Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study.

OBJECTIVE: Although insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. RESEARCH DESIGN AND METHODS: We included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of ß-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. RESULTS: During median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86-0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. CONCLUSIONS: Fasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

BACKGROUND: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). RESULTS: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. CONCLUSIONS: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.

The Neutrophil to Lymphocyte Ratio Modifies Lipoprotein (a)-Related Poor Prognosis in Patients After Percutaneous Coronary Intervention.

Lipoprotein (a) [Lp(a)] could contribute to coronary artery disease (CAD) through proinflammatory effects. The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker. We consecutively enrolled 7,922 CAD patients to investigate the synergistic association of Lp(a) and NLR with prognosis in patients undergoing percutaneous coronary intervention (PCI). NLR was calculated as the neutrophil count divided by the lymphocyte count. Cutoff for NLR was a median of 2.07. The threshold value was set at 30 mg/dL for Lp(a). The primary endpoint was major adverse cardiac events (MACEs), including all-cause mortality and myocardial infarction. During 2 years follow-up, 111 (1.40%) MACEs occurred. Lp(a) > 30 mg/dL was associated with an increased MACE risk in participants with NLR ≥2.07 [adjusted hazard ratio (HR), 1.84; 95% CI, 1.12-3.03], but not in participants with NLR <2.07 (adjusted HR, 0.74; 95% CI, 0.38-1.45) (Pinteraction = 0.021). Subgroup analysis demonstrated that the synergistic association of Lp(a) and NLR with prognosis was more pronounced in female patients (Pinteraction = 0.028). This study suggested that combining Lp(a) and NLR may be useful for risk stratification in CAD population.

Association of triglyceride-glucose index with adverse cardiovascular events in patients with established coronary artery disease according to different inflammatory status.

BACKGROUND AND AIMS: This study aimed to investigate the association of the triglyceride-glucose (TyG) index, a simple-but-reliable indicator of insulin resistance, with risk of cardiovascular (CV) events in coronary artery disease (CAD) patients with different inflammation status. METHODS AND RESULTS: We consecutively recruited 20,518 patients with angiograph-proven-CAD from 2017 to 2018 at Fuwai Hospital. Patients were categorized according to baseline TyG index tertiles (T) (tertile 1: ≤8.624; T2: 8.624-9.902 and T3: >9.902) and further assigned into 6 groups by high-sensitivity C-reactive protein (hsCRP) medians. The primary endpoint was CV events including CV death, nonfatal myocardial infarction and nonfatal stroke. During the 3.1-year-follow-up, 618 (3.0%) CV events were recorded. Overall, patients with high TyG index levels (T2 or T3) showed significantly increased risk of CV events (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.01-1.53; HR: 1.33; 95%CI: 1.05-1.68, respectively) compared with those with lowest Tyg index (T1) after adjusting for confounding factors. Upon stratification by hsCRP levels, elevated TyG index was associated with increased risk of CV events only in patients with hsCRP levels > median (per-1-unit-increase HR: 1.39; 95%CI: 1.11-1.74), rather than in those with hsCRP levels ≤ median. Furthermore, adding the TyG index to the predicting model led to a significant improvement in patients with hsCRP > median rather than in those with hsCRP ≤ median. CONCLUSIONS: We firstly found that elevated TyG index levels were associated with increased risk of CV events in CAD patients, especially in those with increased inflammatory status, suggesting that it could help in risk stratification and prognosis in this population.

Achieving High-Performance Lithium-Sulfur Batteries by Modulating Li+ Desolvation Barrier with Liquid Crystal Polymers.

Lithium-sulfur (Li-S) batteries offer high theoretical capacity but are hindered by poor rate capability and cycling stability due to sluggish Li2S precipitation kinetics. Here a sulfonate-group-rich liquid crystal polymer (poly-2,2'-disulfonyl-4,4'-benzidine terephthalamide, PBDT) is designed and fabricated to accelerate Li2S precipitation by promoting the desolvation of Li+ from electrolyte. PBDT-modified separators are employed to assemble Li-S batteries, which deliver a remarkable rate capacity (761 mAh g-1 at 4 C) and cycling stability (500 cycles with an average decay rate of 0.088% per cycle at 0.5 C). A PBDT-based pouch cell even delivers an exceptional capacity of ≈1400 mAh g-1 and an areal capacity of ≈11 mAh cm-2 under lean-electrolyte and high-sulfur-loading condition, demonstrating promise for practical applications. Results of Raman spectra, molecular dynamic (MD) and density functional theory (DFT) calculations reveal that the abundant anionic sulfonate groups of PBDT aid in Li+ desolvation by attenuating Li+-solvent interactions and lowering the desolvation energy barrier. Plus, the polysulfide adsorption/catalysis is also excluded via electrostatic repulsion. This work elucidates the critical impact of Li+ desolvation on Li-S batteries and provides a new design direction for advanced Li-S batteries.

Acute Ammonia Causes Pathogenic Dysbiosis of Shrimp Gut Biofilms.

Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with shrimp mortality. Exposure to a lethal concentration of ammonia for 48 h resulted in increased mortality in L. vannamei, with severe damage to the hepatopancreas. Ammonia exposure led to a significant decrease in gut microbial diversity, along with the loss of beneficial bacterial taxa and the proliferation of pathogenic Vibrio strains. A phenotypic analysis revealed a transition from the dominance of aerobic to facultative anaerobic strains due to ammonia exposure. A functional analysis revealed that ammonia exposure led to an enrichment of genes related to biofilm formation, host colonization, and virulence pathogenicity. A species-level analysis and experiments suggest the key role of a Vibrio harveyi strain in causing shrimp disease and specificity under distinct environments. These findings provide new information on the mechanism of shrimp disease under environmental changes.

Association of platelet-to-lymphocyte ratio levels with the risk of cardiac adverse events in people with type 2 diabetes undergoing percutaneous coronary intervention: A large-scale prospective cohort study.

BACKGROUND: The platelet-to-lymphocyte ratio (PLR), a promising inflammatory biomarker, contributes to the development of atherosclerosis and type 2 diabetes (T2D). Therefore, this study aimed to elucidate the importance of PLR in predicting adverse events in people undergoing percutaneous coronary intervention (PCI) with T2D. METHODS: We consecutively enrolled 8831 people who underwent PCI and divided them into four groups according to PLR and glycemic metabolic status (PLR-Low/High without T2D, PLR-Low/High with T2D). The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and stent thrombosis. A multivariate Cox regression analysis was performed to determine this association. RESULTS: During the 2.4-year follow-up, 663 (7.5%) MACCE and 75 (0.85%) stent thromboses were recorded. The risk of MACCE (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.10-1.53, P = 0.002) and stent thrombosis (HR: 2.32, 95% CI: 1.38-3.90, P = 0.002) was significantly higher in people with high PLR levels than in those with low PLR. Among people with T2D, the PLR-High group showed a significantly higher risk of MACCE (HR: 1.59, 95% CI: 1.21-2.09, P = 0.001) and stent thrombosis (HR: 3.15, 95% CI: 1.32-7.52, P = 0.010). However, these associations were not significant in people without T2D. CONCLUSIONS: PLR has been originally documented as a significant predictor of poor prognosis and a high incidence of stent thrombosis in people undergoing PCI, especially in those with T2D.

Triglyceride-glucose index as a suitable non-insulin-based insulin resistance marker to predict cardiovascular events in patients undergoing complex coronary artery intervention: a large-scale cohort study.

BACKGROUND: Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. METHODS: This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. RESULTS: During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13-1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96-1.45) or METS-IR (HR, 1.00; 95%CI 0.98-1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model. CONCLUSIONS: The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

Glycemic control and cardiovascular outcomes in patients with diabetes and coronary artery disease according to triglyceride-glucose index: a large-scale cohort study.

BACKGROUND: The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. METHODS: A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1: <8.895; T2: 8.895-9.400; T3: ≥9.400). According to American Diabetes Association guidelines, controlled glycemia was defined as targeting glycosylated hemoglobin Alc (HbA1c) < 7%. The primary endpoint was CV events including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median 3-year follow-up, 381 (3.8%) CV events occurred. Overall, high TyG index (T3) was associated with increased risk of CV events (hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.02-1.94) compared with the lowest TyG index (T1) after multivariable adjustment. Upon stratification by the TyG index, in fully adjusted models, controlled glycemia was associated with reduced risk of CV events in the high TyG index (T3) subgroup (HR: 0.64; 95%CI: 0.42-0.96) but not in the low (T1; HR: 0.79; 95%CI: 0.53-1.16) and moderate (T2; HR: 0.84; 95%CI: 0.56-1.25) TyG index subgroups. CONCLUSIONS: Controlled glycemia was associated with improved CV outcomes in patients with diabetes and established CAD, especially in those with high TyG index levels. Our study, for the first time, provided valuable information that TyG index could help making risk stratification on the glycemic management in diabetic patients with CAD.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention　- A Subanalysis of the PANDA III Trial.

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined. METHODS AND RESULTS: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Multiple Mittag-Leffler Stability of Almost Periodic Solutions for Fractional-Order Delayed Neural Networks: Distributed Optimization Approach.

This article proposes new theoretical results on the multiple Mittag-Leffler stability of almost periodic solutions (APOs) for fractional-order delayed neural networks (FDNNs) with nonlinear and nonmonotonic activation functions. Profited from the superior geometrical construction of activation function, the considered FDNNs have multiple APOs with local Mittag-Leffler stability under given algebraic inequality conditions. To solve the algebraic inequality conditions, especially in high-dimensional cases, a distributed optimization (DOP) model and a corresponding neurodynamic solving approach are employed. The conclusions in this article generalize the multiple stability of integer-or fractional-order NNs. Besides, the consideration of the DOP approach can ameliorate the excessive consumption of computational resources when utilizing the LMI toolbox to deal with high-dimensional complex NNs. Finally, a simulation example is presented to confirm the accuracy of the theoretical conclusions obtained, and an experimental example of associative memories is shown.

Discordance Between Neutrophil to Lymphocyte Ratio and High Sensitivity C-Reactive Protein to Predict Clinical Events in Patients with Stable Coronary Artery Disease: A Large-Scale Cohort Study.

Purpose: Neutrophil to lymphocyte ratio (NLR), a novel inflammatory biomarker, has been shown to positively predict prognosis independent of high-sensitivity C-reactive protein (hsCRP) in patients with coronary artery disease (CAD). This study aimed to use discordance analysis to evaluate the effectiveness of NLR and hsCRP to predict adverse events in patients with stable CAD. Patients and Methods: This observational cohort study included 7827 consecutive CAD patients at Fuwai Hospital from March 2011 to April 2017. Discordant NLR with hsCRP was defined by the highest quartiles and medians. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Results: During a median 36-month follow-up, 624 (8.0%) MACCEs occurred. Compared with the lowest NLR quartile, a significantly higher risk of MACCEs was observed in the highest NLR quartile after adjusting for confounding factors (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.09-1.71). High NLR and low hsCRP discordance were also associated with an increased risk of MACCEs in the fully adjusted model (HR, 1.39; 95% CI, 1.05-1.84). Conclusion: This study demonstrated that discordantly elevated NLR levels were associated with a greater risk of adverse clinical events in patients with stable CAD, suggesting the potential clinical significance of NLR as a goal of inflammatory risk management.

High triglyceride-glucose index predicts cardiovascular events in patients with coronary bifurcation lesions: a large-scale cohort study.

BACKGROUND: Coronary bifurcation lesion, as a complex coronary lesion, is associated with higher risk of long-term poor prognosis than non-bifurcation lesions. The triglyceride-glucose (TyG) index has been shown to predict cardiovascular (CV) events in patients with coronary artery disease (CAD). However, the prognostic value of the TyG index in patients with bifurcation lesions who are at high risk of CV events remains undetermined. Therefore, this study aimed to investigate the association between the TyG index and CV events in patients with bifurcation lesions. METHODS: A total of 4530 consecutive patients with angiography-proven CAD and bifurcation lesions were included in this study from January 2017 to December 2018. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Patients were assigned into 3 groups according to TyG tertiles (T) (T1: <8.633; T2: 8.633-9.096 and T3: ≥9.096). The primary endpoint was CV events, including CV death, nonfatal myocardial infarction and nonfatal stroke at 3-year follow-up. Restricted cubic spline (RCS) analysis, Kaplan-Meier curves and Cox proportional hazard models were used to investigate the associations between the TyG index and study endpoints. RESULTS: During a median follow-up of 3.1 years, 141 (3.1%) CV events occurred. RCS analysis demonstrated a linear relationship between the TyG index and events after adjusting for age and male sex (non-linear P = 0.262). After multivariable adjustments, elevated TyG index (both T2 and T3) was significantly associated with the risk of CV events (hazard ratio [HR], 1.68; 95% confidence interval [CI],1.06-2.65; HR, 2.10; 95%CI, 1.28-3.47, respectively). When study patients were further stratified according to glycemic status, higher TyG index was associated with significantly higher risk of CV events in diabetic patients after adjusting for confounding factors (T3 vs. T1; HR, 2.68; 95%CI, 1.17-6.11). In addition, subgroup analysis revealed consistent associations of the TyG index with 3-year CV events across various subgroups. Furthermore, adding the TyG index to the original model significantly improved the predictive performance. CONCLUSIONS: High TyG index was associated with CV events in patients with bifurcation lesions, suggesting the TyG index could help in risk stratification and prognosis in this population.

Uric Acid Levels, Number of Standard Modifiable Cardiovascular Risk Factors, and Prognosis in Patients With Coronary Artery Disease: A Large Cohort Study in Asia.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0-1 versus 2-3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow-up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high-UA-level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197-1.804]) and medium-UA-level group (adjusted HR, 1.478 [95% CI, 1.012-2.160]), compared with the low-UA-level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence-based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Association Between MIND Diet Adherence and Mortality: Insights from Diabetic and Non-Diabetic Cohorts.

BACKGROUND/OBJECTIVES: To date, evidence regarding the protective roles of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet in patients with type 2 diabetes mellitus (T2DM) is scarce. This study aims to estimate the impact of adhering to the MIND diet on the mortality in patients with and without T2DM. SUBJECTS/METHODS: In this cohort study, 6887 participants (1021 patients with T2DM) from the NHANES dataset were analyzed. The exposure is the MIND diet adherence. The primary outcomes are all-cause and cardiovascular (CV) deaths. RESULTS: We documented 1087 all-cause deaths consisting of 377 CV deaths during the follow-up (median time of 10 years). Among participants with T2DM, those with a high MIND score (> 8.0, range of MIND score: 4.5-13) had a significantly lower risk of all-cause death (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.59, 0.96, P = 0.021) and CV death (HR 0.50, 95% CI: 0.29, 0.87, P = 0.014) compared to those with a low MIND score (≤ 8.0). In participants without T2DM, a high MIND score was associated with a significant decrease in the risk of all-cause death (HR = 0.83, 95% CI: 0.70, 0.99, P < 0.001), but the association with CV death risk was not statistically significant. CONCLUSION: This study uncovered significant associations between the MIND diet and decreased risk of all-cause and CV death in patients with T2DM. The findings highlight the potential benefits of following the MIND diet in managing and enhancing the outcomes of individuals with T2DM.

Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomization.

Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM). Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666). Findings: The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11-1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13-1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06-1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07-1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02-1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02-1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98-0.99) was associated with reduced T2DM risk. Interpretation: Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies. Funding: CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).

Prognostic Value of Multiple Complete Blood Count-Derived Indices in Intermediate Coronary Lesions.

Complete blood count (CBC)-derived indices have been proposed as reliable inflammatory biomarkers to predict outcomes in the context of coronary artery disease. These indices have yet to be thoroughly validated in patients with intermediate coronary stenosis. Our study included 1527 patients only with intermediate coronary stenosis. The examined variables were neutrophil-lymphocyte ratio (NLR), derived NLR, monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). The primary endpoint was the composite of major adverse cardiovascular events (MACEs), including all-cause death, non-fatal myocardial infarction, and unplanned revascularization. Over a follow-up of 6.11 (5.73-6.55) years, MACEs occurred in 189 patients. Receiver operator characteristic curve analysis showed that SIRI outperformed other indices with the most significant area under the curve. In the multivariable analysis, SIRI (hazard ratio [HR] 1.588, 95% confidence interval [CI] 1.138-2.212) and AISI (HR 1.673, 95% CI 1.217-2.300) were the most important prognostic factors among all the indices. The discrimination ability of each index was strengthened in patients with less burden of modifiable cardiovascular risk factors. SIRI also exhibited the best incremental value beyond the traditional cardiovascular risk model.

High triglyceride-glucose index and stress hyperglycemia ratio as predictors of adverse cardiac events in patients with coronary chronic total occlusion: a large-scale prospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO. METHODS: This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve. RESULTS: During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58-11.37; SHR: HR 5.14, 95% CI 1.89-13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54-3.97; SHR: HR 2.91, 95% CI 1.84-4.60) compared with those with a low Tyg index and a low SHR (TyG < 8.56, SHR < 0.76). The area under the curve (AUC) values were 0.623 (TyG index) and 0.589 (SHR) for CV death/TVMI and 0.659 (TyG index) and 0.624 (SHR) for MACCEs. Furthermore, patients with both a high TyG index and a high SHR showed the highest risk of clinical outcomes among patients with different levels of these two biomarkers, and the AUC for the TyG-SHR combination was larger than the TyG index alone in predicting MACCE risk. CONCLUSIONS: The study revealed that a high TyG index and a high SHR were significantly correlated with poor prognosis in patients with CTO and suggested that these two biomarkers are reliable in predicting long-term prognosis in CTO patients.

Prevalence and prognostic impact of stress-induced hyperglycemia in patients with acute type A aortic dissection.

AIMS: To explore the prevalence of stress-induced hyperglycemia (SIH) in acute type A aortic dissection (ATAAD) patients without diabetes, and its impact on short-term and long-term clinical outcomes. METHODS: A total of 1098 patients with confirmed diagnosis of ATAAD were consecutively enrolled. According to the admission blood glucose (BG), patients were divided into the normoglycemia group (BG < 7.8 mmol/L), mild to moderate SIH group (7.8 ≤ BG < 11.1 mmol/L) and severe SIH group (BG ≥ 11.1 mmol/L). Multivariate regression analysis were used to explore the association between SIH and mortality risk. RESULTS: There were 421 ATAAD patients (38.3%) with SIH, including 361 cases (32.9%) in the mild to moderate group and 60 cases (5.46%) in the severe group. The proportion of high-risk clinical manifestations and conservative treatment was greater in the SIH group than the normoglycemia group. Severe SIH was associated with high risk of 30-day (OR: 3.773, 95%CI: 1.004-14.189, P = 0.0494) and 1-year mortality risk (OR: 3.522 95%CI: 1.018-12.189, P = 0.0469). CONCLUSIONS: Approximately 40% of the patients with ATAAD had SIH, and were more likely to present with high-risk clinical features and receive non-surgical treatment. Severe SIH could be used as an independent predictor of increased short-term and long-term mortality risk and reflect the disease severity of ATAAD.

The impact of sleep quality and its change on the long-term risk of stroke in middle-aged and elderly people: Findings from the English Longitudinal Study of Ageing.

OBJECTIVE: This study focused on middle-aged and elderly adults (mean age ≥60 years) in England and aimed to evaluate the impact of sleep quality and change in sleep quality on the long-term risk of stroke. PATIENTS/METHODS: The current prospective study enrolled 6214 participants without stroke from wave 4 (2008-2009) of the English Longitudinal Study Aging (ELSA) dataset. From the ELSA questionnaires, sleep quality scores were calculated and used to evaluate the sleep quality of each participant. Cox proportional hazards regression models were used to assess the association between sleep status and stroke risk. Restricted cubic spline (RCS) was employed for the relationship between sleep quality score and the risk of stroke. RESULTS: During the 8-year follow-up, 130 (2.1%) cases of stroke were recorded. Participants with poor baseline sleep quality had a significantly higher long-term risk of stroke compared with those with good sleep quality (hazard ratio [HR] 2.37, 95% confidence intervals [CI] 1.44, 3.91). For the influence of change in sleep quality on stroke risk, worsened sleep quality was associated with a significant increase in the risk of stroke in the good (HR 2.08, 95% CI, 1.02, 4.26) and intermediate sleep quality groups (HR 2.15, 95% CI, 1.16, 3.98). Moreover, improved sleep quality decreased stroke risk among subjects with poor sleep quality (HR 0.31, 95% CI, 0.15, 0.61). CONCLUSIONS: Poor and worsened sleep quality is associated with an increased risk of stroke. Emphasis should be placed on improving sleep quality in middle-aged and elderly individuals.