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 obstructive sleep apnea (OSA) defined by the apnea-hypopnea index (AHI) or degree of nocturnal hypoxemia is associated with increased hazard 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: (i) AHI>30 and (ii) ≥10 minutes of sleep time spent with SaO2<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 regressions and controlling for confounders, hazards were compared between four groups: AHI>30 with COPD, AHI>30 without COPD, AHI≤30 with COPD, and AHI≤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 (PAP) 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 PAP device.

Results — Among 10,149 participants, 30% had AHI>30, 25% spent at least 10 minutes of sleep with SaO2<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<90% (HR=1.91 [1.60-2.28]), but not with AHI>30; a synergistic effect was found in women (RERI = 1.18 [0.05 to 2.30]), but not men (RERI = -0.08 [-0.47 to 0.32]). The highest hazard of outcome was associated with the co-occurrence of AHI>30 and COPD in untreated individuals (HR=2.01 [1.55-2.62]); 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 synergistic effect found only in women.