Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately
5% to 15% of the population. It is usually associated with an increased risk of cardiovascular
disease. Diagnosis of OSA is based on polysomnography, and its severity is measured with an
apnea-hypopnea index. Most of the adverse effects of OSA on the cardiovascular system are
reversible with treatment. In addition to continous positive airway pressure therapy, precautions
such as weight loss, avoidance of central nervous system depressants, treatment of nasal
congestion and sleeping in the lateral position may help to treat OSA. (Cardiol J 2007; 14: 534-537)

Gunduz, Huseyin

Karaaslan, Kazim

Ozyildirim, Serhan

Talay, Fahrettin

Yilmaz, Fahrettin

English

Via Medica Journals

REVIEW ARTICLECardiology Journal2007, Vol. 14, No. 6, pp. 534–537Copyright © 2007 Via MedicaISSN 1897–5593534 www.cardiologyjournal.orgAddress for correspondence:Fahrettin Yilmaz, Assist. Prof.Abant Izzet Baysal UniversityIzzet Baysal Faculty of MedicineDepartment of Cardiology, Bolu, Turkeye-mail: yilmazfahrettin@yahoo.comReceived: 13.07.2007 Accepted: 20.09.2007Obstructive sleep apnea as a risk factorfor cardiovascular diseasesFahrettin Yilmaz1, Serhan Ozyildirim2, Fahrettin Talay3,Kazim Karaaslan4 and Huseyin Gunduz21Department of Otorhinolaryngology, Abant Izzet Baysal University,Izzet Baysal Faculty of Medicine, Bolu, Turkey2Department of Cardiology, Abant Izzet Baysal University,Izzet Baysal Faculty of Medicine, Bolu, Turkey3Department of Pneumonology, Abant Izzet Baysal University,Izzet Baysal Faculty of Medicine, Bolu, Turkey4Department of Anesthesiology, Abant Izzet Baysal University,Izzet Baysal Faculty of Medicine, Bolu, TurkeyAbstractObstructive sleep apnea (OSA) is a common medical condition that occurs in approximately5% to 15% of the population. It is usually associated with an increased risk of cardiovasculardisease. Diagnosis of OSA is based on polysomnography, and its severity is measured with anapnea-hypopnea index. Most of the adverse effects of OSA on the cardiovascular system arereversible with treatment. In addition to continous positive airway pressure therapy, precau-tions such as weight loss, avoidance of central nervous system depressants, treatment of nasalcongestion and sleeping in the lateral position may help to treat OSA. (Cardiol J 2007; 14: 534–537)Key words: obstructive sleep apnea, cardiovascular systemIntroductionObstructive sleep apnea (OSA) is a disorder,characterised by repeated episodes of breath ces-sation during sleep, which is usually seen togetherwith daytime sleepiness and/or altered cardiac func-tion. It is usually associated with increased cardio-vascular morbidity and mortality [1].The main objectives of this paper is to summa-rize the pathophysiological and clinical aspects ofOSA and to discuss its cardiovascular effects andthe treatment of this condition.Definition and frequencySleep apnea is defined as a cessation of breath-ing activity during sleep due to either dysfunctionof the central respiratory control mechanisms ora mechanical collapse and obstruction of the upperairways. The former is known as central sleep ap-nea and the latter as OSA [2].Obstructive sleep apnea is the more commonform of sleep apnea and occurs in approximately 5%to 15% of the population [2, 3]. It is characterizedby hypopnea and apnea intervals leading to a 4% de-crease in oxygen saturation usually in overweightpatients who suffer from daytime sleepiness [2].During collapse periods the pharynx is partially or535Fahrettin Yilmaz et al., Obstructive sleep apnea as a risk factor for CVDwww.cardiologyjournal.orgcompletely closed and sleep is fragmented, so pa-tients suffer from daytime sleepiness [4]. The ap-nea-hypopnea index (AHI), which is the number ofapneic and hypopneic events per hour, is used to de-termine the severity of sleep apnea, defining apneaas mild if AHI is between 5 and 15, moderate be-tween 15 and 30 and severe if AHI is above 30. Car-diovascular risk is increased in patients whose AHIis over 30 per hour [5].The effects of obstructive sleep apneaon the cardiovascular systemAlthough known to be a benign disease, retro-spective studies have shown that OSA is usuallyassociated with increased morbidity and mortalitydue to systemic and/or pulmonary hypertension,heart failure, myocardial infarction and stroke [1].However, it is good to remember that most of theadverse effects of OSA on the cardiovascular sys-tem are reversible with treatment. Moreover, con-tinuous positive airway pressure (CPAP) ventila-tion therapy has been shown to have cardioprotec-tive effects and to decrease mortality and morbidityamong those patients. Increased cardiovascular riskin OSA is independent of confounding factors suchas obesity, hyperlipidemia or metabolic disease [6].The effects of OSA on the cardiovascular sys-tem can be divided into long- and short-term impli-cations. Short-term effects are known to be relatedto mechanical effects such as sudden intrathoracicpressure changes, hypoxia, hypercapnia inducedchemical substance release, sympathetic-mediatedvasoconstriction, increased after-load, increasedleft ventricular transmural pressure and arousalfrom sleep. However, long-term effects are the re-sults of some complex dysfunctions which are notvery well known. Autonomic dysfunction (mainly byrepetitive increase in sympathetic tone), malfunc-tioning of the carotid body, production of free oxy-gen radicals, decreased nitric oxide levels and en-dothelial dysfunction, pro-inflammatory changes(increased levels of cell adhesion molecules, inter-leukin 6, tumour necrosis factor alpha and C-reac-tive protein), tendency to coagulation by increasedthrombocyte aggregation, higher leptin levels andenhanced atherosclerosis are potential mechanismsfor long term effects [4, 6, 7].It has been shown that manoeuvres such asinduction of hypoxia can cause blood pressurechanges during sleep [8]. Systemic arterial hyper-tension, with a prevalence of 50%, is the leadingcardiovascular abnormality that is related to OSA [9].The association between OSA and hypertension isindependent of age, sex, previous blood pressurehistory, body mass index and smoking [10, 11].Hypoxia and hypercapnia induced sympathetic acti-vation, increased endothelin and decreased nitricoxide levels and hence endothelial dysfunction, in-creased arterial stiffness and vascular resistance arepossible mechanisms behind this predisposition [12].In a prospective follow up of 709 patients, Peppardet al. [10] found that OSA was predictive of the pres-ence of hypertension four years later.Associated with OSA, pulmonary hypertensionis seen approximately 30%, coronary artery disease20–30%, congestive heart failure 10%, and strokecan be seen as much as 10%. Arrhythmias are theother disorders which can be induced by OSA dur-ing the sleep period [13].Obstructive sleep apnea is an independent riskfactor for coronary artery disease. Increased C-re-active protein and oxidative stress, hypoxia itself,increased sympathetic activity, tachycardia, cardi-ac oxygen demand increase, increased systemicvascular resistance, increased tendency to throm-bosis and many other unknown mechanisms causean increased risk for coronary events in OSA pa-tients. Moreover, in a study by Tan et al. [14] in-terestingly it was found that OSA has a negativeeffect on the preventive functions of high-densitylipoprotein, which contributes to the effect of OSAincreasing the risk for coronary artery disease.Obstructive sleep apnea associated heart fail-ure has a prevalence of approximately 10% [11, 15].Besides causing left ventricular systolic functionimpairment through the well-known causes of heartfailure such as hypertension and coronary arterydisease, OSA can directly affect the ventricularfunctions [11, 16, 17]. Increased sympathetic drive,increased endothelin and endothelial dysfunction,increased systemic vascular resistance, inflamma-tory cytokines and transmural pressures are well-known OSA induced mechanisms deteriorating ven-tricular systolic and diastolic functions [4]. Tanriv-erdi et al. [16] illustrated that OSA patientsexhibited a mild decrease in left ventricle systolicfunction, which was not attributable to the well-known causes of left ventricle dysfunction. Theyconcluded that aortic elasticity was also deteriorat-ed and increased aortic stiffness might be respon-sible for many of the cardiovascular alterationscaused by this disease. Likewise, a cross sectionalcohort study by Phillips et al. [18] concluded thatsystemic arterial stiffness was positively correlat-ed with the severity of OSA.Obstructive sleep apnea is also associated withan increased risk of stroke, independent of any536Cardiology Journal 2007, Vol. 14, No. 6www.cardiologyjournal.orgother cardiovascular risk factors [19]. The factors thatmay increase the risk of stroke in OSA include acutereduction in cerebral blood flow due to apnea, hy-poxemia and prothrombotic state and a tendencytowards atherosclerosis, and hypertension. Strokeis an important cause of mortality and morbidityamong patients suffering from OSA [4, 11, 19, 20].Obstructive sleep apnea is associated witha broad range of arrhythmias such as atrial fibrilla-tion (AF), sinoatrial or atrioventricular block, sinusnode dysfunction, bradyarrhythmia and asystole.Rhythm disturbances such as bradycardia areknown as a typical feature of OSA [21]. Additional-ly, a study by Harbison et al. [22] showed the pres-ence of a relationship between rhythm disturbanc-es and the severity of OSA.Hypoxia and apnea induced vagal tone increasetrigger, especially nocturnal bradyarrhythmias.Therefore, physicians have to evaluate carefully anynocturnal dysrhythmia in terms of OSA coexistencein order not to make an unnecessary pacemakerimplantation decision [4, 11]. Consequently, in sucha case, only CPAP therapy may successfully over-come the arrhythmia [19]. The hypoxemia, sympa-thetic overactivation, pressure surges, increasedcardiac wall stress and transmural pressures mayincrease the likelihood of AF in OSA patients. Fur-thermore, in patients who underwent cardioversionfor AF, if sleep apnea is accompanying, there is a two-fold increase in the risk of recurrence of AF within12 months compared with OSA patients treated withCPAP. Accordingly, CPAP therapy in OSA patientsis shown to decrease AF recurrence [4, 23].Reynolds et al. [24] showed that among OSApatients, heart rate variability increased as apneaseverity increased. However, during REM sleepthere was a decrease in heart rate variability whichalso suggested autonomic dysfunction in OSA pa-tients. Yang et al. [25] found that there were chang-es in heart rate turbulence of the OSA patients inthe absence of overt cardiac disease, which corre-lates with the severity of OSA and are again relatedto the abnormalities in cardiac autonomic activity.Besides systemic hypertension, long lastingOSA can cause pulmonary hypertension and rightventricular failure without any underlying pulmo-nary or cardiovascular disease [11].Diagnosis and treatmentPatients possibly having OSA were identifiedusing the Epworth Sleepiness Scale (an eight-itemquestionnaire assessing sleep quality and symptomsrelated to OSA). The standard test for OSA diagno-sis is polysomnography including electrocardiogra-phy, oxygen saturation measurements, electroen-cephalography, electro-oculography, snoring micro-phone and assessment of body positions by videorecording with an infrared camera for the wholenight during the patient’s habitual sleep hours. Poly-somnography shows an obvious drop in tidal volume— a decrease in oxygen saturation during the ap-nea and hypopnea episodes which are terminated byan arousal detected by EEG [26].Precautions such as weight loss, avoidance ofcentral nervous system depressants, treatment ofnasal congestion and sleeping in the lateral positionmay help to treat OSA, as well as CPAP, the noninva-sive treatment shown to normalize oxygen saturation,improve regulation of systemic and pulmonaryhypertension, improve cognitive performance andmood, decrease somnolence and improve daytimealertness and quality of life and reduce mortality[27–30]. CPAP treatment may also prevent noctur-nal ST-segment depression, improve left ventricu-lar systolic and diastolic functions, improve func-tional class and decrease the risk of cardiac arrhyth-mias in patients with heart failure [31]. In recentyears, a number of automatic CPAP systems in thevariable-pressure mode have been in use, which hasresulted in decreased overnight cumulative CPAPlevels, which seems to improve the efficacy andtolerability of OSA treatment [32]. Other than non-invasive treatment strategies, surgical proceduresto overcome the obstruction such as uvulopalat-opharyngoplasty, laser uvulopalatoplasty, tonsillec-tomy, partial resection or ablation of the tongue,reconstruction of the mandible or maxille and tra-cheostomy may be used for selected cases [24, 32].ConclusionsObstructive sleep apnea is a common, treata-ble but underdiagnosed disease state, which shouldbe kept in mind by physicians dealing with cardio-vascular disorders. Sleep quality has to be a part ofroutine history taking in cardiovascular practicebecause a broad spectrum of cardiovascular disor-ders can be effectively prevented merely by treat-ing OSA. Because of its systemic effects, manyother disease states such as pulmonary throm-boembolism or even aortic aneurysm and dissec-tion are areas for concern that should be studiedfor a direct association with OSA [26, 33].537Fahrettin Yilmaz et al., Obstructive sleep apnea as a risk factor for CVDwww.cardiologyjournal.orgReferences1. Strollo PJ Jr, Rogers RM. Obstructive sleep apnea.N Engl J Med, 1996; 334: 99–104.2. Flemons WW, Littner MR, Rowley JA et al. Homediagnosis of sleep apnea: a systematic review of theliterature. An evidence review cosponsored by theAmerican Academy of Sleep Medicine, the AmericanCollege of Chest Physicians, and the American Tho-racic Society. Chest, 2003; 124: 1543–1579.3. Parish JM, Somers VK. Obstructive sleep apnea andcardiovascular disease. Mayo Clin Proc, 2004; 79:1036–1046.4. Chervin RD. Sleepiness, fatigue, tiredness, and lackof energy in obstructive sleep apnea. Chest, 2000;118: 372–379.5. Shamsuzzaman AS, Gersh BJ, Somers VK. Obstruc-tive sleep apnea: implications for cardiac and vascu-lar disease. JAMA, 2003; 290: 1906–1914.6. Schulz R, Grebe M, Eisele HJ, Mayer K, Weissmann N,Seeger W. Obstructive sleep apnea-related cardio-vascular disease. Med Klin (Munich), 2006; 101:321–327.7. Bonsignore MR, Marrone O, Insalaco G, Bonsignore G.The cardiovascular effects of obstructive sleep ap-noeas: analysis of pathogenic mechanisms. EurRespir J, 1994; 7: 786–805.8. Plante GE. Sleep and vascular disorders. Metabo-lism, 2006; 55: 45–49.9. Kasasbeh E, Chi DS, Krishnaswamy G. Inflammatoryaspects of sleep apnea and their cardiovascular con-sequences. South Med J, 2006; 99: 58–67.10. Peppard PE, Young T, Palta M, Skatrud J. Prospec-tive study of the association between sleep-disor-dered breathing and hypertension. N Engl J Med,2000; 342: 1378–1384.11. Wolk R, Kara T, Somers VK. Sleep-disorderedbreathing and cardiovascular disease. Circulation,2003; 108: 9–12.12. Somers VK, Dyken ME, Clary MP, Abboud FM.Sympathetic neural mechanisms in obstructive sleepapnea. J Clin Invest, 1995; 96: 1897–1904.13. Schulz R, Grebe M, Eisele HJ, Mayer K, Weissmann N,Seeger W. Obstructive sleep apnea-related cardio-vascular disease. Med Klin (Munich), 2006; 101:321–327.14. Tan KC, Chow WS, Lam JC et al. HDL dysfunctionin obstructive sleep apnea. Atherosclerosis, 2006;184: 377–382.15. Javaheri S, Parker TJ, Liming JD et al. Sleep apnea in81 ambulatory male patients with stable heart fail-ure: types and their prevalence, consequences, andpresentations. Circulation, 1998; 97: 2154–2159.16. Tanriverdi H, Evrengul H, Kaftan A et al. Effect ofobstructive sleep apnea on aortic elastic parameters:relationship to left ventricular mass and function.Circ J, 2006; 70: 737–743.17. Shahar E, Whitney CW, Redline S et al. Sleep--disordered breathing and cardiovascular disease.Am J Respir Crit Care Med, 2001; 163: 19–25.18. Phillips C, Hedner J, Berend N, Grunstein R. Diurnaland obstructive sleep apnea influences on arterialstiffness and central blood pressure in men. Sleep,2005; 28: 604–609.19. Dyken ME, Somers VK, Yamada T, Ren ZY,Zimmerman MB. Investigating the relationship be-tween stroke and obstructive sleep apnea. Stroke,1996; 27: 401–407.20. Netzer N, Werner P, Jochums I, Lehmann M, Strohl KP.Blood flow of the middle cerebral artery with sleep--disordered breathing: correlation with obstructivehypopneas. Stroke, 1998; 29: 87–93.21. Guilleminault C, Connolly S, Winkle R, Melvin K,Tilkian A. Cyclical variation of the heart rate in sleepapnoea syndrome: mechanisms and usefulness of 24 helectrocardiography as a screening technique.Lancet, 1984; 1: 126–131.22. Harbison J, O’Reilly P, McNicholas WT. Effects ofnasal continuous positive airway pressure therapy,cardiac rhythm disturbances in the obstructive sleepapnea syndrome. Chest, 2000; 118: 591–595.23. Kanagala R, Murali NS, Friedman PA et al. Obstruc-tive sleep apnea and the recurrence of atrial fibrilla-tion. Circulation, 2003; 107: 2589–2594.24. Reynolds EB, Seda G, Ware JC, Vinik AI, Risk MR,Fishback NF. Autonomic function in sleep apnea pa-tients: increased heart rate variability except duringREM sleep in obese patients. Sleep Breath, 2006;15 (Epub ahead of print).25. Yang A, Schafer H, Manka R et al. Influence of ob-structive sleep apnea on heart rate turbulence. BasicRes Cardiol, 2005; 100: 439–445.26. Piccirillo JF, Duntley S, Schotland H. Obstructivesleep apnea. JAMA, 2000; 284: 1492–1494.27.  Strollo PJJ, Sanders MH, Atwood CW. Positive pres-sure therapy. Clin Chest Med, 1998; 19: 55–68.28. Flemons WW. Obstructive sleep apnea. N Engl JMed, 2002; 347: 498–504.29. Farre R, Hernandez L, Montserrat JM, Rotger M,Ballester E, Navajas D. Sham continuous positiveairway pressure for placebo-controlled studies insleep apnoea. Lancet, 1999; 353: 1154–1154.30. Jenkinson C, Davies RJ, Mullins R, Stradling JR.Comparison of therapeutic and subtherapeutic nasalcontinuous positive airway pressure for obstructivesleep apnoea: a randomised prospective parallel trial.Lancet, 1999; 353: 2100–2105.31. Javaheri S. Effects of continuous positive airwaypressure on sleep apnea and ventricular irritabilityin patients with heart failure. Circulation, 2000; 101:392–397.32. Loube DI. Technologic advances in the treatment ofobstructive sleep apnea syndrome. Chest, 1999; 116:1426–1433.33. Shivalkar B, Van de Heyning C, Kerremans M et al.Obstructive sleep apnea syndrome more insightson structural and functional cardiac alterations, andthe effects of treatment with continuous positiveairway pressure. J Am Coll Cardiol, 2006; 47:1433–1439.

Obstructive sleep apnea as a risk factor for cardiovascular diseases

https://journals.viamedica.pl/cardiology_journal/article/download/21649/17253

Obstructive sleep apnea as a risk factor for cardiovascular diseases

Abstract

Similar works

Full text

Available Versions

Via Medica Journals