|Ph.D Student||Itzhaki Sarah|
|Subject||Endothelial Disfunction in Obstructive Sleep Apnea Syndrome|
and the Effect of Treatment
|Department||Department of Medicine||Supervisors||Professor Giora Pillar|
|Dr. Lena Lavie|
|Full Thesis text|
Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete and/or partial airway collapse resulting in frequent episodes of apnea and hypopnea associated with oxygen desaturations. The severity of the syndrome is determined by two cirtieria: a. Apnea-Hypopnea Index (AHI) - Frequency of partial and complete airflow cessation per one hour of sleep. B. oxygen desaturation. OSA is defined when AHI is >10/h. OSA is considered to be a risk factor for cardiovascular disease. At least 2 mechanisms are suggested to explain the OSA-induced cardiovascular complications:
1. Increased activity of sympathetic nerves during sleep.
2. oxidative stress - At the reoxygenation phase a flood of free radicals are produced. These radicals activate an inflamatory response. Concomitantly, nitric oxide availability is compromised. All lead to endothelial dysfunction.
The hypothesis is that endothelial dysfunction will correlate with severity of OSA and that effective treatment may improve endothelial function by decreasing sleep fragmantation and oxidative stress. Initially, endothelial function and oxidative stress were studied in patients with OSA. Then several therapeutic modalities were evaluated, namely nasal continuous positive airway pressure (nCPAP), mandibular advancement splint (MAS), and 3 months of antioxidants which counteract the increased free radicals.
The results of the study confirm a state of endothelial dysfunction, which was correlated with OSA severity. Oxidative stress and endothelial dysfunction were signficantly higher in patients with severe OSA. Vitamin E status in OSA patients was compromised, suggesting increased utilization for antioxidant defense. Also, the significant negative correlation between OSA and endothelial function, was apparent only at low plasma vitamin E levels suggesting a possible role of antioxidant defense on endothelial function. Indeed, antioxidant vitamins supplementation on untreated OSA patients revealed improved endothelial function compared to placebo, in a double blinded controled setting.
OSA treatment led to reversal of oxidative stress and consequently reversal of endothelial dysfunction in correlation with treatment efficiency. Thus, nCPAP, by ameliorating OSA, was found to be the most efficient treatment, followed by MAS, which improved OSA but did not eliminate it. Antioxidants, while not treating OSA were constantly employed in antioxidant defense, possibly accounting for lack of effect on lipid peroxidation, but did improve endothelial function.
In conclusion, this research further proved the relationship between OSA, oxidative stress and cardiovascular sub-clinical pathophysiology. For the first time different treatment modalities were compared under the same setting and antioxidants were offered as a possible treatment venue for otherwise untreated patients.