Cardiometabolic multimorbidity in relation to the metabolic score for insulin resistance and creatinine-to-cystatin C ratio in a middle-aged and aged population

Objective: With the aging population, cardiometabolic multimorbidity (CMM) has become a major public health concern, increasing disease burden and impairing quality of life. The metabolic score for insulin resistance (METS-IR) and creatinine-to-cystatin C (CCR) are promising biomarkers linked to metabolic dysfunction and muscle-renal status, respectively. However, their combined effects on cardiometabolic multimorbidity (CMM), especially in both community and hospitalized populations, remain unclear. This study aims to explore the associations of METS-IR, CCR, and 1/CCR×METS-IR (MRII) with CMM using data from the China Health and Retirement Longitudinal Study (CHARLS) and clinical sources. Research design and methods: This cross-sectional study included 10,811 participants from the 2014-2015 CHARLS follow-up and 437 elderly inpatients from the Second Affiliated Hospital of Chongqing Medical University. CMM was defined as the coexistence of two or more of heart disease, diabetes, and stroke. METS-IR and CCR were calculated using standard formulas. Logistic regression analyses with multi-model adjustment, restricted cubic spline (RCS) curves, receiver operating characteristic (ROC) curves, and subgroup analyses were performed to assess associations, nonlinear relationships, predictive value, and effect modification. Results: In both datasets, participants with CMM had higher METS-IR, older age, and higher prevalence of metabolic risk factors. METS-IR was independently and dose-dependently associated with increased CMM risk. CCR showed context-dependent associations, with inverse links in partially adjusted CHARLS models but no significance in clinical data. The "Low CCR and High METS-IR" combination and highest quartile of MRII were consistently linked to elevated CMM risk. METS-IR had moderate predictive value (AUC = 0.712 in CHARLS, 0.618 in clinical data), outperforming CCR. RCS curves revealed linear associations for METS-IR and U-shaped patterns for CCR in CHARLS. Subgroup analyses showed heterogeneity by age, comorbidities, and hypertension. Conclusion: METS-IR is a robust independent predictor of CMM in both community and hospitalized populations, while CCR's role is context-dependent. The MRII enhances CMM risk stratification, highlighting the value of concurrent assessment of metabolic and muscle-renal status for CMM prevention and personalized risk management.