Assessing the impact of insulin resistance trajectories on cardiovascular disease risk using longitudinal targeted maximum likelihood estimation

Abstract Background Cardiovascular disease (CVD) is closely associated with Insulin Resistance (IR). However, there is limited research on the relationship between trajectories of IR and CVD incidence, considering both time-invariant and time-varying confounders. We employed advanced causal inference methods to evaluate the longitudinal impact of IR trajectories on CVD risk. Methods The data for this study were extracted from a Chinese nationwide cohort, named China Health and Retirement Longitudinal Study (CHARLS). Triglyceride-glucose (TyG) index and TyG body mass index (BMI) were used as surrogate markers for IR, and their changes were recorded as exposures. Longitudinal targeted maximum likelihood estimation (LTMLE) was used to study how dynamic shifts in IR trajectories (i.e., increase, decrease, etc.) influence long-term CVD risk, adjusting for both time-invariant and time-varying confounders. Results A total of 3,966 participants were included in the analysis, with 2,152 (54.3%) being female. The average age at baseline was 58.28 years. Over the course of a 7-year follow-up period, 499 (12.6%) participants developed CVD. Four distinct trajectories of TyG index and TyG-BMI were identified: low stable, increasing, decreasing, and high stable. LTMLE analyses revealed individuals in the ‘high stable’ and ‘increasing’ groups had a significantly higher risk of developing CVD compared to those in the ‘low stable’ group, while the ‘decreasing’ group showed no significant differences. Specifically, when the exposure was set as TyG-BMI, the odds of CVD in the ‘high stable’ group were 1.694 (95% CI: 1.361–2.108) times higher than in the ‘low stable’ group. Similar trends were observed across other models, with ORs of 1.708 (95% CI: 1.367–2.134) in Model 2, 1.389 (1.083–1.782) in Model 3, 1.675 (1.185–2.366) in Model 4, and 1.375 (95% CI:1.07 − 1.768) in Model 5. When the exposure was changed to the TyG index, the results remained consistent, with a slightly lower magnitude of the odds ratios. Conclusions High stable and increasing TyG-BMI and TyG index trajectories were associated with the risk of CVD. TyG-BMI consistently exhibited higher odds ratios (ORs) of CVD risk when comparing with TyG index. Early identification of IR trajectories could provide insights for preventing CVD later in life.