Log N-terminal Pro-brain Natriuretic Peptide Research Articles

Superiority of high sensitivity cardiac troponin I over NT-proBNP and adiponectin for 7-year mortality in stable patients receiving haemodialysis

Patients on haemodialysis (HD) have high mortality risk, and prognostic values of the major cardiovascular biomarkers cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and adiponectin should be ascertained over longer follow-up periods using higher-sensitivity assays, which we undertook. In 221 HD patients, levels of high-sensitivity (hs)-cTnI, NT-proBNP, and adiponectin, were measured using high-sensitivity assays, and their associations with all-cause mortality (ACM) and cardiovascular mortality (CVM) were prospectively investigated for 7 years. Higher hs-cTnI and NT-proBNP levels were significant risk factors for ACM and CVM in the Kaplan–Meier analysis. Multivariate Cox proportional hazards analyses in a model including hs-cTnI and NT-proBNP identified log hs-cTnI, but not log NT-proBNP, as an independent risk factor for ACM (HR 2.12, P < 0.02) and CVM (HR 4.48, P < 0.0005). Stepwise analyses identified a high hs-cTnI tertile as a risk factor for ACM (HR 2.31, P < 0.01) and CVM (HR 6.70, P < 0.001). The addition of hs-cTnI to a model including age, CRP, DM, and NT-proBNP significantly improved the discrimination of ACM and CVM each over 7 years. Conclusively, hs-cTnI was superior to NT-proBNP and adiponectin in predicting ACM and CVM over 7 years in HD patients, suggesting the significance of baseline hs-cTnI measurements in long-term management.

Efficacy of Tafamidis in Patients with Ala97Ser Hereditary Transthyretin Cardiac Amyloidosis: A Six-Month Follow-Up Study.

Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m2, and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.

Increased levels of NT-proBNP and troponin T 2 years after coronary artery bypass grafting complicated by mediastinitis.

Mediastinitis after coronary bypass grafting (CABG) increases the risk of the internal mammary artery (IMA) graft obstruction, and has a detrimental effect on long-term survival. The pathogenesis for this increased mortality is poorly understood. In the present study, we aimed to investigate the relationship between mediastinitis and persistently elevated cardiac-specific biomarkers [troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)] and C-reactive protein (CRP) at mid-term follow-up following CABG. The epidemiologic design was of an exposed (mediastinitis, n = 41) vs. randomly selected non-exposed (non-mediastinitis) controls (n = 41) cohort. Serum samples for measurements of NT-proBNP, TnT, and CRP were obtained at a median follow up time of 2.7 (range 0.5-5.2) years after CABG surgery. NT-proBNP (mean 65.0 pg/ml vs. 34.8 pg/ml, p = 0.007) and TnT levels (mean 14.7 ng/L vs. 11.2 ng/L, p = 0.004) were significantly higher in the mediastinitis group than in the control group. Patients with mediastinitis had also higher body mass index (BMI) and were more likely to have diabetes and previous myocardial infarction. There was no difference in serum CRP level between the groups. After controlling for potential confounders (previous myocardial infarction, age, and BMI), the presence of mediastinitis was associated with higher levels of log NT-proBNP (p = 0.02) and log TnT (p = 0.04). Mediastinitis increases the concentrations of cardiac-specific biomarkers NT-proBNP and TnT at mid-term follow-up, representing persistent myocardial injury and impaired cardiac function.

Abstract 11915: Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Patients With Left Ventricular Noncompaction

Introduction: Left ventricular noncompaction (LVNC) is a limited knowledge myocardial disease. Risk stratification in such patients remains a controversy. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable predictor for risk stratification in patients with heart failure. However, data on the effect of NT-proBNP on patients with LVNC is limited. This study aimed to evaluate the predicted effect of NT-proBNP on patients with LVNC. Hypothesis: NT-proBNP can be a predictor for adverse outcomes in patients with LVNC. Methods: This retrospective study enrolled 287 patients diagnosed with LVNC through imaging criteria (Jenni criteria or Petersen criteria). The primary endpoint was major adverse cardiovascular events (MACEs), which represented a composite event of all-cause death, heart transplantation, stroke/TIA, intracardiac thrombi, and venous thrombosis. Results: Patients were divided into 2 groups based on the median of NT-pro BNP: group 1(NT-pro BNP &lt;1008.1 fmol/L, n=143) and group 2(NT-pro BNP ≥1008.1 fmol/L, n=144). During a median of 2.8 years follow-up, 64 patients (22.3%) occurred MACEs. Patients in group 2 (36.8%) had a higher incidence of MACEs than group 1 (7.69%). The Kaplan-Meier curves showed that patients in group 2 were associated with a higher risk of MACEs (Log rank test, P &lt;0.001). Crude Cox regression model results revealed that log NT-proBNP levels were associated with increased risk of MACEs (Crude HR 4.49, 95% CI 2.84-7.09, P &lt;0.001). After adjusting for risk factors including BMI, systolic blood pressure, NYHA functional class, hypertension, prior thromboembolism, atrial fibrillation, left atrial diameter, and LVEF, log NT-proBNP level was an independent risk factor for MACEs (Adjusted HR 2.72, 95% CI 1.53-4.82, P &lt;0.001). The ROC curves showed that the AUC of NT-proBNP was 0.767. Conclusions: NT-proBNP was independently associated with MACEs and can be a robust predictor for the risk stratification in patients with LVNC.

Sex-related differences in clinical outcomes and predictive factors in the very elderly patients with ACS undergoing PCI.

BackgroundAs shown in previous studies, there may be sex-related differences in clinical outcomes in patients with acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI). However, the benefits of PCI in very elderly ACS patients and the gender differences were poorly described and understood. We investigated the clinical characteristics and outcomes after PCI by sex stratification, and the predictive factors of major adverse cardiovascular and cerebrovascular events (MACCE) in this very elderly ACS cohort.MethodsA total of 1,676 consecutive ACS patients (50.2% women) aged ≥80 years old between January 2013 and May 2020 were recruited in this study. All patients were divided into four groups according to gender and treatment: male PCI (n = 321) and conservative management groups (n = 513), and female PCI (n = 283) and conservative management groups (n = 559). Clinical and coronary lesion characteristics were compared among four groups, also the clinical outcomes. MACCE and their predictive factors were assessed using Kaplan–Meier curve and Cox regression analysis.ResultsPCI procedures were conducted in 604 patients, and 1,072 were conservative management. Men were most likely to present with prior myocardial infarction (MI), peripheral artery disease, and chronic total occlusion (CTO); women had a higher prevalence of hypertension and dyslipidemia. The proportion of men receiving PCI procedures was significantly higher than that of women (38.5 vs. 33.6%, p = 0.038). Compared to conservative management, successful PCI significantly improved composite MACCE in both men (33.9 vs. 18.4%, p < 0.001) and women (27.9 vs. 20.8%, p = 0.026). There were no differences between sex in the improvement of clinical outcomes after PCI. In addition, age, ST-segment elevation myocardial infarction (STEMI), log N-terminal pro-brain natriuretic peptide (NT-proBNP), P2Y12 receptor antagonist, and β-blocker were independently associated with the incidence of MACCE after PCI tested by the Cox regression model, but not gender (male: hazard ratio (HR) 1.275, 95% confidence interval (CI) 0.853–1.905, p = 0.236).ConclusionIn this very elderly ACS cohort, men presented with more complex clinical conditions, and women were less likely to receive PCI treatment. Both women and men had similar benefits from the PCI procedure in the decrease of MACCE.

Heart failure in Fabry disease revisited: application of current heart failure guidelines and recommendations.

Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow-up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58±11years, 62% male). HF with preserved ejection fraction (HF-pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e'>9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N-terminal pro-brain natriuretic peptide correlated significantly with LVMi (r=0.60), E/e' (r=0.54), and GLS (r=0.52) (all Ps<0.001) but not with left ventricular ejection fraction (r=-0.034, P=0.72). During follow-up (mean 1208±444days), patients diagnosed with HF had a higher rate of all-cause mortality and worsening HF (33% vs. 1.5%, P<0.001). Abnormal LVMi, E/e'>9, and GLS<16% were all associated with higher all-cause mortality and worsening HF. This study found a high prevalence of symptomatic HF in FD patients. HF-pEF was the dominant phenotype. LVMi, E/e', and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow-up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF.

Risk stratification and mortality prediction in octo- and nonagenarians with peripheral artery disease: a retrospective analysis

ObjectivesAmong changes in demographics, aging is the most relevant cardiovascular risk factor. The prevalence of peripheral artery disease (PAD) is high in elderly patients and is associated with a worse prognosis. Despite optimal treatments, mortality in the high-risk population of octo- and nonagenarians with PAD remains excessive, and predictive factors need to be identified. The objective of this study was to investigate predictors of mortality in octo- and nonagenarians with PAD.MethodsCases of treated octo- and nonagenarians, including the clinical characteristics and markers of myocardial injury and heart failure, were studied retrospectively with respect to all-cause mortality. Hazard ratios [HR] were calculated and survival was analyzed by Kaplan-Meyer curves and receiver operating characteristic curved were assessed for troponin-ultra and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and chronic limb-threatening ischemia (CLTI).ResultsA total of 123 octo- and nonagenarians admitted for PAD were eligible. The troponin level was the major predictor of all-cause mortality (HR: 4.6, 95% confidence interval [CI]: 1.4–15.3), followed by the NT-proBNP level (HR: 3.9, 95% CI 1.8–8.8) and CLTI (HR: 3.1, 95% CI 1.6–5.9). Multivariate regression revealed that each increment of 1 standard deviation in log troponin and log NT-proBNP was associated with a 2.7-fold (95% CI 1.8–4.1) and a 1.9-fold (95% CI 1.2–2.9) increased risk of all-cause death. Receiver operating characteristic curve analysis using a combination of all predictors yielded an improved area under the curve of 0.888. In a control group of an equal number of younger individuals, only NT-proBNP (HR: 4.2, 95% CI 1.2–14.1) and CLTI (HR: 6.1, 95% CI 1.6–23.4) were predictive of mortality.ConclusionOur study demonstrates that cardiovascular biomarkers and CLTI are the primary predictors of increased mortality in elderly PAD patients. Further risk stratification through biomarkers in this high-risk population of octo- and nonagenarians with PAD is necessary.

N-terminal pro-brain natriuretic peptide and coronary collateral formation in patients undergoing primary percutaneous coronary intervention

There is insufficient information on the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and collateral circulation (CC) formation after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. We analyzed 857 patients who underwent primary PCI. The serum NT-proBNP levels were measured on the day of admission, and the CC was scored according to Rentrop’s classification. Log-transformed NT-proBNP levels were significantly higher in patients with good CC compared to those with poor CC (6.13 ± 2.01 pg/mL versus 5.48 ± 1.97 pg/mL, p < 0.001). The optimum cutoff value of log NT-proBNP for predicting CC was 6.04 pg/mL. Log NT-proBNP ≥ 6.04 pg/mL (odds ratio 2.23; 95% confidence interval 1.51–3.30; p < 0.001) was an independent predictor of good CC. CC development was higher in patients with a pre-TIMI flow of 0 or 1 than those with a pre-TIMI flow of 2 or 3 (22.6% versus 8.8%, p = 0.001). The incidence of left ventricular (LV) dysfunction (< 50%) was greater in patients with a pre-TIMI flow of 0 or 1 (49.8% versus 35.5%, p < 0.001). The release of NT-proBNP was greater in patients with LV dysfunction (34.3% versus 15.6%, p < 0.001). The incidence of good CC was greater in patients with log NT-proBNP levels ≥ 6.04 pg/ml (16.8% versus 26.2%, p = 0.003). The association between NT-proBNP and collateral formation was not influenced by pre-TIMI flow and LV function. NT-proBNP appears to reflect the degree of collateral formation in the early phase of STEMI and might have a new role as a useful surrogate biomarker for collateral formation in patients undergoing primary PCI.

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy

ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in...

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension

BackgroundAdiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH).MethodsPatients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function.ResultsA total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 μg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, − 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = − 5.4, 95% CI -9.4, − 1.5, p = 0.013; direct effect c’ = − 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67–1.00 vs AUC = 0.74, 95% CI 0.51–0.97, p = 0.23).ConclusionsAdiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

Relationship between left ventricular preload and N-terminal pro-brain natriuretic peptide in obese patients

BackgroundThe reason for low plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with a high body mass index (BMI) is unknown. Although left ventricular end-diastolic pressure (LVEDP) is the gold standard of preload, the estimated trans left ventricular end-diastolic transmural pressure (eLVTMP) may be true preload especially in obese patients. Materials and methodsWe measured hemodynamic parameters and the plasma NT-proBNP level in the aortic root (AO) and coronary sinus (CS) in 602 left-sided heart disease patients. We defined normal as BMI < 25 kg/m2 (n = 436), overweight as 25 ≤ BMI<30 kg/m2 (n = 117), and obese as BMI ≥ 30 kg/m2 (n = 49). ResultsThere were no significant differences in left ventricular ejection fraction (LVEF) or LVEDP among the three groups, and log (CSAO) NT-proBNP was significantly lower in overweight or obese patients than in normal patients. From stepwise multivariate analyses, eLVTMP (eLVTMP = LVEDPright atrial pressure), LVEF, and BMI were independent predictors of log (CSAO) NT-proBNP, but LVEDP was not. The eLVTMP was significantly lower in obese patients than in overweight patients (7.5 ± 5.1 vs. 9.6 ± 5.3 mmHg, p < 0.05) or normal patients (7.5 ± 5.1 vs. 9.6 ± 4.7 mmHg, p < 0.01). ConclusionLower eLVTMP, as a marker of left ventricular preload, may contribute to the lower NT-proBNP secretion from the heart in obese patients.

Prognostic Value of Serum N-Terminal Pro-Brain Natriuretic Peptide Level over Heart Failure for Stroke Events and Deaths in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance > 60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.

Cross-Sectional Relationship between Carotid-Femoral Pulse Wave Velocity and Biomarkers in Vascular-Related Diseases.

Objectives The present study was done to investigate the relationship between carotid-femoral pulse wave velocity (CFPWV) and biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin (microalbumin) (UAE) in vascular-related diseases. Methods 656 subjects were enrolled into our study. There were 377 patients with hypertension, 231 with coronary heart disease, 154 with diabetes mellitus, and 186 healthy subjects. They were divided into four groups according to the number of suffered diseases: group 1 had only one of three diseases, group 2 had two, and group 3 had all of three diseases. CFPWV was measured by Complior apparatus. Results CFPWV was significantly higher in group 3 than in the healthy group, group 1, and group 2 (12.71 ± 2.38 vs 10.11 ± 2.28, 10.70 ± 2.12, and 11.92 ± 2.55, all p < 0.05). The level of Hcy was significantly higher in group1, group 2, and group 3 than in healthy subjects, respectively. Levels of Log NT-proBNP and Log UAE were significantly higher in group 3 than in group 1 (2.27 ± 0.4 vs 2.10 ± 0.4, 1.00 ± 0.65 vs 0.68 ± 0.56, both p < 0.05). Positive correlation between CFWV and Hcy, Log UAE, and Log NT-proBNP was found in the entire study group (r = 0.109, 0.196, and 0.119, all p < 0.05). Multivariate analysis showed that pulse pressure, age, fasting plasma glucose, diastolic blood pressure, body mass index, and Log UAE were independent associating factors of CFPWV in all subjects (β = 0.334, p < 0.001; β = 0.333, p < 0.001; β = 0.126, p=0.004; β = 0.137, p=0.003; β = −0.142, p=0.002; and β = 0.098, p=0.031). Conclusions CFPWV was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between CFPWV and biomarkers such as NT-proBNP, Hcy, and urine albumin (microalbumin).

The Predictive Value of NT-Pro-Brain Natriuretic Peptide for Risk of Pneumonia in Patients on Maintenance Hemodialysis

Background/Aims: Pneumonia is a common type of infection in maintenance hemodialysis (MHD) patients, while the treatment and prevention progress still keep limited. N-terminal-pro-brain natriuretic peptide (NT-proBNP) is an important marker in reflecting cardiac failure which also is a risk factor for pneumonia. This study aimed to determine the possible predictive value of NT-proBNP for pneumonia in MHD patients. Methods: In this prospective study, the basic information of 276 MHD patients was collected in Fudan university Zhongshan hospital, followed up for 1 year. The primary endpoint was the first pneumonia event during follow-up. The value of NT-proBNP in patients with pneumonia and without pneumonia was analyzed, to elucidate the predictive value of the NT-proBNP in hemodialysis patients with pneumonia. Results: Two hundred and seventy-six patients were finally enrolled in this prospective study, including 170 men. The mean age was 59.7 ± 14.0 years old. The average duration of hemodialysis is 56 (30–82.8) months. Enrolled patients were followed up for 1 year. During follow-up, 38 patients got pneumonia. After adjustment for other confounding factors, age (hazard ratio [HR] 1.031, 95% CI 1.003–1.060, p = 0.028), log NT-proBNP (HR 2.512, 95% CI 1.124–5.612, p = 0.025), history of smoking (HR 6.326, 95% CI 2.505–15.974, p < 0.001), β2-microglobin (HR 1.042, 95% CI 1.007–1.079, p = 0.019), and history of cerebrovascular disease (HR 2.303, 95% CI 1.107–4.719, p = 0.026) were independent predictors of pneumonia. Receiver operating characteristic curves of log NT-proBNP to predict 1 year pneumonia cases, log NT-proBNP had an area under the curve of 0.647 (95% CI [0.564–0.729], p < 0.01). Conclusions: NT-proBNP is a predictive factor of pneumonia in hemodialysis patients.

Serum retinol-binding protein 4 as a predictor of cardiovascular events in elderly patients with chronic heart failure.

AimsRBP4 is an adipokine with adverse effects on cardiovascular system. Increased circulating retinol‐binding protein 4 (RBP4) has been linked to chronic heart failure (CHF). However, whether elevated RBP4 is correlated with a poor prognosis in elderly patients with CHF remains unclear. The aim of this study was to evaluate the prognostic value of serum RBP4 in elderly patients with CHF.Methods and resultsWe enrolled 934 consecutive elderly patients (aged 60 years and older) with CHF and 138 age‐matched and sex‐matched control subjects in a prospective cohort study and explored the association of serum RBP4 levels with the clinical outcomes using multivariate Cox regression analyses. Serum RBP4 levels were elevated in CHF patients when compared with controls (46.66 ± 12.38 μg/mL vs. 40.71 ± 7.2 μg/mL, P < 0.001). Patients with the highest RBP4 concentrations had higher N terminal pro brain natriuretic peptide (NT‐proBNP) levels but lower left ventricular eject fraction (LVEF) and estimated glomerular filtration rate (P < 0.001). Serum RBP4 levels were increased as the New York Heart Association functional class increased and LVEF decreased (P < 0.001) and were negatively correlated with LVEF (r = −0.154, P < 0.001) but positively correlated with NT‐proBNP levels (r = 0.074, P = 0.023). Multivariate Cox regression analysis suggested that log RBP4 was an independent predictor for major adverse cardiac event(s) [hazard ratio (HR) = 2.61, 95% confidence interval (CI) = 1.19–5.70], together with age, male, LVEF, log NT‐proBNP, and estimated glomerular filtration rate. Moreover, log RBP4 was also an independent predictor for cardiovascular mortality (HR = 2.24, 95% CI = 1.35–5.39) and CHF rehospitalization (HR = 2.54, 95% CI = 1.09–5.60) even after adjustment for the established adverse prognostic factors for CHF. The Kaplan–Meier survival curves showed that high concentration of RBP4 was a prognostic indicator of major adverse cardiac event(s) in patients with CHF.ConclusionsOur findings demonstrate for the first time that elevated serum RBP4 is correlated with worse outcome in elderly patients with CHF.

NT-proBNP level in stage 3-4 chronic kidney disease and mortality in long-term follow-up: HAPPY study subgroup analysis.

This was an investigation of the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and mortality in patients with stage 3-4 chronic kidney disease (CKD). This study was designed as a subgroup analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) study. The HAPPY study included 4650 randomly selected individuals from the 7 geographical regions of Turkey. A total of 191 subjects from the original cohort with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.1.73 m² were enrolled in this study and the relationship between NT-proBNP and mortality was investigated. Prognostic variables for total and cardiovascular mortality were also examined using Cox regression analysis. The mean length of follow-up was 76.12±22.45 months. The mean NT-proBNP level was 423.54±955.88 pg/mL. During follow-up, 51 subjects (26.7%) died from any cause and 36 subjects (18.8%) died from a cardiovascular cause. The presence of hypertension (hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.01-3.50; p=0.048), anemia (HR: 2.49; 95% CI: 1.20-5.15; p=0.014), male gender (HR: 2.64; 95% CI: 1.44-4.86; p=0.002) and log NT-proBNP (HR: 4.93; 95% CI: 2.83-8.58; p<0.001) were independent variables for total mortality. The presence of hypertension (HR: 2.47; 95% CI: 1.09-5.56; p=0.029), male gender (HR: 2.79; 95% CI: 1.38-5.62; p=0.004), eGFR (HR: 0.94; 95% CI: 0.91-0.98; p=0.005) and log NT-proBNP (HR: 6.31; 95% CI: 3.11-12.81; p<0.001) were independent predictors of cardiovascular mortality. NT-proBNP was found to be an independent prognostic marker in patients with stage 3-4 CKD.

Association of Common Carotid Artery Measurements with N-terminal Pro B-type Natriuretic Peptide in Elderly Participants.

Objective Numerous studies have reported an association between common carotid artery (CCA) parameters and atherosclerotic cardiovascular disease (CVD). However, the association between CCA parameters and hemodynamic stress on the left ventricle in elderly patients remains unclear. Methods We assessed CCA parameters, including the height-adjusted CCA interadventitial diameter (diameter/height), mean intima-media thickness (IMT), number of plaques, plaque score, resistance index (RI), and pulsatility index (PI) with ultrasonography, using serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels as a marker for hemodynamic stress on the left ventricle in 1,315 participants ≥70 years old without CVD. Of these participants, 706 had hypertension, defined as taking antihypertensive medications, having a systolic blood pressure ≥140 mmHg, and/or having a diastolic blood pressure ≥90 mmHg. Results After adjusting for the confounding factors, the CCA interadventitial diameter/height was significantly associated with the log NT-proBNP in both the normotensive group (β=0.125, p=0.002) and hypertensive group (β=0.080, p=0.029). The RI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.176, p<0.001) but not in the normotensive group. In addition, the PI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.156, p<0.001) but not in the normotensive group. However, no significant association was observed between the mean IMT, number of plaques, and plaque score and log NT-proBNP. Conclusion CCA measurements may be useful markers for hemodynamic stress on the left ventricle in elderly patients.

P4550Growth differentiation factor 15 as an integrative biomarker of heart failure in patients with acute myocardial infarction

Abstract Background Growth differentiation factor 15 (GDF15), a stress-responsive cytokine member of the transforming growth factor-β family, is an emerging biomarker in cardiovascular (CV) diseases. GDF15 is weakly expressed in normal condition but increased in pathological situations such as inflammation, oxidative stress, and left ventricular remodeling. Recent data suggest GDF15 as a marker in heart failure (HF). Purpose We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI). Methods In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit from our University Hospital were included. Chronic HF patients were excluded. In-hospital severe HF was defined as killip class&gt;2. Blood samples were taken on admission and serum levels of GDF15 were measured using a commercially available ELISA kit. Results Among the 284 AMI patients, median age was at 67 (57–78) y, 27% were women, 23% had diabetes and 59% were hypertensive. GDF15 levels (median = 1,144 (775–1,891) ng/L were strongly correlated with age (r=0.493, p&lt;0.001), and elevated with most CV risk factors (i.e. hypertension, diabetes), prior CAD, chronic kidney disease (p&lt;0.001 for all) and in patients with CRP &gt;3 mg/L (p&lt;0.001). When compared with patients who didn't develop severe HF (274/284), patients experiencing HF (10/284), GDF15 was more than twice higher (figure). By Receiving Operating Curve analysis, GDF15 was associated with HF (AUC (95% CI) = 0.716 (0.52–0.91), p=0.021). Moreover, GDF15 levels were negatively correlated with Left Ventricular Ejection Fraction (LVEF) (r=−0.193, p=0.001). Multivariate logistic regression analysis showed that GDF15 &gt;5,000 ng/L [OR: 8.43; 95% CI (1.57–45.32)] is as independent estimate of HF, beyond age and other confounding (i.e. admission systolic blood pressure, LVEF and Log N-terminal pro-Brain Natriuretic Peptide). GDF15 levels according to HF development Conclusions These preliminary results suggest that GDF15 could be an integrative biomarker of severe HF in patient with AMI. Further studies are needed to elucidate the underlying mechanisms linking the cytokine with the development of HF.

Renal Clearance of N-Terminal pro-Brain Natriuretic Peptide Is Markedly Decreased in Chronic Kidney Disease.

Background: The ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) secretion from the heart to peripheral NT-proBNP remains unknown in patients with chronic kidney disease (CKD).Methods and Results: We measured plasma NT-proBNP in the aortic root (AO; NT-proBNPAO) and in the coronary sinus (CS; NT-proBNPCS) in 544 patients. Patients were classified into 6 categories based on estimated glomerular filtration rate (eGFR): G1, n=44, eGFR ≥90 mL/min/1.73 m2; G2, n=221, 60≤eGFR<90 mL/min/1.73 m2; G3a, n=132, 45≤eGFR<60 mL/min/1.73 m2; G3b, n=77, 30≤eGFR<45 mL/min/1.73 m2; G4, n=34, 15≤eGFR<30 mL/min/1.73 m2; and G5, n=36, eGFR <15 mL/min/1.73 m2. In non-CKD patients, hemodynamics but not eGFR were independent predictors of log NT-proBNP. In CKD patients, eGFR and hemodynamics were independent predictors of log NT-proBNP. The ratio of NT-proBNP secretion from the heart to NT-proBNPAO significantly decreased with decreasing eGFR in 6 groups (P<0.0001): G1, 67±38%; G2, 50±24%; G3a, 40±21%; G3b, 30±16%; G4, 14.8±7.9%; and G5, 3.5±2.4%, respectively.Conclusions: eGFR contributes to the value of NT-proBNP for prediction of hemodynamic overload in CKD patients but not in non-CKD patients, and the ratio of NT-proBNP secretion from the heart to peripheral NT-proBNP is markedly decreased in CKD patients, especially those with eGFR <30 mL/min/1.73 m2.

Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.