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- Title
Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response.
- Authors
Cederberg, Katie L. J.; Hanif, Umaer; Peris Sempere, Vicente; Hédou, Julien; Leary, Eileen B.; Schneider, Logan D.; Lin, Ling; Zhang, Jing; Morse, Anne M.; Blackman, Adam; Schweitzer, Paula K.; Kotagal, Suresh; Bogan, Richard; Kushida, Clete A.; Ju, Yo-El S.; Petousi, Nayia; Turnbull, Chris D.; Mignot, Emmanuel
- Abstract
Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.
- Subjects
SLEEP apnea syndromes; PROTEOMICS; PATHOLOGICAL physiology; APNEA; BIOMARKERS; BLOOD coagulation factor IX
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 14, p7983
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23147983