Trends in gastro-oesophageal reflux in a Norwegian general population: the Tromsø Study 1979–2016

Background - The prevalence of overweight and smoking has changed over time. However, whether the changes in the risk factors are reflected in the prevalence of gastro-oesophageal reflux disease (GORD) is unknown. The aims of this study were to assess the changes in prevalence of GORD and the associated risk factors over time in a general population. Methods - This was a population-based study using repeated surveys of the Tromsø Study: Tromsø2 (1979–1980, n = 14,279), Tromsø6 (2007–2008, n = 11,460) and Tromsø7 (2015–2016, n = 20,664). Complaints of heartburn and acid regurgitation and common risk factors were reported, and height and weight were measured. The prevalence of GORD was calculated and the association with risk factors was assessed at each time point by odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. Results - The prevalence of GORD was 13% in 1979–1980, 6% in 2007–2008 and 11% in 2015–2016. In all three surveys, the risk of GORD was consistently increased with overweight and smoking. However, overweight was a weaker risk factor in the first (OR 1.58, 95% CI 1.42–1.76) compared to the last (OR 2.16, 95% CI 1.94–2.41) survey. Smoking was a stronger risk factor in the first (OR 1.45, 95% CI 1.31–1.60) than at the last (OR 1.14, 95% CI 1.01–2.29) survey. Conclusion - During four decades of follow-up of the same population, no clear change in prevalence of GORD was found. GORD was clearly and consistently associated with overweight and smoking. However, overweight has become a more important risk factor than smoking over time

Metabolic predispositions and increased risk of colorectal adenocarcinoma by anatomical locations: a large population-based cohort study in Norway

Whether different definitions of metabolic syndrome (MetS) are differently associated with colorectal adenocarcinoma (CA) by anatomical location is unclear. A population-based cohort study, the Cohort of Norway (CONOR) Study, was conducted in Norway from 1995 to 2010. Anthropometric measurements, blood samples, and lifestyle data were collected at recruitment. CAs were identified through linkage to the Norwegian Cancer Register. A composite index of MetS as defined by the International Diabetes Federation (IDF) or/and the National Cholesterol Education Program's Adult Treatment Panel III (ATP III) and single components of MetS, including anthropometric factors, blood pressure, lipids, triglycerides, and glucose, were analyzed. Cox proportional hazards regression was performed to estimate hazard ratios and 95% confidence intervals. Significant associations between single MetS components and CA, except for reduced high-density lipoprotein cholesterol and nonfasting glucose levels, were observed. MetS defined by 2 criteria separately showed a similar association with CA in general, and MetS defined by both the IDF and ATP III showed consistent results. Stronger associations were observed in the proximal colon among men (IDF: hazard ratio (HR) = 1.51, 95% confidence interval (CI): 1.24, 1.84; ATP III: HR = 1.40, 95% CI: 1.15, 1.70) and in the rectum among women (IDF: HR = 1.42, 95% CI: 1.07, 1.89; ATP III: HR = 1.43, 95% CI: 1.08, 1.90).Swedish Society of MedicineKarolinska InstitutetSwedish Research CouncilAccepte

Tobacco smoking cessation and improved gastroesophageal reflux : a prospective population-based cohort study : the HUNT study

Objective Tobacco smoking increases the risk of gastroesophageal reflux symptoms (GERS), but whether tobacco smoking cessation improves GERS is unclear. The aim of this study was to clarify if tobacco smoking cessation improves GERS. Design The study was based on the Nord-Trøndelag health study (the HUNT study), a prospective population-based cohort study conducted from 1995-1997 to 2006-2009 in Nord-Trøndelag County, Norway. All residents of the county from 20 years of age were invited. The study included 29,610 individuals (61% response rate) who reported whether they had heartburn or acid regurgitation. The association between tobacco smoking cessation and improvement in GERS was assessed by logistic regression, providing odds ratios (ORs) with 95% confidence intervals (CIs). The analyses were stratified by antireflux medication, and the results were adjusted for sex, age, body mass index (BMI), alcohol consumption, education, and physical exercise. Subgroup analyses were also stratified by BMI. Results Among individuals using antireflux medication at least weekly, cessation of daily tobacco smoking was associated with improvement in GERS from severe to no or minor complaints (adjusted OR 1.78, 95% CI 1.07 to 2.97), compared with persistent daily smoking. This association was present among individuals within the normal range of BMI (OR 5.67, 95% CI 1.36 to 23.64), but not among overweight individuals. There was no association between tobacco smoking cessation and GERS status among individuals with minor GERS or individuals using antireflux medication less than weekly. Conclusion Tobacco smoking cessation was associated with improvement in severe GERS only in individuals of normal BMI using antireflux medication at least weekly, but not in other individual with GERS.Swedish Research CouncilLiaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and TechnologyAccepte

Changes in prevalence, incidence and spontaneous loss of gastro-oesophagealreflux symptoms : a prospective population-based cohort study, the HUNT study

OBJECTIVE: Changes in the occurrence of gastro-oesophageal reflux symptoms (GORS) in the population remain uncertain. This study aimed to determine the prevalence changes, the incidence and the spontaneous loss of GORS. DESIGN: This population-based cohort study was conducted within the Nord-Trondelag Health Study (the HUNT study), a longitudinal series of population-based health surveys in Nord-Trondelag County, Norway. The study base encompassed all adult residents in the county, and the participants reported the degree of GORS during the previous 12 months. The number of participants included were 58,869 (64% response rate) in 1995-7 and 44,997 (49%) in 2006-9. Of these, 29,610 persons (61%) were prospectively followed up for an average of 11 years. RESULTS: Between 1995-7 and 2006-9, the prevalence of any, severe and at least weekly GORS increased by 30% (from 31.4% to 40.9%), 24% (from 5.4% to 6.7%) and 47% (from 11.6% to 17.1%), respectively. The average annual incidence of any and severe GORS was 3.07% and 0.23%, respectively. In women, but not men, the incidence of GORS increased with increasing age. The average annual spontaneous loss (not due to antireflux medication) of any and severe GORS was 2.32% and 1.22%, respectively. The spontaneous loss of GORS decreased with increasing age. CONCLUSION: Between 1995-7 and 2006-9 the prevalence of GORS increased substantially. At least weekly GORS increased by 47%. The average annual incidence of severe GORS was 0.23%, and the corresponding spontaneous loss was 1.22%. The incidence and spontaneous loss of GORS were influenced by sex and age.Swedish Research CouncilLiaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and TechnologyAccepte

Weight loss and reduction in gastroesophageal reflux : a prospective population-based cohort study : the HUNT study

OBJECTIVES: High body mass index (BMI) is an established risk factor of gastroesophageal reflux symptoms (GERS). The aim of this study was to clarify if weight loss reduces GERS. METHODS: The study was part of the Nord-Trondelag health study (the HUNT study), a prospective population-based cohort study conducted in Nord-Trondelag County, Norway. All residents of the county from 20 years of age were invited. In 1995-1997 (HUNT 2) and 2006-2009 (HUNT 3), 58,869 and 44,997 individuals, respectively, responded to a questionnaire on heartburn and acid regurgitation. Among these, 29,610 individuals (61% response rate) participated at both times and were included in the present study. The association between weight loss and reduction of GERS was calculated using logistic regression. The analyses were stratified by antireflux medication and the results adjusted for sex, age, cigarette smoking, alcohol consumption, education, and physical exercise. RESULTS: Weight loss was dose-dependently associated with a reduction of GERS and an increased treatment success with antireflux medication. Among individuals with >3.5 units decrease in BMI, the adjusted odds ratio (OR) of loss of any (minor or severe) GERS was 1.98 (95% confidence interval (CI) 1.45-2.72) when using no or less than weekly antireflux medication, and 3.95 (95% CI 2.03-7.65) when using at least weekly antireflux medication. The corresponding ORs of loss of severe GERS was 0.90 (95% CI 0.32-2.55) and 3.11 (95% CI 1.13-8.58). CONCLUSIONS: Weight loss was dose-dependently associated with both a reduction of GERS and an increased treatment success with antireflux medication in the general population.Swedish Research CouncilLiaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and TechnologyAccepte

All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study)

OBJECTIVE: Gastro-oesophageal reflux is a public health concern which could have associated oesophageal complications, including adenocarcinoma, and possibly also head-and-neck and lung cancers. The aim of this study was to test the hypothesis that reflux increases all-cause and cancer-specific mortalities in an unselected cohort. DESIGN: The Nord-Trondelag health study (HUNT), a Norwegian population-based cohort study, was used to identify individuals with and without reflux in 1995-1997 and 2006-2008, with follow-up until 2014. All-cause mortality and cancer-specific mortality were assessed from the Norwegian Cause of Death Registry and Cancer Registry. Multivariable Cox regression was used to calculate HRs with 95% CIs for mortality with adjustments for potential confounders. RESULTS: We included 4758 participants with severe reflux symptoms and 51 381 participants without reflux symptoms, contributing 60 323 and 747 239 person-years at risk, respectively. Severe reflux was not associated with all-cause mortality, overall cancer-specific mortality or mortality in cancer of the head-and-neck or lung. However, for men with severe reflux a sixfold increase in oesophageal adenocarcinoma-specific mortality was found (HR 6.09, 95% CI 2.33 to 15.93) and the mortality rate was 0.27 per 1000 person-years. For women, the corresponding mortality was not significantly increased (HR 3.68, 95% CI 0.88 to 15.27) and the mortality rate was 0.05 per 1000 person-years. CONCLUSIONS: Individuals with severe reflux symptoms do not seem to have increased all-cause mortality or overall cancer-specific mortality. Although the absolute risk is small, individuals with severe reflux symptoms have a clearly increased oesophageal adenocarcinoma-specific mortality.Swedish Research CouncilAccepte

Association between metformin use and risk of esophageal squamous cell carcinoma in a population-based cohort study

Objectives: Esophageal cancer is a highly fatal malignant neoplasm, with two etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma, with metformin therapy. This study aims to determine the association between metformin use and incident esophageal squamous cell carcinoma risk. Methods: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched non-users of metformin (n=4,116,030) by age and sex. Metformin use was treated as a time-varying variate and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for esophageal squamous cell carcinoma, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of non-steroidal anti-inflammatory drugs or statins. Results: The incidence rates of esophageal squamous cell carcinoma were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the non-users. Metformin users overall were at a decreased risk of esophageal squamous cell carcinoma compared with non-users (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). Conclusions: Metformin use decreases the risk of developing esophageal squamous cell carcinoma.Swedish Research CouncilSwedish Cancer SocietyUnited European Research PrizeManuscrip

Anthropometry-based obesity phenotypes and risk of colorectal adenocarcinoma : a large prospective cohort study in Norway

BACKGROUND: It is unclear whether obesity phenotypes measured by different anthropometric indices are associated with a risk of colorectal adenocarcinoma by anatomical location. METHODS: We compiled harmonized population-based cohort studies (Cohort of Norway, CONOR) with 143,477 participants that were conducted between 1994 and 2010. General, abdominal, and gluteofemoral obesity were assessed by body mass index (BMI, kg/m(2)), waist circumference (cm), and hip circumference (cm). Other measures examined were waist to hip ratio, waist to height ratio, and body adiposity index. We performed Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of obesity relative to a risk of colorectal adenocarcinoma. RESULTS: In total, 2,044 incident cases of colorectal adenocarcinoma were identified. We observed a positive association between waist circumference (high versus low) and adenocarcinoma in the proximal colon (HR = 1.9, 95% CI = 1.5, 2.5) and distal colon (HR = 1.7, 95% CI = 1.3, 2.3) when adjusted for BMI. The association with waist circumference was especially strong in men. BMI was not associated with adenocarcinoma in the colon or rectum after adjusting for waist circumference. We found no association between hip circumference and colorectal adenocarcinoma. When adjusted for BMI plus waist circumference, body adiposity index was negatively associated with adenocarcinoma in the proximal or distal colon. CONCLUSION: Abdominal obesity, but not general or gluteofemoral obesity, was associated with an increased risk of adenocarcinoma in the proximal and the distal colon, especially in men. Muscularity may be negatively associated with risk of colon adenocarcinoma.Swedish Research CouncilAccepte

Risk factors of having cholecystectomy for gallstone disease in a prospective population-based cohort study

BACKGROUND: The relationship between different lifestyle factors and the risk of needing cholecystectomy for gallstone disease is not clear. This study aimed to assess the association between anthropometric, lifestyle and sociodemographic risk factors and the subsequent risk of requiring cholecystectomy for gallstone disease during long-term follow-up in a defined population cohort. METHODS: Data from a large population-based cohort study performed from 1995 to 1997 were used (the second Norwegian Nord-Trondelag health study, HUNT2). Following HUNT2, from 1998 to 2011, all patients operated on for gallstone disease with cholecystectomy at the two hospitals in the county, Levanger Hospital and Namsos Hospital, were identified. A Cox proportional hazards model was used for multivariable risk analysis. RESULTS: The HUNT2 cohort included 65 237 individuals (69.5 per cent response rate), aged 20-99 years. During a median follow-up of 15.3 (range 0.6-16.4) years, 1162 cholecystectomies were performed. In multivariable analysis, overweight individuals (body mass index (BMI) 25.0-29.9 kg/m(2) ) had a 58 per cent increased risk of cholecystectomy compared with individuals with normal weight (BMI less than 25.0 kg/m(2) ). Obese individuals (BMI 30 kg/m(2) or above) had a twofold increased risk. Increasing waist circumference independently increased the risk of cholecystectomy. In women, current hormone replacement therapy (HRT) increased the risk, whereas hard physical activity and higher educational level were associated with reduced risk of cholecystectomy. CONCLUSION: High BMI and waist circumference increased the risk of having cholecystectomy for both sexes. In women, the risk was increased by HRT, and decreased by hard physical activity and higher educational level.Swedish Research CouncilAccepte

Quality of life and psychological and gastrointestinal symptoms after cholecystectomy : a population-based cohort study

OBJECTIVE: The study aims to examine gastrointestinal symptoms, quality of life and the risk of psychological symptoms after cholecystectomy. DESIGN: This is a prospective population-based cohort study based on the Nord-Trondelag Health Study (HUNT) Norway. HUNT is a repeated health survey of the county population and includes a wide range of health-related items. In the present study, all 3 HUNT surveys were included, performed between 1984 and 2008. Selected items were scores on quality of life, the Hospital Anxiety and Depression Scale (HADS) and selected gastrointestinal symptoms. Participants who underwent cholecystectomy for gallstone disease between 1 January 1990 and until 1 year before attending HUNT3 were compared with the remaining non-operated cohort. Associations between cholecystectomy and the postoperative scores and symptoms were assessed by multivariable regression models. RESULTS: Participants in HUNT1, HUNT2 and HUNT3 were 77 212 (89.4% of those invited), 65 237 (69.5%) and 50 807 (54.1%), respectively. In the study period, 931 participants were operated with cholecystectomy. Cholecystectomy was associated with an increased risk of diarrhoea and stomach pain postoperatively. In addition, cholecystectomy was associated with an increased risk of nausea postoperatively in men. We found no associations between cholecystectomy and quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation following surgery. CONCLUSIONS: In this large population-based cohort study, cholecystectomy was associated with postoperative diarrhoea and stomach pain. Cholecystectomy for gallstone colic was associated with nausea in men. There were no associations between quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation.Levanger Hospital, HNT NorwayNTNU, Norwegian University of Science and TechnologyPublishe