Sleep‐Disordered Breathing, Hypoxia, and Pulmonary Physiologic Influences in Atrial Fibrillation

Abstract

Background We leverage a large clinical cohort to elucidate sleep‐disordered breathing and sleep‐related hypoxia in incident atrial fibrillation (AF) development given the yet unclear contributions of sleep‐related hypoxia and pulmonary physiology in sleep‐disordered breathing and AF. Methods and Results Patients who underwent sleep studies at Cleveland Clinic January 2, 2000, to December 30, 2015, comprised this retrospective cohort. Cox proportional hazards models were used to examine apnea hypopnea index, percentage time oxygen saturation <90%, minimum and mean oxygen saturation, and maximum end‐tidal carbon dioxide on incident AF adjusted for age, sex, race, body mass index, cardiopulmonary disease and risk factors, antiarrhythmic medications, and positive airway pressure. Those with spirometry were additionally adjusted for forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second/forced vital capacity. This cohort (n=42 057) was 50.7±14.1 years, 51.3% men, 74.1% White individuals, had median body mass index 33.2 kg/m 2 , and 1947 (4.6%) developed AF over 5 years. A 10‐unit apnea hypopnea index increase was associated with 2% higher AF risk (hazard ratio [HR], 1.02 [95% CI, 1.00–1.03]). A 10‐unit increase in percentage time oxygen saturation <90% and 10‐unit decreases in mean and minimum oxygen saturation were associated with 6% (HR, 1.06 [95% CI, 1.04–1.08]), 30% (HR, 1.30 [95% CI, 1.18–1.42]), and 9% (HR, 1.09 [95% CI, 1.03–1.15]) higher AF risk, respectively. After adjustment for spirometry (n=9683 with available data), only hypoxia remained significantly associated with incident AF, although all coefficients were stable. Conclusions Sleep‐related hypoxia was associated with incident AF in this clinical cohort, consistent across 3 measures of hypoxia, persistent after adjustment for pulmonary physiologic impairment. Findings identify a strong role for sleep‐related hypoxia in AF development without pulmonary physiologic interdependence.