Atrial Cardiopathy in the Absence of Atrial Fibrillation Increases Risk of Ischemic Stroke, Incident Atrial Fibrillation, and Mortality and Improves Stroke Risk Prediction

BACKGROUND: Atrial fibrillation (AF) is a major, often undetected, cardiac cause of stroke. Markers of atrial cardiopathy, including left atrial enlargement (LAE) or excessive atrial ectopy (EAE) increase the risk of AF and have shown associations with stroke. We sought to determine whether these markers improve stroke risk prediction beyond traditional vascular risk factors (eg CHA(2)DS(2)-VASc score). METHODS AND RESULTS: Retrospective longitudinal cohort of 32 454 consecutive community-dwelling adults aged >= 65 years referred for outpatient echocardiogram or Holter in Ontario, Canada (2010-2017). Moderate-severe LAE was defined as men >47 mm and women >43 mm, and EAE was defined as >30 APBs per hour. Cause-specific competing risks Cox proportional hazards used to estimate risk of ischemic stroke (primary), incident AF, and death (secondary). C-statistics, incremental discrimination improvement and net reclassification were used to compare CHA(2)DS(2)-VASc with LAE and EAE to CHA(2)DS(2)-VASc alone. Each 10 mm increase in left atrial diameter increased 2- and 5-year adjusted cause-specific stroke hazard almost 2-fold (LAE: 2-year hazard ratio (HR), 1.72; P=0.007; 5-year HR, 1.87; P<0.0001), while EAE showed no significant associations with stroke (2-year HR, 1.00; P=0.99; 5-year HR, 1.08, P=0.70), adjusting for incident AF. Stroke risk estimation improved significantly at 2 (C-statistics=0.68-0.75, P=0.008) and 5 years (C-statistics=0.70-0.76, P=0.003) with LAE and EAE. CONCLUSIONS: LAE was independently associated with an increased risk of ischemic stroke in the absence of AF and both LAE and EAE improved stroke risk prediction. These findings have implications for stroke risk stratification, AF screening, and stroke prevention before the onset of AF.