Stephanie Fitzgerald

Obesity increases oesophageal acid exposure

Background: Obesity has been associated with gastro-oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear. Aim: To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures. Methods: A cross-sectional study of consecutive patients undergoing 24 h pH-metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses. Results: 206 patients (63% women) with a mean age of 51.4 years who were not on acid-suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m2 (compared with BMI<25 kg/m2) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m2 and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure. Conclusions: Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure.

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study

Objective Abdominal obesity has been associated with increased risk of Barretts oesophagus (BE) but the underlying mechanism is unclear. We examined the association between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the risk of BE. Design A case-control study among eligible patients scheduled for elective oesophagastroduodenoscopy (EGD) and in a sample of patients eligible for screening colonoscopy recruited at the primary care clinic. All cases with definitive BE and a random sample of controls without BE were invited to undergo standardised mid-abdomen non-contrast computerised axial tomography images, which were analysed by semiautomated image segmentation software. The effect of VAT and SAT surface areas and their ratio (VAT to SAT) on BE were analysed in logistic regression models. Results A total of 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls underwent study EGD and CT scan. Participants with BE were more than twice as likely to be in the highest tertile of VAT to SAT ratio (OR: 2.42 (1.51 to 3.88) and adjusted OR 1.47 (0.88 to 2.45)) than colonoscopy controls, especially for those long (≥3 cm) segment BE (3.42 (1.67 to 7.01) and adjusted OR 1.93 (0.92 to 4.09)) and for white men (adjusted OR 2.12 (1.15 to 3.90)). Adjustment for gastroesophageal reflux disease (GERD) symptoms and proton pump inhibitors (PPI) use attenuated this association, but there was a significant increase in BE risk even in the absence of GERD or PPI use. Conclusions Large amount of visceral abdominal fat relative to subcutaneous fat is associated with a significant increase in the risk of BE. GERD may mediate some but not all of this association.

Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress

Background  The burden of functional GI disorders and their associations with psychological distress in women veterans is unclear.

Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated With an Increased Risk of Barrett's Esophagus in White Men

BACKGROUND & AIMS Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barretts esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia.

Circulating Inflammatory Cytokines and Adipokines Are Associated With Increased Risk of Barrett's Esophagus: A Case–Control Study

BACKGROUND & AIMS Obesity is associated with Barretts esophagus (BE) and with changes in circulating levels of adipokines (leptin and adiponectin) and cytokines. Although studies have reported that adipokines and inflammatory cytokines are necessary for the development of BE, their role is controversial. METHODS We performed a case-control study; cases (n = 141) were patients who underwent esophagogastroduodenoscopy and were found to have BE, which was based on endoscopy and histology, and controls (n = 139) were primary care patients eligible for screening colonoscopies who agreed to undergo esophagogastroduodenoscopy. We examined the association between BE and circulating levels of adipokines and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and IL-12p70; tumor necrosis factor-α; and interferon-γ). Cases and controls were compared by calculating odds ratios (ORs) and 95% confidence intervals (CIs) and using unadjusted and multiple logistic regression, adjusting for age, sex, race, waist-hip ratio, use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. RESULTS The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and 8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of levels of IL-12p70, IL-8, and leptin, respectively, but the OR was not significant for IL-6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14 for highest quintile of IL-10 compared with lowest quintile (95% CI, 0.05-0.35) and 0.03 for IL-1β ≥ median vs none detected (95% CI, 0.006-0.13). Higher levels of IL-8 and leptin and lower levels of IL-10 and IL-1β were associated with the presence of long-segment (≥3 cm) and short-segment BE. There were no differences between cases and controls in levels of interferon-γ, tumor necrosis factor-α, adiponectin, or insulin. CONCLUSIONS BE is associated with circulating inflammatory cytokines and leptin and low levels of anti-inflammatory cytokines. These findings could partly explain the effect of obesity on BE.

Helicobacter pylori-negative gastritis: prevalence and risk factors.

OBJECTIVES:Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis.METHODS:Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire.RESULTS:Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06).CONCLUSIONS:We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

OBJECTIVES:The estimated association between Helicobacter pylori and Barretts esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.METHODS:We conducted a case–control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.RESULTS:We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35–0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).CONCLUSIONS:The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

The extent and determinants of prescribing and adherence with acid-reducing medications: a national claims database study.

OBJECTIVES:No community-based, large-scale studies have examined the extent of prescribing acid-reducing medications or adherence and persistence to these medication regimens.METHODS:We conducted a retrospective cohort study of patients with Barretts esophagus (BE) and gastroesophageal reflux disease (GERD) without BE, diagnosed between 2000 and 2005, who had undergone an upper endoscopy within 1 year through a managed care plan in the United States. We identified filled prescriptions for oral proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) within 365 days after the index date of BE or GERD, and several measures of adherence (medication-ownership ratio (MOR)) and persistence (length of therapy, fill–refill ratio, discontinuation rate) for PPI treatment.RESULTS:We identified 10,159 patients with BE and 48,965 GERD patients with no BE. The mean duration of filled PPI prescriptions accounted for only 30.2% of the available year after the index date, whereas that of either PPI or H2RA prescriptions accounted for only 31.7%. PPI prescriptions were filled by 66.6 and 60.4% of patients with and without BE, respectively. These proportions declined significantly between 2000 and 2005. For those with at least one prescription, the median duration of therapy was 241 days for PPIs and 159 for H2RAs. Both groups had low MOR and length of treatment and high discontinuation rates; however, adherence and persistence were significantly higher in BE than in non-BE patients, and significantly lower in 2005 than in 2000.CONCLUSIONS:The use of prescription PPIs or H2RAs, as well as adherence and persistence with these medications, is lower than expected. The absence of BE and more recent diagnosis are associated with even lower prescription rates.