Abstract: OBJECTIVE: In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. MATERIAL AND METHODS: We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995-1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. RESULTS: Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60-2.03] in women and 0.94 [95% CI 0.53-1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17-7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68-1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35-3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. CONCLUSIONS: C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.

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: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

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: BACKGROUND: A wide range in the prevalence (<0.01-0.25%) and incidence (0.5-23.1/100 000) of psoriatic arthritis (PsA) is reported. The main objective of this study was to examine the prevalence and incidence of PsA in central Norway. METHOD: The patients were recruited from the Nord-Trondelag Health Study 3, a population study carried out in 2006-2008. All 94 194 inhabitants aged >20 years were invited and 50 806 (54%) responded. The study consisted of a questionnaire (Q1) and a brief medical examination. Q1 included questions if the persons suffered from psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Patients with self-reported psoriasis further answered a specific questionnaire on psoriasis including a questionnaire concerning PsA. In order to identify patients with PsA we used the following criteria: Persons reporting they had or may have PsA; persons answering that they had psoriasis and RA; and persons answering that they had psoriasis and AS. Using this approach, 1278 patients were identified. Hospital files were evaluated by a rheumatologist according to a predefined protocol to verify the diagnosis of PsA. RESULTS: 338 patients, 144 men and 194 women, were verified to have PsA. The prevalence of PsA was 6.7 (95% CI 5.9 to 7.4) per 1000 inhabitants >20 years with no significant difference between men and women. In the 9-year period of 2000-2008, a total of 188 patients were diagnosed with PsA, which give an incidence rate of 41.3/100 000 (35.8-47.6). CONCLUSIONS: The prevalence of PsA in central Norway appears to be higher than previously reported. The reason for this is unknown and may include environmental factors, life style factors and genetic differences.

Abstract: AIM: To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. METHODS: The Nord-Trondelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995-97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006-08) (n=36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. RESULTS: Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score>/=8 at baseline (OR 1.30 95% CI, 1.07-1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR=1.95 95% CI, 1.02-3.74) for those reporting a HADS-D score of 8-10, and 3-fold (OR=3.06 95% CI, 1.24-7.54) for HADS-D scores>/=11, compared to HADS-D scores

Abstract: The relationship between alcohol consumption and dementia risk is unclear. This investigation estimates the association between alcohol consumption reported in a population-based study in the mid-1980s and the risk for dementia up to 27 years later. The entire adult population in one Norwegian county was invited to the Nord-Trondelag Health Study during 1984-1986 (HUNT1): 88 % participated. The sample used in this study includes HUNT1 participants born between 1905 and 1946 who completed the questionnaire assessing alcohol consumption. A total of 40,435 individuals, of whom 1084 have developed dementia, are included in the analysis adjusted for age, sex, years of education, hypertension, obesity, smoking, and symptoms of depression. When adjusting for age and sex, and compared to reporting consumption of alcohol 1-4 times during the last 14 days (drinking infrequently), both abstaining from alcohol and reporting consumption of alcohol five or more times (drinking frequently) were statistically significantly associated with increased dementia risk with hazard ratios of 1.30 (95 % CI 1.05-1.61) and 1.45 (1.11-1.90), respectively. In the fully adjusted analysis, drinking alcohol frequently was still significantly associated with increased dementia risk with a hazard ratio of 1.40 (1.07-1.84). However, the association between dementia and abstaining from alcohol was no longer significant (1.15, 0.92-1.43). Equivalent results for Alzheimer's disease and vascular dementia indicated the same patterns of associations. When adjusting for other factors associated with dementia, frequent alcohol drinking, but not abstaining from alcohol, is associated with increased dementia risk compared to drinking alcohol infrequently.

Abstract: BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trondelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromso study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria >/=30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

Abstract: The impact of low vitamin D status on asthma development is unclear. The authors investigated the relation between the baseline serum 25-hydroxyvitamin D (25(OH)D) level and incident asthma in adults, including possible effect modification by allergy status, using allergic rhinitis as a proxy measure. A cohort of 25,616 Norwegian adults aged 19-55 years participated in 2 surveys of the Nord-Trondelag Health Study known as HUNT 2 (1995-1997) and HUNT 3 (2006-2008). Of this cohort, a nested case-control study included 584 new-onset asthma cases and 1,958 nonasthma controls whose baseline serum 25(OH)D levels were measured. After adjustment for potential asthma risk factors, the baseline serum level of 25(OH)D (<50 nmol/L) was not significantly associated with asthma in either women (adjusted odds ratio = 0.94, 95% confidence interval (CI): 0.67, 1.32) or men (adjusted odds ratio = 1.47, 95% CI: 0.93, 2.32). In men, allergic rhinitis modified the association with the adjusted odds ratio being 0.87 (95% CI: 0.36, 2.06) among men with allergic rhinitis and 2.32 (95% CI: 1.06, 5.10) among men without allergic rhinitis. The serum 25(OH)D level was not associated with incident asthma in women, regardless of allergy status. Low vitamin D status was not significantly associated with incident asthma in most adults, but it may have increased risk among men without allergy.

Abstract: AIMS: To examine whether physical activity and adiposity modify the increased risk of cancer associated with diabetes. METHODS: We prospectively examined the association of diabetes and risk of cancer among 73,726 persons stratified by physical activity and body mass index (BMI). Adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were estimated from Cox regression. RESULTS: During a median follow-up of 22.0 years, 9572 people were diagnosed with incident cancer. There was no clear association between diabetes and cancer risk in those reporting high levels of physical activity (>/=2.0h per week) (HR 0.93; 95% CI: 0.70-1.24) or those with a normal weight (BMI

Abstract: BACKGROUND: A new, high-sensitivity assay for cardiac troponin I (hs-cTnI)11 permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying pathophysiological mechanisms and prognostic implications are unclear. The aim of this study was to assess the potential impact of sex on the association between hs-cTnI and cardiovascular death. METHODS: By use of the Architect STAT High-Sensitive Troponin assay, we measured hs-cTnI in 4431 men and 5281 women aged >/=20 years participating in the prospective observational Nord-Trondelag Health Study (HUNT). RESULTS: hs-cTnI was detectable in 98.5% of men and 94.7% of women. During a mean follow-up period of 13.9 years, 708 cardiovascular deaths were registered. hs-cTnI was associated with the incidence of cardiovascular death [adjusted hazard ratio (HR) per 1 SD in log hs-cTnI 1.23 (95% CI 1.15-1.31)], with higher relative risk in women than men [HR 1.44 (1.31-1.58) vs 1.10 (1.00-1.20); Pinteraction

Abstract: BACKGROUND: Staphylococcus aureus is one of the most common and lethal causes of bloodstream infection and the incidence is increasing. We carried out a prospective observational study of patients with Staphylococcus aureus bloodstream infection and sepsis in Nord-Trondelag county in Norway from 1996-2011. The main outcome of interest was all-cause mortality within 30 and 90 days. METHODS: Positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were retrospectively registered from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between clinical characteristics and mortality was studied using logistic regression analysis, and adjusted 30- and 90-day mortality risks were estimated. RESULTS: Among 373 patients, the median age was 74 years and 60.3% were male. 0.8% of the patients were diagnosed with MRSA. 29.8% of the patients developed severe sepsis and 12.9% developed septic shock. The all-cause mortality was 14.5%, 27.3% and 36.2% at 7, 30 and 90 days, respectively. Compared to patients with sepsis without organ failure (Mortality risk 13.3%, 95% CI 7.5-16.3%), the 30-day mortality risk was 3-fold higher among those with severe sepsis (39.9%, 95% CI 29.5-48.5%) and more than 4-fold higher for those with septic shock (57.3%, 95% CI 42.5-72.2%). The 30-day all-cause mortality varied by focus of infection, with the highest 30-day mortality risk among those with a pulmonary focus (42.4%, 95% CI 26.0-58.5%) and unknown focus of infection (38.7%, 95% CI 27.5-48.2%). The mortality risk did not differ between the first and second halves of the study period with a 30-day mortality risk of 27.3%, (95% CI 18.1-33.1%) for 1996-2003 versus 27.4% (95% CI 19.4-31.4%) for 2004-2011. The same pattern was seen for 90-day mortality risk. CONCLUSION: Staphylococcus aureus bloodstream infection carries a high case fatality rate, especially among those with severe sepsis and septic shock and among those with a pulmonary or unknown focus of infection. There was no decrease in 30- or 90-day mortality risk during the study period. This underscores the importance of continuing surveillance and efforts to improve the outcome of this serious disease.