Interaction between atrial fibrillation or flutter and the CHA2DS2-VASc score on the risk of ischemic stroke: A population-based cohort study

The CHA2DS2-VASc score predicts ischemic stroke risk in patients with atrial fibrillation or flutter (AF/AFL). However, it is unknown whether AF/AFL and the CHA2DS2-VASc score interact to increase the risk of ischemic stroke beyond their individual effects. We conducted a cohort study of all adult Danish patients with a hospital diagnosis of AF/AFL from 1996 to 2021 (n = 287,990), and a comparison cohort matched on age, sex, and CHA2DS2-VASc score components (n = 1,404,705). During 1-, 1-5-, and 5-10-year follow-up, we calculated ischemic stroke rates across CHA2DS2-VASc score categories (0, 1, 2, and ≥ 3). We also estimated the interaction effect between AF/AFL and the CHA2DS2-VASc score components individually. Interaction was assessed via interaction contrasts. During the 1-year follow-up, the ischemic stroke rate per 1000 person-years in individuals with a CHA2DS2-VASc score of 0 was 5.47 in the AF/AFL cohort and 2.11 in the comparison cohort. For persons with a CHA2DS2-VASc score of 1, the rate was 10.19 in the AF/AFL cohort and 5.76 in the comparison cohort. The corresponding interaction contrast of 1.07 ([10.19-5.47]-[5.76-2.11]) suggested that 11 % of the ischemic stroke rate was due to interaction. Another interaction was observed between AF/AFL and a CHA2DS2-VASc score ≥ 3 during 5-10-year follow-up (6 %). No other interactions were observed, except for female sex, which showed a large interaction effect in all follow-up periods. AF/AFL and the CHA2DS2-VASc score interacted to increase ischemic stroke rate beyond their individual effects. Among individual CHA2DS2-VASc score components, female sex was associated with the largest interaction effect.