Steffen J. Rosenstock

Serum ferritin, hemoglobin, and Helicobacter pylori infection: A seroepidemiologic survey comprising 2794 Danish adults

BACKGROUND & AIMS Helicobacter pylori infection was recently associated with iron-deficiency anemia. The aim of this study was to examine the relationship between H. pylori infection, hemoglobin, and iron status using serum ferritin as a marker for total body iron. METHODS Serum ferritin, hemoglobin, and immunoglobulin G (IgG) antibodies against H. pylori were assessed in 2794 Danish adults who attended a population survey. IgG antibodies were measured with an in-house enzyme-linked immunosorbent assay, serum ferritin with an immunoradiometric assay, and hemoglobin with Coulter-S. RESULTS The seroprevalence of H. pylori infection did not relate to hemoglobin. Serum ferritin levels were significantly lower in men (114 vs. 120 microg/L; P = 0.01) and in postmenopausal women (63 vs. 77 microg/L; P = 0.02) who were IgG positive than in seronegative individuals. IgG-positive people more often had reduced serum ferritin levels (</=30 microg/L) than seronegative people. This association persisted in multivariate analysis after adjusting for possible confounding factors (odds ratio, 1.4; 95% confidence interval 1.1-1. 8). CONCLUSIONS Serum ferritin levels are reduced in people with increased IgG antibodies to H. pylori. H. pylori infection affects iron metabolism in humans.

Risk factors for peptic ulcer disease: a population based prospective cohort study comprising 2416 Danish adults

Background: No population based prospective cohort study has previously assessed the impact of multiple risk factors, including Helicobacter pylori infection, on the incidence of peptic ulcer disease (PUD). Aims: To identify risk factors for PUD and estimate their relative impact on ulcer incidence. Subjects: Random sample of 2416 Danish adults with no history of PU. Methods: Sample members were interviewed in 1982 and 1994. PUs diagnosed within the observation period were verified through medical records. Information on psychosocial factors, lifestyle practices, and medication was obtained from a questionnaire completed at study entry. H pylori infection status was determined by ELISA. Results: The main risk factors for PUD were H pylori infection (odds ratio 4.3 (95% confidence interval 2.2; 8.3)), tobacco smoking (3.8 (1.7; 9.8)), and use of minor tranquillisers (3.0 (1.4; 6.6)). Intake of non-steroid anti-inflammatory drugs did not affect the incidence of PUD (0.4 (0.1; 2.3)). In those with increased antibodies to H pylori, tobacco smoking (12.7 (2.8; 56.8)) and intake of spirits (2.4 (1.1; 5.4)) increased the risk of PUD whereas moderate leisure time physical activity (0.3 (0.2; 0.7)) protected against PUD. Conclusions: Tobacco smoking and H pylori infection are the main risk factors for PUD in Danish adults. Physical activity may protect against PUD in those infected with H pylori.

Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes

Background—Helicobacter pylori is a human pathogen that colonises the gastric mucosa and causes permanent gastric inflammation. Aims—To assess the symptoms of H pylori infection in an adult unselected population. Subjects—A random sample of 3589 adult Danes who were examined in 1982 and 1987 (n=2987). Methods—Abdominal symptoms within the preceding year were recorded at both attendances. Circulating IgG antibodies against H pylori in serum samples drawn in 1982 were measured by using in-house indirect enzyme linked immunosorbent assays (ELISA). Results—People with increased levels of IgG antibodies to H pylori were more likely than uninfected individuals to report heartburn (odds ratio (OR) = 1.26, 95% confidence interval (CI) 1.03–1.54) and abdominal pain characterised by daily length (OR = 1.33, 95% CI 0.92–1.91), nocturnal occurrence (OR = 1.62, 95% CI 1.19–2.19), spring aggravation (OR = 1.68, 95% CI 0.70–4.05), and no relation to meals (OR = 0.62, 95% CI 0.43–0.91) or stress (OR = 0.69, 95% CI 0.50–0.95). The inclusion of people with increased levels of IgG antibodies to H pylori, but without upper dyspepsia, at study entry significantly increased the likelihood of reporting upper dyspepsia at follow up (OR = 1.71, 95% CI 1.24–2.36). People with epigastric pain and increased levels of IgM antibodies to H pylori only indicative of acute H pylori infection were more likely to report nocturnal pain, heartburn, nausea, and vomiting. Conclusions—H pylori infection may precede the development of dyspepsia and is associated with a variety of gastrointestinal symptoms in people with no history of peptic ulcer disease.

Association of Helicobacter pylori infection with lifestyle, chronic disease, body-indices, and age at menarche in Danish adults

This study examines the association between lifestyle factors, chronic disease, body-indices, and the seroprevalence of Helicobacter pylori infection in Danish adults. The relationship between age at menarche and H. pylori infection is also assessed. A random sample of 3,608 Danish adults completed a questionnaire about lifestyle factors (smoking habits, alcohol consumption, and coffee and tea intake), doctor diagnosed chronic diseases (heart conditions, diabetes, chronic bronchitis, and hypertension), menarche, and socio-demographic factors. A total of 2,913 participants were eligible for the present study. Electrocardiographs were recorded and blood pressure and serum lipid levels (HDL cholesterol, triglyceride, and cholesterol) were measured. Height and weight were determined and body mass index (BMI) calculated. Sera were analysed with an enzyme-linked immunosorbent assay for the presence of H. pylori specific IgG antibodies. The seroprevalence of H. pylori infection was associated with weekly alcohol intake ≥6 drinks (odds ratio 0.7, 95% confidence interval 0.6-0.9) due to a low rate of H. pylori infection among wine drinkers (odds ratio 0.6, 95% confidence interval 0.5- 0.7). No associations were found with smoking habits or serum lipids. People with upper quartile BMI (≥26.8 kg/m 2) were more likely to be seropositive for antibodies to H. pylori (odds ratio 1.6, 95% confidence interval 1.1-2.4). Chronic bronchitis (odds ratio 1.6, 95% confidence interval 1.1-2.5) and unspecified heart condition (odds ratio 2.0, 95% confidence interval 1.1-3.3) was more often seen in IgG seropositive women than in uninfected women. The likelihood of being seropositive for IgG antibodies to H. pylori increased with age at menarche (odds ratio per year 1.10, 95% confidence interval 1.02-1.19). Previously reported associations with age and socioeconomic status were confirmed. We conclude that wine drinking is associated with lower rates of H. pylori infection in Danish adults. The seroprevalence of H. pylori infection is increased in people with high BMI. H. pylori infection may relate to a history of late menarche and chronic bronchitis in Danish women.

Prevalence and incidence of peptic ulcer disease in a Danish County--a prospective cohort study.

Peptic ulcer prevalence and five year incidence were assessed in a sex and age stratified population sample of 3608 Danish subjects aged 30-60 years. Statements of peptic ulcer disease obtained from questionnaires were scrutinised by reviewing medical records. Life time ulcer prevalence (95% confidence intervals) was 5.6 (4.9-6.4) per cent. Male to female prevalence ratio was 2.2:1, and duodenal to gastric ulcer prevalence ratio was 3.8:1. Thirty two participants with no previous history of peptic ulceration developed an ulcer within the observation period resulting in a five year ulcer incidence of 11.3 (7.4-15.2) per 1000 persons at risk with no demonstrable sex difference. The prevalence of duodenal ulcer has declined in Denmark whereas gastric ulcer prevalence in men has increased slightly. A decline in male duodenal ulcer incidence has probably contributed to the low male to female ulcer incidence ratio, implying that women today incur the same risk of developing an ulcer as men. If such trends continue, they will bring about a new era in ulcer epidemiology characterised by equal incidence in men and women and an even distribution of lesions in the stomach and duodenum.

Seroconversion and seroreversion in IgG antibodies to Helicobacter pylori: a serology based prospective cohort study.

STUDY OBJECTIVES To assess the incidence of seroconversion and seroreversion in IgG antibodies to Helicobacter pylori within a 11 year observation period using these events as markers for acquisition and loss of the infection, respectively. DESIGN Population based prospective cohort study SETTING Northern part of Copenhagen County, Denmark PARTICIPANTS AND METHODS A random sample of 2527 Danish adults were examined and blood obtained in 1983 and in 1994. Matching pairs of sera were analysed for the presence of IgG and IgM antibodies toH pylori with an in house enzyme linked immunosorbent assay. Participants who were seronegative at study entry and seropositive at follow up and had a fourfold increase in baseline IgG antibody levels were categorised as seroconverters and regarded as having acquired H pylori infection. Participants who were seropositive at study entry and had at least a fourfold decrease in baseline IgG antibody levels at follow up were assumed to have lost the infection (seroreverters). RESULTS The seroprevalence of H pylori infection was 24.7 (95% confidence intervals (95% CI) 23.0, 26.4) % in 1983 and 24.5 (95% CI 22.8, 26.2) % in 1994. A total of 14 participants seroconverted within the observation period (cumulative 11 year incidence proportion: 1.0 (95% CI 0.5, 1.5) %). Having increased IgM antibody levels at study entry significantly increased the likelihood of IgG seroconversion (relative risk 6.4 (95% CI 2.1, 19.6). Seroreversion was seen in 48 participants (cumulative 11 year incidence proportion: 7.7 (95% CI 5.6, 9.8) %). CONCLUSIONS Changes inH pylori infection status with time are rare in Danish adults. Few adults become infected with H pylori in Denmark.

Does Helicobacter pylori infection explain all socio‐economic differences in peptic ulcer incidence? Genetic and psychosocial markers for incident peptic ulcer disease in a large cohort of Danish adults

Background: Peptic ulcer epidemiology has changed considerably within the past century. The aim of this study was to assess the 11‐year cumulative incidence of peptic ulcer disease and examine the relationship between ulcer incidence and psychosocial and genetic factors. Methods: A random sample of 2416 Danish adults with no history of peptic ulcer disease residing in Copenhagen County, Denmark, attended a population‐based prospective cohort study in 1983 and 1994. All participants reported whether they had had an ulcer diagnosed within the observation period. Information on socio‐economic factors, family history of peptic ulcer disease (PUD) and lifestyle practices was obtained from a questionnaire. Lewis blood group antigens were assessed from blood samples and Helicobacter pylori infection status was determined with an in‐house IgG ELISA. Results: The overall 11‐year cumulative incidence proportion of PUD was 2.9% (95% CI (2.2; 3.6)), i.e. 1.6% (95% CI (1.1; 2.1)) for duodenal ulcer, and 1.3% (95% CI (0.8; 1.7)) for gastric ulcer. Poor socio‐economic status increased the risk of PUD independently of H. pylori infection (odds ratio 2.7, 95% CI (1.1; 6.1)) and accounted for 17% of all ulcer cases. High physical activity at work increased the risk of PUD in people infected with H. pylori (odds ratio 2.6, 95% CI (0.8; 8.0)). Family history of PUD or Lewis blood group antigens did not relate to ulcer incidence. Conclusions: Poor socio‐economic status is an important risk factor for PUD that exerts its effect independently of H. pylori infection. Strenuous work may increase the risk of PUD in people with H. pylori infection. Genetic factors do not influence the risk of PUD in Danish adults.

Socioeconomic factors in Helicobacter pylori infection among Danish adults

OBJECTIVES This study examined the relationship between housing conditions, educational level, occupational factors, and serologically diagnosed acute and chronic Helicobacter pylori infection. METHODS Immunoglobulin G and immunoglobulin M serum antibodies against H. pylori were measured in 3589 Danish adults who participated in a population study. RESULTS Low socioeconomic status (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.7, 3.0), short duration of schooling (OR = 2.0, 95% CI = 1.3, 2.5), lack of training/education (OR = 1.4, 95% CI = 1.2, 1.7]), unskilled work (OR = 1.7, 95% CI = 1.2, 2.5), and high work-related energy expenditure (OR = 1.4, 95% CI = 1.1, 1.9) increased the likelihood of chronic H. pylori infection. Infection was frequent in people who had lived abroad. Increased levels solely of immunoglobulin M antibodies were found more often in people who were divorced (OR = 2.3, 95% CI = 1.2, 4.4) or unmarried (OR = 2.0, 95% CI = 1.1, 3.8) or who worked long hours (OR = 2.0, 95% CI = 1.1, 4.0). CONCLUSIONS Educational and occupational factors relate to the likelihood of chronic H. pylori infection in adults. The rate of acute infection is high in single individuals.

Mental vulnerability, Helicobacter pylori, and incidence of hospital-diagnosed peptic ulcer over 28 years in a population-based cohort

Abstract Objective: To examine whether mental vulnerability, an enduring personality characteristic, predicts incident hospital-diagnosed ulcer over three decades. Materials and methods: A population-based cohort study enrolled 3365 subjects with no ulcer history, ages 30–60, in 1982–3. Mental vulnerability, Helicobacter pylori IgG antibodies, socioeconomic status, and sleep duration were determined at baseline; non-steroidal antiinflammatory drug use, smoking, leisure time physical activity, and alcohol consumption both at baseline and in 1993–4. Hospital diagnoses of incident ulcer through 2011 were detected using the Danish National Patient Registry. Results: Ulcers were diagnosed in 166 subjects, including 83 complicated by bleeding or perforation. Age-, gender-, and socioeconomic status-adjusted associations were significant for mental vulnerability (Hazard Ratio (HR) 2.0, 95% Confidence Interval 1.4–2.8), Helicobacter pylori (HR 1.7, CI 1.2–2.3), smoking (HR 2.0, CI 1.3–3.1), heavy drinking (HR 1.6, CI 1.1–2.4), abstinence (HR 1.6, CI 1.1–2.5), non-steroidal antiinflammatory drugs (HR 2.1, CI 1.5–3.0), and sedentary lifestyle (HR 1.9, CI 1.4–2.7). Adjusted for all behavioral mediators, the HR for mental vulnerability was 1.5 (CI 1.0–2.2, p = .04). Mental vulnerability raised risk in Helicobacter pylori seropositive subjects and those exposed to neither Helicobacter pylori nor non-steroidal antiinflammatory drugs; its impact was virtually unchanged when analysis was limited to complicated ulcers. Conclusions: A vulnerable personality raises risk for hospital-diagnosed peptic ulcer, in part because of an association with health risk behaviors. Its impact is seen in ‘idiopathic’ and Helicobacter pylori-associated ulcers, and in acute surgical cases.