The interaction effect of CHA2DS2-VASc components on ischemic stroke risk after atrial fibrillation: a population-based cohort study
Authors: Bonnesen K , Szepligeti S K , Heide-Jorgensen U , Sorensen H T , Schmidt M 
Published: October 2022

Abstract

Background
In the European Union, almost nine million individuals 55 years or older had atrial fibrillation in 2010. It is estimated that around a quarter of all ischemic stroke cases in individuals 80 to 89 years can be attributed to atrial fibrillation. The CHA2DS2-VASc is the most commonly used clinical tool to predict ischemic stroke and incorporates congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack/systemic embolism, vascular disease, age 65 to 74 years, and female sex. It remains unknown whether the CHA2DS2-VASc components and atrial fibrillation interact biologically, i.e. whether the CHA2DS2-VASc components and atrial fibrillation increase ischemic stroke rate beyond their individual effects.

Purpose
We examined the interaction effect between CHA2DS2-VASc and atrial fibrillation and on ischemic stroke rate.

Methods
We conducted a population-based cohort study of all adult atrial fibrillation or flutter patients from 1996 through 2016 and a one-to-five comparison cohort from the general population. Members of the comparison cohort were matched on year of birth, sex, and the individual CHA2DS2-VASc components. We followed each individual from the index date (the date of atrial fibrillation or date of matching) until the first of ischemic stroke, death from any cause, loss-to follow-up, 10 years follow-up, or 31 December 2016. We calculated ischemic stroke rates per 1,000 person-years (PYs) and interaction contrasts, which is the proportion of the summed ischemic stroke rate of the CHA2DS2-VASc components and atrial fibrillation that is beyond their individual effects.

Results
After one-year follow-up, the ischemic stroke rate per 1,000 PY among individuals with CHA2DS2-VASc score zero was 5.69 (95% confidence interval [CI]: 4.68–6.69) in the atrial fibrillation cohort and 1.86 (95% CI: 1.60–2.12) in the comparison cohort. Among individuals with CHA2DS2-VASc score one, the mortality rate per 1,000 PY increased to 10.9 (95% CI: 9.75–12.0) in the atrial fibrillation cohort and 7.45 (95% CI: 7.01–7.88) in the comparison cohort. The interaction contrast in individuals with CHA2DS2-VASc score one was −0.41 (10.8 − 7.45 − 5.69 + 1.86) indicating that the ischemic stroke rate was not explained by interaction (−0.41 / 10.8 = −3.8%). The interaction effect was −2.75 in individuals with CHA2DS2-VASc score two and −2.79 in individuals with CHA2DS2-VASc score three or higher, again indicating no interaction. Interaction did not explain the ischemic stroke rate after one to five years follow-up either, but did explain 16% of the ischemic stroke rate in individuals with CHA2DS2-VASc score three or higher after five to 10 years follow-up.

Conclusion
Biological interaction between the CHA2DS2-VASc components and atrial fibrillation does not contribute substantially to the ischemic stroke risk.

Funding Acknowledgement
Type of funding sources: None.