Abstract Body (Do not enter title and authors here): Background: Sustained ventricular arrhythmias (VAs) are associated with an elevated risk of sudden cardiac death (SCD). Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which in turn associated with increased risk of VAs. However, whether Lp(a) is linked with VAs independent of ASCVD remains unknown.

Objective: To examine the association of Lp(a) with VAs in a population-based, retrospective cohort study utilizing data from the TriNetX Research Network.

Methods: We conducted a retrospective analysis of the data from 89 healthcare organizations within the TriNetX Research Network. Patients over 18 years old with available serum Lp(a) measurement were included. Participants were divided into two cohorts based on their Lp(a) levels: cohort 1 (Lp(a) ≤75 nmol/L), and cohort 2 (Lp(a) ≥76 nmol/L). Follow-up time to VA occurrence was calculated from the time of Lp(a) level measurement within each cohort. The composite endpoint was the incidence of VAs to include ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest due to underlying cardiac conditions. We compared the two cohorts using Kaplan-Meier survival analysis along with cox proportional hazard regression analysis after propensity score matching.

Results: 50,752 patients were included in cohort 1 and 24,474 in cohort 2. After propensity score matching, both cohorts had 23,668 patients. In cohort 1, 307 patients experienced VAs, compared to 303 in cohort 2 (Table 1). The mean age was 53.3 ± 15.7 years, with 53.35% of participants being female, 10.75% being Black, and 69.89% being White. The Kaplan-Meier survival analysis showed a higher survival probability at the end of the study period for the Lp(a) ≤75 compared to the Lp(a) ≥76 cohort (95.11% vs 85.35%, p=0.002). The hazard ratio (HR) for VA was 0.768 (95% CI: 0.652-0.904, p = 0.002), indicating that lower Lp(a) levels are associated with reduced VA risk.

Conclusion: This study shows that increased Lp(a) levels are independently associated with a higher incidence of VA. Future research should focus on the mechanisms underlying the relationship between Lp(a) levels and VA, and whether Lp(a) reduction can reduce the risk of VA and other cardiovascular outcomes.