Zhixing Fan, Tonghuan Shi, Chaojun Yang, Tao Zheng, Marcel Sieme, Benjamin Sasko, Jan Wintrich, Muchtiar Khan, Xinyi Liu, Assem Aweimer, A Mugge, Pasquale Maffia, Pierpaolo Pellicori, Ibrahim Akin, Loek van Heerebeek, I El-Battrawy, U S Schotten, G Danilo Norata, Francesco Paneni, Jian Yang, Nazha Hamdani
BACKGROUND: The triglyceride-glucose (TyG) index and its obesity-related derivatives have emerged as surrogate markers of insulin resistance associated with cardiovascular outcomes. However, whether these indicators influence atrial fibrillation (AF) risk through cardiac structural and functional remodeling remains unclear. METHODS: This is a post-hoc analysis of a prospective cohort study of 32,500 UK Biobank participants free of AF who underwent baseline cardiac magnetic resonance (CMR) imaging. The TyG index and its obesity-related derivatives (TyG-body mass index (BMI), TyG-waist circumference (WC), and TyG-waist-to-height ratio (WHtR)) were calculated at baseline. Multivariable Cox regression models were used to assess associations with incident AF, and mediation analyses quantified the contribution of CMR-derived cardiac parameters to these associations. RESULTS: Over a median follow-up of 13.61 years, 1,288 incident AF cases occurred. The TyG index alone showed no independent association with AF risk. In contrast, all TyG obesity-related derivatives were significantly associated with incident AF, with TyG-WC demonstrating the strongest association (HR = 1.245, 95% CI 1.169-1.325), followed by TyG-BMI (HR = 1.223, 95% CI 1.158-1.293) and TyG-WHtR (HR = 1.190, 95% CI 1.122-1.262). Mediation analyses identified left atrial maximum volume (LAVmax) as the predominant mediator, accounting for 70.63%, 47.83%, and 40.79% of the associations for TyG-BMI, TyG-WHtR, and TyG-WC, respectively. CONCLUSIONS: TyG obesity-related derivatives, particularly TyG-WC, were independently associated with incident AF. Cardiac structural remodeling, especially LA enlargement, appeared to be a key mediating pathway. These findings support the importance of early metabolic intervention to prevent adverse atrial remodeling and reduce AF susceptibility.