Is obstructive sleep apnea a circadian rhythm disorder?

Abstract

Obstructive sleep apnea is the most common sleep-related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life and work performance as well as an increased risk of death. Standard treatment seems to have limited effects on cardiovascular and metabolic aspects of the disease, emphasising the need for early diagnosis and additional therapeutic approaches. Recent evidence suggests that the dysregulation of circadian rhythms, processes with endogenous rhythmicity that are adjusted to the environment through various cues, is involved in the pathogenesis of comorbidities.In patients with obstructive sleep apnea, altered circadian gene expression patterns have been demonstrated. Obstructive respiratory events may promote circadian dysregulation through the effects of sleep disturbance and intermittent hypoxia, with subsequent inflammation and disruption of neural and hormonal homeostasis. In this review, current knowledge on obstructive sleep apnea, circadian rhythm regulation, and circadian rhythm sleep disorders is summarised. Studies that connect obstructive sleep apnea to circadian rhythm abnormalities are critically evaluated. Furthermore, pathogenetic mechanisms that may underlie this association, most notably hypoxia signalling, are presented. A bidirectional relationship between obstructive sleep apnea and circadian rhythm dysregulation is proposed. Approaching obstructive sleep apnea as a circadian rhythm disorder may prove beneficial for the development of new, personalised diagnostic, therapeutic and prognostic tools. However, further studies are needed before the clinical approach to obstructive sleep apnea includes targeting the circadian system.

Approach the Patient With Obstructive Sleep Apnea and Obesity

“…The sleep disorders most commonly comorbid with OSA are insomnia and restless legs, and in those with obesity, obesity hypoventilation syndrome (OHS). A circadian rhythm disorder may also be present and OSA may induce abnormal patterns of circadian gene expression and disordered circadian rhythmicity ( 152 ).…”

Obstructive Sleep Apnea and Circadian Rhythms

“…Chronotherapy, the administration of medication or other interventions at specific times of the day based on the individual's circadian rhythm, has been suggested as a promising approach for the management of OSA and related metabolic disorders. [75][76][77][78][79][80][81]…”

Clinical significance of elevated soluble T-cell immunoglobulin and mucin domain 1 and soluble P-selectin in individuals with obstructive sleep apnea-hypopnea syndrome

“…19 The most notable pathophysiological change in patients with OSAHS caused by chronic intermittent hypoxia is the secretion of adhesion molecules and inflammatory mediators. 20 Substantial activation of immune cells in OSAHS leads to a pro-inflammatory cytokine microenvironment. The cytokine IL-6 is released by a variety of circulating blood cells, including macrophages and lymphocytes.…”