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Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity

Published:September 17, 2022DOI:https://doi.org/10.1016/j.numecd.2022.09.006

      Highlights

      • Balance of holesterol synthesis and absorption is markedly altered in OSA patients.
      • Enhanced cholesterol synthesis is associated with more severe form of OSA.
      • Evaluation of cholesterol metabolism could improve cardiovascular prevention in OSA.

      Abstract

      Background and aims

      Obstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity.

      Methods and results

      This study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO2) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022).

      Conclusions

      Our results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.

      Keywords

      Abbreviations:

      OSA (Obstructive sleep apnea), NCS (Non-cholesterol sterols), AHI (Apnea-hypopnea index), SaO2 (Oxygen saturation), NAFLD (Non-alcoholic fatty liver disease), CPAP (Continuous positive airway pressure), BMI (Body mass index), FBG (Fasting blood glucose), TG (Triglycerides), TC (Total cholesterol), HDL-C (High-density lipoprotein cholesterol), LDL-C (Low-density lipoprotein cholesterol), hsCRP (High-sensitivity C-reactive protein), γ-GT (γ-glutamyl transferase), oxLDL (Oxidized LDL), oxHDL (Oxidized HDL), FLI (Fatty liver index), ODI (Oxygen desaturation index), LC-MS/MS (Liquid chromatography-tandem mass spectrometry), MRM (Multiple-reaction-monitoring), L/C (Lathosterol/cholesterol ratio), D/C (Desmosterol/cholesterol ratio), C/C (Campesterol/cholesterol ratio), B/C (β-sitosterol/cholesterol ratio), Cholsynthesis (Cholesterol synthesis markers), Cholabsorption (Cholesterol absorption markers), VIF (Variance inflation factor), COPD (Chronic obstructive pulmonary disease), RBC (Red blood cells), WBC (White blood cells), PLT (Platelets)
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