Abstract
Abstract
Gastroesophageal reflux disease (GERD) and obesity coexist in many patients in the Western population. The association is not coincidental, since GERD pathophysiology is, in part, linked to obesity. Visceral adipose tissue secretes hormones, which increase the risk of GERD. Obesity increases esophageal motor disorders and higher number of transient lower esophageal sphincter relaxations. Central obesity increases abdominal–thoracic pressure gradient and disrupts the gastroesophageal junction by inducing hiatal hernia formation. Obese patients benefit from weight loss by diet to decrease GERD symptoms; however, Roux-en-Y gastric bypass surgery is associated with a higher weight loss and a decrease in GERD symptoms, and is considered the best way to treat both diseases at the same time.
Introduction
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GERD is undoubtedly a disease directly related to obesity. Overweight doubles the chance of GERD, and the prevalence of GERD symptoms in patients with morbid obesity reaches 50%. 3 Moreover, the prevalence of GERD is proportional to the severity of obesity: 23% in individuals with body mass index (BMI) <25 kg/m2, 27% when BMI is between 25 and 30 kg/m2, and 50% if BMI is >30 kg/m2. Women who increase BMI by 3.5 points have twice the incidence of GERD than those who remained with BMI within normal range. 4
It is not only the frequency of GERD symptoms in the obese population that is of concern, but also the severity of the disease, which is more severe in this population, with a higher incidence of erosive esophagitis and Barrett's esophagus (BE). A direct correlation between erosive esophagitis degree and BMI has been reported by different studies as summarized by a recent meta-analysis. 5 The association of BE and obesity was well demonstrated by Stein et al. 6 who showed that for every 5 U of increase in BMI, the incidence of BE increases 35%. For this risk, 7 visceral obesity seems to be more important than peripheral obesity. Obesity also increases the chance of esophageal and cardia cancer. 8 The chance of developing esophageal carcinoma is four times higher in overweight patients than in individuals with normal BMI. 9
It is necessary to understand the pathophysiology of GERD in obese individuals to adequately treat this now common association between GERD and overweight.
Pathophysiology
Defective gastroesophageal barrier
A defective lower esophageal sphincter (LES) is not always observed in the obese. Some studies did not show a difference in basal pressure when lean and obese individuals with GERD were compared. 10 Moreover, other studies showed an increased basal pressure probably linked to compensatory mechanisms due to the increased intra-abdominal pressure.11,12 Transient LES relaxation (TLESR), however, seems to be more frequent in the obese and this might explain GERD in the setting of a normal LES basal pressure. The number of episodes of TLESR is higher in the obese13,14 and there is a correlation between the number of episodes of TLESR with BMI and abdominal circumference.15,16
The angle of His is an important antireflux mechanism. The more acute the angle of His is, the more the gastric fundus will be projected toward the esophagus when gastric distension occurs such as during a meal. The deposition of fat in the gastroesophageal junction, common and excessive in obese individuals, can make this angle obtuse. 17
Hiatal hernia (HH) is more frequent in the obese. 18 Obese women are two and a half times more likely to have HH than nonobese women. 19 In fact, Pandolfino et al. 20 using high-resolution manometry showed in a seminal work progressive disruption of the esophagogastric junction anatomy with obesity.
Defective esophageal clearance
Esophageal clearance is determined by salivation, gravity, and esophageal motility. Obese patients have decreased salivation 21 and esophageal motility may be impaired in a quarter of obese individuals.18,22 Data are conflicting when evaluating the gastric emptying time in obese population, which may be normal or delayed.23–25
Altered transdiaphragmatic pressure gradient
Abdominal pressure is increased in obese individuals due to deposition of abdominal fat and its mechanical effect on gastric pressure. For each point of increase in BMI, there is a 10% increase in intragastric pressure. 26
Obese patients may also have increased intrathoracic pressure due to diaphragm elevation due to abdominal fat and consequent decrease in pulmonary expansion. Intrathoracic pressure may also be increased by the frequent occurrence of obstructive apnea in these patients. Apnea itself may be a cause for GERD due to increase of TLESR. 27
Altered hormonal profile
Abdominal fat accumulation decreases adiponectin (anti-inflammatory cytokine) and causes an increase in inflammatory agents such as leptin. These altered cytokines may contribute to the higher incidence of erosive esophagitis and BE in the obese population than in nonobese individuals. 28 Increased secretion of estrogen by adipose tissue contributes to the increase of reflux symptoms in obese women. Women of reproductive age and those who are in menopause but receiving estrogen therapy have a higher incidence of GERD than menopausal women without hormone replacement. 3
Diet
Consumption of high-fat diet (more common in obese individuals) increases the occurrence of GERD symptoms compared with consumption of a high-fiber diet, regardless of caloric intake, due to decrease in gastric emptying, decrease in LES pressure, and increase in the number of episodes of TLESR as a result of the action of cholecystokinin. 29
Some foods such as eggs, chocolate, soft drinks, and fat can induce GER and these foods are consumed more frequently by obese individual
Visceral sensitivity
There are several putative factors for an increased visceral sensitivity in the obese. First, overweight leads to a permanent inflammatory state, releasing inflammatory molecules that decrease the perception threshold to refluxate stimuli. 30 Chronic stress to which the obese are subjected, by physical limitation or psychological aggression, favors the occurrence of GERD symptoms by increasing visceral sensitivity. 31 Sleep deprivation, which occurs more frequently in the obese population due to sleep apnea, also induces to chronic state of stress.32,33
Treatment of GERD in Obese Subjects
Clinical treatment
Treatment of obese patients with GERD may be aimed toward GERD, obesity, or both.
Weight loss may alleviate symptoms due to a decrease in intra-abdominal pressure, and perhaps change in hormonal status. It has been shown that a decrease of 3.5 kg/m2 in BMI reduces the risk of GER symptoms by 40%. 8 Other studies are very clear in demonstrating the decrease in acid exposure of the esophagus using pH monitoring after weight loss.34,35 Weight loss has a positive impact on GERD symptoms by reducing intra-abdominal pressure.36–38 Loss of 14 kg reduces the incidence of GERD from 37% to 15%, and 75% of the population evaluated showed improvement in DeMeester index in a study. 39
It is not clear whether obese people respond differently from lean people regarding the use of protein pump inhibitors. 40 There is no evidence that obese subjects should be treated differently, such as with increased dosage from lean individuals with GERD. 41
Surgical treatment
Antireflux surgery in the obese is highly controversial. 26 GERD pathophysiology is, in fact, different in the obese as compared with that in lean individuals. A fundoplication acts at the level of the gastroesophageal barrier only, which is not the only factor causing GERD in the obese. Furthermore, a fundoplication may be technically more demanding in the overweight and the raised intra-abdominal pressure is a challenge to the long-term integrity of the fundoplication and the hiatoplasty. The procedure is, however, feasible in the obese. A meta-analysis 42 analyzing 3772 obese patients who underwent a fundoplication did not find significant difference in the conversion rate, reoperation due to recurrence, and migration of the fundoplication among the obese group compared with procedures performed in lean patients. There was a significant difference, however, in the operative and hospitalization time, which was higher in the obese group. The authors concluded that antireflux surgery in obese patients is safe and the results are comparable with those of patients with normal BMI.
Bariatric operations, in contrast, decrease weight. The Roux-en-Y gastric bypass seems to be the ideal bariatric procedure in patients with GERD. 43 Regardless of the weight loss, the Roux-en-Y controls any type of refluxate: acid, because of the few parietal cells in the small gastric pouch, and bilious, because of the Roux loop configuration. A sleeve gastrectomy should be avoided, as it is definitively a refluxogenic procedure despite some controversial results suggesting GERD control. 44
Conclusions
The pathophysiology of GERD is different in lean and obese individuals. Visceral adipose tissue secretes hormones, which increase the risk of GERD. Obesity increases esophageal motor disorders and the number of episodes of TLESR. Central obesity increases thoracic abdominal pressure gradient, disrupts the gastroesophageal junction, and induces HH formation.
Obese patients benefit by weight loss secondary to diet; however, the Roux-en-Y gastric bypass is associated with a higher weight loss and with a decrease in GERD symptoms.
Footnotes
Disclosure Statement
No competing financial interests exist.