OBEZ OLGULARDA ÜRİK ASİT DÜZEYİNİN UYKUDA SOLUNUM BOZUKLUKLARI İLE İLİŞKİSİ

Abstract

Amaç: Bu çalışmada obez ve uyku ile ilişkili solunum bozuklukları (UİSB) olan olgularda serum ürik asit (ÜA) düzeyinin obstruktif uyku apne (OUA) şiddeti, nokturnal hipoksemi (NH) ve obezite hipoventilasyon sendromu (OHS) ile ilişkisi araştırıldı. Gereç ve Yöntem: Uyku laboratuarına başvuran vücut kitle indeksi (VKİ) ≥30 kg/m2 olan polisomnografi ile UİSB saptanan tüm olgular çalışmaya alındı. Demografik özellikler, antropometrik ölçümler ve serum ÜA düzeyleri kaydedildi. Apne-hipopne indeksi (AHİ) ve ODİ (oksijen desaturasyon indeksi) hesaplandı. AHİ 5-14 olay/sa hafif, 15-29 olay/sa orta ve ≥30 olay/sa ağır şiddette OUA olarak değerlendirildi. Nokturnal SpO2<%90 olan sure ≥%30 ise NH kabul edildi. PaCO2>45 mmHg ise OHS tanısı koyuldu. Bulgular: Çalışmaya 159 UİSB olan olgu (79 kadın, 80 erkek, yaş: 50,0±10,5 yıl, VKİ: 40,1±5,7 kg/m2) dahil edildi. Olguların 76'sında OHS ve 83'ün de saf OUA tanısı mevcuttu. NH %25,8'inde (n=41) saptandı. NH olanlarda ÜA düzeyi anlamlı olarak yüksekti (6,22±1,37 mg/dl, 5,67±1,51 mg/dl, p=0,008). OHS olgularında ÜA düzeyi saf OUA olguları ile benzerdi (5,91±1,25 mg/dl, 5,72±1,68 mg/dl, p=0,1). OUA şiddeti arttıkça ÜA düzeyi artmaktaydı (hafif: 5,03±1,41 mg/dl, orta: 5,46±1,55 mg/ dl, ağır: 6,19±1,8 mg/dl, p=0,039). Erkek OUA olgularında ÜA düzeyleri daha yüksekti (6,86±1,64 mg/dl, 4,84±1,10 mg/dl, p<0,001). ÜA düzeyi boyun çevresi (r=0,366, p<0,001), bel/kalça oranı (r=0,358, p<0,001), OUA şiddeti (r=0,224, p=0,005), AHİ (r=0,250, p=0,001), ODİ (r=291, p<0,001), nokturnal SpO2<%90 geçen süre (r=0,228, p=0,004) ile korelasyon göstermekteydi. Erkek cinsiyet, NH ve bel/kalça oranı ÜA düzeyi ile bağımsız ilişkili faktörler olarak bulundu (sırasıyla; p<0,001, p=0,03, p=0,03). Sonuç: UİSB olan obez olgularda, yüksek serum ÜA düzeyleri erkek cinsiyet, NH ve OUA şiddeti ile ilişkili bulunmuştur.

Keywords

• Nokturnal hipoksemi
• obezite
• obezite hipoventilasyon sendromu
• obstruktif uyku ap
• ürik asit

RELATIONSHIP BETWEEN SERUM URIC ACID LEVELS AND SLEEP-RELATED BREATHING DISORDERS IN OBESE SUBJECTS

Abstract

Objective: We examined the serum uric acid (UA) levels among patients with sleep-related breathing disorders (SRBD) and the relationship between UA levels and obstructive sleep apnea (OSA) severity, nocturnal hypoxemia (NH) and obesity hypoventilation syndrome (OHS). Material and Method: Subjects with body mass index (BMI) ≥30 kg/m2 who, according to polysomnography results, have SRBD were included. Demographics, anthropometric measurements and serum UA were recorded. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were recorded. The OSA severity was graded as mild (AHI 5-14 events/hour), moderate (AHI 15-29 events/hour) or severe (AHI ≥30 events/hour). NH was considered when sleep time spent with SpO2<90% was ≥30%. PaCO2>45 mmHg was considered OHS. Results: The study included 159 patients with SRBD (79 female, 80 males, age: 50.0±10.5 years, BMI: 40.1±5.7 kg/m2). Seventy- six had OHS and 83 had pure OSA. NH was detected in 25.8% of patients. UA levels were higher in subjects with NH (6.22±1.37 mg/dl, 5.67±1.51 mg/dl, p=0.008). UA levels were similar in patients with OHS and pure OSA (5.91±1.25 mg/dl, 5.72±1.68 mg/ dl, p=0.1). UA levels increased as OSA severity increased (mild: 5.03±1.41 mg/dl, moderate: 5.46±1.55 mg/dl, severe: 6.19±1.8 mg/dl, p=0.039). UA levels were higher in males with OSA (6.86±1.64 mg/dl, 4.84±1.10 mg/dl, p<0.001). UA levels were correlated with neck circumference (r=0.366, p<0.001), waist/ hip ratio (r=0.358, p<0.001), OSA severity (r=0.224, p=0.005), AHI (r=0.250, p=0.001), ODI (r=291, p<0.001) and sleep time with SpO2<90% (r=0.228, p=0.004). Male gender, waist/hip ratio and NH were factors independently related with UA levels (retrospectively; p<0.001, p=0.03, p=0.03). Conclusion: In obese subjects with SRBD, serum UA levels were associated with male gender, NH and OSA severity.

Keywords

• nocturnal hypoxemia
• obesity
• obesity hypoventilation syndrome
• obstructive sleep apnea
• uric acid

References

1. 1. Saito H, Nishimura M, Shibuya E, Makita H, Tsujino I, Miyamoto K, et al. Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine. Chest 2002;122(5):1686-94. [CrossRef]
2. 2. Rodwell VW. Metabolism of Purine and Pyrimidine Nucleotides. In: Murray RK, Granner DK, Rodwell VW, editors. Harper’s Illustrated Biochemistry. 27th ed. Singapore: McGraw-Hill Education (Asia); 2006. p. 301-10.
3. 3. Braghiroli A, Sacco C, Erbetta M, Ruga V, Donner CF. Over night urinary uric acid: creatinine ratio for detection of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure. Am Rev Respir Dis 1993;148(1):173-8. [CrossRef]
4. 4. Janghorbani M, Ghanbari H, Aminorroaya A, Amini M. Relationship Between Serum Uric Acid and Incident Hypertension in Patients with Type 2 Diabetes. Rev Diabet Stud 2018;14(4):354-63. [CrossRef]
5. 5. Ekici B, Kütük U, Alhan A, Töre HF. The relationship between serum uric acid levels and angiographic severity of coronary heart disease. Kardiol Pol 2015;73(7):533-8. [CrossRef]
6. 6. Fouad M, Fathy H, Zidan A. Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients. J Bras Nefrol 2016;38(4):403-10. [CrossRef]
7. 7. Shankar A, Klein BE, Nieto FJ, Klein R. Association between serum uric acid level and peripheral arterial disease. Atherosclerosis 2008;196(2):749-55. [CrossRef]
8. 8. Gonzaga C, Bertolami A, Bertolami M, Amodeo C, Calhoun D. Obstructive sleep apnea, hypertension and cardiovascular diseases. J Hum Hypertens 2015;29(12):705- 12. [CrossRef]

9. 9. Bouzerda A. Risque cardiovasculaire et syndrome d’apnées obstructives du sommeil Pan Afr Med J 2018;29:47. [CrossRef]
10. 10. Dredla BK, Castillo PR. Cardiovascular Consequences of Obstructive Sleep Apnea. Curr Cardiol Rep 2019;21(11):137. [CrossRef]
11. 11. Kheirandish-Gozal L, Gozal D. Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. Int J Mol Sci 2019;20(3):459. [CrossRef]
12. 12. Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol 2013;62(7):569-76. [CrossRef]
13. 13. Seetho IW, Parker RJ, Craig S, Duffy N, Hardy KJ, Wilding JP, et al. Serum urate and obstructive sleep apnoea in severe obesity. Chron Respir Dis 2015;12(3):238-46. [CrossRef]
14. 14. Hira HS, Shukla A, Kaur A, Kapoor S. Serum uric acid and lactate levels among patients with obstructive sleep apnea syndrome: which is a better marker of hypoxemia? Ann Saudi Med 2012;32(1):37-42. [CrossRef]
15. 15. Sunnetcioglu A, Gunbatar H, Yıldız H. Red cell distribution width and uric acid in patients with obstructive sleep apnea. Clin Respir J 2018;12(3):1046-52. [CrossRef]
16. 16. Zheng C, Song H, Wang S, Liu J, Lin T, Du C, et al. Serum Uric Acid Is Independently Associated with Risk of Obstructive Sleep Apnea-Hypopnea Syndrome in Chinese Patients with Type 2 Diabetes. Dis Markers 2019;2019:4578327. [CrossRef]
17. 17. Sari O, Akpak YK, Yerebasmaz N, Arslan I, Dagcioglu BF, Oral S. Evaluation of obstructive sleep apnea prevalence in mothers of infants with low birth weight and its relationship with serum uric acid levels as a hypoxia marker. J Matern Fetal Neonatal Med 2020:1-8. [CrossRef]
18. 18. Lai CH, Huang RJ, Wong JK, Chang SW, Chung AH, Chi YC, et al. Confounded by obesity and modulated by urinary uric acid excretion, sleep-disordered breathing indirectly relates to hyperuricaemia in males: A structural equation model. J Sleep Res 2020:e13108. [CrossRef]
19. 19. Bouloukaki I, Mermigkis C, Tzanakis N, Kallergis E, Moniaki V, Mauroudi E, et al. Evaluation of Inflammatory Markers in a Large Sample of Obstructive Sleep Apnea Patients without Comorbidities. Mediators Inflamm 2017;2017:4573756. [CrossRef]
20. 20. Fleming WE, Holty JC, Bogan RK, Hwang D, Ferouz-Colborn AS, Budhiraja R, et al. Use of blood biomarkers to screen for obstructive sleep apnea. Nat Sci Sleep 2018;10:159-67. [CrossRef]
21. 21. Chen Q, Lin G, Chen L, Huang J, Huang Y, Li P, et al. Does Continuous Positive Airway Pressure Therapy in Patients with Obstructive Sleep Apnea Improves Uric Acid? A Meta-Analysis. Oxid Med Cell Longev 2019;2019:4584936. [CrossRef]
22. 22. Shi T, Min M, Sun C, Cheng C, Zhang Y, Liang M, et al. A meta-analysis of the association between gout, serum uric acid level, and obstructive sleep apnea. Sleep Breath 2019;23(4):1047-57. [CrossRef]
23. 23. Kanbay A, Inonu H, Solak Y, Erden A, Uslu E, Yuksel SA, et al. Uric acid as a potential mediator of cardiovascular morbidity in obstructive sleep apnea syndrome. Eur J Intern Med 2014;25(5):471-6. [CrossRef]
24. 24. Kosacka M, Brzecka A, Piesiak P, Korzeniewska A, Jankowska R. Soluble ligand CD40 and uric acid as markers of atheromatosis in patients with obstructive sleep apnea. Adv Exp Med Biol 2015;839:55-60. [CrossRef]
25. 25. Pływaczewski R, Bednarek M, Jonczak L, Górecka D, Sliwińiski P. [Hyperuricaemia in males with obstructive sleep apnoea (osa)]. Pneumonol Alergol Pol 2005;73(3):254-9.
26. 26. Miller MR, Hankinson J, Brusasco V, et al. ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J 2005;26(2):319-38. [CrossRef]
27. 27. Berry RB, Brooks R, Gamaldo CE, et al. The AASM Manual forthe Scoring of Sleep and Associated Events: Terminology and Technical Specifications. Version 2.0.2. Darien, IL: AmericanAcademy of Sleep Medicine; 2013. www.aasmnet. org
28. 28. Wiener RC, ShankarA. Association between SerumUric Acid Levels and Sleep Variables: Results from the National Health and Nutrition Survey 2005-2008. Int J Inflam 2012;2012:363054. [CrossRef]
29. 29. Pialoux V, Hanly PJ, Foster GE, Brugniaux JV, Beaudin AE, Hartmann SE, et al. Effects of exposureto intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am J Respir Crit Care Med 2009;180(10):1002-9. [CrossRef]