Background Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST-segment elevation myocardial infarction (STEMI). Treatment delay significantly affects the prognosis of STEMI patients. Objectives The aim of this study was to investigate the treatment delay and its influencing factors for STEMI in Beijing. Methods STEMI patients undergoing PPCI at 65 hospitals between 2018 and 2022 were enrolled. Treatment delays were collected and analyzed using mixed-effects models to assess the impact of admission time, arrival mode, and hospital level. Results Among 13,445 individuals, median total ischemic time (TIT), symptom onset-to-door time (S2D), and door-to-balloon time (D2B) were 188 minutes (Q1-Q3: 133-288 minutes), 116 minutes (Q1-Q3: 60-200 minutes), and 72 minutes (Q1-Q3: 58-89 minutes), respectively. Compared with off-hours admissions, S2D was longer and D2B was shorter for on-hours admissions (P < 0.001 for both). Median TIT, S2D, and D2B were longer for self-transported patients than for ambulance-transported patients (P < 0.001 for all). Median TIT and S2D were shorter and D2B was longer at nontertiary hospitals than at tertiary hospitals (P < 0.001 for all). According to linear mixed-effects models adjusting for confounders, off-hours admission was linked to 6.6% shorter S2D but 11.6% longer D2B. Ambulance transport was independently associated with 9.0% shorter S2D and 10.3% shorter D2B. Treatment at tertiary hospitals was associated with 19.0% longer S2D. Conclusions Despite advances in STEMI management, prehospital delay remains the dominant component of TIT in Beijing. Future strategies should focus on improving hospital preparedness, increasing ambulance use, and minimizing interhospital disparities to reduce treatment delay.

Background and Objectives:This study aimed to explore the correlation between free fatty acid (FFA) levels and adverse outcomes in patients undergoing percutaneous coronary intervention (PCI) with or without diabetes mellitus. Methods:In total, 10,230 patients treated with PCI were included in this study and divided into three equal groups according to FFA levels (FFA-L, FFA-M, and FFA-H groups). Subsequently, the patients were further stratified based on their diabetes status. A 5-year follow-up was conducted, with the primary endpoint defined as major adverse cardiovascular and cerebrovascular events (MACCE). Results:During follow-up, 2108 (20.6%) patients experienced MACCE. In patients without diabetes, no significant difference was observed in the risk of MACCE among the different FFA groups. However, in patients with diabetes, the risk of MACCE was significantly higher in the FFA-L and FFA-H groups than in the FFA-M group [adjusted hazard ratio (HR), 1.238, 95% confidence interval (CI), 1.054-1.454, P = 0.009; adjusted HR: 1.220, 95% CI, 1.054-1.412, P = 0.008; respectively]. The restricted cubic spline curves showed a nonlinear U-shaped relationship between the FFA levels and the risk of MACCE in patients with diabetes, with the lowest risk observed at an FFA level of 372 μmol/L. The results of the subgroup analysis stratified by different clinical presentations and BMI were similar to those of the primary findings. Conclusions:In patients with diabetes undergoing PCI, both elevated and decreased FFA levels were significantly associated with an increased risk of MACCE. Monitoring FFA levels is essential to help identify those at high risk.

Patients with acute myocardial infarction (AMI) continue to face a considerable risk of death, even in the era of contemporary reperfusion and secondary prevention. Metabolic abnormalities may partly explain this residual risk. The cholesterol, high-density lipoprotein, and glucose (CHG) index, calculated as Ln[total cholesterol (TC, mg/dL) × fasting blood glucose (FBG, mg/dL)]/[2 × high-density lipoprotein cholesterol (HDL-C, mg/dL)], is a recently proposed marker integrating lipid and glucose metabolism. We primarily aimed to examine the association between the CHG index and mortality in patients with AMI. We analyzed two prospective cohorts, including 8,782 patients with AMI from the China Acute Myocardial Infarction (CAMI) registry and 3,466 AMI patients undergoing percutaneous coronary intervention at Fuwai Hospital. Outcomes included in-hospital, 1-year, and 2-year all-cause mortality in the CAMI cohort, and all-cause mortality in the Fuwai Hospital cohort. Associations between the CHG index and mortality were assessed using Cox proportional hazards models and restricted cubic splines. Discrimination, reclassification, and decision curve analyses were performed as secondary exploratory analyses. In the CAMI cohort, higher CHG levels were associated with a graded increase in mortality risk. After multivariable adjustment, patients in the highest CHG tertile had higher risks of in-hospital mortality [hazard ratio (HR): 2.66, 95

ObjectiveTongxinluo (TXL), a traditional Chinese medicine, has demonstrated cardioprotective effects in acute myocardial infarction (AMI), yet its impact on myocardial protein profiles remains largely unexplored. This study aimed to elucidate the proteomic mechanisms underlying the therapeutic effects of TXL in AMI.MethodsAMI was induced via left anterior descending artery ligation in C57BL/6J mice. TXL was administered by oral gavage during the acute phase. Myocardial tissues and serum were subjected to 4D label-free quantitative proteomics, Western blotting, ELISA, immunofluorescence, TUNEL staining, and molecular docking analyses. Cardiac function was evaluated by echocardiography and fibrosis was quantified by Sirius red staining.ResultsProteomic analysis identified 1,061 differentially expressed proteins between TXL- and vehicle-treated AMI mice, with KEGG enrichment highlighting significant downregulation of complement and coagulation cascades. Key complement components C1qa and C1s were markedly upregulated post-AMI but significantly suppressed by TXL. Molecular docking suggested potential interactions between multiple TXL bioactive compounds and C1qa/C1s. TXL treatment reduced complement activation (serum C3a), inhibited cardiomyocyte apoptosis (Bax/Bcl-2, TUNEL), improved left ventricular ejection fraction, and attenuated fibrosis. Notably, TXL monotherapy outperformed C1 inhibitor (C1i) alone, while combining C1i with TXL conferred no additional benefit, indicating that C1 complement inhibition is an intrinsic component of TXL’s mechanism.ConclusionModulation of C1-associated complement activation may be one of the mechanisms through which TXL protects against AMI, providing novel proteomic-level insights into the cardioprotective actions of this traditional Chinese medicine.

AIMS:Although growing evidence suggests that obesity/central adiposity predisposes to the development and exacerbation of heart failure with preserved ejection fraction (HFpEF), it remains to be clarified whether there is a causal relationship between adiposity and HFpEF pathogenesis. METHODS AND RESULTS:HFpEF was induced in male C57BL/6N mice using a high-fat diet + Nω-nitro-l-arginine methyl ester. Resection or transplantation of visceral adipose tissue (VAT) blunted or exacerbated HFpEF phenotypes, respectively, in mice. VAT from HFpEF mice displayed greater weight and secreted more small extracellular vesicles (sEVs) than those from chow-fed mice. Either systemic inhibition of sEV secretion or VAT-specific knockdown of Rab27b (an indispensable GTPase for sEV secretion) protected against HFpEF. Discovery-driven experiments identified miR-295-3p within sEVs as a possible mediator of the VAT-heart axis, which impaired cardiac autophagy by binding to Ulk1 mRNA. MiR-295-3p antagomir treatment mitigated HFpEF phenotypes. Additionally, neonatal mouse cardiomyocytes (NMCMs) manifested blunted autophagic flux after treatment with plasma sEVs from HFpEF mice. Notably, HFpEF patients displayed downregulated cardiac Ulk1 and autophagy compared with healthy individuals. Restoration of cardiac autophagy with rapamycin or ULK1 overexpression via AAV-9 attenuated the HFpEF phenotype in mice. CONCLUSION:The present work unveils a mechanism whereby obesity promotes HFpEF progression, emphasizing the role of VAT-heart crosstalk. Specifically, VAT-derived sEVs, miR-295-3p, and the resultant disruption of cardiac autophagy contribute significantly to the pathogenesis of HFpEF.

PURPOSE:This study assessed whether China's workday-rescheduling policy is associated with short-term and long-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI), particularly in occupational groups more likely to be affected by rescheduling. METHODS:A prospective cohort study was conducted using data from the China Acute Myocardial Infarction registry between January 2013 and September 2014. A total of 15 854 STEMI patients were included. Since individual adherence to workday rescheduling is not directly measured in the registry, occupational category was used as a proxy to define groups more likely versus less likely to be affected by the workday-rescheduling policy. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) and 2 year all-cause mortality. Multivariable logistic and Cox regression models were used for analysis. FINDINGS:Using occupational category as a proxy for the likelihood of exposure to workday rescheduling, we stratified patients into a rescheduling-likely group (n=3141) and a rescheduling-unlikely group (n=12 713). Among patients in the rescheduling-likely occupational group, in-hospital mortality was significantly higher during abnormal workdays than conventional weekdays (7.8% vs 3.44%; adjusted OR=3.01; 95% CI 1.40 to 6.45). Two-year mortality was also higher (adjusted HR=1.99; 95% CI 1.20 to 3.30). Among 12 713 patients in the rescheduling-unlikely occupational group, no significant mortality differences were observed across temporal groups. Within the rescheduling-likely group, baseline characteristics and care quality indicators were generally comparable across the four temporal groups. CONCLUSIONS:Workday-rescheduling-induced abnormal work cycles are associated with higher in-hospital and 2 year adverse events in affected ST-segment elevation myocardial infarction patients. These findings should be interpreted as heterogeneity in the association between abnormal workdays and mortality by occupational likelihood of rescheduling exposure rather than as a direct individual-level causal effect of rescheduling.

Patients with diabetes constitute a substantial proportion of those with acute myocardial infarction (AMI) and exhibit distinct pathophysiological characteristics. However, existing guideline-recommended traditional and generic risk prediction models show limited performance in this specific population. Based on the China Acute Myocardial Infarction (CAMI) registry, 6,091 diabetic patients with AMI were enrolled and randomly divided into training and test sets (8:2). A comprehensive set of 62 multidimensional candidate features was extracted, and three feature selection strategies were applied to develop 12 machine learning models across six algorithm categories. All models underwent hyperparameter tuning via five-fold cross-validation in the training set, with the optimal combination selected according to the area under the receiver operating characteristic curve (AUROC). Two post-hoc ensemble strategies-stacking and probability averaging-were then employed to explore various combinations of top-performing models from different algorithm categories. Across six algorithm categories, the predictive models developed using 11 features selected by Elastic Net had the optimal performance. After evaluating various fusion strategies, the ensembled GLM + TabNet model was ultimately selected as the CAMI-DM model 2.0, achieving an AUROC of 0.875 in the test set. To balance the predictive performance and model simplicity, the CAMI-DM model 1.0 adopted a linear framework and was developed using five features from consensus feature selection Strategy, with an AUROC of 0.821 in the test set. Comparative analyses revealed that the CAMI-DM 2.0 outperformed CAMI-DM 1.0 in terms of discrimination, accuracy, calibration, and clinical net benefit. Furthermore, CAMI-DM 1.0, with its simplified structure, still outperformed the GRACE score in the overall predictive performance and generalizability. This study focused on the specific population of AMI patients with diabetes, and for the first time developed two dedicated models to predict in-hospital mortality risk.

Dysglycemia and hyperglycemia often coexist with coronary artery disease (CAD), but how gut microbiota and circulating metabolites differ across glycated hemoglobin (HbA1c)-defined glycemic categories and relate to cardiovascular risk remains incompletely understood. We aimed to characterize cross-sectional microbial and metabolic profiles across HbA1c-defined glycemic categories and to compare the patterns identified at the species and species-level genome bin (SGB) levels. In 600 participants from the ACS-GUT CARDIOME cohort, glycemic status was categorized as Normoglycemic, Dysglycemic, or Hyperglycemic according to HbA1c criteria. Fecal metagenomic sequencing and plasma metabolomics/lipidomics were performed. Species-level, SGB-level, polar-metabolite, and lipid features were associated with glycemic status using multivariable models adjusted for CAD status, demographic and anthropometric characteristics, lifestyle factors, and medication exposures. We used Light Gradient Boosting Machine (LightGBM) models to explore whether microbial and metabolic profiles could discriminate HbA1c-defined glycemic states. In individuals with elevated glycemia, we compared those with and without CAD to identify CAD-related multi-omics patterns. We additionally used SGB co-abundance networks, cross-comparison concordance, and matched association analyses to connect the glycemic and CAD findings. Across the HbA1c-defined categories, selected commensal taxa were less abundant in the elevated-HbA1c groups, accompanied by differences in sugars, amino-acid-related metabolites, and lipids. Species- and SGB-level analyses showed concordant alpha-diversity patterns, whereas significant community-level separation was detected only at the SGB level. Selected SGBs assigned to the same species also showed divergent glycemic associations, indicating that SGB-level profiling provided additional resolution for selected microbial associations beyond species-level summaries. SGB-level microbial models yielded higher area under the receiver operating characteristic curve (AUC) point estimates than species-level models across all three comparisons, with the largest difference observed for Hyperglycemic versus Normoglycemic classification. Combined microbial and metabolic models showed moderate discrimination for comparisons involving the Hyperglycemic group but limited discrimination between Dysglycemic and Normoglycemic participants. Among participants with elevated glycemia, CAD was associated with additional microbial and metabolic differences. An integrative analysis identified concordant microbial and metabolic candidates across glycemic and CAD comparisons and a denser SGB co-abundance network in CAD among matched participants with elevated glycemia. HbA1c-defined glycemic categories are associated with coordinated differences in gut microbial composition, SGB-level features, and circulating metabolites, with additional CAD-related multi-omics variation. These findings provide hypothesis-generating candidates for future longitudinal, mechanistic, and intervention studies of glycemic dysregulation and cardiometabolic risk.

Patients undergoing percutaneous coronary intervention (PCI) remain at substantial residual inflammatory risk, potentially driven by clonal hematopoiesis of indeterminate potential (CHIP), a novel pro-inflammatory contributor to atherogenesis. However, the clinical implications of CHIP-inflammation interplay in secondary prevention remain insufficiently understood. We aimed to investigate the joint impact of CHIP and systemic inflammation on prognosis among PCI patients. This cohort included PCI patients receiving guideline-directed lipid-lowering and dual antiplatelet therapies. CHIP mutations were identified by targeted sequencing with a mean sequencing depth of 985 × . Systemic inflammation was assessed using 12 routine inflammatory indices. Cox proportional hazards models were used to assess the impact of CHIP and inflammatory indices on 5-year all-cause mortality, the primary outcome. Major adverse cardiac and cerebrovascular events (MACCE) comprised all-cause mortality, nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and unplanned revascularization. Among 3640 PCI patients, 799 (21.95

Background The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) signaling pathway plays a critical role in mediating inflammation and cell death following myocardial ischemia, representing a promising therapeutic target. However, the systemic inhibition of cGAS/STING is limited by its protective physiological functions, highlighting the need for targeted delivery strategies. The safety and efficacy of nanoparticle-based delivery of cGAS/STING inhibitors to mitigate cardiac ischemia-reperfusion (I/R) injury remain unknown. Methods We constructed macrophage membrane-coated polydopamine nanoparticles for the preferential accumulation of the cGAS inhibitor RU.521 in the injured myocardium (RU.521-PDA@M). The PDA core was designed to respond to the ischemic myocardial microenvironment (e.g., low pH, elevated H2O2, and glutathione). Double-stranded DNA-transfected Raw264.7 macrophages and murine models of cardiac I/R were utilized. Results RU.521-PDA@M exhibited favorable physicochemical properties, biocompatibility and enhanced cardiac accumulation due to macrophage membrane coating. Both in vitro and in vivo, treatment with RU.521-PDA@M markedly suppressed the phosphorylation of key cGAS/STING pathway proteins (p-STING, p-TBK1 [TANK binding kinase 1], p-IRF3 [Interferon regulatory factor 3]) and reduced the expression of downstream inflammatory genes. In mice subjected to I/R, RU.521-PDA@M demonstrated superior efficacy over both free RU.521 and control treatments (PBS or blank nanoparticles), markedly attenuating cardiac fibrosis, improving cardiac function, and exhibiting no significant systemic toxicity, as evidenced by serum biochemistry and histopathology of major organs. Conclusions The macrophage membrane biomimetic drug-loaded nanoparticles established in this study represent a novel strategy for targeting the cGAS/STING signaling pathway following myocardial I/R. This approach offers new insights into the clinical translation of this promising mechanism.

BACKGROUND:A myocardial bridge (MB) is frequently observed after recanalization of a left anterior descending coronary artery (LAD) chronic total occlusion (CTO); however, the long-term prognostic impact of MBs in this specific setting remains controversial. OBJECTIVES:The aim of this study was to determine the impact of MBs on long-term outcomes in patients undergoing percutaneous coronary intervention of LAD CTOs. METHODS:Consecutive patients with LAD CTOs who underwent intravascular ultrasound-guided percutaneous coronary intervention from January 2019 to December 2021 were retrospectively analyzed. The primary endpoint was the 5-year rate of major adverse cardiac events (MACE), a composite of cardiac death, spontaneous myocardial infarction, and ischemia-driven revascularization. RESULTS:Among 685 patients analyzed, MBs were identified in 393 (57.4%) on intravascular ultrasound; stent extension into the bridged segment occurred in 44.3% of these cases (174 of 393). After a median 5-year follow-up, patients with MBs had a higher incidence of MACE compared with those without MBs (16.1% vs 8.9%; P = 0.006), driven primarily by more ischemia-driven revascularization in the MB group (15.1% vs 7.9%; P = 0.004). Stent extension into the MB was associated with a higher rate of MACE compared with sparing the MB (21.4% vs 11.9%; P = 0.0017). MACE rates did not differ between patients with MBs spared from stenting and those without MBs (11.9% vs 8.9%; P = 0.25). CONCLUSIONS:MBs are prevalent after LAD CTO recanalization. Although their presence is associated with adverse outcomes, the risk is driven mainly by stent extension into the bridged segment.

BACKGROUND:Chronic inflammation and insulin resistance (IR) are key drivers of cardiovascular disease (CVD); however, their joint impact on cardiovascular risk remains poorly understood. METHODS:We developed the metabolic-inflammatory index (eMII) based on estimated glucose disposal rate (eGDR) in a derivation cohort (ELSA) and evaluated its transportability in two external validation cohorts (CHARLS, HRS). Multivariate Cox regression was utilised to assess the joint impact of IR and inflammation on long-term CVD risk. RESULTS:A total of 14,168 middle-aged and older adults were included (mean age 61.68 ± 9.67 years). In fully adjusted Cox models, low eGDR, elevated hs-CRP and their combined status were all associated with increased CVD risk, with the highest risk observed in participants with both poor metabolic function and high inflammation. Exploratory mediation analysis indicated that eGDR accounted for 41.14%, 46.50% and 75.47% of the inflammation-CVD association in ELSA, CHARLS and HRS, respectively. In terms of the new index-eMII, higher eMII levels were consistently linked to elevated CVD risk across all cohorts; compared with the lowest quartile, the highest quartile showed hazard ratios of 1.66 (ELSA), 2.28 (CHARLS) and 1.83 (HRS) (all p < 0.001). Lastly, incorporating eMII into traditional risk models showed potential for improving cardiovascular risk prediction, with a more noticeable reclassification benefit observed within CHARLS. CONCLUSIONS:eMII is a cross-population predictor of CVD, highlighting metabolic impairment as a key factor through which inflammation drives cardiovascular risk. It provides a practical perspective for observing joint metabolic-inflammatory burdens in middle-aged and older adults.

While Western studies often show an inverse association between occupational status and cardiovascular mortality, its impact on acute myocardial infarction (AMI) characteristics and prognosis in Eastern middle-income countries remains unclear. Using data from the multi-center prospective China Acute Myocardial Infarction (CAMI) registry from January 2013 to January 2016, 11,318 admission AMI patients aged 18–60 years were stratified by occupation: white-collar (22.1

Background:The benefit of statin pretreatment before primary percutaneous coronary intervention (PCI) on myocardial reperfusion and prognosis in ST-segment elevation myocardial infarction (STEMI) remains unclear. In this study, we evaluated whether atorvastatin pretreatment could improve ST-segment resolution (STR) and long-term clinical outcomes in this setting. Methods:From the China Acute Myocardial Infarction Registry, we conducted propensity score matching to compare STR and 2-year major adverse cardiovascular events (MACE, all-cause death, reinfarction, and stroke) in 2426 STEMI patients undergoing primary PCI (1213 patients per group). Results:Within the pretreatment group, 75, 726, 60, and 691 patients received 20 mg, 40 mg, 60 mg or 80 mg atorvastatin respectively. In the matched cohort of 2426 patients with available STR data (1213 pretreated), STR < 50 % occurred in 258 (21 %) patients in the control group versus 159 (13 %) in the pretreatment group (adjusted hazard ratio [HR]: 0.53; 95 % CI: 0.41-0.70). Multivariable analysis showed that atorvastatin pretreatment was significantly associated with lower 2-year MACE rates (6.9 % vs 8.7 %; adjusted HR: 0.68; 95 % CI: 0.48-0.97), which were consistent across multiple subgroups. Conclusion:A single dose of atorvastatin pretreatment before primary PCI significantly improves myocardial reperfusion parameters and may be associated with long-term clinical benefits, supporting further validation in randomized trials.