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(Chest. 2006;130:766-773.)
© 2006 American College of Chest Physicians

Low Socioeconomic Status Is a Risk Factor for Cardiovascular Disease Among Adult Obstructive Sleep Apnea Syndrome Patients Requiring Treatment*

Ariel Tarasiuk, PhD; Sari Greenberg-Dotan, MA; Tzahit Simon, MA; Asher Tal, MD; Arie Oksenberg, PhD and Haim Reuveni, MD

* From the Sleep-Wake Disorders Unit (Drs. Tarasiuk, Tal, and Reuveni, Mrs. Greenberg-Dotan, and Mrs. Simon), Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva; and Sleep Disorders Unit (Dr. Oksenberg), Loewenstein Hospital-Rehabilitation Center, Raanana, Israel.

Correspondence to: Ariel Tarasiuk, PhD, Sleep-Wake Disorders Unit, Soroka University Medical Center, PO Box 151, Beer-Sheva, 84105 Israel; e-mail: tarasiuk{at}bgu.ac.il

Abstract

Study objective: To evaluate the possible role of low socioeconomic status (SES) as a risk factor for cardiovascular disease (CVD) among obstructive sleep apnea syndrome (OSAS) patients requiring treatment.

Design: Polysomnographic and demographic characteristics and associated morbidity were measured in 686 prospectively recruited adult OSAS patients from two regions in Israel.

Setting: Two university-affiliated sleep laboratories.

Measurements and results: The multiple logistic regression (after adjusting for gender, body mass index [BMI], and smoking) revealed that the following are independent determinants for CVD in OSAS patients requiring treatment: each decrease in income level category (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1 to 1.7), age ≥ 1 year (OR, 1.07; 95% CI, 1.04 to 1.1), hypertension (OR, 2.0; 95% CI, 1.3 to 3.1), and hyperlipidemia (OR, 3.7; 95% CI, 2.4 to 5.8); area under the receiver operating characteristic (ROC) = 81.9%. The multivariate determinants describing the low-SES OSAS patients included: minorities and immigrants combined (OR, 6.0; 95% CI, 2.9 to 12), female gender (OR, 2.4; 95% CI, 1.6 to 3.9), increased BMI (OR, 1.9; 95% CI, 1.3 to 2.9), unmarried status (OR, 1.9; 95% CI, 1.2 to 3.1), and years of education (≥ 1 year) [OR, 0.8; 95% CI, 0.7 to 0.8]; area under the ROC = 78.1%.

Conclusion: In addition to the already known traditional risk factors, low SES was found to be a novel independent risk factor for CVD among adult OSAS patients requiring treatment.

Key Words: cardiovascular disease • immigrants • low socioeconomic status • minorities • obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder that affects 4% of middle-aged men and 2% of middle-aged women. OSAS is characterized by repetitive episodes of cessation of breathing followed by arousals from sleep and nocturnal hypoxemia. It is well documented that OSAS is a risk factor for chronic conditions, such as hypertension and cardiovascular disease (CVD).1 The frequent association of OSAS with obesity, increasing age, hypertension, and hypercholesterolemia challenges the hypothesis that OSAS represents an independent risk factor for CVD.1 At the time of diagnosis, patients often report a long history of symptoms going back many years.2 OSAS morbidity results in heavy consumption of health-care resources234 due to CVD.35678910 Mechanisms linking OSAS with CVDs are complex and certainly multifactorial. They may include hemodynamic, neural, metabolic, endothelial, coagulatory, and inflammatory consequences of nocturnal respiratory events and hypoxia. Interestingly, none of the polysomnographic objective indexes of severity predict the 2.5-fold increase of CVD among OSAS patients.34 The lack of correlation between CVD and apnea-hypopnea index (AHI) is probably related to the fact that AHI is an imperfect measure of severity.3 The participation of other, independent risk factors may help to better understand the relationship between OSAS and CVD.

Low socioeconomic status (SES), regardless of the methodology used for determination, is inversely related to health and closely related to both mortality and morbidity from CVD.1112131415161718192021 Patients with OSAS1 and people with low SES have higher rates of obesity, glucose intolerance, and cigarette smoking.2022 However, little is known about whether risk factors associated with low SES per se contribute to the diagnosis of CVD, in addition to the already known risk factors among OSAS patients, specifically among the subgroup of patients requiring treatment.

In Israel, the largest minority group is Arabian (Bedouin and non-Bedouin), who comprise approximately 20% of the total Israeli population. A mass influx of > 1 million immigrants from the former Soviet Union to Israel followed the demise of the Soviet Bloc at the beginning of the 1990s. According to the National Social Security Institute Report on Poverty in Israel,23 these two groups are living below the poverty line and represent the majority of the low-SES population in the country.

The aim of the study was to evaluate the possible role of low SES as an independent risk factor for CVD among a group of OSAS patients requiring treatment. Low SES is a known risk factor for CVD morbidity regardless of OSAS. In most OSAS patients who met the inclusion criteria for treatment, CVD was usually present. However, little is known of whether SES contributes to CVD morbidity among these patients, in which other risk factors for CVD exist. We hypothesize that low SES is an independent risk factor for CVD among adult OSAS patients requiring treatment.

Materials and Methods

Study Design and Population
This study began in June 2003 in two universities with affiliated sleep-wake disorders centers. Prospective data were collected on consecutively recruited OSAS patients aged ≥ 18 years requiring treatment who underwent polysomnography and a healthy control group during the 13-month study period.

To reconfirm morbidity among OSAS patients, we compared 686 patients with OSAS to healthy subjects matched 1:1 by age, gender, geographic location, and family physician (p = 0.999). The control group was selected randomly from the healthy general population in the Clalit Health Care Services (CHS) database. Excluded patients were those receiving noninvasive positive pressure for COPD and patients with other conditions leading to nocturnal hypoventilation, such as neuromuscular diseases. Patients with facial abnormalities, genetic disorders, cancer, or autoimmune disorders, and patients hospitalized > 50 days in the 5 years preceding the research were also excluded.3 None of the control subjects met these inclusion criteria (ie, in the control group, only 4% of the subjects [n = 27] were hospitalized ≥ 11 days up to 30 days in the 5 years preceding the research); however, in the OSAS patients requiring treatment, 10.5% of the subjects (n = 72) were hospitalized ≥ 11 days up to 50 days in the 5 years preceding the research. Patients were not matched to control subjects for body mass index (BMI) because that information is not included in the CHS database. Due to ethical considerations, we were not able to contact the control subjects. We confirmed that the control group was healthy and that none of these subjects had a chronic disease by verifying that they did not receive any regular prescribed medications. However, it is possible that 2 to 4% of the control subjects might have undiagnosed OSAS.1 All subjects are enrollees of CHS, the largest health maintenance organization in Israel, providing medical services to approximately 60% of the total Israeli population. The research was carried out in two sleep-wake disorders centers (Soroka University Medical Center and Loewenstein Hospital-Rehabilitation Center) in two districts (center and south). In these sleep laboratories, >70% and > 95% of patients are enrollees of CHS, respectively. The southern region (Negev) of CHS includes 470,472 enrollees, 17.4% of whom are of Arab Bedouin origin and 14.9% are immigrants. The center region (Sharon-Shomron) includes 542,180 enrollees; 24.8% and 7.1% are of Arab origin and immigrants, respectively.

Selection of Patients
We included only patients with polysomnography-proven OSAS requiring treatment with an AHI ≥ 30/h of sleep, regardless of symptoms, and patients with an AHI of 5 to 30/h of sleep accompanied by symptoms of excessive daytime sleepiness according to an Epworth sleepiness scale (ESS) score of ≥ 10,24 and/or documented CVD to include hypertension, ischemic heart disease, and/or stroke. We did not include asymptomatic patients without CVD who demonstrate mild-to-moderate OSAS (AHI < 30/h without clinical symptoms) on polysomnography who did not require treatment.25

Definitions
SES:
SES was evaluated according to individual monthly income and educational attainment.18202627 Since immigrants are considered highly educated but from low SES (see immigrant definition below), for the purpose of this study, we used household monthly income as the main determinant of SES. We asked participants to rate their individual monthly income level according to three categories: below (< 20%), equal to (± 20%), and above (> 20%) the average monthly income level. Education level was assessed according to years of study. In addition, responders categorized their education level as elementary education or lower, some high school, high school graduate, some college, or higher. We defined the variable of consumption of vitamins and food supplements as an index for health consciousness.28 Reduced intake of vitamins and food supplements is reported among low-SES populations.29 The low-SES population was defined as subjects with a monthly income below the national average and with low educational attainment. This variable correlates with Israeli census data on SES according to area of residency.30

According to the National Social Security Report on Poverty in Israel in 2005, 57.5%, 43.0%, and 30.0% of minorities, immigrants, and native Jewish residents respectively, were living below the poverty line in 2004.23 Thus, minorities and immigrants experience 91.6% and 43.3% more poverty, respectively, compared to native Jewish residents in Israel.

Minorities:
According to the Israeli census, Arabs (Bedouin and non-Bedouin) comprise approximately 20% of the total Israeli population. Bedouin live mainly in the south: approximately one half live nomadic lives, and the other half live in villages and urban centers. Non-Bedouin Arabs living in the center region are mainly in villages and urban centers.

Immigrants:
Large demographic changes occur in Israel, as the country continuously absorbs waves of immigrants from all areas of the world. A mass influx of > 1 million immigrants from the former Soviet Union to Israel followed the demise of the Soviet Bloc at the beginning of the 1990s. We included all immigrants who have arrived since January 1990. This group is highly educated and has fewer children than others living in Israel. Due to acculturation, this group is considered low SES due to language difficulties, lack of professional endorsement, older age, and psychological stress, all leading to high unemployment rate and lower household monthly income.31

Data Collection
Questionnaires:
Each individual’s personal lifestyle, sleeping habits, and clinical history were recorded using a standardized self-administered questionnaire.2832 Questionnaires were administered to all patients undergoing polysomnography and not to the control subjects. All questionnaires were completed prior to polysomnography. Life habits were evaluated by determining smoking habits, consumption of coffee and tea,18 and daily consumption of vitamins and food supplements.29 The ESS, a self-administered eight-item questionnaire commonly used to assess sleepiness,24 was employed. Daytime functional status and quality of life were assessed using the Functional Outcomes of Sleep Questionnaire (FOSQ),33 a self-administered 30-item questionnaire designed to assess the impact of disorders of excessive sleepiness on five domains of everyday living: activity level, vigilance, intimacy, general productivity, and social outcome.

Two weeks prior to the polysomnography, questionnaires were delivered via mail to the patients. On arrival at the sleep laboratory, a nighttime technologist clarified questions as necessary. Language was not a barrier to completing the questionnaire, as it was validated in three languages (Hebrew, Arabic, and Russian) and we used research assistants fluent in these languages. The Institutional Ethics Committee approved the protocol, and informed consent was obtained from all OSAS subjects.

Comorbid Diagnoses:
CHS has a cumulative database that allows tracking medical diagnoses according to the International Classification of Diseases, Ninth Revision (ICD-9). Physicians enter these diagnoses during hospital visits and in a community setting. This database is highly reliable and contains > 98% of all patient diagnoses. We reviewed the accumulated diagnoses of CVD along with their respective ICD-9 codes, including hypertension (401–405), ischemic heart disease (410–414), cardiac arrhythmia, congestive heart failure, valvular cardiac disease, cerebrovascular accident (426–438), and peripheral vascular disease (443). A definition of CVD diagnosis20 includes at least one of the following ICD-9 codes: 410–414, 426–438, and 443. In addition, we included medical conditions that increase the risk of CVD: hyperlipidemia (272) and diabetes mellitus (250). We calculated the BMI based on measurements of body weight and height obtained before polysomnography.

Polysomnography:
Overnight polysomnography was performed according to previously described methods from our sleep-wake disorders centers.3435 Briefly, this involved multichannel monitoring, including EEG, electrooculography, and electromyography, applied over the submental muscles and bilateral anterior tibialis muscles for detection of periodic limb movements, ECG, respiratory activity (airflow and chest/abdominal effort), body position, and arterial oxygen saturation (SaO2).

Statistical Analysis
All analyses were done using statistical software (v 12.0; SPSS; Chicago, IL). Continuous variables are presented as mean with SD unless otherwise specified. We used one-way analysis of variance (ANOVA-1) and the {chi}2 test to determine statistical significance between variables. Following descriptive and quantitative analysis, logistic regression analysis was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Independent variables included age, gender, BMI, hypertension, smoking, monthly income level, hyperlipidemia, diabetes, polysomnographic findings (AHI, SaO2 < 90%, and percentage of time sleeping with SaO2 < 90% [T90%]), and ESS. The multiple logistic regression model was fitted to establish the primary determinants of CVD and low-income subjects (dependent variables). For each model, the area under the receiver operating characteristic (ROC) was calculated. Therefore, the main outcome of this study is diagnosis of CVD among OSAS patients. The null hypothesis was rejected at the 5% level.

Results

A total of 1,214 subjects underwent polysomnography during the 13-month study period. Of those, 116 patients (9.6%) refused to participate in the study and 79 patients (6.5%) did not meet the inclusion criteria. Therefore, 1,019 patients were eligible for the study. Following polysomnography, 333 patients (32.7%) did not meet the inclusion criteria of OSAS severity. Finally, the study population included 686 OSAS patients requiring treatment. Of those, 364 patients (53.1%) had an AHI ≥ 30 (99, 101, and 70 patients had CVD, ESS score > 10, and CVD plus ESS score > 10, respectively; 94 patients had no morbidity). Three hundred twenty-two patients (46.9%) had an AHI of 5 to 30/h (123, 144, and 55 patients had CVD, ESS score > 10, and CVD plus ESS score > 10, respectively). Patients who refused to be included or were included in the study were similar in age, gender, BMI, and percentage of minority or immigrant status.

Table 1 describes the characteristics of our OSAS patients; 12.2% were minorities and immigrants and had significantly higher BMI and AHI, and lower FOSQ scores, than native Jewish residents. All five FOSQ domains were significantly lower among minorities and immigrants: activity level, vigilance, intimacy, general productivity, and social outcome (p < 0.0001). ESS score as an index of excessive daytime sleepiness inversely correlates with FOSQ score (r = – 0.26, p < 0.0001). At the time of OSAS diagnosis, minorities were 10 years younger than both immigrants and native Jewish residents (p < 0.0001).


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  		Table 1. Demographic, Polysomnographic, and Clinical Characteristics of OSAS Patients Requiring Treatment*

 
We examined the probability of a given cardiovascular disorder in OSAS patients requiring treatment, compared with their control subjects. OSAS patients had statistically significant increased odds of having a diagnosis in all of the selected disease categories (Table 2 ). For four specific cardiovascular diagnoses (hypertension, ischemic heart disease, cardiac arrhythmia, and congestive heart failure), as well as overall CVD, OSAS patients were more than twice as likely as their control subjects to have received a diagnosis for CVD. OSAS patients also were more likely to have diagnoses of hyperlipidemia and diabetes (Table 2).


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  		Table 2. Prevalence and ORs of Comorbid Cardiovascular-Related Diagnoses in 686 OSAS Patients Requiring Treatment vs Matched Control Subjects

 
Table 3 shows the key demographic characteristics of minorities, immigrants, and native Jewish residents. Low SES/income level was twice as prevalent among immigrants and minorities compared to native Jewish residents (p < 0.0001). Monthly income levels are associated with education level categories ({chi}2 = 47.2, p < 0.0001). Only 20% of the minorities completed ≥ 12 years of education, compared to 67.5% among immigrants and approximately 40% of the native Jewish residents (p < 0.0001). Tobacco smoking is higher (p < 0.05) in immigrants and minorities compared to native Jewish residents in Israel. Consumption of vitamins and food supplements among immigrants and minorities was 57% and 39% less (p < 0.05) compared to native Jewish residents, respectively. Dividing the native Jewish population living in Israel according to monthly income level revealed that education level (– 3 years) and FOSQ (– 11%) scores were lower, while BMI was 2.5 kg/m2 higher (p < 0.0001) within the low-income subgroup.


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  		Table 3. Education, Income, and Other Characteristics of Minorities, Immigrants, and Native Jewish OSAS Patients Requiring Treatment*

 
The prevalence of comorbidities according to income level is presented in Table 4 . Approximately 50% of low-income patients have the five medical diagnoses as presented in Table 4. Three medical diagnoses (CVD, ischemic heart disease, and diabetes) have a significantly lower occurrence among higher-income patients.


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  		Table 4. Prevalence of Comorbidities According to Income Level in OSAS Patients Requiring Treatment*

 
The multivariate ORs of the determinants of low-income level (n = 686) [low SES] are as follows: minorities and immigrants combined (OR, 6.0; 95% CI, 2.9 to 12), female vs male gender (OR, 2.4; 95% CI, 1.6 to 3.9), increased BMI (+ 1 kg/cm2) [OR, 1.9; 95% CI, 1.3 to 2.9], and unmarried status (OR, 1.9; 95% CI, 1.2 to 3.1). Years of education (≥ 1 year) considerably reduces the risk (OR, 0.8; 95% CI, 0.7 to 0.8) of being included among the low-income group. The model predicting low-income level (low SES) had area under the ROC of 78.1%. None of the polysomnographic objective findings were predictors for low-income level.

We explored whether SES (according to personal income level) has an independent effect on CVD over and above the conventional reported CVD risk factors among OSAS patients. The univariate and multivariate ORs of determinants of CVD are presented in Table 5 . After adjusting for gender, BMI, and smoking, multiple logistic regression analysis revealed that for each decrease in income level (OR, 1.4; 95% CI, 1.1 to 1.7), age + 1 year (OR, 1.07; 95% CI, 1.04 to 1.1), hypertension (OR, 2.0; 95% CI, 1.3 to 3.1), and hyperlipidemia (OR, 3.7; 95% CI, 2.4 to 5.8) are independent determinants for CVD in OSAS patients. The model predicting CVD had area under the ROC of 81.9%. For each decrease in category of income level (SES level), the independent risk for CVD in OSA patients increases. Therefore, the increased risk for CVD in OSA patients in the lower-third income level, compared with those in the higher-third income level, is 1.96. None of the polysomnographic objective findings (AHI, SaO2 < 90%, and ESS) add to the prediction of CVD among OSAS patients (Table 5).


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  		Table 5. Determinants of CVD in OSAS Patients Requiring Treatment

 
Discussion

The main novel finding of our study is that in addition to the already known traditional risk factors (age, gender, BMI, hypertension, and hyperlipidemia), low SES is an independent risk factor for CVD among OSAS patients requiring treatment.

Studied Population
Israeli society is comprised primarily of two groups of Semitic origin: Jews and Arabs (Bedouin and non-Bedouin). Life expectancy at birth in Israel is lower among minorities compared to native Jewish residents.36 This study represents results of "typical" adult OSAS patients.6 According to the Israeli National Health Insurance Law, all patients have free access to polysomnography; thus, physicians do not have any economic incentives to prevent or deter patients from the study.27 In this study, minorities (both Bedouin and non-Bedouin) with OSAS were younger (on average by 10 years) and more ill than native Jewish OSAS patients living in Israel. Persistent higher manifestation of poverty among minorities than among Jews has sufficed to maintain the gap in life expectancy between the two nationality groups.3037 Both minorities and immigrants had a greater risk of being included among low-income/low-SES patients (OR; 6.0, 95% CI, 2.9 to 12). Immigrants have a lower SES compared to other Jews living in Israel, ie, they have a high level of unemployment and a low income level.3038 Immigrants to Israel report a higher rate of diseases and suboptimal health after adjustment for other variables, partially reflecting the poor state of health in the former Soviet Union compared to Israel.38 In England, South Asian immigrants3940 also have higher rates of CVD, probably attributable to SES risk factors similar to those seen in Israel.

Although we matched case patients and control subjects by family physician, age, gender, and area of residence, we were not permitted to contact the control subjects to obtain their SES and other medical data because of legislation protecting patient confidentiality. ORs between OSAS patients and control subjects with regard to CVD may actually be higher than reported, since the control group may include some patients with undiagnosed OSAS. A possible limitation of our selected control group is the fact that we did not explore the level of SES in this group. This information is not included in the CHS database, and we were not permitted to contact the control subjects. However, we matched the study and control group by family physician, serving patient populations in the same geographic region. Since subjects living in the same residential area have similar SES levels,18 it is reasonable to assume that our study and control groups have comparable SES levels. Although we assume that this limitation has limited effect on our results, studies are needed to further clarify this issue.

Low SES and CVD:
Established evidence shows that low SES is associated with adverse health outcomes.131617 Low SES is an established risk factor for CVD.131415161741 Those with lower SES have a higher likelihood of exposure to SES risk behaviors, such as smoking, excessive alcohol consumption, physical inactivity, poor diet, and nonattendance to health checkups.1314171842 As in previous studies37384243444546 from Israel, we found that low-SES patients have lower health status (overweight, type 2 diabetes, and increased odds for CVD) and more risk behaviors such as high smoking rate compared with higher SES patients. These risk factors are all associated with a lower income level.313243444546 Possible explanations for excess mortality due to CVD among Palestinian residents of Jerusalem include a higher prevalence of conventional risk factors such as diabetes, obesity, smoking, stress, and low SES.47 Minorities and immigrants reported significantly lower use of vitamins and food supplements. Poor dietary habits are associated with being overweight, and low consumption of vitamins and food supplements can be regarded as indexes of low health consciousness.29

Low SES, CVD, and OSAS:
In a multivariate analysis comparing women with OSAS requiring treatment vs men, it was found that female gender was an independent risk factor for low SES. One possible explanation is the fact that the average monthly income of women in Israel is considerably lower than that of men.2330 It is known that low SES is a risk factor for CVD morbidity. Our preliminary results support the evidence that women, compared to men, with OSAS requiring treatment have a higher risk for comorbidity, including CVD (OR, 1.29; 95% CI, 1.1 to 1.65). In fact, Smith et al3 found that women with OSAS consumed more health-care services (OR, 1.6) and drugs compared to men. In our study,4 utilization of health-care services was approximately twofold greater in women than men with OSAS.

This report provides evidence that low SES is an independent risk factor for CVD among adult OSAS patients requiring treatment. As expected, the studied population has an increase probability of CVD relative to healthy control subjects (Table 2). Prior to diagnosis (but not necessarily prior to disease onset), OSAS patients more frequently received diagnoses of CVD.1367910 Mechanisms linking OSAS with CVD may include, among others, consequences of nocturnal hypoxia due to cessation of respiratory events during sleep.568 Similar to the Manitoba study,4 variables such as AHI, ESS score, and T90% have little predictive value of CVD in our OSAS patients. The information that polysomnographic findings did not predict CVD may result from the fact that we included only OSAS patients requiring treatment, and these patients probably had an AHI above the CVD threshold. Furthermore, it has been published48 that not infrequently on diagnosis, many patients with OSAS do not yet have a diagnosis of CVD, which can come later if the OSAS remains untreated. This study suggests that low SES is an independent risk factor for CVD among OSAS patients, with 1.96-fold odds of having CVD compared with the highest income level OSAS patients (Table 5). Minority-serving institutions have low-SES patients with greater BMI, higher daytime BP, more OSAS-related CVD comorbidity, and lower minimum sleep SaO2 than voluntary hospitals.49 Our findings are novel and should be supported by further studies that will explore the association between polysomnographic findings, SES, and CVD in population-based studies. Other possible reasons why SES might uniquely influence CVD in OSAS patients include lack of education and knowledge about OSAS, which would impair recognition of sleep symptoms and delay diagnosis50; cultural differences affecting the recognition of sleep-related symptoms or acceptance of the diagnosis of OSAS; lack of access to care; and differences in adherence with treatment in lower SES groups.27

Summary
In addition to the already known traditional risk factors, low SES was found to be a novel independent risk factor for CVD among adult OSAS patients requiring treatment. For each decrease in income level category, the risk for CVD increases by 40%.

Footnotes

Abbreviations: AHI = apnea-hypopnea index; ANOVA-1 = one-way analysis of variance; BMI = body mass index; CHS = Clalit Health Care Services; CI = confidence interval; CVD = cardiovascular disease; ESS = Epworth sleepiness scale; FOSQ = Functional Outcomes of Sleep Questionnaire; ICD-9 = International Classification of Diseases, Ninth Revision; OR = odds ratio; OSAS = obstructive sleep apnea syndrome; ROC = receiver operating characteristic; SaO2 = arterial oxygen saturation; SES = socioeconomic status; T90% = percentage of time sleeping with arterial oxygen saturation < 90%

This study was supported by a competitive grant from the Israeli Institute for Health Policy and Health Services Research, award No. B/17/2000.

The authors declare that they have no financial conflict of interest with any manufacturers or products mentioned in this article.

Received for publication November 23, 2005. Accepted for publication February 24, 2006.

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