Vascular Medicine Vascular Inflammation in Obesity and Sleep Apnea

Background—Unrecognized obstructive sleep apnea (OSA) is highly prevalent in obesity. Both obesity and OSA are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. We investigated directly whether the endothelial alterations that are attributed commonly to obesity are in fact related to OSA. Methods and Results—Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, we quantified the expression of nuclear factor-␬B and nitrotyrosine by immunofluorescence in freshly harvested venous endothelial cells. To evaluate basal endothelial nitric oxide (NO) production and activity, we quantified the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation. Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (nϭ38) than in OSA-free subjects (nϭ33) regardless of central adiposity. Expression of nuclear factor-␬B was greater in obese OSA patients than in obese OSA-free subjects (Pϭ0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased whereas expression of nitrotyrosine and nuclear factor-␬B significantly decreased in OSA patients who adhered to continuous positive airway pressure Ն4 hours daily. Conclusions—Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation , and elevated oxidative stress in obese patients. T he prevalence of obstructive sleep apnea (OSA) increases markedly with increasing adiposity. 1 Fifty to seventy percent of overweight and obese subjects have OSA. 2 Despite such an overwhelming association, OSA remains unrecognized in the vast majority of obese subjects. 3,4 Obesity and OSA are considered independent risk factors for cardiovascular diseases. 5,6 Both obesity and OSA have been associated with the vascular endo-thelial alterations that underlie the development and progression of atherosclerosis. 7–13 Whereas obesity is regarded as a confounding factor in evaluations of vascular endothelial function in patients with OSA, the likely presence of OSA is not routinely considered in evaluations of endothelial function in obesity. Considering the high prevalence of unsuspected OSA among obese subjects, the vascular endothelial alterations that are commonly attributed to obesity may, in fact, be related to OSA. Muscle sympathetic nerve activity is increased when obesity and OSA …