Abstract 4122348: APOL1 Risk Variants and Risk of Incident Atrial Fibrillation in Systolic Blood Pressure Intervention Trial (SPRINT)

Background: Apolipoprotein L1 gene (APOL1) G1 and G2 risk variants (RVs) have been associated with the progression of chronic kidney disease in individuals of recent African descent. However, the association of APOL1 RVs with atrial fibrillation (AF) is unknown and may help identify individuals at risk. Aim: To examine the association of APOL1 RVs with incident AF in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: This post-hoc analysis included SPRINT participants free of AF at baseline who had baseline APOL1 and follow-up AF data. Cox proportional hazard regression models were used to examine the risk of AF for Black individuals with high-risk APOL1 (2 RVs) compared with low-risk (0-1 RVs) (reference). Additionally, three analyses were performed: a comparison of the risk of AF between all Black and White participants, Black participants with low-risk APOL1 RVs and White participants, and Black participants with high-risk APOL1 RVs and White participants. Results: 2,254 Black and 4694 White participants were included in the analysis. During a median follow-up of 2 years, there were 16 and 134 cases of incident AF among Blacks and Whites, respectively. In a multivariable-adjusted model, compared with Black individuals with low-risk APOL1 RVs, high-risk APOL1 RVs were associated with approximately 3.5 times greater risk of AF. This association was stronger among participants without chronic kidney disease (CKD) compared to those with CKD (hazard ratio (HR) (95% confidence interval (CI)), 6.01 (1.44-25.0) vs. 2.98 (0.21-41.7), respectively, interaction p -value=0.11). Compared to White participants, all Black and Black participants with low-risk APOL1 RVs had a significantly lower risk of AF. In contrast, Black individuals with high-risk APOL1 RVs had a similar risk of AF compared to White participants ( Table ). Conclusions: In hypertensive, non-diabetic Black participants, high-risk APOL1 RVs are associated with a higher risk of AF, and these individuals had an AF risk comparable to White participants. These hypothesis-generating findings underlie the need for future investigation to confirm this association and whether APOL1 status can explain racial differences in the risk of AF.