Abstract 4369896: Association Between Elevated Lipoprotein(a) and New-Onset Atrial Fibrillation: A Retrospective Analysis Using the TriNetX Research Network

Background: Atrial fibrillation (AF) is the most prevalent clinically encountered cardiac arrhythmia and is associated with an increased risk of heart failure, stroke, and all-cause mortality. Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), yet its independent role in the onset of AF remains uncertain. Objective: Understanding the relationship between Lp(a) levels and incident AF could offer new insights into cardiovascular risk stratification beyond traditional ASCVD pathways. Methods: This retrospective cohort study utilized data from the TriNetX Research Network health records from 100 healthcare organizations. Adults aged ≥18 years with documented lipoprotein(a) [Lp(a)] levels and no history of atrial fibrillation (AF) or cardiac devices were included. Two groups were defined: Elevated Lp(a) (≥125 nmol/L or ≥50 mg/dL) and Normal Lp(a) (<125 nmol/L or <50 mg/dL). The index date was the first qualifying Lp(a) result. Propensity score matching (1:1) was applied to 74 characteristics. The primary outcome was new-onset AF; secondary outcomes included hospitalizations and emergency department visits. Statistical analysis included risk estimates and t-tests with significance set at p < 0.05. Results: After matching, 43,989 patients were included in each cohort. The median follow-up was 817 days (elevated Lp(a)) vs. 899 days (normal Lp(a)). New-onset AF occurred in 3.9% of the elevated Lp(a) group vs. 4.9% of the normal group (risk ratio 0.785, 95% CI: 0.738–0.835, p < 0.001). Hospitalization or emergency visits occurred in 41.1% vs. 43.0% of patients, respectively (risk ratio 0.956, p < 0.001). The average number of visits was also lower in the elevated group (7.5 vs. 11.2, p < 0.001). Elevated Lp(a) was unexpectedly associated with a reduced risk of AF and lower healthcare utilization. Elevated Lp(a) in race and age subgroups yielded different results.(Table 1) Conclusion: In this large propensity score-matched cohort study, elevated [Lp(a)] levels were associated with a significantly lower risk of new-onset atrial fibrillation compared to normal Lp(a) levels. Additionally, patients with elevated Lp(a) experienced slightly fewer hospitalizations and emergency visits. These findings suggest a complex and potentially protective role of Lp(a) in atrial arrhythmogenesis, warranting further investigation into its underlying mechanisms and clinical implications.