Association of Insulin Resistance, Sarcopenia, and Risk of Cardiovascular Disease: Findings From the China Health and Retirement Longitudinal Study.

Background: Cardiovascular disease (CVD) is the main cause of death in middle-aged and older people in China. The interplay between sarcopenia and insulin resistance (IR) in driving CVD risk has not been fully understood, particularly regarding sarcopenia severity and IR heterogeneity. Objective: This study aimed to investigate the relationship between IR and sarcopenia and the risk of new-onset CVD. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS). Cox proportional hazards models were used to assess associations of sarcopenia status (nonsarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia) and 6 IR indices (triglyceride-glucose, TyG; TyG-BMI; TyG-waist circumference; TyG-waist-to-height ratio; triglyceride/high-density lipoprotein cholesterol, TG/HDL-C; and metabolic score for insulin resistance, METS-IR) with incident CVD. Additive and multiplicative interaction analyses and subgroup analyses by age and sex were performed. Receiver operating characteristic analysis was used to determine clinically relevant cutoffs. Results: In this study, during a median 9-year follow-up, we included 5514 middle- and older-aged (≥45 y) residents, of whom 550 presented with CVD incidence. Participants with possible sarcopenia and high IR exhibited 1.24-1.85-fold higher CVD risk versus nonsarcopenia and low-IR counterparts (P<.05) after adjustment for potential confounders. While TyG-BMI and TyG-waist circumference were the strongest independent predictors, formal interaction analysis revealed that the TG/HDL-C ratio and METS-IR demonstrated the most consistent synergistic effects with possible sarcopenia (relative excess risk due to interaction=0.139 and 0.074, respectively). In subgroups of different ages and sexes, the combination of IR and sarcopenia is associated with the highest risk of CVD. Receiver operating characteristic analysis provided clinically applicable cutoffs for these indices, including TG/HDL-C ≥2.09 and METS-IR ≥34.26. Conclusions: We found that IR and sarcopenia, especially early-stage sarcopenia, synergistically increase the incidence of CVD in older adults. These findings advocate for dual-targeted CVD interventions (muscle preservation and IR mitigation) in aging societies, particularly during the transitional phase of possible sarcopenia.