Abstract
Background Atrial fibrillation (AF) is increasingly viewed as a substrate-based disease in which atrial structural remodeling confers vulnerability to arrhythmia, but the relative relationships of systemic inflammation, metabolic burden, and left atrial remodeling with future AF risk remain incompletely defined. Objective To investigate associations among systemic inflammation, metabolic burden, cardiac MRI-assessed left atrial remodeling, and subsequent recorded incident AF. Methods We analyzed 15,882 UK Biobank participants with cardiac MRI-derived left atrial volume index (LAVi) and biomarker data. Systemic inflammation was assessed using high-sensitivity C-reactive protein (hs-CRP), and metabolic status using HbA1c and body mass index (BMI). Multivariable linear regression evaluated associations with LAVi, Cox models assessed recorded incident AF, restricted cubic splines tested non-linearity, and mediation analyses explored the role of LAVi. Results Higher BMI was strongly associated with larger LAVi after multivariable adjustment (β per SD increase, 5.81; 95% CI, 5.40-6.21), whereas higher log-transformed CRP was inversely associated with LAVi (β per SD increase, -1.70; 95% CI, -2.15 to -1.25). HbA1c was not significantly associated with LAVi. During a median follow-up of 17.1 years, 729 participants developed recorded incident AF. BMI was independently associated with AF (HR per SD 1.23, 95% CI 1.14-1.33). LAVi was strongly associated with AF risk (HR per SD 1.77, 95% CI 1.68-1.87), whereas CRP and HbA1c were not independently associated with AF. Conclusions BMI and LAVi showed the most consistent associations with recorded incident AF risk. In contrast, hs-CRP did not explain AF susceptibility through left atrial enlargement.</p>