Background Limited data have suggested that sleep-disorderedbreathing, a condition of repeated episodes of apnea and hypopneaduring sleep, is prevalent among adults. Data from the WisconsinSleep Cohort Study, a longitudinal study of the natural historyof cardiopulmonary disorders of sleep, were used to estimatethe prevalence of undiagnosed sleep-disordered breathing amongadults and address its importance to the public health.
Methods A random sample of 602 employed men and women 30 to60 years old were studied by overnight polysomnography to determinethe frequency of episodes of apnea and hypopnea per hour ofsleep (the apnea-hypopnea score). We measured the age- and sex-specificprevalence of sleep-disordered breathing in this group usingthree cutoff points for the apnea-hypopnea score ( 5, 10, and 15); we used logistic regression to investigate risk factors.
Results The estimated prevalence of sleep-disordered breathing,defined as an apnea-hypopnea score of 5 or higher, was 9 percentfor women and 24 percent for men. We estimated that 2 percentof women and 4 percent of men in the middle-aged work forcemeet the minimal diagnostic criteria for the sleep apnea syndrome(an apnea-hypopnea score of 5 or higher and daytime hypersomnolence).Male sex and obesity were strongly associated with the presenceof sleep-disordered breathing. Habitual snorers, both men andwomen, tended to have a higher prevalence of apnea-hypopneascores of 15 or higher.
Conclusions The prevalence of undiagnosed sleep-disordered breathingis high among men and is much higher than previously suspectedamong women. Undiagnosed sleep-disordered breathing is associatedwith daytime hypersomnolence.
Recent attempts to assess the public health burden attributableto sleep disorders1,2 have underscored the need for epidemiologicdata on sleep-disordered breathing. The condition is characterizedby repeated pauses in breathing during sleep, which lead tothe fragmentation of sleep and decreases in oxyhemoglobin saturation3.The physiologic spectrum of sleep-disordered breathing rangesfrom partial airway collapse and increased upper-airway resistance,manifested as loud snoring and episodes of hypopnea, to completeairway collapse and episodes of apnea lasting 60 seconds ormore4. Sleep apnea syndrome, clinically defined by frequentepisodes of apnea and hypopnea and symptoms of functional impairment,5can be life-threatening and has been associated with extremedaytime hypersomnolence, automobile accidents, and cardiovascularmorbidity and mortality6,7,8. Reports that snoring is associatedwith myocardial infarction, stroke, and hypertension9,10,11,12suggest that even a mild degree of sleep-disordered breathingmay have adverse health effects.
Epidemiologic investigation of sleep-disordered breathing hasbeen hampered by difficulties in obtaining valid data from anadequate population-based sample. Polysomnography is the currentstandard for the evaluation of sleep-disordered breathing13,14.It provides detailed data on respiratory effort, airflow, oxygenation,sleep state, and other variables, but it is costly and requiressubjects to sleep overnight in a laboratory. Previous studieshave been limited to polysomnography in small samples of men15,16and, in larger samples, to home-based recordings that rely onsingle indicators of abnormal breathing, without an objectivemeasure of sleep state17,18,19. In spite of limitations thatmade age- and sex-specific estimates of occurrence impossible,these studies concluded that sleep-disordered breathing is prevalentand drew attention to a potential public health burden.
In this report we have used data from the Wisconsin Sleep CohortStudy, initiated in 1988, to address the public impact of sleep-disorderedbreathing. The Sleep Cohort Study is a population-based prospectivestudy using overnight polysomnography to investigate the epidemiologicfeatures of sleep-disordered breathing. We estimated the age-specificprevalence of sleep-disordered breathing among middle-aged menand women, analyzed the spectrum of severity, and investigatedage, sex, and obesity as risk factors.
Methods
Sample
This investigation was based on a random sample of state employeesin Wisconsin. A two-stage sampling scheme, designed to optimizethe study's precision by oversampling subjects more likely tohave sleep-disordered breathing, was used to construct a cohortrepresenting a wide range of sleep-disordered breathing. Inthe first stage, all employees 30 to 60 years of age who workedfor three large state agencies were surveyed about their sleeppatterns and other characteristics by a mailed questionnaire(*). In the second stage, data from six survey questions, answeredby a five-point frequency scale and "do not know" category,were used to classify survey participants as habitual snorersaccording to whether they reported habitual (almost every nightor every night) snoring, snorting, or breathing pauses, or extremelyloud snoring. Given the clinic observations that most patientswith sleep apnea snore and snort habitually and loudly,3 wepredicted that recruiting 100 percent of the habitual snorersand a 25 percent random sample of those who were not habitualsnorers would yield a cohort with adequate variance in sleep-disorderedbreathing.
Completed questionnaires were returned by 3513 subjects (responserate, 82 percent). A comparison of respondents and nonrespondentswith respect to personnel data, including sex, age, and jobcategory, revealed no significant differences (P>0.1). Thedistribution of surveyed men and women according to samplingstratum is shown in Table 1.
Table 1. Distribution of Survey Population According to Sampling Stratum.
Subjects were recruited by telephone. The criteria for exclusionwere as follows: pregnancy; unstable or decompensated cardiopulmonarydisease, including myocardial infarction; airway cancers; recentupper-airway surgery; and tracheostomy. Eight respondents wereexcluded. The participation rate was 43 percent. The most commonreason for declining to participate was the inconvenience ofsleeping away from home.
Collection of Polysomnographic Data
Studies were conducted at the University of Wisconsin GeneralClinical Research Center. Before bedtime, the subjects wereinterviewed about their sleep characteristics and health history.Measures of body habitus were recorded by standard anthropometricmethods20. The polysomnography consisted of continuous polygraphicrecording (Polygraph model 78, Grass Instruments, Quincy, Mass.)from surface leads for electroencephalography, electrooculography,electromyography, and electrocardiography, and from noninvasivesensors for nasal airflow (thermocouples), oral airflow (end-tidalcarbon dioxide gauge), tracheal sounds (microphone), thoracicand abdominal respiratory effort (inductance plethysmograph[Respitrace, Ambulatory Monitoring, Ardsley, N.Y.]), and oxyhemoglobinlevel (finger-pulse oximeter [Ohmeda 3740, Englewood, Colo.]).The transducers and lead wires permitted normal positional changesduring sleep. Bedtime and awakening time were at each subject'sdiscretion; the polysomnography was terminated after final wakening.
The reproducibility of single-night polysomnography was investigatedby conducting second studies in 40 subjects one to two weeksafter the first.
Interpretation of Polysomnographic Data
Polysomnography records were scored for sleep, breathing, oxygenation,and movement in 30-second periods. Sleep data were staged (stagesI, II, III, and IV and rapid-eye-movement [REM] sleep) accordingto the system of Rechtschaffen and Kales21. An abnormal breathingevent during objectively measured sleep was defined accordingto the commonly used clinical criterion of either a completecessation of airflow lasting 10 seconds or more (apnea) or adiscernible reduction in respiratory airflow accompanied bya decrease of 4 percent or more in oxyhemoglobin saturation(hypopnea).
The average number of episodes of apnea and hypopnea per hourof sleep (the apnea-hypopnea score) was calculated as the summarymeasurement of sleep-disordered breathing. For categorical analysis,cutoff points of 5, 10, and 15 were used. Subjects with apnea-hypopneascores of less than 5 were further classified according to whetherthey were habitual snorers or not. These cutoff points are widelyused to describe sleep apnea, but it is important to note thatthe clinical importance of any particular cutoff point has notbeen adequately determined.
Assessment of Hypersomnolence
Daytime hypersomnolence was assessed before the polysomnographystudy with three subjective questions on sleepiness22. Usinga five-point scale, the subjects rated how often they felt excessivelysleepy during the daytime; woke up unrefreshed, regardless ofhow long they had slept; and had uncontrollable daytime sleepinessthat interfered with daily living. Responses of "frequent" or"habitual" ( 2 days per week) were considered to indicate hypersomnolence.
Statistical Analysis
Data were analyzed with SAS software modules for descriptivestatistics, contingency tables, and multiple logistic regression23.Repeated polysomnography studies were compared with use of pairedt-tests. Pearson's chi-square and ordinary t-tests were usedfor other comparisons of means and proportions. Two-tailed Pvalues of less than 0.05 were considered to indicate statisticalsignificance.
We calculated age- and sex-specific prevalences of sleep apneaamong the habitual snorers and those who were not habitual snorersusing cutoff points of 5, 10, and 15 in the apnea-hypopneascores. Within age and sex groups, we combined the estimatesinto weighted averages using the survey population proportionsgiven in Table 1. Standard formulas for stratified samplingwere used to calculate 95 percent confidence intervals24. Thisresulted in age- and sex-specific estimates of sleep-disorderedbreathing in middle-aged adults. The sex-specific age distributionin the survey population (Table 1) was used as a standard toestimate summary prevalences of sleep-disordered breathing inemployed men and women.
The prevalence of the joint occurrence of an apnea-hypopneascore of 5 or higher and all three symptoms of hypersomnolencewas calculated as the prevalence of sleep apnea syndrome meetingminimal diagnostic criteria.
The association of sleep-disordered breathing with obesity,as indicated by variables for weight, body-mass index (the weightin kilograms divided by the square of the height in meters),circumferences, and skin-fold thicknesses, was examined by multiplelogistic regression. A separate model was fit for each measureof body habitus because of multicollinearity. Terms for ageand sex were included in all the models. Two-way interactionsof body-habitus variables, age, and sex were examined; resultsare reported for terms with P values of 0.1 or less.
Results
Representativeness of the Sample
Subjects who agreed to undergo polysomnography and those whorefused were compared with regard to their responses to allquestionnaire items on sleep characteristics, body habitus,sex, and age; no significant differences were found. The frequenciesof snoring, other breathing abnormalities during sleep, andhypersomnolence did not differ significantly whether the subjectsagreed to participate or not. There was no evidence of selectionbias that would compromise the representativeness of the sample.
Quality of Polysomnographic Data
The overnight polysomnographic studies of 625 subjects wereanalyzed. Twenty-three subjects who had insufficient total sleeptime (less than 240 minutes) or no REM sleep were excluded,resulting in the final sample of 602 subjects for whom high-qualitypolysomnographic data were available (Table 2). The subjectsslept, on average, less than the seven to eight hours consideredusual. However, since the percentages of total sleep spent ineach sleep stage were similar to normative values for adults25and since the number of REM periods indicated adequate repeatedsleep cycles, we are confident that the breathing during monitoredsleep was a valid indicator of breathing during usual sleep.
Table 2. Time the Study Subjects Spent in Each Sleep Stage, According to Sex.
Data from 40 pairs of polysomnographic studies separated by7 to 14 days showed that the subjects slept 32 minutes longer,on average, during the second study (P<0.05). However, therewas no significant difference between study nights in the percentageof time spent in each sleep stage or in the apnea-hypopnea score.The mean (±SE) apnea-hypopnea scores for the first andsecond studies were 3.0 ±1.1 and 3.9 ±1.1, respectively.
Spectrum of Severity of Sleep-Disordered Breathing
A wide range of sleep-disordered breathing, ranging from apnea-hypopneascores of zero to 89, was found (Figure 1). Most subjects hadsome episodes of apnea or hypopnea; 76 percent of the habitualsnorers and 64 percent of those who were not habitual snorershad apnea-hypopnea scores greater than zero. As compared withthe distribution of scores among the habitual snorers, however,the distribution among the subjects who were not habitual snorerswas more skewed toward scores under 5.
Figure 1. Cumulative Distribution of Apnea-Hypopnea Scores According to Study Stratum.
Prevalence of Sleep-Disordered Breathing
Table 3 shows the proportions of the habitual snorers and subjectswho were not habitual snorers, according to the apnea-hypopneascore. Habitual snorers, both men and women, were more likelyto have apnea-hypopnea scores of 15 or higher. The prevalenceof mild sleep-disordered breathing (an apnea-hypopnea scoreof at least 5 but less than 15), however, was higher among habitualsnorers for women only.
Table 3. Sex-Specific Prevalence of Sleep-Disordered Breathing, According to Apnea-Hypopnea Score and Sampling Stratum.
The prevalence of sleep-disordered breathing at apnea-hypopneascores of 5, 10, and 15 was extrapolated from the cohortto the general population (Table 4). For men, the prevalenceat all three levels was significantly higher among those 40to 49 years old than among those 30 to 39 years old. Among women,the only statistically significant difference was that apnea-hypopneascores of 5 or higher were more prevalent among those 50 to60 years old than among younger women.
Table 4. Age-Specific Estimates of Sleep-Disordered Breathing in the General Population, According to Apnea-Hypopnea Score and Sex.
Men had a higher prevalence of sleep apnea than women in allage groups and at all cutoff points for the apnea-hypopnea score;all the differences were statistically significant except amongsubjects 30 to 39 years old who had apnea-hypopnea scores of15 or higher. Men were 2.0 to 3.7 times as likely as women tohave sleep-disordered breathing.
Occurrence of Hypersomnolence
The prevalence of hypersomnolence did not vary according toage (P>0.1), but it was higher among women than men (P<0.01)(Figure 2). As compared with subjects with little or no sleep-disorderedbreathing, habitual snorers and subjects with apnea-hypopneascores of 5 or higher were significantly (P<0.001) more likelyto have hypersomnolence. In subjects with apnea-hypopnea scoresof 5 or higher, 22.6 percent of the women and 15.5 percent ofthe men reported the frequent occurrence ( 2 days per week)of all three indicators of hypersomnolence. Although these indicatorswere based on questions used in clinical evaluations, self-reportedsleepiness is not an objective measure and is believed to underestimatethe physiologic state of sleepiness26. Thus, the actual prevalenceof hypersomnolence may be higher than these data indicate.
Figure 2. Proportion of Men and Women Who Reported Hypersomnolence, According to Category of Sleep-Disordered Breathing.
On the basis of these data, we estimate that the proportionof middle-aged adults who have both sleep-disordered breathing(an apnea-hypopnea score of 5 or higher) and self-reported hypersomnolenceis 2 percent among women (9 percent with sleep-disordered breathing,22.6 percent of whom have hypersomnolence) and 4 percent amongmen (24 percent with sleep-disordered breathing, 15.5 percentof whom have hypersomnolence).
Obesity and Sleep-Disordered Breathing
Table 5 shows the odds ratios estimating the increased riskof sleep-disordered breathing associated with an increase of1 SD (adjusted for sampling design) in the value of the specificmeasure of body habitus. Obesity, as indicated by any of thesemeasures, was a significant (P<0.001) risk factor for anapnea-hypopnea score of 5 or higher.
Table 5. Odds Ratios for Sleep-Disordered Breathing and Measures of Body Habitus.
Discussion
There are three major findings from our data. First, there isa wide spectrum of undiagnosed sleep-disordered breathing amongadults, ranging from a few episodes of apnea or hypopnea duringsleep to 89 abnormal breathing events per hour of sleep. Second,undiagnosed sleep-disordered breathing, as indicated by fiveor more episodes of apnea or hypopnea per hour of sleep, isprevalent among both women (9 percent) and men (24 percent)of middle age. Finally, 4 percent of men and 2 percent of womenin the middle-aged work force are likely to meet minimal diagnosticcriteria for the sleep apnea syndrome.
Strengths and Limitations of the Study
Our findings use the apnea-hypopnea score as an indicator ofsleep-disordered breathing and rely on the results of a single-nightpolysomnography study conducted in a laboratory. These definitionsand methods mirror those recommended for clinical practice13.The apnea-hypopnea score is commonly used to describe the spectrumof severity among patients in clinics, but there has been concernabout the usefulness of this measurement alone outside clinics27,28,29.Although the primary abnormal event is the apnea or hypopnea,the immediate consequences include varying degrees of increasednegative intrapleural pressure, arterial hypoxemia and hypercapnia,central nervous system arousal, fragmented sleep states, andfluctuations in heart rate and blood pressure30. It is possiblethat the immediate consequences are more severe in patientsin sleep clinics, even at the same apnea-hypopnea score. Thus,the relation between the apnea-hypopnea score and the immediateconsequences in the asymptomatic general adult population needsinvestigation.
There have been some studies of the ability of a single-nightlaboratory study to represent usual sleep. Studies of the concordancebetween data obtained by laboratory polysomnography and by homemonitoring have indicated that apnea-hypopnea scores are notinfluenced by the laboratory environment31. Most studies haveindicated that although there may be a higher proportion oflighter sleep during the first night under laboratory conditions,abnormal breathing during sleep has less night-to-night variability.Like some15,32,33 but not all34 studies, our investigation foundthat the distribution of sleep stages and the mean apnea-hypopneascore were not significantly different between the initial andsecond laboratory studies conducted in 40 subjects.
The strengths of our study include the generalizability of itsresults to other middle-aged populations. The employed differfrom the entire population in their sex and age distribution,but one can extrapolate the prevalence of sleep-disordered breathingto other populations of different composition using standardage-adjustment procedures in conjunction with our age- and sex-specificprevalences. However, since employed people are healthier thanthose who do not work, our findings may underestimate the prevalenceof sleep-disordered breathing in the entire population.
Assessment of the Public Health Burden of Undiagnosed Sleep Apnea
Reliable and generalizable polysomnographic data, collectedaccording to clinical standards of practice, enhance the abilityto address the implications of our estimates within the contextof current sleep medicine. We estimate that 2 percent of womenand 4 percent of men in the middle-aged work force meet thecurrent minimal diagnostic criteria for sleep apnea syndrome5.If the men and women who were found in this study to have frequentepisodes of apnea and hypopnea are pathophysiologically similarto patients in sleep clinics who have similar apnea-hypopneascores, then undiagnosed sleep-disordered breathing among adultsrepresents a public health burden.
Health care costs arising from the diagnosis and treatment ofsleep apnea syndrome are substantial. Evaluation by currentstandards includes full-night polysomnography, at a cost perprocedure of approximately $1,10035. Sleep-disordered breathingcan usually be eliminated by the nightly use of a nasal devicethat delivers continuous positive pressure to the upper airway36.Since patients must continue to receive this therapy throughouttheir lives, it is often viewed as a hardship. The demand forsleep medicine has spiraled upward over the past few years,in part because of increased awareness of sleep apnea, and currentresources are barely adequate to evaluate and treat the patientswho seek care37,38. If the condition of frequent episodes ofapnea and hypopnea during sleep is indeed a sign of substantialmorbidity that would be ameliorated with treatment, our findingsindicate that men and women who seek evaluation for sleep-disorderedbreathing are merely a fraction of the total. Consequently,it is imperative that we evaluate the clinical and physiologicimportance of sleep-disordered breathing at the mild end ofthe spectrum. Data from longitudinal studies of asymptomatic,untreated sleep-disordered breathing are needed to determineits progression, acute and chronic pathophysiologic sequelae,and other vital aspects of its natural history. Such informationwill be necessary to identify features that best describe thespectrum of severity of sleep-disordered breathing, and forclinical decision making about whom to treat.
Risk Factors
The lack of a continuous increase in the prevalence of sleep-disorderedbreathing with increasing age in our study suggests that ageis not a strong risk factor for sleep-disordered breathing overthe middle adult years. Our results do indicate that male sexand obesity are important risk factors for sleep apnea in people30 to 60 years old. The male:female ratio for the prevalenceof sleep-disordered breathing was approximately 3:1. Althoughthis risk ratio indicates an important difference in morbidity,it is lower than the widely cited clinic-based ratio of 8:1or 10:15,39,40. The higher ratio of diagnosed sleep apnea inclinical settings may be a result of greater self-selectionand referral bias. Alternatively, the higher ratio in clinicpopulations may reflect sex differences in the natural historyof sleep apnea, including differences in symptom response tothe same frequency of apnea and hypopnea, or differences indisease progression.
In agreement with observations in clinics, our findings indicatedthat obesity was strongly related to undiagnosed sleep-disorderedbreathing. An increase of 1 SD in any measure of body habituswas related to a threefold increase in the risk of an apnea-hypopneascore of 5 or higher. Obesity clearly has an important rolein sleep-disordered breathing. Because it is a modifiable riskfactor, further research on its association with sleep apneais particularly justified.
In summary, our finding is that undiagnosed sleep-disorderedbreathing, as measured according to clinical criteria, is prevalentand has a wide range of severity among middle-aged women andmen. Consequently, further data on the natural and pathophysiologicimportance of the spectrum of abnormal breathing during sleepare essential to rational health planning and clinical decisionsabout whom to treat.
Supported by grants (PO1 HL 42242, HL 02588, and RR 03186) fromthe National Institutes of Health.
We are indebted to Dan Zaccaro, Thomas Bidwell, Wayne Zimmerman,Ron Leder, Karen Paulus, Linda Evans, Patty Moeser, DeborahBrown, Dana Derryberry, Leah Steinberg, Rassan Tarabein, LisaTerada, Andrea Darner, Sharon Boeder, Peter Mitchell, RobertMulroy, Hyon Kim, and the staff members of the University ofWisconsin General Clinical Research Center for technical assistance,and to Dana VanHoesen for assistance in the preparation of themanuscript.
* See NAPS document no. 05017 for four pages of supplementarymaterial. To order, contact NAPS c/o Microfiche Publications,248 Hempstead Tpk., West Hempstead, NY 11552.
Source Information
From the Departments of Preventive Medicine (T.Y., M.P., J.D.), Medicine (J.S., S.B.), and Neurology (S.W.), University of Wisconsin School of Medicine, Madison.
Address reprint requests to Dr. Young at the Department of Preventive Medicine, University of Wisconsin, 504 N. Walnut St., Madison, WI 53705.
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Sleep-Disordered Breathing
Barsh L. I., Garcia A., Halberstadt J., Young T., Palta M., Badr M. S.
Extract |
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N Engl J Med 1993;
329:1429-1430, Nov 4, 1993.
Correspondence
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