Normal Sleep Physiology

The state of sleep is determined by an array of coordinated neuronal processes. Sleep is typically divided into stages based on electroencephalogram (EEG) features, eye movements (electro-oculography), and muscle tone (electromyogram). Stages N1 through N3 are called collectively non-rapid eye movement (NREM) 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 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 physiologic correlates. As we 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 the occurrence of central apnea events and periodic breathing. As the individual becomes drowsy, the heart rate may decrease with a subtle drop in blood pressure. In sustained NREM sleep, parasympathetic regulation of cardiovascular activity predominates, characterized by decreased blood pressure, greater high-frequency heart rate variability, and more regular breathing as compared with quiet wakefulness. In REM sleep, muscle atonia results in a decrease in peripheral vascular tone, and surges in sympathetic output cause increased variability of heart rate, blood pressure, and respiratory rate. Respiratory response to hypercapnia and hypoxia is also reduced. This fluctuation in sympathetic output leads to accelerations and pauses of heart rate and breathing and increased afterload. Thus, in individuals with underlying cardiac disease (e.g., heart failure, conduction disturbances, coronary artery disease) or pulmonary disease, this physiologic vulnerability during REM sleep may increase the risk of arrhythmias, reduced coronary blood flow, hypoxia, and/or obstructive apneas.

Sleep Length and Health

Our society has progressively shortened the amount of time dedicated to sleep. At the beginning of the twentieth century, it is estimated that individuals spent approximately 9 to 10 hours per night in bed. As of 2008, the average working American is sleeping less than 7 hours per night. Sleep deprivation in the short term is associated with greater sympathetic nerve activation, higher blood pressure, increased appetite, lower leptin levels, higher cortisol levels, and increased inflammatory markers. Epidemiologic studies suggest that chronic sleep deprivation is associated with weight gain and obesity. Additionally, individuals who sleep fewer than 5 hours per night are at greater risk for coronary artery disease and development of diabetes, and have a higher mortality risk at 10 years, even after adjustment for other risk factors. Similarly, individuals who sleep longer than 9 hours are also at greater risk for diabetes and cardiovascular events. 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 and increases in inflammation contribute to the development of hypertension, vascular disease, and weight gain. Regardless of the mechanism, sleep duration may impact cardiovascular health.

Sleep-Related Breathing Disorders

Sleep can be disrupted by several disorders (Box 67-1), many of which have not been extensively studied for their relationships to cardiovascular health. Patients presenting to a sleep disorders center 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 impact 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.

Box 67-1 Categories of Sleep Disorders

Circadian rhythm disorders

Sleep-related breathing disorders

Insomnias

Hypersomnias

Parasomnias

Sleep-related movement disorders

Other disorders

Obstructive Sleep Apnea

OSA is defined by repetitive collapse of upper airway structures for 10 seconds or longer, causing cessation of airflow in the setting of continued respiratory effort (Fig. 67-1). These events are commonly accompanied by a decrease in the blood oxygen saturation and a constellation of clinical symptoms (Box 67-2). Significant pathophysiology is also seen with hypopnea events, defined as airflow diminished by more than 30% and oxygen desaturation of at least 4%. The number of apnea and hypopnea events per hour, termed apnea-hypopnea index (AHI), is used to determine disease severity (Table 67-1). Population studies estimate that 1 in 5 individuals has at least mild disease, being more prevalent in males. The mechanisms for both obstructive apnea and hypopnea are linked to airway compromise at one of three levels: the nose, the retroglossal and retropalatal regions, and the pharynx (Box 67-3; Fig. 67-2). Common factors associated with increased risk of OSA include male sex, older age, obesity, anatomically small airway, and others (Box 67-4).