Cardiovascular Consequences of Obstructive Sleep Apnea
Gerald Hurowitz, M.D.·Published 16 May 2010·10 min read
Key points
As our understanding of the prevalence and pathophysiology of obstructive sleep apnea (OSA) expands, so does the list of adverse consequences imposed by this disease on both health and quality of life.
Episodes of sleep-disordered breathing cause pathologic vascular changes and dysfunction, both of which can cause and contribute to cardiovascular disease, independent of confounding factors.
The causal link between OSA and systemic hypertension has been clearly established.
OSA results in hemodynamic derangements and dysfunction of the pulmonary vasculature and may contribute to the progression of underlying pulmonary hypertension.
Does Obstructive Sleep Apnea Cause Cardiovascular Disease?
As our understanding of the prevalence and pathophysiology of obstructive sleep apnea (OSA) expands, so does the list of adverse consequences imposed by this disease on both health and quality of life. Of note, OSA has been identified as a significant cause of and/or contributor to cardiovascular disease.
OSA has been shown to increase the risk for hypertension, pulmonary vascular disease, ischemic heart disease, cerebral vascular accidents, congestive heart failure, and arrhythmias, independent of confounding or concomitant risk factors.[1-13] However, despite the growing body of evidence that links OSA to the development of cardiovascular disease, the true causal relationship remains controversial. Many risk factors for OSA are also known risk factors for cardiovascular disease, such as age, male gender, and obesity. In addition, OSA is associated with numerous conditions that are known to increase the risk for cardiac disease, such as diabetes mellitus and hypertension. Therefore, it is difficult to prove whether OSA independently causes cardiovascular disease.
Pathophysiology of Sleep-Disordered Breathing
Episodes of sleep-disordered breathing cause pathologic vascular changes and dysfunction, both of which can cause and contribute to cardiovascular disease, independent of confounding factors. The adverse effects that OSA imposes on cardiovascular function are thought to arise from several overlapping mechanisms. Apneic events, intermittent hypoxia, and the resulting arousals result in an increased sympathetic tone and endothelial dysfunction. This recurrent cycle of events ultimately leads to vasoconstriction and vascular remodeling, which in turn leads to the development of vascular and cardiac dysfunction.
Recurrent arousals resulting from episodic apneic episodes cause repetitive catecholamine surges and a marked increase in sympathetic tone. The increase in vascular sympathetic nerve activity and circulating catecholamines subsequently lead to increased peripheral vascular resistance, episodic elevations in nocturnal blood pressure, and propagation of atherosclerosis. Daytime hypertension develops secondary to the persistently elevated sympathetic state.[14] Intermittent hypoxia that follows these apneic events can further add to vascular dysfunction.[5,15] Hypoxic vasoconstriction and hypoxia-reperfusion oxidative stresses lead to vascular remodeling and the release of pro-inflammatory mediators such as cyclooxygenase-2, tissue necrosis factor-alpha, and interleukins, which ultimately cause vascular endothelium dysfunction and the development of arterial noncompliance.[16,17]
Hypertension
The causal link between OSA and systemic hypertension has been clearly established. Several studies have shown that sleep apnea increases the relative risk for hypertension, independent of other confounding factors.[1-4] In a cross-sectional analysis of more than 6000 patients, the Sleep Heart Health Study showed a linear relationship between mean systolic and diastolic blood pressures and OSA severity.[1] Likewise, the prevalence of hypertension linearly increased with the presence and severity of OSA.[1,2] A large Canadian population-based study found that each apneic event per hour increased the odds of hypertension by 1%, and each 10% reduction in nocturnal oxygen saturation increased the likelihood of hypertension developing by 13%.[2]
Written and revised by
Gerald Hurowitz, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
Approximately 50% of patients with OSA have hypertension, compared with only 30% of the general public. Because of the strength of evidence linking OSA with the development of hypertension, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VII) now lists sleep apnea as a significant cause of secondary hypertension.[3]
{pagebreak}
Pulmonary Hypertension
OSA results in hemodynamic derangements and dysfunction of the pulmonary vasculature and may contribute to the progression of underlying pulmonary hypertension. The 2004 American College of Chest Physicians (ACCP) consensus panel found that pulmonary hypertension occurred in 17% to 53% of individuals with OSA, and a review from Johns Hopkins found that 82% of patients with pulmonary hypertension had underlying sleep-disordered breathing.[4] The nocturnal desaturation, hypoxic-vasoconstriction, reperfusion injuries, ventilatory instability, impaired nitric oxide synthesis, endothelial dysfunction, and vascular remodeling that result from repetitive obstructive respiratory events can lead to the development of pulmonary vascular disease. However, whether OSA independently causes clinically significant pulmonary hypertension remains controversial. Thus, the current ACCP guidelines do not recommend evaluating patients with OSA for pulmonary hypertension unless it is clinically suspected.
Ischemic Heart Disease
Because of overlapping risk factors, the true association between OSA and coronary artery disease (CAD) remains difficult to prove, especially in the presence of mild disease. However, more substantial evidence links CAD with moderate-to-severe OSA. Several studies have suggested that the prevalence of CAD is 3 to 5 times higher in patients with OSA compared with control populations.[7,18] More importantly, long-term observational studies found that severe OSA significantly increases the risk for both fatal and nonfatal cardiovascular events.[6,19] OSA may be an independent risk factor for CAD. OSA causes or contributes to hypertension, arterial noncompliance, atherosclerosis, and glucose intolerance. Moreover, OSA produces carotid arterial wall thickness in a dose-response manner, which has been shown to be a marker of cardiovascular disease and a predictor of morbidity and mortality[18] Similarly, among patients with known CAD, the respiratory disturbance index was the only independent predictor of mortality in a 5-year study.[20] Ablation of obstructive respiratory events during sleep by continuous positive airway pressure (CPAP) has been shown to decrease the risk for cardiovascular events and prevent the development of new ischemic heart disease.[20] Given the growing body of evidence, it appears that OSA is an independent contributor to ischemic heart disease. The treatment of OSA should mitigate this increased risk; however, the true effects on cardiovascular morbidity and mortality remain controversial.
Heart Failure
Underlying sleep-disordered breathing is highly prevalent among patients with heart failure, and obstructive respiratory events are common in individuals with systolic and diastolic dysfunction.[8-10] Numerous risk factors for OSA and heart failure overlap, as they do between OSA and CAD. The role of sleep-disordered breathing in the development of left ventricular dysfunction is not well-defined. However, a prospective study of patients with left ventricular failure found concurrent sleep apnea in 50% of patients.[8] Furthermore, CPAP has been shown to be effective in patients with heart failure, regardless of the presence of underlying OSA. Randomized controlled trials have shown that treatment of OSA with CPAP is associated with significant improvements in cardiac function, sympathetic activity, and quality of life.[9,10] Similarly, patients with severe OSA experience a reduction in left ventricular hypertrophy after 6 months of CPAP therapy.[10] In the Canadian Positive Airway Pressure study, CPAP improved nocturnal oxygenation, increased left ventricular function, lowered norepinephrine levels, and improved functional capacity among patients with central sleep apnea and heart failure.[21] Unfortunately, CPAP therapy did not improve survival. Given the increasing awareness of this association, it is prudent to assess for OSA in individuals diagnosed with heart failure, because treatment of the underlying sleep-disordered breathing may improve cardiac function and quality of life.
{pagebreak}
Arrhythmias
Cardiac arrhythmias, especially tachy-brady syndrome, ventricular ectopy, and atrial fibrillation are commonly identified in patients with OSA.[11-13] The Sleep Heart Health Study noted that patients with sleep-disordered breathing have a higher likelihood of having complex arrhythmias compared with control patients.[12] Specifically, these patients had a fourfold increase in atrial fibrillation, a threefold increase in nonsustained ventricular tachycardia, and a twofold increase in complex ventricular ectopy.[12] These rhythm disturbances likely correlate with nocturnal hypoxia, sleep fragmentation, and elevated sympathetic tone. Treatment of OSA in patients with known congestive heart failure has been shown to reduce the frequency of premature beats, which in turn may decrease the morbidity of ventricular arrhythmias.[22] In addition, CPAP therapy has been shown to reduce the rate of arrhythmias even after controlling for heart failure and other independent variables.[13]
Final Perspective and Clinical Recommendations
Regardless of whether a true causal relationship can be proven, it is known that cardiovascular disease is common among patients with OSA and is associated with worse outcomes. It appears that OSA likely causes, or at least potentiates, cardiovascular disease. Although OSA clearly affects quality of life, the growing evidence that it also affects cardiovascular health should further compel clinicians to evaluate patients with OSA for these potential consequences and at least consider underlying sleep-disordered breathing in patients with known cardiovascular diseases.
Recommendations for Practitioners Managing Patients With OSA
* OSA increases the risk for cardiovascular disease. Patients with OSA should be regularly screened for these potential complications; * Given the common association of these disorders, patients with cardiovascular disease should be screened for OSA and patients with OSA should be monitored for the development of cardiovascular sequelae, particularly hypertension; * OSA is one of the most significant causes of secondary hypertension, which occurs in half of all patients with sleep apnea; * Ischemic heart disease is significantly more common in patients with OSA and may increase the risk for both fatal and nonfatal cardiovascular events; * Patients with heart failure should be assessed for OSA because treatment of the underlying sleep-disordered breathing may improve both cardiac function and quality of life; * OSA is commonly associated with atrial fibrillation, and untreated OSA may impair the success of cardioversion; and * Treatment of OSA improves quality of life and may reduce the development or progression of cardiovascular complications. Practitioners must stress the importance of therapeutic adherence.
-- Christopher J. Lettieri, MD
Associate Professor of Medicine, Uniformed Services University, Bethesda, Maryland; Staff Physician, Pulmonary, Critical Care and Sleep Medicine, Walter Reed Army Medical Center, Washington, DC
Disclosure: Christopher Lettieri, MD, has disclosed the following financial relationships: Received grants for clinical research from: Sepracor Inc. Served as a speaker or member of the speakers bureau for: Cephalon, Inc.
References
1. 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. 2. Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ. 2000;320:479-482. 3. US Department of Health and Human Services. The National Heart, Lung, and Blood Institute: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 2003. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension/ Accessed April 27, 2010. 4. Krishnan V, Hassaun P, Hummers L, Collop NA. Sleep disordered breathing and pulmonary hypertension. Sleep. 2005;20:A300. 5. Peker Y, Kraiczi H, Hedner J, Lo"th S, Johansson A, Bende M. An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J.1999;14:179-184. 6. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046-1053. 7. Peker Y, Hedner J, Kraiczi H, Loth S. Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. Am J Respir Crit Care Med. 2000;162:81-86. 8. Javaheri S. Sleep disorders in systolic heart failure: a prospective study of 100 male patients. Int J Cardiol. 2006;106:21-28. 9. Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med. 2004;169:361-366. 10. 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. 11. Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and conduction disturbances during sleep in patients with sleep apnea syndrome. Am J Cardiol. 1983;52:490-494. 12. Mehra R, Benjamin EJ, Shahar E, et al. Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2006;173:910-916. 13. Harbison J, O'Reilly P, McNicholas WT. Cardiac rhythm disturbances in the obstructive sleep apnea syndrome, effects of nasal continuous positive airway pressure therapy. Chest. 2000;118:591-595. 14. Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand. 2003;177:385-390. 15. Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913. 16. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated c-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105:2462-2464. 17. Yamauchi M, Nakano H, Maekawa J, et al. Oxidative stress in obstructive sleep apnea. Chest. 2005;127:1674-1679. 18. Unruh ML, Enright PL, Polak JF, et al. The relationship of sleep apnea to carotid wall thickness among a large cohort of older adults. Sleep. 2005;20:A112. 19. Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913. 20. Doherty LS, Kiely JL, Swan V, McNicholas WT. Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest. 2005;127:2076-2084. 21. Bradley TD, Logan AG, Kimoff RJ. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med. 2005;353:2025-2033. 22. Ryan CM, Usui K, Floras JS, Bradley TD. Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea. Thorax. 2005;60:781-785.
News
News
News
