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.

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.

Abstract: BACKGROUND: Age at menopause may affect women's subsequent morbidity and mortality. In contrast to numerous other health outcomes, little is known about the possible effects of physical activity on age at menopause. OBJECTIVES: To assess the relationship between leisure-time physical activity and age at menopause. METHODS: Premenopausal women participating in a population-based health survey (HUNT 2) conducted in the county of Nord-Trondelag, Norway reported their physical activity in the period of 1995-1997. Age at menopause was reported during 2006-2008 (HUNT 3). Cox proportional hazards models were used to estimate hazard ratios for menopause and logistic regression to estimate odds ratios for early menopause, with 95% confidence intervals, adjusting for age at menarche, parity, use of oral contraceptives prior to the 6 months preceding participation in HUNT 2, symptoms of depression, smoking status, and education. RESULTS: Women aged 40-49 years at baseline had lower hazard ratios for menopause when participating in any light leisure-time physical activity compared with no activity (p < 0.05) and similar results were observed in 19-39-year-olds. In 50-59-year-old women, the results varied greatly and did not reach statistical significance. CONCLUSIONS: The effects of leisure-time physical activity on age at menopause may be age-dependent. We found indications of earlier menopause for the least active women aged 19-49 years at baseline.

Abstract: BACKGROUND: The association between mental distress and divorce is well established in the literature. Explanations are commonly classified within two different frameworks; social selection (mentally distressed people are selected out of marriage) and social causation (divorce causes mental distress). Despite a relatively large body of literature on this subject, selection effects are somewhat less studied, and research based on data from both spouses is scarce. The purpose of the present study is to investigate selection effects both at the individual level and the couple level. METHODS: The current study is based on couple-level data from a Norwegian representative sample including 20,233 couples. Long-term selection effects were tested for by means of Cox proportional hazard models, using mental distress in both partners at baseline as predictors of divorce the next 16 years. Three identical sets of analyses were run. The first included the total sample, whereas the second and third excluded couples who divorced within the first 4 or 8 years after baseline, respectively. An interaction term between mental distress in husband and in wife was specified and tested. RESULTS: Hazard of divorce was significantly higher in couples with one mentally distressed partner than in couples with no mental distress in all analyses. There was also a significant interaction effect showing that the hazard of divorce for couples with two mentally distressed partners was higher than for couples with one mentally distressed partner, but lower than what could be expected from the combined main effects of two mentally distressed partners. CONCLUSIONS: Our results suggest that mentally distressed individuals are selected out of marriage. We also found support for a couple-level effect in which spouse similarity in mental distress to a certain degree seems to protect against divorce.

Abstract: BACKGROUND: Lifestyle risk behaviours are responsible for a large proportion of disease burden and premature mortality worldwide. Risk behaviours tend to cluster in populations. We developed a new lifestyle risk index by including emerging risk factors (sleep, sitting time, and social participation) and examine unique risk combinations and their associations with all-cause and cardio-metabolic mortality. METHODS: Data are from a large population-based cohort study in a Norway, the Nord-Trondelag Health Study (HUNT), with an average follow-up time of 14.1 years. Baseline data from 1995-97 were linked to the Norwegian Causes of Death Registry. The analytic sample comprised 36 911 adults aged 20-69 years. Cox regression models were first fitted for seven risk factors (poor diet, excessive alcohol consumption, current smoking, physical inactivity, excessive sitting, too much/too little sleep, and poor social participation) separately and then adjusted for socio-demographic covariates. Based on these results, a lifestyle risk index was developed. Finally, we explored common combinations of the risk factors in relation to all-cause and cardio-metabolic mortality outcomes. RESULTS: All single risk factors, except for diet, were significantly associated with both mortality outcomes, and were therefore selected to form a lifestyle risk index. Risk of mortality increased as the index score increased. The hazard ratio for all-cause mortality increased from 1.37 (1.15-1.62) to 6.15 (3.56-10.63) as the number of index risk factors increased from one to six respectively. Among the most common risk factor combinations the association with mortality was particularly strong when smoking and/or social participation were included. CONCLUSIONS: This study adds to previous research on multiple risk behaviours by incorporating emerging risk factors. Findings regarding social participation and prolonged sitting suggest new components of healthy lifestyles and potential new directions for population health interventions.

Abstract: BACKGROUND: The role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear. METHODS: This was a large nationwide cohort study based on data from 11 prospective population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trondelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. RESULT: Among 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95 % CI 1.14-1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95 % CI 0.77-2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95 % CI 0.64-1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48, 95 % CI 1.27-4.85). No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95 % CI 1.05-2.80), hypertension (HR 2.41, 95 % CI 1.44-4.03) and non-fasting glucose (HR 1.74, 95 % CI 1.18-2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men. CONCLUSION: Metabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma.

Abstract: AIMS: To examine whether physical activity and adiposity modify the increased risk of cancer associated with diabetes. METHODS: We prospectively examined the association of diabetes and risk of cancer among 73,726 persons stratified by physical activity and body mass index (BMI). Adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were estimated from Cox regression. RESULTS: During a median follow-up of 22.0 years, 9572 people were diagnosed with incident cancer. There was no clear association between diabetes and cancer risk in those reporting high levels of physical activity (>/=2.0h per week) (HR 0.93; 95% CI: 0.70-1.24) or those with a normal weight (BMI

Abstract: OBJECTIVE: To examine if leisure-time physical activity could cancel out the adverse effect of diabetes on cardiovascular mortality. RESEARCH DESIGN AND METHODS: This study prospectively examined the combined effect of clinical diabetes and reported leisure-time physical activity on cardiovascular mortality. Data on 53,587 Norwegian men and women participating in the population-based Nord-Trondelag Health (HUNT) Study (1995-1997) were linked with the Cause of Death Registry at Statistics Norway. RESULTS: Overall, 1,716 people died of cardiovascular disease during follow-up through 2008. Compared with the reference group of 3,077 physically inactive people without diabetes, 121 inactive people with diabetes had an adjusted hazard ratio (HR) of 2.81 (95% CI 1.93-4.07). The HR (95% CI) among people who reported >/=3 h of light activity per week was 0.89 (0.48-1.63) if they had diabetes (n = 403) and 0.78 (0.63-0.96) if they did not (n = 17,714). Analyses stratified by total activity level showed a gradually weaker association of diabetes with mortality with increasing activity level (P(interaction) = 0.003). CONCLUSIONS: The data suggest that even modest physical activity may cancel out the adverse impact of diabetes on cardiovascular mortality.

Abstract: OBJECTIVE: To assess the predictive value of estimated cardiorespiratory fitness (eCRF) and evaluate the additional contribution of traditional risk factors in cardiovascular disease (CVD) mortality prediction. PARTICIPANTS AND METHODS: The study included healthy men (n=18,721) and women (n=19,759) aged 30 to 74 years. A nonexercise algorithm estimated cardiorespiratory fitness. Cox proportional hazards models evaluated the primary (CVD mortality) and secondary (all-cause, ischemic heart disease, and stroke mortality) end points. The added predictive value of traditional CVD risk factors was evaluated using the Harrell C statistic and net reclassification improvement. RESULTS: After a median follow-up of 16.3 years (range, 0.04-17.4 years), there were 3863 deaths, including 1133 deaths from CVD (734 men and 399 women). Low eCRF was a strong predictor of CVD and all-cause mortality after adjusting for established risk factors. The C statistics for eCRF and CVD mortality were 0.848 (95% CI, 0.836-0.861) and 0.878 (95% CI, 0.862-0.894) for men and women, respectively, increasing to 0.851 (95% CI, 0.839-0.863) and 0.881 (95% CI, 0.865-0.897), respectively, when adding clinical variables. By adding clinical variables to eCRF, the net reclassification improvement of CVD mortality was 0.014 (95% CI, -0.023 to 0.051) and 0.052 (95% CI, -0.023 to 0.127) in men and women, respectively. CONCLUSION: Low eCRF is independently associated with CVD and all-cause mortality. The inclusion of traditional clinical CVD risk factors added little to risk discrimination and did not improve the classification of risk beyond this simple eCRF measurement, which may be proposed as a practical and cost-effective first-line approach in primary prevention settings.

Abstract: AIMS: Socioeconomic inequalities in disability pensioning are well established, but we know little about the causes. The main aim of this study was to disentangle educational inequalities in disability pensioning in Norwegian women and men. METHODS: The baseline data consisted of 32,948 participants in the Norwegian Nord-Trondelag Health Study (1995-97), 25-66 years old, without disability pension, and in paid work. Additional analyses were made for housewives and unemployed/laid-off persons. Information on the occurrence of disability pension was obtained from the National Insurance Administration database up to 2008. Data analyses were performed using Cox regression. RESULTS: We found considerable educational inequalities in disability pensioning, and the incidence proportion by 2008 was higher in women (25-49 years 11%, 50-66 years 30%) than men (25-49 years 6%, 50-66 years 24%). Long-standing limiting illness and occupational, psychosocial, and behavioural factors were not sufficient to explain the educational inequalities: young men with primary education had a hazard ratio of 3.1 (95% CI 2.3-4.3) compared to young men with tertiary education. The corresponding numbers for young women were 2.7 (2.1-3.1). We found small educational inequalities in the oldest women in paid work and no inequalities in the oldest unemployed/laid-off women and housewives. CONCLUSIONS: Illness and occupational, psychosocial, and behavioural factors explained some of the educational inequalities in disability pensioning. However, considerable inequalities remain after accounting for these factors. The higher incidence of disability pensioning in women than men and the small or non-existing educational inequalities in the oldest women calls for a gender perspective in future research.

Abstract: As possible markers of biological age, telomere length (TL) has been associated with age-related diseases such as myocardial infarction (MI) with conflicting findings. We sought to assess the relationship between TL and risk of future MI in 915 healthy participants (51.7% women) 65 years or older from a population-based prospective cohort (the HUNT 2 study, Norway). Mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio, and log-transformed. During a mean follow up of 13.0 (SD, 3.2) years and 11,923 person-years, 82 participants were diagnosed with MI. We used Cox proportional hazard regressions to estimate hazard ratios (HR) and 95% confidence interval (CI). Relative TL was associated with age in women (P=0.01), but not in men (P=0.43). Using relative TL as a continuous variable, we observed a higher risk of MI in participants with longer telomeres with HRs of 2.46 (95% CI; 1.13 to 4.54) in men, and 2.93 (95% CI; 1.41 to 6.10) in women. Each 1-SD change in relative TL was associated with an HR of 1.54 (95% CI; 1.15 to 2.06) and 1.67 (95% CI; 1.18 to 2.37) in men and women, respectively. Compared with the bottom tertile of relative TL, HR of incident MI in top tertile was 2.71 (95% CI; 1.25 to 5.89) in men, and 3.65 (95% CI; 1.35 to 9.90) in women. Longer telomeres in healthy participants 65 years or older are associated with a high risk of incident MI. Future large scale prospective studies are needed to confirm these findings and explore the potential association between TL and MI.

Abstract: RATIONALE, AIMS AND OBJECTIVES: Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. METHODS: We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trondelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). RESULTS: Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality <5.0 and >/=7.0 mmol L(-1) . Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern. CONCLUSION: Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.