Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome and Their Correlation with Disease Severity

Year 2024, , 44 - 48, 31.08.2024

Kübra Mehel Metin , Selda Keskin Güler , Seçil Özercan , Tahir Yoldaş

https://doi.org/10.20492/aeahtd.1287208

Abstract

ÖZET:
AMAÇ: Obstrüktif uyku apne sendromu (OUAS) uyku boyunca üst hava yolunun tekrarlayıcı şekilde, tam veya kısmen tıkanmasıyla karakterize bir durumdur. Etiyopatogenezinde inflamasyon rol aldığı gösterilmiştir. Bu çalışmanın amacı inflamasyon belirteçleri olarak önerilen parametrelerin kliniğimizde OUAS tanısı alan hastalarda incelenmesidir.
GEREÇ VE YÖNTEM: 2016-2019 yılları arasında polisomnografi yapılan 80 hasta çalışmaya dahil edildi. Apne hipopne indeksi (AHİ) 30’un üstü ağır OUAS (n=20), 15-30 arası orta OUAS (n=20), 5-15 arası olanlar hafif OUAS (n=20), olarak gruplandırıldı. AHI 5’in altında olanlar kontrol grubu olarak çalışmaya alındı (n=20). Kontrol grubu ile OUAS saptanan grup ve OUAS şiddetine göre ayrılmış gruplar arasında monosit/HDL, trombosit/lenfosit, nötrofil/lenfosit oranları, sedimentasyon, CRP, hsCRP, homosistein değerleri karşılaştırıldı.
BULGULAR: Kontrol ve OUAS olan gruplar cinsiyet açısından benzerdi. Ağır şiddette OUAS olan grubun yaş ortalaması diğer gruplara göre daha yüksekti. Gruplar arasında trombosit/lenfosit oranları, nötrofil/lenfosit oranları, monosit/HDL oranları, sedimentasyon, homosistein ve hsCRP değerleri açısından istatistiksel anlamlı fark saptanmadı (p>0.05). Kontrol ve OUAS grupları arasında ağır OUAS grubunda CRP düzeyi yüksek olup anlamlı istatistiksel fark saptandı (p<0.05). Kontrol ve OUAS grubu arasında trombosit/lenfosit oranları, nötrofil/lenfosit oranları, monosit/HDL oranları, sedimentasyon, homosistein, hsCRP ve CRP oranları arasında anlamlı fark saptanmadı. CRP seviye-leri AHI, desaturasyon indeksi, oksijen saturasyonu %90’ın altında geçen süre, vücut kitle indeksi (VKİ) ve yaşla pozitif; minimum oksijen saturasyonu ve ortalama oksijen saturasyonuyla negatif korelasyon göstermekteydi. hsCRP ise desaturasyon indeksi, oksijen saturasyonu %90’ın altında geçen süre, VKİ ve yaşla pozitif; minimum oksijen saturasyonu ve ortalama oksijen saturasyonuyla negatif korelasyon gösterdi.
TARTIŞMA: Ağır şiddette OUAS hastalarında diğer gruplara göre CRP oranları yüksek saptanmış olup ağır şiddette OUAS hastalarında inflamasyon açısından değerlendirebileceğimiz bir parametre olabilir.
SONUÇ: CRP ağır şiddette OUAS hastalarında inflamasyon açısından değerlendirebileceğimiz bir parametre olabilir.
ANAHTAR KELİMELER: High density lipoprotein, monosit, nötrofil, lenfosit, CRP, obstrüktif uyku apne sendromu

ABSTRACT
AIM: Obstructive sleep apnea syndrome (OSAS) is a condition characterized by repetitive, complete or partial obstruction of the upper airway during sleep. Inflammation has been shown to play a role in its etiopathogenesis. The aim of this study is to examine the parameters suggested as inflammati-on markers in patients diagnosed with OSAS in our clinic.
MATERIAL AND METHOD: Eighty patients who underwent polysomnography between 2016-2019 were in-cluded in the study. Apnea hypopnea index (AHI) above 30 was grouped as severe OSAS (n=20), 15-30 as moderate OSAS (n=20), 5-15 as mild OSAS (n=20). Those with AHI <5 were included in the study as the control group (n=20). Monocyte/HDL, platelet/lymphocyte, neutrophil/lymphocyte ratios, sedimentation, CRP, hsCRP, homocysteine values were compared between the control group and the group with OSAS and the groups separated according to the severity of OSAS.
RESULTS: The control and OSAS groups were similar in terms of gender. The mean age of the group with severe OSAS was higher than the other groups. There was no statistically significant difference between the groups in terms of platelet/lymphocyte ratios, neutrophil/lymphocyte ratios, mono-cyte/HDL ratios, sedimentation, homocysteine and hsCRP values (p>0.05). CRP level was high in the severe OSAS group and a statistically significant difference was found between the control and OSAS groups (p<0.05). There was no significant difference in platelet/lymphocyte ratios, neutro-phil/lymphocyte ratios, monocyte/HDL ratios, sedimentation, homocysteine, hsCRP and CRP ratios between the control and OSAS groups. CRP levels have showed positive with AHI, desaturation index, time elapsed below 90%, body mass index, and age; showed a negative correlation with mi-nimum oxygen saturation and mean oxygen saturation. hsCRP is positive with desaturation index, time elapsed below 90%, body mass index and age; showed a negative correlation with the minimum oxygen saturation and the mean oxygen saturation.
DISCUSSION: CRP rates were found to be higher in severe OSAS patients compared to other groups, and it may be a paramater that we can evaluate in terms of inflammation in severe OSAS patients.
CONCLUSION: CRP may be a paramater that we can evaluate in terms of inflammation in severe OSAS patients.
KEYWORDS: High density lipoprotein, monocytes, neutrophils, lymphocytes, CRP, obstructive sleep apnea syndrome.

Keywords

High density lipoprotein, monocytes, neutrophils, lymphocytes, CRP

Project Number

YOK

Obstruktif Uyku Apne Sendromunda İnflamasyon Biyobelirteçleri ve Hastalık Şiddeti İle İlişkisi

Abstract

ÖZ:
Amaç: Obstrüktif uyku apne sendromu (OUAS) uyku boyunca üst hava yolunun tekrarlayıcı şekil-de, tam veya kısmen tıkanmasıyla karakterize bir durumdur. Etiyopatogenezinde inflamasyon rol aldığı gösterilmiştir. Bu çalışmanın amacı inflamasyon belirteçleri olarak önerilen parametrelerin kliniğimizde OUAS tanısı alan hastalarda incelenmesidir.
Gereç ve Yöntem: 2016-2019 yılları arasında polisomnografi yapılan 80 hasta çalışmaya dahil edildi. Apne hipopne indeksi (AHİ) 30’un üstü ağır OUAS (n=20), 15-30 arası orta OUAS (n=20), 5-15 arası olanlar hafif OUAS (n=20), olarak gruplandırıldı. AHI 5’in altında olanlar kontrol grubu olarak çalışmaya alındı (n=20). Kontrol grubu ile OUAS saptanan grup ve OUAS şiddetine göre ayrılmış gruplar arasında monosit/HDL, trombosit/lenfosit, nötrofil/lenfosit oranları, sedimentasyon, CRP, hsCRP, homosistein değerleri karşılaştırıldı.
Bulgular: Kontrol ve OUAS olan gruplar cinsiyet açısından benzerdi. Ağır şiddette OUAS olan grubun yaş ortalaması diğer gruplara göre daha yüksekti. Gruplar arasında trombosit/lenfosit oranları, nötrofil/lenfosit oranları, monosit/HDL oranları, sedimentasyon, homosistein ve hsCRP değerleri açısından istatistiksel anlamlı fark saptanmadı (p>0.05). Kontrol ve OUAS grupları arasında ağır OUAS grubunda CRP düzeyi yüksek olup anlamlı istatistiksel fark saptandı (p<0.05). Kontrol ve OUAS grubu arasında trombosit/lenfosit oranları, nötrofil/lenfosit oranları, monosit/HDL oranları, sedimentasyon, homosistein, hsCRP ve CRP oranları arasında anlamlı fark saptanmadı. CRP seviye-leri AHI, desaturasyon indeksi, oksijen saturasyonu %90’ın altında geçen süre, vücut kitle indeksi (VKİ) ve yaşla pozitif; minimum oksijen saturasyonu ve ortalama oksijen saturasyonuyla negatif korelasyon göstermekteydi. hsCRP ise desaturasyon indeksi, oksijen saturasyonu %90’ın altında geçen süre, VKİ ve yaşla pozitif; minimum oksijen saturasyonu ve ortalama oksijen saturasyonuyla negatif korelasyon gösterdi.
Tartışma: Ağır şiddette OUAS hastalarında diğer gruplara göre CRP oranları yüksek saptanmış olup ağır şiddette OUAS hastalarında inflamasyon açısından değerlendirebileceğimiz bir parametre olabilir.
Sonuç: CRP OUAS hastalarında inflamasyon açısından değerlendirebileceğimiz bir parametre olabilir.

Anahtar kelimeler: High density lipoprotein, monosit, nötrofil, lenfosit, CRP, obstrüktif uyku apne sendromu

ABSTRACT:

Aim: Obstructive sleep apnea syndrome (OSAS) is a condition characterized by repetitive, complete or partial obstruction of the upper airway during sleep. Inflammation has been shown to play a role in its etiopathogenesis. The aim of this study is to examine the parameters suggested as inflammati-on markers in patients diagnosed with OSAS in our clinic.
Material-Method: Eighty patients who underwent polysomnography between 2016-2019 were in-cluded in the study. Apnea hypopnea index (AHI) above 30 was grouped as severe OSAS (n=20), 15-30 as moderate OSAS (n=20), 5-15 as mild OSAS (n=20). Those with AHI <5 were included in the study as the control group (n=20). Monocyte/HDL, platelet/lymphocyte, neutrophil/lymphocyte ratios, sedimentation, CRP, hsCRP, homocysteine values were compared between the control group and the group with OSAS and the groups separated according to the severity of OSAS.
Results: The control and OSAS groups were similar in terms of gender. The mean age of the group with severe OSAS was higher than the other groups. There was no statistically significant difference between the groups in terms of platelet/lymphocyte ratios, neutrophil/lymphocyte ratios, mono-cyte/HDL ratios, sedimentation, homocysteine and hsCRP values (p>0.05). CRP level was high in the severe OSAS group and a statistically significant difference was found between the control and OSAS groups (p<0.05). There was no significant difference in platelet/lymphocyte ratios, neutro-phil/lymphocyte ratios, monocyte/HDL ratios, sedimentation, homocysteine, hsCRP and CRP ratios between the control and OSAS groups. CRP levels have showed positive with AHI, desaturation index, time elapsed below 90%, body mass index, and age; showed a negative correlation with mi-nimum oxygen saturation and mean oxygen saturation. hsCRP is positive with desaturation index, time elapsed below 90%, body mass index and age; showed a negative correlation with the minimum oxygen saturation and the mean oxygen saturation.
Discussıon: CRP rates were found to be higher in severe OSAS patients compared to other groups, and it may be a paramater that we can evaluate in terms of inflammation in severe OSAS patients.
Conclusıon: CRP may be a paramater that we can evaluate in terms of inflammation in severe OSAS patients.

Keywords: High density lipoprotein, monocytes, neutrophils, lymphocytes, CRP, obstructive sleep apnea syndrome.

Keywords

High density lipoprotein, monosit, nötrofil, lenfosit, CRP, obstrüktif uyku apne sendromu

Supporting Institution

YOK

Project Number

YOK

Thanks

YOK

References

• 1. Atan D, Kundi FCS, Özcan KM, Dere H. A New Predictor for Obstructive Sleep Apnea Syndrome: Monocyte to HDL Ratio. Indian J Otolaryngol Head Neck Surg. 2017; 69(2): 142-146.
• 2. Bozkuş F, Dikmen N, Samur A, Bilal N, Atilla N, Arpağ H. Does the neutrophil-to-lymphocyte ratio have any importance between subjects with obstructive sleep apnea syndrome with obesity and without obesity? Tuberk Toraks. 2018; 66(1): 8-15. 3. Rha MS, Kim CH, Yoon JH, Cho HJ. Association between the neutrophil-to-lymphocyte ratio and obstructive sleep apnea: a meta- analysis. Sci Rep. 2020; 10(1): 10862.
• 4. Korkmaz M, Korkmaz H, Küçüker F, Ayyıldız SN, Çankaya S. Evaluation of the association of sleep apnea-related systemic inflammation with CRP, ESR, and neutrophil-to-lymphocyte ratio. Med Sci Monit. 2015; 21: 477-81.
• 5. Faraut B, Boudjeltia KZ, Vanhamme L, Kerkhofs M. Immune, inflammatory and cardiovas-cular consequences of sleep restriction and recovery. Sleep Med Rev. 2012; 16(2): 137–49.
• 6. Koseoglu HI, Altunkas F, Kanbay A, Doruk S, Etikan I, Demir O. Platelet-lymphocyte ratio is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome. J Thromb Thrombolysis. 2015; 39(2): 179-85.
• 7. Inonu Koseoglu H, Pazarli AC, Kanbay A, Demir O. Monocyte Count/HDL Cholesterol Ratio and Cardiovascular Disease in Patients With Obstructive Sleep Apnea Syndrome: A Multicenter Study. Clin Appl Thromb Hemost. 2018; 24(1): 139-144.
• 8. Uygur F, Tanriverdi H, Aktop Z, Erboy F, Altınsoy B, Damar M, et al. The neutrophil-to-lymphocyte ratio in patients with obstructive sleep apnoea syndrome and its relationship with cardiovascular disease. Heart Lung. 2016 ; 45(2): 121-5.
• 9. Koseoglu S, Ozcan KM, Ikinciogullari A, Cetin MA, Yildirim E, Dere H. Relationship Between Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio and Obstructive Sleep Apnea Syndrome. Adv Clin Exp Med. 2015; 24(4): 623-7.
• 10. Ancuta P, Wang J, Gabuzda D. CD16þ monocytes produce IL- 6, CCL2, and matrix metallo-proteinase-9 upon interaction with CX3CL1-expressing endothelial cells. J Leukoc Biol. 2006; 80(5): 1156-64.
• 11. Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of sys-temic inflammation and stress in critically ill. Bratisl Lek Listy. 2001; 102(1): 5–14.
• 12. Smyth SS, McEver RP, Weyrich AS, Morrell CN, Hoffman MR, Arepally GM,et al. Platelet functions beyond hemostasis. J Thromb Haemost. 2009; 7(11): 1759–66.
• 13. Ulusoy B, Oğuzhan T, Akyol M, Bozdemir K, Çiftçi B, Korkmaz MH. Insufficiency of posi-tive airway pressure treatment on increased mean platelet volume: a prospective controlled study in patients with obstructive sleep apnea syndrome. Sleep Breath. 2020; 24(3): 885-91.
• 14. Song YJ, Kwon JH, Kim JY, Kim BY, Cho KI. The platelet-to-lymphocyte ratio reflects the severity of obstructive sleep apnea syndrome and concurrent hypertension. Clin Hypertens. 2016; 22: 1.
• 15. Sariman N, Levent E, Aksungar FB, Soylu AC, Bektaş O. Homocysteine levels and echocar-diographic findings in obstructive sleep apnea syndrome. Respiration. 2010; 79(1): 38-45.
• 16. Mehra R, Redline S. Sleep apnea: a proinflammatory disorder that coaggregates with obesity. J Allergy Clin Immunol. 2008; 121(5): 1096–102.
• 17. Tam CS, Wong M, Tam K, Aouad L, Waters KA. The effect of acute intermittent hypercap-nic hypoxia treatment on IL-6, TNF-alpha, and CRP levels in piglets. Sleep. 2007; 30(6): 723–27.
• 18. Punjabi NM, Beamer BA. C-reactive protein is associated with sleep disordered breathing independent of adiposity. Sleep. 2007; 30(1): 29–34.
• 19. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
• 20. Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea; implications for cardiac and vasculer disease. JAMA. 2003; 290(14): 1906–14.
• 21. Kohler M, Stradling JR. Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol. 2010; 7(12): 677-85.
• 22. Takahashi K, Takeya M, Sakashita N . Multifunctional roles of macrophages in the devel-opment and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc. 2002; 35(4): 179–203.
• 23. Archontogeorgis K, Voulgaris A, Papanas N, Nena E, Froudarakis M, Mikhailidis DP, et al . Mean Platelet volume and platelet distribution width in patients with obstructive sleep apnea syndrome and concurrent chronic obstructive pulmonary disease. Clin Appl Thromb Hemost. 2018; 24(8): 1216–22.
• 24. Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by in-termittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005; 112(17): 2660-67.
• 25. Ryan S, Taylor CT, McNicholas WT. Systemic inflammation: a key factor in the pathogene-sis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax. 2009; 64(7): 631-36.
• 26. Oyama J, Nagatomo D, Yoshioka G, Yamasaki A, Kodama K, Sato M, et al. The relations-hip between neutrophil to lymphocyte ratio, endothelial function, and severity in patients with obstructive sleep apnea. J Cardiol. 2016; 67(3): 295–302.
• 27. Wu M, Zhou L, Zhu D, Lai Tianwen, Chen Z, Shen H. Hematological indices as simple, in-expensive and practical severity markers of obstructive sleep apnea syndrome: a meta-analysis. J Thorac Dis. 2018;10(2): 6509-21.
• 28. Kokturk O, Ciftci TU, Mollarecep E, Ciftci B. Serum homocysteine levels and cardiovascular morbidity in obstructive sleep apnea syndrome. Respir Med. 2006; 100(3): 536-41.
• 29. Kumor M, Bielicki P, Przybyłowski T, Rubinsztajn R, Zielinski J, Chazan R. Three month continuous positive airway pressure (CPAP) therapy decreases serum total and LDL cholesterol, but not homocysteine and leptin concentration in patients with obstructive sleep apnea syn-drome (OSAS). Pneumonol Alergol Pol. 2011; 79(3): 173- 83.
• 30. Ryan S, Nolan GM, Hannigan E, Cunningham S, Taylor C, McNicholas WT. Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax. 2007; 62(6): 509- 14.
• 31. Kokturk O, Ciftci TU, Mollarecep E, Ciftci B. Elevated Creactive protein levels and increa-sed cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J. 2005; 46(5): 801-9.
• 32. Panoutsopoulos A, Kallianos A, Kostopoulos K, Seretis C, Koufogiorga E, Protogerou A, et al. Effect of CPAP treatment on endothelial function and plasma CRP levels in patients with sleep apnea. Med Sci Monit. 2012; 18(12): 747–51.
• 33. Lui MM, Lam JC, Mak HK, Xu A, Ooi C, Lam DC, et al. C-reactive protein is associated with obstructive sleep apnea independent of visceral obesity. Chest. 2009; 135(4): 950–56.
• 34. Guven SF, Turkkani MH, Ciftci B, Çiftçi TU, Erdoğan Y. The relationship between high-sensitivity C-reactive protein levels and the severity of obstructive sleep apnea. Sleep Breath. 2012; 16(1): 217- 21.
• 35. Lee LA, Chen NH, Huang CG, Lin SW, Fang TJ, Li HY. Patients with severe obstructive sleep apnea syndrome and elevated high- sensitivity C-reactive protein need priority treatment. Otolaryngol Head Neck Surg. 2010; 143: 72-7.
• 36. Sharma SK, Mishra HK, Sharma H, Goel A, Sreenivas V, Gulati V, et al. Obesity, and not obstructive sleep apnea, is responsible for increased serum hs-CRP levels in patients with sleep-disordered breathing in Delhi. Sleep Med . 2008; 9(2): 149–56.
• 37. Li K, Wei P, Qin Y, Wei Y. Is C-reactive protein a marker of obstructive sleep apnea? A meta-analysis. Medicine. 2017; 96(19): e6850.
• 38. Imani MM, Sadeghi M, Farokhzadeh F, Khazaie H, Brand S, Dürsteler KM, et al. Evaluation of blood levels of C-Reactive protein marker in Obstructive Sleep Apnea: A systematic review, Meta-Analysis and Meta- Regression. Life (Basel) . 2021;11(4): 362