B68-03 Measurement of Biochemical and Physiological Markers of Vascular Function in Sleep Apnea Patients

Background Obstructive sleep apnea (OSA) is characterized by arousals and oxygen desaturation events caused by a variety of factors including obesity and loss of respiratory drive. Systemically, oxygen delivery is tightly regulated by endothelial function including the production of nitric oxide (NO). Endothelial function can be compromised by poor NO production by the endothelial form of Nitric Oxide Synthase (eNOS) or NO consumption by oxidative stress. Conversely, inflammation can increase NO production by stimulating inducible NOS (iNOS) synthesis, while also increasing oxidative stress. We predict that, through these mechanisms, OSA causes worsening endothelial function. Methods To investigate, pre- and post-sleep plasma samples were collected from 38 subjects with OSA and assessed for inflammation (IL-6, TNFR1, TNFR2), altered NO production (nitrite and nitrate) and oxidative stress (8-isoprostane). The collected biomarkers were correlated with OSA severity as defined by the American Academy of Sleep Medicine recommended criteria: mild OSA (apnea-hypopnea index [AHI] = 5-15 events/hr; n = 11), moderate(AHI = 15-30 events/hr; n = 19) or severe (AHI ≥30 events/hr; n = 9) and the reactive hyperemia index (RHI), a metric of endothelial dysfunction. IL-6, TNFR1, TNFR2, and 8-isoprostane were measured by ELISA, while NO was assessed by chemical reduction and chemiluminescence. Results Post sleep TNFR1 and TNFR2 were correlated (R2=0.60) consistent with inflammatory activation. Detectable levels of 8-isoprostane, which are not seen in normal, healthy populations, were found in all subjects indicating oxidative modification of lipids. In subjects with severe OSA, TNFR1 was negatively correlated with nitrite (R2=0.19), and AHI was negatively correlated with RHI (R2=0.40). AHI was positively correlated with nitrite (R2=0.45) in the mild group, but this correlation was not seen in the severe group. Overnight we observed a significant decrease in nitrate (75.8±56.0µM vs 47.6±32.1µM p < 0.01), nitrite (413.2±380.9nM vs 282.9±145.3nM p = 0.022), 8-isoprostane(5.2±7.2pg/mg vs 2.6±4.3pg/mg p = 0.047) and significant increases in TNFR1(12.1±4.7pg/mg vs 13.4±6.0pg/mg p = 0.041) and TNFR2(27.2±9.0pg/mg vs 30.7±11.1pg/mg p = 0.019). Conclusion The decrease in oxidative markers may be due to lower metabolic rate while sleeping however the TNFR1/2 increase does indicate inflammatory activation during sleep apnea. These studies aid in demonstrating a relationship between sleep apnea and decline in vascular function.