Triglyceride glucose index, metabolic comorbidity, and cardiovascular disease: a national cohort study

The triglyceride-glucose (TyG) index, a widely accepted surrogate biomarker of insulin resistance, strongly predicts cardiovascular disease (CVD) risk. However, the mediating role of metabolic comorbidities in explaining the relationship between the TyG index and cardiovascular disease remains underexplored. Leveraging the longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS), this longitudinal study investigates how metabolic comorbidities mediate the association between the TyG index and cardiovascular risk. This analysis included 9,400 participants aged ≥ 45 years from CHARLS without baseline CVD. The TyG index was computed as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Incident cardiovascular events, which were defined as physician-confirmed heart disease or stroke, were monitored until 2020. Adjusted Cox proportional hazards models estimated hazard ratios (HR). The mediation analysis quantified the percentage of excess risk (PERM) attributable to metabolic comorbidities. The mean age of the participants was 59.0 ± 9.5 years, and 4 862 (51.7%) were females. Among eligible participants, 2,152 developed cardiovascular diseases over a 9-year follow-up, with 1,627 heart disease cases and 765 strokes. Compared with people with a lower TyG index (< 8.59 [median level]) and no comorbidity, those concurrently with a higher TyG and comorbidity had the highest risk of CVD (adjusted HR, 1.66; 95% CI, 1.47–1.88), coronary heart disease (aHR, 1.44; 95% CI, 1.25–1.66) and stroke (aHR, 2.94; 95% CI, 2.31–3.75). Metabolic comorbidities mediated 48.3% of the TyG-associated CVD risk, predominantly through hypertension, renal impairment, inflammation, and obesity. These findings underscore the partial mediating role of metabolic comorbidities in the TyG index-CVD association. Future research should explore residual pathways to fully elucidate this association.