Prediabetes, an intermediate metabolic state preceding diabetes, independently accelerates cardiovascular pathology through dysglycemia-driven mechanisms. This study evaluates the heterogeneous cardiovascular risk stratification by directly comparing two major diagnostic criteria (ADA vs. WHO/IEC) and assesses the causal cardiovascular consequences of prediabetes, an area requiring further elucidation. After excluding participants with baseline cardiovascular disease, the remaining cohort with complete glycemic and relevant assessment data (n = 278,697) was stratified into normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM). Prediabetes was subsequently classified according to both ADA (fasting plasma glucose, FPG 5.6–6.9 mmol/L and/or glycosylated hemoglobin A1c, HbA1c 5.7–6.4

Introduction:High residual inflammatory risk (hs-CRP≥2mg/L) predicts worse prognosis and increased ischemic risk following percutaneous coronary intervention (PCI). The optimal duration of dual antiplatelet therapy (DAPT) and its risk-benefit profile in post-PCI patients with high residual inflammatory risk remain unclear. Methods:Patients undergoing PCI with high residual inflammatory risk at Fuwai Hospital were consecutively enrolled. Patients were stratified into two groups based on DAPT duration: prolonged (>12 months) and conventional (≤12 months) groups. The primary outcome was a composite endpoint of all-cause death, myocardial infarction, definite or probable stent thrombosis, or stroke at 3 years. The key safety outcome was the 3-year rate of Bleeding Academic Research Consortium 2, 3, or 5 bleeding. Results:Among post-PCI patients with high residual inflammatory risk, 2440 individuals (69.5%) continued DAPT beyond 12 months. After three years of follow-up, prolonged DAPT was associated with a significantly lower risk of the primary outcome (1.5% vs. 4.2%; adjusted hazard ratio [HR]: 0.347, 95% CI: 0.224-0.539). Similar benefits were observed for net adverse clinical events (1.4% vs. 4.1%; adjusted HR: 0.338, 95% CI: 0.216-0.53) and for the composite endpoint of all-cause death or myocardial infarction (0.6% vs. 3.1%; adjusted HR: 0.182, 95% CI: 0.097-0.341). Notably, the key safety endpoint did not differ significantly between the two DAPT durations during follow-up (1.0% vs. 1.2%; adjusted HR: 0.793, 95% CI: 0.401-1.57). Conclusion:In patients who underwent PCI with high residual inflammatory risk, prolonged DAPT improved clinical outcomes by mitigating ischemic risk without increasing clinically significant bleeding.

Background Type 2 diabetes (T2D) is a known risk factor for arrhythmias, yet evidence for prediabetes is limited, and the two main diagnostic criteria (ADA, prioritizing sensitivity; WHO/IEC, prioritizing specificity) have not been directly compared across arrhythmia subtypes. Methods In this prospective cohort study of 383,995 UK Biobank participants, glycemic status was defined by ADA and WHO/IEC criteria. Outcomes included atrial fibrillation, supraventricular tachycardia, bradyarrhythmia, and ventricular arrhythmia. Cox models were adjusted for clinical, lifestyle, and genetic confounders. Mendelian randomization (MR) was performed to infer causality. Results Over a median 13.0 years, prediabetes and T2D were each associated with increased risks of all arrhythmias. Under ADA criteria, prediabetes hazard ratios ranged from 1.12 to 1.16; risks were higher for T2D and for progression from prediabetes to T2D. ECG changes included shortened RR and prolonged QTc intervals.MR analyses provided genetic evidence supporting a potential causal role of dysglycemia in arrhythmogenesis. Conclusions These findings highlight the differential prognostic utility of ADA and WHO/IEC criteria for arrhythmia risk stratification: the ADA criteria offer broader sensitivity for early detection, whereas the stricter WHO/IEC criteria identify a higher-risk subgroup warranting more intensive management.

Aims Despite advancements in primary percutaneous coronary intervention (PCI), cardiac dysfunction remains a challenge in patients with ST-segment elevation myocardial infarction (STEMI). Although thymosin beta 4 has shown cardioprotective effects in preclinical MI models, its impact on chronic cardiac functional recovery post ischemia/reperfusion (I/R), especially in STEMI, warrants further investigation. This study aims to explore the therapeutic potential of recombinant human thymosin beta 4 (rhTB4) in both murine models subjected to I/R and in subjects with STEMI post-PCI.Methods and results In C57BL/6J mice, 7-day rhTB4 treatment prevented cardiac dysfunction and fibrosis 28 days post-I/R surgery and significantly reduced plasma NT-proBNP levels at both 1 day and 28 days post-I/R. Similarly, in a permanent ligation model, rhTB4 improved cardiac function and reduced infarct size at 8 weeks post-MI. RNA-seq analysis of I/R heart tissues revealed that rhTB4 modulated the ErbB signaling pathway. In vitro hypoxia/reoxygenation (H/R) models (HL-1, neonatal mouse cardiomyocytes, H9C2) demonstrated that rhTB4 activated the ErbB2/Raf1 signaling pathway, attenuated cardiomyocyte apoptosis and suppressed pro-apoptotic protein Bad expression. The cardioprotective effects of rhTB4 on cardiac function and adverse cardiac remodeling in I/R mice were abolished by ErbB2 inhibition. In a randomized, placebo-controlled, double-blind trial involving 96 STEMI patients, the infarcted areas were significantly reduced in the rhTB4 group, which received the first dose of rhTB4 within 8 h after PCI (n = 43), as compared to the placebo group at the 90-day follow-up. However, the overall differences in infarcted areas were not significantly between the rhTB4 group and the placebo group (n = 96).Conclusion These findings underscore the crucial role of rhTB4 in mitigating cardiac dysfunction in an ErbB2-dependent manner. The clinical relevance of rhTB4 is demonstrated through a randomized controlled trial, emphasizing its translational potential. Further rigorous randomized studies are needed to assess the significance of early rhTB4 use post-myocardial infarction reperfusion.

Purpose:Inflammation represents a key driver of type 2 diabetes (T2DM) and is associated with major adverse cardiovascular and cerebrovascular events (MACCEs). Residual inflammatory risk, defined as persistent inflammation despite lipid-lowering therapy, differs from residual cholesterol risk, which refers to suboptimal lipid levels post-treatment. This study aims to evaluate the impact of T2DM on the relationship between residual inflammatory risk, as assessed by a simple, economical, and easily measurable biomarker-high-sensitivity C-reactive protein (hs-CRP)-and clinical outcomes in statin-treated coronary heart disease (CHD) patients with drug-eluting stent (DES) implantation. Patients and Methods:8,628 individuals with CHD treated with statins and DES implantation at Fuwai Hospital were included. Participants were first stratified according to T2DM status, and then baseline hs-CRP levels were further divided into three groups using 1 mg/L and 2 mg/L as the cut-off points. The primary endpoint was MACCEs, defined as the composite of all-cause mortality, myocardial infarction, stroke, and target vessel revascularization. Results:After 2.4 years of median follow-up duration, 999 patients were defined as MACCEs, whose hs-CRP levels were significantly higher compared to the non-MACCEs group (p = 0.007). The cohort was stratified into T2DM (n = 3,729) and Non-T2DM (n = 4,899) groups. In full adjusted model: for the Non-T2DM group, hs-CRP ≥ 2 mg/L remained significantly associated with MACCEs [HR = 1.39, 95% CI (1.14-1.85), p = 0.002]. In the T2DM group, no significant association was observed [HR = 1.02, 95% CI (0.73-1.23), p = 0.453] (p for interaction= 0.040). Conclusion:Among CHD patients receiving contemporary statin therapy following DES implantation, higher hs-CRP levels appeared to be associated with future MACCEs in those without T2DM, though not in T2DM patients. Hs-CRP, an important diagnostic marker of inflammation, shows different value depending on diabetes status, revealing how diabetes and inflammation jointly influence cardiovascular outcomes and providing clinical insights for optimizing the application of inflammatory biomarkers in personalized cardiovascular risk stratification.

This prospective cohort study evaluated the prognostic value of the triglyceride-glucose (TyG) index and its metabolic mediation pathways in 16 499 patients with complex coronary lesions (American College of Cardiology/American Heart Association type B2/C) undergoing percutaneous coronary intervention (PCI). Over a median 3-year follow-up, 535 patients (3.2%) experienced cardiovascular (CV) events. Patients in the highest TyG tertile (T3: >9.10) demonstrated a 2.442-fold increased CV risk compared with the lowest tertile (T1: <8.63; 95% CI 1.923-3.102, P < .001), with a significant dose-response relationship (P-trend < .001). Structural equation modeling revealed that metabolic burden (hypertension, dyslipidemia, type 2 diabetes mellitus) mediated 50.0% of TyG-associated risk (indirect effect P = .038). TyG index exhibited superior predictive accuracy for CV events compared with the TG/HDL-C ratio (area under the curve [AUC] 0.617 vs 0.577, P = .004), though their combination did not significantly improve discrimination over TyG alone (△AUC = 0.001, P = .694). Type 2 diabetes mellitus accounted for 62.3% of the mediation effect, surpassing hypertension (20.8%), and dyslipidemia (16.9%). These findings establish the TyG index as an independent predictor of CV outcomes in complex coronary lesions, with metabolic comorbidities explaining half its prognostic impact. Integration of TyG-driven metabolic phenotyping may optimize risk stratification and targeted interventions in high-risk PCI populations.

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.

BACKGROUND:Inflammation and hyperlipidaemia contribute with similar magnitude to the risk of future atherothrombotic events. However, the relative importance of high-sensitivity CRP (hsCRP) and lipoprotein(a) (Lp[a]) as determinants of risk of major adverse cardiovascular events (MACE) are not well defined among patients aged 75 years or older with established atherosclerotic cardiovascular disease (ASCVD). METHODS:The present study prospectively enrolled 2,333 patients aged 75 years or older diagnosed with ASCVD with measurement of hsCRP and Lp(a) at Fuwai Hospital. The primary endpoint was MACE, defined as a composite of all-cause death, myocardial infarction (MI), stroke or ischaemia-driven coronary revascularisation. RESULTS:The median follow-up time was 3.0 years (interquartile range [IQR]: 2.5-3.2 years). hsCRP was significantly associated with an increased risk of MACE (adjusted hazard ratio [aHR]: 1.05, 95% confidence interval [CI]: 1.03-1.08 per 1 mg/l increment, P < 0.001; highest versus lowest quartile: aHR: 1.70 [1.22-2.38]), whereas there was no significant association between Lp(a) and MACE risk (aHR: 1.02 [0.98-1.06] per 10 mg/dl increment, P = 0.341; highest versus lowest quartile: aHR: 1.06 [0.77-1.47]). Risks of MACE were significantly higher in participants with hsCRP ≥2 mg/l than in those with hsCRP <2 mg/l, irrespective of Lp(a) strata (aHR: 1.41 [1.12-1.79]; P = 0.004). Concomitant elevation of hsCRP (≥2 mg/l) and Lp(a) (≥30 mg/dl) was associated with the greatest risk of MACE (aHR, 1.54 [1.13-2.12]; P = 0.007). CONCLUSIONS:Inflammation assessed by hsCRP predicted risk of future cardiovascular events more strongly than Lp(a) in patients aged 75 years or older with established ASCVD. These results provided real-world evidence on older patients potentially benefit by targeted anti-inflammatory strategies for secondary ASCVD prevention.

Introducción y objetivos: La mala calidad del sueño plantea importantes problemas de salud pública en todo el mundo. El objetivo de este estudio es investigar la asociación entre la calidad del sueño y el riesgo de hipertensión.Métodos: El estudio analizó datos de 284.250 adultos del Biobanco del Reino Unido (UKB) y 6.104 participantes del English Longitudinal Study of Ageing (ELSA) sin hipertensión en la situación basal. La exposición de interés fue la calidad del sueño, que se evaluó mediante cuestionarios. Se dividió a los participantes en 3 grupos según su calidad del sueño. La duración del sueño se evaluó mediante un informe de cada participante de sus horas de sueño. El objetivo primario fue la aparición de hipertensión.Resultados: En la cohorte del UKB, los participantes con mala calidad del sueño mostraron un riesgo de hipertensión significativamente mayor que aquellos con calidad de sueño saludable (HR = 1,277; IC95%, 1,21-1,346]. Los resultados de la cohorte del ELSA validaron los de la cohorte del UKB; los participantes con mala calidad del sueño tenían un riesgo de hipertensión notablemente mayor (HR = 1,264; IC95%, 1,02-1,566). Prolongar la duración del sueño se asoció con menor riesgo de hipertensión en individuos con calidad del sueño intermedia o saludable. A pesar de que varios factores se asociaron de forma independiente con menor riesgo de hipertensión (p < 0,001), la asociación entre calidad del sueño y mayor riesgo de hipertensión se mantuvo significativa independientemente de la susceptibilidad genética a la hipertensión (p para la interacción = 0,067).Conclusiones: Teniendo en cuenta la predisposición genética a la hipertensión, la mala calidad del sueño se asocia con alto riesgo de hipertensión. En niveles intermedios o saludables de calidad del sueño, prolongar la duración del sueño se relaciona con un menor riesgo de hipertensión.

BACKGROUND:Coronary embolism is an uncommon etiology of acute myocardial infarction, particularly in patients with mechanical heart valves. CASE:A 47-year-old woman with mechanical aortic valve replacement presented with non-ST-segment elevation myocardial infarction after temporary warfarin interruption. Computed tomography angiography and coronary angiography revealed a mobile thrombus in the mid-left anterior descending artery, which was confirmed as embolic origin by intravascular ultrasound. MANAGEMENT:Initial thrombus aspiration yielded suboptimal results. Subsequent balloon angioplasty was performed, achieving TIMI flow grade 3 restoration. Anticoagulation therapy with warfarin was reinitiated for long-term management. CONCLUSIONS:This case highlights the critical role of intravascular imaging in diagnosing embolic acute myocardial infarction and the efficacy of mechanical thrombus modification when thrombus aspiration alone is inadequate.

INTRODUCTION AND OBJECTIVES:Poor sleep quality poses significant public health challenges worldwide. This study aimed to investigate the association between sleep quality and the risk of hypertension. METHODS:The study analyzed 284 250 adults from the UK Biobank (UKB) and 6104 participants from the English Longitudinal Study of Ageing (ELSA) without hypertension at baseline. The exposure of interest was sleep quality, which was evaluated based on questionnaires. Participants were divided into 3 groups based on the assessment of sleep quality. Sleep duration was assessed by self-reported sleep hours by each participant. The primary endpoint was new onset hypertension. RESULTS:In the UKB cohort, participants with poor sleep quality showed a significantly higher risk of hypertension than those with healthy sleep quality (HR, 1.277; 95%CI, 1.21-1.346]. The results from the ELSA cohort effectively validated those from the UKB cohort; participants with poor sleep quality had a notably heightened risk of hypertension (HR, 1.264; 95%CI, 1.02-1.566). Prolonging sleep duration was associated with a decrease in the risk of hypertension in individuals with intermediate or healthy sleep quality. Although several factors were independently associated with a lower risk of hypertension (P<.001), the association between sleep quality and an increased risk of hypertension remained significant regardless of genetic susceptibility to hypertension (P for interaction=.067). CONCLUSIONS:Considering the genetic predisposition to hypertension, poor sleep quality is associated with an elevated risk of hypertension. In intermediate or healthy levels of sleep quality, prolonging sleep duration is linked to a reduced risk of hypertension.

Background and aims: The relationship between the triglyceride-glucose (TyG) index and the incidence of atrial fibrillation (AF) remains insufficiently explored. This investigation aims to elucidate the association between the TyG index and the long-term risk of developing AF. Methods and results: This cohort study analyzed data from 409,705 participants sourced from the UK Biobank database. Participants were stratified into three groups based on TyG index tertiles. The association between the TyG index and AF was evaluated using Cox proportional hazards models. Restricted cubic spline (RCS) analysis was employed to investigate potential linear or nonlinear relationships. During a mean follow-up period of 13.9 years, 26,092 AF cases were recorded. Compared with the T2 group, participants in the T1 group and T3 group presented a significantly higher risk of AF (T1: HR: 1.22, 95%CI: 1.17-1.27; T3: HR: 1.09, 95%CI: 1.05-1.14). RCS analysis documented a U-shaped relationship between the TyG index and the risk of AF (P for non-linearity <0.001). In non-type 2 diabetes (T2D) participants, TyG levels were associated with AF risk in a U-shaped relationship. Among T2D participants, only the T3 group had an increased risk of AF (reverse "L" pattern). The U-shaped relationship between TyG levels and AF risk remained consistent across heart valve disease (HVD) and non-HVD patients, as well as different strata of genetic susceptibility to AF. Conclusions: This study demonstrates a U-shaped association between the TyG index and the risks of AF, underscoring the index's potential utility in identifying individuals at elevated risk for these conditions.

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.

Background: The platelet-to-lymphocyte ratio (PLR) is a promising inflammatory biomarker contributing to the development of atherosclerosis and type 2 diabetes mellitus (T2DM). Therefore, this study aims to document the value of PLR in predicting adverse events in patients undergoing percutaneous coronary intervention (PCI) with and without T2DM. Methods: This study consecutively enrolled 8831 patients who received PCI, and we divided them into 4 groups according to the PLR level and glycemic metabolic statuses (PLR-low/high with non-T2DM, PLR-low/high with T2DM). The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and stent thrombosis. Multivariate COX regression analysis was used to determine the association. Results: During the 2.4-year follow-up, a total of 663 (7.5%) MACCE and 75 (0.85%) stent thrombosis were recorded. Results showed that patients with high PLR levels presented a significantly higher risk of MACCE (HR: 1.26, 95%CI: 1.07 to 1.47, P = 0.005) and stent thrombosis (HR: 2.29, 95%CI, 1.39 to 3.79, P = 0.001) when compared with the PLR-low group. When focused on patients with T2DM, the PLR-high group showed a significantly higher risk of MACCE (HR: 1.53, 95%CI: 1.17 to 2.00, P = 0.002) and stent thrombosis (HR: 3.79, 95%CI, 1.62 to 8.86, P = 0.002). However, these associations were not significant in patients without T2DM. Conclusions: For the first time, PLR is documented as a great predictor for the poor prognosis and high incidence of stent thrombosis in patients with CAD, especially in those with T2DM.

BackgroundThe Mediterranean-Dietary Approaches to Stop Hypertension for neurodegenerative delay (MIND) has been regarded as a novel healthy dietary pattern with huge benefits. However, its value in preventing and treating hypertension has not been investigated. The objective of this study is to investigate the impact of adhering to the MIND diet on the prevalence of hypertension in the entire population and long-term mortality in hypertensive patients.MethodsIn this cross-sectional and longitudinal study, 6,887 participants consisting of 2,984 hypertensive patients in the National Health and Nutritional Examination Surveys were analyzed and divided into 3 groups according to the MIND diet scores (MDS; groups of MDS-low [<7.5], MDS-medium [7.5–8.0] and MDS-high [≥8.5]). In the longitudinal analysis, the primary outcome was all-cause death and the secondary outcome was cardiovascular (CV) death. Hypertensive patients received a follow-up with a mean time of 9.25 years (median time: 111.1 months, range 2 to 120 months). Multivariate logistics regression models and Cox proportional hazards models were applicated to estimate the association between MDS and outcomes. Restricted cubic spline (RCS) was used to estimate the dose–response relationship.ResultsCompared with the MDS-low group, participants in the MDS-high group presented a significantly lower prevalence of hypertension (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.58, 0.97, p = 0.040) and decreased levels of systolic blood pressure (β = −0.41, p = 0.033). Among hypertensive patients, 787 (26.4%) all-cause death consisting of 293 (9.8%) CV deaths were recorded during a 10-year follow-up. Hypertensive patients in the MDS-high group presented a significantly lower prevalence of ASCVD (OR = 0.71, 95% CI, 0.51, 0.97, p = 0.043), and lower risk of all-cause death (hazard ratio [HR] = 0.69, 95% CI, 0.58, 0.81, p < 0.001) and CV death (HR = 0.62, 95% CI, 0.46, 0.85, p for trend = 0.001) when compared with those in the MDS-low group.ConclusionFor the first time, this study revealed the values of the MIND diet in the primary and secondary prevention of hypertension, suggesting the MIND diet as a novel anti-hypertensive dietary pattern.

Coronary arteritis is a rare but life-threatening cause of coronary artery disease and could manifest as acute coronary syndrome in clinical scenarios. Coronary arteritis could occur in the setting of systematic vasculitis or being isolated. Most of these patients were lacking of conventional risk factors in atherosclerotic cardiovascular disease. Diagnosis of coronary arteritis still be difficult and often be delayed. Clinicians should take in account of comprehensive factors including the evidence of muti-organ involvement (mainly by symptoms, physical examination and radiology imaging findings) and specific laboratory test results. For the treatment of coronary arteritis, systematic drug therapy (i.e., corticosteroid and immunosuppressive therapy) combined with revascularization were applied in the most cases. However, problems of frequently in-stent restenosis and recurrent myocardial infarction still needed to be solved. It is still unclear whether revascularization is efficient and safe for these patients, and the strategy to prevent restenosis and re-ischemia still needs to be studied in the future. In this study, we reviewed the specific clinical manifestations, laboratory results, imaging findings, diagnosis criteria and therapeutic strategies for patients with coronary arteritis presented as acute coronary syndrome.

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 lone-liness. 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.

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.