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(2017). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants (Vol. 389).
Abstract: BACKGROUND: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. METHODS: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. FINDINGS: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7-128.3) in men and 122.3 mm Hg (121.0-123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9-79.5) for men and 76.7 mm Hg (75.9-77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4-27.1) in men and 20.1% (17.8-22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. INTERPRETATION: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. FUNDING: Wellcome Trust.
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Hoff, M., Meyer, H. E., Skurtveit, S., Langhammer, A., Sogaard, A. J., Syversen, U., et al. (2017). Validation of FRAX and the impact of self-reported falls among elderly in a general population: the HUNT study, Norway. Osteoporos Int, 28(10), 2935–2944.
Abstract: Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) for hip fracture prediction was validated in a Norwegian population 50-90 years. Fracture risk increased with higher FRAX score, and the observed number of hip fractures agreed well with the predicted number, except for the youngest and oldest men. Self-reported fall was an independent risk factor for fracture in women. INTRODUCTION: The primary aim was to validate FRAX without BMD for hip fracture prediction in a Norwegian population of men and women 50-90 years. Secondary, to study whether information of falls could improve prediction of fractures in the subgroup aged 70-90 years. METHODS: Data were obtained from the third survey of the Nord-Trondelag Health Study (HUNT3), the fracture registry in Nord-Trondelag, and the Norwegian Prescription Database (NorPD), including 15,432 women and 13,585 men. FRAX hip without BMD was calculated, and hip fractures were registered for a median follow-up of 5.2 years. The number of estimated and observed fractures was assessed, ROC curves with area under the curve (AUC), and Cox regression analyses. For the group aged 70-90 years, self-reported falls the last year before HUNT3 were included in the Cox regression model. RESULTS: The risk of fracture increased with higher FRAX score. When FRAX groups were categorized in a 10-year percentage risk for hip fracture as follows, <4, 4-7.9, 8-11.9, and >/=12%, the hazard ratio (HR) for hip fracture between the lowest and the highest group was 17.80 (95% CI: 12.86-24.65) among women and 23.40 (13.93-39.30) in men. Observed number of hip fractures agreed quite well with the predicted number, except for the youngest and oldest men. AUC was 0.81 (0.78-0.83) for women and 0.79 (0.76-0.83) for men. Self-reported fall was an independent risk factor for fracture in women (HR 1.64, 1.20-2.24), and among men, this was not significant (1.09, 0.65-1.83). CONCLUSIONS: FRAX without BMD predicted hip fracture reasonably well. In the age group 70-90 years, falls seemed to imply an additional risk among women.
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Jaremko, J. L., Azmat, O., Lambert, R. G., Bird, P., Haugen, I. K., Jans, L., et al. (2017). Validation of a Knowledge Transfer Tool for the Knee Inflammation MRI Scoring System for Bone Marrow Lesions According to the OMERACT Filter: Data from the Osteoarthritis Initiative. J Rheumatol, 44(11), 1718–1722.
Abstract: OBJECTIVE: To assess feasibility and reliability of scoring bone marrow lesions (BML) on knee magnetic resonance imaging (MRI) in osteoarthritis using the Outcome Measures in Rheumatology Knee Inflammation MRI Scoring System (KIMRISS), with a Web-based interface and online training with real-time iterative calibration. METHODS: Six readers new to the KIMRISS (3 radiologists, 3 rheumatologists) scored sagittal T2-weighted fat-saturated MRI in 20 subjects randomly selected from the Osteoarthritis Initiative data, at baseline and 1-year followup. In the KIMRISS, the reader moves a transparent overlay grid within a Web-based interface to fit bones, then clicks or touches each region containing BML per slice, to score 1 if BML is present. Regional and total scores are automatically calculated. Outcomes include the interreader intraclass correlation coefficients (ICC) and the smallest detectable change (SDC). RESULTS: Scoring took 3-12 min per scan and all readers rated the process as moderately to very user friendly. Despite a low BML burden (average score 2.8% of maximum possible) and small changes, interobserver reliability was moderate to high for BML status and change in the femur and tibia (ICC 0.78-0.88). Four readers also scored the patella reliably, whereas 2 readers were outliers, likely because of image artifacts. SDC of 1.5-5.6 represented 0.7% of the maximum possible score. CONCLUSION: We confirmed feasibility of knee BML scoring by new readers using interactive training and a Web-based touch-sensitive overlay system, finding high reliability and sensitivity to change. Further work will include adjustments to training materials regarding patellar scoring, and study in therapeutic trial datasets with higher burden of BML and larger changes.
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Rasouli, B., Andersson, T., Carlsson, P. - O., Grill, V., Groop, L., Martinell, M., et al. (2017). Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). Diabet Med, 34(4), 514–521.
Abstract: AIMS: It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). METHOD: Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. RESULTS: No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). CONCLUSION: The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.
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Naicker, K., Johnson, J. A., Skogen, J. C., Manuel, D., Overland, S., Sivertsen, B., et al. (2017). Type 2 Diabetes and Comorbid Symptoms of Depression and Anxiety: Longitudinal Associations With Mortality Risk. Diabetes Care, 40(3), 352–358.
Abstract: OBJECTIVE: Depression is strongly linked to increased mortality in individuals with type 2 diabetes. Despite high rates of co-occurring anxiety and depression, the risk of death associated with comorbid anxiety in individuals with type 2 diabetes is poorly understood. This study documented the excess mortality risk associated with symptoms of depression and/or anxiety comorbid with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using data for 64,177 Norwegian adults from the second wave of the Nord-Trondelag Health Study (HUNT2), with linkage to the Norwegian Causes of Death Registry, we assessed all-cause mortality from survey participation in 1995 through to 2013. We used Cox proportional hazards models to examine mortality risk over 18 years associated with type 2 diabetes status and the presence of comorbid affective symptoms at baseline. RESULTS: Three clear patterns emerged from our findings. First, mortality risk in individuals with diabetes increased in the presence of depression or anxiety, or both. Second, mortality risk was lowest for symptoms of anxiety, higher for comorbid depression-anxiety, and highest for depression. Lastly, excess mortality risk associated with depression and anxiety was observed in men with diabetes but not in women. The highest risk of death was observed in men with diabetes and symptoms of depression only (hazard ratio 3.47, 95% CI 1.96, 6.14). CONCLUSIONS: This study provides evidence that symptoms of anxiety affect mortality risk in individuals with type 2 diabetes independently of symptoms of depression, in addition to attenuating the relationship between depressive symptoms and mortality in these individuals.
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Simic, A., Hansen, A. F., Asvold, B. O., Romundstad, P. R., Midthjell, K., Syversen, T., et al. (2017). Trace element status in patients with type 2 diabetes in Norway: The HUNT3 Survey. J Trace Elem Med Biol, 41, 91–98.
Abstract: Several epidemiological studies have indicated that a number of trace elements may play a role in type 2 diabetes (T2D). We investigated the association between prevalent T2D and the concentrations of 25 trace elements in whole blood, and the relationships between T2D duration and blood levels of the trace elements that we found to be related to T2D prevalence. In this population based case-control study, 267 patients with self-reported T2D and 609 controls (frequency matched), were selected from the third Nord-Trondelag Health Survey. Trace element blood levels were determined by high resolution inductively coupled plasma-mass spectrometry. Multivariable conditional logistic regression and multivariable linear regression were used to estimate associations. The prevalence of T2D was positively associated with boron, calcium and silver, and inversely associated with indium, lead and magnesium (Ptrend<0.05). We found no statistical evidence for associations between blood levels of arsenic, bromine, cadmium, cesium, chromium, copper, gallium, gold, manganese, mercury, molybdenum, nickel, rubidium, selenium, strontium, tantalum, thallium, tin and zinc and T2D prevalence. After corrections for multiple testing, associations remained significant for calcium and lead (Qtrend<0.05), and borderline significant for magnesium, silver and boron. With increasing disease duration, higher calcium levels were observed (P<0.05). This study suggests an association between prevalent T2D and blood levels of boron, calcium, indium, lead, magnesium and silver.
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Ness-Jensen, E., & Lagergren, J. (2017). Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol, 31(5), 501–508.
Abstract: Gastro-oesophageal reflux disease (GORD) develops when reflux of gastric content causes troublesome symptoms or complications. The main symptoms are heartburn and acid regurgitation and complications include oesophagitis, strictures, Barrett's oesophagus and oesophageal adenocarcinoma. In addition to hereditary influence, GORD is associated with lifestyle factors, mainly obesity. Tobacco smoking is regarded as an aetiological factor of GORD, while alcohol consumption is considered a triggering factor of reflux episodes and not a causal factor. Yet, both tobacco smoking and alcohol consumption can reduce the lower oesophageal sphincter pressure, facilitating reflux. In addition, tobacco smoking reduces the production of saliva rich in bicarbonate, which is important for buffering and clearance of acid in the oesophagus. Alcohol also has a direct noxious effect on the oesophageal mucosa, which predisposes to acidic injury. Tobacco smoking cessation reduces the risk of GORD symptoms and avoidance of alcohol is encouraged in individuals where alcohol consumption triggers reflux.
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Henriksen, A. H., Langhammer, A., Steinshamn, S., Mai, X. - M., & Brumpton, B. M. (2017). The Prevalence and Symptom Profile of Asthma-COPD Overlap: The HUNT Study. Copd, , 1–9.
Abstract: The concept of asthma and COPD as separate conditions has been questioned, and the term asthma-COPD overlap syndrome has been introduced. We assessed the prevalence, symptoms, and lifestyle factors of asthma-COPD overlap (ACO) in a large Norwegian population-based study. From 2006 to 2008, a total of 50,777 residents of Nord-Trondelag participated in the Nord-Trondelag Health Study, Norway. They completed questionnaires regarding respiratory symptoms, disease status, and medication use. We estimated the prevalence and 95% confidence intervals of ACO. Additionally, spirometry was used to estimate the prevalence of ACO in a subgroup. The prevalence of self-reported ACO was 1.9%, and in age groups <40, 40-60 and >/=60 years it was 0.7%, 1.4%, and 3.2%, respectively. Among those reporting COPD, the proportion of ACO was 0.56. In the spirometry subgroup when ACO was defined as doctor diagnosed asthma ever and FEV1/FVC < 0.70, the prevalence of ACO was 2.0%. All respiratory symptoms, separately or in combination, as well as medication use were reported most frequently in those with ACO compared to the other groups. Strikingly, we observed a two-fold higher proportion of allergic rhinitis in ACO compared to COPD only. In this Norwegian population, the prevalence of self-reported ACO was 1.9%, and the corresponding proportion of ACO among those with COPD was 0.56. Participants with ACO generally had the highest proportions of respiratory symptoms compared to asthma or COPD.
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Neumann, L., Dapp, U., Jacobsen, W., van Lenthe, F., & von Renteln-Kruse, W. (2017). The MINDMAP project: mental well-being in urban environments : Design and first results of a survey on healthcare planning policies, strategies and programmes that address mental health promotion and mental disorder prevention for older people in Europe. Z Gerontol Geriatr, 50(7), 588–602.
Abstract: BACKGROUND: The MINDMAP consortium (2016-2019) aims to identify opportunities provided by the urban environment for the promotion of mental well-being and functioning of older people in Europe by bringing together European cities with urban longitudinal ageing studies: GLOBE, HAPIEE, HUNT, LASA, LUCAS, RECORD, Rotterdam Study, Turin Study. A survey on mental healthcare planning policies and programmes dedicated to older persons covering the range from health promotion to need of nursing care was performed for profound data interpretation in Amsterdam, Eindhoven, Hamburg, Helsinki, Kaunas, Krakow, London, Nord-Trondelag, Paris, Prague, Rotterdam and Turin. OBJECTIVES: To collect detailed information on healthcare planning policies and programmes across these European cities to evaluate variations and to delineate recommendations for sciences, policies and planners using experience from evidence-based practice feedback from the MINDMAP cities. MATERIALS AND METHODS: The MINDMAP partners identified experts in the 12 cities with the best background knowledge of the mental health sector. After pretesting, semi-structured telephone interviews (1-2 h) were performed always by the same person. A structured evaluation matrix based on the geriatric functioning continuum and the World Health Organization (WHO) Public Health Framework for Healthy Ageing was applied. RESULTS: A complete survey (12 out of 12) was performed reporting on 41 policies and 280 programmes on the city level. It appeared from extensive analyses that the focus on older citizens, specific target groups, and multidimensional programmes could be intensified. CONCLUSION: There is a broad variety to cope with the challenges of ageing in health, and to address both physical and mental capacities in older individuals and their dynamic interactions in urban environments.
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Johnsen, M. B., Hellevik, A. I., Smastuen, M. C., Langhammer, A., Furnes, O., Flugsrud, G. B., et al. (2017). The mediating effect of body mass index on the relationship between smoking and hip or knee replacement due to primary osteoarthritis. A population-based cohort study (the HUNT Study). PLoS One, 12(12), e0190288.
Abstract: To investigate the total effect of smoking on total hip or knee replacement (THR/TKR) due to primary osteoarthritis (OA) and to quantify the indirect effect of smoking through body mass index (BMI). Participants from the Nord-Trondelag Health Study (the HUNT Study) were linked to the Norwegian Arthroplasty Register to detect the first THR or TKR due to primary OA. A mediation analysis was used to decompose the total effect of smoking into a direct and indirect effect. BMI was considered a mediator in the analysis. All effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). The indirect effect of smoking mediated through BMI was expressed as a percentage (proportion*100). In total 55 188 participants were followed up during 17.2 years (median). We identified 1322 THRs and 754 TKRs. For men, the total effect of current vs. never smoking revealed a decreased risk of THR (HR 0.59, 95% CI 0.46-0.76) and TKR (HR 0.47, 95% CI 0.32-0.66). For women, current smoking increased the risk of THR (HR 1.34, 95% CI 1.11-1.60). For men, 6% and 7% of the risk reduction for THR and TKR, respectively, was mediated by BMI. We found a negative association between smoking and THR or TKR for men. On the contrary, smoking was associated with increased risk of THR for women. Most of the effect of smoking on joint replacement risk remained unexplained by BMI.
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Nordstoga, A. L., Nilsen, T. I. L., Vasseljen, O., Unsgaard-Tondel, M., & Mork, P. J. (2017). The influence of multisite pain and psychological comorbidity on prognosis of chronic low back pain: longitudinal data from the Norwegian HUNT Study. BMJ Open, 7(5), e015312.
Abstract: OBJECTIVES: This study aimed to investigate the prospective influence of multisite pain, depression, anxiety, self-rated health and pain-related disability on recovery from chronic low back pain (LBP). SETTING: The data is derived from the second (1995-1997) and third (2006-2008) wave of the Nord-Trondelag Health Study (HUNT) in Norway. PARTICIPANTS: The study population comprises 4484 women and 3039 men in the Norwegian HUNT Study who reported chronic LBP at baseline in 1995-1997. PRIMARY OUTCOME MEASURES: The primary outcome was recovery from chronic LBP at the 11-year follow-up. Persons not reporting pain and/or stiffness for at least three consecutive months during the last year were defined as recovered. A Poisson regression model was used to estimate adjusted risk ratios (RRs) with 95% CIs. RESULTS: At follow-up, 1822 (40.6%) women and 1578 (51.9%) men reported recovery from chronic LBP. The probability of recovery was inversely associated with number of pain sites (P-trend<0.001). Compared with reporting 2-3 pain sites, persons with only LBP had a slightly higher probability of recovery (RR 1.10, 95% CI 0.98 to 1.22 in women and RR 1.10, 95% CI 1.01 to 1.21 in men), whereas people reporting 6-9 pain sites had substantially lower probability of recovery (RR 0.58, 95% CI 0.52 to 0.63 in women and RR 0.70, 95% CI 0.63 to 0.79 in men). Poor/not so good self-rated general health, symptoms of anxiety and depression, and pain-related disability in work and leisure were all associated with reduced probability of recovery, but there was no statistical interaction between multisite pain and these comorbidities. CONCLUSIONS: Increasing number of pain sites was inversely associated with recovery from chronic LBP. In addition, factors such as poor self-rated health, psychological symptoms and pain-related disability may further reduce the probability of recovery from chronic LBP.
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Borte, S., Winsvold, B. S., Stensland, S. O., Smastuen, M. C., & Zwart, J. - A. (2017). The effect of foetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study. PLoS One, 12(4), e0175908.
Abstract: BACKGROUND: There is little knowledge about how factors early in life affect the development of migraine and tension-type headache. We aimed to examine whether growth restriction in utero is associated with development of migraine and frequent tension-type headache in adults. METHODS: The population-based Nord-Trondelag Health Study (HUNT 3) contained a validated headache questionnaire, which differentiated between migraine and tension-type headache. These data were linked to information on weight and gestational age at birth from the Norwegian Medical Birth Registry. In total 4557 females and 2789 males, aged 19-41 years, were included in this registry-based study. Participants were categorized as appropriate for gestational age (AGA, 10th-90th percentile), small for gestational age (SGA, 3rd-10th percentile) or very small for gestational age (VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for migraine and tension-type headache, with exposure being growth restriction at birth. RESULTS: The effect of growth restriction on migraine was modified by sex, with a significant association in males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA were at increased risk of developing migraine (OR 2.73, 95% CI 1.63-4.58, p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96-2.35, p = 0.08) compared to those born AGA. There was no significant association between growth restriction and frequent TTH (p = 0.051). CONCLUSION: Growth restriction was associated with increased risk of migraine in adulthood among males, but not among females. This suggests that migraine might, in part, be influenced by early life events, and that males seem to be particularly vulnerable.
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Karlsen, T., Nauman, J., Dalen, H., Langhammer, A., & Wisloff, U. (2017). The Combined Association of Skeletal Muscle Strength and Physical Activity on Mortality in Older Women: The HUNT2 Study. Mayo Clin Proc, 92(5), 710–718.
Abstract: OBJECTIVE: To assess the isolated and combined associations of leg and arm strength with adherence to current physical activity guidelines with all-cause and cause-specific mortality in healthy elderly women. PATIENTS AND METHODS: This was a prospective cohort study of 2529 elderly women (72.6+/-4.8 years) from the Norwegian Healthy survey of Northern Trondelag (second wave) (HUNT2) between August 15, 1995, and June 18, 1997, with a median of 15.6 years (interquartile range, 10.4-16.3 years) of follow-up. Chair-rise test and handgrip strength performances were assessed, and divided into tertiles. The hazard ratio (HR) of all-cause and cause-specific mortality by tertiles of handgrip strength and chair-rise test performance, and combined associations with physical activity were estimated by using Cox proportional hazard regression models. RESULTS: We observed independent associations of physical activity and the chair-rise test performance with all-cause and cardiovascular mortality, and between handgrip strength and all-cause mortality. Despite following physical activity guidelines, women with low muscle strength had increased risk of all-cause mortality (HR chair test, 1.37; 95% CI, 1.07-1.76; HR handgrip strength, 1.39; 95% CI, 1.05-1.85) and cardiovascular disease mortality (HR chair test, 1.57; 95% CI, 1.01-2.42). Slow chair-test performance was associated with all-cause (HR, 1.32; 95% CI, 1.16-1.51) and cardiovascular disease (HR, 1.41; 95% CI, 1.14-1.76) mortality. The association between handgrip strength and all-cause mortality was dose dependent (P value for trend <.01). CONCLUSION: Handgrip strength and chair-rise test performance predicted the risk of all-cause and CVD mortality independent of physical activity. Clinically feasible tests of skeletal muscle strength could increase the precision of prognosis, even in elderly women following current physical activity guidelines.
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Johnsen, M. B., Vie, G. A., Winsvold, B. S., Bjorngaard, J. H., Asvold, B. O., Gabrielsen, M. E., et al. (2017). The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study. Osteoarthritis Cartilage, 25(6), 817–823.
Abstract: OBJECTIVE: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal. METHOD: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex. RESULTS: Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results. CONCLUSION: This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association.
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Modalsli, E. H., Asvold, B. O., Snekvik, I., Romundstad, P. R., Naldi, L., & Saunes, M. (2017). The association between the clinical diversity of psoriasis and depressive symptoms: the HUNT Study, Norway. J Eur Acad Dermatol Venereol, 31(12), 2062–2068.
Abstract: BACKGROUND: While a number of observational hospital-based studies have reported an association between psoriasis and depression, less is known about the clinical diversity of psoriasis and depressive symptoms. OBJECTIVE: To investigate the associations of inverse psoriasis, psoriasis severity and psoriasis duration with depressive symptoms in a general population. METHODS: We linked data from the population-based third Nord-Trondelag Health Study (HUNT3) to the Norwegian Prescription Database (NorPD) and Statistics Norway. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Associations between psoriasis and depressive symptoms (HADS >/= 8) were estimated using logistic regression. RESULTS: Among 37 833 participants in HUNT3, we found a weak association between any psoriasis and the prevalence of depressive symptoms [fully adjusted odds ratio (OR) 1.12, 95% confidence interval (CI) 0.97-1.28]. The association with depressive symptoms was stronger when psoriasis was characterized by inverse anatomical distribution (OR 1.32, 95% CI 1.02-1.70), requirement of systemic psoriasis medication (OR 1.47, 95% CI 1.00-2.17) or long disease duration (OR 1.33, 95% CI 1.09-1.64). Conversely, when there was no inverse psoriasis distribution, no requirement of systemic medication, or shorter disease duration, psoriasis was not meaningfully associated with depressive symptoms. CONCLUSION: Overall, depressive symptoms do not seem to be a major concern among subjects with psoriasis in a general Norwegian population. However, among subjects with inverse anatomical distribution, requirement of systemic psoriasis medication or long disease duration, depressive symptoms may be particularly important to address when evaluating the burden of psoriasis.
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Thomsen, L. C. V., McCarthy, N. S., Melton, P. E., Cadby, G., Austgulen, R., Nygard, O. K., et al. (2017). The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia. J Hypertens, 35(1), 132–139.
Abstract: OBJECTIVE: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia. METHODS: We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model. RESULTS: The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53-0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case-control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83-1.32, minor allele frequency = 0.15). CONCLUSION: MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.
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Vie, G. A., Pape, K., Krokstad, S., Johnsen, R., & Bjorngaard, J. H. (2017). Temporal changes in health within 5 years before and after disability pension-the HUNT Study. Eur J Public Health, 27(4), 653–659.
Abstract: Background: Health status has been reported to change before, during and after disability pension receipt. These associations might be subject to temporal changes according to changes in policy, incidence of disability pensions and other contextual factors. We compared the perceived health around time of disability retirement among persons receiving disability pension in the 1990 s and 2000 s in Norway. Methods: We linked data from two consecutive cross-sectional population based Norwegian health surveys, HUNT2 (1995-97) and HUNT3 (2006-08), to national registries, identifying those who received disability pension within 5 years before or after participation in the survey (HUNT2: n = 5362, HUNT3: n = 4649). We used logistic regression to assess associations of time from receiving a disability pension with self-rated health, insomnia, depression and anxiety symptoms and subsequently estimated adjusted prevalence over time. Results: Prevalence of poor self-rated health peaked around time of receiving disability pension in both decades. For those aged 50+, prevalence the year before disability pension was slightly lower in 2006-08 (74%, 95% CI 70-79%) than in 1995-97 (83%, 95% CI 79-87%), whereas peak prevalence was similar between surveys for those younger than 50. Depression symptoms peaked more pronouncedly in 1995-97 than in 2006-08, whereas prevalence of anxiety symptoms was similar at time of receiving disability pension between surveys. Conclusions: We found no strong evidence of differences in health selection to disability pension in the 2000 s compared to the 1990 s. However, we found indication of less depression symptoms around time of disability pension in the 2000 s compared to the 1990 s.
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Webb, T. R., Erdmann, J., Stirrups, K. E., Stitziel, N. O., Masca, N. G. D., Jansen, H., et al. (2017). Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. J Am Coll Cardiol, 69(7), 823–836.
Abstract: BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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Naicker, K., Overland, S., Johnson, J. A., Manuel, D., Skogen, J. C., Sivertsen, B., et al. (2017). Symptoms of anxiety and depression in type 2 diabetes: Associations with clinical diabetes measures and self-management outcomes in the Norwegian HUNT study. Psychoneuroendocrinology, 84, 116–123.
Abstract: OBJECTIVE: To determine if symptoms of depression and anxiety are differentially associated with clinical diabetes measures and self-management behaviours in individuals with Type 2 diabetes, and whether these associations vary by patient sex. RESEARCH DESIGN AND METHODS: A cross-sectional analysis using data from 2035 adults with Type 2 diabetes in the Nord-Trondelag Health Study. Multivariate logistic regression was used to explore associations between symptoms of depression and anxiety and waist girth, HDL cholesterol, systolic blood pressure, triglycerides, c-reactive protein, glycemic control, diet adherence, exercise, glucose monitoring, foot checks for ulcers, and the subjective patient experience. Analyses were stratified by sex. RESULTS: Depression was associated with a lower likelihood of avoiding saturated fats (OR=0.20 [95% CI: 0.06, 0.68]) and increased odds of physical inactivity (OR=1.69 [95% CI: 1.37, 2.72]). Anxiety was associated with increased odds of eating vegetables (OR=1.66 [95% CI: 1.02, 2.73]), and an over two-fold increase of feeling that having diabetes is difficult. In women, anxiety was associated with elevated c-reactive protein levels (OR=1.57 [95% CI: 1.05, 2.34]). In men, depressive symptoms were associated with elevated HbA1c (OR=5.00 [95% CI: 1.15, 8.23). CONCLUSIONS: Symptoms of depression and anxiety were differentially associated with some key diabetes-related measures. Our results suggest sex-specific differences with respect to two important clinical outcomes (i.e., anxiety and CRP in women and depression and glycemic control in men). These findings should alert practitioners to the importance of detection and management of psychological symptoms in individuals with Type 2 diabetes.
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Islam, M. K., Folland, S., & Kaarboe, O. M. (2017). Social capital and cigarette smoking: New empirics featuring the Norwegian HUNT data. Econ Hum Biol, 26, 174–185.
Abstract: Using a rich Norwegian longitudinal data set, this study explores the effects of different social capital variables on the probability of cigarette smoking. There are four social capital variables available in two waves of our data set. Our results based on probit (and OLS) analyses (with municipality fixed-effects) show that the likelihood of smoking participation is negatively and significantly associated with social capital attributes, namely, community trust (-0.017), participation in organizational activities (-0.032), and cohabitation (-0.045). Significant negative associations were also observed in panel data, pooled OLS, and random effects models for community trust (-0.024; -0.010) and cohabitation (-0.040; -0.032). Fixed-effects models also showed significant negative effects for cohabitation (-0.018). Estimates of alternative instrumental variables (IV) based on recursive bivariate probit and IV-GMM models also confirmed negative and significant effects for three of its characteristics: cohabitation (-0.030; -0.046), community trust (-0.065; -0.075), and participation in organizational activities (-0.035; -0.046). The limitations of our conclusions are discussed, and the significance of our study for the field of social capital and health is described, along with suggested avenues for future research.
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Lie, T. M., Bomme, M., Hveem, K., Hansen, J. M., & Ness-Jensen, E. (2017). Snus and risk of gastroesophageal reflux. A population-based case-control study: the HUNT study. Scand J Gastroenterol, 52(2), 193–198.
Abstract: OBJECTIVE: Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS). MATERIAL AND METHODS: The study was based on the third Nord-Trondelag health study (HUNT3), a population-based study of all adult residents in Nord-Trondelag County, Norway, performed in 2006-2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression. RESULTS: Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% confidence interval [CI] 0.64-0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00-1.46 and OR 1.41, 95% CI 1.02-1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02-2.16), while those aged between 50-60 and 60-70 years had a reduced risk (OR 0.67, 95% CI 0.49-0.93 and OR 0.51, 95% CI 0.28-0.94, respectively). CONCLUSIONS: Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.
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Ferreira, M. A., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., et al. (2017). Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology (Vol. 49).
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.
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Sun, Y. - Q., Langhammer, A., Skorpen, F., Chen, Y., & Mai, X. - M. (2017). Serum 25-hydroxyvitamin D level, chronic diseases and all-cause mortality in a population-based prospective cohort: the HUNT Study, Norway. BMJ Open, 7(6), e017256.
Abstract: OBJECTIVE: To investigate the association of vitamin D status with all-cause mortality in a Norwegian population and the potential influences of existing chronic diseases on the association. DESIGN: A population-based prospective cohort study. SETTING: Nord-Trondelag County, Norway. PARTICIPANTS: A random sample (n=6613) of adults aged 20 years or older in a cohort. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in blood samples collected at baseline (n=6377). Mortality was ascertained from the Norwegian National Registry. Cox regression models were applied to estimate the HRs with 95% CIs for all-cause mortality in association with serum 25(OH)D levels after adjustment for a wide spectrum of confounding factors as well as chronic diseases at baseline. RESULTS: The median follow-up time was 18.5 years, during which 1539 subjects died. The HRs for all-cause mortality associated with the first quartile level of 25(OH)D (<34.5 nmol/L) as compared with the fourth quartile (>/=58.1 nmol/L) before and after adjustment for chronic diseases at baseline were 1.30 (95% CI 1.11 to 1.51) and 1.27 (95% CI 1.09 to 1.48), respectively. In the subjects without chronic diseases at baseline and with further exclusion of the first 3 years of follow-up, the corresponding adjusted HR was 1.34 (95% CI 1.09 to 1.66). CONCLUSIONS: Low serum 25(OH)D level was associated with increased all-cause mortality in a general Norwegian population. The association was not notably influenced by existing chronic diseases.
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Brunes, A., Flanders, W. D., & Augestad, L. B. (2017). Self-reported visual impairment, physical activity and all-cause mortality: The HUNT Study. Scand J Public Health, 45(1), 33–41.
Abstract: AIMS: To examine the associations of self-reported visual impairment and physical activity (PA) with all-cause mortality. METHODS: This prospective cohort study included 65,236 Norwegians aged 20 years who had participated in the Nord-Trondelag Health Study (HUNT2, 1995-1997). Of these participants, 11,074 (17.0%) had self-reported visual impairment (SRVI). The participants' data were linked to Norway's Cause of Death Registry and followed throughout 2012. Hazard ratios and 95% confidence intervals (CI) were assessed using Cox regression analyses with age as the time-scale. The Cox models were fitted for restricted age groups (<60, 60-84, 85 years). RESULTS: After a mean follow-up of 14.5 years, 13,549 deaths were identified. Compared with adults with self-reported no visual impairment, the multivariable hazard ratios among adults with SRVI were 2.47 (95% CI 1.94-3.13) in those aged <60 years, 1.22 (95% CI 1.13-1.33) in those aged 60-84 years and 1.05 (95% CI 0.96-1.15) in those aged 85 years. The strength of the associations remained similar or stronger after additionally controlling for PA. When examining the joint associations, the all-cause mortality risk of SRVI was higher for those who reported no PA than for those who reported weekly hours of PA. We found a large, positive departure from additivity in adults aged <60 years, whereas the departure from additivity was small for the other age groups. CONCLUSIONS: Adults with SRVI reporting no PA were associated with an increased all-cause mortality risk. The associations attenuated with age.
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Videm, V., Thomas, R., Brown, M. A., & Hoff, M. (2017). Self-reported Diagnosis of Rheumatoid Arthritis or Ankylosing Spondylitis Has Low Accuracy: Data from the Nord-Trondelag Health Study. J Rheumatol, 44(8), 1134–1141.
Abstract: OBJECTIVE: Self-reported diagnoses of inflammatory arthritis are not accurate. The primary study aim was to ascertain self-reported diagnoses of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in the Norwegian population-based Nord-Trondelag Health Study (HUNT) using hospital case files. The secondary aim was to provide updated estimates of the prevalence and incidence of RA and AS. METHODS: All inhabitants >/= 20 years old from the county of Nord-Trondelag were invited. Data from 70,805 unique participants from HUNT2 (1995-1997) and HUNT3 (2006-2008) were included. For participants who self-reported RA or AS, case files from all 3 hospitals in the catchment area were evaluated using standardized diagnostic criteria. RESULTS: Of 2703 self-reported cases of RA, 19.1% were verified in hospital files. Of 1064 self-reported cases of AS, 15.8% were verified. Of 259 cases self-reporting both RA and AS, 8.1% had RA and 5.4% had AS. Overall, a self-report of 1 or both diagnoses could not be verified in 82.1%, including 22.8% with insufficient information or no case file. The prevalence of RA was 768 (95% CI 705-835) per 100,000. The incidence of RA from HUNT2 to HUNT3 was 0.48 (0.41-0.56) per 1000 per year. The prevalence of AS was 264 (228-305) per 100,000. The incidence of AS from HUNT2 to HUNT3 was 0.19 (0.15-0.24) per 1000 per year. CONCLUSION: Self-reported diagnoses of RA and AS are often false-positive. The prevalence and incidence of RA were comparable to reports from similar populations. The incidence of AS was higher than previously reported in a mixed population from Norway.
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