Abstract: Objective This study aimed to investigate the cross-sectional association between the cumulative number of cardiometabolic diseases and the Frailty Index (FI) among middle-aged and older adults, and to examine the effect modification of this association by urban-rural residency, based on data from the 2018 China Health and Retirement Longitudinal Study (CHARLS). Methods We included participants aged 45 years and older with complete data. The exposure variable was the cumulative number of prevalent cardiometabolic diseases (hypertension, diabetes, heart disease, and stroke), categorized as 0, 1, 2, or ≥3. The presence of two or more of these conditions was defined as cardiometabolic multimorbidity (CMM). The outcome, frailty, was assessed using a Frailty Index (FI) constructed based on the Rockwood model, with frailty defined as FI ≥ 0.25. The analysis employed weighted linear and logistic regression models, stratified analyses, Bootstrap methods, and models with interaction terms. Results A total of 10 842 participants were included in the analysis. Weighted linear regression demonstrated a positive dose-response relationship between the cumulative number of cardiometabolic diseases and the FI (P <0.05). Stratified analyses by residency showed that while the cumulative number of diseases was associated with an elevated FI in both urban and rural populations, the strength of this association was more pronounced in the rural subgroup. Furthermore, weighted logistic regression revealed that CMM was associated with an increased risk of frailty, with the adjusted odds ratio (AOR) being higher for rural residents compared to their urban counterparts. Interaction analysis confirmed a statistically significant interaction (P <0.05) between the cumulative number of diseases and urban-rural residency. These findings remained consistent across a series of sensitivity analyses, which included altering the threshold for missing items in the FI calculation, excluding cases of stroke or heart disease, removing overlapping items between the FI and disease count, and applying propensity score weighting. Conclusion The accumulation of cardiometabolic diseases is significantly associated with an increased risk of frailty among middle-aged and older adults. This health detriment is more pronounced in rural populations. These findings underscore the need for comprehensive assessments of CMM, enhanced frailty screening, and the development of differentiated intervention strategies tailored to urban and rural contexts.

Key words: China Health and Retirement Longitudinal Study (CHARLS), Frailty index, Cardiometabolic multimorbidity, Urban-rural disparities, Middle-aged and older adults