Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure

Obstructive sleep apnea (OSA) is associated with recurrent episodes of nocturnal hypoxia and increased risk for development of systemic hypertension. Prior studies have been limited, however, in their ability to show reduction in blood pressure after continuous positive airway pressure (CPAP) therapy, and the effect of supplemental oxygen alone on blood pressure in OSA has not been evaluated. We performed a randomized, double-blind, placebo-controlled study comparing the effects of 2 weeks of CPAP versus sham-CPAP versus supplemental nocturnal oxygen on 24-hour ambulatory blood pressure in 46 patients with moderate-severe OSA. We found that 2 weeks of CPAP therapy resulted in a significant reduction in daytime mean arterial and diastolic blood pressure and nighttime systolic, mean, and diastolic blood pressure (all Ps <0.05). Although nocturnal supplemental oxygen therapy improved oxyhemoglobin saturation, it did not affect blood pressure. We conclude that CPAP therapy reduces both daytime and nighttime blood pressure in patients with OSA, perhaps through mechanisms other than improvement of nocturnal oxyhemoglobin saturation.     

Obstructive sleep apnea and hypertension: Mechanisms,evaluation, and management

Obstructive sleep apnea (OSA) is a recognized cause of secondary hypertension. OSA episodes produce surges in systolic and diastolic pressure that keep mean blood pressure levels elevated at night. In many patients, blood pressure remains elevated during the daytime, when breathing is normal. Contributors to this diurnal pattern of hypertension include sympathetic nervous system overactivity and alterations in vascular function and structure caused by oxidant stress and inflammation. Treatment of OSA with nasal continuous positive airway pressure (CPAP) abolishes apneas, thereby preventing intermittent arterial pressure surges and restoring the nocturnal “dipping” pattern. CPAP treatment also has modest beneficial effects on daytime blood pressure. Because even small decreases in arterial pressure can contribute to reducing cardiovascular risk, screening for OSA is an essential element of evaluating patients with hypertension.     

Are sleep-related breathing disorders important contributing factors to the production of essential hypertension?

About 50% of all patients with essential hypertension have obstructive sleep apnea (OSA), and another 40% of essential hypertension patients are habitual snorers, but without OSA. There is now convincing evidence that both OSA and habitual snoring are independent risk factors for essential hypertension, and that treatment of OSA will reduce the blood pressure. There is also some evidence that treatment of habitual snoring will also reduce the blood pressure. If this is the case, then we postulate a unifying hypothesis: that these two sleep-related breathing disorders (SRBD) (OSA and habitual snoring) are very common contributing factors to what is called "essential hypertension." The many epidemiologic, clinical, hematologic, biochemical, and physiologic findings seen in essential hypertension could also be due to the associated SRBD. A routine search for SRBD by asking a few simple questions of all patients (especially those with hypertension) and their bed partners could increase the number of patients detected and treated significantly. Successful treatment of SRBD would improve sleep quality and the associated excessive daytime sleepiness, and thus improve the quality of life. In addition, there is a good chance that the hypertension will improve as well.     

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.     

Sympathetic activity is reduced by nCPAP in hypertensive obstructive sleep apnoea patients.

There is increasing evidence that nasal continuous positive airway pressure (nCPAP) lowers blood pressure in obstructive sleep apnoea (OSA) patients, not only during sleep but also in the daytime. However, both the mechanisms of blood pressure reduction and the considerable differences in the magnitude of the effect in the studies presented to date are not fully understood. Therefore, the authors prospectively studied the effect of nCPAP on noradrenaline plasma levels (NApl), blood pressure and heart rate (HR) in 10 normotensive and eight hypertensive OSA patients before and after 41.6 +/- 16.9 days of nCPAP therapy. Polysomnography and invasive blood pressure were continuously monitored over 24 h in the supine position before and with nCPAP. NApl were analysed every 15 min. In hypertensives, nCPAP reduced NApl by 36 +/- 25%, lowered mean arterial blood pressure substantially (night-time: -8.89 +/- 14.09 mmHg; daytime: -7.94 +/- 10.47 mmHg) and decreased HR by 6.6 +/- 5.4 beats x min(-1), whereas in normotensives there were only minor changes. The decrease in heart rate was associated with a decrease in mean arterial blood pressure and noradrenaline plasma levels, suggesting a causal effect of nasal continuous positive airway pressure therapy. This nasal continuous positive airway pressure effect occurs mainly in hypertensive obstructive sleep apnoea patients, whereas the effect is small in normotensives. This may explain, at least in part, some of the discrepant results in previous treatment studies.     

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Hypertension, cardiac arrhythmias, myocardial infarction, and stroke in relation to obstructive sleep apnea.

The cyclical changes in heart rate and systemic blood pressure that accompany apneic events are predominantly mediated by fluctuations in the activity of the autonomic nervous system. Increased vagal efferent parasympathetic activity is responsible for the cyclical reductions in heart rate during apnea. In contrast, the cyclical elevations in systemic blood pressure are believed to result from recurrent peripheral vasoconstriction mediated by repetitive activation of the sympathetic nervous system. Maximal activation and pressures coincide with apnea termination and brief arousal from sleep. These cyclical elevations in systemic pressure during sleep increase ventricular workload and, thereby, may contribute to the development of ventricular hypertrophy. Systemic hypertension is present during wakefulness in approximately 50% of patients with OSA. Although age and obesity are the predominant risk factors for diurnal hypertension, OSA probably makes an independent contribution in younger obese men. Sinus bradycardia, Mobitz type 1 second-degree heart block, and prolonged sinus arrest have all been documented in association with the apneic events. Increased ventricular ectopy has been observed with oxyhemoglobin desaturations below 60%. Myocardial ischemia, infarction, sudden death, and stroke all demonstrate similar circadian variations in time of onset. Peak frequencies occur between 6 AM and noon, generally within several hours of awakening. Although sleep is associated with decreased frequencies of these adverse cardiovascular events in the general population, evidence exists linking REM sleep to an increased risk of myocardial ischemia. In men who habitually snore, epidemiologic data have detected an increased risk for ischemic heart disease and stroke. Habitual snoring has also been associated with an increased risk of sudden death during sleep. In patients with clinically significant OSA, there is reasonable information indicating excessive mortality in the absence of treatment. This mortality is predominantly cardiovascular and tends to occur during sleep.     

Obstruktive Schlafapnoe bei Patienten mit Typ-2-Diabetes

In patients with type 2 diabetes obstructive sleep apnea (OSA) is in addition to obesity, hyperlipidemia and arterial hypertension a common comorbidity which is characterized by repetitive apnea, arousals from sleep and surges of heart rate and arterial blood pressure. Symptoms related to OSA include morning tiredness, daytime hypersomnolence, nocturnal dyspnea and nocturia and justify treatment of OSA. Patients with type 2 diabetes can profit from treatment of OSA in terms of symptom relief, blood pressure lowering effects and potential beneficial effects on lipid and glucose metabolism. Diagnostics of OSA with an ambulatory polygraphy is indicated in patients with type 2 diabetes and OSA-related symptoms or other typical clinical signs for OSA, such as arterial hypertension refractory to drug treatment or non-dipping in 24?h blood pressure monitoring.     

Sleep disorders in patients with congestive heart failure

PURPOSE OF REVIEW: This review of recent literature pertains to the growing evidence that obstructive sleep apnea contributes to the development of systemic hypertension and congestive heart failure. RECENT FINDINGS: There is irrefutable evidence that OSA causes systemic hypertension and that continuous positive airway pressure (CPAP) treatment of OSA causes a reduction in blood pressure. Moreover there is evidence that untreated OSA is associated with left ventricular diastolic and systolic failure and that treatment with CPAP improves systolic function. SUMMARY: OSA should be considered in patients with systemic hypertension or heart failure.     

Sleep apnea in the elderly

Obstructive sleep apnea (OSA) is a common clinical condition associated with obesity. A high prevalence of sleep apnea exists in the elderly, presumably because of changes in oropharyngeal collapsibility. Elderly patients may be less likely to seek medical attention for this condition, because they are less likely to be symptomatic. Excessive daytime somnolence is a known consequence of untreated OSA, but adverse cardiovascular consequences, such as hypertension, arrhythmias, and congestive heart failure, are more serious in older patients. Continuous positive airway pressure therapy is the most effective treatment of OSA, although compliance remains an issue.     

Deleterious effects of sleep-disordered breathing on the heart and vascular system

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 the general public. Awareness and timely initiation of an effective treatment may prevent potential deleterious cardiovascular effects of OSA.     

Sleep, Slow-Wave Sleep, and Blood Pressure

There is increasing evidence that alterations in sleep continuity due to central nervous system arousal and/or reductions in deeper stages of sleep adversely affect blood pressure and contribute to hypertension. Disturbed sleep also blunts the normal nocturnal dip in blood pressure and may lead to sustained daytime hypertension as well. Nocturnal drops in blood pressure result from increased parasympathetic and reduced sympathetic activity during sleep. Slow-wave sleep, considered to be the most "restorative," is the specific sleep state associated with the largest decline in sympathetic activity. The time in slow-wave sleep declines with age as well as in association with other health problems. A reduction in the time in slow-wave sleep has recently been reported to predict increased incident hypertension. The mechanisms by which this occurs have not been well described but may include alterations in dipping patterns, sympathetic nervous system activity, corticotrophin pathways, and the renin-angiotensin system. This article reviews the overall association between sleep and hypertension, with a specific focus on slow-wave sleep, a possible novel target for future blood pressure interventions.     

Home Blood Pressure Monitoring: Primary Role in Hypertension Management

Two main sleep disturbances, namely obstructive sleep apnea (OSA) and sleep deprivation, have gained growing interest in the field of hypertension research. This fact is supported not only by evidence that both disturbances are quite common in modern societies but also that OSA and sleep deprivation are associated with several pathways that may contribute to a predisposition to hypertension or even exacerbate blood pressure levels in hypertensive patients. In the present review, we will discuss current evidence supporting a potential role of these sleep disturbances in the resistant hypertension scenario.     

Bilateral leg edema, obesity, pulmonary hypertension, and obstructive sleep apnea

BACKGROUND: Pulmonary hypertension is usually due to an underlying cardiac or pulmonary condition. An association between unexplained pulmonary hypertension and bilateral leg edema in primary care patients was found previously. We undertook this study to identify the frequency of obstructive sleep apnea (OSA) in ambulatory, adult patients with pulmonary hypertension who initially presented with bilateral leg edema. METHODS: Twenty ambulatory adults with bilateral leg edema, echocardiocardiographic evidence of pulmonary hypertension (estimated pulmonary artery systolic pressure >30 mm Hg) without left ventricular dysfunction, and no clinically apparent pulmonary disease [corrected] were enrolled from a suburban family practice and an inner-city family practice during a 3-year period. Spirometric assessment, pulse oximetry, rheumatologic evaluation, polysomnography, and questionnaire information regarding risk factors for pulmonary hypertension were obtained for each subject. RESULTS: Fifteen patients (75%) completed the study. Almost all of the subjects were obese. Nine (60%) of the 15 had OSA. None of the subjects demonstrated an obstructive pattern on spirometric evaluation results, but 9 (60%) had a restrictive spirometry pattern, consistent with their obesity. None of the subjects had daytime hypoxemia. Systemic hypertension was present in two-thirds of the subjects with OSA, and was absent in all of the subjects who lacked OSA. CONCLUSIONS: Bilateral leg edema in obese primary care patients is associated with both OSA and modest pulmonary hypertension. If these findings are generalizable, then bilateral leg edema may be an important clinical marker for underlying OSA.     

Obesity, sleep apnea, and hypertension

Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.     

Chronic obstructive pulmonary disease and obstructive sleep apnoea—the overlap syndrome

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are highly prevalent disorders and the co-existence of both disorders, termed the overlap syndrome, affects at least 1% of the adult population. Patients with the overlap syndrome typically experience more pronounced nocturnal oxygen desaturation and there is a high prevalence of pulmonary hypertension in such patients. Recent evidence suggests that the prevalence of each disorder together is higher than might be predicted by simple prevalence statistics, although the evidence is not clear-cut in this regard. Sleep itself can have several negative effects in patients with COPD. Sleep quality is diminished with reduced amounts of slow wave and rapid-eye-movement (REM) sleep, which may contribute to daytime symptoms such as fatigue and lethargy. Furthermore, normal physiological adaptations during sleep that result in mild hypoventilation in normal subjects are more pronounced in COPD, which can result in clinically important nocturnal oxygen desaturation. Management of sleep disorders in patients with COPD should address both sleep quality and disordered gas exchange. Non-invasive pressure support is beneficial in selected cases, particularly during acute exacerbations associated with respiratory failure, and is particularly helpful in patients with the overlap syndrome. There is limited evidence of benefit from pressure support in the chronic setting in COPD patients without OSA.     

Obstructive sleep apnea and cardiovascular disease - time to act!

Sleep related breathing disorders are common and their potential to disrupt sleep leading to daytime fatigue and hypersomnolence is widely acknowledged. In the future, obstructive sleep apnoea (OSA) may become even more important because obesity as a main risk factor is increasingly prevalent. Apart from disturbing sleep, OSA has also been recognised as a risk factor for hypertension, acute cardiovascular events and metabolic disturbance such as insulin resistance. Several randomised controlled trials demonstrated a positive effect of nasal continuous positive airway pressure (CPAP) treatment on arterial blood pressure, leading the "Joint National Council on High Blood Pressure" to list obstructive sleep apnoea as the first identifiable cause of arterial hypertension. Recently, a growing body of evidence demonstrated also a risk reduction of fatal and non-fatal cardiovascular events by treatment of obstructive sleep apnoea. A beneficial effect of treatment of OSA was also shown for patients with heart failure, or heart rhythm disturbance. Obstructive sleep apnoea may no longer be seen as a cause for daytime sleepiness and impaired quality of life only, but also as an independent risk factor, at least for the occurrence of hypertension but probably for any cardiovascular and cerebrovascular disease. While prospective controlled trials to document a reduction of cardiovascular morbidity and mortality are awaited, therapeutic nihilism seems no longer appropriate. With effective treatment available, subgroups that may profit best remain to be identified.     

Sleep Related Breathing Disorders Are Common Contributing Factors to the Production of Essential Hypertension But Are Neglected, Underdiagnosed, and Undertreated

There is now strong evidence from animal studies and, in humans, from epidemiological studies as well as from retrospective and prospective intervention studies, that obstructive sleep apnea (OSA) can cause persistent hypertension not only during sleep but during waking hours as well. There is also some evidence that habitual snoring alone, even without OSA, can do the same. Many of the hitherto unexplained epidemiological, clinical, biochemical, hematological, and physiological abnormalities seen in essential hypertension (EH) could be explained by the accompanying sleep related breathing disorders (SRBD). Many cases of resistant hypertension are probably due to SRBD. Recent studies show that SRBD are extremely common in EH but that the vast majority of patients with these sleep disorders are being missed by physicians who are treating the accompanying hypertension, even when the patients already have blatant symptoms of OSA. Recent investigations have shown that the probable reason for this underdiagnosis of OSA is lack of physician knowledge about the condition. This lack of knowledge is prevalent not only among family physicians, but among hypertension specialists and researchers in the field of hypertension as well. OSA is a common, easily diagnosed, and eminently treatable condition that is associated not only with disturbed sleep, loud snoring and excessive daytime sleepiness (which greatly increases the risk of traffic accidents), but also with hypertension, especially resistant hypertension, a broad range of cardiovascular problems, decreased sexual functioning, memory deficits, difficulty concentrating, and changes in personality and mood. It deserves much more attention by physicians treating hypertension than it is currently getting.     

Previously Unrecognized Obstructive Sleep Apnea in Chinese Subjects With Essential Hypertension

Obstructive sleep apnea (OSA) is found to affect 2–4% of the middle-aged population in several Caucasian studies, whereas the prevalence among other ethnic groups have not been clearly documented. It has been reported that OSA and systemic hypertension are highly associated; we therefore conducted a study on Chinese subjects who were receiving treatment for essential hypertension to assess the prevalence of OSA among this group. Ninety-two consecutive patients being followed up at a hypertension clinic were recruited for a questionnaire survey. The entire study group was aged 54.7 ± 11.7 years, with 40 men. One male subject had a diagnosis of obstructive sleep apnea on nasal continuous positive airway pressure (nCPAP) treatment and 46 subjects agreed to an overnight sleep study. Those who underwent sleep study showed selection bias with a higher body mass index and more symptoms associated with OSA. Of the 46 who underwent sleep study, 16 (34.8%) had an obstructive apnea-hypopnea (AHI) score of ≥5 and excessive daytime sleepiness, with a median score of 26.2 (range, 8.3–64.9). Patients in the group with obstructive sleep apnea syndrome (OSAS) thus defined compared with those without OSAS had more men (64.7 vs 17.20%, p= 0.001) and an excess of smokers (31.5 vs 3.3%. p= 0.01) and had significantly more symptoms of excessive daytime sleepiness (p= 0.001), daytime fatigue (p= 0.007), and witnessed apneas (p= 0.008). Seven patients accepted treatment with nCPAP and reported improvement in symptoms, but there was no detectable change in clinic blood pressure measurements after 3 months of nCPAP treatment. This study demonstrated a high prevalence of previously unidentified OSAS among Chinese patients with essential hypertension. Increased awareness of both doctors and patients toward this potentially treatable problem is warranted. Accepted for publication: 16 August 1999     

Pharmacologic approaches for the management of symptoms and cardiovascular consequences of obstructive sleep apnea in adults

Introduction

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, arousals from sleep, and daytime sleepiness. Accumulating evidence indicates that hypoxemia and sleep disruption contribute to the development of cardiovascular abnormalities in OSA. OSA is effectively treated with continuous positive airway pressure (CPAP) therapy that splints open the airway during sleep. Studies have shown that CPAP therapy improves daytime sleepiness and attenuates cardiovascular abnormalities in patients with OSA. However, not all patients with OSA tolerate or adhere to CPAP therapy. Even patients who regularly use CPAP therapy may have a few hours each night exposed to the negative effects of untreated OSA. As a result, complementary pharmacologic therapies that can be used with CPAP therapy have the potential to reduce symptoms and consequences of OSA.

Discussion

The wake-promoting medications modafinil and armodafinil effectively improve residual sleepiness in patients treated with CPAP therapy. Although results are equivocal so far, modafinil and armodafinil may also improve quality of life and global clinical condition in patients with OSA and residual sleepiness treated with CPAP therapy. Pharmacologic therapies also have the potential to be used with CPAP therapy to minimize cardiovascular perturbations and risk of cardiovascular disease. Preliminary studies suggest that inhibition of the enzyme xanthine oxidase and inhibition of sympathetic nervous system overactivity may have therapeutic potential to reduce cardiovascular harm in patients with OSA.

Conclusion

Future studies of pharmacologic therapies to reduce symptoms and cardiovascular consequences of OSA should be increasingly performed as our understanding of the mechanisms mediating the adverse effects of OSA continues to evolve.