The cholesterol, high-density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new-onset cardiovascular-liver-metabolic multimorbidity: A prospective cohort study.
5 affiliations
- 1Medical School of Nanjing University, Nanjing, China.
- 2Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
- 3Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
- 4Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- 5Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Abstract
Background
Cardiovascular-liver-metabolic multimorbidity (CLMM), defined as the co-occurrence of at least two of cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, is an increasing health burden. We evaluated the cholesterol, high-density lipoprotein, and glucose (CHG) index and its obesity- and inflammation-derived variants for predicting incident CLMM.Methods
This prospective cohort included 6,534 adults aged ≥45 years from the China Health and Retirement Longitudinal Study. CHG, eight obesity-derived indices, and CHG-CRP were assessed, with the triglyceride-glucose index and TG/HDL-C ratio as comparators. Associations with incident CLMM were evaluated using logistic regression, restricted cubic splines, and threshold analysis. Predictive performance was compared using receiver operating characteristic analysis, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI), with additional joint-effect, interaction, subgroup, and sensitivity analyses.Results
At the 2015 follow-up, 406 participants (6.2%) met the criteria for CLMM. Higher CHG was linearly associated with incident CLMM (highest vs lowest quartile: OR 1.64, 95% confidence interval [CI] 1.22-2.22). Obesity-derived variants showed stronger associations, particularly CHG-BMI (OR 3.13, 95% CI 2.21-4.43), which also had the highest discrimination (AUC 0.643, 95% CI 0.616-0.669) and continuous NRI (34.08%). Participants with both high CHG and high BMI had the greatest CLMM risk (OR 2.59, 95% CI 1.94-3.51). Results were robust in sensitivity analyses.Conclusions
The CHG index and its obesity-derived variants, particularly CHG-BMI, are accessible and inexpensive candidate metabolic markers for predicting new-onset CLMM. CHG-BMI showed the highest apparent discrimination among the evaluated indices, although its AUC was modest. External population validation is needed.
Related
- Small dense low-density lipoprotein cholesterol and risk of cardiovascular events in general adults: a systematic review and meta-analysis of prospective studies.
- Joint association of the cholesterol–high-density lipoprotein–glucose index and waist-to-height ratio with incident cardiovascular disease in a high-risk Chinese cohort
- Predictive value of the combined cholesterol, high-density lipoprotein, glucose and frailty indices for cardiometabolic multimorbidity incidence: evidence from a national prospective cohort study
- Isolated Low Levels of High-density Lipoprotein Cholesterol are Associated with an Increased Risk of Ischemic Cardiovascular Events: The Shizuoka Kokuho Database Study
- Combined Triglyceride–High-density Lipoprotein Cholesterol Phenotypes and Cardiovascular Outcomes in Japanese Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights from Clinical Deep Data Accumulation System-PCI
BibTeX
@article{sun2026cholesterol,
title = {{The cholesterol, high-density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new-onset cardiovascular-liver-metabolic multimorbidity: A prospective cohort study.}},
author = {Zhonghua Sun and Aikeliyaer Ainiwaer and Yameng Xu and Ge Zhang and Xiangyu Sun and Xinliang Peng and Yuanhui Dai and Kaisaierjiang Kadier},
journal = {Journal of diabetes investigation},
year = {2026},
month = oct,
doi = {10.1111/jdi.70462},
url = {https://europepmc.org/article/MED/42852842},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - The cholesterol, high-density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new-onset cardiovascular-liver-metabolic multimorbidity: A prospective cohort study.
AU - Zhonghua Sun
AU - Aikeliyaer Ainiwaer
AU - Yameng Xu
AU - Ge Zhang
AU - Xiangyu Sun
AU - Xinliang Peng
AU - Yuanhui Dai
AU - Kaisaierjiang Kadier
PY - 2026
DA - 2026/10/09
JO - Journal of diabetes investigation
DO - 10.1111/jdi.70462
UR - https://europepmc.org/article/MED/42852842
AB - Background Cardiovascular-liver-metabolic multimorbidity (CLMM), defined as the co-occurrence of at least two of cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, is an increasing health burden. We evaluated the cholesterol, high-density lipoprotein, and glucose (CHG) index and its obesity- and inflammation-derived variants for predicting incident CLMM.Methods This prospective cohort included 6,534 adults aged ≥45 years from the China Health and Retirement Longitudinal Study. CHG, eight obesity-derived indices, and CHG-CRP were assessed, with the triglyceride-glucose index and TG/HDL-C ratio as comparators. Associations with incident CLMM were evaluated using logistic regression, restricted cubic splines, and threshold analysis. Predictive performance was compared using receiver operating characteristic analysis, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI), with additional joint-effect, interaction, subgroup, and sensitivity analyses.Results At the 2015 follow-up, 406 participants (6.2%) met the criteria for CLMM. Higher CHG was linearly associated with incident CLMM (highest vs lowest quartile: OR 1.64, 95% confidence interval [CI] 1.22-2.22). Obesity-derived variants showed stronger associations, particularly CHG-BMI (OR 3.13, 95% CI 2.21-4.43), which also had the highest discrimination (AUC 0.643, 95% CI 0.616-0.669) and continuous NRI (34.08%). Participants with both high CHG and high BMI had the greatest CLMM risk (OR 2.59, 95% CI 1.94-3.51). Results were robust in sensitivity analyses.Conclusions The CHG index and its obesity-derived variants, particularly CHG-BMI, are accessible and inexpensive candidate metabolic markers for predicting new-onset CLMM. CHG-BMI showed the highest apparent discrimination among the evaluated indices, although its AUC was modest. External population validation is needed.
SN - 2040-1116
SN - 2040-1124
ER -