Hypertension and obstructive sleep apnea

Obstructive sleep apnea is a common disorder that is often unrecognized and underappreciated. Emerging evidence suggests that there is a causal link between obstructive sleep apnea and hypertension. This relationship appears to be independent of other comorbidities that have been previously linked to hypertension, such as obesity. The majority of studies support the contention that alleviation of sleep disordered breathing has a clinically significant beneficial impact on decreasing both nighttime and daytime blood pressure. A pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension is not fully elucidated. However, there is consistent evidence that autonomic mechanisms are implicated. Sympathetic activation along with humoral responses to repetitive episodes of hypoxemia and apnea over the longer term may cause vasoconstriction, endothelial dysfunction, and possibly hypertension. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to hypertension in this patient population.     

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.     

Sleep apnea and cardiovascular disease. Implications for understanding erectile dysfunction

BACKGROUND AND PURPOSE: There is increasing recognition of the high and rising prevalence of obstructive sleep apnea (OSA). It has been suggested that OSA may contribute to erectile dysfunction. This review will examine the evidence and potential mechanisms, including abnormalities of neural, endothelial and hormonal function, linking OSA to erectile dysfunction. CONCLUSION: Available data suggest, but do not prove, a higher prevalence of erectile dysfunction in OSA. Certainly, the pathologic processes activated by OSA are also those that may predispose to impaired erectile function. Further well-designed and controlled studies are needed to show conclusively that any increased prevalence of erectile dysfunction in OSA is secondary to the OSA per se and not a consequence of the frequently associated comorbidities, such as obesity and vascular disease, that characterize this patient population.     

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.     

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.     

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.     

Obstructive sleep apnea and hypertension

There is growing evidence of a causal relationship between obstructive sleep apnea (OSA) and hypertension. Untreated OSA may have direct and deleterious effects on cardiovascular function and structure through several mechanisms, including sympathetic activation, oxidative stress, inflammation, and endothelial dysfunction. OSA may contribute to or augment elevated blood pressure levels in a large proportion of the hypertensive patient population. It is important to consider OSA in the differential diagnosis of hypertensive patients who are obese. OSA should be especially considered in those hypertensive patients who respond poorly to combination therapy with antihypertensive medications.     

The Role of Obesity and Obstructive Sleep Apnea in the Pathogenesis and Treatment of Resistant Hypertension

The incidence of resistant hypertension, obesity, and obstructive sleep apnea (OSA), three highly prevalent conditions in the United States, is rising. Approximately one in three adults in the US has hypertension, and a significant proportion of these individuals have hypertension that is difficult to treat, or resistant. Obesity and OSA are well-established risk factors for resistant hypertension, a condition that portends significant cardiovascular risk. Awareness of the various mechanisms by which obesity and OSA impact systemic blood pressure is essential to better understand how best to effectively care for patients with resistant hypertension. In this review, we discuss the clinical and pathophysiologic associations between obesity, OSA, and resistant hypertension. Furthermore, we will explore the effect of continuous positive airway pressure therapy (CPAP) and other therapeutic interventions on blood pressure control in patients with resistant hypertension. Key Points ? Obesity, obstructive sleep apnea, and resistant hypertension are highly prevalent conditions, with increasing overall incidence [1–3]. ? Both obesity and obstructive sleep apnea are independent risk factors for the development of resistant hypertension. ? OSA is characterized by a physiologic cascade of collapse of the upper airway, which can lead to intermittent hypoxia, hypercapnia, significant negative intra-thoracic pressure, and increased SNS output. ? Intermittent hypoxia leads to activation of the endothelin system [17, 18, 19?], which can lead to the development of resistant hypertension. ? Intermittent hypoxia can lead to the over activation of the SNS, which can also contribute to the development of resistant hypertension [20, 21]. ? OSA leads to state of elevated adrenergic tone, which in turn may contribute to resistant hypertension [25–27]. ? OSA patients have a higher incidence of “non-dipping” of nocturnal systolic blood pressure, a marker of increased adrenergic tone. This potentially represents a risk factor for hypertensive end organ disease [31, 32]. ? The prevalence of OSA is significantly higher in patients predisposed to fluid accumulation: including kidney disease, heart failure and resistant hypertension [33]. ? Interventions (such as the daytime use of compression stocking) which reduce daytime lower extremity fluid accumulation can significantly reduce the severity of OSA, particularly in patients with comorbid resistant hypertension [35, 36]. ? CPAP therapy can significantly reduce blood pressure in patients with comorbid hypertension and OSA. The treatment effect is most pronounced in those with resistant hypertension and OSA [16??, 38–42].     

Obesity-related cardiovascular disease: implications of obstructive sleep apnea

Obesity and obstructive sleep apnea (OSA) often coexist. OSA has been linked to cardiovascular disease. Thus, OSA may contribute to the cardiovascular consequences of obesity. In this review, we explore clinical and pathophysiological interactions between obesity, cardiovascular disease and OSA. We discuss the mechanisms whereby OSA may contribute to hypertension, atherosclerosis, insulin resistance and atrial fibrillation associated with obesity, and emphasize the potential implications for understanding why only a subgroup of obese patients develop cardiovascular disease. Identification of the OSA-dependent and OSA-independent pathways in the cardiovascular pathophysiology of obesity may hold clinical and therapeutic promise.     

Obstructive sleep apnea: an update on mechanisms and cardiovascular consequences

Background and aimThere is growing recognition of the widespread incidence and health consequences of obstructive sleep apnea (OSA). This review examines the evidence linking sleep apnea with cardiovascular disease and discusses potential mechanisms underlying this link.Data synthesisThe weight of evidence provides increasing support for a causal relationship between OSA and hypertension. Furthermore, OSA may contribute to the initiation and progression of cardiac ischemia, heart failure and stroke. Chronic sympathetic activation appears to be a key mechanism linking OSA to cardiovascular disease. Other potential mechanisms include inflammation, endothelial dysfunction, increased levels of endothelin, hypercoagulability and stimulation of the renin angiotensin system. OSA, hypertension and obesity often coexist and interact, sharing multiple pathophysiological mechanisms and cardiovascular consequences. Effective treatment of OSA may attenuate neural and humoral abnormalities in circulatory control, improve blood pressure control and conceivably reduce the risk of future cardiovascular events.ConclusionPatients with OSA are at increased risk for cardiovascular disease. OSA should be considered in the differential diagnosis of hypertensive patients who are obese. In particular, OSA should be excluded in patients with hypertension resistant to conventional drug therapy.     

Daytime hypertension in obstructive sleep apnea. Prevalence and contributing risk factors

We examined the prevalence of daytime hypertension in a modern sample of patients with obstructive sleep apnea (OSA) and assessed the relative risk factors contributing to the development of hypertension in this disorder. Daytime hypertension was present in 92 (45 percent) of 206 male and female patients with OSA. Stepwise logistic regression revealed that only age and body mass index (BMI) were predictors of hypertension in this population. A subsample of 152 male patients with OSA was then compared to 904 men identified from a geographically and ethnically similar general population. When one controlled for age and BMI, the prevalence of hypertension in the two groups was the same except for those aged 25 to 44 years who were markedly obese (BMI greater than 31 kg/m2). In this group, 47 percent of the patients with OSA were hypertensive vs 26 percent of control subjects (p less than 0.05). Our data suggest that the high prevalence of hypertension in OSA is primarily related to age and the excess obesity seen in these patients. In morbidly obese young patients with OSA, factors directly related to OSA may also be contributing to the development of hypertension. With increasing age, other competitive risks may obscure any independent effect that OSA may exert.     

Sleep disordered breathing and hypertension.

Patients with sleep apnea may be at increased risk for cardiovascular disease. Recently, the link between hypertension and sleep apnea has been strengthened by findings of two large epidemiologic studies. Neurohumoral and hemodynamic responses to repetitive episodes of hypoxemia and apnea may offer a pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension. Sympathetic, humoral, and cellular responses to sleep apnea over the long term may cause vascular dysfunction and consequent hypertension. These responses may be exacerbated by sleep deprivation, which occurs commonly in patients with sleep apnea because of poor sleep architecture. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to cardiovascular risk in this patient population. Alleviation of sleep disordered breathing may be accompanied by lower blood pressure in hypertensive patients with sleep apnea.     

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.     

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.     

Left Ventricular Dysfunction, Pulmonary Hypertension, Obesity, and Sleep Apnea

The purpose of this study was to determine the frequency of central and obstructive sleep apnea in adult patients who have echocardiographic evidence of left ventricular dysfunction and pulmonary hypertension. Subjects with left ventricular dysfunction, pulmonary hypertension (pulmonary artery systolic pressure >30 mm Hg) and no lung disease were evaluated for risk factors associated with pulmonary hypertension. Of eight eligible adults, six completed the study. Subjects were from suburban and inner city family practices. Spirometric assessment, pulse oximetry on room air, rheumatologic evaluation, polysomnography, and additional history were taken. All six subjects had sleep apnea (apnea-plus-hypopnea index, or AHI, 20): obstructive, central, or mixed. All were obese, and almost all the subjects had a restrictive pattern on spirometry, which is consistent with obesity. All had a pulmonary artery systolic blood pressure of 35 mm Hg or greater. None had daytime hypoxemia or collagen vascular disease, and none had ever used appetite suppressants. This study found a strong association between pulmonary hypertension and obstructive or central sleep apnea in obese patients with congestive heart failure (CHF). We propose that a pulmonary artery systolic pressure of 35 mm Hg or greater in ambulatory patients with CHF may signify an increased risk of sleep apnea.     

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.     

Neural and humoral mechanisms mediating cardiovascular responses to obstructive sleep apnea

Patients with obstructive sleep apnea are at increased risk for hypertension. The mechanisms underlying this increased risk are not known. During sleep, repetitive apneic episodes result in hypoxemia and carbon dioxide retention, which cause increases in sympathetic nerve activity and elicit humoral vasoconstrictor responses. While these mechanisms explain nocturnal elevations in blood pressure, it is unclear why hypertension and elevated sympathetic nerve activity prevail even during the daytime. This review will examine briefly some of the neural and humoral mechanisms that are activated by nocturnal apneas and which may contribute to persistent increases in blood pressure even during daytime normoxia. Disruption of the autonomic and hemodynamic profile of normal sleep by apneic events manifests as raised blood pressure and heightened sympathetic nerve traffic during sleep. During awake daytime normoxia, baroreflex and chemoreflex dysfunction may contribute to maintenance of higher blood pressure and sympathetic activity. Sustained vasoconstrictor effects of nocturnal endothelin release may also be implicated in the elevated daytime blood pressures.     

Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea

The prevalence of obstructive sleep apnea (OSA) defined at an apnea-hypopnea index (AHI) ≥5 was a mean of 22% (range, 9-37%) in men and 17% (range, 4-50%) in women in eleven published epidemiological studies published between 1993 and 2013. OSA with excessive daytime sleepiness occurred in 6% (range, 3-18%) of men and in 4% (range, 1-17%) of women. The prevalence increased with time and OSA was reported in 37% of men and in 50% of women in studies from 2008 and 2013 respectively. OSA is more prevalent in men than in women and increases with age and obesity. Smoking and alcohol consumption are also suggested as risk factors, but the results are conflicting. Excessive daytime sleepiness is suggested as the most important symptom of OSA, but only a fraction of subjects with AHI >5 report daytime sleepiness and one study did not find any relationship between daytime sleepiness and sleep apnea in women. Stroke and hypertension and coronary artery disease are associated with sleep apnea. Cross-sectional studies indicate an association between OSA and diabetes mellitus. Patients younger than 70 years run an increased risk of early death if they suffer from OSA. It is concluded that OSA is highly prevalent in the population. It is related to age and obesity. Only a part of subjects with OSA in the population have symptoms of daytime sleepiness. The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design and characteristics of included subjects including effects of the obesity epidemic. Cardiovascular disease, especially stroke is related to OSA, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA.     

Sleep-related breathing disorders, loud snoring and excessive daytime sleepiness in obese subjects

OBJECTIVE: To investigate the prevalence of sleep breathing disorders, loud snoring and excessive daytime sleepiness in a group of obese subjects, and to identify the predictors of obstructive sleep apnea (OSA) severity in these patients. SUBJECTS: A total of 161 consecutive obese patients (body mass index (BMI)> or =30.0 kg/m(2)), ranging between 30.0 and 67.3, represented by 57 men and 104 women, aged 16-75 y. Forty (15 men and 25 women) age-matched (20-70 y) nonobese (BMI<27 kg/m(2)) volunteers were also recruited for the study. MEASUREMENTS: Respiratory function parameters, nocturnal sleep quality (evaluated by a specific questionnaire), nocturnal hypoventilation and OSA (evaluated by night polysomnography) were examined in all subjects. Anthropometric parameters (neck circumference, waist circumference, waist-to-hip ratio) were also investigated. RESULTS: Eighty-three obese patients (51.5% of the obese group) had a respiratory disturbance index (RDI)> or =10, corresponding to a moderate or severe sleep apnea. In particular, 24.8% (40/161), ie a quarter of all obese patients, were affected by severe OSA and this alteration was present in 42.1% of obese men (24/57) and in 15.4% (16/104) of obese women. When a stepwise multiple regression analysis was performed, neck circumference in men and BMI in women were shown to be the strongest predictors of sleep apnea. Twenty-nine percent of all obese subjects (40.3% of men and 23.1% of women) showed nocturnal hypoventilation; however, it was present as a unique breathing alteration in only 5% of the obese population. The percentage of patients having excessive daytime sleepiness was significantly higher than in nonobese subjects, even when only nonapneic obese patients were considered (P<0.001). CONCLUSION: This study shows that OSA is present in more than 50% of a population of obese patients with a mean BMI higher than 40.0, this percentage being much higher than that commonly reported in previous studies, particularly in women. Neck circumference in men and BMI in women seem to be the strongest predictors of the severity of OSA in obese patients. Nocturnal hypoventilation seems to be present in more than 29% of a severe obese population. Moreover, this study indicates that morbid obesity can be associated with excessive daytime sleepiness even in the absence of sleep apnea.     

Cardiovascular consequences of obstructive sleep apnea

Sleep apnea is associated with several cardiovascular disease conditions. A causal relationship between sleep apnea and each of these diseases is likely, but remains to be proven. The clearest evidence implicating OSA in the development of new cardiovascular disease involves data that show an increased prevalence of new hypertension in patients with OSA followed over 4 years [3]. Circumstantial evidence and data from small study samples suggest that OSA, in the setting of existing cardiovascular disease, may exacerbate symptoms and accelerate disease progression. The diagnosis of OSA always should be considered in patients with refractory heart failure, resistant hypertension, nocturnal cardiac ischemia, and nocturnal arrhythmias, especially in individuals with risk factors for sleep apnea (e.g., central obesity, age, and male gender). Treating sleep apnea may help to achieve better clinical control in these diseases and may improve long-term cardiovascular prognosis.