Gastroesophageal reflux disease and obesity: not as simple as we may think.

There is no doubt that, over the last 20 years, westernized countries are seeing a dramatic increase in obesity [1]. This comes at the same time that we are seeing the rates of H. pylori infection in these populations decreasing from 80 % to less than 20 % [2]. Therefore, healthy stomachs with more acid and the refluxogenic contributions of obesity are together leading to an epidemic of GERD and its complications. The epidemiologic data are conclusive that obesity increases the rates of reflux symptoms, frequency and severity of esophagitis, and the frequency of Barrett’s esophagus and adenocarcinoma of the esophagus [3–6]. Recent studies are also suggesting that symptom relief from proton pump inhibitors (PPIs) is more difficult to obtain in the obese patient, with more failing ‘‘on demand’’ therapy and single dose PPIs [7, 8]. Therefore, these patients may more frequently need to be on maintenance once or twice a day PPI regimens, possibly increasing the risk of long-term complications to this class of drugs. What are the physiologic mechanisms by which obesity contributes to GERD? Recent studies suggest that central or abdominal obesity, as measured by the waist-to-hip ratio, may be more important than general obesity as measured by the body mass index (BMI). For example, a large cross-sectional study of 80,111 individuals from the Kaiser Permanente health system found a significant relationship between increased abdominal diameter and reflux symptoms independent of BMI (OR 1.85, 95 % CI 1.55–2.21). Interestingly, this correlation was much more pronounced in the white population and in male subjects [9]. In theory, central obesity should raise intragastric pressure, thereby predisposing to reflux. This was proven in a seminal study by Pandolfino et al. [10] where they studied 285 patients (81 overweight: BMI 25–30 kg/m; and 75 obese: BMI [ 30 kg/m) with high resolution manometry. They found that the pressure morphology within and across the esophagogastric junction is altered in obesity in a fashion that would promote the flow of gastric juices into the esophagus. Particularly, during the inspiratory phase of respiration, increased intragastric pressure and the gastroesophageal pressure gradient (GEPG) were strongly correlated with increased BMI. Both factors correlated even more strongly with waist circumference, suggesting that this is the mediator in the causal pathway of the BMI effect. There was a dose-dependent relationship such that the higher the BMI and waist circumference, the greater the intragastric pressure and GEPG. From an anatomic standpoint, obesity was also associated with increased axial separation between the LES and extrinsic crural diaphragm, an objective measure of the disruption of the esophagogastric junction (EGJ) culminating in the development of hiatal hernia. This confirms older studies where obesity was a significant independent risk factor for hiatal hernia, especially in whites [11]. Not to be forgotten in these mechanistic studies, a prospective study of 84 patients observed that obesity was associated with an increased frequency of transient lower esophageal sphincter relaxation and increased acid exposure [12]. Using both catheter and wireless pH systems, studies have shown that obesity increases acid reflux. In a crosssectional study of 206 patients, El-Serag et al. [13] found that BMI of [30 kg/m (compared to \25 kg/m) was associated with a significant increase in acid reflux J. E. Richter (&) Division of Digestive Diseases and Nutrition, Joy McCann Culverhouse Center for Esophageal and Swallowing Disorders, University of South Florida, Tampa, FL, USA e-mail: jrichte1@health.usf.edu