Does Hypoxic Burden Better Explain Sex Differences in Functional Impairments Than Apnoea-Hypopnoea Index in Obstructive Sleep Apnoea?

Women with obstructive sleep apnoea (OSA) report more severe functional impairments than men, despite lower apnoea-hypopnoea index (AHI) values. This raises questions about the adequacy of AHI for capturing OSA severity. We explored sex differences in functional outcomes in OSA patients and examined whether AHI or hypoxic burden (HB) better explained these differences. We analysed cross-sectional data from Sydney Sleep Biobank (2018-2023). Adults with OSA (AHI ≥ 5 events/h on polysomnography) with data on mood (Depression, Anxiety and Stress Scale; DASS-21) and daytime functioning (Functional Outcomes of Sleep Questionnaire; FOSQ-10) were included. Linear regression models examined associations between sex, AHI, HB and functional outcomes. Interaction effects of sex and AHI/HB were explored. Among 518 untreated OSA patients (67.7% men, mean age = 54.0, SD = 14.6 years), women had significantly higher DASS-21 (15.4 vs. 12.1, p < 0.01) and lower FOSQ-10 (14.1 vs. 16.0, p < 0.0001) scores, despite lower AHI (28.7 vs. 32.9, p = 0.10) and HB (47.4 vs. 82.7, p < 0.001). Neither AHI nor HB was associated with worse mood, although AHI was linked to poorer mood in women in sensitivity analyses. AHI and HB were associated with worse FOSQ-10. In multivariable models adjusting for demographics, anthropometry, comorbidities and medications, neither AHI nor HB consistently predicted mood or daytime functioning. Sex differences in mood were explained by comorbid mood disorders, insomnia and chronic pain. Women had more severe functional impairments despite milder respiratory indices. Given the greater influence of comorbidities on functional outcomes than respiratory metrics, comprehensive comorbidity assessment in OSA evaluation is warranted, especially in females.