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Background Atrial fibrillation (AF ) is associated with a 5‐fold increased stroke risk. While most patients withAF warrant anticoagulation, optimal treatment remains uncertain for patients withAF without cardiovascular comorbidities because the risk of stroke in this population has not been well‐characterized.Methods and Results Participants (N=28 253; 55% women, mean age 64.6±9.4 years), from theREGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003–present) were classified into 1 of 4 groups based on the presence or absence ofAF and the presence or absence of cardiovascular comorbidities. Cox proportional hazards analysis was used to compare the risk of stroke between groups. During 244 560 person‐years of follow‐up (median 8.7 years), 1206 strokes occurred. Compared with patients with neitherAF nor cardiovascular comorbidities, we did not find an increased stroke risk (hazard ratio [HR], 1.23; 95%CI , 0.62–2.18 [P =0.511]) among participants withAF alone. Participants withoutAF but with cardiovascular comorbidities had both an elevated stroke risk (HR, 1.77; 95%CI , 1.48–2.18 [P &lt;0.0001]) and an increased risk of cardioembolic stroke (HR, 2.34; 95%CI , 1.48–3.90 [P =0.0002]).Conclusions In this large cohort of participants withAF without cardiovascular comorbidities, we found thatAF itself, without cardiovascular comorbidities, did not confer increased risk of stroke. Cardiovascular comorbidities, however, were associated with an increased risk of both stroke of any type and cardioembolic stroke, even in the absence ofAF .

Association of Atrial Fibrillation Without Cardiovascular Comorbidities and Stroke Risk: From the REGARDS Study