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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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Bye, A., Rosjo, H., Aspenes, S. T., Condorelli, G., Omland, T., & Wisloff, U. (2013). Circulating microRNAs and aerobic fitness--the HUNT-Study. PLoS One, 8(2), e57496.
Abstract: Aerobic fitness, measured as maximal oxygen uptake (VO2max), is a good indicator of cardiovascular health, and a strong predictor of cardiovascular mortality. Biomarkers associated with low VO2max may therefore represent potential early markers of future cardiovascular disease (CVD). The aim of this study was to assess whether circulating microRNAs (miRs) are associated with VO2max-level in healthy individuals. In a screening study, 720 miRs were measured in serum samples from healthy individuals (40-45 yrs) with high (n = 12) or low (n = 12) VO2max matched for gender, age and physical activity. Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05). In addition, miR-21 was increased in male participants with low VO2max (p<0.05). There were no correlations between traditional risk factors for CVD (blood pressure, cholesterol, smoking habit, or obesity) and miR-21, miR-210 and miR-222. DIANA-mirPath identified 611 potential gene-targets of miR-21, miR-210 and miR-222, and pathway analysis indicated alterations in several important signaling systems in subjects with low VO2max. Potential bias involve that blood was collected from non-fasting individuals, and that 8 performed exercise within 24 h before sampling. In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max. The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.
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Bye, A., Vettukattil, R., Aspenes, S. T., Giskeodegard, G. F., Gribbestad, I. S., Wisloff, U., et al. (2012). Serum levels of choline-containing compounds are associated with aerobic fitness level: the HUNT-study. PLoS One, 7(7), e42330.
Abstract: BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of people at risk is continuously growing. New methods for early risk prediction are therefore needed to actuate prevention strategies before the individuals are diagnosed with CVD. Several studies report that aerobic fitness level, measured as maximal oxygen uptake (VO(2max)), is the single best predictor of future CVD mortality in healthy people. Based on this, we wanted to study differences between healthy individuals with a large difference in VO(2max)-level to identify new biomarkers of low aerobic fitness that may also have potential as early biomarkers of CVD risk. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 218 healthy individuals with a low VO(2max) (n = 108, 63 women) or high VO(2max) (n = 110, 64 women) were analysed with MR metabolomics. In addition, standard clinical-chemical analyses for glucose, lipids, liver enzymes, micro-CRP, and colorimetric analysis on circulating choline were performed. Individuals in the low VO(2max)-group had increased serum levels of free choline, decreased phosphatidylcholine, increased glucose and decreased unsaturated fatty acids compared to the individuals in the high VO(2max)-group. CONCLUSIONS/SIGNIFICANCE: Aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholine are observed. They should be further studied as potential early markers of CVD risk.
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Fimland, M. S., Vie, G., Holtermann, A., Krokstad, S., & Nilsen, T. I. L. (2018). Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway. Occup Environ Med, 75(1), 23–28.
Abstract: OBJECTIVES: To prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension. METHODS: A population-based cohort study in Norway on 32 362 persons aged 20-65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs. RESULTS: During a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA. CONCLUSIONS: We observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension.
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Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., et al. (2017). Genome-wide physical activity interactions in adiposity – A meta-analysis of 200,452 adults (Vol. 13).
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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Grunseit, A. C., Chau, J. Y., Rangul, V., Holmen, T. L., & Bauman, A. (2017). Patterns of sitting and mortality in the Nord-Trondelag health study (HUNT). Int J Behav Nutr Phys Act, 14(1), 8.
Abstract: BACKGROUND: Current evidence concerning sedentary behaviour and mortality risk has used single time point assessments of sitting. Little is known about how changes in sitting levels over time affect subsequent mortality risk. AIM: To examine the associations between patterns of sitting time assessed at two time points 11 years apart and risk of all-cause and cardio-metabolic disease mortality. METHODS: Participants were 25,651 adults aged > =20 years old from the Nord-Trondelag Health Study with self-reported total sitting time in 1995-1997 (HUNT2) and 2006-2008 (HUNT3). Four categories characterised patterns of sitting: (1) low at HUNT2/ low at HUNT3, 'consistently low sitting'; (2) low at HUNT2/high at HUNT3, 'increased sitting'; (3) high at HUNT2/low at HUNT3, 'reduced sitting'; and (4) high at HUNT2 /high at HUNT3, 'consistently high sitting'. Associations of sitting pattern with all-cause and cardio-metabolic disease mortality were analysed using Cox regression adjusted for confounders. RESULTS: Mean follow-up was 6.2 years (158880 person-years); 1212 participants died. Compared to 'consistently low sitting', adjusted hazard ratios for all-cause mortality were 1.51 (95% CI: 1.28-2.78), 1.03 (95% CI: 0.88-1.20), and 1.26 (95% CI: 1.06-1.51) for 'increased sitting', 'reduced sitting' and 'consistently high sitting' respectively. CONCLUSIONS: Examining patterns of sitting over time augments single time-point analyses of risk exposures associated with high sitting time. Whilst sitting habits can be stable over a long period, life events (e.g., changing jobs, retiring or illness) may influence sitting trajectories and therefore sitting-attributable risk. Reducing sitting may yield mortality risks comparable to a stable low-sitting pattern.
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Gudmundsdottir, S. L., Flanders, W. D., & Augestad, L. B. (2013). Physical activity and cardiovascular risk factors at menopause: the Nord-Trondelag health study. Climacteric, 16(4), 438–446.
Abstract: BACKGROUND: Lowered physical activity levels may partially explain changes in metabolic risk factors in women after menopause. OBJECTIVES: To evaluate the association between physical activity and metabolic risk factors at baseline and after 11 years, as well as the change in that association over time in women who were premenopausal and >/= 40 years at baseline. METHODS: Subjects in a Norwegian population-based health survey answered questionnaires and had body and serum measurements during 1995-1997 (HUNT 2) and in a follow-up study during 2006-2008 (HUNT 3). Repeated-measures analyses were used to estimate the association between physical activity and metabolic factors, adjusting for age, smoking status, education, alcohol intake, and parity. Adjustment for hormonal treatment and medication was made, as appropriate. RESULTS: In women remaining premenopausal, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01) and waist-hip ratio (p < 0.01) and higher high density lipoprotein (HDL) cholesterol in HUNT 3 (p < 0.01). In women that were postmenopausal by the time of follow-up, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01), waist-hip ratio (p < 0.01), triglycerides (p < 0.01), and higher total cholesterol (p < 0.05), HDL cholesterol (p < 0.01), and diastolic blood pressure (p < 0.05) in HUNT 3. The association of total physical activity score with weight and waist-hip ratio was stronger in HUNT 3 than in HUNT 2 (p < 0.01). CONCLUSION: Increased physical activity may reduce the risk of adverse outcomes and use of pharmacological management in women of menopausal age.
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Harvey, S. B., Overland, S., Hatch, S. L., Wessely, S., Mykletun, A., & Hotopf, M. (2018). Exercise and the Prevention of Depression: Results of the HUNT Cohort Study. Am J Psychiatry, 175(1), 28–36.
Abstract: OBJECTIVE: The purpose of the present study was to address 1) whether exercise provides protection against new-onset depression and anxiety and 2) if so, the intensity and amount of exercise required to gain protection and, lastly, 3) the mechanisms that underlie any association. METHOD: A “healthy” cohort of 33,908 adults, selected on the basis of having no symptoms of common mental disorder or limiting physical health conditions, was prospectively followed for 11 years. Validated measures of exercise, depression, anxiety, and a range of potential confounding and mediating factors were collected. RESULTS: Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety. The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity. After adjustment for confounders, the population attributable fraction suggests that, assuming the relationship is causal, 12% of future cases of depression could have been prevented if all participants had engaged in at least 1 hour of physical activity each week. The social and physical health benefits of exercise explained a small proportion of the protective effect. Previously proposed biological mechanisms, such as alterations in parasympathetic vagal tone, did not appear to have a role in explaining the protection against depression. CONCLUSIONS: Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety. Relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a substantial number of new cases of depression.
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Hjerkind, K. V., Stenehjem, J. S., & Nilsen, T. I. L. (2017). Adiposity, physical activity and risk of diabetes mellitus: prospective data from the population-based HUNT study, Norway. BMJ Open, 7(1), e013142.
Abstract: BACKGROUND: Physical activity may counteract the adverse effects of adiposity on cardiovascular mortality; however, the evidence of a similar effect on diabetes is sparse. This study examines whether physical activity may compensate for the adverse effect of adiposity on diabetes risk. METHODS: The study population consisted of 38 231 individuals aged 20 years or more who participated in two consecutive waves of the prospective longitudinal Nord-Trondelag Health Study in Norway: in 1984-1986 and in 1995-1997. A Poisson regression model with SEs derived from robust variance was used to estimate adjusted risk ratios of diabetes between categories of body mass index and physical activity. RESULTS: Risk of diabetes increased both with increasing body mass (Ptrend <0.001) and with decreasing physical activity level (Ptrend <0.001 in men and 0.01 in women). Combined analyses showed that men who were both obese and had low activity levels had a risk ratio of 17 (95% CI 9.52 to 30) compared to men who were normal weight and highly active, whereas obese men who reported high activity had a risk ratio of 13 (95% CI 6.92 to 26). Corresponding analysis in obese women produced risk ratios of 15 (95% CI 9.18 to 25) and 13 (95% CI 7.42 to 21) among women reporting low and high activity levels, respectively. CONCLUSIONS: This study shows that overweight and obesity are associated with a substantially increased risk of diabetes, particularly among those who also reported being physically inactive. High levels of physical activity were associated with a lower risk of diabetes within all categories of body mass index, but there was no clear evidence that being physically active could entirely compensate for the adverse effect of adiposity on diabetes risk.
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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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Loe, H., Nes, B. M., & Wisloff, U. (2016). Predicting VO2peak from Submaximal- and Peak Exercise Models: The HUNT 3 Fitness Study, Norway. PloS one, 11(1), e0144873.
Abstract: PURPOSE: Peak oxygen uptake (VO2peak) is seldom assessed in health care settings although being inversely linked to cardiovascular risk and all-cause mortality. The aim of this study was to develop VO2peak prediction models for men and women based on directly measured VO2peak from a large healthy population. METHODS: VO2peak prediction models based on submaximal- and peak performance treadmill work were derived from multiple regression analysis. 4637 healthy men and women aged 20-90 years were included. Data splitting was used to generate validation and cross-validation samples. RESULTS: The accuracy for the peak performance models were 10.5% (SEE = 4.63 mLkg(-1)min(-1)) and 11.5% (SEE = 4.11 mLkg(-1)min(-1)) for men and women, respectively, with 75% and 72% of the variance explained. For the submaximal performance models accuracy were 14.1% (SEE = 6.24 mLkg(-1)min(-1)) and 14.4% (SEE = 5.17 mLkg(-1)min(-1)) for men and women, respectively, with 55% and 56% of the variance explained. The validation and cross-validation samples displayed SEE and variance explained in agreement with the total sample. Cross-classification between measured and predicted VO2peak accurately classified 91% of the participants within the correct or nearest quintile of measured VO2peak. CONCLUSION: Judicious use of the exercise prediction models presented in this study offers valuable information in providing a fairly accurate assessment of VO2peak, which may be beneficial for risk stratification in health care settings.
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Moe, B., Augestad, L. B., & Nilsen, T. I. L. (2013). Diabetes severity and the role of leisure time physical exercise on cardiovascular mortality: the Nord-Trondelag Health study (HUNT), Norway. Cardiovasc Diabetol, 12, 83.
Abstract: BACKGROUND: Physical activity has been associated with lower cardiovascular mortality in people with diabetes, but how diabetes severity influence this association has not been extensively studied. METHODS: We prospectively examined the joint association of diabetes severity, measured as medical treatment status and disease duration, and physical exercise with cardiovascular mortality. A total of 56,170 people were followed up for 24 years through the Norwegian Cause of Death Registry. Cox proportional adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were estimated. RESULTS: Overall, 7,723 people died from cardiovascular disease during the follow-up. Compared to the reference group of inactive people without diabetes, people with diabetes who reported no medical treatment had a hazard ratio (HR) of 1.65 (95% CI: 1.34, 2.03) if they were inactive and a HR of 0.99 (95% CI: 0.68, 1.45) if they reported >/=2.0 hours physical exercise per week. Among people who received oral hypoglycemic drugs or insulin, the corresponding comparison gave HRs of 2.46 (95% CI: 2.08-2.92) and 1.58 (95% CI: 1.21, 2.05), respectively. CONCLUSIONS: The data suggest a more favourable effect of exercise in people with diabetes who used medication than in those who did not, suggesting that physical exercise should be encouraged as a therapeutic measure additional to medical treatment.
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Nes, B. M., Gutvik, C. R., Lavie, C. J., Nauman, J., & Wisloff, U. (2017). Personalized Activity Intelligence (PAI) for Prevention of Cardiovascular Disease and Promotion of Physical Activity. Am J Med, 130(3), 328–336.
Abstract: PURPOSE: To derive and validate a single metric of activity tracking that associates with lower risk of cardiovascular disease mortality. METHODS: We derived an algorithm, Personalized Activity Intelligence (PAI), using the HUNT Fitness Study (n = 4631), and validated it in the general HUNT population (n = 39,298) aged 20-74 years. The PAI was divided into three sex-specific groups (</=50, 51-99, and >/=100), and the inactive group (0 PAI) was used as the referent. Hazard ratios for all-cause and cardiovascular disease mortality were estimated using Cox proportional hazard regressions. RESULTS: After >1 million person-years of observations during a mean follow-up time of 26.2 (SD 5.9) years, there were 10,062 deaths, including 3867 deaths (2207 men and 1660 women) from cardiovascular disease. Men and women with a PAI level >/=100 had 17% (95% confidence interval [CI], 7%-27%) and 23% (95% CI, 4%-38%) reduced risk of cardiovascular disease mortality, respectively, compared with the inactive groups. Obtaining >/=100 PAI was associated with significantly lower risk for cardiovascular disease mortality in all prespecified age groups, and in participants with known cardiovascular disease risk factors (all P-trends <.01). Participants who did not obtain >/=100 PAI had increased risk of dying regardless of meeting the physical activity recommendations. CONCLUSION: PAI may have a huge potential to motivate people to become and stay physically active, as it is an easily understandable and scientifically proven metric that could inform potential users of how much physical activity is needed to reduce the risk of premature cardiovascular disease death.
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Perreault, K., Bauman, A., Johnson, N., Britton, A., Rangul, V., & Stamatakis, E. (2017). Does physical activity moderate the association between alcohol drinking and all-cause, cancer and cardiovascular diseases mortality? A pooled analysis of eight British population cohorts. Br J Sports Med, 51(8), 651–657.
Abstract: OBJECTIVE: To examine whether physical activity (PA) moderates the association between alcohol intake and all-cause mortality, cancer mortality and cardiovascular diseases (CVDs) mortality. DESIGN: Prospective study using 8 British population-based surveys, each linked to cause-specific mortality: Health Survey for England (1994, 1998, 1999, 2003, 2004 and 2006) and Scottish Health Survey (1998 and 2003). PARTICIPANTS: 36 370 men and women aged 40 years and over were included with a corresponding 5735 deaths and a mean of 353 049 person-years of follow-up. EXPOSURES: 6 sex-specific categories of alcohol intake (UK units/week) were defined: (1) never drunk; (2) ex-drinkers; (3) occasional drinkers; (4) within guidelines (<14 (women); <21 (men)); (5) hazardous (14-35 (women); 21-49 (men)) and (6) harmful (>35 (women) >49 (men)). PA was categorised as inactive (</=7 MET-hour/week), active at the lower (>7.5 MET-hour/week) and upper (>15 MET-hour/week) of recommended levels. MAIN OUTCOMES AND MEASURES: Cox proportional-hazard models were used to examine associations between alcohol consumption and all-cause, cancer and CVD mortality risk after adjusting for several confounders. Stratified analyses were performed to evaluate mortality risks within each PA stratum. RESULTS: We found a direct association between alcohol consumption and cancer mortality risk starting from drinking within guidelines (HR (95% CI) hazardous drinking: 1.40 (1.11 to 1.78)). Stratified analyses showed that the association between alcohol intake and mortality risk was attenuated (all-cause) or nearly nullified (cancer) among individuals who met the PA recommendations (HR (95% CI)). CONCLUSIONS: Meeting the current PA public health recommendations offsets some of the cancer and all-cause mortality risk associated with alcohol drinking.
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