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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 prevalence of GERD was increased in female OSAS patients


Background It is claimed that gastroesophageal reflux disease (46.6 %) compared to males (35.7 %) (p=0.002). In OSAS
(GERD) increases in patients with obstructive sleep apnea patients with GERD, body mass index was greater (34.0±7.0
syndrome (OSAS). We aimed to evaluate the prevalence of vs. 33.1±6.8, p=0.049), waist (115.5±13.9 vs. 113.1±13.4,
GERD in patients with OSAS and primary snoring and iden- p=0.007) and hip (117.9±13.7 vs. 114.2±12.8, p<0.0001)
tify OSAS-related risk factors associated with GERD. circumferences were larger, and Epworth sleepiness scores
Methods In this prospective, cross-sectional, multicenter study, were higher (10.3±6.0 vs. 8.8±5.6, p<0.0001) than OSAS
in total 1,104 patients were recruited for polysomnography: patients without GERD. Multivariate analysis showed that
147 subjects were in non-OSAS (primary snoring) and 957 GERD was significantly associated with female gender, hip
patients were in OSAS group. All patients completed a vali- circumference, and daytime sleepiness.
dated GERD questionnaire. Demographic, anthropometric Conclusions In this large cohort, the prevalence of GERD
characteristics, and medical history were recorded. was significantly increased in those with primary snoring
Results The prevalence of GERD was similar in OSAS and OSAS compared to the general population, but severity
(38.9 %) and non-OSAS (32.0 %) groups (p=0.064). There of OSAS did not influence GERD prevalence. The present
was no difference in terms of major gastroesophageal reflux results suggest that OSAS was not likely a causative factor but
(GER) symptoms (heartburn/acid regurgitation) between non- female gender, obesity, and sleepiness were related with prev-
OSAS and mild, moderate, and severe OSAS groups. The alence of GERD in OSAS patients.

O. K. Basoglu (*) : M. S. Tasbakan


Department of Chest Diseases, Ege University Faculty of Medicine,
Keywords Obstructive sleep apnea syndrome . Primary
Bornova, 35100 Izmir, Turkey
e-mail: ozen.basoglu@ege.edu.tr snoring . Gastroesophageal reflux disease . Gender . Obesity .
Daytime sleepiness
R. Vardar : S. Bor
Section of Gastroenterology and Ege Reflux Study Group, Ege
University Faculty of Medicine, Bornova, 35100 Izmir, Turkey
Abbreviations
Z. Z. Ucar AHI Apnea-hypopnea index
Department of Sleep Disorders, Dr. Suat Seren Chest Diseases and BMI Body mass index
Surgery Training and Research Hospital, Yenisehir, Izmir, Turkey
GER Gastroesophageal reflux
S. Ayik GERD Gastroesophageal reflux disease
Department of Chest Diseases, Katip Celebi University Faculty of NS Not significant
Medicine, Izmir, Turkey OSAS Obstructive sleep apnea syndrome
REM Rapid eye movement
T. Kose
Department of Biostatistics, Ege University Faculty of Medicine, SDB Sleep-disordered breathing
Izmir, Turkey SpO2 Pulse oximeter oxygen saturation
586 Sleep Breath (2015) 19:585–592

Introduction effects of sleep apnea on GERD which are highly


driven by obesity [21]. Furthermore, it is not clearly
Obstructive sleep apnea syndrome (OSAS) is a common known whether the severity of OSAS has any influence
disorder which is characterized by instability of the upper on GER. Therefore, the primary objective of the present
airway during sleep resulting in reduction or elimination of multicenter study was to evaluate prospectively the
airflow, oxygen desaturation, and sleep disruption. It is a prevalence of gastroesophageal reflux disease using a
prevalent disorder, with at least 4 % of middle-aged males validated GERD questionnaire [22] in a large number
and 2 % of middle-aged females estimated to be affected in of subjects with primary snoring and OSAS. The sec-
population studies [1]. The risk factors for OSAS include ondary objectives were to assess the relation between OSAS
advanced age, male gender, obesity, family history, craniofa- severity and GERD and to identify OSAS-related risk factors
cial abnormalities, smoking, and alcohol consumption. Obe- associated with GERD.
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 Methods
control [2–4]. OSAS is highly associated with cardiovascular
and cerebrovascular disorders including hypertension, con- Study population
gestive heart failure, myocardial infarction, cardiac arrhyth-
mias, and stroke [5–7]. In addition, OSAS is increasingly In this multicenter, cross-sectional, observational study, we
recognized as a risk factor for metabolic dysfunction including prospectively evaluated 1,209 consecutive subjects admitted
a spectrum of glucose disorders from insulin resistance to to the sleep laboratory of two university hospitals and a
overt type 2 diabetes mellitus, dyslipidemia, and metabolic tertiary referral hospital for an evaluation of suspected sleep-
syndrome [8, 9]. disordered breathing disorders and underwent
Gastroesophageal reflux disease (GERD) is accepted as polysomnography between February 2012 and February
one of the most common chronic diseases in adults, and its 2013. Out of 1,209 subjects, 105 were excluded because of
prevalence reaches to 20 % in our population [10]. Obesity is the following reasons: 62 participants did not complete the
clearly a risk factor for the development of the disease [11, questionnaire accurately, polysomnography results of 15 sub-
12]. GERD and sleep disorders are both common health jects could not be found, and the questionnaire was adminis-
problems and often coexist. The sleeping state is accompanied tered twice to 28 subjects during polysomnography and titra-
by many changes in gastroesophageal function that may be of tion days. One hundred forty seven subjects who were all
importance in the pathogenesis of GERD. At nighttime, gas- snoring and had an apnea-hypopnea index (AHI) of <5
tric acid production is increased, gastric emptying is delayed, events/h were diagnosed as primary snoring, and the primary
esophageal clearance is markedly delayed, and upper esoph- snoring subjects were considered as non-OSAS (control
ageal sphincter pressure diminishes significantly. Sleep- group). The remaining 957 patients with an AHI of 5 events/
related disorders also increase nocturnal gastroesophage- h or higher were diagnosed as OSAS (study group). Flow
al reflux (GER). OSAS is associated with a high fre- chart of the study is presented in Fig. 1.
quency of GER, probably due to the generation of Demographic data (age, gender, smoking history, alcohol
negative intrathoracic pressures during obstructive ap- and drug use), anthropometric measurements [height, weight,
neas and arousals [13–15]. GERD has been shown to body mass index (BMI), circumferences of neck, waist, and
be prevalent in patients with OSAS on the basis of hip], upper gastrointestinal and sleep-related symptoms, and
studies recording symptoms and esophageal pH detailed medical history were evaluated. All subjects
[16–19]. However, prospective and comparative studies underwent full-night in-laboratory polysomnography and
are limited and contradictory. In some of the studies, the filled out the validated GERD questionnaire with 54 questions
number of subjects is small [16, 20], there is no control on the day of polysomnography [22]. Subjective daytime
group, or polysomnography is not performed to diag- sleepiness was assessed by using the Turkish version of
nose and exclude sleep apnea. Epworth Sleepiness Scale and scores higher than 10 were
OSAS and GERD share similar risk factors. It is considered as sleepiness [23].
unclear whether the co-occurrence of these conditions Demographic, anthropometric, and polysomnographic pa-
represents a causal relationship or is simply a reflection rameters of OSAS patients were compared with those of non-
of shared risk factors. Obesity increases intra-abdominal OSAS group. The relationship between GERD and OSAS-
pressure and decreases esophageal clearance. Due to the related risk factors were examined to evaluate potential un-
common presence of obesity in patients with OSAS, it derlying factors. The local ethics committee approved the
is not easy to irrefutably demonstrate independent study and all subjects gave written informed consent.
Sleep Breath (2015) 19:585–592 587

Subjects performed PSG


respondent using Cohen’s kappa coefficients, and Cronbach’s
(n = 1209)
alpha values were all higher than 70 % for all major symp-
toms. Questions were employed which related to the presence
of the following:
105 subjects excluded
62 did not complete the questionnaire
15 no polysomnography results 1. Major (heartburn, regurgitation, dyspepsia) and related
28 completed the questionnaire twice (dysphagia, odynophagia, chest pain) symptoms and trigger-
ing factors of these symptoms
2. Associated medical conditions
Non-OSAS OSAS 3. Past medical history: upper (dyspepsia, nausea, vomiting,
(n = 147) (n = 957) belching) and lower gastrointestinal symptoms (abdominal
pain or discomfort), respiratory, throat and cardiac problems
(cough, dyspnea, hoarseness, hiccups, globus, asthma), num-
Mild OSAS Moderate OSAS Severe OSAS
ber of physician visits and diagnostic procedures related to
(n = 188) (n = 209) (n=560)
upper gastrointestinal symptoms, medication use (NSAID,
aspirin and all related drugs with upper gastrointestinal com-
Fig. 1 Flow chart of the study. OSAS obstructive sleep apnea syndrome,
PSG polysomnography 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
Polysomnography households and children, total monthly income, age, weight,
height, employment, level of education, and marital status
All patients underwent full overnight in-laboratory diagnostic
polysomnography. Electroencephalography electrodes were po- “Frequent symptoms,” means, a major symptom (heartburn
sitioned according to the international 10–20 system. PSG and/or regurgitation) occurs at least once a week or common and
consisted of monitoring of sleep by electroencephalography, “occasional symptoms” means, an episode of one of the major
electrooculography, electromyography, airflow, and respiratory symptoms less than once a week within the past year as previ-
muscle effort and included measures of electrocardiographic ously defined by us [10]. Frequent heartburn and/or regurgita-
rhythm and blood oxygen saturation. Thoracoabdominal plethys- tion were defined as GERD. The period prevalence of symp-
mograph, oronasal temperature thermistor, and nasal-cannula- toms was the previous 12 months. Each symptom (heartburn,
pressure transducer system were used to identify apneas and regurgitation, dysphagia, and chest pain) was scored for frequen-
hypopneas. Transcutaneous finger pulse oximeter was used to cy and severity by the subject. Symptom frequency was mea-
measure oxygen saturation. Sleep was recorded and scored ac- sured on the following five-point scale: less than once a month,
cording to the standard method [24]. AHI was the sum of the once a month, once a week, several times a week, and daily.
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, Statistical analysis
witnessed apneas, and nocturnal choking or AHI of 15 events/h
without any OSAS symptoms [25]. Besides, an AHI of <5 Statistical analysis was performed with IBM SPSS 20.0 for
events/h was considered within normal limits, and numbers of Windows packaged software. All analyses comparing the study
5 to<15, 15 to<30, and >30 represent mild, moderate, and groups were performed twice: first to compare two groups,
severe OSAS, respectively [26]. No split-night studies were “GERD present” versus “GERD absent,” and then three groups,
performed. “Never,” “Occasional,” and “Frequent.” Numerical variables
were summarized with mean±standard deviation and categorical
Gastroesophageal reflux disease questionnaire variables with frequency and percentage. The significance of
differences among groups was assessed by Student’s t test or
We used a reflux questionnaire derived from Locke et al. [27] two-way ANOVA (when correction was needed for gender), and
previously validated in an English-speaking Western culture, analysis of categorical variables was examined by chi-square test.
which was translated into Turkish, linguistically validated, A value of p<0.05 was considered significant for all statistical
and adapted to the cultural profile of Turkey [22]. As a analysis. Multiple logistic regression analysis was used to deter-
summary, the process of translation included an independent mine the relationship between the demographic, anthropometric,
translation, a back translation, a pilot test using 15 subjects, and polysomnographic parameters with GERD. Besides, odds
and a review and approval by the original questionnaire de- ratio (OR) and 95 % confidence intervals (95 % CI) were
velopers. Test-retest reliability was analyzed for each calculated to show the association.
588 Sleep Breath (2015) 19:585–592

50 Non-OSAS Mild OSAS


Results
Moderate OSAS Severe OSAS
41
40 39
Prevalence of GERD in non-OSAS and OSAS groups 40 37
33 33 32
Overall, 419 of the 1,104 study subjects (38.0 %) reported 29 29 29 30 30

Subjects (%)
30
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), 20
whereas 47 subjects (32.0 %) had GERD in non-OSAS group
and the difference was not statistically significant (p=0.064). 10
As shown in Fig. 2, there was no difference in terms of major
GER symptoms (heartburn, regurgitation) between non-
0
OSAS and mild, moderate, and severe OSAS groups.
No symptoms Occasional GERD
Additional symptoms, namely extraesophageal symptoms, symptoms
alarm symptoms, and epigastric pain of non-OSAS subjects Fig. 2 Gastroesophageal reflux symptoms of non-OSAS and OSAS
and mild, moderate, and severe OSAS patients with GERD, patients (p>0.05 for all comparisons). GERD gastroesophageal reflux
were evaluated. It was found that the patients with OSAS and disease, OSAS obstructive sleep apnea syndrome
GERD reported cough (p=0.046) and odynophagia (p=0.015)
more frequently than non-OSAS patients with GERD (Table 1). Risk factors for GERD in OSAS patients in the multivariate
When the clinical characteristics of non-OSAS subjects with linear regression analysis
GERD were compared to the ones without GERD, no significant
difference was observed (Table 2). However, in OSAS patients The relationship between GERD and other variables was exam-
with GERD, body mass index (p=0.049) was greater, waist (p= ined to determine factors underlying development of reflux in
0.007) and hip (p<0.0001) circumferences were larger, and OSAS patients. There was a significant difference between
Epworth sleepiness scores were higher (p<0.0001) when com- OSAS patients with and without GERD according to female
pared to the patients without GERD as shown in Table 2. gender, daytime sleepiness assessed by Epworth Sleepiness
In OSAS group, the prevalence of GERD was increased in Scale, and circumferences of neck and hip. Consequently, these
female patients (46.6 %) than in male patients (35.7 %) (p= four variables were considered as potential predictors for GERD
0.002). Gender-specific characteristics of OSAS patients were and included in the multivariate linear regression analysis. It was
assessed according to the presence of GERD, and it was found that female gender (p=0.027), Epworth sleepiness score
determined that neck circumference of male OSAS patients (p=0.001), and circumference of hip (p=0.021) were significant-
with GERD was larger than that of the males with no GERD ly associated with GERD (Table 5).
(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 Discussion
BMI in females but the difference was not significant (Table 3).
It is claimed that GERD is common in patients with OSAS but
Sleep parameters of non-OSAS and OSAS patients with and prospective and comparative studies are limited and contra-
without GERD dictory. OSAS and GERD share similar risk factors, and it is
unclear whether the co-occurrence of these conditions repre-
As shown in Table 4, there was no difference with regard to sents a causal relationship or is simply a reflection of shared
polysomnographic parameters in non-OSAS subjects with risk factors. In the present large-cohort study, it was shown
and without GERD. In OSAS patients with GERD, the per- that 38.9 % of OSAS patients and 32.0 % of non-OSAS
centages of sleep efficiency (p=0.044) and stage N2 sleep (p= subjects reported GERD, and the prevalence of GERD was
0.017) were higher, and the percentage of stage N1 sleep considerably increased compared to the general population.
(p<0.0001) was lower than in OSAS patients without GERD. There was no relationship between the severity of OSAS and
However, the indicators of OSAS severity including AHI, the presence of GERD. In OSAS patients with GERD, mea-
oxygen desaturation index, lowest nocturnal oxygen saturation surements of obesity including BMI and circumferences of
(SpO2) (%), sleep time with SpO2 <90 % (min), and sleep time waist and hip were greater and daytime sleepiness was higher
with SpO2 <90 % (%) did not correlate with GERD. In addi- than in the patients without GERD. Besides, the prevalence of
tion, reflux symptoms were not associated with sleep position GERD was increased in female OSAS patients. The present
assessed by position sensor during polysomnography. 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 research area (n=694) [29]. Since all three studies revealed very
the prevalence of GERD in OSAS patients. similar results with the same questionnaire, it is possible to claim
In our large cohort referred for sleep studies, 419 of the 1,104 that GERD prevalence was significantly increased compared to
subjects (38.0 %) reported symptoms consistent with GER ex- the general population. In a study with a similar design, the
perienced at least once at a week in the last year. The prevalence prevalence of symptomatic GER was investigated in 135 sub-
of GERD was 38.9 % in OSAS and 32.0 % in non-OSAS jects with obstructive sleep apnea (OSA) and 93 with snoring. It
subjects, and there was no significant difference between two was found that symptomatic GER is common in subjects with
groups. In our previous studies, the prevalence of GERD was SDB, but there was no difference between those with OSAS and
20 % in a small town near the study area (n=630) [10], 22.8 % in snoring [19]. Additionally, Shepherd et al. [30] showed that the
a country-wide study (n=3,200) [28], and 19.4 % in the same 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) 19:585–592 591

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