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

Literature - Singleton MJ, Imtiaz-Ahmad M, Kamel H et al., - J Am Heart Assoc. 2020. doi: 10.1161/JAHA.120.016380.

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 [11].

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).

Main results

  • 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.


1. Ruddox V, Sandven I, Munkhaugen J, Skattebu J, Edvardsen T, Otterstad JE. Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: a systematic review and meta-analysis. Eur J Prev Cardiol. 2017;24:1555–1566.

2. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82:2N–9N.

3. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial-fibrillation and risk of stroke—Framingham Study. Neurology. 1978;28:973–977.

4. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130:E199–E267.

5. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation. 2019;140:e125–e151.

6. Kim EJ, Yin X, Fontes JD, Magnani JW, Lubitz SA, McManus DD, Seshadri S, Vasan RS, Ellinor PT, Larson MG, et al. Atrial fibrillation without comorbidities: prevalence, incidence and prognosis (from the Framingham Heart Study). Am Heart J. 2016;177:138–144.

7. Andersson T, Magnuson A, Bryngelsson IL, Frobert O, Henriksson KM, Edvardsson N, Poci D. Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: a nationwide cohort study of 9519 patients. Int J Cardiol. 2014;177:91–99.

8. Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med. 2002;113:359–364.

9. Kopecky SL, Gersh BJ, McGoon MD, Whisnant JP, Holmes DR Jr, Ilstrup DM, Frye RL. The natural history of lone atrial fibrillation. A population-based study over three decades. N Engl J Med. 1987;317:669–674.

10. Jahangir A, Lee V, Friedman PA, Trusty JM, Hodge DO, Kopecky SL, Packer DL, Hammill SC, Shen WK, Gersh BJ. Long-term progression and outcomes with aging in patients with lone atrial fibrillation: a 30-year follow-up study. Circulation. 2007;115:3050–3056.

11. Howard VJ, Cushman M, Pulley L, Gomez CR, Go RC, Prineas RJ, Graham A, Moy CS, Howard G. The reasons for geographic and racial differences in stroke study: objectives and design. Neuroepidemiology. 2005;25:135–143.

Find this article online at J Am Heart Assoc.

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free