Sleep Disorders and the Cardiovascular System

Normal Sleep Physiology

The state of sleep is determined by an array of coordinated neuronal processes. Sleep is typically divided into stages based on electroencephalographic (EEG) features, eye movements (electrooculography), and muscle tone (electromyography). Stages N1 through N3 are collectively called nonrapid eye movement sleep. Stage N1 sleep is frequently associated with the perception of drowsiness and is characterized by EEG features of mild slowing and vertex sharp waves. Stage N2 (light sleep) is characterized by the presence of K complexes or sleep spindles. In stage N3 (deep sleep), high-amplitude slow waves predominate in EEG activity. Rapid eye movement (REM) sleep (or stage R) is characterized by a low-amplitude, mixed-frequency pattern on the EEG, absence of muscle tone in voluntary muscles, and intermittent REMs. Dreams can occur in all stages of sleep but are more vividly recalled from REM sleep. Healthy adults display a reproducible pattern of sleep organization. They enter sleep through stage N1, progress to stage N2, and after 15 to 25 minutes progress to stage N3, followed by reemergence of stage N2 sleep. The first REM sleep period occurs after approximately 90 minutes. This pattern repeats approximately every 90 minutes throughout the sleep period, with progressively less slow-wave sleep and longer periods of REM sleep in each cycle.

All of these stages have other physiological correlates. As individuals progress normally through the stages of sleep, there are variations in heart rate, blood pressure, peripheral vascular tone, oxygen delivery, coronary blood flow, and respiration. In a healthy individual, transitional periods between quiet wakefulness and light sleep are characterized by mild instability in breathing, making these periods particularly subject to periodic breathing. As the individual becomes drowsy, the heart rate may decrease, with a subtle drop in blood pressure. In sustained nonrapid eye movement sleep, parasympathetic regulation of cardiovascular activity predominates, characterized by decreased blood pressure, greater high-frequency heart rate variability, and more regular breathing compared with quiet wakefulness. In REM sleep, skeletal muscles are paralyzed, except for a select few, including the diaphragm. This muscle atonia results in a decrease in peripheral vascular tone. Surges in sympathetic and parasympathetic output cause increased variability of heart rate, blood pressure, and respiratory rate. This fluctuation in autonomic output leads to accelerations and slowing of the heart rate and breathing, as well as increased afterload. This, combined with the decreased respiratory response to hypercapnia and hypoxia, makes individuals with underlying cardiac disease (e.g., heart failure, conduction disturbances, coronary artery disease) or pulmonary disease vulnerable during REM sleep and may increase the risk of arrhythmias and reduced coronary blood flow.

Sleep Length and Health

Our society has progressively shortened the amount of time dedicated to sleep. At the beginning of the 20th century, it was estimated that individuals spent approximately 9 to 10 hours per night in bed. As of 2008, the average working American sleeps <7 hours per night. Sleep deprivation in the short term is associated with autonomic instability, higher blood pressure, increased appetite, higher cortisol levels, and increased inflammatory markers. Epidemiological studies suggest that chronic sleep deprivation is associated with weight gain and obesity. In addition, individuals who sleep <5 hours per night are at higher risk for vascular disease, development of diabetes, and a shorter life span. Similarly, individuals who sleep >9 hours also appear to have a shorter life span. The underlying mechanism for the link of sleep deprivation and disease is unclear. Yet, some believe that dysregulation of the endocrine and autonomic nervous systems, as well as increases in inflammation contribute to the development of hypertension, vascular disease, and weight gain. Regardless of the mechanism, sleep duration may affect cardiovascular health.

Sleep-Related Breathing Disorders

Sleep can be disrupted by several disorders ( Box 71.1 ), many of which have not been extensively studied for their relationships to cardiovascular health. Patients presenting to a sleep specialist are typically those with sleep-related breathing disorders. Common sleep problems, including obstructive sleep apnea (OSA), central sleep apnea (CSA), and obesity hypoventilation, can adversely affect cardiovascular health. Sleep-related breathing patterns, such as Cheyne-Stokes respiration (CSR), may reflect underlying cardiovascular issues. These disorders offer an opportunity to identify predisposing and exacerbating factors of cardiovascular disease and improve long-term risks.

Obstructive Sleep Apnea

In OSA, apneas are defined in adults as the absence of airflow for ≥10 seconds as a result of collapse of upper airway structures, in the setting of continued respiratory effort ( Fig. 71.1 ). Hypopneas are defined in adults as impairment of airflow by >30% and are associated with oxygen desaturation of at least 3% or an EEG arousal. Some insurance programs only allow counting those events associated with a 4% desaturation. Significant pathophysiology is also seen with apnea and hypopnea events, including swings in blood pressure, heart rate, and vascular resistance. The number of apnea and hypopnea events per hour, termed the apnea–hypopnea index (AHI), is used to determine disease severity ( Table 71.1 ). Population studies estimate that more than one in five middle-aged individuals have at least mild disease, with incidence being more prevalent in males. The mechanisms for this airway obstruction are linked to airway compromise, typically at multiple levels: the nose, retropalatal and retroglossal regions, and the pharynx ( Box 71.2 , Fig. 71.2 ). Common factors associated with an increased risk of OSA include male sex, older age, obesity, anatomically small airway, and others ( Box 71.3 ).

TABLE 71.1

Apnea Severity

AHI	Apnea Severity (Events/Hour)
0–4.9	Normal
5–14.9	Mild
15–29.9	Moderate
≥30	Severe

AHI , Apnea-hypopnea index.

Box 71.2

Symptoms of Obstructive Sleep Apnea

• Snoring

• Daytime sleepiness

• Witnessed apneas or gasping events during sleep

• Insomnia

• Hypertension

• Decreased cognition

• Morning headaches

• Sexual dysfunction

Box 71.3

Mechanisms of Obstructive Sleep Apnea

Neural

• Pharyngeal muscular relaxation (neural control, medication or drug effect)

• Diminished response to upper airway load

• Upper airway neural impairment (vibration injury of sensory nerves, neuropathy, neuromuscular junction disease)

Structural

• Infiltration of pharyngeal tissues (adiposity, tumor, mucopolysaccharidoses)

• Tonsillar or adenoid hypertrophy

• Retrognathia or micrognathia

• Macroglossia

• Nasal obstruction

• Chronic mucosal edema (vibration injury allergies, sinusitis, gastroesophageal reflux)

Obstructive Sleep Apnea Link to Hypertension

OSA is associated with a series of vascular changes. During each respiratory event, a gradual increase in peripheral vascular tone and decrease in cardiac output occurs. This is followed by a sudden opening of the airway, and the cardiac output increases against high peripheral vasoconstriction and results in a dramatic increase in blood pressure. Beyond the repetitive respiratory events, other influences may increase systemic blood pressure. Possible mechanisms of causation include intermittent, repeated hypoxia episodes that cause chemoreceptor stimulation, increased sympathetic activation, decreased baroreceptor responsiveness, cardiovascular remodeling, decreased mechanisms of vascular relaxation, and activation of the renin-angiotensin system. Epidemiological studies suggest a moderate link between OSA and hypertension. Analysis of data from the Wisconsin Sleep Cohort shows a linear relationship between severity of the AHI and elevations in 24-hour blood pressure monitoring. Similar relationships were seen in the Sleep Heart Health Study.

OSA can also precede the appearance of hypertension, as evident in the prospective analysis of this group. Clinicians should suspect OSA in patients who have failed to respond to two or more antihypertensive medications and especially in patients lacking a physiological nocturnal dip in blood pressure. This relationship of sleep apnea to hypertension provides therapeutic opportunities. Although nocturnal oxygen therapy does not appear to decrease the elevated blood pressure in patients with OSA, short-term studies have shown that treatment with continuous positive airway pressure (CPAP) decreased sympathetic activity during sleep and modestly improved both nocturnal and daytime blood pressure. These studies are encouraging, and more studies are needed to determine longer term outcomes.

Obstructive Sleep Apnea and Cardiac Disease

Evidence from the Sleep Heart Health Study, a cross-sectional study of >6000 adults, indicates that blood oxygen desaturations correlate with a higher prevalence of cardiovascular disease, independent of other risk factors. The study showed a greater effect for events associated with at least 4% desaturation, but events associated with 3% desaturation also appeared significant. Untreated OSA is associated with an increased incidence of hypertension, myocardial ischemia, infarction, early cardiac death, heart failure, pulmonary hypertension, and arrhythmias (particularly, atrial fibrillation). Although several studies showed the benefits of CPAP, a recent study in the New England Journal of Medicine found that CPAP did not prevent cardiovascular events more than usual care alone. This study was criticized because of the high inclusion of patients who were noncompliant with the therapy, with a cohort average of only 3.3 hours per night of CPAP use. OSA is frequently found in patients with congestive heart failure (~11%–50% have OSA) and is more common in men of any age and in women older than 60 years. OSA can lead to and exacerbate heart failure by repeated oxygen desaturations, increased sympathetic activation, and increased afterload. In addition, increased swings in intrathoracic pressure caused by untreated OSA can also lead to increased myocardial oxygen demand. The greater negative intrathoracic pressure also results in atrial stretch, causing the release of atrial natriuretic peptide, which can result in nocturia. Compounding the effect is an inflammatory response that appears to advance coronary artery disease and elevate C-reactive protein levels, and release of vasoactive substances (e.g., endothelin and nitric oxide synthetase), which leads to endothelial dysfunction.

Cardiovascular diseases can also have a significant impact on sleep. Heart failure can disrupt normal sleep architecture, selectively decreasing REM sleep and leading to REM sleep deprivation. Untreated OSA results in more fragmented, less restorative sleep, due to frequent arousals.