OSAS and hypertension are frequently associated and studies now show that treating the first may help reverse the second.
Obstructive sleep apnea syndrome (OSAS) is the most frequently seen disorder in sleep centers1—a concerning statistic since this disorder does not just damage health by itself, but likely also plays a role in other serious disorders. One of the most well known of these associated disorders is hypertension. OSAS has been linked with hypertension in clinical reports since the early 1980s.2-5 Although some studies found an independent association between snoring and hypertension,6,7 others found that this relationship may be explained by the confounding effects of age, sex, or obesity.8,9
What is known is that the apneas and hypopneas of OSAS do cause temporary elevations in blood pressure in association with blood-oxygen desaturation, arousal, and sympathetic activation. This, in turn, may cause elevated blood pressure during the daytime and, ultimately, sustained hypertension.10,11 Epidemiologic data support a link between obesity and hypertension as well as between OSAS and hypertension. For example, untreated OSAS predisposes to an increased risk of new hypertension, and treatment of OSAS lowers blood pressure, even during the daytime.10
Pathogenesis of OSAS and OSAS-Associated Hypertension
OSAS affects approximately 4% of middle-aged adults and up to 50% of elderly persons.12,13 Of the approximately 75,000 patients seen annually in sleep disorder centers, roughly 75% are diagnosed with OSAS.1 Projections of the prevalence of OSAS in the United States range from 7 to 18 million people.1
Despite this high prevalence of OSAS, the pathogenetic mechanisms of this disorder remain incompletely understood. The occurrence of upper airway obstruction during sleep and not wakefulness implicates the removal of the wakefulness stimulus to breathe as a key factor underlying upper airway obstruction during sleep. Most of the data on sleep effect are derived from studies during non–rapid eye movement (NREM) sleep, given the difficulty in achieving REM during invasive studies in the laboratory environment.
The reduction of tonic upper airway dilating muscle activity caused by sleep is associated with reduced upper airway caliber and increased pharyngeal wall compliance.14 The mechanical corollary of decreased caliber is an increase in upper airway resistance.15 In addition to increased resistance, increased pharyngeal wall compliance during sleep in snorers is manifested by the occurrence of inspiratory flow limitation as flow plateaus during inspiration.15
The combination of increased resistance and inspiratory flow limitation leads to an increased work of breathing, hypoventilation, frequent arousals from sleep, and ensuing excessive daytime sleepiness. This has been described as a distinct clinical entity referred to as the upper airway resistance syndrome.16
The ability of the ventilatory control system to compensate for added loads is essential for the preservation of chemoreceptor homeostasis. However, immediate compensation to added loads is compromised during NREM sleep. Therefore, resistive loading results in decreased tidal volume and minute ventilation and, consequently, alveolar hypoventilation with subsequent elevation of arterial PaCO2.17 Furthermore, NREM sleep abolishes the ability of upper airway dilating muscles to respond to negative pressure.
In awake humans and animals, application of negative pressure to the upper airway elicits a reflex activation of the genioglossus muscle, presumably dilating the upper airway. The fact that this reflex is absent during NREM sleep suggests that sleep eliminates a protective reflex that maintains upper airway patency in the face of narrowing or deformation.18,19 The mechanical consequences of such reflex activation have not yet been determined.
The pathogenic mechanisms responsible for hypertension in patients with OSAS are believed to include activation of the sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS); oxidative stress; and systemic and vascular inflammation, all of which could link OSAS to a sustained increase in blood pressure.1
Two recent studies demonstrated that a self-reported history of snoring is associated with an increased incidence of hypertension in middle-aged men and women.20,21 Other studies have used polysomnography, a more objective measure of OSAS.22-25 Most of these studies found an association between OSAS and hypertension, independent of age, sex, and other potential confounding factors.23,24 With the exception of the reports from the Wisconsin Sleep Cohort Study of middle-aged employed persons,23,26 most previous studies were based on a small number of patients in clinical settings.
Given the strong association between OSAS and obesity, some investigators have cautioned that even in studies controlling for body mass index (BMI‚ see sidebar), there is a potential for residual confounding, because fat distribution may be the strongest confounding component of obesity.27
OSAS and Hypertension in a Community-Based Study
Investigators performed a large-scale, cross-sectional analysis of 6,132 subjects that were 40 years of age or older recruited from ongoing population-based sleep studies.28 The objective of the analysis was to assess the association between OSAS and hypertension in a large cohort of middle-aged and older persons. The main outcome measure was the apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with hypopnea defined as a >30% reduction in airflow or thoracoabdominal excursion accompanied by a >4% drop in oxyhemoglobin saturation), obtained by unattended home polysomnography. Other outcome measures included arousal index; percentage of time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as a resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.
The mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing OSAS measures, although some of this association was explained by BMI. After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol use and cigarette smoking, the odds ratio for hypertension, comparing the highest category of AHI (≥30 per hour) with the lowest category (<1.5 per hour), was 1.37. The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (≥12% vs <0.05%) was 1.46. In stratified analyses, associations of hypertension with either measure of OSAS was seen in both men and women, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and insignificant associations were observed for the arousal index or self-reported history of habitual snoring.
This well-designed analysis of a large study population provides compelling evidence of the association between OSAS and hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.
More Research Is Needed
The mechanisms underlying the association between OSAS breathing and hypertension remain to be established. One leading hypothesis is that OSAS increases sympathetic neural traffic. Patients with untreated OSAS exhibit elevated muscle sympathetic nerve activity during sleep and wakefulness. Such patients also have greater levels of plasma and urinary catecholamines in comparison with control subjects—a finding that lends support to the hypothesized role of the sympathetic nervous system. Furthermore, effective treatment with CPAP has been shown to improve autonomic function and lower sympathetic tone.29 Appropriate CPAP therapy can resolve OSAS in many patients.
A second possible mechanism that may explain the observed relationship between OSAS and hypertension is an impairment in vascular endothelial function in patients with OSAS.33 Endothelium-dependent vascular relaxation in patients with OSAS is reduced during wakefulness. The disruption of sleep and the hypoxic stress that accompany OSAS may also be associated with a number of metabolic abnormalities that are well-recognized risk factors for hypertension. These include impaired glucose tolerance, insulin resistance, and altered corticotropic function.
Mounting evidence indicates that treatment of sleep apnea using positive airway pressure, palatonasal surgery, and/or weight reduction corrects the associated hypertension.34 Interestingly, antihypertensive therapy appears to be less effective.34,35
Further research is needed to more definitively assess the relationship between OSAS and hypertension. Clear elucidation of the pathogenic mechanisms of hypertension in patients with OSAS may lead to new, more targeted therapies, and offer improved quality of life to those who suffer from OSAS and its comorbidities.
Recent evidence supports the probability that untreated OSAS has direct negative effects on cardiovascular function via several mechanisms, including sympathetic activation, oxidative stress, inflammation, and endothelial dysfunction, any or all of which may lead to hypertension.36 When a patient with known or suspected OSAS presents to the respiratory care practitioner, it is important to check for the presence of hypertension. OSAS should be considered especially in the differential diagnosis of hypertension in patients who are obese and in those who respond poorly to antihypertensive medications.36,37
John D. Zoidis, MD, is a contributing writer for Sleep Review.
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