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Early Signs of Atherosclerosis in Obstructive Sleep Apnea

Hypertension Unit and Sleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil

Correspondence and requests for reprints should be addressed to Luciano F. Drager, M.D., Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Enéas Carvalho de Aguiar, 44, CEP 05403-900 São Paulo, Brazil. E-mail: luciano.drager{at}incor.usp.br

Background: Obstructive sleep apnea (OSA) is associated with several cardiovascular diseases. However, the mechanisms are not completely understood. Recent studies have shown that OSA is associated with multiple markers of endothelial damage. We hypothesized that OSA affects functional and structural properties of large arteries, contributing to atherosclerosis progression. Methods and Measurements: Twelve healthy volunteers, 15 patients with mild to moderate OSA, and 15 with severe OSA matched for age, sex, and body mass index were studied by using (1) full standard overnight polysomnography; (2) carotid-femoral pulse wave velocity with a noninvasive automatic device; and (3) a high-definition echo-tracking device to measure intima-media thickness, diameter, and distensibility. All participants were free of hypertension, diabetes, and smoking, and were not on any medications. Patients with OSA were naive to treatment. Main Results: Significant differences existed between control subjects and patients with mild to moderate and severe OSA (apnea–hypopnea index, 3.1 ± 0.3, 16.2 ± 1.7, and 55.7 ± 5.9 events/hour, respectively) in pulse wave velocity (8.7 ± 0.2, 9.2 ± 0.2, and 10.3 ± 0.2 m/second; p < 0.0001), intima-media thickness (604.4 ± 25.2, 580.2 ± 29.0, and 722.2 ± 35.2 µm; p = 0.004), and carotid diameter (6,607.8 ± 126.7, 7,152.3 ± 114.4, and 7,539.9 ± 161.2 µm; p < 0.0001). Multivariate analyses showed that the apnea–hypopnea index correlated independently with pulse wave velocity and intima-media thickness variability (r = 0.61, p < 0.0001, and r = 0.44, p = 0.004, respectively), whereas minimal oxygen saturation correlated with the carotid diameter (r = –0.60, p < 0.0001). Conclusions: Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis. All vascular abnormalities correlated significantly with the severity of the OSA, which further supports the hypothesis that OSA plays an independent role in atherosclerosis progression.

Key Words: arterial stiffness • atherosclerosis • cardiovascular diseases • carotid remodeling • obstructive sleep apnea

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