Louise Eriksen

The Danish Health Examination Survey 2007-2008 (DANHES 2007-2008)

Aims: The Danish Health Examination Survey (DANHES 2007—2008) was carried out by the National Institute of Public Health, University of Southern Denmark, in 13 Danish municipalities in 2007—2008. The focus of the survey was diet, smoking, alcohol, and physical activity. The aim of the survey was to establish a research database for future cross-sectional and follow-up studies. Methods: DANHES 2007—2008 included internet-based questionnaires and a health examination. There were two different questionnaires: a basic questionnaire on socio-demography, health behaviour, self-reported health status, and living conditions, and a supplementary food frequency questionnaire. The health examination contained measurements of blood pressure, resting heart rate, height, weight, fat percentage, waist and hip circumference, blood and hair samples, spirometry, bone mineral density, physical performance, muscle strength, and aerobic fitness. Results: A total of 76,484 people completed the basic questionnaire, and 18,065 adult individuals participated in the health examination, corresponding to a response rate of 14% and a participation rate of 10%, respectively. Conclusions: The database from DANHES 2007—2008 is unique in its size and diversity of measurements and questionnaire contents. Data can be linked to various registers through the Danish civil registration system, and blood samples are stored in a biobank allowing for genetic analyses. Hence, DANHES 2007—2008 forms the basis for future research projects with a focus on health behaviour and prevention of lifestyle-related diseases.

A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys

BACKGROUND Treatment of cardiovascular risk factors based on disease risk depends on valid risk prediction equations. We aimed to develop, and apply in example countries, a risk prediction equation for cardiovascular disease (consisting here of coronary heart disease and stroke) that can be recalibrated and updated for application in different countries with routinely available information. METHODS We used data from eight prospective cohort studies to estimate coefficients of the risk equation with proportional hazard regressions. The risk prediction equation included smoking, blood pressure, diabetes, and total cholesterol, and allowed the effects of sex and age on cardiovascular disease to vary between cohorts or countries. We developed risk equations for fatal cardiovascular disease and for fatal plus non-fatal cardiovascular disease. We validated the risk equations internally and also using data from three cohorts that were not used to create the equations. We then used the risk prediction equation and data from recent (2006 or later) national health surveys to estimate the proportion of the population at different levels of cardiovascular disease risk in 11 countries from different world regions (China, Czech Republic, Denmark, England, Iran, Japan, Malawi, Mexico, South Korea, Spain, and USA). FINDINGS The risk score discriminated well in internal and external validations, with C statistics generally 70% or more. At any age and risk factor level, the estimated 10 year fatal cardiovascular disease risk varied substantially between countries. The prevalence of people at high risk of fatal cardiovascular disease was lowest in South Korea, Spain, and Denmark, where only 5-10% of men and women had more than a 10% risk, and 62-77% of men and 79-82% of women had less than a 3% risk. Conversely, the proportion of people at high risk of fatal cardiovascular disease was largest in China and Mexico. In China, 33% of men and 28% of women had a 10-year risk of fatal cardiovascular disease of 10% or more, whereas in Mexico, the prevalence of this high risk was 16% for men and 11% for women. The prevalence of less than a 3% risk was 37% for men and 42% for women in China, and 55% for men and 69% for women in Mexico. INTERPRETATION We developed a cardiovascular disease risk equation that can be recalibrated for application in different countries with routinely available information. The estimated percentage of people at high risk of fatal cardiovascular disease was higher in low-income and middle-income countries than in high-income countries. FUNDING US National Institutes of Health, UK Medical Research Council, Wellcome Trust.

Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity

Oxidatively damaged DNA base lesions are considered to be mainly repaired by 8-oxoguanine DNA glycosylase (OGG1) mediated pathways. We investigated the effect of the OGG1 Ser326Cys polymorphism on the level and repair of oxidatively damaged DNA in mononuclear blood cells (MNBC) by means of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype (Ser/Ser). Carriers of the Cys/Cys genotype had higher levels of formamidopyrimidine DNA glycosylase (FPG) sensitive sites in MNBC (0.31 ± 0.03 lesions/10(6)bp) compared to Ser/Ser (0.19 ± 0.02 lesions/10(6)bp, P<0.01). The level of hOGG1 sensitive sites in MNBC from the Ser326Cys carriers (0.19 ± 0.16 lesions/10(6) bp) was also higher compared to the Ser/Ser genotype (0.11 ± 0.09 lesions/10(6) bp, P<0.05). Still, there was no genotype-related difference in DNA repair incision activity of MNBC extracts on nucleoids with oxidatively damaged DNA induced by Ro19-8022/white light (P=0.20). In addition, there were no differences in the expression of OGG1 (P=0.69), ERCC1 (P=0.62), MUTYH (P=0.85), NEIL1 (P=0.17) or NUDT1 (P=0.48) in whole blood. Our results indicate that the OGG1 Ser326Cys polymorphism has limited influence on the DNA repair incisions by extracts of MNBC, whereas the apparent increased risk of cancer in subjects with the Cys/Cys genotype may be because of higher levels of oxidatively damaged DNA.

Occupational heavy lifting and risk of ischemic heart disease and all-cause mortality

BackgroundOccupational heavy lifting is known to impose a high cardiovascular strain, but the risk of ischemic heart disease (IHD) from occupational heavy lifting is unknown. The objective was to investigate the association between occupational heavy lifting and risk of IHD and all-cause mortality, and the influence of occupational and leisure time physical activity on this association.MethodsData were analyzed from 1987, 1994, and 2000 from the Danish National Health Interview Surveys providing a sample of 6,692 working men and 5,921 working women aged 16–85 years without cardiovascular disease at baseline. Conventional risk factors for the outcomes IHD and all-cause mortality were controlled for in Cox analyses.ResultsAmong men, heavy lifting was associated with increased risk for IHD (hazard ratio (HR): 1.52, 95% Confidence interval (95% CI): 1.15, 2.02), while a decreased risk was associated with occupational (HR: 0.50, 95% CI: 0.37, 0.68) and leisure time (HR: 0.73, 95% CI: 0.56, 0.95) physical activity. Referencing men with high occupational physical activity and no heavy lifting, men with high occupational physical activity and heavy lifting did not have an increased risk (HR: 1.11, 95% CI:0.68, 1.82), while men with low occupational physical activity and heavy lifting had a substantial increased risk (HR: 2.56, 95% CI:1.52, 4.32). No significant associations were found for all-cause mortality or for females.ConclusionThese findings indicate an excessive risk for IHD from occupational heavy lifting among men, particularly among those with low occupational and leisure time physical activity.

Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells

It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18-83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16-1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio (P < 0.05) and plasma concentrations of glycosylated hemoglobin (P = 0.07). However, multivariate regression analysis only showed an inverse association between age and DNA repair activity (P < 0.05), indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary, the results show an inverse association between age and DNA repair activity of oxidatively damaged DNA.

Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.

BACKGROUND Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ≥20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING National Institutes of Health.

Cardiorespiratory fitness in 16 025 adults aged 18-91 years and associations with physical activity and sitting time.

Our aim was to provide up‐to‐date cardiorespiratory fitness reference data for adults of all ages and to investigate associations between cardiores‐piratory fitness and leisure time physical activity as well as sitting time. In the Danish Health Examination Survey 2007–2008, cardiorespiratory fitness was estimated in 16 025 individuals aged 18–91 years from validated cycle ergometer exercise tests. Level of leisure time physical activity (sedentary, light, moderate, and vigorous) and daily sitting time in hours was obtained from a self‐administered questionnaire. Men had 20–33% higher cardiorespiratory fitness than women, depending on age, and cardiorespiratory fitness decreased by 0.26 and 0.23 mL/min/kg per year in men and women, respectively. Cardiorespiratory fitness was higher among participants who reported a high level of physical activity in leisure time compared with participants who were sedentary. Among sedentary or lightly physically active participants, inverse associations between total daily sitting time and cardiorespiratory fitness were found, while there was no association between sitting time and cardiorespiratory fitness among moderately or vigorously physically active participants. These data on cardiorespiratory fitness can serve as useful reference material. Although reluctant to conclude on causality, sitting time might impact cardiorespiratory fitness among individuals with low levels of leisure time physical activity.

Schistosoma japonicum infection and serum and tissue concentrations of retinol and zinc in pigs

The effects of Schistosoma japonicum infection on the concentrations of zinc in serum, liver, spleen and muscle and on the concentrations of retinol in serum and liver were studied in 48 pigs. Twenty-four of the pigs were each infected by intramuscular inoculation with 2000 cercariae of S. japonicum in medium and the rest were similarly inoculated with parasite-free medium, as controls. On each of weeks 4, 11, 17 and 24 post-inoculation (PI), 12 pigs (six of which were infected) were killed. Tissue samples were collected at necropsy. Blood samples were taken prior to infection and at necropsy from all pigs, and bi-weekly from the pigs killed 24 weeks post-infection. In an analysis of variance in which serum retinol was the dependent variable, the interaction infection x time was found to be significant (P = 0.009). The main reason for this significance was that the concentration of retinol in the sera collected from infected pigs at necropsy at 11 weeks PI was significantly lower than in the control pigs killed at the same time (P = 0.02). Although, overall, infection led to higher zinc concentrations in the liver (P = 0.04) and spleen tissue (P = 0.01), it had no apparent effect on liver retinol, muscle zinc or serum zinc. However, among the pigs which were tested bi-weekly, serum zinc was consistently lower in the infected pigs than in the controls (P = 0.01). The transient declines seen in the concentrations of retinol and zinc in sera from the infected pigs were not accompanied by similar changes in the tissue concentrations, and may reflect an acute-phase response to infection. Schistosoma japonicum infection in pigs is considered a useful model of S. japonicum infection (and probably also of S. mansoni infection) in humans. Similar effects, if they occur in the human infections, may lead to misclassification of vitamin-A and zinc status in endemic populations if this status is based on serum retinol and serum zinc.

A Maximal Cycle Test with Good Validity and High Repeatability in Adults of All Ages

In 11 680 individuals (18-85 years) maximal oxygen consumption (VO2max) was estimated indirectly in a maximal cycle test using a prediction model developed in a young population (15-28 years). A subsample of 182 individuals (23-77 years) underwent 2 maximal cycle tests with VO2max estimated indirectly in both tests and measured directly in one test. Agreement between the direct measurement and the indirect estimate of VO2max and repeatability of the indirect estimates of VO2max were examined by Bland-Altman plots, limits of agreement (LOA) and coefficient of repeatability (CR). The indirect method (mean VO2max=3 132 ml · min(-1)) underestimated VO2max as compared to the direct method (mean VO2max=3 190 ml · min(-1)) in men (bias: 58 ml · min(-1) (95% LOA-450 and 565)) and overestimated VO2max in women (mean VO2max=2 328 vs. 2 258 ml · min(-1), bias: - 70 ml · min(-1) (95% LOA-468 and 328)). The mean difference between the 2 indirect estimates was non-significant (men: - 11.9 ml · min(-1), women: 18.3 ml · min(-1)) with a CR of 279 ml · min(-1) (8.9%) in men and 274 ml · min(-1) (11.7%) in women. The validity of the indirect method was good despite minor sex-specific bias. Owing to this bias we suggest a new prediction model of VO2max. The maximal cycle test was highly repeatable.

Development in Alcohol-Related Harm in Denmark 1990–2005

Aims This article, as part of a Nordic project, aims at studying the development of alcohol-related harms in the Danish society in the 1990s and early 2000s, a period when alcohol consumption was stable at a relatively high Nordic level. Data The study is based on data on sales of alcohol and on register data on alcohol-related morbidity, mortality, traffic accidents and the development of violent crimes. Analysis Both total alcohol consumption and alcohol-related harm have been practically unchanged during the period, in spite of large changes in consumption of the different types of alcohol. Pancreatitis mortality and hospitalisations of men due to alcoholism, alcohol psychosis and poisoning have increased, while alcohol-related traffic accidents and detentions due to drunkenness have decreased. These developments may mirror changes in the activities and structure of various authorities. Conclusions To properly estimate the effects of changes in drinking patterns on alcohol-related harms new measures of alcohol-related harms are needed that take into account the attributable etiological fraction of alcohol to for instance coronary heart disease. There is also a need for better measures of social consequences of drinking.