Insulin resistance indicators in aortic disease: A large cohort study.

BACKGROUND: The triglyceride-glucose index (TyG), a novel marker of insulin resistance, is recognised as a risk factor for multiple cardiovascular diseases. The link between its risk and aortic dissection and aortic aneurysm (AD/AA) is not well-defined. This research seeks to explore the relationship. METHODS: This study analysed 386 063 participants from the UK Biobank, a large prospective cohort, all initially free of AD/AA. The main focus was on the occurrence rate of AD/AA. Multivariate Cox regression models were used to analyse the association between the TyG index, its related parameters, and the risk of AD/AA. Association was further validated using a real-world clinical cohort from Central China Fuwai Hospital. A two-sample Mendelian randomisation (MR) analysis utilising the inverse variance weighting method was conducted to investigate the causal link between TyG and AD/AA. RESULT: Among the 386 063 participants in the UK Biobank cohort, 3805 cases of AD/AA were reported. After controlling for covariates, a higher TyG index and its related parameters were associated with an increased incidence of AD/AA. The hazard ratios (HRs) were as follows: TyG (HR = 1.14, 95% CI: 1.07-1.22, p <.001), TyG-WHR (HR = 1.17, 95% CI: 1.12-1.22, p <.001), and TyG-WHtR (HR = 1.11, 95% CI: 1.06-1.16, p <.001). Association between TyG and the risk of aortic diseases was also replicated in the single-centre cohort. Two-sample MR analysis indicated strong evidence of a causal relationship between genetically predicted TyG levels and AA (OR = 1.97, 95% CI: 1.37-2.84, p <.001), while no significant association was observed with AD (OR = 0.79, 95% CI: 0.31-1.99, p = .61). CONCLUSION: Through complementary epidemiological, clinical, and genetic approaches, our findings indicate that elevated TyG index represents a robust and potentially causal risk factor for aortic diseases (especially AA). These results highlight the importance of metabolic risk assessment in aortic disease prevention and emphasise the need for further mechanistic studies to understand the differential links between TyG and specific aortic phenotypes. HIGHLIGHTS: Higher TyG index and related ratios are linked to increased AD/AA risk. Prospective cohort analysis confirms robust linear associations. Mendelian randomisation supports a causal role of TyG in AA. Findings highlight TyG as a potential target for early prevention.