Impact Of Obstructive Sleep Apnoea and Its Severity On The Mechanisms Of Aortic Valve Atherosclerosis

Obstructive sleep apnoea (OSA) is a common chronic condition associated with cardiovascular disease including calcific aortic valve disease (CAVD). The aim of this study was to assess the impact of OSA on mechanisms of atherosclerosis involved in CAVD, particularly autophagy, inflammation, oxidative stress and calcification. Thirty-one patients scheduled for surgical aortic valve replacement were prospectively enrolled, 18 of whom had OSA (AHl≥15/h) on polysomnography. Native aortic valves were harvested during surgery and isolated into 3 sections based on macroscopic appearance (healthy, intermediate, calcified). Quantification of gene and protein expression were performed by RT-qPCR and Western blot. Factors associated with transcriptional and translational expression were investigated in a multivariate analysis. OSA severity was associated with decreased Beclin-1 gene expression (impairment of autophagy) in healthy valve tissue in the minimal SaO2 <88% group vs. ≥88% group (p<0.05); and with decreased P62 protein expression (increase of autophagy) in intermediate valve tissue in severe OSA vs. non-OSA (p=0.03). In calcified valve tissue, Beclin-1 gene expression was reduced (p<0.001), suggesting a deregulation of autophagy independent of OSA status. Increased osteocalcin gene expression was associated with desaturation index (p=0.02). This is the first study to evaluate the impact of OSA on human valvular atherosclerosis mechanisms. The severity of OSA as assessed by hypoxic measurement is associated with a decrease in autophagy and pro-calcifying activity. This work opens therapeutic perspectives to modulate these mechanisms to limit valve damage and atherosclerosis in OSA.