Etiology of gastroesophageal reflux

Sammanfattning: Although gastroesophageal reflux disease is among the most common disorders at all in Western populations, the etiology is largely unknown. The objective of this thesis is to increase the knowledge of the etiology of reflux disease by studying a number of potential risk factors, using population-based methods. The first paper of the thesis estimates the prevalence of reflux symptoms, both totally and as a function of age and sex, in a public health survey of the adult population of Nord-Trondelag, Norway. Among the 58,596 persons included in this study 15,233 (26%) had experienced minor symptoms of heartburn or regurgitation while 3,154 (5.4%) had severe symptoms of heartburn or regurgitation. Among women there was a gradual increase in the prevalence of reflux symptoms with age, while among men the prevalence of reflux symptoms peaked in the 51 - 70 age groups, only to decline among the oldest men. In the second paper, which was based on a case-control study including 184 cases of esophagitis and 184 control subjects, matched to the cases with regard to age, sex and area of residence, there was a dosedependent association between increasing body-mass and endoscopically verified esophagitis among women, while no association was found among men. The association between body-mass and esophagitis among women was strengthened by the use of postmenopausal hormone replacement therapy. The third paper, a cross-sectional case-control study nested within the public health survey from NordTrondelag, including 3,113 case subjects with severe reflux symptoms and 39,872 asymptomatic control subjects (pregnant women were excluded), assessed the influence of body-mass and female sex-hormones on the risk of reflux symptoms. Dose-dependent associations between increasing body-mass and reflux symptoms were seen both among men and women, although 2-fold stronger among women. The association among women was stronger premenopausally than postmenopausally, and was significantly augmented by postmenopausal hormone replacement therapy (effect-modification), especially by estrogenonly hormone therapy. Weight loss during the ten year period between the two data collections of the health survey was associated to a significant 40% decrease in the risk of reflux symptoms. The last paper, a case-control study investigating the effect of life-style exposures on the risk of symptomatic reflux, was nested within the above-mentioned Norwegian public health survey, and included 3,153 case subjects with severe reflux symptoms and 40,210 asymptomatic control subjects. Tobacco smoking, alcohol use, tea and coffee drinking, table salt use, dietary fibers in bread and physical exercise were assessed. The study demonstrated dose-dependent positive associations between tobacco smoking as well as table salt intake and the risk of reflux symptoms. Negative associations were seen between dietary fibers in bread and reflux symptoms and between physical exercise and reflux symptoms. No associations were seen between alcohol intake and reflux or tea drinking and reflux. A negative association was observed between coffee drinking and reflux, although this finding may be explained by reversed causality.