Abstract
BACKGROUND: The triglyceride-glucose (TyG) index is a recognized marker of insulin resistance, yet its role in the dynamic progression from cardiovascular disease (CVD) to cardiovascular multimorbidity (CVM) remains unclear. This study aimed to evaluate the association between the TyG index and transitions from a CVD-free state to first CVD and subsequently to CVM. METHODS: In this prospective cohort study, we included participants from the Shanghai Suburban Adult Cohort who were free of CVD at baseline (2016). The TyG index was measured at baseline. Disease transitions were tracked over a median follow-up of 6.26 years. First CVD event was defined as the initial occurrence of coronary heart disease (CHD), stroke, or heart failure (HF), and CVM was defined as the presence of two or more of these conditions. Multi-state models were used to assess the association between the TyG index and transitions across health states, including disease-specific pathways. RESULTS: During a median follow-up of 6.26 years, 1,182 (3.79%) participants developed first CVD event, 671 (2.15%) developed CVM. TyG index played crucial but different roles in all transitions from healthy to first CVD event, to CVM (HR = 1.162, 95% CI: 1.074, 1.257; HR = 1.148, 95% CI: 1.010, 1.305). When we further divided first CVD events into CHD, Stroke, and HF, we found that TyG index played different roles in disease-specific transitions even within the same transition stage (HR = 1.145, 95% CI: 1.029, 1.273; HR = 1.228, 95% CI: 1.085, 1.391; HR = 1.213, 95% CI: 1.057, 1.391). CONCLUSIONS: The TyG index is an independent predictor of dynamic progression toward cardiovascular multimorbidity, showing significant associations with atherosclerosis-driven conditions such as CHD and stroke but not with heart failure. These findings support its potential utility in risk stratification and preventive strategies across the cardiovascular disease continuum.