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Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Background— Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown. Methods and Results— We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33 165 person-years off anticoagulation among 10 908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate ≥60 mL · min−1 · 1.73 m−2: relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL · min−1 · 1.73 m−2 and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL · min−1 · 1.73 m−2 (P=0.0082 for trend). Conclusions— Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.