Chest
Volume 140, Issue 2, August 2011, Pages 534-542
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Postgraduate Education Corner
Contemporary Reviews in Sleep Medicine
Obstructive Sleep Apnea: An Emerging Risk Factor for Atherosclerosis

https://doi.org/10.1378/chest.10-2223Get rights and content

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area.

Section snippets

Atherosclerosis: Fundamental Concepts

In the past, atherosclerosis was considered a lipid storage disease. The current view is that atherosclerosis is a complex phenomenon involving chronic inflammation of the vascular wall.7 According to the American Heart Association, there are six identified histologic categories of atherosclerotic lesions.8 Atherosclerotic lesions begin with the fatty streaks composed of macrophages engulfing lipids (foam cells), T lymphocytes, and smooth muscle cells. Further accumulation of lipids results in

Mechanisms Linking OSA to Atherosclerosis

The mechanisms by which OSA may contribute to atherosclerosis progression comprise a cascade of multiple, interrelated, and not completely known mechanisms that are under investigation. Therefore, any attempt to simplify this entangled cascade of mediators may be misleading. Having this potential limitation in mind, Figure 1 summarizes several key mechanisms involved in the atherogenesis induced by OSA. The primary mechanisms that may link OSA to atherosclerosis are consequences of recurrent

Markers of Atherosclerosis in Patients With OSA

Performing a search in PubMed (search terms were “apnea,” “obstructive sleep apnea,” “sleep apnea syndromes,” “atherosclerosis,” “arteriosclerosis,” “intima-media thickness,” “plaque,” “catheterization,” “ultrasound,” “intravascular ultrasound,” and “coronary artery calcium”) for articles that evaluated atherosclerosis in patients with OSA (excluding studies that evaluated only endothelial function, arterial stiffness, and coronary flow), we found 36 studies from 1998 (the year of the first

Future Directions

As suggested by Figure 1, OSA can induce atherosclerosis via multiple mechanisms. As discussed in this review, there is a growing body of evidence from clinical studies and animal models suggesting that OSA contributes to the progression of atherosclerosis. However, the majority of human data is based on cross-sectional studies focused on the carotid bed. It must be stressed that increased markers of atherosclerosis were observed mainly in patients with moderate and severe OSA. These findings

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

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    Funding/Support: This study was funded by the National Institutes of Health [Grants R01 HL80105, 5P50HL084945]; Fundação Zerbini; Fundação de Amparo à Pesquisa do Estado de São Paulo [Research Fellowship Grant 2010/11681-0]; and the American Heart Association [Grant-in-Aid 10GRNT3360001].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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