Diagnosed Sleep Apnea and Cardiovascular Disease in Atrial Fibrillation Patients The Role of Measurement Error from Administrative Data

Background: Atrial fibrillation and obstructive sleep apnea are common conditions, but little is known about obstructive sleep apnea and cardiovascular risk among atrial fibrillation patients. Methods: Using the Truven Health MarketScan databases, we constructed a prospective cohort of atrial fibrillation patients from 2007 to 2014. Atrial fibrillation, obstructive sleep apnea, stroke, myocardial infarction, and confounders were defined using the International Classification of Disease-9-CM codes. We matched individuals with an obstructive sleep apnea diagnosis with up to five individuals without a diagnosis by age, sex, and enrollment date. Cox proportional hazards models adjusted for confounders and high-dimensional propensity scores. We included migraines as a control outcome. Bias analysis used published sensitivities and specificities to generate rate ratios adjusted for obstructive sleep apnea misclassification. Results: We matched 56,969 individuals with an obstructive sleep apnea diagnosis to 323,246 without. During a mean follow-up of 16 months, 3234 incident strokes and 4639 incident myocardial infarctions occurred. After adjustment, obstructive sleep apnea diagnosis was strongly associated with reduced risk of incident stroke (hazard ratio = 0.48, 95% confidence interval = 0.43, 0.53) and myocardial infarction (0.40, [0.37, 0.44]) and a smaller reduced risk of migraines (0.82, [0.68, 0.99]). Bias analysis produced wide-ranging or inestimable rate ratios adjusted for misclassification of obstructive sleep apnea. Conclusions: Obstructive sleep apnea diagnosis in atrial fibrillation patients was strongly associated with reduced risk of incident cardiovascular disease. We discuss misclassification, selection bias, and residual confounding as potential explanations.