Sinem Berik Safçi, Leyla Yılmaz Aydın, Ramazan Memişoğulları, Özlem Admış, Şengül Cangür, Ali Annakkaya, Peri Arbak, Ege Güleç Balbay, Betül Arı

SERUM ASİMETRİK DİMETİL ARJİNİN DÜZEYİ VE OBSTRUKTİF UYKU APNE SENDROMU AĞIRLIĞI ARASINDAKİ İLİŞKİ

Amaç: Obstrüktif Uyku Apne Sendromu (OUAS) olan hastalarda ortaya çı- kan tekrarlayan hipoksemi ve reoksijenasyon oksidatif stres mekanizmala- rını tetikleyebilir. Oksidatif stres OUAS hastalarında Asimetrik dimetilargi- nin (ADMA) düzeylerini artırır. Çalışmamızda Serum Asimetrik Dimetil Ar- jinin (ADMA) düzeyi ve Obstrüktif Uyku Apne Sendromu (OUAS) ağırlığı arasındaki ilişkiyi incelemeyi amaçladık. Yöntemler: Polisomnografi yapılan 330 hasta kayıtları retrospektif olarak değerlendirildi. Anormal serum glukozu, lipid, tiroid, böbrek ve karaciğer bozuklukları olan hastalar çalışma dışı bırakıldı. Kabul kriterleri 72 sağladı. Hastalar apne hipopne indekslerine göre beş gruba ayrıldılar. Asimetrik Dimetil Arjinin ölçümleri ELİSA kiti ile yapıldı. Bulgular: Ortalama yaş 44,19 ± 14,24 idi. Hastaların %31,9'u kadındı. Has- talar normal, ağır, orta, hafif, rem-pozisyonel olarak gruplandığında; %26, %25, %6,9, %16,7 ve %25 oranlarındaydılar. AHI ve ADMA arasında an- lamlı korelasyon saptandı (r= 0,483; p10) ve negatif olabilirlik oranı (LR-) 0,28 (LR-

RELATIONSHIP BETWEEN SERUM ASYMMETRIC DIMETHYLARGININE LEVEL AND OBSTRUCTIVE SLEEP APNEA SYNDROME SEVERITY

Aim: The repetitive hypoxemia can induce oxidative stress mechanisms. Oxidative stress increases serum asymmetric dimethylarginine (ADMA) levels in patients with obstructive sleep apnea syndrome (OSAS). To in- vestigate the relationship between serumlevels of ADMA and OSAS severity. Methods: 330 patient’s records, who underwent overnight polysomnogra- phy (PSG) were retrospectively examined. The patients who had an abnor- mal serum glucose, lipid, thyroid, renal and liver function tests levels, had excluded. 72 patients had participating criteria. Patients were categorized into five groups according to apnea/hipopnea index (AHI). Measurement of ADMA levels were performed by ELISA kit. Results: The mean age was 44,19 ± 14,24 years. 31,9 % of the patients were female. Patients in normal group, severe, medium, mild and posi- tional–REM dependent OSAS group were 26,4%, 25%, 6,9 %, 16,7% and 25%; respectively. A significant positive correlation was found between AHI and ADMA (r= 0,483; p 10) and the negative likelihood ratio was (LR-) 0,28 (R-

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1. Dempsey JA, Veasey SC, Morgan BJ, et al. Pathophysiology of sleep apnea. Physiol Rev. 2010 Jan;90(1):47-112. doi: 10.1152/physrev.00043.2008
2. Riha RL. Defining obstructive sleep apnoea syndrome: a failure of semantic rules. Breathe (Sheff). 2021 Sep;17(3):210082. doi: 10.1183/20734735.0082-2021
3. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217-39. doi:10.1164/rccm.2109080
4. Sedeek MH, Llinas MT, Drummond H, et al. Role of reactive oxygen species in endothelin- induced hypertension. Hypertension. 2003;42(4):806-810. doi:10.1161/01.HYP.0000084372.91932.BA
5. Parish JM, Somers VK. Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc. 2004;79(8):1036-46. doi:10.4065/79.8.1036
6. Eisele HJ, Markart P, Schulz R. Obstructive Sleep Apnea, Oxidative Stress, and Cardiovascular Disease: Evidence from Human Studies. Oxid Med Cell Longev. 2015;-608438. doi:10.1155/2015/608438
7. May AM, Mehra R. Obstructive sleep apnea: role of intermittent hypoxia and inflammation. Semin Respir Crit Care Med. 2014;35(5):531-44. doi:10.1055/s-0034-1390023
8. Semelka M, Wilson J, Floyd R. Diagnosis and Treatment of Obstructive Sleep Apnea in Adults. Am Fam Physician. 2016;94(5):355-60.
9. Lugaresi E, Plazzi G. Heavy snorer disease: from snoring to the sleep apnea syndrome--an overview. Respiration. 1997;64(1):11-4. doi:10.1159/000196730
10. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine. 2017;13:479–504.
11. Pansani AP, Schoorlemmer GH, Ferreira CB et al. Chronic apnea during REM sleep increases arterial pressure and sympathetic modulation in rats. Sleep. 2021;14;44(5):zsaa249. doi: 10.1093/sleep/zsaa249
12. Polysomnography Task Force, American Sleep Disorders Association Standards of Practice Committee. Practice parameters for the indications for polysomnography and related procedures. Sleep. 1997;20:406-22.
13. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the use of portable recording in the assessment of obstructive sleep apnea. Sleep 1994;17:372-7.
14. Sleep related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research. The report of the American Academy of Sleep Medicine Task Force. Sleep 1999;22:667-89.
15. Kovács K, Karvaly GB, Farkas R, et al. Clinical and diagnostic relevance of asymmetric and symmetric dimethyl arginine (ADMA/SDMA). Orv Hetil. 2022;163(13):500-5. doi:10.1556/650.2022.32394
16. Teerlink T. ADMA metabolism and clearance. Vasc Med. 2005;10:S73-S81. doi:10.1191/1358863x05vm597oa
17. Leiper J, Murray-Rust J, McDonald N, et al. S- nitrosylation of dimethylarginine dimethyl- aminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci. 2002;99(21):135272. doi:10.1073/pnas.212269799
18. Valkonen VP, Laaksonen R. Asymmetric dimethylarginine (ADMA) and acute vascular events. Clin Chim Acta. 2004;348(1-2):9-17. doi:10.1016/j.cccn.2004.05.020
19. Noris M, Perico N, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol. 2005;1(2):98-120. doi:10.1038/ncpneph0035
20. Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4(4):41-51. doi:10.1016/s1567-5688(03)00033-3
21. Christou K, Moulas AN, Pastaka C, Gourgoulianis KI. Antioxidant capacity in obstructive sleep apnea patients. Sleep Med. 2003;4(3):225-228. doi:10.1016/s1389-9457(02)00253-8
22. Arrigoni FI, Vallance P, Haworth SG, et al. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation. 2003;107(8):1195-201. doi:10.1161/01.cir.0000051466.00227.13
23. Winnicki M, Shamsuzzaman A, Lanfranchi P, et al. Erythropoietin and obstructive sleep apnea. Am J Hypertens. 2004;17(9):783-6. doi:10.1016/j.amjhyper.2004.04.011
24. Barceló A, Piérola J, de la Peña M, et al. Day- night variations in endothelial dysfunction markers and haemostatic factors in sleep apnoea. Eur Respir J. 2012;39(4):913-8. doi:10.1183/09031936.00039911
25. Hannemann J, Böger R. Dysregulation of the Nitric Oxide/Dimethylarginine Pathway in Hypoxic Pulmonary Vasoconstriction-Molecular Mechanisms and Clinical Significance. Front Med (Lausanne). 2022;9:835481. doi:10.3389/fmed.2022.835481
26. İn E, Özdemir C, Kaman D, et al. Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome. Arch Bronconeumol. 2015;51(11):544-50. doi:10.1016/j.arbres.2015.02.020