Evidence for Lipid Peroxidation in Obstructive Sleep Apnea

Abstract

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with an increased rate of cardiovascular morbidity, which has been suggested to be related to oxidative stress. The present study investigated the concentration of lipid peroxidation biomarkers in patients with OSA in comparison with nonapneic controls and the effects of treatment with nasal continuous positive airway pressure (nCPAP) on these biomarkers. DESIGN: In Experiment 1, morning plasma levels of the oxidative-stress biomarkers, thiobarbituric reactive substances (TBARS) and peroxides (PD), and of the antioxidant protective enzyme paraxonase-1 (PON1), were measured in OSA patients with and without cardiovascular disease (CVD) and in nonapneic controls after an overnight fasting. The concentrations of the biomarkers were compared between patients and controls and were correlated with respiratory disturbance index (RDI). In Experiment 2, TBARS and PD were measured at hourly intervals during sleep in sleep-apnea patients before and after nCPAP treatment as well as in controls. PATIENTS: In the first experiment, 114 consecutive patients with sleep apnea, 55 without (+OSA/-CVD) and 59 with CVD (+OSA/+CVD), and 30 nonapneic controls were investigated. Nine patients and 6 controls participated in Experiment 2. Five of the patients were also studied 9.3 +/- 3.9 months after nCPAP treatment. MEASUREMENTS AND RESULTS: Morning levels of TBARS and PD were found to be significantly higher in both groups of OSA patients than in controls. The PON1 was lower in +OSA/+CVD patients than in controls and +OSA/-CVD patients, but the difference between the 2 OSA groups bordered on statistical significance. The concentrations of TBARS and PD were significantly positively correlated with RDI (.43, P < .0001 and .36, P < .0002, respectively), while a negative correlation was found between RDI and PON1 activity (-.24, P < .01). Stepwise regression analysis revealed that RDI was an independent significant predictor of all 3 lipid-peroxidation biomarkers. In the second experiment, nocturnal levels of TBARS and PD were significantly higher in sleep-apnea patients than in controls and were significantly lowered by nCPAP treatment. CONCLUSIONS: These results support the existence of an increased state of oxidative stress in OSA and its possible involvement in cardiovascular morbidity.