Prohormone Brain Natriuretic Peptide Research Articles

Alcohol and cause-specific mortality in Russia: the Know Your Heart Study 2015–23

BackgroundAlcohol-related mortality in Russia exceeds the world average and presents a critical public health concern. This study assesses the impact of alcohol consumption levels on mortality and investigates mortality predictors among Russians, including people treated for alcohol-related diagnoses (narcology patients).MethodsWe examined 2629 men and women aged 35–69 years who participated in the Know Your Heart study (2015–17), Arkhangelsk, Russia. The participants were categorized into five drinking levels (non-drinking, low-risk, hazardous, harmful, narcology patients) and followed up using a regional mortality database. We used Cox proportional hazards regressions to analyze sociodemographic and cardiovascular biomarkers as mortality predictors among narcology patients and general population and to compare mortality risks across the five drinking levels.ResultsDuring a median follow-up of 6.3 years, 223 (8.5%) participants died. Age- and sex-standardized all-cause mortality rates per 100,000 person-years were 1229 (95% CI: 691–1767) in non-drinking participants, 890 (95%CI: 684–1096) and 877 (95%CI: 428–1325) in low-risk and hazardous drinking participants, 2170 (95%CI: 276–4064) in those with harmful drinking, and 4757 (95%CI: 3384–6131) in narcology patients. The largest proportions of deaths were caused by cardiovascular diseases (37.2%), neoplasms (20.2%), and external causes (13.9%). Compared with low-risk drinkers, narcology patients had higher risks of death with hazard ratios of 3.23 (95%CI: 2.02–5.16) for all-cause mortality, 3.25 (95%CI: 1.52–6.92) for cardiovascular diseases, 9.36 (95%CI: 2.63–33.3) for external causes, and 7.79 (95%CI: 3.34–18.1) for other causes. Neoplasm-related mortality did not differ between groups. All-cause mortality in the general population had positive associations with smoking, waist-to-hip ratio, resting heart rate, systolic blood pressure, high-sensitivity C-reactive protein, and negative associations with left ventricular ejection fraction (LVEF) and higher education. These associations were substantially weaker and non-significant in narcology patients. Cardiovascular mortality in narcology patients was increased with higher education, while male sex, LVEF and N-terminal prohormone of brain natriuretic peptide had less impact compared to the general population sample.ConclusionNarcology patients face markedly higher mortality risks—threefold from all causes and cardiovascular diseases, ninefold from external causes, and sevenfold from other causes. Compared with the general population, conventional mortality risk factors were less predictive of deaths in narcology patients.

Ferric carboxymaltose reduces the burden of arrhythmic events in heart failure with reduced ejection fraction: the role of the non-invasive arrhythmic biomarkers

BackgroundTreating iron deficiency (ID) with ferric carboxymaltose (FCM) in patients with heart failure with reduced ejection fraction (HFrEF) enhances morbidity, quality of life (QoL), and exercise capacity. MethodsThis single center, prospective follow-up study aims to assess FCM's impact on arrhythmic events and non-invasive markers in HFrEF patients with cardiac implantable electronic devices (CIEDs) and ID. Symptomatic HFrEF patients with ID and CIEDs scheduled for IV FCM were followed for 12-months. Arrhythmic activity was evaluated from CIEDs and non-invasive markers from Holter recordings pre- and post-FCM. Ventricular tachycardia/ventricular fibrillation (VT/VF) episodes, non-sustained VT (nsVT), late potentials (LPs), Microvolt T-wave alternans (MTWA), heart rate variability, turbulence (HRT) QTc, and premature ventricular contractions (PVCs, number and Lown and Wolf classification) were assessed. Left ventricular EF (LVEF), global longitudinal strain (LV GLS), QoL (KCCQ, EQ-5D-5L), six-minute walking distance (6MWD), peak oxygen consumption, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were also recorded. ResultsNinety-six patients in optimal medical treatment participated (median age 71.9 [12.3] years, 83% male). Post-FCM treatment, VT/VF (P=0.043) and nsVT (P<0.001) frequency decreased significantly. The Lown and Wolf classification improved (P=0.002) and predicted VT/VF episodes better than other markers (AUC 0.737, P=.001). MTWA, LPs and HRT improved statistically significantly post-FCM. Hospitalization rates and NT-proBNP levels decreased, while LVEF, LV GLS, 6MWD, QoL and peak VO2 improved statistically significantly (P<0.001). ConclusionsOur study provides real-world evidence that IV FCM led to statistically significant reduction in ventricular arrhythmic episodes, as well as an improvement in non-invasive arrhythmic markers.

N-terminal prohormone of brain natriuretic peptide predicts recurrent cardiovascular events in patients with acute coronary syndrome both in the acute and post-discharge setting: a TRACER substudy

Abstract Background N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a circulating peptide released by the heart in response to increased wall tension and stretching, for example, occurring during myocardial and/or atrial dysfunction. NT-proBNP is a diagnostic and prognostic marker in patients with heart failure but might also have prognostic utility in the acute phase of patients with acute coronary syndrome (ACS) and at one month after ACS. Purpose To assess the prognostic value of NT-proBNP over time in patients with ACS both in the acute setting and when re-assessed after one month. Methods The TRACER study randomized 12,944 patients with non-ST-segment elevation ACS (NSTE-ACS) to treatment with vorapaxar vs. placebo. Plasma samples for biomarker analyses were obtained at randomization (median 21 hours after hospital admission) in 6,800 patients and at an outpatient visit after one month in 5,313 patients. NT-proBNP was analysed using the Elecsys electrochemiluminescence immunoassays method. The primary composite endpoint in this substudy was the one-year risk of cardiovascular (CV) mortality, myocardial infarction, or ischaemic stroke. Associations between continuous natural log-transformed NT-proBNP levels and outcomes were assessed using Cox regression models accounting for study treatment and established risk factors. Results The median concentration of NT-proBNP during hospitalization for ACS and after one month was 496 ng/L and 264 ng/L, respectively. Higher age, female sex, a history of heart failure, and lower body mass index were independently associated with higher levels of NT-proBNP among patients in the acute setting, with renal disease also being an important factor after one month. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 901 patients (incidence rate 10.1 per 100 person-years) included at baseline and in 381 patients (incidence rate 5.4 per 100 person-years) included at one month. Higher circulating levels of NT-proBNP were independently associated with a higher risk of the composite endpoint at baseline (adjusted hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 1.25 [1.03 – 1.51]) and at one month (1.56 [1.15 – 2.11]) (Figure 1 and 2). Incorporating NT-proBNP at baseline into a model with other established risk factors increased the concordance index of the multivariable model from 0.656 to 0.660 (p &amp;lt; 0.001), and after one month, from 0.711 to 0.733 (p &amp;lt; 0.001). These findings remained consistent across the various components of the composite endpoint. Conclusions In patients with ACS, the level of NT-proBNP is an indicator of increased risk of CV outcomes both in the acute setting and, even more pronounced, one month after the index ACS. Measuring NT-proBNP provided incremental prognostic information beyond established risk factors, both in the acute and post-discharge settings.Fig 1.NT-proBNP quartile groupsFig 2.NT-proBNP and CV outcome

A young male patient with cardiomyopathy associated with human immunodeficiency virus infection in the era of highly active antiretroviral therapy

Background: Cardiomyopathy in young people, especially those associated with HIV infection, has been reduced since the era of Highly Active Antiretroviral Therapy (HAART). In the era of post-HAART, manifestations of human immunodeficiency virus (HIV)-associated cardiomyopathy with impaired left ventricular (LV) systolic function are approximately about 1-3% of HIV-infected people. In this case, we presented how to diagnose and appropriately manage such a patient. Case Illustration: A 27-year-old male patient who works as a health worker came to the emergency room with complaints of shortness of breath; it worsened in the last 2 weeks. He got vital signs: blood pressure 97/60 mmHg, heart rate 118 bpm, respiratory rate 23 tpm, and oxygen saturation 99 % with oxygen supplementation of 8 lpm. Risk factors in patients such as smoking, family history, hypertension, diabetes mellitus, and dyslipidemia were denied. He was diagnosed with HIV on (antiretroviral therapy) ART 3 years ago with risk factors for free sex without protection. The last CD4 value was 796 cells/ul (normal value 637 – 1485). The echocardiography showed all chamber dilatation, global hypokinetic, and a significant decrease in LV systolic function (LVEF 16%). Laboratory examination showed an increase of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) into 6824 pg/mL (normal value &lt;85.8). It was then treated by optimizing HF therapy continue HIV therapy. Conclusion: In HIV patients who have fallen into heart failure, a proper diagnosis using relevant tools could be a reference for clinicians to make the right decision. Prompt treatment combination of optimal HF therapy and HIV therapy are becoming the keys to the treatment. Keyword: antiretroviral, cardiomyopathy, heart failure, human immunodeficiency virus

Improved prognosis prediction of idiopathic pulmonary arterial hypertension using targeted plasma proteomics in disease management

Abstract Background Idiopathic pulmonary arterial hypertension (IPAH), a special subgroup of PAH with unclear etiology, is characterized by rapid progression and poor prognosis underscoring the need for optimization of IPAH management and the accurate prediction of prognosis. However, it is disappointing that specific plasma biomarkers for IPAH management and prognosis are lacking in clinical practice. Up to date, the plasma biomarkers used for assessment of IPAH severity and prognosis are relied solely on indicators such as N-terminal prohormone of brain natriuretic peptide, or brain natriuretic peptide, which could reflect cardiac function but fail to promptly response to the dynamic change of disease condition due to the complexity of IPAH pathogenesis. Purpose We evaluated the prognostic value of plasma proteins in addition to current clinical predictors for prognosis prediction of IPAH. Methods Olink Immune-Response panel was used to measure 92 plasma proteins in a prospective IPAH cohort with 169 patients and a mean follow-up period of 2.4 ± 0.9 years. Six machine learning methods were used to construct predictive models, including plasma proteins-based Olink models, clinical parameters-based clinical models, and integrative models. Results A total of 18 proteins showed differential expression between patients with or without adverse clinical outcomes. Three proteins (STC1, CXADR, and IL6) were strongly correlated with clinical indicators of IPAH severity and their concentrations showed upward trends along with increased risk stratification. Elevated levels of STC1, CXADR, and IL6 are all associated with an increased risk of adverse clinical events, indicated by survival analysis, restricted cubic splines, and multivariable Cox regression analysis (STC1 HR=3.474, 95%CI: 1.129-10.692, P=0.030; CXADR: HR=1.602, 95%CI: 1.074-2.387, P=0.021; IL6: HR=1.883, 95%CI: 1.376-2.576, P&amp;lt;0.001). The inclusion of these three proteins into the predictive model could significantly increase the predictive power on the basis of the clinical model (AUC: 0.746 vs 0.626). Conclusions High levels of STC1, CXADR, and IL6 in plasma were associated with severe clinical phenotype and increased risk of adverse clinical events in patients with IPAH. These plasma proteins could significantly improve the prognostic performance of pre-existing clinical models, facilitating the clinical management of IPAH patients.The predictive efficient of models

Association of preoperative NT-proBNP with 30-day and five-year mortality after cardiac surgery

Abstract Background Elevated levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) reflect cardiac status in heart failure patients and are independently associated with mortality and adverse cardiovascular outcomes in elective patients undergoing non-cardiac surgery. However, there is scarce evidence about the association between NT-proBNP and outcome after cardiac surgery in large patient populations. Purpose The aim of this study was to analyze the association of preoperative NT-pro-BNP levels with 30-day and five-year mortality after cardiac surgery. Methods A consecutive cohort of 6938 patients undergoing cardiac surgery was analyzed retrospectively. The relationship between preoperative NT-proBNP and 30-day and five-year mortality adjusted for EuroSCORE II was explored using a Cox proportional hazards model. The dynamics of preoperative NT-proBNP were analyzed by comparing the values at the time of diagnosis or assignment to surgery with the values on the day before surgery (n= 4739). Results were validated in an external cohort from the SWEDEHEART registry (n=3415). Results Median preoperative NT-proBNP was 552 ng/l. Death within 30 days occurred in 2.1% of the patients. High preoperative NT-proBNP levels were associated with a higher 30-dayand 5-yearmortality. Preoperative NT-proBNP thresholds to identify patients at high-risk (&amp;gt;4000 ng/l), intermediate-risk (2000-4000 ng/l) and low-risk (&amp;lt;2000 ng/l) for 30-day mortality were determined. Patients in the intermediate or high-risk category had a higher risk for prolonged ICU stay (OR 2.52), ultrafiltration (OR 3.68), ECMO (OR 3.63), 30-day mortality (HR 2.79), and 5-year mortality (HR 2.41) (p-value all &amp;lt;0.001). Patients who improved in the preoperative NT-proBNP risk had a significant 30-day and five-year survival benefit. Conclusions Preoperative NT-proBNP levels are independently associated with 30-day and five-year mortality after cardiac surgery. NT-proBNP reduction prior to surgery might decrease 30-day and five-year mortality after cardiac surgery.NTproBNP is associated with outcome

The use of sodium-glucose cotransporter type 2 inhibitors for the treatment of chronic heart failure in cancer patients receiving cardiotoxic chemotherapy. Preliminary results.

Background. Chronic heart failure (CHF) is one of the most serious and late manifestations of cardiotoxicity during treatment with antitumor drugs in cancer patients. As of today, only 2 groups of drugs have proven significant cardioprotective effects in this category of patients: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and beta-blockers (BABs). Only recently has data emerged on the successful use of sodium-glucose cotransporter type 2 inhibitors (SGLT-2) in patients with CHF on anthracycline therapy.Aim. To evaluate the role of SGLT-2 inhibitors in the complex treatment of CHF in cancer patients receiving cardiotoxic chemotherapy.Methods. A prospective observational open study, including 60 patients with verified CHF who received cardiotoxic chemotherapy and dual cardioprotective therapy: ACEIs/ARBs + BABs (control group); and 56 patients who receive similar therapy with the addition of Dapagliflozin 10 mg 1 time in the morning (study group). The results were monitored after 6 months using laboratory and instrumental research methods, as well as additional control methods. Results. Troponin T, N-terminal prohormone of brain natriuretic peptide (NTproBNP) and left ventricular longitudinal strain (GLS) levels were compared in 47 patients who had completed all follow-up studies at 6 months. It was noted that the dynamics of troponin in both groups did not differ significantly (p0.753 and p0.260, respectively), and the level of NTproBNP significantly decreased in the study group by 7.8% compared to the control group (p0.006). Comparable data were obtained for GLS (a decrease in the study group by 6.5% in relative values) compared to the control group (p0.008)). 22 (46.8%) patients had CHF before the start of chemotherapy, and in 25 (53.2%) CHF arose during antitumor drug therapy. There were 17 (16%) deaths, but there were no deaths from heart failureinbothgroups.Conclusion. We believe that a decrease in the marker of heart failure and a less pronounced impairment of the longitudinal deformation of the left ventricle with the addition of SGLT-2 inhibitors to the basic therapy of CHF in cancer patients receiving cardiotoxic chemotherapy can slow down the progression of CHF.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study.

The PERFECT study, a randomized, controlled, double-blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH-COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH-COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N-terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH-COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies.

The Relationship between Vascular Biomarkers (Serum Endocan and Endothelin-1), NT-proBNP, and Renal Function in Chronic Kidney Disease, IgA Nephropathy: A Cross-Sectional Study

IgA nephropathy (IgAN) is the most common primary glomerular disease. Endothelin-1 (ET-1) is one of the strongest vasoconstrictor materials in the blood. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is associated with renal function and poor outcomes in chronic kidney disease (CKD). Serum endocan is a biomarker associated with proinflammatory cytokines, and the increase in the serum level plays a critical role in inflammatory, proliferative, and neovascularization processes and is associated with poor cardiovascular outcomes in patients with CKD too. Identifying high-risk patients using biomarkers could help to optimize their treatment. Ninety patients with biopsy-confirmed IgAN were included in the study (50 males/40 females, mean age: 54.9 ± 14.4 years). Serum endocan, ET-1, and NT-proBNP were measured by enzyme-linked immunosorbent assay kits. Echocardiography was performed, and carotid-femoral pulse wave velocity (cfPWV) was measured by SphygmoCor in this cross-sectional study. Patients were divided into two groups based on serum endocan median level (cut-off: 44 ug/L). There was significantly higher aorta systolic blood pressure (SBPao) (p = 0.013), NT-proBNP (p = 0.028), albumin/creatinine ratio (p = 0.036), and uric acid (p = 0.045) in the case of the higher endocan group compared to the lower. There was also significantly higher SBPao (p = 0.037) and NT-proBNP (p = 0.038) in the case of higher endothelin-1 (ET-1) levels compared to the lower (cut-off: 231 pg/mL) group by the two-sample t-test. Then, we divided the patients into two groups based on the eGFR (CKD 1–2 vs. CKD 3–5). The levels of serum endocan, NT-proBNP, cfPWV, SBPao, left ventricular mass index (LVMI), uric acid, and albuminuria were significantly higher in the CKD 3–5 group compared to the CKD 1–2 group. The serum endocan and NT-proBNP levels were significantly higher in the diastolic dysfunction group (p = 0.047, p = 0.015). There was a significant increase in serum endocan levels (CKD 1 vs. CKD 5; p = 0.008) with decreasing renal function. In IgAN, vascular biomarkers (endocan, ET-1) may play a role in endothelial dysfunction through vascular damage and elevation of SBPao. Serum endocan, ET-1, and NT-proBNP biomarkers may help to identify IgAN patients at high risk.

Thoracic Fluid Content as an Indicator of High Intravenous Diuretic Requirements in Hospitalized Patients with Decompensated Heart Failure.

Background: The main cause of hospitalization in patients with heart failure is hypervolemia. Therefore, the primary treatment strategy involves diuretic therapy using intravenous loop diuretics to achieve decongestion and euvolemia. Some patients with acutely decompensated heart failure (ADHF) do not respond well to diuretic treatment, which may be due to diuretic resistance (DR). Such cases require high doses of diuretic medications and combination therapy with diuretics of different mechanisms of action. Although certain predisposing factors for diuretic resistance have been identified (such as hypotension, type 2 diabetes, impaired renal function, and hyponatremia), further research is needed to identify other pathophysiological markers of DR. Objective: This study aims to identify admission markers that can predict a high requirement for intravenous diuretics in hospitalized patients with decompensated heart failure. Methods: This study included 102 adult patients hospitalized for ADHF. At admission, patients underwent clinical assessment, laboratory parameter evaluation (including the N-terminal prohormone of brain natriuretic peptide [NT-proBNP] levels), and hemodynamic assessment using impedance cardiography (ICG). Hemodynamic profiles were based on the use of parameters such as heart rate (HR), blood pressure (BP), and thoracic fluid content (TFC) as markers of volume status. The analysis included 97 patients with documented doses of intravenous diuretic use. Patients were stratified into two groups based on median diuretic consumption (equivalent to 540 mg of intravenous furosemide): the high-loop diuretic utilization (LDU) group (n = 49) and the low-LDU group (n = 48). Results: Compared to low-LDU patients, high-LDU patients had greater thoracic fluid content at admission, both quantitatively (37.4 ± 8.1 vs. 34.1 ± 6.9 kOhm-1; p = 0.024) and qualitatively (TFC ≥ 35 kOhm-1: 59.2% vs. 33.3%; p = 0.011). Anemia was more common in the high-LDU group (67.4% vs. 43.8%; p = 0.019), as was elevated NT-proBNP (≥median of 3952 pg/mL: 60.4% vs. 37.5%; p = 0.024). High LDU was associated with a significantly longer hospitalization duration (12.9 ± 6.4 vs. 7.0 ± 2.6 days; p < 0.001). Logistic regression analysis identified anemia, elevated NT-proBNP, and high TFC as predictors of high LDU (HR: 2.65, 2.54, and 2.90, respectively). In a multifactorial model, only high TFC remained an independent predictor (HR: 2.60, 95% CI 1.04-6.49; p = 0.038). Conclusions: TFC was the sole independent admission marker of a high requirement for intravenous diuretics in patients hospitalized for decompensated heart failure. An objective assessment of volume status by impedance cardiography may support intensive personalized decongestion therapy.

Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study

Background and aimsUnderstanding molecular processes of the early phase of atherosclerotic cardiovascular disease conditions is of utmost importance for early prediction and intervention measures. MethodsWe measured 92 cardiovascular-disease-related proteins (Olink, Cardiovascular III) in 2024 elderly participants of the population-based LIFE-Adult study. We analysed the impact of 27 covariables on these proteins including blood counts, cardiovascular risk factors and life-style-related parameters. We also analysed protein associations with 13 subclinical cardiovascular traits comprising carotid intima media thickness, plaque burden, three modes of Vicorder-based pulse-wave velocities, ankle-brachial index and ECLIA-based N-terminal prohormone of brain natriuretic peptide (NT-proBNP). ResultsEstimated glomerular filtration rate, triglycerides and sex where the most relevant covariables explaining more than 1 % variance of 49, 22 and 20 proteins, respectively. A total of 43 proteins were significantly associated with at least one of the analysed subclinical cardiovascular traits. NT-pro-BNP, brachial-ankle pulse-wave velocity (baPWV) and parameters of carotid plaque burden accounted for the largest number of associations. Association overlaps were relatively sparse. Only growth/differentiation factor 15, low density lipoprotein receptor and interleukin-1 receptor type 2 are associated with these three different cardiovascular traits. We confirmed several literature findings and found yet unreported associations for carotid plaque presence (von-Willebrand factor, galectin 4), carotid intima-media thickness (carboxypeptidase A1 andB1), baPWV (cathepsin D) and NT-proBNP (cathepsin Z, low density lipoprotein receptor, neurogenic locus homolog protein 3, trem-like transcript 2). Sex-interaction effects were observed, e.g. for spondin-1 and growth/differentiation factor 15 likely regulated by androgen response elements. ConclusionsWe extend the catalogue of proteome biomarkers possibly involved in early stages of cardiovascular disease pathologies providing targets for early risk prediction or intervention strategies.

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

BackgroundThe pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium. ObjectivesThis study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM. MethodsForty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups. ResultsATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, β = 0.139, P < 0.001), native T1 time (r = 0.432, β = 0.020, P = 0.005), RV-LS (r = 0.445, β = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, β = 2.842, P = 0.003), troponin T (r = 0.422, β = 0.048, P = 0.007), 6MWD (r = 0.385, β = −0.007, P = 0.017), and NAC stage (r = 0.490, β = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021). ConclusionsIn ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

The Level of Markers Stimulating Growth Factor 2 (ST2), N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP), and D-Dimer in Healthy Volunteer Testers in 21-Day Head-Down -6° Tilt Bed Rest as a Model of Hypodynamia.

The paper presents an analysis of the proteomic composition in relation to both the risk of thrombosis and changes in the state of cardiomyocytes associated with the risk of cardiac fibrosis and heart failure. We examined 12 practically healthy male volunteers exposed to head-down -6° tilt bed rest (HDBR) for 21 days. The revealed decrease in the level of stimulating growth factor 2 (ST2) on days 10 and 21 relative to the initial values (background; 5 days before HDBR) indicated a decrease in the myocardial load and cardiomyocyte extensibility. The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increased on day 2, decreased on days 10 and 21 of HDBR relative to the background levels, and returned to baseline values after the recovery period (5 days after HDBR). The revealed changes in the level of NT-proBNP reflected the increase in circulating blood volume corresponding to HDBR duration and the role of the gravity component in increasing the functional load on the myocardium. Unchanged blood level of D-dimer at all points of the study indicates that there is no risk of thrombosis under the conditions of this study.

Hypothesis paper: GDF15 demonstrated promising potential in Cancer diagnosis and correlated with cardiac biomarkers

BackgroundCardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction).MethodsAnalysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG).ResultsGDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort.ConclusionGDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

Deep learning algorithm for predicting left ventricular systolic dysfunction in atrial fibrillation with rapid ventricular response.

Although evaluation of left ventricular ejection fraction (LVEF) is crucial for deciding the rate control strategy in patients with atrial fibrillation (AF), real-time assessment of LVEF is limited in outpatient settings. We aimed to investigate the performance of artificial intelligence-based algorithms in predicting LV systolic dysfunction (LVSD) in patients with AF and rapid ventricular response (RVR). This study is an external validation of a pre-existing deep learning algorithm based on residual neural network architecture. Data were obtained from a prospective cohort of AF with RVR at a single centre between 2018 and 2023. Primary outcome was the detection of LVSD, defined as a LVEF ≤ 40%, assessed using 12-lead electrocardiography (ECG). Secondary outcome involved predicting LVSD using 1-lead ECG (Lead I). Among 423 patients, 241 with available echocardiography data within 2 months were evaluated, of whom 54 (22.4%) were confirmed to have LVSD. Deep learning algorithm demonstrated fair performance in predicting LVSD [area under the curve (AUC) 0.78]. Negative predictive value for excluding LVSD was 0.88. Deep learning algorithm resulted competent performance in predicting LVSD compared with N-terminal prohormone of brain natriuretic peptide (AUC 0.78 vs. 0.70, P = 0.12). Predictive performance of the deep learning algorithm was lower in Lead I (AUC 0.68); however, negative predictive value remained consistent (0.88). Deep learning algorithm demonstrated competent performance in predicting LVSD in patients with AF and RVR. In outpatient setting, use of artificial intelligence-based algorithm may facilitate prediction of LVSD and earlier choice of drug, enabling better symptom control in AF patients with RVR.

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.

Chemiluminescence immunoassay amplified by functional acridinium ester for the detection of NT-proBNP in clinical samples

High sensitivity and accuracy of heart failure biomarker, N-terminal prohormone brain natriuretic peptide (NT-proBNP), is critical for the early detection of heart failure. However, traditional chemiluminescent (CL) probe still face the challenges of poor solubility, in particular, significant disappointing bioavailability, which profoundly limit its clinical applications. In this paper, we demonstrate functional CL probe acridinium ester (AE-2) for the detection of NT-proBNP, through introducing a hydrophilic unit for ensuring high water dispersity and reactive group for promoting better bioavaiability with antibody. Compared to the traditional CL probe, the functional CL probe AE-2 exhibits extraordinary features, such as better biocompatibility, higher label rate with antibody, as well as significant chemiluminescence signal. In addition, this CL probe exhibits excellent linearity with the test data of Longhua Hospital, suggesting that AE-2 could be used as a clinical examination assay to detect NT-proBNP in real clinical samples. Thus, this functional CL probe AE-2 can be a powerful tool for elucidating the roles of NT-proBNP in clinical samples.

Frailty, multimorbidity and polypharmacy: exploratory analyses of the effects of empagliflozin from the EMPA-KIDNEY trial.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recommended treatment for adults with chronic kidney disease (CKD), but uncertainty exists regarding their use in patients with frailty and/or multimorbidity, among whom polypharmacy is common. We derived a multivariable logistic regression model to predict hospitalization (reflecting frailty) and assessed empagliflozin's risk-benefit profile in a post-hoc analysis of the double-blind, placebo-controlled EMPA-KIDNEY trial. The EMPA-KIDNEY trial randomized 6609 patients with CKD (estimated glomerular filtration rate [eGFR] ≥20<45 mL/min/1.73m2, or ≥45<90 mL/min/1.73m2 with urinary albumin-to-creatinine ratio ≥200 mg/g) to receive either empagliflozin 10 mg daily or matching placebo and followed for two years (median). Additional characteristics analysed in subgroups were multimorbidity, polypharmacy and health-related quality of life (HRQoL) at baseline. Cox regression analyses were performed with subgroups defined by approximate thirds of each variable. The strongest predictors of hospitalization were N-terminal prohormone of brain natriuretic peptide, poor mobility and diabetes; then eGFR and other comorbidities. Empagliflozin was generally well-tolerated independent of predicted risk of hospitalization. In relative terms, allocation to empagliflozin reduced the risk of the primary outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.64-0.82); and all-cause hospitalization by 14% (HR 0.86, 95% CI 0.78-0.95); with broadly consistent effects across subgroups of predicted risk of hospitalization, multimorbidity, polypharmacy or HRQoL. In absolute terms, the estimated benefits of empagliflozin were greater in those at highest predicted risk of hospitalization (reflecting frailty) and outweighed potential serious harms. These findings support the use of SGLT2 inhibitors in CKD, irrespective of frailty, multimorbidity or polypharmacy.

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program

BackgroundIn the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. ObjectivesThe goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. MethodsThis was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. ResultsMore semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, −8.4% [95% CI: −9.4% to −7.3%]; NYHA functional classes III/IV, −8.3% [95% CI: −9.9% to −6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). ConclusionsIn patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; NCT04916470)