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Translational Approaches to Understanding Metabolic Dysfunction and Cardiovascular Consequences of Obstructive Sleep Apnea

Drager, L., Polotsky, V., O'Donnell, C., Cravo, S., Lorenzi-Filho, G., Machado, B.

Am J Physiol Heart Circ Physiol 2015;309(7):H1101-11. (Epub 2015 Jul 31)

PMID: 26232233

        Obstructive Sleep Apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction, and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant pathophysiological disturbance in OSA-intermittent hypoxia.

         Despite several limitations in translating data from animal models to the clinical arena, significant progress has been made in our understanding of how OSA confers increased cardiovascular risk. It is clear now that the hypoxic stress associated with OSA can elicit a broad spectrum of pathological system events including sympathetic activation, systemic inflammation, impaired glucose and lipid metabolism, and endothelial dysfunction, among others. This review provides an update of the basic, clinical, and translational advances in our understanding of the metabolic dysfunction and cardiovascular consequences of OSA and highlights the most recent findings and perspectives in the field.

Perspectives: The potential effects of OSA on circadian variability sleep structure, sleep fragmentation, and deprivation have received little attention and deserve further investigation. Much progress has been made with respect to hypertension, there is a need to systematically explore the impact of OSA treatment on the progression and regression of atherosclerosis. Animal models of OSA and cell culture provided evidence that OSA promotes vascular dysfunction and premature atherosclerosis via multiple pathways, including impaired metabolism and inflammation. Hypoxic mice presented more severe dyslipidemia and atherosclerosis lesions. Emergent evidence suggests that nonalcoholic fatty liver disease (NAFLD) is independently associated with OSA, and so far, CPAP had no effect on liver enzymes. Relationships between OSA and dyslipidemia have not yet been fully characterized. Data from the Sleep Heart Health Study showed that fasting levels of total serum cholesterol and triglycerides directly correlated and HDL cholesterol levels inversely correlated with the severity of OSA. The prevalence of OSA frequently surpasses 50% in patients with cardiovascular diseases. More than a common comorbidity, OSA triggers several mechanisms that impact cardiovascular risk.

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