Coeliac disease : studies of its frequency and consequence

Background The development of serological tests for the diagnosis of coeliac disease, including tests for endomysial and tissue transglutaminase antibodies, has made population screening for coeliac disease a realistic possibility. Several serological screening studies from European countries have shown that as many as 1% of the general population may have undetected coeliac disease. The implications of this diagnosis are unclear since the only data on the morbidity and physiological characteristics associated with previously undetected disease come from small, selected, case series. Most adult screening studies in the general population have identified only small numbers (i.e. less than 20 cases) of previously undetected cases and have therefore been unable to examine these issues through lack of statistical power. Clinically diagnosed coeliac disease has traditionally been linked with a variety of adverse co-morbid conditions including osteoporosis, non-Hodgkin’s lymphoma and an increased mortality in general. These conditions are thought to be partly a consequence of the altered nutritional status associated with the malabsorption that occurs with villous atrophy of the small bowel in coeliac disease. Although some of the adverse effects of, for example, vitamin and calcium deficiencies in coeliac disease have previously been explored whether there may be potentially beneficial effects of mild malabsorption have not. There are two main aspects in this thesis. The first is to estimate the prevalence of undetected coeliac disease in England and explore the important physiologic correlates of this condition. The second is to examine the risk of fracture, vascular disease, malignancy and mortality in people with diagnosed coeliac disease compared to the general population. Objectives 1. To estimate the seroprevalence of undetected coeliac disease in England. 2. To explore the relationship between undetected coeliac disease and various socio-demographic characteristics and physiological measures. 3. To quantify the impact of diagnosed coeliac disease (compared to the general population) on the risk of: a. Fracture b. Vascular disease (hypertension, high cholesterol, atrial fibrillation, myocardial infarction and stroke) c. Malignancy and mortality Methods To examine objectives 1 and 2 I utilised the Cambridge General Practice Health Study. This study identified individuals aged 45-76 registered with 12 general practices and invited them to complete a health survey, have a bone density measurement and submit a blood sample between 1990 and 1995. Serum samples from 7550 participants were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was defined by EMA positivity. Differences between EMA positive and negative participants of various physiological measures and reported characteristics were estimated using multivariate logistic and linear regression and adjusted for age, gender, social class and smoking behaviour. To examine objective 3 I performed a population based cohort study using the General Practice Research Database to quantify the risk of fracture, vascular disease, malignancy and mortality in people with coeliac disease compared to the general population. I identified 4732 people with coeliac disease and 23620 age and sex matched control subjects. I used Cox regression to estimate hazard ratios for fracture, myocardial infarction, stroke, malignancy and mortality, and conditional logistic regression to estimate the risk of diagnosed hypertension, hypercholesterolaemia and atrial fibrillation, in people with coeliac disease compared to the general population. Findings The studies show that undetected coeliac disease is likely to affect about 1% of the population of England aged 45-76, a figure similar to several other countries. Those affected more commonly reported “good or excellent health”, however they do have an increased risk of osteoporosis and mild anaemia. In contrast they have a favourable cardiovascular risk profile including lower serum cholesterol and blood pressure. In people with clinically diagnosed coeliac disease, compared to the general population, there were small increases in both the absolute and relative overall fracture incidence with a 2-fold increase in the risk of hip fracture. Adults with treated coeliac disease did have a favourable vascular disease risk factor profile but numbers having heart attacks or strokes were modest and rates of heart attack and stroke were not reduced. There were modest increases in the overall risks of malignancy and mortality in people with coeliac disease and most of this excess risk occurred in the first year of follow up after diagnosis, suggesting ascertainment bias. I found a marked reduction in the risk of breast and lung cancer in people with coeliac disease and the mechanism of this merits further attention as it may provide insight into the aetiology of these common malignancies. Conclusions I found that approximately 1% of general adult population of the UK has undetected coeliac disease. The findings suggest that although coeliac disease is associated with some adverse conditions; it may also have some beneficial health effects. Please note: This version does not include the copies of journal articles which were included in the original thesis, but just details of the articles.