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Original Paper

Digestion 2009;79:196201 DOI: 10.1159/000211715

Prevalence and Risk Factors for Overlaps between Gastroesophageal Reflux Disease, Dyspepsia, and Irritable Bowel Syndrome: A Population-Based Study

Soon Young Lee a Kwang Jae Lee b Soo Jeong Kim a Sung Won Cho b

Departments of a Preventive Medicine and Public Health, and b Gastroenterology, Ajou University School of Medicine, Suwon , South Korea

tween GERD, dyspepsia, and IBS are common in the gen-eral population. These overlaps occur predominantly in in-dividuals with anxiety. Copyright 2009 S. Karger AG, Basel

Introduction

Gastroesophageal reflux disease (GERD), dyspepsia and irritable bowel syndrome (IBS) are common gastro-intestinal disorders in the general population. Twenty per-cent of the general adult population have GERD-related symptoms at least once a week [1, 2] . The prevalence of dyspepsia is reported to be 15% in the general population [3] . IBS is experienced by up to 20% of the general popula-tion [4] . Since these disorders are very prevalent, coexis-tence of two or more conditions may often be observed [57] . Evidence shows a strong overlap between GERD and IBS that exceeds the individual presence of each con-dition [7, 8] . A recent study demonstrated that the overlap of these two conditions occurs more commonly than ex-pected by chance [9] . Disturbances of gastrointestinal sen-sory and motor function are commonly accepted as the underlying pathogenesis of GERD, functional dyspepsia, and IBS. Thus, these conditions may have more in com-mon than once appreciated and may be linked to each

Key Words Dyspepsia Gastroesophageal reflux disease Irritable bowel syndrome

Abstract Background/Aims: People may have symptoms of multiple disorders at the same time. We aimed to determine preva-lence and risk factors for overlaps between gastroesopha-geal reflux disease (GERD), dyspepsia and irritable bowel syndrome (IBS) in a Korean population. Methods: A cross-sectional survey was performed on 1,688 randomly select-ed Korean subjects. Data on 1,443 subjects could be ana-lyzed. Dyspepsia and IBS were diagnosed using modified Rome II criteria. Results: The prevalences of GERD, dyspep-sia and IBS were 8.5, 9.5 and 9.6%. Overlaps between GERD and dyspepsia, GERD and IBS, and dyspepsia and IBS were observed in 2.3 (95% CI 1.43.0), 2.0 (95% CI 1.22.6%) and 1.3% (95% CI 0.61.8%) of the population. 27 and 24% of GERD subjects suffered from dyspepsia and IBS. 24 and 14% of dyspeptic subjects had GERD and IBS. 21 and 14% of IBS subjects had GERD and dyspepsia. Anxiety was significant-ly associated with GERD overlap (OR 2.73, 95% CI 1.136.57), dyspepsia overlap (OR 3.19, 95% CI 1.337.63) and IBS over-lap (OR 4.92, 95% CI 2.0411.84), compared with GERD alone, dyspepsia alone and IBS alone. Conclusions: Overlaps be-

Received: January 12, 2009 Accepted: February 25, 2009 Published online: April 3, 2009

Kwang Jae Lee, MD Department of Gastroenterology, Ajou University HospitalAjou University School of Medicine, San5, Wonchon-dong, Yeongtong-gu 443-721 Suwon (Korea) Tel. +82 2 219 5102, Fax +82 2 219 5999, E-Mail kjleemd@hotmail.com

2009 S. Karger AG, Basel00122823/09/07930196$26.00/0

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other. A subgroup with two or more of these conditions may have a common pathophysiology and share risk fac-tors. Thus, an understanding of the overlap between GERD, dyspepsia, and IBS could provide valuable insights into the pathophysiologies of these conditions.

Although these disorders include common symptoms affecting many people throughout the world, their preva-lences are thought to vary in different populations. In particular, in the case of GERD, several population stud-ies have shown that GERD is less common in the East than in the West [1012] . Outpatient observations in Western studies have shown that IBS is prevalent among patients diagnosed as having GERD, whereas IBS is rela-tively uncommon in the absence of GERD [7, 9] . How-ever, little population-based data are available to confirm the presence of overlaps between GERD, dyspepsia, and IBS in the East. Furthermore, there is a paucity of infor-mation on risk factors that might explain overlaps. Since more life stress and psychological distress have been re-ported in patients with these common disorders than in healthy controls [1317] , psychological factors might be implicated in their overlaps.

Thus, in the present study, we aimed to determine if overlaps between GERD, dyspepsia, and IBS occur in a Ko-rean population at levels that cannot be simply explained by chance, and to identify risk factors for these overlaps.

Subjects and Methods

Study Population This study was a cross-sectional and population-based study

conducted from November 2005 to February 2006 in the city of Gwangju, which is located in the northwest region of South Ko-rea, where approximately 167,000 citizens reside. The Koreans are mostly homogeneous in ethnicity and regional differences in terms of sociodemographic environments are minimal. Gwangju City represents a mixture of urban and rural lifestyles, and its ha-bitants sociodemographically reflect the general Korean popula-tion. A documented list of citizens was provided by the regional public health office of city hall. Those older than 19 years of age were considered eligible. The goal of sampling was to obtain a manageable community sample representative of non-institu-tionalized persons residing in Gwangju City, which has average characteristics in terms of demographic and socioeconomic sta-tus. To achieve this goal, 1,000 households were randomly select-ed by multistage systemic sampling, using a computerized sam-pling procedure. The community is stratified into 10 smaller ad-ministrative areas (sampling unit 1, SU1). Based on the number of households in each area, the sample size was assigned to each SU1, which was again divided into smaller units of administrative areas (SU2). The final sample size of households in each SU2 was determined proportionally by the number of households. The households in each PS2 were randomly sampled.

Before conducting the interview, interviewers explained the purpose of the questionnaire to all eligible individuals and ob-tained informed consent. The study protocol was approved by the Institutional Review Board of Ajou University Hospital.

Questionnaire The questionnaire requested information on demographics,

lifestyle factors, a hospital anxiety and depression scale [18] , the presence and frequency of heartburn, and Rome II criteria used to diagnose functional dyspepsia and IBS [19] . BMIs were calculated as weight in kilograms divided by height in meters squared. For analysis purposes, we categorized BMI into two groups namely, ! 25 and 6 25. The questionnaire also included questions on life-style factors including smoking (never or former smoker, current smoker), alcohol drinking (abstainer or former drinker, current drinker), and regular exercise ( ! 3 or 6 3 days per week for 6 30 min of exercise/day). The hospital anxiety and depression scale is a self-assessment measure of anxiety and depression severities. This scale consists of 14 items, allocated to anxiety and depression sub-scales containing 7 items apiece. Four-grade Likert scale scores (03) were awarded to each item, where a higher score indicated great-er levels of depression or anxiety. Definite anxiety and depression were defined as anxiety or depression scores of 11 or more.

GERD was diagnosed when subjects reported that heartburn and/or acid regurgitation had occurred at least once a week dur-ing the preceding 12 months. Heartburn was defined as a burning sensation that rises through the chest. Acid regurgitation was de-fined as the regurgitation of bitter or sour liquid into the mouth. The definition of dyspepsia was based on modified Rome II cri-teria as follows: discomfort (postprandial fullness, early satiety, nausea, or upper abdominal bloating) or pain centered in the up-per abdomen present at least once a week during the preceding 12 months without any evidence that dyspepsia was exclusively re-lieved by defecation or associated with onset of a change in stool frequency or stool form. IBS was also defined, using modified Rome II criteria as follows: abdominal discomfort or pain, present at least once a week during the preceding 12 months, with two of the following three features: relief after defecation, an onset as-sociated with a change in stool frequency, or an onset associated with a change in stool form. Symptom frequency was measured using the following scale: 1 = none during the past year; 2 = less than once a week, and 3 = at least once a week.

Study Conduct The subjects were also asked to complete a self-administered

questionnaire on health habits, disease history and present symp-toms including anxiety and depression and bring it with them to the Community Health Center on the date of their appointment.

The survey consists of an interview and the self-administered questionnaire. Our interviewers, who were well-trained health personnel, visited selected households and conducted an initial face-to-face interview at each home for the identification of eligible family members over 19 years old. Subsequently, the interviewers asked eligible subjects to participate in the survey, and explained details of the questionnaire to those who wanted to participate. Subjects were excluded if they could not be contacted, if they had a history of major psychotic episodes, mental retardation, demen-tia, a history of a major abdominal operation, or a significant ill-ness that impaired ability to complete the questionnaire. The in-terviewers handed the survey questionnaires to the participants,

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and asked them to fill them in. The interviewers assisted those who had difficulties in reading or understanding the questions. The working status of the interviewed person is shown in table 1 . The percentage of the unemployed including housewives was 36.8%, which is not different from the average percentage in Korea.

Of the selected eligible subjects, 1,688 individuals (778 men and 910 women, aged 1979 years) completed the survey. The data of subjects who inadequately completed the questionnaire were excluded. Finally, the data of 1,443 individuals (672 men and 771 women, aged 1979 years) were available for analysis.

Statistical Analysis The Students t test and the 2 test were carried out to compare

continuous and categorical variables between two independent groups. Risk factors were evaluated by logistic regression analysis adjusted for age. Confidence intervals (CI) of odds ratios (OR) were obtained from the asymptotic 2 distributional properties of the log-likelihood ratio. p values of ! 0.05 were considered statis-tically significant.

Results

The Prevalence of GERD, Dyspepsia, IBS, and Their Overlaps Figure 1 shows the prevalence of GERD, dyspepsia, IBS,

and their overlaps. The proportion of subjects with at least one of these three disorders among the 1,443 study subjects was 22.3%. The prevalences of GERD, dyspepsia, and IBS were 8.5, 9.5 and 9.6%. The prevalences of GERD alone, dyspepsia alone, and IBS alone were 4.6 (95% CI 3.45.7), 6.3 (95% CI 4.97.6) and 6.6% (95% CI 5.27.9). The ob-served prevalence of an overlap between two or more con-ditions was 4.8%. Overlaps between GERD and dyspepsia, GERD and IBS, and dyspepsia and IBS were observed in 2.3 (95% CI 1.43.0), 2.0 (95% CI 1.22.6%) and 1.3% (0.61.8%) of the study population. Among those subjects diag-nosed as having GERD, the proportions of subjects who suffered from dyspepsia or IBS were 27 and 24%. Among those subjects diagnosed as having dyspepsia, the propor-tions of subjects who suffered from GERD or IBS were 24 and 14%. Of those with IBS, the proportions of subjects with GERD or dyspepsia were 21 and 14%.

Demographic and Clinical Characteristics of theStudy Subjects No significant differences were observed between the

following subgroups in terms of age and gender: subjects without any of the three disorders, with one disorder, and with two or more disorders. Furthermore, there was no significant association of BMI, smoking, alcohol drinking, exercise and depression with the presence of one disorder in isolation or the presence of two or more

disorders. However, anxiety was significantly more prevalent in those with one disorder or two or more dis-orders than in those without any of the three disorders. The prevalence of anxiety in those with two or more dis-orders was significantly greater than in those with one disorder ( table 2 ).

Table 1. The working status of the study participants

Occupations %

Executive, administrative, and managerial 1.6Professional 3.5Engineering and technical 6.1Administrative support, including clerical 10.7Service 11.6Sales 5.1Farming, fishing, and forestry 3.9Precision production, craft, and repair 2.1Machine operators, assemblers, and inspectors 0.3Transportation and material moving 3.0Military 0.4Students 11.4Unemployed and housewives 36.8Missing (no response) 3.5Total 100.0

Dyspepsia (n = 91)

IBS (n = 95)

GERD (n = 67)

23

6

27

13

Neither (n = 1,121)

Fig. 1. The observed prevalences of gastroesophageal reflux dis-ease (GERD), dyspepsia, irritable bowel syndrome (IBS), and their overlaps in the 1,443 study subjects.

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Risk Factors for Overlaps between Two or More Disorders Anxiety was found to be significantly more associated

with the presence of two or more disorders as opposed to one disorder by logistic regression analysis. The other pa-rameters such as gender, BMI, smoking, alcohol, and ex-ercise were not found to be significantly associated with the overlap between two or more conditions ( table 3 ).

Discussion

This population-based, case-control study suggests that overlaps between GERD, dyspepsia, and IBS are greater than predictions based on coincidence. Actually,

the overlap between two or more conditions was observed in 4.8% of our study subjects. The prevalences of GERD in dyspepsia or IBS, of dyspepsia in GERD or IBS and of IBS in GERD or dyspepsia were substantially higher than their prevalences in the general population. The popula-tion prevalences of GERD, dyspepsia, and IBS were 8.5, 9.5 and 9.6%, while the observed prevalences of GERD alone, dyspepsia alone, and IBS alone were 4.6, 6.3 and 6.6%. Thus, after eliminating patients with two or more conditions, the prevalences of each condition in the pop-ulation are clearly low.

The age and gender distribution in our sample popula-tion was in line with the data of the most recent national census. In addition, Gwangju City consists of urban and rural areas. Thus, its population seems to be reasonably

Table 2. Demographic and clinical characteristics of the study population

None(n = 1,121)

GERDalone (n = 67)

Dyspepsiaalone (n = 91)

IBSalone (n = 95)

Overlap(n = 69)

Mean age, years 49815 48814 50815 47815 43814Female 589 (52) 32 (48) 47 (52) 56 (59) 43 (62)Mean BMI 2583 2483 2583 2483 2484Current smoker 258 (25) 12 (20) 19 (22) 24 (26) 9 (13)Current alcohol user 184 (17) 14 (22) 10 (11) 12 (13) 8 (12)Regular exercise 125 (11) 10 (15) 12 (13) 16 (17) 10 (14)Anxietya 113 (10) 28 (42)b 27 (30)c 38 (40)d 44 (64)dDepression 99 (9) 8 (12) 13 (14) 10 (11) 8 (12)

Figures are numbers with percentages in parentheses or means 8 SD. BMI = Body mass index; none = sub-jects without any of the three disorders; overlap = subjects with two or more disorders.

a p < 0.001 using 2 tests; b p < 0.05, c p < 0.005, d p < 0.001 compared with the none subgroup, using the2 tests.

Table 3. Risk factors for overlaps between two or more disorders as compared with a single disorder

GERD overlapvs. GERD alone

Dyspepsia overlapvs. dyspepsia alone

IBS overlapvs. IBS alone

OR 95% CI OR 95% CI OR 95% CI

Female gender 2.47 0.936.56 2.17 0.795.98 1.33 0.493.62High BMI (25) 1.61 0.654.00 0.86 0.352.14 1.06 0.432.67Current smoker 1.71 0.426.87 0.71 0.212.39 0.36 0.101.39Current alcohol user 0.41 0.101.67 0.69 0.153.23 0.53 0.093.22No regular exercise 0.61 0.182.03 0.81 0.252.67 0.98 0.273.51Anxiety 2.73 1.136.57a 3.19 1.337.63a 4.92 2.0411.84aDepression 1.04 0.283.90 1.57 0.435.72 0.90 0.223.66

a Statistically significant by logistic regression analysis adjusted for age.

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representative of the Korean population. Misclassifica-tion bias in relation to the exclusion of organic disease in this community survey may be an important issue. How-ever, the medical histories of all subjects were examined as completely as possible, and chronic and recurrent symptoms were considered to be an essential factor in diagnosing these disorders. Accordingly, we believe that organic conditions were reliably excluded in diagnosing GERD, dyspepsia, and IBS. The Rome II criteria state 12 nonconsecutive weeks of symptoms during the past 12 months. This study defined IBS and dyspepsia as at least once a week during the preceding 12 months in order to make the questions understandable and easily complet-ed. Since these modified criteria were tighter than origi-nal Rome II criteria, our IBS or dyspepsia population may have been underestimated.

In the present study, GERD was defined as heartburn and/or acid regurgitation at least once a week. GERD prevalence as determined by the present survey was 8.5%. In a population-based study carried out in South Korea in 2000, the prevalence of GERD is reported to be 3.5% [12] , and thus, the incidence and prevalence of GERD appears to be rapidly increasing in Korea. Of these three disorders, IBS was most prevalent; dyspepsia ranked second, followed by GERD. GERD was diag-nosed in 24% of subjects with dyspepsia and in 21% sub-jects with IBS, which suggests that GERD is related to dyspepsia and IBS. Probably, a common pathophysiolog-ical mechanism is responsible for these conditions. For example, diffuse motor disturbances, altered visceral sensitivity, and/or brain-gut dysfunction may be shared. Overlaps between these disorders may be manifestations of a widespread functional gut disturbance. If they have visceral hypersensitivity, they are probably hypersensi-tive to physiologic reflux rather than having pathologic reflux. However, IBS is also reported to be common in true GERD patients with abnormal 24-hour pH study findings [20] . Accordingly, further investigation on the pathogenesis of GERD symptoms in patients with dys-pepsia or IBS is warranted.

The mechanism of how these different problems occur concomitantly is important and requires further study. In the present study, we investigated risk factors, particu-larly psychological factors, for the overlap between two or more conditions. In particular, anxiety was found to be significantly more prevalent in the subjects with GERD alone, dyspepsia alone, or IBS alone than in subjects with-out these conditions. Anxiety was significantly more common in individuals with two or more of these condi-tions than in those with a single condition. Multiple lo-

gistic regression analysis revealed that anxiety, but not depression, was independently associated with the pres-ence of two or more conditions. In keeping with our find-ings, psychological factors have been reported to be as-sociated with functional gastrointestinal disorders. Psy-chiatric diseases are found to be diagnosed in 65.5% of patients with functional gastrointestinal disorders and conversely, 48% of psychiatric patients are found to have a functional gut disorder [21] . In addition, clinic-based studies have shown that functional dyspepsia patients re-port more life stress and psychological distress than healthy controls [1315] . Similarly, patients with IBS, who presented to tertiary referral centers, have higher prevalences of psychological distress, major depression, somatization, hypochondriasis and anxiety than healthy controls [16] . Furthermore, experimentally induced anx-iety has been shown to alter gastric sensorimotor func-tion [22] , and auditory stress to modulate visceral percep-tion in IBS patients [23] . Thus, it appears that anxiety may be linked to etiopathogenesis rather than just healthcare seeking. Pathogenetic mechanisms related to anxiety seem to contribute to the development of overlaps be-tween GERD, dyspepsia, and IBS.

In the present study, a high BMI ( 6 25) was not identi-fied as a risk factor for overlap. However, in a previous study, a higher BMI is reported to be a risk factor for IBS-GERD overlap [9] . Unlike that study, the overlap sub-group of the present study included GERD-dyspepsia and dyspepsia-IBS, and IBS-GERD overlaps. Further-more, the proportion of the Korean population with a BMI of 6 25 is substantially lower than that found in the West. These differences may have contributed to this dis-crepancy. Thus, the negative conclusions about the role of obesity may be understated by the population of study.

We conclude that overlaps between GERD, dyspepsia, and IBS are common in the general population. Further-more, our findings show that anxiety is an independent risk factor for these overlaps, but that depression is not. Our results suggest that a common pathophysiological mechanism related to anxiety is likely to be involved in patients with overlaps between these three disorders.

Acknowledgment

This study was partially supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (A010383).

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