What causes sleep apnea?

Causes of Sleep Apnea

Sleep apnea is primarily caused by repetitive upper airway obstruction during sleep due to a combination of anatomic narrowing, functional neuromuscular deficiencies, and modifiable risk factors, with obesity being the single most important contributor. 1

Primary Pathophysiologic Mechanism

Obstructive sleep apnea (OSA) occurs when the upper airway collapses during sleep while respiratory effort continues, resulting from an imbalance between anatomic airway narrowing and inadequate compensatory neuromuscular responses. 2, 1

• The fundamental problem is upper airway collapsibility during sleep when muscle tone naturally decreases. 1, 3
• Complete cessation of airflow (apnea) or partial reduction (hypopnea) leads to hypoxemia, arousal from sleep, and fragmented sleep architecture. 1, 4

Central sleep apnea results from temporary loss of ventilatory drive due to central nervous system or cardiac dysfunction, commonly seen in congestive heart failure patients. 2

Anatomic Causes

Structural narrowing of the upper airway is the foundational anatomic cause:

• Craniofacial abnormalities including small or recessed jaw (micrognathia), narrow airway structures, and altered facial bone structure significantly increase OSA risk. 2, 1
• Small airway anatomy (Modified Mallampati score 3 or 4) indicates posterior pharyngeal crowding that predisposes to collapse. 2, 5
• Increased neck circumference (≥17 inches in men, ≥15.5 inches in women) reflects soft tissue crowding around the airway. 2
• Macroglossia (enlarged tongue) and tonsillar hypertrophy physically encroach on the pharyngeal lumen. 2, 1

Pediatric-Specific Anatomic Causes

• Adenotonsillar hypertrophy is the primary cause in children, with enlarged adenoids and tonsils significantly larger in OSA patients compared to controls. 2
• Craniofacial syndromes, achondroplasia, Beckwith-Wiedemann syndrome, and trisomy 21 create structural airway compromise. 2

Obesity: The Dominant Modifiable Cause

Obesity is present in 60-90% of adult OSA patients and represents the most important modifiable risk factor. 2, 1

• Adipose tissue deposits around the pharynx mechanically narrow the airway and increase collapsibility. 2, 1
• Systemic inflammatory mediators associated with obesity exacerbate pharyngeal collapse mechanisms. 2
• Weight gain directly induces or worsens OSA, creating a bidirectional relationship where OSA may also predispose to further weight gain. 2, 1

Functional/Neuromuscular Causes

Inadequate upper airway dilator muscle response during sleep fails to maintain patency:

• Impaired mechanoreceptor sensitivity and reflexes that normally maintain pharyngeal patency contribute to collapse. 1, 3
• Reduced muscle tone during sleep, particularly REM sleep, allows anatomically vulnerable airways to collapse. 1
• Respiratory control system instability and altered arousal thresholds affect the ability to restore airway patency. 1, 3

Medications That Cause or Worsen OSA

Opioids are the most significant pharmacologic cause:

• Activate μ- and δ-receptors causing CNS respiratory depression, upper airway muscle relaxation, and tongue collapse. 2
• Induce both obstructive and central apneas, with 75-85% of chronic opioid users having at least mild sleep apnea. 2

Testosterone worsens OSA by increasing apnea-hypopnea index and prolonging hypoxemia time, consistent with higher male prevalence. 2

Benzodiazepines and muscle relaxants (particularly baclofen) may worsen OSA through respiratory depression and muscle relaxation, though evidence is mixed. 2

Medications causing weight gain (atypical antipsychotics, certain antidepressants, anticonvulsants) indirectly cause or worsen OSA. 2

Demographic and Non-Modifiable Causes

Male sex confers 2-3 times higher risk than females, related to differences in fat distribution, hormonal influences, and upper airway anatomy. 2, 1

Aging increases both prevalence and severity:

• OSA occurs in up to 70% of older men and 56% of older women. 2
• Age-related changes in upper airway anatomy, muscle function, and respiratory control contribute. 2

Postmenopausal status in women increases risk, suggesting protective hormonal effects in premenopausal women. 2

Genetic factors and family history influence predisposition through inherited craniofacial structure and obesity tendency. 2, 1

Race/ethnicity affects risk independent of obesity:

• Asian populations (particularly East Asian) have elevated risk at lower BMI levels due to craniofacial differences. 2
• African Americans and Hispanics show higher prevalence. 2, 1

Medical Comorbidities as Contributing Causes

Untreated hypothyroidism causes myxedematous infiltration of upper airway tissues. 2

Cardiovascular disease (heart failure, atrial fibrillation) is both a consequence and contributor, particularly for central sleep apnea. 2

Type 2 diabetes shows bidirectional relationship with OSA, possibly through insulin resistance mechanisms. 2

Resistant hypertension (requiring ≥2 medications) is strongly associated with OSA. 2

Clinical Pitfalls

• Over 80% of sleep apnea remains undiagnosed, particularly in women due to provider bias toward screening men. 2
• Elderly OSA patients may not be obese, unlike younger patients where obesity is nearly universal. 2
• Children with OSA are frequently misdiagnosed with ADHD when behavioral symptoms are actually due to sleep fragmentation. 2
• Absence of reported symptoms (particularly sleepiness) does not exclude OSA—objective findings are more reliable than subjective complaints. 2