No increased risk of stroke in AF patients without CV comorbidities
Association of Atrial Fibrillation Without Cardiovascular Comorbidities and Stroke Risk: From the REGARDS Study
Introduction and methods
Atrial fibrillation (AF) is associated with a 2-fold increased risk of all-cause mortality and a 5-fold increased risk of stroke [1-3]. Anticoagulant therapy is indicated for the majority of nonvalvular AF patients with a CHA2DS2VASc score of ≥2 [4,5]. However, the risk/benefit profile of anticoagulation among AF patients without CV comorbidities remains unclear. There is no consensus in the literature about the risk of stroke among AF patients without CV comorbidities. Some studies have found an elevated stroke risk in these patients [6-8], while other studies report that the risk of stroke is indistinguishable from the general population [9,10]. This study evaluated the risk of stroke in patients with and without AF and with and without comorbidities in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study .
The REGARDS study was a longitudinal population-based cohort study which enrolled 30239 black and white participants, ≥45 years old. The study was designed to understand regional and racial disparities in stroke risk. For the current study, a total of 28,253 eligible participants from the REGARDS study were divided into 4 groups: 1: Participants without AF or CV comorbidities (reference group, n=7837, 27.7%), 2: Participants with no AF but with CV comorbidities (n=18103, 64.1%), 3: Participants with AF but no CV comorbidities (n=386, 1.4%), and 4: Participants with AF and CV comorbidities (n=1927, 6.8%).
The primary aim was to evaluate the risk of stoke in patients with AF but without CV comorbidities (group 3), compared with those without AF or CV comorbidities (group 1). The median follow-up was 8.7 years (IQR 5.8-11.6).
- Compared with participants without AF and no CV comorbidities (group 1), the HR for stroke was not significantly different in participants with AF without CV comorbidities (group 3), after adjustment for covariates (HR 1.23, 95%CI 0.62-2.18).
- Participants without AF, but with comorbidities (group 2) and participants with AF and with comorbidities (group 4) had a higher risk of stroke, compared to the reference group (group 2: covariate-adjusted HR 1.77, 95%CI 1.48-2.14, group 4: covariate-adjusted HR 2.52, 95%CI 1.93-3.28).
- TOAST (Trial of Org 10172 in Acute Stroke Treatment [ischemic stroke specification schema]) stroke subtype incidence rates were evaluated in the different study groups. Incidence of cardioembolic strokes was higher in groups with participants with AF, with and without comorbidities, compared to groups with participants without AF (fraction of cardioembolic strokes over all ischemic strokes: 12.9% in group 1 [no AF, no comorbidities] , 16.7% in group 2 [no AF, with comorbidities], 69.2% in group 3 [with AF, no comorbidities], and 54.8% in group 4 [with AF, with comorbidities]).
- While participants in groups 1 and 3 had a comparable total stroke risk, the risk for cardioembolic stroke was higher in group 3 compared to group 1 (covariate-adjusted HR 3.12, 95%CI 1.15-8.46). Risk for cardioembolic stroke was also higher in group 2 and group 4 compared to group 1 (group 2: covariate-adjusted HR 2.34, 95%CI 1.48-3.90, group 4: covariate-adjusted HR 8.25, 95%CI 4.79-14.21).
- The consistency of associations was examined in prespecified subgroups. The relationships were consistent when stratified by sex, race, BMI, and smoking. However, an interaction between age and group was found as an effect modifier (P=0.02). Participants <64 years old had a higher magnitude of risk explained by group than older participants.
This analysis of the REGARDS study showed that AF patients without CV comorbidities had no increased risk of stroke compared to those without AF or CV comorbidities. Individuals with CV comorbidities, with and without AF, had an elevated risk of both stroke of any type and cardioembolic stroke.