Oxidized-LDL and Paraoxonase-1 As Biomarkers of Coronary Artery Disease in Patients with Sleep-Disordered Breathing

F.S.      Hackenhaar; D.      Martinez; T.M.      Medeiros; C.      Klein; P.V.G.      Alabarse; M.V.      Wainstein; S.C.      Goncalves; M.S.      Benfato

doi:10.2174/092986712802884312

Abstract

Coronary Artery Disease (CAD) and Objectives: Sleep Disordered Breathing (SDB) are both oxidative stress disorders. SDB intermittent hypoxia induces oxidative stress, and reduces NO• availability, causing endothelial dysfunction. Low-density lipoprotein (LDL) peroxidation is involved in atherosclerosis, and is reported in SDB. Oxidized LDL (ox-LDL) and malondialdehyde (MDA) are lipid peroxidation markers. High-density lipoprotein (HDL) presents antiatherosclerotic properties related to paraxonase-1 (PON-1) activity. PON-1 hydrolyseyses lipid peroxides as ox-LDL. This study compares the relationship of HDL and PON-1, the lipid peroxidation markers ox-LDL and MDA, and 8-OHdG DNA damage marker in the association of SDB and CAD. Design and Methods: 29 controls and 27 cases with CAD (defined as > 30% coronary narrowing) patients were included. The apnea-hypopnea index (AHI), and several lipid and oxidative stress parameters were measured in these patients. Results: AHI is increased in CAD patients, and PON-1 activity and HDL levels are decreased. Regression analyseyses showed that lower PON-1 activity and higher ox-LDL levels are important CAD predictors, compared to HDL or MDA levels and present an age-dependent increase. Nitrites and nitrates, indirect NO• markers, are positive vs correlated with PON-1 and are negatively correlated to ox-LDL. SDB is not correlated to PON-1 activity decrease or ox-LDL increase. AHI is inversely correlated to HDL levels. Conclusions: These results indicate that PON-1 and ox-LDL are important predictors of CAD, however they may not be directly related to SDB.

Keywords: Atherosclerosis, HDL, LDL, NO•, obstructive sleep apnea, ox-LDL, PON-1, Coronary Artery Disease (CAD), Sleep Disordered Breathing (SDB), endothelial dysfunction