Pro Natriuretic Peptide Research Articles

High Serum Adrenomedullin and Mid-Regional Pro-Atrial Natriuretic Peptide Concentrations in Early Pregnancy Predict the Development of Gestational Hypertension

Objectives: Adrenomedullin (AM) and natriuretic peptide levels are elevated in pre-eclampsia. The aim of the present study was to determine AM and natriuretic peptide concentrations before 20 weeks of pregnancy in women who later developed gestational hypertension and in normal pregnancies. Methods: 95 pregnant Caucasian women were included in the study. Gestational hypertension (GH) was diagnosed in 18 patients. The control group consisted of 41 patients with normal pregnancies (non-GH). Blood samples were taken during the first trimester of pregnancy. Results: Analysis of NT-proBNP showed no significant differences between the group of patients who later developed GH and those with normal pregnancies. Patients who developed GH later in pregnancy had higher levels of both MR-proANP (p < 0.001) and adrenomedullin (p < 0.001). Higher levels of MR-proANP were found in the GH with pre-eclampsia group compared with the GH without pre-eclampsia group. Higher levels of AM (p < 0.05) and MR-proANP (p < 0.005) correlated with the risk of preterm birth. Conclusions: (1) Plasma adrenomedullin and MR-proANP concentrations were higher before the 20th week of pregnancy in women who later developed GH; (2) NT-proBNP concentrations did not differ between women with pregnancy-induced hypertension and normal pregnancies; (3) MR-proANP concentrations were highest in patients who developed pre-eclampsia in advanced pregnancy; and (4) there was a correlation between higher plasma adrenomedullin, MR-proANP concentrations before the 20th week of pregnancy, and the risk of preterm birth.

Laboratory and instrumental parameters associated with the risk of death in the long-term follow-up period in patients after myocardial infarction

BACKGROUND: In patients who successfully survived the 1st year after myocardial infarction, the risk of death remains elevated. AIM: To determine laboratory and instrumental parameters of myocardial remodeling associated with a lethal outcome in the long-term follow-up period in patients 1 year after myocardial infarction. MATERIAL AND METHODS: The study included 184 patients 12 months after myocardial infarction: the first group — living patients at the 5-year follow-up point (n=160), the second group — deceased patients at the 5-year follow-up point (n=24). A comparative analysis of inflammation and myocardial dysfunction biomarkers, as well as echocardiographic parameters reflecting the types of left ventricular remodeling, linear dimensions of the cavities and wall thickness of the heart, chamber volumes, and ventricular systolic function was retrospectively performed. After assessing the distribution of quantitative data, the Student's t-test or Mann–Whitney U-test and the χ2 criterion for categorical data were used. The model was built on the basis of logistic regression. The ROC curve, the Hosmer–Lemeshow test, and the bootstrap method were used to assess the model itself and its reliability. RESULTS: Patients in the second group were older (p=0.007), and more often had myocardial infarction with ST-segment elevation during hospitalization (p 0.001). Twelve months after myocardial infarction, a multidirectional pattern of changes in the level of N-terminal brain natriuretic propeptide was revealed: a decrease was registered in the first group, while an increase was registered in the second group. In the dynamics of the second group, the index of end-diastolic volume (p=0.014) and the size of left ventricular asynergy were higher (p=0.043), and the ejection fraction was lower (p=0.015) than in the first group. The model for predicting 4-year mortality in patients who survived myocardial infarction during the 1st year included such parameters as the index of the left ventricular end-diastolic volume, the content of the N-terminal fragment of the natriuretic peptide and the presence of concentric hypertrophy of the left ventricle. CONCLUSION: In patients who survived 1 year after myocardial infarction, the long-term risk of death is associated with a set of parameters reflecting left ventricular remodeling and the development of heart failure.

New cardiovascular biomarkers in patients with advanced cancer-A prospective study comparing MR-proADM, MR-proANP, copeptin, high-sensitivity troponin T and NT-proBNP.

Traditional cardiovascular (CV) biomarkers (high-sensitivity troponinT [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) are important to monitor cancer patients' cardiac function and to assess prognosis. Newer CV biomarkers (mid-regional pro-adrenomedullin [MR-proADM], C-terminal pro-arginine vasopressin [copeptin], and mid-regional pro-atrial natriuretic peptide [MR-proANP]) might outperform traditional biomarkers. Overall, 442 hospitalized cancer patients without significant CV disease or current infection were enrolled (61 ± 15 years, 52% male, advanced cancer stage: 85%) and concentrations of CV biomarkers were analysed. Differences in echocardiographic, clinical, laboratory parameters were assessed. Patients were followed for up to 69 months for all-cause mortality. In univariable analyses, MR-proADM, hsTnT, copeptin, MR-proANP, and NT-proBNP predicted all-cause mortality. In multivariable analyses (adjusted for sex, age, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate [eGFR], C-reactive protein, anti-cancer therapy, reason for hospitalization, cancer stage and type), only MR-proADM remained an independent predictor of mortality (MR-proADM per 1 ln: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.47-3.50], p < 0.001). MR-proADM had the highest area under the curve (AUC) using receiver operating characteristic analysis (AUC [95% CI] 0.74 [0.69-0.79]; hsTnT: AUC 0.69; copeptin: AUC 0.66; MR-proANP: AUC 0.63; NT-proBNP: AUC 0.62). Optimal cut-point for mortality prediction with MR-proADM was 0.94 nmol/L (HR 2.43 [95% CI 1.92-3.06], p < 0.001). Patients with MR-proADM >0.94 nmol/L were older, more often had cancer stage IV, showed reduced performance status, eGFR, haemoglobin, diastolic left ventricular function, and elevated systolic pulmonary artery pressure. MR-proADM is an independent predictor of mortality in advanced stage, hospitalized cancer patients without significant CV disease or current infection. The optimal MR-proADM cut-point for mortality prediction was 0.94 nmol/L with hazards for mortality being approximately 2.5 times higher. There was a continuous increase in mortality risk with stepwise increase of MR-proADM concentrations. Elevated concentrations of MR-proADM were also associated with reduced performance status and mildly reduced left ventricular diastolic function as well as higher age and more often cancer stage IV.

Abstract 4136605: Effect Of A Bone Morphogenetic Protein Receptor Type 2 Mutation On The Cardiomyocyte Response To Pressure Overload

Introduction: A mutation in the Bone Morphogenetic Protein Receptor Type 2 ( BMPR2 ) gene is in 70% of hereditary pulmonary arterial hypertension (hPAH) patients the causative mutation of the disease. Previous work demonstrated that right ventricular function is more impaired in hPAH patients with a BMPR2 mutation. However, the underlying mechanism remains elusive. Moreover, natriuretic peptides, such as N-terminal Brain Natriuretic Peptides (NTproBNP) and Mid Regional proAtrial Natriuretic Peptides (MRproANP), are secreted from cardiomyocytes upon stretch as adaptation to increased pressure overload. We hypothesize that the BMPR2 mutation impairs the response to increased pressure overload. For this purpose, we make use of ventricular induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of hPAH patients carrying a BMPR2 mutation and their isogenic controls in which the mutation was corrected. Aim: To study the effect of a BMPR2 mutation on the response to pressure overload in vitro . Methods: iPSCs from 2 hPAH patients and its isogenic controls were used. iPSCs were differentiated into ventricular iPSC-CMs and stretched 10% equiaxially for 24h at 1Hz on the Flexcell FX-6000 system. Natriuretic peptides gene expressions were quantified via RT-PCR. NTproBNP and MRproANP release were measured on cell supernatants throughout specific immunoassays. Normality of the data was checked, and statistics were performed accordingly. Results: No differences were observed on natriuretic peptides gene expression on static and stretched iPSC-CMs. There is a clear correlation between NTproBNP and MRproANP release (R 2 =0.83, p&lt;0.0001, Figure 1A). Interestingly, hPAH iPSC-CMs showed higher baseline values for NTproBNP release compared to isogenic iPSC-CMs (p&lt;0.01, Figure 1B). Furthermore, stretching resulted in increased NTproBNP and MRproANP secretion in both hPAH and isogenic iPSC-CMs (Figure 1B-C). Conclusions: Secretion of NTproBNP and MRproANP was closely correlated in iPSC-CMs. iPSC-CMs of hPAH patients with a BMPR2 mutation showed higher baseline values of NTproBNP. Increased secretion of NTproBNP and MRproANP upon mechanical stimulation was similar between hPAH and isogenic iPSC-CMs. Experiments in atrial iPSC-CMs are currently ongoing to test potential differences in natriuretic peptide secretion between ventricular and atrial cardiomyocytes as the right atrium is also under stretch in PAH.

Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55–71) years. Median LVEDP was 13.5 (8–19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20–0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22–0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11–0.46]), sST2 (p < 0.0001, r = 0.47 [0.30–0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e’, sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable model.

Serum concentrations of chromogranin A, serotonin and natriuretic peptide are decreased in patients with neuroendocrine tumors with overweight and obesity compared to healthy donors

Background: Neuroendocrine tumors (NETs) are a group of neoplasms, in which circulating biomarkers chromogranin A (CgA), serotonin, and N-terminal brain natriuretic pro-peptide (NT-proBNP), used as a marker of carcinoid heart disease, are especially important in the diagnosis and monitoring. A number of pre-analytical factors, including patients' body mass index (BMI), have an impact on NETs biomarker concentrations. Aim: To perform a comparative analysis of serum concentrations of CgA, serotonin and NT-proBNP in patients with NETs of various locations with normal body weight and with overweight or obesity. Methods: This cross-sectional study included 94 patients with NETs of various locations and 78 provisionally healthy individuals without cancer and cardiovascular disorders, matched by gender and age to the patients. Serum biochemical markers were measured before a course of chemotherapy/biotherapy or surgery with the use of standardized enzyme-linked immunosorbent assays Chromogranin A NEOELISA (Eurodiagnostica), Serotonin ELISA (IBL), and the electrochemiluminescent assay (Cobas e601 analyzer, Roche). All NETs patients were divided into 2 subgroups: 46 patients with normal bodyweight (BMI 18 to 24.9) and 48 patients with overweight/obesity (BMI ≥ 25). Results: The median BMI in the NET patients did not vary depending on their tumor extension, functional activity and malignancy grade. The median concentrations of CgA (150 ng/ml), serotonin (188 ng/ml) and NT-proBNP (117 pg/ml) in the NET patients with obesity and overweight were significantly lower (p = 0.008, p = 0.005 and p = 0.012, respectively) than in the NET patients with normal body weight (769 ng/ml, 704 ng/ml and 197 pg/ml, respectively). In the control group, significantly (p = 0.0001) lower levels in the subgroup with BMI ≥ 25 were obtained only for serotonin. The ROC analysis showed a decrease of the diagnostic efficiency of NET biomarkers in obesity: in the normal BMI group AUC (CgA) was 0.87 and AUC (serotonin) 0.78, whereas in those with BMI ≥ 25, the AUC (CgA) and AUC (serotonin) were 0.81 and 0.62, respectively. Conclusion: Obesity may make it difficult to identify biochemical markers of NETs – CgA, serotonin and NT-proBNP.

Myeloperoxidase and N-terminal proatrial natriuretic peptide as predictors for atrial fibrillation recurrence in patients undergoing redo ablation

BackgroundAtrial fibrillation (AF) is a progressively developing arrhythmia. Electroanatomic remodeling may play an important role, both in the development of the disease as well as in the perpetuation and thus in the recurrence of AF. ObjectiveThis study aimed to investigate potential biomarkers Myeloperoxidase (MPO), N-terminal pro-atrial natriuretic peptide (NT-proANP), intercellular adhesion molecule-1 (ICAM-1), and matrix metalloproteinase-2 (MMP-2) and their predictive value for AF recurrence in patients undergoing redo ablation. MethodsIn this single-center prospective cohort study 50 consecutive patients underwent ultra-high-density mapping and redo ablation. Biomarkers were determined before ablation and at 6 months follow-up. Seven-day Holter was conducted to check for AF recurrence (>30 seconds). ResultsEleven (22%) patients showed AF recurrence after redo ablation. ROC analysis revealed venous MPO and NT-proANP (AUC 0.755, 95% CI 0.599 – 0.912, p=0.010 and AUC 0.752, 95% CI 0.551 – 0.953, p=0.011) as acceptable predictors for intermediate AF recurrence, whereas MMP-2, ICAM-1, and established cardiovascular biomarkers such as NT-proBNP, Troponin T, and C-reactive protein were not (all AUC <0.600). MPO and NT-proANP correlated with AF burden (ρ 0.365, p=0.005 and ρ 0.362, p=0.005). While MPO was associated with atrial fibrosis in the endocardial map (ρ 0.280, p=0.024), NT-proANP correlated with left atrial volume index (ρ 0.256, p=0.037). There were no significant differences in biomarkers concentrations with regard to venous and coronary sinus samples. ConclusionMPO and NT-proANP are of predictive value for AF recurrence in patients undergoing redo ablation. While MPO correlated with endocardial fibrosis, NT-proANP was associated with left atrial volume.

Natriuretic Peptides to Classify Risk of Atrial Fibrillation Detection After Stroke: Analysis of the BIOSIGNAL and PRECISE Cohort Studies.

Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM. We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection. We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log10MR-proANP (0.72, 0.66-0.78; p = 0.001) or log10NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log10MR-proANP vs log10NT-proBNP (p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log10NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log10MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log10MR-proANP vs log10NT-proBNP (p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log10MR-proANP), 27% (clinical and log10NT-proBNP), or 20% (clinical only). MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected. NCT02274727; clinicaltrials.gov/study/NCT02274727.

Clinical Effects of Glucagon-Like Peptide-1 Agonist Use for Weight Loss in Women With Polycystic Ovary Syndrome: A Scoping Review.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal regulatory hormone that stimulates insulin release from the pancreas. While GLP-1 receptor agonists (GLP-1 RAs) have traditionally been utilized to address insulin resistance, their potential application in treating polycystic ovary syndrome (PCOS) has recently garnered attention. This study aimed to investigate the therapeutic efficacy of GLP-1 RAs use for weight loss in women diagnosed with PCOS. We conducted a scoping review following the Joanna Briggs Institute (JBI) methodology and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our investigation delved into the clinical effects experienced by women of diverse racial and ethnic backgrounds with PCOS who were prescribed GLP-1 RAs for weight loss. Peer-reviewed articles from Ovid Medline, Web of Science, CINAHL, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov spanning from 2012 to 2023 were scrutinized. After eliminating duplicates, 811 articles were identified, and ultimately, eight met the eligibility criteria for inclusion. All studies were published in English and exhibited wide geographic diversity. The included studies uniformly reported reductions in weight and body mass index (BMI) among patients who were prescribed GLP-1 RAs, specifically liraglutide or exenatide. Additionally, evidence pointed towards improvements in anthropometric parameters (MF1) (including total body weight, BMI, reduction in waist circumference, and total fat percentage), glucose homeostasis, cardiovascular inflammatory markers (midregional pro-atrial natriuretic peptide (MR-proANP) and mid-regional pro-adrenomedullin (MR-proADM)), rates of pregnancy, and menstrual regulation. However, findings regarding the impact of GLP-1 RAs on lipid profiles were inconsistent. Although some short-term adverse effects were noted, long-term effects of GLP-1 RAs use remain undetermined. GLP-1 RA use demonstrated promising clinical outcomes for women with PCOS, including reduced BMI, improved metabolic parameters, menstrual regularity, and increased rates of natural pregnancy. While the current evidence is encouraging, further research is warranted to elucidate both short- and long-term adverse effects of GLP-1 RAtherapy for PCOS.

The value of percutaneous transcatheter mitral valve regurgitation repair in the combination treatment of chronic heart failure patients: Results from a 6-month observational prospective study

Rationale: Surgical interventions have been recognized as the main method to repair of valvular disorders. Percutaneous transcatheter intervention with a clipping system is being actively introduced into the treatment of chronic heart failure (CHF) patients and mitral valve insufficiency (MVI) for correction of mitral regurgitation (MR), along with drug therapy. Aim: To establish the effect of the mitral valve leaflet clipping in the combination treatment of CHF patients on the clinical course of heart failure and the remodeling process. Methods: This single center prospective comparative study included 80 patients with CHF NYHA class II–IV and secondary MR grade 3–4. The patients were on optimal medical treatment (OMT) for CHF for at least 3 months before inclusion into the study. The main group included 55 patients who underwent transcatheter mitral valve repair with the use of MitraClip system, and the control group consisted of 25 patients in whom the surgery for MR was waived for various reasons (refusal of the surgery by the patient, some valve characteristics), and only OMT for CHF was used. At baseline, main clinical and demographic characteristics of the patients in the both groups were comparable. The duration of the follow-up was 6 months. Echocardiography (echoCG), a 6-minute walk test, and measurements of the brain natriuretic propeptide level were performed in all patients at baseline and at 6 months of the follow-up. Results: At 6 months, there was a significant reduction in CHF NYHA class and an increase in the 6-minute walk test distance and a decrease in diuretic requirements (converted to furosemide, from 58.4 ± 17.2 to 38.1 ± 20.7 mg daily, р = 0.02) in the group with the MitraClip implant, but not in the control group. In the OMT only group, there were no changes over 6 months in the diuretic requirements (48.1 ± 6.68 and 43.8 ± 27.15 mg daily, respectively, р = 0.8). The number of hospital readmissions due to CHF decompensation was 7 (12.7%) in the implanted MitraClip group and 4 (16%) in the OMT group (р = 0.69). EchoCG performed at 6 months after the surgical intervention identified no cases of MR grade 2. In the MitraClip implant group, there was a decrease in the size and volumes of the left atrium (р = 0.02 and р = 0.05, respectively), left ventricle (for end-diastolic diameter p = 0.002, end-diastolic volume p = 0.03), mean pulmonary artery pressure (p = 0.03), as well as an increase in cardiac output (р = 0.04). In the patients receiving OMT only, there were no significant changes in EchoCG parameters over time. Conclusion: Our study has shown benefits of the implantation of the mitral valve leaflet clipping system, compared to OMT only, in CHF. The clipping procedure promotes a significant improvement in clinical course of CHF, reverse myocardial remodeling, and reduction in diuretic requirements.

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m2, abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients

PurposeBone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality.MethodsThis prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied.ResultsATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality.ConclusionSoft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes.

Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

BackgroundPatients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD.Research questionWe investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD.MethodsParticipants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses.ResultsAmong 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density.InterpretationMRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization.Trial registrationClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Predictors of unfavorable neurological outcomes in premature children: a modern view on the problem

Objective: to assess the prognostic significance of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor and brain natriuretic propeptide (NTproBNP) as predictors of unfavorable neurological outcomes in premature children.Materials and methods: A prospective cohort continuous study included 151 premature children, with a gestational age (GA) of 26–32 weeks and a body weight of 590–1990 gr. The children were measured the quantitation of NTproBNP level in the cord blood and level of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor in the blood serum on the 21st day of life. The division of children into groups was carried out in accordance with the assessment of neurological outcomes at control points of the research: 1 control point — at the time of discharge from the hospital, 2 control point — at the age of 1 year of corrected age (CA), 3 control point — 4 years of life.Results: in the course of the study, it was found a “cascade” increase in the cohort of children with unfavorable neurological outcomes from 36.4% at the time of discharge from the hospital to 70% by the age of 4 years. High values of NT-proBNP level in cord blood and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor were established on 21st day of postnatal life in children with both macrostructural brain damages in the neonatal period and having an unfavorable neurological outcome at the age of 1 year of corrected age (CA) and at 4 years of life.Conclusion: modern neurochemical markers of CNS damages N-proBNP and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor open up the possibilities of early diagnosis of brain damages at the cellular level and the start of neuroprotective therapy to reduce neurological disability.

Evaluation of N-terminal pro-atrial natriuretic peptide and Soluble ST2 as Predictors for Cardiovascular Diseases in Patients with Type 2 Diabetes in Al-Basra, Iraq

Evaluation of N-terminal pro-atrial natriuretic peptide and Soluble ST2 as Predictors for Cardiovascular Diseases in Patients with Type 2 Diabetes in Al-Basra, Iraq

The serine protease CORIN promotes progression of gastric cancer by mediating the ERK1/2 MAPK pathway.

The serine protease CORIN catalyzes pro-atrial natriuretic peptide (pro-ANP) into an active ANP and maintains homeostasis of the internal environment. However, it is unclear whether CORIN participates in the regulation of tumor progression. We analyzed the expression profile of CORIN in gastric cancer tissues (GCs) and adjacent nontumoral tissues (NTs). We investigated the prognostic value of CORIN in GC patients. We characterized the in vitro and in vivo activity of CORIN in cultured GC cells with gain-of-function and loss-of-function experiments. The underlying mechanism was explored by using bioinformatics, a signaling antibody array, and confirmative western blot analyses, as well as rescue experiments with highly selective small-molecule inhibitors targeting the ERK1/2 MAPK signaling pathway. CORIN was upregulated in GCs than in NTs. Overexpression of CORIN was correlated with unfavorable prognoses in patients with GC. Ectopic expression of CORIN was promoted, whereas silencing of CORIN suppressed proliferation, colony formation, migration and invasion of GC cells, and tumor growth in vivo. Overexpression of CORIN-induced epithelial-mesenchymal transition (EMT) and activation of the ERK1/2 MAPK signaling pathway, while silencing of CORIN yielded opposite results. The in vitro tumor-promoting potency of CORIN could be antagonized by selective inhibitors targeting the ERK1/2 MAPK pathway. In conclusion, CORIN is a potential prognostic marker and therapeutic target for GC patients, which may promote tumor progression by mediating the ERK1/2 MAPK signaling pathway and EMT in GC cells.

Low irisin levels predict acutely decompensated heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements None. Background Acutely decompensated heart failure (ADHF) continues to be associated with unacceptably increasing in-hospital mortality rates and one-year mortality rates. Distinct scenarios of the natural course of ADHF relate to clinical heterogeneity among patients admitted to hospitals, cardiac dysfunction etiology, precipitating factors contributing to heart failure (HF) decompensation including type 2 diabetes mellitus (T2DM). The aim of this study was to determine the discriminative value of irisin for ADHF in T2DM patients with hemodynamically stable chronic HF. Methods A total of 738 patients with T2DM were prescreened using the local database of "Vita Center" (Ukraine). Using criteria of inclusion (male/female with age of ≥18 years, established T2DM with hemodynamically stable chronic HF, glycosylated hemoglobin &amp;lt; 6.9%, informed consent to participate in the study), we enrolled 489 patients with T2DM with concomitant chronic HF I-IV New York Heart Association (NYHA) functional classes. We enrolled 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. Results We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin &amp;lt; 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP &amp;gt; 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots (Figure) showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (&amp;lt;7.85 ng/mL versus ≥7.85 ng/mL). The intra-class correlation coefficient for inter-observer reproducibility of LV dimensions was 0.88 (95% CI = 0.83–0.92), of LVEF was 0.93 (95% CI = 0.90–0.97), of LAVI was 0.92 (95% CI = 0.89–0.94), and of E/e’ was 0.90 (95% CI = 0.87–0.94). Along with it, the intra-class correlation coefficient for the intra-observer reproducibility of LV dimensions was 0.91 (95% CI = 0.88–0.95), of LVEF was 0.94 (95% CI = 0.90–0.98), of LAVI was 0.95 (95% CI = 0.93–0.97), and of E/e’ was 0.92 (95% CI = 0.90–0.95). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.Flow chart of the study designThe Kaplan–Meier analysis of ADHF

Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Biomarkers for predicting atrial fibrillation: An explorative sub-analysis of the randomised SCREEN-AF trial

Background Atrial fibrillation (AF) is a common treatable risk factor for stroke. Screening for paroxysmal AF in general practice is difficult, but biomarkers might help improve screening strategies. Objectives We investigated six blood biomarkers for predicting paroxysmal AF in general practice. Methods This was a pre-specified sub-study of the SCREEN-AF RCT done in Germany. Between 12/2017-03/2019, we enrolled ambulatory individuals aged 75 years or older with a history of hypertension but without known AF. Participants in the intervention group received active AF screening with a wearable patch, continuous ECG monitoring for 2x2 weeks and usual care in the control group. The primary endpoint was ECG-confirmed AF within six months after randomisation. High-sensitive Troponin I (hsTnI), brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), N-terminal pro atrial natriuretic peptide (NT-ANP), mid-regional pro atrial natriuretic peptide (MR-pro ANP) and C-reactive protein (CRP) plasma levels were investigated at randomisation for predicting AF within six months after randomisation. Results Blood samples were available for 291 of 301 (96.7%) participants, including 8 with AF (3%). Five biomarkers showed higher median results in AF-patients: BNP 78 vs. 41 ng/L (p = 0.012), NT-pro BNP 273 vs. 186 ng/L (p = 0.029), NT-proANP 4.4 vs. 3.5 nmol/L (p = 0.027), MR-pro ANP 164 vs. 125 pmol/L (p = 0.016) and hsTnI 7.4 vs. 3.9 ng/L (p = 0.012). CRP levels were not different between groups (2.8 vs 1.9 mg/L, p = 0.1706). Conclusion Natriuretic peptide levels and hsTnI are higher in patients with AF than without and may help select patients for AF screening, but larger trials are needed.