What are the causes and risk factors of obstructive sleep apnea (OSA)?

Etiology of Obstructive Sleep Apnea

Obstructive sleep apnea results from repetitive upper airway collapse during sleep due to a complex interaction between anatomical narrowing of the pharyngeal airway and inadequate compensatory neuromuscular responses, with obesity being the single most important modifiable risk factor. 1

Primary Pathophysiologic Mechanism

The fundamental pathophysiology involves obstruction of the upper airway manifested by greatly diminished or absent airflow despite continued respiratory effort 2. This occurs when:

• The pharyngeal and/or laryngeal airway collapses during sleep due to elevated mechanical loads exceeding compensatory neuromuscular responses 2, 3
• Marked swings in intrathoracic pressure occur during obstructive events 4
• Episodes result in hypoxemia, autonomic nervous system changes, and sleep fragmentation through recurrent arousals 2

Anatomical Risk Factors

Structural abnormalities that narrow the upper airway are fundamental predisposing factors:

• Small upper airway lumen is the primary anatomical contributor 5, 3
• Craniofacial anomalies including micrognatia and macroglosia significantly increase risk 2, 1
• Adenotonsillar hypertrophy is the principal cause in children 2, 1
• Pharyngeal fat deposits from obesity decrease pharyngeal patency and increase critical closing pressure 2

Major Modifiable Risk Factors

Obesity stands as the most important and prevalent risk factor, present in 60-90% of OSA patients 1:

• A 10% increase in body weight within 4 years produces a six-fold increase in odds ratio for developing OSA 2
• Weight gain has greater influence on increasing apnea-hypopnea index (AHI) than weight loss has on decreasing it 2
• The effect of body weight is significantly greater in males than females 2

Other modifiable factors include:

• Certain medications (opioids, muscle relaxants, testosterone) that worsen OSA 1
• Fluid retention states 5
• Smoking 5

Non-Modifiable Demographic Risk Factors

Male sex confers 2-3 times higher prevalence than females 1:

• OSA is much more common in postmenopausal than premenopausal women 2
• Prevalence increases with aging in both genders 2

Age is a critical factor:

• In older adults, OSA occurs in up to 70% of men and 56% of women 2
• Elderly patients may not necessarily be obese despite having OSA 2

Ethnicity influences risk:

• Higher prevalence among Asians compared to Caucasians in older populations 2
• African Americans, Hispanics, and people of East Asian origin have increased predisposition 1

Genetic factors contribute to individual susceptibility 1, 5

Functional and Neuromuscular Factors

Defects in compensatory mechanisms contribute significantly:

• Inadequate response of upper airway dilator muscles during sleep fails to maintain patency 1, 6
• Increased upper airway collapsibility during sleep represents a key functional abnormality 1, 6
• Unstable respiratory control (loop gain) contributes to breathing instability 6, 5
• Low arousal threshold affects the ability to terminate obstructive events 6, 5
• Small lung volume reduces tracheal traction on the upper airway 5, 3

Chronic OSA causes pathological transformation:

• Intermittent hypoxemia, inflammation, increased sympathetic tone, and mechanical stress transform muscle fibers in the upper airway 7
• This results in reduced muscle mass and strength, perpetuating the condition 7

Associated Comorbid Conditions

Several conditions are both risk factors and consequences of OSA:

• Heart failure, atrial fibrillation, and stroke are more common in OSA patients and may worsen the condition 2, 4
• Hypothyroidism is often associated with OSA, particularly in women 2
• Arterial hypertension (often difficult to control) is strongly linked 2
• Diabetes mellitus and insulin resistance show association with OSA 2

Clinical Pitfalls

Common diagnostic errors to avoid:

• Do not assume elderly OSA patients must be obese - older adults with OSA may have normal weight 2
• Consider OSA in males with nocturia - this symptom is commonly misattributed to prostatic hypertrophy rather than OSA 2
• Recognize that daytime sleepiness may be absent in young children despite significant OSA 2
• Evaluate for OSA in patients with unexplained syncope, especially those with cardiovascular risk factors 4