OBJECTIVE:While depressive symptoms are a known risk factor for cardiovascular disease (CVD), their influence over time in individuals without standard modifiable risk factors ('SMuRF-less' adults) is unclear. This study examined the association between depressive symptoms and incident CVD in SMuRF-less middle-aged and older adults. METHODS:This prospective cohort study analyzed data from the China Health and Retirement Longitudinal Study (CHARLS; n = 2095) and the English Longitudinal Study of Ageing (ELSA; n = 798). Depressive symptoms were assessed at baseline and at a roughly 2-year follow-up using the CES-D scale. Participants were categorized into four patterns: 'Never', 'Onset', 'Remission', and 'Persistence'. The primary outcome was the first occurrence of self-reported, physician-diagnosed CVD (heart disease or stroke). Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS:Over follow-up, compared with the Never group, participants with Onset (CHARLS: HR 1.55, 95% CI 1.16-2.08; ELSA: HR 1.28, 95% CI 1.01-1.62) and Persistence (CHARLS: HR 2.11, 95% CI 1.68-2.65; ELSA: HR 1.77, 95% CI 1.12-2.79) depressive symptoms had a significantly higher risk of incident CVD. The Remission group did not show a significantly elevated risk (CHARLS: HR 1.15, 95% CI 0.87-1.52; ELSA: HR 1.14, 95% CI 0.71-1.82). A dose-response relationship was observed, with higher cumulative depressive symptom scores associated with linearly increasing CVD risk. CONCLUSIONS:Among SMuRF-less middle-aged and older adults, the onset and persistence of depressive symptoms were associated with an increased risk of incident CVD.

OBJECTIVE:This study aimed to examine the prospective associations of loneliness and social isolation with the risk of Cardiovascular-Kidney-Metabolic Syndrome Stages 0-3 progression to cardiovascular disease (CVD) and to compare the relative importance of loneliness and social isolation with traditional risk factors. In addition, the interactions of loneliness or isolation with the degree of risk factor control in relation to CVD risk were evaluated. METHOD:This national prospective cohort study included 3,500 participants from the China Health and Retirement Longitudinal Study. Loneliness and social isolation were self-reported. The degree of risk factor control was defined as the number of glycated hemoglobin (HbA1c), blood pressure, low-density lipoprotein cholesterol, smoking, and kidney condition controlled within the target range. Cox proportional hazards models and interaction analyses were used to estimate risk for CVD. RESULTS:Of the 3,500 participants (Mage [SD] = 58.58 [8.72] years), 1,615 (45.1%) were men. Over a median follow-up of 7.1 years, 714 participants developed CVD. Loneliness, but not social isolation, was independently associated with increased CVD risk (adjusted hazard ratio = 1.25, 95% confidence interval [1.02, 1.52]. Loneliness ranked fourth among predictors, following low-density lipoprotein cholesterol, systolic blood pressure, and body mass index. Joint analysis showed that individuals who were lonely and had a low risk factor control had the highest CVD risk (hazard ratio = 1.91, 95% confidence interval [1.43, 2.54], with significant additive and multiplicative interactions. CONCLUSIONS:Loneliness, but not social isolation, is associated with a higher risk of cardiovascular-kidney-metabolic syndrome progression to CVD and shows an interaction with the degree of risk factor control. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

BACKGROUND:The emergence of the 'SMuRF-less' (absence of Standard Modifiable Risk Factors) phenotype challenges traditional cardiovascular disease (CVD) prediction models. While depression is an established CVD risk factor, its pathogenic role in the absence of hypertension, diabetes, hypercholesterolemia, and smoking remains unclear, especially regarding potential sex differences. METHODS:This prospective analysis included 2484 middle-aged and older adults (≥45 years) free of baseline CVD and all SMuRFs (hypertension, diabetes, hypercholesterolemia, smoking) from the China Health and Retirement Longitudinal Study. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association between depressive symptoms and CVD events after adjusting for potential confounders. Dose-response associations were examined using restricted cubic splines, and all analyses were stratified by sex. RESULTS:Over a median follow-up of 10.3 years, 523 CVD events occurred. Elevated depressive symptoms were associated with increased risks of CVD (adjusted HR = 1.47, 95% CI: 1.22-1.77), stroke (HR = 1.61, 95% CI: 1.13-2.28), and heart disease (HR = 1.42, 95% CI: 1.16-1.74) in the overall population. However, stratified analysis revealed this association was entirely driven by women, with significant risks for CVD (HR = 1.50, 95% CI: 1.22-1.86) and stroke (HR = 2.08, 95% CI: 1.35-3.21). No significant association was observed in men. A linear negative association was evident in women but not in men. CONCLUSIONS:In this SMuRF-less cohort, depressive symptoms independently predicted incident CVD, with the association being particularly strong in women. Our findings identify a "SMuRF-less but depressed" women phenotype that warrants targeted attention in primary prevention.

The independent associations of air pollution and frailty with cardiovascular disease (CVD) risk are well established, but their combined impact remains unclear. While physical activity (PA) supports cardiovascular health and may mitigate frailty-related risks, it also increases air pollution exposure, potentially offsetting its benefits. This study examines their joint associations and the potential modifying role of PA using data from 6433 individuals aged ≥45 years in the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective cohort. Frailty, PA, and air pollution were assessed at baseline. Logistic regression models with multivariable adjustment were used to evaluate associations and interactions. Higher PM1, PM2.5 and PM10 levels were significantly associated with increased CVD risk, with PM10 showing the strongest association. Frailty was also strongly associated to CVD, while PA was associated with lower CVD risk but without statistical significance. Frailty and air pollution jointly elevated CVD risk, with pre-frail and frail individuals experiencing progressively higher risks, particularly in high-pollution areas. Significant multiplicative and additive interactions were observed, but PA did not significantly modify these associations. Frailty and air pollution synergistically increase CVD risk. Although PA correlates with lower CVD risk, it does not counteract the combined harm of frailty and pollution, underscoring the need for broader interventions to protect vulnerable populations.

OBJECTIVE:To examine the association of depressive symptoms with cardiovascular disease (CVD) risk in middle-aged and older adults with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3 and to assess whether this association varies by CKM syndrome stages. Also, interactions of depressive symptoms with CKM syndrome stages in relation to CVD risk were evaluated. METHODS:This study analyzed data from the China Health and Retirement Longitudinal Study (CHARLS). Incident CVD events were identified based on self-reported physician-diagnosed (Participants were asked whether they had ever been diagnosed with disease by a physician). Cox proportional hazards regression models were used to estimate the association between depressive symptoms and CVD risk with interaction analyses across CKM syndrome stages. RESULTS:Among 3440 participants, 1833 (53.3 %) were women. Over the 7-year follow-up, 696 (20.2 %) developed CVD. After full adjustment, elevated depressive symptoms were associated with a 27.0 % higher CVD risk (HR, 1.27; 95 % CI, 1.07-1.50). Of the 10 individual depressive symptoms, only restless sleep (HR, 1.23; 95 % CI, 1.04-1.44), loneliness (HR, 1.26; 95 % CI, 1.05-1.52), and bothered by little things (HR, 1.21; 95 % CI, 1.01-1.45) were significantly associated with incident CVD. Moreover, depressive symptoms and CKM syndrome stages exhibited both multiplicative and additive interactions. Notably, in CKM syndrome stage 3, depressive symptoms were associated with a 36.0 % higher CVD risk (HR, 1.36; 95 % CI, 1.09-1.70). CONCLUSIONS:Elevated depressive symptoms are associated with increased CVD risk in middle-aged and older adults with CKM syndrome stages 0-3, with a synergistic effect observed as CKM syndrome progresses. Highlighting the integration of mental health assessments into CKM risk stratification may enhance early intervention strategies and reduce CVD burden.

BACKGROUND:Restless sleep and loneliness are common in older adults and may contribute to cardiovascular disease (CVD) risk. However, the joint associations of these factors with incident CVD have not been fully elucidated. METHODS:The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative prospective cohort study initiated in 2011. The primary outcome was incident CVD, defined by self-reported physician diagnoses of heart disease or stroke during follow-up (2011-2018). Cox proportional hazard models were used to calculate hazard ratios (HRs) for CVD, adjusting for demographic, lifestyle, and health-related factors. RESULTS:Among 12,212 participants (mean [SD] age, 58.39 [9.34] years; 48.4 % men), 2353 (19.3 %) participants have both restless sleep and loneliness at baseline. During the 7 years of follow-up, 2323 experienced CVD. Restless sleep (hazard ratio [HR], 1.28; 95 % confidence interval [CI], 1.18-1.40) and loneliness (HR, 1.31; 95 % CI, 1.19-1.43) were independently associated with increased CVD risk. Participants with both restless sleep and loneliness had a 53.0 % higher risk of CVD (HR, 1.53; 95 % CI, 1.37-1.71) compared with those with neither. Synergistic interactions between restless sleep and loneliness on CVD were observed on both the multiplicative (HR, 1.36; 95 % CI, 1.20-1.54) and additive scales (synergy index [SI], 1.20; 95 % CI, 1.07-2.81). Similar results were observed for stroke and heart disease. CONCLUSIONS:The joint presence of restless sleep and loneliness increases CVD risk, suggesting that addressing both factors may help mitigate CVD risk in middle-aged and older adults.

BACKGROUND AND AIMS:Tertiary lymphoid structures (TLSs) may promote immune responses to HCC and thereby potentiate PD-1 inhibitor therapy; whether the structures are associated with a better prognosis for patients who receive adjuvant PD-1 inhibitors after curative hepatectomy is unclear. APPROACH AND RESULTS:We analyzed the prevalence and maturity of TLS in tumors, the associations of such structures with survival after hepatectomy that was followed or not by adjuvant PD-1 inhibitor therapy, and the associations of the structures with the extent and profile of immune cells infiltrating tumors. Of 195 patients in prospective cohort who underwent hepatectomy followed by adjuvant PD-1 inhibitor therapy, the tumors in 109 (56%) contained TLS, and those patients showed significantly better recurrence-free (HR 0.69, 95% CI 0.44-0.98) and overall survival (HR 0.57, 95% CI 0.33-0.98) than those whose tumors lacked such structures. A nomogram taking into account the presence of such structures predicted recurrence at 1, 2, or 3 years with areas >0.75 under the receiver operating characteristic curve. Tumors with TLS contained higher levels of CD3 + CD8 + PD-1 + T cells, PD-1 + natural killer T cells, B cells, and granzyme B + cells, but lower levels of regulatory T cells and macrophages than tumors without such structures. CONCLUSIONS:The TLS may be associated with significantly longer recurrence-free and overall survival. This association may reflect synergy between TLS and adjuvant PD-1 inhibitor therapy in activating antitumor immune responses within tumors.

BACKGROUND:Current guidelines for hepatocellular carcinoma (HCC) lack standardized adjuvant therapy recommendations, particularly for patients with high-risk of recurrence after curative resection. This multicenter retrospective study aimed to evaluate the efficacy and safety of adjuvant sintilimab (a programmed death protein-1 inhibitor) in this underserved population. METHODS:Patients with high-risk recurrence factors after curative resection were enrolled from five medical centers. All patients received sintilimab (200 mg), with or without tyrosine kinase inhibitors (TKIs). The primary endpoint was recurrence-free survival (RFS), with secondary endpoints including overall survival (OS). RESULTS:A total of 101 patients were included. The median RFS was 32.1 months [95% confidence interval (CI): 12.9-51.1], with 1-, 2-, and 3-year RFS rates of 73.1, 58.3, and 49.4%, respectively. Median OS was not reached, with 1-, 2-, and 3-year OS rates of 90.1, 83.0, and 76.2%, respectively. No significant differences in RFS (hazard ratio: 0.75, 95% CI: 0.40-1.40) or OS (hazard ratio: 0.65, 95% CI: 0.26-1.62) were observed between patients with ( n  = 34; 33.7%) or without TKIs ( n  = 67; 66.3%). In addition, no significant difference in RFS (hazard ratio: 0.97, 95% CI: 0.50-1.86) or OS (hazard ratio: 0.54, 95% CI: 0.19-1.53) was found between patients receiving adjuvant therapy for up to 6 months versus longer than 6 months. CONCLUSION:These findings support the potential of 6 months sintilimab monotherapy or in combination with TKIs as an effective adjuvant therapy for patients with HCC at high risk of recurrence. Further large-scale randomized controlled trials should be warranted.

Pre-diabetes, pre-hypertension, and pre-dyslipidemia are early metabolic abnormalities associated with cardiovascular disease (CVD), but their joint effects on CVD and metabolic disease progression remain unclear. This study examines their joint associations and interactions on CVD and progression to diabetes, hypertension, and dyslipidemia in Chinese adults aged ≥ 45 years. A prospective cohort of 3405 adults (mean age 57.07 years, 49.9

BackgroundObesity is a major global health issue, driving high morbidity and mortality rates. The body roundness index (BRI), which includes waist circumference, offers a more accurate measure of visceral and total body fat. However, despite evidence of BRI's effectiveness in predicting obesity-related diseases, national-level data, especially from non-Western populations like China, remain limited.MethodsThis study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a large, nationally representative cohort of Chinese adults, to examine the temporal trends of BRI, identify associated risk factors, and investigate the longitudinal associations between BRI and cardiovascular disease (CVD) outcomes. BRI was calculated using height and waist circumference measurements. Temporal trends and risk factors were analyzed cross-sectionally, while longitudinal associations were examined using Cox proportional hazards models adjusted for confounders. Mediation analyses were conducted to assess the role of intermediate factors such as hypertension and diabetes in the relationship between BRI and CVD.ResultsA total of 12,902 participants were included for risk factor analysis, 10,525 for longitudinal analysis, and 7,310 for cumulative analysis. BRI continued to rise slowly across survey cycles but was higher in women, older adults, and urban residents. Multivariable analysis identified age, alcohol consumption, elevated blood pressure, and diabetes as positive predictors of BRI, while male sex, rural residence, and smoking were negatively associated. Higher baseline BRI was significantly associated with increased CVD risk (HR: 1.44, 95% CI: 1.22–1.69), stroke (HR: 1.49, 95% CI: 1.12–1.98), and heart disease (HR: 1.47, 95% CI: 1.22–1.77). Cumulative BRI similarly predicted increased risks of CVD, stroke, and heart disease. Mediation analysis showed that hypertension accounted for 20.69% of the association between BRI and CVD risk.ConclusionsBRI is a robust predictor of CVD risk. Targeting hypertension and other metabolic conditions could mitigate the elevated CVD risk associated with high BRI in Chinese adults. These findings underscore the importance of incorporating BRI into public health strategies to better manage obesity-related health risks in China.

Background: This study examined the association between specific depressive symptoms and incident diabetes, and whether overweight or obesity mediates this relationship among middle-aged and older adults in China. Methods: In a nationally representative prospective cohort study of 11,893 middle-aged and older Chinese adults without baseline diabetes, we used Cox models to assess the association between depressive symptoms and diabetes. The quantile g-computation (qgcomp) model evaluated the contribution of 10 specific depressive symptoms to diabetes risk, and a two-stage regression method explored the mediation effect of overweight or obesity. Results: Over a median follow-up of 7.1 years, 1,314 cases of diabetes were identified. Elevated depressive symptoms were associated with increased diabetes risk (HR 1.23; 95 % CI 1.09-1.38). Eight out of 10 depressive symptoms were significantly associated to diabetes, with loneliness (weight = 18 %; HR 1.23; 95 % CI 1.10-1.39), restless sleep (weight = 17 %; HR 1.16; 95 % CI 1.04-1.29), and bother (weight = 15 %; HR 1.19; 95 % CI 1.07-1.33) being the primary contributors. Mediation analysis showed that overweight and obesity reduced the depression-diabetes risk association by 8.21 % and 12.61 %, respectively. Limitations: Diagnosis of diabetes was self-reported. Conclusions: Eight out of ten specific depressive symptoms were associated to diabetes, overweight and obesity may partially mitigate the effect of depressive symptoms on diabetes among middle-aged and older adults in China. Clinical implications: Our results highlight the importance of tailoring diabetes prevention and management strategies according to specific depressive symptoms among middle-aged and older adults in China.

To identify the classes of sleep quality trajectories in patients with hepatocellular carcinoma (HCC) and analyze differences in patient characteristics across these classes and to explore the relationship between sleep quality trajectory and quality of life (QOL) in patients. A total of 205 patients completed sleep quality assessments at four time points (before surgery and 1, 3, and 6 months after surgery). Classes of heterogeneous sleep quality trajectories were identified using a latent class mixed-effects model. The differences in the characteristics of patients across classes were identified by unordered multicategorical logistic regression. The relationship between sleep quality trajectory and QOL was assessed using a generalized estimation equation model. Three latent classes of sleep quality trajectories were identified in HCC patients: persistent good sleep (19.5

Backgroud Although both the atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hs-CRP) are recognized as risk markers for stroke, their combined effect has yet to be fully understood. To address this gap, we introduced the inflammatory atherogenic index (IAI), a composite measure incorporating AIP and hs-CRP, and investigated its potential in predicting stroke ris Methods We analyzed data from the China Health and Retirement Longitudinal Study (CHARLS). IAI was calculated using the formula: IAI = AIP × hs-CRP / 10. Cox proportional hazard models were used to estimate stroke risk associated with IAI. Mediation analysis using VanderWeele’s method evaluated the mediating role of systolic and diastolic blood pressures. Results The study included 9,687 participants with a mean baseline age of 58.66 years (SD = 9.23), of whom 4,542 (46.9%) were male. Over the 7-year follow-up period, 662 incident stroke cases (6.8%) were recorded. After adjusting for all covariates, each standard deviation (SD) increase in the inflammatory atherogenic index (IAI) was linked to an 11.0% higher stroke risk (HR = 1.11, 95% CI: 1.03–1.19). A nonlinear, inverted U-shaped relationship between IAI and stroke risk was observed (P = 0.015). Mediation analysis showed that systolic and diastolic blood pressures mediated 19.64% and 25.79% of the IAI-stroke association. Hs-CRP and AIP also interacted synergistically to increase stroke risk (synergy index = 1.35, 95% CI: 1.03–1.76). Conclusions IAI is associated with increased stroke risk, with mediation by blood pressure. This highlights the potential of IAI as a biomarker for stroke risk, with early intervention in patients with high IAI potentially reducing stroke risk.

Introduction:Uncertainty exists regarding whether hepatectomy enhances the prognosis for initially unresectable hepatocellular carcinoma (HCC) that becomes resectable subsequent to conversion therapy. This study conducted a comparative analysis of survival rates between patients who underwent hepatectomy and those who did not, following complete or partial response to conversion therapy. Methods:This retrospective study examined 300 patients with HCC who underwent hepatectomy following conversion therapy, along with 265 nonsurgical control subjects (215 receiving locoregional/systemic therapy and 50 under active surveillance) across 20 Chinese medical centers from 2019 to 2023. The primary outcomes assessed included overall survival (OS), event-free survival (EFS), recurrence-free survival, and the rate of complete pathological response. Results:Hepatectomy was associated with significantly better OS than locoregional or systemic therapy or active surveillance (the 3-year OS rates were 79.9% and 58.5%, respectively, p < 0.001) but comparable EFS (median: 40.6 vs 33.4 months, p = 0.403). These results were confirmed after analyzing subgroups matched to each other based on propensity scoring. Among patients who underwent hepatectomy, those who responded completely to conversion therapy showed significantly better OS than those who responded partially (HR: 0.40, 95% CI: 0.21-0.75) as well as significantly better EFS (HR: 0.45, 95% CI: 0.29-0.70). Among patients who did not undergo hepatectomy, OS and EFS were comparable between those who responded partially and those who responded completely to conversion therapy. Additionally, locoregional or systemic therapy showed significantly better results in terms of OS and EFS compared to active surveillance. Of the patients who underwent hepatectomy, 116 (38.7%) showed complete pathological response. In patients underwent hepatectomy, those who experienced complete pathological response showed significantly better OS than those who did not (HR: 0.34, 95% CI: 0.18-0.65) as well as significantly better recurrence-free survival (HR: 0.38, 95% CI: 0.25-0.59). Conclusions:Hepatectomy can provide a significant OS benefit to patients with initially unresectable HCC that responds partially or completely to conversion therapy.

BACKGROUND:To examine sex-specific risks for cardiovascular disease across the specific depressive symptoms spectrum: a national prospective cohort in China. METHODS:Using data from the China Health and Retirement Longitudinal Study (CHARLS), involving 11,735 individuals aged 45 and older in China. Ten specific depressive symptoms, assessed at baseline using the CES-D short form. Cox proportional hazard models estimated hazard ratios (HRs) for each symptom's association with CVD. RESULTS:During the 7 years of follow-up, 1246 (20.8 %) incident CVD cases were identified among women, compared to 985 (17.1 %) among men. All ten specific depressive symptoms exhibited a higher incidence in women than in men. Nine of these symptoms were associated with an increased risk of CVD in both sexes. Restless sleep was more strongly associated with CVD in women (HR, 1.44; 95 % CI, 1.28-1.62) than in men (HR, 1.18; 95 % CI, 1.04-1.34) at baseline (P = 0.013 for interaction), whereas the HRs for other specific depressive symptoms were similar among women and men. Loneliness was the most important symptom for CVD risk in men, while restless sleep was the most significant for women. CONCLUSIONS:Nine of 10 specific depressive symptoms may increase the risk of CVD in Chinese adults, regardless of gender. Notably, the association between restless sleep and CVD was strong in women, while loneliness showed a stronger association with CVD in men. These findings highlight the importance of considering specific depressive symptoms in assessing CVD risk among middle-aged and older adults, particularly across sexes.

Background Depression is prevalent among individuals with cancer. This prospective cohort study aims to examine the relationships between depressive symptoms and both quality of life (QoL) and treatment efficacy in patients with intermediate or advanced hepatocellular carcinoma (HCC) who are receiving immunotherapy. Methods A cohort of 156 patients with intermediate or advanced HCC who were receiving immunotherapy was included in the analysis. Depressive symptoms were evaluated utilizing the Patient Health Questionnaire-9 (PHQ-9). The primary outcome was progression-free survival (PFS), whereas the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and QoL. Results Nearly half (48.7%) of the patients exhibited depressive symptoms. Over a median follow-up period of 10 months, patients with depressive symptoms had significantly lower PFS (HR 4.31, 95% CI: 2.75–6.76) and significantly shorter OS (HR 5.39, 95% CI: 1.84–15.82). Furthermore, the ORR and DCR were notably lower in patients with depressive symptoms (ORR 10.5% compared with 37.5%; DCR 52.6% compared with 91.2%). QoL scores were significantly lower at all assessed time points for patients with depressive symptoms, indicating worse overall well-being. Conclusions Depression is significantly associated with the efficacy of immunotherapy in HCC patients and is negatively associated with both clinical outcomes and QoL. Addressing mental health is essential for optimizing treatment strategies and improving overall patient outcomes in this population.

Background:Body mass index (BMI) consistently correlates with the triglyceride-glucose (TyG) index, a marker of insulin resistance, which in turn is linked to heightened cardiovascular disease (CVD) risk. Thus, insulin resistance could potentially mediate the association between BMI and CVD risk. However, few studies have explored this mechanism in the general population. Methods:We used data from the China Health and Retirement Longitudinal Study, which is an ongoing prospective cohort study. It initially enrolled 7233 middle-aged and older Chinese adults who were free of heart disease and stroke at baseline. The exposure variable was BMI. Incident CVD, defined as self-reported physician-diagnosed heart disease and stroke combined, served as the main outcome. Results:Of the 7 233 participants (mean [SD] age, 58.93 [9.33] years), 3 415 (47.2%) were men. During the 7 years of follow-up, 1 411 incident CVD cases were identified. Both BMI and TyG index were associated with CVD risk (HR per 1-SD increase: BMI, 1.23; 95% CI, 1.17-1.29; TyG, 1.13; 95% CI, 1.07-1.19). The 4-way decomposition analysis show that, overweight increased CVD risk by 28% (HR [total association], 1.28; 95% CI, 1.14-1.45), with 18.1% (95% CI, 2.2%-34.0%) mediated by TyG index (HR [pure indirect association], 1.05; 95% CI, 1.02-1.09); while obesity increased CVD risk by 91% (HR [total association], 1.91; 95% CI, 1.63-2.23), with 9.5% (95% CI, 2.2%-16.7%) mediated by TyG index (HR [pure indirect association], 1.09; 95% CI, 1.03-1.15). No evidence suggested TyG index modified BMI's association with incident CVD. Conclusions:The study revealed that the TyG index was associated to CVD risk and acted as a small partial mediator in the relationship between BMI and CVD among middle-aged and older Chinese adults. Consequently, solely addressing insulin resistance might not significantly mitigate the impact of body weight on CVD. Thus, exploring alternative pathways and potential mediators of CVD risk becomes imperative.

Background The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. Methods This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. Results Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). Conclusion The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.