Abstract
PURPOSE: This study aimed to investigate the association between serum insulin-like growth factor 1 (IGF1) levels and cardiovascular disease (CVD) risk, and to further evaluate the potential mediating role of triglyceride-glucose (TyG)-related indices. METHODS: A total of 3,613 participants from the English Longitudinal Study of Ageing (ELSA) were included. Serum IGF1 was categorized into quintiles. Cox proportional hazards models, Kaplan–Meier survival curves, and restricted cubic splines (RCS) were applied to assess the relationship between IGF1 and CVD as well as stroke risk. Subgroup and interaction analyses were performed across demographic and clinical strata. Causal mediation analysis was conducted to evaluate the mediating effects of TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR. Sensitivity analyses were carried out to test the robustness of findings. RESULTS: IGF1 demonstrated a U-shaped association with CVD risk. Participants with intermediate levels (Q2–Q3) had the lowest risk (e.g., Q2: HR = 0.73, 95% CI: 0.57–0.94; Q3: HR = 0.63, 95% CI: 0.46–0.85), while both the lowest and highest quintiles were associated with higher risk. Kaplan–Meier curves indicated significant differences across quintiles (log-rank P = 0.007). Mediation analyses revealed significant average causal mediation effects (ACME) for TyG-BMI, TyG-WC, and TyG-WHtR (all P < 0.05). Sensitivity analyses confirmed the robustness of results. CONCLUSION: Both low and high serum IGF1 levels may increase the risk of cardiovascular disease (CVD) by modulating TyG-related metabolic indices. Incorporating these indices into risk assessment may improve risk stratification and provide a scientific basis for individualized prevention strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-026-05539-9.