Respiration 2006;73:124–130
(DOI:10.1159/000089814)

Deleterious Effects of Sleep-Disordered Breathing on the Heart and Vascular System

Dincer H.E.a · O’Neill W.b, c
aPulmonary, Critical Care and Sleep Medicine, VA Southern Nevada Health Care System, Las Vegas, Nev., bPulmonary, Critical Care and Sleep Medicine, Medical College of Wisconsin, and cVA Medical Center, Milwaukee, Wisc., USA
email Corresponding Author


 Outline


 goto top of outline Key Words

  • Sleep apnea
  • Hypertension
  • Atherosclerosis
  • Continuous positive airway pressure

 goto top of outline Abstract

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5–15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias. Of these possible cardiovascular consequences, the association between OSA and hypertension has been found to be the most convincing. Although the exact mechanism has not been understood, there is some evidence that OSA is associated with frequent apneas causing mechanical effects on intrathoracic pressure, cardiac function, and intermittent hypoxemia, which may in turn cause endothelial dysfunction and increase in sympathetic drive. Therapy with continuous positive airway pressure has been demonstrated to improve cardiopulmonary hemodynamics in patients with OSA and may reverse the endothelial cell dysfunction. Despite the availability of diagnostic measures and effective treatment, many patients with sleep-disordered breathing remain undiagnosed. Therefore, OSA continues to be a significant health risk both for affected individuals and for thegeneral public. Awareness and timely initiation of an effective treatment may prevent potential deleterious cardiovascular effects of OSA.

Copyright © 2006 S. Karger AG, Basel


goto top of outline Introduction

Obstructive sleep apnea (OSA) is arguably the most prevalent disease to be discovered in the twentieth century [1,2,3]. Although its definition continues to evolve, the syndrome involves a group of obese and non-obese patients in whom elevated airway resistance and/or apnea/hypopnea occurs during sleep, leading to intermittent hypoxemia with profound disruption of sleep architecture. Apnea in adults is defined as the absence of airflow at the nose or mouth for 10 s or more. Hypopnea is defined as a 30% or more reduction in airflow from baseline that lasts 10 s or more, with or without significant desaturation (more than 4% from baseline) [4]. Patients with OSA frequently complain of excessive daytime sleepiness, abnormal mentation, impaired concentration while performing daily tasks, impotence, morning headaches, nocturia, depression, excessive fatigue, and insomnia. Bed partners may also report apnea, snoring, irritability, choking, and restlessness. Consequences of OSA are variable; in addition to adversely impacting the patients’ social life, employment, and productivity, OSA may also have significant deleterious effects on patients’ health, as there is significant evidence which suggests both an increased risk for certain cardiovascular diseases and motor vehicle accidents in affected individuals [5,6,7].

The pathophysiology of possible deleterious cardiovascular effects of OSA is thought to involve two major components: first, the mechanical effect of apneas on intrathoracic pressures and heart function, and second, intermittent hypoxemia resulting in sympathetic overdrive and endothelial cell dysfunction (fig. 1). Although there is no definitive evidence to determine whether OSA directly causes cardiovascular disease, the available data do suggest an increased risk of having cardiovascular events in sleep apnea patients. However, there is more substantial data to support an association between OSA and hypertension.

FIG01
Fig. 1. Possible cardiovascular changes in OSA. Pit = Intrathoracic pressure; RV = right ventricle; LV = left ventricle; PLVTm = left ventricular transmural pressure; NO = nitric oxide; BP = blood pressure; HR = heart rate; SVR = systemic vascular resistance.

 

goto top of outline Hypertension and OSA

Hypertension is one of the commonest diseases in North America, affecting approximately 15–20% of the adult population. OSA is now recognized as an independent risk factor for hypertension [8, 9], and about 40% of patients with OSA are documented to be hypertensive while awake, according to standard criteria [10]. How OSA causes a sustained elevation in blood pressure is not well understood. It is possible that sympathetic over-activity plays at least some role in the elevated blood pressure found in OSA patients [11]. Other potential mechanisms include hyperleptinemia, insulin resistance, elevated angiotensin II and aldosteron levels, endothelial cell dysfunction, and impaired baroreflex function [12]. Studies using animal models of obstructive sleep apnea revealed diurnal hypertension in dogs and rats [13, 14]. Several population-based studies have yielded a relationship between OSA and hypertension. The Sleep Heart Health Study, which enrolled more than 6,000 individuals, showed a definite independent association between OSA and hypertension, and the prevalence of hypertension was increased with the severity of OSA [15]. Similarly, the Wisconsin Cohort Study of 1,069 patients and a prospective follow-up of 893 patients revealed the apnea-hypopnea index as being an independent predictor of daytime hypertension [16, 17].

OSA has been found to be more common in patients with treatment-refractory hypertension [18]; conversely, controlling hypertension by conventional therapeutic means has been found to be more difficult in patients with OSA than in hypertensive individuals without OSA [19]. Continuous positive airway pressure (CPAP) treatment leads to a fall in blood pressure as measured by both an intra-arterial device [20] and by ambulatory blood pressure measurements [21], with a greater effect noted in patients with severe OSA [22, 23]. The fact that a 50% reduction in the respiratory disturbance index did not result in a decrease in blood pressure emphasizes the importance of highly effective treatment and the need for a close follow-up to establish the effectiveness of CPAP therapy. Mild OSA does not appear to be associated with a substantial decline in blood pressure with CPAP therapy, but is apparently independently associated with elevated blood pressure in this population [24]. Several uncontrolled studies have reported that CPAP therapy or tracheostomy in OSA patients with or without congestive heart failure was associated with a reduction in blood pressure during sleep [25,26,27,28]. These data suggest that untreated OSA plays an independent role in the pathogenesis of hypertension, and emphasizes the importance of detecting and treating OSA for optimal management of hypertension. Physicians should be aware of OSA as a reversible and treatable cause of hypertension.

 

goto top of outline Atherosclerotic Effect of OSA on the Cardiovascular System

OSA is suspected to be an independent risk factor for atherosclerotic artery disease.

Most OSA patients share similar features to patients with metabolic syndrome, such as central obesity, insulin resistance [29], and systemic hypertension [8, 9]. Different studies have proposed possible mechanisms for the atherosclerotic effect of OSA. These include repetitive surges in blood pressure due to sympathetic over-activity, oxidative stress [30, 31], endothelial cell dysfunction [32, 33] resulting in increased plasma levels of endothelin-1 [34], decreased nitric oxide production [35], and elevated inflammatory response [36] as evidenced by increased C-reactive protein and interleukin-6 [37]. On the other hand, elevated plasma levels of various adhesion molecules and increased expression of adhesion molecules on leukocytes and their adherence to endothelial cells have been reported and are thought to have a role in endothelial cell dysfunction, formation of atherosclerosis, and clot formation [38, 39]. Studies on OSA treated with CPAP have demonstrated improved insulin resistance [40, 41], a reversal of the inflammatory response as evidenced by a decrease in serum endothelin-1 [34], an increase in serum nitric oxide levels [35], and a decrease in C-reactive protein and interleukin-6 [42], thus further supporting a relationship between OSA and the metabolic syndrome. Nachtman et al. [43] found an independent association of the presence of atherosclerosis in carotid, vertebral and peripheral arteries in stroke patients. Although these studies suggest a relationship between OSA and atherosclerosis formation, there is presently no definite evidence to prove this. At the present time, we can only state that there is a complex relationship between OSA, atherosclerosis and the metabolic syndrome.

 

goto top of outline Acute Coronary Syndromes

Individuals who snore without documentation of apnea have been found to have an increased risk of myocardial infarction [44]. A few studies have demonstrated a possible correlation between OSA and myocardial infarction [45, 46], and patients with coronary artery disease and ongoing untreated OSA were found to have higher mortality rates than patients treated with CPAP [47]. CPAP treatment has also been shown to abolish nocturnal angina [48]. ST segment depression in association with OSA was noted with or without clinically significant coronary artery disease, and reduced by CPAP treatment [49]. Moreover, several studies have reported a high incidence of OSA in patients with coronary artery disease [50,51,52,53]. Newman et al. [54] assessed nearly 6,000 patients and found that daytime sleepiness was the only symptom of sleep disturbance that was associated with mortality, coronary artery morbidity, and mortality. The Sleep Heart Health Study found an association with increased multivariate adjusted relative odds of self-reported coronary heart disease [15]. Although these findings do not establish a definite relationship between OSA and coronary artery disease, they do suggest that sleep apnea may be associated with or may even predispose to coronary artery disease. Possible mechanisms include an indirect effect of hypertension, the formation of atherosclerosis, oxygen desaturation, sympathetic nervous system overactivity, increased coagulopathy, and increased inflammatory response. Currently, it is not known if OSA can cause nocturnal myocardial ischemia in patients without ischemic coronary artery disease. Further studies are needed to better understand the effect of OSA in the pathogenesis of coronary artery disease.

 

goto top of outline Stroke

A high incidence of OSA (45–90%) is found in stroke patients [55,56,57]. Snoring has been found to be a risk factor for cardiovascular events, including stroke, in a large prospective study in women [58]. Similarly, the Sleep Heart Health Study revealed a modest but clear increased prevalence of stroke in studied patients [15]. It is presently not well understood whether stroke causes OSA or if OSA is a risk factor for stroke. Considering the cardiovascular effects of OSA and decreased muscle tone of the upper airways which is commonly seen in stroke patients, it is likely that both statements are true. Although there is evidence that OSA is linked to stroke occurrence, there is no published direct evidence that demonstrates that CPAP treatment prevents stroke. Proposed mechanisms for the causative effect of OSA in the pathogenesis of stroke include atherosclerotic influences, hypertension, decreased cerebral perfusion due primarily to increased carotid wall thickness [59], low cardiac output, increased intracranial pressure, increased coagulopathy, and increased risk of clot formation due to arrhythmia [60, 61]. Because of high incidence of OSA and its potential adverse effects on morbidity and mortality, a routine search for OSA may be recommended in this population [62].

 

goto top of outline Arrhythmia

Both bradyarrhythmias and tachyarrhythmias have been described in patients with OSA. However, bradyarrhythmias are more commonly observed, the most common being sinus bradycardia, sinus arrest, and complete heart block [63]. The risk of arrhythmia appeared to be related to the severity of OSA [64,65,66]. The likely explanation of bradyarrhythmia in OSA is chemoreceptor-mediated increase in vagal tone secondary to apneas and hypoxemia [67]. The observation that bradyarrhythmias occur only at night in association with apneic episodes in otherwise asymptomatic patients supports this theory. Gillis et al. [68] found QT prolongation at the onset of apnea, with subsequent shortening during the apnea and post-apnea hyperpneic phase. Reversion of OSA with CPAP or tracheostomy has been shown to abolish arrhythmia in most patients [66, 69]. Atrial overdrive pacing during sleep has been shown to reduce the number of episodes of OSA or central sleep apnea (CSA) without reducing the total sleep time [70]. Arrhythmias, especially tachyarrhythmias, may have a role in the pathogenesis of stroke by thrombus formation and embolism.

 

goto top of outline Left Ventricle and OSA

At least 50% of patients with heart failure have OSA or CSA [71]. Association between OSA and CSA is beyond the scope of this review. Left ventricular hypertrophy, systolic and diastolic dysfunctions have been demonstrated in OSA patients; these findings resolved with CPAP treatment [72,73,74]. The severity of the dysfunction correlated with the severity of OSA. Minimum oxygen saturation of less than 70% was an independent predictor for diastolic dysfunction, irrespective of age and hypertension [74]. In the Sleep Heart Health Study, the presence of OSA conferred a 2.38 relative increase in the likelihood of having heart failure independent of other known risk factors [15]. In case series of patients with heart failure, OSA was detected with a greater prevalence in men (38%) than in women (31%). OSA is common in heart failure, with approximately 11% of heart failure patients being affected. However, CSA is more common than OSA in patients with heart failure [64]. Some patients may have both OSA and CSA, with OSA being more common in the first, and CSA more common in the second half of the night [75]. Possible mechanisms of OSA-induced left ventricular dysfunction include impaired myocardial contraction secondary to hypoxemia, intermittent changes in intrathoracic pressures during apneic episodes, sympathetic overactivity, daytime hypertension, and loss of vagal heart rate regulation. Negative intrathoracic pressure decreases left ventricular relaxation. These effects may cause myocyte necrosis and apoptosis, leading to cardiomyopathy and cardiac remodeling.

 

goto top of outline Right Ventricle, Pulmonary Hypertension and OSA

Acute pulmonary hemodynamic changes during apneic episodes due to OSA are well recognized. However, persistent changes in pulmonary pressures due to OSA are somewhat controversial, as studies demonstrated a relationship between OSA and elevated pulmonary pressures included patients who had concurrent diseases which could have affected their pulmonary pressures. For example, patients with overlap syndrome (OSA and chronic obstructive pulmonary disease) have a higher incidence of pulmonary arterial hypertension [76, 77]. The reported prevalence of pulmonary arterial hypertension in OSA varies from 20 to 41% in different studies [78,79,80]. A possible mechanism is thought to be secondary to hypoxemia-induced endothelial cell dysfunction and pulmonary artery remodeling [81]. This may be related to hypoxia upregulation vascular endothelial growth factor, which is a mediator in angiogenesis, resulting in vascular remodeling [82, 83]. Most experts feel that OSA may modestly increase pulmonary arterial pressures, and evaluation for OSA should be part of the initial work-up in patients with pulmonary hypertension [84]. Therapy with CPAP has been shown to decrease pulmonary pressures in OSA patients with either high or normal pulmonary pressures [84, 85].

Several studies have addressed the effect of OSA on the right ventricle. These have demonstrated a decrease in ejection fraction as well as the presence of right ventricular hypertrophy [86, 87]. It is likely that right ventricular dysfunction is due to other hemodynamic changes associated with OSA, such as pulmonary hypertension, rather than being an isolated finding. Similarly, treatment with CPAP reverses right ventricular dysfunction in individuals with OSA [88].

 

goto top of outline Conclusion

There is a complex relationship between OSA and cardiovascular disease, and an understanding of the various mechanisms between these two conditions continues to evolve. Studies show a convincing link between hypertension and OSA. The data regarding ischemic heart disease and other cardiovascular pathology are not as convincing; however, OSA appears to be a risk factor for cardiovascular diseases. Treatment of OSA reverses or corrects the adverse cardiovascular effects of OSA, although the exact mechanisms have not been clearly elucidated. More animal and clinical studies are needed to understand the mechanisms underlying the deleterious cardiovascular effects of OSA. Physicians caring for patients with cardiovascular disease should be aware of the possible coexistence of OSA and should also recognize that most patients with OSA are either not diagnosed or have inadequate therapy for their disease. Initiating effective therapy for OSA may help treat underlying cardiovascular pathology, eliminate unnecessary work-up and decrease health care expenses.

 

goto top of outline Acknowledgement

We thank Angelica Honsberg, MD, for reviewing the manuscript.


 goto top of outline References
  1. Young T, Palta M, Dempsey J, et al: The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–1235.
  2. Ancoli-Israel S, Klauber MR, Stepnowsky C, et al: Sleep-disordered breathing in African-American elderly. Am J Respir Crit Care Med 1995;152:1946–1949.
  3. Redline S: Epidemiology of sleep-disordered breathing. Semin Respir Crit Care Med 1998;19:113–122.
  4. Meoli AL, Casey KR, Clark RW, Clinical Practice Review Committee, et al: Hypopnea in sleep-disordered breathing in adults. Sleep 2001;24:469–470.
  5. Findley L, Unverzagt M, Guchu R, et al: Vigilance and automobile accidents in patients with sleep apnea or narcolepsy. Chest 1995;108:619–624.
  6. Findley L, Bonnie RJ: Sleep apnea and auto crashes: what is the doctor to do? Chest 1988;94:225–226.
  7. Rodenstein DO: Sleep apnea syndrome: the health economics point of view. Monaldi Arch Chest Dis 2000;55:404–410.
  8. Worsnop CT, Naughton MT, Barter CE, et al: The prevalence of obstructive sleep apnea in hypertensives. Am J Respir Crit Care Med 1998;157:111–115.
  9. Gislason T, Almqvist M: Somatic diseases and sleep complaints: an epidemiologic study of 3,201 Swedish men. Acta Med Scand 1987;221:475–481.
  10. Pepperell JCT, Ramdassigh-Dow S, Crosthawite N, et al: Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomized parallel study. Lancet 2001;359:204–210.
  11. Fletcher EC: Sympathetic overactivity in the etiology of hypertension of obstructive sleep apnea. Sleep 2003;1:15–19.

    External Resources

  12. Wolk R, Shamsuzzaman ASM, Somers VK: Obesity, sleep apnea and hypertension. Hypertension 2003;42:1067–1074.
  13. Brooks D, Horner RL, Kozar LF, et al: Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest 1997;99:106–109.
  14. Bao G, Metreveli N, Fletcher EC, et al: Acute and chronic blood pressure response to recurrent acoustic arousal in rats. Am J Hypertens 1999;12:504–510.
  15. Nieto FJ, Young TB, Lind BK, et al: Association of sleep-disordered breathing, sleep apnea and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000;283:1829–1836.
  16. Young T, Peppard PE, Palta M, et al: Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746–1752.
  17. Peppard PE, Young T, Palta M, et al: Prospective study of the association between sleep disordered breathing and hypertension. N Engl J Med 2000;342:1378–1384.
  18. Logan AG, Tkacova R, Tisler A, et al: High prevalence of unrecognized obstructive sleep apnea in drug-resistant hypertension. J Hypertens 2001;19:2271–2277.
  19. Hirshkowitz M, Karaca I, Gurakar A, et al: Hypertension, erectile dysfunction and occult sleep apnea. Sleep 1989;12:223–232.
  20. Mayer J, Becker H, Brandenburg U, et al: Blood pressure and sleep apnea: results of long-term nasal continuous positive airway pressure therapy. Cardiology 1991;79:84–92.
  21. Wilcox I, Grunstein RR, Hedner JA, et al: Effect of nasal continuous positive airway pressure during sleep on 24-hour blood pressure in obstructive sleep apnea. Sleep 1993;16:539–544.
  22. Somers VK, Dyken ME, Clary MP, et al: Sympathetic neural mechanism in obstructive sleep apnea. J Clin Invest 1995;96:1897–1904.
  23. Dursuno N, Dursuno D, Cuhadaro C, et al: Acute effects of automated continuous positive airway pressure in patients with sleep apnoea and hypertension. Respiration 2005;72:150–155.
  24. Monasterio C, Vidal S, Duran J, et al: Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001;164:939–943.
  25. Fletcher EC, Miller J, Schaaf JW, et al: Urinary cathecholamines before and after tracheostomy in patients with obstructive sleep apnea and hypertension. Sleep 1987;98:772–776.
  26. Tkacova R, Rankin F, Fitzgerald FS, et al: Effects of nasal continuous positive airway pressure in obstructive sleep apnea and left ventricular afterload in patients with heart failure. Circulation 1998;98:2269–2275.
  27. Grunstein R, Wilcox I, Yang TS, et al: Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Dis 1993;17:533–540.
  28. Becker HF, Jerrentrup A, Ploch T, et al: Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003;107:68–73.
  29. Elmasry A, Lindberg E, Berne C, et al: Sleep disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med 2001;249:153–161.
  30. Schulz R, Mahmoudi S, Hattar K, et al: Enhanced released of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea: impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 2000;162:566–570.
  31. Dyugovskaya L, Lavie P, Lavie L: Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 2002;165:934–939.
  32. Carlson JT, Rangemark C, Hedner JA, et al: Attenuated endothelium-dependent vascular relaxation in patients with sleep apnoea. J Hypertens 1996;14:577–584.
  33. Kato M, Robert-Thomson P, Phillips BG, et al: Impairment of endothelium-dependent vasodilatation of resistance vessels in patients with obstructive sleep apnea. Circulation 2000;102:2607–2610.
  34. Phillips BG, Narkiewicz K, Pesek CA, et al: Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J Hypertens 1999;17:61–66.
  35. Ip MS, Lam B, Chan LY, et al: Circulating nitric oxide is suppressed in obstructive sleep apnea and reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med 2000;162:2166–2171.
  36. Ross R: Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–126.
  37. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al: Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002;105:2462–2464.
  38. Ohga E, Nagase T, Tomita T, et al: Increased levels of circulating ICAM-1, VCAM-1 and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol 1999;87:10–14.
  39. El-Solh AA, Mador MJ, Sikka P, et al: Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest 2002;121:1541–1547.
  40. Harsch IA, Schahin SP, Radespiel-Troger M, et al: Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2004;169:156–162.
  41. Harsch IA, Schain SP, Bruckner K, et al: The effects of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes. Respiration 2004;71:252–259.
  42. Yokoe T, Minoguchi K, Matsuo H, Oda N, et al: Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreasing by nasal continuous positive airway pressure. Circulation 2003;107:1129–1134.
  43. Nachtman A, Stang A, Wang Y, et al: Association of obstructive sleep apnea and stenotic artery disease in ischemic stroke patients. Atherosclerosis 2003;169:301–307.
  44. D’Alessandro R, Magelli C, Gamberini G, et al: Snoring every night as a risk factor for myocardial infarction: a case-control study. BMJ 1990;300:1557–1558.
  45. Peker Y, Karaiczi H, Hedner J, et al: An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J 1999;14:179–184.
  46. Peker Y, Hedner J, Karaiczi H, et al: Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. Am J Respir Crit Care Med 2000;162:81–86.
  47. Mooe T, Franklin KA, Wiklund U, et al: Sleep-disordered breathing and myocardial ischemia in patients with coronary artery disease. Chest 2000;117:1597–1602.
  48. Franklin KA, Nilsson JB, Sahlin C, et al: Sleep apnoea and nocturnal angina. Lancet 1995;345:1085–1087.
  49. Hanly P, Sasson Z, Zuberi N, et al: ST segment depression during sleep in obstructive sleep apnea. Am J Cardiol 1993;71:1341–1345.
  50. Mooe T, Rabben T, Wiklund U, et al: Sleep-disordered breathing in women: occurrence and association with coronary artery disease. Am J Med 1996;101:251–256.
  51. Mooe T, Rabben T, Wiklund U, et al: Sleep-disordered breathing in men: occurrence and association with coronary artery disease. Am J Med 1996;109:959–963.
  52. Shahar E, Whitney CW, Redline S, et al: Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001;163:19–25.
  53. Schafer H, Koehler U, Ewig S, et al: Obstructive sleep apnea as a risk marker in coronary artery disease. Cardiology 1999;92:79–84.
  54. Newman AB, Spiekerman CF, Enright P, et al: Daytime sleepiness predict mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group. J Am Geriatr Soc 2000;48:115–123.
  55. Mohsenin V, Valor R: Sleep apnea in patients with hemispheric stroke. Arch Phys Med Rehabil 1995;76:71–76.
  56. Wessendorf TE, Teschler H, Wang YM, et al: Sleep-disordered breathing among patients with first-ever stroke. J Neurol 2000;247:41–47.
  57. Bassetti C, Aldrich MS: Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep 1999:22;217–223.
  58. Hu FB, Willett WC, Manson JE, et al: Snoring and risk of cardiovascular disease in women. J Am Coll Cardiol 2000;35:308–313.
  59. Silvestrini M, Rizzoto B, Placidi F, et al: Carotid artery wall thickness in patients with obstructive sleep apnea syndrome. Stroke 2002;33:1782–1785.
  60. Netzer N, Werner P, Jachums T, et al: Blood flow of the middle cerebral artery with sleep-disordered breathing correlation with obstructive hypopneas. Stroke 1998;29:87–93.
  61. Hoffstein V, Mateika S: Cardiac arrhythmia, snoring and sleep apnea. Chest 1994;106:466–471.
  62. Disler P, Hansford A, Skelton J, et al: Diagnosis and treatment of obstructive sleep apnea, in a stroke rehabilitation unit: a feasibility study. Am J Phys Med Rehabil 2002;81:622–625.
  63. Guilleminault C, Connolly SJ, Winkle RA: Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol 1983;52:490–494.
  64. Javaheri S, Parker TJ, Liming JD, et al: Sleep apnea in 81 ambulatory male patients with stable heart failure: types and their prevalences, consequences and presentations. Circulation 1998;97:2154–2159.
  65. Shepard JW, Garison MW, Grither DA, et al: Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea. Chest 1985;88:335–340.
  66. Becker H, Brandenburg U, Peter JH, et al: Reversal of sinus arrest and atrioventricular conduction block in patients with sinus arrest during nasal continuous positive airway pressure. Am J Respir Crit Care Med 1995;151:215–218.
  67. Koehler U, Fus E, Grimm W, et al: Heart block in patients with obstructive sleep apnoea: pathogenic factors and effects of treatment. Eur Respir J 1998;11:434–439.
  68. Gillis AM, Stoohs R, Guilleminault C, et al: Changes in QT interval during obstructive sleep apnea. Sleep 1991;14:346–350.
  69. Javaheri S: Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation 2000;101:392.
  70. Garrigue S, Bordier P, Jais P, et al: Benefit of atrial pacing in sleep apnea syndrome. N Engl J Med 2002;346:404–412.
  71. Alchanatis M, Tourkohoriti G, Kosmas EN, et al: Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 2002;20:1239–1245.
  72. Cloward TV, Walker JM, Farney RJ, Anderson JL: Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure. Chest 2003;124:594–601.
  73. Laaban JP, Pascal-Sebaoun S, Bloch E, et al: Left ventricular systolic dysfunction in patients with obstructive sleep apnea syndrome. Chest 2002;122:1133–1138.
  74. Fung JW, Li TS, Choy DK, Yip GW, et al: Severe obstructive sleep apnea is associated with left ventricular diastolic dysfunction. Chest 2002;121:422–429.
  75. Tkacova R, Niroumand M, Lorenzi-Filho G, et al: Overnight shift from obstructive to central sleep apneas in patients with ventilatory failure: role of pCO2 and respiratory delay. Circulation 2001;103:238–243.
  76. Weitzenblum E, Krieger J, Apprill, et al: Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 1988;138:345–349.
  77. Chaouat A, Weitzenblum E, Krieger J, et al: Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest 1996;109:380–386.
  78. Sanner BM, Doberauer C, Konermann M, et al: Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med 1997;157:2483–2487.
  79. Sajkov D, Cowie RJ, Thornton AT, et al: Pulmonary hypertension and hypoxemia in obstructive sleep apnea. Am J Respir Crit Care Med 1994;149:416–422.
  80. Bady E, Achkar A, Pascal S, et al: Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax 2000;55:934–939.
  81. Atwood SW, McCrory D, Garcia JG, et al: Pulmonary artery hypertension and sleep-disordered breathing. Chest 2004;126:72S–77S.

    External Resources

  82. Gozal D, Lipton AJ, Jones KL, et al: Circulating vascular endothelial growth factor levels in patients with obstructive sleep apnea. Sleep 2002;25:59–65.
  83. Lavie L, Kraiczi H, Hefetz A, et al: Plasma vascular endothelial growth factor in obstructive sleep apnea syndrome: effects of nasal continuous positive airway pressure treatment. Am J Respir Crit Care Med 2002;165:1624–1628.
  84. Alchanatis M, Tourkohoriti G, Kakouros S, et al: Daytime hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics. Respiration 2001;68:566–572.
  85. Sajkov D, Wang T, Saunders NA, et al: Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2002;165:152–158.
  86. Sanner BM, Konermann M, Sturm A, et al: Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 1997;10:2079–2083.
  87. Berman EJ, DiBenedetto RJ, Causey DE, et al: Right ventricular hypertrophy detected by echocardiography in patients with newly diagnosed obstructive sleep apnea. Chest 1991;100:347–350.
  88. Nahmias J, Lao R, Karetzky M, et al: Right ventricular dysfunction in obstructive sleep apnoea: reversal with nasal continuous positive airway pressure. Eur Respir J 1996;9:945–951.

 goto top of outline Author Contacts

H. Erhan Dincer, MD, FCCP
VA Southern Nevada Health Care System, PO Box 360001
North Las Vegas, NV 89036 (USA)
Tel. +1 702 636 6355, Fax +1 702 636 4008
E-Mail Huseyin.Dincer@med.va.gov or erhan_dincer@yahoo.com


 goto top of outline Article Information

H. Erhan Dincer, MD, FCCP, VA Southern Nevada Health Care System, PO Box 360001, North Las Vegas, NV 89036 (USA) or H. Erhan Dincer, MD, FCCP, 630 S Rancho Road, Las Vegas, NV 89106 (USA), (only for courier mails), Tel. +1 702 6366355, Fax +1 702 6364008, E-Mail: Huseyin.Dincer@med.va.gov or erhan_dincer@yahoo.com

Received: April 25, 2005
Accepted after revision: August 23, 2005
Published online: November 15, 2005
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 0, Number of References : 88


 goto top of outline Publication Details

Respiration (International Journal of Thoracic Medicine)

Vol. 73, No. 1, Year 2006 (Cover Date: February 2006)

Journal Editor: Bolliger, C.T. (Cape Town)
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/RES


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