To investigate the longitudinal association between the metabolic score for insulin resistance (METS-IR) and the risk of cardiovascular disease (CVD) and its subtypes (heart disease and stroke) in middle-aged and older adults.

This study used data from 4 567 participants in the China Health and Retirement Longitudinal Study (CHARLS) cohort. METS-IR levels measured in 2011 and 2015 were standardized, and K-means cluster analysis was used to classify participants into four categories (Class 1-4). Cumulative METS-IR exposure levels were calculated. Multivariable Cox regression models, adjusted for potential confounders, were used to evaluate the association between METS-IR and incident CVD. Restricted cubic spline analysis assessed the dose-response relationship between cumulative METS-IR exposure and CVD risk. Subgroup analyses explored heterogeneity by gender and age. The predictive performance of METS-IR for CVD was evaluated using time-dependent receiver operating characteristic (ROC) curves.

Over a median follow-up of 3 years, 531 CVD events occurred among 4 567 participants. Cox regression analysis showed that compared to Class 1 (lowest persistent METS-IR levels), Class 4(highest persistent METS-IR levels) was associated with a 77% increased risk of incident CVD (HR=1.77, 95%CI: 1.24-2.52), including a 67% increased risk of heart disease (HR=1.67, 95%CI: 1.10-2.54) and a significant 117% increased risk of stroke (HR=2.17,95%CI: 1.31-3.59). A significant linear dose-response relationship was observed between cumulative METS-IR exposure and CVD risk. ROC curve analysis indicated that cumulative METS-IR had the best predictive performance for CVD, with an area under the curve (AUC) of 0.613.

Persistently elevated longitudinal levels of METS-IR are associated with an increased risk of incident CVD. Dynamic monitoring of METS-IR levels is important for the prevention and treatment of CVD.