Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response

Authors:
Open Access
Publisher website
Google Scholar
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.
Funding Information
  • National Institutes of Health (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • Bryte Foundation (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • Klarman Family Foundation (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • Oxford Radcliffe Hospital Charitable Funds (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • ResMed UK (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • Philips Respironics (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • National Institutes of Health (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • NIH National Center for Advancing Translational Sciences (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)
  • NIHR Academic Clinical Lectureships (R24 HL114473, 75N92019R002, T32HL110952, K23NS089922, UL1RR024992, KL2TR000450, UL1TR000448)

This publication has 52 references indexed in Scilit: