Faculty Bibliography

PURPOSE: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist. METHODS: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test. RESULTS: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night's sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption. CONCLUSIONS: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that share considerable overlapping symptoms, including sleep-related complaints. However, differences between the two conditions have been reported, and we hypothesized that dynamic aspects of sleep, recently attracting scientific interests, would be different in the two groups of patients. We thus study transition probabilities between sleep stages of CFS patients with or without FM. Subjects were 26 healthy controls, 14 CFS patients without FM (CFS alone) and 12 CFS patients with FM (CFS+FM) - all women. We studied transition probabilities between sleep stages (waking, REM sleep and Stage I, Stage II and slow-wave sleep (Stage III+IV)). We found that probabilities of transition from REM sleep to waking were significantly greater in CFS alone than in controls; we have reported previously this sleep disruption as the specific sleep problem for CFS alone [Kishi et al., 2008]. Probabilities of transitions from waking, REM sleep and Stage I to Stage II, and those from slow-wave sleep to Stage I, were significantly greater in CFS+FM than in controls; the former might indicate increased sleep pressure in CFS+FM and the latter may be the specific sleep problem of CFS+FM. These results suggest that CFS and FM are different illnesses associated with different problems of sleep regulation

BACKGROUND: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. METHODS AND FINDINGS: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea-hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0-14.9 events/h), moderate (AHI: 15.0-29.9 events/h), and severe (AHI: >or=30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80-1.08), 1.17 (95% CI: 0.97-1.42), and 1.46 (95% CI: 1.14-1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40-70 y (hazard ratio: 2.09; 95% CI: 1.31-3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease-related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality. CONCLUSIONS: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40-70 y with severe sleep-disordered breathing. Please see later in the article for the Editors' Summary

RATIONALE: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension. OBJECTIVES: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons aged 40 years and older. METHODS: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mmHg or taking antihypertensive medication. Apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during five years of follow-up according to baseline AHI. RESULTS: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index (BMI). Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio = 1.51, 95% CI 0.93, 2.47) does not exclude the possibility of a modest association. CONCLUSION: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for BMI, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded

The term obesity hypoventilation syndrome (OHS) refers to the combination of obesity and chronic hypercapnia that cannot be directly attributed to underlying cardiorespiratory disease. Despite a plethora of potential pathophysiological mechanisms for gas exchange and respiratory control abnormalities that have been described in the obese, the etiology of hypercapnia in OHS has been only partially elucidated. Of particular note, obesity and coincident hypercapnia are often associated with some form of sleep disordered breathing (apnea/hypopnea or sustained periods of hypoventilation). From a conceptual point of view, even transient reductions of ventilation from individual sleep disordered breathing events must produce acute hypercapnia during the period of low ventilation. What is less clear, however, is the link between these transient episodes of acute hypercapnia and the development of chronic sustained hypercapnia persisting into wakefulness. A unifying view of how this comes about is presented in the following review. In brief, our concept is that chronic sustained hypercapnia (as in obesity hypoventilation) occurs when the disorder of ventilation that produces acute hypercapnia interacts with inadequate compensation (both during sleep and during the periods of wakefulness); neither alone is sufficient to fully explain the final result. The following discussion will amplify on both the potential reasons for acute hypercapnia in the obese and on what is known about the failure of compensation that must occur in these subjects