BackgroundTo investigate the association between body mass index (BMI) and both in-hospital and 10-year all-cause mortality in critically ill non−ST−segment elevation myocardial infarction (NSTEMI) patients, and to evaluate the incremental value of C-reactive protein (CRP) in risk stratification.MethodsThis multinational study included 7,815 critically ill NSTEMI patients from three cohorts. We first analyzed an original discovery cohort (TAMI, n = 5,010) from a Chinese tertiary hospital, then externally validated the findings in two independent US cohorts (MIMIC-IV, n = 1,208; eICU-CRD, n = 1,597). BMI was categorized according to WHO criteria, and CRP was dichotomized at 2 mg/L. Multivariable Cox regression and restricted cubic splines were used to assess mortality risks.ResultsIn the TAMI cohort, severe obesity (BMI ≥ 35 kg/m2) was independently associated with increased risks of in-hospital (HR 1.69; 95% CI: 1.08-2.65; p = 0.022) and 10-year (HR 1.68; 95% CI: 1.31-2.15; p < 0.001) all-cause mortality. Overweight and obesity I were associated with lower mortality risk compared with normal weight. The absolute in-hospital mortality rate was 8.36% in the severe obesity group, compared with 1.55% in the overweight group. The coexistence of severe obesity and elevated CRP (≥ 2 mg/L) identified a high-risk clinical profile, with no significant interaction between these two factors for either outcome (p for interaction = 0.178 for in-hospital and 0.169 for 10-year all-cause mortality). Adding CRP to the base model (Model 3) significantly improved risk prediction, with an increase in AUC from 0.764 to 0.768 (p = 0.021) and significant improvements in reclassification and discrimination metrics (all p < 0.05). The pooled meta-analysis results across the three databases were consistent.ConclusionsBMI exhibits a U-shaped association with mortality in critically ill NSTEMI patients. Severe obesity combined with elevated inflammation identifies a high-risk clinical profile, supporting integrated metabolic-inflammatory risk stratification.

5-Methoxytryptophan (5-MTP) is an endogenous tryptophan metabolite with anti-inflammatory and anti-fibrotic properties. Its clinical significance in acute myocardial infarction (AMI) and underlying mechanisms remain largely unknown. In a prospective cohort, 407 AMI patients undergoing successful percutaneous coronary intervention (PCI) were enrolled. Plasma 5-MTP was measured by ELISA. SYNTAX score was used to assess coronary artery disease complexity. In-hospital heart failure (HF) and 1-year major adverse cardiovascular events (MACE) were recorded. Associations were assessed using logistic/Cox regression, restricted cubic splines (RCS) and propensity score matching (PSM). In parallel, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) and treated with 5-MTP (10 μM); cell viability, apoptosis and NF-κB pathway activation were evaluated. Primary rat cardiac fibroblasts were stimulated with TGF-β1 with or without 5-MTP; migration, α-SMA, collagen I and MMP-9 were measured. Plasma 5-MTP was inversely correlated with SYNTAX score (r = − 0.431, P < 0.001). Higher 5-MTP was independently associated with lower SYNTAX score (medium vs. low: OR 0.40, 95% CI 0.24–0.66, P < 0.001; high vs. low: OR 0.14, 95% CI 0.08–0.23, P < 0.001). Higher 5-MTP levels predicted reduced in-hospital HF (OR 0.20, 95% CI 0.08–0.52, P < 0.001) and 1-year MACE (HR 0.39, 95% CI 0.19–0.79, P = 0.009). RCS analyses confirmed a linear dose–response pattern across all outcomes (all P for nonlinear > 0.05). In vitro, 5-MTP attenuated H/R-induced cardiomyocyte apoptosis, suppressed IκBα phosphorylation, p65 nuclear translocation and reduced IL-1β, IL-6, TNF-α, MCP-1 and COX-2 expression. In fibroblasts, 5-MTP inhibited TGF-β1-induced migration, α-SMA/collagen I expression and MMP-9 secretion. Low plasma 5-MTP is independently associated with severe coronary artery disease, in-hospital HF and worse 1-year outcomes after AMI. Its cardioprotective effects may be mediated, at least in part, through inhibition of NF-κB-driven inflammation in cardiomyocytes and suppression of TGF-β1-induced fibroblast activation. These findings suggest that 5-MTP may serve as a prognostic biomarker and a potential therapeutic target in AMI, pending further validation.

To analyze the risk factors for type 4b acute myocardial infarction (AMI) caused by very late stent thrombosis (VLST) and develop a predictive model using machine learning techniques. Patients who had a history of coronary stent implantation and developed AMI more than 1 year later, and had undergone coronary angiography were included. Based on the presence of VLST on coronary angiography, patients were classified into the VLST-4b-AMI group and the de novo AMI group. Data including the first coronary stent implantation, drug treatment, baseline hospitalization data, and coronary angiographic findings were collected and compared between the two groups. Logistic regression and Lasso machine learning were used to identify risk factors for VLST-4b-AMI, and a predictive model was developed using machine learning techniques, followed by performance evaluation. Univariate logistic regression analysis identified risk factors and protective factors for VLST-4b-AMI. Lasso regression selected 12 variables closely associated with VLST-4b-AMI occurrence. Based on these risk factors, predictive models were developed using eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), random forest (RF), and k-nearest neighbors (KNN). The XGBoost model demonstrated the best predictive performance (AUC = 0.724, 95

Background Complete revascularization (CR) has been shown to reduce the risk of adverse cardiovascular events compared with culprit-only revascularization (COR) in acute ST-segment elevation myocardial infarction (STEMI) patients with multi-vessel disease (MVD). However, the optimal timing of staged complete revascularization (SCR) after primary percutaneous coronary intervention (PCI) remains unclear. Trial design The STAGED trial is an investigator-initiated, multicenter, randomized study involving 37 sites, aiming to include 1,586 acute STEMI patients with MVD undergoing successful primary PCI of the culprit lesion followed by SCR. Eligible patients will be assigned to two groups based on the timing of SCR: early-staged PCI and delayed-staged PCI. The primary endpoint is major adverse cardiac event (MACE), including cardiovascular death, myocardial infarction, or ischemia-driven revascularization for both culprit and non-culprit vessels at 12 months since the randomization. The secondary endpoint is individual components of primary endpoint, all-cause death, heart failure-related rehospitalization, stroke, contrast-induced nephropathy, and radiation exposure dose . Follow-up will be conducted through clinic visits or telephone interviews at 1, 3, and 12 months after the index procedure. Conclusion The STAGED trial is the first randomized controlled study specifically designed to evaluate the clinical efficacy and safety of different timing strategies for SCR in acute STEMI patients with MVD. Trial registration clinicaltrials.gov, NCT04918030.

BackgroundWhile proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the incidence of major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI), the anti-inflammatory effects and impact on early cardiac remodeling of PCSK9i remain unclear. This study investigated the effects of PCSK9i on early inflammatory factors [interleukin (IL)- 1β, IL-18, IL-17A, and C-C chemokine receptor 2 (CCR2)] and left ventricular (LV) function in STEMI patients.MethodsTotally 257 STEMI participants were divided into 2 groups based on their real-world prescriptions: those treated with statin only (statin group) and those treated with statin in addition to the evolocumab (evolocumab group). All patients were observed for 12 weeks.ResultsAt 4 weeks, the evolocumab group exhibited a greater reduction in IL-1β compared to statin alone (−29.35% vs −25.27%, P = 0.012). Similarly, IL-17A decreased more significantly with evolocumab than with statin therapy (−30.22% vs −25.35%, P = 0.023). By 12 weeks, evolocumab significantly improved left ventricular ejection fraction (LVEF) especially in the patients with LVEF<50% at baseline (11.36% vs 7.40%, P = 0.014) and increased the incidence of LV global function improvement (ΔEF≥ 5%: 78.2% vs 55.1%, P < 0.001) compared to statin alone. Multivariate analysis identified the use of evolocumab, reductions in IL-1β and IL-17A at 4 weeks as independent predictors of ΔEF≥ 5% at 12 weeks. Mediation analysis showed that 8.74% and 9.60% of LV functional improvement were attributable to reductions in IL-1β and IL-17A respectively.ConclusionOur findings support evolocumab’s role beyond lipid-lowering, suggesting that early PCSK9i as a potential strategy to mitigate early inflammation-driven cardiac dysfunction in STEMI management.

BACKGROUND & AIMS:Malnutrition is associated with poor outcomes in various diseases. This study aimed to evaluate the independent prognostic value of the Geriatric Nutritional Risk Index (GNRI) for long-term all-cause mortality in older patients with non-ST-segment elevation myocardial infarction (NSTEMI), and to further explore its joint effects with obesity, inflammation, hypercoagulability, and cardiac dysfunction, as well as potential underlying pathways. METHODS:This single-center cohort study consecutively enrolled 1686 patients aged ≥60 years hospitalized with NSTEMI at Tianjin Chest Hospital between March 2016 and December 2020. According to admission GNRI, patients were categorized into nutritional risk (GNRI ≤98) and no nutritional risk (GNRI >98) groups. The endpoint was all-cause mortality. Restricted cubic spline analyses and Cox proportional hazards models were used to assess the dose-response relationship and independent association between GNRI and mortality. Joint and mediation analyses were further performed to evaluate combined prognostic effects and explore potential mediating pathways. RESULTS:During a median follow-up of 5.36 years (interquartile range, 4.17-6.57 years), 249 (14.8%) deaths occurred. GNRI showed a near-linear inverse association with mortality in both the overall NSTEMI cohort and the diabetes mellitus and metabolic syndrome subgroups. Each 1-SD decrease in GNRI was associated with a 24% higher mortality risk (HR 1.24, 95% CI 1.10-1.41; P < 0.001). Compared with GNRI >98, GNRI ≤98 was independently associated with increased all-cause mortality after full adjustment (HR 1.45, 95% CI 1.11-1.88; P = 0.006). Joint analyses revealed that all-cause mortality risk further increased when GNRI ≤98 coexisted with BMI ≥28 kg/m2, hs-CRP >5 mg/L, D-dimer >0.5 mg/L, or NT-proBNP ≥945 pg/mL, with the highest risk observed in patients with concomitant elevation of NT-proBNP (HR 2.23, 95% CI 1.47-3.39; P < 0.001). Furthermore, hs-CRP and NT-proBNP mediated 8.6% and 12.4% of the association between GNRI and mortality, respectively. CONCLUSIONS:Poor nutritional status independently increases the risk of long-term all-cause mortality in older patients with NSTEMI. Low GNRI combined with obesity, high inflammation, hypercoagulability, and cardiac dysfunction further exacerbates this risk, highlighting their combined value in identifying individuals at extremely high risk of mortality.

BackgroundLipoprotein(a) [Lp(a)] is a causal driver of atherosclerosis, yet the interaction between Lp(a)-driven lipid accumulation and a prothrombotic state induced by hyperhomocysteinemia has not been systematically investigated in this high-risk population. From a clinical nutrition perspective, homocysteine (HCY) is a critical modifiable metabolite influenced by B vitamins and folate, making this interaction particularly relevant for dietary or supplementation strategies. This study aims to systematically evaluate the independent and combined prognostic significance of Lp(a) and homocysteine (HCY) in premature myocardial infarction (PMI).MethodsThis prospective cohort study enrolled 1741 PMI patients (aged ≤55 years) at Tianjin Chest Hospital (January 2018–June 2023). Restricted cubic spline (RCS) was used to explore nonlinearity between Lp(a)/HCY and major adverse cardiovascular events (MACE). HCY was analyzed both as a continuous variable and, for exploratory stratification, dichotomized at the clinically referenced threshold of 15 μmol/L. The cutoff for Lp(a) was pre-specified as 50 mg/dL based on clinical guidelines and further validated by maximally selected rank statistics (MSRS). Survival analyses assessed the effects of these factors on MACE. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) quantified incremental model value.ResultsDuring a median follow-up of 19.6 months, 224 (12.87%) patients experienced MACE. RCS revealed a nonlinear association between Lp(a) and MACE (p = 0.003), whereas HCY showed no significant nonlinear trend. High Lp(a; HR = 2.266, 95% CI: 1.685–3.046, p < 0.001) and high HCY (HR = 1.597, 95% CI: 1.204–2.117, p = 0.001) are independent MACE risk factors. Compared with the low Lp(a) + low HCY group, the high Lp(a) + high HCY group had a 3.566-fold greater MACE risk (95% CI, 2.427–5.239, p < 0.001). Additive interaction analysis revealed a statistically significant interaction: RERI = 1.630 (95% CI, 0.314–2.945, p = 0.015), AP = 0.456 (95% CI, 0.197–0.716, p < 0.001), SI = 1.840 (95% CI, 0.960–2.719, p = 0.061).ConclusionThis study systematically characterizes the combined prognostic role of Lp(a) and HCY in PMI patients, validating a pragmatic “50–15” dual-threshold strategy for MACE risk stratification. The findings support a precision nutrition approach, suggesting that patients with dual elevation may benefit from targeted B-vitamin or folate supplementation as a low-cost adjunctive strategy.

Background: Danshen-Gegen is a classic herb pair in traditional Chinese medicine, which has been used to treat cardiovascular and cerebrovascular diseases. Ischemic stroke (IS) is a prevalent cerebrovascular condition; ferroptosis is one of the contributing factors driving the progression of IS. This study aims to determine the underlying mechanism and examine if Danshen-Gegen (DG) extract may prevent cerebral ischemia-reperfusion injury by preventing ferroptosis. Methods: The comprehensive compositional characterization of DG was analyzed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-orbitrap MS). The experiments were conducted in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen-glucose deprivation/re-oxygenation (OGD/R) cells. The neuroprotective effects of DG on IS were assessed by examining rat survival rates, infarct volume, behavioral scores, and cerebral water content. Then, we tested the accumulation of Fe2+ and lipid peroxidation products such as reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and 4-hydroxynonenal (4-HNE) in rats and cells. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), Solute Carrier Family 7 Member 11 (-xCT), Glutathione peroxidase 4 (GPX4), Cyclooxygenase-2 (COX-2), Transferrin Receptor 1 (TFR1), and Long-chain-fatty-acid-CoA ligase 4 (ACSL4) was also assessed in vivo and in vitro. Results: UPLC-Q-orbitrap MS analysis was performed to characterize the chemical profile of DG, and a total of 33 chemical constituents were successfully identified. DG significantly alleviated the ischemic damage to brain tissue, reduced infarct volume, and improved neurological dysfunction. The content of Fe2+ and lipid peroxidation products was markedly decreased. Furthermore, DG could restore the expression of Nrf2, -xCT, and GPX4 with the inhibition of COX-2, TFR1, and ACSL4, thus achieving a suppressive effect on ferroptosis. Conclusions: The regulatory influence of DG via the Nrf2/System xc-/GPX4 axis may play a crucial role in alleviating ferroptosis and enhancing recovery from cerebral ischemia injury.

Background:Real-world selection of lipid-lowering therapies (LLT) is often affected by patient prognosis, leading to residual bias in comparing treatment effects. We used negative control outcomes (NCOs) to assess the comparability in a traditional active comparator design (evolocumab vs other LLT initiators) and in a study design between patients treated and non-treated after evolocumab initiation. Methods:Using Tianjin Regional Healthcare Database, an electronic health records (EHR) database in China, we identified patients who initiated evolocumab and patients who initiated other LLT from 2018 to 2023. Within the evolocumab cohort, we further defined patients who filled the second prescription of evolocumab as "treated" and patients who did not as "non-treated" after evolocumab initiation. We evaluated residual confounding by calculating hazard ratios (HR) to compare the one-year risk of NCOs in the domains of frailty and health-seeking behavior in the two designs after applying inverse probability of treatment weighting (IPTW). Results:14,978 evolocumab initiators (5708 patients treated and 9270 patients non-treated), and 658,255 other LLT initiators were identified. Compared to other LLT initiators, evolocumab initiators showed a lower risk of fracture in domain of frailty (HR 0.75, 95% CI 0.56-1.00), and a higher risk of visual test in domain of health-seeking behavior (HR 2.41, 95% CI 1.31-4.47). Between patients treated and non-treated after evolocumab initiation, no association was identified in domain of frailty: fracture (HR 1.02, 95% CI 0.81-1.54) and incident cancers excluding nonmelanoma skin cancers (HR 1.01, 95% CI 0.81-1.28), whereas event numbers were insufficient for evaluating NCOs in the health-seeking behavior domain. Conclusion:Comparing evolocumab to other LLTs may result in biased estimates, while the treated and non-treated evolocumab initiators are more comparable in the measured confounding and the NCO domain of frailty. This study provides important insights for consideration when designing a comparative study in China.

Background:Insulin resistance (IR) alternative markers, including the triglyceride-glucose index (TyG), TyG combined with body mass index (TyG-BMI), and the triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), have been shown to be significantly associated with prognosis of acute myocardial infarction (AMI). However, the prognostic value of these markers in patients with premature myocardial infarction (PMI) remains unclear. This study aims to investigate the association between IR markers and major adverse cardiovascular events (MACEs) in PMI patients. Methods:This was a prospective cohort study that consecutively enrolled 1,688 PMI patients (male ≤ 50 years, female ≤ 55 years) from Tianjin Chest Hospital between February 2015 and December 2024. TyG, TyG-BMI and TG/HDL-C indices were calculated. The median follow-up time was 17.4 months (IQR: 11.4-31.9), with the endpoint being MACEs. IR indices were grouped by quartiles. The risk association between IR indices and MACEs was analyzed using Cox proportional hazards models and restricted cubic spline analysis. The predictive performance of IR indices was assessed using Harrell's C-index, net reclassification improvement (NRI), integrated discrimination improvement (IDI). Results:Among 1,688 patients, 211 (12.5%) occurred MACEs. Restricted cubic spline analysis showed a positive nonlinear relationship between TyG-BMI and MACEs risk, while TyG and TG/HDL-C were linearly associated with MACEs risk. In the fully adjusted Cox proportional hazards model, the hazard ratios of occurring MACEs in the fourth quartile versus the first quartile were 2.88 [95% confidence interval (CI): 1.83-4.53] for TyG-BMI, 1.77 (95% CI: 1.11-2.82) for TyG, 1.44 (95% CI: 0.93-2.22) for TG/HDL-C. In the fourth quartile versus the first quartile of TyG-BMI, the hazard ratios of occurring MACEs were 3.85 (95% CI: 1.79-8.27) in patients with diabetes and 3.38 (95% CI: 1.78-6.43) in patients with high high-sensitivity C-reactive protein (hsCRP). Additionally, TyG-BMI demonstrated higher C-index, NRI and IDI for predicting MACEs risk in PMI patients. Conclusion:In patients with PMI, TyG-BMI is an independent predictor of MACEs demonstrating significantly superior predictive performance compared to TyG and TG/HDL-C. The association between elevated TyG-BMI and MACEs risk was significant in patients with diabetes and high hsCRP levels. The effect was particularly stronger in patients with diabetes.

BackgroundPremature myocardial infarction (PMI) is increasingly recognized as a metabolic disease, driven by a cluster of dysregulations including insulin resistance and central obesity. While homocysteine (Hcy)—an intermediate of one-carbon metabolism—is implicated in these atherothrombotic processes, its synergistic effect with coexisting cardiometabolic risk factors for the long-term prognosis of PMI patients remains unclear.MethodsWe conducted a prospective cohort study of 1,220 consecutive PMI patients who underwent percutaneous coronary intervention (PCI) (men ≤45 years, women ≤55 years) at Tianjin Chest Hospital from January 2017 to December 2024. Plasma Hcy was measured at baseline and classified as high (≥15 µmol/L) or normal (<15 µmol/L). The primary endpoint was major adverse cardiovascular events (MACE), including cardiac death, rehospitalization for severe heart failure, non-fatal myocardial infarction, ischemic stroke, readmission for unstable angina, and target lesion revascularization. Multivariable Cox models and joint effect analyses were used to assess independent and synergistic associations.ResultsOver a median follow-up of 582 days, 136 patients (11.1%) experienced MACE. After multivariable adjustment, high Hcy remained independently associated with MACE (aHR=2.72; 95% CI 1.87-3.95, P<0.001). This risk was higher when cardiometabolic factors coexisted, increasing from a 3.1-to 4.1-fold higher risk when combined with high D-Dimer, high-normal blood pressure, Lp(a), or hs-CRP (aHRs 3.13-4.12), to a 6.5-fold higher risk with coexisting obesity (aHR=6.54; 95% CI 3.01-14.20, P<0.001) compared to patients with normal Hcy and normal BMI. In the exploratory three-way analyses, the combination of high Hcy, obesity, and elevated D-Dimer (D-Dimer>0.5mg/L) conferred a nearly 10-fold higher risk (aHR=9.91; 95% CI 3.68–26.66, P<0.001), while the triad of high Hcy, obesity, and high hs-CRP (hs-CRP >2 mg/L) was associated with a 17.5-fold higher risk (aHR=17.51; 95% CI 2.28-134.52, P=0.006).ConclusionElevated plasma Hcy is an independent predictor of MACE in PMI patients and may be used to identify subgroups at particularly high risk. This effect is more pronounced in individuals who are obese or have other adverse metabolic characteristics.

Background:The CLIMA study [Relationship between Optical Coherence Tomography (OCT) Coronary Plaque Morphology and Clinical Outcome; NCT02883088] introduced the concept of high-risk plaque (HRP) and demonstrated that HRP was associated with a high risk of major coronary events. HRP is defined by four simultaneous characteristics: minimum lumen area (MLA) <3.5 mm2, fibrous cap thickness (FCT) <75 μm, lipid arc circumferential extension >180°, and macrophage infiltration. Early prediction of HRP formation is critical for preventing and treating acute coronary syndrome (ACS), but no studies have been conducted on this topic. Purpose:To identify the risk factors associated with OCT HRP in ACS and develop a risk prediction model for HRPs in ACS. Methods:A prospective observational study was conducted on patients with ACS between September 2019 and August 2022. A total of 169 patients were divided into two groups: OCT HRP (n = 55) and OCT non-HRP (n = 114) groups. Clinical data, laboratory results, and OCT characteristics of the patients were collected. Least absolute shrinkage and selection operator (LASSO) regression was used to screen variables, while multivariate logistic regression was used to create a risk prediction model. A nomogram was created, and the receiver operating characteristic curve was used to assess the model's discrimination, as well as the bootstrap method to internally validate it. Results:The most commonly observed HRP characteristic was lipid plague >180° (147 patients), followed by MLA < 3.5 mm2 (141 patients), macrophages (127 patients), and FCT < 75 μm (64 patients). The LASSO regression model was used to screen variables and develop an HRP risk factor model. The nomogram includes five predictors: age, BMI ≥ 25 kg/m2, triglycerides, low-density lipoprotein cholesterol, and Log N-terminal brain natriuretic peptide precursor. The model is highly differentiated (area under the curve 0.780, 95% confidence interval 0.705-855) and calibrated. The calibration curve and decision curve analysis demonstrated the model's clinical usefulness. Conclusion:A simple and practical nomogram for predicting HRPs accurately in patients with ACS was developed and validated, and is expected to help clinicians diagnose and prevent plaque stability.

Background: The dose-response relationship and independent prognostic value of free fatty acids (FFA) for major adverse cardiovascular events (MACE) in patients with premature myocardial infarction are not well established. This study aimed to evaluate the impact of FFA levels on long-term outcomes and their combined effects with inflammatory markers, obesity, and insulin resistance. Methods: This prospective cohort study enrolled 1168 consecutive patients with premature myocardial infarction admitted to the coronary care unit ward of Tianjin Chest Hospital from March 2017 to December 2024. Participants were categorized into 4 groups (Q1-Q4) by baseline FFA quartiles. Over a median follow-up of 2.83 years (interquartile range, 2.58-3.10), the primary end point was MACE. Cox proportional hazards models and restricted cubic splines were used to assess associations and nonlinear relationships between FFA levels and MACE risk. Results: FFA levels showed a U-shaped association with long-term prognosis in patients with premature myocardial infarction. Using Q2 (0.43-0.61 mmol/L) as reference, adjusted hazards for MACE were significantly higher in Q1 (hazard ratio [HR], 1.89 [95% CI, 1.11-2.96], P=0.009), Q3 (HR, 2.47 [95% CI, 1.55-3.93], P<0.001), and Q4 (HR, 2.94 [95% CI, 1.86-4.65], P<0.001). Joint analyses indicated synergistic risks increased when abnormal FFA coexisted with hs-CRP (high-sensitivity C-reactive protein) >5 mg/L, body mass index >28 kg/m2, or triglyceride-glucose index >9.21 mmol/L. Conclusions: Both elevated and decreased FFA levels independently increase MACE risk in patients with premature myocardial infarction. Abnormal FFA levels combined with high inflammation, obesity, and insulin resistance significantly increase the risk of MACE, highlighting their combined value in the long-term poor prognosis.

Background:Heart Failure with Preserved Ejection Fraction (HFpEF) in patients with Premature Myocardial Infarction (PMI) is a crucial factor affecting long-term prognosis. This study aims to develop a model based on a machine learning algorithm that can predict the risk of in-hospital HFpEF in patients with PMI early and quickly. Methods:This prospective study consecutively included PMI patients from January 2017 to December 2022. Lasso-Logistic, XGBoost, Random Forest, K-Nearest Neighbor, and Support Vector Machine models were constructed. The prediction performance of the models was compared through AUC, Accuracy, Precision, F1 score, and Brier score. Shapley Additive exPlanations is used to explain the model. A prediction system was developed to identify high-risk patients. Results:The study finally included 840 PMI patients. 268 (31.90%) developed in-hospital HFpEF. The XGBoost model has the best prediction performance (AUC 0.854; Accuracy 0.798; Precision 0.686; F1 score 0.586; Brier score 0.143). The final model included ten variables, which were Brain natriuretic peptide (BNP) > 100pg/ml, SYNTAX Score > 14.5, Age, Monocyte to Lymphocyte Ratio (MLR) > 0.3, Hematocrit (HCT) < 45%, Heart rate (HR) > 75 bpm, Body Mass Index (BMI) ≥ 24 kg/m2, C-reactive Protein to Lymphocyte Ratio (CLR) > 2.83, Hypertension and Fibrinogen (Fg) > 4 g/L. Conclusions:The explainable prediction model established based on the XGBoost algorithm can accurately predict the risk of in-hospital HFpEF in PMI patients and is available at https://hfpefpmi.shinyapps.io/apppredict/. This system is expected to assist clinicians in decision-making by providing timely, prioritized, and precise interventions for PMI patients, ultimately reducing the incidence of HFpEF and improving long-term prognosis.

INTRODUCTION:Cardiovascular disease (CVD) is more likely to occur in old people with mildly reduced kidney function. We aimed to identify target features in this cohort to reduce cardiovascular death using deep learning models. METHODS:A total of 12,650 older people (age ≥60) with mildly reduced kidney function from Tianjin Community Health Promotion Prospective Study were recruited from 2014 to 2020. Cardiovascular death was verified by the death certificates from the provincial vital statistics offices. Mildly reduced kidney function was defined when estimated glomerular filtration rate (eGFR) between 45 mL/min/1.73 m2 ≤ and 90 mL/min/1.73 m2. Data were analyzed using Cox regression, random survival forest (RSF), DeepHit (DH), and Dynamic DH (DDH). Concordance Index (C-index) and Brier Score (B-S) were used to compare the models' performances. RESULTS:During the follow-up of 7 years, 838 people died of CVD (6.62%). Age, gender, hypertension, diabetes, and eGFR were closely related to cardiovascular death. Both accuracy and precision of models, predictive performance gets better as the number of follow-up visits increases. In predicting cardiovascular death, the C-index and B-S value of COX were only 0.711 and 0.001 at the first follow-up, and values were 0.767 and 0.073 at last time, respectively. This trend is similar in the other three models, with the DDH model standing, which showed the individual survival prediction with more accuracy at different time points (for the 6-year survival prediction, the C-index = 0.797 and B-S = 0.022 for the average of all time points) than the Cox, RSF, and DH. CONCLUSION:A novel deep learning algorithm used in our study has shown its superior performance in the prediction of individual dynamics in longitudinal studies, which improves predictive power with increasing data input over time.

Myocardial ischemia/reperfusion (I/R) injury is a significant complication following acute myocardial infarction (AMI) and lacks effective therapies. The involvement of gut microbiota in regulating ferroptosis during myocardial I/R injury has not been thoroughly explored. This study aimed to investigate the effect of Lactobacillus on myocardial I/R injury and explore its potential mechanisms. One hundred fifty eight patients with ST-elevation myocardial infarction (STEMI) were enrolled in our prospective observational study. The correlations between Lactobacillus levels and myocardial injury markers, inflammatory factors, oxidative stress, and ferroptosis were evaluated. Furthermore, 30 rats were treated with Lactobacillus or vehicle control for 4 weeks, followed by myocardial I/R surgery. The protective effects of Lactobacillus against I/R injury were assessed by quantifying myocardial apoptosis, inflammation, oxidative stress, and ferroptosis. In addition, the above results were verified in vitro. The signaling pathways were investigated through the knockdown and overexpression of sirtuin 1 (Sirt1) and nuclear factor erythroid 2-related factor 2 (Nrf2). In clinical study, Lactobacillus levels were significantly negatively correlated with myocardial injury markers, inflammatory factors, and malondialdehyde (MDA), but positively correlated with glutathione (GSH). In rats, Lactobacillus decreased the levels of myocardial injury markers, reduced the size of the myocardial infarction area, ameliorated the disordered myocardial cell arrangement, and improved cardiac function. In both in vivo and in vitro studies, Lactobacillus inhibited cardiomyocyte apoptosis by upregulated B-cell lymphoma-2 (Bcl-2), downregulated Bcl-2 associated X (Bax), and caspase-3. Furthermore, Lactobacillus decreased inflammatory factors, MDA, reactive oxygen species (ROS) levels, and increased superoxide dismutase (SOD) activity. For ferroptosis, Lactobacillus upregulated the expression of glutathione peroxidase 4 (GPX4) and downregulated the expressions of acyl-CoA synthetase long-chain family member 4 (ACSL4) and transferrin receptor protein 1 (TfR1). Finally, knockdown and overexpression of Sirt1 and Nrf2 in vitro demonstrated that Lactobacillus exerted the effect by upregulating the Sirt1/Nrf2/HO-1 pathway. Our findings reveals that Lactobacillus protects against myocardial I/R injury by inhibiting apoptosis, inflammation, oxidative stress, and ferroptosis through the Sirt1/Nrf2/HO-1 signaling axis, suggesting a novel probiotic-based therapeutic potential for I/R injury.

To compare different interventional strategies for patients with 4b-AMI because of very late stent thrombosis (VLST) in real world. 316 patients with VLST-4bAMI were enrolled and divided into Re-stent group, drug coated balloon (DCB) group and plain old balloon angioplasty(POBA) group. The MACE was observed at 1 year follow up including cardiac death, recurrent AMI(re-AMI), target lesion revascularization (TLR) and recurrent ST(RST). The Kaplan-Meier survival curves were used to compare the survival of free-MACE events, and the propensity score matching was used for further analysis. 66 MACEs were observed at 1 year follow-up. There was no significant difference in the MACE between the three groups (P > 0.05), but TLR in the POBA group was the highest (P = 0.023). Kaplan-Meier survival analysis showed that there was no significant difference in the survival of 1-year cumulative free-MACE events between the three groups (P > 0.05), the survival of free-TLR in the POBA group was the lowest (P = 0.015). There was no significant difference in the incidence of MACE after propensity score matching. There is no significant difference in prognosis between the three interventional treatment strategies of VLST-4bAMI. DCB did not have less favorable clinical outcomes than Re-stent or POBA.The treatment of VLST-4bAMI is still a major clinical challenge.

Objectives: Real-world evidence that supports decision-making must meet numerous criteria, including validated identification of clinical outcomes. This study aimed to develop and validate a method for identifying new cases of myocardial infarction (MI) and ischemic stroke (IS) within real-world clinical data in China. Methods: Algorithms to identify MI and IS events were developed using ICD-10-CM codes and Chinese diagnosis keywords within the Tianjin Regional Healthcare Database. Validation followed predefined criteria: MI required cardiac troponin elevation and ischemic symptoms or cardiac troponin elevation and electrocardiogram changes; IS required clinical symptoms and neuroimaging confirmation of cerebral Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) reports. Positive predictive value (PPV) with 95% confidence intervals (CI) was calculated for each outcome. Results: Among 304 MI and 302 IS cases randomly selected, approximately half were identified using ICD-10-CM codes and half through Chinese diagnosis keywords. Overall PPV for MI was 69% (95% CI: 63–74%), with similar PPVs across identification methods. PPV increased to 88% for inpatient MI and 97% for primary inpatient MI. For IS, overall PPV was 65% (95% CI: 58–71%), with higher PPV for cases identified by ICD-10-CM codes (76%) compared to keyword-only cases (56%). PPV increased to 76% for inpatient IS and 91% for primary inpatient IS. Conclusions: The use of ICD-10-CM codes and Chinese diagnosis keywords in primary inpatient diagnoses provides a validated approach for the identification of clinical outcomes of MI and IS within real-world clinical data in China.

Anti-oxidant/Pro-oxidant oxidant imbalance leads to chronic inflammation and insulin resistance can lead to the development of metabolic syndrome (MetS). The oxidative balance score (OBS) is a tool for assessing oxidative stress associated with MetS risk. However, the association between OBS and mortality in patients with MetS remains unclear. This study analyzed 10,647 MetS patients from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). OBS were calculated using a combination of 16 dietary and 4 lifestyle factors. Multivariate Cox proportional hazards regression models, Kaplan-Meier survival analysis, restricted cubic splines (RCS), and subgroup analyses were used to evaluate the potential association between OBS and the risk of all-cause and cardiovascular mortality. Sensitivity analyses confirmed the robustness of the results. This study found that OBS was inversely associated with all-cause and cardiovascular mortality in patients with MetS, a result consistent across most subgroups. Both the Kaplan-Meier curve and RCS analysis supported these findings. Sensitivity analysis was used to verify the robustness of the results. Maintaining an antioxidant-based diet and lifestyle may help reduce the risk of all-cause and cardiovascular mortality in patients with MetS. These findings underscore the significance of incorporating antioxidant-rich dietary patterns and behavioral practices in strategies aimed at preventing and managing MetS.

Clinical trials have shown that adding evolocumab to statin therapy reduces low-density lipoprotein cholesterol (LDL-C) levels by approximately 60