Association of the remnant cholesterol inflammatory index and frailty with cardiometabolic multimorbidity among Chinese middle-aged and elderly populations: a nationwide cohort study

Cardiometabolic multimorbidity (CMM) is the co-occurrence of two or more cardiometabolic disorders including heart disease, diabetes and stroke. While the remnant cholesterol inflammatory index (RCII) and frailty have been independently associated with CMM, their joint association with CMM has not been fully elucidated. This study examined the joint-category associations of RCII or CumRCII with frailty in relation to incident CMM to characterize their combined epidemiological relationships with CMM risk. Based on the 2011–2020 China Health and Retirement Longitudinal Study (CHARLS), 5,779 participants were included in the final analysis. CumRCII represented time-weighted cumulative RCII exposure during 2011–2015. Kaplan–Meier curves were used to calculate CMM incidence across exposure groups. Multivariable Cox models were used to evaluate the joint-category associations of RCII or CumRCII with frailty in relation to incident CMM. Additive and multiplicative interactions were assessed separately. Restricted cubic spline models investigated potential nonlinear associations of RCII and CumRCII with CMM risk. Receiver operating characteristic curves were used in an exploratory analysis of in-sample model discrimination. The stability of the findings was assessed through subgroup and sensitivity analyses. A total of 510 participants were diagnosed with CMM. Higher RCII or CumRCII in combination with frailty was associated with increased CMM incidence. RCII and CumRCII exhibited positive nonlinear associations with CMM risk. Compared with individuals with low RCII and without frailty, those with concurrent high RCII and frailty showed a higher risk of incident CMM (HR = 2.622, 95% CI 1.972–3.488). Similar results were observed for CumRCII (above optimal threshold) combined with frailty (HR = 2.849, 95% CI 2.178–3.726). However, additive and multiplicative interaction analyses did not remain statistically significant after full adjustment. The model incorporating CumRCII and frailty had a modestly higher in-sample AUC than the CumRCII-only model (0.757 vs. 0.740; ΔAUC = 0.017; DeLong P < 0.001). Subgroup and sensitivity analyses supported the robustness of the main findings. In joint-category Cox analyses, participants with concurrent elevated RCII or CumRCII and frailty showed the highest observed risk of incident CMM. These findings suggest that lipid-inflammatory burden and frailty may represent complementary dimensions of CMM risk.