Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Construction of a Near-Infrared Fluorescent Probe for Dynamic Monitoring and Early Diagnosis of Heart Failure.

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.

Canada acute coronary syndrome risk score predicts no-/slow-reflow in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background: The no-/slow-reflow phenomenon following primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI)is associated with poor prognosis. The early identification of high-risk patients with no-/slow-reflow is critical. This study aimed to evaluate the predictive ability of the Canada Acute Coronary Syndrome (C-ACS) risk score for no-/slow-reflow in these patients. Methods: Patients with STEMI who underwent primary PCI were consecutively enrolled and divided into three groups based on their C-ACS scores: 0, 1, and ≥2. The C-ACS score was computed using the four clinical variables evaluated at admission (one point for each): age ≥75 years, heart rate >100 beats/min, systolic blood pressure <100 mmHg, and Killip class >1. No-/slow-reflow was defined as thrombolysis in a myocardial infarction flow grade of 0-2 after primary PCI. The predictive ability of the C-ACS score for no-/slow-reflow was evaluated using a receiver operating characteristic curve. Results: A total of 834 patients were enrolled, of whom 109 (13.1 %) developed no-/slow-reflow. The incidence of no-/slow-reflow increased from the C-ACS 0 group to the C-ACS ≥2 group (6.1 % vs 17.7 % vs 34.3 %, respectively, p < 0.001). After multivariable adjustment, the C-ACS score was an independent predictor of no-/slow-reflow (odd ratio 2.623, 95 % confidence interval 1.948-3.532, p < 0.001). Furthermore, the C-ACS score showed good discrimination for no-/slow-reflow (area under the curve 0.707, 95 % confidence interval 0.653-0.762, p < 0.001). Further subgroup analyses indicated a significant interaction between the C-ACS score and patient sex (p for interaction = 0.011). The independent association between the C-ACS score and no-/slow-reflow was only observed in male patients (odd ratio 3.061, 95 % confidence interval 1.931-4.852, p < 0.001). During a median follow-up duration of 4.3 years, the C-ACS score was independently associated with major adverse cardiovascular events independent of the occurrence of no-/slow-reflow (p for interaction = 0.212). Conclusion: The C-ACS risk score could independently predict the no-/slow-reflow in patients with STEMI undergoing primary PCI, particularly in male patients.

Design and rationale of the ATTRACTIVE trial: a randomised trial of intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion in ST-segment elevation myocardial infarction patients with high thrombus burden.

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) with high thrombus burden is associated with a poor prognosis. Manual aspiration thrombectomy reduces coronary vessel distal embolisation, improves microvascular perfusion and reduces cardiovascular deaths, but it promotes more strokes and transient ischaemic attacks in the subgroup with high thrombus burden. Intrathrombus thrombolysis (ie, the local delivery of thrombolytics into the coronary thrombus) is a recently proposed treatment approach that theoretically reduces thrombus volume and the risk of microvascular dysfunction. However, the safety and efficacy of intrathrombus thrombolysis lack sufficient clinical evidence. METHODS AND ANALYSIS: The intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion trial is a multicentre, prospective, open-label, randomised controlled trial with the blinded assessment of outcomes. A total of 2500 STEMI patients with high thrombus burden who undergo primary percutaneous coronary intervention will be randomised 1:1 to intrathrombus thrombolysis with a pierced balloon or upfront routine manual aspiration thrombectomy. The primary outcome will be the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, heart failure readmission, stent thrombosis and target-vessel revascularisation up to 180 days. ETHICS AND DISSEMINATION: The trial was approved by Ethics Committees of China-Japan Friendship Hospital (2022-KY-013) and all other participating study centres. The results of this trial will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05554588.

Triglyceride-glucose index is associated with recurrent revascularization in patients with type 2 diabetes mellitus after percutaneous coronary intervention.

BACKGROUND: The Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). METHOD: A total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike's information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples. RESULTS: During a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458-1.7959), P = 0.002]. The likelihood ratio test and Akaike's information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724-0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023-0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009-0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method. CONCLUSION: The findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.

Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study.

BACKGROUND: Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score. METHODS: This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality. RESULTS: After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48-2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64-2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90-3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes. CONCLUSIONS: In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.

The triglyceride-glucose index predicts 1-year major adverse cardiovascular events in end-stage renal disease patients with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index has been suggested as a dependable indicator for predicting major adverse cardiovascular events (MACE) in individuals with cardiovascular conditions. Nevertheless, there is insufficient data on the predictive significance of the TyG index in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). METHODS: This study, conducted at multiple centers in China, included 959 patients diagnosed with dialysis and CAD from January 2015 to June 2021. Based on the TyG index, the participants were categorized into three distinct groups. The study's primary endpoint was the combination of MACE occurring within one year of follow-up, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. We assessed the association between the TyG index and MACE using Cox proportional hazard models and restricted cubic spline analysis. The TyG index value was evaluated for prediction incrementally using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The three groups showed notable variations in the risk of MACE (16.3% in tertile 1, 23.5% in tertile 2, and 27.2% in tertile 3; log-rank P = 0.003). Following complete adjustment, patients with the highest TyG index exhibited a notably elevated risk of MACE in comparison to those in the lowest tertile (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.14-2.35, P = 0.007). Likewise, each unit increase in the TyG index correlated with a 1.37-fold higher risk of MACE (HR 1.37, 95% CI 1.13-1.66, P = 0.001). Restricted cubic spline analysis revealed a connection between the TyG index and MACE (P for nonlinearity > 0.05). Furthermore, incorporating the TyG index to the Global Registry of Acute Coronary Events risk score or baseline risk model with fully adjusted factors considerably enhanced the forecast of MACE, as demonstrated by the C-statistic, continuous NRI, and IDI. CONCLUSIONS: The TyG index might serve as a valuable and dependable indicator of MACE risk in individuals with dialysis and CAD, indicating its potential significance in enhancing risk categorization in clinical settings.

Association of triglyceride-glucose index with coronary severity and mortality in patients on dialysis with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is validated as a reliable biomarker of insulin resistance and an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients on dialysis with coronary artery disease (CAD) remained unexplored. This study aimed to determine the association between the TyG index and CAD severity and mortality in these patients. METHODS: A total of 1061 dialysis patients with CAD were enrolled in this multi-center cohort study from January 2015 to June 2021. The extent and severity of CAD were evaluated using the multivessel disease and Gensini score (GS). Patients were followed up for all-cause death and cardiovascular death. RESULTS: The multivariable logistic regression model indicated that the TyG index was significantly associated with multivessel disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.18-1.94, P = 0.001), and high GS (OR 1.33, 95% CI 1.10-1.61, P = 0.003). After adjusting for baseline risk factors, the hazards of all-cause death and cardiovascular death were 1.23 (95% CI 1.06-1.43, P = 0.007), and 1.33 (95% CI 1.11-1.59, P = 0.002), independent of CAD severity. Restricted cubic spline analysis identified a dose-response association between the TyG index and both CAD severity and mortality (all P for nonlinearity > 0.05). When modeling the TyG index as a categorical variable, these independent associations remained. Subgroup analyses did not substantially modify the results. Furthermore, incorporating the TyG index into the existing risk prediction model improved the predictive accuracy for all-cause death and cardiovascular death, as evaluated by C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In patients on dialysis with CAD, the TyG index was significantly associated with more severe CAD as well as mortality. These results highlight the clinical importance of the TyG index for assessing CAD severity and risk stratification in patients on dialysis with CAD.

Dynamic Assessments of Coronary Flow Reserve after Myocardial Ischemia Reperfusion in Mice.

After cardiac ischemia, there is often insufficient myocardial perfusion, even if flow has been successfully and completely restored in an upstream artery. This phenomenon, known as the "no-reflow phenomenon," is attributed to coronary microvascular dysfunction and has been associated with poor clinical outcomes. In clinical practice, a reduction in coronary flow reserve (CFR) is frequently used as an indicator of coronary artery disease. CFR is defined as the ratio of the peak flow velocity induced by pharmacologic or metabolic factors to the resting flow velocity. This protocol focused on assessing the dynamic changes in CFR before and after ischemia-reperfusion (IR) using pulse wave Doppler measurements. In this study, normal mice exhibited the ability to increase the peak velocity of coronary blood flow up to two times higher than the resting values under isoflurane stimulation. However, after ischemia-reperfusion, the CFR at 1 h significantly decreased compared to the pre-operation baseline. Over time, the CFR showed gradual recovery, but it remained below the normal level. Despite the preservation of systolic function, early detection of microvascular dysfunction is crucial, and establishing a practical guide could aid doctors in this task, while also facilitating the study of cardiovascular disease progression over time.

Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study.

Purpose: The pandemic of coronavirus disease 2019 (COVID-19) has highlighted the intricate relationship between underlying conditions and death. We designed this study to determine whether metformin therapy for type 2 diabetes mellitus (T2D) is associated with low in-hospital mortality in patients hospitalized for COVID-19. Materials and Methods: This was a retrospective study including patients with COVID-19 and T2D in Wuhan, from February 4th to April 11th, 2020. Patients were divided into two groups according to metformin exposure. The hazard ratio (HR) of COVID-19-related mortality and invasive mechanical ventilation was estimated using Cox regression. Results: There were 571 T2D patients among the 4330 confirmed COVID-19 patients. Of those patients, 241 received metformin therapy. The in-hospital mortality and invasive mechanical ventilation of metformin group was lower than non-metformin group. In the multivariate model, metformin use was linked to a decreased in-hospital mortality and invasive mechanical ventilation when compared with that of the control group (HR: 0.376 [95% CI 0.154-0.922]; P = 0.033). Conclusion: Our study indicated that metformin therapy was associated with decreased death risk in COVID-19 patients with T2D.

Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials.

Purpose: Approximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). Results: Seven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = -2.40, 95% confidence interval (CI): -3.38 to -1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001]. Conclusions: Ticagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes.

Association between the triglyceride glucose index and in-hospital and 1-year mortality in patients with chronic kidney disease and coronary artery disease in the intensive care unit.

OBJECTIVE: This study aimed to explore the association between the triglyceride glucose index (TyG) and the risk of in-hospital and one-year mortality in patients with chronic kidney disease (CKD) and cardiovascular disease (CAD) admitted to the intensive care unit (ICU). METHODS: The data for the study were taken from the Medical Information Mart for Intensive Care-IV database which contained over 50,000 ICU admissions from 2008 to 2019. The Boruta algorithm was used for feature selection. The study used univariable and multivariable logistic regression analysis, Cox regression analysis, and 3-knotted multivariate restricted cubic spline regression to evaluate the association between the TyG index and mortality risk. RESULTS: After applying inclusion and exclusion criteria, 639 CKD patients with CAD were included in the study with a median TyG index of 9.1 [8.6,9.5]. The TyG index was nonlinearly associated with in-hospital and one-year mortality risk in populations within the specified range. CONCLUSION: This study shows that TyG is a predictor of one-year mortality and in-hospital mortality in ICU patients with CAD and CKD and inform the development of new interventions to improve outcomes. In the high-risk group, TyG might be a valuable tool for risk categorization and management. Further research is required to confirm these results and identify the mechanisms behind the link between TyG and mortality in CAD and CKD patients.

Thermal Decomposition Assisted Construction of Nano-Li3 N Sites Interface Layer Enabling Homogeneous Li Deposition.

Lithium (Li) metal is a highly desirable anode for all-solid-state lithium-ion batteries (ASSLBs) due to its high theoretical capacity and being well matched with solid-state electrolytes. However, the practical applications of Li metal anode are hindered by the uneven Li metal plating/stripping behavior and poor contact between electrolyte and Li anode. Herein, a convenient and efficient strategy to construct the Li3 N-based interlayer between solid poly(ethylene oxide) (PEO) electrolyte and Li anode is proposed by in situ thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) additive. The evolved Li3 N nanoparticles are capable of combining LiF, cyano derivatives and PEO electrolyte to form a buffer layer of about 0.9 µm during the cell cycle, which can buffer Li+ concentration and homogenize Li deposition. The Li||Li symmetric cells with Li3 N-based interlayer show excellent cycle stability at 0.2 mA cm-2 , which is at least 4 times longer cycle life than that of PEO electrolytes without Li3 N layer. This work provides a convenient strategy for designing interface engineering between solid-state polymer electrolyte and Li anode.

The prediction of in-hospital mortality in chronic kidney disease patients with coronary artery disease using machine learning models.

OBJECTIVE: Chronic kidney disease (CKD) patients with coronary artery disease (CAD) in the intensive care unit (ICU) have higher in-hospital mortality and poorer prognosis than patients with either single condition. The objective of this study is to develop a novel model that can predict the in-hospital mortality of that kind of patient in the ICU using machine learning methods. METHODS: Data of CKD patients with CAD were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Boruta algorithm was conducted for the feature selection process. Eight machine learning algorithms, such as logistic regression (LR), random forest (RF), Decision Tree, K-nearest neighbors (KNN), Gradient Boosting Decision Tree Machine (GBDT), Support Vector Machine (SVM), Neural Network (NN), and Extreme Gradient Boosting (XGBoost), were conducted to construct the predictive model for in-hospital mortality and performance was evaluated by average precision (AP) and area under the receiver operating characteristic curve (AUC). Shapley Additive Explanations (SHAP) algorithm was applied to explain the model visually. Moreover, data from the Telehealth Intensive Care Unit Collaborative Research Database (eICU-CRD) were acquired as an external validation set. RESULTS: 3590 and 1657 CKD patients with CAD were acquired from MIMIC-IV and eICU-CRD databases, respectively. A total of 78 variables were selected for the machine learning model development process. Comparatively, GBDT had the highest predictive performance according to the results of AUC (0.946) and AP (0.778). The SHAP method reveals the top 20 factors based on the importance ranking. In addition, GBDT had good predictive value and a certain degree of clinical value in the external validation according to the AUC (0.865), AP (0.672), decision curve analysis, and calibration curve. CONCLUSION: Machine learning algorithms, especially GBDT, can be reliable tools for accurately predicting the in-hospital mortality risk for CKD patients with CAD in the ICU. This contributed to providing optimal resource allocation and reducing in-hospital mortality by tailoring precise management and implementation of early interventions.

Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia.

BACKGROUND: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents. METHODS: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant. Arterial ligation or wire injury was used to induce neointima in mice, whereas ApoE-/- and LDLR-/- (LDLR [low-density lipoprotein receptor]) mice fed a high-fat diet were applied to assess atherosclerosis. In addition, coronary stent implantation was performed on vaccine-immunized Bama miniature pigs, followed by optical coherence tomography to evaluate coronary intimal hyperplasia. RESULTS: A vaccine, ATS7vac, was screened out from 3 candidates to effectively inhibit intimal thickening in murine carotid artery ligation models after vaccination. As well, immunization with ATS7vac alleviated neointima formation in murine wire injury models and mitigated atherosclerotic lesions in both hyperlipidemic ApoE-/- and LDLR-/- mice without lowering lipid levels. Preclinically, ATS7vac markedly impeded intimal hyperplasia in swine stented coronary arteries, but without significant immune-related organ injuries. Mechanistically, ATS7vac vaccination produced specific antibodies against ADAMTS-7, which markedly repressed ADAMTS-7-mediated COMP (cartilage oligomeric matrix protein) and TSP-1 (thrombospondin-1) degradation and subsequently inhibited vascular smooth muscle cell migration but promoted re-endothelialization. CONCLUSIONS: ATS7vac is a novel atherosclerosis vaccine that also alleviates in-stent restenosis. The application of ATS7vac would be a complementary therapeutic avenue to the current lipid-lowering strategy for atherosclerotic disease.

The triglyceride glucose index is associated with future cardiovascular disease nonlinearly in middle-aged and elderly Chinese adults.

OBJECTIVE: We aimed to investigate the association between triglyceride glucose index and cardiovascular disease (CVD) development in the Chinese middle-aged and elderly population using the China Health and Retirement Longitudinal Study dataset 2011-2018. METHODS: Basic characteristics of participants, including sociodemographic information, and health conditions, were acquired. Logistic regression analyses and restricted cubic spline regression analyses were conducted to investigate the association between the triglyceride glucose index and future CVD risks. Subgroup analyses were performed to evaluate potential interaction. RESULTS: Seven hundred fifty-three of 6114 (12.3%) participants have developed CVD in 2018 over an approximately 7-year follow-up. The logistic regression analysis exhibited that compared to the lowest triglyceride glucose index group, the multivariable OR for future CVD was 0.985 (95%CI 0.811-1.198) in the T2 triglyceride glucose index group and 1.288 (95%CI 1.068-1.555) in the T3 TyG index (P for trend 0.006). The restricted cubic spline regression analysis showed the nonlinear association between triglyceride glucose index and CVD incidence; the cut-off values were 8.07 and 8.57, respectively, after total adjustment. Gender, fast blood glucose, and triglycerides interacted with triglyceride glucose index and CVD except for BMI. CONCLUSION: The triglyceride glucose index was nonlinearly related to the risk of future cardiovascular disease in the middle-aged and elderly Chinese population.

Evaluating the predictive value of diabetes mellitus diagnosed according to the Chinese guidelines (2020 edition) for cardiovascular events.

OBJECTIVE: Chinese diabetes society has published the new diagnostic criteria for diabetes in China (2020 edition). We aimed to investigate the predictive value of new diabetes-diagnosed criteria for cardiovascular diseases (CVD). METHODS: A total of 5884 individuals from the China Health and Retirement Longitudinal Study in 2011 and 2018 were enrolled. Baseline characteristics and outcome data were compared. The association between diabetes diagnosed by two criteria and future CVD was identified by Kaplan-Meier curves, Cox regression analyses, and receiver-operating characteristic analyses. Delong's test was conducted to compare the predictive value for future CVD between diabetes diagnosed by the 2020 edition and diabetes diagnosed by the previous version. RESULTS: After multivariate adjustment, both diabetes diagnosed by the 2020 edition and diabetes diagnosed by the previous edition is associated with CVD (HR 1.607, 95% CI 1.221-2.115, P < 0.001; HR 1.244, 95% CI 1.060-1.460, P = 0.007, respectively). The Kaplan-Meier analysis indicated that diabetes patients have more cardiovascular risk (log-rank P<0.001). Moreover, diabetes diagnosed in the 2020 edition illustrated an area under the curve (AUC) of 0.673 for predicting CVD, while diabetes diagnosed in the previous edition showed an AUC of 0.638 (DeLong's test P<0.01). CONCLUSION: Diabetes diagnosis criteria (2020 edition) in China had better performance in predicting cardiovascular diseases than the previous edition.

Triglyceride glucose index exacerbates the risk of future cardiovascular disease due to diabetes: evidence from the China Health and Retirement Longitudinal Survey (CHARLS).

OBJECTIVE: We aimed to investigate the effect of the triglyceride glucose (TyG) index on the association between diabetes and cardiovascular disease (CVD). METHODS: Data from 6,114 individuals were extracted and analyzed from the China Health and Retirement Longitudinal Survey (CHARLS) from 2011 to 2018. Logistic regression analyses were conducted to assess the relationship between diabetes and CVD across the various TyG index groups. The statistical method of subgroup analysis was used to determine the correlation between diabetes and CVD for each TyG index group by sex, history of hypertension and dyslipidemia, smoking, and drinking. RESULTS: Diabetes was positively associated with CVD risk after adjustment in 2011(odds ratio (OR) 1.475, 95% CI 1.243-1.752, P < 0.001). There was a gradient increase in the OR for new-onset CVD in 2018 due to diabetes at baseline across the value of the TyG index based on a fully adjusted model (P for trend < 0.05). The ORs of diabetes at baseline for CVD in 2018 were 1.657 (95% CI 0.928-2.983, P = 0.098), 1.834(95% CI 1.064-3.188, P = 0.037) and 2.234(95% CI 1.349-3.673, P = 0.006) for T1, T2 and T3 of the TyG index respectively. The gradient of increasing risk of CVD still existed among those with hypertension and nondrinkers in the subgroup analysis. CONCLUSION: Elevated TyG index strengthens the correlation between diabetes mellitus and CVD in middle-aged and elderly Chinese adults.

The relationship between lipoprotein(a) and cardiovascular events in acute coronary syndrome patients with and without chronic kidney disease.

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) have high residual risk of cardiovascular events, whether the residual risk is associated with elevated level of lipoprotein(a) [Lp(a)] is unascertained. We aimed to explore the impact of Lp(a) levels on the risk of major adverse clinical events (MACEs) in CKD patients hospitalized for acute coronary syndrome (ACS) compared to those without CKD. METHODS: The data of patients hospitalized for ACS were collected at the China-Japan Friendship Hospital from January 2015 to December 2019. Patients were divided into 2 groups according to renal function: non-CKD group (eGFR≥60 ml/min/1.73 m2) and CKD group (eGFR <60 ml/min/1.73 m2). Multivariate Cox regression analysis and restricted cubic splines were performed to explore the relationship between Lp(a) levels and MACEs. RESULTS: A total of 1306 patients were enrolled. Patients with CKD had higher Lp(a) concentrations compared with those without CKD. During a median follow-up of 3.9 years, an elevated Lp(a) value was an independent predictor for MACEs in the overall population. Patients with a high Lp(a) level had higher risk of MACEs than those with a low Lp(a) level, regardless of renal function. The association between higher Lp(a) levels and MACEs remained consistent using the cut-off value of median (11.57 mg/dL), 30 mg/dL and 50 mg/dL in patients with CKD. On the contrary, Lp(a) higher than 50 mg/dL was associated with significantly higher risk of MACEs in patients without CKD. CONCLUSIONS: We confirmed that a high Lp(a) level was associated with long term adverse outcomes in ASC patients, especially in those with CKD.

Predictive Value of the CHA2DS2-VASc Score for Mortality in Hospitalized Acute Coronary Syndrome Patients With Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) patients have a high prevalence of coronary artery disease and a high risk of cardiovascular events. The present study assessed the value of the CHA2DS2-VASc score for predicting mortality among hospitalized acute coronary syndrome (ACS) patients with CKD. Methods: This was a retrospective cohort study that included CKD patients who were hospitalized for ACS from January 2015 to May 2020. The CHA2DS2-VASc score for each eligible patient was determined. Patients were stratified into two groups according to CHA2DS2-VASc score: <6 (low) and ≥6 (high). The primary endpoint was all-cause mortality. Results: A total of 313 eligible patients were included in the study, with a mean CHA2DS2-VASC score of 4.55 ± 1.68. A total of 220 and 93 patients were assigned to the low and high CHA2DS2-VASc score groups, respectively. The most common reason for hospitalization was unstable angina (39.3%), followed by non-ST-elevation myocardial infarction (35.8%) and ST-elevation myocardial infarction (24.9%). A total of 67.7% of the patients (212/313) received coronary reperfusion therapy during hospitalization. The median follow-up time was 23.0 months (interquartile range: 12-38 months). A total of 94 patients (30.0%) died during follow-up. The high score group had a higher mortality rate than the low score group (46.2 vs. 23.2%, respectively; p < 0.001). The cumulative incidence of all-cause death was higher in the high score group than in the low score group (Log-rank test, p < 0.001). Multivariate Cox regression analysis indicated that CHA2DS2-VASc scores were positively associated with all-cause mortality (hazard ratio: 2.02, 95% confidence interval: 1.26-3.27, p < 0.001). Conclusion: The CHA2DS2-VASc score is an independent predictive factor for all-cause mortality in CKD patients who are hospitalized with ACS. This simple and practical scoring system may be useful for the early identification of patients with a high risk of death.