Arnulf Langhammer

Cohort Profile: The HUNT Study, Norway

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

The HUNT study: participation is associated with survival and depends on socioeconomic status, diseases and symptoms

BackgroundPopulation 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.MethodsQuestionnaire 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.ResultsParticipation 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.ConclusionNonparticipants 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.

Cigarette smoking gives more respiratory symptoms among women than among men The Nord-Trøndelag Health Study (HUNT)

STUDY OBJECTIVE Studies have indicated that women are more vulnerable to the effect of tobacco smoking compared with men. The aim of this study was to explore the prevalence of reported respiratory symptoms and diseases according to smoking burden, age and sex. DESIGN Questionnaire in a cross sectional population based study. SETTING The BONT (Bronchial obstruction in Nord-Trøndelag) study is part of a comprehensive health survey of all inhabitants aged above 19 years in the county of Nord-Trøndelag, Norway, which was carried out from 1995 to 1997. PARTICIPANTS A total of 65 717 subjects, 71.3% of the total population aged 20–100, answered the main questionnaire. MAIN RESULTS In all, 12.7% men and 12.1% women reported episodes of wheezing or breathlessness during the past 12 months, 8.8% men and 8.4% women reported that they had or had had asthma, 7.5% men and 8.2% women had ever used asthma medication, and 4.0% men and 3.0% women reported chronic bronchitis. Thirty per cent of men and 31% of women were smokers, and average pack years of smoking were 15.9 and 10.3, respectively. Among previous and current smokers, significant more women reported episodes of wheezing or breathlessness, current asthma and persistent coughing compared with men with the same smoke burden (pack years) and daily number of cigarettes. CONCLUSION The prevalence of reported asthma and use of asthma medication was higher than reported in previous Scandinavian studies. Respiratory symptoms increased by smoking burden. Comparing the prevalence of symptoms and current asthma among women and men with the same smoke burden or daily cigarette consumption, women seemed to be more susceptible to the effect of tobacco smoking than men.

Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk.

Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 × 10−8). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.

Sex differences in lung vulnerability to tobacco smoking

Studies have indicated that females are more vulnerable to the deleterious effect of tobacco smoking than males. The current study aimed to investigate the associations between tobacco smoking and reported respiratory symptoms, self-rated health, and lung function by sex. In 1995–1997 65,225 subjects aged ≥20 yrs (71% of invited) attended for screening within the Nord-Trøndelag Health Study. Among these, 10,941 subjects selected randomly or because they reported having asthma or asthma-related symptoms, participated in the Bronchial Obstruction in Nord-Trøndelag study consisting of spirometry and a personal interview. Tobacco smoking was associated with increased prevalence of respiratory symptoms, reduced lung function, and lower score on global self-rated health (SRH). Adjusted for smoking burden and lung function, females had a higher risk for reporting respiratory symptoms and lower SRH compared with males. Further, smoking burden was associated with a larger relative reduction in expiratory lung function in females than in males. Females reported more symptoms and lower self-rated health compared with males with similar smoking burden. Even if smoking in females was associated with a larger reduction in per cent predicted lung function compared with males, this does not fully explain the higher symptom prevalence in females.

Forced spirometry reference values for Norwegian adults: the Bronchial Obstruction in Nord-Trondelag Study

The purpose of this study was to develop new prediction equations for flow/volume spirometry parameters in asymptomatic, never-smoking adults in Norway, and to assess any differences of these parameters when applying the new and most commonly used equation sets. Flow/volume spirometry was measured according to the American Thoracic Society criteria in 2,792 subjects aged > or = 20 yrs, randomly selected from participants in the Nord-Trøndelag Health Study. Ever-smokers and subjects with respiratory symptoms and/or diseases reported in this questionnaire were excluded. A total of 546 females and 362 males met the inclusion criteria and were included in the analyses. Most lung function variables were nonlinear by age and had to be transformed. After a plateau in younger adults, the variables declined by age. The reference values for forced expiratory volume in one second and forced vital capacity from the present study, were higher than those given by prediction equations from the European Community for Coal and Steel, but in closer agreement with later studies from Europe, Australia and the USA. Healthcare providers should be encouraged to reconsider their choice of prediction equations of spirometry in order to improve management of obstructive lung diseases.

Is Headache Related to Asthma, Hay Fever, and Chronic Bronchitis? The Head-HUNT Study

Objectives.—To examine the relationship between migraine and nonmigrainous headache and asthma, hay fever, and chronic bronchitis in a large cross‐sectional population‐based study.

Cross-Sectional and Prospective Cohort Study of Serum 25-Hydroxyvitamin D Level and Obesity in Adults The HUNT Study

Experimental studies suggest that vitamin D modulates the activity of adipocytes. The authors examined baseline serum 25-hydroxyvitamin D (25(OH)D) level in relation to prevalent and cumulative incident obesity in Norway. A cohort of 25,616 adults aged 19-55 years participated in both the second and third surveys of the Nord-Trøndelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)). Serum 25(OH)D levels measured at baseline and anthropometric measurements taken at both baseline and follow-up were available for a random sample of 2,460 subjects. Overall, 40% of the 2,460 subjects had a serum 25(OH)D level less than 50.0 nmol/L, and 37% had a level of 50.0-74.9 nmol/L. The prevalence and cumulative incidence of obesity, defined as body mass index (weight (kg)/height (m)(2)) ≥30, were 12% and 15%, respectively. Lower serum 25(OH)D level was associated with a higher prevalence of obesity. In the 2,165 subjects with baseline BMI less than 30, a serum 25(OH)D level less than 50.0 nmol/L was associated with a significantly increased odds ratio for incident obesity during follow-up (adjusted odds ratio = 1.73, 95% confidence interval: 1.24, 2.41). When prevalent and incident obesity were classified according to waist circumference (≥88 cm for women, ≥102 cm for men), similar results were obtained. In addition to prevalent obesity, a serum 25(OH)D level less than 50.0 nmol/L was significantly associated with new-onset obesity in adults.

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

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

General and abdominal obesity and incident asthma in adults: the HUNT study

Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. While high BMI has been established as a risk factor for asthma in adults, waist circumference has seldom been investigated. To determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trøndelag, Norway in 1995–2008. Baseline BMI and waist circumference were measured and categorised as general obesity (BMI ≥30.0 kg·m2) and abdominal obesity (waist circumference ≥88 cm in females and ≥102 cm in males). Incident asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds ratios for asthma associated with obesity were calculated using multivariable logistic regression. General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52–2.52) and males (OR 1.84, 95% CI 1.30–2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04–2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone.