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.

Preclinical modeling of metabolic syndrome to study the pleiotropic effects of novel antidiabetic therapy independent of obesity.

Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model.

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-?), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-?, and TNI were significantly elevated, and these changes were statistically significant (P<0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-?, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P<0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE. Keywords: Animal model of pulmonary embolism, B-type natriuretic peptide, Electrocardiogram, Pulmonary thromboembolism, Troponin I, Tumor necrosis factor-alpha.

Heart failure biomarkers and prediction of early left ventricle remodeling after acute coronary syndromes.

INTRODUCTION: Several biomarkers are characteristically elevated in patients with acute heart failure (AHF). Our hypothesis was they could predict early changes in left ventricular (LV) characteristics in acute coronary syndrome (ACS) patients. The objective of this study was two-fold: a) compare circulating concentrations of NT-pro BNP, CA-125, ST2, galectin-3 and pro-adrenomedullin among 4 groups of individuals (healthy controls; patients with ACS without AHF; patients with ACS and AHF and patients admitted for AHF); and b) evaluate whether these biomarkers predict adverse LV remodeling and ejection fraction changes in ACS. METHODS: 6 biomarkers (NT-pro BNP, CA-125, ST2, galectin-3, pro-adrenomedullin and C-reactive) were measured within the first 48 h of admission. Echocardiograms were performed during admission and at 3 months. Variables associated with LV end-diastolic volume (EDV) and ejection fraction (LVEF) change were assessed by multivariate linear regression. RESULTS: We analyzed 51 patients with ACS, 16 with AHF and, 20 healthy controls. NT-pro BNP and ST2 concentrations were elevated at similar values in patients admitted for AHF and ACS complicated with HF but CA-125 concentrations were higher in AHF patients. NT-pro BNP concentrations were positively correlated with CA-125 (rho = 0.58; p < 0.001), ST2 (rho = 0.58; p < 0.001) and galectin-3 (rho = 0.37; p < 0.001) Median change (median days was 83 days after) in EDV and LVEF was 5 %. CA-125 concentrations were positively associated to LV EDV change (ß-coefficient 1.56) and negatively with LVEF trend (ß-coefficient = -0.86). No other biomarker predicted changes in EDV or LVEF. CONCLUSIONS: CA-125 correlates with early LV remodeling and LVEF deterioration in ACS patients.

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.

Cardiovascular Risks and Outcomes Among Chinese American Immigrants: Insights From the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Immigrants experience changes in cardiovascular risk factors and racial disparities in both cardiovascular health prevention and outcomes upon immigration. We aimed to examine cardiovascular risk factors and outcomes among Chinese American immigrants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort. METHODS AND RESULTS: We analyzed data from 746 Chinese American immigrants in the MESA study with a median follow-up period of 17.8 years. The mean age of the cohort was 62.3 years, with 52.7% being women. Kaplan-Meier curves and Cox proportional hazards models were used to assess the association of immigration history, geographic location, biomarkers, and cardiac imaging parameters with cardiovascular risk factors and cardiovascular outcomes. The Cox hazards models were adjusted for known family history of heart disease, education level, sex, diabetes, hypertension, age, and body mass index. Although immigration history categorized as earlier (<20 years) versus later (≥20 years) showed no association with cardiovascular outcomes, the duration of residence in the United States emerged as a strong predictor for an increased risk of cardiovascular disease death (hazard ratio 1.39 [95% CI, 1.07-1.8]; P=0.012). All-cause mortality differed significantly between the Chinese immigrants from Los Angeles and those from Chicago, with higher survival probability in Chicago (log-rank test, P=0.018). Furthermore, elevated levels of N-terminal pro-brain natriuretic peptide levels, left ventricular mass, and coronary artery calcium scores were associated with the risk of cardiovascular disease among Chinese immigrants. CONCLUSIONS: Within the MESA cohort, the duration of residence and geographic location were associated with the risk of cardiovascular disease outcomes among Chinese immigrants.

Prognostic value of NT-proBNP in the new era of heart failure treatment.

BACKGROUND: Heart failure is one of the leading causes of mortality and hospitalization in cardiovascular patients. Guideline-directed medical treatment (GDMT) in the current era includes novel medications such as ARNI and SGLT2 inhibitors, as well as an approach to treatment based on clinical phenotypes. To assess prognostic factors for mortality and hospital readmissions plays a crucial role in patient care. OBJECTIVES: This study aimed to determine the rate of 90-day post-discharge events in patients having heart failure with reduced ejection fraction (HFrEF) and investigate the associated clinical factors. METHOD: A prospective study was conducted on 110 HFrEF patients at the cardiology department of Cho Ray Hospital. The 90-day events included all-cause mortality and rehospitalization due to heart failure. RESULTS: The rate of 90-day events was 45.6%. After multivariable Cox regression analysis, NT-proBNP level ≥ 1858 pg/mL was identified as an independent factor associated with the 90-day events. CONCLUSION: NT-proBNP cut-off ≥ 1858 pg/mL can be used for the prognosis of 90-day events in HFrEF.

Efficacy of ozonated autohemotherapy for improvement of myocardial injury following traumatic brain injury.

BACKGROUND: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). METHODS: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. RESULTS: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). CONCLUSION: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. TRIAL REGISTRATION: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020.

Diabetes mellitus in stable chronic heart failure and the combination with humoral activation, their association, and prediction of 2-year adverse outcomes. Data from the FAR NHL registry.

BACKGROUND/AIM: The study aims to describe the role of diabetes in patients with heart failure. METHODS: In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. RESULTS: More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis. CONCLUSION: The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

CICARE communication model and hierarchical responsibility nursing coordination in the application research of elderly patients with chronic heart failure.

The aim of this study was to evaluate the efficacy of implementing the CICARE communication model and hierarchical responsibility nursing coordination in managing chronic heart failure among elderly patients. From June 2021 to June 2023, 120 elderly patients diagnosed with chronic heart failure were admitted to our hospital. They were divided into 2 groups according to different treatment methods: the regular group and the observation group. Both groups of patients received nursing interventions for 3 months. Before and after the intervention, we assessed the levels of cardiac function indicators (left ventricular end-diastolic diameter, left ventricular ejection fraction, and B-type natriuretic peptide levels) and exercise tolerance (6-minute walk test) in both groups of patients. The time to clinical symptom relief, self-efficacy, and quality of life scores were compared between the 2 groups of patients. Before the intervention, there were no significant differences in cardiac function indicators between the 2 groups (P > .05). However, after the intervention, both groups exhibited improvements in left ventricular end-diastolic diameter and B-type natriuretic peptide levels, with the observation group demonstrating greater reductions compared to the control group. Furthermore, both groups showed increased left ventricular ejection fraction levels, with the observation group experiencing a significantly higher improvement. Although exercise tolerance did not differ significantly between the groups before the intervention, post-intervention analysis revealed a greater increase in 6-minute walk test distance in the observation group compared to the control group (P < .05). The time to relief of breathlessness and edema did not significantly differ between the groups (P > .05). Similarly, there were no significant differences in self-efficacy and quality of life scores between the groups before the intervention (P > .05); however, post-intervention analysis showed higher self-efficacy scores in the observation group. Application of the CICARE communication model and hierarchical responsibility nursing coordination in elderly patients with chronic heart failure can effectively improve the patients' cardiac function levels and significantly enhance their exercise tolerance, self-efficacy, and quality of life.

Editorial on the article «Natriuretic Peptide Concentrations and Echocardiography Findings in Patients with Micro-atrial Fibrillation¼.

In relation with the published article "Natriuretic Peptide Concentrations and Echocardiography Findings in Patients with Micro-atrial Fibrillation", we have issued a comment. The authors of the article addressed a widely discussed topic of "Short episodes of fast arrhythmias initially detected in records on implantable devices". Further, these episodes are studied already by Holter monitoring of different durations with assessment of their clinical significance. This is the subject of the cited article and our comment.

Natriuretic Peptide Concentrations and Echocardiography Findings in Patients with Micro-atrial Fibrillation.

AIM: Atrial fibrillation (AF) is a rhythm disorder characterized by very rapid and disorganized atrial-derived electrical activations with uncoordinated atrial contractions. Very short periods of AF-like activity (micro-AF) may be precursors of undetected, silent episodes of atrial fibrillation. Here, we examined the relationship between natriuretic peptide concentrations and echocardiography findings in patients with micro-AF. MATERIAL AND METHODS: The electrocardiograms (ECGs) of patients complaining of palpitations were recorded with a 24­hour Holter monitor, and the patients were consecutively included in the study. Micro-AF was defined as sudden, irregular atrial tachycardia lasting less than 30 sec with episodes of ≥5 consecutive supraventricular depolarizations with the absolute absence of p-waves. After a G-power test, patients were consecutively included in the study: 45 patients in the micro-AF group and 45 patients in the control group. Laboratory parameters, ECG and echocardiographic findings of the two groups were compared. RESULTS: N-terminal pro B-type natriuretic peptide (Pro-BNP) and serum troponin T concentrations were higher in the micro-AF group, (375.5±63.6 pg / ml vs. 63.1±56.8 pg / ml, p<0.001; 13±11.4 ng / dl vs. 4.4±2.4 ng / dl, p<0.001 respectively.) Each 1 pg / ml increase in serum Pro-BNP increased the risk of micro-AF by 1.8 %. In the ROC analysis, the cut-off value of Pro-BNP for the diagnosis of micro-AF was 63.4 pg / ml, with a sensitivity of 91.1 % and a specificity of 73.3 %. Atrial electro-mechanical delay durations were significantly higher in the micro-AF group. To predict micro-AF, the inter-annulus plane electromechanical delay time (inter-annulus plane AEMD) had a cut-off value of 18.5 sec, with a sensitivity of 93.3 % and a specificity of 91.1 %. Left intra-annulus plane electro-mechanical delay time (intra-annulus AEMD LEFT) had a cut-off value of 11.5 sec with a 95.6 % sensitivity and 75.6 % specificity. In the ECG evaluation, maximum P wave duration (Pmax) (113±10.2 ms vs. 98±10.4 ms; p<0.001), minimum P wave duration (Pmin) (73.8±5.5 ms vs.70±6.3 ms; p<0.001) and P wave dispersion (PWD) (39.1±7.9 ms vs.28±7.6 ms; p<0.001) were longer in the micro-AF group. CONCLUSIONS: Micro-AF in patients may be predicted by evaluating ECG, echocardiographic, and serum natriuretic peptide data.

[Laboratory Aspects of Using the Results of NT-Probnp Concentration Immunochemical Determination in the Management of Patients With Heart Failure: Support For Clinical Decision-Making].

The burden of heart failure (HF) has been increasing worldwide in recent decades. Early diagnosis of HF based on the outpatient measurement of natriuretic peptide (NP) concentration will allow timely initiation of the treatment and reducing the incidence of adverse outcomes in HF. Unfortunately, the frequency of NP testing remains low worldwide. At the online expert meeting held on March 15, 2024, the features of the N-terminal pro-brain natriuretic peptide (NT-proBNP) test (Elecsys proBNP by Roche) were discussed along with the interpretation of test results and presentation of results in laboratory reports. The experts addressed the features of the Elecsys proBNP test in patients with suspected HF in various clinical scenarios (chronic and acute HF). The limits of clinical decision for the NT-proBNP test were established depending on the clinical scenario. Changes in the Elecsys proBNP test results depending on the comorbidities were addressed. The experts suggested ways to optimize the format of the Elecsys proBNP test result reports in the Russian Federation, which will accelerate the implementation of the test in clinical practice and optimize the management of HF patients.

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.

Monitoring of myocardial injury by serial measurements of QRS area and T area: The MaastrICCht cohort.

BACKGROUND: Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID-19 patients in earlier studies, while increased high-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. METHODS: All mechanically ventilated COVID-19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs-cTnT and NT-proBNP concentrations were measured daily. Conversion of daily 12-lead ECGs to VCGs by a MATLAB-based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed-effect models investigated trajectories in serum and VCG markers over time between non-survivors and survivors, adjusted for confounders. RESULTS: In 322 patients, 5461 hs-cTnT, 5435 NT-proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non-survivors had higher hs-cTnT concentrations at intubation and both hs-cTnT and NT-proBNP significantly increased compared with survivors. In non-survivors, the following VCG parameters decreased more when compared to survivors: QRS area (-0.27 (95% CI) (-0.37 to -0.16, p < .01) µVs per day), T area (-0.39 (-0.62 to -0.16, p < .01) µVs per day), and maximal QRS amplitude (-0.01 (-0.01 to -0.01, p < .01) mV per day). QRS duration did not differ. CONCLUSION: VCG-derived QRS area and T area decreased in non-survivors compared with survivors, suggesting that an increase in myocardial damage and tissue loss play a role in the course of critical illness and may drive mortality. These VCG markers may be used to monitor critically ill patients.

Interleukin-6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients.

Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL-6 plasma level and cardiac biomarker NT-proBNP, HS-CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL-6 and NT-proBNP plasma levels were measured by the ELISA. Also, HS-CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL-6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL-6 with DAS-28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = -0.270), in the patients. Also, IL-6 plasma level positively correlated with HS-CRP (p = 0.021, r = 0.297) and NT-proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL-6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL-6 with various variables of CVD, IL-6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients.