Original ArticlesRisk factors of gastroesophageal reflux disease: methodology and first epidemiological results of the ProGERD study
Introduction
Gastroesophageal reflux disease (GERD) is a common condition with considerable medical and socioeconomic implications [1], [2]. In primary care, patients with GERD are among the most common cases [3]. It has been estimated that each year almost $2 billion are spent in the United States on over-the-counter antacids and histamine-2 receptor antagonists, and another $6 billion on prescriptions for histamine-2 receptor antagonists and proton pump inhibitors [4]. However, detailed population-based data on the frequency of GERD are still limited. In studies of selected subjects, prevalence rates of reflux symptoms ranged from 34 to 44% [5], [6], [7], [8], [9], [10]. These results were confirmed by a survey of a population-based sample in Minnesota. Among 1,511 responders, the age- and sex-adjusted prevalence rate for any episode of heartburn in the past year was 42%, and the prevalence of either heartburn or acid regurgitation in the past year was 59% [11]. As outlined in the Genval guidelines, heartburn and acid regurgitation seem to be the symptoms most frequently associated with GERD [12]. However, a variety of other symptoms are also associated with reflux, including dysphagia, dyspepsia, globus, and extraesophageal disorders. In fact, up to 50% of subjects with endoscopically diagnosed esophagitis reported symptoms other than heartburn and acid regurgitation [8], [12], [13].
GERD patients are not a homogenous group, and can characterized according to a range of reflux-associated symptoms and endoscopic findings. The whole spectrum of the disease includes subgroups of patients with nonerosive reflux disease (NERD), erosive disease (ERD), and/or Barrett's esophagus (BE). Factors such as age, obesity, alcohol consumption, and cigarette smoking seem to influence the occurrence of symptoms [8], [14]. However, very little is known about the differences in risk factors for NERD, ERD, and BE. Neither typical symptoms nor exposure of the esophageal mucosa to acid can adequately predict the occurrence and severity of esophagitis [13], [15], [16], [17]. Only long-standing GERD symptoms have been repeatedly reported to be a risk factor for BE [18], [19]. Patients who develop BE may have an increased risk of esophageal adenocarcinoma. About 10% of patients with BE at the time of their initial endoscopic examination have coexistent adenocarcinoma [20]. The incidence of esophageal adenocarcinoma has substantially increased over the past 2 decades in Western and Southern Europe, the United States, and Australia [21], [22], [23]. However, the absolute incidence and risk of esophageal adenocarcinoma is low (between 0.7 and 7.0 per 100,000 White males per year) [23], [24].
Systematic data are needed to further our understanding of the epidemiology and the natural history of GERD [25]. There have been only a few small, endoscopically defined cohorts with a follow-up period of more than 1 year [26], [27]. In our study, we have been able to investigate systematically a reflux population that includes several thousand patients with nonerosive GERD, erosive GERD, or BE. Here, we report the first epidemiologic results of this prospective cohort study of GERD. These will include information on the design of the study and on important patient-related factors, such as GERD history, symptoms, risk factors, and related health care utilization data. Our two main objectives were to investigate (1) which factors are related to the occurrence of NERD, ERD, or BE, and (2) to what extent patients with long-standing GERD differ from patients with a short-term disease, and whether some differences are based on factors that can potentially be modified for preventive purposes.
Section snippets
Study design
The Progression of GERD (ProGERD) study is a prospective, multicenter, open cohort study currently being conducted in Germany, Austria, and Switzerland, in which patients with symptoms suggestive of GERD are being followed up for 5 years after they have been healed on esomeprazole treatment. The primary objective of this ongoing study is to determine the endoscopic and symptomatic progression of GERD in endoscopically assessed GERD patients under routine care. Secondary objectives include the
Results
Sociodemographic characteristics and risk factors among the 6,215 patients at baseline are provided in Table 1 and history of GERD in Table 2, categorized according to endoscopy status. Almost all patients included in the study are Caucasian (99%). Because concurrent BE was diagnosed in 11% of the patients (4% in NERD and 18% in ERD patients and significantly more often in men than in women (13% vs. 8%, P<.001), we report these BE patients as a separate group. An adenocarcinoma of the esophagus
Discussion
Previous reports have not revealed clear differences in risk factors for NERD, ERD, and BE [13], [15], [16], [17]. In our analysis, neither the frequency or severity of symptoms were differently related to the three GERD subgroups nor other characteristic disease factors such as extraesophageal disorders and H. pylori status. Such lacking relations were previously reported for patients with BE [16]. We found, however, that the factors age, male sex, BMI, long-standing reflux disease, and
Acknowledgements
The study was supported by a grant from AstraZeneca. We wish to thank all participating investigators and patients for their cooperation and support.
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