Investigating the Relationship between Obstructive Sleep Apnoea, Inflammation and Cardio-Metabolic Diseases

Abstract

Obstructive sleep apnoea (OSA) is a prevalent underdiagnosed disorder whose incidence increases with age and weight. Uniquely characterised by frequent breathing interruptions during sleep—known as intermittent hypoxia (IH)—OSA disrupts the circadian rhythm. Patients with OSA have repeated episodes of hypoxia and reoxygenation, leading to systemic consequences. OSA consequences range from apparent symptoms like excessive daytime sleepiness, neurocognitive deterioration and decreased quality of life to pathological complications characterised by elevated biomarkers linked to endocrine-metabolic and cardiovascular changes. OSA is a well-recognized risk factor for cardiovascular and cerebrovascular diseases. Furthermore, OSA is linked to other conditions that worsen cardiovascular outcomes, such as obesity. The relationship between OSA and obesity is complex and reciprocal, involving interaction between biological and lifestyle factors. The pathogenesis of both OSA and obesity involve oxidative stress, inflammation and metabolic dysregulation. The current medical practice uses continuous positive airway pressure (CPAP) as the gold standard tool to manage OSA. It has been shown to improve symptoms and cardiac function, reduce cardiovascular risk and normalise biomarkers. Nonetheless, a full understanding of the factors involved in the deleterious effects of OSA and the best methods to eliminate their occurrence are still poorly understood. In this review, we present the factors and evidence linking OSA to increased risk of cardiovascular conditions.

Impact of Intermittent Hypoxia Related to Obstructive Sleep Apnoea Syndrome on Low-Grade Inflammation in Hypertensive Patients: Potential Implications for Cardiovascular Risk

“…In addition, in hypertensive patients with moderate to severe OSAS, this central role played by intermittent hypoxia in the occurrence of low-grade inflammation could be explained by the fact that unlike hypopnoeas associated with micro-arousals, only hypopnoeas associated with oxygen desaturation appear to be involved in the development of cardiovascular risk factors [63]. Pathophysiologically, this occurrence of low-grade inflammation associated only with obstructive respiratory events inducing intermittent hypoxia may explain the activation of several deleterious mechanisms (induction of oxidative stress, reactive oxygen species production, activation of critical proinflammatory transcription factors, elevated expression of proinflammatory cytokines and chemokines, recruitment and infiltration of proinflammatory M1 macrophages) favouring inadequate activation of the inflammatory cascade [16,17,64]. Thus, in this study, we demonstrated the existence of a particular subtype of hypertensive patients at high cardiovascular risk characterised by the presence of low-grade inflammation induced by high intermittent hypoxia related to moderate to severe OSAS, which justifies systematic screening for this pathology in hypertensive patients with low-grade inflammation [65].…”

“…In the general population, it has been shown that some sleep disorders are associated with the presence of high CRP levels [13][14][15]. Among these sleep disorders, obstructive sleep apnoea syndrome (OSAS) seems to play a central role in the development of this chronic low-grade inflammation [16,17]. Indeed, sleep alterations specific to OSAS (intermittent hypoxia, excessive sleep fragmentation and sleep deprivation) may promote inadequate activation of the inflammatory cascade inducing the occurrence of high CRP levels [16,17].…”

“…Among these sleep disorders, obstructive sleep apnoea syndrome (OSAS) seems to play a central role in the development of this chronic low-grade inflammation [16,17]. Indeed, sleep alterations specific to OSAS (intermittent hypoxia, excessive sleep fragmentation and sleep deprivation) may promote inadequate activation of the inflammatory cascade inducing the occurrence of high CRP levels [16,17]. However, even if this particular relationship between OSAS and high CRP levels has been demonstrated in the general population [18], there are few data on this specific problem in hypertensive patients despite the frequent co-occurrence between these two pathologies [19,20].…”

Gender Differences in Insulin Resistance: New Knowledge and Perspectives

“…The discontinuity of sleep has been compared independently from obesity to the syndrome of sleep apnea (OSAS) and as a consequence of the onset of insulin resistance [105][106][107]. Furthermore, it has been shown that the severity of apneas inversely correlates with insulin sensitivity [108][109][110] while nocturnal ventilation enhanced by c-PAP improves insulin sensitivity [111]. At the basis of the association between insulin resistance, sleep disturbances, and OSAS is hypoxia which occurs during the apnea phases, increases by the discharge of the sympathetic nervous system, simultaneously inhibits insulin secretion, and reduces the availability of glucose to the arrangement of neurons [111].…”

Approach the Patient With Obstructive Sleep Apnea and Obesity

“…OSA-related factors associated with insulin resistance and elevated blood glucose include the degree and duration of hypoxia ( 15 ), particularly during REM sleep ( 16 ), sleep ( 17 ), and circadian clock disruptions ( 18 ), inflammation ( 18 , 19 ), increased sympathetic nervous system activity ( 20 ), increased morning cortisol and lipolysis ( 21 ), and altered GLUT4 translocation ( 22 ). Conversely, diabetes-mediated nerve damage may affect reflexes controlling the upper airway and the central control of respiration, increasing the propensity to develop, or severity of, OSA.…”