Serum Asimetrik Dimetil Arjinin (ADMA) Düzeyi ve Obstruktif Uyku Apne Sendromu (OUAS) Ağırlığı Arasındaki İlişki

Yıl 2022, Cilt: 5 Sayı: 1, 68 - 75, 30.04.2022

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

Öz

Giriş: Obstrüktif Uyku Apne Sendromu (OUAS) olan hastalarda ortaya çıkan tekrarlayan hipoksemi ve reoksijenasyon oksidatif stres mekanizmalarını tetikleyebilir. Oksidatif stres OUAS hastalarında Asimetrik dimetilarginin (ADMA) düzeylerini artırır.
Amaç: Serum Asimetrik Dimetil Arjinin (ADMA) düzeyi ve ObstrÜktif Uyku Apne Sendromu (OUAS) ağırlığı arasındaki ilişkiyi incelemeyi amaçladık.
Method: 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 . Hastalar normal, ağır, orta, hafif, rem-pozisyonel olarak gruplandığında; %26, %25, %6,9 , %16,7 ve %25 oranlarındaydılar. AHI ve ADMA arasında anlamlı korelasyon saptandı (r= 0,483; p<0,001). ADMA için uygun cut-off değeri 1,39 olarak belirlendi. Bu değer için duyarlılık %73,58 (%95 güven aralığı (CI): 61,71- % 85,45 %), özgünlük %94,74 (95 % CI: 84,70- % 100%)idi. oğruluk ya da doğru sınıflandırma
oranı %79,17 olarak bulundu. Pozitif kestirim değeri %97,5 ve negatif kestirim değeri ise %56,25 idi. Pozitif olabilirlik oranı (LR+) 13,98 (LR+>10) ve negatif olabilirlik oranı (LR-) 0,28 (LR-<1) olarak saptandı.
Sonuç: ADMA test yöntemi; normal glukoz, lipid, tiroid, karaciğer ve böbrek fonksiyon testine sahip hastalarda ,güçlü ve iyi bir tanı testi kriteri
olma özelliklerine sahip olabilir.

Anahtar Kelimeler

obstrüktif uyku apne sendromu, hipoksemi, ADMA

Relationship Between Serum Asymmetric Dimethylarginine (ADMA) Level And Obstructive Sleep Apnea Syndrome (OSAS) Severity

Öz

Introduction: The repetitive hypoxemia can induce oxidative stress mechanisms. Oxidative stress increases serum ADMA levels in patients with OSAS.
Aim: To investigate the relationship between serum levels of ADMA and OSAS severity.
Methods: 330 patient’s records, who underwent overnight polysomnography (PSG) were retrospectively examined. The patients who had a abnormal 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 was 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 positional–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<0,001). Appropriate cut-off criterion was set at 1,39 for ADMA. Sensitivity for this value was 73,58 % (95 % Confidence Interval (CI): 61,71- % 85,45 %) and specificity was 94,74 % (95 % CI: 84,70- % to 100%). Accuracy or correct classification rate was found to be 79,17 %. The positive predictive value was 97,5 % and negative predictive value was 56,25 %. The positive likelihood ratio (LR +) was 13,98 (LR + > 10) and the negative likelihood ratio was (LR-) 0,28 (R- <1).
Conclusions: ADMA was found to be a strong and good diagnostic tool among patients with normal levels for glucose, lipid, TSH, creatinine and liver function tests.

Anahtar Kelimeler

obstructive sleep apnea, hypoxemia, ADMA

Kaynakça

• 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. Erratum in: Physiol Rev.2010 Apr;90(2):797-8. PMID: 20086074; PMCID: PMC3970937
• 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. PMID: 35035552; PMCID: PMC8753646
• 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):1217-1239. 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):1036-1046. 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;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):531-544. 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):355-360
• 9. Lugaresi E, Plazzi G. Heavy snorer disease: from snoring to the sleep apnea syndrome--an overview. Respiration. 1997;64 Suppl 1:11-14. doi:10.1159/000196730
• 10. V. K. Kapur, D. H. Auckley, S. Chowdhuri 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, vol. 13, no. 3, pp. 479–504, 2017.
• 11. Pansani AP, Schoorlemmer GH, Ferreira CB et al. Chronic apnea during REM sleep increases arterial pressure and sympathetic modulation in rats. Sleep. 2021 May 14;44(5):zsaa249. doi: 10.1093/sleep/zsaa249. PMID: 33231257.
• 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, Vásárhelyi B. Az aszimmetrikus és a szimmetrikus dimetilált arginin (ADMA/SDMA) klinikai és diagnosztikai jelentősége [Clinical and diagnostic relevance of asymmetric and symmetric dimethyl arginine (ADMA/SDMA)]. Orv Hetil. 2022;163(13):500-505. Published 2022 Mar 27. doi:10.1556/650.2022.32394
• 16. Teerlink T. ADMA metabolism and clearance. Vasc Med. 2005;10 Suppl 1:S73-S81. doi:10.1191/1358863x05vm597oa
• 17. Leiper J, Murray-Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci U S A. 2002;99(21):13527-13532. 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, Leiper JM. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation. 2003;107(8):1195-1201. 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):783-786. doi:10.1016/j.amjhyper.2004.04.011
• 25. 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):913-918. doi:10.1183/09031936.00039911
• 26. 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. Published 2022 Feb 17. doi:10.3389/fmed.2022.835481
• 27. İn E, Özdemir C, Kaman D, Sökücü SN. Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome. Arch Bronconeumol. 2015;51(11):544-550. doi:10.1016/j.arbres.2015.02.020