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.     

Sleepiness and hypertension in obstructive sleep apnea.

In order to assess the complications of sleep apnea, we have reviewed a data base of 619 consecutive admissions to a university sleep disorders center. Although patients with obstructive sleep apnea (OSA) described more subjective sleepiness than patients with central sleep apnea (CSA) or primary snoring (PS), the multiple sleep latency test (MSLT) indicated similar levels of physiologic sleepiness in the two apneic groups, which was greater than among those with PS. There was no significant relationship between individual subjective estimates of habitual sleepiness and the MSLT values. Among the OSA patients the mean minimum arterial oxygen desaturation during REM sleep accounted for 65 percent of the variance of the mean sleep latency on the MSLT, with an additional, smaller, contribution of the disordered breathing rate per hour. Subjective reports of sleepiness were associated with sleep efficiency and the number of disordered breathing events in NREM sleep. Patients with OSA or CSA had similar diastolic blood pressures and frequencies of history of treatment for hypertension, which were significantly higher in OSA than in the PS group. In the OSA group the absolute minimum arterial oxygen desaturation during NREM sleep was the most significant contributor to waking diastolic blood pressure, with an additional small contribution by weight. A history of treatment for hypertension was most strongly associated with weight, without significant additional contributions by measures of disordered breathing events or oxygen desaturation; however, weight was highly intercorrelated with measures of the apnea/hypopnea index and minimum arterial oxygen desaturation. In summary, these data support recent findings which show a close relation of obesity to a history of hypertension in OSA, and extend to this group a previous observation that in regular heavy snorers, there may be a disparity between levels of physiologic and subjective sleepiness.     

Causes and consequences of blood pressure alterations in obstructive sleep apnea

The obstructive sleep apnea (OSA) syndrome has been considered to be a cause of both transient blood pressure elevations during sleep and sustained hypertension during the awake state. The purpose of this review was to examine critically the existing literature regarding (1) the blood pressure alterations associated with OSA, (2) causal mechanisms relating specific blood pressure alterations to OSA, and (3) potential consequences of the systemic circulatory abnormalities associated with OSA. Particular attention was directed at studies that assessed the prevalence of OSA in patients with hypertension and that examined the effects on blood pressure of treatment of OSA. We conclude that patients with OSA have abnormal sleep blood pressure patterns, manifested most frequently by apnea-associated blood pressure elevations. Confounding factors such as obesity and antihypertensive drug therapy, and conflicting evidence regarding changes in daytime blood pressure after therapy for OSA, make it premature to conclude that OSA and daytime hypertension are directly associated. Circumstantial evidence suggests that the blood pressure alterations that occur during sleep could contribute to the high cardiovascular morbidity in patients with OSA. Further research into the relationship between OSA and hypertension should improve the future care of patients with these conditions and enhance our understanding of cardiopulmonary pathophysiology.     

Obstruktive Schlafapnoe und kardiovaskuläre Komorbidität

Obstructive sleep apnea (OSA) is the most common entity of sleep-disordered breathing in Germany. OSA is independently associated with an increased risk of cardiovascular disease. It predisposes to arterial hypertension in particular, but also to coronary artery disease, cardiac arrhythmias and atrial fibrillation. OSA has been established as an independent risk factor for arterial hypertension, and treatment of OSA with continuous positive airway pressure (CPAP) causes a significant and persistent drop in blood pressure. Long-term CPAP treatment reduces the rate of important cardiovascular comorbidities.     

Obstructive sleep apnea and heart failure

Obstructive sleep apnea (OSA) exerts several effects that may be particularly deleterious in patients with heart failure (HF). OSA should be considered especially in HF patients who are obese or have the metabolic syndrome, systemic hypertension, or pulmonary hypertension. HF patients in whom OSA is suspected should undergo a full evaluation by a sleep specialist, including a polysomnogram, to diagnose OSA and differentiate this disease from central sleep apnea. Those found to have OSA should then receive continuous positive airway pressure and/or other interventions, and standard disease management strategies should be used to maximize compliance. Those who cannot tolerate continuous positive airway pressure may be candidates for mandibular advancement devices or surgical therapies including tracheostomy. Standard HF medications should be used to treat HF, and optimization of fluid balance may help minimize OSA severity. However, it is still unknown whether treatment of OSA in HF patients will reduce hospitalizations or mortality.     

Obstructive sleep apnea and abnormal glucose metabolism

Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially in subjects with obesity or diabetes. OSA is related to several metabolic abnormalities, including diabetes, insulin resistance, hypertension, and cardiovascular diseases. Although Koreans are less obese than Caucasians, the prevalence of OSA is comparable in both groups. Thus, the impact of OSA on metabolism may be similar. Many epidemiologic and experimental studies have demonstrated that OSA is associated with glucose intolerance and insulin resistance via intermittent hypoxia, sleep fragmentation, and sleep deprivation. The effect of continuous positive airway pressure treatment on glucose metabolism is still controversial. Randomized controlled trials are needed to evaluate the ability of OSA treatment to reduce the risk of diabetes and insulin resistance in subjects without diabetes and to ameliorate glucose control in patients with diabetes.     

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.     

Influence of antihypertensive drug therapy on sleep pattern and sleep apnea activity.

Sleep apnea, which affects 10% of men in the mean age group, is a common illness, and arterial hypertension one of its early symptoms. For the large group of, mainly young, patients with mild to moderate sleep apnea and arterial hypertension it is important to have a drug treatment available which will effectively control blood pressure without exacerbating symptoms of sleep apnea. We studied the effects of antihypertensive agents on blood pressure, sleep and sleep apnea in a randomized double-blind study of 24 patients with a sleep apnea activity of more than 10 apnea phases per hour of sleep and arterial hypertension with diastolic blood pressure values in the sitting position greater than or equal to 95 mm Hg. Mean age was 51 (range: 33-69) years, mean body mass index 31.4 (24.9-40.6) kg/m2. The study protocol envisaged two baseline measurements in the sleep laboratory, after which the medication was administered for 8 days. On the last 2 days of the treatment, polysomnographic leads were once again recorded in the sleep laboratory. The patients received either the beta-blocker metoprolol (1 x 100 mg/day) or the angiotensin-converting enzyme inhibitor cilazapril (1 x 2.5 mg/day). Systolic and diastolic blood pressure were decreased by both substances as expected. Total sleep time was 358 (233-425) min vs. 332 (255-383) min in the metoprolol group and 368 (295-424) min vs. 341 (265-434) min in the cilazapril group which is statistically not different between the two groups nor between the proportions of non-REM and REM sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

持续气道正压通气对于阻塞性睡眠呼吸暂停相关性高血压的治疗效果研究进展

阻塞性睡眠呼吸暂停常影响睡眠质量并引起心血管疾病,其中高血压发病率最高。目前对于阻塞性睡眠呼吸暂停与高血压之间的关系及机制仍在探索中,而持续气道正压通气作为阻塞性睡眠呼吸暂停的有效治疗方法,对于血压的降压作用说法不一。了解阻塞性睡眠呼吸暂停与高血压之间的关系机制及持续气道正压通气的治疗效果,将有助于更好的临床实践。     

Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea

Obstructive sleep apnea (OSA) is a very common risk factor for hypertension, and continuous positive airway pressure (CPAP) has been widely used to treat OSA. We conducted a meta-analysis of randomized, controlled trials to evaluate the effects of CPAP on blood pressure, reported as either a primary or secondary end point, among patients with OSA. Studies were retrieved by searching Medline (January 1980 to July 2006), the Cochrane Database of Systematic Reviews, conference abstracts, and bibliographies of review and original articles. From 255 relevant reports, 16 randomized clinical trials were selected that compared CPAP to control among participants with OSA, had a minimum treatment duration of 2 weeks, and reported blood pressure changes during the intervention or control period. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 16 trials representing 818 participants were examined using a random-effects model. Mean net change in systolic blood pressure for those treated with CPAP compared with control was -2.46 mm Hg (95% CI: -4.31 to -0.62); mean net change in diastolic blood pressure was -1.83 mm Hg (95% CI: -3.05 to -0.61); and mean net change in mean arterial pressure was -2.22 mm Hg (95% CI: -4.38 to -0.05). Net reductions in blood pressure were not statistically different between daytime and nighttime. These results indicate that CPAP decreases blood pressure among those with OSA and may help prevent hypertension.     

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.     

慢性间歇低氧对心脏B超和血压影响的观察

目的 探讨慢性间歇低氧对OSAHS患者左心功能的影响,以及持续气道正压通气(CPAP)治疗后左心功能和血压的变化.方法 顺序收集2007年5月至2008年12月于吉林大学第一医院就诊的、符合OSAHS诊断标准的门诊或住院患者75例(OSA组),其中非高血压者35例,合并高血压者40例.另选30名健康人为对照组,其中男20名,女10名,年龄30～65岁,与患者组年龄匹配,均为经系统检查无异常发现的健康人.对两组左心室射血分数(left ventricular ejection fraction,LVEF)、短轴缩短率(shortening fraction,FS)、E峰、A峰,并计算E/A进行比较.CPAP治疗后的血压、LVEF、E/A进行分析.结果 所有患者晨起血压(150.80±20.73/108.0±15.34)mm Hg(1 mm Hg=0.133 kPa)均较睡前血压(134.16±18.33/90.09±11.24)mm Hg明显升高.OSA组E/A明显降低(P<0.01),LVEF、FS明显降低(P<0.05);与对照组及OSA非高血压组比较,OSA合并高血压的患者左室射血分数和短轴缩短率均减少,提示高血压的出现是OSA左室收缩功能减退的重要因素;与对照组比较,OSA非高血压组E/A明显降低;非高血压组和高血压组比较,高血压组E/A下降显著,说明OSA本身可直接影响左心室舒张功能,而高血压的出现加重了左心室的舒张功能的降低.经CPAP治疗6个月后晨起血压(142.59±15.34/96.52±9.81)mmHg较治疗前(150.80±20.73/108.0±15.34) mm Hg显著下降(P<0.001);左室射血分数(59.70±11.1)%较治疗前(56.40±9.74)%增加(P<0.05);E/A值1.16±0.25较治疗前0.87±0.17明显增加(P<0.01).结论 (1)CIH可引起左心结构和功能发生改变,高血压的出现加重了这种变化.(2)CPAP对于纠正OSA患者高血压、改善左心功能,提高生活质量有重要意义.     

Obstructive sleep apnea: role in the risk and severity of diabetes

Obstructive sleep apnea (OSA) is a treatable sleep disorder that is pervasive among overweight and obese individuals. Current evidence supports a robust association between OSA and insulin resistance, glucose intolerance and the risk of type 2 diabetes, independent of obesity. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is independently associated with poorer glucose control. Evidence from animal and human models that mimic OSA supports a potential causal role for OSA in altered glucose metabolism. Robust prospective and randomized clinical trials are still needed to test the hypothesis that effective treatment of OSA may prevent the development of type 2 diabetes and its complications, or reduce its severity. Type 2 diabetes is occurring at alarming rates worldwide and despite available treatment options, the economic and public health burden of this epidemic remains enormous. OSA might represent a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes.     

Obstructive Sleep Apnea and Hypertension

Obstructive sleep apnea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure. However, these studies do indicate a wide variation in the blood pressure effects of CPAP, with some patients, on an individual basis, manifesting a large antihypertensive benefit. OSA is particularly common in patients with resistant hypertension. The reason for this high prevalence of OSA is not fully explained, but data from our laboratory suggest that it may be related to the high occurrence of hyperaldosteronism in patients with resistant hypertension. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid in the neck, which then contributes to increased upper airway resistance.     

伴及不伴OSA高血压患者的血压变异性和OSA相关性研究

目的研究伴或不伴睡眠呼吸暂停(obstructive sleep apnea,OSA)高血压患者的血压变异性和OSA的相关性。方法纳入阴虚阳亢型轻中度高血压患者90例,对患者行便携式睡眠仪监测、24h动态血压(ABPM)监测。观察患者血压的均值、变异性,及昼夜节律和OSA的关系;采用多元逐步回归法分析OSA和血压的关系。结果与不伴OSA的高血压患者相比,伴OSA患者的血压变异性和非杓型血压发生率明显增高,夜间血压下降率明显降低(P<0.05);其中夜间平均收缩压、24h收缩压血压标准差与睡眠呼吸暂停低通气指数(apnea hypopnea index,AHI)呈正相关,夜间收缩压下降率和AHI呈负相关(P<0.05)。结论伴OSA患者的血压变异性增高,昼夜节律紊乱。     

Sleep apnea and type 2 diabetes

The aim of the present review was to clarify the association between obstructive sleep apnea (OSA) and type 2 diabetes, and discuss the therapeutic role of continuous positive airway pressure (CPAP) in type 2 diabetes. OSA patients are more likely than non‐OSA populations to develop type 2 diabetes, while more than half of type 2 diabetes patients suffer from OSA. Similar to Western countries, in the East Asian population, the association between these two disorders has also been reported. CPAP is the primary treatment for OSA, but the effect of CPAP on comorbid diabetes has not been established. CPAP improved glucose metabolism determined by the oral glucose tolerance test in OSA patients, and several studies have shown that CPAP improves insulin resistance, particularly in obese populations undergoing long‐term CPAP. Diabetes is associated with other sleep‐related manifestations as well, such as snoring and excessive daytime sleepiness. Snoring is associated with the development of diabetes, and excessive daytime sleepiness appears to modify insulin resistance. Well‐designed studies are required to clarify the therapeutic effect of CPAP on diabetes. As both diabetes and OSA lead to cardiovascular disease, clinicians and healthcare professionals should be aware of the association between diabetes and OSA, and should take CPAP and health‐related behaviors into consideration when treating patients with diabetes and/or OSA.     

Analysis of arterial hypertension pharmacotherapy in patients with obstructive sleep apnea syndrome

IntroductionObstructive sleep apnea (OSA) is often connected with arterial hypertension and it could also be a cause of secondary hypertension. Treatment of arterial hypertension and optimal blood pressure level are important for prevention of cardiovascular complications. It is not well known how to treat patients with OSA and arterial hypertension. Also many patients with OSA suffer from metabolic syndrome which worsen their prognosis.AimThe aim of our study was to assess arterial hypertension compensation in patients with metabolic syndrome and moderate to severe OSA and to analyze used pharmacotherapy.Materials and methods85 hypertensive patients (75 men) with metabolic syndrome, average age 53.6 ± 9.3 years, were evaluated using overnight sleep study with diagnosis of OSA, average apnea–hypopnea index (AHI) 56.3 ± 23. Patients underwent 24 h ambulatory blood pressure monitoring (ABPM) and their current pharmacotherapy data were obtained. Appropriate combinations of antihypertensive drugs (patients with metabolic syndrome) were derived from ESH/ESC 2013 guidelines.ResultsArterial hypertension was well compensated in only 11.8% of the patients. 24.7% patients were treated according to current guidelines. Fisher's exact test with analysis of adjusted residues has found higher rate of blood pressure subcompensation in patients treated with triple+ combination of drugs (p = 0.035, 51.4% vs 10%).ConclusionOnly a small number of patients had optimal blood pressure level and were treated according to current ESH/ESC guidelines. We have to constantly appeal to all physicians to perform ABPM in patients with OSA.     

The acute effects of continuous positive airway pressure and oxygen administration on blood pressure during obstructive sleep apnea.

We have measured blood pressure continuously with a digital artery blood pressure monitor in eight patients with severe obstructive sleep apnea (OSA) during 30 min each of wakefulness, OSA, OSA with added oxygen to keep saturation above 96 percent at all times (OSA+O2), and nasal continuous positive airway pressure (CPAP) therapy. Mean blood pressures were not different between wakefulness, OSA, OSA+O2, and CPAP, although the variability in blood pressure was significantly greater during OSA and OSA+O2 than during wakefulness and CPAP. The addition of oxygen did not attenuate the variability in blood pressure. Using multiple linear regression modeling to further dissect out the principal variables determining the postapneic blood pressure rise, we found that only apnea length (r2 = 0.28, p less than 0.0001) and pulse rate changes (r2 = 0.15, p less than 0.0001) remained significantly related to SBPmax, while hypoxemia did not. We found the same trends in the other variables SBPten, DBPmax, and DBPten. Hypoxemia made a small contribution to the size of DBPmax, although this was small by comparison with apnea length. We conclude that CPAP treatment of OSA does not lower mean blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen in patients with untreated OSA. The rise in blood pressure following each apnea is not primarily due to arterial desaturation but is related to apnea length and may be caused by increased sympathetic activity secondary to arousal.     

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.     

Hypertension research in sleep apnea

Obstructive sleep apnea (OSA) is characterized by repetitive partial and total collapse of the upper airway that induces stressful arousals throughout sleep to reestablish breathing. Although estimates vary, prevalence has been reported as high as 20% in the adult population. OSA is common in several chronic diseases, the most common of which is obesity. Evidence is strong that OSA increases the risk of hypertension and both fatal and nonfatal cardiovascular events. Several mechanisms linking OSA to hypertension have been proposed, with increased sympathetic activation implicated as the prime mediator. This review summarizes recent data on the influence of OSA on blood pressure, the effect of standard OSA therapy on improving blood pressure, and the potential of lifestyle modification for further decreasing hypertension risk. Challenges confronting the investigation of blood pressure outcomes in response to treatment in OSA patients are discussed.