Abstract
Obstructive sleep apnea (OSA) is characterized by repetitive apnea–hypopnea cycles during sleep, which are associated with oxygen desaturation and sleep disruption. Up to 30% of the adult population in Western countries are thought to be affected by asymptomatic OSA and approximately 2–4% by symptomatic OSA (also known as obstructive sleep apnea syndrome, or OSAS). Controlled trials have demonstrated that OSAS causes hypertension and prospective epidemiological studies have indicated that OSAS might be an independent risk factor for stroke and myocardial ischemia. Three biological mechanisms are thought to underpin the association of OSA with endothelial dysfunction and arterial disease: intermittent hypoxia leading to increased oxidative stress, systemic inflammation, and sympathetic activity; intrathoracic pressure changes leading to excessive mechanical stress on the heart and large artery walls; and arousal-induced reflex sympathetic activation with resultant repetitive blood-pressure rises. More clinical interventional trials are needed to determine the magnitude of the effect OSA has on cardiovascular damage and to enable a comparison with conventional vascular risk factors.
Key Points
-
The main acute physiological consequences of obstructive sleep apnea (OSA) are intermittent hypoxia, intrathoracic pressure changes, and arousals
-
All three acute physiological consequences of OSA trigger consecutive mechanisms that might result in endothelial dysfunction and arterial disease
-
Continuous positive airway pressure treatment is the standard therapy for patients with symptomatic OSA and has been associated with improvements in vascular abnormalities
-
Alternative treatments are needed for nonsleepy patients with OSA, who are less likely to agree to continuous positive airway pressure treatment; these therapies should target the known mechanisms of vascular damage
-
OSA is independently associated with arterial hypertension
-
Whether OSA is also independently associated with cardiovascular events is currently under investigation in large, multicenter, international interventional trials
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stradling, J. R. & Crosby, J. H. Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. Thorax 46, 85–90 (1991).
Young, T., Evans, L., Finn, L. & Palta, M. Estimation of the clinicallcy diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep 20, 705–706 (1997).
Jenkinson, C., Davies, R. J., Mullins, R. & Stradling, J. R. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 353, 2100–2105 (1999).
Haentjens, P. et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch. Intern. Med. 167, 757–764 (2007).
Marin, J. M., Carrizo, S. J., Vicente, E. & Agusti, A. G. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365, 1046–1053 (2005).
Monahan, K. et al. Triggering of nocturnal arrhythmias by sleep-disordered breathing events. J. Am. Coll. Cardiol. 54, 1797–1804 (2009).
Redline, S. et al. Obstructive sleep apnea-hypopnea and incident stroke. Am. J. Respir. Crit. Care Med. 182, 269–277 (2010).
Gottlieb, D. J. et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure. Circulation 122, 352–360 (2010).
Punjabi, N. M. et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLOS Med. 6, e1000132 (2009).
Narkiewicz, K. et al. Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea. Circulation 100, 2332–2335 (1999).
Kohler, M. et al. CPAP and measures of cardiovascular risk in males with OSAS. Eur. Respir. J. 32, 1488–1496 (2008).
Foster, G. E. et al. Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans. J. Physiol. 587, 5303–5304 (2009).
Peters, J., Kindred, M. K. & Robotham, J. L. Transient analysis of cardiopulmonary interactions: II: systolic events. J. Appl. Physiol. 64, 1518–1526 (1988).
Levy, P., Bonsignore, M. R. & Eckel, J. Sleep, sleep-disordered breathing and metabolic consequences. Eur. Respir. J. 34, 243–260 (2009).
Von Kanel, R. & Dimsdale, J. E. Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 124, 1956–1967 (2003).
Lavie, L. & Lavie, P. Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur. Respir. J. 33, 1467–1484 (2009).
Garvey, J. F., Taylor, C. T. & McNicholas, W. T. Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur. Respir. J. 33, 1195–1205 (2009).
Kanagy, N. L., Walker, B. R. & Nelin, L. D. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension 37, 511–515 (2001).
Lesske, J., Fletcher, E. C., Bao, G. & Unger, T. Hypertension caused by chronic intermittent hypoxia - influence of chemoreceptors and sympathetic nervous system. J. Hypertens. 15, 1593–1603 (1997).
Peng, Y., Yuan, G., Overholt, J. L., Kumar, G. K. & Prabhakar, N. R. Systemic and cellular responses to intermittent hypoxia: evidence for oxidative stress and mitochondrial dysfunction. Adv. Exp. Med. Biol. 536, 559–564 (2003).
Xu, W. et al. Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience 126, 313–323 (2004).
Zhan, G. et al. NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am. J. Respir. Crit. Care Med. 172, 921–929 (2005).
Li, J., Savransky, V., Nanayakkara, A., Smith, P. L., O'Donnell, C. P. & Polotsky, V. Y. Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J. Appl. Physiol. 102, 557–563 (2007).
Pialoux, V. et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am. J. Respir. Crit. Care Med. 180, 1002–1009 (2009).
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. 165, 934–939 (2002).
Schulz, R. et al. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 162, 566–570 (2000).
Jelic, S. et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117, 2270–2278 (2008).
Barcelo, A., Miralles, C., Barbe, F., Vila, M., Pons, S. & Agusti, A. G. Abnormal lipid peroxidation in patients with sleep apnoea. Eur. Respir. J. 16, 644–647 (2000).
Lavie, L., Vishnevsky, A. & Lavie, P. Evidence for lipid peroxidation in obstructive sleep apnea. Sleep 27, 123–128 (2004).
Wali, S. O. et al. Susceptibility of LDL to oxidative stress in obstructive sleep apnea. Sleep 21, 290–296 (1998).
Svatikova, A. et al. Oxidative stress in obstructive sleep apnoea. Eur. Heart J. 26, 2435–2439 (2005).
Alonso-Fernandez, A. et al. Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial. Thorax 64, 581–586 (2009).
El Solh, A. A., Saliba, R., Bosinski, T., Grant, B. J., Berbary, E. & Miller, N. Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study. Eur. Respir. J. 27, 997–1002 (2006).
Ryan, S., Taylor, C. T. & McNicholas, W. T. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112, 2660–2667 (2005).
Greenberg, H., Ye, X., Wilson, D., Htoo, A. K., Hendersen, T. & Liu, S. F. Chronic intermittent hypoxia activates nuclear factor-kappaB in cardiovascular tissues in vivo. Biochem. Biophys. Res. Commun. 343, 591–596 (2006).
Ryan, S., Taylor, C. T. & McNicholas, W. T. Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am. J. Respir. Crit. Care Med. 174, 824–830 (2006).
Minoguchi, K. et al. Elevated production of tumor necrosis factor-{alpha} by monocytes in patients with obstrcutive sleep apnea syndrome. Chest 126, 1473–1479 (2004).
Yokoe, T. et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107, 1129–1134 (2003).
Minoguchi, K. et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 172, 625–630 (2005).
Shamsuzzaman, A. S. et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105, 2462–2464 (2002).
Can, M. et al. Serum cardiovascular risk factors in obstructive sleep apnea. Chest 129, 233–237 (2006).
Phillips, C. L. et al. The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea. J. Sleep Res. 16, 217–225 (2007).
Taheri, S. Austin, D., Lin, L., Nieto, F. J., Young, T. & Mignot, E. Correlates of serum C-reactive protein (CRP) - no association with sleep duration or sleep disordered breathing. Sleep 30, 991–996 (2007).
Barcelo, A. et al. Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am. J. Med. 117, 118–121 (2004).
Kohler, M. et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax 64, 67–73 (2009).
West, S. D., Nicoll, D. J., Wallace, T. M., Matthews, D. R. & Stradling, J. R. The effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax 62, 969–974 (2007).
Drager, L. F., Bortolotto, L. A., Figueiredo, A. C., Krieger, E. M. & Lorenzi-Filho, G. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 176, 706–712 (2007).
Marasciulo, F. L., Montagnani, M. & Potenza, M. A. Endothelin-1: the yin and yang on vascular function. Curr. Med. Chem. 13, 1655–1665 (2006).
Allahdadi, K. J., Walker, B. R. & Kanagy, N. L. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension 45, 705–709 (2005).
Phillips, B. G., Narkiewicz, K., Pesek, C. A., Haynes, W. G., Dyken, M. E. & Somers, V. K. Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J. Hypertens. 17, 61–66 (1999).
Gjorup, P. H., Sadauskiene, L., Wessels, J., Nyvad, O., Strunge, B. & Pedersen, E. B. Abnormally increased endothelin-1 in plasma during the night in obstructive sleep apnea: relation to blood pressure and severity of disease. Am. J. Hypertens. 20, 44–52 (2007).
Grimpen, F., Kanne, P., Schulz, E., Hagenah, G., Hasenfuss, G. & Andreas, S. Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea. Eur. Respir. J. 15, 320–325 (2000).
Jordan, W. et al. Obstructive sleep apnea: plasma endothelin-1 precursor but not endothelin-1 levels are elevated and decline with nasal continuous positive airway pressure. Peptides 26, 1654–1660 (2005).
Fletcher, E. C., Bao, G. & Li, R. Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension 34, 309–314 (1999).
Fletcher, E. C, Orolinova, N. & Bader, M. Blood pressure response to chronic episodic hypoxia: the renin-angiotensin system. J. Appl. Physiol. 92, 627–633 (2002).
Kraiczi, H., Hedner, J., Peker, Y. & Carlson, J. Increased vasoconstrictor sensitivity in obstructive sleep apnea. J. Appl. Physiol. 89, 493–498 (2000).
Moller, D. S., Lind, P., Strunge, B. & Pedersen, E. B. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am. J. Hypertens. 16, 274–280 (2003).
Svatikova, A. et al. Obstructive sleep apnea and aldosterone. Sleep 32, 1589–1592 (2009).
Issa, F. G. & Sullivan, C. E. Upper airway closing pressures in snorers. J. Appl. Physiol. 57, 528–535 (1984).
Ali, N. J., Davies, R. J. O., Fleetham, J. A. & Stradling, J. R. The acute effects of continuous positive airway pressure and oxygen administration on blood pressure during obstructive sleep apnea. Chest 101, 1526–1532 (1992).
Peters, J., Kindred, M. K. & Robotham, J. L. Transient analysis of cardiopulmonary interactions: I: diastolic events. J. Appl. Physiol. 64, 1506–1517 (1988).
Magder, S. A., Lichtenstein, S. & Adelman, A. G. Effects of negative pleural pressure on left ventricular hemodynamics. Am. J. Cardiol. 52, 588–593 (1983).
Kohler, M. et al. The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan's syndrome. Thorax 64, 162–166 (2009).
Sampol, G. et al. Obstructive sleep apnea and thoracic aorta dissection. Am. J. Respir. Crit. Care Med. 168, 1528–1531 (2003).
Serizawa, N. et al. Obstructive sleep apnea is associated with greater thoracic aortic size. J. Am. Coll. Cardiol. 52, 885–886 (2008).
Somers, V. K., Mark, A. L., Zavala, D. C. & Abboud, F. M. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J. Appl. Physiol. 67, 2101–2106 (1989).
Rothwell, P. M. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet 375, 938–948 (2010).
Rothwell, P. M. et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet 375, 895–905 (2010).
Bonsignore, M. R. et al. Continuous positive airway pressure treatment improves baroreflex control of heart rate during sleep in severe obstructive sleep apnea syndrome. Am. J. Respir. Crit. Care Med. 166, 279–286 (2002).
Marrone, O., Riccobono, L., Salvaggio, A., Mirabella, A., Bonanno, A. & Bonsignore, M. R. Catecholamines and blood pressure in obstructive sleep apnea syndrome. Chest 103, 722–727 (1993).
Dematteis, M. et al. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am. J. Respir. Crit. Care Med. 177, 227–235 (2008).
La Rovere, M. T., Bigger, J. T., Marcus, F. I., Mortara, A. & Schwartz, P. J. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351, 478–484 (1998).
Prabhakar, N. R., Kumar, G. K. & Nanduri, J. Intermittent hypoxia-mediated plasticity of acute O2 sensing requires altered red-ox regulation by HIF-1 and HIF-2. Ann. N. Y. Acad. Sci. 1177, 162–168 (2009).
Rey, S., Del Rio, R., Alcayaga, J. & Iturriaga, R. Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia. J. Physiol. 560, 577–586 (2004).
Horner, R. L., Brooks, D., Kozar, L. F., Tse, S. & Phillipson, E. A. Immediate effects of arousal from sleep on cardiac autonomic outflow in the absence of breathing in dogs. J. Appl. Physiol. 79, 151–162 (1995).
Somers, V. K., Dyken, M. E., Mark, A. L. & Abboud, F. M. Sympathetic-nerve activity during sleep in normal subjects. N. Engl. J. Med. 328, 303–307 (1993).
Somers, V. K., Dyken, M. E. & Skinner, J. L. Autonomic and hemodynamic responses and interactions during the Mueller maneuver in humans. J. Autonom. Nerv. Sys. 44, 253–259 (1993).
Somers, V. K., Dyken, M. E., Clary, M. P. & Abboud, F. M. Sympathetic neural mechanisms in obstructive sleep apnea. J. Clin. Invest. 96, 1897–1904 (1995).
Fletcher, E. C., Miller, J., Schaaf, J. W. & Fletcher, J. G. Urinary catecholamines before and after tracheostomy in patients with obstructive sleep apnea and hypertension. Sleep 10, 35–44 (1987).
Eisenberg, E., Zimlichman, R. & Lavie, P. Plasma norepinephrine levels in patients with sleep apnea syndrome. N. Engl. J. Med. 322, 932–933 (1990).
Ziegler, M. G., Mills, P. J., Loredo, J. S., Ancoli-Israel, S. & Dimsdale, J. E. Effect of continuus positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea. Chest 120, 887–893 (2001).
Mills, P. J., Kennedy, B. P., Loredo, J. S., Dimsdale, J. E. & Ziegler, M. G. Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J. Appl. Physiol. 100, 343–348 (2006).
Norman, D. et al. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension 47, 840–845 (2006).
Bonsignore, M. R. et al. Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP. Eur. Respir. J. 27, 128–135 (2006).
Noda, A. et al. Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome. Hypertens. Res. 30, 669–676 (2007).
Carlson, J., Rangemark, C. & Hedner, J. Attenuated endothelium-dependent vascular relaxation in patients with sleep apnea. J. Hypertens. 14, 577–584 (1996).
Kato, M. et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102, 2607–2610 (2000).
Ip, M. S. M. et al. Circulating nitric oxide is suppressed in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 162, 2166–2171 (2000).
El Solh, A. A., Akinnusi, M. E., Baddoura, F. H. & Mankowski, C. R. Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. Am. J. Respir. Crit. Care Med. 175, 1186–1191 (2007).
Ip, M. S. M., Tse, H. F., Lam, B., Tsang, K. W. T. & Lam, W. K. Endothelial function in obstructive sleep apnea and response to treatment. Am. J. Respir. Crit. Care Med. 169, 348–353 (2004).
Cross, M. D. et al. Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial. Thorax 63, 578–583 (2008).
Knepler, J. L. Jr et al. Peroxynitrite causes endothelial cell monolayer barrier dysfunction. Am. J. Physiol. Cell Physiol. 281, C1064–C1075 (2001).
Jelic, S. et al. Vascular inflammation in obesity and sleep apnea. Circulation 121, 1014–1021 (2010).
Takase, B. et al. Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans. Clin. Cardiol. 27, 223–227 (2004).
Kohler, M., Craig, S., Nicoll, D., Leeson, P., Davies, R. J. O. & Stradling, J. R. Endothelial function and arterial stiffness in minimally symptomatic obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 178, 984–988 (2008).
Pepperell, J. C. T. et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 359, 204–210 (2002).
Becker, C., Jerrentrup, A., Ploch, T., Grote, L., Penzel, T. & Sullivan, C. Effect of nasal continuous positive airway pressure treatment on BP in patients with obstructive sleep apnoea. Circulation 107, 68–73 (2003).
Peppard, P. E., Young, T., Palta, M. & Skatrud, J. Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl. J. Med. 342, 1378–1384 (2000).
Buchner, N. J., Sanner, B. M., Borgel, J. & Rump, L. C. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am. J. Respir. Crit. Care Med. 176, 1274–1280 (2007).
McArdle, N., Devereux, G., Heidarnejad, H., Engleman, H. M., Mackay, T. W. & Douglas, N. J. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am. J. Respir. Crit. Care Med. 159, 1108–1114 (1999).
Kohler, M., Smith, D., Tippett, V. & Stradling, J. R. Predictors of long-term compliance with continuous positive airway pressure. Thorax 65, 829–832 (2010).
Bloch, K. E. et al. A randomized, controlled crossover trial of two oral appliances for sleep apnea treatment. Am. J. Respir. Crit. Care Med. 162, 246–251 (2000).
Gotsopoulos, H., Kelly, J. J. & Cistulli, P. A. Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial. Sleep 27, 934–941 (2004).
Itzhaki, S., Dorchin, H., Clark, G., Lavie, L., Lavie, P. & Pillar, G. The effects of 1-year treatment with a Herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. Chest 131, 740–749 (2007).
Young, T., Skatrud, J. & Peppard, P. E. Risk factors for obstructive sleep apnoea in adults. JAMA 291, 2013–2016 (2004).
Tuomilehto, H. P. et al. Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 179, 320–327 (2009).
Johansson, K. et al. Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial. Br. Med. J. 339, b4609 (2009).
Kohler, M., Bloch, K. E. & Stradling, J. R. Pharmacological approaches to the treatment of obstructive sleep apnoea. Expert Opin. Investig. Drugs 18, 647–656 (2009).
Aittokallio, J. et al. Overnight variability in transcutaneous carbon dioxide predicts vascular impairment in women. Exp. Physiol. 93, 880–891 (2008).
Lee, S. A. et al. Heavy snoring as a cause of carotid artery atherosclerosis. Sleep 31, 1207–1213 (2008).
Young, T. et al. Predictors of sleep-disordered breathing in community-dwelling adults. Arch. Intern. Med. 162, 893–900 (2002).
Kapur, V. K., Resnick, H. E. & Gottlieb, D. J. Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association? Sleep 31, 1127–1132 (2008).
Barbe, F. et al. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness: a randomized, controlled trial. Arch. Intern. Med. 134, 1015–1023 (2001).
Robinson, G. V., Smith, D. M., Langford, B. A., Davies, R. J. & Stradling, J. R. Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients. Eur. Respir. J. 27, 1229–1235 (2006).
Barbe, F. et al. Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea. Am. J. Respir. Crit. Care Med. 181, 718–726 (2010).
Protocol 06PRT/2675: Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular Trial (MOSAIC) (ISRCTN34164388). TheLancet.com [online], (2010).
Calvin, A. D. & Somers, V. K. Obstructive sleep apnea and risk of stroke: time for a trial. Nat. Clin. Pract. Cardiovasc. Med. 6, 90–91 (2009).
Sleep Apnea Cardiovascular Endpoints Study (SAVE) [online], (2010).
Author information
Authors and Affiliations
Contributions
M. Kohler and J. R. Stradling contributed to discussion of content for the article, researched data to include in the manuscript, wrote, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.
Corresponding author
Ethics declarations
Competing interests
J. R. Stradling was supported by an unrestricted charitable donation from ResMed UK in 2006 and 2008 for research work in the Oxford Sleep Unit. M. Kohler declares no competing interests.
Rights and permissions
About this article
Cite this article
Kohler, M., Stradling, J. Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol 7, 677–685 (2010). https://doi.org/10.1038/nrcardio.2010.145
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrcardio.2010.145
This article is cited by
-
Effect of mandibular advancement splint therapy on cardiac autonomic function in obstructive sleep apnoea
Sleep and Breathing (2024)
-
The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury
Sleep and Breathing (2024)
-
The association between blood pressure control and long-term cardiovascular outcomes in Hypertension coexistent with obstructive sleep apnea
BMC Cardiovascular Disorders (2023)
-
Impact of site, size and severity of ischemic cerebrovascular stroke on sleep in a sample of Egyptian patients a polysomnographic study
BMC Neurology (2023)
-
Obstructive sleep apnoea heterogeneity and cardiovascular disease
Nature Reviews Cardiology (2023)