BMC Cardiovascular Disorders

BackgroundVenous congestion (VC) sets in weeks before visible clinical decompensation, progressively increasing cardiac strain and leading to acute heart failure (HF) decompensation. Currently, the field lacks a universally acknowledged gold standard and early detection methods for VC. MethodsUsing data from the GEO database, we identified VCs impact on HF through key genes using Limma and STRING databases. The potential mechanisms of HF exacerbation were explored via GO and KEGG enrichment analyses. Diagnostic genes for acute decompensated HF were discovered using LASSO, RF, and SVM-REF machine learning algorithms, complemented by single-gene GSEA analysis. A nomogram tool was developed for the diagnostic models evaluation and application, with validation conducted on external datasets. ResultsOur findings reveal that VC influences 37 genes impacting HF via 8 genes, primarily affecting oxygen transport, binding, and extracellular matrix stability. Four diagnostic genes for HFs pre-decompensation phase were identified: SMOC2, OGN, FCN3, and SERPINA3. These genes showed high diagnostic potential, with AUCs for each gene exceeding 0.9 and a genomic AUC of 0.942. ConclusionsOur study identifies four critical diagnostic genes for HFs pre-decompensated phase using bioinformatics and machine learning, shedding light on the molecular mechanisms through which VC worsens HF. It offers a novel approach for clinical evaluation of acute decompensated HF patient congestion status, presenting fresh insights into its pathogenesis, diagnosis, and treatment.

Background: Socioeconomic factors impact cardiovascular health. We investigated the association between patient education level and incident heart failure (HF), acute myocardial infarction (AMI), and stroke following a first hospitalization with atrial fibrillation (AF). Methods: In this nationwide retrospective cohort study using linked Swedish national registers, we included all patients receiving a diagnosis of AF while hospitalized in Sweden from 1995 through 2008; categorized education level as primary, secondary, or academic; and followed patients for up to five years. Outcomes were first hospitalization for HF, AMI, or stroke. Associations were assessed using sex-stratified Cox proportional hazards models adjusted for age, calendar year of AF diagnosis, and measures of comorbidity burden (Charlson Comorbidity Index) and thromboembolic risk (CHA2DS2VA score). Results: The cohort comprised 263,172 patients (mean age 72.5 {+/-} 10.4 years; 56.2% male). Compared with primary education, secondary and academic education attainment were associated with lower adjusted risk of HF and AMI in both females and males. For HF, adjusted hazard ratios (HR) were 0.96 (95% CI 0.93 - 1.00) for secondary and 0.82 (95% CI 0.77 - 0.87) for academic education for females and 0.93 (95% CI 0.90 - 0.96) and 0.76 (95% CI 0.72 - 0.80), respectively, for males. For AMI, adjusted HRs were 0.89 (95% CI 0.85 - 0.93) and 0.71 (95% CI 0.65 - 0.78) for females and 0.91 (95% CI 0.87 - 0.94) and 0.75 (95% CI 0.71 - 0.80) for males. For stroke, lower adjusted risk was observed only in the academic education group. Baseline comorbidity burden and thromboembolic risk were higher in lower education groups. Conclusions: Education level was inversely associated with risk of incident HF and AMI over five years, while the association with stroke risk was weaker. Documenting education level may help identify patients at increased risk who could benefit from careful monitoring and optimized preventive care.

BackgroundPoor physical function has been associated with higher cardiovascular disease (CVD) risk. However, the association between physical function and atrial fibrillation (AF) remains understudied. The comprehensive investigation of the association between physical function and incident AF risk could highlight a novel target for AF prevention. MethodsA total of 4,803 participants without diagnosed AF from the Atherosclerosis Risk in Communities (ARIC) Study cohort with physical function assessed in 2011-2013 were studied. Physical function was measured using Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength. Hospital discharge codes and death certificates were used to ascertain incident AF through 2022, and through 2020 for participants from Jackson. Cox regression was used to assess the association between physical function and incident AF risk, adjusting for multiple covariates. Z-score transformations were performed to identify the physical function measure most strongly associated with incident AF risk, and SPPB component analysis was performed to identify the most influential SPPB component. ResultsMean age of the study participants was 75.1 {+/-} 5.0 years, with 41.2% being male participants and 22.2% being black participants. During a median follow-up of 9.2 years, there were 809 incident AF events. SPPB (HR: 0.93, 95% CI: 0.90-0.96, per 1-point increase) and grip strength (HR: 0.87, 95% CI: 0.78-0.96, per 10kg increase) were inversely associated with incident AF risk, while 4-meter walk time (HR: 1.08, 95% CI: 1.03-1.13, per 1-second increase) was positively associated with incident AF risk. SPPB had the strongest association with incident AF risk. Within SPPB, only the chair stand component was significantly associated with incident AF risk. ConclusionsThe findings suggest that better physical function is associated with reduced incident AF risk, with higher SPPB having the strongest association. Given the modifiable nature of physical function, these findings highlight a potential novel target for AF prevention in aging populations. What is KnownO_LIPhysical function has been associated with cardiovascular diseases, however, the relationship between physical function and incident atrial fibrillation (AF) remains understudied. C_LI What the Study AddsO_LIThis study found that better Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength were all independently associated with reduced risk of incident AF. C_LIO_LIIn this study, higher SPPB was most strongly associated with reduced risk of incident AF, implying the importance of multi-domain measures of physical function. C_LIO_LIThis study found that within SPPB, higher chair stand component score was the only component significantly associated with reduced risk of incident AF, highlighting the critical role of muscle strength in the association between physical function and risk of incident AF. C_LIO_LIThe results suggest that physical function may be a novel modifiable target for AF prevention. C_LI

AbstractO_ST_ABSBackgroundC_ST_ABSThis study aims to explore the causal relationships between inflammatory cytokines (ICs), metabolites, and the risk of arrhythmia through Mendelian Randomization (MR) analysis. MethodsThe causal associations were analyzed using five different MR analysis methods. Additionally, reverse MR analysis was performed to assess the impact of arrhythmias on these ICs and their metabolites. ResultsThe MR analysis revealed that Oncostatin-M receptor (OSM) was significantly associated with an increased risk of arrhythmia (OR = 1.0812, p < 0.05), along with other ICs such as CXCL11 (OR = 1.0586), SIRT2 (OR = 1.0521), and FGF5 (OR = 1.0520). Five were positively correlated with arrhythmia risk, including X-22776 (OR = 1.071, p = 0.022) and tricosanoylsphingomyelin (OR = 1.066, p = 0.035).Mediation analysis demonstrated that FGF5 influences arrhythmia risk through its metabolite 1-palmitoyl-2-oleoyl-GPE, with a mediated effect accounting for 5.1% of the total effect. ConclusionsOur findings suggest that specific ICs and metabolites contribute to the pathogenesis of arrhythmia. In particular, FGF5 and its metabolite 1-palmitoyl-2-oleoyl-GPE are implicated in increased arrhythmia risk, highlighting potential metabolic targets for therapeutic intervention.

This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.

Background Atrial fibrillation (AF) is associated with declines in physical function. While physical activity is linked to better physical function in the general population, its long-term impact in people with AF remains unclear. Investigating this relationship could provide insights and inform interventions for this population. Methods 624 participants with AF from the Atherosclerosis Risk in Communities (ARIC) cohort assessed in 2011-2013 were studied. Physical activity was assessed using the modified Baecke Physical Activity Questionnaire. Physical function was measured using the Short Physical Performance Battery (SPPB), grip strength, and 4-meter walk time up to 3 times over an 8-year period, with 4-meter walk speed as a secondary outcome evaluated in supplemental analyses. Confounder-adjusted linear mixed models were used to assess associations between physical activity and change in physical function trajectories over time. Results Participants had a mean age of 78.5 {+/-} 5.4 years, with 52.6% males and 13.8% Black. Median follow-up was 6.6 years. At baseline, greater sport-related leisure time, non-sport leisure time, and total moderate-to-vigorous physical activity (MVPA) were cross-sectionally associated with better physical function. However, physical activity measures were not significantly associated with temporal trajectories in physical function over time. Conclusions In participants with AF, greater habitual physical activity was significantly associated with better baseline physical function but not with future trajectories. Randomized trials are needed to examine whether interventions that improve habitual physical activity or MVPA can improve physical functioning in individuals with AF.

The link between atrial fibrillation (AF) and stroke has gained attention due to AFs significant impact on stroke risk. Detecting AF, especially paroxysmal AF, presents challenges, highlighting the necessity for continuous Holter monitoring. In our investigation, we utilized commercial data archives to examine AF prevalence and associated cardiac arrhythmias among stroke patients and controls. We also analyzed various factors, such as age, gender, symptoms, test duration, and duration post-stroke, to identify predictors of arrhythmias and enhance paroxysmal detection rates. We included 98 stroke patients and 98 controls for comparing AF prevalence within 72 hours post-stroke and analyzed 779 stroke patients within 4 days to 10 weeks post-stroke. Our findings revealed a higher AF detection rate in stroke patients compared to controls, with AF being the most prevalent arrhythmia observed. Older age and symptom presence were associated with significant findings, particularly AF. Temporal analysis showed a negative correlation between AF and complete heart block occurrence over time, while ventricular tachycardia exhibited a positive correlation. Paroxysmal fibrillation detection rates were highest within the initial month, with the optimal duration of Holter monitoring being 10 days, underscoring the importance of extended monitoring for detecting paroxysmal atrial fibrillation. Detecting paroxysmal atrial fibrillation could influence stroke management. Furthermore, our study suggests the potential utility of commercial data in yielding comparable outcomes to research data.

BackgroundExploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis. MethodsWe studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models. ResultsThe participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. ConclusionIn an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.

BackgroundThe Endothelial Activation and Stress Index (EASIX) reflects endothelial dysfunction and has prognostic value in cardiovascular diseases. This study investigates the association between EASIX and all-cause mortality in critically ill atrial fibrillation (AF) patients. MethodsUsing MIMIC-IV (v3.1) data, 4722 AF patients were stratified by EASIX quartiles. Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) models assessed mortality risk at 7, 30, 180, and 365 days. Subgroup analyses evaluated consistency. ResultsEASIX was significantly associated with increased mortality at all time points. The Kaplan-Meier survival curve shows that as the EASIX quartile increases, the 7-day, 30-day, 180-day, and 365-day mortality rates of AF patients significantly increase. RCS analyses showed that there was a significant non-linear relationship between EASIX and the 7-day, 30-day, 180-day, and 365-day mortality rates of patients with AF. The Cox analysis before and after adjusting for confounding factors showed that EASIX was an independent risk factor for 7-day, 30-day, 180-day, and 365-day all-cause mortality in AF patients. Subgroup analyses further indicated the robustness of these results. ConclusionsEASIX levels are significantly correlated with all-cause mortality at 7, 30, 180, and 365 days in patients with AF, and endothelial dysfunction plays an important role in poor prognosis in AF patients.

Background: Higher METS-IR has been shown to be associated with a higher risk of major adverse cardiovascular events, but data are lacking regarding cardiac arrhythmias. Objectives: The aim of this study was to assess the association between METS-IR and atrial fibrillation/flutter, ventricular arrhythmia and bradyarrhythmia. Methods: Data from the Atherosclerosis Risk in Communities study spanning 1987 to 2013 was utilized for this analysis. METS-IR scores were assessed at baseline (1987-1989) and arrhythmia episodes were identified using ICD-9 codes. Multivariate-adjusted Cox proportional hazard models were constructed to evaluate the relationship between METS-IR and arrhythmia risk, with dose-response analyses conducted. In addition, we analyzed the predictive value of METS-IR for arrhythmias. Results: Over a mean follow-up of 21.9 years, 2493 cases of AF, 688 cases of bradyarrhythmia, and 1315 cases of ventricular arrhythmia were recorded. Each interquartile range increase in METS-IR was associated with a 49% higher risk of atrial fibrillation(P<0.001), 29% higher risk of bradyarrhythmia(P<0.001), and 42% higher risk of ventricular arrhythmia(P<0.001). After correction for relevant confounders, the METS-IR index was significantly and positively associated with the risk of new-onset atrial fibrillation, bradyarrhythmia, and ventricular arrhythmia (P overall<0.05, P for non-linearity>0.05). Most of the results of the subgroup analyses were not significantly different. The inclusion of METS-IR in the base model improves the predictive value of the risk of arrhythmogenesis. Conclusions: There is a significant association between METS-IR and increased risk of arrhythmias.

BackgroundOral anticoagulants (OAC) reduce the risk of ischemic stroke, but may increase the risk of major bleeding in non-valvular atrial fibrillation (NVAF) patients. Various risk scores, such as HAS-BLED, ATRIA, and ORBIT, have been proposed to assess the risk of major bleeding in NVAF patients receiving OAC. However, limited data are available on bleeding risk stratification in Japanese NVAF patients. MethodsOf the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OAC (median age, 71 years; female, 39.6%; median CHADS2 score, 2). Multivariable Cox-hazard proportional analysis was performed to explore significant risk factors for major bleeding. Using those factors, we developed a novel bleeding risk stratification scheme and compared its predictive performance with previously reported risk scores. ResultsDuring the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). On multivariable analysis, advanced age, uncontrolled hypertension, history of bleeding, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with higher incidence of major bleeding. We developed a novel risk stratification system, J-RISK bleeding score, that had good predictive performance (C-statistics 0.67) for major bleeding. The predictive performance of our score was better than previous scores. ConclusionOur findings suggest that our novel risk stratification system, the J-RISK bleeding score, is more useful than previous score systems for Japanese NVAF patients receiving OAC.

BackgroundThis study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with CHF. Methods and ResultsWe enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into Group 1 (ALI<24.60 and GNRI<94.41), Group 2 (ALI<24.60 and GNRI[&ge;]94.41), Group 3 (ALI[&ge;]24.60 and GNRI<94.41) and Group 4 (ALI[&ge;]24.60 and GNRI[&ge;]94.41), according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r= 0.348, p< 0.001) and no interaction (p=0.140) between the ALI and GNRI. Kaplan-Meier analysis showed that the cumulative incidence of all-cause mortality in patients with CHF was highest in Group 1 (log-rank {chi}2 126.244, p<0.001). Multivariate Cox proportional hazards analysis revealed that ALI and GNRI were independent predictors of all-cause mortality in CHF patients (ALI: HR 0.313, 95% CI 0.228-0.430, p <0.001; GNRI: HR 0.966, 95% CI 0.953-0.979, p <0.001). The area under the curve (AUC) for ALI combined with GNRI was 0.711 (p<0.001), according to the time-dependent ROC curve. ConclusionALI and GNRI were independent predictors of all-cause mortality in CHF patients. Patients with CHF had the highest risk of all-cause mortality when the ALI was <24.60 and the GNRI was <94.41. ALI combined with the GNRI has good predictive value for the prognosis of CHF patients.

BackgroundThis study aimed to investigate the causal relationship between coronary artery bypass grafting (CABG) and atrial fibrillation (AF) using Mendelian Randomization (MR) and a retrospective cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. MethodsWe performed two-sample MR analysis using GWAS summary statistics (UK Biobank and EBI) to identify genetic instruments for CABG, followed by sensitivity analyses (MR-Egger, weighted median) to validate causality. Concurrently, 1, 835 ICU patients from MIMIC-IV were analyzed via multivariable logistic regression to assess CABG-AF association, stratified by age, hemodynamic, and coagulation profiles. ResultsMR analysis demonstrated a robust causal effect of CABG on AF (IVW OR=1.8, P=2.33x10-), corroborated by cohort data showing doubled AF risk post-CABG (OR=2.1, 95% CI:1.4-3.1, P<0.001). Subgroups with autonomic instability (low heart/respiratory rates) or coagulopathy (INR>2.5) exhibited heightened susceptibility. ConclusionCABG independently elevates AF risk via autonomic, inflammatory, and hemostatic pathways, necessitating tailored perioperative monitoring and prophylactic interventions.

BackgroundThe triglyceride glucose (TyG) index has been proposed to be a surrogate of insulin resistance. In the study, we aimed to examine the relationship between TyG index and the risk of new onset DM and secondary outcomes included atrial fibrillation (AF), heart failure (HF), acute myocardial infarction (AMI), ventricular tachycardia/fibrillation (VTF), cardiovascular mortality (CAD) and all-cause mortality. MethodsThe retrospective observational study analyzed patients recruited from 1st January 2000 to 31st December 2003 and followed up until 31st December 2019. Demographics, past comorbidities, medications and laboratory tests were extracted. At baseline and follow-up, DM was defined as 1) any occasion Hb1Ac [&ge;]14 g/dL, 2) fasting glucose[&ge;]7 mmol/L on two occasions, or 3) with DM diagnosis. We excluded 1) patients with prior DM or with the use of antidiabetic medications; 2) patients with prior AMI/HF/AF or with the use of diuretic/beta blockers for HF were excluded. Univariate analysis and multivariate Cox analysis with adjustments on demographics, past comorbidities and medications were conducted to identify the significant risk predictors of primary and secondary outcomes. Optimal cutoffs of TyG index for the primary and secondary outcomes were found with maximally selected rank statistics approach. ResultLager TyG index is significantly associated with new onset DM (HR: 1.51, 95% CI: [1.47, 1.55], P vlaue<0.0001), new onset HF (HR: 1.27, 95% CI: [1.2, 1.34], P vlaue<0.0001), new onset AF (HR: 2.36, 95% CI: [2.26, 2.46], P vlaue<0.0001), new onset AMI (HR: 1.51, 95% CI: [1.42, 1.6], P vlaue<0.0001), new onset VTF (HR: 1.22, 95% CI: [1.13, 1.31], P vlaue<0.0001), new onset CAD (HR: 1.56, 95% CI: [1.45, 1.69], P value<0.0001) and all-cause mortality (HR: 1.21, 95% CI: [1.18, 1.25], P vlaue<0.0001). TyG index and its 3rd tertile remained significant after being adjusted with significant demographics, past comorbidities and medicactions in multivariate cox models (HR>1, P value<0.05). Optimal cut-off values of baseline TyG index and adjusted multivariate restricted cubic spline models further uncovered detailed associations of larger baseline TyG index with the primary and secondary outcome. ConclusionHigher TyG index remained significantly associated with the elevated risk of new onset DM, AF, HF, AMI, VTF, CAD and all-cause mortality after adjustments on demographics, past comorbidities, and medications.

Background and aimsThe atherogenic index of plasma (AIP) has been confirmed as a contributor of cardiovascular disease. But few evidence on the longitudinal pattern of AIP during follow-up. This study aimed to explore the associations between baseline and long-term AIP with the risk of myocardial infarction (MI). MethodsA total of 98 861 participants without MI at baseline were included from the Kailuan study. The baseline AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). The long-term AIP was calculated as the updated mean AIP and the number of visits with high AIP. The updated mean AIP was calculated as the mean of AIP from baseline to the first occurrence of MI or to the end of follow-up. The number of visits with high AIP was defined as higher than the cutoff value at the first three visits. Univariable and multivariable Cox proportional hazard models were used to determine the association between AIP and the risk of MI. ResultsDuring a median follow-up of 12.80 years, 1804 participants developed MI. The multivariable models revealed that elevated levels of baseline and updated mean AIP increased the risk of MI, compared with quartile 1 the HR in quartile 4 was 1.63 (95% CI, 1.41-1.88) and 1.59 (95% CI, 1.37-1.83), respectively. Compared to those without high AIP, the risk of individuals with three times was 1.94 (95% CI,1.55-2.45). ConclusionsElevated levels of both baseline and long-term AIP displayed a higher risk of MI.

BackgroundAccumulating evidence indicates that moderate exercise may reduce the incidence of Stanford type A aortic dissection (TAAD), but the specific mechanisms remain unclear. This study aims to identify exercise-related biomarkers in TAAD patients and to investigate their underlying mechanisms. MethodsTranscriptome data related to TAAD and exercise-related genes were obtained from publicly available databases. Candidate biomarkers for TAAD were identified through an integrative approach incorporating differential expression analysis, machine learning, and expression level assessment, leading to the construction of a diagnostic model. Subsequently, functional enrichment, immune infiltration, regulatory network analysis, and computational drug prediction were conducted to systematically investigate the pathological mechanisms and translational potential of the indentified biomarkers. ResultsABCA3 and SCN4B were identified as exercise-related biomarkers in TAAD progression. A nomogram incorporating these two biomarkers exhibited strong diagnostic performance for identifying the disease. Functional enrichment analysis revealed potential involvement of these biomarkers in disease progression through pathways including circadian rhythm regulation and ribosome biosynthesis. Additionally, immune cells like M1 macrophages and naive B cells, as well as regulatory factors including hsa-miR-1343-3p and XIST, were found to be involved in this process. Finally, zonisamide and MRS1097 were identified through computation prediction as potential therapeutic drugs. ConclusionABCA3 and SCN4B were identified as exercise-related biomarkers associatied with TAAD and represent potential valuable targets for both diagnosis and treatment strategies.

BackgroundThe role of immune cells in the pathogenesis of ischaemic heart failure (IHF) is well-established. However, identifying key diagnostic candidate genes in patients with IHF remains a challenge. Therefore, this study aimed to use bioinformatics and machine learning algorithms to identify potential diagnostic genes for IHF. MethodsTwo IHF datasets were obtained from the GEO database, and key genes for IHF were identified using Limma and WGCNA. Functional enrichment analysis was performed to explore the potential mechanisms of IHF. Next, we used three machine learning algorithms, namely LASSO, RF, and SVM-REF, to identify immune-related diagnostic genes for IHF. ssGSEA enrichment analysis was also completed. To assess the diagnostic value of the identified genes, we developed nomogram and validated them on additional GEO datasets. Finally, an immune infiltration analysis was conducted using the CIBERSORT algorithm to explore immune cell dysregulation in IHF. ResultsOur analysis yielded a total of 92 key genes associated with IHF. Enrichment analysis revealed that the mechanisms underlying IHF are mostly associated with immunity and inflammation. Using the machine learning algorithms, we identified four IHF diagnostic genes, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets. The results showed that these four genes had high diagnostic value (AUC value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely Macrophages M2, Monocytes, and T cells gamma delta. ConclusionIn summary, our study identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms. We also explored the potential molecular mechanisms of IHF and the immune cell infiltration environment of the failing myocardium. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF.

AimsThe diagnosis and assessment of coronary artery disease (CAD) in women remain challenging, as conventional diagnostic tools often show limited sensitivity and risk underdiagnosis. This study aimed to examine the associations between routinely available clinical and laboratory parameters and the severity of coronary artery lesions, quantified by the Gensini score, in female patients. In addition, we sought to develop and validate a predictive model to identify women at high risk of severe atherosclerosis. MethodsThis retrospective, cross-sectional study was conducted at the Second Hospital of Shanxi Medical University and included 91 patients with established CAD. Laboratory assessments comprised complete blood counts, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), lipid profiles, and uric acid (UA). Sleep quality was measured using the Athens Insomnia Scale (AIS). Statistical analyses included Spearman correlation, multiple linear regression, and logistic regression to evaluate the relationships between these variables and the Gensini score, and to assess their predictive value for high-risk disease. ResultsIn univariate analysis, the Gensini score was significantly correlated with inflammatory markers (IL-6: r = 0.61, P < 0.001; hs-CRP: r = 0.43, P = 0.012) and diabetes (r = 0.36, P = 0.037). Multiple linear regression identified insomnia, hypertension, diabetes, IL-6, and hs-CRP as independent predictors of the Gensini score, yielding a high goodness of fit (R{superscript 2} = 0.823, adjusted R{superscript 2} = 0.783, F = 20.19, P < 0.001). A logistic regression model for predicting high-risk disease (Gensini score >20) demonstrated excellent discrimination, with an area under the curve (AUC) of 0.964 in the training set and 0.833 in the test set. ConclusionIn women with CAD, the severity of coronary atherosclerosis is strongly associated with inflammation, metabolic dysregulation, and insomnia, with risk profiles distinct from those observed in men. A significant interaction between hs-CRP and diabetes was identified as a key modulator of CAD severity. These findings highlight the value of integrated statistical models that account for interacting risk factors, offering improved risk stratification and supporting proactive, personalized interventions in female patients with CAD.

BackgroundAtrial fibrillation and heart failure are closely related and share multiple risk factors. We aimed to apply the mendelian randomization (MR) analysis to explore the bidirectional causal link between atrial fibrillation and heart failure, and the independent effect of potential risk factors on the risk of both conditions. MethodsThis is a two-sample MR study using publicly available summary-level statistics of genome-wide association studies (GWAS). Bidirectional MR was performed to explore the relation between atrial fibrillation and heart failure. A total of 14 factors were selected as potential risk factors, univariable MR analyses were used to identify shared risk factors, and then the multivariable MR analyses were further used to investigate the independent effect of these factors on both conditions. Inverse-variance-weighted MR (IVW-MR) were used to obtain the effect estimates. ResultsMR analysis found evidence of causal relationship between atrial fibrillation and heart failure (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.19-1.29), as well as between heart failure and atrial fibrillation (OR, 3.88; 95% CI, 1.45-10.37). Univariable MR analyses identified several shared risk factors for both conditions, including body mass index (BMI), blood pressure, smoking, coronary heart disease and myocardial infarction. After adjusting for atrial fibrillation, the observed associations between shared factors and heart failure kept stable, such as BMI, smoking, coronary heart disease and myocardial infarction. However, after adjusting for heart failure, the relationships between most risk factors and atrial fibrillation attenuated to null. ConclusionsThis two-sample MR study found a bidirectional relationship between atrial fibrillation and heart failure, and identified several shared risk factors of both conditions, which had an independent effect on the risk of heart failure while probably affected the risk of atrial fibrillation via cardiac impairment. FundingStart-up Fund for high-level talents of Fujian Medical University (grant no.XRCZX2021026) and Natural Science Foundation of Fujian Province (grant no. 2022J01706).

BackgroundInvestigation of sex-specific associations between longitudinal resting heart rate (RHR) and new-onset heart failure (HF) using both change in RHR and RHR trajectories. MethodsParticipants from the Trondelag Health Study attending two or three surveys between 1995-2019 were included. We investigated the association between new-onset HF and RHR, using RHR categories according to the mean baseline RHR standard deviation (12 bpm), continuous RHR in restricted cubic splines (n=47712, mean 12-year follow-up), and latent class trajectory models (n=47162, mean 7-year follow-up). Cox regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). ResultsDuring follow-up, 2880 of the 47712 participants developed HF. The HF incidence rate was lower in women than men (4.27 vs. 5.68 per 1000 person-years, ratio (95% CI) 0.67 (0.57-0.77). Baseline RHR was 74 bpm in women and 70 bpm in men, and 74% maintained their RHR ({+/-}12 bpm) from baseline to their second attendance (mean change -2{+/-}12 bpm). Each 10-bpm higher RHR was associated with higher risk of HF for both women and men with HR (95% CI) 1.15 (1.03-1.28) and 1.09 (1.00-1.20), respectively. Participants with a high RHR trajectory had higher risk of HF compared to the low RHR-trajectories with HR (95% CI) 1.43 (1.14-1.79) for women and 1.41 (1.16-1.72) for men. ConclusionAll-cause HF was similarly associated with increased RHR and a high RHR trajectory for women and men. Estimating HF risk using RHR trajectories provided stronger associations between RHR and HF compared to using a single RHR measurement. Lay summaryWe investigated sex-specific associations between longitudinal resting heart rate (RHR) and all-cause new-onset of heart failure for 47 712 participants from the Trondelag Health Study, using RHR categories, continuous RHR in restricted cubic splines, and latent class trajectory models. O_LIEach 10-bpm increase in RHR was associated with a similar higher risk of heart failure for both women and men, with 15% higher risk for women and 9% higher for men C_LIO_LIParticipants with a high RHR trajectory had 41-43% increased risk of heart failure compared to the low RHR-trajectory C_LIO_LILong term RHR measurements can reveal changes in HF risk profiles that might not be detectable with a single RHR measurement and highlight individuals with a high RHR who should be further evaluated C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/25339723v1_figa1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@e276d9org.highwire.dtl.DTLVardef@1e8bbaeorg.highwire.dtl.DTLVardef@79de1dorg.highwire.dtl.DTLVardef@e54643_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract.C_FLOATNO Sex-specific associations between longitudinal resting heart rate (RHR) and heart failure (HF) from The Trondelag Health Study, 1995-2019. In fully adjusted analyses, women and men with an increase in RHR or a high RHR trajectory had a similar risk of developing all-cause new-onset HF. C_FIG