Obesity impact on GERD
Relationship between Obesity and Gastroesophageal Reflux
Disease as Recorded by 3-Hour Esophageal pH Monitoring
Georgios Kouklakis3, John Moschos2, Jannis Kountouras1, Alexandros Mpoumponaris 2, Epaminondas Molyvas 2,
Georgios Minopoulos3
1) Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital. 2) Department
of Gastroenterology, 424 General Military Hospital, Thessaloniki. 3) Endoscopy Unit, Surgical Department, Demokrition
University of Thrace, Alexandroupolis, Greece
Abstract
Objective. To evaluate the presence of gastroesophageal
reflux disease (GERD) in a Greek cohort in relationship to
the body mass index (BMI), using the 3-hr postprandial
esophageal pH monitoring.
Methods. Sixty-four consecutive patients (55 males, 9
females; mean age 40.7±13.7 years) with at least weekly
attacks of heartburn or acid regurgitation for a period longer
than one year, were screened endoscopically for esophagitis
and underwent a 3-hr postprandial pH monitoring to quantify
the reflux. DeMeester score was calculated.The patients
were allocated to three groups: group A (reference group,
n=23) with BMI <25kg/m2 (normal); group B (n=25) with
BMI 25-30kg/m2 (overweight), and group C (n=16) with BMI
>30kg/m2 (obese).
Results. A higher DeMeester score, as well as a
decreased lower esophageal sphincter pressure were
evidenced with increasing BMI. Moreover, there was an
association between increasing BMI and the point scale of
reflux symptoms. The number of cases with severe reflux
symptoms increased significantly among overweight (odds
ratio: 4.94, 95%CI: 0.95-25.56) and obese (odds ratio: 8.18,
95%CI: 1.19-56.00) patients.
Conclusions. The shorter 3-hr postprandial test appears
to be diagnostic for GERD and acceptable by patients,
reducing discomfort and enhancing compliance. Our study
confirms the link between obesity and GERD. BMI is strongly
associated with the point scale of reflux symptoms both in
overweight and obese patients.
Key words
Obesity - gastroesophageal reflux - pH monitoring - body
mass index - DeMeester score
Romanian Journal of Gastroenterology
June 2005 Vol.14 No.2, 117-121
Address for correspondence: John Moschos, Gastroenterologist
10 Papadimitriou St, Kalamaria
551 31, Thessaloniki, Macedonia
Greece
E-mail: gut@in.gr
Rezumat
Obiectiv. Evaluarea prezenþei bolii de reflux gastroesofagian (BRGE) la o serie de pacienþi din Grecia în relaþie
cu indexul de masã corporalã (IMC), prin monitorizarea timp
de 3 ore postprandial a pH-ului esofagian.
Metodã. 64 pacienþi consecutiv internaþi (55 bãrbaþi, 9
femei, cu vârsta medie 40,7±13,7 ani) care prezentau perioade
cel puþin sãptãmânale de pirozis sau regurgitare acidã de cel
puþin un an, au fost examinaþi endoscopic pentru screeningul esofagitei. Acestora li s-a monitorizat pH-ul esofagian
postprandial timp de 3 ore pentru cuantificarea refluxului. Sa calculat scorul DeMeester. Pacienþii au fost înpãrþiþi în trei
grupuri: grupul A (de referinþã, n=23) cu IMC <25kg/m2
(normal); grupul B (n=25) cu IMC 25-30kg/m 2
(supraponderal), ºi grupul C (n=16) cu IMC >30kg/m2 (obez).
Rezultate. Am constatat un scor DeMeester mai mare ºi
o presiune mai scãzutã în sfincterul esofagian inferior pe
mãsura creºterii IMC. Mai mult, creºterea IMC s-a asociat
cu scala simptomelor de reflux. Pacienþii cu simptome severe
de reflux au fost semnificativ mai mulþi în grupul
supraponderal (odds ratio: 4,94, 95%CI: 0,95-25,56) ºi obez
(odds ratio: 8,18, 95%CI: 1,19-56,00).
Concluzii. Testul postprandial scurt de 3 ore are valoare
diagnosticã pentru BRGE ºi este acceptabil pentru pacienþi,
reducând disconfortul ºi ameliorând complianþa. Studiul
nostru confirmã relaþia dintre obezitate ºi BRGE. IMC este
strâns asociat cu scala simptomelor de reflux, atât la pacienþii
supraponderali cât ºi la cei obezi.
Introduction
Obesity and gastroesohageal reflux disease (GERD) are
both rapidly escalating throughout the world, particularly
in Western societies (1-5). Moreover, both diseases appear
to have an unfavorable impact (biological and/or
psychological) on the quality of life (6,7) and are independent
risk factors for esophageal adenocarcinoma (7,8). Notably,
during the last decades, the incidence of adenocarcinoma
of the esophagus and the esophagogastric junction has
118
increased fivefold in Europe and the United States (9,10).
Although there is a general belief that obese people are
more likely to develop GERD, scientific evidence suggesting
that obesity plays a causal role in this disease is limited and
inconsistent (7,8).
The history of the most common symptoms of GERD
(heartburn, acid regurgitation, and some degree of
dysphagia) is usually sufficient to confirm the diagnosis of
GERD and to permit proper treatment (11). In addition,
ambulatory 24-hour (hr) esophageal pH monitoring is the
most commonly used test for establishing the existence of
excessive GERD, for correlating symptoms temporally with
reflux and for quantifying esophageal acid exposure (11).
However, a limitation of the long-lasting 24-hr pH monitoring
is that it represents an uncomfortable experience (12), thereby
leading to low acceptance of this test by patients. Moreover,
patients do not constantly keep the probe in for 24 hours
(13). Therefore, a shorter trial may be more tolerable to the
patients.
In this study, we have introduced the 3-hr postprandial
esophageal pH monitoring as a more flexible and tolerable
test to evaluate the presence of GERD in a Greek cohort of
patients, presenting the classical symptoms of reflux disease,
in relationship to their body mass.
Patients and methods
Sixty-four consecutive patients (55 males and 9 females;
mean age 40.7±13.7 years) with at least weekly attacks of
heartburn or acid regurgitation for a period no less than one
year, were screened for the presence of endoscopic findings
of esophagitis and the performance of 3-hr postprandial pH
monitoring study to quantify the reflux. Since heartburn
and acid regurgitation are the chief symptoms of GERD,
participants answered a question if symptoms were mild,
moderate or severe. In particular, heartburn was evaluated
using a 4-point scale: none (no heartburn), mild (awareness
of heartburn, but easily tolerated), moderate (discomforting
heartburn sufficient to cause interference with normal
activities including sleep) and severe (incapacitating
heartburn, with inability to perform normal activities
including sleep). All participants underwent certain physical
examinations, including assessment of body weight, height,
and body mass index (BMI; weight in kilograms divided by
the square of height in meters). The patients were then
allocated in three groups, according to predetermined BMI
cut-off points of the World Health Organization classification
of overweight and obesity. In this regard, group A (reference
group) consisted of 23 patients (19 males, 4 females; mean
age 40.1±18.0 years) with BMI <25 kg/m2 (normal); group B
included 25 patients (22 males, 3 females; mean age 40.4±10.6
years) with BMI between 25 and 30 kg/m2 (overweight), and
group C consisted of 16 patients (15 males, 1 female; mean
age 40.5±11.5 years) with BMI >30 kg/m2 (obese). Among
the obese patients, there were 4 severely obese cases (BMI
>35 kg/m2).
Kouklakis et al
Exclusion criteria included a past history of gastric or
esophageal surgery (apart from cholecystectomy), malignant
disease, esophageal ring stricture or esophagitis secondary
to systemic events (e.g. scleroderma or ingested irritants),
primary esophageal motility disorders and age <18 years
(13,14). Patients with endoscopic evidence of active
gastrointestinal bleeding, those with Zollinger-Ellison’s
syndrome, women who were pregnant or lactating, and those
with any condition likely to result in poor compliance were
also excluded from the study. All patients had stopped acid
suppression therapy (four days beforehand for those taking
antacids, or one month beforehand for those using H2receptor antagonists or proton pump inhibitors), and
underwent a four-week wash-out period during which any
medications that affect motility, including tricyclic
antidepressants and laxatives, were tapered. None of the
patients received oral medications that could cause reflux
disease symptoms (e.g., alendronate sodium, nifedipine,
non-steroidal anti-inflammatory drugs). After having given
informed consent, all 64 patients underwent elective
diagnostic upper gastrointestinal endoscopy to assess the
severity of reflux esophagitis according to the Los Angeles
classification (15).
Study design
The subjects reported at 9 a.m. after a 12-hr fast. Intravenous sedation was given, and a routine upper endoscopic
examination (Fujinon EPX-201 endoscope system; Fujinon
Optical, Tokyo, Japan) was carried out to identify evidence
of macroscopic abnormalities. Endoscopes were sterilized
between procedures according to standard guidelines (16).
After an overnight fast, esophageal manometry was
performed using a 4-channel, silicone rubber, low
compliance, pneumohydraulic, perfused manometric
assembly (model PIP-4-8SS, Mui Scientific, Mississauga,
Ontario, Canada). The manometric assembly was passed
transnasally and the position of the lower esophageal
sphincter was determined using the station pull-through
technique on 0.5 cm intervals. After removal of the
manometric catheter, a monocrystalline antimony pH catheter
was passed transnasally and the electrode was positioned
5 cm above the manometrically determined upper margin of
the lower esophageal sphincter. The electrode was calibrated
in buffering solutions of pH 4 and pH 7 before each study.
Three-hr postprandial ambulatory esophageal pH
monitoring was then carried out. Patients were instructed to
mark the event recorder with regard to meal and recumbency
and to work according to their daily routine except that
coffee, alcohol, fruit juices and antacids had to be avoid
(17). Data acquisition was performed using a portable data
logger (pHmetry UPS-2020, Medical Measurement Systems
b.v., Enschede, The Netherlands). Semi-automated analysis
was performed with the aid of commercially available
software. Reflux episode was defined as esophageal pH<4
in the distal esophagus. Parameters of esophageal acid
Obesity impact on GERD
119
exposure included the standard DeMeester score. All
analyses were performed by a single investigator (JM).
For comparisons of the age (years) among the three
groups of patients, the nonparametric Mann-Whitney U test
was used and there was no significant difference between
the groups. Comparisons of mean values of DeMeester
score and mean values of lower esophageal sphincter
pressure among the three study groups were made by
analysis of variance (ANOVA). Finally, concerning the
gastroesophageal reflux symptomatology and the
endoscopical findings, the odds ratios of groups B and C
versus reference group A were calculated. P value <0.05
was regarded as statistically significant.
There was an association between increasing BMI and
the point scale of reflux symptoms (Table I). Compared with
those with BMI less than 25, the cases with severe reflux
symptoms increased significantly among the overweight
(odds ratio: 4.94, 95%CI: 0.95-25.56) and obese patients (odds
ratio: 8.18, 95%CI: 1.19-56.00).
When compared with the reference group, there was
also a propensity of increasing severity of endoscopic
appearing esophagitis, according to the Los Angeles
classification system, in overweight and obese patients
(Table II).
Discussion
There is conflicting evidence that obesity per se
predisposes to GERD. Although some large cross-sectional
population-based studies examining the relationship
between body mass and GERD found that BMI was strongly
positively related to the frequency of symptoms of GERD
(18-21) others showed disbelief in such an association,
suggesting that gastro-esophageal reflux symptoms occur
independently of BMI and weight reduction may not be
justifiable as an antireflux therapy (22). Our study confirms
the link between obesity (defined as BMI >30 kg/m2) and
reflux symptoms, showing that BMI is strongly associated
with the point scale of reflux symptoms both in overweight
and obese patients compared with those with normal BMI.
We strictly used the main symptoms, heartburn and
regurgitation, which are considered to be the most useful
for the diagnosis of GERD. These symptoms occurred at
least once a week, indicating the good validity of reflux
symptom data and the fact that our selected subjects were
representative of the population at large. However, a
limitation of our study was the small number of women (n=9
in all 3 categories of BMI), thereby not allowing for
comparisons between the two sexes. On the other hand,
Results
Group A (reference group) patients had a mean BMI
23.4 ±1.4 kg/m2 and their mean DeMeester score was 27.8
±20.7. Group B (overweight) patients had a mean BMI 27.4
±1.0 kg/m2 and a mean DeMeester score 39.1 ±42.1. Group C
(obese) patients had a mean BMI 32.6 ±3.2 kg/m2 and a mean
DeMeester score 62.5 ±45.3. A significantly higher
DeMeester score (F-ratio: 4.24, P=0.019) was evidenced as
the BMI increased. All subjects found it tolerable to wear
the probe for 3-hr postprandial analysis, and kept the probe
in for the shorter 3-hr test.
Group A (reference group) patients had a mean BMI
23.4 ±1.4 kg/m2 and their mean lower esophageal sphincter
pressure was 16.04 ± 2.117. Group B (overweight) patients
had a mean BMI 27.4 ±1.0 kg/m2 and their mean lower
esophageal sphincter pressure was 14.08 ± 2.361. Group C
(obese) patients had a mean BMI 32.6 ±3.2 kg/m2 and their
mean lower esophageal sphincter pressure was 10.94±2.175.
A significantly decreased lower esophageal sphincter
pressure (F-ratio: 26.827, P<0.001) was evidenced as the BMI
increased.
Table I Comparison of gastroesophageal reflux symptomatology of groups B and C versus reference group A;
ellipses indicate not applicable
No
Mild
Moderate
Severe
Group A
n=23
Group B
n=25
Group C
n=16
Odds ratio
B vs. A (95% CI)
Odds ratio
C vs. A (95% CI)
0 (0%)
16 (69.6%)
5 (21.7%)
2 (8.7%)
1
8
8
8
0
4
5
7
0.21 (0.06-0.70)
1.70 (0.47-6.19)
4.94 (0.95-25.56)
0.15 (0.04-0.60)
1.64 (0.37-7.19)
8.18 (1.19-56.00)
(4%)
(32%)
(32%)
(32%)
(0%)
(25%)
(31.2%)
(43.8%)
Table II Comparison of endoscopical findings of groups B and C versus reference group A; ellipses indicate not
applicable
Normal
Esophagitis A
Esophagitis B
Esophagitis C
Barrett’s esophagus
Hiatal hernia
Group A
n=23
Group B
n=25
Group C
n=16
Odds ratio
B vs. A (95% CI)
Odds ratio
C vs. A (95% CI)
11 (47.8%)
7 (30.4%)
4 (17.4%)
0 (0%)
1 (4.3%)
9 (39.1%)
10 (40%)
7 (28%)
7 (28%)
1 (4%)
0 (0%)
14 (56%)
4
2
6
2
2
7
0.73
0.89
1.85
1.98
0.36
0.33
2.85
3.18
1.21
(25%)
(12.5%)
(37.5%)
(12.5%)
(12.5%)
(43.8%)
(0.23-2.29)
(0.26-3.10)
(0.47-7.32)
(0.63-6.26)
(0.09-1.42)
(0.06-1.67)
(0.61-13.34)
(0.21-47.94)
(0.33-4.45)
120
Nilsson et al, who found a significant association between
body mass and reflux esophagitis in female in contrast to
male patients, hypothesized that this might be caused by
increased estrogen activity in overweight and obese females
(19), thereby suggesting that estrogens may play an
important role in the etiology of reflux disease (8). If the
latter hypothesis is correct, then our findings might be of
more value, as our cohort consisted mainly of male patients.
The causation between the BMI and reflux symptoms is
still not clearly known but factors such as increased
sensitivity of the esophagus to acid, increased intraabdominal pressure, and vagal abnormalities in obese
patients may cause higher bile and pancreatic enzyme output,
thus making the resulting refluxate more toxic (23). In our
study, we implemented strict exclusion criteria involving any
obvious causes other than the BMI that might have been
responsible for the reflux symptoms. Furthermore, although
it has been postulated that the presence of hiatus hernia
and a higher BMI are associated with the development of
reflux esophagitis (24,25), such a finding was not observed
in our cohort. Indeed, hiatal hernia incidence was about the
same in all three categories of BMI.
From another viewpoint, body composition affects the
pharmacokinetics of drugs administered for GERD.
Although there are few data about the efficacy of drug
treatments in obese patients, poor absorption or a larger
distribution of body mass may lead to the medications being
less effective in their action. Subsequently, less effective
treatment can lead to further complications in the long term
(26). However, larger distribution of body mass was observed
only in a minority of our patients (4 severely obese cases),
and all the patients in our study had stopped acid
suppression therapy that would have altered our results
and had not received any oral medications that could cause
reflux disease symptoms.
The association between BMI and endoscopically
verified case subjects with reflux esophagitis is also
ambiguous. Some population-based case-control
endoscopical studies found a strong and dose-dependent
association between body mass and reflux esophagitis (24),
particularly in women rather than among men (19), while
other studies found that massive overweight is not
associated with an increased prevalence of GERD (27). Our
results seem to be in accordance with the first studies; a
propensity of increasing severity of endoscopic appearing
esophagitis (according to the LA classification) and Barrett’s
esophagus was observed in the overweight and obese
subjects of our study. However, due to the small number of
cases included in our study, large-scale studies are needed
to draw definite conclusions.
There are few published studies on the use of the
ambulatory 24-hr pH monitoring to investigate the
prevalence of GERD with regard to BMI, reporting a more or
less strong correlation between BMI and severity of
gastroesophageal reflux (28-30). Although the ambulatory
pH study is currently the best test available that identifies
the presence of GERD in a physiological manner, our
Kouklakis et al
previous experience in using this method on Greek patients
yielded uncomfortable experiences, also reported by others
(12), leading to a very low acceptance of this test by our
patients. Therefore, we decided to introduce the 3-hr
postprandial esophageal pH monitoring as a more flexible
and tolerable test to evaluate the presence of GERD in
relationship with their body mass. We believe this is not a
disadvantage because, according to previously published
data, the sensitivity and specificity of a 3-hr postprandial
test were found to be 88% and 98%, respectively, compared
with the 24-hr pH study for the assessment of GERD (13). In
our study, reflux was defined and quantified using the
DeMeester score (30). The shorter 3-hr postprandial test
appears to be diagnostic for GERD and acceptable by
patients, reducing discomfort and enhancing compliance.
However, larger prospective evaluations of this test are
needed to draw more definite conclusions.
Our results indicate that there was a strong correlation
between BMI and the severity of gastroesophageal reflux.
Indeed, patients who were overweight and obese had
significantly higher distal esophageal acid exposure time
and so a higher DeMeester score. It can be assumed that
the barrier to gastroesophageal reflux is rendered insufficient
in patients who are overweight (30). We found that a
significantly decreased lower esophageal sphincter pressure
was evidenced as the BMI increased. Another possible
mechanism could be that in obese subjects, cholecystokininstimulated pancreatic enzyme secretion, emptying of bile
acids and gastrin release are reduced compared with patients
with normal BMI. Notably, the changes in the pancreatic
and gallbladder function found in obesity may alter the
composition of the refluxate, thus rendering it more toxic to
the esophageal mucosa (31). Future larger cohort studies
are needed to elucidate these mechanisms.
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