Abstract: OBJECTIVES: To study the extent to which otitis media (OM) in childhood is associated with adult hearing thresholds. Furthermore, to study whether the effects of OM on adult hearing thresholds are moderated by age or noise exposure. DESIGN: Population-based cohort study of 32,786 participants who had their hearing tested by pure-tone audiometry in primary school and again at ages ranging from 20 to 56 years. Three thousand sixty-six children were diagnosed with hearing loss; the remaining sample had normal childhood hearing. RESULTS: Compared with participants with normal childhood hearing, those diagnosed with childhood hearing loss caused by otitis media with effusion (n = 1255), chronic suppurative otitis media (CSOM; n = 108), or hearing loss after recurrent acute otitis media (rAOM; n = 613) had significantly increased adult hearing thresholds in the whole frequency range (2 dB/17-20 dB/7-10 dB, respectively). The effects were adjusted for age, sex, and noise exposure. Children diagnosed with hearing loss after rAOM had somewhat improved hearing thresholds as adults. The effects of CSOM and hearing loss after rAOM on adult hearing thresholds were larger in participants tested in middle adulthood (ages 40 to 56 years) than in those tested in young adulthood (ages 20 to 40 years). Eardrum pathology added a marginally increased risk of adult hearing loss (1-3 dB) in children with otitis media with effusion or hearing loss after rAOM. The study could not reveal significant differences in the effect of self-reported noise exposure on adult hearing thresholds between the groups with OM and the group with normal childhood hearing. CONCLUSIONS: This cohort study indicates that CSOM and rAOM in childhood are associated with adult hearing loss, underlining the importance of optimal treatment in these conditions. It appears that ears with a subsequent hearing loss after OM in childhood age at a faster rate than those without; however this should be confirmed by studies with several follow-up tests through adulthood.

Abstract: Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring's cardiovascular risk profile in young adulthood and their siblings' cardiovascular risk profile. From the HUNT study (Nord-Trondelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8-3.5) mm Hg higher systolic blood pressure, 1.5 (0.9-2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31-1.01) kg/m2 higher body mass index, and 1.49 (0.65-2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non-high-density lipoprotein cholesterol (0.14 mmol/L, 0.03-0.25) and triglycerides (0.13 mmol/L, 0.06-0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease.

Abstract: OBJECTIVE: In a mortality follow-up of the HUNT Study, serum TSH within the reference range was positively associated with the risk of coronary death in women. We now aimed to confirm the association of high serum TSH with the risk of coronary heart disease, using hospital-based diagnoses of myocardial infarction. DESIGN: Prospective population-based study with linkage to hospital information on myocardial infarction and to the national Cause of Death Registry. PARTICIPANTS: A total of 26, 707 people without previously known thyroid or cardiovascular disease or diabetes at baseline. MEASUREMENTS: Hazard ratios (HR) of coronary death and HRs of hospitalization with a first-time acute myocardial infarction, by baseline thyroid function. RESULTS: During 12, years of follow-up, 960 (3.6%) participants had been hospitalized with first-time myocardial infarction and 558 (2.1%) had died from coronary heart disease. High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0.005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0.50-1.4 mU/l. However, thyroid function was not associated with the risk of being hospitalized with myocardial infarction. CONCLUSIONS: High serum TSH was associated with increased mortality from coronary heart disease in women, but we found no association of thyroid function with the risk of being hospitalized with myocardial infarction. Thus, the morbidity finding does not confirm the suggestion that low thyroid function within the clinically normal range is associated with increased risk of coronary heart disease.

Abstract: BACKGROUND: Most studies of physical activity (PA) epidemiology use behaviour measured at a single time-point. We examined whether 'PA patterns' (consistently low, consistently high or inconsistent PA levels over time) showed different epidemiological relationships for anthropometric and mortality outcomes, compared to single time-point measure of PA. METHODS: Data were the Danish MONICA (MONItoring Trends and Determinants in CArdiovascular Disease) study over three waves 1982-3 (time 1), 1987-8 (time 2) and 1993-4 (time 3). Associations between leisure time single time-point PA levels at time 1 and time 3, and sport and active travel at times 1 and 2 with BMI, waist, hip circumference and mortality (death from coronary heart disease (CHD) and cardiovascular disease (CVD)) were compared to 'PA patterns' spanning multiple time points. PA pattern classified participants' PA as either 1) inactive or low PA at both time points; 2) moderate level PA at time 1 and high activity at time 3; or 3) a 'mixed PA pattern' indicating a varying levels of activity over time. Similarly, sport and active travel were also classified as indicating stable low, stable high and mixed patterns. RESULTS: The moderately and highly active groups for PA at times 1 and 3 had up to 1.7 cm lower increase in waist circumference compared with the inactive/low active group. Across 'PA patterns', 'active maintainers' had a 2.0 cm lower waist circumference than 'inactive/low maintainers'. Waist circumference was inversely related to sport but not active travel. CHD risk did not vary by activity levels at time 1, but was reduced significantly by 43% for high PA at time 3 (vs 'inactive' group) and among 'active maintainers' (vs 'inactive/low maintainers') by 62%. 'Sport pattern' showed stronger reductions in mortality for cardiovascular disease and CHD deaths among sport maintainers, than the single time point measures. CONCLUSIONS: PA patterns demonstrated a stronger association with a number of anthropometric and mortality outcomes than the single time-point measures. Operationalising PA as a sustained behavioural pattern may address some of the known under-estimation of risk for poor health in PA self-report measurements and better reflect exposure for epidemiological analysis of risk of health outcomes.

Abstract: BACKGROUND: COPD is a major cause of morbidity and mortality across the world and new estimates of prevalence and trend are of great importance. We aimed to estimate the prevalence and trend of COPD from 1995-1997 to 2006-2008 in Norwegian adults >/=40 years from the Nord-Trondelag Health Study. MATERIAL AND METHODS: COPD was assessed using a fixed-ratio and lower limit of normal (LLN) criteria. Pre-bronchodilator spirometry was performed during 1995-1997 (n=7158) and 2006-2008 (n=8788). The prevalence of COPD was weighted using the inverse probability of selection and predicted probability of response. RESULTS: The prevalence of pre-bronchodilator COPD was 16.7% in 1995-1997 and 14.8% in 2006-2008 using fixed-ratio criteria, and 10.4% in 1995-1997 and 7.3% in 2006-2008 using LLN criteria. The prevalence of LLN COPD was higher among men (13.0% in 1995-1997, 7.7% in 2006-2008) than women (8.0% in 1995-1997, 6.9% in 2006-2008). From 1995-1997 to 2006-2008, the prevalence decreased among men but remained relatively stable among women. Over the 11-year period, the cumulative incidence of pre-bronchodilator COPD using LLN criteria was 3.3% and 2.7% among men and women respectively. The prevalence of self-reported asthma and respiratory symptoms increased. CONCLUSIONS: The prevalence declined in men but not in women from 1995-1997 to 2006-2008, and was consistently higher among men than women.

Abstract: BACKGROUND AND OBJECTIVE: People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. METHODS: In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. RESULTS: The mean decline in forced expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)). The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: -2 mL/year (95% CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: -0.14%/year (95% CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: -4 mL/year (95% CI: -9 to 1)). CONCLUSION: We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

Abstract: OBJECTIVES: To examine associations of total sitting time, TV-viewing and leisure-time computer use with cardiometabolic risk biomarkers in adults. DESIGN: Population based cross-sectional study. METHODS: Waist circumference, BMI, total cholesterol, HDL cholesterol, blood pressure, non-fasting glucose, gamma glutamyltransferase (GGT) and triglycerides were measured in 48,882 adults aged 20 years or older from the Nord-Trondelag Health Study 2006-2008 (HUNT3). Adjusted multiple regression models were used to test for associations between these biomarkers and self-reported total sitting time, TV-viewing and leisure-time computer use in the whole sample and by cardiometabolic disease status sub-groups. RESULTS: In the whole sample, reporting total sitting time >/=10 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, diastolic blood pressure, systolic blood pressure, non-fasting glucose, GGT and triglyceride levels compared to those reporting total sitting time <4h/day (all p<0.05). TV-viewing >/=4 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, systolic blood pressure, GGT and triglycerides compared to TV-viewing <1h/day (all p<0.05). Leisure-time computer use >/=1 h/day was associated with poorer BMI, total cholesterol, diastolic blood pressure, GGT and triglycerides compared with those reporting no leisure-time computing. Sub-group analyses by cardiometabolic disease status showed similar patterns in participants free of cardiometabolic disease, while similar albeit non-significant patterns were observed in those with cardiometabolic disease. CONCLUSIONS: Total sitting time, TV-viewing and leisure-time computer use are associated with poorer cardiometabolic risk profiles in adults. Reducing sedentary behaviour throughout the day and limiting TV-viewing and leisure-time computer use may have health benefits.

Abstract: BACKGROUND: Environment, health behavior, and genetic background are important in the development of obesity. Adolescents spend substantial part of daily leisure time on cultural and social activities, but knowledge about the effects of participation in such activities on weight is limited. METHODS: A number of 1450 adolescents from the Norwegian HUNT study (1995-97) were followed-up in 2006-08 as young adults. Phenotypic data on lifestyle and anthropometric measures were assessed using questionnaires and standardized clinical examinations. Genotypic information on 12 established obesity-susceptibility loci were available for analyses. Generalized estimating equations were used to examine the associations between cultural and social activities in adolescence and adiposity measures in young adulthood. In addition, interaction effects of a genetic predisposition score by leisure time activities were tested. RESULTS: In girls, participation in cultural activities was negatively associated with waist circumference (WC) (B = -0.04, 95%CI: -0.08 to -0.00) and with waist-hip ratio (WHR) (B = -0.058, 95%CI: -0.11 to -0.01). However, participation in social activities was positively associated with WC (B = 0.040, CI: 0.00 to 0.08) in girls and with BMI (B = 0.027, CI: 0.00 to 0.05) in boys. The effect of the obesity-susceptibility genetic variants on anthropometric measures was lower in adolescents with high participation in cultural activities compared to adolescents with low participation. CONCLUSION: This study suggests that the effects of cultural activities on body fat are different from the effects of participation in social activities. The protective influence of cultural activities in female adolescents against overweight in adulthood and their moderating effect on obesity-susceptibility genes suggest that even cultural activities may be useful in public health strategies against obesity.

Abstract: Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 x 10(-8)), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Abstract: CONTEXT: Associations between autoimmune diabetes and autoimmune thyroid disease are known but insufficiently characterized. Some evidence suggests that type 2 diabetes may also be associated with hypothyroidism. OBJECTIVE: The objective of the study was to investigate associations of autoimmune and type 2 diabetes with the prevalence of hypo- and hyperthyroidism. DESIGN AND SETTING: This was a cross-sectional, population-based study of adults in two surveys of the Nord-Trondelag Health (HUNT) Study. PARTICIPANTS: A total of 34 235 participants of HUNT2 (1995-1997) and 48 809 participants of HUNT3 (2006-2008) participated in the study. MAIN OUTCOME MEASURES: Prevalence of hypo- and hyperthyroidism was estimated, assessed by self-report, serum measurements, and linkage with the Norwegian Prescription Database. RESULTS: In HUNT2, autoimmune diabetes was associated with a higher age-adjusted prevalence of hypothyroidism among both women (prevalence ratio 1.79, 95% confidence interval [CI] 1.30-2.47) and men (prevalence ratio 2.71, 95% CI 1.76-4.19), compared with having no diabetes. For hyperthyroidism, the corresponding cumulative prevalence ratios were 2.12 (95% CI 1.36-3.32) in women and 2.54 (95% CI 1.24-5.18) in men with autoimmune diabetes. The age-adjusted excess prevalence of hypothyroidism ( approximately 6 percentage points) and the presence of thyroid peroxidase antibodies (8-10 percentage points) associated with autoimmune diabetes was similar in women and men. Type 2 diabetes was not associated with the prevalence of hypothyroidism. In HUNT3, associations were broadly similar to those in HUNT2. CONCLUSIONS: Autoimmune diabetes, but not type 2 diabetes, was strongly and gender neutrally associated with an increased prevalence of hypo- and hyperthyroidism and the presence of thyroid peroxidase antibodies. Increased surveillance for hypothyroidism appears not necessary in patients with type 2 diabetes.

Abstract: BACKGROUND: A lot of attention has been paid to the relationship of blood pressure and dementia because epidemiological research has reported conflicting evidence. Observational data has shown that midlife hypertension is a risk factor for cognitive decline and dementia later in life, whereas there is evidence that low blood pressure is predictive in later life. The aim of the present study was to examine the association between dementia and blood pressure measured up to 27 years (mean 17.6 years) prior to ascertainment. METHODS: In Nord-Trondelag County, Norway, incident dementia data were collected during 1995-2011, and the diagnoses were validated by a panel of experts in the field. By using the subjects' personal identification numbers, the dementia data were linked to data from the Nord-Trondelag Health Study (the HUNT Study), a large, population-based health study performed in 1984-1986 (HUNT 1) and 1995-1997 (HUNT 2). A total of 24,638 participants of the HUNT Study were included in the present study, 579 of whom were diagnosed with Alzheimer disease, mixed Alzheimer/vascular dementia, or vascular dementia. Multiple logistic regression analyses were conducted to analyze the association between dementia and blood pressure data from HUNT 1 and HUNT 2. RESULTS: Over the age of 60 years, consistent inverse associations were observed between systolic blood pressure and all-cause dementia, mixed Alzheimer/vascular dementia, and Alzheimer disease, but not with vascular dementia, when adjusting for age, sex, education, and other relevant covariates. This was observed for systolic blood pressure in both HUNT 1 and HUNT 2, regardless of antihypertensive medication use. There was an adverse association between systolic blood pressure, pulse pressure, and Alzheimer disease in individuals treated with antihypertensive medication under the age of 60 years. CONCLUSIONS: Our data are in line with those in previous studies demonstrating an inverse association between dementia and systolic blood pressure in individuals over the age of 60 years. We cannot exclude a survival effect, however. Among middle-aged subjects (<60 years), elevated systolic blood pressure and pulse pressure were associated with eventual Alzheimer disease in individuals who reported using antihypertensive medication.

Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

Abstract: BACKGROUND: Current evidence concerning sedentary behaviour and mortality risk has used single time point assessments of sitting. Little is known about how changes in sitting levels over time affect subsequent mortality risk. AIM: To examine the associations between patterns of sitting time assessed at two time points 11 years apart and risk of all-cause and cardio-metabolic disease mortality. METHODS: Participants were 25,651 adults aged > =20 years old from the Nord-Trondelag Health Study with self-reported total sitting time in 1995-1997 (HUNT2) and 2006-2008 (HUNT3). Four categories characterised patterns of sitting: (1) low at HUNT2/ low at HUNT3, 'consistently low sitting'; (2) low at HUNT2/high at HUNT3, 'increased sitting'; (3) high at HUNT2/low at HUNT3, 'reduced sitting'; and (4) high at HUNT2 /high at HUNT3, 'consistently high sitting'. Associations of sitting pattern with all-cause and cardio-metabolic disease mortality were analysed using Cox regression adjusted for confounders. RESULTS: Mean follow-up was 6.2 years (158880 person-years); 1212 participants died. Compared to 'consistently low sitting', adjusted hazard ratios for all-cause mortality were 1.51 (95% CI: 1.28-2.78), 1.03 (95% CI: 0.88-1.20), and 1.26 (95% CI: 1.06-1.51) for 'increased sitting', 'reduced sitting' and 'consistently high sitting' respectively. CONCLUSIONS: Examining patterns of sitting over time augments single time-point analyses of risk exposures associated with high sitting time. Whilst sitting habits can be stable over a long period, life events (e.g., changing jobs, retiring or illness) may influence sitting trajectories and therefore sitting-attributable risk. Reducing sitting may yield mortality risks comparable to a stable low-sitting pattern.