Obstructive Sleep Apnea and Stroke/IN RESPONSE

COMMENTS AND RESPONSES

TO THE EDITOR: The review on obstructive sleep apnea by Caples and colleagues (1) made for interesting reading, but the authors overlooked the association between obstructive sleep apnea and cerebrovascular disease. The most difficult challenge in understanding the link between hypertension and cardiovascular and cerebrovascular disease is the presence of significant obesity in most adult patients with obstructive sleep apnea. Obesity tends to be differentially distributed in the abdomen and upper body, probably producing much of its effect on sleep apnea through the deposition of fat in the neck, narrowing the pharyngeal airway. Whether this fat distribution pattern rather than obstructive sleep apnea itself actually explains the cardiovascular and cerebrovascular morbidity in affected patients is hotly debated. However, it has been shown beyond reasonable doubt that obstructive sleep apnea contributes to hypertension (1), also offering a potential causal link with stroke.

The strongest epidemiologic evidence indicating the association between obstructive sleep apnea and stroke comes from the Sleep Heart Health Study (2). In this study, in a large sample of 6424 persons who underwent unattended overnight polysomnography at home, even mild to moderate obstructive sleep apnea was significantly associated with development of coronary artery disease, congestive heart failure, and stroke, independent of known cardiovascular risk factors (2).

Another bone of contention regarding the association between obstructive sleep apnea and stroke has been the temporal relationship between the two. It has been argued that stroke may cause residual neuromuscular effects that may lead to obstructive sleep apnea. However, patients with transient ischemic attack (which by definition lacks the permanent sequelae of stroke) have also been shown to have higher prevalence of obstructive sleep apnea when compared with controls (3). These patients were also similar to patients with stroke when such variables as habitual snoring, apnea- hypopnea index, and maximal apnea duration were considered (3).

While the weight of evidence supporting obstructive sleep apnea as an independent risk factor for stroke is suggestive, cross- sectional studies can never give a definitive result about the cause- and-effect relationship. Confirmation awaits the results of large prospective studies evaluating the relationship between the polysomnographic indices of sleep-disordered breathing and stroke. Preliminary data from one such study, published so far only as an abstract (4), support the conclusion that obstructive sleep apnea is a risk factor for the development of stroke or transient ischemic attack, independent of sex, body mass index, diabetes, and hypertension.

Pankaj Madan, MD

University College of Medical Sciences and Guru Teg Bahadur Hospital

Delhi 110095, India

Potential Financial Conflicts of Interest: None disclosed.

References

1. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med. 2005;142:187-97. [PMID: 15684207]

2. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleep-disordered breaching and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163:19-25. [PMID: 11208620]

3. Bassetti C, Aldrich MS. Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep. 1999;22:217-23. [PMID: 10201066]

4. Yaggi K, Kernan W, Mohsenin V. The association between obstructive sleep apnea and stroke [Abstract]. Am J Respir Crit Care Med. 2003;167:A173.

IN RESPONSE: We thank Dr. Madan for these comments about the association between obstructive sleep apnea and stroke. Because of the abundance of data published on obstructive sleep apnea, we limited our discussion of disease associations to those with the highest level of published evidence. The Sleep Heart Health Study has generated large amounts of data and has yielded a number of important publications. However, current evidence does not support a causal role of obstructive sleep apnea in stroke. Rather, studies like the Sleep Heart Health Study suggest that obstructive sleep apnea is prevalent in those who have a history of stroke (1).

As Madan suggests, confidently implicating obstructive sleep apnea in the etiology of cerebrovascular disease will require rigorous, long-term prospective data. Moreover, it has been shown that stroke may actually cause transient centrally mediated apnea. That said, the hemodynamic and hemostatic changes seen in obstructive sleep apnea, along with indirect effects related to the high prevalence of concomitant systemic hypertension, suggest a potentially important role of obstructive sleep apnea in cerebrovascular disease. Available evidence, however, has been conflicting. A prospective cohort study of patients admitted for stroke or transient ischemic attack demonstrated a higher prevalence of obstructive sleep apnea than in the general population (2). This was not the case in a small case-control study of patients with transient ischemic attack, which showed no significant difference in the severity or prevalence of obstructive sleep apnea between groups (3).

Sean M. Caples, DO

Virend K. Somers, MD, PhD

Mayo Clinic

Rochester, MN 55905

Potential Financial Conflicts of Interest: None disclosed.

References

1. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163:19-25. [PMID: 11208620]

2. Parra O, Arboix A, Bechich S, Garcia-Eroles L, Montserrat JM, Lopez JA, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med. 2000;161:375-80. [PMID: 10673174]

3. McArdle N, Riha RL, Vennelle M, Coleman EL, Dennis MS, Warlow CP, et al. Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case-control study in patients with transient ischemic attacks. Stroke. 2003;34:2916-21. [PMID: 14657548]

Copyright American College of Physicians Sep 6, 2005