N-terminal pro-B-type Natriuretic Peptide Levels Research Articles

Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy.

Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89-3.08), and 2.28 (95% CI: 1.28-4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40-3.65] and 2.03 [95% CI: 1.07-3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.

Biomarkers of myocardial injury in surgical treatment of lung cancer: perioperative dynamics and prognostic value

Aim. To study the perioperative dynamics of myocardial injury biomarkers and determine their significance in assessing the postoperative mortality risk in patients with nonsmall cell lung cancer.Methods. The study included 82 male patients with non-small cell lung cancer undergoing pneumonectomy. The median age was 64 (59; 67) years. The blood levels of cardiac troponin I (cTnI), N-terminal pro b-type natriuretic peptide (NT-proBNP) and fatty acid-binding protein (FABP) were noted before and after surgery. The rate of myocardial injury after non-cardiac surgery (MINS) was determined. The postoperative cTnI level above 0.023 μg/L was considered as MINS criterion. The significance of the studied biomarkers in predicting the total mortality within 6 months after surgery was assessed using the univariate and multivariate Cox regression and ROC analysis.Results. Compared to baseline levels, all myocardial injury biomarkers increased in 24 and 48h after surgery: cTnI by 120 and 85%, NT-proBNP by 128 and 129%, FABP by 207 and 31%, respectively. The postoperative cTnI levels met the MINS criterion in 45.1% of patients. During the follow-up period 12 patients died, 9 (75%) of those were diagnosed with MINS. Based on the results of the univariate Cox regression overall postoperative mortality was associated with NTproBNP levels before and after the surgery, cTnI growth rate after the surgery and MINS. According to the multivariate Cox regression (adjusted for age and other clinical parameters), preoperative NT-proBNP and atrial fibrillation proved to be the independent predictors of postoperative mortality. The cut-off value of preoperative NT-proBNP was 225 pg/mL; relative risk of death above that value was 5.9 and 95% confidence interval of 1.74–20.0.Conclusion. In patients with non-small cell lung cancer the increase of cTnI, NT-proBNP and FABP mean levels was observed in 24 and 48 hours after pneumonectomy. MINS was diagnosed in 45.1% of patients. According to the univariate regression analysis, MINS and preoperative and postoperative NT-proBNP levels were associated with the risk of total six-month postoperative mortality. The preoperative NT-proBNP was proved to be an independent predictor of adverse outcome.

Application of Combined Detection of Echocardiography and Serum NT-ProBNP in the Diagnosis of Diastolic Heart Failure and Its Effect on Left Ventricular Morphology and Diastolic Function.

Objective This study is to assess the application of combined detection of echocardiography and serum N-terminal pro B-type natriuretic peptide (NT-ProBNP) in the diagnosis of diastolic heart failure (DHF) and its effect on left ventricular morphology and diastolic function. Methods Thirty patients with DHF with enrolled in our hospital between January 2019 and January 2021 were included in the experimental group, and thirty healthy individuals during the same period were included in the control group. The blood pressure, heart rate (HR), left ventricular morphology, diastolic function, and serum NT-ProBNP levels were compared between the two groups. Results DHF was associated with higher levels of diastolic blood pressure (DBP), systolic blood pressure (SBP), HR, left ventricular diameter (LVD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial volume index (LAVI), left ventricular end-diastolic volume (LVEDV), serum NT-ProBNP, maximum early ventricular filling velocity/early diastolic velocity of the mitral annulus (E/Ea) ratio, and aortic regurgitation (AR) and lower levels of left ventricular ejection fraction (LVEF), flow propagation velocity (VP), and systolic/diastolic (S/D) ratio versus healthy subjects (all at P < 0.05). Conclusion The combined detection of echocardiography and serum NT-ProBNP yields a high clinical value in the diagnosis of DHF deficiency, as it can accurately evaluate the patient's left heart morphology and diastolic function, so it is worthy of clinical promotion and application.

Elevated Serotonin and NT-proBNP Levels Predict and Detect Carcinoid Heart Disease in a Large Validation Study.

Simple SummaryA relevant proportion of patients with neuroendocrine tumors (NET) develop carcinoid heart disease (CHD). This rare cardiac condition leads to worsened survival rates in patients with NET. In this study, we investigated various biomarkers in the blood that could detect and, more specifically, predict which patients are at high risk of developing CHD. In this large study of patients with CHD, we found two biomarkers, NT-proBNP and serotonin, that together are very useful in the prediction and detection of CHD. Moreover, we found cut-off values for NT-proBNP that will aid in the screening of patients with NET, thereby increasing focus on patients at high risk of developing CHD, and releasing patients with a low risk of CHD from burdening screening.Carcinoid heart disease (CHD) is a rare fibrotic cardiac complication of neuroendocrine tumors. Besides known biomarkers N-Terminal pro-B-type natriuretic peptide (NT-proBNP) and serotonin, activin A, connective tissue growth factor (CTGF), and soluble suppression of tumorigenicity 2 (sST2) have been suggested as potential biomarkers for CHD. Here, we validated the predictive/diagnostic value of these biomarkers in a case-control study of 114 patients between 1990 and 2021. Two time-points were analyzed: T0: liver metastasis without CHD for all patients. T1: confirmed CHD in cases (CHD+, n = 57); confirmed absence of CHD five or more years after liver metastasis in controls (CHD–, n = 57). Thirty-one (54%) and 25 (44%) females were included in CHD+ and CHD– patients, respectively. Median age was 57.9 years for CHD+ and 59.7 for CHD- patients (p = 0.290). At T0: activin A was similar across both groups (p = 0.724); NT-proBNP was higher in CHD+ patients (17 vs. 6 pmol/L, p = 0.016), area under the curve (AUC) 0.84, and the most optimal cut-off at 6.5 pmol/L. At T1: activin A was higher in CHD+ patients (0.65 vs. 0.38 ng/mL, p = 0.045), AUC 0.62, without an optimal cut-off value. NT-pro-BNP was higher in CHD+ patients (63 vs. 11 pmol/L, p < 0.001), AUC 0.89, with an optimal cut-off of 27 pmol/L. Serotonin (p = 0.345), sST2 (p = 0.867) and CTGF (p = 0.232) levels were similar across groups. This large validation study identified NT-proBNP as the superior biomarker for CHD. Patients with elevated serotonin levels and NT-proBNP levels between 6.5 and 27 pmol/L, and specifically >27 pmol/L, should be monitored closely for the development of CHD.

MO722: Cardiac Biomarkers (NT-proBNP, Troponin I) and Heart Failure in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Patients with chronic kidney disease (CKD) stage 5 on haemodialysis are at a high risk of cardiovascular disease according to 10-year estimation validated risk models (SCORE system) [1, 2]. Cardiac biomarkers, such as N-terminal pro-BNP (NT-proBNP) and troponin I (Tn-I), have been studied in this population enabling patient classification and prediction of cardiovascular morbimortality in chronic haemodialysis [3–5]. The primary objective of this study is to determine serum levels of the cardiac biomarkers NT-proBNP and TnI, and to evaluate the relationships between ecocardiographic signs of heart failure and its treatment, and to identify those patients in chronic haemodialysis at the highest cardiovascular risk. METHOD We performed an observational, descriptive study in patients on maintenance haemodialysis at our haemodialysis unit (n = 118). We collected different data: gender, age, dialysis vintage and etiology of CKD. We examined medical records and transthoracic echocardiography reports of the last year and classified patients according to heart failure diagnosis (yes/no). Levels of NT-proBNP were divided into three categories with different cut-off points: group 1 (&amp;lt;50-year-old, NT-proBNP &amp;lt; 450 pg/mL), group 2 (50–75-year-old, NT-proBNP &amp;lt; 900 pg/mL), group 3 (&amp;gt;75-year-old, NT-proBNP &amp;lt; 1800 pg/mL). TnI levels were considered positive above 20 pg/mL in all age groups. RESULTS Participants’ mean age was 64.65 ± 2.84 years, and 62.7% were identified as male. The mean age was 4.4 years older in women (67.43 years in women and 62.92 years in men). A total of 66.9% of patients had started renal replacement therapy in the last 5 years. The most common etiology of CKD (number of patients) was diabetes (31) followed in decreasing order by unknown (22), glomerular disease (18), hypertension (13), hereditary disease (8), systemic disease (4) and other kidney and urologic disorders (22). The diagnosis of heart failure stated by medical records and echocardiography was positive only in 26.27% (31 patients), thus the 73.73% (87 patients) did not present that diagnosis. Of those 31 patients with heart failure, 26 patients had raised NT-proBNP levels, in accordance with their predefined age-group (group 1, 2 or 3). On the other hand, 77 (or 65% of the total sample) of the 87 patients without clinically diagnosed heart failure had elevated cardiac biomarkers that could support a heart failure diagnosis, not previously stated in their medical history. Tn-I levels were positive in 35% (39 patients) without dyspnea, chest pain or other heart disease symptoms. CONCLUSION In conclusion, cardiac biomarkers allowed us to broaden the diagnostic process of heart failure and to identify those patients at a higher cardiovascular risk. Our results suggest the majority of patients of our haemodialysis unit would benefit of a closer monitoring, with echocardiography and assessment of serum cardiac biomarkers.

Echocardiographic Evaluation of Initial Ambrisentan Plus Phosphodiesterase Type 5 Inhibitor on Right Ventricular Pulmonary Artery Coupling in Severe Pulmonary Arterial Hypertension Patients.

Introductionambrisentan and phosphodiesterase type 5 inhibitor (PDE5i) have been approved for treating patients with pulmonary arterial hypertension (PAH). Echocardiographic right ventricular pulmonary artery coupling (RVPAC) has been shown to be a valid non-invasive and alternative measurement method to assess the predicted outcomes in PAH patients. The aim of this study was to study the effect and clinical correlates of initial ambrisentan plus PDE5i combination therapy on RVPAC in patients with severe PAH.Method and ResultsWe retrospectively studied and analyzed comprehensive clinical data, hemodynamics, and echocardiography in 27 patients with severe PAH before and after 6 months of initial combination therapy. Compared with the baseline, significant improvements in RVPAC ratios were observed, including RVFAC/PASP (0.31 ± 0.10 vs. 0.44 ± 0.15%/mmHg, p < 0.001), TAPSE/PASP (0.15 ± 0.05 vs. 0.21 ± 0.06 mm/mmHg, p = 0.001), S’/PASP (0.10 ± 0.03 vs. 0.14 ± 0.05 cm/s∙mmHg, p = 0.001), and RVSV/RVESV (0.79 ± 0.22 vs. 1.02 ± 0.20, p < 0.001). Functional status indices [World Health Organization functional classifications (WHO-FC) and 6 min walk distance (6MWD) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels] showed significant improvements. Right heart catheterization (RHC) evaluations for hemodynamic measurements between baseline and the 6–12 month follow-up were sPAP (96 ± 22 vs. 86 ± 24 mmHg, p = 0.002), mPAP (64 ± 18 vs. 56 ± 17 mmHg, p < 0.001) and TPVR (17.3 ± 6.7 vs. 12.1 ± 5.4 WU, p = 0.001). Simultaneously, significant associations between RVPAC ratios and NT-proBNP levels and WHO-FC and 6MWD were observed.ConclusionAmbrisentan plus PDE-5i combination therapy resulted in a significant improvement in RVPAC in severe PAH. Importantly, RVPAC parameters correlated with known prognostic markers of PAH.

Subclinical cardiovascular disease and frailty risk: the atherosclerosis risk in communities study

BackgroundCardiovascular disease (CVD) is associated with a greater frailty risk, but it remains unknown if pathways that contribute to CVD are associated with the frailty risk. Thus, we aimed to investigate whether elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for those without known CVD at baseline are associated with a higher frailty risk.MethodsThis study used data from the Atherosclerosis Risk in Communities study. Cardiac biomarkers were measured from stored plasma samples collected at Visit 2 (1991–1993). Frailty was recorded at Visit 5 (2011–2013). Cox regression models were used to determine the association of cardiac biomarkers with frailty risk.ResultsOverall, 360/5199 (6.9%) participants aged 55.1 ± 5.1 years developed frailty during a median follow-up of 21.7 years. The incidence of frailty was significantly higher in participants with hs-cTnT ≥14 ng/L (vs. < 14 ng/L: 17.9% vs. 6.7%) or NT-proBNP ≥300 pg/ml (vs. < 300 pg/ml: 19.7% vs. 6.8%) (all P < 0.001). Comparing higher vs. lower cut-off levels of either hs-cTnT (14 ng/l) or NT-proBNP (300 pg/ml) demonstrated a greater than two-fold higher frailty risk, with hazard ratios (HRs) of 2.13 (95% confidence interval (CI): 1.130–4.01, P = 0.020) and 2.61 (95% CI: 1.28–5.33, P = 0.008), respectively. Individuals with both elevated hs-cTnT and NT-proBNP had a higher frailty risk than those without it (HR: 4.15; 95% CI: 1.50–11.48, P = 0.006).ConclusionsHigh hs-cTnT and NT-proBNP levels are strongly associated with incident frailty in the community-dwelling population without known CVD. Subclinical cardiac damage (hs-cTnT) and/or wall strain (NT-proBNP) may be the key pathway of CVD patients developing frailty. Detection of hs-cTnT and NT-proBNP may help for early screening of high-risk frailty and providing individualised intervention.Trial registrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005131.

Prognostic value of the combination of uric acid and NT-proBNP in patients with chronic heart failure

ObjectiveHyperuricemia is associated with poor outcomes in chronic heart failure (HF). We aimed to evaluate whether uric acid (UA) alone or in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a good predictor of all-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality in chronic HF. MethodsUA and NT-proBNP levels were evaluated retrospectively in 861 chronic HF patients with a left ventricular ejection fraction of ≤50%. The patients were compared by dividing them into 4 groups according to the cut-off values of UA and NT-proBNP. ResultsSerum UA concentrations were ≥ 7.0 mg/dL in 46.5% of the subjects. With a median follow-up of 30 months, 201 (23.3%) patients died and 308 (35.8%) patients were hospitalized during the study. The all-cause mortality rate was higher in the hyperuricemic group than that of the normouricemic group (p < 0.001). A multivariate Cox regression model revealed that UA and NT-proBNP were independent predictors of all-cause mortality (HR: 1.105, 95% CI: 1.019-1.198, p = 0.016 and HR: 3.743, CI: 2.647-5.292, p < 0.001, respectively). Patients were divided into 4 groups based on UA (≥ 7 and < 7 mg/dL) and NT-proBNP (≥ 2279 and < 2279 ng/L) levels. All-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality rates were higher in the group with high UA and NT-proBNP levels (p < 0.001, p < 0.001, p < 0.001, respectively). ConclusionHyperuricemia alone is an independent predictor of all-cause mortality in chronic HF. However, the combination of UA and NT-proBNP appears to be a stronger predictor of poor outcomes.

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats.

BackgroundThis study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats.MethodsA total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg·d). After modeling or treatment, the value of E/A and E/e' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot.ResultsCompared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05).ConclusionsKangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function.

Prognosis Implication of N-Terminal Pro-B-Type Natriuretic Peptide in Adult Patients With Acute Myocarditis.

BackgroundThe aim of this study is to investigate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in assessing the poor outcomes of adult patients with acute myocarditis.MethodsA total of 170 adult patients with available NT-proBNP information were included in the study. They were grouped according to quartiles of NT-proBNP concentrations at admission. Baseline and follow-up information was collected. Thirty-day major adverse cardiac events (MACE) were death and heart transplantation. Long-term MACE included all-cause death, heart transplantation, re-hospitalization due to heart failure, sustained ventricular arrhythmia, and myocarditis relapse.ResultsDuring a median follow-up of 3.8 years, patients in the highest NT-proBNP quartile suffered from the highest risk both of 30-day and long-term MACE (P < 0.001 by log-rank test). Multivariate analysis showed that apart from left ventricular ejection fraction (LVEF), an increased baseline NT-proBNP > 3,549 pg/mL (hazard ratio 3.535, 95% CI 1.316–9.499, P = 0.012) and NT-proBNP > 7,204 pg/mL (hazard ratio 22.261, 95% CI 1.976–250.723, P = 0.012) was independent predictor of long-term and 30-day MACE, respectively.ConclusionsHigher baseline NT-proBNP level was an independent predictor of poor outcomes in adult patients with acute myocarditis. Therefore, NT-proBNP may serve as a useful biomarker for risk stratification in acute myocarditis patients.

Cardiac biomarkers in pediatric CKD—a prospective follow-up study

BackgroundThe N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac-specific troponin T (hs-cTnT) are associated with abnormal cardiac structure and function and an increased risk of cardiovascular death in chronic kidney disease (CKD) patients. There is limited knowledge about these cardiac markers in pediatric CKD patients.MethodsLongitudinal levels of NT-proBNP and hs-cTnT were analyzed in 48 pediatric patients, 22 with CKD (GFR range 8.8–68 mL/min/1.73 m2) and 26 transplanted patients (CKD-T; GFR range 30–99 mL/min/1.73 m2). Follow-up was scheduled after 1 and 3 years. Longitudinal patterns and associations to kidney function, cardiovascular risk markers, and echocardiographic parameters were assessed.ResultsHigh NT-proBNP was present in 27% of CKD and 11% of CKD-T patients. Similarly 32% of CKD and 8% of CKD-T patients had elevated hs-cTnT levels. In longitudinal multivariate analyses, high log NT-proBNP was associated with low GFR (β = − 0.01, p = 0.01) and elevated left ventricular mass index (LVMI; β = 0.02, p = 0.05). The strong association to LVMI remained when using GFR-adjusted NT-proBNP in similar analysis. Patients with left ventricular hypertrophy (LVH) also had higher NT-proBNP (235 [146–301] ng/L) than patients without LVH (86 [11–477] ng/L), p = 0.02. High hs-cTnT over-time was also associated with low GFR (β = − 0.007, p = 0.01) and a low cc-TDI e´/a´, indicating a worse LV diastolic function (β = − 0.09, p = 0.05). This association did not persist for GFR-adjusted hs-cTnT.ConclusionsNT-proBNP and hs-cTnT are elevated in pediatric CKD and CKD-T patients. GFR-adjusted NT-proBNP was associated with longitudinal levels of elevated LVMI suggesting this might be a marker for early subclinical myocardial damage.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of monthly vitamin D supplementation on cardiac biomarkers: A post-hoc analysis of a randomized controlled trial

The effects of vitamin D supplementation on cardiovascular diseases are controversial. Data on effects of vitamin D upon cardiac biomarkers, as surrogate endpoints of cardiovascular diseases, are limited and inconclusive. Therefore, we carried out a post-hoc analysis of sub-samples of a randomized, double-blinded, placebo-controlled trial with community-based older adults who were randomized to receive monthly 100,000-IU vitamin D or placebo, to determine effect of monthly vitamin D supplementation on high-sensitivity cardiac troponin I (hs-cTnI), troponin T (hs-cTnT) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP). Adjusted relative difference (aRD) of follow-up geometric mean of biomarkers and adjusted relative risk (aRR) of elevated biomarkers between two groups were calculated. A total of 779 participants aged 50–84 y, randomized to vitamin D (n = 395) or placebo (n = 384) groups underwent sampling for measurement of plasma biomarkers at baseline and after one or two years treatment. Over a mean follow-up of 1.6 years, we did not find significant relative difference of geometric mean levels of three biomarkers at follow-up between vitamin D and placebo groups: hs-cTnI (aRD=1.03, 95%CI=0.97–1.09), hs-cTnT (aRD=0.99, 95%CI=0.95–1.04), and NT-proBNP (aRD=1.01, 95%CI=0.92–1.10). No significant differences were found in likelihood of clinically elevated biomarkers between two groups: hs-cTnI (aRR=0.92, 95%CI=0.51–1.69), hs-cTnT (aRR=1.11, 95%CI=0.86–1.42), and NT-proBNP (aRR=1.03,95%CI=0.89–1.20). However, among participants with initial low vitamin D status (<50 nmol/L, n = 200), follow-up NT-proBNP were significantly lower in the vitamin D group compared to placebo (geometric mean 75.9 vs 94.5 pg/mL, respectively; aRD=0.84, 95%CI=0.71-<1.00). The same results were observed for the NT-proBNP levels change from baseline between two groups. Overall, in older adults, monthly vitamin D supplementation did not reduce concentrations of hs-cTnI, hs-cTnT, and NT-proBNP. In those with low vitamin D status, vitamin D treatment was associated, on follow up and change from baseline, with lower plasma NT-proBNP compared with placebo. This potentially signals reduced risk of subsequent heart failure within this sub-group. However, we acknowledge that these findings need to be considered exploratory. Further research is required to replicate them.

Serum N-terminal-pro-B-type natriuretic peptide is dependent on age and sex: a cross-sectional analysis in healthy adults from Northeast China

Abstract Background: Previous studies suggested higher serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level with older age and in women, but the reference intervals (RIs) recommended by assay manufacturers do not fully recognize such pattern. Aims: In this study, we aimed to establish a set of age- and sex-specific RIs for serum NT-proBNP in healthy adults from Northeast China. Methods: Healthy adult subjects (20 to ≤95 years old) were recruited from the physical examination center at a teaching hospital during a period from March 2020 to July 2020. Serum NT-proBNP concentration was measured using the VITROS 5600 Integrated System with a chemiluminescence method. RIs were calculated based on the EP28-A3c guidelines by the Clinical and Laboratory Standards Institute. A generalized linear model was performed to factors that were associated with NT-proBNP level. Results: The final analysis included 2,183 subjects (1,074 men and 1,109 women, mean age 54.2 ± 19.5 years). Serum NT-proBNP level increased with advancing age (20 to &lt;50, 50 to &lt;60, 60 to &lt;75 and ≥75 years), and was significantly higher in women than in men with the exception of the ≥75 age group. Higher NT-proBNP level was associated with the female sex, older age, lower body mass index, higher urea nitrogen, higher creatinine, lower uric acid, and lower triglyceride (P &lt; 0.05 for all). The strongest association was with the female sex, followed by age. Conclusions: Serum NT-proBNP level must be interpreted with consideration of sex and age. Higher NT-proBNP is associated with the female sex and older age.

N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification of Heart Failure Patients With Implantable Cardioverter-Defibrillator.

BackgroundThe prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear.ObjectiveTo determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients.Methods and resultsN-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1).ConclusionIn HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.

NT-proBNP and ICD in Nonischemic Systolic Heart Failure: Extended Follow-Up of the DANISH Trial

ObjectivesIn this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro–B-type natriuretic peptide (NT-proBNP) level. BackgroundIn the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation. MethodsIn the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause. ResultsAll 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (Pinteraction = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (Pinteraction = 0.20 and 0.08 for CV death and SCD, respectively). ConclusionsLower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945)

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein in Patients With Previous Myocardial Infarction.

BackgroundPatients with previous myocardial infarction (MI) have a poor prognosis and stratification for recurrent major adverse cardiovascular events (MACE) among these patients is of considerable interest. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) are considered to be potential cardiovascular risk factors, but less is known about their prognostic importance in post-MI patients. This study aimed to evaluate the prognostic value of NT-proBNP and hs-CRP alone or together in patients who reported a prior MI.MethodsIn this prospective study, we consecutively enrolled 3,306 post-MI patients to assess the recurrent MACE. The predictive values of NT-proBNP and hs-CRP alone and together were assessed by multivariable Cox regression using hazard ratios (HR) and 95% confidence intervals (CI).ResultsDuring the 4-year follow-up period, 335 patients developed recurrent MACE. Multivariate Cox regression analysis showed a significant correlation between NT-proBNP levels and MACE (HR: 2.99, 95%CI: 2.06–4.36, p < 0.001), hard endpoints (HR: 5.44, 95%CI: 2.99–9.90, p < 0.001), cardiac mortality (HR: 5.92, 95%CI: 2.34–14.96, p < 0.001) and all-cause mortality (HR: 5.03, 95%CI: 2.51–10.09, p < 0.001). However, hs-CRP was not an independent predictor after adjusting for NT-proBNP. When patients were divided into six groups by using tertiles values of NT-proBNP and median values of hsCRP, patients with high NT-proBNP/hs-CRP values were 3.27 times more likely to experience MACE than patients with low NT-proBNP/hs-CRP values. The addition of NT-proBNP and hs-CRP to a prognostic model revealed a significant improvement in C-statistic, net reclassification, and integrated discrimination.ConclusionsIncreased NT-proBNP levels were associated with long-term worse outcomes and the combination of NT-proBNP and hs-CRP has an incremental value in the further risk stratification of post-MI patients.

The relationship between apelin and carotid intima media thickness, and the presence of plaque in dialysis patients.

Apelin is a peptide that has important effects on the cardiovascular system due to its anti-atherogenic properties and regulating blood pressure. There is not enough research evaluating the effects of apelin levels on the cardiovascular system in hemodialysis (HD) and peritoneal dialysis (PD) patients concurrently. The aim of this study was to determine apelin levels in dialysis, and control groups and to investigate the relationship between apelin and carotid intima media thickness (CIMT). Thirty three HD patients, 35 PD patients, and 15 healthy individuals were included in the study. All laboratory data, N-terminal pro-B-type natriuretic peptide (NT-proBNP), IL-6, and apelin-13 levels were analyzed. To prevent interobserver errors in CIMT measurement, the analyses were performed by a single radiologist. CIMT, presence of plaque, apelin, NT-proBNP, IL-6, and C-reactive protein (CRP) levels were higher in dialysis patients. There was a relationship between apelin and CIMT, and between apelin and high-density lipoprotein (HDL) in PD patients. Age, apelin, HDL, parathormone (PTH), glucose, and smoking were found to affect the presence of plaque in dialysis patients. Apelin levels were high in dialysis patients. Especially in PD patients, there was a negative correlation between apelin and CIMT, and between apelin and HDL. Therefore, apelin may play a role in the pathogenesis of cardiovascular diseases in PD patients.

Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were − 10.4%, − 62.0% and − 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and − 9.4% in patients with recurrent AF, for a between-group difference of − 13.5% (95% confidence interval [CI] − 19.3% to − 7.6%; P < 0.001), − 63.1% (95% CI − 76.6% to − 49.6%; P < 0.001) and − 16.3% (95% CI − 27.9% to − 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (β coefficient per 1 − SD decrease, − 3.85; 95% CI − 6.34 to − 1.35; P = 0.003 for BMP10 and − 5.84; 95% CI − 10.22 to − 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

Evaluation of plasma N-terminal pro-B-type natriuretic peptide levels in healthy North American Salukis with normal echocardiographic measurements

Measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels has been shown to have clinical significance for diagnosis and management of heart disease in dogs. Evaluation of current reference limits for specific breeds is necessary to ensure the test can accurately distinguish between healthy and diseased animals. The objective of this study is to evaluate the adequacy of currently established NT-proBNP reference limits for clinical use in healthy Salukis. Cardiac health of 33 clinically healthy Salukis was evaluated via echocardiography using available breed standards. Plasma concentrations of NT-proBNP were measured using a commercially available assay. A one-sided 97.5% upper reference limit for the NT-proBNP concentrations was calculated using non-parametric percentile method. The 97.5% upper reference limit was 769 pmol/L (90% CI, 547-1214 pmol/L) for the study dogs. This upper reference limit was within the currently established non-breed specific NT-proBNP upper reference limit of 900 pmol/L. No relationship between sex, age, or body weight on plasma levels of NT-proBNP was noted. Results of this study supports the use of currently available non-breed specific NT-proBNP cut-off values for clinical evaluation of healthy Salukis.

Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012–2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760–6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120–19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740–28,100 ng/L); or surgery, 32,300 ng/L (29,100–35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001–18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54–0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.