Predictive value of the combined cholesterol, high-density lipoprotein, glucose and frailty indices for cardiometabolic multimorbidity incidence: evidence from a national prospective cohort study
5 affiliations
- 1Department of Pharmacy, Foshan University Affiliated Third Hospital, Foshan, Guangdong, China
- 2Department of Pulmonary and Critical Care Medicine, Northeast Yunnan Central Hospital, Northeast Yunnan Hospital of Kunming Medical University, Northeast Yunnan Clinical School of Kunming Medical University, Zhaotong, 657000, Yunnan, China
- 3Kunming Medical University, Kunming, 650500, Yunnan, China
- 4Department of cardiovascular medicine, Foshan University Affiliated Third Hospital, Foshan, Guangdong, China
- 5School of Artificial Intelligence, South China Normal University, Guangzhou, Guangdong, China. [email protected]
Abstract
BACKGROUND: The cholesterol, high-density lipoprotein, and glucose (CHG) is a surrogate of insulin resistance, while frailty reflects cumulative physiological decline, yet their combined utility for cardiometabolic multimorbidity (CMM) is underexplored. We evaluated a combined CHG-frailty index (CHG-FI) for incident heart disease, stroke, diabetes, and CMM. METHODS: We conducted a retrospective cohort study of 6812 Chinese adults aged ≥ 45 years enrolled in the 2011-2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). Participants with baseline lipid and fasting glucose measurements were included and followed prospectively for incident heart disease, stroke, diabetes, and cardiometabolic multimorbidity (≥ 2 conditions). FI was calculated using the cumulative deficit approach, and CHG was incorporated according to established procedures. Multivariable Cox regression estimated associations; CHG-FI interaction was assessed on multiplicative and additive scales. Incremental predictive utility of CHG, FI, TYG‑FI, and CHG‑FI was compared using receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and decision curve analysis (DCA). Stratified and sensitivity analyses evaluated robustness. RESULTS: Over a median follow‑up of 9.0 years, we observed 1,304 heart disease events, 554 strokes, 932 diabetes cases, and 467 CMM cases. Each 1-unit increase in CHG-FI was associated with higher risk: heart disease (HR 1.34, 95% CI 1.23-1.45), stroke (HR 1.85, 95% CI 1.65-2.06), diabetes (HR 1.29, 95% CI 1.17-1.42), and CMM (HR 1.79, 95% CI 1.58-2.04). Associations showed dose-response patterns and nonlinearity. The multiplicative interaction between CHG and FI for CMM was 0.54 (95% CI 0.35-0.83), reflecting a "risk saturation" or ceiling effect. Despite this, the combined CHG -FI index offered superior predictive performance for CMM relative to individual components: AUC 0.652 (95% CI 0.627-0.678), with significant improvement in reclassification (NRI 0.329, 95% CI 0.236-0.423) and discrimination (IDI 0.011, 95% CI 0.008-0.015). CHG -FI and TyG -FI showed broadly comparable performance across outcomes. CONCLUSION: The combined CHG-frailty index was significantly associated with incident cardiometabolic multimorbidity and its individual components, demonstrating predictive performance comparable to established combined indices. As an accessible tool integrating routine metabolic and physiologic reserve measures, CHG-FI offers a practical alternative approach for risk stratification.
Related
- 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.
- Ultra-processed food indices and component food groups in relation to incident type 2 diabetes and cardiometabolic multimorbidity: a prospective cohort study
- Small dense low-density lipoprotein cholesterol and risk of cardiovascular events in general adults: a systematic review and meta-analysis of prospective studies.
- Associations of high-density lipoprotein cholesterol concentration and particle count with mortality: a prospective study of 50,000 men and 100,000 women
- Triglyceride–HDL cholesterol–glucose body index and cardiometabolic multimorbidity: evidence from a national longitudinal cohort and a subplateau health-screening population
BibTeX
@article{fan2026predictive,
title = {{Predictive value of the combined cholesterol, high-density lipoprotein, glucose and frailty indices for cardiometabolic multimorbidity incidence: evidence from a national prospective cohort study}},
author = {Huanqiong Fan and Guosong Jiang and Jun Cheng and Hengfa Chen},
journal = {Cardiovascular Diabetology},
year = {2026},
month = may,
doi = {10.1186/s12933-026-03213-0},
url = {https://doi.org/10.1186/s12933-026-03213-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - Predictive value of the combined cholesterol, high-density lipoprotein, glucose and frailty indices for cardiometabolic multimorbidity incidence: evidence from a national prospective cohort study
AU - Huanqiong Fan
AU - Guosong Jiang
AU - Jun Cheng
AU - Hengfa Chen
PY - 2026
DA - 2026/05/17
JO - Cardiovascular Diabetology
DO - 10.1186/s12933-026-03213-0
UR - https://doi.org/10.1186/s12933-026-03213-0
AB - BACKGROUND: The cholesterol, high-density lipoprotein, and glucose (CHG) is a surrogate of insulin resistance, while frailty reflects cumulative physiological decline, yet their combined utility for cardiometabolic multimorbidity (CMM) is underexplored. We evaluated a combined CHG-frailty index (CHG-FI) for incident heart disease, stroke, diabetes, and CMM. METHODS: We conducted a retrospective cohort study of 6812 Chinese adults aged ≥ 45 years enrolled in the 2011-2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). Participants with baseline lipid and fasting glucose measurements were included and followed prospectively for incident heart disease, stroke, diabetes, and cardiometabolic multimorbidity (≥ 2 conditions). FI was calculated using the cumulative deficit approach, and CHG was incorporated according to established procedures. Multivariable Cox regression estimated associations; CHG-FI interaction was assessed on multiplicative and additive scales. Incremental predictive utility of CHG, FI, TYG‑FI, and CHG‑FI was compared using receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and decision curve analysis (DCA). Stratified and sensitivity analyses evaluated robustness. RESULTS: Over a median follow‑up of 9.0 years, we observed 1,304 heart disease events, 554 strokes, 932 diabetes cases, and 467 CMM cases. Each 1-unit increase in CHG-FI was associated with higher risk: heart disease (HR 1.34, 95% CI 1.23-1.45), stroke (HR 1.85, 95% CI 1.65-2.06), diabetes (HR 1.29, 95% CI 1.17-1.42), and CMM (HR 1.79, 95% CI 1.58-2.04). Associations showed dose-response patterns and nonlinearity. The multiplicative interaction between CHG and FI for CMM was 0.54 (95% CI 0.35-0.83), reflecting a "risk saturation" or ceiling effect. Despite this, the combined CHG -FI index offered superior predictive performance for CMM relative to individual components: AUC 0.652 (95% CI 0.627-0.678), with significant improvement in reclassification (NRI 0.329, 95% CI 0.236-0.423) and discrimination (IDI 0.011, 95% CI 0.008-0.015). CHG -FI and TyG -FI showed broadly comparable performance across outcomes. CONCLUSION: The combined CHG-frailty index was significantly associated with incident cardiometabolic multimorbidity and its individual components, demonstrating predictive performance comparable to established combined indices. As an accessible tool integrating routine metabolic and physiologic reserve measures, CHG-FI offers a practical alternative approach for risk stratification.
SN - 1475-2840
ER -