Abstract

AIM: The triglyceride-glucose (TyG) index, recognized as a surrogate marker for insulin resistance, is an established cardiovascular risk factor. We aimed to prospectively investigate the association between the TyG index and aortic valve calcific (AVC) progression, as well as its relationship with incident calcific aortic valve stenosis (CAVS). MATERIALS AND METHODS: A post hoc analysis was conducted on 5589 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. The TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariate Cox regression assessed the association between baseline TyG index and AVC progression. Two-sample Mendelian randomization (MR) analysis was employed to evaluate the potential causality between the TyG index and CAVS. RESULTS: Over a median 2.4 years follow up, 567 cases of AVC progression were idenrified. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in the TyG index was associated with a 20.8% increased risk of AVC progression. Robustness was confirmed in sensitivity analyses and nearly all subgroups. Two sample MR analysis supported a causal relationship between a higher TyG index and increased risk of CAVS. CONCLUSION: A higher TyG index independently predicts AVC progression and causally influences CAVS incidence in the general population.