The purpose of this study was to describe the prevalence of EDS and the factors associated it in adults with HF. Although correlates of EDS have been tested in other populations, this is the first study of this kind in adults with HF. Almost one quarter of our sample reported EDS and even more reported fatigue. Interestingly, there was a moderately low correlation between EDS and fatigue in this sample. Our EDS prevalence rate was lower than that found in other HF studies. Redeker and Stein (2006)
found EDS in 44% of their HF sample and Staniforth et al (1998)
identified EDS in 35% of their HF sample. EDS prevalence differences may reflect medical management of the populations studied. We are unable to make further comparisons between our study and these studies as Redeker and Stein did not report the pharmacologic treatment of their sample. Staniforth et al reported on ACE inhibitor and diuretic use, but beta-blockers were not in wide use at the time their study was conducted.
The factors associated with EDS in these HF patients were poorer sleep quality, worse functional class, lack of physical activity, and not taking a diuretic. These factors explained more of the variance in fatigue than in EDS, although physical activity and diuretic use were not significantly associated with fatigue. SDB was not associated with either EDS or fatigue in this sample.
Poor sleep quality was a significant determinant of both EDS and fatigue, a finding similar to that of prior investigators studying other patient groups (Kim & Young, 2005
; Pack, et al., 2006
; Whitney, et al., 1998
). The relationship between sleep quality and EDS and/or fatigue may be explained by results from Redeker and Stein (2006)
who reported that adults with HF had more difficulty falling asleep, poor sleep efficiency, and more sleep disturbances, early awakenings, and frequent napping than adults without HF.
Others have found a relationship between worse NYHA functional class and EDS in adults with HF (Redeker & Stein, 2006
; Staniforth, et al., 1998
). A similar relationship was found in the Cardiovascular Health Study (Whitney, et al., 1998
) and in community-dwelling older Americans enrolled in the National Sleep Foundation’s Sleep in America Poll
(Chasens, Sereika, Weaver, & Umlauf, 2007
). One explanation for this finding is that subjects with NYHA class IV HF have difficulty staying asleep in the supine position because of fluid shifts from the peripheral to the central circulation (Yumino et al., 2010
). It is also possible that the direction of causation is reversed with EDS impairing functional abilities. The direction of the effect cannot be determined from these cross-sectional data.
Subjects reporting engaging in physical activity between 1–3 hours each week experienced significantly less EDS compared to those doing less activity. Others have previously noted a relationship between physical activity and EDS (Chasens, et al., 2007
; Whitney, et al., 1998
). Physical activity is thought to improve sleep quality (Driver & Taylor, 2000
; Youngstedt, 2005
) and, in population studies, elders who are physically active report better sleep than sedentary individuals (de Castro Toledo Guimaraes, de Carvalho, Yanaguibashi, & do Prado, 2008
; Paparrigopoulos, Tzavara, Theleritis, Soldatos, & Tountas, 2010
; Sherrill, Kotchou, & Quan, 1998
). Studies testing the effects of various forms of physical activity on sleep parameters in older subjects have noted that sleep quality and duration are improved in subjects who engage in endurance, weight, stretching, and/or balance training (King, Oman, Brassington, Bliwise, & Haskell, 1997
; King et al., 2008
; Richards et al., in press; Singh, Clements, & Fiatarone, 1997
). Notably, however, these studies were not performed in adults with HF.
Not taking a diuretic was associated with significantly more EDS in our sample. This was a surprising finding, as diuretic use has been implicated as a factor interrupting sleep and causing EDS (Asplund, 2004
; Foley, et al., 2007
). Reviewing the side effect profiles of the major diuretic classes provided little insight into this finding but three possible scenarios may explain the results. One plausible explanation is that subjects who were not taking a diuretic were more likely to experience nocturnal dyspnea while in the supine position, which would interrupt sleep. However, no interaction was found between NYHA functional class and diuretic use. And, those taking a diuretic were no more likely to report sleep disturbances than those not taking a diuretic (analysis not shown). Another possibility is that not taking a diuretic is a surrogate marker of diastolic HF because some patients with diastolic heart failure are sensitive to the preload reduction associated with diuretic use and may develop hypotension or severe prerenal azotemia (Satpathy, Mishra, Satpathy, Satpathy, & Barone, 2006
). But, in this study diuretic use did not differ by HF type. The most likely explanation for the association between a lack of diuretic use and EDS might be linked to the reticular activating system (RAS), that area of the brainstem that regulates wakefulness. Neurons in the RAS that play a role in wakefulness are dopaminergic, noradrenergic, serotonergic, histaminic, and orexinic. The counterbalance to this arousal system is the inhibitory influence of the GABAergic system, activation of which overrides the wakefulness network and allows sleep (Jones & Jones, 2005
). Sleep occurs when an area of the anterior hypothalamus uses GABA and galanin to initiate sleep by inhibiting the arousal regions of the brain (Foldvary-Schaefer et al., 2002
). Prior investigators have demonstrated that furosemide competitively blocks GABA from binding at the receptor sites on the chloride inward channel, thus rendering them inadequately polarized to be effective (Pond et al., 2006
; Wall, 2003
). Given this well established neurochemistry, it is plausible that furosemide given during the day inhibits the GABAergic system, leaving the arousal/wakefulness system relatively unopposed and inhibiting EDS.
We did not find EDS to be associated with SDB. SDB is exceedingly common in adults with HF (MacDonald, Fang, Pittman, White, & Malhotra, 2008
) and often assumed to be associated with the high rates of EDS (Brostrom & Johansson, 2005
; Redeker, 2006
). However, our results are consistent with those of recent studies of adults with HF in which no association was found between SDB and EDS (Johansson et al., 2009
; Redeker, Muench, et al., 2010
; Roure et al., 2008
). The explanation for this lack of association remains unclear, although Artz and colleagues (2006)
note the HF patients appear to have a reduced propensity to fall asleep, which may be explained by the increased sympathetic nervous system activity in HF. The sympathetic stimulation is further accentuated by SDB. This finding is important because it focuses our attention on issues such as functional class, sleep quality, the medication regimen, and physical activity, which may be even more amenable to treatment.
To our knowledge, this is the first study to simultaneously explore both EDS and fatigue in the same sample. Several variables with univariate differences may help to explain the differences between EDS and fatigue. Both those with EDS and with fatigue were significantly younger than those without either symptom. Sensitivity of younger individuals to symptoms could reflect age-related differences in interoception or the ability to receive and process stimuli that originate inside the body (Cameron, 2001
). Fatigued HF patients were more likely to report an inadequate income and fair or poor health compared to patients without fatigue. This picture suggests that fatigue may reflect depression better than EDS. However, fatigued HF patients were also more likely to be anemic and to be taking more medicines—including those known to cause daytime somnolence—than patients who are not fatigued. These characteristics suggest that patients who report fatigue should have their medication regimen reevaluated and be checked for anemia.
A strength of this study is the relatively large sample size for a study of this nature. In addition, the sample was older and more obese than prior studies of EDS, which makes these results unique. Another strength was the inclusion of both EDS and fatigue. A limitation was that a significant proportion of the sample refused Embletta testing so we had to depend on historical data obtained from the medical record. Another limitation was the cross-sectional nature of the data, which limits our ability to identify whether EDS is a cause or an effect. Another limitation was the subjective nature of the symptom measures. However, symptoms are defined as sensations or changes in bodily function experienced by a patient, so self-report may be considered the gold standard for assessment. The sample itself was another limitation; these subjects were fairly well-educated and overweight or obese. They were also well-managed medically and had had HF longer than many published samples. Thus, these results may not reflect the general population of HF patients elsewhere.
In this sample, the major factors associated with EDS were poor sleep quality, worse NYHA functional class, lack of physical activity, and not taking a diuretic. These results suggest that medications that improve functional class, including diuretics, may decrease daytime sleepiness in these patients. Sleep quality should be explored even in HF patients without SDB; even mild decrements in sleep quality warrant concern and treatment.
These results are important because although SDB is widely studied in adults with HF, EDS is not routinely addressed. Almost one-quarter of this sample experienced a high and bothersome level of excessive daytime sleepiness, which illustrates the importance of screening for this symptom in patients with HF. Patients with HF and risks for SDB should be referred for testing, even if they do not have EDS.