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1.  The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies 
Background
Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies.
Methods
Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18–80 years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI ≥ 30 kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease.
Results
Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes.
Conclusions
Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics defining the metabolically healthy obese phenotype across ten cohort studies. There is considerable variability in the prevalence of healthy obesity across the different European populations studied, even when unified criteria were used to classify this phenotype.
doi:10.1186/1472-6823-14-9
PMCID: PMC3923238  PMID: 24484869
Harmonization; Obesity; Metabolic syndrome; Cardiovascular disease; Metabolically healthy
2.  Social and spatial patterns of obesity diffusion over three decades in a Norwegian county population: the HUNT Study 
BMC Public Health  2013;13:973.
Background
In order to develop effective preventive strategies, knowledge of trends in socioeconomic and geographical differences in risk factor levels is important. The objective of this study was to examine social and spatial patterns of obesity diffusion in a Norwegian population during three decades.
Methods
Data on adults aged 30–69 years from three cross-sectional health surveys eleven years apart in the Nord-Trøndelag Health Study, Norway, HUNT1 (1984–1986), HUNT2 (1995–1997) and HUNT3 (2006–2008) were utilized. Body mass index (BMI) was used as a measure of obesity. Height and weight were measured clinically. Age standardized prevalences, absolute prevalence differences and ratios, prevalence odds ratios for BMI and the Relative Index of Inequality (RII) were calculated. Multilevel statistical models were fitted for analysing geographical patterns.
Results
The prevalence of obesity was systematically higher in groups with lower socio-economic status and increased successively in all groups in the population during the three decades. The relative socioeconomic inequalities in obesity measured by level of education did not change substantially in the period. In HUNT1 (1984–86) obesity was most prevalent among low educated women (14.1%) and in HUNT3 (2006–08) among low educated men (30.4%). The RII for men changed from 2.60 to 1.91 and 2.36 in HUNT1, HUNT2 and HUNT3. In women the RIIs were 1.71, 2.28 and 2.30 correspondingly. However, the absolute obesity prevalence inequalities increased, and a geographical diffusion from central to distal districts was observed from HUNT2 to HUNT3.
Conclusions
The prevalence of obesity increased in all socioeconomic groups in this Norwegian adult county population from the 1980ies up to present time. The data did not suggest increasing relative inequalities, but increasing absolute socioeconomic differences and a geographical diffusion towards rural districts. Public health preventive strategies should be oriented to counteract the obesity epidemic in the population.
doi:10.1186/1471-2458-13-973
PMCID: PMC3853702  PMID: 24138786
3.  Urinary albumin excretion as a marker of endothelial dysfunction in migraine sufferers: the HUNT study, Norway 
BMJ Open  2013;3(8):e003268.
Objective
To investigate urine albumin leakage as a marker of endothelial dysfunction in migraine patients.
Design
A population-based health study.
Participants
303 patients with migraine, 1009 patients with non-migraine headache and 5287 headache-free controls.
Outcomes
The association between urine albumin- to-creatine ratio (ACR) and headache status was investigated in the Nord-Trøndelag Health Study (HUNT-2). Patients were selected in two strata, based on either (1) self-reported hypertension/diabetes (morbid sample) or (2) a random sample. Analyses were performed using analysis of covariance.
Results
There was no association between headache status and ACR in the study population (p=0.23, mean ACR for migraine 1.66, 95% CI 1.31 to 2.01, for non-migraine headache 1.90, 95% CI 1.71 to 2.09 and for no headache 1.73, 95% CI 1.64 to 1.81) after relevant adjustments. Similarly, no association between headache status and ACR was seen when the analysis was stratified for morbid and random samples, or for migraine with and without aura.
Conclusions
We found no evidence of increased urine albumin leakage in migraine sufferers when compared with headache-free controls. This could indicate that systemic endothelial dysfunction is not a prominent feature of migraine.
doi:10.1136/bmjopen-2013-003268
PMCID: PMC3740253  PMID: 23943777
Vascular Medicine
4.  Leisure time activities in adolescence in the presence of susceptibility genes for obesity: risk or resilience against overweight in adulthood? The HUNT study 
BMC Public Health  2012;12:820.
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.
doi:10.1186/1471-2458-12-820
PMCID: PMC3491037  PMID: 22998931
Leisure time activities; Adolescents; Adults; Obesity; Overweight; Obesity-susceptibility loci; Genetic predisposition score
5.  The HUNT study: participation is associated with survival and depends on socioeconomic status, diseases and symptoms 
Background
Population based studies are important for prevalence, incidence and association studies, but their external validity might be threatened by decreasing participation rates. The 50 807 participants in the third survey of the HUNT Study (HUNT3, 2006-08), represented 54% of the invited, necessitating a nonparticipation study.
Methods
Questionnaire data from HUNT3 were compared with data collected from several sources: a short questionnaire to nonparticipants, anonymous data on specific diagnoses and prescribed medication extracted from randomly selected general practices, registry data from Statistics Norway on socioeconomic factors and mortality, and from the Norwegian Prescription Database on drug consumption.
Results
Participation rates for HUNT3 depended on age, sex and type of symptoms and diseases, but only small changes were found in the overall prevalence estimates when including data from 6922 nonparticipants. Among nonparticipants, the prevalences of cardiovascular diseases, diabetes mellitus and psychiatric disorders were higher both in nonparticipant data and data extracted from general practice, compared to that reported by participants, whilst the opposite pattern was found, at least among persons younger than 80 years, for urine incontinence, musculoskeletal pain and headache. Registry data showed that the nonparticipants had lower socioeconomic status and a higher mortality than participants.
Conclusion
Nonparticipants had lower socioeconomic status, higher mortality and showed higher prevalences of several chronic diseases, whilst opposite patterns were found for common problems like musculoskeletal pain, urine incontinence and headache. The impact on associations should be analyzed for each diagnosis, and data making such analyses possible are provided in the present paper.
doi:10.1186/1471-2288-12-143
PMCID: PMC3512497  PMID: 22978749
Epidemiologic studies; Participation rate; Validity; Selection bias; Mortality
6.  Being Normal Weight but Feeling Overweight in Adolescence May Affect Weight Development into Young Adulthood—An 11-Year Followup: The HUNT Study, Norway 
Journal of Obesity  2012;2012:601872.
Objectives. To explore if self-perceived overweight in normal weight adolescents influence their weight development into young adulthood and if so, whether physical activity moderates this association. Methods. A longitudinal study of 1196 normal weight adolescents (13–19 yrs) who were followed up as young adults (24–30 yrs) in the HUNT study. Lifestyle and health issues were assessed employing questionnaires, and standardized anthropometric measurements were taken. Chi square calculations and regression analyses were performed to investigate the associations between self-perceived overweight and change in BMI or waist circumference (WC) adjusted for age, age squared, sex, and other relevant cofactors. Results. Adolescents, defined as being normal weight, but who perceived themselves as overweight had a larger weight gain into young adulthood than adolescents who perceived themselves as normal weight (difference in BMI: 0.66 units [CI95%: 0.1, 1.2] and in WC: 3.46 cm [CI95%: 1.8, 5.1]). Level of physical activity was not found to moderate this association. Conclusions. This study reveals that self-perceived overweight during adolescence may affect development of weight from adolescence into young adulthood. This highlights the importance of also focusing on body image in public health interventions against obesity, favouring a “healthy” body weight taking into account natural differences in body shapes.
doi:10.1155/2012/601872
PMCID: PMC3362140  PMID: 22666556
7.  Does Death of a Family Member Moderate the Relationship between Religious Attendance and Depressive Symptoms? The HUNT Study, Norway 
Background. The death of a family member is a stressful life event and can result in an increased level of depressive symptoms. Previous American research has shown inverse relationships between religious involvement and depression. European investigations are few and findings inconsistent; different contexts may have an important influence on findings. We therefore investigated the relationship between attendance at church/prayer house and depressive symptoms, and whether this relationship was moderated by the death of a close family member, in Norway. Methods. A population-based sample from the Nord-Trøndelag Health Study, Norway (HUNT 3, N = 37,981), was the population examined. Multiple regression and interaction tests were utilised. Results. Religious attendees had lower scores on depressive symptoms than non-attendees; death of a close family member moderated this relationship. The inverse relationships between attendance at church/prayer house and depressive symptoms were greater among those experiencing the death of an immediate family member in the last twelve months compared to those without such an experience, with men's decrease of depressive symptoms more pronounced than women's. Conclusion. In a population-based study in Norway, attendance at church/prayer house was associated with lower depressive symptoms, and the death of a close relative and gender moderated this relationship.
doi:10.1155/2012/396347
PMCID: PMC3359664  PMID: 22655182
8.  Genome-Wide Association Study to Identify Common Variants Associated with Brachial Circumference: A Meta-Analysis of 14 Cohorts 
PLoS ONE  2012;7(3):e31369.
Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.
doi:10.1371/journal.pone.0031369
PMCID: PMC3315559  PMID: 22479309
9.  Anxiety and depression lowers blood pressure: 22-year follow-up of the population based HUNT study, Norway 
BMC Public Health  2011;11:601.
Background
For decades, symptoms of anxiety and depression have been included among psychological factors associated with development of hypertension. Although this has been questioned in recent studies, most findings have been based on a single assessment of mental distress at baseline. We examined these associations using repeated assessments of anxiety, depression and blood pressure.
Methods
Data on 17,410 men and women aged 20 to 67 participating in the Nord-Trøndelag Health Study (HUNT) in Norway in 1984-86 were re-examined 11 and 22 years later. The main outcome was change in mean blood pressure (mm Hg) during follow-up.
Results
We found that a high symptom level score (≥80th percentile) of combined anxiety and depression at baseline, as compared to a lower symptom level, was associated with lower mean systolic (-0.67 mm Hg, p = 0.044) and diastolic (-0.25 mm Hg, p = 0.201) blood pressure at year 22. A high symptom level present at all three examinations was associated with a stronger decrease in mean systolic (-1.59 mm Hg, p = 0.004) and diastolic (-0.78 mm Hg, p = 0.019) blood pressure and with a 20% (p = 0.001) lower risk of developing hypertension (BP ≥140/90 mm Hg) at year 22. The associations were only slightly attenuated in multivariate analyses, with no evidence of a mediating effect of alteration in heart rate.
Conclusions
This study do not support previous hypothesis that emotional stress may be a cause of hypertension. Our findings indicate that symptoms of anxiety and depression are associated with decrease in blood pressure, particularly when a high symptom level can be detected over decades.
doi:10.1186/1471-2458-11-601
PMCID: PMC3162525  PMID: 21797992
10.  Body mass index and mortality in elderly men and women: the Tromsø and HUNT studies 
Background
The impact of body mass index (BMI; kg/m2) and waist circumference (WC) on mortality in elderly individuals is controversial and previous research has largely focused on obesity.
Methods
With special attention to the lower BMI categories, associations between BMI and both total and cause-specific mortality were explored in 7604 men and 9107 women aged ≥65 years who participated in the Tromsø Study (1994–1995) or the North-Trøndelag Health Study (1995–1997). A Cox proportional hazards model adjusted for age, marital status, education and smoking was used to estimate HRs for mortality in different BMI categories using the BMI range of 25–27.5 as a reference. The impact of each 2.5 kg/m2 difference in BMI on mortality in individuals with BMI<25.0 and BMI≥25.0 was also explored. Furthermore, the relations between WC and mortality were assessed.
Results
We identified 7474 deaths during a mean follow-up of 9.3 years. The lowest mortality was found in the BMI range 25–29.9 and 25–32.4 in men and women, respectively. Mortality was increased in all BMI categories below 25 and was moderately increased in obese individuals. U-shaped relationships were also found between WC and total mortality. About 40% of the excess mortality in the lower BMI range in men was explained by mortality from respiratory diseases.
Conclusions
BMI below 25 in elderly men and women was associated with increased mortality. A modest increase in mortality was found with increasing BMI among obese men and women. Overweight individuals (BMI 25–29.9) had the lowest mortality.
doi:10.1136/jech.2010.123232
PMCID: PMC3368492  PMID: 21321065
Body mass index; waist circumference; aged; chronic disease; mortality, elderly; mortality si; nutrition; smoking rb
11.  Association of low blood pressure with anxiety and depression: the Nord‐Trøndelag Health Study 
Background
Low blood pressure has mainly been regarded as ideal, but recent studies have indicated an association with depression in elderly people.
Objective
To investigate whether low blood pressure is associated with anxiety and depression in the general population.
Design
Cross‐sectional study.
Setting
Participants in the population‐based Nord‐Trøndelag Health Study (HUNT‐2, 1995–7), Norway.
Participants
60 799 men and women aged 20–89 years filled in the Hospital Anxiety and Depression Scale as part of a general health study. Systolic and diastolic blood pressure was classified in age‐stratified and sex‐stratified centile groups.
Main results
Compared with participants with systolic blood pressure within the 41–60 centile (reference) group, the odds ratio for anxiety was 1.31 (95% confidence intervals (CI) 1.16 to 1.49), for depression 1.22 (95% CI 1.03 to 1.46), and for comorbid anxiety and depression 1.44 (95% CI 1.24 to 1.68) in the group with ⩽5 centile systolic blood pressure. Slightly weaker associations were found of low diastolic blood pressure with anxiety and depression. These associations were similar across sex and age groups. Physical impairment, smoking and angina pectoris influenced the associations only marginally, whereas stroke, myocardial infarction, use of drugs for hypertension, body mass index and several other covariates had no influence.
Conclusions
This study represents epidemiological evidence for an association of low blood pressure with anxiety and depression, which is not caused by cardiovascular disease.
doi:10.1136/jech.2005.044966
PMCID: PMC2465598  PMID: 17183016
13.  Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey 
BMJ : British Medical Journal  2006;333(7577):1047.
Objective To find an effective screening strategy for detecting patients with chronic kidney disease and to describe the natural course of the disease.
Design Eight year follow-up of a cross sectional health survey (the HUNT II study).
Setting Nord-Trøndelag County, Norway
Participants 65 604 people (70.6 % of all adults aged ≥20 in the county).
Main outcome measures Incident end stage renal disease (ESRD) and cardiovascular mortality monitored by individual linkage to central registries.
Results 3069/65 604 (4.7%) people had chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m2), so we would need to screen 20.6 people (95% confidence interval 20.0 to 21.2) to identify one case. Restriction of screening to those with hypertension, diabetes, or age >55 would identify 93.2% (92.4% to 94.0%) of patients with chronic kidney disease, with a number needed to screen of 8.7 (8.5 to 9.0). Restriction of screening according to guidelines of the United States kidney disease outcomes quality initiative (US KDOQI) gave similar results, but restriction according to the United Kingdom's chronic kidney disease guidelines detected only 60.9% (59.1% to 62.8%) of cases. Screening only people with previously known diabetes or hypertension detected 44.2% (42.7% to 45.7%) of all cases, with a number needed to screen of six. During the eight year follow-up only 38 of the 3069 people with chronic kidney disease progressed to end stage renal disease, and the risk was especially low in people without diabetes or hypertension, women, and those aged ≥70 or with a glomerular filtration rate 45-59 ml/min/1.73 m2 at screening. In contrast, there was a high cardiovascular mortality: 3.5, 7.4, and 10.1 deaths per 100 person years among people with a glomerular filtration rate 45-59, 30-44, and <30 ml/min/1.73 m2, respectively.
Conclusion Screening people with hypertension, diabetes mellitus, or age >55 was the most effective strategy to detect patients with chronic kidney disease, but the risk of end stage renal disease among those detected was low.
doi:10.1136/bmj.39001.657755.BE
PMCID: PMC1647344  PMID: 17062598
14.  Gender differences in health care use among the elderly population in areas of Norway and Finland. A cross-sectional analysis based on the HUNT study and the FINRISK Senior Survey 
Background
The aim of the study was to examine gender differences in the self-reported use of health care services by the elderly in rural and metropolitan areas of two Nordic countries with slightly different health care systems: Finland and Norway.
Methods
Population based, cross-sectional surveys conducted in Nord-Tröndelag Norway (1995–97) and in rural and metropolitan areas of Finland (1997) were employed. In the Norwegian data, a total of 7,919 individuals, aged 65–74 years old were included, and the Finnish data included 1,500 individuals. The outcome variables comprised whether participants had visited a general practitioner or a specialist, or had received hospital care or physiotherapy during the past 12 months. Gender differences in the use of health care services were analysed by multiple logistic regression, controlling for health status and socio-demographic characteristics.
Results
In Norway, elderly women visited a specialist or were hospitalised less often than men. In Finland, elderly women used all health care services except hospital care more often than men. In Norway, less frequent use of specialist care by women was not associated with self-reported health or chronic diseases.
Conclusion
The findings revealed differences in self-reported use of secondary care among different genders in areas of Norway and Finland.
doi:10.1186/1472-6963-6-110
PMCID: PMC1569836  PMID: 16952306
15.  Estimating the high risk group for cardiovascular disease in the Norwegian HUNT 2 population according to the 2003 European guidelines: modelling study 
BMJ : British Medical Journal  2005;331(7516):551.
Objective To estimate the high risk group for cardiovascular disease in a well defined Norwegian population according to European guidelines and the systematic coronary risk evaluation system.
Design Modelling study.
Setting Nord-Tröndelag health study 1995-7 (HUNT 2), Norway.
Participants 5548 participants of the Nord-Tröndelag health study 1995-7, aged 40, 50, 55, 60, and 65.
Main outcome measures Distribution of risk categories for cardiovascular disease, with emphasis on the high risk group.
Main results At age 40, 22.5% (95% confidence interval 19.3% to 25.7%) of women and 85.9% (83.2% to 88.6%) of men were at high risk of cardiovascular disease. Corresponding numbers at age 50 were 39.5% (35.9% to 43.1%) and 88.7% (86.3% to 91.0%) and at age 65 were 84.0% (80.6% to 87.4%) and 91.6% (88.6% to 94.1%). At age 40, one out of 10 women and no men would be classified at low risk for cardiovascular disease.
Conclusion Implementation of the 2003 European guidelines on prevention of cardiovascular disease in clinical practice would classify most adult Norwegians at high risk for fatal cardiovascular disease.
doi:10.1136/bmj.38555.648623.8F
PMCID: PMC1200589  PMID: 16103030

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