Obstructive sleep apnea syndrome attenuated high-density lipoprotein function

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. High-density lipoproteins (HDLs) exert anti-atherogenic effects, even on cholesterol efflux capacity (CEC). The HDL proteome is reportedly altered in patients with coronary artery disease.

We hypothesized that OSA attenuates HDL function through an altered HDL proteome, which could be alleviated by continuous positive airway pressure (CPAP) therapy.

Patients aged ≥ 20 years (n = 115) with suspected OSA were enrolled in this cross-sectional study, with 34 patients diagnosed with moderate and severe OSA included in the interventional study and treated with CPAP therapy for 12 weeks. To further investigate the HDL proteome in OSA, we conducted a discovery study by analyzing HDL proteomes in 10 patients.

In this study, CEC was significantly lower in the sleep apnea syndrome (SAS) group (apnea-hypopnea index [AHI] ≥ 5) than in the non-SAS group (AHI < 5; 0.96 ± 0.14 vs. 1.06 ± 0.15, p = 0.01). Multiple regression analysis revealed that minimal pulse oxygen saturation (MinSpO₂) was positively correlated with CEC. In the interventional study, 12-week CPAP therapy did not affect CEC. We identified orosomucoid 1 (ORM1), an acute-phase inflammatory molecule, as a candidate protein for OSA-induced HDL dysfunction. Further validation study revealed that serum ORM1 levels were inversely associated with CEC, independent of HDL-cholesterol and high-sensitivity C-reactive protein.

HDL function was impaired in patients with OSA and a reduced CEC. However, CPAP therapy did not affect CEC. An altered HDL proteome, particularly with increased ORM1 levels, may be associated with impaired HDL function.

This clinical study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000025335 and UMIN000025341).