Association between proteomics and obstructive sleep apnea phenotypes in a community-based cohort of women

Proteomic-based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep-disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease-related proteins in a population-based cohort of women. In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek^® Inflammation panel and Olink Proseek^® Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women. p-Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea-hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement-apnea-hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea-hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement-apnea-hypopnea index ≥ 30) was associated with decreased levels of two anti-inflammatory proteins; Sirt2 (q-value .016) and LAP-TGF-β₁ (q-value .016). There was also a negative association between rapid eye movement-apnea-hypopnea index of ≥ 30 and Axin1 (q-value .095), a protein thought to facilitate TGF-β-signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP-TGF-β₁ and Axin1, anti-inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index.