Elucidation of the pathogenic mechanism(s) of hypertension in patients with SBD may lead to new, more targeted therapies and offer improved quality of life

photoScreening studies in the United States, Europe, and Australia have shown that a substantial proportion of the adult population has mild-to-moderate sleep-disordered breathing (SDB),1,2 a condition characterized by repeated episodes of apnea and hypopnea during sleep. Apnea and hypopnea cause temporary elevations in blood pressure in association with blood-oxygen desaturation, arousal, and sympathetic activation, and may cause elevated blood pressure during the daytime and, ultimately, sustained hypertension.

Early Observations
SDB has been associated with hypertension in clinical reports since the early 1980s.3-6 Although some studies found an independent association between snoring and hypertension,7,8 others found that this relationship may be explained by the confounding effects of age, sex, or obesity.9,10 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.11,12 Other studies have used polysomnography, a more objective measure of SDB.13-16 Most of these studies found an association between obstructive sleep apnea syndrome (OSAS) and hypertension, independent of age, sex, and other potential confounding factors.14-15 With the exception of the reports from the Wisconsin Sleep Cohort Study of middle-aged employed persons,14,17 most previous studies were based on a small number of patients in clinical settings.

Given the strong association between SDB and obesity, some investigators have cautioned that even in studies controlling for body mass index (BMI), there is a potential for residual confounding because fat distribution may be the strongest confounding component of obesity.18

Body mass index (BMI) is a nutritional parameter that can be used to diagnose protein-calorie malnutrition. This index is independent of height and the same standards apply to both men and women.

BMI may be determined from the use of a nomogram or calculated by using the following formula:

BMI (kg/m2) = weight (kg)/height (m2)

A BMI >28 defines significant obesity, while a BMI of 20 to 25 is considered normal. A BMI <18 implies moderate malnutrition.

Association Between SDB, Sleep Apnea, and Hypertension
Recently, investigators performed a large-scale, cross-sectional analysis of 6,132 subjects aged >40 years recruited from ongoing population-based sleep studies.19 The objective of the analysis was to assess the association between SDB 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 SDB 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 SDB were seen in both men and women, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant 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 SDB and hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

More Research Is Needed
The mechanisms underlying the association between SDB with hypertension remain to be established. One leading hypothesis is that SDB increases sympathetic neural traffic. Patients with untreated SDB 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 continuous positive airway pressure (CPAP) has been shown to improve autonomic function and lower sympathetic tone.20

A second possible mechanism that may explain the observed relationship between SDB and hypertension is an impairment in vascular endothelial function in patients with SDB.21 Endothelium-dependent vascular relaxation in patients with SDB is reduced during wakefulness. The disruption of sleep and the hypoxic stress that accompany sleep-disordered breathing 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.

Further research is needed to more definitively assess the relationship between SDB and hypertension. Clear elucidation of the pathogenic mechanism(s) of hypertension in patients with SDB may lead to new, more targeted therapies, and offer improved quality of life to those who suffer from SDB and its comorbidities.

John D. Zoidis, MD is a contributing writer for RT Magazine.

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