Abstract Body (Do not enter title and authors here): Background: African Americans (AAs) have higher levels of lipoprotein(a) (Lp(a)), a proinflammatory particle, and high-sensitivity C-reactive protein (hs-CRP) but a lower rate of atrial fibrillation (AF) than White Americans. While it is known that Lp(a) is associates associated with various cardiovascular diseases and that inflammation plays a crucial role in AF pathogenesis, the relationship between Lp(a) and AF remains unclear especially in AAs. This study investigated the association between Lp(a) levels and incident AF in AAs, focusing on the potential interaction with inflammatory status assessed by hs-CRP.

Methods: From the Jackson Heart Study, 3,865 AAs without AF or missing variables at baseline (mean age 53.6±12.7, women 64%) were included in the study. Participants were stratified by Lp(a) levels (<30, 30-49, 50-99, and ≥100 mg/dL) and hs-CRP levels (<3 mg/L (low) vs ≥3 mg/L (high)) based on current guidelines and studies. Cox proportional hazards models were used to evaluate the association between Lp(a) categories and incident AF, adjusting for demographic, clinical, and laboratory variables.

Results: During a median follow-up of 13.7 years, 304 participants developed AF (incidence rate 6.3/1,000 person-years). Kaplan-Meier survival analysis showed no significant association between Lp(a) levels and AF risk in the overall cohort (p = 0.60). When stratified by hs-CRP levels, divergent relationships were observed: in the low hs-CRP group, elevated Lp(a) was associated with increased AF risk (HR: 1.71, 95% CI: 1.03–2.83, for Lp(a) ≥100 vs <30 mg/dL, Table). Conversely, in the high hs-CRP group, elevated Lp(a) was associated with decreased AF risk (HR: 0.52, 95% CI: 0.30–0.92). A significant interaction was observed between hs-CRP and Lp(a) levels (p < 0.004 across models).

Conclusion: In this community-based AA cohort, the relationship between Lp(a) and AF risk differed by inflammatory status. The interaction between Lp(a) and inflammation may partially explain the lower AF incidence in AAs.