Pediatric reference values of NT-proBNP and Galectin-3 based on a French cohort.

BACKGROUND: In pediatric cardiology, the fact that some new biomarkers have assay-specific normal values has to be considered for correct clinical decisions. The current study aimed to provide age-adjusted normative values for NT-proBNP and Galectin-3 using the Abbott immunoassay system from a prospective French pediatric cohort sera collection and to validate our data for NT-proBNP on a second retrospective cohort. METHODS: We analyzed 283 consecutive samples for NT-proBNP and 140 samples for Galectin-3 collected from apparently healthy children (0-18 years) with outpatient treatment at our institution (Hôpital Necker-Enfants malades, Paris, France) during 24 months. RESULTS: For NT-proBNP and Galectin-3, we establish four age partitions, respectively two (<2 years / >2 years) and establish upper reference values and their 90 % CI for each biomarker (Galectin-3 (ng/mL): 56 [44-70] / 26 [23-29]). We evaluated the diagnostic performance of our upper reference values of NT-proBNP on a retrospective cohort (n = 428) with positive predictive value of 0.92. CONCLUSIONS: Using Abbott immunoassay system, we report age-specific reference values for NT-proBNP and for the first time for Galectin-3 in a healthy French pediatric cohort. These data call for larger cohort studies to define more robustly percentiles and diagnostic performance for NT-proBNP.

Emergency department clinical performance of ADVIA Centaur n-terminal prohormone of B-type natriuretic peptide assay.

BACKGROUND: Natriuretic peptide testing is guideline recommended as an aid to the diagnosis of heart failure (HF). We sought to evaluate the performance of the ADVIA Centaur (Siemens Healthcare Diagnostics, Tarrytown, NY) NT-proBNPII assay (PBNPII) in emergency department (ED) dyspneic patients. METHODS: Eligible patients presented to the ED with dyspnea, with their gold standard diagnosis determined by up to 3 cardiologists blinded to the PBNPII results. Patients were stratified into 3 groups based on PBNPII resultsa rule out group of NT-proBNP<300  pg/mL, an age-specific rule in group using cutoffs of 450, 900, and 1800 pg/mL, for <50, 50-75, and > 75 years respectively, and an intermediate cohort for results between the rule out and rule in groups. RESULTS: Of 3128 eligible patients, 1148 (36.7 %) were adjudicated as acute heart failure (AHF). The gold standard AHF diagnosis rate was 3.7, 24.3, and 67.2 % for patients with NTproBNPII in the negative, indeterminate, and positive groups, respectively. Overall likelihood ratios (LR) were 0.07 (95 % CI: 0.05,0.09), 0.55 (0.45,0.67), and 3.53 (3.26,3.83) for the same groups, respectively. Individual LR+for age dependent cutoffs were 5.01 (4.25,5.91), 3.71 (3.25,4.24), and 2.38 (2.10,2.69), respectively. NTproBNPII increased with increasing severity of HF when stratified by NYHA classification. CONCLUSIONS: The ADVIA Centaur PBNPII assay demonstrates acceptable clinical performance using the recommended single rule out and age dependent rule in cutoffs for an AHF diagnosis in dyspneic ED patients.

Molecular biomarkers of blunt cardiac injury: recent advances and future perspectives.

INTRODUCTION: Blunt cardiac injury (BCI), associated with high morbidity and mortality, involves multiple injuries. With no widely accepted gold standard diagnostic test and molecular biomarkers still in debate and far from application in clinical practice, exploring specific molecular biomarkers of BCI is of great significance. The clarification of molecular biomarkers can improve the diagnosis of BCI, leading to more precise care for victims in various situations. AREAS COVERED: Using the search term 'Biomarker AND Blunt cardiac injury,' we carefully reviewed related papers from June 2004 to June 2024 in PubMed and CNKI. After reviewing, we included 20 papers, summarizing the biomarkers reported in previous studies, and then reviewed molecular biomarkers such as troponins, Nterminal proBtype natriuretic peptide (NT proBNP), hearttype fatty acid binding protein (hFABP), and lactate for BCI diagnosis. Finally, valuable views on future research directions for diagnostic biomarkers of BCI were presented. EXPERT OPINION: Several advanced technologies have been introduced into clinical medicine, which have ultimately changed the research on cardiac diseases in recent years. Some biomarkers have been identified and utilized for BCI diagnosis. Herein, we summarize the latest relevant information as a reference for clinical practice and future studies.

Cancer-associated fibroblasts promote the progression and chemoresistance of HCC by inducing IGF-1.

Crosstalk between cancer-associated fibroblasts (CAFs) and tumour cells plays a critical role in multiple cancers, including hepatocellular carcinoma (HCC). CAFs contribute to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. However, effect and mechanism of CAF-mediated promotion of hepatocellular carcinoma cells are still unclear. In study, we demonstrated CAFs promoted the proliferation and inhibited the apoptosis of HCC cells by secreting interleukin-6 (IL-6), which induced autocrine insulin-like growth factor-1 (IGF-1) in HCC. IGF-1 promoted the progression and chemoresistance of HCC. IGF-1 receptor (IGF-1R) inhibitor NT157 abrogated the effect of CAF-derived IL-6 and autocrine IGF-1 on HCC. Mechanistic studies revealed that NT157 decreased IL-6-induced IGF-1 expression by inhibiting STAT3 phosphorylation and led to IRS-1 degradation, which mediated the proliferation of tumour by activating AKT signalling in ERK-dependent manner. Inhibition of IGF-1R also enhanced the therapeutic effect of sorafenib on HCC, especially chemoresistant tumours. STATEMENT OF SIGNIFICANCE: Our study showed IL-6-IGF-1 axis played crucial roles in the crosstalk between HCC and CAFs, providing NT157 inhibited of STAT3 and IGF-1R as a new targeted therapy in combination with sorafenib.

Changes of clinical characteristics, distribution of red flags and prognosis in contemporary patients with wild-type transthyretin amyloidosis cardiomyopathy.

AIM: Increased diagnostic awareness and specific disease treatments have changed the landscape of transthyretin cardiac amyloidosis (ATTR). Patients with wild-type ATTR (ATTRwt) are increasingly being diagnosed, potentially changing the clinical profile and prognosis compared with existing retrospective data. We aimed to study the clinical characteristics, distribution of red flags and prognosis of contemporary ATTRwt patients. METHODS: From January 1st 2017, to December 31st 2022, 213 consecutive patients were diagnosed with ATTRwt and prospectively followed up. Data on clinical characteristics, biomarkers, echocardiography findings, hospitalization due to worsening heart failure (WHF) and all-cause mortality were collected. RESULTS: A 37% increase in newly diagnosed patients from 2017-2019 (n = 90) vs. 2020-2022 (n = 123) was observed. The majority of patients presented with NAC disease stage I in the latter period (49% in 2017-2019 vs. 58% in 2020-2022, p = .16). Red flags were primarily cardiac-related, including elevated NT-proBNP, impaired left ventricular longitudinal systolic strain with an apical sparing pattern, heart failure with increased left ventricular wall thickness and elevated troponins. NAC disease stage I as well as low NT-proBNP levels (<1000 ng/L) were significantly associated with better survival (both p < .001). When compared with NAC disease stage II + III combined, patients with NAC disease stage I had a significantly lower risk of WHF hospitalization or death (log rank test: p = .0001). Independent predictors of the combined endpoint WHF hospitalization or death were NT-proBNP (HR 1.03 [95% CI 1.00-1.07], p < .049) and prior implantation of permanent pacemaker (HR 2.01 [1.30-3.11], p = .002). CONCLUSION: Increased diagnostic awareness resulted in a 37% increase in newly diagnosed patients in 2020-2022 vs. 2017-2019. As expected all-cause mortality but also the morbidity in terms of risk of hospitalization with WHF were significantly lower in patients with NAC disease stage I, as well as in those with low NT-proBNP levels <1000 ng/L. These findings underline the importance of continuous attention to diagnostic awareness, as early diagnosis is critical for initiating both general and specific ATTR treatment, thus improving prognosis.

Cardiac biomarker profiles in dogs with naturally occurring precapillary pulmonary hypertension.

INTRODUCTION/OBJECTIVES: This study evaluated circulating amino-terminal pro-B-type natriuretic peptide (NT-proBNP), amino-terminal pro-A-type natriuretic peptide (NT-proANP), and cardiac troponin I (cTnI) concentrations in dogs with precapillary pulmonary hypertension (Pre-PH) and control dogs with respiratory clinical signs but no Pre-PH. ANIMALS: Twenty-six dogs (17 affected, and 9 controls) were involved in the study. MATERIALS AND METHODS: This was a sub-study of a large prospective single-center observational study. Dogs underwent blood sample collection, physical examination, and echocardiographic evaluation. Pre-PH was diagnosed when a calculated right ventricular-to-right atrial pressure gradient (RV:RA PG) measuring ≥40 mmHg was identified echocardiographically, barring right ventricular outflow obstruction and/or left-sided cardiac disease. RESULTS: Two, nine, and six dogs had mild, moderate, and severe Pre-PH, respectively. Plasma concentrations of NT-proBNP, NT-proANP, and cTnI were significantly higher in the affected group than in the control group (P=0.020, P=0.009, P=0.011, respectively). There was a positive correlation between RV:RA PG and NT-proBNP (r = 0.52), NT-proANP (r = 0.54), and cTnI (r = 0.67) concentrations. DISCUSSION: Pre-PH should be included in the differential diagnosis list of elevated cardiac biomarker concentrations in dogs with respiratory signs. STUDY LIMITATIONS: Strict selection criteria reduced group sizes. There were rare missing data points. The diagnosis of Pre-PH was obtained from Doppler echocardiographic RV:RA PG. The disease process causing Pre-PH was not evaluated histopathologically. CONCLUSIONS: Circulating cardiac biomarker concentrations are increased in dogs with Pre-PH and there is a positive correlation between RV:RA PG and NT-proBNP, NT-proANP, and cTnI concentrations.

Recurrent depression predicts high leptin concentrations in patients with coronary artery disease over an 18-months follow-up period: Findings from the prospective multicenter randomized controlled SPIRR-CAD Trial.

BACKGROUND: Leptin, an adipokine suspected to play a role in coronary artery disease (CAD), may also be associated with deteriorated mental health. We investigated the prospective impact of recurrent depressed mood (RDM) on heightened plasma leptin levels in CAD patients. METHODS: Derived from the randomized SPIRR-CAD trial, plasma leptin were measured by the Human Leptin DuoSet ELISA at baseline in 539 patients (including 115 (21.3 %) women and 424 (78.7 %) men) and in 373 participants after 18-months follow up (T3). RDM was based on the clinical course from baseline to follow-up assessed by the Hamilton Depression Rating Scale (HAMD). Multivariate binary logistic regression models identified predictors for heightened leptin at T3. RESULTS: At baseline, highest leptin level (3rd tertile) was associated with type 2 diabetes (p = 0.009), heart failure symptoms (NYHA III) (p < 0.001), female sex and BMI ≥30 (p < 0.001) but not with age and depression. At study endpoint (T3), RDM was associated with a substantially increased risk of experiencing the highest plasma leptin level (OR 2.92 (95 % CI 1.27-6.75)) followed by increased NT-proBNP (the most prominent indicator of CHF) with an OR of 2.73 (1.22-6.11) - both after adjustment for concurrent factors including weight gain (diff BMI T3-T1) over the study period - the latter accounting for an OR of 1.41 (1.17-1.70). LIMITATIONS: Findings are limited to people of Caucasian ancestry which prevents being generalized to other ethnicities. Although relying upon a prospective design, reverse causality cannot be excluded but is unlikely. CONCLUSIONS: In CAD patients, RDM is a significant predictor of heightened leptin -a finding opening room for a new pathway of the psychobiological underpinning of depression on CAD risk.

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

BACKGROUND: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification. RESULTS: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36-1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population. CONCLUSIONS: EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.

Assessment of the diagnostic value of NT-proBNP in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a common concern in the medical field due to its prevalence in an ageing western population. HFpEF is associated with significant morbidity and mortality not dissimilar to heart failure (HF) with reduced ejection fraction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and echocardiography are the guideline diagnostic indicators of HF and their use is being examined in this study, with the aim to consider NT-proBNP thresholds performance as a rule-out test. The current National Institute for Health and Care Excellence (NICE) and European guidelines recommend a single NT-proBNP threshold of >400 ng/L and >125 ng/L, respectively, to trigger echocardiographic assessment of HF in the outpatient setting. NT-proBNP levels are known to increase with age and worsening renal function. Unsurprisingly, a single threshold significantly increases demand for echocardiography. NT-proBNP measurements and echocardiograms performed within six months of each other were included for 469 patients with suspected HF. A significant relationship between NT-proBNP levels and diastolic dysfunction was established. NT-proBNP levels and age are significant predictors of diastolic dysfunction in uni-variant (odds ratio 1.251, 95% confidence interval [CI], p<0.001) and multi-variant analysis (odds ratio 1.174, 95%CI, p=0.002). High negative-predictive values (NPVs) were obtained in severe diastolic impairment with the NPV being 95% at the European NT-proBNP cut-off of 125 ng/L, 95% at the NICE cut-off of 400 ng/L, 93% at 1,000 ng/L and 92% at 2,000 ng/L. There is a significant association between NT-proBNP and diastolic dysfunction. NT-proBNP and age can predict diastolic dysfunction, and age can predict NT-proBNP levels, thus, these variables should be considered when considering referral for an echocardiogram. Most importantly, at higher NT-proBNP cut-offs the NPVs remain above 90% suggesting that different thresholds for subpopulations could yield a more effective strategy and mitigate the increased demand for echocardiography.

Association of Cancer with Heart Failure and the Prognostic Value of NT-proBNP in Cancer Patients: Findings from the NHANES (1999-2018).

Evidence regarding the association between cancer and heart failure (HF) is scarce. This study is to investigate the association between HF and cancer and explore the prognostic value of NT-proBNP in cancer patients. This cohort study used National Health and Nutrition Examination Survey data from 1999 to 2018 and linked mortality information until 2019. We included all participants with valid answer to questions regarding self-reported cancer and HF. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Our study included data from 54,847 adult participants. During a median (IQR) follow-up of 9.6 (4.0-15.1) years, 7674 deaths were recorded. HF was associated with an increased occurrence of cancer after propensity score matching (OR = 1.46, 95% CI: 1.17-1.82, p < 0.001). Cancer was associated with a higher occurrence of HF (OR = 1.33, 95% CI: 1.11-1.59, p = 0.002). Kaplan-Meier survival analysis over 10 years revealed the shortest survival in patients with both HF and cancer (log-rank p < 0.0001). Importantly, NT-proBNP was significantly higher in cancer patients, no matter whether with known HF (p < 0.01). In cancer patients without HF, NT-proBNP higher than 51.51 pg/mL was associated with shorter survival (log-rank p < 0.0001). Findings from this cohort study suggest that HF is significantly associated with cancer. NT-proBNP was higher in cancer patients, with significant prognostic value in cancer patients.

Prognostic value of sst2 in long-term mortality in acute heart failure.

BACKGROUND: The use of biochemical markers in ADHF is considered valuable both in the diagnosis and treatment of diseases and in follow-up. This study aimed to investigate the prognostic power of serum sST2 and NT-proBNP levels in predicting long-term mortality in patients with ADHF using serial measurement. METHODS: A total of 122 patients with ADHF were included in this prospective study. Venous blood samples were taken from the patients at the time of first admission to the emergency department and 48 h after hospitalisation. Serial measurements were performed using the same blood samples to determine NT-proBNP and sST2 levels. RESULTS: The 1st time sST2 value was found to be significantly higher in the deceased group than in the living group, and this increase was found to be statistically significant (p < 0.001). The cut-off value for the 1st time value of sST2 was > 56.79 ng/mL, with 91.2% sensitivity and 79.5% specificity (area under the curve (AUC): 0.902, 95% confidence interval (CI): 0.835-0.948, p < 0.001). The cut-off value for the 2nd time sST2 value was > 38.91 ng/mL, with 97.1% sensitivity and 81.8% specificity (AUC: 0.932, 95% CI: 0.872-0.970, p < 0.001). CONCLUSION: In our study, sST2 gained value as a marker that should be included in panels with multiple markers. It seems more appropriate to recommend the serial measurement of sST2 in heart failure. LIMITATIONS OF OUR STUDY: The sample size is relatively small and there is no standard in timing and numbers in serial measurements.

Assessment and Comparison of N-Terminal-Probrain Natriuretic Peptide (NT-proBNP) in Saliva and Serum of Healthy Subjects, Periodontitis Patients, and Periodontitis Patients With Myocardial Infarction.

Introduction Periodontitis is a multifactorial oral disease causing destruction of the periodontium. Systemic diseases can exacerbate periodontal inflammation through immune dysregulation. N-terminal-probrain natriuretic peptide (NT-proBNP) a prohormone, released by myocardial cells is a known biomarker for cardiovascular disease (CVD). Existing literature discloses a bidirectional relationship between periodontitis and CVD. NT-proBNP release can be regulated by mediators of the systemic inflammation. Cardiocyte NT-proBNP release might get stimulated through proinflammatory cytokines. NT-proBNP levels can also be influenced by systemic inflammation in the absence of cardiac dysfunction. Accordingly, we postulated that the inflammation of periodontium could aid in increased levels of NT-proBNP in serum and saliva in participants without cardiovascular disorders. Saliva is said to be the mirror of the body. Assessing NT-pro BNP in saliva allows for a non-invasive method. The present research evaluated the salivary and serum concentrations of NT-proBNP in a healthy group, patients suffering from periodontal disease and periodontal disease along with myocardial infarction (MI). Material and method A total of 90 patients, 30 in each group i.e., healthy group, periodontitis patients and patients suffering from periodontitis with myocardial infarction, were enrolled. The periodontitis patients were selected according to the Classification of Periodontal and Peri-implant Diseases and Conditions 2017. Patients clinically diagnosed with MI by the physician were selected following World Health Organization criteria for detection of MI. Case history was recorded and periodontal parameter analysis like plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL) were measured. Salivary and serum samples were collected from the participants after obtaining informed consent. The samples were subjected to human NT-proBNP sandwich type enzyme-linked immunosorbent assay (ELISA) for quantitative evaluation. The obtained data was analysed and compared using ANOVA, Tukey's post hoc test and Pearson's correlation. The p-value<0.05 was considered statistically significant. Result PI and GI were highest in subjects with periodontitis only (p<0.05). Patients suffering from periodontitis with MI exhibited significantly higher PPD and CAL values (p<0.05). Salivary and serum concentrations of NT-proBNP were significantly higher with p-value=0.000 in subjects suffering from periodontitis with MI. The salivary NT-proBNP levels were significantly higher than serum NT-proBNP levels in periodontitis and periodontitis with MI patients. The levels of NT-proBNP in periodontitis along with MI patients were 1.570 pg/mL in serum and 1.694 pg/mL in saliva. Conclusion Salivary NT-proBNP levels were highest in subjects affected from periodontitis along with MI. Elevated salivary NT-proBNP levels can be due to systemic inflammation and cardiovascular stress linking periodontitis to MI. The positive correlation between periodontal parameters and NT-proBNP levels validates the biomarker's role in reflecting the extent of periodontal destruction and its association with cardiovascular stress. Salivary NT-proBNP can be used as a non-invasive diagnostic marker for diagnosing periodontitis and MI. Future research could explore targeted therapies for the shared inflammatory pathways between periodontitis and MI.

BMP10 reflects pre-capillary pulmonary hemodynamics: association of biomarkers and hemodynamic parameters in pulmonary hypertension.

BACKGROUND AND AIMS: The role of biomarkers in diagnosing pulmonary hypertension (PH) and distinguishing between pre- and post-capillary PH remains poorly understood. We aimed to identify biomarkers with a strong association with mean pulmonary arterial pressure, mPAP (PH diagnosis) and pulmonary vascular resistance, PVR (pre-capillary component), but not with pulmonary arterial wedge pressure, PAWP (post-capillary component). METHODS: Blood samples were collected in patients undergoing right heart catheterization within a prospective cross-sectional study. Biomarkers measured included BMP10, NT-proBNP, ANG2, ESM1/endocan, FGF23, GDF15, IGFBP7, IL6, MyBPC3, proC3, and proC6/endotrophin. Primary outcomes were mPAP, PVR, and PAWP, while secondary outcomes included PH diagnosis (mPAP > 20 mmHg) and elevated PVR (> 2 Wood units). Multivariable linear and logistic regression models were used to assess the relationship between biomarkers and outcomes. RESULTS: Of the 127 patients included (age 66 ± 13 years, 54% female), 73% were diagnosed with PH. BMP10, NT-proBNP, ANG2, MyBPC3, and FGF23 showed a strong association with mPAP (p < 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p < 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p < 0.001). NT-proBNP had the strongest association with the diagnosis of PH (area under the curve = 0.76). BMP10 was the only biomarker associated with elevated PVR (OR 1.60, 95%CI 1.01-2.54, p = 0.04) but not with PAWP (p = 0.86). CONCLUSIONS: Several biomarkers were strongly associated with mPAP, PAWP, and PVR. BMP10 was the only biomarker strongly associated with mPAP and PVR, but not with PAWP, thus reflecting the pre-capillary PH component. Measurement of BMP10 along with NT-proBNP may aid in diagnosing PH.

Increased neutrophil to lymphocyte ratio as a possible marker to detect neuroinflammation in patients with narcolepsy type 1.

STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is an autoimmune disease caused by the selective attack of orexin-producing neurons. However, the pathophysiology of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remains controversial. The neutrophil-to-lymphocyte ratio (NLR) is an easily calculated parameter from the white blood cell (WBC) count, which has already been extensively used as an inflammatory marker in immunological disorders. In this study, by examining the WBC counts of patients with NT1, NT2, and IH compared to controls, and evaluated the NLR to test the possibility of identifying an easy biofluid marker for detecting inflammation and distinguishing patients from healthy controls (HC). METHODS: WBC counts and NLR were compared in 28 NT1, 17 NT2, and 11 IH patients, in addition to 21 sex/age-matched HC. These parameters were correlated with cerebrospinal fluid (CSF) levels of orexin-A, the CSF/serum albumin ratio (as a marker of blood-brain barrier integrity), and polysomnographic parameters. RESULTS: NT1 (2.01±0.44) patients showed higher NLR than NT2 (1.59±0.53), IH (1.48±0.37), and HC (1.48±0.43), with no significant difference between NT2 and IH patients. The ROC curve analysis detected an optimal cut-off value to discriminate patients with NT1 from NT2, IH, and HC for values of NLR≥1.60, 1.62, 1.59, respectively. CONCLUSIONS: Patients with NT1 showed a higher NLR than those with NT2, IH, and HC, possibly reflecting lymphocyte migration within the CNS, supporting the hypothesis of a neuroinflammatory attack of lymphocytes on orexin-producing neurons. Considering its sensitivity, this easily obtainable biofluid marker could help to screen NT1 patients.

Recent insights into the pathophysiology of narcolepsy type 1.

Narcolepsy type 1 (NT1) is a sleep-wake disorder in which people typically experience excessive daytime sleepiness, cataplexy and other sleep-wake disturbances impairing daily life activities. NT1 symptoms are due to hypocretin deficiency. The cause for the observed hypocretin deficiency remains unclear, even though the most likely hypothesis is that this is due to an auto-immune process. The search for autoantibodies and autoreactive T-cells has not yet produced conclusive evidence for or against the auto-immune hypothesis. Other mechanisms, such as reduced corticotrophin-releasing hormone production in the paraventricular nucleus have recently been suggested. There is no reversive treatment, and the therapeutic approach is symptomatic. Early diagnosis and appropriate NT1 treatment is essential, especially in children to prevent impaired cognitive, emotional and social development. Hypocretin receptor agonists have been designed to replace the attenuated hypocretin signalling. Pre-clinical and clinical trials have shown encouraging initial results. A better understanding of NT1 pathophysiology may contribute to faster diagnosis or treatments, which may cure or prevent it.

Prognostic value of NT-proBNP and uric acid in acute ST-segment elevation myocardial infarction patients after complete revascularization.

OBJECTIVES: To explore the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and uric acid (UA) in acute ST-segment elevation myocardial infarction (STEMI) patients after complete revascularization (CR). METHODS: The clinical and physical data from 125 acute STEMI patients (research group) who underwent CR between December 2017 and December 2020 and 60 healthy individuals (control group) who concurrently underwent physical examinations in the Affiliated Hospital of Guizhou Medical University were retrospectively analyzed in this study. Serum samples were collected from both groups to determine the levels of NT-proBNP and UA. The 3-year follow-up data of acute STEMI patients were collected, which were used to group the patients into a good and a poor prognosis group based on their prognoses to comparatively analyze NT-proBNP and UA levels. Receiver operating characteristic (ROC) curves were drawn to analyze the prognostic value of NT-proBNP and UA in STEMI patients following CR, and survival curves were plotted to observe their influences on patients' 3-year overall survival (OS). Meanwhile, a univariate analysis was conducted to identify factors associated with the 3-year OS of acute STEMI patients after CR. RESULTS: The data showed significantly higher expression levels of serum NT-proBNP and UA in acute STEMI patients than in the controls. Besides, the good prognosis group exhibited markedly lower serum NT-proBNP and UA levels than the poor prognosis group. The areas under the curve (AUCs) of NT-proBNP and UA in predicting the prognosis of acute STEMI patients after CR were all above 0.700, and the AUC of their combined detection reached over 0.800. In addition, high serum NT-proBNP and UA levels were strongly associated with lower 3-year OS rates. As indicated by the univariate analysis, a history of smoking and alcoholism as well as high NT-proBNP and UA levels were closely associated with 3-year OS in acute STEMI patients after CR. CONCLUSIONS: NT-proBNP and UA have promising prognostic value in acute STEMI after CR.

EASIX (endothelial activation and stress index) predicts mortality in patients with coronary artery disease.

BACKGROUND: Coronary interventions reduce morbidity and mortality in patients with acute coronary syndrome. However, the risk of mortality for patients with coronary artery disease (CAD) additionally depends on their systemic endothelial health status. The 'Endothelial Activation and Stress Index' (EASIX) predicts endothelial complications and survival in diverse clinical settings. OBJECTIVE: We hypothesized that EASIX may predict mortality in patients with CAD. METHODS: In 1283 patients undergoing coronary catheterization (CC) and having a diagnosis of CAD, EASIX was measured within 52 days (range - 1 year to - 14 days) before CC and correlated with overall survival. In an independent validation cohort of 1934 patients, EASIXval was measured within 174 days (+ 28 days to + 11 years) after CC. RESULTS: EASIX predicted the risk of mortality after CC (per log2: hazard ratio (HR) 1.29, 95% confidence interval: [1.18-1.41], p < 0.001) in multivariable Cox regression analyses adjusting for age, sex, a high-grade coronary stenosis ≥ 90%, left ventricular ejection fraction, arterial hypertension and diabetes. In the independent cohort, EASIX correlated with EASIXval with rho = 0.7. The long-term predictive value of EASIXval was confirmed (per log2: HR 1.53, [1.42-1.64], p < 0.001) and could be validated by integrated Brier score and concordance index. Pre-established cut-offs (0.88-2.32) associated with increased mortality (cut-off 0.88: HR training: 1.63; HR validation: 1.67, p < 0.0001 and cut-off 2.32: HR training: 3.57; HR validation: 4.65, p < 0.0001). CONCLUSIONS: We validated EASIX as a potential biomarker to predict death of CAD patients, irrespective of the timing either before or after catheterization.

Excess long-term risk of adverse outcomes in heart failure patients with high and low levels of NT-proBNP: A 7-year follow-up study (NorthStar Trial).

Background: This study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide). Methods: Patients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF.

BACKGROUND: Heart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. OBJECTIVES: The goal of this study was to investigate the incremental prognostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. METHODS: Individual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. RESULTS: In 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. CONCLUSIONS: NT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.