Cardiovascular Outcomes and All-Cause Mortality in Patients with Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease (Overlap Syndrome).

RATIONALE: The combined impact of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) on cardiovascular outcomes remains controversial.

OBJECTIVES: We determined whether the combined presence of COPD and severe OSA defined by the apnea-hypopnea index (AHI) or degree of nocturnal hypoxemia is associated with increased hazards of cardiovascular events and mortality.

METHODS: Prospectively collected data from adults with suspected OSA who underwent sleep study between 1994 and 2010 were linked to provincial administrative data to determine a presence of COPD and composite outcome. Exposures of interest were: 1) AHI greater than 30, and 2) 10 or more minutes of sleep time spent with oxygen saturation (SaO2 ) less than 90%. The primary outcome was a composite of hospitalization due to myocardial infarction, stroke, congestive heart failure, cardiac revascularization procedures, or death from any cause. Using Cox regression and controlling for confounders, hazards were compared between four groups: AHI greater than 30 with COPD, AHI greater than 30 without COPD, AHI less than or equal to 30 with COPD, and AHI less than or equal to 30 without COPD (reference). A similar approach was used for the degree of nocturnal hypoxemia. Relative excess risk due to interaction (RERI) was calculated. To adjust for the effect of positive airway pressure treatment, given that information on its acceptance, but not adherence, was available, a separate analysis was conducted only on untreated individuals who never claimed a positive airway pressure device.

RESULTS: Among 10,149 participants, 30% had AHI greater than 30, 25% spent at least 10 minutes of sleep with SaO2 less than 90%, and 12% had COPD. Over a median of 9.4 years, 16.4% developed an outcome. In the total sample, a greater hazard of outcome was observed in individuals with COPD who spent at least 10 minutes of sleep with SaO2 less than 90% (hazard ratio, 1.91; 95% confidence interval [CI], 1.60 to 2.28) but not with AHI greater than 30; a synergistic effect was found in women (RERI, 1.18; 95% CI, 0.05 to 2.30), but not men (RERI, -0.08; 95% CI, -0.47 to 0.32). The highest hazard of outcome was associated with the co-occurrence of AHI greater than 30 and COPD in untreated individuals (hazard ratio, 2.01; 95% CI, 1.55 to 2.62); a synergistic effect was not found.

CONCLUSIONS: In adults with suspected OSA, the co-occurrence of nocturnal hypoxemia and COPD was associated with an increased hazard of cardiovascular events and mortality with a synergistic effect found only in women.