Prognostic significance of triglyceride-glucose index in acute coronary syndrome patients without standard modifiable cardiovascular risk factors.

BACKGROUND: A significant percentage of patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) are being identified. Nonetheless, the prognostic influence of the TyG index on adverse events in this type of patient remains unexplored. The aim of this study was to assess the prognostic value of the TyG index among ACS patients without SMuRFs for predicting adverse outcomes. METHODS: This study involved 1140 consecutive patients who were diagnosed with ACS without SMuRFs at Beijing Anzhen Hospital between May 2018 and December 2020 and underwent coronary angiography. Each patient was followed up for a period of 35 to 66 months after discharge. The objective of this study was to examine major adverse cardiac and cerebrovascular events (MACCE), which included all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, as well as ischemia-driven revascularization. RESULTS: During the median follow-up period of 48.3 months, 220 (19.3%) MACCE events occurred. The average age of the participants was 59.55 ± 10.98 years, and the average TyG index was 8.67 ± 0.53. In the fully adjusted model, when considering the TyG index as either a continuous/categorical variable, significant associations with adverse outcomes were observed. Specifically, for each 1 standard deviation increase in the TyG index within the highest TyG index group, there was a hazard ratio (HR) of 1.245 (95% confidence interval CI 1.030, 1.504) for MACCE and 1.303 (95% CI 1.026, 1.653) for ischemia-driven revascularization (both P < 0.05), when the TyG index was analyzed as a continuous variable. Similarly, when the TyG index was examined as a categorical variable, the HR (95% CI) for MACCE in the highest TyG index group was 1.693 (95% CI 1.051, 2.727) (P < 0.05) in the fully adjusted model, while the HR (95% CI) for ischemia-driven revascularization was 1.855 (95% CI 0.998, 3.449) (P = 0.051). Additionally, the TyG index was found to be associated with a poor prognosis among the subgroup. CONCLUSION: The TyG index is correlated with poor prognosis in patients with ACS without SMuRFs, suggesting that it may be an independent predictive factor of adverse events among these individuals.

Anlotinib plus Sintilimab achieved in an antitumor effect of complete remission in a patient with advanced hepatocellular carcinoma: a case report.

Systemic therapies-based combination treatments have been developed rapidly in patients with advanced hepatocellular carcinoma (HCC). However, there are still a few patients not applicable to any recommended therapies, making it considerable to try new therapeutic options. Among them, anlotinib, a new oral tyrosine kinase inhibitor, is being widely used for many advanced malignancies. We present the first case of the antitumor effect of complete remission by anlotinib combined with an anti-programmed cell death protein 1 antibody, sintilimab, in a patient with advanced HCC. In April 2020, a 51-year-old male patient was diagnosed with large HCC and underwent hepatectomy with R0 resection. Two months later, he was admitted to our hospital because of a tumor relapse with multiple liver and lung metastases. After the failure of comprehensive treatment containing sorafenib, camrelizumab and transhepatic arterial chemotherapy and embolization, 2 months after tumor relapse, the patient started to receive anlotinib and sintilimab. The multiple tumor nodules were remarkable repressed both in the liver and lung. Six months after anlotinib plus sintilimab treatment, there were no residual tumors, and the alpha-fetoprotein level was decreased from 2310.9 mg/L to normal. Also, the patient continued to receive anlotinib to date. In subsequent follow-up visits until now, there was no sign of recurrence found on imaging. Anlotinib is a promising alternative for patients insensitive to the first-line targeted drugs. More clinical studies should be conducted to further broaden the clinical indications of anlotinib and immunotherapy in patients with HCC.

Combined effect of inflammation and malnutrition for long-term prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cohort study.

BACKGROUND: Inflammation is a key driver of atherosclerotic diseases and is often accompanied by disease-related malnutrition. However, the long-term burden of dysregulated inflammation with superimposed undernutrition in patients with acute coronary syndrome (ACS) remains unclear. This study sought to investigate the double burden and interplay of inflammation and malnutrition in patients with ACS undergoing percutaneous Coronary Intervention (PCI). METHODS: We retrospectively included 1,743 ACS patients undergoing PCI from June 2016 through November 2017 and grouped them according to their baseline nutritional and inflammatory status. Malnutrition was determined using the nutritional risk index (NRI) with a score lower than 100 and a high-inflamed condition defined as hs-CRP over 2 mg/L. The primary outcome was major adverse cardiovascular events (MACEs), compositing of cardiac mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Long-term outcomes were examined using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding. The reclassification index (NRI)/integrated discrimination index (IDI) statistics estimated the incremental prognostic impact of NRI and hs-CRP in addition to the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: During a median follow-up of 30 months (ranges 30-36 months), 351 (20.1%) MACEs occurred. Compared with the nourished and uninflamed group, the malnourished and high-inflamed group displayed a significantly increased risk of MACEs with an adjusted hazard ratio of 2.446 (95% CI: 1.464-4.089; P < 0.001). The prognostic implications of NRI were influenced by patients' baseline inflammatory status, as it was only associated with MACEs among those high-inflamed (P for interaction = 0.005). Incorporating NRI and hs-CRP into the GRACE risk score significantly improved its predictive ability for MACEs (NRI: 0.210, P < 0.001; integrated discrimination index; IDI: 0.010, P < 0.001) and cardiac death (NRI: 0.666, P < 0.001; IDI: 0.023, P = 0.002). CONCLUSIONS: Among patients with ACS undergoing PCI, the double burden of inflammation and malnutrition signifies poorer outcomes. Their prognostic implications may be amplified by each other and jointly improve the GRACE risk score's risk prediction performance.

Prognostic Significance of Peripheral Artery Disease in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background: Peripheral artery disease (PAD) elevates the risk of adverse outcomes. The current work aimed to evaluate the influence of PAD in acute coronary syndrome (ACS) cases administered percutaneous coronary intervention (PCI), and to determine whether PAD adds incremental prognostic value to the global registry of acute coronary events (GRACE) scale. Methods: To retrospectively analyze a single-center, prospective cohort trial, we consecutively included ACS cases administered PCI. Individuals with and without PAD were comparatively examined for clinical outcomes. The primary endpoint was major adverse cardiovascular events (MACEs), a compound item encompassing all-cause death, myocardial infarction (MI), stroke and repeat revascularization. The added value of PAD based on a reference model was examined. Results: PAD was detected in 179 (10.4%) of the 1,770 included patients. The incidence rates of MACEs (40.3% vs. 17.9%), all-cause death (11.2% vs. 1.6%), cardiovascular death (8.9% vs. 1.4%), MI (8.4% vs. 2.2%) and repeat revascularization (30.2% vs. 15.2%) were all markedly elevated in PAD cases in comparison with the non-PAD group (p < 0.001). After adjusting for other confounding variates, PAD independently predicted MACE occurrence (hazard ratio = 1.735, 95% confidence interval: 1.281-2.351). Addition of PAD resulted in remarkably increased predictive performance for MACE compared to the baseline GRACE score (Harrell's C-statistic: 0.610 vs. 0.587, p < 0.001; net reclassification improvement: 0.134, p < 0.001; integrated discrimination improvement: 0.035, p < 0.001). Conclusions: In ACS cases administered PCI, PAD independently worsens clinical outcomes and adds incremental value to the GRACE risk score.

Prognostic Value of Estimated Glucose Disposal Rate in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

Background: Estimated glucose disposal rate (eGDR) is highly associated with all-cause mortality in type 2 diabetes mellitus (T2DM) cases undergoing coronary artery bypass grafting (CABG). Nevertheless, eGDR's prognostic value in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) following percutaneous coronary intervention (PCI) remains unknown. Methods: The population of this retrospective cohort study comprised NSTE-ACS patients administered PCI in Beijing Anzhen Hospital between January and December 2015. The primary endpoint was major adverse cardiac and cerebral events (MACCEs). eGDR was calculated based on waist circumference (WC) ( eGDR WC ) or body mass index (BMI) ( eGDR BMI ). Results: Totally 2308 participants were included, and the mean follow-up time was 41.06 months. The incidence of MACCEs was markedly increased with decreasing eGDR. Multivariable analysis showed hazard ratios (HRs) for eGDR WC and eGDR BMI of 1.152 (95% confidence interval [CI] 1.088-1.219; p < 0.001) and 0.998 (95% CI 0.936-1.064; p = 0.957), respectively. Addition of eGDR WC to a model that included currently recognized cardiovascular risk factors markedly enhanced its predictive power compared with the baseline model (Harrell's C-index, eGDR WC versus Baseline model, 0.778 versus 0.768, p = 0.003; continuous net reclassification improvement (continuous-NRI) of 0.125, p < 0.001; integrated discrimination improvement (IDI) of 0.016, p < 0.001). Conclusions: Low eGDR independently predicts low survival of NSTE-ACS cases who underwent PCI.

Prognostic implication of serum glycated albumin for patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: It has been demonstrated that glycated albumin (GA) is significantly associated with diabetes complications and mortality. However, among patients diagnosed with non-ST-elevation acute coronary syndrome (NSTE-ACS) administered percutaneous coronary intervention (PCI), the predictive value of GA for poor prognosis is unclear. METHODS: This study eventually included 2247 NSTE-ACS patients in Beijing Anzhen Hospital, Capital Medical University in January-December 2015 who received PCI. All patients were followed up until death or for 48 months post-discharge. The primary endpoint was major adverse cardio-cerebral events (MACCEs), including all-cause death, non-fatal myocardial infarction, ischemia-induced revascularization and non-fatal ischemic stroke. RESULTS: In total, 547 (24.3%) MACCEs were recorded during the follow-up period. Upon adjusting for potential confounders, GA remained an important risk predictor of MACCEs (As nominal variate: hazard ratio [HR] 1.527, 95% confidence interval [CI] 1.236-1.886, P < 0.001; As continuous variate: HR 1.053, 95% CI 1.027-1.079, P < 0.001). GA addition significantly enhanced the predictive ability of the traditional risk model (Harrell's C-index, GA vs. Baseline model, 0.694 vs. 0.684, comparison P = 0.002; continuous net reclassification improvement (continuous-NRI) 0.085, P = 0.053; integrated discrimination improvement (IDI) 0.007, P = 0.020). CONCLUSION: GA is highly correlated with poor prognosis in NSTE-ACS patients undergoing PCI, suggesting that it may be a major predictive factor of adverse events among these individuals.

Association of B-type natriuretic peptide with rapid progression in patients with aortic stenosis.

BACKGROUND: Rapid progression of aortic stenosis (AS) is associated with poor outcomes, and the impact of B-type natriuretic peptide (BNP) on AS progression remains unknown. OBJECTIVES: The purpose of the present study was to investigate the association between BNP level and the AS progression rate. METHODS: From January 2016 to June 2021, 200 AS patients with progression who had at least two transthoracic echocardiograms with a maximum interval of 180 days were retrospectively analyzed. Rapid progression of AS was defined as the annual increase of aortic jet velocity (Vmax) ≥0.3 m/s/year. For analyses, both the log-transformed BNP and the BNP ratio were used. The linear regression and binary logistic regression analyses were used to determine the association between BNP and the AS progression. RESULTS: At a median echocardiographic follow-up of 595 days, the annual median (interquartile) progression of Vmax was 0.26 (0.09-0.58) m/s/year. Patients with rapid progression had higher age, log BNP, and higher percentage of diabetes and male gender. Higher tertiles of log BNP and BNP ratio had more rapid increase in Vmax (p = 0.018 and 0.033, respectively). BNP ratio significantly correlated with Vmax progression in univariate and multivariate linear regression analyses (p < 0.001 and p = 0.001, respectively). Moreover, both the univariate and multivariate binary logistic regression analyses showed that the log BNP and BNP ratio were associated with the rapid progression of AS (p < 0.050 for all). CONCLUSIONS: Higher BNP was independently associated with the rapid progression of AS.

Effect of lipoprotein(a) levels on long-term outcome in octogenarians with coronary artery disease after drug-eluting stent implantation.

BACKGROUND: High levels of lipoprotein(a) [Lp(a)] are linked to adverse cardiovascular events. The significance of Lp(a) for the survival of octogenarians with coronary artery disease (CAD) after drug-eluting stent (DES) insertion is, however, not known. The purpose of the study is to investigated the connection between Lp(a) and outcome in octogenarians with CAD after DES implantation. METHODS: We retrospectively enrolled a total of 506 consecutive octogenarians with CAD and DES implantation in our institution between January 2015 to August 2018. Two patient groups were established: a low group with plasma Lp(a) lower than 50 mg/dL (n = 408) and a high group with values above 50 mg/dL (n = 98). RESULTS: After following up for a median of 31.53 ± 8.22 months, Kaplan-Meier curves indicated that poorer outcome censored for major cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) in the high group relative to the low group (log-rank test p = 0.001, p = 0.008, and p < 0.001, respectively). High Lp(a) independently predicted MACE (hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.28-2.84; p = 0.002), MI (HR 2.74; 95% CI 1.23-6.11; p = 0.014), and TVR (HR 3.65; 95% CI 1.99-6.69; p < 0.001) after covariate adjustment. CONCLUSIONS: High Lp(a) was also significantly related to poor long-term outcome in octogenarians with CAD after DES implantation.

Triglyceride glucose index for predicting cardiovascular outcomes after percutaneous coronary intervention in patients with type 2 diabetes mellitus and acute coronary syndrome.

BACKGROUND: The triglyceride glucose (TyG) index, a simple surrogate estimate of insulin resistance, has been demonstrated to predict cardiovascular (CV) disease morbidity and mortality in the general population and many patient cohorts. However, to our knowledge, the prognostic usefulness of the TyG index after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) has not been determined. This study aimed to evaluate the association of the TyG index with adverse CV outcomes in patients with T2DM and ACS who underwent PCI. METHODS: The TyG index was calculated using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The primary endpoint was the composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization. The association between the TyG index and adverse CV outcomes was assessed by Cox proportional hazards regression analysis. RESULTS: In total, 776 patients with T2DM and ACS who underwent PCI (mean age, 61 ± 10 years; men, 72.2%) were included in the final analysis. Over a median follow-up of 30 months, 188 patients (24.2%) had at least 1 primary endpoint event. The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles. The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.17 (95% CI 1.45-3.24; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared. CONCLUSIONS: The TyG index was significantly and positively associated with adverse CV outcomes, suggesting that the TyG index may be a valuable predictor of adverse CV outcomes after PCI in patients with T2DM and ACS.

Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI. METHODS: This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke. RESULTS: During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517, P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440, P = 0.044, respectively). CONCLUSIONS: A higher AIP value on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

Biomimetic Mineralization of Protein Nanogels for Enzyme Protection.

Protein nanogels have found a wide variety of applications, ranging from biocatalysis to drug/protein delivery. However, in practical applications, proteins in nanogels may suffer from enzymic hydrolysis and denaturation. Inspired by the structure and functionalities of the fowl eggshells, biomimetic mineralization of protein nanogels was studied in this research. Protein nanogels with embedded porcine pancreas lipase (PPL) in the cross-linked nanostructures were synthesized through the thiol-disulfide reaction between thiol-functionalized PPL and poly(N-isopropylacrylamide) with pendant pyridyl disulfide groups. The nanogels were further reacted with reduced bovine serum albumin (BSA) and BSA molecules were coated on the nanogels. Mineralization of BSA leads to the synthesis of biomineralized shells on the nanogels. With the growth of CaCO3 on the shells, the nanogels aggregate into suprastructures. Thermogravimetric analysis, XRD, dynamic light scattering, and TEM were employed to study the mechanism of the biomineralization process and analyze the structures of the mineralized nanogels. The biomineralized shells can effectively protect the PPL molecules from hydrolysis by trypsin; meanwhile, the nanosized channels on the mineralized shells allow the transport of small-molecule substrates across the shells. Bioactivity measurements indicate that PPL in the nanogels maintains more than 80 % bioactivity after biomineralization.

Hydrophobic Interaction-Induced Coassembly of Homopolymers and Proteins.

Studies on the fabrication of polymer-protein hybrid self-assemblies have aroused great interest over the past years because of a broad range of applications of the materials in drug/protein delivery, biosensors, and enhancement of protein stability. The hybrid assemblies are usually fabricated from polymer-protein bioconjugates, which may suffer from the damages to the protein structures and the loss of functionalities in the synthesis. Herein, we report a simple and efficient approach to the fabrication of vesicle-like structures based on coassembly of homopolymer chains and protein molecules. At room temperature, poly(N-isopropylacrylamide) (PNIPAM) and bovine serum albumin (BSA) are able to form complexes through hydrophobic interactions in aqueous solution. Upon heating to a temperature above the cloud point of PNIPAM, vesicle-like structures with collapsed PNIPAM in the walls and BSA at the surfaces are formed. The size and membrane thickness of the assemblies can be tuned by the molar ratio of PNIPAM to BSA. The hydrophobic interaction between PNIPAM and BSA plays a key role in the complex formation and self-assembly process. The complexes and assembled structures are analyzed by using micro differential scanning calorimetry, light scattering, and transmission electron microscopy. BSA in the assemblies retains over 90% of its activity, and the protein stability is enhanced because of the hydrophobic interaction between proteins and polymers. This approach allows us to prepare polymer-protein assemblies without bioconjugate synthesis. Meanwhile, possible damages to the protein structures and the loss of bioactivities of proteins can be avoided.

Culprit Lesion Characteristics in Young Patients with Hyperhomocysteinemia.

BACKGROUND The relationships between culprit coronary plaque characteristics and hyperhomocysteinemia (HHcy) are not fully understood in young patients. In this study we investigated the relationship between culprit atherosclerotic plaque phenotype assessed by optical coherence tomography (OCT) and hyperhomocysteinemia (HHcy) in young patients. MATERIAL AND METHODS We investigated the OCT imaging and HHcy of 123 lesions in 123 young patients (≤45 years of age). According to OCT images, culprit lesions were classified as thin-cap fiber atheroma (TCFA), thrombus, and other. The 123 patients were grouped as: HHcy group (53 cases, HHcy ≥15.5 µmol/l) and control group (70 cases, HHcy <15.5 µmol/l). RESULTS Compared with the control group, the HHcy group had a higher proportion of OCT-TCFA (p=0.03), OCT-vasa vasorum (p=0.013), and OCT-thrombus (p=0.012), and a larger lipid arc (p=0.002). HHcy (P=0.037) and metabolic syndrome (MetS) (P=0.016) remained independent predictors of TCFAs. HHcy (P=0.026) and smoking (P=0.005) remained independent determinants of thrombus. CONCLUSIONS HHcy and MetS are associated with TCFAs, and HHcy and smoking are associated with thrombus in young patients with coronary artery disease.

Value of Absolute Eosinophil Count in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.

The effect of hsCRP on TyG index-associated cardiovascular risk in patients with acute coronary syndrome undergoing PCI.

The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI.

Potential Mechanisms of Epicardial Adipose Tissue Influencing Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is the predominant terminal stage and the leading cause of mortality in cardiac disease. Heart failure with preserved ejection fraction (HFpEF) affects roughly 50% of HF patients globally. Due to the global aging population, the prevalence, morbidity, and mortality of HFpEF have gradually increased. Epicardial adipose tissue (EAT), as a key visceral adipose tissue around the heart, affects cardiac diastolic function and exercise reserve capacity. EAT closely adheres to the myocardium and can produce inflammatory factors, neurotransmitters, and other factors through autocrine or paracrine mechanisms, affecting the heart function by inflammatory response, cardiac metabolism and energy supply, cardiomyocyte structure and electrical activity, and pericardial vascular function. Currently, research on the mechanism and treatment methods of HFpEF is constantly improving. EAT may play a multi-level impact on the occurrence and development of HFpEF. This review also summarizes the potential impact of EAT on the heart in HFpEF combined with other metabolism-related diseases such as obesity or diabetes over other obesity-related measures, such as body mass index (BMI) or other adipose tissue. Above all, this review comprehensively summarizes the potential mechanisms by which EAT may affect HFpEF. The objective is to enhance our comprehension and management of HFpEF. Future research should delve into the mechanistic relationship between EAT and HFpEF, and investigate interventions aimed at EAT to improve the prognosis of patients with HFpEF.

CVaR-Constrained Policy Optimization for Safe Reinforcement Learning.

Current constrained reinforcement learning (RL) methods guarantee constraint satisfaction only in expectation, which is inadequate for safety-critical decision problems. Since a constraint satisfied in expectation remains a high probability of exceeding the cost threshold, solving constrained RL problems with high probabilities of satisfaction is critical for RL safety. In this work, we consider the safety criterion as a constraint on the conditional value-at-risk (CVaR) of cumulative costs, and propose the CVaR-constrained policy optimization algorithm (CVaR-CPO) to maximize the expected return while ensuring agents pay attention to the upper tail of constraint costs. According to the bound on the CVaR-related performance between two policies, we first reformulate the CVaR-constrained problem in augmented state space using the state extension procedure and the trust-region method. CVaR-CPO then derives the optimal update policy by applying the Lagrangian method to the constrained optimization problem. In addition, CVaR-CPO utilizes the distribution of constraint costs to provide an efficient quantile-based estimation of the CVaR-related value function. We conduct experiments on constrained control tasks to show that the proposed method can produce behaviors that satisfy safety constraints, and achieve comparable performance to most safe RL (SRL) methods.

The synergistic effect of the atherogenic index of plasma and hyperuricemia on the prediction of coronary chronic total occlusion lesion: an observational cross-sectional study.

Background: The atherogenic index of plasma (AIP) and hyperuricemia (HUA) have been shown to be closely associated with morbidity and mortality of coronary artery disease. However, studies targeting predictive value of AIP and HUA for chronic total occlusion (CTO) lesions are still lacking. Methods: In total, 5,238 patients meeting the eligibility criteria were recruited in this analysis. CTO was defined as the condition of lesions without forward blood flow and with over three months of occlusion time. AIP was calculated as log10 [triglycerides (mmol/L)/high-density lipoprotein cholesterol (mmol/L)]. HUA was defined based on sex-specific criteria: serum uric acid 420 and 360 µmol/L for males and females, respectively. Results: CTO lesions were presented in 907 (17.3%) patients. Compared with patients showing lower AIP levels and non-HUA, the CTO lesion risks increased by 5.225 and 2.765 times in patients with higher AIP levels and HUA. Patients with AIP >0.15 and HUA exhibited the greatest CTO incidence (odds ratio 11.491; 95% confidence interval 9.019-14.641, P < 0.001). In addition, AIP combined with HUA had significantly increased effects (a 38.5% increase in CTO risk) relative to the sum of respective effects. Conclusion: Patients having higher AIP levels and HUA exhibited the highest CTO incidence, in comparison with patients who have the increased single index. AIP combined with HUA displayed significant synergistic effect on the prediction of CTO lesion.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

Off-target effects in CRISPR/Cas9 gene editing.

Gene editing stands for the methods to precisely make changes to a specific nucleic acid sequence. With the recent development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, gene editing has become efficient, convenient and programmable, leading to promising translational studies and clinical trials for both genetic and non-genetic diseases. A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome. To date, many methods have been developed to nominate or detect the off-target sites of CRISPR/Cas9, which laid the basis for the successful upgrades of CRISPR/Cas9 derivatives with enhanced precision. In this review, we summarize these technological advancements and discuss about the current challenges in the management of off-target effects for future gene therapy.