.4 pg/mL; (2) 54.4–85.9 pg/mL; and (3) 86–54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) −6.2 (−131–11.7) pg/mL; (2) 19.8 (11.8–30.1) pg/mL; (3) 44.0 (30.2–67.9) pg/mL; and (4) 111.2 (68.0–3749.9) pg/mL. Results The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P = 0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. Conclusion This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a ‘physiological range’ of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP. PMID:26047677

SES, Heart Failure, and N-terminal Pro-b-type Natriuretic Peptide: The Atherosclerosis Risk in Communities Study.

PubMed

Vart, Priya; Matsushita, Kunihiro; Rawlings, Andreea M; Selvin, Elizabeth; Crews, Deidra C; Ndumele, Chiadi E; Ballantyne, Christie M; Heiss, Gerardo; Kucharska-Newton, Anna; Szklo, Moyses; Coresh, Josef

2018-02-01

Compared with coronary heart disease and stroke, the association between SES and the risk of heart failure is less well understood. In 12,646 participants of the Atherosclerosis Risk in Communities Study cohort free of heart failure history at baseline (1987-1989), the association of income, educational attainment, and area deprivation index with subsequent heart failure-related hospitalization or death was examined while accounting for cardiovascular disease risk factors and healthcare access. Because SES may affect threshold of identifying heart failure and admitting for heart failure management, secondarily the association between SES and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, a marker reflecting cardiac overload, was investigated. Analysis was conducted in 2016. During a median follow-up of 24.3 years, a total of 2,249 participants developed heart failure. In a demographically adjusted model, the lowest-SES group had 2.2- to 2.5-fold higher risk of heart failure compared with the highest SES group for income, education, and area deprivation. With further adjustment for time-varying cardiovascular disease risk factors and healthcare access, these associations were attenuated but remained statistically significant (e.g., hazard ratio=1.92, 95% CI=1.69, 2.19 for the lowest versus highest income), with no racial interaction (p>0.05 for all SES measures). Similarly, compared with high SES, low SES was associated with both higher baseline level of NT-proBNP in a multivariable adjusted model (15% higher, p<0.001) and increase over time (~1% greater per year, p=0.023). SES was associated with clinical heart failure as well as NT-proBNP levels inversely and independently of traditional cardiovascular disease factors and healthcare access. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

PubMed Central

Zheng, Li-hui; Wu, Ling-min; Yao, Yan; Chen, Wen-sheng; Bao, Jing-ru; Huang, Wen; Shi, Rui; Zhang, Kui-jun; Zhang, Shu

2014-01-01

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients. PMID:25144363

Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery.

PubMed

Goei, Dustin; van Kuijk, Jan-Peter; Flu, Willem-Jan; Hoeks, Sanne E; Chonchol, Michel; Verhagen, Hence J M; Bax, Jeroen J; Poldermans, Don

2011-02-15

Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels improve preoperative cardiac risk stratification in vascular surgery patients. However, single preoperative measurements of NT-pro-BNP cannot take into account the hemodynamic stress caused by anesthesia and surgery. Therefore, the aim of the present study was to assess the incremental predictive value of changes in NT-pro-BNP during the perioperative period for long-term cardiac mortality. Detailed cardiac histories, rest left ventricular echocardiography, and NT-pro-BNP levels were obtained in 144 patients before vascular surgery and before discharge. The study end point was the occurrence of cardiovascular death during a median follow-up period of 13 months (interquartile range 5 to 20). Preoperatively, the median NT-pro-BNP level in the study population was 314 pg/ml (interquartile range 136 to 1,351), which increased to a median level of 1,505 pg/ml (interquartile range 404 to 6,453) before discharge. During the follow-up period, 29 patients (20%) died, 27 (93%) from cardiovascular causes. The median difference in NT-pro-BNP in the survivors was 665 pg/ml, compared to 5,336 pg/ml in the patients who died (p = 0.01). Multivariate Cox regression analyses, adjusted for cardiac history and cardiovascular risk factors (age, angina pectoris, myocardial infarction, stroke, diabetes mellitus, renal dysfunction, body mass index, type of surgery and the left ventricular ejection fraction), demonstrated that the difference in NT-pro-BNP level between pre- and postoperative measurement was the strongest independent predictor of cardiac outcome (hazard ratio 3.06, 95% confidence interval 1.36 to 6.91). In conclusion, the change in NT-pro-BNP, indicated by repeated measurements before surgery and before discharge is the strongest predictor of cardiac outcomes in patients who undergo vascular surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

Diverse molecular forms of plasma B-type natriuretic peptide in heart failure.

PubMed

Nishikimi, Toshio; Minamino, Naoto; Nakao, Kazuwa

2011-06-01

Recent studies have shown that not only plasma B-type natriuretic peptide (BNP)-32, but also plasma proBNP-108 is increased in heart failure (HF), and that the current BNP-32 assay kit crossreacts with proBNP-108. It also was shown that both BNP-32 and proBNP-108 were higher in HF than in normal. The proBNP-108/total BNP (BNP-32 + proBNP-108) ratio was widely distributed and patients with HF with ventricular overload had higher proBNP-108/total BNP ratio than HF patients with atrial overload. Consistent with this finding, proBNP-108 was the major molecular form in ventricular tissue, and BNP-32 was the major molecular form in atrial tissue. In addition, proBNP-108 was the major molecular form of BNP in pericardial fluid. The proBNP-108/total BNP ratio increased with deterioration of HF and decreased with improvement of HF. Thus, not only BNP-32, but also proBNP-108 is increased in HF and the proBNP-108/total BNP ratio also rises in association with pathophysiological conditions such as ventricular overload. A new hypothesis that O-glycosylation at Thr71 in a region close to the cleavage site impairs proBNP-108 processing was proposed. In the future, the precise mechanism of increased proBNP-108 in HF should be elucidated.

Association of N-Terminal Pro B-Type Natriuretic Peptide With Blood Pressure and Pulse Pressure in Elderly People　- A Cross-Sectional Population Study.

PubMed

Sasaki, Nobuo; Yamamoto, Hideya; Ozono, Ryoji; Fujiwara, Saeko; Kihara, Yasuki

2018-05-23

N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.Methods and Results:The present cross-sectional study involved 6,529 participants, aged ≥70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those ≥125 pg/mL. Subjects were divided into five groups based on PP (<50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT-proBNP. The odds ratios for high NT-proBNP concentrations in the PP ≥80 and ≥70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia. The results suggest that NT-proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD.

N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes.

PubMed

Heeschen, Christopher; Hamm, Christian W; Mitrovic, Veselin; Lantelme, Nicte-Ha; White, Harvey D

2004-11-16

Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date. NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non-ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels >250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P<0.001). In troponin T-negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P<0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T-positive patients (9.8%; P=0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; -24%; 72 hours, -49%; both P<0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (< or =250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P<0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to >250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P<0.001). Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more

N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

PubMed

Potgieter, Danielle; Simmers, Dale; Ryan, Lisa; Biccard, Bruce M; Lurati-Buse, Giovanna A; Cardinale, Daniela M; Chong, Carol P W; Cnotliwy, Miloslaw; Farzi, Sylvia I; Jankovic, Radmilo J; Lim, Wen Kwang; Mahla, Elisabeth; Manikandan, Ramaswamy; Oscarsson, Anna; Phy, Michael P; Rajagopalan, Sriram; Van Gaal, William J; Waliszek, Marek; Rodseth, Reitze N

2015-08-01

N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Prognostic value of N-terminal pro-B-type natriuretic peptide in patients with acute coronary syndromes undergoing left main percutaneous coronary intervention.

PubMed

Jaberg, Laurenz; Toggweiler, Stefan; Puck, Marietta; Frank, Michelle; Rufibach, Kaspar; Lüscher, Thomas F; Corti, Roberto

2011-01-01

Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality and natriuretic peptides such as N-terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in patients with acute coronary syndromes. The present study looked at the prognostic value of NT-proBNP in these patients. We studied all consecutive patients undergoing acute LM coronary artery percutaneous coronary intervention between January 2005 and December 2008 in whom NT-proBNP was measured (n=71). We analyzed the clinical characteristics and the short- and long-term outcomes in relation to NT-proBNP level at admission. Median NT-proBNP was 1,364 ng/L, ranging from 46 to 70,000 ng/L. NT-proBNP was elevated in 63 (89%) patients and was ≥1,000ng/L in 42 (59%). Log NT-proBNP (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.55-7.97, P=0.003) and left ventricular ejection fraction (HR 0.95, 95%CI 0.91-0.99, P=0.007) were predictors for all-cause mortality. Log NT-proBNP was the only independent significant predictor of cardiovascular mortality. In-hospital mortality was 0% for patients with NT-proBNP <1,000, but 17% for those with NT-proBNP ≥1,000 (P=0.036). NT-proBNP is a strong predictor of outcome in patients undergoing acute LM coronary artery stenting. Mortality in such patients is high, but those with NT-proBNP < 1,000ng/L may have a favorable short- and long-term prognosis. Further research, including a larger patient population, is needed to determine the optimal cut-off value for NT-proBNP in patients undergoing acute LM coronary artery intervention.

B-type natriuretic peptides and mortality after stroke

PubMed Central

García-Berrocoso, Teresa; Giralt, Dolors; Bustamante, Alejandro; Etgen, Thorleif; Jensen, Jesper K.; Sharma, Jagdish C.; Shibazaki, Kensaku; Saritas, Ayhan; Chen, Xingyong; Whiteley, William N.

2013-01-01

Objective: To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information. Methods: Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes. Results: Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10–406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32–4.01 for BNP; and odds ratio 2.63, 95% CI 1.75–3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality. Conclusion: BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP/NT-pro

Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment

PubMed Central

Node, Koichi; Inoue, Teruo; Boyko, Valentin; Goldberg, Ilan; Fisman, Enrique Z; Adler, Yehuda; Schwammenthal, Ehud; Matas, Zipora; Behar, Solomon; Tenenbaum, Alexander

2009-01-01

Background The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. Methods Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. Results During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). Conclusion Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment. PMID:19173749

Association between N-terminal proB-type Natriuretic Peptide and Depressive Symptoms in Patients with Acute Myocardial Infarction

PubMed Central

Ren, Yan; Jia, Jiao; Sa, Jian; Qiu, Li-Xia; Cui, Yue-Hua; Zhang, Yue-An; Yang, Hong; Liu, Gui-Fen

2017-01-01

Background: While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI), the relationship between them remains largely unexplored. We examined the association between depressive symptoms and biomarkers in patients with AMI. Methods: We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014. The levels of depression, N-terminal proB-type natriuretic peptide (NT-proBNP), and troponin I (TnI) were measured at baseline. The patients were divided into two groups: those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score. Baseline comparisons between two groups were made using Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical variables, and Wilcoxon test for variables in skewed distribution. Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables. Results: Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5, 2474.0] vs. 384.0 [133.0, 990.0], Z = −2.470, P = 0.013). Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] = 2.348, 95% CI: 1.344 to 4.103, P = 0.003) and higher body mass index (OR = 1.169, 95% confidence interval [CI]: 1.016 to 1.345, P = 0.029). The total SDS score was associated with the NT-proBNP level (β = 0.327, 95% CI: 1.674 to 6.119, P = 0.001) after multivariable adjustment. In particular, NT-proBNP was associated with three of the depressive dimensions, including core depression (β = 0.299, 95% CI: 0.551 to 2.428, P = 0.002), cognitive depression (β = 0.320, 95% CI: 0.476 to 1.811, P = 0.001), and somatic depression (β = 0.333, 95% CI: 0.240 to 0.847, P = 0.001). Neither the

Increased serum N-terminal pro-B-type natriuretic peptide levels in patients with medial arterial calcification and poorly compressible leg arteries.

PubMed

Jouni, Hayan; Rodeheffer, Richard J; Kullo, Iftikhar J

2011-01-01

To determine whether serum levels of N-terminal (NT) pro-B-type natriuretic peptide (pro-BNP) are higher in patients with poorly compressible arteries (PCA) than in patients with peripheral artery disease (PAD) and control subjects without PCA or PAD. Medial arterial calcification in the lower extremities results in PCA and may be associated with increased arterial stiffness and hemodynamic/myocardial stress. PCA was defined as having an ankle-brachial index >1.4 or an ankle blood pressure >255 mm Hg, whereas PAD was defined as having an ankle-brachial index ≤0.9. Study participants with PCA (n=100; aged 71±10 years; 70% men) and age- and sex-matched patients with PAD (n=300) were recruited from the noninvasive vascular laboratory. Age- and sex-matched controls (n=300) were identified from a community-based cohort and had no history of PAD. NT pro-BNP levels were approximately 2.5-fold higher in patients with PCA than in patients with PAD and approximately 4-fold higher than in age- and sex-matched controls. In multivariable regression analyses that adjusted for age, sex, smoking, hypertension, history of coronary heart disease/stroke, systolic blood pressure, and serum creatinine, NT pro-BNP levels remained significantly higher in patients with PCA than in patients with PAD and controls (P<0.001). Patients with medial arterial calcification and PCA have higher serum levels of NT pro-BNP than patients with PAD and controls, which is suggestive of an adverse hemodynamic milieu and increased risk for adverse cardiovascular outcomes.

Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms.

PubMed

Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas

2016-01-01

Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide.

PubMed

Shiraishi, Yasuyuki; Nagai, Toshiyuki; Kohsaka, Shun; Goda, Ayumi; Nagatomo, Yuji; Mizuno, Atsushi; Kohno, Takashi; Rigby, Alan; Fukuda, Keiichi; Yoshikawa, Tsutomu; Clark, Andrew L; Cleland, John G F

2018-05-21

Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71-88) vs. Japan: 78 (70-84) years; p = 0.947], glomerular filtration rate [UK: 49 (34-68) vs. Japan: 49 (33-65) ml/min/1.73 m 2 ; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278-10,977) vs. Japan: 4155 (1972-9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105-131) vs. 137 (118-159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan.

Association of plasma N-terminal pro-B-type natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with asymptomatic degenerative mitral valve disease.

PubMed

Chetboul, V; Serres, F; Tissier, R; Lefebvre, H P; Sampedrano, C Carlos; Gouni, V; Poujol, L; Hawa, G; Pouchelon, J -L

2009-01-01

The clinical outcome of dogs affected by degenerative mitral valve disease (MVD) without overt clinical signs is still poorly defined, and criteria for identification of animals that are at a higher risk of early decompensation have not yet been determined. N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) is correlated with mitral regurgitation (MR) severity and can predict disease progression in dogs with asymptomatic MVD. Seventy-two dogs with asymptomatic MVD, with or without heart enlargement (International Small Animal Cardiac Health Council: ISACHC classes 1a and 1b), and a control group of 22 dogs were prospectively recruited. Severity of MR was quantitatively assessed from the regurgitation fraction (RF) by the proximal isovelocity surface area method. Consequences of MR were evaluated from measurements of the left atrium/aorta ratio (LA/Ao), fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes indexed to body surface area (EDVI and ESVI). The relevance of these echo-Doppler indices and NT-proBNP for prediction of outcome at 12 months was studied. A significant correlation was found between NT-proBNP and RF, LA/Ao, FS, and EDVI (P < .05). NT-proBNP was higher in dogs with MVD (ISACHC classes 1a and 1b) compared with the control group (P= .025 and < .001, respectively). The difference was not significant when only dogs from ISACHC class 1a with RF < 30% were considered. Lastly, NT-proBNP was higher in dogs that underwent MVD decompensation at 12 months (P < .05). NT-proBNP is correlated with MVD severity and prognosis in dogs with asymptomatic MVD.

No effect of group-based aerobic interval training on N-terminal pro- B-type natriuretic peptide levels in patients with chronic heart failure.

PubMed

Nilsson, Birgitta Blakstad; Westheim, Arne; Risberg, May Arna; Arnesen, Harald; Seljeflot, Ingebjørg

2010-08-01

Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT pro-BNP), is associated with the severity of the disease, and has been reported to be an independent predictor of outcome in CHF. We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF. We have previously reported improved functional capacity in 80 patients after exercise in this exercise program. Seventy-eight patients with stable CHF (21% women; 70+/-8 years; left ventricular ejection fraction 30+/-8.6%) on optimal medical treatment were randomized either to interval training (n=39), or to a control group (n=39). Circulating levels of NT pro-BNP, a six minute walk test (6MWT) and cycle ergometer test were evaluated at baseline, post exercise, and further after 12 months. There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups. Inverse correlations were observed between NT pro-BNP and 6MWT (r=-0.24, p=0.035) and cycle exercise time (r=-0.48, p<0.001) at baseline. But no significant correlations were observed between change in NT pro-BNP and change in functional capacity (6MWT; r=0.12, p=0.33, cycle exercise time; r=0.04, p=0.72). No significant changes in NT pro-BNP levels were observed after interval training, despite significant improvement of functional capacity.

N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates: A Cohort Study

PubMed Central

Sellmer, Anna; Hjortdal, Vibeke Elisabeth; Bjerre, Jesper Vandborg; Schmidt, Michael Rahbek; McNamara, Patrick J.; Bech, Bodil Hammer; Henriksen, Tine Brink

2015-01-01

Background Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) has been suggested as a marker that may predict BPD within a few days after birth. Objectives To investigate the association between NT-proBNP day three and bronchopulmonary dysplasia (BPD) or death and further to assess the impact of patent ductus arteriosus (PDA) on this association in neonates born before 32 gestational weeks. Methods A cohort study of 183 neonates born before 32 gestational weeks consecutively admitted to the Neonatal Intensive Care Unit, Aarhus University Hospital, Denmark. On day three plasma samples were collected and echocardiography carried out. NT-proBNP was measured by routine immunoassays. The combined outcome BPD or death was assessed at 36 weeks of postmenstrual age. Receiver operator characteristic (ROC) analysis was performed to determine the discrimination ability of NT-proBNP by the natural log continuous measure to recognize BPD or death. The association of BPD or death was assessed in relation to natural log NT-proBNP levels day three. Results The risk of BPD or death increased 1.7-fold with one unit increase of natural log NT-proBNP day three when adjusted for gestational age at birth (OR = 1.7, 95% CI 1.3; 2.3). The association was found both in neonates with and without a PDA. Adjusting for GA, PDA diameter, LA:Ao-ratio, or early onset sepsis did not change the estimate. Conclusion We found NT-proBNP to be associated with BPD or death in very preterm neonates. This association was not only explained by the PDA. We speculate that NT-proBNP may help the identification of neonates at risk of BPD as early as postnatal day three. PMID:26452045

Cautious Application of Pleural N-Terminal Pro-B-Type Natriuretic Peptide in Diagnosis of Congestive Heart Failure Pleural Effusions among Critically Ill Patients

PubMed Central

Yeh, Jiann-Horng; Huang, Chun-Ta; Liu, Chia-Hsiung; Ruan, Sheng-Yuan; Tsai, Yi-Ju; Chien, Ying-Chun; Yang, Ching-Yao; Huang, Chun-Kai; Hsu, Chia-Lin; Kuo, Lu-Cheng; Lee, Pei-Lin; Ku, Shih-Chi; Kuo, Ping-Hung; Yu, Chong-Jen

2014-01-01

Background and Objective Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations. Methods NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions. Results One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001). Conclusions Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings. PMID:25502236

B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

PubMed Central

Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

2014-01-01

Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

Association of cardiac and renal function with extreme N-terminal fragment pro-B-type natriuretic peptide levels in elderly patients.

PubMed

Cui, Hua; Huo, Guoliang; Liu, Lin; Fan, Li; Ye, Ping; Cao, Jian; Bai, Yongyi; Wang, Fan; Hu, Yixin

2012-07-26

The data are inconsistent regarding whether extreme N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP) levels are associated with impaired renal function. Furthermore, the relationship between extreme NT pro-BNP levels and cardiac and renal function in elderly patients has not been reported. The aim of the present study was to examine a hypothesis that extreme NT pro-BNP levels may be associated with impaired cardiac and renal function in elderly patients. We retrospectively analyzed the data of demographic, clinical, and echocardiographic features on 152 consecutive elderly patients aged more than 80 years old (average age, 83.65 ± 3.58 years) with NT pro-BNP levels ≥ 3000 pg/ml. The participants were divided into two categories according to their NT pro-BNP levels: (1) 3000-10000 pg/mL and (2) >10000 pg /mL. The number of patients with impaired renal function (P = 0.019) and the mortality (P < 0.001) in the period of inpatient was higher in the group with NT pro-BNP > 10000 pg /mL. The levels of serum creatinine and creatine kinase MB (CK-MB) in the group of NT pro-BNP > 10000 pg / mL were higher than those in the group of NT pro-BNP = 3000-10000 pg/mL (P = 0.001 and P = 0.023, respectively). Furthermore, no significant difference in the distribution by NYHA class in different NT pro-BNP levels was observed. Multiple linear regression analyses demonstrated that with NT pro-BNP levels as the dependent variable, NT pro-BNP levels were positively correlated with CK-MB (β = 0.182, P = 0.024) and creatinine levels (β = 0.281, P = 0.001). The area under the receiver-operating characteristic (ROC) curve of NT pro-BNP levels and clinical diagnosis of impaired renal function was 0.596 and reached significant difference (95%CI:0.503-0.688, P = 0.044). These data suggest that the extreme elevation of NT pro-BNP levels (≥3000 pg/ml) is mainly determined by impaired renal function in

N-terminal fraction of pro-B-type natriuretic peptide versus clinical risk scores for prognostic stratification in chronic systolic heart failure.

PubMed

Arzilli, Chiara; Aimo, Alberto; Vergaro, Giuseppe; Ripoli, Andrea; Senni, Michele; Emdin, Michele; Passino, Claudio

2018-05-01

Background The Seattle heart failure model or the cardiac and comorbid conditions (3C-HF) scores may help define patient risk in heart failure. Direct comparisons between them or versus N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) have never been performed. Methods Data from consecutive patients with stable systolic heart failure and 3C-HF data were examined. A subgroup of patients had the Seattle heart failure model data available. The endpoints were one year all-cause or cardiovascular death. Results The population included 2023 patients, aged 68 ± 12 years, 75% were men. At the one year time-point, 198 deaths were recorded (10%), 124 of them (63%) from cardiovascular causes. While areas under the curve were not significantly different, NT-proBNP displayed better reclassification capability than the 3C-HF score for the prediction of one year all-cause and cardiovascular death. Adding NT-proBNP to the 3C-HF score resulted in a significant improvement in risk prediction. Among patients with Seattle heart failure model data available ( n = 798), the area under the curve values for all-cause and cardiovascular death were similar for the Seattle heart failure model score (0.790 and 0.820), NT-proBNP (0.783 and 0.803), and the 3C-HF score (0.770 and 0.800). The combination of the 3C-HF score and NT-proBNP displayed a similar prognostic performance to the Seattle heart failure model score for both endpoints. Adding NT-proBNP to the Seattle heart failure model score performed better than the Seattle heart failure model alone in terms of reclassification, but not discrimination. Conclusions Among systolic heart failure patients, NT-proBNP levels had better reclassification capability for all-cause and cardiovascular death than the 3C-HF score. The inclusion of NT-proBNP to the 3C-HF and Seattle heart failure model score resulted in significantly better risk stratification.

Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure.

PubMed

Halfinger, Bernhard; Hammerer-Lercher, Angelika; Amplatz, Benno; Sarg, Bettina; Kremser, Leopold; Lindner, Herbert H

2017-01-01

Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. © 2016 American Association for Clinical Chemistry.

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

PubMed

Giallauria, Francesco; De Lorenzo, Anna; Pilerci, Francesco; Manakos, Athanasio; Lucci, Rosa; Psaroudaki, Marianna; D'Agostino, Mariantonietta; Del Forno, Domenico; Vigorito, Carlo

2006-08-01

N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Natriuretic peptides: Diagnostic and therapeutic use

PubMed Central

Pandit, Kaushik; Mukhopadhyay, Pradip; Ghosh, Sujoy; Chowdhury, Subhankar

2011-01-01

Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones. PMID:22145138

Coincidence of moderately elevated N-terminal pro-B-type natriuretic peptide, endothelial progenitor cells deficiency and propensity to exercise-induced myocardial ischemia in stable angina.

PubMed

Surdacki, Andrzej; Marewicz, Ewa; Rakowski, Tomasz; Szumańska, Monika; Szastak, Grzegorz; Pryjma, Juliusz; Dubiel, Jacek S

2010-01-01

To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors - N-terminal pro-B-type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia - in stable coronary artery disease (CAD) with preserved LV systolic function. We studied 30 non-diabetic men with one-vessel CAD, LV ejection fraction 60% and normal LV diastolic function (n=16) or impaired LV relaxation (by ultrasound including tissue Doppler) (n=14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry. CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP-CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score. Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors.

B-type and N-terminal pro-B-type natriuretic peptides are equally useful in assessing patent ductus arteriosus in very preterm infants.

PubMed

König, Kai; Guy, Katelyn J; Drew, Sandra M; Barfield, Charles P

2015-04-01

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size. This prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination. Of the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27(+3) (2(+2)) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219-1316) pg/mL for infants with a PDA and 190 (95.5-514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319-42 108) pg/mL for infants with a PDA and 7488 (3363-14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size. BNP and NTproBNP are similarly useful for assessing PDA size in preterm infants. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The influence of metabolic syndrome and diabetes mellitus on the N-terminal pro-B-type natriuretic peptide level and its prognostic performance in patients with coronary artery disease.

PubMed

Huang, Fang-Yang; Peng, Yong; Deng, Xue-Xue; Huang, Bao-Tao; Xia, Tian-Li; Gui, Yi-Yue; Liu, Rui-Shuang; Yang, Yong; Pu, Xiao-Bo; Chen, Shi-Jian; Chen, Fei; Zhu, Ye; Chen, Mao

2017-03-01

Our aim was to investigate whether the presence of metabolic syndrome (MetS) and diabetes mellitus (DM) influenced the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in coronary artery disease (CAD). The present study enrolled a total of 1638 CAD patients. Multivariate regression analyses were carried out to relate NT-proBNP to metabolic components, nondiabetic MetS, DM, and MetS score. Furthermore, we examined the prognostic performance of NT-proBNP in patients with non-MetS, nondiabetic MetS, and DM. NT-proBNP levels correlated inversely with BMI (β=-0.11, P=0.003) and correlated positively with fasting glucose (β=0.12, P=0.001). There were no significant relationships of NT-proBNP with other metabolic parameters. Compared with non-MetS, the presence of DM significantly increased NT-proBNP levels (P=0.004), whereas nondiabetic MetS did not influence NT-proBNP levels (P=0.954). During the median follow-up of 21 months, 109 all-cause deaths occurred. NT-proBNP levels independently predicted all-cause deaths irrespective of the presence of nondiabetic MetS and DM (Pinteraction=0.43). DM, but not nondiabetic MetS, is associated with higher NT-proBNP levels. NT-proBNP can still predict death in patients with CAD, even with the confounding effect of MetS and diabetes.

The Prognostic Value of Serum Levels of Heart-Type Fatty Acid Binding Protein and High Sensitivity C-Reactive Protein in Patients With Increased Levels of Amino-Terminal Pro-B Type Natriuretic Peptide.

PubMed

Jeong, Ji Hun; Seo, Yiel Hea; Ahn, Jeong Yeal; Kim, Kyung Hee; Seo, Ja Young; Kim, Moon Jin; Lee, Hwan Tae; Park, Pil Whan

2016-09-01

Amino-terminal pro-B type natriuretic peptide (NT-proBNP) is a well-established prognostic factor in heart failure (HF). However, numerous causes may lead to elevations in NT-proBNP, and thus, an increased NT-proBNP level alone is not sufficient to predict outcome. The aim of this study was to evaluate the utility of two acute response markers, high sensitivity C-reactive protein (hsCRP) and heart-type fatty acid binding protein (H-FABP), in patients with an increased NT-proBNP level. The 278 patients were classified into three groups by etiology: 1) acute coronary syndrome (ACS) (n=62), 2) non-ACS cardiac disease (n=156), and 3) infectious disease (n=60). Survival was determined on day 1, 7, 14, 21, 28, 60, 90, 120, and 150 after enrollment. H-FABP (P<0.001), NT-proBNP (P=0.006), hsCRP (P<0.001) levels, and survival (P<0.001) were significantly different in the three disease groups. Patients were divided into three classes by using receiver operating characteristic curves for NT-proBNP, H-FABP, and hsCRP. Patients with elevated NT-proBNP (≥3,856 pg/mL) and H-FABP (≥8.8 ng/mL) levels were associated with higher hazard ratio for mortality (5.15 in NT-proBNP and 3.25 in H-FABP). Area under the receiver operating characteristic curve analysis showed H-FABP was a better predictor of 60-day mortality than NT-proBNP. The combined measurement of H-FABP with NT-proBNP provides a highly reliable means of short-term mortality prediction for patients hospitalized for ACS, non-ACS cardiac disease, or infectious disease.

Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography.

PubMed

Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

2016-08-01

The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47-82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA.

Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography

PubMed Central

Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

2016-01-01

The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47–82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA. PMID:27446259

Troponin T and Pro–B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

PubMed Central

Russell, Noirin E.; Higgins, Mary F.; Amaruso, Michael; Foley, Michael; McAuliffe, F.M.

2009-01-01

OBJECTIVE Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function. RESEARCH DESIGN AND METHODS This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester. RESULTS Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05). CONCLUSIONS Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants. PMID:19690080

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

PubMed

Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

2015-10-01

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Prognostic utility of the Seattle Heart Failure Score and amino terminal pro B-type natriuretic peptide in varying stages of systolic heart failure.

PubMed

Adlbrecht, Christopher; Hülsmann, Martin; Neuhold, Stephanie; Strunk, Guido; Pacher, Richard

2013-05-01

Cardiac transplantation represents the best procedure to improve long-term clinical outcome in advanced chronic heart failure (CHF), if pre-selection criteria are sufficient to outweigh the risk of the failing heart over the risk of transplantation. Although the cornerstone of success, risk assessment in heart transplant candidates is still under-investigated. Amino terminal pro B-type natriuretic peptide (NT-proBNP) is regarded as the best predictor of outcome in CHF, and the Seattle Heart Failure Score (SHFS), including clinical markers, is widely used if NT-proBNP is unavailable. The present study assessed the predictive value for all-cause death of the SHFS in CHF patients and compared it with NT-proBNP in a multivariate model including established baseline parameters known to predict survival. A total of 429 patients receiving stable HF-specific pharmacotherapy were included and monitored for 53.4 ± 20.6 months. Of these, 133 patients (31%) died during follow-up. Several established predictors of death on univariate analysis proved significant for the total study cohort. Systolic pulmonary arterial pressure (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05); p < 0.001, Wald 15.1), logNT-proBNP (HR, 1.51; 95% CI, 1.22-1.86; p < 0.001, Wald 14.9), and the SHFS (HR, 0.99; 95% CI, 0.99-1.00; p < 0.001, Wald 12.6) remained within the stepwise multivariate Cox regression model as independent predictors of all-cause death. Receiver operating characteristic curve analysis revealed an area under the curve of 0.802 for logNT-proBNP and 0.762 for the SHFS. NT-proBNP is a more potent marker to identify patients at the highest risk. If the NT-proBNP measurement is unavailable, the SHFS may serve as an adequate clinical surrogate to predict all-cause death. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab−/− mice

PubMed Central

Yoder, Andrea R.; Kruse, Andrew C.; Earhart, Cathleen A.; Ohlendorf, Douglas H.; Potter, Lincoln R.

2015-01-01

C-type natriuretic peptide (CNP) stimulates endochondrial ossification by activating the transmembrane guanylyl cyclase, natriuretic peptide receptor-B (NPR-B). Recently, a spontaneous autosomal recessive mutation that causes severe dwarfism in mice was identified. The mutant, called long bone abnormality (lbab), contains a single point mutation that converts an arginine to a glycine in a conserved coding region of the CNP gene, but how this mutation affects CNP activity has not been reported. Here, we determined that thirty to greater than one hundred-fold more CNPlbab was required to activate NPR-B as compared to wild-type CNP in whole cell cGMP elevation and membrane guanylyl cyclase assays. The reduced ability of CNPlbab to activate NPR-B was explained, at least in part, by decreased binding since ten-fold more CNPlbab than wild-type CNP was required to compete with [125I][Tyr0]CNP for receptor binding. Molecular modeling suggested that the conserved arginine is critical for binding to an equally conserved acidic pocket in NPR-B. These results indicate that reduced binding to and activation of NPR-B causes dwarfism in lbab−/− mice. PMID:18554750

Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

PubMed

Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

2017-12-20

Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

B-type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy.

PubMed

Seror, Jeremy; Lefevre, Guillaume; Berkane, Nathalie; Richard, Frederic; Bornes, Marie; Uzan, Serge; Berkane, Nadia

2014-12-01

Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow-up. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women.

PubMed

Reyna-Villasmil, Eduardo; Mejia-Montilla, Jorly; Reyna-Villasmil, Nadia; Mayner-Tresol, Gabriel; Herrera-Moya, Pedro; Fernández-Ramírez, Andreina; Rondón-Tapía, Marta

2018-05-11

To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Fall in readmission rate for heart failure after implementation of B-type natriuretic peptide testing for discharge decision: a retrospective study.

PubMed

Valle, Roberto; Aspromonte, Nadia; Carbonieri, Emanuele; D'Eri, Alessandra; Feola, Mauro; Giovinazzo, Prospero; Noventa, Federica; Prevaldi, Carolina; Barro, Sabrina; Milani, Loredano

2008-06-06

B-type natriuretic peptide is the most powerful predictor of long term prognosis in patients hospitalised with heart failure. On an outsetting basis, a decrease in B-type natriuretic peptide levels is associated to a decrease in event rate for outpatients managed using the neuro-hormone levels as the target in heart failure therapy. We have retrospectively checked whether the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure reduced readmission rate for heart failure and related cost. We studied two series of consecutive patients admitted to the Heart Failure Unit due to acute heart failure as a main diagnosis. One-hundred and forty-nine patients discharged on the basis of the sole clinical acumen were compared to one hundred and sixty-six subjects discharged adding B-type natriuretic peptide levels to the decisional score. During a six-month follow-up period, there were 52 readmissions (35%) among the clinical group (n=149) compared with 38 (23%) readmissions in the B-type natriuretic peptide group (n=166) (chi(2)=5.5; P=0.02). Survival did not differ between groups (87%). Changes in B-type natriuretic peptide values were correlated to clinical events: a B-type natriuretic peptide value on discharge of < or =250 pg/ml or a reduction of > or =30% in B-type natriuretic peptide values predicted a 23% event rate (death, plus readmission for heart failure), whereas a far higher percentage (71%) were observed in the remaining patients (chi(2)=32.7; P=0.001). Likewise, the overall costs of care were lower (-7%) in the B-type natriuretic peptide group: 2.781+/-923 vs 2.978+/-1.057 euros per patient respectively. our study suggest that the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure may contribute to reduce the number of readmissions and

21 CFR 862.1117 - B-type natriuretic peptide test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1117 - B-type natriuretic peptide test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1117 - B-type natriuretic peptide test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1117 - B-type natriuretic peptide test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1117 - B-type natriuretic peptide test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

Association of N-Terminal Pro-B-Type Natriuretic Peptide with Left Ventricular Structure and Function in Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC])

PubMed Central

Mishra, Rakesh K.; Li, Yongmei; Ricardo, Ana C.; Yang, Wei; Keane, Martin; Cuevas, Magdalena; Christenson, Robert; DeFilippi, Christopher; Chen, Jing; He, Jiang; Kallem, Radhakrishna R.; Raj, Dominic S.; Schelling, Jeffrey R.; Wright, Jackson; Go, Alan S.; Shlipak, Michael G.

2017-01-01

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without clinical heart failure (HF), the Chronic Renal Insufficiency Cohort (n=3,232). Associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated by multivariable logistic and linear regression models. Reclassification of participants’ predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement (NRI) index that compared a clinical model with and without NT-proBNP. The median (interquartile range) NT-proBNP was 126.6 pg/ml (55.5–303.7). The highest quartile of NT-proBNP was associated with nearly three-fold odds of LVH (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.8–4.0) and LV systolic dysfunction (2.7, 1.7–4.5) and two-fold odds of diastolic dysfunction (2.0, 1.3–2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve, AUC 0.66) and LV systolic dysfunction (AUC 0.62), and poorly for the detection of diastolic dysfunction (AUC 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants’ likelihood of having LVH (NRI 0.14, 95% CI 0.13–0.15; p<0.001) and LV systolic dysfunction (0.28, 0.27–0.30; p<0.001), but not diastolic dysfunction (0.10, 0.10–0.11; p=0.07). In conclusion, in this large CKD cohort without HF, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. PMID:23178053

N-terminal pro-brain natriuretic peptide in prevalent peritoneal dialysis patients.

PubMed

Adachi, Yoko; Nishio, Akira

2008-01-01

Previous reports have shown that N-terminal pro-brain natriuretic peptide (NT-Pro-BNP) is a predictive marker for mortality in both peritoneal dialysis (PD) and hemodialysis (HD) patients. The aim of the present study was to clarify whether NT-Pro-BNP reflects a specific status in PD patients. We analyzed 40 stable PD patients, allocating them to one of two groups (20 each) according to the median value of NT-Pro-BNP: group A below and group B above 5423 pg/mL. In group B as compared with group A, red blood cell (RBC) counts, hemoglobin, hematocrit, sodium, chlorine, albumin, and daily urinary volume were significantly lower, and cardiothoracic ratio (CTR) and daily ultrafiltration volume were significantly higher. Patients using icodextrin and diabetic patients showed significantly higher NT-Pro-BNP values. We observed significant correlations between NT-Pro-BNP and RBC count, hematocrit, hemoglobin, sodium, chlorine, albumin, lactate dehydrogenase, CTR, daily urinary volume, and ultrafiltration volume. Multiple regression analysis revealed that increasing CTR and hyponatremia were significant predictors of an increase in NT-Pro-BNP. Our results indicate that increased serum NT-Pro-BNP well reflects anemia status, water balance, hyponatremia, and hypoalbuminemia in prevalent PD patients.

The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide: the effect on predicting postoperative cardiac outcome in vascular surgery patients.

PubMed

Goei, Dustin; Flu, Willem-Jan; Hoeks, Sanne E; Galal, Wael; Dunkelgrun, Martin; Boersma, Eric; Kuijper, Ruud; van Kuijk, Jan-Peter; Winkel, Tamara A; Schouten, Olaf; Bax, Jeroen J; Poldermans, Don

2009-11-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T measurements and 12-lead electrocardiograms were performed on postoperative days 1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the study was the composite of 30-day postoperative cardiovascular death, nonfatal myocardial infarction, and troponin T release. Receiver operating characteristic curve analysis was used to assess the optimal cutoff value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (beta coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). Both anemia and NT-proBNP are independently associated with an increased risk for

Predictive abilities of baseline measurements of fluid overload, assessed by bioimpedance spectroscopy and serum N-terminal pro-B-type natriuretic peptide, for mortality in hemodialysis patients

PubMed Central

Siriopol, Ianis; Voroneanu, Luminita; Covic, Adrian

2017-01-01

Introduction Fluid overload is one of the most important, yet modifiable, risk factors associated with worse outcomes in hemodialysis (HD) patients. However, its precise assessment in clinical practice is still under investigation. Material and methods This is an observational prospective study which included 285 stable patients with end-stage renal disease on standard thrice-weekly HD therapy. Overhydration was assessed by the combination of relative fluid overload (RFO), using bioimpedance spectroscopy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The outcome of interest was all-cause mortality. Results The median values for NT-proBNP and RFO were 4595 pg/ml and 6.9%, respectively. We divided the study population into four groups according to these median levels: group 1 – low NT-proBNP and low RFO; group 2 – high NT-proBNP and low RFO; group 3 – low NT-proBNP and high RFO; group 4 – high NT-proBNP and high RFO. During the follow-up (mean: 41.1, median: 48.7 months), 89 (31.2%) patients died. In the univariable Cox survival analysis only patients in group 4, and not those from group 2 or 3, had significantly higher HRs as compared to those in group 1 (HR = 1.5, 95% CI: 0.8–2.8, HR = 1.6, 95% CI: 0.8–2.9 and HR = 2.4, 95% CI: 1.3–4.2, for group 2, 3 and 4, respectively). Furthermore, these results were maintained in the multivariable Cox analysis. Conclusions Including both bioimpedance and NT-proBNP monitoring in a more comprehensive fluid status assessment could improve the diagnosis of fluid overload with a final improvement in patients’ outcome. PMID:28883854

Association between N-terminal pro B-type natriuretic peptide and day-to-day blood pressure and heart rate variability in a general population: the Ohasama study.

PubMed

Satoh, Michihiro; Hosaka, Miki; Asayama, Kei; Kikuya, Masahiro; Inoue, Ryusuke; Metoki, Hirohito; Tsubota-Utsugi, Megumi; Hara, Azusa; Hirose, Takuo; Obara, Taku; Totsune, Kazuhito; Hoshi, Haruhisa; Mano, Nariyasu; Node, Koichi; Imai, Yutaka; Ohkubo, Takayoshi

2015-08-01

In addition to day-to-day variability in blood pressure (BP) or heart rate (HR), N-terminal pro B-type natriuretic peptide (NT-proBNP) has been reported to be a predictor of cardiovascular disease. Here, we tested the hypothesis that day-to-day BP or HR variability calculated as the intraindividual standard deviation (SD) of home BP or HR is associated with elevated NT-proBNP in a cross-sectional study. Among 664 participants (mean age, 61.9 years; female, 70.5%) from a general Japanese population without a history of heart disease, 86 (13.0%) had NT-proBNP at least 125 pg/ml. Each 1 SD increase in the SD of home systolic BP (SBP) [odds ratio (OR), 1.82; P < .0001) and in the SD of home HR (OR, 1.44; P = 0.008) were significantly associated with the prevalence of NT-proBNP at least 125 pg/ml after adjustment for possible confounding factors including home SBP and HR. Among the four groups defined by the median SD of home SBP and of home HR, the group with higher SDs in home SBP (≥8.0 mmHg) and HR (≥5.0 bpm) had the greatest OR for the prevalence of NT-proBNP at least 125 pg/ml (OR, 4.80; P = 0007 vs. a reference group with lower SDs of home SBP and HR). These results suggest that day-to-day variability in BP and HR may be associated with target-organ damage or complications, which can lead to an elevated NT-proBNP level. An elevated NT-proBNP level may be involved in the prognostic significance of day-to-day variability in BP or HR.

Predicting short-term mortality in advanced decompensated heart failure - role of the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic Peptide risk score.

PubMed

Scrutinio, Domenico; Ammirati, Enrico; Passantino, Andrea; Guida, Pietro; D'Angelo, Luciana; Oliva, Fabrizio; Ciccone, Marco Matteo; Iacoviello, Massimo; Dentamaro, Ilaria; Santoro, Daniela; Lagioia, Rocco; Sarzi Braga, Simona; Guzzetti, Daniela; Frigerio, Maria

2015-01-01

The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes.

PubMed

Colombo, Marco; Looker, Helen C; Farran, Bassam; Agakov, Felix; Brosnan, M Julia; Welsh, Paul; Sattar, Naveed; Livingstone, Shona; Durrington, Paul N; Betteridge, D John; McKeigue, Paul M; Colhoun, Helen M

2018-05-21

Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP.

PubMed

Bayes-Genis, Antoni; Barallat, Jaume; Galán, Amparo; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Gastelurrutia, Paloma; Vila, Joan; Peñafiel, Judith; Gálvez-Montón, Carolina; Lupón, Josep

2015-12-01

Neprilysin breaks down numerous vasoactive peptides. The soluble form of neprilysin, which was recently identified in heart failure, is associated with cardiovascular outcomes. Within a multibiomarker strategy, we directly compared soluble neprilysin and N-terminal pro-B-type natriuretic peptide as risk stratifiers in a real-life cohort of heart failure patients. Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failure patients followed up for 4.7 years. Comprehensive multivariable analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head-to-head assessments of performance were performed. A primary composite endpoint included cardiovascular death or heart failure hospitalization. A secondary endpoint explored cardiovascular death alone. Median soluble neprilysin and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and 1187 ng/L, respectively. Both biomarkers significantly correlated with age (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide significantly correlated with estimated glomerular filtration rate (P<.001), body mass index (P<.001), left ventricular ejection fraction (P=.02) and high-sensitivity troponin T (P<.001). In multivariable Cox regression analyses, soluble neprilysin remained independently associated with the composite endpoint (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N-terminal pro-B-type natriuretic peptide did not. The head-to-head soluble neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good calibration and similar discrimination and reclassification for both neurohormonal biomarkers, but only soluble neprilysin improved overall goodness-of-fit. When added to a multimarker strategy, soluble neprilysin remained an independent

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation.

PubMed

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M; Rørth, Rasmus; Abraham, William T; Desai, Akshay; Dickstein, Kenneth; Rouleau, Jean L; Zile, Michael R; Swedberg, Karl; Packer, Milton; Solomon, Scott D; Køber, Lars; McMurray, John J V

2017-10-01

Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without ( P <0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P <0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found

N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study.

PubMed

Moe, Gordon W; Howlett, Jonathan; Januzzi, James L; Zowall, Hanna

2007-06-19

The diagnostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare resource use, and randomized evidence for utility of NT-proBNP was lacking. We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure (P<0.00001). Knowledge of NT-proBNP results reduced the duration of ED visit by 21% (6.3 to 5.6 hours; P=0.031), the number of patients rehospitalized over 60 days by 35% (51 to 33; P=0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per patient; P=0.023) over 60 days from enrollment. Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 (P<0.00001). In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes.

N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

PubMed

Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

2013-06-04

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright �

Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study.

PubMed

Gergei, Ingrid; Krämer, Bernhard K; Scharnagl, Hubert; Stojakovic, Tatjana; März, Winfried; Mondorf, Ulrich

The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF). We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP). Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years). Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF. The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF. Big-ET-1improves risk stratification in patients referred for coronary angiography.

Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis.

PubMed

Brueckmann, Martina; Huhle, Guenter; Lang, Siegfried; Haase, Karl K; Bertsch, Thomas; Weiss, Christel; Kaden, Jens J; Putensen, Christian; Borggrefe, Martin; Hoffmann, Ursula

2005-07-26

Increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been identified as predictors of cardiac dysfunction and prognosis in congestive heart failure and ischemic heart disease. In severe sepsis patients, however, no information is available yet about the prognostic value of natriuretic peptides. Therefore, the aim of the present study was to determine the role of the N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C [drotrecogin alfa (activated)] on plasma levels of natriuretic peptides in severe sepsis was evaluated. Fifty-seven patients with severe sepsis were included. Levels of NT-proANP and NT-proBNP were measured on the second day of sepsis by ELISA. Septic patients with NT-proBNP levels >1400 pmol/L were 3.9 times more likely (relative risk [RR], 3.9; 95% CI, 1.6 to 9.7) to die from sepsis than patients with lower NT-proBNP values (P<0.01). NT-proANP levels, however, were not predictive of survival in our patient population. A highly significant correlation was found between troponin I levels and plasma concentrations of NT-proBNP in septic patients (r=0.68, P<0.0001). In addition, troponin I significantly accounted for the variation in NT-proBNP levels (P<0.0001), suggesting an important role for NT-proBNP in the context of cardiac injury and dysfunction in septic patients. Twenty-three septic patients who received treatment with drotrecogin alfa (activated) presented with significantly lower concentrations of NT-proANP, NT-proBNP, and troponin I compared with patients not receiving drotrecogin alfa (activated). NT-proBNP may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide.

PubMed

Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

2018-01-01

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

A combination of increased Rho kinase activity and N-terminal pro-B-type natriuretic peptide predicts worse cardiovascular outcome in patients with acute coronary syndrome

PubMed Central

Dong, Ming; Liao, James K.; Yan, Bryan; Li, Ruijie; Zhang, Mang; Yu, Cheuk-Man

2013-01-01

Background Recent experimental evidence suggests that the Rho/Rho-kinase (ROCK) system may play an important role in the pathogenesis of acute coronary syndrome (ACS) but there are little clinical data. This study examined if ROCK activity is increased in patients with acute coronary syndrome and if ROCK activity predicts long-term cardiovascular event. Method Blood samples were collected from 188 patients within 12 h after admission for ACS (53% men; aged 70±13) and from 61 control subject. The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) from presentation within around 2 years (mean:14.4±7.2 months; range: 0.5 to 26 months). Results ROCK activity increased in ST elevation myocardial infarction (STEMI, n=90) (3.33±0.93), non-STEMI (NSTEMI, n=68) (3.37±1.04) and unstable angina (UA, n=30) (2.53±0.59) groups when compared with disease controls (n=31) (2.06±0.38, all p<0.001) and healthy controls (n=30) (1.54±0.43, all p<0.001). There were 24 deaths, 34 readmissions with ACS and 15 admissions with CHF within 2 years. Patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high ROCK activity on admission had a five-fold risk of a cardiovascular event (RR: 5.156; 95% CI: 2.180–12.191) when compared to those with low NT-proBNP and low ROCK activity. Conclusion ROCK activity was increased in patients with ACS, particularly in those with myocardial infarction. The combined usage of both ROCK activity and NT-proBNP might identify a subset of ACS patients at particularly high risk. PMID:22921817

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

PubMed

Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

2015-03-01

Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

B-type natriuretic peptides and mortality after stroke: a systematic review and meta-analysis.

PubMed

García-Berrocoso, Teresa; Giralt, Dolors; Bustamante, Alejandro; Etgen, Thorleif; Jensen, Jesper K; Sharma, Jagdish C; Shibazaki, Kensaku; Saritas, Ayhan; Chen, Xingyong; Whiteley, William N; Montaner, Joan

2013-12-03

To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information. Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes. Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10-406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32-4.01 for BNP; and odds ratio 2.63, 95% CI 1.75-3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality. BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP/NT-proBNP add only minor predictive value to clinical

PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments.

PubMed

Terada, Y; Tomita, K; Nonoguchi, H; Yang, T; Marumo, F

1994-08-01

The present study was undertaken to investigate the presence of C-type natriuretic peptide (CNP) mRNA and its receptor, natriuretic peptide B-type receptor (ANPR-B) mRNA, in rat renal structures. The microlocalization of mRNAs coding for CNP and ANPR-B was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments, glomeruli, vasa recta bundle, and arcuate arteries. The PCR signal for CNP was detected in glomerulus, vasa recta bundle, and arcuate artery. The PCR product of ANPR-B was widely present in renal structures. Relatively large amounts of ANPR-B PCR product were detected in glomerulus, vasa recta bundle, arcuate artery, and distal nephron segments. A relatively high concentration of CNP (10(-7) M) stimulated guanosine 3',5'-cyclic monophosphate accumulation in glomerulus, medullary thick ascending limb, cortical collecting duct, and inner medullary collecting duct. Our data demonstrate that CNP can be produced locally in the glomerulus and renal vascular system and that ANPR-B is widely distributed in renal structures. Thus CNP may influence renal function and act in autocrine and paracrine fashions in the kidney.

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides.

PubMed

Nishikimi, Toshio; Kuwahara, Koichiro; Nakao, Kazuwa

2011-03-01

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Endothelial actions of atrial and B-type natriuretic peptides.

PubMed

Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

State of the art of immunoassay methods for B-type natriuretic peptides: An update.

PubMed

Clerico, Aldo; Franzini, Maria; Masotti, Silvia; Prontera, Concetta; Passino, Claudio

2015-01-01

The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1-32, should reduce the systematic differences between methods and result in better harmonization of results.

Association of N-terminal pro-B-type natriuretic peptide with contrast-induced nephropathy and long-term outcomes in patients with chronic kidney disease and relative preserved left ventricular function.

PubMed

Liu, Yuan-hui; Liu, Yong; Zhou, Ying-ling; Yu, Dan-qing; He, Peng-cheng; Xie, Nian-jin; Li, Hua-long; Wei-Guo; Chen, Ji-yan; Tan, Ning

2015-04-01

The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22-6.97, P < 0.001). Furthermore, lg-NT-pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57-6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67-0.84, P < 0.001). In addition, NT-pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI.

Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study.

PubMed

Celik, Onder; Sahin, Ibrahim; Celik, Nilufer; Hascalik, Seyma; Keskin, Lezzan; Ozcan, Hamdi; Uckan, Ahmet; Kosar, Feridun

2007-11-01

In addition to the negative effect on fertility, polycystic ovary syndrome (PCOS) has been associated with cardiac pathology. Brain natriuretic peptide (BNP) is a possible marker for cardiac risk, therefore we investigated whether N-terminal pro-B-type BNP (NT-proBNP) increases in women with PCOS compared with healthy women of comparable age and body mass index. Thirty women with PCOS and 30 healthy women not suffering from overt cardiac disease were involved in the study. Fasting insulin and serum NT-proBNP levels were measured, and M-Mode echocardiography was performed. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA-IR). PCOS subjects had higher NT-proBNP levels than the control subjects (P < 0.001). Abnormal echocardiography indices were detected in 14 of the PCOS subjects (but none of the controls), including valvular heart disease in nine, diastolic dysfunction in two, right ventricular enlargement in one, right atrial enlargement in one and pulmonary hypertension in one. PCOS subjects (n = 30) showed an increased left ventricular mass (LVM) (P < 0.001) and left ventricular posterior wall thickness (LVPWT) (P = 0.006). In addition, NT-proBNP concentration was positively correlated with LVM (r = 0.587, P = 0.001) and negatively correlated with sex-hormone-binding globulin (r = -0.528, P = 0.003). There was a positive correlation between LVM and HOMA-IR (r = 0.295, P = 0.03) while LVPWT was positively correlated with fasting insulin and HOMA-IR (r = 0.335, P = 0.031 and r = 0.346, P = 0.045, respectively) in PCOS subjects (n = 30). The present study demonstrated that the level of NT-proBNP was increased in PCOS subjects with asymptomatic heart disease.

Blood B-type natriuretic peptide level increases in patients who complain shortness of breath and chest pain in the course of panic attack.

PubMed

Vural, Mutlu; Akbas, Befru; Acer, Mehmet; Karabay, Ocal

2007-04-25

Blood pro-B-type natriuretic peptide (pro-BNP) level increases in case of myocardial ischemia and myocardial volume or pressure overload. The aim of this study is to measure changes in blood pro-BNP level during the course of panic attack with symptoms of chest pain and/or dyspnea. Patients who were admitted to the emergency room with panic attack have been regarded as the study group. Blood pro-BNP level has been measured during follow-up of the patients upon admission and 2h later. Systolic and diastolic blood pressure and pulse rate were significantly decreased (p<0.0001) during follow-up of the patients (ages between 18 and 43 years; mean 26+/-6.13 years). Paradoxically, blood pro-BNP level of patients was significantly increased during the same period (52.86+/-59.73 versus 50.97+/-57.42 U/L; p<0.0001). Blood pro-BNP level has increased among patients who have complained chest pain and/or dyspnea as symptoms of panic attack. It is thought that chest pain and dyspnea in the course of panic attack may not be purely psychological.

Obesity and Natriuretic Peptides, BNP and NT-proBNP: Mechanisms and Diagnostic Implications for Heart Failure

PubMed Central

Madamanchi, Chaitanya; Alhosaini, Hassan; Sumida, Arihiro; Runge, Marschall S.

2014-01-01

Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-Type Natriuretic Peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients. PMID:25156856

B-type natriuretic peptide levels and continuous-flow left ventricular assist devices.

PubMed

Sareyyupoglu, Basar; Boilson, Barry A; Durham, Lucian A; McGregor, Christopher G A; Daly, Richard C; Redfield, Margaret M; Edwards, Brooks S; Frantz, Robert P; Pereira, Naveen L; Park, Soon J

2010-01-01

We postulated that postoperative B-type natriuretic peptide (BNP) levels would be reflective of the degree of hemodynamic support rendered by various pump speeds settings (RPM) of continuous-flow left ventricular assist devices (LVADs). Twenty LVAD patients were evaluated prospectively (Jarvik 2000: n = 9, HeartMate II: n = 11). The mean age was 57.7 ± 14.9 years, and 14 were male. B-type natriuretic peptide levels were drawn while the patients were supported on LVADs at variable RPM settings. The RPM settings were correlated with the changes in BNP levels. Eleven patients underwent LVAD implantation for a lifelong support while the rest were as a bridge therapy to transplantation. Four patients required LVAD change out for various causes of pump failure. Postoperative BNP levels decreased dramatically with the initiation of LVAD support. The levels correlated inversely with the degree of hemodynamic support rendered at various RPM settings of the HeartMate II (p < 0.001). Overall, BNP levels decreased significantly in 2 days after RPM increase. We observed a significant inverse correlation between the postoperative BNP levels and the degree of LVAD support. The effective LVAD support seems to result in a marked reduction in BNP levels, and monitoring serial BNP levels may be helpful in managing patients supported on continuous LVAD.

Effects of Transdermal Testosterone on Natriuretic Peptide Levels in Women: A Randomized Placebo-Controlled Pilot Study

PubMed Central

Lin, Eleanor; McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Buys, Emmanuel; Wang, Thomas; Miller, Karen K.

2011-01-01

Objective To investigate whether testosterone administration alters natriuretic peptide levels in women. Design Three-month, double-blind, randomized, placebo-controlled study. Setting Clinical research center. Patients 51 women with hypoandrogenemia due to hypopituitarism. Intervention Transdermal testosterone (300 mcg daily) or placebo patch. Main Outcome Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Results NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01). Conclusions Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number NCT00027430 PMID:22137497

The effects of continuous positive airway pressure therapy on Troponin-T and N-terminal pro B-type natriuretic peptide in patients with obstructive sleep apnoea: a randomised controlled trial.

PubMed

Chang, Ya-Shu; Yee, Brendon J; Hoyos, Camilla M; Wong, Keith K; Sullivan, David R; Grunstein, Ronald R; Phillips, Craig L

2017-11-01

Untreated obstructive sleep apnoea (OSA) is associated with increased risk of coronary artery disease (CAD) and heart failure. High-sensitivity cardiac troponin (hs Trop-T) and B-type natriuretic peptide (NT-pro-BNP) are sensitive biomarkers for myocardial injury and heart failure respectively. No randomised controlled trials have examined the treatment effect of continuous positive airway pressure (CPAP) in patients with OSA on these biomarkers. Patients >21 years old with apnoea-hypopnoea index (AHI) ≥25/h by overnight polysomnography were recruited. Main exclusion criteria were previous CPAP use and any significant comorbidities including CAD and heart failure. Eligible subjects were randomised to receive CPAP or sham CPAP for eight weeks each in a crossover design with a wash out period of one month between the treatments. Blood samples were collected at 8pm, 3am, and 8am during sleep studies conducted at the end of each eight-week treatment period. Of the 37 patients who were randomised, 28 patients had stored frozen samples available for analysis. In comparison to sham treatment, CPAP significantly lowered the NT-pro-BNP level by 0.91 pmol/L (p = 0.0002). The reduction of 0.235 ng/L in hs Trop-T on CPAP therapy was not statistically significant (p = 0.052). There were no overnight changes, across the three time points, in either biomarker with either treatment. Our study confirms CPAP therapy in patients with moderate-severe OSA reduces NT-pro-BNP, but we did not confirm a significant effect on hs Trop-T. Future larger studies of longer duration incorporating biomarkers and cardiac functional measures are needed to better establish the benefit of OSA treatment. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

[Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease].

PubMed

Higueras, Javier; Martín-Ventura, José Luis; Blanco-Colio, Luis; Cristóbal, Carmen; Tarín, Nieves; Huelmos, Ana; Alonso, Joaquín; Pello, Ana; Aceña, Álvaro; Carda, Rocío; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Asensio, Dolores; Almeida, Pedro; Rodríguez-Artalejo, Fernando; Farré, Jerónimo; López Bescós, Lorenzo; Egido, Jesús; Tuñón, José

2015-01-01

At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); P<0.001. A composite score was developed by adding the scores of the LIPID and scale decile levels of MCP -1, galectin -3 and NT-proBNP. The predictive value improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Association of N-Terminal Pro-B-Type Natriuretic Peptide With Contrast-Induced Nephropathy and Long-Term Outcomes in Patients With Chronic Kidney Disease and Relative Preserved Left Ventricular Function

PubMed Central

Liu, Yuan-hui; Liu, Yong; Zhou, Ying-ling; Yu, Dan-qing; He, Peng-cheng; Xie, Nian-Jin; Li, Hua-long; Wei-Guo; Chen, Ji-yan; Tan, Ning

2015-01-01

Abstract The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22–6.97, P < 0.001). Furthermore, lg-NT-pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57–6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67–0.84, P < 0.001). In addition, NT-pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI. PMID:25837748

N-terminal ProBNP distribution and correlations with biological characteristics in apparently healthy Greek population: ATTICA study.

PubMed

Fragopoulou, Elizabeth; Panagiotakos, Demosthenes B; Pitsavos, Christos; Chrysohoou, Christina; Nomikos, Tzortzis; Evangelopoulos, Angelos; Katsagoni, Christina; Skoumas, John; Antonopoulou, Smaragdi; Stefanadis, Christodoulos

2010-05-01

Brain natriuretic peptides are widely used as biomarkers of cardiovascular diseases and mainly heart failure. However, these markers are often found to be high even in apparently healthy participants, and little is known about which factors contribute to physiological change in plasma brain natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NTproBNP) concentration in general populations. In this study, a random subsample of the ATTICA study was used (486 individuals) and serum NT-proBNP was measured. Approximately 20% of the participants had no detectable NT-proBNP values. Women had higher values of NT-proBNP than men (median [25th-75th percentiles]: 30.2 [15.8-54.3] vs 14.9 [4.0-28.1] pg/mL, P < .001]. Amino-terminal pro-B-type natriuretic peptide values were positively correlated with age (rho = .140, P = .006) and inversely with body mass index (BMI; rho = -.142, P = .005), creatinine (Cr) clearance (rho = -.349, P < .001), and hemoglobin (rho = -.249, P < .001) values. Linear regression analysis revealed that gender is the main contributor of NT-proBNP levels, followed by age, BMI, and Cr values.

Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies

PubMed Central

Pfister, Roman; Sharp, Stephen; Luben, Robert; Welsh, Paul; Barroso, Inês; Salomaa, Veikko; Meirhaeghe, Aline; Khaw, Kay-Tee; Sattar, Naveed; Langenberg, Claudia; Wareham, Nicholas J.

2011-01-01

Background Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. Methods and Findings We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%–36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91–0.97) was similar to that expected (0.96, 0.93–0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74–0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15–0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. Conclusions Our results provide evidence for a potential causal role of the BNP

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

PubMed

Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

B-type natriuretic peptide in the recognition of critical congenital heart disease in the newborn infant.

PubMed

Das, Srikant; Chanani, Nikhil K; Deshpande, Shriprasad; Maher, Kevin O

2012-08-01

Infants with congenital heart disease having obstruction to the left ventricular outflow and ductal-dependent systemic circulation can present critically ill with shock. Prompt disease recognition and initiation of prostaglandins are necessary to prevent excess morbidity and mortality. We assessed a large cohort of newborn infants with ductal-dependent systemic circulation to determine if B-type natriuretic peptide (BNP) is consistently elevated at presentation, potentially aiding in diagnosis and treatment. The clinical records of infants with left-sided obstructive lesions admitted from January 2005 to June 2009 were reviewed. Infants were divided into 2 groups: group 1 was diagnosed with cardiogenic/circulatory shock at presentation, and group 2 consisted of infants with ductal-dependent systemic circulation without evidence of shock. B-type natriuretic peptide levels and other variables between the groups were compared. All patients with critical congenital heart disease presenting with shock had elevated BNP levels, ranging from 553 to greater than 5000 pg/mL. Infants in group 1 (shock, n = 36) had significantly higher median BNP levels of 4100 pg/mL at presentation compared with group 2 patients (no shock, n = 86), who had a median BNP of 656 pg/mL (range, 30-3930 pg/mL; P < 0.001). Every 100 U of increase in BNP at presentation increased the likelihood of shock (odds ratio, 100; P < 0.001). B-type natriuretic peptide is markedly elevated in neonates presenting in shock secondary to left-sided obstructive heart disease and is an important diagnostic tool to aid in the rapid identification and treatment of these patients.

Monitoring the response to pharmacologic therapy in patients with stable chronic heart failure: is BNP or NT-proBNP a useful assessment tool?

PubMed

Balion, Cynthia M; McKelvie, Robert S; Reichert, Sonja; Santaguida, Pasqualina; Booker, Lynda; Worster, Andrew; Raina, Parminder; McQueen, Matthew J; Hill, Stephen

2008-03-01

B-type natriuretic peptides are biomarkers of heart failure (HF) that can decrease following treatment. We sought to determine whether B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) concentration changes occurred in parallel to changes in other measures of heart failure following treatment. We conducted a systematic review of the literature for studies that assessed B-type natriuretic peptide measurements in treatment monitoring of patients with stable chronic heart failure. Selected studies had to include at least three consecutive measurements of BNP or NT-proBNP. Of 4338 citations screened, only 12 met all of the selection criteria. The selected studies included populations with a wide range of heart failure severity and therapy. BNP and NT-proBNP decreased following treatment in nine studies and was associated with improvement in clinical measures of HF. There was limited data to support using BNP or NT-proBNP to monitor therapy in patients with HF.

Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.

PubMed

Skoglund, Per H; Arpegård, Johannes; Ostergren, Jan; Svensson, Per

2014-03-01

Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro-B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Kristensen, Søren L; Jhund, Pardeep S; Køber, Lars; McKelvie, Robert S; Zile, Michael R; Anand, Inder S; Komajda, Michel; Cleland, John G F; Carson, Peter E; McMurray, John J V

2015-06-01

The aim of this study was to investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure - preserved ejection fraction (HF-PEF). Recently, doubt has been expressed about the value of a history of HF hospitalization as a predictor of adverse cardiovascular outcomes in patients with HF and HF-PEF. We estimated rates and adjusted hazard ratios (HRs) for the composite endpoint of cardiovascular death or HF hospitalization, according to history of recent HF hospitalization and baseline NT-proBNP level in the I-PRESERVE (Irbesartan in Heart Failure with Preserved systolic function) trial. Rates of composite endpoints in patients with (n = 804) and without (n = 1,963) a recent HF hospitalization were 12.78 (95% confidence interval [CI]: 11.47 to 14.24) and 4.49 (95% CI: 4.04 to 4.99) per 100 person-years, respectively (HR: 2.71; 95% CI: 2.33 to 3.16). For patients with NT-proBNP concentrations >360 pg/ml (n = 1,299), the event rate was 11.51 (95% CI: 10.54 to 12.58) compared to 3.04 (95% CI: 2.63 to 3.52) per 100 person-years in those with a lower level of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523; HR: 6.18; 95% CI: 4.96 to 7.69). Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease.

PubMed

Oyama, M A; Solter, P F; Thorn, C L; Stern, J A

2017-06-01

An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3',5'-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs. Six privately owned dogs. Dogs were enrolled in a modified 3 + 3 phase I trial. Three dogs initially received doses of 2.5 and 5 μg/kg SC syncBNP followed by an additional three dogs dosed at 5 and 10 μg/kg. Hemodynamic monitoring was performed for 120 min after each injection. Blood and urine samples were collected at 45 and 120 min after injection of 5 μg/kg. Major adverse clinical events that would potentially halt testing were pre-defined. Four healthy dogs and two dogs with stage B1 mitral valve disease were recruited. Synthetic canine B-type natriuretic peptide was well tolerated at all doses. Synthetic canine B-type natriuretic peptide at 5 μg/kg significantly increased median plasma cGMP (baseline cGMP, 131.5 pmol/mL [range, 91.9-183.6 pmol/mL]; 45 min, 153.6 pmol/mL [140.3-214.3 pmol/mL]; 120 min, 192.7 pmol/mL [139.1-240.1 pmol/mL]; p=0.041). We report for the first time administration of syncBNP in privately owned dogs. Administration of SC syncBNP was feasible, well tolerated, safe, and increased plasma cGMP concentration. Further studies using exogenous syncBNP for treatment of heart disease are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.

PubMed

Kyrzopoulos, Stamos; Adamopoulos, Stamatis; Parissis, John T; Rassias, John; Kostakis, George; Iliodromitis, Efstathios; Degiannis, Dimitrios; Kremastinos, Dimitrios Th

2005-03-30

Plasma B-type natriuretic peptide (BNP) and interleukin 6 (IL-6) levels have recently been demonstrated as significant neurohormonal markers associated with the progression of chronic heart failure (CHF). Additionally, clinical studies have shown that the calcium sensitizer, levosimendan, beneficially affects the central hemodynamics of CHF patients and improves their long-term prognosis. This study investigates whether levosimendan-induced hemodynamic improvement of CHF patients is related to the respective changes of NT-proBNP and IL-6 levels. Circulating levels of NT-pro BNP and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 12 patients with decompensated advanced CHF at baseline, immediately after the end of a 24-h levosimendan infusion and 72 h after the initiation of treatment. Hemodynamic parameters of patients (pulmonary wedge and pulmonary artery pressure (PAP), systemic and pulmonary vascular resistance (PVR), stroke volume, and cardiac output and index) were also monitored during the same period. NT-proBNP and IL-6 levels were significantly reduced in severe CHF patients within 72 h after the initiation of levosimendan treatment (p<0.01 and p<0.05, respectively). A significant reduction of pulmonary wedge (p<0.01) and artery pressure values (p<0.05) was also found during the same period. A good correlation between the levosimendan-induced changes in NT-proBNP levels and the respective reduction of pulmonary wedge pressure (r(s)=0.65, p<0.05) was observed. Our results indicate that changes of NT-pro BNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.

Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis

PubMed Central

Sanchez, Otto A.; Mariana, Lazo-Elizondo; Irfan, Zeb; Tracy, Russell P; Bradley, Ryan; Duprez, Daniel A.; Bahrami, Hossein; Peralta, Carmen A.; Daniels, Lori B.; Lima, João A.; Maisel, Alan; Jacobs, David R.; MJ, Budoff

2016-01-01

Background and aims N-terminal pro B-type natriuretic peptide (NT-proBNP) is inversely associated with diabetes mellitus, obesity and metabolic syndrome. We aim to characterize the association between NT-proBNP and nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with metabolic syndrome. Methods 4529 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) free of cardiovascular disease, without self-reported liver disease and not diabetic at their baseline visit in 2000- 2002 were included in this analysis. NAFLD was defined by a liver attenuation <40 HU. Relative prevalence (RP) for NAFLD was assessed adjusted for age, race, and sex, percent of dietary calories derived from fat, total intentional exercise, alcoholic drinks per week, and interleukin-6 by quintiles of NT-proBNP. Adjusted linear spline model was used to characterize a non-linear association between NT-proBNP and liver fat. The inflection point (IP) was the NT-proBNP concentration where there was a change in slope in the association between liver attenuation and NT-proBNP. Results RP for NAFLD decreased by 30% from the lowest to the highest quintile of NT-proBNP, p = 0.01. We observed an inverse linear association between NT-proBNP and liver fat, which plateaued (IP) at an NT-proBNP concentration of 45 pg/mL. Linear regression coefficient (SE) per unit of NT-proBNP < and ≥ IP was of 0.05 (0.02), p = 0.001 and 0.0006 (0.0008), p = 0.5, respectively, differences between slopes p < 0.0001. Conclusions In this cross-sectional study of a community based multiethnic sample of non-diabetic adults, low levels of NT-proBNP are associated with greater prevalence of NAFLD. PMID:27085779

Characterization and prediction of adverse events from intensive chronic heart failure management and effect on quality of life: results from the pro-B-type natriuretic peptide outpatient-tailored chronic heart failure therapy (PROTECT) study.

PubMed

Gandhi, Parul U; Szymonifka, Jackie; Motiwala, Shweta R; Belcher, Arianna M; Januzzi, James L; Gaggin, Hanna K

2015-01-01

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01). NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Relation of adiponectin and high-sensitivity C-reactive protein to pulse-wave velocity and N-terminal pro-B-type natriuretic peptide in the general population.

PubMed

Sung, Shih-Hsien; Chuang, Shao-Yuan; Sheu, Wayne Huey-Herng; Lee, Wen-Jane; Chou, Pesus; Chen, Chen-Huan

2009-05-15

The roles of metabolic syndrome and chronic subclinical inflammation in arterial stiffening and the development of heart failure remain to be elucidated. Whether adiponectin and high-sensitivity C-reactive protein (hs-CRP) were independently related to brachial-ankle pulse-wave velocity (ba-PWV) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in the general population were investigated. Eligible study subjects were 445 Chinese residents aged > or =40 years who participated in a community-based survey, underwent examination of ba-PWV, and had complete data of serum adiponectin, hs-CRP (<10 mg/L), and NT-pro-BNP. Adiponectin, but not hs-CRP, was independently related to ba-PWV (standardized regression parameter -0.107, p <0.05) when age, gender, body mass index, and number of metabolic syndrome components were accounted for. On the other hand, ba-PWV, adiponectin, and hs-CRP were independently related to NT-pro-BNP (standardized regression parameters 0.116, 0.188, and 0.094, respectively; all p <0.05) when age, gender, body mass index, number of metabolic syndrome components, and renal function were accounted for. In conclusion, adiponectin, but not hs-CRP, is independently associated with both ba-PWV and NT-pro-BNP in the general population. Because adiponectin, hs-CRP, ba-PWV, and NT-pro-BNP may represent markers for metabolic syndrome, chronic subclinical inflammation, arterial stiffness, and ventricular dysfunction, respectively, our results suggest that adiponectin may directly modulate both arterial stiffening and ventricular dysfunction. In contrast, hs-CRP may independently contribute to ventricular dysfunction, but not arterial stiffening.

Effects of oral contraceptives on natriuretic peptide levels in women with hypothalamic amenorrhea: a pilot study.

PubMed

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K

2011-06-30

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60%-75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives (OC) increases natriuretic peptide levels and that end-of-study free T levels are inversely associated with amino-terminal pro-B-type natriuretic peptide levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations-estrogens (E) or androgens. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.

PubMed

Torres-Courchoud, I; Chen, H H

2016-10-01

Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

PubMed Central

Feinkohl, Insa; Sattar, Naveed; Welsh, Paul; Reynolds, Rebecca M.; Deary, Ian J.; Strachan, Mark W. J.; Price, Jackie F.

2012-01-01

Background Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS). Methodology and Principal Findings Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores). Conclusion Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and

Renal C-type natriuretic peptide and natriuretic peptide receptor B mRNA expression are affected by water deprivation in the Spinifex Hopping mouse.

PubMed

Heimeier, Rachel A; Donald, John A

2003-11-01

This study investigated the effect of water deprivation on the expression of C-type natriuretic peptide (CNP) and natriuretic peptide receptor B (NPR-B) mRNA, and the ability of NPR-B to generate cGMP in the Spinifex Hopping mouse, Notomys alexis. This rodent is a native of central and western Australia that is well adapted to survive in arid environments. Initially, CNP and NPR-B cDNAs (partial for NPR-B) were cloned and sequenced, and were shown to have high homology with those of rat and mouse. RT-PCR analysis showed CNP mRNA expression in the kidney, proximal and distal colon and small intestine, whilst NPR-B mRNA expression was found in the kidney, proximal and distal colon and the atria. Using a semi-quantitative multiplex PCR technique, the expression of renal CNP and NPR-B mRNA was determined in 7- and 14-day water-deprived hopping mice, in parallel with control hopping mice (access to water). Water deprivation significantly decreased the relative levels of CNP and NPR-B mRNA expression in both the 7- and 14-day water-deprived hopping mice, when compared to control hopping mice. In contrast, the ability of CNP to stimulate cGMP production was significantly increased after 14 days of water deprivation. This study shows that alterations in the renal CNP/NPR-B system may be an important physiological adjustment when water is scarce.

Absence of C-type natriuretic peptide receptors in hamster glomeruli.

PubMed

Luk, J K; Wong, E F; Wong, N L

1994-01-01

The distribution of atrial natriuretic peptide receptor B (ANPR-B) varies between tissues and species. The aim of this study is to determine whether ANPR-B is present in the hamster glomeruli. In vitro C-type natriuretic peptide (CNP)- and atrial natriuretic factor (ANF)-stimulated cGMP accumulation studies were performed in hamster glomeruli. Elevated cGMP accumulations were observed upon ANF addition. No cGMP response was seen with CNP. Competitive receptor-binding experiments were performed with 125I-CNP and 125I-ANF against their respective cold peptides in hamster glomeruli. Although no CNP binding was detected, positive ANF binding was found and two types of ANF receptor were demonstrated. The affinity (Kdl) and maximum binding capacity (Bmaxl) of the high-affinity ANF receptor were 0.014 +/- 0.001 nM and 60.4 +/- 10.2 fmol/mg protein, respectively. Those of the low-affinity receptor (Kd2 and Bmax2) were 45.7 +/- 6.2 nM and 28.3 +/- 6.3 pmol/mg protein, respectively. Similarly, saturation binding experiments also failed to show any CNP receptor binding in hamster glomeruli. This finding suggests that ANPR-B is not present in hamster glomeruli and CNP is not a direct physiological regulator of hamster renal function.

C-type natriuretic peptide and atrial natriuretic peptide receptors of rat brain.

PubMed

Brown, J; Zuo, Z

1993-03-01

Natriuretic peptide receptors in rat brain were mapped by in vitro autoradiography using 125I-labeled [Tyr0]CNP-(1-22) to bind atrial natriuretic peptide receptor (ANPR)-B and ANPR-C receptors selectively, and 125I-labeled alpha-ANP to select ANPR-A and ANPR-C receptors. Des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23)-amide (C-ANP) was used for its selectivity for ANPR-C over ANPR-A. Specific binding of 125I-[Tyr0]CNP-(1-22) with a dissociation constant (Kd) approximately 1 nM occurred in olfactory bulb, cerebral cortex, lateral septal nucleus, choroid plexus, and arachnoid mater. This binding was abolished by C-type natriuretic peptide [CNP-(1-22)], alpha-ANP and C-ANP, and conformed to ANPR-C. 125I-alpha-ANP bound to all structures that bound 125I-[Tyr0]CNP-(1-22). This binding was also inhibited by both CNP-(1-22) and C-ANP, confirming the presence of ANPR-C-like binding sites. However, ANPR-C-like binding sites were heterogenous because only some had high affinities for 125I-[Tyr0]CNP-(1-22) and CNP-(1-22). 125I-alpha-ANP also bound sites without affinities for C-ANP or CNP-(1-22). These sites were consistent with ANPR-A. They occurred mainly on the olfactory bulb, the choroid plexus, and the subfornical organ. Guanosine 3',5'-cyclic monophosphate production was strongly stimulated by alpha-ANP but not by CNP-(1-22) in olfactory bulb. Neither ligand stimulated it in cortical tissue. Thus the natriuretic peptide binding sites of rat brain conformed to ANPR-A and to heterogenous ANPR-C-like sites. No ANPR-B were detected.

Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J

2018-02-03

Higher body mass index (BMI) is associated with lower circulating levels of N-terminal-pro-b-type natriuretic peptide (NT-proBNP). The Interaction between BMI and NT-proBNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. A total of 686 patients from the biomarker substudy of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT-proBNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI <30 kg/m 2 , Class I obesity: BMI 30-34.9 kg/m 2 , Class II obesity BMI 35-39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30- and 180-day outcomes by BMI class and explored the interaction between BMI and NT-proBNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT-proBNP levels were inversely correlated with BMI ( P <0.001). Higher NT-proBNP levels were associated with higher 180-day mortality (adjusted hazard ratio for each doubling of NT-proBNP, 1.40; 95% confidence interval, 1.16, 1.71; P <0.001), but not 30-day outcomes. The effect of NT-proBNP on 180-day death was not modified by BMI class (interaction P =0.24). The prognostic value of NT-proBNP was not modified by BMI in this acute heart failure population. NT-proBNP remains a useful prognostic indicator of long-term mortality in acute heart failure even in the obese patient. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Higher Natriuretic Peptide Levels Associate with a Favorable Adipose Tissue Distribution Profile

PubMed Central

Neeland, Ian J.; Winders, Benjamin R.; Ayers, Colby R.; Das, Sandeep R.; Chang, Alice Y.; Berry, Jarett D.; Khera, Amit; McGuire, Darren K.; Vega, Gloria L.; de Lemos, James A.; Turer, Aslan T.

2013-01-01

Objectives To investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models but data are lacking in humans. Methods 2619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and NT-proBNP and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results Median BNP and NT-proBNP levels in the study cohort (mean age 44 years, 56% women, 48% African-Americans, 32% obese) were 3.0 and 28.1 pg/mL, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance including lower visceral fat, liver fat, and HOMA-IR; and more lower body fat and higher adiponectin (p<0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral (β= −0.08, p<0.0001) and liver fat (β= −0.14, p<0.0001) and positively associated with lower body fat (β= 0.07, p<0.0001) independent of age, sex, race, and obesity-status; findings were similar with BNP. Adjustment for body composition, HOMA-IR, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. PMID:23602771

Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin.

PubMed

Wang, Rui-lan; Kang, Fu-xin

2010-06-01

Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights

Echocardiographic assessment and N-terminal pro-brain natriuretic peptide in hypertensives with metabolic syndrome.

PubMed

Krzesiński, Paweł; Uziebło-Życzkowska, Beata; Gielerak, Grzegorz; Stańczyk, Adam; Piotrowicz, Katarzyna; Piechota, Wiesław; Smurzyński, Paweł; Skrobowski, Andrzej

2017-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) release is associated with left ventricular expansion and pressure overload. Elevation of serum levels of natriuretic peptides is observed in patients with impaired as well as preserved left ventricular systolic function. High NT-proBNP has been shown to be related not only to preload but also to increased afterload, especially blood pressure and arterial stiffness. The aim of the study was to evaluate the association of NT-proBNP and echocardiographic parameters in hypertensives with metabolic syndrome. The study group comprised 133 patients (99 men; mean age 45.9 ± 9.4 years) with at least a 3-month history of arterial hypertension (stages 1 and 2) and fulfilling the diagnostic criteria for metabolic syndrome. Following initial clinical assessment, which included NT-proBNP levels, they underwent two-dimensional echocardiography. Echocardiographic abnormalities were observed in 60 subjects (45.1%), including left ventricular diastolic dysfunction (LVDdf) in 41 (30.8%) and left ventricular hypertrophy (LVH) in 35 (26.3%). Higher NT-proBNP concentrations were observed in patients with LVH, especially in the presence of LVDdf. Further analysis demonstrated that NT-proBNP correlated negatively with septal E' (r = -0.38; p = 0.015) and heart rate (r = -0.42; p = 0.006) in patients with LVDdf, and positively with left ventricular end diastolic diameter (r = 0.46; p = 0.006) and left ventricular mass index (r = 0.49; p = 0.005) in subjects with LVH. However, the analysis of ROC curves revealed no NT-proBNP level of good sensitivity and specificity in diagnosing LVDdf/LVH (maximal area under the curve 0.571). Even a relatively low NT-proBNP concentration can be a useful marker of left ventricular hypertrophy and end-diastolic wall stretch. However, in the present study there was no NT-proBNP level of satisfactory predictive value to diagnose LV abnormalities.

N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR)

PubMed Central

Mirjafari, Hoda; Welsh, Paul; Verstappen, Suzanne M M; Wilson, Paddy; Marshall, Tarnya; Edlin, Helena; Bunn, Diane; Chipping, Jacqueline; Lunt, Mark; Symmons, Deborah P M; Sattar, Naveed; Bruce, Ian N

2014-01-01

Background We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. Methods Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. Results We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels ≥100 pg/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. Conclusions In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD. PMID:23511225

N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

PubMed

Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

2015-09-01

To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

Assessment of N-terminal prohormone B-type natriuretic peptide as a measure of vascular and ventricular function in pediatric pulmonary arterial hypertension

PubMed Central

Dunning, Jamie; Truong, Uyen; Ivy, D. Dunbar; Hunter, Kendall A.; Shandas, Robin

2015-01-01

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease that puts excessive mechanical loads on the ventricle due to a gradual increase in pulmonary vascular impedance. We hypothesize that the increase in right ventricular (RV) afterload is reflected in the concentration of circulating biochemical markers of ventricular strain and stress (B-type natriuretic peptide [BNP] and N-terminal prohormone BNP [NT-proBNP]). We retrospectively analyzed right heart catheterization (RHC) and serum biochemical analysis data () for a pediatric PAH cohort with no sign of left ventricular dysfunction. Using RHC data, we computed an estimate of pulmonary vascular resistance (PVR), compliance, and ventricular-vascular coupling. We also compared how the early onset of interventricular decoupling (characterized as septal flattening) impacts serum NT-proBNP concentrations. Our data revealed correlated NT-proBNP expression with both the resistive and reactive components of RV afterload, an estimate of ventricular-vascular coupling, and a significant increase in biomarker expression in patients with a flattened interventricular septum. Furthermore, the strong correlation between PVR and NT-proBNP appears to break down under flat septum morphology. Over 80% of resistive RV afterload variance is reflected in serum NT-proBNP concentration in pediatric patients with PAH with no sign of left ventricular dysfunction. Reactive afterload appears to contribute to myocardial NT-proBNP release at advanced stages of PAH. Therefore, in mild-to-moderate PAH, resistive afterload is likely the greatest contributor to RV wall stress. These findings could also be used to estimate invasive RHC measurements from serum biochemical analysis, but more work is needed to improve correlations and overcome the issue of interventricular decoupling. PMID:26697173

Plasma B-type natriuretic peptide concentration in beta-thalassaemia patients.

PubMed

Aessopos, Athanasios; Farmakis, Dimitrios; Polonifi, Aikaterini; Tsironi, Maria; Fragodimitri, Christina; Hatziliami, Antonia; Karagiorga, Markisia; Diamanti-Kandarakis, Evanthia

2007-05-01

Plasma B-type natriuretic peptide (BNP) concentration has significant diagnostic accuracy and prognostic value in various forms of heart disease. Whether BNP is also useful in the evaluation and management of thalassaemia heart disease remains to be determined. Eighty three thalassaemia major patients; 8 with acutely decompensated heart failure (New York Heart Association [NYHA] class III or IV, group A), 25 with NYHA class II symptoms and impaired systolic left ventricular function (ejection fraction<55% or fractional shortening<30%, group B) and 50 with normal systolic function (group C), as well as 50 healthy controls, were studied. Assessment included history, physical examination, Doppler echocardiography and plasma BNP determination. Mean BNP levels were 431+/-219 pg/mL (range, 283-890 pg/mL) in group A, 158+/-31 pg/mL in group B, 176+/-54 pg/mL in group C and 43+/-24 pg/mL in controls. BNP levels were significantly higher in group A (p<0.001), but did not differ between groups B and C. Moreover, BNP was not correlated with left ventricular end-diastolic diameter, left ventricular mass, right ventricular diameter index, Doppler diastolic indexes (except in group C), the mean 2-year serum ferritin concentration or the peak serum ferritin concentration in any of the three patient groups. A potential deficiency of BNP-related neurohormonal mechanisms may impair its clinical usefulness in thalassaemia major.

Racial differences in natriuretic peptide levels: the Dallas Heart Study

PubMed Central

Gupta, Deepak K.; de Lemos, James A.; Ayers, Colby R.; Berry, Jarett D.; Wang, Thomas J.

2015-01-01

Background Natriuretic peptides (NP) are hormones with natriuretic, diuretic, and vasodilatory effects. Experimental NP deficiency promotes salt-sensitive hypertension and cardiac hypertrophy, conditions that are more common among black individuals. We hypothesized that black individuals have lower N-terminal pro B-type natriuretic peptide (Nt-proBNP) levels than white and Hispanic individuals. Objectives To assess whether Nt-proBNP levels differ according to race/ethnicity. Methods We examined plasma Nt-proBNP levels according to race/ethnicity in 3,148 individuals (51% black, 31% white, 18% Hispanic) free of prevalent cardiovascular disease in the Dallas Heart Study. Nt-proBNP values in the bottom sex-specific quartile were defined as low. Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates and MRI measurements of cardiac structure and function. Results Hypertension was present in 41%, 25%, and 16% of black, white, and Hispanic individuals, respectively. Unadjusted Nt-proBNP levels were lowest in blacks (median 24 pg/ml; IQR 10, 52) as compared with Hispanic (30 pg/ml; IQR 14, 59) and white individuals (32 pg/ml; IQR 16, 62), P < 0.0001. In multivariable-adjusted models, black individuals still had significantly lower Nt-proBNP levels (-39% [95%CI -46%, -31%]; P < 0.0001) and greater odds of having low Nt-proBNP (OR: 2.46, [95% CI 1.86, 3.26]), compared with whites. In contrast, Nt-proBNP levels did not significantly differ between Hispanic and white individuals (P = 0.28). The finding of lower Nt-proBNP levels in blacks was similar when analyses were restricted to healthy participants without cardiovascular risk factors. Conclusions In this multi-ethnic cohort, Nt-proBNP levels differ substantially according to race/ethnicity. Despite a higher prevalence of hypertension, blacks had significantly lower NP levels than white and Hispanic individuals. A relative NP “deficiency” among black individuals may lead

Comparative measurement of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in ambulatory patients with heart failure.

PubMed

Masson, Serge; Vago, Tarcisio; Baldi, Gabriella; Salio, Monica; De Angelis, Noeleen; Nicolis, Enrico; Maggioni, Aldo P; Latini, Roberto; Norbiato, Guido; Bevilacqua, Maurizio

2002-08-01

It is not clear whether brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) is superior as a diagnostic and prognostic indicator in cardiac diseases. Here, we compare the clinical correlations of both peptides in a population of 92 ambulatory patients with heart failure, using a well-established immunoradiometric assay (IRMA) for BNP and an automated electrochemiluminescence immunoassay for NT-proBNP. The analytical correlation between the two peptides was satisfactory over a wide range of concentrations (1-686 pM for BNP) with the equation: NT-proBNP = 3.48 x BNP -19 and a correlation coefficient r2=0.94. In addition, the concentration of both peptides increased in a similar fashion according to the severity of the disease New York Heart Association (NYHA) functional class, left ventricular ejection fraction, etiology) and age; for instance, the ratios between median levels measured in NYHA class III vs. class II patients were comparable for BNP (383 vs. 16 pM, ratio 24) and NT-proBNP (1306 vs. 57 pM, ratio 23). We conclude that N-terminal proBNP, as assayed in the present study, correlates equally to BNP with clinical variables in patients with heart failure.

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Amino terminal pro brain natriuretic peptide predicts all-cause mortality in patients with chronic obstructive pulmonary disease: Systematic review and meta-analysis.

PubMed

Pavasini, Rita; Tavazzi, Guido; Biscaglia, Simone; Guerra, Federico; Pecoraro, Alessandro; Zaraket, Fatima; Gallo, Francesco; Spitaleri, Giosafat; Contoli, Marco; Ferrari, Roberto; Campo, Gianluca

2017-05-01

Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF). HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, the prognostic role of NP in COPD patients remains unclear. The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients. We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients. Nine studies were considered for qualitative analysis for a total of 2788 patients. Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis. Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively). The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age). NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD.

Serum N-terminal-pro-brain natriuretic peptide level and its clinical implications in patients with atrial fibrillation.

PubMed

Bai, Mei; Yang, Jiefu; Li, Yingying

2009-12-01

Brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure. However, the role of BNP in patients with atrial fibrillation (AF) and normal left ventricular function has not been determined. This study investigates serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and its clinical implications in patients with AF. Serum NT-proBNP levels were measured by enzyme-linked immunosorbent assay (ELISA) and transthoracic echocardiography was performed in 136 subjects (90 cases with AF and 46 cases with sinus rhythm [SR]). Subjects were excluded if they had a history of myocardial infarction, cardiomyopathy, rheumatic heart disease, or hyperthyroidism that preceded the onset of AF. Controls (n = 30) were from a healthy outpatient primary care population. Potential determinants of serum NT-proBNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher serum NT-proBNP levels (689.56 +/- 251.87 fmol/ml) than those with SR (456.11 +/- 148.14 fmol/ml, P < 0.01) and control subjects (415.83 +/- 62.02 fmol/ml, P < 0.01). Individuals with SR and control subjects did not show significant difference at serum NT-proBNP levels (P > 0.05). The regression model of serum NT-proBNP levels and clinical predictors showed that presence of AF, older age, and larger right atrial diameter were independently predictive of higher serum NT-proBNP values. Patients with AF were associated with increased serum NT-proBNP levels. Examining the change of serum NT-proBNP levels is helpful to evaluate the cardiac function in patients with AF. Copyright 2009 Wiley Periodicals, Inc.

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations.

PubMed

Oyama, Mark A; Sisson, D David; Solter, Phil F

2007-01-01

To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). 118 client-owned dogs. Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.

Direct comparison of serial B-type natriuretic peptide and NT-proBNP levels for prediction of short- and long-term outcome in acute decompensated heart failure

PubMed Central

2011-01-01

Introduction Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome. Methods This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission. Results During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions. Conclusions BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-pro

The predictive value of plasma biomarkers in discharged heart failure patients: role of plasma NT-proBNP.

PubMed

Leto, Laura; Testa, Marzia; Feola, Mauro

2016-04-01

Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). We searched Medline for English-language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission". Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all-cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT-proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role. SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations.

N-terminal B-type natriuretic peptide concentrations are similarly increased by 30 minutes of moderate and brisk walking in patients with coronary artery disease.

PubMed

Scharhag, Jürgen; Herrmann, Markus; Weissinger, Melanie; Herrmann, Wolfgang; Kindermann, Wilfried

2007-04-01

Elevated concentrations of B-type natriuretic peptide (BNP) and N-terminal pro- BNP (NT-proBNP) reflect elevated myocardial wall stress due to volume or pressure overload in cardiac disease. Recently, exercise-induced elevations of (NT-pro)BNP in coronary artery disease (CAD) patients have been reported to result from exercise-induced ischemia associated regional wall abnormalities. Therefore, the study aimed to examine NT-proBNP concentrations in patients with CAD after moderate and brisk walking (MW, BW). We hypothesized that BW induces higher increases than MW. In randomized order 14 patients with stable CAD (12 male symbol/2 female symbol; 63 +/- 9 years; LV ejection fraction: 59+/-9%) of a out-patient rehabilitation group performed MW with 4.5 +/- 0.6 km/h (mean heart rate: 80 +/- 11/min) or BWat their allowed upper exercise heart rate of 102+/-9/min with a speed of 6.2 +/- 0.6 km/h for 30 min on a tartan track on two separate days. Blood samples were taken before, immediately, 1 h, 3 h and 1 day after exercise to determine NT-proBNP and cardiac troponin T (cTnT). Echocardiographic LV function was determined before and 1 h after exercise. Median concentrations of NT-proBNP significantly increased from 222 to 295 ng/l (MW) and from 222 to 296 ng/l (BW) without a difference between both modalities. cTnT remained below the detection limit of 0.01 microg/l. LV functions remained unchanged. A cutoff level of 250 ng/l distinguished CAD patients with elevated exercise-induced increases in NT-proBNP and a diminished LV ejection fraction at rest. BW and MW induce similar increases in NT-proBNP in CAD patients without myocardial damage, which have to be considered when NT-proBNP is determined. Derived from the exercise- induced increase in NTproBNP, the myocardial strain in BW is not elevated in comparison to MW.

Usefulness of N-terminal pro-brain natriuretic Peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction.

PubMed

Grewal, Jasmine; McKelvie, Robert S; Persson, Hans; Tait, Peter; Carlsson, Jonas; Swedberg, Karl; Ostergren, Jan; Lonn, Eva

2008-09-15

More than 40% of patients hospitalized with heart failure have preserved left ventricular ejection fraction (HF-PLVEF) and are at high risk for cardiovascular (CV) events. The purpose of this study was to determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in predicting CV outcomes in patients with HF-PLVEF. Participants with an ejection fraction >40% in the prospective CHARM Echocardiographic Substudy were included in this analysis. Plasma NT-proBNP levels were measured, and 2 cut-offs were selected prospectively at 300 pg/ml and 600 pg/ml. BNP cut-off was set at 100 pg/ml. Clinical characteristics were recorded, and systolic and diastolic function were evaluated by echocardiography. The primary substudy outcome was the composite of CV mortality, hospitalization for heart failure, and myocardial infarction or stroke. A total of 181 patients were included, and there were 17 primary CV events (9.4%) during a median follow-up time of 524 days. In a model including clinical characteristics, echocardiographic measures, and BNP or NT-proBNP, the composite CV event outcome was best predicted by NT-proBNP >300 pg/ml (hazard ratio 5.8, 95% confidence intervals [CI] 1.3 to 26.4, p = 0.02) and moderate or severe diastolic dysfunction on echocardiography. When NT-proBNP >600 pg/ml was used in the model, it was the sole independent predictor of primary CV events (hazard ratio 8.0, 95% CI 2.6 to 24.8, p = 0.0003) as was BNP >100 pg/ml (hazard ratio 3.1, 95% CI 1.2 to 8.2, p = 0.02) in the BNP model. In conclusion, both elevated NT-proBNP and BNP are strong independent predictors of clinical events in patients with HF-PLVEF.

Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance.

PubMed

Kanai, Yugo; Yasoda, Akihiro; Mori, Keita P; Watanabe-Takano, Haruko; Nagai-Okatani, Chiaki; Yamashita, Yui; Hirota, Keisho; Ueda, Yohei; Yamauchi, Ichiro; Kondo, Eri; Yamanaka, Shigeki; Sakane, Yoriko; Nakao, Kazumasa; Fujii, Toshihito; Yokoi, Hideki; Minamino, Naoto; Mukoyama, Masashi; Mochizuki, Naoki; Inagaki, Nobuya

2017-11-01

Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.

Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study.

PubMed

De Geer, Lina; Fredrikson, Mats; Oscarsson, Anna

2012-06-01

Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Prospective, observational cohort study. A mixed non-cardiothoracic tertiary ICU in Sweden. NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearman's correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. An NT-pro-BNP more than 1380 ng -l on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng -1, and 14.6% of patients below that threshold died within 30 days (log rank P=0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearman's ρ 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an

Natriuretic Peptides, 6-Min Walk Test, and Quality-of-Life Questionnaires as Clinically Meaningful Endpoints in HF Trials.

PubMed

Ferreira, João Pedro; Duarte, Kevin; Graves, Todd L; Zile, Michael R; Abraham, William T; Weaver, Fred A; Lindenfeld, JoAnn; Zannad, Faiez

2016-12-20

The Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions document was issued as a guidance for industry and for the Food and Drug Administration. The Expedited Access Pathway was designed as a new program for medical devices that demonstrated the potential to address unmet medical needs for life threatening or irreversibly debilitating conditions. The Food and Drug Administration would consider assessments of a device's effect on intermediate endpoints that, when improving in a congruent fashion, are reasonably likely to predict clinical benefit. The purpose of this review is to provide evidence to support the use of 3 such intermediate endpoints: natriuretic peptides, such as N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide, the 6-min walk test distance, and health-related quality of life in heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Correlation of plasma B-type natriuretic peptide levels with metabolic risk markers.

PubMed

Ahued-Ortega, José Armando; León-García, Plácido Enrique; Hernández-Pérez, Elizabeth

2018-04-17

Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient. A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05). Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

The use of N-terminal pro-brain natriuretic Peptide to evaluate vascular disease in elderly patients with mental illness.

PubMed

Nilsson, Karin; Gustafson, Lars; Hultberg, Björn

2012-01-01

Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment. In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease. Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. Thus, elevated serum NT-proBNP level might be helpful to detect patients who have a more severe cardiovascular disease.

The clinical use of N-terminal-pro brain natriuretic peptide in elderly patients with mental illness.

PubMed

Nilsson, Karin; Gustafson, Lars; Hultberg, Björn

2010-11-01

Serum N-terminal-pro brain natriuretic peptide (NT-proBNP) is regarded as a marker of vascular disease and has previously been shown to exhibit an increased frequency of pathological values in elderly patients with mental illness with vascular disease compared to patients without vascular disease. Vascular disease plays an important role in cognitive impairment in elderly patients with mental illness. We have investigated the relation between NT-proBNP, vascular disease and cognition in consecutively enrolled elderly patients with mental illness. NT-proBNP level is increased in patients with vascular disease compared to patients without vascular disease, and a logistic regression analysis showed that NT-proBNP was a significant predictor of vascular disease. However, NT-proBNP level did not predict cognition as assessed by MMSE score. NT-proBNP level also showed a highly significant relation to mortality in all patients. Determinations of NT-proBNP could be used in elderly patients with mental illness to detect patients in need of control and treatment of vascular risk factors. The levels of NT-proBNP may also provide prognostic information. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Relation of N-Terminal Pro-B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function.

PubMed

Hwang, Ji-Won; Park, Sung-Ji; Cho, Eun Jeong; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-06-01

An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3 hours. Patients were divided in 2 groups based on lower (<26 ml/kg/min, n = 47) or higher (≥26 ml/kg/min, n = 49) peak oxygen consumption (VO 2 ) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3 hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO 2 was inversely related to NT-proBNP before (r = -0.352, p <0.001) and after exercise (r = -0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation.

PubMed

Weber, Michael; Hausen, Michael; Arnold, Roman; Moellmann, Helge; Nef, Holger; Elsaesser, Albrecht; Mitrovic, Vesselin; Hamm, Christian

2008-07-21

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001). NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

B-type natriuretic peptide-guided treatment for heart failure

PubMed Central

McLellan, Julie; Heneghan, Carl J; Perera, Rafael; Clements, Alison M; Glasziou, Paul P; Kearley, Karen E; Pidduck, Nicola; Roberts, Nia W; Tyndel, Sally; Wright, F Lucy; Bankhead, Clare

2016-01-01

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a

Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study.

PubMed

Pervez, Mohammad Osman; Winther, Jacob A; Brynildsen, Jon; Strand, Heidi; Christensen, Geir; Høiseth, Arne Didrik; Myhre, Peder L; Røysland, Ragnhild; Lyngbakken, Magnus Nakrem; Omland, Torbjørn; Røsjø, Helge

2018-05-07

To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately. The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve was 0.85 (95% CI 0.81-0.89) for MR-proANP and 0.86 (0.82-0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio ( ln MR-proANP) 1.98 (95% CI 1.17-3.34). MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

Plasma N-terminal pro-brain natriuretic peptide concentrations before and after pericardiocentesis in dogs with cardiac tamponade secondary to spontaneous pericardial effusion.

PubMed

Baumwart, R D; Hanzlicek, A S; Lyon, S D; Lee, P M

2017-10-01

To determine if concentrations of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) are increased in dogs with cardiac tamponade and if there is a significant increase in plasma NT-proBNP after pericardiocentesis. Ten client-owned dogs with spontaneous cardiac tamponade. Prospective clinical study. Cardiac tamponade was suspected from physical examination and confirmed with echocardiography. Blood was collected and plasma NT-proBNP concentrations were measured before and 30-60 min following pericardiocentesis and resolution of cardiac tamponade. Within-subject changes in plasma NT-proBNP were compared by the Wilcoxon signed-rank test. The plasma NT-proBNP concentrations measured within the reference interval in seven of 10 dogs before pericardiocentesis and in six of 10 dogs following pericardiocentesis. Following pericardiocentesis, there was a statistically significant increase in median NT-proBNP concentration (733 pmol/L, range 250-3,297) compared with the values measured before (643 pmol/L, range 250-3,210, P = 0.004). The NT-proBNP concentration increased in 90% of the dogs following pericardiocentesis. An upper reference limit of 900 pmol/L for plasma NT-proBNP is insensitive for the diagnosis of pericardial effusion and cardiac tamponade in dogs. Plasma NT-proBNP concentration commonly increases following pericardiocentesis, perhaps related to improved ventricular filling and stretch. Published by Elsevier B.V.

Utility of N-terminal pro-brain natriuretic peptide for assessing hemodynamic significance of patent ductus arteriosus in dogs undergoing ductal repair.

PubMed

Hariu, Crystal D; Saunders, Ashley B; Gordon, Sonya G; Norby, Bo; Miller, Matthew W

2013-09-01

Determine if plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) correlates with markers of hemodynamically significant patent ductus arteriosus (PDA) in dogs. Ten dogs with PDA and 30 healthy dogs of similar ages. Prospective case series with control population. Dogs with PDA were initially evaluated with thoracic radiographs, transthoracic echocardiography, pulmonary capillary wedge pressure (PCWP) and NT-proBNP. Following ductal occlusion, NT-proBNP and echocardiography were repeated within 24 h and at day 90. PCWP was repeated at day 90. Correlation between NT-proBNP and hemodynamic measurements was assessed, and accuracy of NT-proBNP for identifying PDA severity was estimated. NT-proBNP was significantly higher (median; absolute range) in dogs with PDA (895; 490-7118 pmol/L) than controls (663; 50-1318 pmol/L) (p = 0.025). NT-proBNP decreased significantly 90 days post-ductal closure (597; 154-1858 pmol/L) (p = 0.013). Left atrial and ventricular size decreased significantly within 24 h and at day 90 as did PCWP (day 90 only). NT-proBNP correlated with vertebral heart size (VHS) and indexed left ventricular systolic diameter (iLVIDs); concentrations ≥ 1224 pmol/L distinguished dogs with elevated VHS and iLVIDs. NT-proBNP is elevated in dogs with PDA, decreases following PDA closure and correlates with select radiographic and echocardiographic markers of cardiac remodeling. Copyright © 2013 Elsevier B.V. All rights reserved.

Practical use of natriuretic peptide measurement: questionnaire results from general practitioners and cardiologists.

PubMed

Husby, Simon; Lind, Bent; Goetze, Jens P

2012-02-01

To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker. We performed a questionnaire-based study on the use of BNP/NT-proBNP measurement among doctors; 21 general practitioners and 23 randomly chosen doctors at cardiology departments were interviewed. 12 general practitioners (57%) answered 'yes', eight (38%) answered 'no' and one (5%) was 'undecided' for use of BNP/NT-proBNP measurement to exclude a diagnosis of heart failure. Among cardiologists, 11 (48%) answered 'yes', ten (43%) answered 'no' and two (9%) were 'undecided' (no difference between groups, p = 0.56). The majority of doctors were familiar with BNP/NT-proBNP being affected by age but were unaware of the impact of gender and obesity. We propose that BNP/NT-proBNP measurement results should be supplied with age- and gender-related cut-off values, along with a notion of the negative predictive value and other parameters affecting the concentration in plasma.

B-Type Natriuretic Peptide Assay for the Diagnosis and Prognosis of Patent Ductus Arteriosus in Preterm Infants

PubMed Central

Kim, Joon Sik

2012-01-01

Background and Objectives Patent ductus arteriosus (PDA) is a significant cause of morbidity and mortality in preterm infants. Measurement of plasma B-type natriuretic peptide (BNP) has been reported to be a useful bedside screening tool for the presence of hemodynamically significant PDA (hsPDA) in neonates. This study was conducted to investigate the usefulness of a BNP assay as a biochemical marker for the diagnosis of hsPDA and predictive biomarker of the response to indomethacin in preterm infants. Subjects and Methods Preterm infants born at <37 weeks' gestational age were prospectively enrolled within 24 hours of birth. Plasma BNP levels were measured on days 1, 4, and 7. Significant PDA was diagnosed by large ductal flow with left to right shunt on color Doppler echocardiography, along with clinical features of PDA. Following that, hsPDA was treated with indomethacin. Results A total of 28 preterm infants were prospectively enrolled in this study. Seven infants with PDA had higher on day 4 plasma BNP values (median 654.68 pg/mL; range 428.29-1280.00) compared to the control group (median 124.52 pg/mL; range 37.21-290.49). The area under the receiver operator characteristic curve for the detection of hsPDA was high: 0.998 (95% confidence interval: 0.995-1.002). The cutoff of BNP concentration for the diagnosis of hsPDA was determined to be 412 pg/mL (sensitivity: 100%; specificity: 95%). Conclusion B-type natriuretic peptide can be a useful biomarker for the screening and diagnosis of PDA in preterm infants. Serial BNP measurements are valuable for assessing the clinical course and indomethacin responsiveness of PDA. PMID:22493614

Favourable effects of exercise training on N-terminal pro-brain natriuretic peptide plasma levels in elderly patients after acute myocardial infarction.

PubMed

Giallauria, Francesco; Lucci, Rosa; De Lorenzo, Anna; D'Agostino, Mariantonietta; Del Forno, Domenico; Vigorito, Carlo

2006-11-01

regional or global impairment of left ventricular (LV) systolic or diastolic function leading to increased LV wall stress results in increased circulating levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP). this study aims at evaluating the effect of exercise training (ET) on NT-pro-BNP plasma levels in older patients recovering from acute myocardial infarction (AMI). prospective randomised study. Academic Medical Centre. forty older patients (33 males and 7 females) who experienced AMI. patients were randomised into two groups, each composed of 20 patients: Group A were enrolled in a 3-month exercise-based cardiac rehabilitation (CR) programme and Group B were discharged home with generic instructions to continue physical activity. NT-pro-BNP, cardiopulmonary and Doppler-echocardiographic parameters were measured at baseline and at 3-month follow-up. in Group A, ET reduced NT-pro-BNP levels (from 1446 +/- 475 to 435 +/- 251 pg/ml, P<0.001) and increased maximal exercise parameters; there was also an inverse correlation between changes in NT-pro-BNP levels and in VO(2peak) (r = -0.67, P<0.01), E-wave (r = -0.42, P<0.01) and E/A ratio (r = -0.60, P<0.01). In Group B, after 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. LV volumes and left ventricular ejection fraction (LVEF) were unchanged after 3 months in both groups. three months ET in older patients after AMI was associated with a reduction in NT-pro-BNP levels and an overall improvement of exercise capacity, without negative LV remodelling and with improvement in early LV filling. Further investigation is required to evaluate whether in these patients the reduction of NT-pro-BNP levels at 3 months could be useful as a surrogate marker of favourable LV remodelling at a later follow-up.

C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa

PubMed Central

Blier, Anne-Sophie; Veron, Wilfried; Bazire, Alexis; Gerault, Eloïse; Taupin, Laure; Vieillard, Julien; Rehel, Karine; Dufour, Alain; Le Derf, Franck; Orange, Nicole; Hulen, Christian; Feuilloley, Marc G. J.

2011-01-01

Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during

Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

PubMed Central

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, Christophe; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

2014-01-01

Background ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established. Methods and Results We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017). Conclusions In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-pro

Characterization of C-type natriuretic peptide receptors in human mesangial cells.

PubMed

Zhao, J; Ardaillou, N; Lu, C Y; Placier, S; Pham, P; Badre, L; Cambar, J; Ardaillou, R

1994-09-01

Our aim was to examine whether the human glomerulus was a target for C-type natriuretic peptide (CNP) and how A, B and C receptors of natriuretic peptides (ANPR-A, ANPR-B, ANPR-C) were distributed in glomerular mesangial and epithelial cells. CNP stimulated cyclic GMP production in cultured human mesangial and epithelial cells with similar threshold concentrations (1 nM) and maximum effects (basal value x 30 at 1 microM). In contrast, atrial natriuretic peptide (ANP) was only stimulatory in epithelial cells. [125I] CNP bound specifically to mesangial cells with a Kd of 0.47 nM and Bmax of 42 fmol/mg. Equilibrium of binding was obtained after four to five hours at +4 degrees C and nonspecific binding represented 10 to 20% of total binding. HS142-1 (100 micrograms/ml), a specific inhibitor of ANPR-A and ANPR-B, suppressed 90% of CNP-dependent cyclic GMP production whereas it had little effect on [125I]-CNP binding, suggesting that C receptors were largely predominant in mesangial cells. No biological effect of CNP on mesangial cells, including change in basal or angiotensin II-induced contractility and inhibition of basal or serum-dependent proliferation, could be demonstrated. Similar results were obtained with 8-bromo-cyclic GMP and sodium nitroprusside. Intraglomerular localization of ANPR-A, ANPR-B and ANPR-C mRNA was studied using reverse transcriptase-polymerase chain reaction with amplification of their corresponding cDNA by different primers. Amplification products were identified on gel electrophoresis by their predicted sizes and sequencing. ANPR-A, ANPR-B and ANPR-C mRNA were present in epithelial cells whereas only ANPR-B and ANPR-C mRNA were detected in mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

N-terminal-pro brain natriuretic peptides in dogs and cats: A technical and clinical review

PubMed Central

de Lima, Gabriela Vieira; Ferreira, Felipp da Silveira

2017-01-01

Biomarkers are quantitative indicators of biological processes performed by an organ or system. In recent years, natriuretic peptides (NPs) have emerged as important tools in the diagnosis and therapeutic monitoring of heart diseases. Research has shown that serum and plasma levels of N-terminal pro brain NP (NT-proBNP) in dogs and cats are the only biomarkers that afford to diagnose and monitor congestive processes and, indirectly, the myocardial function of small animals. The present review discusses the peer-reviewed specialized literature about NT-proBNP and presents and compares the potential clinical applications of this NP in veterinary medicine of small animals, considering diagnosis, follow-up, and prognosis of myocardial or systemic diseases. The relevance of NT-proBNP is associated with sample stability, easy determination in laboratory, sensitivity, accuracy, and the possibility to analyze myocardial function. These advantages are specially important when NT-proBNP is compared with other cardiac biomarkers, mostly those that indicate the integrity of the myocardial cell. Fast NT-proBNP assays are marketed today and may be used in association with complementary tests. Together, these methods are an important source of information in differential diagnosis of heart and lung diseases as well in the early diagnosis of cardiopathy in dogs and cats, proving valuable tools in treatment and prognosis. PMID:29062197

Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb.

PubMed

Luk, J K; Wong, E F; Sun, A; Wong, N L

1994-12-01

The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion.

Exercise dependence of N-terminal pro-brain natriuretic peptide in patients with precapillary pulmonary hypertension.

PubMed

Grachtrup, Sabine; Brügel, Mathias; Pankau, Hans; Halank, Michael; Wirtz, Hubert; Seyfarth, Hans-Jürgen

2012-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by cardiac ventricular myocytes upon pressure and volume overload and is a prognostic marker to monitor the severity of precapillary pulmonary hypertension and the extent of right heart failure. The impact of physical exercise on NT-proBNP levels in patients with left heart disease was demonstrated previously. No data regarding patients with isolated right heart failure and the influence of acute exercise on NT-proBNP serum levels exist. Twenty patients with precapillary pulmonary hypertension were examined. Hemodynamic parameters were measured during right heart catheterization. Serum NT-proBNP of patients was measured at rest, after a 6-min walking test, during ergospirometry and during recovery, all within 7 h. Significant differences in sequential NT-proBNP values, relative changes compared to values at rest and the correlation between NT-proBNP and obtained parameters were assessed. At rest, the mean serum level of NT-proBNP was 1,278 ± 998 pg/ml. The mean level of NT-proBNP at maximal exercise was increased (1,592 ± 1,219 pg/ml), whereas serum levels decreased slightly during recovery (1,518 ± 1,170 pg/ml). The relative increase of serum NT-proBNP during exercise correlated with pulmonary vascular resistance (r = 0.45; p = 0.026) and cardiac output (r = -0.5; p = 0.015). In this study, we demonstrated acute changes in NT-proBNP levels due to physical exercise in a small group of patients with precapillary pulmonary hypertension. Our results also confirm the predominant usefulness of NT-proBNP as an intraindividual parameter of right heart load. Copyright © 2012 S. Karger AG, Basel.

C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

PubMed

Olney, Robert C; Prickett, Timothy C R; Espiner, Eric A; Mackenzie, William G; Duker, Angela L; Ditro, Colleen; Zabel, Bernhard; Hasegawa, Tomonobu; Kitoh, Hiroshi; Aylsworth, Arthur S; Bober, Michael B

2015-02-01

C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP). This was a prospective, observational study. Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P < .0005). NTproCNP levels correlated with height velocity. Levels were also elevated in adults with achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

Dynamic detection of N-terminal pro-B-type natriuretic peptide helps to predict the outcome of patients with major trauma.

PubMed

Qian, A; Zhang, M; Zhao, G

2015-02-01

NT-proBNP and BNP have been demonstrated to be prognostic markers in cardiac disease and sepsis. However, the prognostic value and the dynamic changes of BNP or NT-proBNP in trauma patients remain unclear. The present study was conducted to investigate the dynamic changes of NT-proBNP in patients with major trauma (injury severity score ≥16), determine whether NT-proBNP could be used as a simple index to predict mortality in major trauma patients. This prospective observational study included 60 patients with major trauma. Serum NT-proBNP levels were measured on the 1st, 3rd and 7th day after injury The NT-proBNP levels in survivors were compared with those in non-survivors. The efficacy of NT-proBNP to predict survival was analyzed using receiver operating characteristic curves. An analysis of correlations between NT-proBNP and various factors, including injury severity score, Glasgow coma score, acute physiology and chronic health evaluation II, central venous pressure, creatine kinase-MB, cardiac troponin I and procalcitonin (PCT) was performed. NT-proBNP levels in patients with traumatic brain injury were compared with those in patients without traumatic brain injury. A comparison of NT-proBNP levels between patients with and without sepsis was also performed at each time point. NT-proBNP levels in non-survivors were significantly higher than those in survivors at all the indicated time points. In the group of non-survivors, NT-proBNP levels on the 7th day were markedly higher than those on the 1st day. In contrast, NT-proBNP levels in survivors showed a reduction over time. The efficacy of NT-proBNP to predict survival was analyzed using ROC curves, and there was no difference in the area under the ROC between NT-proBNP and APACHE II/ISS at the three time points. A significant correlation was found between NT-proBNP and ISS on the 1st day, NT-proBNP and CK-MB, Tn-I and APACHE II on the 3rd day, NT-proBNP and PCT on the 7th day. There were no significant

Biologic variability of N-terminal pro-brain natriuretic peptide in adult healthy cats.

PubMed

Harris, Autumn N; Estrada, Amara H; Gallagher, Alexander E; Winter, Brandy; Lamb, Kenneth E; Bohannon, Mary; Hanscom, Jancy; Mainville, Celine A

2017-02-01

Objectives The biologic variability of N-terminal pro-brain natriuretic peptide (NT-proBNP) and its impact on diagnostic utility is unknown in healthy cats and those with cardiac disease. The purpose of this study was to determine the biologic variation of NT-proBNP within-day and week-to-week in healthy adult cats. Methods Adult cats were prospectively evaluated by complete blood count (CBC), biochemistry, total thyroxine, echocardiography, electrocardiography and blood pressure, to exclude underlying systemic or cardiac disease. Adult healthy cats were enrolled and blood samples were obtained at 11 time points over a 6 week period (0, 2 h, 4 h, 6 h, 8 h, 10 h and at weeks 2, 3, 4, 5 and 6). The intra-individual (coefficient of variation [CV I ]) biologic variation along with index of individuality and reference change values (RCVs) were calculated. Univariate models were analyzed and included comparison of the six different time points for both daily and weekly samples. This was followed by a Tukey's post-hoc adjustment, with a P value of <0.05 being significant. Results The median daily and weekly CV I for the population were 13.1% (range 0-28.7%) and 21.2% (range 3.9-68.1%), respectively. The index of individuality was 0.99 and 1 for daily and weekly samples, respectively. The median daily and weekly RCVs for the population were 39.8% (range 17.0-80.5%) and 60.5% (range 20.1-187.8%), respectively. Conclusions and relevance This study demonstrates high individual variability for NT-proBNP concentrations in a population of adult healthy cats. Further research is warranted to evaluate NT-proBNP variability, particularly how serial measurements of NT-proBNP may be used in the diagnosis and management of cats with cardiac disease.

Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP

PubMed Central

Lisy, Ondrej; Huntley, Brenda K.; McCormick, Daniel J.; Kurlansky, Paul A.; Burnett, John C.

2008-01-01

Objectives Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Background Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Methods Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Results Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. Conclusions The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides. PMID:18582636

Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP.

PubMed

Lisy, Ondrej; Huntley, Brenda K; McCormick, Daniel J; Kurlansky, Paul A; Burnett, John C

2008-07-01

Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis).

PubMed

Gupta, Deepak K; Daniels, Lori B; Cheng, Susan; deFilippi, Christopher R; Criqui, Michael H; Maisel, Alan S; Lima, Joao A; Bahrami, Hossein; Greenland, Philip; Cushman, Mary; Tracy, Russell; Siscovick, David; Bertoni, Alain G; Cannone, Valentina; Burnett, John C; Carr, John Jeffrey; Wang, Thomas J

2017-09-15

Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and restricted cubic splines were used to estimate differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and ancestry. Ancestry was determined using genetic ancestry informative markers. NT-proBNP concentrations differed significantly by race and ethnicity (black, median 43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23 to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to -41) in Chinese, compared with white individuals. Hispanic individuals had intermediate concentrations. Self-identified blacks and Hispanics were the most genetically admixed. Among self-identified black individuals, a 20% increase in genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP. Among Hispanic individuals, genetic European and African ancestry were positively and negatively associated with NT-proBNP levels, respectively. In conclusion, NT-proBNP levels differ according to race and ethnicity, with the lowest concentrations in black and Chinese individuals. Racial and ethnic differences in NT-proBNP may have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP concentrations, respectively. Copyright © 2017 Elsevier Inc. All

Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease.

PubMed

Bhattacharyya, Sanjeev; Toumpanakis, Christos; Caplin, Martyn Evan; Davar, Joseph

2008-10-01

We sought to investigate whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be used as a biomarker for the detection of carcinoid heart disease (CHD); 200 patients with carcinoid syndrome were screened for CHD using transthoracic echocardiography. A carcinoid score was formulated to quantify severity of CHD. NT-pro-BNP was measured in all patients before echocardiography. Patients were categorised into New York Heart Association class. CHD was present in 39 patients (19.5%). NT-pro-BNP was significantly higher in those with CHD (median 1,149 pg/ml) than in those without CHD (median 101 pg/ml, p <0.001). The sensitivity and specificity of NT-pro-BNP at a cut-off level of 260 pg/ml for detection of CHD were 0.92 and 0.91, respectively. NT-pro-BNP positively correlated both with carcinoid score (r = 0.81, p <0.001) and New York Heart Association class (p <0.001). The number of patients screened to diagnose 1 case of CHD decreased from 5.1 to 1.4. In conclusion, NT-pro-BNP seems to be an excellent biomarker of CHD. A high negative predictive value may allow it to provide a screening test for CHD.

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

PubMed

Chokengarmwong, Nalin; Yeh, Daniel Dante; Chang, Yuchiao; Ortiz, Luis Alfonso; Kaafarani, Haytham M A; Fagenholz, Peter; King, David R; DeMoya, Marc; Butler, Kathryn; Lee, Jarone; Velmahos, George; Januzzi, James Louis; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent

2017-09-01

New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0

N-terminal pro-brain natriuretic peptide is a strong predictor of mortality in systemic sclerosis.

PubMed

Allanore, Yannick; Komocsi, Andras; Vettori, Serena; Hachulla, Eric; Hunzelmann, Nicolas; Distler, Jörg; Avouac, Jérôme; Gobeaux, Camille; Launay, David; Czirjak, Laszlo; Kahan, André; Meune, Christophe

2016-11-15

Cardiovascular involvement is a major contributor to mortality in systemic sclerosis (SSc). We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor of mortality in SSc. This multicentre prospective cohort study included 523 patients presenting with SSc, whose mean age was 54±13years, mean disease duration 8±9years, and diffuse cutaneous form in 168. Plasma NT-proBNP was measured at baseline and the patients were followed yearly. Overall mortality was measured at 3years. At baseline, cardiovascular involvement was present in 37 patients, including 17 with pulmonary artery hypertension (PAH) and 20 with a left ventricular ejection fraction (LVEF) <55%. At 3years, 32 (7%) patients had died. The median [25th-75th percentile] NT-proBNP concentration was 203ng/l [129-514] in patients who died within 3years, versus 88ng/l [47-167] in survivors (P<0.001). NT-proBNP was an independent predictor of 3-years mortality in multivariate analysis (P=0.046). The optimal cut-off derived from the ROC curve was 129ng/l; sensitivity and specificity to predict 3y mortality were 78.1 and 66.7%. Using the previously recommended 125-ng/l concentration as threshold value, NT-proBNP reliably and independently predicted 3year mortality, with a sensitivity of 78.1 and a negative predictive value of 97.6%, respectively (P=0.006). The consideration of SSc patients without PAH or LVEF<55% at baseline yielded similar results. NT-proBNP appears as a reliable and independent predictor of mortality in patients with SSc. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

PubMed

Elmas, Elif; Doesch, Christina; Fluechter, Stephan; Freundt, Miriam; Weiss, Christel; Lang, Siegfried; Kälsch, Thorsten; Haghi, Dariush; Papassotiriou, Jana; Kunde, Jan; Schoenberg, Stefan O; Borggrefe, Martin; Papavassiliu, Theano

2011-04-01

We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

Electrochemiluminescence quenching of luminol by CuS in situ grown on reduced graphene oxide for detection of N-terminal pro-brain natriuretic peptide.

PubMed

Li, Xiaojian; Lu, Peng; Wu, Bin; Wang, Yaoguang; Wang, Huan; Du, Bin; Pang, Xuehui; Wei, Qin

2018-07-30

A novel electrochemiluminescence (ECL) signal-off strategy based on CuS in situ grown on reduced graphene oxide (CuS-rGO) quenching luminol/H 2 O 2 system was firstly proposed. Luminol was grafted on the surface of Au@Fe 3 O 4 -Cu 3 (PO 4 ) 2 nanoflowers (Luminol-Au@Fe 3 O 4 -Cu 3 (PO 4 ) 2 ) which exhibited excellent catalytic effect towards the reduction of H 2 O 2 to enhance the ECL intensity of luminol. Cu 3 (PO 4 ) 2 nanoflowers showed large surface area which can immobilize more Fe 3 O 4 and Au nanoparticles. The quenching mechanism of CuS-rGO was due to ECL resonance energy transfer (RET). The spectral overlap between fluorescence spectrum of Luminol-Au@Fe 3 O 4 -Cu 3 (PO 4 ) 2 and UV-vis absorption spectrum of CuS-rGO revealed that resonance energy transfer was possible. Au nanoparticles were immobilized on the surface of CuS-rGO to capture secondary antibodies. After a sandwich-type immunoreaction, a remarkable decrease of ECL signal was observed. Under the optimal conditions, the immunosensor showed excellent performance for N-terminal pro-brain natriuretic peptide (NT-proBNP) detection with a wide detection range from 0.5 pg mL -1 to 20 ng mL -1 and a low detection limit of 0.12 pg mL -1 (S/N = 3). The prepared NT-proBNP immunosensor displayed high sensitivity, excellent stability and good specificity. Copyright © 2018 Elsevier B.V. All rights reserved.

N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease

PubMed Central

Tarín, Nieves; Cristóbal, Carmen; Lorenzo, Óscar; Blanco-Colio, Luis; Martín-Ventura, José Luis; Huelmos, Ana; Alonso, Joaquín; Aceña, Álvaro; Pello, Ana; Carda, Rocío; Asensio, Dolores; Mahíllo-Fernández, Ignacio; López Bescós, Lorenzo; Egido, Jesús; Farré, Jerónimo

2015-01-01

Objective Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD). Methods We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death. Results After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol. Conclusions NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings. PMID:26046344

B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

PubMed

Vila, Greisa; Grimm, Gabriele; Resl, Michael; Heinisch, Birgit; Einwallner, Elisa; Esterbauer, Harald; Dieplinger, Benjamin; Mueller, Thomas; Luger, Anton; Clodi, Martin

2012-10-01

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

PubMed Central

Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Falck, John R.; Graves, Joan P.; Zeldin, Darryl C.; Seubert, John M.

2009-01-01

Aims This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). Methods and results Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. Conclusion Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events. PMID:19401302

N-terminal pro-brain natriuretic peptide levels and abnormal geometric patterns of left ventricle in untreated hypertensive patients.

PubMed

Elbasan, Zafer; Gür, Mustafa; Sahin, Durmuş Yıldıray; Kırım, Sinan; Akyol, Selahattin; Kuloğlu, Osman; Koyunsever, Nermin Yıldız; Seker, Taner; Kıvrak, Ali; Caylı, Murat

2014-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts cardiovascular events and mortality in hypertensive patients. Relationship between NT-proBNP level and left ventricular (LV) hypertrophy is well known in hypertensive patients. However, the studies investigating relationship between LV geometric patterns and serum NT-proBNP level have conflicting results and are in a limited number. The goal of the present study is to investigate relation between NT-proBNP and abnormal LV geometric patterns in untreated hypertensive patients. Measurements were obtained from 273 patients with untreated essential hypertension (mean age = 51.7 ± 5.8 years) and 44 healthy control subjects (mean age; 51.3 ± 4.7). Four different geometric patterns (NG: normal geometry; CR: concentric remodelling; EH: eccentric hypertrophy; CH: concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness. NT-proBNP and other biochemical markers were measured in all subjects. The highest NT-proBNP levels were determined in the CH group compared with the control group and other geometric patterns (p < 0.05). NT-proBNP levels of all geometric patterns were higher than the control group (p < 0.05, for all). NT-proBNP levels were similar between CR and NG groups (p > 0.05). NT-proBNP was independently associated with LV geometry (β = 0.304, p = 0.003) and LVMI (β = 0.266, p = 0.007) in multiple linear regression analysis. Serum NT-proBNP level was independently associated with LVMI and LV geometry in untreated hypertensive patients with preserved ejection fraction.

Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells.

PubMed

Fujio, N; Gossard, F; Bayard, F; Tremblay, J

1994-06-01

Two types of natriuretic peptide receptors (NPR-A and NPR-B) are membrane guanylate cyclases whose relative expression varies in different tissues. Because natriuretic peptides have been shown to inhibit aortic smooth muscle proliferation, we investigated the regulation of NPR-A and NPR-B in these cells under different proliferative conditions. NPR subtype mRNA levels were measured by our newly developed quantitative reverse transcription-polymerase chain reaction assay using mutated NPR-A and NPR-B cRNA as internal standards. The functional impact of their expression was determined by atrial natriuretic peptide (ANP)- and C-type natriuretic peptide (CNP)-induced stimulation of cyclic GMP production. In the intact aorta, NPR-B mRNA levels were found to be 10-fold higher than those of NPR-A. This dominance was further amplified (1000-fold) in long-term cultures (10 to 15 passages) of aortic smooth muscle cells (ASMC). Higher cyclic GMP production with CNP than with ANP was observed in cultured ASMC from Wistar-Kyoto (WKY) rats. Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells. The present study also evaluated NPR-A and NPR-B mRNA control by transforming growth factor-beta 1 (TGF-beta 1), an important regulator of cell proliferation that is overexpressed in SHR ASMC. TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

The Association of Menopausal Age and NT-proBrain Natriuretic Peptide: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Ebong, Imo A.; Watson, Karol E.; Goff, David C.; Bluemke, David A.; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G.

2014-01-01

Objective Menopausal age could affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before 45 years of age) and menopausal age with NT-pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure (HF). Methods Our cross-sectional study included 2275 postmenopausal women, aged 45–85 years, without clinical CVD (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Results There were 561 women with early menopause. The median NT-proBNP value was 79.0 (41.1–151.6) pg/ml for all participants with values of 83.4 (41.4–164.9) pg/ml and 78.0 (40.8–148.3) pg/ml for women with and without early menopause respectively. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause respectively. There were no significant interactions between menopausal age and ethnicity. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP while each year increase in menopausal age was associated with a 0.7% decrease in NT-proBNP. Conclusion Early menopause is associated with greater NT-proBNP levels while each year increase in menopausal age is associated with lower NT-proBNP levels in postmenopausal women. PMID:25290536

Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Ebong, Imo A; Watson, Karol E; Goff, David C; Bluemke, David A; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G

2015-05-01

Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women.

Short sleep duration is associated with B-type natriuretic peptide levels and predicts the death of Japanese patients with type 2 diabetes.

PubMed

Hamasaki, Hidetaka; Katsuyama, Hisayuki; Sako, Akahito; Yanai, Hidekatsu

2017-08-01

To investigate the associations of sleep duration with all-cause mortality, glycemic control, and other clinical parameters of patients with type 2 diabetes. From April 2013 to December 2015, we conducted a retrospective cohort study. Study participants were divided into three groups according to their sleep duration. Multiple regression analysis and Cox proportional hazards analysis were performed to assess the independent associations of sleep duration with clinical parameters and all-cause mortality. We enrolled 1233 patients who were then followed for 860 ± 264 days. During the follow-up period, 20 patients (1.6%) died. Sleep duration inversely associated with plasma B-type natriuretic peptide levels (β = -0.203, p = 0.012) in short (<7 h) sleepers, whereas it was positively associated with hemoglobin A1c levels (β = 0.156, p = 0.021) in long (≥9 h) sleepers. Moreover, Cox proportional hazard analysis revealed that short sleep duration was a significant predictor of all-cause mortality (hazard ratio = 0.473; confidence interval 0.248-0.905, p = 0.024). Short sleep duration may serve as a prognostic indicator of mortality in Japanese patients with type 2 diabetes and may increase cardiovascular stress. Adequate sleep is essential for the management of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock.

PubMed

Varpula, Marjut; Pulkki, Kari; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

2007-05-01

The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). A total of 254 patients with severe sepsis or septic shock. After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.

The Effects of Super-Flux (High Performance) Dialyzer on Plasma Glycosylated Pro-B-Type Natriuretic Peptide (proBNP) and Glycosylated N-Terminal proBNP in End-Stage Renal Disease Patients on Dialysis

PubMed Central

Nakagawa, Yasuaki; Nishikimi, Toshio; Kuwahara, Koichiro; Yasuno, Shinji; Kinoshita, Hideyuki; Kuwabara, Yoshihiro; Nakao, Kazuhiro; Minami, Takeya; Yamada, Chinatsu; Ueshima, Kenji; Ikeda, Yoshihiro; Okamoto, Hiroyuki; Horii, Kazukiyo; Nagata, Kiyoshi; Kangawa, Kenji; Minamino, Naoto; Nakao, Kazuwa

2014-01-01

Background Plasma BNP levels are predictive of prognosis in hemodialysis patients. However, recent studies showed that the current BNP immunoassay cross-reacts with glycosylated proBNP, and the NT-proBNP assay underestimates glycosylated NT-proBNP. In addition, the recently developed high performance dialyzer removes medium-sized molecular solutes such as β2-microgloburin. We therefore investigated the effects of high performance dialysis on measured levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related peptides in end-stage renal disease (ESRD) patients on hemodialysis. Method The relationships between clinical parameters and BNP-related molecule were also investigated. We used our newly developed immunoassay to measure plasma total BNP and proBNP in 105 normal subjects and 36 ESRD patients before and after hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with or without deglycosylating enzymes. We also measured plasma ANP and cGMP using radioimmunoassays. Results All the measured BNP-related peptides were significantly higher in ESRD patients than healthy subjects. Total BNP (−38.9%), proBNP (−29.7%), glycoNT-proBNP (−45.5%), nonglycoNT-proBNP (−53.4%), ANP (−50.4%) and cGMP (−72.1%) were all significantly reduced after hemodialysis, and the magnitude of the reduction appeared molecular weight- dependent. Both the proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after hemodialysis. The former correlated positively with hemodialysis vintage and negatively with systolic blood pressure, while the latter correlated positively with parathyroid hormone levels. Conclusion These results suggest that hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly molecular weight-dependent manner. The ProBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related parameters in ESRD patients on hemodialysis. PMID:24667631

[Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

PubMed

Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

2013-01-01

Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

Value of serum N-terminal B-type natriuretic peptide in asymptomatic structural heart disease in Taiwanese population: Comparisons with current ESC Guidelines.

PubMed

Hung, Ta-Chuan; Wang, Kuang-Te; Yun, Chun-Ho; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Liu, Chia-Yuan; Wu, Tung-Hsin; Bezerra, Hiram G; Cheng, Hsiao-Yang; Hung, Chung-Lieh; Yeh, Hung-I

2017-03-15

The relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac structural or functional anomalies in pre-clinical, asymptomatic Asian populations has not been well identified. From October 2005 to March 2008, we enrolled consecutive asymptomatic adults with preserved global left ventricular (LV) function (ejection fraction>50%) who underwent annual cardiovascular health survey. Circulating NT-proBNP was used to identify echo-defined cardiac structural/functional anomalies and compared to current recommended cut-off from the European Society of Heart Failure. Among 976 eligible subjects, 371 (38%) had structural heart diseases. Echocardiography-based left atrial diameter (Coef: 71.2), diastolic dysfunction (Coef: 35.4), and presence of pulmonary hypertension (Coef: 83.1) or valvular heart disease (Coef: 56.1, all p<0.05) of any form independently predicted circulating NT-ProBNP. NT-ProBNP cut-off values of 32.8 and 115.4pg/ml for subjects aged ≤ and >75years, respectively, demonstrated areas under the receiver operating characteristic curve of 0.76 (95% CI: 0.73-0.80) and 0.70 (95% CI: 0.52-0.88) for predicting structural or functional anomaly. We examined the feasibility of NT-ProBNP for identifying cardiac structural and functional anomaly in an asymptomatic ethnic Taiwanese population with a relatively lower cut-off value, indicating its potential role for pre-clinical screening of Asian patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prognostic value of N-terminal pro-brain natriuretic peptide in hospitalised patients with community-acquired pneumonia.

PubMed

Jeong, Ki Young; Kim, Kyuseok; Kim, Tae Yun; Lee, Christopher C; Jo, Si On; Rhee, Joong Eui; Jo, You Hwan; Suh, Gil Joon; Singer, Adam J

2011-02-01

The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with community-acquired pneumonia (CAP) has not been evaluated. The aim of the present study was to investigate whether NT-proBNP level could predict mortality in hospitalised CAP patients. We performed a structured medical record review of all hospitalised CAP patients from May 2003 to October 2006, and classified patients into the 30-day survival and non-survival group. Data included demographic and clinical characteristics, and laboratory findings including NT-proBNP levels. The APACHE II scores, PSI (pneumonia severity index) and CURB65 (confusion, urea, respiratory rate, blood pressure and aged 65 or more) scores were calculated. Comparisons between survivors and non-survivors were made with χ(2), non-parametric tests and logistic regression and ROC analysis were used to compare the ability of NT-proBNP (adjusted for age, heart failure and creatinine), APACHE II, PSI and CURB65 to predict mortality. Of 502 patients, 61 (12.2%) died within 30 days. NT-proBNP levels were measured in 167 patients and were significantly higher in non-survivors compared to survivors (median 841.7 (IQR 267.1-3137.3) pg/ml vs 3658.0 (1863.0-7025.0) pg/ml, p=0.019). NT-proBNP was an independent predictor of mortality (adjusted OR 1.53; 95% CI 1.16 to 2.02, p=0.002). The AUC for NT-proBNP was 0.712 (95% CI, 0.613 to 0.812), which was comparable to those of PSI (0.749, p=0.531) and CURB65 (0.698, p=0.693), but inferior to that of APACHE II (0.831, p=0.037). Adding NT-proBNP to APACHE II, PSI and CURB65 did not significantly increase the AUCs, respectively. NT-proBNP level is an independent predictor of mortality in hospitalised CAP patients. The performance of NT-proBNP level is comparable to those of PSI and CURB65 in predicting mortality.

Blood N-terminal Pro-brain Natriuretic Peptide and Interleukin-17 for Distinguishing Incomplete Kawasaki Disease from Infectious Diseases.

PubMed

Wu, Ling; Chen, Yuanling; Zhong, Shiling; Li, Yunyan; Dai, Xiahua; Di, Yazhen

2015-06-01

To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease. Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared. 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively. Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.

Diagnostic value of N-terminal pro-brain natriuretic peptide for pleural effusion due to heart failure: a meta-analysis.

PubMed

Zhou, Q; Ye, Z J; Su, Y; Zhang, J C; Shi, H Z

2010-08-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker useful in diagnosis of pleural effusion due to heart failure. Thus far, its overall diagnostic accuracy has not been systematically reviewed. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural NT-proBNP for identifying pleural effusion due to heart failure. After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of NT-proBNP concentrations in pleural fluid in the diagnosis of pleural effusion resulting from heart failure were pooled using fixed-effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. Eight publications met the inclusion criteria. The summary estimates for pleural NT-proBNP in the diagnosis of pleural effusion attributable to heart failure were: sensitivity 0.95 (95% CI 0.92 to 0.97), specificity 0.94 (0.92 to 0.96), positive likelihood ratio 14.12 (10.23 to 19.51), negative likelihood ratio 0.06 (0.04 to 0.09) and diagnostic OR 213.87 (122.50 to 373.40). NT-proBNP levels in pleural fluid showed a high diagnostic accuracy and may help accurately differentiate cardiac from non-cardiac conditions in patients presenting with pleural effusion.

N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

PubMed

Fujioka, Kazumichi; Mizobuchi, Masami; Sakai, Hitomi; Iwatani, Sota; Wada, Keiko; Yoshimoto, Seiji; Nakao, Hideto

2014-03-04

Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

N-terminal Pro-brain Natriuretic Peptide, High-sensitivity Troponin and Pulmonary Artery Clot Score as Predictors of Right Ventricular Dysfunction in Echocardiography.

PubMed

Granér, Marit; Harjola, Veli-Pekka; Selander, Tuomas; Laiho, Mia K; Piilonen, Anneli; Raade, Merja; Mustonen, Pirjo

2016-06-01

We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE). Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58±19 years) and without (n=31, age 55±16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission. The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months. Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Impact of tocilizumab on N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis without cardiac symptoms.

PubMed

Yokoe, I; Kobayashi, H; Kobayashi, Y; Giles, J T; Yoneyama, K; Kitamura, N; Takei, M

2018-05-28

To prospectively investigate the effect of tocilizumab (TCZ) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), as a predictor of congestive heart failure (CHF) in patients with active rheumatoid arthritis (RA). Seventy patients with RA (median age 59 years, 86% female) free of cardiovascular disease were treated with TCZ and followed for 24 weeks. The NT-proBNP levels were measured at baseline and week 24. Thirty healthy controls were included for comparison of normal NT-proBNP levels with those of RA patients. The NT-proBNP level was significantly higher in patients with RA than in controls (median 42.5 pg/mL vs 109.0 pg/mL, p < 0.001). NT-proBNP levels decreased by 63% over the 24 weeks of TCZ treatment. Multiple linear regression analysis indicated that the percentage change in the NT-proBNP level was significantly associated with that of the Simplified Disease Activity Index (β = 0.356, p = 0.014), even after adjusting for the levels of rheumatoid factor, duration of RA, age, and anti-cyclic citrullinated peptide antibody. TCZ decreased the NT-proBNP level in patients with RA without preceding cardiovascular disease and CHF. TCZ may have a cardioprotective effect in those with active RA.

Diagnostic value of pleural fluid N-terminal pro-brain natriuretic peptide levels in patients with cardiovascular diseases.

PubMed

Liao, Huai; Na, Moon Jun; Dikensoy, Oner; Lane, Kirk B; Randal, Barnette; Light, Richard W

2008-01-01

The diagnosis of the cause of pleural effusions caused by cardiovascular diseases such as congestive heart failure (CHF) and acute pulmonary embolism is sometimes difficult. The purpose of the present study was to evaluate the utility of pleural fluid levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in differentiating pleural effusions due to CHF, pulmonary embolism and post-coronary artery bypass graft (CABG) surgery. The levels of pleural fluid NT-proBNP were measured by ELISA in a total of 40 patients: 10 with CHF, 10 with pulmonary embolism, 10 post-CABG and 10 with carcinoma. The median level of NT-proBNP in the pleural fluid of patients with CHF was 5390 pg/mL (25th to 75th percentiles, 4566 to 8158 pg/mL), which was significantly higher than that in patients with post-CABG effusions (424 pg/mL, 352 to 873), with pulmonary embolism (311 pg/mL, 212 to 1159), or with carcinoma (302 pg/mL, 208 to 626) (P < 0.001, CHF group vs all other groups). In receiver-operating curve analysis, an NT-proBNP level of >or=2220 pg/mL demonstrated a sensitivity of 100% and a specificity of 96.7% for the identification of CHF. Measurement of the NT-proBNP level in pleural fluid is accurate in diagnosing the etiology of the effusion as CHF. Pleural fluid levels above 2220 pg/mL are essentially diagnostic that the pleural effusion is due to CHF.

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity.

PubMed

Kistorp, Caroline; Bliddal, Henning; Goetze, Jens P; Christensen, Robin; Faber, Jens

2014-01-01

Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = -0.359; P = 0.011) and Δglucose (r = -0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = -0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. Plasma NT-proBNP and MR-pro

Cardiac distribution of the binding sites for natriuretic peptides in vertebrates.

PubMed

Cerra, M C

1994-12-01

Natriuretic peptides are hormones that play an important role in the cardiovascular control of mammalian and non-mammalian vertebrates. They have been classified into four groups. Of these, ANP (atrial natriuretic peptide), BNP (brain atriuretic peptides), CNP (C-type natriuretic peptide) are detected in cardiac and non cardiac tissues of all vertebrates; while VNP (ventricular natriuretic peptide) has been isolated only from the fish ventricle. All peptides have shown a high degree of sequence homology. The expression of the three principal types of natriuretic peptide (ANP, BNP and CNP) in cardiac tissues is developmentally and functionally regulated in a highly tissue-specific manner. Three types of natriuretic peptide receptors have been identified in numerous target tissues. Two receptors are transmembrane guanylyl cyclases (ANPR-A and ANPR-B) that mediate biological effects of natriuretic peptides; the third one (ANPR-C) has no guanylyl cyclase and is called "clearance receptor." The presence of natriuretic peptide binding sites in the heart suggests new aspects of paracrine control of cardiac function. A relevant localization of natriuretic peptide receptors was found in those cardiac regions particularly suitable for monitoring blood volume and pressure oscillations such as the inflow tract and the outflow tract. For example, in birds (quail) the highest levels of natriuretic peptide receptors were detected in the inflow tract represented by the vena cava. In both fish and birds, the outflow chamber, the bulbus cordis, had a high number of natriuretic peptide binding sites. In mammals, a remarkable concentration of natriuretic peptide receptors was also observed in the coronary vessels. This zoning of cardiac natriuretic peptide receptors indicates an intracardiac action of the hormones and adds a humoral dimension to the morphofunctional design of the vertebrate heart.

Behavior of B-type natriuretic peptide during mechanical ventilation and spontaneous breathing after extubation.

PubMed

Principi, T; Falzetti, G; Elisei, D; Donati, A; Pelaia, P

2009-04-01

The behavior of B-type natriuretic peptide (BNP) is assessed during mechanical ventilation (MV) and spontaneous breathing after extubation in critical patients. Thirty patients admitted in the Intensive Care Unit (ICU) were enrolled. BNP, fluid balance (FB), airway pressure (AP) and dobutamine infusion needing (DP) were registered in three stages: T0, admission to ICU; T1, before extubation; T2, 24 h after extubation. Patients with congestive heart failure (CHF) had BNP values higher than other patients. The value of BNP during MV was greater than normal in all patients. The cut-off to discriminate patients with heart failure during MV was 286 pgxmL(-1)(sensitivity: 86%; specificity: 90%). The increase of BNP during MV directly correlated with FB and inversely correlated with AP and DP. The plasmatic level of BNP remained higher than normal values 24 h after extubation. The underlying disease of an ICU patient seems to play a relevant role for BNP production and is probably linked to different aspects of therapeutic approach required by the patient. Our data suggest a cut-off value of BNP higher than the usual is necessary to discriminate mechanically-ventilated patients without CHF. This study should be repeated with an enlarged population.

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

PubMed

Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

2014-10-15

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

NT-pro-BNP is associated with inducible myocardial ischemia in mildly symptomatic type 2 diabetic patients.

PubMed

Wiersma, Jacobijne J; van der Zee, P Marc; van Straalen, Jan P; Fischer, Johan C; van Eck-Smit, Berthe L F; Tijssen, Jan G P; Trip, Mieke D; Piek, Jan J; Verberne, Hein J

2010-11-19

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (p<0.001). In addition, NT-pro-BNP ≥180 pg/ml was an independent predictor of the presence of myocardial ischemia (OR 2.36, 95%CI 1.40-3.97, p=0.001). Possible confounding factors such as age and creatinine clearance were of no influence on the predictive value in this specific patient population. These findings strengthen the idea that NT-pro-BNP may be of value in the early detection of diabetic patients with hemodynamic significant coronary artery disease. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

N-terminal fragment of probrain natriuretic peptide is associated with diabetes microvascular complications in type 2 diabetes.

PubMed

Hamano, Kumiko; Nakadaira, Ikue; Suzuki, Jun; Gonai, Megumi

2014-01-01

Circulating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes. In total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications. Mean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001). In this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP.

PubMed

Chien, Tzu-I; Chen, Hui-Hou; Kao, Jau-Tsuen

2006-07-15

B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP=7.23xAxSYM BNP+2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 degrees Celsius or 25 degrees Celsius for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.

Time course and prognostic value of plasma levels of N-terminal pro-brain natriuretic peptide in patients after ischemic stroke.

PubMed

Yip, Hon-Kan; Sun, Cheuk-Kwan; Chang, Li-Teh; Chen, Mien-Cheng; Liou, Chia-Wei

2006-04-01

The association between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognostic outcomes in patients after ischemic stroke remains unknown. The present study tested the hypothesis that NT-proBNP level is noticeably increased after ischemic stroke and that elevated NT-proBNP is associated with unfavorable clinical outcomes (UFCO). Blood samples for NT-proBNP levels were collected serially and examined with sandwich immunoassay after acute ischemic stroke in 86 consecutive patients. The NT-proBNP levels were also measured in 30 healthy control volunteers and 30 at-risk control subjects. The NT-proBNP levels were significantly higher at 4 intervals after ischemic stroke than in healthy and at-risk control subjects (all p<0.001). The NT-proBNP decreased to a significantly lower level on day 21 and to a substantially lower level on day 90. Additionally, the NT-proBNP level at any of the 4 intervals was significantly higher in patients with than in patients without UFCO (defined as combined congestive heart failure > or = class 3, acute myocardial infarction, recurrent stroke or any cause of death) (all p<0.01). Multivariate analysis demonstrated that age and NIH Stroke Scale were the 2 strongest independent predictors of increased NT-proBNP levels (all p<0.01). Furthermore, increased NT-proBNP (> or = 150 pg/ml) was the strongest independent predictor of long-term (mean follow-up: 24 months) UFCO (26 patients) (all p<0.05). The NT-proBNP level was markedly elevated after acute ischemic stroke and declined substantially thereafter. An increased NT-proBNP level was strongly and independently correlated with UFCO in patients after ischemic stroke.

Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

PubMed Central

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-01-01

Background Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in

Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study.

PubMed

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-05-21

Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population. © 2015 The Authors. Published on

Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

PubMed

Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

2008-03-01

Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes <35 years old, who were examined immediately after exercising as well as 2 days later, 21 age-matched male patients classified as stage-B according to ACC/AHA guidelines and 35 healthy age-matched males, we evaluated NT-proBNP and 3rd generation's cTnT by electrochemiluminescence immunoassay. All participants underwent a detailed cardiac protocol including echocardiography and electrocardiogram (ECG). In athletes, cTnT consistently remained <0.01 mg/L after exercising as well as after 2 days. NTproBNP immediately after exercising was 58.27+/-19.48 ng/L, without reaching pathological levels, decreasing 2 days later to 22.93+/-10.22 ng/L. Our patients maintained high levels of NTproBNP, as much as a six-fold increase with reference to the levels of our study's control group and with cTnT <0.01 mg/L. In the control group, cTnT and NTproBNP levels were statistically similar with those of the athletes 2 days after exercising. NT-proBNP as a biological marker can reliably discriminate pathological from physiological cardiac hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

The role of N-terminal PRO-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study.

PubMed

Betti, Irene; Castelli, Gabriele; Barchielli, Alessandro; Beligni, Cinzia; Boscherini, Vittorio; De Luca, Leonardo; Messeri, Gianni; Gheorghiade, Mihai; Maisel, Alan; Zuppiroli, Alfredo

2009-06-01

Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care. A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 +/- 206 and 859 +/- 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 +/- 169 in normal subjects (P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity [Sens] 87.5%, specificity [Spec] 92.7%, negative predictive value [NPV] 99.5%, positive predictive value [PPV] 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males >or=67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females >or=67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%). The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.

Use of N-terminal prohormone brain natriuretic peptide assay for etiologic diagnosis of acute dyspnea in elderly patients.

PubMed

Berdagué, Philippe; Caffin, Pierre-Yves; Barazer, Isabelle; Vergnes, Christine; Sedighian, Shahin; Letrillard, Sébastien; Pilossof, Romain; Goutorbe, Frédéric; Piot, Christophe; Reny, Jean-Luc

2006-03-01

B-type peptide assay (brain natriuretic peptide [BNP] and N-terminal prohormone brain natriuretic peptide [NT-proBNP]) is useful for the diagnosis of heart failure (HF), but few data are available on the use of these markers in elderly subjects. The aim of this study was to evaluate NT-proBNP assay for the diagnosis of acute left HF in patients older than 70 years hospitalized for acute dyspnea. We prospectively enrolled 256 elderly patients with acute dyspnea. They were categorized by 2 cardiologists unaware of NT-proBNP values into a cardiac dyspnea subgroup (left HF) and a noncardiac dyspnea subgroup (all other causes). Mean age was 81 +/- 7 years, and 52% of the patients were women. The diagnoses made in the emergency setting were incorrect or uncertain in 45% of cases. The median NT-proBNP value was higher (P < .0001) in patients with cardiac dyspnea (n = 142; 7906 pg/mL) than in patients with noncardiac dyspnea (n = 112; 1066 pg/mL). The area under the receiver operating characteristic curve was 0.86 (95% CI 0.81-0.91). At a cutoff of 2000 pg/mL, NT-proBNP had a sensitivity of 86%, a specificity of 71%, and an overall accuracy of 80% for cardiac dyspnea. The use of 2 cutoffs (< 1200 and > 4500 pg/mL) resulted in an 8% error rate and a gray area englobing 32% of values. NT-proBNP appears to be a sensitive and specific means of distinguishing pulmonary from cardiac causes of dyspnea in elderly patients. An optimal diagnostic strategy requires the use of 2 cutoffs and further investigations of patients with values in the gray area.

Excessive Adiposity and Metabolic Dysfunction Relate to Reduced Natriuretic Peptide During RAAS Activation in HIV.

PubMed

Murphy, Caitlin A; Fitch, Kathleen V; Feldpausch, Meghan; Maehler, Patrick; Wong, Kimberly; Torriani, Martin; Adler, Gail K; Grinspoon, Steven K; Srinivasa, Suman

2018-02-01

Natriuretic peptides (NPs) negatively feedback on the renin-angiotensin-aldosterone system (RAAS) and play a critical role in preserving cardiac structure and maintaining metabolic homeostasis. Well-treated HIV-infected individuals are at risk for fat redistribution and demonstrate evidence of RAAS dysregulation, which relates to metabolic dysfunction. We investigated circulating NPs in relation to RAAS physiology and metrics of body composition for the first time in HIV. We assessed atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and amino terminal pro B-type natriuretic peptide (NT-proBNP) during acute activation of the RAAS using a low sodium controlled diet among 20 HIV-infected and 10 non-HIV-infected individuals well-phenotyped for body composition. BNP(60[44,152] vs. 196[91,251], P=.04) was significantly lower and serum aldosterone higher among HIV-infected vs. non-HIV-infected individuals. BNP was significantly and inversely associated with body composition [waist circumference(r=-0.46, P=.04), BMI(r=-0.55, P=.01), body adiposity index (r=-0.49, P=.03)], metabolic indices [total cholesterol(r=-0.44, P=.05), HOMA-IR(r=-0.44, P=.05), MAP (r=-0.44, P=.05)], and serum aldosterone(r=-0.49,P=.03) among the HIV group. These relationships were not demonstrated in the non-HIV group. In a four-group comparison stratifying by HIV serostatus and above/below BMI 25 kg/m2, BNP decreased significantly across groups, being highest in non-HIV with BMI<25 kg/m2 and lowest in HIV with BMI >25 kg/m2 (overall P=.01). Relatively reduced NP, particularly BNP, among HIV-infected individuals with excess adiposity may contribute to reduced suppression of aldosterone and potentially drive aldosterone-mediated metabolic complications. Novel strategies which target RAAS blockade and/or augment NPs may be potentially useful to reduce cardiometabolic disease among HIV-infected individuals in whom these systems are perturbed. Copyright © 2018 Endocrine Society

B-type natriuretic peptide levels in patients with pericardial effusion undergoing pericardiocentesis.

PubMed

Lauri, Gianfranco; Rossi, Chiara; Rubino, Mara; Cosentino, Nicola; Milazzo, Valentina; Marana, Ivana; Cabiati, Angelo; Moltrasio, Marco; De Metrio, Monica; Grazi, Marco; Campodonico, Jeness; Assanelli, Emilio; Riggio, Daniela; Sandri, Maria Teresa; Bonomi, Alice; Veglia, Fabrizio; Marenzi, Giancarlo

2016-06-01

Pericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. We prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0-2), intermediate (3-4), or high (5-7) severity score. Out of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=-0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). The results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

N-terminal pro-brain natriuretic peptide and associated factors in the general working population: a baseline survey of the Uranosaki cohort study.

PubMed

Tanaka, Atsushi; Yoshida, Hisako; Kawaguchi, Atsushi; Oyama, Jun-Ichi; Kotooka, Norihiko; Toyoda, Shigeru; Inoue, Teruo; Natsuaki, Masafumi; Node, Koichi

2017-07-19

Few data on clinical characteristics associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) or the clinical value of measuring NT-proBNP in the working population are available. The aim of the present study was to investigate the levels of NT-proBNP and their association with clinical variables in the Japanese general working population by using baseline data from the Uranosaki cohort study. In the study, the plasma concentration of NT-proBNP and some biomarkers were measured in addition to the standard health checkups at the workplace. Questionnaires regarding health-related quality of life (HR-QOL) were also completed. A total of 2140 participants were enrolled in the study. Plasma levels of NT-proBNP were positively associated with age, female sex, systolic blood pressure, pulse pressure, prevalent hypertension, smoking habit, high-density lipoprotein cholesterol (HDL-C), and prevalent proteinuria, and negatively associated with body mass index, lipid profiles except HDL-C, uric acid, renal function, and hemoglobin. Both the plasma concentration of high-molecular weight adiponectin and that of high-sensitivity troponin T were positively and independently associated with NT-proBNP. In addition, the HR-QOL score regarding sleep disorder was independently associated with NT-proBNP. Thus, we have obtained evidence that the plasma NT-proBNP is affected by several clinical variables in the general working population.

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

PubMed Central

Cheng, Juan-Juan; Zhao, Shi-Di; Gao, Ming-Zhu; Huang, Hong-Yu; Gu, Bing; Ma, Ping; Chen, Yan; Wang, Jun-Hong; Yang, Cheng-Jian; Yan, Zi-He

2015-01-01

Background Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion. Methods PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model. Results In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies. Conclusions BNP, NT-proBNP, and MR-proANP, either in blood

Endothelial C-type natriuretic peptide maintains vascular homeostasis

PubMed Central

Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

2014-01-01

The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

B-type natriuretic peptide-guided treatment for heart failure.

PubMed

McLellan, Julie; Heneghan, Carl J; Perera, Rafael; Clements, Alison M; Glasziou, Paul P; Kearley, Karen E; Pidduck, Nicola; Roberts, Nia W; Tyndel, Sally; Wright, F Lucy; Bankhead, Clare

2016-12-22

Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a clinical outcome were included. Two review authors

The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting.

PubMed

Roberts, Emmert; Ludman, Andrew J; Dworzynski, Katharina; Al-Mohammad, Abdallah; Cowie, Martin R; McMurray, John J V; Mant, Jonathan

2015-03-04

To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure. Systematic review and diagnostic meta-analysis. Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides. Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded. 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0.90-0.98) to 0.97 (0.95-0.98) and a negative predictive value ranging from 0.90 (0

NT-pro Brain Natriuretic Peptide Levels and the Risk of Death in the Cooperative Study of Sickle Cell Disease

PubMed Central

Machado, Roberto F.; Hildesheim, Mariana; Mendelsohn, Laurel; Remaley, Alan T.; Kato, Gregory J.; Gladwin, Mark T.

2011-01-01

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160 ng/l was present in 27.6 % of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0.001), high lactate dehydrogenase (P<0.001), and high total bilirubin levels (P<0.007). A NT-proBNP level ≥160 ng/l was an independent predictor of mortality (RR 6.24, 95% CI 2.9–13.3, P<0.0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population. PMID:21689089

NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease.

PubMed

Machado, Roberto F; Hildesheim, Mariana; Mendelsohn, Laurel; Remaley, Alan T; Kato, Gregory J; Gladwin, Mark T

2011-08-01

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population. © 2011 Blackwell Publishing Ltd.

Soluble ST2 and N-terminal pro-brain natriuretic peptide combination. Useful biomarker for predicting outcome of childhoodpulmonary arterial hypertension.

PubMed

Chida, Ayako; Sato, Hiroki; Shintani, Masaki; Nakayama, Tomotaka; Kawamura, Yoichi; Furutani, Yoshiyuki; Inai, Kei; Saji, Tsutomu; Matsuoka, Rumiko; Nonoyama, Shigeaki; Nakanishi, Toshio

2014-01-01

Some potential biomarkers have been reported recently in patients with pulmonary arterial hypertension (PAH), but the most clinically useful among these potential biomarkers, especially in childhood PAH, has not been identified. Therefore, this study investigated which biomarker is useful in assessing severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable PAH (HPAH). Fifty-nine patients who were younger than 16 years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates were quantified: high-sensitivity troponin T, human heart fatty acid-binding protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3, soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated well with New York Heart Association class. On area under the receiver operating characteristic curve analysis, sST2 had a significantly good relationship with prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated sST2 and NT-proBNP level predicted poor outcome of the present patients with childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP. The sST2 and NT-proBNP combination is a useful biomarker to predict clinical condition and outcome in patients with childhood IPAH/HPAH.  

Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease.

PubMed

Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete; Jensen, Gorm B; Mogelvang, Rasmus

2015-12-15

Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease. Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. ECG changes were present in 907 persons and were associated with high levels of pro-BNP. In a fully adjusted model both high pro-BNP and ECG changes remained significant predictors: all-cause mortality(high pro-BNP, no ECG changes: HR: 1.43(1.12-1.82);P=0.005, low pro-BNP, ECG changes: HR: 1.22(1.05-1.42);P=0.009, and both high pro-BNP and ECG changes: HR: 1.99(1.54-2.59);P<0.001), CVD event(high pro-BNP, no ECG changes: HR: 1.94(1.45-2.58);P<0.001, low pro-BNP, ECG changes: HR: 1.55(1.29-1.87);P<0.001, and both high pro-BNP and ECG changes: HR: 3.86(2.94-5.08);P<0.001). Adding the combination of pro-BNP and ECG changes to a fully adjusted model correctly reclassified 33.9%(26.5-41.3);P<0.001 on the continuous net reclassification scale for all-cause mortality and 49.7%(41.1-58.4);P<0.001 for CVD event. Combining ECG changes and pro-BNP improves risk prediction in persons without known heart disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

PubMed

Adlbrecht, Christopher; Hülsmann, Martin; Strunk, Guido; Berger, Rudolf; Mörtl, Deddo; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Jakowitsch, Johannes; Maurer, Gerald; Lang, Irene M; Pacher, Richard

2009-04-01

The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

Pro-Brain Natriuretic Peptide and Troponin T-Hypersensitivity Levels Correlate With the Severity of Liver Dysfunction in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Li, Sai; Ren, Linan; Guo, Xiaozhong; Qi, Xingshun

2017-08-01

Increased pro-brain natriuretic peptide (pro-BNP) or troponin T-hypersensitivity (TnT-HSST) levels are common in liver cirrhosis. We conducted a retrospective observational study aimed to evaluate the correlation of pro-BNP and TnT-HSST levels with the clinical characteristics, laboratory data and in-hospital outcomes of patients with liver cirrhosis. We selected cirrhotic patients admitted to our hospital between January 2011 and June 2014. All eligible patients had pro-BNP or TnT-HSST data, or both. The pro-BNP and TnT-HSST data were further divided according to the presence of cardiac diseases. The prevalence of pro-BNP level >900pg/mL was 41.72% (63 of 151 patients). The prevalence of TnT-HSST level >0.05ng/mL was 11.22% (45 of 401 patients). In the overall analysis, pro-BNP level significantly correlated with red blood cell (RBC), platelet, ascites, blood urea nitrogen (BUN), creatinine (Cr), Child-Pugh score, model for end-stage liver disease (MELD) score and in-hospital death; TnT-HSST level significantly correlated with white blood cell, ascites, albumin (ALB), BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients with cardiac diseases, pro-BNP level significantly correlated with RBC, ascites, BUN, Cr, Child-Pugh score and MELD score; TnT-HSST level significantly correlated with sex, ascites, white blood cell, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients without cardiac diseases, pro-BNP level significantly correlated with ascites, RBC, platelet, BUN, Cr, MELD score and in-hospital death; TnT-HSST level significantly correlated with age, ascites, RBC, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. Pro-BNP and TnT-HSST levels significantly correlated with the severity of liver dysfunction and in-hospital mortality in cirrhosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Sandwich-Type Electrochemiluminescence Sensor for Detection of NT-proBNP by Using High Efficiency Quench Strategy of Fe3O4@PDA toward Ru(bpy)32+ Coordinated with Silver Oxalate.

PubMed

Shi, Li; Li, Xiaojian; Zhu, Wenjuan; Wang, Yaoguang; Du, Bin; Cao, Wei; Wei, Qin; Pang, Xuehui

2017-12-22

Heart failure (HF) is a burgeoning public health problem trigged by a heart circulation disorder. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been acknowledged as a prognostic biomarker for cardiac disease. Herein, a sandwich-type electrochemiluminescence (ECL) immunosensor was introduced for sensitive detection of NT-proBNP. Gold nanoparticle modified graphene oxide-Ru(bpy) 3 2+ /Ag 2 C 2 O 4 was used as a luminophore and a desirable platform for immobilization of the captured antibodies. The more stable immobilization of plentiful Ru(bpy) 3 2+ could be implemented by direct covalent bonding chelation with Ag 2 C 2 O 4 . More importantly, significant quenching can be achieved by introducing polydopamine (PDA) coated Fe 3 O 4 onto the electrode via sandwich immunoreactions. The quenching mechanism mainly showed that the excited states of Ru(bpy) 3 2+ could be annihilated by quinone units in PDA via energy transfer. The ECL quenching efficiency was logarithmically related to the concentration of the NT-proBNP in the range from 0.0005 ng/mL to 100.0 ng/mL with a detection limit of 0.28 pg/mL. Furthermore, this specific immunosensor presented good stability and repeatability as well as selectivity, which offers a guiding significance in both fundamental and clinical diagnosis of NT-proBNP.

Sacubitril/valsartan: beyond natriuretic peptides.

PubMed

Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

2017-10-01

Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study.

PubMed

Morgenthaler, Nils G; Struck, Joachim; Christ-Crain, Mirjam; Bergmann, Andreas; Müller, Beat

2005-02-01

Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization.

PubMed

Nagai-Okatani, Chiaki; Kangawa, Kenji; Minamino, Naoto

2017-07-01

Atrial natriuretic peptide (ANP) is primarily produced in the heart tissue and plays a pivotal role in maintaining cardiovascular homeostasis in endocrine and autocrine/paracrine systems and has clinical applications as a biomarker and a therapeutic agent for cardiac diseases. ANP is synthesized by atrial cardiomyocytes as a preprohormone that is processed by a signal peptidase and stored in secretory granules as a prohormone. Subsequent proteolytic processing of ANP by corin during the secretion process results in a bioactive form consisting of 28 amino acid residues. Mechanical stretch of the atrial wall and multiple humoral factors directly stimulates the transcription and secretion of ANP. Secreted ANP elicits natriuretic and diuretic effects via cyclic guanosine monophosphate produced through binding to the guanylyl cyclase-A/natriuretic peptide receptor-A. Circulating ANP is subjected to rapid clearance by a natriuretic peptide receptor-C-mediated mechanism and proteolytic degradation by neutral endopeptidase. In humans, ANP is present as three endogenous molecular forms: bioactive α-ANP, a homodimer of α-ANP designated as β-ANP, and an ANP precursor designated as proANP (also referred to as γ-ANP). The proANP and especially β-ANP, as minor forms in circulation, are notably increased in patients with cardiac diseases, suggesting the utility of monitoring the pathophysiological conditions that result in abnormal proANP processing that cannot be monitored by inactive N-terminal proANP-related fragments. Emerging plate-based sandwich immunoassays for individual quantitation of the three ANP forms enables evaluation of diagnostic implications and net ANP bioactivity. This new tool may provide further understanding in the pathophysiology of cardiac diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Natriuretic peptides buffer renin-dependent hypertension.

PubMed

Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

2014-06-15

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II. Copyright © 2014 the American Physiological Society.

Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomeruli.

PubMed

Itoh, K; Nonoguchi, H; Shiraishi, N; Tomita, K

1999-01-01

Atrial natriuretic peptide (ANP) has three types of receptor. We investigated the gene regulation of three types of ANP receptors (ANPR-A, B, and C) in rat glomeruli using reverse transcription coupled with competitive polymerase chain reaction (PCR). Competitive PCR revealed that ANPR-C mRNA expression was most abundant (ANPR-C > A > B) in glomeruli from control rats among mRNA expressions of three receptors, which were 20- to 15,000-fold higher than those in inner medullary collecting ducts. Two days' dehydration caused reversible decreases of ANPR-A, B, and C mRNAs by 50-80%. To determine the mechanisms of down-regulation of mRNA expression, isolated glomeruli were incubated in isotonic or hypertonic solution. Hyperosmolality induced by NaCl, mannitol or raffinose caused significant increases of ANPR-A, B, and C mRNA expression. Hypertonicity by urea showed smaller effects. ANP stimulated the expression of ANPR-A, B, and C mRNA in vitro. These results indicate that dehydration caused reversible decreases of ANPR-A, B, and C mRNA expression in glomeruli, and these decreases were not caused by increased plasma osmolality but probably by lower circulating levels of ANP.

Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure.

PubMed

Wu, Alan H B; Smith, Andrew

2004-03-15

B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.

Cardio-adipose tissue cross-talk: relationship between adiponectin, plasma pro brain natriuretic peptide and incident heart failure.

PubMed

Lindberg, Søren; Jensen, Jan Skov; Bjerre, Mette; Pedersen, Sune H; Frystyk, Jan; Flyvbjerg, Allan; Mogelvang, Rasmus

2014-06-01

There is increasing evidence of cross-talk between the heart, body metabolism, and adipose tissue, but the precise mechanisms are poorly understood. Natriuretic peptides (NPs) have recently emerged as the prime candidate for a mediator. In patients with heart failure (HF), infusion of NPs increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF. We prospectively followed 5574 randomly selected men and women from the community without ischaemic heart disease or HF. Plasma adiponectin and proBNP were measured at study entry. Median follow-up time was 8.5 years (interquartile range 8.0-9.1 years). During follow-up 271 participants developed symptomatic HF. Plasma adiponectin and proBNP were strongly associated (P < 0.001). Participants with increasing adiponectin had increased risk of incident HF (P < 0.001). After adjustment for confounding risk factors (including age, gender, smoking status, body mass ratio, waist-hip ratio, glucose, glycated haemoglobin, systolic and diastolic blood pressure, lipid profile, high sensitivity C-reactive protein, estimated glomerular filtration rate, and physical activity) by Cox regression analysis, adiponectin remained an independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD) increase in adiponectin was 1.20 [95% confidence interval (CI) 1.06-1.30; P = 0.003]. However, the association vanished when plasma proBNP was included in the analysis, HR 1.08 (95% CI 0.95-1.23; P = 0.26). In conclusion, plasma adiponectin and proBNP are strongly associated. Increasing plasma adiponectin is associated with increased risk of HF. However, concomitantly elevated proBNP levels appear to explain the positive association between adiponectin and risk of HF. © 2014 The Authors. European Journal of Heart Failure © 2014

Brain natriuretic peptide and insulin resistance in older adults.

PubMed

Kim, F; Biggs, M L; Kizer, J R; Brutsaert, E F; de Filippi, C; Newman, A B; Kronmal, R A; Tracy, R P; Gottdiener, J S; Djoussé, L; de Boer, I H; Psaty, B M; Siscovick, D S; Mukamal, K J

2017-02-01

Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. © 2016 Diabetes UK.

Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction.

PubMed

Adrish, Muhammad; Nannaka, Varalaxmi Bhavani; Cano, Edison J; Bajantri, Bharat; Diaz-Fuentes, Gilda

2017-01-01

B-type natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP (NT-pro-BNP) are established biomarkers of heart failure. Increased levels of natriuretic peptide (NP) have been associated with poor outcomes in acute exacerbation of COPD (AECOPD); however, most studies did not address the conditions that can also increase NT-pro-BNP levels. We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels. We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction. We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data. A total of 167 of 1,420 (11.7%) patients met the study criteria. A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels ( P =0.0031). NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses. Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure ( r =0.3658; 95% confidence interval [CI]: 0.2060-0.5067; P <0.0001). Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P =0.0207) and had a longer hospital length of stay ( P =0.0052). There were no differences in the need for noninvasive positive pressure ventilation ( P =0.1245) or mechanical ventilation ( P =0.9824) or in regard to in-hospital mortality ( P =0.5273). Patients with AECOPD and elevated NT-pro-BNP levels had increased hospital length of stay and need for intensive care. Based on our study, serum NT-pro-BNP levels cannot be used as a biomarker for increased mortality or requirement for invasive or noninvasive ventilation in this group of patients.

N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

PubMed

Tesic, Milorad; Seferovic, Jelena; Trifunovic, Danijela; Djordjevic-Dikic, Ana; Giga, Vojislav; Jovanovic, Ivana; Petrovic, Olga; Marinkovic, Jelena; Stankovic, Sanja; Stepanovic, Jelena; Ristic, Arsen; Petrovic, Milan; Mujovic, Nebojsa; Vujisic-Tesic, Bosiljka; Beleslin, Branko; Vukcevic, Vladan; Stankovic, Goran; Seferovic, Petar

2017-10-01

The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

B-type natriuretic peptide (BNP) serum levels in rats after forced repeated swimming stress.

PubMed

Hadzovic-Dzuvo, Almira; Valjevac, Amina; Avdagić, Nesina; Lepara, Orhan; Zaćiragić, Asija; Jadrić, Radivoj; Alajbegović, Jasmin; Prnjavorac, Besim

2011-02-01

To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n = 8) and stress group (n = 8). Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep) containing tap water (temperature ca. 25 degrees C). The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the first day to 40 minutes on days 6 and 7. Rats were sacrificed and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.). There was no statistically significant difference between mean BNP serum level in the stress group after the swimming period (0.81 +/- 0.14 ng/ml) as compared to the unstressed group of rats (0.8 +/- 0.08 ng/ml). After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs. 272.8 g), but this difference was not statistically significant. The stress period had no influence on food intake in the stress rat group. The workload consisting of 40-minutes long swimming session is not sufficient to provoke BNP release from myocardium in rats.

NT-proBNP concentrations in mountain marathoners.

PubMed

Banfi, Giuseppe; Lippi, Giuseppe; Susta, Daniele; Barassi, Alessandra; D'Eril, Gianvico Melzi; Dogliotti, Giada; Corsi, Massimiliano M

2010-05-01

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

PubMed

Cheng, Hui; Fan, Wei-Ze; Wang, Sheng-Chi; Liu, Zhao-Hui; Zang, Hui-Ling; Wang, Li-Zhong; Liu, Hong-Juan; Shen, Xiao-Hui; Liang, Shao-Qing

2015-06-01

Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05) were significantly higher in the deceased group than those in the survived group. The predicting mortality of APACHE-II score alone was low but largely improved, when it was combined with both NT-proBNP and cTnI (P < .05). The alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in elderly patients with severe sepsis or septic shock. N-terminal pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between N-Terminal Pro-Brain Natriuretic Peptide, Obesity and the Risk of Heart Failure in Middle-Aged German Adults

PubMed Central

Wirth, Janine; Buijsse, Brian; di Giuseppe, Romina; Fritsche, Andreas; Hense, Hans W.; Westphal, Sabine; Isermann, Berend; Boeing, Heiner; Weikert, Cornelia

2014-01-01

Background Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. Methods A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). Results Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49–4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85–3.49), 2.72 (1.42–5.22), and for obese: 3.29 (1.04–10.40), reference, 3.74 (1.52–9.21). Conclusions Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms. PMID:25423197

Relationship between N-terminal pro-brain natriuretic peptide, obesity and the risk of heart failure in middle-aged German adults.

PubMed

Wirth, Janine; Buijsse, Brian; di Giuseppe, Romina; Fritsche, Andreas; Hense, Hans W; Westphal, Sabine; Isermann, Berend; Boeing, Heiner; Weikert, Cornelia

2014-01-01

Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49-4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85-3.49), 2.72 (1.42-5.22), and for obese: 3.29 (1.04-10.40), reference, 3.74 (1.52-9.21). Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

Utility of natriuretic peptides to assess and manage patients with heart failure receiving angiotensin receptor blocker/neprilysin inhibitor therapy.

PubMed

Maisel, Alan S; Daniels, Lori B; Anand, Inder S; McCullough, Peter A; Chow, Sheryl L

2018-04-01

Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

PubMed

Voroneanu, Luminita; Siriopol, Dimitrie; Apetrii, Mugurel; Hogas, Simona; Onofriescu, Mihai; Nistor, Ionut; Kanbay, Mehmet; Dumea, Raluca; Cusai, Silvia; Cianga, Petru; Constantinescu, Daniela; Covic, Adrian

2018-05-01

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Growth-differentiation factor-15, endoglin and N-terminal pro-brain natriuretic peptide induction in athletes participating in an ultramarathon foot race.

PubMed

Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis

2009-09-01

We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise.

Novel biomarkers in acute heart failure: MR-pro-adrenomedullin.

PubMed

Peacock, W Frank

2014-10-01

First isolated from human pheochromocytoma cells, adrenomedullin (ADM) is a peptide hormone with natriuretic, vasodilatory, and hypotensive effects mediated by cyclic adenosine monophosphate (cAMP), nitric oxide, and renal prostaglandin systems. ADM expression occurs in many tissues and organ systems, including cardiovascular, renal, pulmonary, cerebrovascular, gastrointestinal, and endocrine tissues where it acts as a circulating hormone and a local autocrine and paracrine hormone. ADM plasma concentrations are increased in hypertension, chronic renal disease, and heart failure. As ADM is unstable in vitro, it is necessary to measure its mid-regional pro-hormone fragment, the levels of which correspond to ADM concentration (MR-proADM). The prognostic potential of MR-proADM was recently demonstrated in the Biomarkers in Acute Heart Failure (BACH) trial. In this trial of 568 acute heart failure patients, MR-proADM was superior to both brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality within 14 days. MR-proADM also provided significant additive incremental predictive value for 90-day mortality when added to BNP and NT-proBNP.

[The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery].

PubMed

Baysal, Ayse; Saşmazel, Ahmet; Yildirim, Ayse; Ozyaprak, Buket; Gundogus, Narin; Kocak, Tuncer

2014-01-01

In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72h, (2) intensive care unit stay >7days, and (3) mortality. The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n=35, n=16, respectively) showed significant differences in repeated measurement time points (p=0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5pgmL-1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r=0.67, p=0.0001). In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5pgmL-1 are at risk of developing low cardiac output syndrome which is an important postoperative outcome. Copyright © 2013 Sociedade

Biomarkers and diagnostics in heart failure.

PubMed

Gaggin, Hanna K; Januzzi, James L

2013-12-01

Heart failure (HF) biomarkers have dramatically impacted the way HF patients are evaluated and managed. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and studies on natriuretic peptide-guided HF management look promising. An array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation and remodeling. Novel biomarkers, such as mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), highly sensitive troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and Galectin-3, show potential in determining prognosis beyond the established natriuretic peptides, but their role in the clinical care of the patient is still partially defined and more studies are needed. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

PubMed

Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

2017-06-01

Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure.

PubMed

De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Bhardwaj, Anju; Parry, Blair A; Nagurney, John T; Coudriou, Charles; Legrand, Matthieu; Sadoune, Malha; Di Somma, Salvatore; Januzzi, James L

2015-03-01

In order to predict the occurrence of worsening renal function (WRF) and of WRF plus in-hospital death, 101 emergency department (ED) patients with acute decompensated heart failure (ADHF) were evaluated with testing for amino-terminal pro-B-type natriuretic peptide (NT-proBNP), BNP, sST2, and neutrophil gelatinase associated lipocalin (NGAL). In a prospective international study, biomarkers were collected at the time of admission; the occurrence of subsequent in hospital WRF was evaluated. In total 26% of patients developed WRF. Compared to patients without WRF, those with WRF had a longer in-hospital length of stay (LOS) (mean LOS 13.1±13.4 days vs. 4.8±3.7 days, p<0.001) and higher in-hospital mortality [6/26 (23%) vs. 2/75 (2.6%), p<0.001]. Among the biomarkers assessed, baseline NT-proBNP (4846 vs. 3024 pg/mL; p=0.04), BNP (609 vs. 435 pg/mL; p=0.05) and NGAL (234 vs. 174 pg/mL; p=0.05) were each higher in those who developed WRF. In logistic regression, the combination of elevated natriuretic peptide and NGAL were additively predictive for WRF (ORNT-proBNP+NGAL=2.79; ORBNP+NGAL=3.11; both p<0.04). Rates of WRF were considerably higher in patients with elevation of both classes of biomarker. Comparable results were observed in a separate cohort of 162 patients with ADHF from a different center. In ED patients with ADHF, the combination of NT-proBNP or BNP plus NGAL at presentation may be useful to predict impending WRF (Clinicaltrials.gov NCT#0150153).

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Association With Exercise Capacity, Left Ventricular Filling Pressures, Natriuretic Peptides, and Left Atrial Volume.

PubMed

Lam, Carolyn S P; Rienstra, Michiel; Tay, Wan Ting; Liu, Licette C Y; Hummel, Yoran M; van der Meer, Peter; de Boer, Rudolf A; Van Gelder, Isabelle C; van Veldhuisen, Dirk J; Voors, Adriaan A; Hoendermis, Elke S

2017-02-01

This study sought to study the association of atrial fibrillation (AF) with exercise capacity, left ventricular filling pressure, natriuretic peptides, and left atrial size in heart failure with preserved ejection fraction (HFpEF). The diagnosis of HFpEF in patients with AF remains a challenge because both contribute to impaired exercise capacity, and increased natriuretic peptides and left atrial volume. We studied 94 patients with symptomatic heart failure and left ventricular ejection fractions ≥45% using treadmill cardiopulmonary exercise testing and right- and/or left-sided cardiac catheterization with simultaneous echocardiography. During catheterization, 62 patients were in sinus rhythm, and 32 patients had AF. There were no significant differences in age, sex, body size, comorbidities, or medications between groups; however, patients with AF had lower peak oxygen consumption (VO 2 ) compared with those with sinus rhythm (10.8 ± 3.1 ml/min/kg vs. 13.5 ± 3.8 ml/min/kg; p = 0.002). Median (25th to 75th percentile) N-terminal pro-B-type natriuretic peptide (NT-proBNP) was higher in AF versus sinus rhythm (1,689; 851 to 2,637 pg/ml vs. 490; 272 to 1,019 pg/ml; p < 0.0001). Left atrial volume index (LAVI) was higher in AF than sinus rhythm (57.8 ± 17.0 ml/m 2 vs. 42.5 ± 15.1 ml/m 2 ; p = 0.001). Invasive hemodynamics showed higher mean pulmonary capillary wedge pressure (PCWP) (19.9 ± 3.7 vs. 15.2 ± 6.8) in AF versus sinus rhythm (all p < 0.001), with a trend toward higher left ventricular end-diastolic pressure (17.7 ± 3.0 mm Hg vs. 15.7 ± 6.9 mm Hg; p = 0.06). After adjusting for clinical covariates and mean PCWP, AF remained associated with reduced peak VO 2 increased log NT-proBNP, and enlarged LAVI (all p ≤0.005). AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left atrial remodeling in HFpEF. These data support the application of different thresholds of NT-proBNP and LAVI�

N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ndumele, Chiadi E; Matsushita, Kunihiro; Sang, Yingying; Lazo, Mariana; Agarwal, Sunil K; Nambi, Vijay; Deswal, Anita; Blumenthal, Roger S; Ballantyne, Christie M; Coresh, Josef; Selvin, Elizabeth

2016-02-16

Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese. Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population. © 2016 American Heart Association, Inc.

Serial N-terminal pro-brain natriuretic peptide measurement as a predictor of significant patent ductus arteriosus in preterm infants beyond the first week of life.

PubMed

Letshwiti, Johannes Buca; Sirc, Jan; O'Kelly, Ruth; Miletin, Jan

2014-11-01

The aim of the study was to assess the role of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration as a predictor of patent ductus arteriosus (PDA) in very low birth weight infants beyond the first week of life. This was a prospective observational study; newborns with a birth weight < 1500 g were eligible for enrolment. Enrolled infants were screened by echocardiography on day seven of life for the presence of a PDA. This was paired with a blood sample for NT-proBNP level. Echocardiography and NT-proBNP levels were repeated at weekly intervals. The primary outcome was correlation between PDA and NT-proBNP level and between measurements of PDA significance and NT-proBNP. Sixty-nine neonates were enrolled following parental consent. The mean birth weight was 1119 ± 257 g and mean gestational age was 28.6 ± 2.6 weeks. Median NT-proBNP level on day seven was 11469 ng/l in infants with a PDA vs. 898 ng/l in infants without a PDA (p < 0.0001). There was a statistically significant correlation between PDA diameter and NT-proBNP level on day seven, day 14 and day 21. NT-proBNP concentration is significantly increased in infants with a PDA and correlates well with PDA diameter in the first three weeks of life.

Association of N-terminal pro-brain natriuretic peptide with the severity of coronary artery disease in patients with normal left ventricular ejection fraction.

PubMed

Wu, Naqiong; Ma, Fenglian; Guo, Yuanlin; Li, Xiaoling; Liu, Jun; Qing, Ping; Xu, Ruixia; Zhu, Chenggang; Jia, Yanjun; Liu, Geng; Dong, Qian; Jiang, Lixin; Li, Jianjun

2014-01-01

Backround N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor in acute coronary artery disease (CAD). Little is known about patients with stable CAD, especially Chinese patients with CAD. The aim of the present study was to investigate the association of NT-proBNP levels with the severity of CAD in patients with normal left ventricular ejection fraction. A total of 658 consecutive patients were divided into two groups based on angiograms: CAD group (n = 484) and angiographic normal control group (n = 174). The severity of CAD was evaluated by modified Gensini score, and its relationship with NT-proBNP was analyzed. The prevalence of risk factors such as age, male gender, diabetes mellitus (DM), dyslipidemia, smoking, and family history of CAD in the CAD group were higher than that in the control group. In multivariate regression model analysis, age, gender, and DM were determinants of the presence of CAD. NT-pro BNP was found to be an independent predictor for CAD (OR:1.66 (95% CI: 1.06-2.61), P < 0.05). In a receiver operating characteristic (ROC) curve analysis, an NT-proBNP value of 641.15 pmol/L was identified as a cut-off value in the diagnosis or exclusion of CAD (area under curve (AUC) = 0.56, 95% CI: 0.51-0.61). Furthermore, NT-proBNP was positively correlated with Gensini score (r = 0.14, P < 0.001) in patients with CAD. NT-proBNP was an independent predictor for Chinese patients with CAD, suggesting that the NT-proBNP level might be associated with the presence and the severity of CAD.

Characterization and distribution of natriuretic peptide receptors in the rat uterus.

PubMed

Dos Reis, A M; Fujio, N; Dam, T V; Mukaddam-Daher, S; Jankowski, M; Tremblay, J; Gutkowska, J

1995-10-01

Atrial natriuretic peptide (ANP) receptors were characterized in rat uterus. The binding of [125I]ANP to uterine membranes was completely competed for by increasing concentrations of unlabeled ANP (Kd = 0.39 nM) and brain natriuretic peptide (Kd = 1.24 nM) and partially by C-type natriuretic peptide (CNP; Kd = 80.4 nM), but not by C-ANF. Also, [125I]Tyr-CNP bound to uterine membranes was completely competed by unlabeled CNP (Kd = 1.12 nM). Cross-linking of [125I]ANP to uterine membranes revealed the presence of one band of 130 kilodaltons, corresponding to the guanylyl cyclase (GC-A and/or GC-B) subtypes of natriuretic peptide receptors. The presence of messenger RNA coding for genes of both GC-A and GC-B receptors was shown by quantitative reverse transcriptase polymerase chain reaction. Furthermore, ANP and, to a lesser degree, CNP stimulated the production of cGMP in rat uterus. Autoradiographic studies localized the highest binding of [125I]ANP in the endometrium, whereas [125I]Tyr-CNP binding was distributed in the endometrium as well as in the myometrium. These results demonstrate that rat uterine ANP receptors are of the guanylyl cyclase-coupled subtypes. The uterus is a target of natriuretic peptides where ANP induces its biological effects through the production of cGMP.

Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure

PubMed Central

Nishikimi, Toshio; Okamoto, Hiroyuki; Nakamura, Masahiro; Ogawa, Naoko; Horii, Kazukiyo; Nagata, Kiyoshi; Nakagawa, Yasuaki; Kinoshita, Hideyuki; Yamada, Chinatsu; Nakao, Kazuhiro; Minami, Takeya; Kuwabara, Yoshihiro; Kuwahara, Koichiro; Masuda, Izuru; Kangawa, Kenji; Minamino, Naoto; Nakao, Kazuwa

2013-01-01

Background Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure. Methodology/Principal Findings We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%–8.0% in proBNP assay and from 7.0%–8.4% in total BNP assay, and between-run CVs ranged from 5.3–7.4% in proBNP assay and from 2.9%–9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998–1.00), and analytical recovery was 90–101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects. Conclusions/Significance Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma. PMID:23365636

Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.

PubMed

Walford, Geoffrey A; Ma, Yong; Christophi, Costas A; Goldberg, Ronald B; Jarolim, Petr; Horton, Edward; Mather, Kieren J; Barrett-Connor, Elizabeth; Davis, Jaclyn; Florez, Jose C; Wang, Thomas J

2014-05-01

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP). The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887). At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease.

PubMed

von Haehling, Stephan; Papassotiriou, Jana; Hartmann, Oliver; Doehner, Wolfram; Stellos, Konstantinos; Geisler, Tobias; Wurster, Thomas; Schuster, Andreas; Botnar, Rene M; Gawaz, Meinrad; Bigalke, Boris

2012-11-01

In the present study, we investigated the prognostic value of MR-proANP (mid-regional pro-atrial natriuretic peptide). We consecutively evaluated a catheterization laboratory cohort of 2700 patients with symptomatic CAD (coronary artery disease) [74.1% male; ACS (acute coronary syndrome), n=1316; SAP (stable angina pectoris), n=1384] presenting to the Cardiology Department of a large primary care hospital, all of whom underwent coronary angiography. Serum MR-proANP and other laboratory markers were sampled at the time of presentation or in the catheterization laboratory. Clinical outcome was assessed by hospital chart analysis and telephone interviews. The primary end point was all-cause death at 3 months after enrolment. Follow-up data were complete in 2621 patients (97.1%). Using ROC (receiver operating characteristic) curves, the AUC (area under the curve) of 0.73 [95% CI (confidence interval), 0.67-0.79] for MR-proANP was significantly higher compared with 0.58 (95% CI, 0.55-0.62) for Tn-I (troponin-I; DeLong test, P=0.0024). According to ROC analysis, the optimal cut-off value of MR-proANP was at 236 pmol/l for all-cause death, which helped to find a significantly increased rate of all-cause death (n=76) at 3 months in patients with elevated baseline concentrations (≥236 pmol/l) compared with patients with a lower concentration level in Kaplan-Meier survival analysis (log rank, P<0.001). The predictive performance of MR-proANP was independent of other clinical variables or cardiovascular risk factors, and superior to that of Tn-I or other cardiac biomarkers (all: P<0.0001). MR-proANP may help in the prediction of all-cause death in patients with symptomatic CAD. Further studies should verify its prognostic value and confirm the appropriate cut-off value.

[Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

PubMed

Zeng, Q; Sun, R F; Li, Z; Zhai, L Q; Liu, M Z; Guo, X J; Gao, C R

2017-10-01

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （ P <0.05）. The NT-proBNP content in plasma of sudden death of coronary atherosclerotic heart disease group was higher than that of single coronary stenosis group （ P <0.05）. In myocardial ischemia condition, the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

Segmental arterial stiffness in relation to B-type natriuretic peptide with preserved systolic heart function.

PubMed

Yen, Chih-Hsuan; Hung, Chung-Lieh; Lee, Ping-Ying; Tsai, Jui-Peng; Lai, Yau-Huei; Su, Cheng-Huang; Yeh, Hung-I; Hou, Charles Jia-Yin; Chien, Kuo-Liong

2017-01-01

Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive. A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA). Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029). A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage.

Segmental arterial stiffness in relation to B-type natriuretic peptide with preserved systolic heart function

PubMed Central

Yen, Chih-Hsuan; Hung, Chung-Lieh; Lee, Ping-Ying; Tsai, Jui-Peng; Lai, Yau-Huei; Su, Cheng-Huang; Yeh, Hung-I; Hou, Charles Jia-Yin

2017-01-01

Background Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive. Methods A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA). Results Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029). Conclusion A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage. PMID:28922407

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

PubMed

Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

2018-04-01

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( p<0.01). An elevation of both markers exhibited an additive effect on mortality, as those with both NT-proBNP and TnT levels above the median had a 30-day mortality rate of 51.0%, while those with both markers below the median had a 16.7% mortality rate (hazard ratio 3.7). These findings were independent of demographic and clinical parameters ( p<0.05). Our findings regarding the individual predictive properties of NT-proBNP and TnT are in line with literature. However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Natriuretic peptide type C induces sperm attraction for fertilization in mouse

PubMed Central

Kong, Nana; Xu, Xiaoting; Zhang, Yu; Wang, Yakun; Hao, Xiaoqiong; Zhao, Yu; Qiao, Jie; Xia, Guoliang; Zhang, Meijia

2017-01-01

Mammalian spermatozoa undergo selective movement along the isthmus of the oviduct to the ampulla during ovulation, which is a prerequisite for fertilization. The factor(s) that involves in selective spermatozoa movement is still unknown. In this study, we found that the oviductal epithelium in mouse ampulla expressed high levels of natriuretic peptide type C (NPPC) in the presence of ovulated oocyte-cumulus complexes (OCCs). Spermatozoa expressed NPPC receptor natriuretic peptide receptor 2 (NPR2, a guanylyl cyclase) on the midpiece of flagellum. NPPC increased intracellular levels of cGMP and Ca2+ of spermatozoa, and induced sperm accumulation in the capillary by attraction. Importantly, spermatozoa from Npr2 mutant mice were not attracted by NPPC, preventing fertilization in vivo. Oocyte-derived paracrine factors promoted the expression of Nppc mRNA in the ampulla. Therefore, NPPC secreted by oviductal ampulla attracts spermatozoa towards oocytes, which is essential for fertilization. PMID:28054671

Effects of Oral Contraceptives on Natriuretic Peptide Levels in Women with Hypothalamic Amenorrhea: A Pilot Study

PubMed Central

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K.

2011-01-01

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60 – 75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives increases natriuretic peptide levels and that end-of-study free testosterone levels are inversely associated with NT-proBNP levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations – estrogens or androgens. PMID:21620395

Early identification of acute heart failure at the time of presentation: do natriuretic peptides make the difference?

PubMed

Möckel, Martin; von Haehling, Stephan; Vollert, Jörn O; Wiemer, Jan C; Anker, Stefan D; Maisel, Alan

2018-06-01

The early identification of patients with acute heart failure (AHF) is challenging as many other diseases lead to a clinical presentation with dyspnea. The aim of the study was to evaluate the impact of natriuretic peptides at common HF study cut-offs on the diagnosis of patients with dyspnea at admission. For this post hoc analysis, we analysed n = 726 European Union (EU) patients from the prospective BACH (Biomarkers in Acute Heart Failure) study. Cut-offs were 350 ng/L (BNP), 300 pmol/L [pro-atrial natriuretic peptide (proANP)], and 1800 ng/L (NT-proBNP). These cut-offs had equivalent 90 days' mortality in the EU cohort of BACH. We analysed the effect of selection using these cut-offs on the prevalence of the gold standard diagnoses made in the BACH study and the respective mortality. The prevalence of AHF is increased from 47.5 to 75.6% (NT-proBNP criteria) up to 79.7% (BNP criteria). With the use of the proANP criteria, 90 days' mortality of patients with AHF rose from 14 to 17% (P = 0.029). In the group with no-AHF diagnoses, mortality rose from 10 to 25% (P < 0.001). The prevalence of patients with the gold standard diagnoses of AHF among those presenting with dyspnea to the emergency department is significantly increased by the use of natriuretic peptides with common cut-offs used in prospective HF studies. Nevertheless, in the selected groups, patients with no AHF diagnosis have the highest mortality, and therefore, the addition of a natriuretic peptide alone is insufficient to start specific therapies. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Use of biomarkers to guide outpatient therapy of heart failure.

PubMed

DeBeradinis, Benedetta; Januzzi, James L

2012-11-01

Among patients with heart failure, concentrations of natriuretic peptides are strongly linked to the presence and severity of structural heart disease and are strongly prognostic in this setting. Additionally, favorable reduction in the concentration of either B-type natriuretic peptide (BNP) or B-type natriuretic peptide and its amino-terminal cleavage fragment (NT-proBNP) may be seen during treatment of heart failure, with parallel improvement in prognosis. This has led to the hypothesis that intensified treatment directed at reducing natriuretic peptide concentrations may improve outcomes in heart failure. In chronic heart failure, studies suggest that a strategy of standard-of-care management together with a goal to suppress BNP or NT-proBNP concentrations leads to greater application of guideline-derived medical therapy and is well tolerated. In certain studies of this BNP or NT-proBNP 'guided' approach, patients treated with biomarker-guided care had superior outcomes when compared with standard heart failure management alone, particularly in younger study populations, in patients with left ventricular systolic dysfunction, and particularly when substantial reductions in natriuretic peptides were achieved in association with biomarker-guided care. Natriuretic peptide 'guided' management appears promising in patients suffering from chronic heart failure. Large-scale pivotal trials to confirm the approach are planned.

Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease.

PubMed

Law, Yuk M; Keller, Bradley B; Feingold, Brian M; Boyle, Gerard J

2005-02-15

The usefulness of B-type natriuretic peptide (BNP) levels to assess ventricular dysfunction in children and the congenital heart disease population remains largely unknown. We retrospectively analyzed 62 patients with or without known heart disease who had plasma BNP measured for the investigation of new or severity grading of known ventricular dysfunction. BNP levels were significantly higher in patients with ventricular dysfunction (mean 623 +/- 146 pg/ml, range 5 to 5,000) than in patients without ventricular dysfunction (mean 22 +/- 5 pg/ml, range 5 to 63; p <0.01). Using a cutoff of 40 pg/ml, BNP levels detected heart disease associated with ventricular dysfunction at a sensitivity of 85%, specificity of 81%, positive predictive value of 92%, and negative predictive value of 68%. The degree of BNP elevation was also associated with the severity of heart failure and high ventricular filling pressures. Plasma BNP elevation can be a reliable test in children and young adults with various kinds of congenital heart disease resulting in ventricular dysfunction.

Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

PubMed

Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

2009-02-01

With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

PubMed

Castro, A; Dias, P; Pereira, M; Pimenta, J; Friões, F; Rodrigues, R; Ferreira, A; Bettencourt, P

2001-11-01

Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. Prospective study. One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the "natriuretic handicap" in morbidly obese patients.

PubMed

Gentili, Alessandra; Frangione, Maria Rosaria; Albini, Elisa; Vacca, Carmine; Ricci, Maria Anastasia; De Vuono, Stefano; Boni, Marcello; Rondelli, Fabio; Rotelli, Luciana; Lupattelli, Graziana; Orabona, Ciriana

2017-08-01

The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects. The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP. Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

Cocoa flavanols reduce N‐terminal pro‐B‐type natriuretic peptide in patients with chronic heart failure

PubMed Central

De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G.; Khan, Noorafza Q.; Butler, Jane; Johnston, Atholl; Rothman, Martin T.

2015-01-01

Abstract Aims Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) as an index of improved cardiac function. Methods and results Thirty‐two patients with chronic HF, stable on guideline‐directed medical therapy, were randomized to consume 50 g/day of high‐flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low‐flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty‐four patients completed the study. After 4 weeks of HFDC, NT‐proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (−44 ± 69%), LFDC (−33 ± 72%), and follow‐up (−41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (−6.7 ± 10.1 mmHg). Conclusions Reductions in blood pressure and NT‐proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF. PMID:27588209

Relation between N-terminal pro-brain natriuretic peptide levels and response to enhanced external counterpulsation in chronic angina pectoris.

PubMed

Sahlén, Anders; Wu, Eline; Rück, Andreas; Hagerman, Inger; Förstedt, Gunilla; Sylvén, Christer; Berglund, Margareta; Jernberg, Tomas

2014-01-01

Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response. We explored a database of n=53 patients who had undergone clinically indicated EECP during 35 1-h sessions in our unit (65±7 years; 49 male), and sought to clarify which factors are predictive of response. Efficiency of counterpulsation was measured as the diastolic augmentation (DA) ratio, and was recorded both at beginning and end of the EECP treatment course. An increase in 6-min walk (6MW) distance of 5% was indicative of clinical response. Response occurred in 28 patients (53%; nonresponse in n=25, 47%). Responders had shorter baseline 6MW distance (377±81 vs. 445±62 m; P<0.01), lower left ventricular ejection fraction (48±9 vs. 54±8%; P<0.05), frequently had an increase in DA ratio during the EECP treatment course (23/28 vs. 5/28 with unchanged or decreased DA ratio; P<0.05), and higher levels of N-terminal pro-brain natriuretic peptide [NT-proBNP; 256 (123-547) vs. 62 (26-444) ng/l, P<0.01]. In multivariate logistic regression, response was independently predicted by baseline 6MW distance and baseline NT-proBNP levels (P<0.05 for both; model sensitivity: 82%, specificity: 72%, accuracy: 79%). There is larger clinical benefit of EECP in patients with greater functional impairment and higher levels of NT-proBNP.

Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure.

PubMed

Gavin, A D; Struthers, A D

2005-06-01

To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure (CHF) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide (BNP), the other important prognostic marker of CHF. Randomised, double blind, placebo controlled crossover trial. Teaching hospital. 50 patients with CHF (New York Heart Association functional classes II and III) were recruited. 50 patients with CHF were randomly assigned to three months' treatment with allopurinol (300 mg/day) or placebo. At two and three months into treatment, they underwent a modified Bruce exercise protocol and a six minute walk test. Blood was taken for BNP and haemoglobin analysis. Neither exercise test was altered by allopurinol. However, plasma BNP concentrations fell significantly (p = 0.035) with allopurinol (11.9 pmol/l) versus placebo (14.4 pmol/l). Haemoglobin concentrations also fell highly significantly with allopurinol (p = 0.001). An important negative finding is that despite high hopes for it, allopurinol had no effect on exercise capacity in CHF. On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF.

Increasing NT-proBNP Precedes The Development of Arterial Hypertension: The Multi-Ethnic Study Of Atherosclerosis

PubMed Central

Sanchez, Otto A.; Jacobs, David R.; Bahrami, Hossein; Peralta, Carmen A.; Daniels, Lori B.; Lima, João A.; Maisel, Alan; Duprez, Daniel A.

2014-01-01

Background Longitudinal associations between the aminoterminal pro B-type natriuretic peptide (NT-proBNP) and incident hypertension are lacking. Methods We tested associations between baseline NT-proBNP (bNT-proBNP) and also change in NT-proBNP (ΔNT-proBNP) (visit 3 NT-proBNP – bNT-proBNP; 3.2 years apart) with incident hypertension (systolic blood pressure ≥140 and/or diastolic BP ≥90 mmHg or taking anti-hypertensive medications). Incident hypertension was evaluated in 5596 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) without hypertension at baseline (53% females, age range 45 – 84 years without overt cardiovascular disease) and followup for 9.5 years and in a subgroup (1550) who had bNT-proBNP <100 pg/mL and no hypertension at visit 3. Incident hypertension was regressed (proportional hazards) on quintiles of bNT-proBNP (range) 1) reference <19.2, 2) 19.3 – 40.8, 3) 40.9 – 70.9, 4) 71 – 135.2 and 5) >135.5 and also on ΔNT-proBNP categories (reference < −10, −10 — 10, >10 — 50 and >50 pg/mL). Hazard ratios (HRs) were adjusted for age, race, sex, education, diabetes, obesity, LV mass/height, SBP and DBP, IL-6, salt intake, estimated glomerular filtration rate and exercise. Results Compared to the reference category, HRs (95% CI) for incident hypertension compared to the first quintile of bNT-proBNP were 1.47 (1.13–1.93), 1.57 (1.18–2.09), 1.52 (1.12–2.06) and 2.36 (1.62–3.41). HRs for incident hypertension by categories of ΔNT-proBNP from 3.2 to 9.5 years followup were 0.98 (0.62 – 1.56), 1.13 (0.72 – 1.79) and 1.82 (1.07 – 3.12). Conclusion The development of hypertension tended to be preceded by elevated levels of bNT-proBNP or a substantial positive ΔNT-proBNP. PMID:25909698

Correlation between plasma N-terminal pro-brain natriuretic peptide levels and changes in New York Heart Association functional class, left atrial size, left ventricular size and function after mitral and/or aortic valve replacement.

PubMed

Elasfar, Abdelfatah

2012-01-01

Elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in patients with chronic valvular disease. We designed the present study to assess whether changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic valve replacement reflect changes in heart failure (HF) symptoms including New York Heart Association (NYHA) class and changes in left atrium (LA) size, left ventricle (LV) size and LV function. A prospective observational nonrandomized study among consecutive patients undergoing mitral and/or aortic valve replacement in our center. The study population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were males) who underwent surgical mitral valve replacement (12 patients), aortic valve replacement (8 patients) and combined mitral and aortic valve replacement (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA class assessments were performed before and 6 months after surgery. The decrease in NT-proBNP was associated with decrease in left atrial dimension (r = 0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001) after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was associated with improvement in NYHA class. NT-proBNP levels after mitral, aortic and double valve replacement correlates with changes in HF manifestations as well as changes in LA size and LV dimension and function. Thus, we hypothesize that interval measurement of the NT-proBNP level at clinic visits can allow early detection of any clinical deterioration as well as the possibility of assessment of the long-term outcome of those patients.

N-terminal pro–brain natriuretic peptide and abnormal brain aging

PubMed Central

Sabayan, Behnam; van Buchem, Mark A.; de Craen, Anton J.M.; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B.; Gudnason, Vilmundur; Arai, Andrew E.

2015-01-01

Objective: To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. Methods: In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Conclusions: Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. PMID:26231259

Estimated glomerular filtration rate is associated with both arterial stiffness and N-terminal pro-brain natriuretic peptide in newly diagnosed hypertensive patients.

PubMed

Gür, Mustafa; Uçar, Hakan; Kuloğlu, Osman; Kıvrak, Ali; Şeker, Taner; Türkoğlu, Caner; Özaltun, Betül; Kaypaklı, Onur; Şahin, Durmuş Yıldıray; Elbasan, Zafer; Tanboğa, Halil İbrahim; Çaylı, Murat

2014-01-01

Even a slight decrease in the glomerular filtration rate (GFR) is an independent risk factor for cardiovascular disease. Arterial stiffness, left ventricular hypertrophy and N-terminal pro-brain natriuretic peptide (NT-proBNP) are independent risk factors for cardiovascular disease, which are particularly common in end-stage renal disease. We aimed to evaluate the association between GFR with arterial stiffness, left ventricle mass (LVM) and NT-proBNP in hypertensive subjects with normal to mildly impaired renal function. The study population consisted of 285 newly diagnosed hypertensive patients (mean age; 49.9 ± 11.8 years). GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Pulse wave velocity (PWV) and augmentation index (AIx), which reflects arterial stiffness, were calculated using the single-point method via the Mobil-O-Graph® ARCsolver algorithm. LVM was obtained by echocardiography. Plasma NT-proBNP was measured by electrochemiluminescence. The patients were divided into two groups according to the median eGFR value (eGFRlow group <101 ml/min/1.73 m(2) and eGFRhigh group ≥ 101 ml/min/1.73 m(2)). LVM and NT-proBNP values were higher in eGFRlow group compared with eGFRhigh group (p<0.05). Pulse wave velocity and augmentation index values were higher in eGFRlow group compared with eGFRhigh group (p<0.05, for all). Multiple linear regression analysis showed that eGFR was independently associated with PWV (β=-0.422, p<0.001) and NT-proBNP (β=-0.404, p<0.001). Present study showed that eGFR was independently associated with PWV and NT-proBNP values. Importantly, these findings may explain, in part, the increase in cardiovascular risk in with slightly impaired renal function.

B-type natriuretic peptide expression and cardioprotection is regulated by Akt dependent signaling at early reperfusion.

PubMed

Breivik, L; Jensen, A; Guvåg, S; Aarnes, E K; Aspevik, A; Helgeland, E; Hovland, S; Brattelid, T; Jonassen, A K

2015-04-01

Exogenously administered B-type natriuretic peptide (BNP) has been shown to offer cardioprotection through activation of particulate guanylyl cyclase (pGC), protein kinase G (PKG) and KATP channel opening. The current study explores if cardioprotection afforded by short intermittent BNP administration involves PI3K/Akt/p70s6k dependent signaling, and whether this signaling pathway may participate in regulation of BNP mRNA expression at early reperfusion. Isolated Langendorff perfused rat hearts were subjected to 30min of regional ischemia and 120min of reperfusion (IR). Applying intermittent 3×30s infusion of BNP peptide in a postconditioning like manner (BNPPost) reduced infarct size by >50% compared to controls (BNPPost 17±2% vs. control 42±4%, p<0.001). Co-treatment with inhibitors of the PI3K/Akt/p70s6k pathway (wortmannin, SH-6 and rapamycin) completely abolished the infarct-limiting effect of BNP postconditioning (BNPPost+Wi 36±5%, BNPPost+SH-6 41±4%, BNPPost+Rap 37±6% vs. BNPPost 17±2%, p<0.001). Inhibition of natriuretic peptide receptors (NPR) by isatin also abrogated BNPPost cardioprotection (BNPPost+isatin 46±2% vs. BNPPost 17±2%, p<0.001). BNPPost also significantly phosphorylated Akt and p70s6k at early reperfusion, and Akt phosphorylation was inhibited by SH-6 and isatin. Myocardial BNP mRNA levels in the area at risk (AA) were significantly elevated at early reperfusion as compared to the non-ischemic area (ANA) (Ctr(AA) 2.7±0.5 vs. Ctr(ANA) 1.2±0.2, p<0.05) and the ischemic control tissue (Ctr(AA) 2.7±0.5 vs. ischemia 1.0±0.1, p<0.05). Additional experiments also revealed a significant higher BNP mRNA level in ischemic postconditioned (IPost) hearts as compared to ischemic controls (IPost 6.7±1.3 vs. ischemia 1.0±0.2, p<0.05), but showed no difference from controls run in parallel (Ctr 5.4±0.8). Akt inhibition by SH-6 completely abrogated this elevation (IPost 6.7±1.3 vs. IPost+SH-6 1.8±0.7, p<0.05) (Ctr 5.4±0.8 vs. SH-6 1.5±0

Alternative splicing of natriuretic peptide A and B receptor transcripts in the rat brain.

PubMed

Francoeur, F; Gossard, F; Hamet, P; Tremblay, J

1995-12-01

1. In the present study we searched for variants of alternative splicing of guanylyl cyclase A and B mRNA in rats in vivo. 2. Guanylyl cyclase A2 and guanylyl cyclase B2 isoforms of guanylyl cyclase produced by alternative splicing leading to the deletion of exon 9 of both transcripts were quantified in several rat organs. 3. Only one alternative splicing was found in the regulatory domain, encoded by exons 8-15. 4. Quantification of the guanylyl cyclase B2 isoform in different rat organs and in cultured aortic smooth muscle cells showed that this alternative splicing was tissue-specific and occurred predominantly in the central nervous system where the alternatively spliced variant represented more than 50% of the guanylyl cyclase B mRNA. 5. The same alternative splicing existed for guanylyl cyclase A mRNA but at very low levels in the organs studied. 6. Alternative splicing of guanylyl cyclase B exon 9 in the brain may play an important role in signal transduction, since the expressed protein possesses a constitutionally active guanylyl cyclase acting independently of C-type natriuretic peptide regulation.

Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease.

PubMed

Winter, Randolph L; Saunders, Ashley B; Gordon, Sonya G; Buch, Jesse S; Miller, Matthew W

2017-04-01

To determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD). Thirty-eight privately owned dogs: 28 with MMVD and 10 healthy controls. Prospective clinical study with comprehensive evaluation used to group dogs as healthy or into three stages of MMVD based on current guidelines. NTproBNP was measured hourly, daily, and weekly. For each group, analytical (CV A ), within-subject (CV I ), and between-subject (CV G ) coefficients of variability were calculated in addition to percent critical change value (CCV) and index of individuality (IoI). For healthy dogs, calculated NTproBNP values were: CV A  = 4.2%; CV I  = 25.2%; CV G  = 49.3%; IoI = 0.52, and CCV = 70.8%. For dogs with MMVD, calculated NTproBNP values were: CV A  = 6.2%; CV I  = 20.0%; CV G  = 61.3%; IoI = 0.34, and CCV = 58.2%. Biologic variability affects NTproBNP concentrations in healthy dogs and dogs with MMVD. Monitoring serial individual changes in NTproBNP may be clinically relevant in addition to using population-based reference ranges to determine changes in disease status. Copyright © 2016 Elsevier B.V. All rights reserved.

NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: the Heinz Nixdorf Recall Study.

PubMed

Kara, Kaffer; Lehmann, Nils; Neumann, Till; Kälsch, Hagen; Möhlenkamp, Stefan; Dykun, Iryna; Broecker-Preuss, Martina; Pundt, Noreen; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund; Mahabadi, Amir A

2015-03-15

B-type natriuretic peptide (BNP) as well as N-terminal-proBNP (NT-proBNP) are associated with cardiac events in the general population. Yet, data from the general population comparing both peptides for their prognostic value is lacking. Participants from the population-based Heinz-Nixdorf-Recall-study without cardiovascular diseases were included. Associations of BNP and NT-proBNP with incident cardiovascular events (incident myocardial infarction, stroke, or cardiovascular death) were assessed using Cox regression; prognostic value was addressed using Harrell's c statistic. From overall 3589 subjects (mean age: 59.3 ± 7.7 yrs, 52.5% female), 235 subjects developed a cardiovascular event during 8.9 ± 2.2 yrs of follow-up. In regression analysis both natriuretic peptides were associated with incident cardiovascular events, independent of traditional risk factors (hazard ratio (HR) per unit increase on log-scale (95% CI): NT-proBNP: 1.60 (1.39; 1.84); BNP: 1.37 (1.19; 1.58), p<0.0001 respectively). Specifically looking at subjects <60 yrs only NT-proBNP, was linked with events (HR (95% CI): 1.59 (1.19; 2.13) for NT-proBNP, p=0.0019; HR: 1.25 (0.94; 1.65) for BNP, p=0.12, after adjustment for age and gender). Similar results were observed for females (HR (95% CI) 1.65 (1.28; 2.12), p=0.0001 for NT-proBNP, and 1.24 (0.96; 1.61), p=0.10 for BNP after adjustment for age). Adding NT-proBNP/BNP to traditional risk factors increased the prognostic value, with effects being stronger for NT-proBNP (Harrell's c, 0.724 to 0.741, p=0.034) as compared to BNP (0.724 to 0.732, p=0.20). Both, NT-proBNP and BNP are associated with future cardiovascular events in the general population. However, when both are available, NT-proBNP seems to be superior due to its higher prognostic value, especially in younger subjects and females. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

PubMed

Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

2015-03-01

The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. © 2014 American Heart Association, Inc.

ENDOTHELIN-STIMULATED HUMAN B-TYPE NATRIURETIC PEPTIDE GENE EXPRESSION IS MEDIATED BY YY1 IN ASSOCIATION WITH HDAC2

PubMed Central

Glenn, Denis J.; Wang, Feng; Chen, Songcang; Nishimoto, Minobu; Gardner, David G.

2009-01-01

Increased B-type natriuretic peptide (BNP) gene expression is regarded as one of the hallmarks of cardiac myocyte hypertrophy. Here we demonstrate that both basal and endothelin-1 (ET-1) -dependent stimulation of human (h) BNP gene transcription requires the presence of an intact Yin Yang 1 (YY1) binding site positioned at -62 bp relative to the transcription start site. Mutation of this site reduced both basal and stimulated hBNP promoter activity. This site was shown to bind YY1 both in vitro and within the context of the intact cell. The latter interaction increased following ET-1 treatment. Exposure to ET-1 also resulted in increased nuclear localization of YY1 and a reduction in acetylation of the YY1 protein. Overexpression of wild type YY1 increased both basal and endothelin-stimulated hBNP promoter activity, while a carboxy terminal deletion mutant of YY1 was devoid of activity. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) resulted in decreased hBNP reporter activity. YY1 was shown to associate with histone deacetylase 2 (HDAC2), and HDAC2 was shown to associate directly with the hBNP promoter in the intact cell. Collectively these findings demonstrate that YY1 plays an important role in regulating the transcriptional activity of the hBNP gene promoter. These data suggest a model in which YY1 activates hBNP transcription through interaction with HDAC2. PMID:19139378

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

PubMed

Giallauria, Francesco; Cirillo, Plinio; Lucci, Rosa; Pacileo, Mario; De Lorenzo, Anna; D'Agostino, Mariantonietta; Moschella, Sabino; Psaroudaki, Marianna; Del Forno, Domenico; Orio, Francesco; Vitale, Dino Franco; Chiariello, Massimo; Vigorito, Carlo

2008-02-01

To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Impact of history of heart failure on diagnostic and prognostic value of BNP: results from the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study.

PubMed

Boldanova, Tujana; Noveanu, Markus; Breidthardt, Tobias; Potocki, Mihael; Reichlin, Tobias; Taegtmeyer, Anne; Christ, Michael; Laule, Kirsten; Stelzig, Claudia; Mueller, Christian

2010-07-23

This study aimed to examine the influence of history of heart failure (HF) on circulating levels, diagnostic accuracy and prognostic value of B-type natriuretic peptide (BNP) in patients presenting with all cause dyspnea at the emergency department. BNP has been shown to be very helpful in diagnosis and prognosis of HF. Due to chronically elevated cardiac filling pressures, patients with a history of HF might have higher BNP levels and therefore diagnostic and prognostic properties of BNP may be affected. We analyzed circulating levels, diagnostic accuracy and prognostic value of BNP in 388 patients without a previous history of HF and compared these to data to 64 patients with a history of HF included in the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) Study. Baseline BNP levels were higher in patients with a history of HF (median 814 pg/ml [353-1300 pg/ml] vs. 216 pg/ml [45-801 pg/ml], p<0.001). Diagnostic accuracy of BNP to identify HF was comparable in patients with (AUC=0.804; 95% CI 0.628-0.980) and in patients without history of HF (AUC=0.883; 95% CI 0.848-0.919, p=0.389). Prognostic ability of BNP to predict one-year mortality was lower in overall patients with history of HF (AUC=0.458; 95%CI 0.294-0.622) compared to patients without history of HF (AUC=0.710; 95% CI 0.653-0.768, p<0.05). In patients with history of HF, BNP levels retain diagnostic accuracy. Ability to predict one-year mortality was decreased in unselected patients, but not in patients with acute HF-induced dyspnea. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Diagnostic accuracy of point-of-care natriuretic peptide testing for chronic heart failure in ambulatory care: systematic review and meta-analysis.

PubMed

Taylor, Kathryn S; Verbakel, Jan Y; Feakins, Benjamin G; Price, Christopher P; Perera, Rafael; Bankhead, Clare; Plüddemann, Annette

2018-05-21

To assess the diagnostic accuracy of point-of-care natriuretic peptide tests in patients with chronic heart failure, with a focus on the ambulatory care setting. Systematic review and meta-analysis. Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase, Health Technology Assessment Database, Science Citation Index, and Conference Proceedings Citation Index until 31 March 2017. Eligible studies evaluated point-of-care natriuretic peptide testing (B-type natriuretic peptide (BNP) or N terminal fragment pro B-type natriuretic peptide (NTproBNP)) against any relevant reference standard, including echocardiography, clinical examination, or combinations of these, in humans. Studies were excluded if reported data were insufficient to construct 2×2 tables. No language restrictions were applied. 42 publications of 39 individual studies met the inclusion criteria and 40 publications of 37 studies were included in the analysis. Of the 37 studies, 30 evaluated BNP point-of-care testing and seven evaluated NTproBNP testing. 15 studies were done in ambulatory care settings in populations with a low prevalence of chronic heart failure. Five studies were done in primary care. At thresholds >100 pg/mL, the sensitivity of BNP, measured with the point-of-care index device Triage, was generally high and was 0.95 (95% confidence interval 0.90 to 0.98) at 100 pg/mL. At thresholds <100 pg/mL, sensitivity ranged from 0.46 to 0.97 and specificity from 0.31 to 0.98. Primary care studies that used NTproBNP testing reported a sensitivity of 0.99 (0.57 to 1.00) and specificity of 0.60 (0.44 to 0.74) at 135 pg/mL. No statistically significant difference in diagnostic accuracy was found between point-of-care BNP and NTproBNP tests. Given the lack of studies in primary care, the paucity of NTproBNP data, and potential methodological limitations in these studies, large scale trials in primary care

Dwarfism and early death in mice lacking C-type natriuretic peptide

PubMed Central

Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

2001-01-01

Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

Comparison of the clinical utility of atrial and B type natriuretic peptide measurement for the diagnosis of systolic dysfunction in a low‐risk population

PubMed Central

Galasko, Gavin; Collinson, Paul O; Barnes, Sophie C; Gaze, David; Lahiri, Arjivit; Senior, Roxy

2007-01-01

Background Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high‐throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro‐atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care. Methods 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45–89, interquartile range 51–67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton–Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at −70°C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2–2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6–10.1%). Echocardiography was used as the diagnostic “gold standard”, with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of ⩽40%. Patients were dichotomised by ejection fraction from 50% to 30%, and receiver operating characteristic curves constructed and the area under the curve (AUC) compared. Results At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of, respectively, 0.738 (0.601–0.875) and 0.973 (0.958–0.989), p<0.004. Conclusion NTproBNP is superior to NTproANP for detection of systolic dysfunction. PMID:17513518

Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-α.

PubMed

Keane, Fiona M; Nadvi, Naveed A; Yao, Tsun-Wen; Gorrell, Mark D

2011-04-01

Fibroblast activation protein-α (FAP) is a cell surface-expressed and soluble enzyme of the prolyl oligopeptidase family, which includes dipeptidyl peptidase 4 (DPP4). FAP is not generally expressed in normal adult tissues, but is found at high levels in activated myofibroblasts and hepatic stellate cells in fibrosis and in stromal fibroblasts of epithelial tumours. FAP possesses a rare catalytic activity, hydrolysis of the post-proline bond two or more residues from the N-terminus of target substrates. α(2)-antiplasmin is an important physiological substrate of FAP endopeptidase activity. This study reports the first natural substrates of FAP dipeptidyl peptidase activity. Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY were the most efficiently hydrolysed substrates and the first hormone substrates of FAP to be identified. In addition, FAP slowly hydrolysed other hormone peptides, such as the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are efficient DPP4 substrates. FAP showed negligible or no hydrolysis of eight chemokines that are readily hydrolysed by DPP4. This novel identification of FAP substrates furthers our understanding of this unique protease by indicating potential roles in cardiac function and neurobiology. © 2011 The Authors Journal compilation © 2011 FEBS.

Physical and mental recovery after conventional aortic valve surgery.

PubMed

Petersen, Johannes; Vettorazzi, Eik; Winter, Lena; Schmied, Wolfram; Kindermann, Ingrid; Schäfers, Hans-Joachim

2016-12-01

Physical and mental recovery are important factors to consider in the treatment of aortic valve disease, and the process of recovery is not well known. We investigated the course of physical and mental recovery directly after conventional aortic valve surgery. In a longitudinal study, 60 patients undergoing elective aortic valve surgery were studied preoperatively and at intervals of 4 weeks after aortic valve surgery. The last measurement was taken 6 months postoperatively. Measurements included the 6-minute walk test and N-terminal pro-B-type natriuretic peptide. Mental recovery was assessed by the Short Form Health Survey and the Hospital Anxiety and Depression Scale. All parameters were compared with published healthy norms. All parameters except for the anxiety score showed a significant decline after the first postoperative measurement at 1 week after aortic valve surgery. The baseline level was restored at 1 to 3 weeks (anxiety, depression, mental quality of life, Borg scale), 4 to 6 weeks (6-minute walk test, physical quality of life), and 9 weeks (N-terminal pro-B-type natriuretic peptide) after the first postoperative week. Significantly better values than preoperatively for the first time were reached at 2 to 3 weeks (anxiety, depression, mental quality of life), 5 weeks (6-minute walk test), 8 weeks (physical quality of life), and 12 weeks (N-terminal pro-B-type natriuretic peptide) after the first postoperative week. At 3 months postoperatively, significant improvements (P < .001) were seen in walk distance (+212 m), dyspnea (-1.11), physical (+12.38) and mental quality of life (+7.71), anxiety (-3.74), and depression (-3.62) compared with the first week postoperatively. At 6 months postoperatively, all parameters were significantly improved compared with preoperative data and, except for the N-terminal pro-B-type natriuretic peptide value, significantly better or equal compared with published healthy norms. After conventional aortic

Natriuretic peptide-guided management in heart failure.

PubMed

Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

2016-08-01

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Natriuretic peptides and their therapeutic potential in heart failure treatment: An updated review.

PubMed

Namdari, M; Eatemadi, A; Negahdari, B

2016-09-30

Brain natriuretic peptide (BNP), also known as a B-type natriuretic peptide, is one of the important biomarkers with a proven role in the diagnosis of congestive heart failure (CHF). Researchers from the different clinical field have researched into the performance features of BNP testing in the acute care set-up to assist and improve in diagnosing CHF and in predicting future morbidity and mortality rates. The potency of BNP has also been researched into in cases like myocardial ischemia and infarction, cor pulmonale, and acute pulmonary embolism (PE). Based on their vaso-dilatory and diuretic properties and ability to inhibit renin-angiotensin-aldosterone system, natriuretic peptides are able to provide an efficient technique and mechanism of action in the pathophysiologic framework for CHF treatment and management. Recent clinical studies reported that ularitide, a synthetic form of urodilatin, secreted by kidney may be effective in managing and treatment of decompensated heart failure. It has also been reported that Nesiritide, a recombinant natriuretic peptide has been proven to improve dyspnea and hemodynamic parameters in heart failure patients. This review provides an update on natriuretic peptides and their therapeutic potential in CHF treatment.

Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial.

PubMed

Scirica, Benjamin M; Braunwald, Eugene; Raz, Itamar; Cavender, Matthew A; Morrow, David A; Jarolim, Petr; Udell, Jacob A; Mosenzon, Ofri; Im, KyungAh; Umez-Eronini, Amarachi A; Pollack, Pia S; Hirshberg, Boaz; Frederich, Robert; Lewis, Basil S; McGuire, Darren K; Davidson, Jaime; Steg, Ph Gabriel; Bhatt, Deepak L

2014-10-28

Diabetes mellitus and heart failure frequently coexist. However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point. A total of 16 492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo (mean follow-up, 2.1 years). The primary end point was the composite of cardiovascular death, myocardial infarction, or ischemic stroke. Hospitalization for heart failure was a predefined component of the secondary end point. Baseline N-terminal pro B-type natriuretic peptide was measured in 12 301 patients. More patients treated with saxagliptin (289, 3.5%) were hospitalized for heart failure compared with placebo (228, 2.8%; hazard ratio, 1.27; 95% confidence intercal, 1.07-1.51; P=0.007). Corresponding rates at 12 months were 1.9% versus 1.3% (hazard ratio, 1.46; 95% confidence interval, 1.15-1.88; P=0.002), with no significant difference thereafter (time-varying interaction, P=0.017). Subjects at greatest risk of hospitalization for heart failure had previous heart failure, an estimated glomerular filtration rate ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide. There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin (P for interaction=0.46), although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile (2.1%). Even in patients at high risk of hospitalization for heart failure, the risk of the primary and secondary end points were similar between treatment groups. In the context of balanced primary and secondary end points, saxagliptin treatment was associated with an increased risk or hospitalization for heart failure. This increase in risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease. http

Brain natriuretic peptide: Much more than a biomarker.

PubMed

Calzetta, Luigino; Orlandi, Augusto; Page, Clive; Rogliani, Paola; Rinaldi, Barbara; Rosano, Giuseppe; Cazzola, Mario; Matera, Maria Gabriella

2016-10-15

Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with left ventricular function in patients with acute exacerbation of COPD, even without history of heart failure. Several studies have been conducted in vitro and in vivo, both in animals and in humans, in order to assess the potential role of the NPR-A activation as a novel therapeutic approach for treating obstructive pulmonary disorders. Unfortunately, these studies have yielded conflicting results. Nevertheless, further recent specific studies, performed in ex vivo models of asthma and COPD, have confirmed the bronchorelaxant effect of BNP and its protective role against bronchial hyperresponsiveness in human airways. These studies have also clarified the intimate mechanism of action of BNP, represented by an autocrine loop elicited by the activation of NPR-A, localized on bronchial epithelium, and the relaxant response of the surrounding ASM, which does not expresses NPR-A. This review explores the teleological activities and paradoxical effects of BNP with regard to chronic obstructive respiratory disorders, and provides an excursus on the main scientific findings that explain why BNP should be considered much more than a biomarker. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Utility of B-type natriuretic peptide measurement in outpatients with heart failure with preserved ejection fraction].

PubMed

Jorge, Antonio José Lagoeiro; Freire, Monica Di Calafiori; Ribeiro, Mário Luiz; Fernandes, Luiz Cláudio Maluhy; Lanzieri, Pedro Gemal; Jorge, Bruno Afonso Lagoeiro; Lage, João Gabriel B; Rosa, Maria Luiza Garcia; Mesquita, Evandro Tinoco

2013-09-01

Heart failure with preserved ejection fraction (HFPEF) is a highly prevalent syndrome that is difficult to diagnose in outpatients. The measurement of B-type natriuretic peptide (BNP) may be useful in the diagnosis of HFPEF, but with a different cutoff from that used in the emergency room. The aim of this study was to identify the BNP cutoff for a diagnosis of HFPEF in outpatients. This prospective, observational study enrolled 161 outpatients (aged 68.1±11.5 years, 72% female) with suspected HFPEF. Patients underwent ECG, tissue Doppler imaging, and plasma BNP measurement, and were classified in accordance with algorithms for the diagnosis of HFPEF. HFPEF was confirmed in 49 patients, who presented higher BNP values (mean 144.4pg/ml, median 113pg/ml, vs. mean 27.6pg/ml, median 16.7pg/ml, p<0.0001). The results showed a significant correlation between BNP levels and left atrial volume index (r=0.554, p<0.0001), age (r=0.452; p<0.0001) and E/E' ratio (r=0.345, p<0.0001). The area under the ROC curve for BNP to detect HFPEF was 0.92 (95% confidence interval: 0.87-0.96; p<0.001), and 51pg/ml was identified as the best cutoff to detect HFPEF, with sensitivity of 86%, specificity of 86% and accuracy of 86%. BNP levels in outpatients with HFPEF are significantly higher than in those without. A cutoff value of 51pg/ml had the best diagnostic accuracy in outpatients. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Relation between N-terminal pro-brain natriuretic peptide and cardiac remodeling and function assessed by cardiovascular magnetic resonance imaging in patients with arrhythmogenic right ventricular cardiomyopathy.

PubMed

Cheng, Huaibing; Lu, Minjie; Hou, Cuihong; Chen, Xuhua; Wang, Jing; Yin, Gang; Chu, Jianmin; Zhang, Shu; Prasad, Sanjay K; Pu, Jielin; Zhao, Shihua

2015-02-01

Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful screening test of impaired right ventricular (RV) function in conditions affecting the right-sided cardiac muscle, the role of NT-proBNP remains unclear in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study was designed to clarify the relation between the plasma NT-proBNP level and the RV function evaluated by cardiovascular magnetic resonance (CMR) imaging. We selected 56 patients with confirmed ARVC only when their blood specimens for NT-proBNP measurements were collected within 48 hours of a CMR scan. The NT-proBNP level was significantly higher in patients with RV dysfunction than in patients without RV dysfunction (median of 655.3 [interquartile range 556.4 to 870.0] vs 347.0 [interquartile range 308.0 to 456.2] pmol/L, p <0.001). The NT-proBNP levels were positively correlated with RV end-diastolic and end-systolic volume indices (r = 0.49 and 0.70, respectively) and negatively correlated with RV ejection fraction (r = -0.76, all p <0.001), which remained significant after adjustment for age, gender, and body mass index. The area under the receiver-operating characteristic curve for NT-proBNP was 0.91 (95% confidence interval 0.80 to 0.97, p <0.001). The cut-off value of NT-proBNP (458 pmol/L) was associated with sensitivity, specificity, and positive and negative predictive values of 91%, 89%, 67%, and 98%, respectively. In conclusion, NT-proBNP is a useful marker for the detection of RV dysfunction and associated with extent of RV dilatation and dysfunction determined by CMR in patients with ARVC. Copyright © 2015 Elsevier Inc. All rights reserved.

C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma.

PubMed

Wu, Jia-Shuan; Mu, Li-Min; Bu, Ying-Zi; Liu, Lei; Yan, Yan; Hu, Ying-Jie; Bai, Jing; Zhang, Jing-Ying; Lu, Weiyue; Lu, Wan-Liang

2017-06-20

Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.

Rise and fall of NT-proBNP in aortic valve intervention.

PubMed

Hultkvist, Henrik; Holm, Jonas; Svedjeholm, Rolf; Vánky, Farkas

2018-01-01

To describe the dynamics of N-terminal pro-B-type natriuretic peptide (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1-year mortality. At preoperative evaluation, we prospectively included 462 patients accepted for aortic valve intervention. The median time to surgical aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6-month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation and aortic stenosis with and without coronary artery bypass were also analysed. NT-proBNP remained stable in all subgroups during the preoperative waiting period, but displayed a substantial transient early postoperative increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative days 1 and 3 revealed significant discriminatory power with regard to 1-year mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had higher levels of NT-proBNP both preoperatively and at the 6-month follow-up compared with the SAVR group. The dynamic profile of NT-proBNP differed between patients undergoing TAVI and SAVR. NT-proBNP in the perioperative course was associated with increased risk of 1-year mortality in SAVR but not in TAVI.

Alteration of lung atrial natriuretic peptide receptors in genetic cardiomyopathy.

PubMed

Mukaddam-Daher, S; Tremblay, J; Fujio, N; Koch, C; Jankowski, M; Quillen, E W; Gutkowska, J

1996-07-01

These studies were designed to characterize the atrial natriuretic peptide (ANF) receptor subtypes [guanylyl cyclase natriuretic peptide receptors (NPR-A, NPR-B) and NPR-C] in lungs of normal hamsters and to evaluate alterations in receptor kinetics in genetic cardiomyopathy (CMO), a model of human congestive heart failure. Lung membranes were obtained from normal and CMO 200-to 230-day-old hamsters. Cross-linking and competitive binding receptor assays using 125I-labeled human ANF showed that lung membranes exhibit NPR, mainly guanylyl cyclase NPR-A and clearance NPR-C receptors. Stimulation of guanylyl cyclase by ANF and C-type natriuretic peptide (CNP) confirmed the presence of NPR-A and NPR-B. The maximum binding capacity of total ANF binding sites (442 +/- 68 vs. 271 +/- 57 fmol/mg protein, P < 0.05) was reduced, but dissociation constant (0.26 +/- 0.04 vs. 0.41 +/- 0.08 nM) was not altered in CMO animals. Similar reductions were observed in the binding sites for brain natriuretic peptide (BNP; 438 +/- 83 vs. 236 +/- 53 fmol/mg protein) and CNP (321 +/- 80 vs. 165 +/- 56 fmol/mg protein, P < 0.05) which may reflect a decline in NPR-A and NPR-B and/or NPR-C. Acid wash improved binding of 125I-labeled rat ANF to lung membranes of both normal and CMO hamsters, but the tendency towards reduced binding in CMO hamsters did not reach statistical significance, implying that downregulation may not have been due only to prior occupancy of the receptors. Transcripts of NPR-A, NPR-B, and NPR-C receptors in hamster lungs were detected by quantitative polymerase chain reaction. Compared with normal controls, the CMO hamster lung NPR-A mRNA was reduced by 50%, but NPR-B mRNA and NPR-C mRNA were not altered. Moreover, CMO hamster lungs showed less activation of guanylyl cyclase by ANF. These studies demonstrate that lung NPR are downregulated in hamster CMO.

C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice.

PubMed

Kimura, Toru; Nojiri, Takashi; Hino, Jun; Hosoda, Hiroshi; Miura, Koichi; Shintani, Yasushi; Inoue, Masayoshi; Zenitani, Masahiro; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

2016-02-19

Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. C57BL/6 mice were divided into two groups, CNP-treated (2.5 μg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin-CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-β-induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary-cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1β and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-β-induced phosphorylation of Smad2 and increased mRNA and protein expression of α-smooth muscle actin and SM22�

Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Misono, K. S.; Philo, J. S.; Arakawa, T.

2011-06-01

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures ofmore » the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.« less

The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke.

PubMed

Fischer, Marlene; Katan, Mira; Morgenthaler, Nils G; Seiler, Marleen; Müller, Beat; Lackner, Peter; Errath, Mario; Helbok, Raimund; Pfausler, Bettina; Beer, Ronny; Schmutzhard, Erich; Broessner, Gregor

2014-01-01

Atrial natriuretic peptide (ANP) is a well-known prognostic marker of outcome and mortality in patients with cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP) is a stable fragment of the ANP precursor hormone. As a prognostic marker after ischemic stroke, it reliably predicts poststroke mortality and functional outcome. This study aimed to analyze the prognostic value of MR-proANP in patients with hemorrhagic stroke, i.e. subarachnoid (SAH) and intracerebral hemorrhage (ICH). MR-proANP was analyzed in patients with spontaneous SAH or spontaneous ICH. All patients were prospectively randomized into two treatment arms: (1) a prophylactic normothermia group with a target core temperature 36.5°C using endovascular cooling, and (2) a control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on admission and on days 4 and 7. Measurement of MR-proANP was performed in serum using sandwich immunoassay. The primary endpoint was functional outcome [assessed by the Glasgow Outcome Score (GOS)] and the secondary endpoints were mortality within 180 days after hemorrhagic stroke and influence of temperature on MR-proANP. A favorable outcome was defined as GOS 4-5, and the patients were considered to have a poor outcome with a 180-day GOS score between 1 and 3. Analysis of MR-proANP was performed in 24 patients with spontaneous SAH and 22 patients with spontaneous ICH. MR-proANP was elevated on days 4 and 7 as compared to baseline levels (p < 0.05 and p < 0.001, respectively). High MR-proANP levels (>120 pmol/l) were associated with increased mortality and poor outcome (after 180 days; p < 0.05, respectively). There was no significant difference regarding MR-proANP serum concentrations between the endovascular and the control groups. Increased levels of MR-proANP are independently associated with poor functional outcome and increased mortality after 180 days in

B-type natriuretic peptide-guided management and outcome in patients with obesity and dyspnea--results from the BASEL study.

PubMed

Noveanu, Markus; Breidthardt, Tobias; Cayir, Sevgi; Potocki, Mihael; Laule, Kirsten; Mueller, Christian

2009-09-01

Obesity may reduce diagnostic accuracy of B-type natriuretic peptide (BNP) and affect long-term outcome. This study evaluated patients included in the BASEL study (N = 452). We compared BNP levels in patients with (n = 86) and without (n = 366) obesity (body mass index <30 and >30 kg/m(2)) and determined sensitivities and specificities of BNP in both patient groups by receiver-operating characteristic analysis. Impact of BNP measurements on patient management and outcome in obesity, as well as 360-day mortality, was assessed. The BNP levels were lower in obese patients (172 pg/mL [interquartile range 31-515] vs 306 [interquartile range 75-1,040]). The optimal BNP cut-point to detect heart failure was 182 pg/mL in obese patients and 298 pg/mL nonobese patients. Obese patients had lower in-hospital mortality (3.5% vs 8.5%, P = .045) and 360-day mortality (15% vs 30%, P = .001). In obese patients, the determination of BNP levels reduced time to initiation of the appropriate treatment (96 +/- 98 vs 176 +/- 230, P < .05) without impacting other end points. Adjustment of BNP values in the assessment of obese patients presenting with acute dyspnea seems necessary to improve diagnostic accuracy and patient management. Obese patients had half the short- and long-term mortality of nonobese patients, independent of their final discharge diagnosis.

Expression of receptors for atrial natriuretic peptide on the murine bone marrow-derived stromal cells.

PubMed

Agui, T; Yamada, T; Legros, G; Nakajima, T; Clark, M; Peschel, C; Matsumoto, K

1992-05-01

Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [125I]ANP binding assays and Northern blot analyses. The binding of [125I] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [125I]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [125I]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [125I]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.

[The role of natriuretic peptides in heart failure].

PubMed

Ancona, R; Limongelli, G; Pacileo, G; Miele, T; Rea, A; Roselli, T; Masarone, D; Messina, S; Palmieri, R; Golia, E; Iacomino, M; Gala, S; Calabrò, P; Di Salvo, G; Calabrò, R

2007-10-01

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Effects of inspiratory muscle training on autonomic activity, endothelial vasodilator function, and N-terminal pro-brain natriuretic peptide levels in chronic heart failure.

PubMed

Laoutaris, Ioannis D; Dritsas, Athanasios; Brown, Margaret D; Manginas, Athanassios; Kallistratos, Manolis S; Chaidaroglou, Antigoni; Degiannis, Dimitrios; Alivizatos, Peter A; Cokkinos, Dennis V

2008-01-01

To assess the effects of inspiratory muscle training (IMT) on autonomic activity, endothelial function, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure. Using age- and sex-matched controlled study, 23 patients (mean left ventricular ejection fraction 29 +/- 2%) were assigned to either a high-intensity training group (n = 14), New York Heart Association (NYHA) class II (n = 9)/III (n = 5), or a low-intensity training group (n = 9), NYHA class II (n = 6)/III (n = 3), exercising at 60% and 15% of sustained maximum inspiratory pressure (SPImax), respectively, 3 times per week for 10 weeks. Before and following IMT, patients underwent cardiopulmonary exercise testing and dyspnea evaluation on exertion. Sympathovagal balance was assessed by heart rate variability (HRV) from 24-hour electrocardiogram and endothelial function, using venous occlusion plethysmography. Serum levels of NT-proBNP were determined. High-intensity training group improved maximum inspiratory pressure (PImax, 105.4 +/- 5.3 vs 79.1 +/- 5 cm H2O, P = .001), SPImax (511 +/- 42 vs 308 +/- 28 cm H2O/sec/10, P = .001), peak oxygen consumption (19 +/- 1.2 vs 17.1 +/- 0.7 mL.kgmin, P = .01) and dyspnea (17.6 +/- 0.2 vs 18.1 +/- 0.1, P = .02). Endothelium-dependent vasodilation, HRV, and NT-proBNP levels were not altered. Low-intensity training group increased only the PImax (97.6 +/- 11.3 vs 84.2 +/- 8.7 cm H2O, P = .03). Improvement in dyspnea and exercise tolerance after IMT were not associated with changes in markers of HRV, endothelial function, and NT-proBNP in patients with mild to moderate chronic heart failure. Further studies on the effects of IMT in advanced heart failure would be worthwhile.

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis.

PubMed

Natriuretic Peptides Studies Collaboration; Willeit, Peter; Kaptoge, Stephen; Welsh, Paul; Butterworth, Adam; Chowdhury, Rajiv; Spackman, Sarah; Pennells, Lisa; Gao, Pei; Burgess, Stephen; Freitag, Daniel; Sweeting, Michael; Wood, Angela; Cook, Nancy; Judd, Suzanne; Trompet, Stella; Nambi, Vijay; Olsen, Michael; Everett, Brendan; Kee, Frank; Ärnlöv, Johan; Salomaa, Veikko; Levy, Daniel; Kauhanen, Jussi; Laukkanen, Jari; Kavousi, Maryam; Ninomiya, Toshiharu; Casas, Juan-Pablo; Daniels, Lori; Lind, Lars; Kistorp, Caroline; Rosenberg, Jens; Mueller, Thomas; Rubattu, Speranza; Panagiotakos, Demosthenes; Franco, Oscar; de Lemos, James; Luchner, Andreas; Kizer, Jorge; Kiechl, Stefan; Salonen, Jukka; Goya Wannamethee, S; de Boer, Rudolf; Nordestgaard, Børge; Andersson, Jonas; Jørgensen, Torben; Melander, Olle; Ballantyne, Christie; DeFilippi, Christopher; Ridker, Paul; Cushman, Mary; Rosamond, Wayne; Thompson, Simon; Gudnason, Vilmundur; Sattar, Naveed; Danesh, John; Di Angelantonio, Emanuele

2016-10-01

Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model

NT-pro-BNP predicts worsening renal function in patients with chronic systolic heart failure.

PubMed

Pfister, R; Müller-Ehmsen, J; Hagemeister, J; Hellmich, M; Erdmann, E; Schneider, C A

2011-06-01

Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and WRF. A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT-pro-BNP with WRF was analysed during a follow up of 18 months. Twenty-eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063-4765) had significantly higher baseline NT-pro-BNP values than patients without WRF (547 pg/mL, IQR 173-1454). The risk for WRF increased by 4.0 (95% CI 2.1-7.5) for each standard deviation of log NT-pro-BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT-pro-BNP and diabetes were independent predictors of WRF. At a cut-off level of 696 pg/mL, NT-pro-BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF. NT-pro-BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno-protective strategies in patients with elevated NT-pro-BNP. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Stanojevic, Natasa Bogavac; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-11-01

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor. © 2013 Wiley Periodicals, Inc.

[Prognostic value of changes in concentration of brain natriuretic peptide, TNF-alpha factor and Interleukin-6 in chronic cardiac failure].

PubMed

Volkova, S Iu

2008-01-01

During 6 months therapy initial and final N-terminal pro-B-type natriuretic peptide. TNF-alpha, and IL-6 level in blood plasma were determined in 61 ischemic CHI cases with left ventricular ejection fraction below 40%. The patients were followed up for next 24.7 +/- 11.5 months. In period of 6 months following up associated with performed therapy 67.9% of patients showed a positive clinical effect, combined with a decrease of plasma pools of neurohumoral mediators (NM) in 51.4%-71.4% of cases (in dependence on studied NM). There were selected the 4 variants of combinations of clinical efficacy and NM dynamics which failed to coincide in a half of observations for NT-pro BNP and IL-6, and in a third for TNF-alpha. Multivariate analysis of conformities showed, that a decrease of all NM during therapy significantly relates with patient surviving. In a group with a decrease of plasma NT-pro BNP level associated with therapy during consequent following up no lethal outcome was recorded, compared to 16% in a group with a rise in NT-pro BNP (a = 0.2). Lethal outcome was fixed in 4.2% in a group with a decrease in TNF-alpha, compared to 33.3% in a group with elevation in TNF-alpha (a = 0.016); and in 5% in a group with a fall in IL-6, compared to 23.1% in a group with an elevation of IL-6 (a = 0.04).

Correlates of N-Terminal Prohormone Brain Natriuretic Peptides in African Americans with Hypertensive Chronic Kidney Disease: The African American Study of Kidney Disease and Hypertension

PubMed Central

Yi, S.; Contreras, G.; Miller, E.R.; Appel, L.J.; Astor, B.C.

2009-01-01

Background/Aims The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited. Methods The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20–65 ml/min/1.73 m2) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants. Results In unadjusted analyses, GFR (r = −0.39; p < 0.001), hematocrit (r = −0.21; p < 0.001) and body mass index (BMI; r = −0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP. Conclusion Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure. PMID:18824845

Clinical characteristics and serum N-terminal pro-brain natriuretic peptide as a diagnostic marker of Kawasaki disease in infants younger than 3 months of age.

PubMed

Bae, Hyun Kyung; Lee, Do Kyung; Kwon, Jung Hyun; Kim, Hae Soon; Sohn, Sejung; Hong, Young Mi

2014-08-01

The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was 1.36±1.0 days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was 2.8±1.4. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were 4,159±3,714 pg/mL and 957±902 pg/mL, respectively, which decreased significantly in the convalescent phase. Incomplete KD was observed in 87.5% patients. Serum NT-proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

Brain Natriuretic Hormone Predicts Stress Induced Alterations in Diastolic Function

PubMed Central

Choksy, Pratik; Davis, Harry C.; Januzzi, James; Thayer, Julian; Harshfield, Gregory; Robinson, Vincent JB; Kapuku, Gaston K.

2015-01-01

Background Mental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (BNP) mediates the relationship of MS with DF is unknown. Method and Results 160 individuals aged 30 to 50 years underwent 2 hour protocol of 40 minutes rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E’ and E/E’ as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level age, sex, race, height, BMI, pro-BNP, and LVM were permitted to enter the models. The second level consisted of SBP, DBP and HR. The final level contained cross-product terms of race by SBP, DBP and HR. E/A ratio was lower during stress compared to rest, and recovery (p<0.01). Resting E/A ratio was predicted by a regression model of age (−.31), pro-BNP (.16), HR (−.40) and DBP (−.23) with an R2 = .33. Stress E/A ratio was predicted by age (−.24), pro-BNP (.08), HR (−.38), and SBP (−.21), total R2 = .22. Resting E’ model consisted of age (−.22), pro-BNP (.26), DBP (−.27) and LVM (−.15) with an R2 = .29. Stress E’ was predicted by age (−.18), pro-BNP (.35) and LVM (−.18) with an R2 = .18. Resting E/E’ was predicted by race (.17, B>W) and DBP (.24) with an R2 = .10. Stress E/E’ consisted of pro-BNP (−.36), height (−.26) and HR (−.21) with R2 = .15. Conclusion pro-BNP predicts both resting and stress DF suggesting that lower BNP during MS may be a maker of diastolic dysfunction in apparently healthy individuals. PMID:24841419

Predicting functional capacity in patients with a systemic right ventricle: subjective patient self-assessment is better than B-type natriuretic peptide levels and right ventricular systolic function.

PubMed

Book, Wendy; McConnell, Michael; Oster, Matthew; Lyle, Teresa; Kogon, Brian

2013-01-01

Many adults with transposition of the great arteries have an anatomic right ventricle functioning as the systemic ventricle and are known to develop congestive heart failure, premature cardiac death, and need for cardiac transplantation. Predictors of poor clinical outcome and functional status in patients with left ventricular failure do not always apply to these patients. We aimed to identify predictors of poor functional status in those patients with a systemic right ventricle. We performed a prospective study of 51 adults with transposition of the great arteries and systemic right ventricles. Demographic, clinical, laboratory, and imaging data were collected, and patients completed a Minnesota Living with Heart Failure Questionnaire (MLHFQ). Comparisons were made between those patients with d-type transposition of the great arteries (dTGA) who have undergone prior atrial switch and those with congenitally corrected transposition (ccTGA). A correlation analysis was performed to identify predictors of poor functional status, as determined by a 6-minute walk distance test. Median age was 30 years (range 19-65). Median B-type natriuretic peptide was 48 pg/mL (range 16-406). There were 27 patients (53%) with moderate-severe right ventricular dysfunction and 10 (20%) with moderate-severe tricuspid valve regurgitation. The median MLHFQ score was 9 (range 0-78) and 6-minute walk test was 510 m (range 231-703). Forty-one patients had a diagnosis of dTGA atrial switch and 11 patients had ccTGA. Patients with ccTGA were significantly older (40 vs. 28 years, P =.004) and had more tricuspid valve regurgitation (P =.02). Despite this, their MLHFQ scores were significantly lower (2.5 vs. 17, P =.04) and they walked further (635 vs. 504 m, P =.02). Predictors of a short 6-minute walk distance included short stature (P =.009) and dTGA (P =.002). The patient's self-assessment of poor health, as measured by an increased New York Heart Association class (P =.003) and a decreased

Serum A-FABP is increased and closely associated with elevated NT-proBNP levels in type 2 diabetic patients treated with rosiglitazone.

PubMed

Zhou, Mi; Bao, Yuqian; Lu, Junxi; Zhou, Jian; Jia, Weiping

2011-01-01

Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment. A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007). Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.

Ordering human CD34+CD10−CD19+ pre/pro-B-cell and CD19− common lymphoid progenitor stages in two pro-B-cell development pathways

PubMed Central

Sanz, Eva; Muñoz-A., Norman; Monserrat, Jorge; Van-Den-Rym, Ana; Escoll, Pedro; Ranz, Ismael; Álvarez-Mon, Melchor; de-la-Hera, Antonio

2010-01-01

Studies here respond to two long-standing questions: Are human “pre/pro-B” CD34+CD10−CD19+ and “common lymphoid progenitor (CLP)/early-B” CD34+CD10+CD19− alternate precursors to “pro-B” CD34+CD19+CD10+ cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig VH-D-JH sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34highLineage− pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34+CD45RA+CD10−CD19−) directly generate an initial wave of Pax5+TdT− “unilineage” pre/pro-B cells and a later wave of “multilineage” CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the VH-D-JH Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5+TdT− pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway. PMID:20231472

Addition of N-terminal pro-B natriuretic peptide to soluble fms-like tyrosine kinase-1/placental growth factor ratio > 38 improves prediction of pre-eclampsia requiring delivery within 1 week: a longitudinal cohort study.

PubMed

Sabriá, E; Lequerica-Fernández, P; Lafuente-Ganuza, P; Eguia-Ángeles, E; Escudero, A I; Martínez-Morillo, E; Barceló, C; Álvarez, F V

2018-06-01

Short-term prediction of pre-eclampsia (PE) using the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio is characterized by frequent false-positive results. As such, no treatment can be recommended to test-positive patients and multiple measurements are often required. The aim of this study was to evaluate the effectiveness of N-terminal pro-B natriuretic peptide (NT-proBNP), uric acid and the sFlt-1/PlGF ratio for prediction of delivery with PE within 1 week in singleton pregnancies with suspected PE and sFlt-1/PlGF ratio > 38. This was a longitudinal prospective cohort study of singleton pregnancies presenting at 24 + 0 to 36 + 6 weeks of gestation with clinically suspected PE and sFlt-1/PlGF ratio > 38, enrolled between January 2015 and June 2017. Multiple samples per patient were allowed but were restricted to one sample per gestational week. From 495 enrolled patients, 270 blood samples from 134 patients were ultimately analyzed. By using generalized estimating equations (GEE), the best-fit model was selected for prediction of delivery with PE within 1 week. The predictive value of this model was then assessed using area under the paired-ROC curve (AUC) analysis. The best-fit model included the sFlt-1/PlGF ratio, NT-proBNP and the gestational week at the time of the measurement. This combined model was compared with the GEE model based on the sFlt-1/PlGF ratio and the gestational week at the time of the measurement (reduced model). The AUC for the combined model was 0.845 (95% CI, 0.787-0.896), which was significantly greater (P = 0.011) than that of the reduced model (0.786 (95% CI, 0.722-0.844)). The addition of NT-proBNP assessment improves the short-term prediction of delivery as a result of PE compared with sFlt-1/PlGF ratio alone, when the sFlt-1/PlGF ratio is > 38. This finding should be considered in future research on the assessment of short-term risk of delivery as a result of PE. Copyright �

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Relationship of plasma N-terminal pro-brain natriuretic peptide concentrations to heart failure classification and cause of respiratory distress in dogs using a 2nd generation ELISA assay.

PubMed

Fox, P R; Oyama, M A; Hezzell, M J; Rush, J E; Nguyenba, T P; DeFrancesco, T C; Lehmkuhl, L B; Kellihan, H B; Bulmer, B; Gordon, S G; Cunningham, S M; MacGregor, J; Stepien, R L; Lefbom, B; Adin, D; Lamb, K

2015-01-01

Cardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD). Determine the utility of plasma N-terminal pro-brain natriuretic peptide concentration [NT-proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity. Client-owned dogs (n = 291). Multicenter, cross-sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM-HD) schemes without knowledge of [NT-proBNP] results. Receiver-operating characteristic curve analysis assessed the capacity of [NT-proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT-proBNP] and HD severity. Plasma [NT-proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769-8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672-2,704 pmol/L; P < .0001). A cut-off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end-systole, and ACVIM-HD scheme most accurately associated average plasma [NT-proBNP] with HD severity. Plasma [NT-proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT-BNP] increased significantly as a function of HD severity using the ACVIM-HD classification scheme. Copyright © 2014 by the American College of

Elevated myocardial enzymes and natriuretic peptides in anorexia nervosa: prototypic condition for the pathophysiology of cachexia?

PubMed

Zastrow, Arne; Wolf, Johanna; Giannitsis, Evangelos; Katus, Hugo; Herzog, Wolfgang; Friederich, Hans-Christoph; Mussler, Christina

2011-01-01

We report on a patient suffering from chronic anorexia nervosa who in the course of treatment showed elevated high-sensitive troponin T, creatine kinase and most markedly N-terminal pro-brain natriuretic peptide (NT-proBNP). Elevated enzymes improved significantly throughout the course of treatment without cardiac specific medication but exceeded the normal range for weeks. Abnormally high myocardial enzymes and NT-proBNP in cachectic anorectic patients might resemble conditions of cardiac cachexia. A review of the available literature is provided. Further research is required to explain the pathophysiological meaning of the abnormal laboratory findings. Copyright © 2011 S. Karger AG, Basel.

A functional genetic variant (N521D) in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

PubMed

Pereira, Naveen L; Redfield, Margaret M; Scott, Christopher; Tosakulwong, Nirubol; Olson, Timothy M; Bailey, Kent R; Rodeheffer, Richard J; Burnett, John C

2014-01-01

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community. NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown. DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography. Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected. A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.

PubMed

Matusik, Paweł T; Matusik, Patrycja S; Kornacewicz-Jach, Zdzisława; Małecka, Barbara; Ząbek, Andrzej; Undas, Anetta

2017-09-15

Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. We investigated plasma fibrin clot permeability (K s ), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased K s (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower K s (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA 2 DS 2 -VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). K s was inversely correlated with log NT-proBNP (r=-0.34, P<0.0001), plasminogen activator inhibitor-1 (PAI-1) antigen (r=-0.24, P=0.002) and C-reactive protein (r=-0.18, P=0.02), while CLT was positively correlated with log NT-proBNP (R=0.61, P<0.0001) and ETP (r=0.37, P<0.0001), which were interrelated (r=0.59, P<0.0001). After adjustment for potential confounders, PAI-1 (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.02-1.26) was the only independent predictor of low K s (the lowest quartile,≤6×10 -9 cm 2 ), while NT-proBNP (OR: 1.21; 95% CI: 1.12-1.31) and PAI-1 (OR: 1.30; 95% CI: 1.12-1.51) both predicted prolonged CLT (the top quartile,≥109min). In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Epicardial fat thickness in stable coronary artery disease: its relationship with high-sensitive cardiac troponin T and N-terminal pro-brain natriuretic peptide.

PubMed

Börekçi, Abdurrezzak; Gür, Mustafa; Özaltun, Betül; Baykan, Ahmet Oytun; Harbalioğlu, Hazar; Seker, Taner; Sen, Ömer; Acele, Armağan; Gözükara, Mehmet Yavuz; Kuloğlu, Osman; Koç, Mevlüt; Çayli, Murat

2014-12-01

Epicardial adipose tissue is related to coronary atherosclerosis, left ventricle hypertrophy, myocardial dysfunction, cardiomyopathy, and inflammation, which produces a variety of cytokines that influence key pathogenic mechanisms of atherogenesis. The main goal of this study is to examine the relationship between epicardial fat thickness (EFT) and cardiovascular risk markers as well as the complexity of coronary artery disease (CAD) in patients with stable CAD. We prospectively included 439 stable CAD patients undergoing coronary angiography in the present study (mean age: 62.2±10.7 years). Patients were divided into two groups (EFTlow and EFThigh groups) according to their median EFT values. EFT was evaluated by two-dimensional echocardiography before angiography. The SYNTAX score was calculated in all patients. N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP), high-sensitive cardiac troponin T (hs-cTnT), uric acid, and other biochemical markers were also measured. Age, SYNTAX score, frequencies of diabetes, hyperlipidemia, and hypertension, NT-proBNP, hs-CRP, hs-cTnT, and uric acid levels were higher in EFThigh group compared with the EFTlow group (P<0.05 for all). EFT was associated independently with age (β=-0.102, P=0.001), diabetes (β=-0.083, P=0.011), SYNTAX score (β=0.352, P<0.001), hs-CRP level (β=0.217, P<0.001), hs-cTnT level (β=0.197, P<0.001), and NT-proBNP level (β=0.300, P<0.001) in multivariate analysis. EFT obtained by echocardiograpy may not only be an easy tool but also an important tool for early detection of increased cardiac risk as well as the extent and complexity of CAD in patients with stable CAD.

Molecular forms of C-type natriuretic peptide in cerebrospinal fluid and plasma reflect differential processing in brain and pituitary tissues.

PubMed

Wilson, Michele O; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2018-01-01

C-type natriuretic peptide (CNP) is a paracrine growth factor widely expressed within tissues of the central nervous system. Consistent with this is the high concentration of CNP in cerebrospinal fluid (CSF), exceeding levels in the systemic circulation. CNP abundance is high in hypothalamus and especially enriched in pituitary tissue where - in contrast to hypothalamus - processing to CNP-22 is minimal. Recently we have shown that dexamethasone acutely raises CNP peptides throughout the brain as well as in CSF and plasma. Postulating that molecular forms of CNP would differ in central tissues compared to forms in pituitary and plasma, we have characterized the molecular forms of CNP in tissues (hypothalamus, anterior and posterior pituitary gland) and associated fluids (CSF and plasma) using size-exclusion high performance liquid chromatography (SE-HPLC) and radioimmunoassay in control (saline-treated) and dexamethasone-treated adult sheep. Three immunoreactive-CNP components were identified which were consistent with proCNP (1-103), CNP-53 and CNP-22, but the presence and proportions of these different fragments differed among tissues. Peaks consistent with CNP-53 were the dominant form in all tissues and fluids. Peaks consistent with proCNP, conspicuous in hypothalamic extracts, were negligible in CSF whereas proportions of low molecular weight immunoreactivity (IR) consistent with CNP-22 were similar in hypothalamus, posterior pituitary gland and CSF. In contrast, in both plasma and the anterior pituitary gland, proportions of higher molecular weight IR, consistent with CNP-53 and proCNP, predominated, and low molecular weight IR consistent with CNP-22 was very low. After dexamethasone, proCNP like material - but not other forms - was increased in all samples except CSF, consistent with increased synthesis and secretion. In conclusion, immunoreactive forms of CNP in central tissues differ from those identified in anterior pituitary tissue and plasma

Protective effects of recombinant human brain natriuretic peptide in perioperative period during open heart surgery.

PubMed

Xu, Yunbin; Li, Yong; Bao, Weiguo; Qiu, Shi

2018-03-01

The aim of the present study was to evaluate the protective effects and safety aspects of recombinant human brain natriuretic peptide (rhBNP) on cardiac functions of patients undergoing open-heart surgery during perioperative period. In total, 150 patients undergoing open heart surgery in the Second Hospital of Shandong Universty from August 2015 to July 2016 were randomly divided into control group and observation group each with 75 cases. Patients in control group were treated by routine rehabilitation while patients in the observation group were treated by both the routine rehabilitation and rhBNP. All the observations were made before operation, after operation and 7 days after operation. The changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) of patients, the left ventricular ejection fraction (LVEF), cardiac function [Cardiac output (CO), pulmonary capillary wedge pressure (PAWP) and central venous pressure (CVP)] of patients were measured. Further, respirator support time, ICU stay time, incidence of complications and vital signs (BP, HR, SaO2) of patients in the two groups were also compared. NT-proBNP levels of all patients improved after operation but it decreased in both groups after 7 days of operation. The decrease of NT-proBNP levels in observation group was significantly higher than that of control group. Whereas, LVEF, CO, PAWP and CVP of patients in both the groups increased after operation but effects were significantly higher in the observation group after 7 days of medication. Respirator support time and ICU stay time of patients in observation group were significantly shorter than those in control group, and the incidence of postoperative complications of patients in the observation group were significantly lower than the control group. Moreover, BP, HR and SaO2 of patients in observation group were significantly elevated in comparison to control group (P<0.05). Recombinant human brain natriuretic peptide (rhBNP) could significantly

B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

PubMed

Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

2015-07-01

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood. © 2015 American Heart Association, Inc.

Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS.

PubMed

Frøssing, Signe; Nylander, Malin; Kistorp, Caroline; Skouby, Sven O; Faber, Jens

2018-01-01

Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP. To investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin. Seventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined. Baseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45-0.56) nmol/L, MR-proANP 44.8 (34.6-56.7) pmol/L and copeptin 4.95 (3.50-6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM -6% (-11 to 2, P  = 0.058), MR-proANP -25% (-37 to -11, P  = 0.001) and copeptin +4% (-13 to 25, P  = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate. In an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently

Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation

PubMed Central

Wall, Leona; Mohr, Annika; Ripoli, Florenza Lüder; Schulze, Nayeli; Penter, Camila Duarte; Hungerbuehler, StephanOscar; Bach, Jan-Peter; Lucas, Karin

2018-01-01

Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate

Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation.

PubMed

Wall, Leona; Mohr, Annika; Ripoli, Florenza Lüder; Schulze, Nayeli; Penter, Camila Duarte; Hungerbuehler, StephanOscar; Bach, Jan-Peter; Lucas, Karin; Nolte, Ingo

2018-01-01

Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate

N-terminal pro-brain natriuretic peptide as a useful predictor of early surgery in neonates with congenital heart diseases: a prospective observational study.

PubMed

Makimura, Mika; Koga, Hiroshi

2014-01-01

Pediatric studies have found a correlation between the clinical heart failure score and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. However, the clinical usefulness of this marker remains unclear in neonates. At hospitals without pediatric cardiologists, neonatologists or general pediatricians must judge whether surgery is indicated and transfer patients to a specialized hospital in a timely fashion as required. Thus, we tested the hypothesis that increased NT-proBNP levels predict short-term outcomes in neonates with congenital heart diseases (CHDs) and are thus a useful tool for evaluating clinical status and guiding treatment. Subjects were term or near-term newborns (≥36 weeks' gestation) with CHDs confined to left-to-right shunt lesions. Clinical parameters and NT-proBNP levels were measured on the first 7, 14, 21, and 28 days of life (DOL). We divided patients into a surgical (n = 7) and a conservative-treatment group (n = 21), and then compared clinical variables and outcomes between the groups. In the surgical group, NT-proBNP levels had a tendency to increase during the first 14 postnatal days and were significantly greater than in the conservative-treatment group on 7 DOL [median (range), 13,983 pg/mL (4,732-26,524) vs. 1,954 pg/mL (671-10,881); p = 0.0028] and on 14 DOL [29,274 pg/mL (14,006-33,740) vs. 2,050 pg/mL (1,304-9,250); p = 0.0055]. In contrast, NT-proBNP levels tended to decrease sequentially in the conservative-treatment group. The values of additional markers, such as mean NT-proBNP level on 7 and 14 DOLs (M7-14) and NT-proBNP level on 14 DOL minus that on 7 DOL (Δ7-14), were both significantly greater in the surgical group than in the conservative-treatment group. To examine the usability of M7-14 and Δ7-14 when the difference and mean cut-off levels were set at 10,000 and 3,000 pg/mL, respectively, the sensitivity and specificity were both 100 %. In neonates who had CHDs with left

Multi-center validation of the Response Biomedical Corporation RAMP NT-proBNP assay with comparison to the Roche Diagnostics GmbH Elecsys proBNP assay.

PubMed

Lee-Lewandrowski, Elizabeth; Januzzi, James L; Green, Sandy M; Tannous, Bakhos; Wu, Alan H B; Smith, Andrew; Wong, Alicia; Murakami, MaryAnn M; Kaczmarek, Jason; Apple, Fred S; Miller, Wayne L; Hartman, Karen; Jaffe, Allan S

2007-01-01

NT-proBNP measurements aid in the evaluation of patients with suspected heart failure (HF) and may facilitate risk stratification in patients with HF and acute coronary syndrome (ACS). Point-of-care (POC) assays may provide more timely results and potentially improve patient outcomes. We evaluated the analytical performance of the Response Biomedical Corporation whole blood RAMP amino-terminal pro-B type natriuretic peptide (NT-proBNP) POC assay compared to the Roche Elecsys proBNP (NT-proBNP) assay. Intra-day and total imprecision (% CV) ranged from 5.5% to 10.3% at 140, 449 and 1675 ng/L. The lowest concentration that yields a 20% CV was 57 ng/L. The lower limit of detection was 18 ng/L. The upper limit of linearity was validated to 23,428 ng/L with an average recovery of 95%. Correlation by Passing and Bablok regression yielded RAMP=1.01 Elecsys+14.6, r=0.98 (n=540; range of Elecsys values <5 to >35,000). Concordance of RAMP versus Elecsys using cut-offs of 125 ng/L for subjects <75 years and 450 ng/L for subjects > or =75 was 92% (95% CI 89-94%) for a group consisting of 127 apparently healthy individuals and 208 non-healthy subjects without HF, and 99% (95% CI 97-100%) for patients with HF, using the New York Heart Association (NYHA) functional classification. Overall, 80%, 87%, 97% and 100% of the RAMP results and 77%, 85%, 96% and 100% of the Elecsys results were greater than the age appropriate cut-off for NYHA I, II, III or IV groups. For both the RAMP and Elecsys results, the median NT-proBNP value was statistically correlated (increasing) with NYHA I, II, III or IV groups, respectively (p<0.0001), with no significant difference between the two methods. The POC Response Biomedical RAMP NT-proBNP assay provides comparable results that measured on the FDA cleared Roche Elecsys central laboratory platform.

High peripheral levels of h-FABP are associated with poor prognosis in end-stage heart failure patients with mechanical circulatory support.

PubMed

Cabiati, Manuela; Caselli, Chiara; Caruso, Raffaele; Prescimone, Tommaso; Verde, Alessandro; Botta, Luca; Parodi, Oberdan; Del Ry, Silvia; Giannessi, Daniela

2013-06-01

To associate the time-course of h-FABP and N-terminal pro B-type natriuretic peptide (NT-proBNP)after left ventricular assist device (LVAD) implantation to outcome in end-stage heart failure patients. Patients (n = 14, NYHA class III/IV; left ventricular ejection fraction <25% were enrolled; ten survived up to 1 month after LVAD (survivors) and four died of multiorgan failure within 2 weeks (nonsurvivors). Blood samples were obtained at admission; at 4, 24 and 72 h; and at 1 and 4 weeks after LVAD. h-FABP significantly increases after surgery, decreasing since 72 h in all patients. At 72 h all survivor patients present h-FABP lower than the median value. N-terminal pro B-type natriuretic peptide is not associated with patient outcome at any time. High h-FABP levels, indicating the presence of more severe myocardial damage, are associated with a poor prognosis in patients with LVAD, suggesting that an early cardiac injury marker could improve the prediction of clinical outcome.

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients

PubMed Central

2013-01-01

Background Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). Methods We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. Results In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. Conclusions FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients. PMID:23642261

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients.

PubMed

Cabré, Anna; Valdovinos, Pilar; Lázaro, Iolanda; Bonet, Gil; Bardají, Alfredo; Masana, Lluís

2013-05-04

Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.

The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study

PubMed Central

2013-01-01

Introduction Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH. Methods We evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively. Conclusions The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies. PMID:24246100

Fasting glucose, NT-proBNP, treatment with eptifibatide, and outcomes in non-ST-segment elevation acute coronary syndromes: An analysis from EARLY ACS.

PubMed

Farhan, Serdar; Clare, Robert M; Jarai, Rudolf; Giugliano, Robert P; Lokhnygina, Yuliya; Harrington, Robert A; Kristin Newby, L; Huber, Kurt

2017-04-01

Higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels have been linked to a more favorable glucometabolic profile. Little is known about the interaction of NT-proBNP and fasting glucose in non-ST-segment elevation acute coronary syndrome (NSTE ACS). Fasting glucose and NT-proBNP were measured in 2240 patients enrolled in the EARLY ACS trial. Multivariable Cox models were used to assess associations between fasting glucose and NT-proBNP and a 96-hour composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout; 30-day death or MI; and 1-year mortality. In adjusted Cox models, neither NT-proBNP nor fasting glucose was associated with the 96-hour endpoint (p=0.95 and p=0.87). NT-proBNP was associated with 30-day death or MI (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.22, p=0.02) and 1-year mortality (HR 1.63, 95% CI 1.42-1.89, p<0.0001), but fasting glucose was associated only with 1-year death (HR 1.53, 95% CI 1.08-2.16, p=0.02). NT-proBNP×glucose interaction terms were non-significant in all models. As fasting glucose levels increased, the risk of 96-hour and 30-day endpoints increased among patients who received early eptifibatide but not delayed, provisional use (p int =0.035 and p int =0.029). Higher NT-proBNP levels were associated with greater 30-day death or MI among patients who received early eptifibatide but not delayed, provisional use (p int =0.045). NT-proBNP and fasting glucose concentrations were associated with intermediate-term ischemic outcomes and may identify differential response to treatment with eptifibatide. CLINICALTRIALS. NCT00089895. Copyright © 2017. Published by Elsevier B.V.

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

PubMed Central

Wei, C M; Kim, C H; Miller, V M; Burnett, J C

1993-01-01

This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

PubMed

Wang, Tzung-Dau; Tan, Ru-San; Lee, Hae-Young; Ihm, Sang-Hyun; Rhee, Moo-Yong; Tomlinson, Brian; Pal, Parasar; Yang, Fan; Hirschhorn, Elizabeth; Prescott, Margaret F; Hinder, Markus; Langenickel, Thomas H

2017-01-01

Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576. © 2016 American Heart Association, Inc.

Prognostic value of mid-regional pro-adrenomedullin levels taken on admission and discharge in non-ST-elevation myocardial infarction: the LAMP (Leicester Acute Myocardial Infarction Peptide) II study.

PubMed

Dhillon, Onkar S; Khan, Sohail Q; Narayan, Hafid K; Ng, Kelvin H; Struck, Joachim; Quinn, Paulene A; Morgenthaler, Nils G; Squire, Iain B; Davies, Joan E; Bergmann, Andreas; Ng, Leong L

2010-07-06

The purpose of this study was to assess the prognostic value of admission and discharge mid-regional pro-adrenomedullin (sAM) levels in non-ST-elevation myocardial infarction (MI) and identify values to aid clinical decision making. N-terminal pro-B-type natriuretic peptide and GRACE (Global Registry of Acute Coronary Events) score were used as comparators. sAM is a stable precursor of adrenomedullin. We measured plasma sAM on admission and discharge in 745 non-ST-elevation MI patients (514 men, median age 70.0 +/- 12.7 years). The primary end point was a composite of death, heart failure, hospitalization, and recurrent acute MI over mean follow-up of 760 days (range 150 to 2,837 days), with each event assessed individually as secondary end points. During follow-up, 120 (16.1%) patients died, and there were 65 (8.7%) hospitalizations for heart failure and 77 (10.3%) recurrent acute MIs. Both admission and discharge levels were increased (median 0.81 nmol/l [range 0.06 to 5.75 nmol/l] and 0.76 nmol/l [range 0.25 to 6.95 nmol/l], respectively) compared with established normal ranges. Multivariate adjusted Cox regression models revealed that both were associated with the primary end point (hazard ratio: 9.75 on admission and 7.54 on discharge; both p < 0.001). Admission sAM was particularly associated with early (<30 days) mortality (c-statistic = 0.90, p < 0.001), and when compared with N-terminal pro-B-type natriuretic peptide and GRACE score, it was the only independent predictor of this end point. Admission sAM >1.11 nmol/l identified those at highest risk of death (p < 0.001). Patients with above-median admission sAM may benefit from revascularization. sAM level is prognostic for death or heart failure. Admission levels are a strong predictor of early mortality and, when >1.11 nmol/l, complements the GRACE score to improve risk stratification. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

PubMed

Tajima, Yoshitaka; Suzuki, Eiji; Saito, Jun; Murase, Hiroshi; Horikawa, Yukio; Takeda, Jun

2015-01-01

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.

Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

PubMed

Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig; Hansen, Tine W; Rasmussen, Susanne; Wachtell, Kristian; Torp-Pedersen, Christian; Hildebrandt, Per R; Ibsen, Hans

2010-01-01

In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup of 48% with extremely high cardiovascular risk who should be referred for specialist care to optimize treatment.

Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

PubMed

Stockburger, Martin; de Teresa, Eduardo; Lamas, Gervasio; Desaga, Martin; Koenig, Carsten; Habedank, Dirk; Cobo, Erik; Navarro, Xavier; Wiegand, Uwe

2014-01-01

Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study

PubMed Central

2014-01-01

Background The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. Methods In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment. Results NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups. Conclusions Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP. Trial registry ClinicalTrials.gov NCT00469599 May 3 2007. PMID:25112372

Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

PubMed

Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

2015-04-01

Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease.

PubMed

Hallén, Jonas; Madsen, Lene; Ladefoged, Søren; Fagerland, Morten W; Serebruany, Victor L; Agewall, Stefan; Atar, Dan

2011-03-01

To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. This prospective, controlled cohort study included 109 patients. Biomarkers were sampled at inclusion and considered as categorical and continuous variables in Cox proportional hazard models. Mean follow-up ± SD was 926 ± 385 days, during which 52 patients (48%) died. All three markers were predictive of death in univariate analysis. In multivariable analysis, elevated cTnT (> 0.01 μg/l) and CRP (> 1.0 mg/dl) remained significantly associated with mortality [hazard ratio (95% confidence interval), 3.2 (1.2-8.5), p = 0.017 for cTnT; 2.0 (1.0-3.8), p = 0.032 for CRP], while NT-pro-BNP lost independent prognostic power. Addition of cTnT and CRP to established risk factors significantly improved the global fit of the model (p < 0.001), increased the c statistic from 0.726 to 0.758 and significantly increased the integrated discrimination improvement (p < 0.001). The results suggest that cTnT and CRP can be used in combination for risk stratification in patients with ESRD and highlight the additive effect they confer in this regard.

Natriuretic peptide system in the rat submaxillary gland.

PubMed

Jankowski, M; Petrone, C; Tremblay, J; Gutkowska, J

1996-04-09

Natriuretic peptides and their receptors were characterized in rat submaxillary glands (SGs). Reverse phase-high performance liquid chromatography (HPLC) of rat SGs extracts revealed the presence of the 28-amino-acid (AA) circulating peptide ANP (Ser99-Tyr126) and the 126-AA prohormone (Asn1-Tyr126). The presence of ANP prohormone indicated that SGs are a site of ANP synthesis. Indeed, ANP mRNAs were demonstrated. ANP mRNA was 10 times lower than in the lung and only about 7 times lower than in the hypothalamus. ANP content in SG was determined as 30 +/- 8 ng/mg of protein (n = 7). In addition the presence of another member of the natriuretic peptide family, C-type natriuretic peptide (CNP), was found in SG. The CNP level of 293 +/- 38 pg/mg protein was significantly higher than in the lungs (44 +/- 6 pg/mg protein, P < 0.001, n = 5), but about 15 times lower than in hypothalamus (4.5 +/- 0.6 ng/mg protein, P < 0.001, n = 6). Both guanylyl cyclase and clearance receptors were expressed in SG. The presence of natriuretic peptide transcripts and their receptors suggests a role in rat SG functions.

Bone marrow stromal-B cell interactions in polycyclic aromatic hydrocarbon-induced pro/pre-B cell apoptosis.

PubMed

Allan, Lenka L; Mann, Koren K; Matulka, Raymond A; Ryu, Heui-Young; Schlezinger, Jennifer J; Sherr, David H

2003-12-01

Environmental polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons are immunotoxic in a variety of systems. In a model system of B lymphopoiesis, PAH exposure rapidly induces apoptosis in CD43- pre-B and CD43+ pro/pre-B cells. Apoptosis induction by 7,12-dimethylbenzo[a]anthracene (DMBA) is dependent upon AhR+ bone marrow stromal cells and likely involves DMBA metabolism within the stromal cell. However, it is not known if PAH-treated stromal cells release free metabolites or soluble factors that may directly induce B cell death or if the effector death signal is delivered by stromal cell-B cell contact. Here, we demonstrate that supernatants from DMBA-treated bone marrow stromal cells contain an activity capable of inducing apoptosis in pro/pre-B cells cocultured with stromal cells. This activity (1) is not produced when stromal cells are cotreated with DMBA and alpha-naphthoflavone (alpha-NF), an aryl hydrocarbon receptor (AhR) and cytochrome P-450 inhibitor, (2) is > or = 50 kDa, (3) is trypsin and heat sensitive, and (4) is dependent on AhR+ stromal cells, which in turn deliver the effector death signal to pro/pre-B cells. The results (1) argue against a role for a soluble, stromal cell-derived cytokine as the effector of PAH-induced pro/pre-B cell death, (2) exclude the possibility of a free metabolite acting directly on AhR- pro/pre-B cell targets, and (3) suggest the elaboration by stromal cells of a relatively stable, DMBA metabolite-protein complex capable of acting on other stromal cells at some distance. Collectively, these studies suggest that, while stromal cell products, e.g., metabolite-protein complexes, may affect the function of distant stromal cells, the effector death signal delivered by stromal cells to bone marrow B cells is mediated by cell-cell contact.

Decrease in B-Type Natriuretic Peptide Levels and Successful Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure.

PubMed

Yanagisawa, Satoshi; Inden, Yasuya; Kato, Hiroyuki; Fujii, Aya; Mizutani, Yoshiaki; Ito, Tadahiro; Kamikubo, Yosuke; Kanzaki, Yasunori; Hirai, Makoto; Murohara, Toyoaki

2016-03-01

Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction. Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation. After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [-9.0-77.4]% vs -2.4 [-47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001). Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up. ©2015 Wiley Periodicals, Inc.

Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans.

PubMed

Xue, Yang; Taub, Pam R; Iqbal, Navaid; Fard, Arrash; Wentworth, Bailey; Redwine, Laura; Clopton, Paul; Stein, Murray; Maisel, Alan

2012-04-15

Post-traumatic stress disorder (PTSD) is gaining increasing recognition as a risk factor for morbidity and mortality. The aim of this study was to examine the impact of PTSD and abnormal cardiovascular biomarkers on mortality in military veterans. Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the end point of all-cause mortality. Ninety-one patients had PTSD at the time of enrollment. There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality (p = 0.006, p = 0.024, and p = 0.003, respectively). In a multivariate model, PTSD, B-type natriuretic peptide, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for B-type natriuretic peptide, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007). In conclusion, this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Prognostic value of N-terminal prohormone brain natriuretic peptide for in-hospital and long-term outcomes in patients with infective endocarditis.

PubMed

Wei, Xue-Biao; Liu, Yuan-Hui; He, Peng-Cheng; Yu, Dan-Qing; Zhou, Ying-Ling; Tan, Ning; Chen, Ji-Yan

2017-05-01

Background Limited research studies with a large sample size were performed to evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for in-hospital or long-term poor outcomes in patients with infective endocarditis. Methods A total of 703 patients with infective endocarditis were enrolled and divided into four groups according to admission NT-pro-BNP (pg/mL) quartiles: Q1 (<258), Q2 (258-1054), Q3 (1055-3522) and Q4 (>3522). Multivariate regression was used to determine independent risk of NT-proBNP for in-hospital and one-year death. Results In-hospital death occurred in 9.0% of patients. The in-hospital mortality was increased from the lowest to the highest NT-proBNP quartiles (1.1%, 3.4%, 9.1% and 22.3%, P < 0.001, respectively). During the one-year follow-up period, 29 patients died: 0 in Q1, 7 (4.6%) in Q2, 8 (5.7%) in Q3 and 14 (12.0%) in Q4 ( P < 0.001). Log-transformed (lg) NT-proBNP had a linear correlation with lg C-reactive protein ( r = 0.308, P < 0.001). Multivariate analysis showed lgNT-proBNP was an independent predictor for both in-hospital (odds ratio 4.59, 95% confidence interval (CI) 2.45-8.61, P < 0.001) and one-year mortality (hazard ratio 3.11, 95% CI 1.65-5.87, P < 0.001). In addition, NT-proBNP had a higher predictive power for in-hospital death than C-reactive protein (area under the curve 0.797 vs. 0.670, P = 0.005). NT-proBNP > 2260 pg/mL had 76.2% sensitivity and 69.1% specificity for predicting in-hospital death. Kaplan-Meier analysis showed that patients with NT-proBNP > 2260 pg/ml had a worse prognosis than those without (log-rank test 18.84, P < 0.001). Conclusion Increased NT-proBNP was independently associated with in-hospital and one-year mortality in patients with infective endocarditis.

Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System.

PubMed

Grogan, Martha; Scott, Christopher G; Kyle, Robert A; Zeldenrust, Steven R; Gertz, Morie A; Lin, Grace; Klarich, Kyle W; Miller, Wayne L; Maleszewski, Joseph J; Dispenzieri, Angela

2016-09-06

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure. The purpose of this study was to determine the natural history of ATTRwt and the predictors of survival. We retrospectively reviewed patients diagnosed with ATTRwt at the Mayo Clinic through 2013 and recorded clinical data and survival data. Factors affecting overall survival (OS) were identified, and a prognostic staging system was developed. The median age of the 360 patients diagnosed before death was 75 years (range: 47 to 94 years), and 91% were male. Presenting signs and symptoms included dyspnea or heart failure in 67% and atrial arrhythmias in 62%. Median OS from diagnosis was 3.6 years and did not change over time. Multivariate predictors of mortality included age, ejection fraction, pericardial effusion, N-terminal pro-B-type natriuretic peptide, and troponin T. A staging system was developed that used thresholds of troponin T (0.05 ng/ml) and N-terminal pro-B-type natriuretic peptide (3,000 pg/ml). The respective 4-year OS estimates were 57%, 42%, and 18% for stage I (both values below cutoff), stage II (one above), and stage III (both above), respectively. Stage III patients were at an increased risk of mortality after adjustment for age and sex compared with stage I patients (hazard ratio: 3.6; p < 0.001). The natural history of ATTRwt is poor. We report a novel cardiac biomarker staging system that enables risk stratification in an era of emerging treatment strategies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Biomarkers and mortality after transient ischemic attack and minor ischemic stroke: population-based study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-03-01

Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events. Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement. During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease

New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides.

PubMed

Zhai, Yuting; Luo, Yuanyuan; Wu, Pei; Li, Dongye

2018-05-01

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prognostic prediction of troponins in cardiac myxoma: case study with literature review

PubMed Central

Yuan, Shi-Min

2015-01-01

Objective It was supposed that troponins in cardiac myxoma patients might be in a same fashion as in the conditions without myocardial injury. In order to verify this hypothesis, troponins in cardiac myxoma patients were discussed by presenting a comprehensive retrieval of the literature with incorporating the information of a recent patient. Methods Postoperative detections of troponin I, creatine kinase isoenzyme MB (CK-MB) and N-terminal pro-B-type natriuretic peptide revealed elevated troponin I and CK-MB and normal N-terminal pro-B-type natriuretic peptide. Postoperative troponin I and CK-MB shared a same trend, reaching a peak value at postoperative hour 2, gradually decreased on postoperative day 1, and reached a plateau on postoperative days 7 and 13. A significant correlation could be noted between the postoperative values of the two indicators (Y=0.0714X + 0.6425, r2=0.9111, r=0.9545, P=0.0116). No significant linear correlation between troponin I and N-terminal pro-B-type natriuretic peptide were found. Literature review of troponins in cardiac myxoma patients revealed the uncomplicated patients had a normal or only slightly elevated troponin before open heart surgery. However, the complicated patients (with cerebral or cardiac events) showed a normal preoperative troponin in 3 (23.1%) and an elevated troponin in 10 (76.9%) patients (χ2=7.54, P=0.0169, Fisher's exact test). The overall quantitative result of troponin I was 2.45±2.53 µg/L, and that of troponin T was 3.10±4.29 mg/L, respectively. Conclusion Troponins are not necessarily elevated in patients with a cardiac myxoma without coronary syndrome. By contrast, patients with a cardiac myxoma with an elevated troponin may herald the presence of an associated coronary event. An old cerebral infarct does not necessarily cause an elevation of troponin or B-type natriuretic peptide, or new neurological events, but might lead to a delayed awakening. PMID:26107461

Follow-up of congenital heart disease patients with subclinical hypothyroidism.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna

2015-08-01

Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years - 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Separation of plasmacytoid dendritic cells from B-cell-biased lymphoid progenitor (BLP) and Pre-pro B cells using PDCA-1.

PubMed

Medina, Kay L; Tangen, Sarah N; Seaburg, Lauren M; Thapa, Puspa; Gwin, Kimberly A; Shapiro, Virginia Smith

2013-01-01

B-cell-biased lymphoid progenitors (BLPs) and Pre-pro B cells lie at a critical juncture between B cell specification and commitment. However, both of these populations are heterogenous, which hampers investigation into the molecular changes that occur as lymphoid progenitors commit to the B cell lineage. Here, we demonstrate that there are PDCA-1(+)Siglec H(+) plasmacytoid dendritic cells (pDCs) that co-purify with BLPs and Pre-pro B cells, which express little or no CD11c or Ly6C. Removal of PDCA-1(+) pDCs separates B cell progenitors that express high levels of a Rag1-GFP reporter from Rag1-GFP(low/neg) pDCs within the BLP and Pre-pro B populations. Analysis of Flt3-ligand knockout and IL-7Rα knockout mice revealed that there is a block in B cell development at the all-lymphoid progenitor (ALP) stage, as the majority of cells within the BLP or Pre-pro B gates were PDCA-1(+) pDCs. Thus, removal of PDCA-1(+) pDCs is critical for analysis of BLP and Pre-pro B cell populations. Analysis of B cell potential within the B220(+)CD19(-) fraction demonstrated that AA4.1(+)Ly6D(+)PDCA-1(-) Pre-pro B cells gave rise to CD19(+) B cells at high frequency, while PDCA-1(+) pDCs in this fraction did not. Interestingly, the presence of PDCA-1(+) pDCs within CLPs may help to explain the conflicting results regarding the origin of these cells.

C-type natriuretic peptide functions as an innate neuroprotectant in neonatal hypoxic-ischemic brain injury in mouse via natriuretic peptide receptor 2.