Genetic risk score associations for myocardial infarction are comparable in persons with and without rheumatoid arthritis: the population-based HUNT study.

Persons with rheumatoid arthritis (RA) have increased risk of myocardial infarction (MI). Overlapping associations with MI of weighted genetic risk scores (wGRS) for coronary artery disease (CAD) and RA is unknown in a population-based setting. Data from the prospective Nord-Trøndelag Health Study (HUNT2: 1995-1997 and HUNT3: 2006-2008) were used. wGRS added each participant's carriage of all risk variants weighted by the coefficient from published association studies. Published wGRS for CAD and RA were analysed in Cox regression with MI as outcome, age as analysis time, and censoring at the first MI, death, or 31.12.2017. 2609 of 61,465 participants developed MI during follow-up (mean 17.7 years). The best-fitting wGRS for CAD and RA included 157 and 27 single-nucleotide polymorphisms, respectively. In multivariable analysis including traditional CAD risk factors, the CAD wGRS was associated with MI [hazard ratio = 1.23 (95% CI 1.18-1.27) for each SD increase, p < 0.0001] in RA patients (n = 433) and controls. The RA wGRS was not significant (p = 0.06). Independently from traditional risk factors, a CAD wGRS was significantly associated with the risk for MI in RA patients and controls, whereas an RA wGRS was not. The captured genetic risk for RA contributed little to the risk of MI.

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study.

OBJECTIVE: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. DESIGN: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting. RESULTS: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65). CONCLUSION: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.

Comparison of methods to construct a genetic risk score for prediction of rheumatoid arthritis in the population-based Nord-Trøndelag Health Study, Norway.

OBJECTIVES: To evaluate selection methods among published single-nucleotide polymorphisms (SNPs) associated with RA to construct predictive genetic risk scores (GRSs) in a population-based setting. METHODS: The Nord-Trøndelag Health (HUNT) Study is a prospective cohort study among the whole adult population of northern Trøndelag, Norway. Participants in HUNT2 (1995-1997) and HUNT3 (2006-2008) were included (489 RA cases, 61 584 controls). The initial SNP selection from relevant genome-wide studies included 269 SNPs from 30 studies. Following different selection criteria, SNPs were weighted by published odds ratios. The sum of each person's carriage of all weighted susceptibility variants was calculated for each GRS. RESULTS: The best-fitting risk score included 27 SNPs [weighted genetic risk score 27 (wGRS27)] and was identified using P-value selection criterion ≤5 × 10-8, the largest possible SNP selection without high linkage disequilibrium (r2 < 0.8), and lasso regression to select for positive coefficients. In a logistic regression model adjusted for gender, age and ever smoking, wGRS27 was associated with RA [odds ratio 1.86 (95% CI 1.71, 2.04) for each s.d. increase, P < 0.001]. The AUC was 0.76 (95% CI 0.74, 0.78). The positive and negative predictive values were 1.6% and 99.7%, respectively, and the positive predictive value was not improved in sensitivity analyses subselecting participants to illustrate settings with increased RA prevalences. Other schemes selected more SNPs but resulted in GRSs with lower predictive ability. CONCLUSION: Constructing a wGRS based on a smaller selection of informative SNPs improved predictive ability. Even with a relatively high AUC, the low PPV illustrates that there was a large overlap in risk variants among RA patients and controls, precluding clinical usefulness.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Risk factors for requiring 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-Trøndelag 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.

The association of air pollution and depressed mood in 70,928 individuals from four European cohorts.

BACKGROUND: Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. METHODS: Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. RESULTS: A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 µg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 µg/m(3) increase in NO2). CONCLUSIONS: Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood.

Trends in overweight and obesity over 22 years in a large adult population: the HUNT Study, Norway.

Some reports indicate that the obesity epidemic may be slowing down or halting. We followed body mass index (BMI) and waist circumference (WC) in a large adult population in Norway (n = 90 000) from 1984-1986 (HUNT1) through 1995-1997 (HUNT2) to 2006-2008 (HUNT3) to study whether this is occurring in Norway. Height and weight were measured with standardized and identical methods in all three surveys; WC was also measured in HUNT2 and HUNT3. In the three surveys, mean BMI increased from 25.3 to 26.5 and 27.5 kg m-2 in men and from 25.1 to 26.2 and 26.9 kg m-2 in women. Increase in prevalence of obesity (BMI ≥ 30 kg m-2) was greater in men (from 7.7 to 14.4 and 22.1%) compared with women (from 13.3 to 18.3 and 23.1%). In contrast, women had a greater increase in abdominal obesity (WC ≥ 102 cm for men and WC ≥ 88 cm for women). There was a continuous shift in the distribution curve of BMI and WC to the right, demonstrating that the increase in body weight was occurring in all weight groups, but the increase of obesity was greatest in the youngest age groups. Our data showed no signs of a halt in the increase of obesity in this representative Norwegian population.

Cohort Profile: the HUNT Study, Norway.

The HUNT Study includes large total population-based cohorts from the 1980ies, covering 125 000 Norwegian participants; HUNT1 (1984-86), HUNT2 (1995-97) and HUNT3 (2006-08). The study was primarily set up to address arterial hypertension, diabetes, screening of tuberculosis, and quality of life. However, the scope has expanded over time. In the latest survey a state of the art biobank was established, with availability of biomaterial for decades ahead. The three population based surveys now contribute to important knowledge regarding health related lifestyle, prevalence and incidence of somatic and mental illness and disease, health determinants, and associations between disease phenotypes and genotypes. Every citizen of Nord-Trøndelag County in Norway being 20 years or older, have been invited to all the surveys for adults. Participants may be linked in families and followed up longitudinally between the surveys and in several national health- and other registers covering the total population. The HUNT Study includes data from questionnaires, interviews, clinical measurements and biological samples (blood and urine). The questionnaires included questions on socioeconomic conditions, health related behaviours, symptoms, illnesses and diseases. Data from the HUNT Study are available for researchers who satisfy some basic requirements (www.ntnu.edu/hunt), whether affiliated in Norway or abroad.

The associations of high levels of C-reactive protein with depression and myocardial infarction in 9258 women and men from the HUNT population study.

BACKGROUND: Elevated levels of circulating C-reactive protein (CRP) have been associated with coronary heart disease and, in some studies, depression. Most studies have been of populations selected by age and/or gender. We investigate these associations with depression, myocardial infarction (MI), or both, in a large general population sample. METHOD: A cross-sectional population study of 9258 women and men aged ≥ 20 years. The study included clinical examination, self-report of MI and depression and factors known to confound their associations. The Hospital Anxiety and Depression Scale was used to assess severity of depressive symptoms. Elevated high sensitive-CRP was defined as values >2.2 mg/l. RESULTS: The association of elevated CRP with depression was attenuated towards the null [from odds ratio (OR) 1.28, p=0.001 to OR 1.08, p=0.388] following extensive adjustment, while associations with MI (adjusted OR 1.42, p=0.032) and co-morbid MI and depression (adjusted OR 2.66, p=0.003) persisted. Confounders associated with elevated CRP levels were smoking (OR 1.66; p<0.001), chronic physical illness (OR 1.34, p<0.001), BMI ≥ 30 (OR 1.13, p<0.001), employment (OR 0.70, p<0.001) and high coffee consumption (OR 0.83, p=0.017). Interaction tests indicated a lower effect of old age (OR 0.54, p<0.001) and smoking (OR 0.63, p<0.001) on elevated CRP levels in women compared with men. CONCLUSIONS: CRP levels were raised in those with MI and co-morbid MI and depression; the positive association with depression was explained by confounding factors. We found new evidence that might help understand gender-specific patterns. Future studies should explore the neurobiological mechanisms underpinning these interrelations and their relevance for treatment of these conditions.

Severe symptoms of gastro-oesophageal reflux disease are associated with cardiovascular disease and other gastrointestinal symptoms, but not diabetes: a population-based study.

BACKGROUND: Few population-based studies have examined comorbidity in relation to gastro-oesophageal reflux disease (GERD). AIM: To study the association between cardiovascular disease, diabetes, gastrointestinal symptoms and GERD. METHODS: Population-based, cross-sectional, case-control study based on a large Norwegian health survey conducted in 1995-97. Among 65,333 participants, 3153 persons reporting severe reflux symptoms were defined as cases, and 40,210 persons without such symptoms were defined as controls. Data on cardiovascular disease, diabetes, gastrointestinal symptoms and potential confounders were collected through questionnaires. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using unconditional logistic regression, in crude and adjusted models. RESULTS: In the crude models, positive associations were observed between myocardial infarction (OR 1.7, 95% CI 1.4-2.1), angina pectoris (OR 2.5, 95% CI 2.1-2.9) and stroke (OR 1.6, 95% CI 1.2-2.1) and risk of GERD. The associations were attenuated in the adjusted models, but remained significant for angina pectoris (OR 1.9, 95% CI 1.6-2.2). No association was observed between diabetes and GERD. Strong positive associations were seen between all studied gastrointestinal symptoms, i.e. nausea, diarrhoea and constipation, and risk of GERD. CONCLUSIONS: This population-based study indicates that myocardial infarction, angina pectoris, stroke and symptoms of nausea, diarrhoea and constipation are associated with GERD.

Severe gastro-oesophageal reflux symptoms in relation to anxiety, depression and coping in a population-based study.

BACKGROUND: The association between psychiatric disorders and gastro-oesophageal reflux symptoms is uncertain, and few population-based studies are available. AIM: To examine the association between psychiatric and psychological factors and reflux symptoms. METHODS: Population-based, cross-sectional, case-control study based on two health surveys conducted in the Norwegian county Nord-Trondelag in 1984-1986 and 1995-1997. Reflux symptoms were assessed in the second survey, including 65,333 participants (70% of the county's adult population). 3153 subjects reporting severe reflux symptoms were defined as cases and 40,210 subjects without symptoms were defined as controls. Data were collected in questionnaires. Odds ratio with 95% confidence intervals were estimated using unconditional logistic regression, in adjusted models. RESULTS: Subjects reporting anxiety without depression had a 3.2-fold (95% CI: 2.7-3.8) increased risk of reflux, subjects with depression without anxiety had a 1.7-fold (95% CI: 1.4-2.1) increased risk and subjects with both anxiety and depression had a 2.8-fold (95% CI: 2.4-3.2) increased risk, compared to subjects without anxiety/depression. We observed a weak inverse association between one measure of covert coping and risk of reflux and a weak positive association between another coping measure and risk of reflux. CONCLUSIONS: This population-based study indicates that anxiety and depression are strongly associated with reflux symptoms, while no consistent association regarding coping and reflux was found.

Increased serum levels of chromogranin A in male smokers with airway obstruction.

The neuroendocrine (NE) system may play an important role in smoking-induced airway diseases. The aim of the present study was to examine the relationship between serum levels of the general NE marker chromogranin A (CgA) and smoking habits, respiratory symptoms and lung function. The study population consisted of never-smokers with normal lung function, smokers with normal lung function and smokers with airway obstruction who were randomly selected from the lung study of the Nord-Trøndelag Health Study (HUNT). Serum CgA was determined in 151, 138 and 116 subjects, respectively. All subjects were seronegative for Helicobacter pylori. Male smokers with airway obstruction had significantly higher serum CgA levels (median 3.70 nmol x L(-1) (interquartile range 3.10-5.15)) than both smokers with normal lung function (3.00 nmol x L(-1) (2.50-3.67)) and never-smokers with normal lung function (2.90 nmol x L(-1) (2.57-3.30)). The elevated levels of CgA correlated with the degree of airway obstruction. Moreover, the presence of respiratory symptoms and chronic bronchitis among male smokers were associated with increased serum CgA levels. Females had CgA levels similar to male smokers independent of smoking status and lung function. Elevated serum chromogranin A levels in subjects with airway obstruction and respiratory symptoms may represent neuroendocrine activation in inflammatory or remodelling processes in the lung.

Lifestyle related risk factors in the aetiology of gastro-oesophageal reflux.

BACKGROUND/AIM: The aetiology of gastro-oesophageal reflux is largely unknown. The authors' aim was to examine the relation between lifestyle habits and gastro-oesophageal reflux symptoms. SUBJECTS: Participants of two consecutive public health surveys in Nord-Trondelag, Norway. METHODS: In a case control study within the two public health surveys, 3153 individuals who in the second survey reported severe heartburn or regurgitation during the last 12 months were defined as cases, while 40 210 people without reflux symptoms constituted the control group. The risk of reflux symptoms was estimated and multivariately calculated as odds ratios in relation to exposure to tobacco smoking, alcohol, coffee, tea, table salt, cereal fibres, and physical exercise. RESULTS: There was a significant dose response association between tobacco smoking and reflux symptoms. Among people who had smoked daily for more than 20 years the odds ratio was 1.7 (95% confidence interval 1.5 to 1.9) compared with non-smokers. A similar positive association was found for table salt intake. The odds ratio for reflux was 1.7 (95% CI 1.4 to 2.0) among those who always used extra table salt compared with those who never did so. We found moderately strong negative associations between the risk of reflux and exposure to coffee, bread high in dietary fibre content, and frequent physical exercise. Intake of alcohol or tea did not affect the risk of reflux. CONCLUSIONS: Tobacco smoking and table salt intake seem to be risk factors for gastro-oesophageal reflux symptoms. Dietary fibres and physical exercise may protect against reflux. Alcohol, coffee, and tea do not seem to be risk factors for reflux.

Prevalence of gastro-oesophageal reflux symptoms and the influence of age and sex.

BACKGROUND: Most previous studies of reflux symptom prevalence are of small sample size. No reliable data concerning age- and sex-stratified prevalence are available. METHODS: Among 65,363 adult participants in a public health survey in Nord-Trondelag, Norway, 58,596 (90%) responded concerning occurrence and severity of heartburn or regurgitation during the past 12 months. The prevalence of minor, severe and any reflux symptoms was calculated, including stratification for age and sex. In order to examine whether the relative risk of reflux symptoms between sexes, in different age groups, was affected by other potential risk factors for reflux, confounding effects were tested using multivariate logistic regression. Odds ratios and their 95% confidence intervals were used to estimate relative risks. RESULTS: Total prevalence of reflux symptoms was 31.4%, whereof 26.0% were minor symptoms and 5.4% severe symptoms. The prevalence of symptoms occurring at least weekly was 11.6%. Among women, the prevalence increased gradually from 22.1% in the youngest age category to 37.5% in the oldest, while among men it gradually increased from 25.8% in the youngest age group to peak at 36.0% between the ages of 50 and 60 years, after which it declined to 33.8% after age 70. A higher prevalence among women compared to men in the oldest age groups was not explained by confounding by body mass, tobacco smoking, alcohol consumption, dietary factors, or physical exercise. CONCLUSIONS: About every third adult person suffered from reflux symptoms. The prevalence increases linearly with age among women, while among men it peaked between the age of 50 and 70 years and thereafter declined.

Benefit of population-based screening for phenotypic hemochromatosis in young men.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in the body, most notably in the liver. More men than women become clinically ill. The prognosis is excellent if phlebotomy treatment is started before liver cirrhosis develops. Screening has been recommended, but the benefit of population-based screening has never been shown in a randomized clinical trial. In this article, we estimate the benefit of screening young men, using a theoretical model. METHODS: A phenotypic screening scenario was modelled using a decision tree. Gain of quality-adjusted life-years was used as a measure of benefit, and estimated using Markov processes. Data on the accuracy of the screening tests, the prevalence of HH and the risk of liver cirrhosis were mainly derived from a cross-sectional study on the prevalence and morbidity of HH in 30509 men. Data on the excess mortality of cirrhosis were taken from relevant literature. Sensitivity analysis was done for important variables. RESULTS: Assuming basal case values for variables, screening a cohort of 1000 men aged 30 years for phenotypic HH would gain about 8 quality-adjusted life-years, compared to awaiting symptomatic disease. Based on actual costs of our cross-sectional study, the screening cost was US$250 per quality-adjusted life-year gained. The prevalence of phenotypic HH, the excess mortality of liver cirrhosis, the quality of life in non-cirrhotic HH patients, and the fractions of patients compliant with treatment were the most important variables in the sensitivity analysis. CONCLUSION: Incorporating screening for phenotypic HH in health survey programmes for young men may be worthwhile.

Persons with screening-detected haemochromatosis: as healthy as the general population?

BACKGROUND: Hereditary haemochromatosis (HH) is a common genetic disease leading to iron deposition in the liver and other organs. Early treatment will prevent clinical disease and population-based screening for HH has been advocated. However, the benefit of screening depends on the morbidity of HH. We have compared the morbidity in HH persons detected by screening with the morbidity in the rest of the population. METHODS: All inhabitants 20 years or older in a Norwegian county (94,191 persons) were invited to participate in a health survey programme. Of 65,717 participating persons, a blood specimen for transferrin saturation was obtained from 65,238. After repeated laboratory testing and clinical examination, 269 persons were found to have phenotypic HH, while 297 had genotypic HH (the C282/C282Y mutation). Using self-reported data, clinical examinations and analysis of non-fasting blood samples, the morbidity in phenotypic and genotypic HH persons was compared with the morbidity in the rest of the population. All data were collected before subjects were diagnosed with HH, and all comparisons were corrected for age and gender. RESULTS: Compared to control persons, phenotypic and genotypic HH men and women had a higher score on 1 of 17 questions dealing with joint complaints. Phenotypic and genotypic HH women below 50 years of age had a higher prevalence of hypothyroidism (15.2% and 12.5%, respectively, compared to 3.0% in the control population). Phenotypic HH women below 50 years of age had higher diastolic blood pressure than control women. Phenotypic HH men above 50 years of age and genotypic HH men scored lower than control men on a compound myocardial infarction risk score variable, in part due to lower serum cholesterol concentration. Fewer phenotypic HH men above 50 years of age reported having angina pectoris. Otherwise, the health of phenotypic and genotypic HH persons was not different from the health of control persons. CONCLUSION: When corrected for age and gender, the morbidity in persons with screening-detected HH was not very different from the morbidity in the control group, indicating that population-based screening may not be as beneficial as anticipated.

Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened. METHODS: In a Norwegian county, all inhabitants 20 years or older were invited to participate in a population-based health survey programme. Screening for HH was one of several subprojects. Blood samples were obtained from 65,238 persons. Subjects with high serum transferrin saturation in two tests and high serum ferritin were clinically evaluated for HH. All subjects with high serum transferrin saturation in two tests were offered genotyping. RESULTS: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was ascertained in only 4 men. We found no correlation between serum ferritin and age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly discovered HH subject. The estimated prevalence of phenotypical HH not previously known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y mutation was at least 0.68%. CONCLUSION: Large-scale screening for HH can be performed at a relatively low cost if combined with a health survey programme. The yield in terms of newly discovered cases is considerable, but few cases were found seriously ill. Better knowledge of the natural course of HH is necessary if we are to be able to estimate the cost-effectiveness of large-scale screening.