Obstructive sleep apnea-hypopnea (OSAH) is characterized by recurrent episodes of upper airway collapse and obstruction during sleep. These episodes of obstruction are associated with recurrent oxyhemoglobin desaturation and arousals from sleep. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a term frequently used when this is associated with excessive daytime sleepiness. Despite being a common disease, OSAHS is unrecognized by most primary care physicians (an estimated 80% of OSAHS cases in the United States are not diagnosed).
The upper airway is a compliant tube and is therefore subject to collapse. The majority of patients with OSAHS demonstrate upper airway obstruction, either at the level of the soft palate (nasopharynx) or at the level of the tongue (oropharynx). Recent research indicates that both anatomic and neuromuscular factors are important. Anatomic factors, such as enlarged tonsils, macroglossia, or abnormal positioning of the maxilla and mandible, decrease the cross-sectional area of the upper airway and/or increase the pressure surrounding the airway, both of which predispose the airway to collapse.
Upper airway neuromuscular activity, including reflex activity, decreases with sleep, and this decrease may be more pronounced in patients with OSAHS. Reduced ventilatory motor output to upper airway muscles is believed to be the critical initiating event leading to upper airway obstruction; this effect is most pronounced in patients with an upper airway predisposed to collapse for anatomic reasons.
Central breathing instability has been well established to contribute to the development of central sleep apnea, particularly in patients with severe congestive heart failure (Leung, 2001; Xie, 2002; Xie, 1995). Some evidence indicates that central breathing instability also contributes to the development of OSAHS. First, evidence of upper airway obstruction in the absence of ventilatory motor output (central sleep apnea) has been observed (Badr, 1995). Second, reduction in pharyngeal dilator activity has been associated with periodic breathing (Hudgel, 1987; Warner, 1987; Onal, 1986) and hypocapnia in subjects with evidence of inspiratory flow limitation (IFL) (Badr, 1997). Third, men have been shown to be more susceptible to the development of central sleep apnea and have a decreased responsiveness to carbon dioxide than woman (Zhou, 2000); these findings are consistent with the increased prevalence of OSAHS in men.
Retrospective data indicate that mortality rate is higher in patients with an apnea-hypopnea index [AHI] greater than 20 per hour than in those with an AHI less than 20 per hour. Groups treated with tracheostomy or nasal continuous positive airway pressure (CPAP), however, had no premature deaths. Since nasal CPAP became the standard of treatment, the effect of OSAHS on mortality rates has not been re-examined in a large-scale study.
Systemic hypertension is observed in 50-70% of patients with OSAHS. Several large cross-sectional studies have demonstrated that OSAHS is a risk factor for developing hypertension independent of obesity, age, alcohol intake, and smoking (Hla, 1994; Nieto, 2000). More recently, people in the Wisconsin Cohort Study were prospectively monitored for the development of hypertension. The investigators found a dose-response relationship between the degree of OSAHS and the presence of hypertension 4 years later (odds ratio 2.03 for apnea-hypopnea index [AHI] 5-15 and 2.89 for AHI >15) independent of confounding variables. Several small studies have shown small reductions in blood pressure when nasal CPAP is used in the treatment of OSAHS, though whether it was systolic, diastolic, or mean pressure that was lowered varied by study. No definitive study has demonstrated that treating OSAHS with nasal CPAP lowers the blood pressure on a long-term basis.
Relationship to the metabolic syndrome: The metabolic syndrome is now recognized as an important contributor to the development of atherosclerosis and cardiovascular disease. As defined, a patient with the metabolic syndrome has increased fasting glucose levels, increased blood pressure, lipid abnormalities, and obesity. Evidence of pro-inflammatory and oxidative stress also exists in these patients. Growing evidence suggests that OSAHS may contribute to the metabolic derangement’s that characterise the metabolic syndrome.
- Hypertension: The relationship between OSAHS and hypertension is outlined above.
- Insulin resistance: Multiple studies have shown that patients with OSAHS have increased glucose levels and increased insulin resistance (Ip, 2002; Punjabi, 2002; Punjabi, 2004). The most recent study was from the Sleep Heart Health Study (Punjabi, 2004). In this study of 2000 research subjects, the prevalence of diabetic 2-hour glucose tolerance values rose from 9.3% in the group with an AHI less than 5 to 15% in the group with an AHI greater than 15. The odds ratio for having an abnormal glucose tolerance test was 1.44 (p<0.0001) for the group with an AHI greater than 15; insulin resistance was also highest in this group. Correlations were also noted for the degree of oxygen desaturation at night, indicating that the OSAHS may contribute to insulin resistance as a result of the hypoxemia that occurs with the syndrome.
- Oxidative stress: OSAHS has been associated with increased production of reactive oxygen species (Dyugovskaya, 2002) and other oxidative stress biomarkers (Lavie, 2004).
- Vasodilator responses: OSAHS has been associated with decreased production of nitric oxide (Ip, 2000). Several studies have shown impaired vasodilator responses, as measured by either flow-mediated dilatation (Ip, 2004) or reactive hyperemic blood flow (Imadojemu, 2002) techniques. Impaired flow-mediated dilatation was found to best correlated with the degree of oxygen desaturation in an epidemiologic cohort study (Nieto, 2004).
- Note that for most of these abnormalities, evidence from studies with small numbers of subjects suggests that CPAP partially reverses the metabolic abnormality that is the focus of the study (ie, CPAP decreased insulin resistance, decreased lipid peroxidation, increased vasodilator responses).
A large epidemiologic study (the Sleep Heart Health Study) is presently being conducted to provide more definitive data regarding the relationship between sleep apnea and cardiovascular morbidity. Initial findings from the SHHS indicate that a relationship exists between severe OSAHS and an increased risk of coronary artery disease, congestive heart failure, and stroke (Shahar, 2001). This study is ongoing to determine if the presence of OSAHS is associated with the development of cardiovascular morbidity.
A recent study found that OSAHS was associated with an increased risk of sudden death between the hours of midnight and 6 am, as compared to the general population (sudden death more common between 6 am and noon) (Gami, 2005).
Recent evidence indicates that OSAHS is not an independent risk factor for the development of pulmonary hypertension in the absence of other lung disease, as evidenced by the presence of daytime hypoxemia, hypercapnia, or obstructive airways disease.