Obstructive sleep apnea syndrome (OSAS) is a common disease that manifests as a reduction or complete cessation of airflow despite ongoing inspiratory efforts, as well as changes in nasal and oral airflow triggering hypoxemia and hypercapnia [1]. The inspiratory efforts to overcome occlusion lead to arousal from sleep, sleep fragmentation, and oxyhemoglobin desaturation [2]. OSAS is increasingly recognized as a medical cause of morbidity and mortality [3]. The most common symptoms of OSAS include chronic loud snoring, excessive daytime sleepiness, personality changes and deterioration of quality of life [4-6]. Despite the numerous advancements in our understanding of the pathogenesis and clinical consequences of this disorder, the majority of those affected remain undiagnosed [7-11].
Though OSAS was clinically recognized several decades ago [12-14], awareness of this disease has been slow to develop outside the realm of sleep medicine. However, several epidemiological studies have drawn attention to a surprisingly high prevalence of OSAS among middle-aged adults [15,16] and the elderly [17,18].
There has been extensive research on the prevalence of OSAS, but the findings are difficult to compare. First, different tests have been used to diagnose OSAS. Although overnight polysomnography is considered the standard [19], other methods have also been used such as unattended in-home polysomnography and home polygraphy. Second, a variety of definitions have been used to describe apnea and hypopnea. Third, differences in equipment and processing of signals can result in substantial differences in the reported prevalence. For example, there is a lack of standardization in the quantification of airflow (including such methods as thermistry, inductance plethysmography and nasal cannula/pressure transduction). Fourth, there is a lack of consistency in both the definition of clinically significant sleep apnea and the selection of diagnostic cut-off points. Different thresholds applied to conditions based on severity spectra can affect both prevalence estimates and extent of associations with risk factors and outcomes [20,21]. In addition, the validity of some studies has been questioned because of small sample size, methodological limitations, and inadequate control for obesity and other potential confounding factors [22].
Epidemiological studies have generally focused on two levels of disturbance: (1) sleep-disordered breathing (SDB), which is defined by the number of obstructive apnea and hypopnea episodes per hour of sleep (apnea–hypopnea index, AHI); and (2) OSAS, which indicates a clinical entity based on sleep laboratory and clinical criteria (an elevated AHI in conjunction with hypersomnolence or related problems in daytime function). Recommended diagnostic criteria for OSAS include AHI ≥5 by polysomnography and evidence of disturbed or unrefreshing sleep, daytime sleepiness, or other daytime symptoms [23].
A spectrum of sleep-related obstructed breathing has been described [24]. This ranges from snoring [25] and episodic flow limitation terminating in central nervous system arousals, often called ‘upper airway resistance syndrome’ [26], to obesity hypoventilation syndrome [27]. The prevalence of OSAS is the focus of the present review, and its severity lies between these two extremes.
Despite their limitations, earlier epidemiological studies have opened the way to a clearer understanding of the natural history and adverse health consequences of OSAS [28-30]. More recently, large cohort studies have been performed [15,16,31-35].
PREVALENCE STUDIES
A series of epidemiological studies on the prevalence of OSAS has been performed over the last 40 years. Franceschi et al [28] carried out a prospective study of 2518 unselected patients admitted to a general hospital during a one-year period. Among patients with excessive daytime sleepiness, 87 polysomnographic recordings were made with an estimated OSAS prevalence of 1.02%. Lavie [36] interviewed 1502 industrial workers (84% male and 16% female) for sleep disorders. Polysomnographic recordings were performed on 78 male subjects with an estimated prevalence of 0.89% [36]. This prevalence may be an underestimate because physically active workers tend to be healthier than the general population. Nevertheless, four years later, Peter et al [37] reported a higher prevalence of OSAS (2.3%) than did Lavie [36] in a subgroup of industrial workers in Germany. The discrepancy is probably related to the selection of study samples.
Estimates from the study by Gislason et al [38] in Uppsala, Sweden, however, are free of the healthy-worker effect, because their sample was based on the entire male population, aged 30 to 70 years. Like the Lavie [36] study, a two-stage sampling procedure was used involving a survey and a standard night polysomnographic study in the laboratory. The prevalence of OSAS was estimated to be 1.3% [38].
Similar methodology was used in Bologna, Italy, where subjects aged 30 to 69 years were solicited by mail from a 50% random sample of residents in a selected population. A random sample of 40 every-night snorers was subsequently studied by polysomnography. The prevalence of OSAS was estimated to be 2.7% [39].
In 1991, Ancoli-Israel et al [40] conducted the first large population-based study of elderly people. A sample of 427 men and women, 65 to 95 years of age, was studied using home polygraphy. SDB was found in 70% of the men and 56% of the women.
In Japan, Hida et al [41] used a monitor respiratory system to study 170 industrial workers who were referred to a sleep clinic. Those authors found a 7.5% prevalence of subjects with an AHI ≥10 episodes per hour.
In Australia, 2202 individuals, aged 35 to 69 years, were studied by using a questionnaire. Respiratory polygraphy of 441 subjects revealed a prevalence of SDB (defined as AHI ≥25) of 12.6% in men and 3.6% in women [30]. In the same country, based on the Busselton Health Survey, Bearpark et al [42] reported that 26% and 3% of men aged 40 to 65 years had SDB and OSAS, respectively.
In the United States, Young el al [15] studied a sample of 1255 workers between 30 and 60 years of age and found that 24% of the men and 9% of the women had SDB. They also found that 4% of the men and 2% of the women met the criteria for OSAS.
In Singapore, Ng et al [43] studied a random sampling of 2298 adults aged 20 to 74. The overall prevalence of OSAS, defined by clinical criteria, was 0.43%. Neven et al [44] found a similar prevalence among 6747 inhabitants of all ages of a small town in Holland. All men ≥35 years and women ≥50 years (n = 2466) were invited to fill in a specially designed questionnaire on snoring and sleep. All respondents (n = 2182) whose answers suggested the possible occurrence of OSAS (169 men, 25 women) were invited to undergo further investigation. Oronasal thermistry was performed in the subjects’ homes and the results were scored to provide an apnea index (AI). Subjects with an AI ≥5 (24 men, 1 woman) were referred to a sleep laboratory for investigation by polysomnography. The prevalence of OSAS was at least 0.45% in men ≥35 years of age.
Bixler et al [18,45] performed a study on a two-phase random sample from the general population. In Phase I, 12,219 women and 4364 men ranging in age from 20 to 100 years were interviewed; and in Phase II, 1000 women and 741 men of the Phase I subjects were selected for one night of sleep laboratory evaluation. The results indicated that, for OSAS, men had a prevalence of 3.9% and women 1.2%, and the prevalence of central apnea, defined by a central apnea index ≥20, was 0.5%.
Ferini-Strambi et al [46] studied a sample of 750 Italian women aged 40 to 65 years: 10.7% had an AHI between 5 and 9, 7.7% had an AHI between 10 and 19, and 2.2% had an AHI ≥20.
In Spain, another two-stage study was carried out on an initial sample of 3006 subjects, aged 50 to 70 years, chosen at random from the electoral census. A hospital polygraphy performed on 76 individuals revealed a prevalence of SDB of 28.9% and a prevalence of OSAS of 6.8% [47].
In one of the first studies carried out in China, Hui et al [48] estimated the prevalence of OSAS using respiratory polygraphy in a student population from the Chinese University of Hong Kong to be 0.1%. This low prevalence is probably due to the young age of the sample, and underscores the limitation of inaccurately reflecting the general population.
In another Spanish study involving 2148 male and female subjects from the general population between 30 and 70 years of age, Duran et al [16] performed 555 complete polysomnographies and found SDB, defined as AHI ≥5, in 26.3% of the men and 28% of the women. These authors also found a prevalence of OSAS, defined as AHI ≥5 plus clinical symptoms, of 3.5% in men and 3% in women [16]. The overall prevalence of OSAS in women in this study was slightly higher than that reported by Young et al [15] in the Wisconsin Sleep Cohort Study. This discrepancy may be explained by differences in the health status of the populations and/or sample age ranges (30 to 60 years in the study of Young et al [15] versus 30 to 70 years in the study by Duran et al [16]).
In another study carried out in Hong Kong, Ip et al [32] studied 784 male office workers aged 30 to 60 years. Of the initial survey sample, 153 complete polysomnographic studies were carried out. The estimated prevalence of SDB, defined as AHI ≥5, was 8.8%, and OSAS, defined as AHI ≥5 with symptoms, was 4.1%.
In an elderly cohort of Japanese-American men, 718 subjects between 79 and 97 years were studied by in-home sleep study: they presented an SDB prevalence of 19% [49].
In 2004, Udwadia et al [33] carried out one of the first epidemiological studies on OSAS in India. Six hundred and fifty males aged 35 to 65 years from the general population completed a questionnaire, of which 250 underwent an overnight home sleep study. The estimated prevalence of SDB, defined as AHI ≥5, was 19.5%, and OSAS, defined as AHI ≥5 plus symptoms, was 7.5%.
A random sample of 457 Korean men and women aged 40 to 69 years was studied using overnight complete polysomnography. The prevalence of SDB, defined as AHI ≥5, was 27% in men and 16% in women. The prevalence of OSAS was 4.5% in men and 3.2% in women [34]. The prevalence of SDB in the general Korean population is similar to that reported by Young et al [15] in the USA and by Hui et al [48] in China. On the other hand, the prevalence in the Korean study is higher than in the Indian study. These small variations may be due to methodological differences.
In another Indian study, Sharma et al [50] applied polysomnography to 77 habitual snorers and 73 non-habitual snorers taken from an initial sample of 2150 subjects from a semi-urban community of Delhi. This study reported an overall prevalence of 13.7% for SDB and 3.6% for OSAS.
Based on an initial sample of 1503 subjects from the Warsaw electoral register, Plywaczewski et al [35] applied polysomnography to 676 subjects. The prevalence of SDB was 14.3% and OSAS was 7.5%.
Although methodological and age-range differences make comparisons difficult, the major findings of the most important studies have been stratified in Table 1.
 | TABLE 1. Prevalence studies on sleep apnea |
Across studies, the overall prevalence of OSAS ranges from 0.7% to 7.5%. By gender, OSAS prevalence is approximately 3.4% to 4.5% for men and 2% to 3.2% for women. Likewise, we can see that the overall prevalence of SDB, defined as AHI ≥5, ranges from 8.8% to 68.7%.
Until recently, population-based research on the prevalence of OSAS was only available for North America, Europe and Australia. However, studies undertaken to characterize the disease burden in other countries, including China, India and Korea, report similar prevalence levels.
A number of risk factors has been associated with sleep apnea. The most important of these are age, gender and obesity.
AGE
Sleep breathing-related difficulties become increasingly common as age advances, with OSAS being highly prevalent among the elderly population. Ancoli-Israel et al [40] found that 62% of 385 subjects over the age of 65 had an AHI ≥10. A study by Bixler et al [18] found a prevalence of SDB in men, defined as AHI ≥10 events per hour, in 3.2% of 20- to 44-year-olds, 11.3% of 45- to 64-year-olds and 18.1% of 61- to 100-year-olds. In separate analyses of women from the same cohort, the prevalence of AHI ≥15 events per hour was 0.6%, 2.0% and 7.0% for the respective age groups [45].
In a general population study of people between 30 and 70 years of age in Spain, 19% of men and 15% of women presented an AHI ≥10, and the prevalence increased with age [16]. In fact, the prevalence estimates appear to be nearly three times higher in elderly subjects than in middle-aged subjects for AHI ≥5, and more than four times higher for AHI ≥15 [16]. In a cohort of 428 subjects aged 71 to 100 years from the same country, the prevalence of AHI ≥5 was 80% for women and 81% for men, whereas the prevalence of AHI ≥15 was 49% for women and 57% for men [51].
These epidemiological studies seem to reflect a linear relationship between age and OSAS; however, this is not consistent with clinical experience, where peak prevalence is observed between 55 and 60 years. In fact, Bixler et al [18] propose that the relation between OSAS prevalence and age is a quadratic function, which increases from over 1% in the youngest age group to almost 5% in the middle-aged group, and then returns to less than 2% in elderly subjects. This is consistent with the age distribution typically observed in clinical populations.
A variety of research teams has studied the correlation between age and SDB, reporting dissimilar results. Duran et al [16] found a strong association between AHI and age after controlling for gender and body mass index (BMI). Some authors have reported similar findings [32,35,52] and others have not [15,33,53]. Young et al [15,53] concluded that this relationship was found only among middle-aged subjects, but that age ceased to be an independent risk factor for OSAS among elderly subjects. Udwadia et al [33] observed that age was not a significant risk factor, and that the prevalence of SDB did not increase with age. The highest prevalence was found in individuals 45 to 54 years old, but the difference was not significant [33].
All these data suggest that OSAS at advanced age may have less clinical relevance than at middle age. In middle-aged men, both snoring and OSAS are extremely common, and in this age range both are associated with obesity.
Bixler et al [18] have reported that the severity of sleep apnea, as defined by the number of events, minimum oxygen saturation, and clinical significance, decreased with age. This observation was made after adjusting for BMI and was independent of the sleep apnea criteria used.
Similarly, and in support of the above, Krieger et al [54] found that respiratory effort in response to an occlusion in the upper airway was lower with age. Some mechanisms proposed for an age-related increase in prevalence include increased deposition of fat in the parapharyngeal area, lengthening of the soft palate, and changes in body structures surrounding the pharynx [55,56].
All these observations raise a critical question: what is the significance of the high prevalence of OSAS in advanced age? Some data suggest that OSAS in advanced age may be a condition distinct from that in middle age. Several studies of OSAS in older populations report little or no association of OSAS with sleepiness, hypertension or decrements in cognitive function [57,58]. In light of this, some authors have proposed a model involving two types of OSAS [59]. The first has a typical distribution with an incidence peak at around 55 years of age and corresponds to the type of OSAS usually found in sleep units. The other age-dependent OSAS model occurs at age extremes, is less frequent in sleep units (though identifiable in epidemiological studies), and has fewer clear clinical consequences. In others words, the OSAS detected in elderly populations would represent the ‘survivors’ of the middle-age population and would be a consequence of aging. In spite of the attractiveness of this hypothesis, sufficient consistent data are not yet available for its confirmation. Indeed, we are not even certain whether continuous positive airway pressure (CPAP) treatment delays or prevents mortality in elderly patients, nor are we certain of the treatment they should receive. Therefore, until more studies are available, elderly patients with clinically relevant OSAS should be treated in a way similar to middle-aged OSAS patients. The question of whether OSAS in elderly patients represents a distinct clinical entity remains controversial [60].
GENDER
It has long been recognized that men have greater susceptibility than women toward developing OSAS [61]. Clinic-based studies have shown that, in patients referred for clinical evaluation, the ratio of men to women ranges from 5:1 to 10:1 [4,62]. Epidemiological studies have confirmed the higher prevalence of OSAS in men. Most population-based studies that estimate sex-specific prevalence report a 2- to 4-fold greater risk for men. Bixler et al [45] found an OSAS prevalence of 3.9% in men and 1.2% in women. Plywaczewski et al [35] found that the prevalence of OSAS was four times higher in males (11.2%) than in females (3.4%). Another important finding is that the gender disparity in OSAS decreases with age [16,63], and by the age of 50 the incidence rates for men and women are similar [63].
It has been reported that postmenopausal women not receiving hormone replacement therapy had a significantly higher prevalence of OSAS than premenopausal women (2.7 versus 0.6%). In fact, postmenopausal women showed a prevalence similar to that of men (3.9%) [45]. These data suggest that menopause is a significant risk factor for OSAS in women and that hormone replacement appears to reduce this risk.
Several interrelated factors may explain the difference in risk related to gender. These include differences in obesity and the distribution of adipose tissue, differences in upper airway dimensions, and differences in upper-airway muscle tone [64-66]. Moreover, there may be sex differences in exposure to exogenous potential risk factors, such as occupational exposure or smoking.
OBESITY
Excess body weight is a common clinical finding in OSAS patients and is present in the majority of patients referred for diagnostic sleep evaluation [67-71]. A variety of population-based and community-based studies has confirmed that excess body weight is uniformly associated with increased risk for OSAS [15,16,18,32,33,72,73]. In the Wisconsin Sleep Cohort Study, a one-standard-deviation difference in BMI was associated with a 4-fold increase in OSAS prevalence [15]. Duran et al [16] reported that OSAS was present in >50% of individuals from an obese population with a mean BMI >40.
Studies of Asian populations by Ip et al [32] and Udwadia et al [33] also found that higher BMI was a risk factor for SDB. However, Kim et al [34] suggested that other risk factors were more prevalent among Asian populations, such as craniofacial features that compromise the upper airways.
A number of studies have shown that OSAS is frequent in patients with morbid obesity. In a group of morbidly obese patients who underwent bariatric surgery, SDB was detected in 93.6% of patients, and at least 27.8% presented OSAS [74]. Another study of 290 morbidly obese patients who were evaluated for weight loss surgery found that 78% of the total sample presented SDB. The prevalence of SDB among patients with BMI 35-39.9 kg/m2 was 71%, with BMI 40-40.9 kg/m2 it was 74%, and with BMI 50-59.9 kg/m2 it was 77%. For subjects with a BMI of 60 kg/m2 or greater, the prevalence of SDB rose to 95% [75].
Studies on the effects of dietary or surgical weight loss show that reducing the severity of OSAS is possible by reducing body weight. The high frequency of OSAS in morbidly obese patients makes it important to request polysomnography for better therapeutic management [74-78]. The mechanism by which obesity can favor the onset of OSAS is not well understood, but it could be that central obesity precipitates or exacerbates OSAS because fat deposits in the upper airway affect distensibility. In addition, an increased volume of abdominal fat could predispose to hypoventilation during sleep and/or reduce the oxygen reserve, favoring oxygen desaturation during sleep [71,79].
ETHNICITY
Epidemiologists have traditionally investigated geographical distributions of disease occurrence in order to identify etiologic clues. Each geographic area may have its own environmental risk factors and cultural differences with respect to diet, lifestyle and genetic factors.
Until recently, OSAS prevalence had only been established for a few populations. Therefore, the worldwide importance of OSAS as well as the potentially important racial or ethnic prevalence patterns was poorly understood. However, over the last 10 years a number of studies have been performed in Asian populations, providing information regarding the impact of ethnicity in OSAS.
Early population-based studies suggested that OSAS prevalence was higher among African-Americans than Caucasians. Ancoli-Israel et al [80] found that race is associated with the presence of severe OSAS (AHI ≥30), independently of age, sex and BMI. Furthermore, they reported that the AHI for African-Americans was significantly higher than for Caucasians (72.1 versus 43.3). Similar findings for other races have also been reported. The severity of OSAS among Asian patients has been reported to be greater than that for Caucasian patients matched for age, gender and BMI [80,81]. Li et al [82] also described differences between Asians and Caucasians, whereas Coltman et al [83] found differences between Caucasians and Polynesians.
In several studies, Asian race was associated with the presence of OSAS [32-34,43,84]. Udwadia et al [33] proposed that the high prevalence of OSAS that they observed might have been due to Indian facial and anthropometric characteristics. The similarity of the prevalence estimates in studies conducted in Hong Kong and in Western nations is provocative because obesity, a strong risk factor for OSAS, is prevalent in white populations but relatively uncommon in Asian countries. Thus, it follows that other factors must compensate for the obesity effect. Asian researchers have hypothesized that other OSAS risk factors more prevalent in Chinese populations, such as craniofacial features, may compromise the upper airway. Several soft and hard tissue factors can alter the mechanical properties of the upper airway and increase its propensity to collapse during sleep.
Small reductions in mandibular prognathism and a wider bony nasal aperture were major factors associated with OSAS in Polynesians [83]. In the same study, OSAS in Caucasians was associated with a larger neck circumference and reduced retropalatal airway size.
OTHER FACTORS
Ingestion of alcohol before sleep has been found to increase upper airway collapsibility and precipitate obstructive apneas and hypopneas during sleep. Alcohol intake can prolong apnea duration and worsen the severity of associated hypoxemia. Epidemiologic investigations show that current smoking is associated with a higher prevalence of snoring and OSAS [11]. It has been demonstrated that sedatives, hypnotic drugs and barbiturates can favor the appearance of SDB in normal subjects or aggravate pre-existing OSAS. Important genetic factors also exist. Familial aggregation of OSAS was first recognized in the 1970s by Strohl et al [85] in a family with several affected individuals. Since then, several large-scale studies have confirmed the role of inheritance and familial factors in the genesis of OSAS [11].
CONCLUSION
OSAS prevalence studies have been conducted in diverse populations over the past three decades. Age, gender and BMI are risk factors commonly associated with OSAS. Additional variables that also influence onset, development, and worsening include genetic factors, cigarette smoking and alcohol consumption. Given the high prevalence and public health burden of obstructive sleep apnea, the implications of untreated disease for the individual and society are enormous and cannot be ignored.
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