Association between the cholesterol-high-density lipoprotein-glucose index and new-onset stroke in middle-aged and older adults with depressive symptoms: a longitudinal cohort analysis.
Among middle‑aged and older Chinese adults with depressive symptoms, the CHG index shows a significant non-linear positive association with the risk of new-onset stroke, and the risk increases sharply when the index is below 5.59, a potential indicator for the early risk of stroke in this high-risk population.
Abstract
Background
Depression is a global disease that significantly increases the risk of stroke. The cholesterol, high-density lipoprotein, and glucose index (CHG index) as an emerging composite metabolic marker has shown value in cardiovascular diseases and diabetes, but its predictive role in new-onset stroke among depressed individuals remains unclear.
Methods
This study is based on the data from the Chinese Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 5,138 participants aged 45 and above, who had depressive symptoms (CES-D score ≥ 10) at the baseline and had no history of stroke, were included. Sequential Cox proportional hazards regression models were used as the main analysis to evaluate the association between the CHG index and new-onset stroke, and multivariable logistic regression was used as a secondary analysis to verify the consistency of the direction. Multiple imputation (20 datasets) was used to handle missing values of covariates. Restricted cubic splines and two-stage Cox regression models were used to explore potential nonlinear relationships and threshold effects.
Results
During a total follow-up period of 35,554 person-years (with a median follow-up of 7 years), a total of 421 new-onset stroke events occurred. In the fully adjusted Cox model, for every 1-unit increase in the CHG index, the risk of new-onset stroke increased by 48% (HR = 1.48, 95% CI: 1.15-1.90, P = 0.003). However, the restricted cubic spline analysis revealed a significant non-linear relationship (D1 test P = 0.005), with the inflection point occurring at a CHG index of 5.59. When the CHG index was below 5.59, for every 1-unit increase, the risk of stroke increased by 117% (HR = 2.17, 95% CI: 1.37-3.44, P = 0.001); above this inflection point, no statistically significant association was observed (HR = 1.00, 95% CI: 0.62-1.62, P = 0.996). Multivariable logistic regression yielded a consistent significant association (OR = 1.53, 95% CI: 1.16-2.03, P = 0.003). Subgroup analysis and multiple sensitivity analyses (quartile analysis, exclusion of early stroke events, median binary classification analysis) all supported the robustness of the main findings.
Conclusion
Among middle‑aged and older Chinese adults with depressive symptoms, the CHG index shows a significant non-linear positive association with the risk of new-onset stroke, and the risk increases sharply when the index is below 5.59. The CHG index may serve as a potential indicator for the early risk of stroke in this high-risk population.
The global health burden of diabetes continues to grow. While the Chinese Visceral Adiposity Index (CVAI) and low-density lipoprotein cholesterol (LDL-C) are well-established risk factors for diabetes, the potential compounding effect of these factors is not well characterized. This study aimed to explore the relationship between a novel integrative index, the Visceral Lipoprotein Risk (VLR) index, and incident diabetes.
This prospective cohort study included 7,559 participants aged ≥ 45 years without diabetes at baseline from the China Health and Retirement Longitudinal Study (CHARLS). The VLR index was calculated as the product of the CVAI and LDL-C (mg/dL). The association between the VLR index and incident diabetes was evaluated using Kaplan-Meier analysis, multivariable Cox proportional hazards models, and restricted cubic splines (RCS). Subgroup analyses were performed to test the robustness of our findings.
Over a median follow-up of 9 years, 1,264 incident diabetes cases (16.7%) were documented. The incidence of diabetes showed a marked gradient across increasing VLR tertiles (T1: 11.7% vs. T3: 23.8%). After multivariable adjustment, each standard deviation (SD) increase in the VLR index was associated with a significantly higher risk of diabetes (HR: 1.30; 95% CI: 1.24–1.37), The association remained significant in both the prediabetes subgroup (HR: 1.24; 95% CI: 1.16–1.32) and the normoglycemic subgroup (HR: 1.25; 95% CI: 1.16–1.35). These findings remained robust across various subgroup analyses. Furthermore, RCS analysis demonstrated a non-linear positive association between the VLR index and incident diabetes.
This study provides robust evidence linking the novel VLR index to an increased risk of diabetes among middle-aged and older adults. These findings suggest that the VLR index is independently associated with incident diabetes and may hold promise for risk stratification.
Jingpei Dong, Fan Yang, Lei Luo et al.· Diabetology & Metabolic...· 0 citations
The cholesterol, high-density lipoprotein, and glucose (CHG) index has been linked to stroke risk. However, evidence is largely based on single-time-point measurements and has not been compared with cumulative exposure, nor evaluated in individuals with cardiovascular-kidney-metabolic syndrome (CKM) stages 0–3. This study aimed to compare the associations of baseline and cumulative CHG index with incident stroke risk in this population. Data were derived from the China Health and Retirement Longitudinal Study (CHARLS). The exposure measures were the baseline and cumulative levels of the CHG index. Multivariable logistic regression models were employed to examine the association between the baseline and cumulative CHG index and stroke risk. Restricted cubic spline (RCS) analysis was used to test potential dose-response relationships. The receiver operating characteristic (ROC) curve was used to compare the predictive performance of the two measures. Subgroup analyses were conducted to evaluate the consistency of these associations in different populations. Among 4,661 participants with CKM stages 0–3, 476 (10.2%) developed incident stroke during follow-up. After adjustment for demographic characteristics, lifestyle factors, anthropometric measurement, laboratory parameters, medication use and comorbidities, both the baseline CHG index (OR = 1.42, 95% CI: 1.12–1.81) and cumulative CHG index (OR = 1.14, 95% CI: 1.03–1.26) were positively associated with stroke risk. Participants in the highest tertile (T3) of the baseline CHG index had a 35% higher stroke risk than those in the lowest tertile (T1) (OR = 1.35, 95% CI: 1.03–1.76), and a 34% elevated risk was observed for the cumulative CHG index (OR = 1.34, 95% CI: 1.03–1.76). RCS analysis revealed linear relationships for both measures (p for non-linear = 0.331 and 0.817, respectively; overall p < 0.05 for both). ROC curve analysis showed no statistically significant difference in the area under the curve (AUC) between the two measures (0.672 vs. 0.671, p = 0.330). Subgroup analyses indicated that the associations might be modified by gender and drinking status. Among individuals with CKM stages 0–3, both baseline and cumulative CHG indices were independently associated with incident stroke risk. Given its moderate discriminatory capacity, the CHG index—derived from routine blood tests—may serve as a preliminary screening tool to flag high-risk individuals, prompting more comprehensive stroke risk evaluation.
Chen Chen, Xiao Yang, Cheng Li et al.· Cardiovascular Diabetology· 0 citations
BACKGROUND
Early-stage cardiovascular-kidney-metabolic (CKM) syndrome, encompassing stages 0-3, represents a critical window for identifying individuals at risk before the development of clinical cardiovascular disease (CVD). Metabolic dysregulation and frailty-related physiological vulnerability may jointly contribute to cardiovascular susceptibility in middle-aged and older adults. However, conventional single-domain markers may not adequately capture this combined risk burden. This study aimed to evaluate the association and predictive utility of the combined cholesterol, high-density lipoprotein, glucose index and frailty index (CHG-FI) for new-onset CVD, heart disease, and stroke among individuals with early-stage CKM syndrome.
METHODS
This cohort study used longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 4,603 participants with CKM stages 0-3. New-onset CVD, defined as the occurrence of heart disease or stroke during follow-up, was the primary outcome; new-onset heart disease and stroke were analyzed separately as secondary outcomes. CHG-FI was calculated as the product of the cholesterol, high-density lipoprotein, glucose (CHG) index and frailty index (FI). Multivariable Cox proportional hazards models were used to assess the associations of CHG-FI with new-onset cardiovascular outcomes. Restricted cubic splines were applied to examine nonlinear dose-response relationships. Joint-exposure analyses were used to characterize CVD risk across combined CHG and FI categories, and multiplicative and additive interaction analyses were performed to assess whether CHG and FI interacted in relation to new-onset CVD. Predictive performance was compared with CHG, FI, triglyceride-glucose index (TyG), atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR) using receiver operating characteristic curves, DeLong tests, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Formal incremental modeling was further performed by separately adding CHG-FI and comparator indices to the fully adjusted base model.
RESULTS
During a median follow-up of 9 years, 1,189 participants (25.8%) developed new-onset CVD. In fully adjusted models, each one-unit increase in CHG-FI was associated with higher risks of new-onset heart disease (HR = 1.59; 95% CI 1.42-1.77), stroke (HR = 1.56; 95% CI 1.32-1.83), and composite CVD (HR = 1.56; 95% CI 1.41-1.72). Participants in the highest CHG-FI quartile had more than two-fold higher risks of all cardiovascular outcomes compared with those in the lowest quartile. Restricted cubic spline analyses showed nonlinear associations, with cardiovascular risk increasing more steeply across lower to moderate CHG-FI levels. In joint-exposure analyses, participants with both high CHG and high FI had the highest risk of new-onset CVD (HR = 2.05; 95% CI 1.71-2.47); however, no statistically significant multiplicative or additive interaction was observed. CHG-FI showed the highest AUCs for new-onset CVD (0.624) and heart disease (0.622) among the evaluated indices and statistically outperformed CHG, FI, TyG, AIP, and METS-IR for both outcomes; however, the absolute discriminative performance was modest. For new-onset CVD, CHG-FI showed statistically significant reclassification improvements compared with CHG, TyG, AIP, and METS-IR, with NRI values of 13.85%, 9.16%, 11.02%, and 20.90%, respectively, and yielded small but statistically significant IDI improvements ranging from 0.20 to 0.48% compared with all reference indices. In formal incremental models, adding CHG-FI to the fully adjusted base model provided statistically significant but limited improvement, with only small absolute gains over FI alone.
CONCLUSIONS
Higher CHG-FI was independently associated with increased risks of new-onset CVD, heart disease, and stroke among middle-aged and older adults with early-stage CKM syndrome. Participants with both high CHG and high FI had the greatest risk of new-onset CVD, although this pattern did not reflect a statistically significant multiplicative or additive interaction. CHG-FI showed statistically significant but modest discriminative performance, and the incremental improvements beyond comparator indices and clinical covariates were limited in magnitude. These findings suggest that CHG-FI may serve as a complementary marker reflecting integrated glucose-lipid metabolic dysregulation and frailty-related vulnerability, but it should not be considered a standalone clinical prediction tool and requires further validation before clinical application.
Background The present study aims to investigate the association and dose-response relationship between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and sarcopenia in elderly adults. The ultimate objective is to thereby clarify its predictive value for sarcopenia risk. Methods A cross-sectional study was conducted using data from the cohort of 368 elderly individuals aged 60 years and over, as part of the Second Affiliated Hospital of Anhui Medical University. A prospective cohort study was also conducted using CHARLS data, encompassing 3,152 elderly individuals aged 60 years and over, with no instances of sarcopenia at the initial baseline. The median follow-up period for this study is 4.5 years. The association was analyzed using both logistic regression and Cox proportional hazards regression, with the results of this analysis subsequently validated by restricted cubic spline (RCS) analysis and subgroup analysis. Subsequently, the mediating role of the triglyceride glucose (TyG)-related indices was elucidated through mediation analysis. Results Following the adjustment of confounding factors, a unit increase in NHHR was observed to be associated with a 31% reduction in sarcopenia risk in cross-sectional studies (OR = 0.69, 95% CI: 0.56–0.86, P < 0.001). In prospective cohort studies, the risk of sarcopenia decreased by 37% (HR = 0.63, 95% CI: 0.51–0.77, P < 0.001). A stable linear inverse relationship was observed between the two variables, with no threshold effect, and subgroup analyses validated the robustness of this association. Additionally, the TyG-related indices exerted a significant mediating effect on the association between NHHR and sarcopenia risk, with a mediation proportion ranging from 22.48 to 29.47%. Conclusion NHHR is significantly negatively correlated with the risk of sarcopenia in Chinese elderly adults and may serve as a potential biomarker for sarcopenia risk stratification. TyG-related indicators play a partial mediating role in this association.
Ping Zhang, Mengmeng Zheng, Yue Wang et al.· Frontiers in Nutrition· 0 citations
BACKGROUND
Depression is a common mental health issue among older adults, yet few studies have explored whether metabolic biomarkers predicting its onset exist. The CRP-TyG index (CTI), combining C-reactive protein and the triglyceride-glucose index, may more effectively capture inflammatory-metabolic dysregulation than either marker alone. However, prospective evidence on the relationship between CTI and depression in aging populations is limited.
METHODS
We analyzed data from 2,813 depression-free participants aged ≥ 50 years in ELSA, with follow-up through Wave 8. Baseline CTI was assessed from fasting blood biomarkers, and depressive symptoms were evaluated using the CES-D-8 scale. Cox proportional hazards models were used to estimate hazard ratios (HRs). To assess the potential influence of missing data, multiple-imputation analyses were additionally performed as sensitivity analyses.
RESULTS
During follow-up, 136 participants developed incident depressive symptoms. After full adjustment including BMI, each 1-SD increase in CTI was associated with a higher risk of incident depressive symptoms (HR = 1.253; 95% CI: 1.002-1.479; p = 0.035). Multiple-imputation sensitivity analyses yielded directionally consistent results.
CONCLUSION
In this nationally representative cohort of adults aged 50 years and older in England, higher baseline CTI was prospectively associated with an increased risk of incident depressive symptoms. CTI may serve as a scalable biomarker for identifying older adults at elevated risk of depressive symptoms.
Mixue Guo, Mengyuan Cai, Huqiang Dong et al.· Annals of General Psychiatry· 0 citations
Background The cholesterol, high‐density lipoprotein, and glucose (CHG) index and circadian syndrome (CircS) are potential contributors for cardiovascular disease (CVD). This study evaluated their independent, combined associations, and interactions with CVD risk. Methods The study included participants aged ≥ 45 years without baseline CVD. Participants were classified according to the median or quartile levels of the CHG index and the binary status of CircS. Univariate and multivariate Cox regression models, along with Fine–Gray competing risk models assessed individual and joint effects. Both additive and multiplicative interactions were evaluated. Restricted cubic spline (RCS) analyses were conducted to visualize the dose–response relationship between the CHG index and CVD risk. Receiver operating characteristic (ROC) curve analyses assessed the predictive performance with the SCORE2 Asia‐Pacific model for CVD at multiple time points. Results Among 6739 eligible participants, 1420 (21.1%) participants developed CVD during follow‐up. Both higher CHG index and CircS were independently associated with increased CVD risk. Compared with low CHG index and no CircS, participants with high CHG index and CircS had higher CVD risk (hazard ratio (HR)): 1.67, 95% confidence interval (CI): 1.46–1.90). No significant additive or multiplicative interactions were observed, but the significant ones were identified in external validation ELSA cohort. Integrating CHG index and CircS modestly improved SCORE2 Asia‐Pacific model predictions, especially for 5‐, 7‐, and 9‐year long‐term CVD risk. Conclusions Elevated CHG index and CircS independently associated with a higher risk of CVD. Significant interactions were identified, incorporating them into the SCORE2 Asia‐Pacific model modestly enhances long‐term CVD risk prediction. These readily measurable markers may therefore be applied to earlier identify high‐risk individuals, enabling more targeted CVD prevention strategies and optimize risk management in clinical practice.