EPIDEMIOLOGY AND NATURAL HISTORY OF GERD

The Epidemiology of GastroesophagealReflux Disease: What We Know and WhatWe Need to KnowGlenn Eisen, M.D., M.P.H.Vanderbilt University Medical Center, Nashville, Tennessee

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a common GIdisorder. A Gallup poll estimated that up to 50% of adultsin the United States describe heartburn at least once a month(1). More than one fourth of United States adults use anti-secretory medications at least three times per month (2).There is a large economic burden associated with GERD aswell. It has been estimated that almost $2 billion is spent inthe United States each year on over the counter antacids andhistamine-2 receptor antagonists, and another $6 billion isspent on prescription histamine-2 receptor antagonists andproton pump inhibitors (3). Understanding the epidemiol-ogy of GERD and its natural history would facilitate appro-priate and timely diagnosis, therapy, and allocation of healthcare resources. Despite the fact that GERD is a commonentity, the epidemiology of this disorder has not been fullyelucidated. There are several factors that make it difficult tostudy and understand the epidemiology and natural historyof GERD. Among these factors are 1) an evolving definitionof GERD; 2) lack of a diagnostic gold standard; 3) a paucityof population-based incidence, prevalence, and natural his-tory data; and 4) an unclear demarcation between physio-logical reflux and GERD as a disease.

THE EVOLVING DEFINITION OF GERD

Gastroesophageal reflux is defined by gastric and/or duode-nal contents traversing the lower esophageal sphincter (4).Typical symptoms include heartburn and acid regurgitation.Twenty years ago, the finding of a hiatal hernia on exami-nation was felt to be diagnostic (5). As the technology ofendoscopy developed and was widely used, patients withtypical symptoms and even minimal findings on endoscopicexamination (i.e., erythema) were said to have esophagitis.Currently, GERD is described as reflux of gastric contentsassociated with symptoms (esophageal or extraesophageal).There remain arguments as to when the frequency of symp-toms denotes GER the diseaseversusoccasional heartburn.The demarcation between “physiological” and abnormalacid reflux remains undefined.

LACK OF DIAGNOSTIC GOLD STANDARD

There remains no single test that can uniformly detectGERD. Typical GERD can often be diagnosed by a carefulmedical history alone (6). Some would argue that the symp-tom pattern for GERD is the most specific of any GI dis-order (7). However, individuals with supra- and extra-esophageal reflux symptoms will not be diagnosed with astandard history. There are several diagnostic tests that canbe utilized when the diagnosis is in question, includingendoscopy, barium swallow, and 24-h pH probe recording.Abnormal 24-h pH probe results are probably the closest wecan come to a criterion. However, numerous studies haveshown that other indicators of GERD may be present despitea normal pH study (8). Furthermore, differences have beenfound in quantitative acid reflux using pH probes placed sideby side (9). Upper endoscopy had previously been thoughtto be a good diagnostic test for GERD, but it is known that30–70% of patients undergoing endoscopy for GERDsymptoms may have a grossly normal examination (10).Symptoms of heartburn and acid regurgitation have beenshown to be specific but not very sensitive in determiningthe presence of GERD (11). Some authors have utilizedparallel tests (i.e., esophagogastroduodenoscopy, pH probe,validated questionnaires) to determine the presence ofGERD (12).

PAUCITY OF POPULATION-BASED INCIDENCE,PREVALENCE, AND NATURAL HISTORY DATA

There have been few efforts to determine incidence, prev-alence, and natural history of GERD. Incidence data are themost difficult to come by, because it is difficult, if notimpossible, to determine when GERD begins—again, be-cause of lack of a clear and accepted definition of GERD.This is unlike studying the epidemiology of a malignancy,such as breast cancer, where one can estimate new cases ina specified time period, because the majority seek medicalassistance when symptoms develop. We do know that manywith GERD never seek medical care for this disorder. Talleyet al. (13), utilizing survey data, estimated that the annualincidence of GERD is approximately 6%.

Prevalence of GERD is somewhat easier to estimate, but

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available data are still limited. This is highlighted by themethodological deficiencies of the often-quoted literature.Nebel et al. (14) surveyed 1004 individuals in a hospitalsetting. Their sample included volunteers, inpatients, GIclinic outpatients, and pregnant women. Overall, 11% de-scribed daily heartburn, and an additional 12% describedweekly symptoms. The survey was not validated and thesample not representative. A second study frequently quotedwas the previously mentioned Gallup poll from 1988 (1).This study found 44% self-reported having heartburn atleast once a month. This study is suspect because the meth-odology is not described and results were never published.Recently Lockeet al. (15) developed and utilized a vali-dated instrument to study GERD. This instrument was ap-plied to a stratified random sample in Olmstead County,Minnesota, with record linkage for medical service use tothe Mayo Clinic health system. The authors found that 20%of the sample described weekly heartburn and almost 60%had occasional symptoms. Thus, there are scant data eval-uating the incidence or prevalence of GERD in definedpopulations. The external validity of the prevalence studiesto date is suspect and generally can only be applied to whitesof North American or Western European extraction. Al-though incidence and prevalence data may not directly aidcurrent practitioners, health systems, employers, and thirdparty payers may be able to utilize these data for planningand resource utilization.

Evaluating the natural history of GERD is also challeng-ing. The reasons to attempt this are to 1) discern the per-centage of the population with GERD that will progress tocomplications including dysphagia, bleeding, extraesopha-geal complications, Barrett’s esophagus and esophageal ad-enocarcinoma; 2) determine if medical and/or surgical ther-apy has a modifying influence on the natural history ofGERD; 3) define, test, and study risk factors to predict andstratify patients by risk of complications; 4) determine theneed for maintenance therapy to avoid complications andpersistent symptoms; and 5) determine if causal relation-ships exist among GERD, Barrett’s esophagus, and malig-nant neoplasm of the esophagus.

Given these pressing concerns, once again the currentliterature is insufficient. There are a few small case serieswith follow-up of .1 yr. Both Isolauri et al. (16) andMcDougall et al. (17, 18) have followed their small, endo-scopically defined cohorts for several years. It appears thatmost GERD patients with esophagitis at index endoscopycontinue to require long term medical therapy.

A recent, well done, population-based case-control study(19) evaluated reflux symptoms in patients with adenocar-cinoma of the esophagus and gastric cardiaversusnormalcontrols and a second control group of esophageal squa-mous cell malignancies. The authors found that both dura-tion and frequency of GERD were strongly associated withesophageal adenocarcinoma. A second study by these au-thors (20), utilizing the same patient group, found that bodymass index was also an independent predictor of this dis-

ease. This study confirms prior data suggesting these asso-ciations (21). We also know that the incidence of esophagealadenocarcinoma has been on the rise in the past 20 yr(22–24), although the causes remain speculative. This hascreated an impetus for better study and the need to under-stand the relationship of Barrett’s esophagus and GERD.

Because it is much more difficult to assess GERD (clin-ically subjective) than neoplasm, we can only guess as towhether the incidence and prevalence of GERD has in-creased. Veteran’s Administration hospital-based datawould suggest that it has (25). These authors also speculatethat Helicobacter pylori(or the lack thereof) may be re-sponsible for increases in the prevalence of GERD and itssequelae. Although this is an attractive hypothesis, othersfactors may be contributing, such as the population’s shifttowards obesity and use of medications that affect the loweresophageal sphincter. However, one cannot necessarily ex-trapolate an increase in hospital discharges for GERD com-plications to mean an increase in GERD. This is becauseGERD is primarily managed in the outpatient setting.

The use of registry linkages, in countries like Sweden, isamong the best tools we have for studying the naturalhistory of GERD and its complications. Provided consensuscan be reached on the definition and instruments to be usedto assess GERD, these datasets provide an opportunity forpopulation-based study. Unfortunately, no such system cur-rently exists in the United States. Short of that, utilization ofexisting databases such as the VA patient treatment file,Medicare/Medicaid, and the Mayo registry may approxi-mate regional/national study. Multicenter endoscopic data-bases such as the Clinical Outcomes Research Initiative canprovide useful information but are subject to numerousbiases (26). Because most individuals with GERD do notundergo endoscopy, the majority with these symptoms re-main unstudied.

AN UNCLEAR DEMARCATION BETWEENPHYSIOLOGICAL REFLUX AND GER THE DISEASE

The definition of GER has been noted above. Given thatvirtually everyone has experienced heartburn, when doesGER become GERD? Although this demarcation is subjectto endless debate, consensus must be reached to allowmeaningful study of this entity. This problem is similar todefining asthma. Does a single wheeze qualify as a diagno-sis of asthma? In general, bronchospasm that is responsiveto provocation and therapy defines the diagnosis of asthma.Given no single diagnostic test for GERD, we must fall backon clinical criteria. Without coming to terms with a firmdefinition of GERD, it will be difficult to undertake defin-itive study of the epidemiology of this disorder.

QUESTIONS THAT REMAIN TO BE ANSWERED

There are several questions regarding the epidemiology ofGERD that remain unanswered:

S17AJG – August, Suppl., 2001 The Epidemiology of Gastroesophageal Reflux Disease

1. What is the natural history of erosive esophagitis ascompared to nonerosive reflux disease?

2. Can maintenance medical therapy decrease the risk ofcomplications over the long term (.1 yr)?

3. What is the role ofH. pylori in the natural history ofGERD?

4. What is the epidemiology of GERD in minority popula-tions?

Current natural history studies have focused only onendoscopic series. Research is needed inunselectedpopu-lations that can be followed longitudinally for at least 3–5yr. Demographic and clinical information should be col-lected prospectively. A consensus definition of GERD is aprerequisite for these studies. Ideally, a short, validatedinstrument utilizing symptom analysis can be developedfrom existing instruments. Although most research onGERD has been done by GI specialists, analysis of primarycare physician practice and patients should afford a lessskewed assessment of GERD.

SUMMARY

GERD is a common and costly disorder. Despite its prev-alence, the epidemiology and natural history of GERD areincompletely understood. Until now, most studies have beenof short duration and utilized convenience samples of pa-tients presenting for upper endoscopy. There remain severalobstacles, enumerated above, that need to be overcome tobetter study the epidemiology of GERD. Large scale, pro-spective data collection with standardized terminology andlongitudinal follow-up will allow a clearer picture of theincidence, prevalence, natural history, and complications ofGERD. This in turn should lead to timely, cost-effectivediagnosis and management of this disorder.

Reprint requests and correspondence:Glenn Eisen, M.D., As-sociate Professor of Medicine/GI, Vanderbilt University MedicalCenter, Nashville, TN 37232.

Received Oct. 6, 2000; accepted Dec. 26, 2000.

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