エンドウ　ヤスヒロ   YASUHIRO ENDO   遠藤　康弘    所属   新潟薬科大学  医療技術学部 学部付    職種   准教授
言語種別	英語
発行・発表の年月	2024/06/08
形態種別	論文 - 研究論文（学術雑誌）
標題	Obstructive sleep apnea syndrome attenuated high-density lipoprotein function.
執筆形態	単著（従来区分）
掲載誌名	Journal of clinical lipidology
掲載区分	国外
担当区分	筆頭著者,責任著者
著者・共著者	Yasuhiro Endo,Manami Teramoto,Junko Arakawa,Shoko Ukita,Genta Toshima,Yumiko Suenaga,Kei Sasaki,Makoto Ayaori,Hideaki Nakayama,Yuichi Inoue,Katsunori Ikewaki
概要	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).
DOI	10.1016/j.jacl.2024.05.008
PMID	39294021