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Published ahead of print on May 18, 2005, doi:10.1164/rccm.200503-340OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 5, September 2005, 613-618

A more recent version of this article appeared on September 1, 2005
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Submitted on March 3, 2005
Accepted on May 10, 2005

Early Signs of Atherosclerosis in Obstructive Sleep Apnea

Luciano F Drager1*, Luiz A Bortolotto1, Maria Cecilia Lorenzi2, Adelaide C Figueiredo2, Eduardo M Krieger1, and Geraldo Lorenzi-Filho2

1 Hypertension Unit, Heart Institute (InCor) University of Sao Paulo Medical School, Sao Paulo, Brazil, 2 Sleep Laboratory, Pulmonary Division, Heart Institute (InCor) University of Sao Paulo Medical School, Sao Paulo, Brazil

* To whom correspondence should be addressed. 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 mild-to-moderate and 15 severe OSA patients 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; 3) carotid intima-media thickness, diameter, and distensibility with a high-definition echo-tracking device. All participants were free of hypertension, diabetes, smoking, and were not on any medications. OSA patients were naive to treatment. Main Results: Significant differences existed between controls, mild-to-moderate, and severe OSA patients (apnea-hypopnea index 3.1±0.3, 16.2±1.7, and 55.7±5.9 events per hour, respectively) in pulse wave velocity (8.7±0.2, 9.2±0.2, and 10.3±0.2m/s, P<0.0001), intima-media thickness (604.4±25.2, 580.2±29.0, and 722.2±35.2µm; P=0.004) and carotid diameter (6607.8±126.7, 7152.3±114.4, and 7539.9±161.2µm, 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), while 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: obstructive sleep apnea arterial stiffness carotid remodeling atherosclerosis cardiovascular diseases




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