Endothelial and Angiogenic Biomarkers in Obstructive Sleep Apnea: Longitudinal Associations With Continuous Positive...

Continuous positive airway pressure (CPAP) abolishes apneas in obstructive sleep apnea (OSA), but its long-term vascular associations remain uncertain. Findings from cohorts with coronary artery disease suggested higher CPAP pressures may be associated with endothelial biomarker patterns, raising concerns about potential pro-inflammatory responses in broader OSA populations. We therefore assessed the longitudinal associations of CPAP on endothelial and epithelial biomarkers in OSA patients free of cardiovascular comorbidities.

In the EPIOSA study, a 5-year prospective cohort of moderate-to-severe OSA patients and non-OSA controls, plasma angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), Tie-2, and E-selectin were measured at baseline, 1 year, and 5 years. Participants were managed with or without CPAP according to clinical guidelines. Associations between biomarkers and clinical, sleep, and biochemical variables were examined using multivariable regression models.

Among 326 participants (OSA: n=195; controls: n=72), CPAP-treated OSA patients (mean usage 6.7±1.1h/night) showed sustained reductions in VEGF at both follow-up visits, independently related to baseline VEGF and waist-to-hip ratio. Ang-2 increased over time in both OSA and control groups, with no association to CPAP pressure or adherence. Body weight and soluble ST2 (sST2) independently predicted baseline Ang-2. Tie-2 and E-selectin showed minimal temporal variation.

In otherwise healthy OSA patients, long-term CPAP is associated with attenuation of hypoxia-driven VEGF pathways without altering Ang-2 trajectories, supporting non-hypoxic mechanisms of vascular risk that merit further investigation.