Elevation Of N-terminal Pro-brain Natriuretic Peptide Research Articles

A prediction model for estimating NT-proBNP in a general Japanese population: the Toon Health Study.

As part of the Toon Health Study, which is an ongoing population-based cohort study, we aimed to develop a prediction model for N-terminal pro-brain natriuretic peptide (NT-proBNP) in a general Japanese population. We sought to explore the influence of various demographic and clinical factors on NT-proBNP levels and assess the model's performance. In addition, our objectives included internal validation and investigation of the diagnostic potential of the observed-to-predicted NT-proBNP ratio (OPR) at baseline for predicting the risk of heart failure with preserved ejection fraction (HFpEF). In this prospective cohort study, participants were recruited from Toon City, Japan, as part of the larger Toon Health Study, focusing on cardiovascular risk factors. We measured the NT-proBNP levels and used linear regression with penalization (ridge regression) to develop the model. The model incorporated 10 prespecified predictors (age, gender, body mass index, diastolic blood pressure, heart rate, haemoglobin, albumin, total cholesterol, haemoglobin A1c, and estimated glomerular filtration rate) and underwent assessment using R2 and root mean squared error (RMSE). Internal validation was conducted through bootstrapping. In a post hoc analysis, we explored the OPR's diagnostic potential using 5year follow-up data (n=636) to predict the elevation of NT-proBNP>125pg/mL at the 5year follow-up as the risk of HFpEF. A total of 2505 participants (age: 60.4±12.9years, men: 35%) were enrolled in this study. There was a linear relationship between the observed and predicted values of NT-proBNP in which the logarithm of observed NT-proBNP was <6, which corresponds to 403pg/mL in NT-proBNP. The prediction model demonstrated satisfactory performance (R2: 0.291, RMSE: 0.688), with age identified as a dominant predictor. The stability of the model was underscored by the internal validation. The OPR at baseline predicted NT-proBNP>125pg/mL at the 5year follow-up with an area under the curve of 0.793. This study introduces the first prediction model for NT-proBNP in a general Japanese population. Although the model has acceptable performance, ongoing refinement is essential. Our transparent approach to model development, alongside a web-based interactive tool, lays the groundwork for further improvements and external validation. The OPR holds potential for predicting the future risk of HFpEF. This research contributes to understanding the nuanced influence of patient backgrounds on levels of NT-proBNP in asymptomatic individuals within the context of a broader population-based cohort study.

Relation of early-stage renal insufficiency and cardiac structure and function in a large population of asymptomatic Asians: a cross-sectional cohort analysis.

Few studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored. To explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations. A cross-sectional, retrospective cohort study. Registered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012. Asymptomatic individuals. Renal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e' by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Among 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e' and higher NT-proBNP (all p<0.05) even after adjusting for clinical covariates. In general, lower eGFR estimated by CKD-EPI and MDRD displayed similar impacts on worsening e' and NT-proBNP, rather than E/e', in multivariate models. Finally, lower LV e' or higher composite diastolic score, rather than E/e', demonstrated remarkable interaction with eGFR level estimated by either CKD-EPI or MDRD on circulating NT-proBNP level (p interaction <0.05). Proteinuria was estimated using a urine dipstick rather than more accurately by the urine protein-to-creatinine ratio. Also, pertaining drug history and clinical hard outcomes were lacking. Both clinical estimate of renal insufficiency by eGFR or proteinuria, even in a relatively early clinical stage, were tightly linked to impaired cardiac diastolic relaxation and circulating NT-proBNP level. Elevation of NT-proBNP with worsening renal function may be influenced by impaired myocardial relaxation.

The diagnostic and prognostic value of growth differentiation factor-15 in systemic lupus erythematosus-associated pulmonary arterial hypertension.

Growth-differentiation factor (GDF)-15 is a member of transforming growth factor-β-related cytokine and may respond to right ventricular overload. The objective of this article was to assess the diagnosis and prognostic value of GDF-15 in systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). Serum samples were obtained from 65 patients with SLE-PAH, 51 sex and age matched patients of SLE without PAH (SLE-non-PAH), and 32 healthy controls. Serum GDF-15 level was detected by enzyme-linked immunosorbent assayand the optimal cut-off point was determined by receiver operating characteristiccurve. The primary end-point was death from any cause and the secondary end-point was target goal achievement (TGA). Cox regression analyses and Kaplan-Meier method were performed to identify the prognostic value of GDF-15. Serum GDF-15 levels were significantly higher in SLE-PAH patients (1112.14 ± 781.80 pg/mL) than SLE-non-PAH patients (810 ± 408 pg/mL) and healthy controls (442 ± 139 pg/mL) at baseline. The optimal cut-off value of GDF-15 in the diagnosis of SLE-PAH was 733 pg/mL (AUC = 0.84). In patients with SLE-PAH, GDF-15 level was associated with 6 minwalking distance (ρ = -0.385, p = 0.017) and higher serum N terminal-pro brain natriuretic peptide (NT-proBNP) (ρ = 0.605, p < 0.001). Patients with GDF-15 > 733 pg/mL were more likely to death (adjusted hazard ratio[HR] = 4.01, 95% confidence intervals[CI]:1.23-6.27, p = 0.041) and less likely to achieve treatment goal (adjusted HR = 0.57, 95% CI:0.23-0.79, p = 0.028). In addition, patients with simultaneous elevation of GDF-15 and NT-proBNP showed lower proportion of TGA (p = 0.046). In conclusion, GDF-15 is a new and promising biomarker of development and prognosis in SLE-PAH. The combination of GDF-15 and NT-proBNP may provide more accurate prognostic information.

UTILITY OF IRISIN AND APELIN IN PREDICTION OF HEART FAILURE PHENOTYPES IN TYPE 2 DIABETES MELLITUS PATIENTS

Objective: The aim of the study was to investigate whether serum levels of both irisin and apelin predict HF with preserved ejection fraction (HFpEF) in patients with type 2 diabetes mellitus (T2DM). Design and method: One hundred and eight HF patients with T2DM having HFpEF (n = 58), HF with mildly reduced ejection fraction (HFmrEF, n = 22), HF with reduced ejection fraction (HFrEF, n = 28) aged from 41 to 62 years and 20 non-HF patients with T2DM. Healthy control group was consisted of 25 individuals matched with age and sex. All patients gave voluntary written informed consent to participate in the study. We polled at baseline demographic and anthropometric information, data for hemodynamic performances by B-mode echocardiography, Doppler and TDI, and the levels of biomarkers including irisin, apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP) by ELISA. Results: Using ROC curve we revealed that cut-off points for irisin and apelin that distinguished HFpEF from HFrEF/HFmrEF were (6.50 ng/mL; AUC = 0.78; 95% confidence interval [CI] = 6.85 - 10.66 ng/mL and 4.12 ng/mL, AUC = 0.72; 95% CI = 3.90–5.75 ng/mL, respectively). Then we divided all patients with HF having elevation of NT-proBNP &gt; 750 pmol/mL into three subgroups depending on the biomarkers’ levels. Patients from subgroup A had both irisin and apelin levels higher cut-off points, individuals from group B had higher concentration of one of two biomarkers, and patients from subgroup C demonstrated levels of both peptides lower cut-off points. Multivariate logistic regression analysis revealed that discriminative value of irisin and apelin to predict HFpEF in subgroup B (Odds Ratio [OR] = 2.18; 95% CI = 1.26–3.14; P = 0.001) were substantially higher compared with subgroups A and C (OR = 1.03; 95% CI = 1.00–1.05; P = 0.64 and OR = 0.92; 95% CI = 0.89–1.01; P = 0.62, respectively). Adding irisin and apelin to NT-proBNP as independent variables to the predictive model sufficiently improved discriminative ability of whole model for HFpEF. Conclusions: Multidirectional changes in the levels of irisin and apelin in T2DM patients had better predictive value for HFpEF that simultaneous increase and decrease in the circulating levels of these peptides.

Predictive value of both irisin and apelin for heart failure with preserved ejection fraction in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Irisin is skeletal muscle-derived peptide, the expression of which is under close control of peroxisome proliferator-activated receptor-γ co-activator 1α. Apelin is a peptide having positive inotrope ability and acting as an autocrine regulator of cardiac and vascular reparation. Type 2 diabetes mellitus (T2DM). The aim of the study was to investigate whether serum levels of both irisin and apelin predict HF with preserved ejection fraction (HFpEF) in patients with T2DM. Methods One hundred and eight HF patients with T2DM having HFpEF (EF&amp;gt;50%; n=58), HF with mildly reduced ejection fraction (HFmrEF, EF&amp;lt;40%; n=22), HF with reduced ejection fraction (HFrEF, EF&amp;lt;40%; n=28) aged from 41 to 62 years and 20 non-HF patients with T2DM. Healthy control group was consisted of 25 individuals matched with age and sex. All patients gave voluntary written informed consent to participate in the study. We polled at baseline demographic and anthropometric information, data for hemodynamic performances by B-mode echocardiography, Doppler and TDI, and the levels of biomarkers including irisin, apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP) by ELISA. Results We found that the levels of irisin were significantly higher in HFpEF patients than in HFrEF individuals, whereas healthy volunteers and T2DM non-HF patients demonstrated lower concentrations of these peptides. On contrary, apelin levels were significantly increased in HF patients mainly with HFrEF. There were not significant differences between the levels of these biomarkers in HFrEF and HFmrEF (P=0.42 for all cases). Using ROC curve we revealed that cut-off points for irisin and apelin that distinguished HFpEF from HFrEF/HFmrEF were (6.50 ng/mL; AUC=0.78; 95% confidence interval [CI] = 6.85 - 10.66 ng/mL and 4.12 ng/mL, AUC=0.72; 95% CI=3.90-5.75 ng/mL, respectively). Then we divided all patients with HF having elevation of NT-proBNP &amp;gt; 750 pmol/mL into three subgroups depending on the biomarkers’ levels. Patients from subgroup A had both irisin and apelin levels higher cut-off points, individuals from group B had higher concentration of one of two biomarkers, and patients from subgroup C demonstrated levels of both peptides lower cut-off points. Multivariate logistic regression analysis revealed that discriminative value of irisin and apelin to predict HFpEF in subgroup B (Hazard Ratio [HR]= 2.18; 95% CI=1.26-3.14; P=0.001) were substantially higher compared with subgroups A and C (HR = 1.03; 95% CI=1.00-1.05; P=0.64 and HR = 0.92; 95% CI=0.89-1.01; P=0.62, respectively). Adding irisin and apelin to NT-proBNP as independent variables to the predictive model sufficiently improved discriminative ability of whole model for HFpEF. In conclusion: We found that multidirectional changes in the levels of irisin and apelin in T2DM patients had better predictive value for HFpEF that simultaneous increase and decrease in the circulating levels of these peptides.

The integrated role of NT-pro BNP and STE-GLS for the early detection of chemotherapy-induced cardiotoxicity

Abstract Background Chemotherapeutic agents, used for the treatment of breast cancer, have many side effects, among them is cardiomyopathy. Ejection fraction (EF) is fails to detect the subtle alterations of left ventricular (LV) function. There comes the need for a more sensitive tool for the detection of preclinical chemotherapy-induced cardiomyopathy. Aim Detection of subclinical LV systolic dysfunction in breast cancer patients after 6 weeks of the initiation of their chemotherapeutic treatment, using N-terminal pro brain natriuretic peptide (NT-proBNP) plasma level as well as Speckle tracking echo-global longitudinal strain (STE-GLS). Methods Seventy-four asymptomatic, non-metastasizing breast cancer female patients were included. They were assessed before taking their first chemotherapeutic session and 6 weeks thereafter. Assessment included baseline clinical characteristics, conventional two-dimensional (2D) as well as three-dimensional (3D) echocardiography. Loops of different apical views were recorded for later offline STE-GLS analysis. Blood samples for NT-BNP plasma level were collected before and 6 weeks after the initiation of chemotherapy. Samples were later analyzed using a Sandwich ELISA technique. Results The median NT-proBNP almost doubled after 6 weeks of chemotherapy (73.50 vs 34.4 pg/L, p value &amp;lt;0.001). One patient died before her scheduled follow up visit, and the cause of death is unknown. Fifty patients showed NT-proBNP elevation at their follow up, compared to the baseline visit, 22 (44%) of them had worse (less negative) LV-GLS in their follow up visit. Five patients had an abnormally elevated NT-proBNP plasma level, all of them had a worse follow up LV-GLS. Only two patients showed significant reduction of LVEF &amp;gt;10% to less &amp;lt;53% (chemotherapy-induced cardiotoxicity) but their NT-proBNP did not exceed the cutoff limit. Conclusion The integration of LV-GLS and NT-proBNP is useful in the diagnosis of subclinical, subtle chemotherapy-induced cardiotoxicity. Early detection will prompt early cardioprotective measures and thus helps improving the clinical outcomes. Funding Acknowledgement Type of funding source: None

Pregnancy and pulmonary arterial hypertension—improving surveillance and outcomes with multidisciplinary care and N terminal pro-brain natriuretic peptide trends

Objective To describe maternal and fetal outcomes and N Terminal pro-brain natriuretic peptide (NT-proBNP) trends in pregnancy with pulmonary arterial hypertension (PAH). Methods The medical records of all pregnant women with PAH referred to Pulmonary Hypertension Clinic were retrospectively reviewed and analyzed. Results We identified 35 pregnancies in 22 women (mean age 27.9 ± 4.7 years, mean weight 50.6 ± 8.1 kg). The diagnoses were Eisenmenger syndrome (16, 72.7%), postoperative residual PAH (3, 13.6%), idiopathic PAH (2, 9.1%), and one (4.5%) had systemic lupus erythematosus. About 23 babies (65.7%) were born alive, gestational age of 35.1 ± 2.9 weeks, 47.8% at term, with a birth weight of 2.1 ± 0.8 kg. There was an elevation of NT-proBNP in the initial 72 h postdelivery (median 138 pg/ml, IQR 112-561). Those with a persistent rise beyond 72 h (median 686 pg/ml, IQR 370-3691) had prolonged recovery postpartum (median postdelivery hospital stay 18 days, IQR 12–22) reflecting continued right ventricular stress and maladaptation. There was single maternal mortality (4.5%). Conclusions Maternal and fetal outcomes of pregnancy associated with PAH are better with strict surveillance and multidisciplinary team effort. Postpartum period remains the most vulnerable time. NT-proBNP trends during this period may be a promising objective monitoring tool in identifying at-risk subsets thus improving outcomes.

Determinants of Cardiorespiratory Fitness Following Thoracic Radiotherapy in Lung or Breast Cancer Survivors

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO2, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO2 was 16.8 (13.5 to 21.9) ml·kg-1·min-1 or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO2 (R = -0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO2 (ß = +0.813, p <0.01 and ß = -0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO2, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

Comprehensive assessment of physical fitness in patients with depression

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO2, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO2 was 16.8 (13.5 to 21.9) ml·kg−1·min−1 or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO2 (R = −0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO2 (ß = +0.813, p <0.01 and ß = −0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO2, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

Transfusion-associated circulatory overload in a pediatric patient with neuroblastoma

There have been few reports on pediatric transfusion-associated circulatory overload (TACO). A 5-year-old boy with neuroblastoma underwent resection of the residual tumor. Because anemia progressed at the end of the operation, transfusion of red cell component was initiated. Ten minutes later, he suddenly developed hypoxemia, tachypnea, and tachycardia. Although elevated blood pressure and bilateral infiltrative shadows on chest X-rays were not observed, TACO was diagnosed based on positive balance during operation and N-terminal pro-brain natriuretic peptide elevation. He had no cardiac or renal disorder; however, mild cardiac and/or renal damage due to a long history of chemotherapy and bias toward his primary hematological and malignant disease may have affected the development of TACO.

Factors affecting N-terminal pro-brain natriuretic peptide elevation in the acute phase of Kawasaki disease.

The aim of this study was to investigate the clinical significance and factors that affect N-terminal pro-brain natriuretic peptide (NT-proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications. The laboratory and echocardiography results of 44 KD patients in the acute and subacute phases were reviewed. With preserved cardiac function, median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (343 pg/mL, IQR, 162-1182 pg/mL vs 98 pg/mL, IQR, 61-205 pg/mL, respectively; P < 0.0001). The respective levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 were also significantly elevated in the acute phase compared with the subacute phase: TNF-α, 3.3 pg/mL (IQR, 2.6-4.8 pg/mL) versus 2.4 pg/mL (IQR 1.9-4.0 pg/mL; P < 0.01), sTNFR1, 2741 pg/mL (IQR, 2080-3183 pg/mL) versus 976 pg/mL (IQR, 814-1247 pg/mL; P < 0.0001), sTNFR2, 5644 pg/mL (IQR, 4693-7520 pg/mL) versus 3169 pg/mL (IQR, 2132-3878 pg/mL; P < 0.0001). Log-transformed NT-proBNP was correlated with TNF-α (r = 0.29, P = 0.056), sTNFR1 (r = 0.60, P < 0.0001), and sTNFR2 (r = 0.65, P < 0.0001). TNF-α was correlated with sTNFR1 (r = 0.35, P = 0.02) and sTNFR2 (r = 0.51, P < 0.001). Tumor necrosis factor-α may cause NT-proBNP elevation in the acute phase of KD, and NT-proBNP level may be an indicator of TNF-α activity.

Fracción aminoterminal del propéptido natriurético cerebral y troponina ultrasensible en el dolor torácico agudo de origen incierto. Un subestudio del estudio PITAGORAS

Introduction and objectivesHigh-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. MethodsA 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. ResultsAcute 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. ConclusionsIn 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.Full English text available from:www.revespcardiol.org/en.

N-terminal Pro-brain Natriuretic Peptide and High-sensitivity Troponin in the Evaluation of Acute Chest Pain of Uncertain Etiology. A PITAGORAS Substudy

Introduction and objectivesHigh-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. MethodsA 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. ResultsAcute 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. ConclusionsIn 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.

761 ASSOCIATION OF E/Ea AND NT-proBNP WITH RENAL FUNCTION IN PATIENTS WITH ESSENTIAL HYPERTENSION

Background: To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension. Methods: In 406 hypertensive patients(mean age, 59±13 years), LV diastolic function was measured by the ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic Ea wave velocities (E/Ea) and NT-proBNP was determined. The subjects were classified into three groups: E/Ea≤10 group(n = 85), 10 < E/Ea≤15 group(n = 230) and E/Ea>15 group(n = 91). The renal function was estimated by glomerular filtration rate (GFR) with 99mTc-DTPA. GFR from 30 to 59 ml/min/1.73m2 was defined as Stage 3 CKD. Urinary albumin/creatinine ratio (UACR) served to determine albuminuria. Results: GFR and UACR was significantly correlated with E/Ea and NT-proBNP (P < 0.0001). GFR was lower and UACR was higher in E/Ea≤15 group than in 10 < E/Ea≤15 group or E/Ea≤10 group(P < 0.0001). GFR had significant correlation with age, gender, E/Ea, lgNT-proBNP and lgUACR in multivariate analysis. Patients with higher NT-proBNP were characterized by poorer renal function, while GFR was even lower in patients of LV diastolic dysfunction with higher NT-proBNP. Patients with Stage 3 CKD could be detected by an elevation of NT-proBNP at a cut-off point of 103pg/ml or by increased E/Ea at a cut-off point of 12.4. Conclusions: LV diastolic function, assessed with E/Ea and NT-proBNP is associated with renal function in essential hypertension.

Use of a highly sensitive assay for cardiac troponin T and N-terminal pro-brain natriuretic peptide to diagnose acute rejection in pediatric cardiac transplant recipients

Biomarkers have been proposed to augment or replace endomyocardial biopsy (EMB) to diagnose acute transplant rejection (AR). A new, highly sensitive assay for troponin T detects levels of cardiac troponin T (cTnT) 10- to 100-fold lower than standard assays but has not been investigated in transplant patients. N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been evaluated in pediatric transplant patients. The purpose of this pilot study was to evaluate the association of cTnT and NT-proBNP with AR in pediatric cardiac transplant patients. Plasma was obtained at the time of EMB from pediatric patients ≥ 1 year old. N-terminal pro-brain natriuretic peptide was measured in fresh plasma at the time of biopsy, and cTnT was measured from frozen, stored samples using the highly sensitive assay for troponin T. Biomarker data were correlated with EMB results. Cellular AR was defined as an International Society for Heart and Lung Transplantation biopsy score of grade ≥ 2R. Fifty-three blood samples were obtained from 42 patients (mean age 11 years). Seven episodes of AR occurred in 5 patients. Biopsies with vs without AR were associated with higher cTnT (median [interquartile range {IQR}] 66 [45-139] vs 7 [2-13] pg/mL, P = .001) and NT-proBNP (median [IQR] 11,169 [280-23,317] vs 334 [160-650] pg/mL, P < .01). After successful treatment of AR in 5 patients, cTnT fell markedly (median [IQR] 53.5 [44.8-66.5] to 10.7 [1.5-16.4], P = .05). In this pilot study, we found marked elevation of cTnT and NT-proBNP among children with AR. Moreover, reduction in cTnT levels after treatment paralleled improvement in EMB results. If these findings are confirmed in larger prospective studies, monitoring with these biomarkers may obviate surveillance EMB.

Serum A-FABP Is Increased and Closely Associated with Elevated NT-proBNP Levels in Type 2 Diabetic Patients Treated with Rosiglitazone

BackgroundAdipocyte 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.Methodology/Principal FindingsA 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).Conclusions/SignificanceRosiglitazone-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.

E0239 N-terminal pro-brain natriuretic peptide (NT-proBNP): a potential diagnostic biomarker for predicting cardiac dysfunction in patients with liver diseases

BackgroundNT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis...

MYOCARDIAL RESPONSE TO EXERCISE-INDUCED BLOOD PRESSURE ELEVATION EVALUATED BY CARDIAC BIOMARKERS IN RECENTLY DIAGNOSED HYPERTENSIVE PATIENTS UNDER OPTIMAL TREATMENT: PP.12.448

Background: The clinical significance of increased cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) after maximal exercise test in patients with essential hypertension is unclear. The present study was designed to investigate whether the maximal cardiopulmonary exercise test (CPET) may lead to increased levels of cTnT or/and NT-proBNP in patients with recently diagnosed essential hypertension under optimal treatment. Methods: Twenty three (23) non-diabetic, recently diagnosed hypertensive patients under treatment with RAAS antagonists one month prior exercise (group A, 52.7 + 11 years, 17 males) and 17 normotensives (group B, 47.6 + 13 years, 7 males) undergone a maximal CPET in a bicycle ergometer. Maximal oxygen consumption (VO2 max, %VO2 predicted), anaerobic threshold (AT) and both heart rate (HRmax) and blood pressure response at peak exercise (BPpeak) were calculated. Blood samples were collected from each subject before the CPET and 1 h post-exercise in order to determine cTnT and NT-proBNP levels. Results: Hypertension in group A was successfully treated as blood pressure before exercise (BPpre) was measured within normal limits (126 + 7 mmHg). All patients successfully completed the test while no signs of myocardial ischemia in ECG were found. No significant differences were revealed between groups regarding exercise parameters: VO2 max, %VO2 predicted and AT as well as hemodynamic ones HRmax and BPpeak (189 + 16 mmHg vs. 181 + 22 mmHg, p = NS). No significant changes were revealed before and after exercise in both groups regarding cTnT. In contrast, NT-proBNP was significantly increased one hour after exercise in both groups (group A, pre: 52.8 + 44 vs. after: 58.4 + 49, p = 0.007 and group B, pre: 43.8 + 30 vs. after: 50.1 + 34.2, p = 0.001). Conclusions: Optimal antihypertensive treatment with ACE-I or ARBs one month prior exercise test normalizes exercise and hemodynamic parameters. Exercise-induced blood pressure elevation in both treated hypertensive patients and normotensives, stimulates a minor elevation of NT-proBNP, which may reflect a physiological adaptive process after increased myocardial demand. Whether inadequately controlled hypertension leads to different myocardial response has not been studied.

Diastolic but not systolic dysfunction is associated with troponin and N-terminal pro-brain natriuretic peptide elevation in sepsis

Cardiac dysfunction is one of the key features in sepsis and septic shock, yet its mechanism is poorly understood. We aimed to investigate the pathophysiology of cardiac dysfunction in sepsis by integrating echocardiographic with biochemical and inflammatory markers.

Abstract 2466: Increased Plasma Concentrations of N-Terminal Pro Brain Natriuretic Peptide is a More Sensitive Marker of Subclinical Diastolic Dysfunction and Arterial Remodeling in Hypertension: Analytical Performance Comparison with BNP

Concentrations of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) is inversely related to metabolic cardiovascular risk factors and is a valuable prognostic marker of cardiovascular events in arterial hypertension. Whether NT-proBNP levels are connected with diastolic function and arterial function was determined in hypertension. NT-proBNP was measured in 40 untreated patients with hypertension (mean BP 166/96 mmHg) without heart failure and 20 age and gender matched healthy, controls. Hypertensive patients were studied by pulsed Doppler and color M-mode Doppler echocardiography to evaluate LV diastolic function. Plasma NT-proBNP was significantly elevated in patients with hypertension (75.1 ± 75.2 [SD] pg/ml compared with 37.9 ± 38.5 in controls p &lt; 0.05). In hypertensive patients, NT-proBNP values were negatively correlated with the ratio of color M-mode flow propagation velocity to transmitral E velocity (r=−0.33, p&lt;0.05) while those of BNP had no correlation, suggesting that higher plasma NT-proBNP is indicative of subclinical diastolic dysfunction. Moreover, hypertensive patients with higher NT-proBNP values above the mean value in the control group (NT-proBNP &gt; 38 pg/ml) had significantly increased brachial intimal-medial thickness (0.36 ± 0.08 mm vs. 0.32 ± 0.05, p &lt; 0.05) and reduced wall stress (112.4 ± 29.5 kPa vs. 142.2 ± 30.8, p &lt; 0.05) compared with those with lower NT-proBNP, suggesting that the reference value of NT-proBNP plasma concentrations in uncomplicated hypertensives is 38pg/ml and higher NT-proBNP levels were associated with favorable remodeling of the peripheral arteries. Elevation of plasma NT-proBNP can be useful to identify subclinical LV diastolic dysfunction and peripheral arterial remodeling in asymptomatic patients with hypertension.