The Korean Obstructive Sleep Apnea Morbidity Study (KOSMOS) Protocol

Sei Won Kim; Hyeon Hui Kang; Kyu Yean Kim; Jin Woo Kim; Hong Jun Jeon; Doo-Heum Park; Jae Won Choi; Eui Joong Kim; Dong-Hyun Joo; Young Jae Cho; Sei Won Lee; So-Jin Lee; Wan Seok Seo; So-Hyun Ahn; Seok-Jin Hong; Jin Oh Na; Sang Haak Lee

doi:10.33069/cim.2025.0004

Chronobiol Med > Volume 7(2); 2025 > Article

Kim, Kang, Kim, Kim, Jeon, Park, Choi, Kim, Joo, Cho, Lee, Lee, Seo, Ahn, Hong, Na, Lee, and Korean Academy of Sleep Medicine: The Korean Obstructive Sleep Apnea Morbidity Study (KOSMOS) Protocol

Study Protocol

Chronobiology in Medicine 2025;7(2):102-109.

Published online: June 27, 2025

DOI: https://doi.org/10.33069/cim.2025.0004

The Korean Obstructive Sleep Apnea Morbidity Study (KOSMOS) Protocol

Sei Won Kim¹

, Hyeon Hui Kang¹

, Kyu Yean Kim²

, Jin Woo Kim²

, Hong Jun Jeon³

, Doo-Heum Park³

, Jae Won Choi⁴

, Eui Joong Kim⁴

, Dong-Hyun Joo⁵

, Young Jae Cho⁵

, Sei Won Lee⁶

, So-Jin Lee⁷

, Wan Seok Seo⁸

, So-Hyun Ahn⁹

, Seok-Jin Hong¹⁰

, Jin Oh Na¹¹

, Sang Haak Lee¹

;Korean Academy of Sleep Medicine

¹Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

²Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea

³Department of Psychiatry, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea

⁴Department of Psychiatry, Nowon Eulji Medical Center, Eulji University, Seoul, Korea

⁵Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

⁶Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁷Department of Psychiatry, Gyeongsang National University School of Medicine, Jinju, Korea

⁸Department of Psychiatry, Yeungnam University College of Medicine, Daegu, Korea

⁹Department of Psychiatry, Chungnam National University Hospital, Daejeon, Korea

¹⁰Department of Otorhinolaryngology-Head & Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

¹¹Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea

Corresponding author: Sang Haak Lee, MD, PhD, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-ro, Eunpyeong-gu, Seoul 03312, Korea.
Tel: 82-2-2030-4640, E-mail: mdlee@catholic.ac.kr

Received January 27, 2025 Revised February 13, 2025 Accepted February 20, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Obstructive sleep apnea (OSA) is a heterogeneous syndrome with various predisposing factors, pathophysiological mechanisms, clinical presentations, and consequences of respiratory events. Treatment compliance and outcomes vary among the clinical subtypes of OSA. The best OSA treatment approach involves accurate clinical subtype diagnosis and long-term follow-up. However, most of the previous studies were conducted in Western populations, and few analyses of Korean data have been performed. To investigate the characteristics and long-term prognosis of Korean OSA patients, the Korean Obstructive Sleep apnea Morbidity Study (KOSMOS), a prospective large multicenter cohort, was designed. Adults diagnosed with OSA with an apnea-hypopnea index of ≥5 by type 1 polysomnography are enrolled regardless of subsequent positive airway pressure (PAP) treatment. Enrollment is possible through all departments treating patients with OSA. Follow-up will be performed every 12 months, and the study plans to follow the subjects for 30 years. Demographics, health behaviors, medical history, medication, family medical history, presence of snoring, and allergy will be investigated. Anthropometric measurements and blood pressure will be checked in the hospital. Polysomnography, PAP titration, and PAP compliance data will also be collected. Clinical questionnaires will be administered, and survival will be assessed. The KOSMOS cohort is the first and only prospective multicenter multidisciplinary OSA cohort study in Korea. Through this long-term planned cohort study, we will be able to gain a detailed understanding of the characteristics of OSA in Koreans and conduct a thorough analysis of the disease’s progression and prognosis.

Keywords: Obstructive sleep apnea syndrome; Cardiovascular disease; Continuous positive airway pressure; Cohort studies

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway narrowing or collapse during sleep, which causes intermittent hypoxia and sleep fragmentation [1,2]. The estimated prevalence of OSA in the general population is 9%–38% [3]. Moreover, the prevalence of OSA is 20%–50% among the population aged ≥65 years [4,5] and >40% among the obese [6,7]. However, up to 80% of moderate-to-severe OSA cases are undiagnosed despite adequate access to medical services [8,9]. OSA is associated with hypertension, diabetes mellitus, atrial fibrillation, heart failure, coronary heart disease, stroke, and death [10-13]. Intermittent hypoxemia, sympathetic activation, oxidative stress, and inflammation have been proposed as the underlying mechanisms [14-16].

Currently, diagnosis and treatment of OSA relies primarily on the apnea-hypopnea index (AHI). However, OSA is a heterogeneous syndrome, with various predisposing factors, pathophysiological mechanisms, clinical presentations, and consequences of respiratory events [17,18]. As a result, treatment compliance and outcomes vary among the clinical subtypes of OSA [17]. The best OSA treatment approach involves accurate clinical subtype diagnosis and long-term follow-up. A large-scale cohort study of OSA patients is needed.

In Korea, the number of sleep studies has increased sharply since national health insurance coverage started in 2018 [19]. Korean patients with OSA are approached and treated differently by specialists in internal medicine, otolaryngology, neurology, and psychiatry. Therefore, multicenter, multidisciplinary research is essential for determining the clinical characteristics of Korean OSA patients, who have different anatomical structures from those of Westerners, to allow for treatment tailored to Koreans. For this purpose, the Korean Obstructive Sleep apnea Morbidity Study (KOSMOS), a prospective large multicenter cohort, was designed.

METHODS

Objectives

The KOSMOS study is intended to: 1) develop a web-based registration system for inputting data on OSA patients, including important basic characteristics, polysomnography (PSG) results, and follow-up data; 2) identify the current status and characteristics of OSA patients in Korea, observe the long-term clinical course, and identify factors affecting the course of the disease; and 3) analyze mortality from cardiovascular disease in the long-term follow-up according to continuous positive airway pressure (CPAP) adherence.

Patient enrollment

The cohort in this study includes adults aged ≥19 years diagnosed with OSA (AHI ≥5) by type 1 PSG regardless of whether positive airway pressure (PAP) therapy is prescribed. Currently, the home sleep apnea test is not in official use and is not covered by health insurance in Korea. Enrollment is possible through all departments treating patients with OSA. Patient enrollment for this study started in April 2020. The KOSMOS cohort was registered in the Clinical Research Information Service (CRIS), which is a non-profit online registration system for clinical trials (researches) to be conducted in Korea (registration number, KCT0004850, https://cris.nih.go.kr).

Size of the study population

Based on consultation with the Department of Statistics, the study population required to validate the hypothesis that there would be a difference in mortality from cardiovascular disease according to adherence to PAP therapy was calculated. Based on the average daily use time of PAP therapy, the study population was divided into two groups: average time of PAP therapy ≥4 and <4 hours. The goal is to register 1,375 OSA patients per group, or a total of 2,750 OSA patients within 10 years of starting the study.

The number of study subjects required for survival analysis was calculated by referring to the preceding literature on overall survival analysis according to the CPAP treatment group for OSA patients [20]. Referring to the literature, the relative hazard was set at 2.0. For the proportion of subjects whose event was observed without being censored among the total subjects, 0.1 (the ratio of cardiovascular deaths among the total subjects in the reference literature) was applied. The ratio of the CPAP treatment group to the non-treatment group was 0.65 and 0.35, which are the ratios of the CPAP treatment group and the non-treatment group in the reference literature. The number of valid cases per group was calculated to be 962 cases for hypothesis testing that guarantees a two-sided significance level (α) of 5% and a power (1-β) of 90%. Considering the dropout rate of 30%, a total of more than 2,750 subjects, 1,375 per group, should be recruited. Patient enrollment is competitive at each institution.

Follow-up

Upon enrollment, follow-up is performed every 12 months. If a visit cannot be scheduled every 12 months, patients can be followed within 6 months of the scheduled visit date. In principle, all visits are made in person, but if a visit is impossible, a telephone interview can be scheduled instead. The plan is for subjects to participate in the study for 30 years.

Ethics considerations

The institutional review boards of each participating hospital approved the study protocol, and written consent was obtained from all patients: The Catholic University of Korea Eunpyeong St. Mary’s Hospital (XC19OCDE0059), The Catholic University of Korea Uijeongbu St. Mary’s Hospital (XC19OCDE0059), The Eulji University of Korea Nowon Eulji Medical Center (EMCIRB19-93), Seoul National University Bundang Hospital (B-2209-781-302), Chungnam National University Hospital (CNUH 2020-10-052), Yeungnam University College of Medicine, Yeungnam University Hospital (YUMC 2019-09-0455), Konkuk University Medical Center (KUMC 2021-06-010), Ilsan Paik Hospital (2022-09-032), Korea University Guro Hospital (2021GR0445), and Asan Medical Center (2022-0401). Participants were also informed of their right to withdraw from the study at any time without penalty. Patient registration for this study started in April 2020, and 10 university hospitals in Korea are participating as of 2025.

Measurements

Baseline characteristics

Demographic characteristics determined at visit 0 or 1 included sex, age, clinical department enrolled from, employment, shift work, menopause, bed partner, and pets (Table 1). Health-related behaviors such as smoking, alcohol, and caffeine use were examined at visit 1 (V1) and every 12 months thereafter. Smoking history was assessed in terms of current smoking status, amount smoked, and age of smoking initiation/cessation. Smoking status was classified as never-smoker, ex-smoker, current smoker, and unknown. Never-smoker was defined as lifetime smoking of less than five packs (100 cigarettes). Ex-smoker and current smoker were defined as lifetime smoking of more than five packs (100 cigarettes), and participants were classified according to whether they had smoked within the last 30 days. Alcohol history was investigated in terms of the frequency and amount of drinking, and the frequency of excessive drinking. Caffeine intake per day was investigated according to the content of each beverage. Medical and medication history, presence of snoring, allergy, and survival were checked at V1 and every 12 months thereafter. Family medical history was checked at V1 and every 12 months thereafter.

Anthropometric measurements

Anthropometric measurements and blood pressure were taken by trained researchers or nurses in the hospital, with the subjects wearing light clothing with no shoes. Height and neck/waist/hip circumference were measured to the nearest 0.1 cm and body weight to the nearest 0.1 g. Neck, waist, and hip circumference were measured using standardized procedures at the levels of the cricothyroid membrane, midpoint between lowest palpable rib and iliac crest, and greater trochanter, respectively. Circumferences were measured with the patients in a standing position using a flexible anthropometric tape. Circumference measurements are taken while ensuring even breathing and during a gentle exhalation, ensuring that the tape does not compress the skin. Except for height, the anthropometric measurements were checked at V1 and every 12 months thereafter. Height was measured only once, at V1. Body mass index (BMI) was calculated as body weight in kilograms divided by height in meters squared. Blood pressure measured before and after sleep for PSG was recorded at V1 and every 12 months thereafter; the blood pressure was measured once during a clinical visit using an automatic device with the correct cuff size after resting in a stable position for 5 minutes.

Questionnaires

The Fatigue Severity Scale (FSS) [21], Korean Translation of Composite Scale (KtCS) [22], Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) [23], Korean version of the Epworth Sleepiness Scale (KESS) [24], International Prostate Symptom Score (IPSS) [25], Hospital Anxiety and Depression Scale (HADS) [26], Korean version of the Berlin Questionnaire (K-BQ) [27], Snoring, Tiredness, Observed apnea and high blood Pressure–Body mass index, Age, Neck circumference, Gender (STOPBANG) questionnaire [28], Insomnia Severity Index (ISI) [29], and Quality of Life Scale-abbreviated version (QOL BREF) [30] were administered at enrollment. The presence or absence of the four symptoms listed in the diagnostic criteria for restless leg syndrome (RLS) published by the International Restless Legs Syndrome Study Group (IRLSSG) was also checked at enrollment [31]. Except for IRLSSG-based RLS diagnostic criteria and KtCS, all questionnaires are administered at 12-month intervals.

Polysomnography

All PSG raw data were scored by experienced sleep technicians according to the American Academy of Sleep Medicine (AASM) manual for the scoring of sleep and associated events. All reports were reviewed and interpreted by sleep physicians at each sleep center. Total sleep time, sleep efficiency, sleep latency, rapid eye movement (REM) latency, sleep stages, awakenings, arousals, apnea and hypopnea, limb movements, snores, oxygen desaturation, average/minimum/maximum oxygen saturation during desaturation, obstructive/mixed/central/total apnea, obstructive/mixed/central/total hypopnea, AHI, respiratory effort-related arousal, respiratory disturbance index (RDI), and respiratory event duration were recorded at V1. After PSG at V1, treatment options (PAP therapy, non-PAP therapy, or observation without treatment) were assessed. For patients who underwent PAP titration, PAP type, pressure, periodic limb movements, and supplemental oxygen use were also checked at V1.

PAP therapy and compliance

Patients receiving PAP treatment were surveyed at V2 and every 12 months thereafter regarding the method of and compliance to PAP treatment. Interface, PAP type, pressure, usage (average use time [all days] and percentage of days with use ≥4 h), average AHI, supplemental oxygen, leak, and the manufacturer and model of PAP device were recorded.

Data collection and management

Study data are collected by sites and entered into a central e-clinical trial platform (Korea University Medical Center [KUMC] MEBICA System, http://kumc.mebica.net). Data validation and the assessment of missing data are carried out by the KOSMOS cohort’s quality control committee, comprised of statistical cohort experts, in collaboration with the Clinical Trial Center of Korea University Anam Hospital. Regular data reports and reviews are conducted on a quarterly basis. Periodic audits are conducted independent of the site investigators.

Statistical analysis

Demographic and baseline characteristics will be summarized utilizing descriptive statistics. The mean and standard deviation were computed for normally distributed continuous variables, and the median and interquartile range (25th–75th percentiles) were determined for non-normally distributed continuous data. Categorical data are presented as numbers and percentages. Before proceeding with parametric statistical analyses, each dataset will be subjected to a normality verification using the Shapiro-Wilk test. For continuous variables that do not adhere to the normality prerequisites, relevant transformations will be executed to comply with the assumptions underlying parametric methods. In instances where such transformations are either not viable or unsuitable, alternatives in the form of non-parametric approaches will be adopted. For the analysis of the study’s primary endpoint, the hazard of mortality from cardiovascular disease based on adherence to PAP therapy, a Cox proportional hazards regression model will be fitted. This model will facilitate the examination of the impact of CPAP therapy adherence on cardiovascular mortality, controlling for potential confounders. Statistical significance for all tests will be established at a p-value threshold of less than 0.05, unless specified otherwise.

FINDINGS TO DATE

From April 2020 to January 2025, 529 OSA patients (386 males, 143 females) were enrolled. Due to the impact of COVID-19, patient enrollment encountered challenges in the early stages of the research; however, the rate of registration recovered following the pandemic. The median age, BMI, and neck circumference were 60.0 (range: 45.0–68.0) years, 27.4 (range: 24.7–30.5) kg/m², and 38.0 (range: 36.0–41.0) cm, respectively (Table 2). The most common comorbidities were dyslipidemia (43.5%), hypertension (28.2%), diabetes (21.7%), rhinitis (18.7%), asthma (15.3%), and fatty liver (15.3%). The respective prevalences of arrhythmia, coronary artery disease, other heart diseases, and cerebrovascular disease were 7.4%, 6.8%, 10.4%, and 4.0%, respectively. Comparing men and women, there were significant differences in age (p<0.001), neck circumference (p<0.001), waist circumference (p<0.001), and smoking status (p<0.001). The main reasons for visiting a sleep clinic were snoring, apnea, choking, daytime sleepiness, and fatigue (Table 3). Snoring was the most common reason for a hospital visit in both men and women. Apnea and choking were significantly more frequent reasons for a hospital visit in men than women (p<0.001). By contrast, insomnia and lower extremity tremor or discomfort were more frequent reasons for a hospital visit in women (p=0.015 and p=0.022, respectively). The median AHI, RDI, and oxygen desaturation index (ODI) were 34.2 (range: 20.1–55.6), 37.8 (range: 20.7–59.5), and 26.6 (range: 13.9–46.7), respectively (Table 4). Men had significantly higher AHI, RDI, and ODI values than women (p=0.002, p=0.006, and p=0.003, respectively). The minimum oxygen saturation during non-REM (NREM) and REM sleep was 83.0% (range: 78.0–87.0) and 83.0% (range: 76.0–87.0), respectively. Of the enrolled OSA patients, 47.8% received PAP prescriptions. APAP was the most frequently used device, followed by fixed CPAP. The median pressure for the fixed CPAP user was 8.0 (range: 6.0–10.0) cm H₂O.

STRENGTHS AND LIMITATIONS

The KOSMOS cohort is the first and only prospective multicenter multidisciplinary OSA cohort study in Korea. The KOSMOS cohort is designed to accord with the interests of various departments related to sleep medicine, and collaboration among departments is also feasible. The follow-up period for the cohort is 30 years, which is sufficient for detailed analysis of the patients’ progress and prognosis.

An association between OSA and cardiovascular diseases has frequently been reported [16,32,33]. CPAP, a first-line treatment for OSA, is beneficial with respect to the prevention and prognosis of cardiovascular disease [34-37], although some recent randomized controlled trials found that the use of CPAP did not prevent the occurrence or progression of cardiovascular events [38-40]. However, most of the studies were conducted in Western populations, and few analyses of Korean data have been performed. Multicenter research is necessary for assessing the clinical characteristics of Korean OSA patients, who have different anatomical structures and lifestyles from Westerners; this will allow for Korean-specific treatments.

This study had some limitations. The participating sleep centers are mainly large university hospitals, so patients in small hospitals were not enrolled. Therefore, there is a possibility of patient selection bias. In addition, the study includes many questionnaires, which may be difficult to complete if the patient cannot read or does not have enough time. There is also a possibility of bias if less compliant participants drop out. Finally, no biological samples were collected.

CONCLUSION

The KOSMOS cohort is the first and only prospective multicenter multidisciplinary OSA cohort study in Korea. Through this long-term planned cohort study, we will be able to gain a detailed understanding of the characteristics of OSA in Koreans and also conduct a thorough analysis of the disease’s progression and prognosis.

NOTES

Conflicts of Interest

The authors have no potential conflicts of interest to disclose.

Availability of Data and Material

The KOSMOS cohort data are not open to the public, but collaboration with interested researchers is welcome. For further information, contact Sang Haak Lee, at mdlee@catholic.ac.kr or the co-investigator for the KOSMOS cohort, Sei Won Kim, at kseiwon@catholic.ac.kr.

Author Contributions

Conceptualization: all authors. Methodology: Sei Won Kim, Hyeon Hui Kang, Hong Jun Jeon, Jae Won Choi, Sang Haak Lee. Project administration: all authors. Resources: all authors. Supervision: Sang Haak Lee. Writing—original draft: Sei Won Kim, Hyeon Hui Kang, Sang Haak Lee. Writing—review & editing: all authors.

Funding Statement

None

Acknowledgments

None

Table 1.

Summary of the Korean Obstructive Sleep apnea Morbidity Study (KOSMOS) data collection

Categories	Contents	Period
Demographic characteristics	Sex, age, department, presence of occupation, shift work, menopause, bed-partner, pet	V0, V1
Health related behaviors	Smoking, alcohol, caffeine	V1, every 12 months after V1
Medical history & medication	Allergy, comorbidities & medication (Coronary artery disease, cerebrovascular disease, chronic obstructive pulmonary disease, asthma, interstitial lung disease, rhinitis, gout, dementia, depression, osteoarthritis, fatty liver, insomnia, benign prostatic hyperplasia, glaucoma, reflux esophagitis, thyroid disease, autoimmune disease, arrhythmia, hypertension, dyslipidemia, diabetes, liver disease, kidney disease etc.); Malignancy (gastric cancer, colon cancer, liver cancer, prostate cancer, thyroid cancer, pancreatic cancer, kidney cancer, bladder cancer, biliary cancer, breast cancer, cervical cancer, ovarian cancer, lung cancer, brain cancer etc.)	V1, every 12 months after V1
Family medical history	Snoring, rhinitis, obesity, hypertension, tonsillectomy & adenoidectomy, fatty liver, heart disease, cerebrovascular disease	V1, every 12 months after V1
Reason to visit sleep clinic	Snoring, apnea, choking, daytime sleepiness, fatigue, insomnia, lower extremity tremor or discomfort, sleep talk, abnormal behavior during sleep, nightmare	V1
Snoring	Presence of snoring, start age, operation history, recurrence after surgery	V1, every 12 months after V1
Anthropometric	Height^*, Body weight, neck/waist/hip circumference	V1, every 12 months after V1
Blood pressure	Blood pressure before sleep and after sleep (V1), once in the clinic (V2–)	V1, every 12 months after V1
Polysomnography results	Total sleep time, sleep efficiency, sleep latency, REM latency, sleep stages, awakenings, arousals, apneas and hypopneas, limb movements, snores, oxygen desaturations, average/ minimum/maximum oxygen saturation during desaturation, obstructive/mixed/central/ total apneas, obstructive/mixed/central/total hypopneas, AHI, respiratory effort related arousal, respiratory disturbance index, respiratory event duration	V1
PAP titration results	PAP type, pressure, periodic limb movements, supplemental oxygen use	V1
PAP compliance data	Interface, PAP type, pressure, usage (average use time [all days] and percentage of days with usage ≥4 h), average AHI, supplemental oxygen, leak, manufacturer and model of PAP device	V2, every 12 months after V2
Questionnaires	- Fatigue Severity Scale (FSS)	V1, every 12 months after V1^†
	- International Restless Legs Syndrome Study Group (IRLSSG)–based Restless Legs Syndrome (RLS) diagnostic criteria
	- Korean Translation of Composite Scale (KtCS)
	- Korean version of Pittsburgh Sleep Quality Index (PSQI-K)
	- Korean version of Epworth Sleepiness Scale (KESS)
	- International Prostate Symptom Score (IPSS)
	- Hospital Anxiety and Depression Scale (HADS)
	- Korean version of the Berlin Questionnaire (K-BQ)
	- Snoring, Tiredness, Observed apnea and high blood Pressure–Body mass index, Age, Neck circumference, Gender (STOP-BANG) questionnaire
	- Insomnia Severity Index (ISI)
	- Quality of Life Scale abbreviated version (QOL BREF) questionnaire
Survival	Survival, reason of death	V1, every 12 months after V1

^* height was measured only once at V1;

^† except for IRLSSG-based RLS diagnostic criteria and KtCS, all questionnaires are administered at 12-month intervals.

AHI, apnea-hypopnea index; REM, rapid eye movement; PAP, positive airway pressure; CPAP, continuous positive airway pressure; APAP, auto-titrating continuous positive airway pressure; BPAP, bilevel positive airway pressure

Table 2.

Summary of the baseline characteristics of the cohort participants (visit 0 or 1)

Variables	Men (n=386)	Women (n=143)	Total (n=529)	p
Age (yr)	58.0 [43.0; 67.0]	63.0 [54.0; 70.0]	60.0 [45.0; 68.0]	<0.001
Menopause	-	103 (74.6)	-	-
BMI (kg/m²)	27.1 [24.7; 29.8]	28.2 [24.4; 31.6]	27.4 [24.7; 30.5]	0.203
Neck circumference (cm)	40.0 [38.0; 41.0]	35.0 [33.0; 36.0]	38.0 [36.0; 41.0]	<0.001
Waist circumference (cm)	94.0 [87.0; 102.0]	90.0 [82.0; 98.0]	93.0 [86.0; 100.0]	<0.001
Hip circumference (cm)	98.0 [94.0; 104.0]	98.0 [94.0; 104.0]	98.0 [94.0; 104.0]	0.789
Smoking				<0.001
Current smoker	90 (23.4)	3 (2.1)	93 (17.6)
Ex-smoker	181 (47.1)	15 (10.5)	196 (37.2)
Never-smoker	113 (29.4)	125 (87.4)	238 (45.2)
Comorbidities
HTN	102 (26.4)	47 (32.9)	149 (28.2)	0.176
Dyslipidemia	151 (39.1)	79 (55.2)	230 (43.5)	0.001
DM	89 (23.1)	26 (18.2)	115 (21.7)	0.276
Rhinitis	68 (17.6)	31 (21.7)	99 (18.7)	0.348
Asthma	48 (12.4)	33 (23.1)	81 (15.3)	0.004
COPD	30 (7.8)	6 (4.2)	36 (6.8)	0.209
BPH	72 (18.7)	-	-	-
GERD	39 (10.1)	25 (17.5)	64 (12.1)	0.031
Arrhythmia	29 (7.5)	10 (7.0)	39 (7.4)	0.987
CAD	33 (8.5)	3 (2.1)	36 (6.8)	0.015
Other heart diseases	44 (11.4)	11 (7.7)	55 (10.4)	0.280
Fatty liver	62 (16.1)	19 (13.3)	81 (15.3)	0.515
CVA	14 (3.6)	7 (4.9)	21 (4.0)	0.680
Insomnia	27 (7.0)	22 (15.4)	49 (9.3)	0.005
Depression	26 (6.7)	16 (11.2)	42 (7.9)	0.133
Malignancy	31 (8.1)	21 (14.7)	52 (9.9)	0.036

Categorical data are described as numbers and percentages (%). Medians and the interquartile range were used for non-normally distributed continuous data. BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; BPH, benign prostate hyperplasia; GERD, gastroesophageal reflux disease; CAD, coronary artery disease; CVA, cerebrovascular accident

Table 3.

Reasons for visiting a sleep clinic

Variables	Men (n=386)	Women (n=143)	Total (n=529)	p
Snoring	351 (92.1)	133 (93.7)	484 (92.5)	0.684
Apnea, choking	304 (79.6)	84 (59.2)	388 (74.0)	<0.001
Daytime sleepiness, fatigue	283 (73.9)	99 (69.7)	382 (72.8)	0.399
Insomnia	101 (26.4)	54 (37.8)	155 (29.5)	0.015
Lower extremity tremor or discomfort	75 (19.6)	42 (29.4)	117 (22.2)	0.022
Sleep talk, abnormal behavior during sleep	36 (9.4)	16 (11.2)	52 (9.9)	0.654
Nightmare	36 (9.4)	20 (14.0)	56 (10.6)	0.174

Categorical data are described as numbers and percentages (%).

Table 4.

Polysomnography and PAP titration results

Variables	Men (n=386)	Women (n=143)	Total (n=529)	p
AHI	36.8 [21.5; 62.1]	29.1 [17.9; 46.2]	34.2 [20.1; 55.6]	0.002
RDI	40.0 [23.1; 64.8]	32.8 [18.1; 50.0]	37.8 [20.7; 59.5]	0.006
ODI	29.0 [14.8; 51.0]	21.5 [11.9; 39.2]	26.6 [13.9; 46.7]	0.003
Average O₂ saturation (%)
NREM	93.0 [91.4; 94.2]	92.7 [91.3; 93.9]	92.9 [91.4; 94.1]	0.270
REM	92.7 [90.5; 94.4]	92.5 [90.6; 94.0]	92.6 [90.6; 94.1]	0.471
Minimum O₂ saturation (%)
NREM	83.0 [77.0; 86.0]	85.0 [80.0; 88.0]	83.0 [78.0; 87.0]	0.052
REM	83.0 [75.0; 88.0]	83.0 [78.0; 87.0]	83.0 [76.0; 87.0]	0.996
PAP therapy				0.439
Fixed CPAP	81 (43.5)	24 (35.8)	105 (41.5)
APAP	104 (55.9)	43 (64.2)	147 (58.1)
BPAP	1 (0.5)	0 (0.0)	1 (0.4)
Fixed CPAP pressure (cm H₂O)	8.0 [5.0; 10.0]	7.5 [6.0; 9.5]	8.0 [6.0; 10.0]	0.890

Categorical data are described as numbers and percentages (%). Medians and the interquartile range were used for non-normally distributed continuous data. AHI, apnea-hypopnea index; RDI, respiratory disturbance index; ODI, oxygen desaturation index; NREM, non-rapid eye movement; REM, rapid eye movement; PAP, positive airway pressure; CPAP, continuous positive airway pressure; APAP, auto-titrating continuous positive airway pressure; BPAP, bilevel positive airway pressure

REFERENCES

1. American Academy of Sleep Medicine. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667–689.

2. Eckert DJ, Malhotra A. Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008;5:144–153.

3. Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Matheson MC, et al. Prevalence of obstructive sleep apnea in the general population: a systematic review. Sleep Med Rev 2017;34:70–81.

4. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep 1991;14:486–495.

5. Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med 2002;162:893–900.

6. Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A. Sleep apnea and sleep disruption in obese patients. Arch Intern Med 1994;154:1705–1711.

7. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 2002;165:677–682.

8. Kapur V, Strohl KP, Redline S, Iber C, O'Connor G, Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath 2002;6:49–54.

9. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep 1997;20:705–706.

10. Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev 2010;90:47–112.

11. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J Am Coll Cardiol 2008;52:686–717.

12. Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, et al. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol 2017;69:841–858.

13. Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O’Connor GT, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 2009;6:e1000132.

14. Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J. Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med 2002;166:159–165.

15. Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep Med 2010;11:441–446.

16. Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S. Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation 2017;136:1840–1850.

17. Zinchuk A, Yaggi HK. Phenotypic subtypes of OSA: a challenge and opportunity for precision medicine. Chest 2020;157:403–420.

18. Gaisl T, Haile SR, Thiel S, Osswald M, Kohler M. Efficacy of pharmacotherapy for OSA in adults: a systematic review and network meta-analysis. Sleep Med Rev 2019;46:74–86.

19. Health Insurance Review & Assessment Service. Disease subdivision statistics (search with F6290) [Internet]. Available at: https://opendata.hira.or.kr/op/opc/olapDiagBhvInfoTab1.do#none. Accessed February 23, 2021.

20. Martínez-García MA, Campos-Rodríguez F, Catalán-Serra P, Soler-Cataluña JJ, Almeida-Gonzalez C, De la Cruz Morón I, et al. Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study. Am J Respir Crit Care Med 2012;186:909–916.

21. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46:1121–1123.

22. Kook SH, Yoon JS, Lee HY. [Cross validation of the Korean translation of composite scale(KtCS) to measure morningness-eveningness]. J Korean Neuropsychiatr Assoc 1999;38:297–305.Korean.

23. Sohn SI, Kim DH, Lee MY, Cho YW. The reliability and validity of the Korean version of the Pittsburgh Sleep Quality Index. Sleep Breath 2012;16:803–812.

24. Cho YW, Lee JH, Son HK, Lee SH, Shin C, Johns MW. The reliability and validity of the Korean version of the Epworth sleepiness scale. Sleep Breath 2011;15:377–384.

25. Barry MJ, Fowler FJ Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992;148:1549–1557.discussion 1564.

26. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–370.

27. Kang K, Park KS, Kim JE, Kim SW, Kim YT, Kim JS, et al. Usefulness of the Berlin Questionnaire to identify patients at high risk for obstructive sleep apnea: a population-based door-to-door study. Sleep Breath 2013;17:803–810.

28. Chung F, Yegneswaran B, Liao P, Chung SA, Vairavanathan S, Islam S, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;108:812–821.

29. Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med 2001;2:297–307.

30. Min SK, Kim KI, Lee CI, Jung YC, Suh SY, Kim DK. Development of the Korean versions of WHO quality of life scale and WHOQOL-BREF. Qual Life Res 2002;11:593–600.

31. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 2014;15:860–873.

32. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261–264.

33. Molnar MZ, Mucsi I, Novak M, Szabo Z, Freire AX, Huch KM, et al. Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans. Thorax 2015;70:888–895.

34. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046–1053.

35. Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med 2012;156:115–122.

36. Bakker JP, Edwards BA, Gautam SP, Montesi SB, Durán-Cantolla J, Aizpuru F, et al. Blood pressure improvement with continuous positive airway pressure is independent of obstructive sleep apnea severity. J Clin Sleep Med 2014;10:365–369.

37. Iftikhar IH, Valentine CW, Bittencourt LR, Cohen DL, Fedson AC, Gíslason T, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J Hypertens 2014;32:2341–2350.discussion 2350.

38. Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, Martínez-Alonso M, Carmona C, Barceló A, et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA 2012;307:2161–2168.

39. Peker Y, Glantz H, Eulenburg C, Wegscheider K, Herlitz J, Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial. Am J Respir Crit Care Med 2016;194:613–620.

40. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016;375:919–931.