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Abstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I2). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus.

Abstract Background Insulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored. Methods Patients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI). Results A total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P

Abstract Background The coexistence of cardiometabolic diseases (CMDs), defined as cardiometabolic multimorbidity (CMM), has been shown to significantly elevate mortality risk. Insulin resistance (IR) is one of the main contributing factors to the pathogenesis of CMM. Although several surrogates for IR are employed in clinical evaluations, their relationship with mortality in individuals with CMM remains unclear. This study aimed to investigate the associations between various IR surrogates and mortality in individuals with CMM, and to evaluate their prognostic value. Methods This study enrolled 1093 patients diagnosed with CMM. We developed five surrogate markers to assess IR levels: triglyceride-glucose (TyG) index, TyG-waist circumference (TyG-WC), TyG-waist height ratio (TyG-WHtR), homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic score for insulin resistance (METS-IR). To investigate the associations between different IR surrogates and both all-cause and cardiovascular mortality, multivariable Cox proportional hazards models were applied. We employed restricted cubic splines to examine non-linear associations, and Cox models were developed on either side of the inflection point for additional investigation. Meanwhile, the predictive values of five IR surrogates were further assessed. Results Of the 477 all-cause deaths that occurred during a median follow-up of 5.8 years, 197 were related to cardiovascular disease. Among five surrogate markers of IR, the TyG index was the only one that significantly correlates with both all-cause and cardiovascular mortality. The threshold value for both types of mortality was 8.85. A TyG index beneath the inflection point exhibits an inverse correlation with cardiovascular mortality (HR 0.483; 95% CI = 0.281–0.831) and all-cause mortality (HR 0.519; 95% CI = 0.368–0.732). On the other hand, when the TyG index surpassed the inflection point, it demonstrated a positive correlation with cardiovascular mortality (HR 1.413; 95% CI = 1.075–1.857) and all-cause mortality (HR 1.279; 95% CI = 1.070–1.529). Based on the analysis of receiver operating characteristics, the TyG index has been recognized as a dependable predictor of survival outcomes. Conclusions This study emphasizes the prognostic significance of IR surrogates, particularly the TyG index, in predicting mortality among individuals with CMM. The TyG index constitutes a crucial element in the development of management and intervention strategies for these patients. Graphical abstract

Abstract Background Numerous studies have shown that insulin resistance (IR) is closely related to the pathogenesis of cardiovascular disease (CVD). This study aims to summarize the correlation between the triglyceride-glucose-body mass index (TyG-BMI index), a novel surrogate indicator of insulin resistance, and the incidence of CVD in patients without CVD at baseline through meta-analysis. Method Cohort studies assessing multivariate-corrected hazard ratios (HRs) for associations between the TyG-BMI index and cardiovascular disease (CVD) were obtained by searching PubMed, Cochrane Library, EMBASE, and Web of Science. Results were combined using a random-effects model to account for heterogeneity among the included studies. Robust error meta-regression was used to fit the nonlinear dose–response relationship. Statistical analysis was performed using Review Manager 5.4 and STATA 18.0. Result Ten cohort studies involving a total of 871,728 subjects were included. The results indicated that Compared with the lowest TyG-BMI index category, the highest TyG-BMI index was related to a higher incidence of cardiovascular diseases (CVD) (HR = 1.62; 95% confidence interval (CI): 1.35–1.95; I2 = 94%),coronary artery disease (CAD) (HR = 1.69; 95% (CI): 1.23–2.31; I2 = 94%). stroke(HR = 1.57; 95% (CI): 1.11–2.23; I2 = 94%).In the dose–response analysis, there was a linear association of the TyG-BMI index with the risk of CVD (Pnonlinear = 0.223), CAD (Pnonlinear = 0.693), and stroke (Pnonlinear = 0.122)No significant effects were observed regarding participants’ gender, length of follow-up, sample size or mean age(P > 0.05). Conclusion Higher TyG-BMI may be independently associated with an increased risk of CVD in individuals without CVD at baseline. Numerous cohort studies are needed to further validate and elucidate the pathologic role between Tyg-BMI and CVD and to determine whether it can be incorporated into CVD risk prediction tools to enhance predictive accuracy.

Abstract Background Atrial fibrillation (AF) and diabetes mellitus (DM) are associated with an increased risk of ischemic stroke, particularly in geriatric populations. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits, but their effects on stroke risk may vary by age. This study aimed to explore the age-dependent effects of SGLT2i on stroke risk in patients with AF and DM. Methods This historical longitudinal follow-up cohort study included 9,669 patients with AF and DM from the National Taiwan University Hospital database (2010–2020). Patients were stratified into three age groups (

Abstract Background Atherogenic index of plasma (AIP), a novel logarithmic index that combines fasting triglyceride and high-density lipoprotein cholesterol concentrations, is associated with the burden of atherosclerosis. This study aimed to evaluate the relationship between AIP and coronary artery disease (CAD) risk, severity, and prognosis in populations with and without established CAD. Methods PubMed, Embase, and Web of Science were systematically searched from the inception of each database to August 13, 2024. Cross-sectional studies, case-control studies, and prospective or retrospective cohort studies using multivariate analysis were included. Given that the true effect size may differ across studies, a random-effects model for all analyses was applied. Results Fifty-one observational studies were included in this study. Patients with higher AIP were more likely to have CAD (odds ratio (OR): 2.79, 95% CI 1.75–4.45, P

Abstract Background Obesity, a major risk factor for cardiovascular disease (CVD), is associated with hypertension and vascular dysfunction. Perivascular adipose tissue (PVAT), a metabolically active tissue surrounding blood vessels, plays a key role in regulating vascular tone. In obesity, PVAT becomes dysregulated which may contribute to vascular dysfunction; how sex impacts the remodelling of PVAT and thus the altered vascular contractility during obesity is unclear. Objective To investigate sex-specific PVAT dysregulation in the setting of obesity as a potential driver of sex differences in vascular pathologies and CVD risk. Methods Adult male and female C57Bl/6J mice were fed an obesogenic high-fat diet (HFD) or regular chow for 16 weeks. Mesenteric PVAT (mPVAT) was isolated for RNA-sequencing and histological analysis, and mesenteric arteries were isolated for assessment of vascular function by wire myography. In a separate study, female mice were subjected to bilateral ovariectomy prior to dietary intervention to determine the contribution of ovarian hormones to PVAT dysregulation. Results Transcriptomic analysis of mPVAT revealed sexually dimorphic responses to HFD, with upregulation of extracellular matrix (ECM) remodelling pathways in male but not female mice. Histological and RT-qPCR approaches demonstrated increased collagen deposition and ECM remodelling in mPVAT from obese male compared with obese female mice. Assessment of vascular function in mesenteric arteries -/+ PVAT revealed that in obesity, mPVAT impaired endothelium-mediated vasodilation in male but not female mice. Ovariectomy of female mice prior to HFD administration did not alter ECM transcript expression or collagen deposition in mPVAT compared to sham-operated female mice. Conclusions Obesity induces sex-specific molecular remodelling in mPVAT, with male mice exhibiting unique upregulation of ECM pathways and increased collagen deposition compared to females. Moreover, the relative protection of female mice from obesity-induced mPVAT dysregulation is not mediated by ovarian hormones. These data highlight a potential sex-specific mechanistic link between mPVAT and mesenteric artery dysfunction in obesity, and provides crucial insights for future development of treatment strategies that consider the unique cardiovascular risks in men and women. Graphical abstract

Abstract Atherosclerosis, a chronic inflammatory condition characterized by plaque formation, often leads to instability, particularly under Type 2 diabetes mellitus (T2DM) conditions, which exacerbate cardiovascular risks. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the correlation between acute coronary syndrome (ACS) and serum levels of Nε-carboxyethyl-lysin (CEL), a prominent advanced glycation end product (AGE) elevated in T2DM, in a cohort of 225 patients with coronary artery disease. Using a murine model of atherosclerosis complicated by T2DM, we examined the effects of CEL on plaque stability and macrophage autophagy. Our findings revealed that elevated serum CEL levels are independently associated with increased ACS incidence. Metabolomic profiling identified CEL as a key AGE contributing to plaque instability in diabetic conditions. Mechanistically, CEL disrupted macrophage autophagy and plaque stability by perturbing the Receptor for Advanced Glycation End products (RAGE)/Liver Kinase B1 (LKB1)/AMP-activated Protein Kinase 1 (AMPK1)/Sirtuin 1 (SIRT1) signaling cascade. This pathway further regulated autophagic activity through SIRT1-mediated acetylation of Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3). These findings highlight CEL’s critical role in promoting plaque instability in T2DM by impairing key molecular pathways that regulate autophagy, offering potential therapeutic targets for managing atherosclerosis in diabetic patients.

Abstract Aim Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications and prognostic significance of CHIP and T2DM in patients diagnosed with ST-segment elevation myocardial infarction (STEMI). Methods Deep-targeted sequencing employing a unique molecular identifier (UMI) for the analysis of 42 CHIP mutations—achieving an impressive mean depth of coverage at 1000 × —was conducted on a cohort of 1430 patients diagnosed with acute myocardial infarction (473 patients with T2DM and 930 non-DM subjects). Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and T2DM was evaluated by the comparison of (i) the prevalence of CHIP mutations among individuals with diabetes versus those without, (ii) the clinical characteristics delineated by CHIP mutations within the cohort of diabetic patients and (iii) the prognostic significance and correlation of CHIP mutations with mortality rates in T2DM subjects. Furthermore, a two-sample bidirectional Mendelian randomization study was performed using genetic instruments from the genome-wide association study for TET2 mutation CH from the UK Biobank (UKB) (2041 cases,173,918 controls) to investigate the causal relationship with T2DM from the FinnGen consortium (65,085 cases and 335,112 controls), and vice versa. Results (i) Most commonly CHIP mutations exhibiting a variant allele fraction of ≥ 2.0% were identified in 50/473 (10.6%) patients with T2DM, demonstrating a greater prevalence compared to non-DM subjects [69/930 (7.4%); P

Abstract Background The Cardiovascular–kidney–metabolic (CKM) syndrome, a concept recently proposed by the American Heart Association (AHA), highlights the intricate connection between metabolic, renal, and cardiovascular illnesses. Furthermore, the Atherogenic Index of Plasma (AIP), a useful biomarker for evaluating the risk of Cardiovascular Diseases (CVDs), has been associated with the risk of Adverse Cardiovascular Events (ACEs). Nonetheless, its precise function in populations in CKM syndrome Stages 0–3 remains unknown. Methods This prospective study analyzed the data of 7,708 eligible participants (aged ≥ 45 years) from the Chinese Longitudinal Research of Ageing (CHARLS), particularly the 2011–2012 baseline survey (Wave 1). The primary exposure variable was AIP—a natural logarithm of the ratio of Triglycerides (TGs) to High-Density Lipoprotein Cholesterol (HDL-C). On the other hand, the primary endpoint was CVD incidence, which was determined based on self-reported past diagnoses. The relationship between AIP and CVD risk in the population in CKM syndrome stages 0–3 was examined using a Cox proportional risk model. Subgroup and mediation analyses were performed to further elucidate the interactions among these factors. Results This study involved 7,708 participants in the CKM syndrome stages 0–3 [Mean age = 58.00 years; Interquartile Range (IQR) = 52.00–65.00 years]. The risk of developing CVD increased significantly with higher AIP levels. Specifically, the risk ratio for each unit increase in AIP was 1.31 (95% CI 1.11–1.55), while the Hazard Ratio (HR) for the group with the highest AIP levels compared to the group with the lowest AIP levels was 1.22 (95% CI 1.08–1.39). Mediation analysis revealed that metabolic syndrome accounted for 12.3% of the association between AIP levels and CVD risk (p = 0.024), highlighting its significance in CVD risk assessment. Conclusion Herein, AIP levels correlated significantly positively with CVD risk in individuals in CKM stages 0–3, with metabolic syndrome as a key mediating factor. These findings suggest that AIP levels could be valuable not only for CVD risk assessment but also for clinical screening.

Abstract Background Diabetes mellitus (DM) and proteinuria each independently raise the risk of atrial fibrillation (AF). We aimed to investigate the relationship between proteinuria and the risk of incident AF across glycemic stages. Methods A cohort of 4,044,524 individuals without prior AF and type 1 DM was selected from the 2009 Korean National Health Insurance Service health checkup data. The individuals were categorized into five glycemic stages: normal, prediabetes, new-onset DM, early DM (

Abstract Background Insulin resistance (IR) is linked to an increased risk of frailty, yet it remains unclear whether the non-insulin-based IR indicators are associated with frailty trajectories and physical function decline. It aimed to examine the associations of triglyceride-glucose (TyG) index, metabolic score for insulin resistance (METS-IR), estimated glucose disposal rate (eGDR) and with long-term deficit-accumulation frailty trajectories and physical function decline. Methods Data from 6722 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Baseline TyG index, METS-IR, eGDR, along with the frailty index (FI) over nine years, were calculated. FI trajectories were assessed using group-based trajectory model (GBTM). Logistic regression models were used to analyze the associations between IR indicators with FI trajectory and frailty risk. Restricted cubic splines (RCS) models were utilized to detect potential dose-response associations. Linear mixed-effects model was used to evaluate associations with FI development speed. Age, gender, educational level, marital status, smoking status, drinking status, life satisfaction, social activity and sleep duration were adjusted. Additionally, a two-sample Mendelian randomization (MR) was performed to assess the causality of observed associations. Results Three FI trajectories including low-stable frailty, moderate-increasing frailty, and accelerated rising frailty were identified. Regarding the frail risk, each SD increment in TyG index was associated with a 16.1% increase in the risk of frailty (OR = 1.161; 95%CI: 1.092, 1.235). An inverse association was observed for eGDR with the OR (95%CI) being 0.741 (0.696, 0.788). A linear relationship was observed between baseline TyG index and frailty risk (P nonlinear = 0.696), but nonlinear association patterns for eGDR (P nonlinearity

Abstract Background Insulin resistance (IR) is a central pathophysiological factor in metabolic syndrome (MetS) and an essential driver of cardiovascular disease (CVD) and mortality. The estimated glucose disposal rate (eGDR) is a reliable marker of IR and has been associated with CVD prognosis. This study aims to examine the relationship between eGDR, MetS, and their predictive roles in clinical outcomes. Methods Data from the NHANES (2001–2018) were utilized, with a cross-sectional design applied to evaluate the association between eGDR and MetS prevalence, and a cohort design employed for mortality follow-up. Weighted logistic regression models were used to examine the association between eGDR and MetS. Weighted Cox proportional hazard models were applied to assess the link between eGDR and both all-cause and CVD mortality. To examine the non-linear associations between the eGDR, MetS, and mortality outcomes, restricted cubic spline (RCS) analysis was applied. Additionally, the predictive performance of eGDR, and other IR indices (TyG, HOMA-IR), for mortality was assessed using the C-statistic. Results A robust negative association between eGDR and MetS prevalence was found, following full covariate adjustment (p

Abstract Background Previous studies demonstrated that diabetes remission can occur during intensive intervention and in real-world settings. However, the impact of diabetes remission in real-world settings on the incidence of cardiovascular disease (CVD) remains unclear. Methods This retrospective cohort study included 299,967 individuals aged 20–72 years who underwent multiple checkups between 2008 and 2020 and completed ≥ 3 years of follow-up. Patients were divided into four groups according to changes in glycated hemoglobin levels and the use of diabetes medications during the 1-year baseline period: diabetes mellitus (DM)+/no remission, DM+/remission, DM−/no progression, and DM−/progression. The risk of CVD was evaluated using multivariable Cox regression analysis. Results The median follow-up period was 5.0 years. The rates of CVD in the DM+/no remission, DM+/remission, DM−/no progression, and DM−/progression groups were 7.96, 4.76, 1.99, and 5.47 per 1000 person-years, respectively. Compared with DM+/no remission, DM+/remission reduced the risk of CVD [hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.57–0.89]. Meanwhile, the HR for CVD in the DM+/remission group was 0.75 (95% CI = 0.56–0.99) for change in BMI ≤ 0%, versus 0.66 (95% CI = 0.45–0.96) for change in BMI > 0%. Conclusions In a real-world setting without intensive intervention, diabetes remission decreased the risk of CVD by approximately 30% regardless of changes in BMI, suggesting that diabetes remission can prevent CVD without weight loss in routine care and emphasizing the importance of achieving remission. Graphical Abstract

Abstract Objective The triglyceride glucose (TyG) index is a biomarker of insulin resistance and is associated with an increased risk of cardiovascular events. Contrast-induced nephropathy (CIN) is an important complication that causes poor outcomes in patients undergoing percutaneous coronary intervention (PCI). In this study, we aimed to investigate the relationship between the TyG index and CIN and mortality in patients who underwent PCI due to chronic total coronary occlusion (CTO). Methods Two hundred eighteen individuals from three separate medical centers who underwent procedural PCI between February 2010 and April 2012 and had a CTO lesion in at least one coronary artery were recruited. According to the TyG index, patients were divided into two groups. Patients with a TyG index ≥ 8.65 were included in Group 1, and patients with a TyG index

Abstract Objective The effect of sodium intake on atrial fibrillation (AF)/atrial flutter (AFL), with respect to sex and age, has yet to be elucidated. This study aims to compare long-term trends in AF/AFL death and disability due to high sodium intake in China from 1990 to 2019. Methods We utilized data from the Global Burden of Disease study to assess the mortality and disability burden of AF/AFL attributable to high sodium intake (> 5 g/d) in China from 1990 to 2019. Overtime trends and average annual percentage change (AAPC) were analyzed with adjustments for age, sex, period, and cohorts. Results In 2019, the number of AF/AFL deaths and disability-adjusted life years attributable to high sodium intake were 4209.944 (95% UI: [1250.690-8718.238]) and 235484.586 (95% UI: [89136.783-428566.694]), with males comprising 44.81% and 51.95% of cases, respectively. The age-standardized mortality rates (ASMRs) and age-standardized disability rates (ASDRs) of AF/AFL attributable to high sodium intake exhibited downward trends from 1990 to 2019 in China. The AAPC was − 0.221(95% CI: -0.321–0.121)and − 0.631(95% CI: -0.816–0.446) for AF/AFL, respectively. An upward trend was observed in ASMRs for AF and AFL, attributable to high sodium intake due to high salt intake at ages 30–34, 35–39, and 40–44. With an increase in age, the AAPC for ASMRs increased correspondingly, and the AAPC for ASDRs exhibited a decreasing trend. Conclusions Our findings provide strong evidence that high sodium levels in China significantly affect standard ASMRs and ASDRs for AF and AFL. Notably, different patterns of change are identified across various age groups, emphasizing the pronounced effect of salt reduction on AF and AFL.

Abstract Objectives This study aimed to evaluate the feasibility and accuracy of non-electrocardiogram (ECG)-triggered chest low-dose computed tomography (LDCT) with a kV-independent reconstruction algorithm in assessing coronary artery calcification (CAC) degree and cardiovascular disease risk in patients receiving maintenance hemodialysis (MHD). Methods In total, 181 patients receiving MHD who needed chest CT and coronary artery calcium score (CACS) scannings sequentially underwent non-ECG-triggered, automated tube voltage selection, high-pitch chest LDCT with a kV-independent reconstruction algorithm and ECG-triggered standard CACS scannings. Then, the image quality, radiation doses, Agatston scores (ASs), and cardiac risk classifications of the two scans were compared. Results Of the 181 patients, 89, 83, and 9 were scanned at 100, 110, and 120 kV, respectively. Excluding those scanned at 120 kV, 172 patients were enrolled. Although the ASs of non-ECG-triggered LDCT were lower than those of the standard CACS, the agreement and correlation of ASs of the two scans were excellent, and both intraclass correlation coefficients (ICCs) and Pearson’s correlation coefficients were > 0.96. Cardiac risk classifications did not significantly differ between the non-ECG-triggered LDCT and standard CACS (χ2 = 3.933, P = 0.269), and the agreement was excellent (weighted kappa value = 0.936; 95% confidence interval (CI): 0.903–0.970). The effective radiation doses of standard CACS and non-ECG-triggered chest LDCT scannings were 1.34 ± 0.74 and 1.04 ± 0.35 mSv, respectively. Conclusions The non-ECG-triggered, automated tube voltage selection, high-pitch chest LDCT protocol with a kV-independent reconstruction algorithm can obtain chest scans and ASs simultaneously and significantly reduce patients’ radiation exposure.

Abstract Objective This study aimed to evaluate the predictive performance of inflammatory and nutritional indices for adverse cardiovascular events (ACE) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) using a machine learning (ML) algorithm. Methods AMI patients who underwent PCI were recruited and randomly divided into non/ACE groups. Inflammatory and nutritional indices were graded according to the laboratory examination reports. Logistic Regression was used to screen for factors that were significant for ML model establishment. The performances of the algorithms were evaluated in terms of accuracy, kappa, F1, receiver operating characteristic, precision recall curve, etc. Results Age, LVEF%, Killip Grade, heart rate, creatinine, albumin, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were significantly correlated with ACE by Logistic regression analysis (P

Abstract Purpose Catheter ablation (CA) for atrial fibrillation (AF) in heart failure patients with preserved ejection fraction (HFPEF) has shown promising results in reducing mortality and improving heart function. However, previous studies have been limited by a lack of control groups and significant heterogeneity in their methodologies. Hypothesis CA for AF in HFPEF patients may not increase the complications and had similarly the rate of freedom from AF vs. patients without HFPEF, and it may reduce hospitalizations and mortality and improve heart function VS medical treatment. Methods Three groups of AF patients were included in the study: 187 patients with HFPEF for their first CA (AFPHF-CA), 187 patients with HFPEF who were undergoing medical therapy (AFPHF-Med), and 196 patients without HFPEF for their first CA (AF-CA). Results After a mean (± SD) follow-up of 36 ± 3 months, 50.8% of patients in the AFPHF-CA group and 52.0% in the AF-CA group remained in sinus rhythm (P = 0.94), compared to only 12.5% in the AFPHF-Med group (P

Abstract Background Covid-19 is a pandemic viral disease that directly or indirectly affects multiple organ systems, including the cardiovascular system. SPECT GATED MPI is a non-invasive nuclear imaging modality used to assess myocardial perfusion and function. The aim of this study was to evaluate the effect of Covid-19 pandemic on myocardial perfusion imaging in ischemic heart disease. Methods This was a cross-sectional (descriptive-analytical) study of 750 patients requiring myocardial perfusion imaging (MPI) who were referred to the nuclear medicine center of Kowsar Hospital, a teaching hospital in Sanandaj, the center of Kurdistan Province in north-western Iran. Data collection was performed during the Covid-19 pandemic, between 6 April 2020 and 21 March 2021. Data analysis was performed in SPSS using independent samples t-test and chi-squared. Results A total of 750 patients, including 328 (43.7%) Covid-19 positive and 422 (56.3%) Covid-19 negative, were included in the analysis. Although Covid-19 infected obese patients had a significantly higher rate of abnormal MPI (P

Abstract Background The medical community has long been concerned about the cardiovascular disease risk in patients with type 2 diabetes. While liver fibrosis scores were originally designed for application in individuals with liver steatosis, an increasing number of studies have shown that they are also associated with cardiovascular disease risk. However, the association between Fibrosis-4 (Fib-4) in liver fibrosis scores and carotid atherosclerosis (CA) in patients with type 2 diabetes remains unclear. Objective The aim of this study is to investigate the association between the Fib-4 index and CA in patients with Type 2 diabetes. Additionally, it seeks to determine whether this relationship is influenced by factors including gender, age, body mass index (BMI), hypertension, and other variables. Methods Screening based on inclusion and exclusion criteria identified 2658 hospitalized patients with type 2 diabetes. Subsequently, patients were divided into three groups according to Fib-4 values (Fib-4 0.05). The results of the ROC curve analysis indicated that the AUC for Fib-4 predicting CA was 0.602 (P

Abstract Background Evidence-based beta-blockers are essential in managing heart failure with reduced ejection fraction (HFrEF) and are known to improve cardiovascular outcomes. Despite robust nascent guideline recommendations, studies indicate that beta-blockers are often underutilized or administered below target doses. This shivery issue is particularly relevant in Ethiopia, where comprehensive evaluations of beta-blocker utilization and dosing practices are limited. The Northeast region, specifically Dessie, remains underexplored in this context. Objective This study aimed to evaluate the appropriate usage trend and dose optimization of beta-blockers among HFrEF patients attending ambulatory clinics of Dessie Comprehensive Specialized Hospital (DCSH) and Boru Meda General Hospital (BMH), Dessie, Ethiopia, 2024 G.C. Methods A cross-sectional, multi-center study was conducted from February 1 to July 30, 2024, involving 200 randomly selected adult patients with confirmed HFrEF (120 from DCSH and 80 from BMH), who had at least 6-month regular follow-up visits at their respective ambulatory clinics. The study rigorously followed the latest (2022) American Heart Association (AHA) guideline recommendation. Patient’s medical records was reviewed to gather the necessary data. A logistic regression analysis was performed to identify factors associated with beta-blocker use. Statistical significance was declared at p-value

Abstract Objective Arteriosclerosis plays a significant role as one of the key pathological mechanisms underlying Diabetic Kidney Disease (DKD). The estimated Pulse Wave Velocity (ePWV) is used to assess arteriosclerosis, and is considered a potential clinical surrogate for pulse wave velocity. There are no studies on ePWV in relation to DKD. Our research represents the first embark to explore the relationship between ePWV and DKD. Methods In this cross-sectional analysis, we collected ePWV data from a cohort of 4,296 hospitalized Chinese patients. Multivariable-adjusted logistic regression models and restricted cubic spline (RCS) analysis were employed to examine the relationship between eGDR and the prevalence of DKD, UACR ≥ 30 mg/g, and eGFR

Abstract Background The relationship between oxidative balance score (OBS) and heart failure (HF) is controversial. The OBS was used to assess systemic oxidative stress status, with higher OBS scores implying exposure to more antioxidants. This study aimed to explore whether OBS is associated with heart failure in US adults. Methods A cross-sectional investigation was carried out using information from the National Health and Nutrition Examination Survey 2007–2018. The linear link between OBS and HF in adults aged ≥ 45 years was investigated using multivariate linear regression models. Interaction tests and subgroup analysis were also conducted. Results The prevalence of HF was 3.84%. There was a significant negative relationship between OBS (OR: 0.96 ,95%CI: 0.95–0.98, P

Abstract Background ST-elevation myocardial infarction (STEMI) demands near-time reperfusion to reduce the risk of long-term heart failure. This study evaluates the proportion of impaired left ventricular ejection fraction (LVEF) following STEMI in the context of current healthcare settings at a tertiary care center equipped with the most advanced and up-to-date standards of care. Methods Patients experiencing STEMI as their first manifestation of coronary artery disease were analyzed, as these individuals had no prior experience with heart-related chest pain. LVEF was assessed by levocardiography at admission and semiautomatically using TOMTEC in patients with eligible full-cycle echocardiography of 2- and 4-chamber view available at discharge and 1-year follow-up (FU). Pain-to-balloon time was divided into quartiles (Q) [0-111, 112–159, 160–246 and 247–784 min]. Multiple logistic regression analysis identified independent predictors of reduced LVEF

Abstract Context The triglyceride-glucose (TyG) index, a novel health indicator, has been widely employed to assess insulin resistance (IR). However, its relationship with fine particulate matter (PM) exposure remains inadequately investigated. Objective This study endeavors to probe the association between PM2.5 and TyG within the population of eastern China and to determine whether there are disparities in this association among diverse subgroups. Methods We conducted an ecological study on a cohort comprising 39,011 individuals who had undergone at least two physical examinations between 2017 and 2019 at the First Affiliated Hospital of Nanjing Medical University, China. TyG levels concerning short-term PM2.5 exposure were examined using a generalized additive model. Results In the overall population, at lags of 0–7 and 0–14 days in the single-pollutant model, it was observed that a 10 µg/m3 rise in PM2.5 corresponded to a 0.0021 elevation in TyG levels. In the multi-pollutant models, at 0–7 and 0–14 days lags, a comparable increase in PM2.5 resulted in an increase in TyG of 0.0073 and 0.0044, respectively. The association remained significant in the subgroup analyses. Conclusion PM2.5 exposure is related to the TyG index. Controlling air pollution might contribute to maintainin normal lipid metabolism function.

Abstract Background As hypothermic circulatory arrest (HCA) is being more frequently induced in patients undergoing aortic arch surgery, its safety at different degrees has become a crucial area of study. The aim of this study was to assess the surgical outcomes of mild hypothermic circulatory arrest (MI-HCA) during aortic arch surgery. Methods Acute type A aortic dissection (ATAAD) patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) surgery between January 2014 and December 2023 were enrolled in this study. The patients were divided into two groups according to the minimum nasopharyngeal temperature: the moderate hypothermic circulatory arrest (MHCA) group (20–28 °C) and the MI-HCA group (> 28 °C). The inverse probability of treatment weighting (IPTW) was used to balance differences in the baseline characteristics. Perioperative variables were analysed via pairwise comparisons, multivariable logistic regression, and subgroup forest plots to assess the impact of MI-HCA on surgical outcomes. Results A total of 447 patients were included in this study, and the mean minimum nasopharyngeal temperature was 24.80 (23.98, 27.30) °C in the MHCA group and 30.10 (29.80, 30.70) °C in the MI-HCA group. The incidence of acute kidney injury (AKI) in the MI-HCA group was lower than that in the MHCA group (52% vs. 78%, p

Abstract Aims This study explores the clinical application of lung ultrasound scoring(LUS) combined with echocardiography in assessing right heart function in patients undergoing maintenance hemodialysis(MHD) and those with elevated pulmonary artery systolic pressure(PASP), as well as the correlation between LUS and right ventricular(RV) function. Methods Eighty five patients who underwent MHD combined with elevated PASP, at the First Central Hospital of Baoding City were selected. Divided into three groups based on PASP, and perform echocardiography and lung ultrasound examinations. Compare the right heart function parameters and LUS among the three groups. Using Pearson correlation analysis to examine the relationship between LUS and right heart function parameters. Perform multivariate logistic regression analysis to identify predictive factors for RV systolic dysfunction. A receiver operating characteristic (ROC) curve and calculate the area under the curve(AUC) to compare the diagnostic efficacy of various parameters. Results Patients undergoing MHD exhibited varying degrees of reduced left ventricular (LV) and RV systolic function. Correlation analysis revealed that Tricuspid annular plane systolic excursion (TAPSE), Fractional area change (FAC), and Tricuspid annular peak systolic velocity(S') were negatively correlated with LUS(r = -0.81, -0.86, -0.69), while Right ventricular free wall longitudinal strain(RVFWLS) was positively correlated with LUS (r = 0.85, P

Abstract Background Acute lung injury and acute respiratory failure are frequent complications of cardiogenic shock and are associated with increased morbidity and mortality. Even with increased use of temporary mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), acute lung injury related to cardiogenic shock continues to have a determinantal effect on patient outcomes. Objectives To summarize potential mechanisms of acute lung injury described in patients with cardiogenic shock supported by VA-ECMO and determine current knowledge gaps. Methods We searched literature from January 1st, 2010, to December 31st, 2023, using MEDLINE, EMBASE, and Web of Science databases on February 27th, 2024. The search strategy was split into two main domains: (a) cardiogenic shock and ECMO and (b) Acute respiratory failure and ECMO. Results The search yielded 2246 citations. After 743 duplicates were removed, 1465 citations remained. Of these studies, 1456 were excluded based on the exclusion criteria, leaving the final eight studies we included in our scoping review. We identified disruption of the pulmonary blood flow in patients with cardiogenic shock, with cardiac arrest being an extreme form of cardiogenic shock. Placing the patient on VA-ECMO could intensify this process of lung injury. Conclusion Acute lung injury in patients with cardiogenic shock, especially when supported by VA ECMO, is a significant complication that is associated with increased morbidity and mortality. There is a limited understanding of the underlying mechanisms that could represent opportunities for future research to mitigate its development and provide the best approach to protecting and monitoring lung function.

Abstract Background Previous studies have shown that epicardial edipose tissue(EAT) appears to be associated with myocardial inflammation and fibrosis, but this is not clear in patients with new-onset atrial arrhythmias after STEMI. The present study focused on using CMR to assess the association of epicardial fat with myocardial inflammation and fibrosis and its predictive value in patients with new-onset atrial arrhythmias after STEMI. Methods This was a single-centre, retrospective study. We consecutively selected patients who completed CMR during their hospitalisation for PCI after STEMI from May 2019-January 2023, and then underwent regular follow-up, grouped by the presence or absence of new atrial arrhythmias, and enrolled patients were divided into atrial arrhythmia and non-atrial arrhythmia groups. Results In the atrial arrhythmia group, age, heart rate, Peak hs-TnT, PeakNT-proBNP, EATV, LAES, LAED, T1 native, T1*, ECV, and T2 were higher than those in the non-atrial arrhythmia group, and LVEF was lower than those in the non-atrial arrhythmia group. EATV showed a positive and significant correlation with T1native, T1*, ECV, and T2. (T1 native: r = 0.476,p

Abstract Background Pulmonary arterial hypertension (PAH) is a severe and progressive cardiovascular disease. While potential links between clonal hematopoiesis (CH) and cardiovascular diseases have been identified, the causal relationship between CH and PAH remains unclear. This study aims to investigate the causal effect of CH on the risk of PAH using a two-sample Mendelian randomization (MR) approach. Methods We utilized genetic variants associated with CH as instrumental variables, identified from two large genome-wide association studies (GWAS) involving 359,088 participants in the discovery cohort and 184,121 participants in the validation cohort, all of European descent. We obtained GWAS summary statistics for PAH. The inverse-variance weighted (IVW) method was employed as the primary analysis, complemented by sensitivity analyses to assess the robustness of our findings. A bidirectional MR analysis was conducted to estimate the causation between CH and PAH. Results Our results indicate a causal effect of CH on the risk of PAH in the discovery cohort, with TET2 showing an IVW odds ratio (OR) of 1.200 (95% CI: 1.001–1.438, P = 0.049). Sensitivity analysis did not reveal significant pleiotropy or heterogeneity. In the validation cohort, we found that TET2 remains a risk factor for PAH (OR = 2.3E + 08, 95% CI 17.007-3.1E + 15, P = 0.022). Additionally, no causal relationship was found between other CH genes, such as DNMT3A and PAH (P > 0.05). The reverse MR analysis provided no evidence of causal effects of PAH on CH. Conclusion These findings showed that individuals with CH due to TET2 mutations may have a higher risk of developing PAH, suggesting that the CH patients may be tested for TET2 gene mutations.

Abstract Purpose Pacemaker-related infections are serious complications of cardiac implantable electronic devices (CIEDs). This case report aims to describe the occurrence of pacemaker pocket infection and recurrent ventricular tachycardia (VT) in a Chinese amateur violinist with sick sinus syndrome (SSS), and to explore the possible connection between occupational habits and the infection, as well as VT. Methods A 76-year-old male violinist with a Biotronik Evia DR dual-chamber pacemaker presented with syncope and signs of a pacemaker pocket infection three years after implantation. Despite initial antibiotic treatment, the infection persisted with slightly elevated C-reactive protein (CRP) and negative cultures. The VT originated from the right ventricular outflow tract (RVOT), as confirmed by echocardiography and ECG findings. The infection was treated with debridement and extraction of the pacemaker and leads. Results Debridement and extraction of the pacemaker and leads successfully resolved both the VT and the infection. The VT was likely linked to the infected lead, while the pacemaker infection was attributed to the patient’s violin playing, which caused mechanical stress and skin damage at the pacemaker site. Postoperative recovery was uneventful, with no recurrence of infection or arrhythmias at follow-up. Conclusion This case highlights the importance of considering a patient’s occupational habits when selecting pacemaker pocket sites to prevent infections and complications. In this case, the patient’s violin playing likely contributed to mechanical stress at the pacemaker site, leading to infection. Early identification and appropriate management, including device removal, are crucial to prevent further complications.

Abstract Background Cardiovascular disease (CVD), a non-communicable condition, stands as the primary cause of death globally. This study seeks to evaluate the predictive power of atherogenic indices, which are recognized for their influence on CVD, alongside a newly developed index encompassing all three principal risk factors for CVD, referred to as the triglyceride-total cholesterol-body weight index (TCBI). The primary outcomes evaluated include both the incidence and mortality rates associated with CVD. Methods A prospective cohort study was conducted on Mashhad stroke and heart atherosclerotic disorder (MASHAD) study data, involving 9704 healthy participants. Baseline variables were measured, and TCBI, Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC), Castelli risk index I and II (CRI-I & II) were calculated using specific formulas. Results Following a 10-year follow-up period, a significant positive relationship was observed between TCBI (HR: 1.078, 95% CI: 1.012–1.15), CRI-I (HR: 1.16, 95% CI: 1.007–1.337), and CRI-II (HR: 1.199, 95% CI: 1.001–1.437) with CVD mortality. However, no significant relationship was identified between TCBI and atherogenic indices related to CVD incidence, and neither AIP nor AC was associated with CVD mortality. Conclusion In conclusion, TCBI, in contrast to AC and AIP, was linked to increased CVD mortality. However, the more substantial predictive capabilities of CRI-I and CRI-II compared to TCBI emphasize the importance of traditional atherogenic indices for accurate risk assessment. These findings underscore the necessity of enhancing the TCBI formula to improve its effectiveness in assessing CVD risk.

Abstract Background Aerobic capacity measured by maximal oxygen uptake (VO2max) is related to functional capacity and is a strong independent predictor of all-cause and disease-specific mortality. Sex-specific cardiac and vascular responses to endurance training have been observed, however, their relative contributions to VO2max are less understood. The purpose of this study was to evaluate sex-specific ventricular-vascular interactions associated with VO2max in healthy males and females. Methods Sixty-eight males and females (38% females, 35 ± 10y) characterised as recreational exercisers to highly trained endurance athletes, and free of chronic disease underwent a cycle ergometer to assess VO2max. Resting arterial compliance and echocardiographic evaluation of left ventricular (LV) structure and function were measured and indexed to body surface area. Results VO2max was similar between groups (54 ± 6 vs. 50 ± 7 ml/kg/min, p = 0.049). Indexed LV mass (LVMi) was higher (96 ± 15 vs. 81 ± 11, p = 0.001) in males versus females, respectively. Linear regression analysis revealed two models that were significantly associated with VO2max in males and females. In males, the two models included (1) longitudinal diastolic strain rate and LVMi (r2 = 0.31, p = 0.003) and (2) indexed end-diastolic volume (EDVi) and longitudinal diastolic strain rate (r2 = 0.34, p

Abstract Background Breast cancer (BC) and cardiovascular disease (CVD) are prevalent comorbidities in aging populations. Advances in BC treatment have improved survival rates but increased the risk of CVD, particularly among younger patients with BRCA1/2 mutations. BRCA1/2 gene mutations, prevalent in younger BC patients, impair cardioprotective effects, elevating CVD risk alongside cancer treatments. This study examined the prevalence and incidence of CVD and cardiovascular risk factors (CVRFs) before and after BC diagnosis in BRCA1/2 mutation carriers (BRCA-BC) and those with sporadic BC (Sporadic-BC). Methods This descriptive retrospective cohort study analyzed BC patients from 1995 to 2020 in Stockholm-Gotland, Sweden. Data from regional and national registries provided insights into CVRFs, pre-existing CVDs, demographics, and cancer treatments. Analyses focused on single and multiple CVD events, comparing inpatient and outpatient settings across subgroups. Results The cohort included 438 BRCA-BC and 32,626 Sporadic-BC patients. BRCA-BC patients were younger at BC diagnosis (median: 45 years, IQR 37–53) and first CVD event (median: 62 years, IQR 53–68) compared to Sporadic-BC patients (median: 61 years, IQR 51–71; and 74 years, IQR 65–81, respectively). Before BC diagnosis, CVD prevalence was lower in BRCA-BC patients (4.2%) than in Sporadic-BC patients (11.1%). Post-diagnosis, CVD prevalence increased in both groups, reaching 19.7% in BRCA-BC and 24.6% in Sporadic-BC patients. Heart failure (HF) was the most common major adverse cardiovascular event (MACE), affecting 4.6% of BRCA-BC and 9.5% of Sporadic-BC patients. Sporadic-BC patients exhibited a higher overall cardiovascular burden, including arrhythmias, coronary artery disease, and stroke. Conclusions Distinct cardiovascular profiles between BRCA-BC and Sporadic-BC patients underscore the need for tailored survivorship care. Early cardiovascular screening benefits BRCA-BC patients, while Sporadic-BC patients require comprehensive management of pre-existing CVRFs. These findings align with international cardio-oncology guidelines advocating integrated cardiovascular care for BC survivors.

Abstract Curvature of large arteries in the cervical and intracranial regions represents a common morphological vascular alteration. However, the precise mechanisms underlying its formation and progression remain unclear. Increasing evidence suggests a potential correlation between arterial curvature and ischemic stroke. This manuscript involves a review of the relevant literature that delineates the measurement techniques for assessing arterial curvature, the mechanisms contributing to its formation, and recent evidence linking arterial curvature to stroke. Arterial curvature is primarily influenced by genetic factors, hypertension, sex, and age, and it may indicate weakened arterial walls. Furthermore, the haemodynamic changes associated with arterial curvature can result in reduced cerebral perfusion pressure, endothelial dysfunction, oxidative stress, and inflammatory responses. These factors contribute to the development of atherosclerosis and the formation of arterial dissections. The degree of arterial curvature may serve as a risk factor for cerebral ischemia, alongside traditional vascular risk factors. Further investigation into arterial curvature could yield valuable insights for clinicians managing patients with curved vessels.

Abstract Background Triglyceride-glucose (TyG) related indices, which serve as simple markers for insulin resistance, have been closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease (CVD), and mortality. However, the prognostic utility of TyG-related indices in predicting the risk of CVD and mortality among patients with MASLD remains unclear. Methods Data of 97,331 MASLD patients, with a median age of 58.0 years and free of CVD at baseline, were obtained from the UK Biobank. The TyG index, along with its combination with adiposity parameters (i.e. body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR]), were calculated. Cox proportional hazards models and restricted cubic spline (RCS) were performed to evaluate the associations between TyG-related indices and the risk of overall CVD, coronary heart disease (CHD), stroke, all-cause mortality, and cardiovascular mortality. Additionally, Harrell’s C-index, net reclassification index (NRI), and integrated discrimination improvement index (IDI) were used to assess the predictive performance of these indices. Results Over a median follow-up of 13.56 years, we identified 13,256 cases of overall CVD, 10,980 CHD, 2,926 stroke, 8,809 all-cause mortality, and 1,796 cardiovascular mortality. Compared with the lowest quartile of TyG-related indices, participants with MASLD in the high quartile of TyG-related indices had a significantly increased risk of incident overall CVD, CHD, stroke, and mortality. Specifically, the hazard ratios of occurring overall CVD in the fourth versus the first quartiles were 1.19 (95% confidence interval: 1.13–1.25) for TyG, 1.35 (1.28–1.42) for TyG-BMI, 1.33 (1.26–1.40) for TyG-WC, and 1.39 (1.32–1.46) for TyG-WHtR. RCS analyses indicated a nonlinear association of TyG with CVD outcomes (all P values for nonlinearity 0.05, except for TyG-WC with stroke). Furthermore, TyG-WC and TyG-WHtR demonstrated the significantly higher C-index, NRI, and IDI in predicting risk of CVD and mortality in MASLD patients. Conclusion TyG-related indices, especially TyG-WC and TyG-WHtR, had significant predictive values for the risk of incident CVD and mortality in individuals with MASLD. TyG-related indices may serve as effective surrogate predictors of CVD and mortality in MASLD patients.

Abstract Background The aim of this study was to investigate the difference between perceived and calculated diabetes risks among post-myocardial infarction (AMI) patients using the Finnish Diabetes Risk Score (FINDRISC). Methods The study population includes individuals from the Myocardial Infarction Registry in Augsburg, Germany, who had not been previously diagnosed with diabetes and who received a postal follow-up questionnaire after hospital discharge. A total of 466 participants completed the questionnaire, which collected information on age, sex, body mass index (BMI), waist circumference, physical activity, eating habits, use of antihypertensive medication, previous hyperglycemia, and family history of diabetes. These factors are components of the FINDRISC score, which estimates the likelihood of developing diabetes within the next 10 years. Furthermore, the participants were asked, how they would rate their personal risk to develop diabetes. The analysis focused on determining how many post-AMI patients correctly estimated their diabetes risk compared to the risk calculated by the FINDRISC score. Furthermore, multivariable logistic regression was used to analyze determinants associated with risk underestimation. Results Results showed that a significant proportion of the AMI population (58%) underestimated their diabetes risk. This underestimation was significantly associated with older age, higher BMI, greater waist circumference, elevated blood glucose levels, use of antihypertensive medication and a family history of diabetes. Higher education contributed to more accurate risk perception. Conclusion This study contributes to the understanding of diabetes risk perception in AMI patients and highlights the need for improving diabetes risk awareness through targeted education and healthcare communication interventions. These efforts can help patients understand their health risks, which improves health outcomes and preventive care.

Abstract Background Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points. Methods In this longitudinal study, we examined data from the Cooperative Health Research in the Region of Augsburg (KORA) F4 and FF4 studies, conducted approximately seven years apart. Leucocyte DNA methylation was assessed using the Illumina EPIC and 450K arrays. Linear mixed-effects models were employed to identify significant associations between methylation sites and diabetes status, as well as with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homoeostasis model assessment of beta cell function (HOMA-B), and homoeostasis model assessment of insulin resistance (HOMA-IR). Interaction effects between diabetes status and follow-up time were also examined. Additionally, we explored CpG sites associated with persistent prediabetes or T2D, as well as the progression from normal glucose tolerance (NGT) to prediabetes or T2D. Finally, we assessed the associations between the identified CpG sites and their corresponding gene expression levels. Results A total of 3,501 observations from 2,556 participants, with methylation measured at least once across two visits, were included in the analyses. We identified 64 sites associated with T2D including 15 novel sites as well as known associations like those with the thioredoxin-interacting protein (TXNIP) and ATP-binding cassette sub-family G member 1 (ABCG1) genes. Of these, eight CpG sites exhibited different rates of annual methylation change between the NGT and T2D groups, and seven CpG sites were linked to the progression from NGT to prediabetes or T2D, including those annotated to mannosidase alpha class 2a member 2 (MAN2A2) and carnitine palmitoyl transferase 1 A (CPT1A). Longitudinal analysis revealed significant associations between methylation and FPG at 128 sites, HbA1c at 41 sites, and HOMA-IR at 57 sites. Additionally, we identified 104 CpG-transcript pairs in whole blood, comprising 40 unique CpG sites and 96 unique gene transcripts. Conclusions Our study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development. Graphical abstract

Abstract The global increase in human life expectancy, coupled with an unprecedented rise in the prevalence of obesity, has led to a growing clinical and socioeconomic burden of heart failure with preserved ejection fraction (HFpEF). Mechanistically, the molecular and cellular hallmarks of aging are omnipresent in HFpEF and are further exacerbated by obesity and associated metabolic diseases. Conversely, weight loss strategies, particularly caloric restriction, have shown promise in improving health status in patients with HFpEF and are considered the gold standard for promoting longevity and healthspan (disease-free lifetime) in model organisms. In this review, we implicate fundamental mechanisms of aging in driving HFpEF and elucidate how caloric restriction mitigates the disease progression. Furthermore, we discuss the potential for pharmacologically mimicking the beneficial effects of caloric restriction in HFpEF using clinically approved and emerging caloric restriction mimetics. We surmise that these compounds could offer novel therapeutic avenues for HFpEF and alleviate the challenges associated with the implementation of caloric restriction and other lifestyle modifications to reduce the burden of HFpEF at a population level.

Abstract Background Chronic Limb-Threatening Ischemia (CLTI) represents the most advanced stage of Peripheral Artery Disease (PAD) and is associated with dire prognosis, characterized by a substantial risk of limb amputation and diminished life expectancy. Despite significant advancements in therapeutic interventions, the underlying mechanisms precipitating the progression of PAD to CLTI remain elusive. Methods Considering diabetes is one of the main risk factors contributing to PAD exacerbation into CLTI, we compared hind limb ischemia recovery in HFD STZ vs. non-HFD STZ mice to identify new mechanisms responsible for the exacerbation of PAD. Results We used three different mouse models of diabetes and found that blood flow recovery in HFD STZ mice is altered only from day 14 post-surgery. Consistent with this kinetics, we found that angiogenesis and myogenesis which typically occur between day five and day 14 post-surgery are not impaired in mice in which diabetes was induced by a high fat diet and streptozotocin injections (HFD STZ mice). On the contrary, we found that capillary functionality e.i. acquisition of functional intercellular junctions and immune quiescence is impaired in HFD + STZ mice. Notably, 28 days after hind limb ischemia surgery, HFD + STZ mice display significantly increased capillary permeability to IgG and significantly increased levels of ICAM1. This was associated with an increased macrophage infiltration and an impaired myocyte differentiation. Importantly, we used ICAM1-blocking antibodies to demonstrate that increased ICAM1 expression in HFD + STZ mice decreases white blood cell circulation velocity within the microcirculation, which impairs its perfusion. Notably anti-ICAM1 therapy did diminish macrophage infiltration and oxidative stress but not myopathy suggesting that myopathy characterized by small myocytes expressing higher level of MYH2 could be responsible for microangiopathy. Conclusion ICAM1 expression by the microvasculature impairs ischemic muscle reperfusion in HFD + STZ mice. Importantly, the increase in blood flow between day 14 and day 90 post-HLI surgery is not associated with an increased capillary density but with an improved functionality of capillaries.

Abstract Background The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements. Methods This study analyzed saliva DNA methylation patterns in 30 children (15 born to GDM mothers and 15 to non-GDM mothers) from the EPIDG cohort. Samples were collected at two time points: 8–10 weeks postpartum and at one year of age. Epigenome-wide analysis of over 850,000 CpG sites was conducted using the Illumina Methylation EPIC Bead Chip. Differential methylation positions (DMPs) were identified with the limma package, using a significance threshold of p

Abstract Background Insulin resistance proxy indicators are significantly associated with cardiovascular disease (CVD) and diabetes. However, the correlations between the estimated glucose disposal rate (eGDR) index and CVD and its subtypes have yet to be thoroughly researched. Methods 10,690 respondents with diabetes and prediabetes from the NHANES 1999–2016 were enrolled in the study. Three machine learning methods (SVM-RFE, XGBoost, and Boruta algorithms) were employed to select the most critical variables. Logistic regression models were established to evaluate the association between eGDR and CVD. We applied ROC curves, C-statistics, NRI, IDI, calibration curves, and DCA curves to assess model performance. Subgroup analyses were conducted to investigate the association among different subgroups. Results Participants in the higher quartile showed a decreased prevalence of CVD. Multivariate logistic regression models and RCS curves demonstrated that eGDR had an independently negative linear correlation with the likelihood of CVD[Q4 vs. Q1: OR 0.24(0.18,0.32)], CAD[OR 0.81(0.78,0.85)], CHF[OR 0.81(0.76,0.86)], and stroke[0.85(0.80,0.90)]. Model evaluation showed better performance in fully adjusted models than basic models[C-statistics(Model 3 vs. Model 1): CVD(0.683 vs. 0.814), CAD(0.672 vs. 0.807), CHF(0.714 vs. 0.839) and stroke(0.660 vs. 0.790)]. The AUCs of eGDR were significantly higher than the values of other IR surrogates in the unadjusted models, and slightly higher in the fully adjusted models. Subgroup analyses indicated that the results were robust. Conclusion A lower eGDR was significantly associated with a heightened likelihood of CVD and its subtypes in diabetic and prediabetic populations. And eGDR exhibited better performance in evaluating the associations compared to other IR proxies encompassing TyG, HOMA-IR, QCUIKI, METS-IR, etc.

Abstract Globally, cardiovascular diseases remain among the leading causes of mortality, highlighting the urgent need for innovative research models. Consequently, the development of accurate models that simulate cardiac function holds significant scientific and clinical value for both disease research and therapeutic interventions. Cardiac organoids, which are three-dimensional structures derived from the induced differentiation of stem cells, are particularly promising. These organoids not only replicate the autonomous beating and essential electrophysiological properties of the heart but are also widely employed in studies related to cardiac diseases, drug efficacy testing, and regenerative medicine. This review comprehensively surveys the various fabrication techniques used to create cardiac organoids and their diverse applications in modeling a range of cardiac diseases. We emphasize the role of advanced technologies in enhancing the maturation and functionality of cardiac cells, ensuring that these models closely resemble native cardiac tissue. Furthermore, we discuss monitoring techniques and evaluation parameters critical for assessing the performance of cardiac organoids, considering the complex interactions within multi-organ systems. This approach is vital for enhancing precision and efficiency in drug development, allowing for more effective therapeutic strategies. Ultimately, this review aims to provide a thorough and innovative perspective on both fundamental research and clinical treatment of cardiovascular diseases, offering insights that could pave the way for future advancements in understanding and addressing these prevalent health challenges. Graphical abstract

Abstract Background The triglyceride-glucose (TyG) index is now widely recognized as a marker of insulin resistance and has been linked to the development and prognosis of atherosclerotic cardiovascular diseases (ASCVD) in numerous populations, particularly in the Eastern world. Although there are fewer reports from the Western world, and they are sometimes contradictory, the absence of definitive data on the relationship between a raised TyG index and cardiovascular risk suggested the opportunity of testing this biochemical marker against a well-established vascular marker such as the carotid intima media thickness (c-IMT). Methods Primary prevention patients were selected from a cohort of individuals who underwent c-IMT measurement between 1984 and 2018 at the Dyslipidemia Center at the ASST Grande Ospedale Metropolitano Niguarda in Milan, Italy. The TyG index was calculated as the Ln [fasting TG (mg/dL)×fasting glucose (mg/dL)/2]. Carotid ultrasonography was performed using echographic measurements of the far walls of the left and right common, internal carotids, and bifurcations. Patients were followed for up to 20 years with periodic evaluation of biochemical parameters. ASCVD events were monitored through hospital records, where all patients were regularly examined. Results The analysis included 3108 individuals with a mean age of 54.9 ± 13.1 years. Participants were generally non-obese, with an average BMI of 24.6 ± 3.5 Kg/m2. Among the women, 83.1% were postmenopausal. The mean TyG index was 8.65 ± 0.59. There was a significant association between the TyG index and all c-IMT measurements. Those in the highest TyG index quartiles had significantly higher IMTmean and IMTmax compared to those in the lower quartiles. These associations were consistent across all vascular sites examined and remained significant after adjusting for all potential confounders. Kaplan-Meier survival analysis revealed an increased incidence of ASCVD events in the two highest TyG index quartiles. Conclusions TyG index is a sensitive marker of risk in a European population with moderate ASCVD risk, as assessed by c-IMT measurements, in a large cohort of Lipid Clinic patients.

Abstract Background As an emerging concept, Cardiovascular-kidney-metabolic syndrome (CKM) elucidates the intricate interconnection between metabolic disorders(Mets), cardiovascular disease(CVD), and chronic kidney disease(CKD). Within this context, while numerous studies have demonstrated a correlation between the Atherogenic Index of Plasma (AIP) and CVD, the precise relationship between long-term fluctuations in the AIP and the incidence of CVD in patients with CKM syndrome remains unclear. Method The CKM stages 0–3 population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The outcome CVD was defined as self-reported heart disease and/or stroke. AIP control level was classified using k-mean cluster analysis. Logistic regression was used to analyse the effect of cumulative AIP (cumAIP) on the incidence of CVD. Restricted cubic spline models (RCS) were used to explore the potential non-linear relationship between cumulative AIP and CVD risk at different CKM syndrome stages. Results Of the 3429 CKM stages 0–3 participants, 620 patients developed CVD during the 3-year follow-up period. After adjusting for various confounders, the odds ratio (OR) for the well-controlled class 2 compared with the best AIP control class 1 were 1.37 (1.04, 1.81), the OR for the moderately-controlled class 3 were 1.54 (95% CI, 1.04–2.26), the poorly-controlled class 4 were 1.65 (95% CI, 1.13–2.41), and the worst-controlled class 5 were 2.14 (95% CI, 1.15–3.97). In restricted cubic spline regression analyses, changes in AIP were linearly associated with the occurrence of CVD events. Further weighted quartiles and regression analyses indicated that triglyceride(TG) was a key variable for AIP in predicting CVD events in the CKM stages 0–3 population. Conclusions Poor control level of AIP are associated with an increased risk of CVD events in the population of CKM stages 0–3. Long-term dynamic monitoring of changes in AIP may help in the early identification of patients at high risk of developing CVD in the individuals with CKM stages 0–3.

Abstract Background Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations. Objective To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination. Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial was a Phase 3 randomised trial of an aldose reductase inhibitor in patients with well-controlled type 2 diabetes mellitus (T2DM). The 1858 potential participants (age 67 ± 7 years; 50% women) were screened for SBHF based on abnormal echocardiography or biomarkers (N-terminal pro-B-type natriuretic peptide ≥ 40 ng/L or high sensitivity cardiac troponin T ≥ 10 ng/L [women] and ≥ 16 ng/L [men]). Exercise capacity (peak VO2) was reduced in 669 with DbMD (age 68 ± 7, 50% women), and peak VO2 was reassessed at 15 months. Results The 1463 (79%) participants with DbMD were allocated to four clusters; 907 (49%) showed isolated elevation of cardiac biomarkers, 301 (16%) with systolic dysfunction/hypertrophy, 162 (9%) with diastolic dysfunction and 93 (5%) comprised an overlap cluster (combined diastolic, systolic or LV geometric abnormalities). Reduced VO2 (

Background Ischemia with nonobstructive coronary arteries (INOCA) has high morbidity, mortality, and poor quality of life. Metabolic syndrome (MetS) is a complex of multiple cardiac metabolic risk factors, significantly increasing the risk of major adverse cardiovascular events in INOCA patients. The study aimed to investigate the aggravating effect of MetS on left ventricular (LV) deformation and function impairment in INOCA patients. Materials and methods This study collected 104 INOCA patients (INOCA [MetS−]: n = 56; INOCA [MetS+]: n = 48) and 41 sex- and age-matched controls. LV function, indexed myocardial energetic efficiency (MEEI), and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured among the three groups. The independent factors of reduced MEEI and impaired LV function and strain parameters for all INOCA patients were assessed using multivariable linear regression analyses. Results In contrast to the INOCA (MetS-) group, the indexed LV stroke volume (LVSVI) (49.57 ± 11.58 mL/m2 vs. 42.58 ± 12.23 mL/m2, p = 0.007), MEEI [0.85(0.70–1.03) ml/s/g vs. 0.75(0.54–0.91) ml/s/g, p = 0.045] and LV global longitudinal peak strain (GLPS) (− 13.26 ± 2.86% vs. -10.95 ± 3.93%, p = 0.001) reduced in the INOCA (MetS+) group. Compared with the controls, LV GLPS decreased in the INOCA (MetS-) group (− 15.14 ± 2.83% vs. −13.26 ± 2.86%, p = 0.017). MetS was negatively associated with LVSVI, MEEI, and LV GLPS (all p

Abstract Background Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients. Methods Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model’s predictive performance was evaluated using Harrell’s C-index. Results Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011). Conclusions Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine. Graphical abstract