Obstructive sleep apnea and dyslipidemia: from animal models to clinical evidence

Abstract

Lipid metabolism deregulation constitutes the pathogenic basis for the development of atherosclerosis and justifies a high incidence of cardiovascular-related morbidity and mortality. Some data suggest that dyslipidemia may be associated with sleep-disordered breathing, mainly obstructive sleep apnea (OSA), due to alterations in fundamental biochemical processes, such as intermittent hypoxia (IH). The aim of this systematic review was to identify and critically evaluate the current evidence supporting the existence of a possible relationship between OSA and alterations in lipid metabolism. Much evidence shows that, during the fasting state, OSA and IH increase lipid delivery from the adipose tissue to the liver through an up-regulation of the sterol regulatory element-binding protein-1 and stearoyl-CoA desaturase-1, increasing the synthesis of cholesterol esters and triglycerides. In the postprandial state, lipoprotein clearance is delayed due to lower lipoprotein lipase activity, probably secondary to IH-up-regulation of angiopoietin-like protein 4 and decreased activity of the peroxisome proliferator-activated receptor alpha. Moreover, oxidative stress can generate dysfunctional oxidized lipids and reduce the capacity of high-density lipoproteins (HDL) to prevent low-density lipoprotein (LDL) oxidation. In the clinical field, several observational studies and a meta-regression analysis support the existence of a link between OSA and dyslipidemia. Although there is evidence of improved lipid profile after apnea-hypopnea suppression with continuous positive airway pressure (CPAP), the majority of the data come from observational studies. In contrast, randomized controlled trials evaluating the effects of CPAP on lipid metabolism present inconclusive results and two meta-analyses provide contradictory evidence.