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Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity
Institution:1. Department of Medical Biochemistry, University of Belgrade – Faculty of Pharmacy, Belgrade, Serbia;2. Department of Laboratory Diagnostics, University Medical Center “Be?anijska kosa”, Belgrade, Serbia;3. Department of Cardiology, University Medical Center “Be?anijska kosa” and University of Belgrade-Faculty of Medicine, Belgrade, Serbia;4. Department of Pulmonology, University Medical Center “Be?anijska kosa”, Belgrade, Serbia;1. Department of Internal Medicine, “S. Maria delle Grazie” Hospital, Pozzuoli, Italy;2. Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children''s Hospital, Napoli, Italy;3. Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy;4. Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli, Italy;5. Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Italy;6. Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari “Aldo Moro”, Bari, Italy;7. Section of Pediatrics, Department of Translational Medical Science, Regional Center of Pediatric Diabetes, University of Naples Federico II, Napoli, Italy;8. Pediatric Department, “V. Buzzi” Children’s Hospital, Milano and Department of Internal Medicine, University of Pavia, Italy;9. Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy;10. Pediatric Department, Azienda Sanitaria Universitaria del Friuli Centrale, Hospital of Udine, Udine, Italy;11. Department of Movement Sciences and Wellbeing, University “Parthenope”, Napoli, Italy;1. Diabetes and Islet Transplantation Unit, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Palermo, Italy;2. Department of Internal Medicine, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy;3. Dipartimento di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza “G. D''Alessandro”, PROMISE, University of Palermo, Palermo, Italy;1. Department of Cardiac Function, The People''s Hospital of China Medical University and the People''s Hospital of Liaoning Province, Shenyang 110016, China;2. Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang 110001, China;3. Department of Ultrasonography, The People''s Hospital of Zhengzhou University, Zhengzhou 450003, China;4. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, China;1. Department of Urology Surgery, The Second Hospital of Jiaxing City, 1518 North Ring Road, Nanhu District, Jiaxing City, Zhejiang Province, PR China;2. Department of Urology, Huashan Hospital, Fudan University, No.12 Middle Urumqi Road, Shanghai, 200040, PR China;1. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden;2. Research, Education, Development & Innovation, Primary Health Care, R&D Centre Skaraborg, Region Vastra Gotaland, Sweden;3. School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden;4. Department of Medicine, Sahlgrenska University Hospital, Molndal, Sweden;5. Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden;6. Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden;1. Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore;2. Université de Paris, CRESS, Inserm, INRAE, F-75004 Paris, France;3. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore;4. Department of Maternal Fetal Medicine, KK Women''s and Children''s Hospital, Singapore;5. Department of Paediatric Endocrinology, KK Women''s and Children''s Hospital, Singapore;6. Duke-NUS Medical School, Singapore;7. Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore;8. Liggins Institute, University of Auckland, New Zealand;9. MRC Lifecourse Epidemiology Unit & NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, UK;10. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore;11. Department of Reproductive Medicine, KK Women''s and Children''s Hospital, Singapore;12. Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore
Abstract:Background and aimsObstructive 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 resultsThis 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).ConclusionsOur 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:Obstructive sleep apnea  Cholesterol synthesis and absorption  Obesity  Dyslipidemia  Apnea-hypopnea index  Non-cholesterol sterols  OSA"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"Obstructive sleep apnea  NCS"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"Non-cholesterol sterols  AHI"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"Apnea-hypopnea index  SaO2"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"Oxygen saturation  NAFLD"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"Non-alcoholic fatty liver disease  CPAP"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"Continuous positive airway pressure  BMI"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"Body mass index  FBG"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"Fasting blood glucose  TG"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"Triglycerides  TC"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"Total cholesterol  HDL-C"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"High-density lipoprotein cholesterol  LDL-C"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"Low-density lipoprotein cholesterol  hsCRP"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"High-sensitivity C-reactive protein  γ-GT"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"γ-glutamyl transferase  oxLDL"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"Oxidized LDL  oxHDL"}  {"#name":"keyword"  "$":{"id":"kwrd0235"}  "$$":[{"#name":"text"  "_":"Oxidized HDL  FLI"}  {"#name":"keyword"  "$":{"id":"kwrd0245"}  "$$":[{"#name":"text"  "_":"Fatty liver index  ODI"}  {"#name":"keyword"  "$":{"id":"kwrd0255"}  "$$":[{"#name":"text"  "_":"Oxygen desaturation index  LC-MS/MS"}  {"#name":"keyword"  "$":{"id":"kwrd0265"}  "$$":[{"#name":"text"  "_":"Liquid chromatography-tandem mass spectrometry  MRM"}  {"#name":"keyword"  "$":{"id":"kwrd0275"}  "$$":[{"#name":"text"  "_":"Multiple-reaction-monitoring  L/C"}  {"#name":"keyword"  "$":{"id":"kwrd0285"}  "$$":[{"#name":"text"  "_":"Lathosterol/cholesterol ratio  D/C"}  {"#name":"keyword"  "$":{"id":"kwrd0295"}  "$$":[{"#name":"text"  "_":"Desmosterol/cholesterol ratio  C/C"}  {"#name":"keyword"  "$":{"id":"kwrd0305"}  "$$":[{"#name":"text"  "_":"Campesterol/cholesterol ratio  B/C"}  {"#name":"keyword"  "$":{"id":"kwrd0315"}  "$$":[{"#name":"text"  "_":"β-sitosterol/cholesterol ratio  Cholsynthesis"}  {"#name":"keyword"  "$":{"id":"kwrd0325"}  "$$":[{"#name":"text"  "_":"Cholesterol synthesis markers  Cholabsorption"}  {"#name":"keyword"  "$":{"id":"kwrd0335"}  "$$":[{"#name":"text"  "_":"Cholesterol absorption markers  VIF"}  {"#name":"keyword"  "$":{"id":"kwrd0345"}  "$$":[{"#name":"text"  "_":"Variance inflation factor  COPD"}  {"#name":"keyword"  "$":{"id":"kwrd0355"}  "$$":[{"#name":"text"  "_":"Chronic obstructive pulmonary disease  RBC"}  {"#name":"keyword"  "$":{"id":"kwrd0365"}  "$$":[{"#name":"text"  "_":"Red blood cells  WBC"}  {"#name":"keyword"  "$":{"id":"kwrd0375"}  "$$":[{"#name":"text"  "_":"White blood cells  PLT"}  {"#name":"keyword"  "$":{"id":"kwrd0385"}  "$$":[{"#name":"text"  "_":"Platelets
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