Molecular insights into hypoxic burden physiopathology in OSA: a proteomic perspective

<bold>Background:</bold> Hypoxic burden (HB) has emerged as a strong indicator of cardiovascular (CV) risk and response to treatment in obstructive sleep apnea (OSA). The molecular mechanisms and pathways that relate HB to CV disease have not been investigated. <bold>Aim:</bold> To evaluate differences in the circulating proteomic profile of OSA patients stratified by treir HB. <bold>Methods:</bold> Post-hoc analysis of the ISAACC trial (<ext-link>NCT01335087</ext-link>) including subjects with acute coronary syndrome (ACS) who underwent respiratory polygraphy. Fasting blood samples were obtained during hospital admission. OSA patients (AHI ≥15) were categorized according to the median HB value (74.2 %min/h). A subpopulation of 52 patients was selected after matching the study groups by age, sex, BMI, and AHI. We analyzed 344 cardiovascular, inflammatory and organ damage-related plasma proteins using Proximity Extension Assay Technology (Olink, Sweden). <bold>Results:</bold> This pilot analysis included 52 OSA patients (median age =55.5 years, median BMI =28.0 kg/m2, 46% males, and median [CI] AHI =31.2 [20.9;41.8]). High and low HB groups were similar in sociodemographic/anthropometric characteristics and AHI. A total of 10 plasma proteins were downregulated (p-value <0.05 & fold change <0.8) in the high HB group compared to the low HB group. Multivariate analysis defined a proteomic fingerprint that showed a significant dose-response relationship with HB levels, after adjusting for confounders. Identified proteins were mostly implicated in cellular adhesion, extracellular matrix modifications and leukocyte migration. <bold>Conclusion:</bold> A specific proteomic profile with potential CV implications is identified in patients with OSA and ACS, using HB as a novel risk-stratification metric.