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UBC Theses and Dissertations

Oxidative stress and cellular adhesion molecules in obstructive sleep apnea Urbanetto Peres, Bernardo


Background: Obstructive Sleep Apnea (OSA) is the most common respiratory disorder during sleep. OSA is an independent risk factor for developing cardiovascular diseases (CVD). Although risk is increased, it is still challenging to identify which patients will develop CVD as standard disease metrics are not that helpful. Circulating biomarkers could be useful to risk stratify OSA patients. However, current evidence in this regard is limited. Oxidative stress biomarkers and cellular adhesion molecules might be particularly useful as these are elevated in OSA patients and in patients with CVD. Thesis Objectives: 1. Identify and summarize the existing evidence on prognostic biomarkers in OSA (Chapters 1-2). 2. Evaluate the association between cellular adhesion molecules, oxidative stress markers and OSA (Chapters 3-4). 3. Evaluate whether levels of cellular adhesion molecules and oxidative stress markers predict incident CV events in an OSA-cohort (Chapter 5-6). 4. Discuss the implications and future directions of the findings (Chapter 7). Methods: Adult patients (>19 years old) referred for suspected OSA to the University of British Columbia Hospital Sleep Disorder Laboratory for inpatient polysomnography (PSG) were studied. Fasting blood (15 ml) was collected on the morning after PSG, and plasma was stored in a -80C freezer. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin (endothelial selectin) were assessed. Incidence of CV events was assessed by deterministic linkage through Popdata-BC. Results: OSA severity was independently associated with higher circulating E-selectin and 8-isoprostane levels. In patients with suspected OSA, ICAM-1 was an independent predictor of incident CV events (OR=4.12 95% CI 1.47-11.55). In moderate to severe OSA patients, E-selectin was independently associated with CV events (OR = 4.07 95% CI 1.06 – 15.61), but not in patients without OSA. Oxidative stress markers were not associated with incident CV events. Conclusion: E-selectin and 8-isoprostane were independently associated with OSA. Cellular adhesion molecules such as ICAM-1 and E-selectin were associated with incident CV events and might be promising markers in CV disease prediction in OSA. Oxidative stress markers were not associated with incidence of CV events.

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