Project description:BackgroundN-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) are mainly produced and secreted in the heart. In 2008, the European Heart Association recommended that serum BNP/NT-proBNP levels should be included in one of the diagnostic criteria of heart failure. Serum NT-proBNP is more stable than BNP, and the detection results are less affected by objective factors, so it is widely used. At present, NT-proBNP has long been beyond the scope of heart failure markers, and has a wide range of clinical value in the evaluation and prediction of some serious diseases. This study prospectively studied the predictive value of serum NT-proBNP in pediatric intensive care unit (PICU).MethodsThis was a prospective study involving 375 children in the PICU. The patients were divided into three groups: non-risk, low-risk, and high-risk groups. Serum NT-proBNP levels and the 28-day mortality rate were analyzed.ResultsThe serum NT-proBNP levels and the mortality of the high-risk group was significantly higher than those of the low- and non-risk groups (P<0.01 in both cases). Receiver operating characteristic curve (ROC curve) analysis showed that the area under the curve was 0.705 (P<0.001, sensitivity =0.643, specificity =0.692). Death multivariate binary logistic regression analysis indicated that NT-proBNP was not an independent factor for 28-day mortality.ConclusionsSerum NT-proBNP was significantly correlated with the severity of illness for critically ill patients in PICU. Although high levels of NT-proBNP indicated greater severity, this was not an independent risk factor affecting the prognosis of patients.
Project description:BackgroundDemographic differences in expected NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration are not well established. We aimed to establish reference ranges for NT-proBNP and explore the determinants of moderately elevated NT-proBNP under the universal definition of heart failure criteria.MethodsThis is a cross-sectional study. NT-proBNP was measured in serum from 18 356 individuals without previous cardiovascular disease in the Generation Scotland Scottish Family Health Study. Age- and sex-stratified medians and 97.5th centiles were generated. Sex stratified risk factors for moderately elevated NT-proBNP (≥125 pg/mL) were investigated.ResultsIn males, median (97.5th centile) NT-proBNP concentration at age <30 years was 21 (104) pg/mL, rising to 38 (195) pg/ml at 50 to 59 years, and 281 (6792) pg/mL at ≥80 years. In females, median NT-proBNP at age <30 years was 51 (196) pg/mL, 66 (299) pg/mL at 50 to 59 years, and 240 (2704) pg/mL at ≥80 years. At age <30 years, 9.8% of females and 1.4% of males had elevated NT-proBNP, rising to 76.5% and 81.0%, respectively, at age ≥80 years. After adjusting for risk factors, an NT-proBNP ≥125 pg/mL was more common in females than males (OR, 9.48 [95% CI, 5.60-16.1]). Older age and smoking were more strongly associated with elevated NT-proBNP in males than in females (Psex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (Psex interaction=0.007).ConclusionsAn NT-proBNP ≥125 pg/mL is common in females without classical cardiovascular risk factors as well as older people. If NT-proBNP becomes widely used for screening in the general population, interpretation of NT-proBNP levels will require that age and sex-specific thresholds are used to identify patients with potential pathophysiology.
Project description:This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25-18 years participating in a prospective longitudinal population-based cohort study, "LIFE child" in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145-158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).
Project description:BackgroundThe study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics.MethodsThe study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9.ResultsIn males, the 97.5th centile NT-proBNP concentration at age < 45, 45 to 54, 55 to 64, 65 to 74 and ≧ 75 were 89.4 ng/L, 126 ng/L, 206 ng/L, 386 ng/L and 522 ng/L, respectively. In females, the concentration of NT-proBNP at the same age was 132 ng/L, 229 ng/L, 262 ng/L, 297 ng/L and 807 ng/L, respectively. The repeatability precision coefficient of variation (CV%) for NT-proBNP was between 0.86 and 1.65 in analytical performance. In contrast, the reproducibility precision (CV%) for NT-proBNP was between 1.52 and 3.22, respectively. The study found a bias of accuracy of 3.73% in low-value samples (concentration: 148.69) and 7.31% in high-value samples (concentration: 1939.08). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 125 ng/L were 96.6%, 92.3%, 84.2%, and 98.5%, respectively. In contrast, those of 300 ng/L were 94.0%, 98.2%, 95.7% and 97.5%, respectively.ConclusionsThe Mindray NT-proBNP assay showed increased levels in both males and females with age, with higher levels in women. It performs well and aligns with manufacturer specifications. We recommend adjusting cutoff values based on demographic factors.
Project description:BackgroundIt is critically important to assess the prognostic value of NT-proBNP in the form of repeated measures among children undergoing surgery for congenital heart defects (CHD). The aim of the present study is to assess the value of repeated perioperative NT-proBNP in evaluating the time dependent and temporal trajectory in prognostics diagnosis during the perioperative period in a large series of children with CHD.MethodsRepeated measures of NT-proBNP from 329 consecutive children with CHD were obtained before and 1, 12, and 36 h after surgery, respectively. For fully utilizing longitudinal characteristics, we employed parallel cross-sectional logistic regression, a two stage mixed effect model and trajectories over time analysis to mine the predictive value of perioperative NT-proBNP on the binary outcome of prolonged intensive care unit (ICU) stay.ResultsThe two stage mixed effects model confirmed that both the mean NT-proBNP level (aOR = 1.46, P = 0.001) and the time trends had prognostic value on the prediction of prolonged ICU stay. In the fully adjusted logistic regression analyses based on gaussian distributions, "rapidly rising NT-proBNP" put the subjects at 5.4-times higher risk of prolonged ICU stay compared with "slowly rising" group (aOR = 5.40, P = 0.003).ConclusionsComprehensive assessment of the time dependent and temporal trajectory in perioperative NT-proBNP, indicated by repeated measurements, can provide more accurate identification of children with higher risk of prolonged ICU stay after CHD surgery.
Project description:Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.
Project description:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in heart failure (HF) but controversially discussed as a potential surrogate marker in HF trials. We analyzed the NT-proBNP/mortality relationship in real-world data (RWD) of 108,330 HF patients from the IBM Watson Health Explorys database and compared it with the NT-proBNP / clinical event end-point relationship in 20 clinical HF studies. With a hierarchical statistical model, we quantified the functional relationship and interstudy variability. To independently qualify the model, we predicted outcome hazard ratios in five phase III HF studies solely based on NT-proBNP measured early in the respective study. In RWD and clinical studies, the relationship between NT-proBNP and clinical outcome is well described by an Emax model. The NT-proBNP independent baseline risk (R0 , RWD/studies median (interstudy interquartile range): 5.5%/3.0% (1.7-4.9%)) is very low compared with the potential NT-proBNP-associated maximum risk (Rmax : 55.2%/79.4% (61.5-89.0%)). The NT-proBNP concentration associated with the half-maximal risk is comparable in RWD and across clinical studies (EC50 : 3,880/2,414 pg/mL (1,460-4,355 pg/mL)). Model-based predictions of phase III outcomes, relying on short-term NT-proBNP data only, match final trial results with comparable confidence intervals. Our analysis qualifies NT-proBNP as a surrogate for clinical outcome in HF trials. NT-proBNP levels after short treatment durations of less than 10 weeks quantitatively predict hazard ratios with confidence levels comparable to final trial readout. Early NT-proBNP measurement can therefore enable shorter and smaller but still reliable HF trials.
Project description:Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies with large numbers of CSF samples are not available. Our aim was to define age-specific reference values. In 1993 The Nijmegen Observational CSF Study was started. Results of all CSF samples that were analyzed between 1993 and 2008 at our laboratory were systematically collected and stored in our computerized database. After exclusion of CSF samples with an unknown or elevated erythrocyte count, an elevated leucocyte count, elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF samples were further studied for CSF glucose (n = 8,871), CSF/plasma glucose ratio (n = 4,516) and CSF lactate values (n = 7,614). CSF glucose, CSF/plasma glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific reference ranges were defined as 5-95(th) percentile ranges. CSF glucose 5(th) percentile values ranged from 1.8 to 2.9 mmol/L and 95(th) percentile values from 3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5(th) percentile values ranged from 0.41 to 0.53 and 95(th) percentile values from 0.82 to 1.19. CSF lactate 5(th) percentile values ranged from 0.88 to 1.41 mmol/L and 95(th) percentile values from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest in neonates and narrowest in toddlers, with lower and upper limits increasing with age. These reference values allow a reliable interpretation of CSF results in everyday clinical practice. Furthermore, hypoglycemia was associated with an increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the CSF/plasma glucose ratio.
Project description:BackgroundCardiac resynchronization therapy (CRT) is an established therapy for appropriately selected patients with heart failure. Response to CRT has been heterogeneously defined using both clinical and echocardiographic measures, with poor correlation between the two.MethodsThe study cohort was comprised of 202 CRT-treated patients and CRT response was defined at 6 months post-implant. Echocardiographic response (E+) was defined as a reduction in LVESV ≥ 15%, clinical response as an improvement of ≥ 1 NYHA class (C+), and biomarker response as a ≥ 25% reduction in NT-proBNP(B+). The association of response measures (E+, B+, C+; response score range 0-3) and clinical endpoints at 3 years was assessed in landmarked Cox models.ResultsEcho and clinical responders demonstrated greater declines in NT-proBNP than non-responders (median [E+/B+]: -52%, [E+]: -27%, [C+]: -39% and [E-/C-]: -13%; p = 0.01 for trend). Biomarker (HR 0.43 [95% CI: 0.22-0.86], p = 0.02) and clinical (HR 0.40 [0.23-0.70] p = 0.001) response were associated with a significantly reduced risk of the primary endpoint. When integrating each response measure into a composite score, each 1 point increase was associated with a 31% decreased risk for a composite endpoint of mortality, LVAD, transplant and HF hospitalization (HR 0.69 [95% CI: 0.50-0.96], p = 0.03), and a 52% decreased risk of all-cause mortality (HR 0.48 [95% CI: 0.26-0.89], p = 0.02).ConclusionSerial changes in NT-proBNP are associated with clinical outcomes following CRT implant. Integration of biomarker, clinical, and echocardiographic response may discriminate CRT responders versus non-responders in a clinically meaningful way, and with higher accuracy.Trial registrationThe cohort was combined from study NCT01949246 and the study based on local review board approval 2011/550 in Lund, Sweden.