Abstract 4363281: Mitral Annular Calcification, Coronary Artery Calcification, and Risk of Incident Atrial Fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Atrial fibrillation (AF) is a prevalent arrhythmia associated with significant morbidity and mortality. Coronary artery calcification (CAC) and mitral annular calcification (MAC) are markers of cardiovascular aging and systemic atherosclerosis, but data on their joint association with incident AF are limited. We investigated the independent and combined associations of CAC and MAC with incident AF in the Multi-Ethnic Study of Atherosclerosis (MESA) to assess potential synergistic effects and elucidate the mechanisms linking cardiovascular calcification to AF. Hypothesis: We hypothesized that CAC and MAC are independently associated with increased AF risk, and that their combination confers additive risk beyond traditional predictors. Methods: CAC and MAC were assessed by cardiac CT and quantified by Agatston scoring. Participants were stratified into four groups: CAC=0/MAC=0 (reference), CAC>0/MAC=0, CAC=0/MAC>0 and CAC>0/MAC>0. Incident AF was ascertained through hospitalization and medical records as well as Medicare claims. Cox proportional hazard models were used to examine the association between CAC/MAC categories and incident AF, adjusting for demographics (Model 2) and cardiovascular risk factors (Model 3), with model 1 unadjusted. We used Harrell’s C-statistic to assess model performance with the incremental addition of CAC and MAC to the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF risk score. Results: We included 6,588 MESA participants (mean age 62±10 years, 53% female) free of baseline AF and cardiovascular disease. Over a median follow-up of 16.5 years, 1,306 incident AF events occurred. Participants with CAC>0/MAC>0 were at the highest risk of incident AF ( Image 1 ). In the fully adjusted model, compared to those in the reference group (CAC=0/MAC=0), participants with CAC>0/MAC=0, CAC=0/MAC>0, and CAC>0/MAC>0 demonstrated a 39%, 74%, and 96% increased risk of incident AF events, respectively (p<0.01 for all) ( Image 2 ). Addition of CAC and MAC to the CHARGE-AF model significantly improved risk discrimination (C-statistic improved from 0.746 to 0.754, p<0.001). Conclusions: Both CAC and MAC are independently associated with increased risk of incident AF. Their combination identifies individuals at even higher risk and improves predictive performance when added to the CHARGE-AF model. These findings suggest that cardiac CT-derived calcification measures may enhance AF risk stratification.