Combined associations of the frailty index and CHG index with cardiometabolic multimorbidity: a longitudinal study from the CHARLS cohort

Introduction: Frailty and metabolic dysfunction are major contributors to cardiometabolic multimorbidity (CMM). However, the joint influence of frailty and insulin resistance on the onset of CMM is still insufficiently understood. This research aimed to examine the association between FI-CHG [a novel integrative metric combining the frailty index (FI) and the cholesterol-high-density lipoprotein-glucose (CHG) index] and incident CMM. Method: Overall, 8,543 participants aged ≥45 years without CMM at baseline from the China Health and Retirement Longitudinal Study (CHARLS) were recruited. Multivariable Cox regression models were utilized to assess the relationships between baseline FI-CHG levels and cumulative FI-CHG exposure during follow-up with the incidence of CMM. Restricted cubic spline analyses were applied to investigate potential dose-response relationships, while subgroup analyses were implemented to examine possible effect modification. Result: During a maximum follow-up of 8.0 years, CMM occurred in 1,666 participants (19.5%). The risk of CMM increased progressively across higher quartiles of the FI-CHG index. In receiver operating characteristic analyses, the FI-CHG index demonstrated a slightly better predictive performance [area under the curve (AUC) = 0.692] compared with FI or CHG alone. Longitudinal analyses further showed that participants with persistently high FI-CHG levels and those in the top tertile of cumulative FI-CHG exposure exhibited the greatest risk of developing CMM. Conclusion: Our study demonstrated that higher baseline FI-CHG and cumulative FI-CHG exposure were significantly associated with increased risk of CMM. By integrating metabolic and functional indicators, the FI-CHG index may serve as a relatively robust metric with potential clinical prospects for risk stratification of chronic multimorbidity. It may help improve early risk identification and provide evidence for preventive strategies targeting cardiometabolic health.