Arzu TOPELİ, Ebru ERSOY ORTAÇ, Sevgi AKAYDIN, Yeşim ÖZKAN, Recai ERGÜN, Sadık ARDIÇ, Gülbahar YÜCE DARILMAZ, Mine DURUSU, Hikmet FIRAT

Association of obstructive sleep apnea with homocystein, nitric oxide and total antioxidant capacity levels in patients with or without coronary artery disease

Giriş : Obstrüktif uyku apnesi (OUA) kardiyovaskuler morbidite ve mortalite ile ilişkili bir durumdur. OUA' li h astalarda en dotel ba ğım-lı vazodilatasyon da aza lma meydana ge lme ktedir. Nitrik oksit eksikliği ve plazma h omosistein düzeylerinin kardiyovasküler h astalık-ların pato genezin de rolleri mevcuttur. OUA de meydana gelen oksijen desaturasyonu ve arousallar h ipoksi-reoksijenasyon yapara kserbest oksijen radika llerinin oluş umuna neden olur. Ça lışma; OUAn ın kardiyovasküler morbidite ile iliş kisini gösterme k ve koronerarter h astalığı (KAH) olan ve olmayan h asta larda h omosistein, nitrik oksit ve total antioksidan kapasite seviyelerini karşılaş tırmak içinplan lan dı.Materyal ve Metod: Miyokard infarktüsü geçirmiş 27 h astaya ve KAH olmayan 25 kontrol grubuna polisomnografi uygulan dı.Polisomnografi sonrası h astalar OUA + KAH ( grup 1), OU (grup 2), KAH (grup 3), normal ( grup 4) olara k dört gruba ayrıldı.Homosistein, nitric oksit ve total antioksidan ka pasite düzeyleri ölçüldü. Sonuçlar parametric ve non parametric istatistiksel yöntemlerile analiz edildi.Bulg ular: Apne hipopne indeksine (AHİ) gore KAH olanların %44.4 ünde OUA izlendi. Polisomnografi sonuçlarına gore hastalarOUA + KAH (n= 12), OUA (n= 14), KAH (n= 15), norma l (n= 11) gruplara ayrıldı. Homosistein seviyeleri grup 3te yüksek bulun du.AHİ, Ortalama desaturasyon indeksi (MDI) ve desaturasyon süresi 3 damar hastalı ğı olan hastalarda tek dammar ve iki dammarh astalığı olan h asta lara gore yükse k izlen di (p< 0.05) Nitrik oksit seviye leri oksijen desaturasyon süresi ile korele bulun du (r: -0.45;p= 0.031). Antioksidan kapasite düzeyleri gruplar arası farklılık göstermiyordu.Sonuç: OUA, KAH olanlarda sıktır. AHİ , MDI ve desaturasyon süresi a ğır KAH olanlarda sıktır. OUA hastaların ın KAH açısındande ğerlen dirilmesi önemlidir.

Koroner arter hastalığı olan ve olmayan hastalarda obstrüktif uyku apnesinin homosistein, nitrik oksit ve total antioksidan kapasite düzeyleri ile ilişkisi

In troductio n : Ob structive slee p a pnea (OSA) is associate d with cardiovascu lar morb idity an d morta lity. Deficiency of nitric oxide (NO) an d plasma levels of h omocystein h ave been implicated in th e path ogenesis of cardiovascular disease. OSA results in oxygen desaturation an d arousal from sleep. Free oxygen radica ls can be produce d by h ypoxia-reoxygenation. To test for th e h ypoth esis tha t OSA is associated with cardiovascular morbidity, we investigated leve ls of h omocystein, NO an d total antioxidant capacity in OSA patients with an d with out coronary artery disease (CAD) in comparison with norma l subjects an d patients with CAD with out OSA. Materials and Methods: Polysomnograph y was performed in 27 patients wh o h ad a myocardial infarction an d in 25 patients with out evidence of CAD. Patients were groupe d accordin g th eir polysomnograph y results as OSA with CAD (group 1), OSA with out CAD (group 2), CAD (group 3), an d normal (group 4) . Levels of h omocystein, NO an d tota l antioxidant capacity were determined afteran overnight fastin g. Data were analyse d with parametric an d non parametric statistica l tests . Results : Accordin g to apnea-h ypopnea in dex (AHI) 44.4% of CAD patients were OSA. After polysomnograph ic eva luation, th epatients were re-distributed as follows: OSA with CAD (n= 12), OSA with out CAD (n= 14), CAD (n= 15), an d normal (n= 11). Homocystein levels were h igh er in 3 groups compared to controls. AHI, MDI an d desaturation time was h igh er in th ree -vessel dis- ease compared to one an d two- vessel diseases (p< 0.05). NO levels were correlate d with th e period of oxygen desaturation (r: -0.45, p= 0.031). Th e antioxidant capacity did not differ between OSA an d h ea lthy groups. Conclusion: OSA is frequent in CAD. AHI, MDI an d desaturation time are h igh er in patients with severe CAD. It is important toevaluate OSA patients for CAD.

PDF

___

1. Youn g T, Peppa rd EP, Gottieb DJ. Epidemiolo gy of obstruc- tive slee p a pnea. A popu lation h ea lth perpective. Am J Respir Crit Care Me d 2002;165:1217-39 .
2. Stra dling JR. O b structive sleep apnea. Definitions, epidemi- yo lo ji an d natura l h istory. T h orax 1995;50:683-9 .
3. He J, Kryger MH, Zorick FJ, Conway W, Roth T. Morta lity an d a pnea index in o b structive slee p a pnea: experience in 385 ma le patients Ch est 1988;94:9-14 .
4. T h e Re port of American Aca dem y of S lee p Me dicine Slee p- re late d b reath in g disorders in a du lts: recomman dations fo r syn drome definition an d measurement tec h nigues in clini- ca l research . S lee p 1999;22(5):326-31 .
5. Stoo h s R, Guilleminau lt C. Cardiovascu lar c h anges associ- ate d with o b structive s lee p a pnea sy n drome. J Appl Phy sio l 1992 ;72(2):583-9 .
6. Parish JM, Somers VK. O b structive s lee p a pnea an d cardio - vascular disease. Ma yo Clin Proc 2004;79(8):1036-46 .
7. Somers VK, Dyken ME, Mark AL, Abb oud FM. S ym patetic n erve activity during s leep in norma l subjects. N En gl J Me d 1993 ;328:303-7.
8. Rin gler J, Basner RC, S h annon R, Sch wartzstein R, Manning H, Wein b erger SE, et a l. Hypoxemia a lone does not explain blood pressure elevations after obstructive a pneas. J Appl Physio l 1990;69:2143-8 .
9. Somers VK, Mark AL, Zava la DC, Abb oud FM. Contrasting effects of hypoxia an d hyperca pnia on ventilation and sy m - patetic activity in humans. J Appl Physio l 1989;67:2101-6 .
10. Graham IM, Daly LE, Refsum HM, Robinson K, Brattström LE, Ue lan d PM, et a l. Plasma h omoc ysteine as a risk factor for vascu lar disease. T h e Euro pean concerte d action pro - ject. JAMA 1997;277:1775-81 .
11. Lavie L. Obstructive slee p a pnea syndrome- an oxidative stress disorder. S lee p Me d Rev 2003;7:35-51 .
12. He dner JA, Wilcox I, Su llivan CE. Specu lations on th e inter- action between vascular disease and obstructive sleep apnea. In: Sullivan CE (ed). Sleep and Breathin g. 2n d e d. Ph ila de lph ia: Saun ders; 1994 .
13. Parish JM, S h e pard JW. Cardiovascular effects of slee p dis- o rders. Ch est 1990; 97:1220-6 .
14. Weiss JW, Remsb urg S, Garpesta d E, Rin gler J, Sparrow D, Parker JA. Hemodynamic conse q uences of obstructive sleep apnea. Sleep 1996;19(5):388-97.
15. Lanfranch i PA, Bra gh iro li A, Bosimini E, Mazzuero G, Co lom b o R, Donner F, et a l. Pro gnostic va lue of nocturna l Ch e y ne-Sto k es respiration in ch ronic h eart failure. Circu lation 1999 ; 99:1435-40 .
16. Sch u lz R, Ma h mou di S, Hattar K, Sib e lius U, Olsch ewski H , Ma y er K, et a l. En hance d re lease of su peroxide from po lymorph onuc lear neutro ph ils in o b structive slee p a pnea. Im pact of continuous positive airwa y pressure th era py. Am J Respir Crit Care Me d 2000;162:566-70.
17. Hayash i M, Fu jimoto K, Urish ib ata K, Uc h ik awa S, Imamura H , Ku b o K. Nocturna l oxygen desaturation corre lates with severity of coronary ath erosclerosis in coronary artery dis- ease. Ch est 2003 ;124:936-41 .
18. S ha h NA, Ya ggi HK, Concato J, Mo h senin V. Ob structive slee p a pnea as a risk factor for coronary events or cardio- vascular death. Slee p Breath 2010;14(2):131-6.
19. Lee CH, Khoo SM, Tai BC, Chon g EY, Lau C, Than Y, et al. O b structive slee p a pnea in patients a dmitte d for acute m yocardia l infarction. Preva lence, pre dictors, an d effect on microvascular perfusion. Chest 2009;135(6):1488-95.
20. Gainer JL. Hypoxia an d ath erosclerozis: re-eva luation of an o ld hypothesis. Ath erosclersis 1987;68:263-6 .
21. Deanfie ld JE, Maseri A, Se lwy n AP, Rib eiro P, Ch ierc h ia S, Krikler S. Myocardia l isch emia durin g daily life in patients with sta ble an gina: its re lation to symptoms an d h eart rate c han ges. Lancet 1983;2:753-8.
22. Humg J, W h itford EG, Parsons RW, Hillman DR Association of s lee p a pnea with M yocardia l infarction in men Lance t 1 990 ;336:261 -64 1 2 .
23. Gra h am IM, Da ly EL, Refsum HM, Ro b inson K, Brattström LE, Ue lan d PM, et a l. Plasma h omocysteine as a risk factor for vascu lar disease. T h e Euro pean concerte d action pro - ject. JAMA 1997;277:1775-81 .
24. Bousne y CJ, Beresford SAA, Omenn GS, Motu lsky AG. A q ua litative assesment of plasma h omoc ysteine as a risk fac- tor for vascu lar disease: pro b a bl b enefits of increasin g fo lic acid inta kes. JAMA 1995 ;274:1049-57.
25. Ny gard O, Nordrehurg JE, Refsum HE, Ueland PM, Farsta d M, Vo llset SE. Plasma h omocysteine leve ls an d morta lity in patients with coronary artery disease. N En gl J Me d 1997;337:230-6 .
26. Lavie L, Pere lman A, Lavie P. Plasma h omocysteine leve ls in o b structive slee p a pnea. Association with cardiovascu le r morbidity. Chest 2001;120:900-8 .
27. Svatikova A, Wolk R, Ma gera MJ, Shamsuzzaman AS, Ph illips BG, Somers VK. Plasma h omocystein in ob structive slee p a pnea. Eur Heart J 2004;25,1325-9 .
28. Schlaish MP, Jo h n S , Jaco b i J, Lack ner KJ, Sch mie der RE. Mildly e levate d h omocy stein concentrations im pair endoth e lium de pen dent vaso dilatation in hyperch o lester- o lemic patients. Ath erosc lerosis 2000;153:383-9 .
29. Faraci FM. Hyperh omoc ysteinemia. A million wa ys to lose contro l. Ath eroscler T h rom b Vasc Bio l 2003 ;23:371-3 .
30. Kato M, T h om pson R. Im pairment of en dothe lium de pend- ent vaso dilatation of resistance vesse ls in patients with o b structive slee p a pnea. Circu lation 2000;109:2607-10 .
31. Fen g J, Zh an g D, Ch en B. En doth e lia l mec hanisms o f en doth e lia l dysfunction in patients with o b structive slee p a pnea. Slee p Breat 2012;16(2):283-94 .
32. Ip MS, Lam B, Ch an LY, Zh en g L, Tsan g KW, Fun g PC, et a l. Circu latin g nitric oxide is supresse d in ob structive sleep a pne an d reverse d by nasa l continious positive airwa y pres- sure. Am J Respir Crit Care Med 2000;162:2166-71 .
33. Sc h u lz R, Sch midt D, Blum A, Lo pes-Rib eiro X, Lücke C, Ma yer K, et a l. Decrease d plasma leve ls of nitric oxide derivatives in o b structive s lee p a pnoea: response to CPAP th erapy. T h orax 2000;55:1046-51 .
34. Ch ristou K, Mou las AN, Pasta ka C, Gourgou lianis KI. Antioxidant ca pacity in o b structive slee p a pnea patients. Slee p me dicine 2003;4:225-8 .