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Obstructive Sleep Apnea

Sean M. Caples, DO; Apoor S. Gami, MD; and Virend K. Somers, MD, PhD
[+] Article and Author Information

From the Mayo Clinic, Rochester, Minnesota.


Grant Support: By National Institutes of Health grants HL61560, HL65176, HL73211, HL 70302, M01-RR00585 and the Dana Foundation. Dr. Caples is supported as a Mayo Foundation Scholar, and Dr. Gami is supported by the Dr. Ralph and Marian C. Falk Medical Research Trust Fellowship for Clinical Research Training.

Potential Financial Conflicts of Interest: Consultancies: V.K. Somers (Resmed, Respironics).

Requests for Single Reprints: Virend K. Somers, MD, DPhil, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail, somers.virend@mayo.edu.

Current Author Addresses: Drs. Caples, Gami, and Somers: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.


Ann Intern Med. 2005;142(3):187-197. doi:10.7326/0003-4819-142-3-200502010-00010
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Inconsistencies in definitions of disease and sampling biases contribute to the wide range of prevalence of obstructive sleep apnea reported in the literature. The best evidence of the pervasiveness of obstructive sleep apnea derives from pooled data from 4 large prevalence studies that used similar in-laboratory monitoring, diagnostic criteria, and sampling methods. On the basis of these data, it is estimated that 1 of 5 white adults with an average body mass index of 25 to 28 kg/m2 has an apnea–hypopnea index of 5 or greater (at least “mild disease”) and 1 of 15 has an apnea–hypopnea index of 15 or greater (at least “moderate disease”) (48). Up to 5% of adults in western countries probably have the obstructive sleep apnea syndrome (7). Data on the natural history of sleep-disordered breathing from the Wisconsin Sleep Cohort suggest that factors important in progression of disease include baseline obesity, older age, and the presence of snoring (7)(Figure 1).

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Figure 1.
Mean apnea–hypopnea index at baseline and the increase 8 years later in 282 participants in the Wisconsin Sleep Cohort.

Subgroup analysis showed greater progression of disease in patients who were obese, 45 to 60 years of age, or habitual snorers at baseline. Sex did not correlate with disease progression. Data obtained from reference 7. BMI = body mass index.

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Figure 2.
Pathophysiologic events in obstructive sleep apnea.

Representative polysomnographic data are shown. In legend, numbers in parentheses correspond to numbers in the figure. Sleep onset is heralded by electroencephalography (EEG) wave slowing (1) and a reduction in minute ventilation (2). In persons with obstructive sleep apnea, diminution or cessation of airflow results from progressive collapse of the upper airway (3), which leads to reduced oxyhemoglobin saturation (O2 saturation) (4) and consequent stimulation of peripheral chemoreceptors, the carotid bodies (5). Hypercapnic effects are not shown. Chemoreflex stimulation acts through the central nervous system (6) to increase sympathetic neural activity (SNA), which is recorded peripherally as microneurographic bursts (7). Blood pressure (8) increases as the apnea progresses. The exact mechanisms are not clear, but the apnea terminates with a central nervous system arousal, which is marked by an increase in electroencephalographic wave frequency (9). The far right portions of the tracings (10) show the cascade of events resulting from the arousal from sleep and restored upper-airway patency, including temporary supranormal ventilation, normalization of oxyhemoglobin saturation, and instantaneous suppression of sympathetic nervous activity. During resumption of ventilation, sympathetic outflow is inhibited by afferents originating from thoracic mechanoreceptors, which synapse in the brainstem (11). A subset of patients show signs of the diving reflex, in which marked bradycardia accompanies the vascular sympathetic excitation (not shown here). ECG = electrocardiogram.

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Figure 3.
Changes in body fat after long-term treatment with continuous positive airway pressure (CPAP).

Visceral fat was reduced in patients with sleep apnea who used CPAP for 6 months, regardless of whether body weight decreased. Data obtained from reference 71.

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Figure 4.
Obstructive sleep apnea and risk for hypertension.

Each increment in the severity of sleep apnea, represented by the apnea–hypopnea index, confers an increase in the odds ratio for developing hypertension. Data obtained from reference 72.

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Figure 5.
Left ventricular ejection fraction at baseline and at 1 month in persons with congestive heart failure and obstructive sleep apnea who received continuous positive airway pressure(CPAP)(right) or no treatment (left).

In patients in the treatment group, the ejection fraction increased from a mean of 0.25 ± 0.028 to 0.338 ± 0.024 (  < 0.001). The left ventricular ejection fraction did not change significantly in the control group. Reproduced from reference 77: Kaneko Y, Floras JS, Usui K, Plante J, Tkacova R, Kubo T, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003;348:1233-41 with permission from the Massachusetts Medical Society.

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Obstructive Sleep apnea and stroke
Posted on February 6, 2005
Pankaj Madan
University College of Medical Sciences and Guru Teg Bahadur Hospital
Conflict of Interest: None Declared

The review on obstructive sleep apnea (OSA) by Caples et al (1) made an interesting reading but the authors have overlooked the association between the OSA and cerebrovascular disease. So, I thought it would be pertinent to add some information regarding the same.

The most difficult challenge in understanding the link between the hypertension, cardiovascular and cerebrovascular disease is the presence of significant obesity in most adult patients with OSA, and the tendency for this 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. Now, whether this fat distribution pattern is actually the explanation for the cardiovascular and cerebrovascular morbidity in patients with OSA rather than the OSA itself is hotly debated. While, it has been shown beyond reasonable doubt that OSA contributes to hypertension (1) and this also offers a potential causal link with stroke.

The strongest epidemiological evidence indicating the association between OSA and stroke comes from Sleep Heart Health study. In this study, in a large sample of 6424 individuals who underwent unattended overnight polysomnography at home, it was seen that even mild to moderate OSA 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 between the association between the OSA 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 OSA. However, it has been seen that patients with TIA (which by definition lack the permanent sequelae of stroke) also had higher prevalence of OSA when compared to controls and they were similar to stroke patients when variables like habitual snoring, AHI, maximal apnea duration were taken into consideration (3).

While the weight of evidence supporting OSA as an independent risk factor for stroke is suggestive, cross sectional studies can never give a definitive result regarding the cause and effect relationship. Confirmation awaits the 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, supports the conclusion that OSA is a risk factor for the development of stroke or transient ischemic attack (TIA), independently of sex, body mass index, diabetes, and hypertension (4).

Reference:

1. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med 2005 Feb 1;142(3):187-97.

2. Shahar E, Whitney C, Redline S, Lee ET, Newmann AB 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

3. Basseti C, Aldrich M. Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep 1999; 22:217-23

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

Conflict of Interest:

None declared

In Response
Posted on May 4, 2005
Sean M. Caples
Mayo Clinic
Conflict of Interest: None Declared

To the Editor,

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

As alluded to by Madan, confidently implicating OSA 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 OSA, along with indirect effects related to the high prevalence of concomitant systemic hypertension suggest a potentially important role of OSA in cerebrovascular disease. Available evidence, however, has been conflicting. A prospective cohort study of patients admitted for stroke or transient ischemic attack (TIA) demonstrated a higher prevalence of OSA than in the general population (2). This was not the case in a small case-control study of patients who had TIA, showing no significant difference in the severity or prevalence of OSA between groups (3).

Sean M. Caples, D.O. Caples.Sean@mayo.edu Virend K. Somers, M.D., Ph. D. Mayo Clinic Rochester, MN, USA

References

1. Shahar E, Whitney CW, Redline S, 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(1):19-25. 2. PARRA O, ARBOIX A, BECHICH S, 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(2):375-380. 3. McArdle N, Riha RL, Vennelle M, 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(12):2916-2921.

Conflict of Interest:

None declared

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