Risk factors of gastroesophageal reflux disease: methodology and first epidemiological results of the ProGERD study

Abstract

Objective

We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest prospective study of GERD patients.

Study Design and Setting

Patients were recruited at 1,253 centers in Germany, Austria, and Switzerland. Following an assessment of medical history, all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase.

Results

A total of 6,215 patients (53% male, age 54±14) were included. Of these patients, 46% reported at least daily symptoms, 15% were unable to work at least once during the prior year, and 71% had visited a physician due to reflux symptoms. Barrett's esophagus (BE) was found in 11% of our GERD patients. In polychotomous regression analysis, the main factors related to the occurrence of the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender, duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors associated with longer disease duration were increasing age, male gender, BMI, increasing symptom severity, presence of erosive GERD or BE, positive family history, and smoking.

Conclusion

The findings indicate that GERD is a great burden for patients, and has significant socioeconomic implications. The long-term follow-up period with further endoscopic and histologic evaluations, will help further our understanding of the natural course of the disease.

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.