Sleep-disordered breathing is a common finding; approximately one in four men and one in 10 women suffer from five or more events (either apnea or hypopnea) during every hour of sleep.1 More and more, we are seeing links between sleep disturbances and a wide variety of health disorders. Often these issues affect the cardiovascular system in the form of diseases such as hypertension and congestive heart failure, but other systems are affected as well: Consider asthma, COPD, gastroesophageal reflux disease, and renal disease among others.2 This article will explore the links between sleep and comorbidity and consider some of the recent published research in this area.

Systemic Hypertension

Sleep usually gives the body’s systems time to rest and reset. During sleep, the cardiovascular (CV) system takes part in this by reducing the heart rate, lowering the arterial blood pressure, and dropping the cardiac output. This normal occurrence is referred to as dipping.2,3 When obstructive sleep apnea (OSA) or central sleep apnea (CSA) occurs, these resting mechanisms are interrupted and may have a long-lasting impact on the health of the CV system. With OSA and CSA problems, the patients who do not have the drop in blood pressure are referred to as “non-dippers” (some 20% to 40% of patients with OSA fall into this category).

There is ongoing debate about the possibility that OSA can bring about hypertension: Animal studies seem to support this, but it is not as clear in human studies. However, non-dippers with OSA have been shown to have increased rates of stroke and have a worse overall prognosis when compared to dippers with OSA. The Wisconsin Sleep Cohort was a prospective study that started collecting data on people employed by the state of Wisconsin. Some data was collected annually, and overnight polysomnography was performed every 4 years. Researchers found that individuals with a higher apnea-hypopnea index had an increased risk of hypertension in the follow-up visit 4 years later, even after factoring in body mass index, sex, circumference of the waist and neck, and use of alcohol or cigarettes.4 Finally—in the most recent published guidelines from the National Heart, Lung, and Blood Institute (NHLBI) committee on hypertension (the National High Blood Pressure Education Program Coordinating Committee)—sleep apnea is at the top of the list of identifiable causes of hypertension (these guidelines are often referred to as the JNC 7 Report).5

Pulmonary Hypertension

Pulmonary hypertension (PHT) may be another problem that occurs in patients with sleep apnea. The prevalence of PHT has been reported to be between 15% and 53% in patients with sleep apnea. During recurring airflow obstruction and subsequent hypoxia, the pulmonary arteries react with vasoconstriction, which increases pulmonary pressure. As the night progresses and subsequent deeper and longer hypoxic episodes occur, pulmonary pressures show a proportional upward trend. Pulmonary hypertension has not been widely studied, however, and in the studies that are available, only about 10% of the patients have been women. This is an area that needs more investigation.3

Congestive Heart Failure

Studies that have looked at patients with congestive heart failure (CHF) and OSA have found that ventricular function is probably affected by a combination of changes, including the swings in negative thoracic pressure, recurring hypoxemia, and increased sympathetic tone associated with apnea. When patients with cardiomyopathy were treated with nasal continuous positive airway pressure (CPAP), both ejection fraction and patient symptoms improved. For those CHF patients who exhibit CSA in the middle of the crescendo/decrescendo pattern that occurs in Cheyne-Stokes respiration, studies have shown that successful treatment of their apnea appears to improve sleep quality and ejection fraction, and may improve survival. The treatment regime includes optimized medical treatment for heart failure as the leading strategy followed by use of nasal CPAP. Supplemental oxygen reduces the apnea-hypopnea index and degree of desaturation in patients who have CHF and apnea/Cheyne-Stokes respiration, but oxygen alone has not been shown to improve the ejection fraction or survival.2

In a study published in 2003,6 researchers examined the effect of 1 month of CPAP to treat severe sleep apnea in patients who also had congestive heart failure. The congestive heart failure was defined as having an ejection fraction of less than 45% and the apnea-hypopnea indices were between 37 and 45. The 24 patients who participated in the study received either optimal medical treatment alone or CPAP plus optimal medical treatment. At the end of the month, those who received both treatments had a significant increase in ejection fraction, moving from 25% to 34% (P <.001), while those on the single treatment approach did not have a significant change. The CPAP group also had a 10 mm Hg drop in systolic blood pressure.

Arrhythmias

Patients with obstructive sleep apnea show a typical pattern in the heart rate, with the heart slowing at the onset of apnea followed by an increased rate as the apnea ends. A prospective study of 45 patients with a recent diagnosis of OSA evaluated their heart rhythms using an 18-hour Holter monitor recording immediately after the OSA diagnosis was made, then again after 2 to 3 days of CPAP treatment. Eight of the 45 were found to have significant issues with arrhythmias, including ventricular tachycardia, atrial fibrillation, supraventricular tachycardia, and second or third degree heart block in the first Holter recording. After CPAP treatment, only one patient continued to have issues with arrhythmias.7

Gastroesophageal Reflux Disease (GERD)

The lower esophageal sphincter (LES) is the primary structure that blocks reflux. This sphincter normally relaxes during swallowing, but when it relaxes otherwise—a situation called transient LES relaxation—it accounts for some 63% to 100% of gastric esophageal reflux (GER) events. Nighttime occurrence of GER produces such symptoms as multiple awakenings, substernal discomfort, indigestion, heartburn, regurgitation, sour or bitter taste, coughing, and choking. Nighttime GER also has been strongly associated with asthma symptoms, sleep-related laryngospasm, and OSA.2,8

Asthma

Nighttime asthma symptoms are used to evaluate the severity of asthma when initiating therapy and to assess control of asthma symptoms.9 These symptoms include dyspnea, cough, or wheeze. Symptoms increase in the night due to increased activity in the parasympathetic system, increased airway inflammation, changes in the glucocorticosteroid receptors, and an increase in leukotrienes.8 As mentioned earlier, when GER occurs at night, often asthma symptoms will increase; and sleep will be disturbed due to both problems. Normal circadian swings in airway function reveal the highest airflow occurring in the late afternoon and the lowest around 4 am. Treatment for nighttime asthma symptoms includes inhaled cortico-steroids, which affect fluctuations in airway tone related to circadian rhythms.2 Long-acting bronchodilators also help reduce nighttime symptoms along with antireflux actions (such as raising the head of the bed) and medications to reduce GERD.

COPD

Patients with COPD frequently complain of insomnia and have reduced total sleep time, prolonged sleep latency, and decreased periods of slow wave and rapid eye movement (REM) sleep.2,8 As with individuals with asthma, airflow is also worse during the early morning hours in COPD patients. In addition, coughing or dyspnea at night will bring changes in the normal sleep patterns, including increased arousals from deeper sleep and decreased non-REM sleep (stages 3 and 4). Significant drops in oxygen saturation during sleep may occur in cases of moderate to severe COPD, and the deepest drops on SaO2 occur during REM sleep. Increased upper airway resistance and increased ventilation/perfusion mismatching also contribute to hypoxemia. REM sleep brings on decreases in skeletal muscle tone and minute ventilation as irregular breathing combines with reduced respiratory muscle effort and decreased tidal volume. Patients with both COPD and sleep apnea (referred to as overlap syndrome) should be treated with CPAP or bi-level positive airway pressure (bi-level PAP). If indicated, oxygen should be added to the CPAP or bi-level PAP system. However, studies show that treating patients who have overlap syndrome only with oxygen may increase apnea duration while only bringing a partial recovery of adequate oxygenation (as determined by SpO2 levels) and may result in significantly worse nighttime hypoxemia.2

Renal Disease

Sleep disorders are frequently found in patients with end-stage renal disease with several studies finding the incidence as high as 80%, and excessive daytime sleepiness is found in approximately 50% of these patients.8 Of the patients with end-stage renal disease who are receiving dialysis, some 20% complain of restless leg syndrome, which contributes to poor sleep and daytime sleepiness.

Diabetes

Glucose intolerance and insulin resistance are clearly tied to diabetes. Studies have shown that OSA increases these conditions independent of age and obesity, and they both trend upward in correlation to the severity of OSA. Treatment of OSA with nasal CPAP has been shown to improve control of diabetes and reduce insulin resistance.10 One confounding issue in the relationship of sleep disorders and diabetes is that of obesity. Obesity is tied both to development of glucose intolerance and to sleep disorders. Metabolic syndrome is also included when discussing obesity and diabetes and may impact consideration of three topics discussed in this article (sleep, cardiovascular disease, and diabetes). Metabolic syndrome is defined by the following conditions:

  • Abdominal obesity
  • Atherogenic dyslipidemia
  • Raised blood pressure
  • Insulin resistance ± glucose intolerance
  • Proinflammatory state
  • Prothrombotic state

These conditions clearly affect cardiovascular health and carry significant implications for developing other diseases such as diabetes and OSA.11

Conclusion

There are connections between sleep disorders and a multitude of comorbid conditions. In a number of these connections, it is difficult to discern which developed first. Scientists are trying to decipher the order of appearance and see if there is a significance in regard to overall health, treatment, and outcomes. Sleep disorders in and of themselves are complex and significant in the burden of poor or declining health. When adding consideration of other diseases such as those examined in this article, the complexity expands and significance for health is multiplied. Certainly, we have found that treatment of OSA and CSA can greatly improve or even reverse some of the comorbid conditions. This is valuable information for respiratory therapists to know and to convey to patients who are being treated with CPAP or bi-level PAP. Understanding these complex issues and learning more about the ties between sleep disorders and comorbid conditions should be a part of our lifelong learning.

Bill Pruitt, MBA, RRT, CPFT, AE-C, is a senior instructor and director of clinical education in the Department of Cardiorespiratory Sciences, College of Allied Health Sciences, at the University of South Alabama in Mobile, and a PRN therapist at Springhill Medical Center and Mobile Infirmary Medical Center in Mobile. For further information, contact [email protected].

References

  1. Lavie L. Oxidative stress—a unifying paradigm in obstructive sleep apnea and comorbidities. Prog Cardiovasc Dis. 2009;51:303-12.
  2. Berry RB, Harding SM. Sleep and medical disorders. Med Clin North Am. 2004;88:679-703, ix.
  3. Collop N. The effect of obstructive sleep apnea on chronic medical disorders. Cleve Clin J Med. 2007;74:72-8.
  4. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–84.
  5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2000;289:2560-71.
  6. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2005;348:1233–41.
  7. Harbison J, O’Reilly P, McNicholas WT. Cardiac rhythm disturbances in obstructive sleep apnea syndrome: effects of nasal continuous positive airway pressure therapy. Chest. 2000;118:591-5.
  8. Parish JM. Sleep-related problems in common medical conditions. Chest. 2009;135:563-72.
  9. National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. October 2007. Available at: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed March 29, 2010.
  10. See CQ, Mensah E, Olopade CO. Obesity, ethnicity, and sleep-disordered breathing: medical and health policy implications. Clin Chest Med. 2006;27:521-33.
  11. Grundy SM, Brewer HB, Cleeman JI, et al. NHLBI/AHA Conference Proceedings. Definition of Metabolic Syndrome. Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation. 2004;109:433-8.