BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.

Charles University Faculty of Medicine in Pilsen Department of Biology Pilsen Czech Republic

Charles University Faculty of Medicine in Pilsen Department of Pharmacology and Toxicology Pilsen Czech Republic

Charles University University Hospital in Pilsen Faculty of Medicine in Pilsen Department of Immunochemistry Diagnostics Pilsen Czech Republic

Charles University University Hospital in Pilsen Faculty of Medicine in Pilsen Department of Otorhinolaryngology Pilsen Czech Republic

Charles University University Hospital in Pilsen Faculty of Medicine in Pilsen Department of Pathology Pilsen Czech Republic

Charles University University Hospital in Pilsen Faculty of Medicine in Pilsen Department of Pneumology and Phthisiology Pilsen Czech Republic

Masaryk University Faculty of Medicine Department of Otorhinolaryngology and Head and Neck Surgery Brno Czech Republic

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AASM - American Academy of Sleep Medicine (2016). AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Ver. 2.3.0. Darien: AASM. [online] [cit. 2023-10-25]. Available from: https://aasm.org/

Akset M, Poppe KG, Kleynen P, Bold I, Bruyneel M (2023). Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationschip. Clin Endocrinol 98(1) 3-13. DOI: 10.1111/cen.14685. PubMed DOI

Arachchige MA, Steier J (2022). Beyond Usual Care: A Multidisciplinary Approach Towards the Treatment of Obstructive Sleep Apnoea. Front Cardiovas Med 8: 747495. DOI: 10.3389/fcvm.2021.747495. PubMed DOI

Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MS, Morrell MJ, et al. (2019). Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med 7(8): 687-698. DOI: 10.1016/S2213-2600(19)30198-5. PubMed DOI

Cahan C, Decker M, Strohl KP (1990). Humoral correlates of sleep apnea: erythropoietin and hypoxemia: erythropoietin and hypoxemia. Prog Clin Biol Res 345: 317-324.

Chaulin AM (2023). Gender Specificities of Cardiac Troponin Serum Levels: From Formation Mechanism to the Diagnostic Role in Case of Acute coronary Syndrome. Life 13(2): 267. DOI: 10.3390/life13020267. PubMed DOI

Choi JL, Joseph L, Pilote L (2013). Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev 14(3): 232-244. DOI: 10.1111/obr.12003. PubMed DOI

Denver RJ, Bonnet RM, Boorse (2011). Evolution of Leptin Structure and Function. Neuroendocrinology 94(1): 21-38. DOI: 10.1159/000328435. PubMed DOI

Filipovsky T, Kalfert D, Lukavcova E, Zavazalova S, Hlozek J, Kovar D, et al. (2023). The importance of preoperative and perioperative Narrow Band Imaging endoscopy in the diagnosis of pre-tumor and tumor lesions of the larynx. J Appl Biomed 21(3): 107-112. DOI: 10.32725/jab.2023.015. PubMed DOI

Gottlieb DJ, Punjabi NM (2020). Diagnosis and management of obstructive sleep apnea: a review. Jama 323(14): 1389-1400. DOI: 10.1001/jama.2020.3514. PubMed DOI

Goulart MR, Schuh DS, Moraes DW, Barbiero SM, Pellanda LC (2017). Serum C-reactive protein levels and body mass index in children and adolescents with CHD. Cardiol Young 27(6): 1083-1089. DOI: 10.1017/S1047951116002080. PubMed DOI

He Y, Cheng Y, Huang Z, Xu W, Hu R, Cheng L, et al. (2021). A deep convolutional neural network-based method for laryngeal squamous cell carcinoma diagnosis. Ann Transl Med 9(24): 1797. DOI: 10.21037/atm-21-6458. PubMed DOI

Hellemans J, Mortier G, De Paepe A, Speleman F, Vandesompele J (2007). qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8(2): R19. DOI: 10.1186/gb-2007-8-2-r19. PubMed DOI

Hutchinson WL, Koenig W, Frohlich M, Sund M, Lowe GD, Pepys MB (2000). Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Clin Chem 46(7): 934-938. DOI: 10.1093/clinchem/46.7.934. DOI

Imani MM, Sadeghi M, Farokhzadeh F, Khazaie H, Brand S, Dürsteler KM, et al. (2021). Evaluation of Blood Levels of C-Reactive Protein Marker in Obstructive Sleep Apnea: A Systematic Review, Meta-Analysis and Meta-Regression. Life 11(4): 362. DOI: 10.3390/life11040362. PubMed DOI

Jennum P, Ibsen R, Kjellberg J (2014). Social consequences of sleep disordered breathing on patients and their partners: a controlled national study. Eur Respir J 43(1): 134-144. DOI: 10.1183/09031936.00169212. PubMed DOI

Kanbay A, Kaya E, Büyükoğlan H, Kaya MG, Şimşek ZÖ, Tutar N, Demir R (2015). Correlation between pentraxin-3 and endothelial dysfunction in obstructive sleep apnea syndrome. Ann Thorac Med 10(3): 199-203. DOI: 10.4103/1817-1737.160840. PubMed DOI

Kasai T, Inoue K, Kumagai T, Kato M, Kawana F, Sagara M, et al. (2011). Plasma pentraxin3 and arterial stiffness in men with obstructive sleep apnea. Am J Hypertens 24(4): 401-407. DOI: 10.1038/ajh.2010.248. PubMed DOI

Katsoulis K, Kontakiotis T, Spanogiannis D, Vlachogiannis E, Kougioulis M, Gerou S, Daskalopoulou E (2011). Total antioxidant status in patients with obstructive sleep apnea without comorbidities: the role of the severity of the disease. Sleep Breath 15(4): 861-866. DOI: 10.1007/s11325-010-0456-y. PubMed DOI

Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, Van Griensven M (2017). miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep 7(1): 15861. DOI: 10.1038/s41598-017-16113-x. PubMed DOI

Kobukai Y, Koyama T, Watanabe H, Ito H (2014). Morning pentraxin3 levels reflect obstructive sleep apnea - related acute inflammation. J Appl Physiol 117(10): 1141-1148. DOI: 10.1152/japplphysiol.00237.2014. PubMed DOI

Kroh EM, Parkin RK, Mitchell PS, Tewari M (2010). Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50(4): 298-301. DOI: 10.1016/j.ymeth.2010.01.032. PubMed DOI

Lavie L (2009). Oxidative Stress - A Unifying Paradigm in Obstructive Sleep Apnea and Comorbidities. Prog Cardiovasc Dis 51(4): 303-312. DOI: 10.1016/j.pcad.2008.08.003. PubMed DOI

Lee KK, Ferry AV, Anand A, Strachan FE, Chapman AR, Kimenai DM, et al. (2019). Sex-Specific Thresholds of High-Sensitivity Troponin in Patients with Suspected Acute Coronary Syndrome. J Am Coll Cardiol 74(16): 2032-2043. DOI: 10.1016/j.jacc.2019.07.082. PubMed DOI

Lv Q, Sun H, Du Z, Jiao X, Yu H, Sun Q., et al. (2021). Increased levels of VCAM-1 is associated with higher occurrence of coronary artery disease in adults with moderate to severe obstructive sleep apnea. Sleep Med 85: 131-137. DOI: 10.1016/j.sleep.2021.07.002. PubMed DOI

Lyons MM, Bhatt NY, Pack AI, Magalang UJ (2020). Global burden of sleep-disordered breathing and its implications. Respirology 25(7): 690-702. DOI: 10.1111/resp.13838. PubMed DOI

McKeon JL, Saunders NA, Murree-Allen K, Olson LG (1990). Urinary Uric Acid: Creatinine Ratio, Serum Erythropoietin, and Blood 2,3-Diphosphoglycerate in Patients with Obstructive Sleep Apnea. Am Rev Respir Dis 142(1): 8-13. DOI: 10.1164/ajrccm/142.1.8. PubMed DOI

Meder B, Backes C, Haas J, Leidinger P, Stähler C, Großmann T, et al. (2014). Influence of the confounding factors age and sex on microRNA profiles from peripheral blood. Clin Chem 60(9): 1200-1208. DOI: 10.1373/clinchem.2014.224238. PubMed DOI

Neumann JT, Twerenbold R, Ojeda F, Sörensen NA, Chapman AR, Shah AS, et al. (2019). Application of high-sensitivity troponin in suspected myocardial infarction. New Engl J Med 380(26): 2529-2540. DOI: 10.1056/NEJMoa1803377. PubMed DOI

Ohga E, Nagase T, Tomita T, Teramoto S, Matsuse T, Katayama H, Ouchi Y (1999). Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol 87(1): 10-14. DOI: 10.1152/jappl.1999.87.1.10. PubMed DOI

Pak VM, Keenan BT, Jackson N, Grandner MA, Maislin G, Teff K, et al. (2015). Adhesion molecule increases in sleep apnea: beneficial effect of positive airway pressure and moderation by obesity. Int J Obes 39(3): 472-479. DOI: 10.1038/ijo.2014.123. PubMed DOI

Pešta M, Kučera R, Topolčan O, Karlíková M, Houfková K, Polívka J, et al. (2019). Plasma microRNA levels combined with CEA and CA19-9 in the follow-up of colorectal cancer patients. Cancers 11(6): 864. DOI: 10.3390/cancers11060864. PubMed DOI

Pinilla L, Barbe F, De Gonzalo-Calvo D (2021). MicroRNAs to guide medical decision-making in obstructive sleep apnea: A review. Sleep Med Rev 59: 101458. DOI: 10.1016/j.smrv.2021.101458. PubMed DOI

Pinto JA, Ribeiro DK, Cavallini AFDS, Duarte C, Freitas GS (2016). Comorbidities associated with obstructive sleep apnea: a retrospective study. Int Arch Otorhinolaryngol 20(2): 145-150. DOI: 10.1055/s-0036-1579546. PubMed DOI

Potts KJ, Butterfield DT, Sims P, Henderson M, Shames CB (2013). Cost savings associated with an education campaign on the diagnosis and management of sleep-disordered breathing: a retrospective, claims-based US study. Popul Health Manag 16(1): 7-13. DOI: 10.1089/pop.2011.0102. PubMed DOI

Pretl M, Hobzová M, Honnerová M, Lněnička J, Novák V, Sedlák V, et al. (2011). Indikační kriteria pro léčbu poruch dýchání ve spánku pomocí přetlaku v dýchacích cestách u dospělých. Prague

Czech Sleep Research and Sleep Medicine Society Website. [online] [cit. 2023-10-25]. Available from: https://www.sleep-society.cz/doc/doporucene-postupy/Indikacni-kriteria-pro-lecbu-PAP-2011.pdf

Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL (2002). Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Resp Crit Care Med 165(5): 677-682. DOI: 10.1164/ajrccm.165.5.2104087. PubMed DOI

Reutrakul S, Mokhlesi B (2017). Obstructive Sleep Apnea and Diabetes. Chest 152(5): 1070-1086. DOI: 10.1016/j.chest.2017.05.009. PubMed DOI

Rifai N, Ridker PM (2003). Population Distributions of C-reactive Protein in Apparently Healthy Men and Women in the United States: Implication for Clinical Interpretation. Clin Chem 49(4): 666-669. DOI: 10.1373/49.4.666. PubMed DOI

Sahlman J, Miettinen K, Peuhkurinen K, Seppä J, Peltonen M, Herder C (2010). The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea. J Sleep Res 19(2): 341-348. DOI: 10.1111/j.1365-2869.2009.00787.x. PubMed DOI

Sánchez-de-la-Torre M, Khalyfa A, Sánchez-de-la-Torre A, Martinez-Alonso M, Martinez-García MÁ, Barceló A, et al. (2015). Precision medicine in patients with resistant hypertension and obstructive sleep apnea: blood pressure response to continuous positive airway pressure treatment. J Am Col Cardiol 66(9): 1023-1032. DOI: 10.1016/j.jacc.2015.06.1315. PubMed DOI

Sánchez-de-la-Torre A, Soler X, Barbé F, Florés M, Maisel A, Malhotra A, et al. (2018). Cardiac troponin values in patients with acute coronary syndrome and sleep apnea: a pilot study. Chest 153(2): 329-338. DOI: 10.1016/j.chest.2017.06.046. PubMed DOI

Santamaria-Martos F, Benítez I, Ortega F, Zapater A, Giron C, Pinilla L, et al. (2019). Circulating microRNA profile as a potential biomarker for obstructive sleep apnea diagnosis. Sci Rep 9(1): 13456. DOI: 10.1038/s41598-019-49940-1. PubMed DOI

Santamaria-Martos F, Benitez I, Pinilla L, Ortega F, Zapater A, Giron C, et al. (2020). MicroRNA profile of cardiovascular risk in patients with obstructive sleep apnea. Respiration 99(12): 1122-1128. DOI: 10.1159/000511093. PubMed DOI

Schwarzenbach H, Da Silva AM, Calin G, Pantel K (2015). Data normalization strategies for microRNA quantification. Clin Chem 61(11): 1333-1342. DOI: 10.1373/clinchem.2015.239459. PubMed DOI

Slouka D, Kučera R, Gál B, Betka J, Skálová A (2019). Biomarkers - a possibility for monitoring of obstructive sleep apnea syndrome. Neuro Endocrinol Lett 40(2): 85-92.

Solecká Š, Matler K, Kostlivý T, Kubec V, Tomášková H, Betka J (2022). A Comparison of the Reliability of Five Sleep Questionnaires for the Detection of Obstructive Sleep Apnea. Life 12(9): 1416. DOI: 10.3390/life12091416. PubMed DOI

Verma RK, Dhillon G, Grewal H, Prasad V, Munjal RS, Sharma P, et al. (2023). Artificial intelligence in sleep medicine: Present and future. World J Clin Cases 11(34): 8106-8110. DOI: 10.12998/wjcc.v11.i34.8106. PubMed DOI

Wang Y, Hu K, Liu K, Li Z, Yang J, Dong Y, et al. (2015). Obstructive sleep apnea exacerbates airway inflammation in patients with chronic obstructive pulmonary disease. Sleep Med 16(9): 1123-1130. DOI: 10.1016/j.sleep.2015.04.019. PubMed DOI

Welsh P, Preiss D, Shah AS, McAllister D, Briggs A, Boachie C, et al. (2018). Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Xlin Chem 64(11): 1607-1616. DOI: 10.1373/clinchem.2018.292086. PubMed DOI

Xu S, Wan Y, Xu M, Ming J, Xing Y, An F, Ji Q (2015). The association between obstructive sleep apnea and metabolic syndrome: a systematic review and meta-analysis. BMC Pulm Med 15: 105. DOI: 10.1186/s12890-015-0102-3. PubMed DOI

Zapater A, Benítez ID, Santamaria-Martos F, Pinilla L, Targa A, De Gonzalo-Calvo D, et al. (2022). Endogenous controls and microRNA profile in female patients with obstructive sleep apnea. Sci Rep 12(1): 1916. DOI: 10.1038/s41598-022-05782-y. PubMed DOI