Original Article

The American Journal of Gastroenterology (2005) 100, 1243–1250; doi:10.1111/j.1572-0241.2005.41703.x

Obesity Is an Independent Risk Factor for GERD Symptoms and Erosive Esophagitis

Hashem B El-Serag MD, MPH1, David Y Graham MD1, Jessie A Satia PhD, MPH1 and Linda Rabeneck MD, MPH1

1Sections of Gastroenterology and Health Services Research at the Houston Department of Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas; Department of Nutrition, University of North Carolina at Chapel Hill, North Carolina; Department of Medicine, University of Toronto, Canada

Correspondence: Hashem B El-Serag, MD, MPH, , The Houston Veterans Affairs Medical Center (152), 2002 Holcombe Blvd., Houston, TX 77030

Received 21 October 2004; Revised  0000; Accepted 22 December 2004.

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Abstract

INTRODUCTION:

 

An association between obesity and GERD symptoms has been reported; however, study results have been inconsistent and it is not known whether an association persists after adjusting for other known GERD risk factors.

METHODS:

 

We carried out a cross-sectional study to determine the prevalence and risk factors of GERD in volunteers (VA employees). Participants completed a Gastroesophageal Reflux Questionnaire, the Block 98 Food Frequency Questionnaire, provided height and weight information, and were invited for upper endoscopy with biopsies. Associations of body mass index (BMI) with GERD symptoms and erosive esophagitis were examined separately in multiple logistic regression analyses adjusting for age, sex, race, GERD symptoms, dietary intake, education level, family history of GERD, H. pylori infection, and the presence and distribution of gastritis.

RESULTS:

 

Four hundred and fifty-three persons (mean age 44 yr, 70% women and 43% black) provided complete information on heartburn, regurgitation, and BMI (50% of 915 who received questionnaires). Of the 196 who underwent endoscopy, 44 (22%) had esophageal erosions and 118 (26%) reported at least weekly heartburn or regurgitation. A dose–response relationship between frequency of heartburn or regurgitation and higher BMI was observed. Compared to participants without weekly symptoms, a significantly larger proportion of the 118 with these symptoms were either overweight (BMI 25–30) (35%vs 32%) or obese (BMI >30) (39%vs 26%), p for linear trend 0.004. Relative to those with no esophageal erosions, those with erosions were more likely to be overweight (39%vs 26%) or obese (41%vs 32%), p= 0.04. Obese participants were 2.5 times as likely as those with normal BMI (<25) to have reflux symptoms or esophageal erosions. The association between BMI and GERD symptoms persisted in direction and magnitude after adjustment for potential confounders.

CONCLUSIONS:

 

Overweight and obesity are strong independent risk factor of GERD symptoms and esophageal erosions. The amount or composition of dietary intake does not appear to be a likely explanation for these findings.

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INTRODUCTION

The prevalence of obesity in the United States has reached epidemic proportions. Recent results of the Third National Health and Nutrition Examination Survey (NHANES III) in 1999 indicate that an estimated 61% of U.S. adults are either overweight (defined as a body mass index (BMI) between 25 and 30) or obese (BMI > 30.0) (1). The prevalence of obesity has nearly doubled from approximately 15% in 1980 to an estimated 27% in 1999 (2).

Gastroesophageal reflux disease (GERD) is a common disorder that has been linked to obesity. Some but not all studies have shown that high BMI is associated with an elevated risk of GERD symptoms (e.g., heartburn and/or regurgitation). At least four previous population-based cross-sectional studies found positive associations between overweight or obesity and GERD symptoms in the United States, UK, Norwegian, and Spanish populations (4,5,7,8,9,10), and two studies showed a "dose–response" relationship (4,5). In contrast, two other large population-based studies from Sweden and Denmark found no such association (3,6). Several studies have examined associations between obesity and GERD-related esophageal erosions: three reported a modest positive association (11,12,13), one found no association (14), and one study found a positive association in women but not in men (15). However, differences in the age, sex, and race composition of the study populations could explain some of the variations in the findings. For example, the only study conducted in the United States included predominantly Caucasians (4) and the Swedish study that found no association consisted of mostly men (3).

Another potential explanation for the disparate results is the lack of or inconsistent adjustment for confounding risk factors. For example, it has been argued that consumption of foods high in fat, rather than being overweight, is a risk factor for GERD (16), and most of the previous studies did not adjust for the possible confounding effect of diet when examining the association between obesity and GERD symptoms. Finally, and probably most importantly, many of the previous studies of BMI and erosive esophagitis were only conducted among patients referred for endoscopy and therefore are subject to selection bias.

Given the importance of potential implications of an obesity–GERD link, we examined the prevalence and determinants of GERD symptoms and endoscopic findings in a large multi-ethnic sample of volunteers. In this report, we present a detailed examination of the potential role of overweight and obesity on the frequency and severity of GERD symptoms and esophageal erosions in this study sample.

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METHODS

Study Design

A cross-sectional survey was followed by endoscopy.

Study Population

Participants were recruited from a sample of 1,000 employees at the Houston VA Medical Center (VAMC). The Houston VAMC, with 3,095 employees, is one of the largest employers in the Houston area. Of the total number of employees, 1,424 (46%) were African Americans of whom 954 (67%) were women and 1,114 (36%) were Caucasians of whom 635 (57%) were women. The mean age was 45 yr (range 18–70). Every employee belonged to one of 19 hospital services each headed by a Chief of Service, an arrangement that facilitated organized and comprehensive distribution of the study questionnaires. Our sampling frame comprised employees who belonged to 12 selected services within the hospital; these services were specifically chosen to represent the ethnic and professional spectrum of employees. These services include nurses, physicians, administrators, researchers, and building maintenance workers. The 1,000 employees targeted in the study were randomly chosen from the lists of employees in these 12 services. The study was approved by the Institutional Review Board (IRB) for Human Subject Research at Baylor College of Medicine.

Questionnaire

The Gastroesophageal Reflux Questionnaire (GERQ) is a self-administered validated instrument that identifies the onset for GERD symptoms and grades the frequency and severity of symptoms experienced over a prior 1 yr (17). Additional information from the GERQ includes height, weight, tobacco smoking, and family history of GERD. Supplemental questions include the intake of aspirin or non-steroidal antiinflammatory drugs (NSAID), histamine-2-receptor antagonist (H2RA), proton pump inhibitor (PPI), and over-the-counter (OTC) GERD therapy.

Dietary intake was assessed using the 100-item Block food frequency questionnaire (FFQ) (Block 98). The Block FFQ is a self-administered instrument that takes 30–40 min to complete and has been extensively used and validated in several population groups (18,19,20). The participants were asked to estimate their usual frequency of consumption of various foods and typical portion sizes over the previous year. Each food item had nine options for frequency (ranging from "never or less than once per month" to "2+ times per day") and three options for portion size. Nutrient intake was calculated by an analysis program at the National Cancer Institute that incorporates the nutrient content of each food item, the consumption frequency, and a portion size based on age, and employs several checks for completeness and internal validity (12). For these analyses, we examined intakes of total energy, dietary fat, and dietary fiber; the latter two variables were found to be significantly different between participants with and without GERD in previous bivariate analyses (21). FFQ that reported energy intakes <800 kcal and >5000 kcal for men (n = 10) and <600 kcal and >4000 kcal for women (n = 22) were excluded from the analyses because their FFQs were considered to be unreliable (18).

Endoscopy

Upper endoscopy was offered to all participants who responded to the survey. Standardized non-sedated endoscopic examination of the esophagus, stomach, and duodenum was performed by one endoscopist [HE-S] who was blinded to the results of the questionnaire. The severity of erosive esophagitis seen on endoscopy was graded from A to D according to the LA classification (22). Gastric mucosal biopsies were taken (2 from the antrum, 2 from the corpus, and 1 from the incisura angularis) (23).

Histopathology

Sections from the gastric biopsies were stained with the Genta stain, a specialized triple stain (Silver, H&E, Alcian blue) (24). The presence, type, severity, and extent of gastritis and gastric atrophy was identified and graded according to the Updated Sydney System (1996) (25). Biopsies were examined and graded by a single gastrointestinal pathologist who was blinded to the results of questionnaires and endoscopy.

Statistical Analyses

Among the participants with complete responses to questions about GERD symptoms, weight, and height, we calculated the proportion of persons reporting at least weekly heartburn and/or regurgitation. We also calculated the proportion of persons with erosive esophagitis among participants who underwent upper endoscopy. BMI (kg/m2) was calculated as a ratio between weight (kg) and the square of height (m2) and further categorized as follows based on recommended cutoffs: normal (<25), overweight (25,26,27,28,29,30), and obese (>30).

Multiple forward stepwise logistic regression analyses were used to examine associations of the two primary outcomes (weekly heartburn or acid regurgitation, erosive esophagitis) with the main predictor variable, BMI. Models examining weekly heartburn or regurgitation were adjusted for age, sex, race, education, family history of GERD, and tobacco smoking. Among participants who also completed the Block FFQ (82% of the sample), we also controlled for dietary intake of total fat and saturated fat; these two variables were significant in a previous bivariate analysis (21). In this group, we also conducted a stepwise regression in which total energy intake and other dietary variables were added to the models as continuous variables. For models that examined any grade erosive esophagitis, we also controlled for hiatus hernia, H. pylori infection, the presence of corpus gastritis, and the use of aspirin/NSAID, H2-receptor antagonists, or proton pump inhibitors. For all models, the number of covariates examined was determined by the number of outcome events with 10 events required for one covariate (26). p values <0.05 were considered statistically significant.

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RESULTS

Of 1,000 targeted individuals, 915 were verified to have received the study questionnaires (either by hand delivery or to a designated labeled mailbox), 512 (54% response rate) returned the questionnaires, 496 had complete and interpretable answers to both heartburn and regurgitation questions, and 453 had answered questions on weight and height. Among these 453 respondents, 196 (43%) were Black, 149 (33%) White, and the remaining 108 (24%) were of other race (36.1% Hispanic, 48.2% Asian, and 15.7% other). The mean age of participants was 44 yr (SD 10), and 68% were women. There were no significant differences in age or race between participants and noniparticipants; however, there were significantly more women among participants. Upper endoscopy with gastric biopsies was performed on 196 (43% of) participants, 50% Black and 63% female. In a multiple logistic regression model, only the presence of weekly heartburn or regurgitation was found to be an independent predictor of upper endoscopy (adjusted OR: 2.1, 95% CI: 1.2–3.5, p= 0.007). Importantly, there were no significant differences in age, sex, BMI, tobacco smoking, or physician visits for GERD between the two groups. A large subset (371 or 82%) of the 453 participants had complete and interpretable dietary questionnaires.

Table 1 gives a comparison of participants with and without GERD symptoms (weekly heartburn or regurgitation) by various participant characteristics. Twenty-six percent of participants reported weekly heartburn or regurgitation, with no significant differences by age, sex, or race. There was a clear dose–response relationship between weekly heartburn and BMI: participants with at least weekly heartburn or regurgitation were more likely to be overweight (35%vs 32%) or obese (39 vs 26%) than individuals without these symptoms (p <0.0001). Furthermore, there was a significant linear increase in the proportions of increasing categories of BMI; these proportions were 23.3%, 26.7%, 50.0%, for BMI < 25, 25–30, and >30, respectively (data not shown). Respondents with a positive family history of GERD were significantly more likely to have weekly symptoms (37.5%) than those who did not have GERD symptoms (26.0%). Not unexpectedly, participants with frequent heartburn or regurgitation were more likely to report using H2RA or PPI.


Distributions of GERD symptoms and potential GERD risk factors by BMI are given in Table 2. Obese participants (BMI >30) were more likely to be older, female, Black, and have less than a college education. As in earlier analyses, more overweight and obese participants reported weekly GERD symptoms (weekly and severe heartburn or regurgitation, p < 0.05). Similarly, there was a significant increase in erosive esophagitis (12.5%, 29.8%, and 26.9%) with higher BMI (<25, 25–30, and >30, respectively), p= 0.01. There were no significant BMI-related differences in family history of GERD, H. pylori infection, or hiatus hernia (Table 2).


Results from multiple logistic regression analysis examining associations of obesity with GERD symptoms are given in Table 3. Overweight and obesity remained independent risk factors for weekly heartburn or regurgitation after adjustment for age, sex, race, education level, family history of GERD, and smoking. Overweight and obesity were associated with an almost doubling in risk for weekly heartburn or regurgitation (OR = 1.80 and 2.17, respectively). There were no significant interactions between BMI and any of the potential confounding variables, including sex, examined in the model.


Table 4 gives associations of obesity with esophageal erosions unadjusted and after control for various potential confounders. Esophageal erosions were detected in 22% (44 of 196) of participants who underwent endoscopy, with a higher prevalence in Caucasians than African Americans, p= 0.01. Participants with erosive esophagitis were more likely to be overweight (38.6%vs 26.3%) or obese (40.6 vs 32.2%) than individuals without these symptoms, p<0.001. Hiatus hernia of any size (including 3 cm or greater) was more frequent in the erosive esophagitis group compared to those without (25.0%vs 13.2%, p<0.01). Erosive esophagitis was not significantly associated with tobacco smoking, aspirin or NSAID use, H. pylori infection, or corpus gastritis (data not shown).


In multiple logistic regression models controlled for multiple covariates including age and sex, overweight and obesity were associated with a 2.59 to 4.19-fold increased risk of erosive esophagitis compared to normal-BMI participants. Because Blacks had a higher mean BMI as well as a lower prevalence of erosive esophagitis than Caucasians, adjustment for race resulted in a stronger association between BMI and erosive esophagitis (OR = 4.4, 95% CI: 1.7–10.0, p= 0.0017). Adjustment for other potential confounders (one or two variables at a time), e.g., hiatus hernia, aspirin and NSAID use, H pylori, dietary fat, and total energy did not appreciably change the observed associations. However, a dose–response relationship between BMI and erosive esophagitis was not evident, probably due to the small sample size.

In 371 participants (82%), there was complete and interpretable information on dietary intake in addition to GERD symptoms, and BMI. In these participants, BMI 25–30 and BMI >30 were associated with a greater risk of weekly GERD symptoms than those with BMI <25. The unadjusted odds ratios were 1.87 (95% CI: 1.05–3.34; p= 0.03) and 2.67 (95% CI: 1.50–4.74; p= 0.0008), respectively. We constructed a model that controlled for the effects of total energy intake, and each of total fat, and total saturated fat (in two separate models) as these two variables were significantly associated with weekly GERD symptoms in bivariate analyses. The adjusted odds ratios for BMI >25 were 2.17 (95% CI: 1.30–3.62; p= 0.004) when controlling for total fat, 2.10 (1.23–3.44; p= 0.006) for saturated fat. Adjusting for age, gender, race, total caloric intake, and each of fat and saturated fat intake resulted in statistically significant odds ratios for weekly heartburn or regurgitation with BMI >30 are shown in Table 3. The addition of these variables did not significantly affect the fitting of the model.

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DISCUSSION

We found a strong positive association between obesity and frequent GERD symptoms (twofold increase), and between obesity and esophageal erosions (two- to fourfold increase). These associations remained robust even after adjustments for several important potential confounding factors including age, race, and dietary intake. Further, there was a significant dose–response relationship between BMI and GERD symptoms. Taken together, these findings strongly indicate that overweight and obesity are significant risk factors for GERD.

The mechanism by which obesity increases the risk of GERD is unknown. Obesity may affect risk of GERD through dietary intake, mechanical factors, and/or humoral factors. Understanding these mechanisms is important for potential screening and preventive measures for GERD and its potential complications. Below we will discuss some of these mechanisms as they relate to this report.

It has been suggested that dietary fat intake, rather than obesity, is associated with increased risk of GERD. An important observation in this study is that the positive association between obesity and GERD symptoms remained largely unchanged after adjustment for various dietary factors. These results support and extend previous findings by Ruhl et al. who reported in a prospective U.S. population-based cohort study with a 20-yr follow-up, participants in the highest BMI quartile had nearly twice the rate of hospitalization with erosive esophagitis as those in the lowest quartile (13). Furthermore, fat intake was neither a significant risk factor for esophagitis nor did it affect the BMI-related increased risk of esophagitis. In summary, it is unlikely that dietary intake is a central explanation for the effect of obesity on GERD.

One potential mechanism by which obesity may increase risk of GERD is related to mechanical factors whereby abdominal obesity leads to an increase in intragastric pressure, increased frequency of transient lower esophageal sphincter relaxation, and/or the formation of hiatus hernia. Hiatus hernia was more frequent among participants with erosive esophagitis and those who were overweight and obese. Further, the inclusion of hiatus hernia in the model examining the effect of BMI on esophageal erosions reduced the calculated association between BMI and erosions. Although it is tempting to invoke hiatus hernia as a mechanism by which obesity leads to GERD, the cross-sectional nature of the study precludes conclusions about the temporal sequence of events.

Obese individuals in our study tended to be older, female, and Black. Old age has been shown to be associated with increased risk of erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma (27). Therefore higher prevalence of obesity in older age supports its putative role as a risk factor for GERD. However, women and persons of Black race are thought of as groups at a lower risk of complicated GERD (28,29). While this may argue against obesity as a risk factor for GERD, several explanations are possible. The pattern of obesity may be more important than BMI; for example, it is thought that abdominal obesity is a risk factor for GERD. It is known that for the same BMI, the distribution of body fat tends to be more visceral than truncal in high-risk groups for BE: Caucasians (compared with African Americans), and men (compared with women) (30). Other reasons such as high prevalence of H. pylori infection in Blacks (31), and lower parietal cell mass in women (32,33) are potential reasons for the lower risk of GERD in these groups. These, and other mechanisms such as humoral factors, such as insulin, leptin, or growth factors, or hormonal factors such as estrogen, by which obesity may affect risk for GERD were not examined in this study. Future studies should explore these mechanisms.

Given the rising incidence of esophageal adenocarcinoma (29), the importance of the role of obesity in GERD extends beyond symptoms and endoscopic findings. Several case-control studies have reported positive associations between high BMI and elevated risk of esophageal adenocarcinoma (34,35). For example, a recent Swedish population-based case-control study found strong dose-dependent relation between obesity and esophageal adenocarcinoma (36). The role of obesity in the current and future trends of esophageal adenocarcinoma is worthy of future investigation.

These findings support and extend previous studies that indicated a positive association between obesity and GERD symptoms (4,5,7,8,9,10,11,12,13). Strengths of this research include our large, ethnically diverse sample of the general population, the use of single endoscopist who was blinded to the results of the questionnaire and a single pathologist blinded to the results of endoscopy, and control for several potential confounding factors, most notably dietary intake. An added advantage of this study is that the associations of BMI and GERD symptoms and esophageal erosions were evaluated in the same population.

There are a number of limitations that should be acknowledged. The moderate response rate to the questionnaire may have resulted in a selection bias since persons with GERD symptoms may have been more likely to participate in the study. However, this bias is unlikely to affect the primary focus and point of this report, i.e., BMI-related differences in GERD. As in other studies, participants may differ from non-participants with regard to factors that may be associated with exposure or outcomes of interest; specifically, selection bias may have affected the endoscopy phase of the study thus leading to the relatively high prevalence of erosive esophagitis (22%) in the study sample. However, given the lack of differences in BMI among those with or without endoscopy, we believe it is unlikely that the observed BMI-related differences in endoscopic findings were a result of bias related to undergoing endoscopy. Finally, the proportion with morbid obesity was very small and that prohibited the examination of a full range of BMI. Several studies however reported the preoperative prevalence of symptoms and endoscopic findings among samples of morbidly obese patients undergoing bariatric surgery (37,38,39,40,41,42,43). Collectively, these studies suggest an increased prevalence of GERD symptoms (32–57%), erosive esophagitis (24–31%), and hiatus hernia (up to 90%) although the retrospective design, lack of appropriate controls, and small sample size make the interpretation of some of these studies difficult.

In summary, this study indicates that a higher body mass index increases the risk of GERD symptoms as well as erosive esophagitis. This effect is independent of demographic features or dietary intake. Further studies should examine the possible mechanisms by which obesity increases the risk of GERD.

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Acknowledgements

Dr. El-Serag is a VA HSR&D Awardee (RCD 00-013-2). This study has been partly funded by grants from the American Society for Gastrointestinal Endoscopy (ASGE) and Janssen-Eisai Pharmaceuticals to H. El-Serag.

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