Sleep Breath (2015) 19:585–592
DOI 10.1007/s11325-014-1051-4
ORIGINAL ARTICLE
Obstructive sleep apnea syndrome and gastroesophageal reflux
disease: the importance of obesity and gender
Ozen K. Basoglu & Rukiye Vardar &
Mehmet Sezai Tasbakan & Zeynep Zeren Ucar &
Sibel Ayik & Timur Kose & Serhat Bor
Received: 24 April 2014 / Revised: 12 August 2014 / Accepted: 18 August 2014 / Published online: 31 August 2014
# Springer-Verlag Berlin Heidelberg 2014
Abstract
Background It is claimed that gastroesophageal reflux disease
(GERD) increases in patients with obstructive sleep apnea
syndrome (OSAS). We aimed to evaluate the prevalence of
GERD in patients with OSAS and primary snoring and iden-
tify OSAS-related risk factors associated with GERD.
Methods In this prospective, cross-sectional, multicenter study,
in total 1,104 patients were recruited for polysomnography:
147 subjects were in non-OSAS (primary snoring) and 957
patients were in OSAS group. All patients completed a vali-
dated GERD questionnaire. Demographic, anthropometric
characteristics, and medical history were recorded.
Results The prevalence of GERD was similar in OSAS
(38.9 %) and non-OSAS (32.0 %) groups (p=0.064). There
was no difference in terms of major gastroesophageal reflux
(GER) symptoms (heartburn/acid regurgitation) between non-
OSAS and mild, moderate, and severe OSAS groups. The
O. K. Basoglu (*) : M. S. Tasbakan
Department of Chest Diseases, Ege University Faculty of Medicine,
Bornova, 35100 Izmir, Turkey
e-mail: ozen.basoglu@ege.edu.tr
R. Vardar : S. Bor
Section of Gastroenterology and Ege Reflux Study Group, Ege
University Faculty of Medicine, Bornova, 35100 Izmir, Turkey
Z. Z. Ucar
Department of Sleep Disorders, Dr. Suat Seren Chest Diseases and
Surgery Training and Research Hospital, Yenisehir, Izmir, Turkey
S. Ayik
Department of Chest Diseases, Katip Celebi University Faculty of
Medicine, Izmir, Turkey
T. Kose
Department of Biostatistics, Ege University Faculty of Medicine,
Izmir, Turkey
prevalence of GERD was increased in female OSAS patients
(46.6 %) compared to males (35.7 %) (p=0.002). In OSAS
patients with GERD, body mass index was greater (34.0±7.0
vs. 33.1±6.8, p=0.049), waist (115.5±13.9 vs. 113.1±13.4,
p=0.007) and hip (117.9±13.7 vs. 114.2±12.8, p<0.0001)
circumferences were larger, and Epworth sleepiness scores
were higher (10.3±6.0 vs. 8.8±5.6, p<0.0001) than OSAS
patients without GERD. Multivariate analysis showed that
GERD was significantly associated with female gender, hip
circumference, and daytime sleepiness.
Conclusions In this large cohort, the prevalence of GERD
was significantly increased in those with primary snoring
and OSAS compared to the general population, but severity
of OSAS did not influence GERD prevalence. The present
results suggest that OSAS was not likely a causative factor but
female gender, obesity, and sleepiness were related with prev-
alence of GERD in OSAS patients.
Keywords Obstructive sleep apnea syndrome . Primary
snoring . Gastroesophageal reflux disease . Gender . Obesity .
Daytime sleepiness
Abbreviations
AHI Apnea-hypopnea index
BMI Body mass index
GER Gastroesophageal reflux
GERD Gastroesophageal reflux disease
NS Not significant
OSAS Obstructive sleep apnea syndrome
REM Rapid eye movement
SDB Sleep-disordered breathing
SpO2 Pulse oximeter oxygen saturation
586
Introduction
Obstructive sleep apnea syndrome (OSAS) is a common
disorder which is characterized by instability of the upper
airway during sleep resulting in reduction or elimination of
airflow, oxygen desaturation, and sleep disruption. It is a
prevalent disorder, with at least 4 % of middle-aged males
and 2 % of middle-aged females estimated to be affected in
population studies [1]. The risk factors for OSAS include
advanced age, male gender, obesity, family history, craniofa-
cial abnormalities, smoking, and alcohol consumption. Obe-
sity is a major risk factor for sleep apnea. Particularly central
adiposity can increase pharyngeal collapsibility through me-
chanical effects on pharyngeal soft tissues and lung volume,
and through adipokines that may affect airway neuromuscular
control [2–4]. OSAS is highly associated with cardiovascular
and cerebrovascular disorders including hypertension, con-
gestive heart failure, myocardial infarction, cardiac arrhyth-
mias, and stroke [5–7]. In addition, OSAS is increasingly
recognized as a risk factor for metabolic dysfunction including
a spectrum of glucose disorders from insulin resistance to
overt type 2 diabetes mellitus, dyslipidemia, and metabolic
syndrome [8, 9].
Gastroesophageal reflux disease (GERD) is accepted as
one of the most common chronic diseases in adults, and its
prevalence reaches to 20 % in our population [10]. Obesity is
clearly a risk factor for the development of the disease [11,
12]. GERD and sleep disorders are both common health
problems and often coexist. The sleeping state is accompanied
by many changes in gastroesophageal function that may be of
importance in the pathogenesis of GERD. At nighttime, gas-
tric acid production is increased, gastric emptying is delayed,
esophageal clearance is markedly delayed, and upper esoph-
ageal sphincter pressure diminishes significantly. Sleep-
related disorders also increase nocturnal gastroesophage-
al reflux (GER). OSAS is associated with a high fre-
quency of GER, probably due to the generation of
negative intrathoracic pressures during obstructive ap-
neas and arousals [13–15]. GERD has been shown to
be prevalent in patients with OSAS on the basis of
studies recording symptoms and esophageal pH
[16–19]. However, prospective and comparative studies
are limited and contradictory. In some of the studies, the
number of subjects is small [16, 20], there is no control
group, or polysomnography is not performed to diag-
nose and exclude sleep apnea.
OSAS and GERD share similar risk factors. It is
unclear whether the co-occurrence of these conditions
represents a causal relationship or is simply a reflection
of shared risk factors. Obesity increases intra-abdominal
pressure and decreases esophageal clearance. Due to the
common presence of obesity in patients with OSAS, it
is not easy to irrefutably demonstrate independent
Sleep Breath (2015) 19:585–592
effects of sleep apnea on GERD which are highly
driven by obesity [21]. Furthermore, it is not clearly
known whether the severity of OSAS has any influence
on GER. Therefore, the primary objective of the present
multicenter study was to evaluate prospectively the
prevalence of gastroesophageal reflux disease using a
validated GERD questionnaire [22] in a large number
of subjects with primary snoring and OSAS. The sec-
ondary objectives were to assess the relation between OSAS
severity and GERD and to identify OSAS-related risk factors
associated with GERD.
Methods
Study population
In this multicenter, cross-sectional, observational study, we
prospectively evaluated 1,209 consecutive subjects admitted
to the sleep laboratory of two university hospitals and a
tertiary referral hospital for an evaluation of suspected sleep-
disordered breathing disorders and underwent
polysomnography between February 2012 and February
2013. Out of 1,209 subjects, 105 were excluded because of
the following reasons: 62 participants did not complete the
questionnaire accurately, polysomnography results of 15 sub-
jects could not be found, and the questionnaire was adminis-
tered twice to 28 subjects during polysomnography and titra-
tion days. One hundred forty seven subjects who were all
snoring and had an apnea-hypopnea index (AHI) of <5
events/h were diagnosed as primary snoring, and the primary
snoring subjects were considered as non-OSAS (control
group). The remaining 957 patients with an AHI of 5 events/
h or higher were diagnosed as OSAS (study group). Flow
chart of the study is presented in Fig. 1.
Demographic data (age, gender, smoking history, alcohol
and drug use), anthropometric measurements [height, weight,
body mass index (BMI), circumferences of neck, waist, and
hip], upper gastrointestinal and sleep-related symptoms, and
detailed medical history were evaluated. All subjects
underwent full-night in-laboratory polysomnography and
filled out the validated GERD questionnaire with 54 questions
on the day of polysomnography [22]. Subjective daytime
sleepiness was assessed by using the Turkish version of
Epworth Sleepiness Scale and scores higher than 10 were
considered as sleepiness [23].
Demographic, anthropometric, and polysomnographic pa-
rameters of OSAS patients were compared with those of non-
OSAS group. The relationship between GERD and OSAS-
related risk factors were examined to evaluate potential un-
derlying factors. The local ethics committee approved the
study and all subjects gave written informed consent.
Sleep Breath (2015) 19:585–592
Subjects performed PSG
(n = 1209)
105 subjects excluded
62 did not complete the questionnaire
15 no polysomnography results
28 completed the questionnaire twice
Non-OSAS OSAS
(n = 147) (n = 957)
Mild OSAS Moderate OSAS
(n = 188) (n = 209)
Fig. 1 Flow chart of the study. OSAS obstructive sleep apnea syndrome,
PSG polysomnography
Polysomnography
All patients underwent full overnight in-laboratory diagnostic
polysomnography. Electroencephalography electrodes were po-
sitioned according to the international 10–20 system. PSG
consisted of monitoring of sleep by electroencephalography,
electrooculography, electromyography, airflow, and respiratory
muscle effort and included measures of electrocardiographic
rhythm and blood oxygen saturation. Thoracoabdominal plethys-
mograph, oronasal temperature thermistor, and nasal-cannula-
pressure transducer system were used to identify apneas and
hypopneas. Transcutaneous finger pulse oximeter was used to
measure oxygen saturation. Sleep was recorded and scored ac-
cording to the standard method [24]. AHI was the sum of the
number of apneas and hypopneas per hour of sleep. OSAS was
defined as an AHI of 5 events/h and the presence of clinical
symptoms, e.g., excessive daytime sleepiness, loud snoring,
witnessed apneas, and nocturnal choking or AHI of 15 events/h
without any OSAS symptoms [25]. Besides, an AHI of <5
events/h was considered within normal limits, and numbers of
5 to<15, 15 to<30, and >30 represent mild, moderate, and
severe OSAS, respectively [26]. No split-night studies were
performed.
Gastroesophageal reflux disease questionnaire
We used a reflux questionnaire derived from Locke et al. [27]
previously validated in an English-speaking Western culture,
which was translated into Turkish, linguistically validated,
and adapted to the cultural profile of Turkey [22]. As a
summary, the process of translation included an independent
translation, a back translation, a pilot test using 15 subjects,
and a review and approval by the original questionnaire de-
velopers. Test-retest reliability was analyzed for each
587
respondent using Cohen’s kappa coefficients, and Cronbach’s
alpha values were all higher than 70 % for all major symp-
toms. Questions were employed which related to the presence
of the following:
1. Major (heartburn, regurgitation, dyspepsia) and related
(dysphagia, odynophagia, chest pain) symptoms and trigger-
ing factors of these symptoms
2. Associated medical conditions
3. Past medical history: upper (dyspepsia, nausea, vomiting,
belching) and lower gastrointestinal symptoms (abdominal
pain or discomfort), respiratory, throat and cardiac problems
(cough, dyspnea, hoarseness, hiccups, globus, asthma), num-
Severe OSAS
ber of physician visits and diagnostic procedures related to
(n=560)
upper gastrointestinal symptoms, medication use (NSAID,
aspirin and all related drugs with upper gastrointestinal com-
plaints, and for other health problems), pregnancy, present and
previous smoking, ethanol, regular coffee or tea consumption
4. Demographic and socioeconomic data, including number of
households and children, total monthly income, age, weight,
height, employment, level of education, and marital status
“Frequent symptoms,” means, a major symptom (heartburn
and/or regurgitation) occurs at least once a week or common and
“occasional symptoms” means, an episode of one of the major
symptoms less than once a week within the past year as previ-
ously defined by us [10]. Frequent heartburn and/or regurgita-
tion were defined as GERD. The period prevalence of symp-
toms was the previous 12 months. Each symptom (heartburn,
regurgitation, dysphagia, and chest pain) was scored for frequen-
cy and severity by the subject. Symptom frequency was mea-
sured on the following five-point scale: less than once a month,
once a month, once a week, several times a week, and daily.
Statistical analysis
Statistical analysis was performed with IBM SPSS 20.0 for
Windows packaged software. All analyses comparing the study
groups were performed twice: first to compare two groups,
“GERD present” versus “GERD absent,” and then three groups,
“Never,” “Occasional,” and “Frequent.” Numerical variables
were summarized with mean±standard deviation and categorical
variables with frequency and percentage. The significance of
differences among groups was assessed by Student’s t test or
two-way ANOVA (when correction was needed for gender), and
analysis of categorical variables was examined by chi-square test.
A value of p<0.05 was considered significant for all statistical
analysis. Multiple logistic regression analysis was used to deter-
mine the relationship between the demographic, anthropometric,
and polysomnographic parameters with GERD. Besides, odds
ratio (OR) and 95 % confidence intervals (95 % CI) were
calculated to show the association.
588
Results
Prevalence of GERD in non-OSAS and OSAS groups
Overall, 419 of the 1,104 study subjects (38.0 %) reported
symptoms consistent with GER experienced at least once a
week in the last year. Out of 957 OSAS patients, 372 (38.9 %)
had GERD (once a week of heartburn and/or regurgitation),
whereas 47 subjects (32.0 %) had GERD in non-OSAS group
and the difference was not statistically significant (p=0.064).
As shown in Fig. 2, there was no difference in terms of major
GER symptoms (heartburn, regurgitation) between non-
OSAS and mild, moderate, and severe OSAS groups.
Additional symptoms, namely extraesophageal symptoms,
alarm symptoms, and epigastric pain of non-OSAS subjects
and mild, moderate, and severe OSAS patients with GERD,
were evaluated. It was found that the patients with OSAS and
GERD reported cough (p=0.046) and odynophagia (p=0.015)
more frequently than non-OSAS patients with GERD (Table 1).
When the clinical characteristics of non-OSAS subjects with
GERD were compared to the ones without GERD, no significant
difference was observed (Table 2). However, in OSAS patients
with GERD, body mass index (p=0.049) was greater, waist (p=
0.007) and hip (p<0.0001) circumferences were larger, and
Epworth sleepiness scores were higher (p<0.0001) when com-
pared to the patients without GERD as shown in Table 2.
In OSAS group, the prevalence of GERD was increased in
female patients (46.6 %) than in male patients (35.7 %) (p=
0.002). Gender-specific characteristics of OSAS patients were
assessed according to the presence of GERD, and it was
determined that neck circumference of male OSAS patients
with GERD was larger than that of the males with no GERD
(44.2±3.9 vs. 43.6±3.3, p=0.039). In female OSAS patients
with GERD, waist circumference was larger than in the ones
with no GERD (117.6±14.9 vs. 113.5±14.9, p=0.024). Be-
sides, the prevalence of GERD increased with the increase in
BMI in females but the difference was not significant (Table 3).
Sleep parameters of non-OSAS and OSAS patients with and
without GERD
As shown in Table 4, there was no difference with regard to
polysomnographic parameters in non-OSAS subjects with
and without GERD. In OSAS patients with GERD, the per-
centages of sleep efficiency (p=0.044) and stage N2 sleep (p=
0.017) were higher, and the percentage of stage N1 sleep
(p<0.0001) was lower than in OSAS patients without GERD.
However, the indicators of OSAS severity including AHI,
oxygen desaturation index, lowest nocturnal oxygen saturation
(SpO2) (%), sleep time with SpO2 <90 % (min), and sleep time
with SpO2 <90 % (%) did not correlate with GERD. In addi-
tion, reflux symptoms were not associated with sleep position
assessed by position sensor during polysomnography.
Sleep Breath (2015) 19:585–592
50 Non-OSAS Mild OSAS
Moderate OSAS Severe OSAS
41
40 39
40 37
33 33 32
29 29 29 30 30
Subjects (%)
30
20
10
0
No symptoms Occasional GERD
symptoms
Fig. 2 Gastroesophageal reflux symptoms of non-OSAS and OSAS
patients (p>0.05 for all comparisons). GERD gastroesophageal reflux
disease, OSAS obstructive sleep apnea syndrome
Risk factors for GERD in OSAS patients in the multivariate
linear regression analysis
The relationship between GERD and other variables was exam-
ined to determine factors underlying development of reflux in
OSAS patients. There was a significant difference between
OSAS patients with and without GERD according to female
gender, daytime sleepiness assessed by Epworth Sleepiness
Scale, and circumferences of neck and hip. Consequently, these
four variables were considered as potential predictors for GERD
and included in the multivariate linear regression analysis. It was
found that female gender (p=0.027), Epworth sleepiness score
(p=0.001), and circumference of hip (p=0.021) were significant-
ly associated with GERD (Table 5).
Discussion
It is claimed that GERD is common in patients with OSAS but
prospective and comparative studies are limited and contra-
dictory. OSAS and GERD share similar risk factors, and it is
unclear whether the co-occurrence of these conditions repre-
sents a causal relationship or is simply a reflection of shared
risk factors. In the present large-cohort study, it was shown
that 38.9 % of OSAS patients and 32.0 % of non-OSAS
subjects reported GERD, and the prevalence of GERD was
considerably increased compared to the general population.
There was no relationship between the severity of OSAS and
the presence of GERD. In OSAS patients with GERD, mea-
surements of obesity including BMI and circumferences of
waist and hip were greater and daytime sleepiness was higher
than in the patients without GERD. Besides, the prevalence of
GERD was increased in female OSAS patients. The present
results support that OSAS was not likely a causative factor,
Sleep Breath (2015) 19:585–592 589

Table 1 Additional symptoms of non-OSAS and OSAS patients with GERD

Symptoms, n (%) Non-OSAS (n=47) Mild OSAS (n=77) Moderate OSAS (n=78) Severe OSAS (n=215) Total (n=417) p value

Extraesophageal symptoms 40 (85.1) 62 (80.5) 67 (85.9) 161 (74.9) 330 (79.1) 0.132
Cough 25 (56.8) 48 (64.0) 53 (71.6) 112 (53.8) 238 (59.4) 0.046
Hoarseness 23 (48.9) 29 (40.3) 25 (34.7) 84 (42.0) 161 (41.2) 0.478
Chest pain 29 (63.0) 43 (58.1) 38 (52.1) 97 (47.8) 207 (52.3) 0.188
Alarm symptoms 23 (48.9) 43 (57.3) 48 (61.5) 112 (52.1) 226 (54.5) 0.409
Dysphagia 22 (47.8) 42 (56.0) 46 (60.5) 111 (53.4) 221 (54.6) 0.549
Odynophagia 5 (11.1) 19 (25.7) 17 (23.0) 24 (12.1) 65 (16.6) 0.015
Epigastric pain 32 (72.7) 51 (67.1) 49 (67.1) 117 (57.4) 249 (62.7) 0.131

GERD gastroesophageal reflux disease, NS not significant, OSAS obstructive sleep apnea syndrome
p<0.05 was considered significant and written in boldface

but female gender, obesity, and sleepiness were related with
the prevalence of GERD in OSAS patients.
In our large cohort referred for sleep studies, 419 of the 1,104
subjects (38.0 %) reported symptoms consistent with GER ex-
perienced at least once at a week in the last year. The prevalence
of GERD was 38.9 % in OSAS and 32.0 % in non-OSAS
subjects, and there was no significant difference between two
groups. In our previous studies, the prevalence of GERD was
20 % in a small town near the study area (n=630) [10], 22.8 % in
a country-wide study (n=3,200) [28], and 19.4 % in the same
research area (n=694) [29]. Since all three studies revealed very
similar results with the same questionnaire, it is possible to claim
that GERD prevalence was significantly increased compared to
the general population. In a study with a similar design, the
prevalence of symptomatic GER was investigated in 135 sub-
jects with obstructive sleep apnea (OSA) and 93 with snoring. It
was found that symptomatic GER is common in subjects with
SDB, but there was no difference between those with OSAS and
snoring [19]. Additionally, Shepherd et al. [30] showed that the
prevalence of nocturnal reflux symptoms is increased in OSA

Table 2 Characteristics of the non-OSAS and OSAS patients with and without GERD

Non-OSAS p value OSAS p value

GERD (−) (n=100) GERD (+) (n=47) GERD (−) (n=585) GERD (+) (n=372)

Male, n (%) 67 (71.3) 27 (28.7) 0.261 437 (64.3) 243 (35.7) 0.002
Female, n (%) 33 (62.3) 20 (37.7) 148 (53.4) 129 (46.6)
Age (years) 46.5±13.0 46.1±13.9 0.863 52.7±10.9 51.4±11.3 0.098
Smoking history, n (%)
Never smoker 50 (50.0) 18 (38.3) 0.414 259 (44.3) 188 (50.6) 0.149
Former smoker 24 (24.0) 16 (34.0) 194 (33.1) 111 (29.8)
Current smoker 26 (26.0) 13 (27.7) 132 (22.6) 73 (19.6)
Alcohol consumption, n (%) 19 (19.0) 9 (19.1) 0.952 124 (21.2) 70 (18.8) 0.378
Body mass index (kg/m2) 29.2±4.7 29.9±5.4 0.369 33.1±6.8 34.0±7.0 0.049
Neck circumference (cm) 40.7±3.8 39.5±3.4 0.127 42.6±3.8 42.9±4.3 0.249
Waist circumference (cm) 104.5±12.2 102.9±12.0 0.449 113.1±13.4 115.5±13.9 0.007
Hip circumference (cm) 108.0±11.0 110.0±11.1 0.314 114.2±12.8 117.9±13.7 <0.0001
Comorbidities n (%)
Coronary artery disease 6 (6.0) 5 (10.6) 0.364 56 (9.6) 57 (15.3) 0.007
Congestive heart failure 9 (9.0) 3 (6.4) 0.522 40 (8.8) 37 (9.9) 0.077
Hypertension 21 (21.0) 8 (17.0) 0.553 224 (38.3) 158 (42.5) 0.194
Diabetes mellitus 17 (17.0) 8 (17.0) 0.997 113 (19.3) 86 (23.1) 0.152
Epworth sleepiness score 6.9±5.5 7.1±6.1 0.846 8.8±5.6 10.3±6.0 <0.0001

Data are expressed as mean±SD, unless otherwise stated

GERD gastroesophageal reflux disease, NS not significant, OSAS obstructive sleep apnea syndrome
p<0.05 was considered significant and written in boldface
590 Sleep Breath (2015) 19:585–592

Table 3 Gender-specific prevalence of GERD according to BMI in non- Table 5 Multivariate linear regression analysis between GERD and
OSAS and OSAS patients other variables

Non-OSAS (n=147) OSAS (n=957) Beta p value OR

Female Male Female Male Female gender 0.323 0.027 1.381

Epworth sleepiness score 0.037 0.001 1.038
BMI≤24.9 kg/m2 20.0 % 20.0 % 28.6 % 30.8 %
Hip circumference (cm) 0.012 0.021 1.012
BMI 25–29.9 kg/m2 38.1 % 34.8 % 49.1 % 33.5 %
BMI≥30 kg/m2 40.7 % 25.0 % 46.5 % 37.5 %
30–40 % increased risk of nocturnal GER symptoms [30], and
There was no difference in terms of GERD prevalence between different
BMI groups Valipour et al. [19] reported a 60 % increased risk of overall GER
BMI body mass index, GERD gastroesophageal reflux disease, OSAS symptoms for female OSA patients. In addition, Kim et al. [33]
obstructive sleep apnea syndrome evaluated 1,023 patients in terms of GERD and showed that
female gender was more likely to have GERD and had higher
patients (10.2 %) versus the general population (5.5 %). Most of GER scores than men.
the studies support a high prevalence of GERD in patients with The association between BMI and frequency of GER symp-
OSAS although the rates change according to the methods used toms has been reported before. An increased intra-abdominal
to evaluate GERD [31]. pressure and gastroesophageal pressure gradient may cause
Several studies have investigated the risk factors associated GERD in obese patients. In the largest epidemiologic study to
with GERD in patients with OSAS, and a causal link between evaluate the clinical predictors of heartburn during sleep, it was
OSAS and GERD has been proposed. In the present study, the demonstrated that increased BMI was associated with heartburn
clinical characteristics of OSAS patients with and without GERD [34]. However, the relationship between BMI and GERD was
were evaluated, and no difference was shown in terms of age, not always shown in studies with OSAS [19, 30, 32, 35] contrast
smoking, or alcohol consumption. However, the prevalence of to our study. In OSAS patients with GERD, BMI was greater
GERD was significantly increased in female OSAS patients when compared to OSAS patients without GERD in the present
(46.6 %) compared to males (35.7 %), and GERD was associated study. Other measurements that indicate the severity of obesity
with female gender in a multivariate analysis. Ju et al. [32] including circumferences of waist and hip were also larger than
evaluated 564 subjects who were referred to sleep laboratory in the patients without GERD, and neck circumference of male
with a GERD questionnaire and found that GERD was more OSAS patients with GERD was wider than that of those with no
frequent in female subjects. Female gender was associated with a GERD. In a multivariate analysis, GERD was significantly

Table 4 Sleep parameters of non-OSAS and OSAS patients with and without GERD

Non-OSAS p value OSAS p value

GERD (−) (n=100) GERD (+) (n=47) GERD (−) (n=585) GERD (+) (n=372)

Apnea-hypopnea index (/h) 2.2±1.5 2.4±1.4 0.394 44.6±29.9 42.8±28.6 0.354

Oxygen desaturation index (/h) 3.4±5.3 3.6±4.0 0.733 42.8±30.2 41.9±30.3 0.662
Total sleep time (min) 368.2±74.1 360.1±67.3 0.533 327.6±80.9 324.9±89.0 0.632
Sleep efficiency (%) 83.0±12.1 82.2±11.5 0.711 81.0±11.7 82.5±11.0 0.044
Sleep latency (min) 16.4±19.6 20.0±23.3 0.332 17.9±22.3 16.5±19.0 0.292
N1 sleep (%) 3.6±3.1 2.8±2.4 0.133 4.8±4.4 3.6±3.0 <0.0001
N2 sleep (%) 46.6±20.6 43.2±18.7 0.340 56.4±21.1 59.9±22.3 0.017
N3 sleep (%) 35.3±19.4 35.6±21.2 0.943 27.5±19.4 25.3±19.8 0.094
REM sleep (%) 14.5±7.8 17.9±10.8 0.055 11.2±7.5 11.0±7.1 0.704
Lowest SpO2 (%) 88.7±4.7 87.8±6.5 0.381 75.3±12.7 75.0±12.7 0.766
Mean SpO2 (%) 95.3±2.1 94.8±2.8 0.232 91.4±6.5 90.9±6.9 0.248
Sleep time with SpO2 <90 % (%) 2.4±10.6 4.0±16.3 0.475 16.8±22.8 18.4±25.3 0.314

Data are expressed as mean±SD, unless otherwise stated

GERD gastroesophageal reflux disease, NS not significant, OSAS obstructive sleep apnea syndrome, REM rapid eye movement, SpO2 pulse oximeter
oxygen saturation
p<0.05 was considered significant and written in boldface
Sleep Breath (2015) 19:585–592
associated with hip circumference. To the best of our knowledge,
this is the first study evaluating the relation between GERD and
obesity measurements other than BMI in OSAS. Furthermore,
GERD prevalence increased with a higher BMI in females,
although the difference was not significant. It is of interest that
men were less likely than women to have GERD in our study.
This could have been due at least in part to our women subjects
manifesting a higher BMI. An investigation with 136 patients
utilizing a validated reflux questionnaire established a relation-
ship between obesity and GERD [33], and a positive correlation
was observed between GERD and BMI in SDB subjects [30].
In a population-based large cohort, 15,314 subjects completed
questions about heartburn during sleep and 24.9 % reported this
symptom. In a multivariate analysis, daytime sleepiness was a
predictor of heartburn during sleep [34]. In another study, 564
subjects referred to sleep laboratory completed a GERD ques-
tionnaire. The patients with GERD had higher scores in Epworth
Sleepiness Scale and a positive association was observed be-
tween sleepiness and GERD risk [32]. We also found that
daytime sleepiness was higher in OSAS patients with GERD,
and the multivariate analysis showed that GERD was significant-
ly associated with sleepiness. It is known that daytime sleepiness
may increase with the severity of OSAS. However, the severity
of OSAS did not influence the GERD prevalence in this study.
Therefore, frequent arousals caused by nocturnal reflux could be
an explanation for increased sleepiness.
It is plausible that with increasing severity of OSAS, more
GERD would have occurred in a dose-response relationship.
The relation between the prevalence of GERD and the factors
that served as surrogate indicators of OSAS severity like AHI
or nocturnal hypoxemia were examined in several studies.
There was no difference in terms of major GER symptoms
between primary snoring and mild, moderate, and severe
OSAS groups in the present study. Besides, other indicators
of OSAS severity including AHI, oxygen desaturation index,
lowest nocturnal oxygen saturation, and sleep time with oxy-
gen saturation <90 % did not correlate with GERD. These
findings suggest that GERD may be increased in OSAS
patients irrespective of its severity and consistent with other
pertinent reports. In a large cohort, the prevalence of GER
symptoms was similar in those with mild, moderate, and
severe OSA [30]. Kim et al. [33] also showed that the severity
of OSAS did not influence GERD prevalence, and the GERD
score did not correlate with sleep apnea variables like AHI,
supine AHI, REM sleep AHI, maximum apnea duration, or
arousals. It seems that the severity of OSAS does not affect the
prevalence of GERD in many other studies [17, 19, 32, 35].
This study has some limitations to consider. First of all,
GERD was diagnosed based on the questionnaire, instead of
using more objective methods such as 24-hour pH-impedance
monitoring. However, in a multicenter study with such a large
cohort, these investigations would not be feasible, and the GERD
questionnaire used in this study is validated, commonly used,
591
and had been applied in large population-based studies. Second-
ly, our study samples were recruited from sleep disorder centers
and they had a SDB. The control group would have been
recruited from the general population but then control subjects
could have been undiagnosed of SDB and they could have been
less obese. Thirdly, GERD was significantly associated with
daytime sleepiness in the present study, and frequent arousals
caused by nocturnal reflux could be an explanation for increased
sleepiness. However, we could not evaluate the arousal index of
the patients. Finally, the severity of GERD and its complications
like erosive disease and Barrett’s esophagus could not be inferred
as we evaluated the subjects with a GERD questionnaire.
In conclusion, it was demonstrated in this large cohort that
the prevalence of GERD was significantly increased in sub-
jects with primary snoring and OSAS compared to the general
population, but the severity of OSAS did not influence GERD
prevalence. The present results support that female gender,
obesity, and daytime sleepiness were related with the preva-
lence of GERD. Therefore, it can be proposed that a simple
causal link does not exist between OSAS and GERD, but
rather that they are common problems with shared risk factors.
Further investigations are required to elucidate a potential
bidirectional relationship between OSAS and GERD.
Conflict of interest The manuscript entitled “Obstructive sleep apnea
syndrome and gastroesophageal reflux disease: the importance of obesity
and gender” which we submit for consideration to be published in Sleep
and Breathing is not under consideration for publication nor published
elsewhere.
The investigation was performed at the Ege University Faculty of
Medicine, Dr. Suat Seren Chest Diseases and Surgery Training and
Research Hospital, and Katip Celebi University Faculty of Medicine.
The work has been seen and approved by all coauthors. The authors have
no proprietary, financial, professional, or other personal interest of any
nature or kind in any product, service, and/or company that could be
construed as influencing the position presented in, or the review of, the
manuscript.
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