8-isorpostanes – markers for oxidative stress in obstructive sleep apnea patients with systolic dysfunction

Radostina Vlaeva Cherneva,¹ Ognian Borisov Georgiev,¹ Daniela Stoichkova Petrova,¹ Emil Ivanov Manov,² Sylvia Rumenova Ruseva,³ Vanio Ivanov Mitev,³ Julia Ivanova Petrova<sup>4

1</sup>Department of Internal Medicine, Division of Pulmonary Medicine, Medical University of Sofia, Sofia, Bulgaria; ²Department of Internal Medicine, Division of Cardiology, Medical University of Sofia, Sofia, Bulgaria; ³Department of Medical Chemistry and Biochemistry, Laboratory of Synthesis and Analysis of Bioactive Substances, Medical University of Sofia, Sofia, Bulgaria; ⁴Department of Neurology, Medical University of Sofia, Sofia, Bulgaria

Objective: Increased oxidative stress is considered to be an independent risk factor for cardiovascular diseases, but remains disputed in obstructive sleep apnea (OSA). Among oxidative stress markers, isorpostanes are considered to be the most sensitive and specific.
Aims: The aim of the study was to compare urinary isorpostanes in patients with OSA and systolic dysfunction to patients with OSA and preserved ejection fraction (EF) and determine their role as markers for increased oxidative stress and early cardiac damage.
Materials and methods: Urinary 8F2-isorpostanes were measured in 30 patients with OSA and mild systolic dysfunction (EF = 45.7% ± 6.17%) and compared to 15 patients with OSA and normal EF (EF = 60.3% ± 6.3%). Univariate regression analysis was performed to find predictors of left systolic dysfunction. Correlations between 8-isorpostanes, anthropometric, metabolic, and sleep study characteristics were explored. In addition, in 19 patients the effect of bilevel positive airway pressure (BiPAP) therapy was evaluated during a 3 month follow-up. Markers of hemodynamic stress, N-terminal prohormone of brain natriuretic peptide and oxidative stress, measured by 8-isorpostanes were compared before and after the follow-up.
Results: Urinary levels of 8-isorpostanes were significantly higher in the group with mild systolic dysfunction in comparison to the controls with preserved EF (0.149 versus 0.049 pg/µL, P = 0.023). The regression analysis did not define them as predictors for left systolic dysfunction. Their urinary concentration correlated best to the average desaturation index (P = 0.043). Urinary 8-isorpostanes decreased as a result of BiPAP therapy after three months of follow-up (0.164 versus 0.098 pg/µL, P = 0.011).
Conclusion: Urinary isorpostanes are reliable markers for chronic intermittent hypoxia and oxidative stress in OSA patients. They may be of clinical application for the early detection of patients at risk for cardiovascular damage and could help in the monitoring of the restoration of oxidative balance.

Keywords: 8-isorpostanes, oxidative stress, LV systolic dysfunction, OSA