Obstructive sleep apnea syndrome attenuated high-density lipoprotein function

Yasuhiro Endo; Manami Teramoto; Junko Arakawa; Shoko Ukita; Genta Toshima; Yumiko Suenaga; Kei Sasaki; Makoto Ayaori; Hideaki Nakayama; Yuichi Inoue; Katsunori Ikewaki

doi:10.1016/j.jacl.2024.05.008

Obstructive sleep apnea syndrome attenuated high-density lipoprotein function

J Clin Lipidol. 2024 Jun 8:S1933-2874(24)00199-5. doi: 10.1016/j.jacl.2024.05.008. Online ahead of print.

Authors

Affiliations

¹ Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan (Drs Endo, Teramoto, Arakawa, Suenaga, Sasaki, and Ikewaki); Division of Environmental Medicine, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama, Japan (Dr Endo). Electronic address: doc32006@ndmc.ac.jp.
² Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan (Drs Endo, Teramoto, Arakawa, Suenaga, Sasaki, and Ikewaki).
³ Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan (Drs Ukita and Toshima).
⁴ Tokorozawa Heart Center, Saitama, Japan (Dr Ayaori).
⁵ Department of Somnology, Tokyo Medical University, Tokyo, Japan (Dr Nakayama).
⁶ Japan Somnology Center, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inoue).

PMID: 39294021
DOI: 10.1016/j.jacl.2024.05.008

Abstract

Background: 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.

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

Methods: 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.

Results: 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, a 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.

Conclusions: 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.

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

Keywords: Apolipoproteins; Cholesterol/efflux capacity; Lipid; Lipid/Efflux; Lipoprotein.