Obstructive sleep apnea, immuno-inflammation, and atherosclerosis

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia-reoxygenation. This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin-angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.

Figure 1. Polysomnography

Obstructive sleep apnea (OSA) is diagnosed using polysomnography which consists in several recordings, such as nasal pressure, thoraco-abdominal movements and efforts (pulse transit time), oxygen saturation (SaO₂) and sleep stages. The polysomnographic tracing shows complete cessation of flow (nasal pressure) associated with persistent respiratory efforts and oxygen desaturation at each apneic episode. The FiO₂ nadir occurs with a delay compared to the end of the apneic episode due to circulation time and the measurement technique, and ceases due to micro-arousal-related reopening of the upper airway. The sum of thorax and abdominal movements during apneas equals zero due to opposite phase movements of thorax and abdomen.

Figure 2. Intermittent hypoxia-induced atherosclerosis

Intermittent hypoxia triggers hemodynamic, metabolic and inflammatory alterations interacting with each other and leading to vascular changes resulting in atherosclerosis. Pre-atherosclerotic modifications include increased intima (1) - media (2) thickness with smooth muscle cell hypertrophy (5), elastic fiber alterations (6), mucoid degeneration (7) and leukocyte infiltration (8) in the adventitia (3) and peri-adventitia (4) tunica.