The association between serum 25-hydroxyvitamin D levels and psoriasis in a large population-based cohort: a cross-sectional analysis of The Tromsø Study 2015-16.

BACKGROUND: Case-control studies indicate an association between lower serum 25-hydroxyvitamin D [25(OH)D] levels and psoriasis. Data from larger population-based cohorts including mild cases are sparse. OBJECTIVES: To investigate the association between 25(OH)D and psoriasis in a large population-based cohort, and assess possible effect modification by overweight. METHODS: Data from the Tromsø Study 2015-16 (Tromsø7), which included 19 520 participants from the general population aged 40-79 years, were subjected to a cross-sectional analysis. We assessed the shapes of the relationships between 25(OH)D and psoriasis using fractional polynomials. Odds ratios (ORs) for lifetime and active psoriasis were estimated using logistic regression. Adjusted models included month of blood sampling, body mass index (BMI), age and sex. Two-way and additive interaction between BMI and 25(OH)D were explored. RESULTS: From a total of 19 520 participants [10 203 women (52.3%); mean age 56.3 years (SD 10.4); mean 25[OH]D, 63.4 nmol L-1 (SD 21.9)], 2088 (10.7%) reported lifetime psoriasis and 1179 (6.0%) reported active psoriasis the past 12 months. There was no association between 25(OH)D and lifetime psoriasis [OR per 10 nmol L-1 increase in 25(OH)D 1.02, 95% confidence interval (CI) 0.99-1.04]. The relationship between 25(OH)D and active psoriasis was suggested to be nonlinear, but the model was not significant (P = 0.098). There was evidence for a superadditive effect (i.e. larger than the sum of the factors) of BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1 on the odds for active psoriasis (OR 1.92, 95% CI 1.18-3.12), but not for lifetime psoriasis (OR 1.41, 95% CI 0.93-2.15). There was no evidence for two-way interaction between BMI and 25(OH)D. CONCLUSIONS: This large population-based study found no significant relationship between 25(OH)D and psoriasis. The analysis may have been underpowered to detect a threshold effect in the lower 25(OH)D spectrum. Interaction analysis indicates that high BMI and vitamin D deficiency combined increase the odds of active psoriasis more than the sum of these factors, with an estimated 92% higher odds for active psoriasis in participants with BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1. Providing advice to prevent vitamin D deficiency may be considered in the follow-up of overweight patients with psoriasis.

Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study.

BACKGROUND: Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results. METHODS: In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994-2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality. RESULTS: At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39-6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30-0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03-2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11-3.70). INTERPRETATION: In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.

Occupational physical activity and risk of mortality in women and men: the Tromsø Study 1986-2021.

OBJECTIVE: Associations between occupational physical activity (OPA) and mortality risks are inconclusive. We aimed to examine associations between (1) OPA separately and (2) jointly with leisure time physical activity (LTPA), and risk of all-cause, cardiovascular disease (CVD) and cancer mortality, over four decades with updated exposure and covariates every 6-8 years. METHODS: Adults aged 20-65 years from the Tromsø Study surveys Tromsø3-Tromsø7 (1986-2016) were included. We categorised OPA as low (sedentary), moderate (walking work), high (walking+lifting work) or very high (heavy manual labour) and LTPA as inactive, moderate and vigorous. We used Cox/Fine and Gray regressions to examine associations, adjusted for age, body mass index, smoking, education, diet, alcohol and LTPA (aim 1 only). RESULTS: Of 29 605 participants with 44 140 total observations, 4131 (14.0%) died, 1057 (25.6%) from CVD and 1660 (40.4%) from cancer, during follow-up (median: 29.1 years, 25th-75th: 16.5.1-35.3). In men, compared with low OPA, high OPA was associated with lower all-cause (HR 0.83, 95% CI 0.74 to 0.92) and CVD (subdistributed HR (SHR) 0.68, 95% CI 0.54 to 0.84) but not cancer mortality (SHR 0.99, 95% CI 0.84 to 1.19), while no association was observed for moderate or very high OPA. In joint analyses using inactive LTPA and low OPA as reference, vigorous LTPA was associated with lower all-cause mortality combined with low (HR 0.75, 95% CI 0.64 to 0.89), high (HR 0.67, 95% CI 0.54 to 0.82) and very high OPA (HR 0.74, 95% CI 0.58 to 0.94), but not with moderate OPA. In women, there were no associations between OPA, or combined OPA and LTPA, with mortality. CONCLUSION: High OPA, but not moderate and very high OPA, was associated with lower all-cause and CVD mortality risk in men but not in women. Vigorous LTPA was associated with lower mortality risk in men with low, high and very high OPA, but not moderate OPA.

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer.

BACKGROUND: Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. METHODS: Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. RESULTS: A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33-0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01-1.17 for "Normal-overweight"; HR 1.20; 95% CI 1.07-1.33 for "Normal-obesity"). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. CONCLUSIONS: In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight.

Machine-learning-derived heart and brain age are independently associated with cognition.

BACKGROUND AND PURPOSE: A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated. METHODS: Using 12-lead electrocardiograms, heart age was estimated for a population-based sample (N = 7779, age 40-85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis. RESULTS: Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3-36) of the HDA effect on the tapping test score was mediated through BDA. DISCUSSION: Heart delta age, representing the cumulative effects of life-long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA.

Ten-year mortality among older male recreational endurance athletes in the Birkebeiner Aging Study in comparison with older men from the Tromsø Study.

BACKGROUND: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long-term endurance training is unclear. Thus, we aimed to examine 10-year mortality in older male endurance athletes compared with an older male general population. METHOD: Male athletes (n = 503) participating in an annual long-distance ski race (median years of participation: 14, range: 1-53) from the Norwegian Birkebeiner Aging study (BiAS), and non-athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self-reported leisure-time PA with all-cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. RESULTS: After 10 years (median: 10.4, range: 0.5-11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24-0.49) compared with non-athletes, corresponding to a 15% (95% CI: 12-19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose-response relationship with mortality (p < 0.001). Compared to inactive non-athletes, PA was associated with lower mortality in both active non-athletes and athletes. However, the observed benefit among participants reporting moderate-to-vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14-0.32) than non-athletes (HR: 0.43, 95% CI: 0.31-0.59) (p < 0.01). CONCLUSION: Endurance sport practice was associated with reduced 10-year mortality, beyond the effect of PA in older men. This study suggests that long-term endurance sport practice maintained into older adulthood promotes longevity.

Data from national health registers as endpoints for the Tromsø Study: Correctness and completeness of stroke diagnoses.

AIM: To assess whether stroke diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for the Tromsø Study, a population-based epidemiological study. METHOD: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as the gold standard, we calculated correctness (defined as positive predictive value, PPV) and completeness (defined as sensitivity) of stroke cases in four different data subsets derived from the Norwegian Patient Register and the Norwegian Stroke Register. We calculated the sensitivity and PPV with 95% confidence intervals (CIs) assuming a normal approximation of the binomial distribution. RESULTS: In the Norwegian Stroke Register we found a sensitivity of 79.8% (95% CI 74.2-85.4) and a PPV of 97.5% (95% CI 95.1-99.9). In the Norwegian Patient Register the sensitivity was 86.4% (95% CI 81.6-91.1) and the PPV was 84.2% (95% CI 79.2-89.2). The overall highest levels were found in a subset based on a linkage between the Norwegian Stroke Register and the Norwegian Patient Register, with a sensitivity of 88.9% (95% CI 84.5-93.3), and a PPV of 89.3% (95% CI 85.0-93.6). CONCLUSIONS: Data from the Norwegian Patient Register and from the linked data set between the Norwegian Patient Register and the Norwegian Stroke Register had acceptable levels of correctness and completeness to be considered as endpoint sources for the Tromsø Study Cardiovascular Disease Register. The benefits of using data from national registers as endpoints in epidemiological studies must be weighed against the impact of potentially decreased data quality.

Validity of self-reported educational level in the Tromsø Study.

BACKGROUND: Self-reported data on educational level have been collected for decades in the Tromsø Study, but their validity has yet to be established. AIM: To investigate the completeness and correctness of self-reported educational level in the Tromsø Study, using data from Statistics Norway. In addition, we explored the consequence of using these two data sources on educational trends in cardiometabolic diseases. METHODS: We compared self-reported and Statistics Norway-recorded educational level (primary, upper secondary, college/university <4 years, and college/university ⩾4 years) among 20,615 participants in the seventh survey of the Tromsø Study (Tromsø7, 2015-2016). Sensitivity, positive predictive value and weighted kappa were used to measure the validity of self-reported educational level in three age groups (40-52, 53-62, 63-99 years). Multivariable logistic regression was used to compare educational trends in cardiometabolic diseases between self-reported and Statistics Norway-recorded educational level. RESULTS: Sensitivity of self-reported educational level was highest among those with a college/university education of 4 years or more (⩾97% in all age groups and both sexes). Sensitivity for primary educational level ranged from 67% to 92% (all age groups and both sexes). The lowest positive predictive value was observed among women with a college/university education of 4 years or more (29-46%). Weighted kappa was substantial (0.52-0.59) among men and moderate to substantial (0.41-0.51) among women. Educational trends in the risk of cardiometabolic diseases were less pronounced when self-reported educational level was used. CONCLUSIONS: Self-reported educational level in Tromsø7 is adequately complete and correct. Self-reported data may produce weaker associations between educational level and cardiometabolic diseases than registry-based data.

Comparing the sociodemographic characteristics of participants and non-participants in the population-based Tromsø Study.

BACKGROUND: Differences in the sociodemographic characteristics of participants and non-participants in population-based studies may introduce bias and reduce the generalizability of research findings. This study aimed to compare the sociodemographic characteristics of participants and non-participants of the seventh survey of the Tromsø Study (Tromsø7, 2015-16), a population-based health survey. METHODS: A total of 32,591 individuals were invited to Tromsø7. We compared the sociodemographic characteristics of participants and non-participants by linking the Tromsø7 invitation file to Statistics Norway, and explored the association between these characteristics and participation using logistic regression. Furthermore, we created a geographical socioeconomic status (area SES) index (low-SES, medium-SES, and high-SES area) based on individual educational level, individual income, total household income, and residential ownership status. We then mapped the relationship between area SES and participation in Tromsø7. RESULTS: Men, people aged 40-49 and 80-89 years, those who were unmarried, widowed, separated/divorced, born outside of Norway, had lower education, had lower income, were residential renters, and lived in a low-SES area had a lower probability of participation in Tromsø7. CONCLUSIONS: Sociodemographic differences in participation must be considered to avoid biased estimates in research based on population-based studies, especially when the relationship between SES and health is being explored. Particular attention should be paid to the recruitment of groups with lower SES to population-based studies.

Device-measured physical activity, sedentary time, and risk of all-cause mortality: an individual participant data analysis of four prospective cohort studies.

OBJECTIVES: To examine whether moderate-to-vigorous physical activity (MVPA) modifies the association between sedentary time and mortality and vice versa, and estimate the joint associations of MVPA and sedentary time on mortality risk. METHODS: This study involved individual participant data analysis of four prospective cohort studies (Norway, Sweden, USA, baseline: 2003-2016, 11 989 participants ≥50 years, 50.5% women) with hip-accelerometry-measured physical activity and sedentary time. Associations were examined using restricted cubic splines and fractional polynomials in Cox regressions adjusted for sex, education, body mass index, smoking, alcohol, study cohort, cardiovascular disease, cancer, and/or diabetes, accelerometry wear time and age. RESULTS: 6.7% (n=805) died during follow-up (median 5.2 years, IQR 4.2 years). More than 12 daily sedentary hours (reference 8 hours) was associated with mortality risk only among those accumulating <22 min of MVPA per day (HR 1.38, 95% CI 1.10 to 1.74). Higher MVPA levels were associated with lower mortality risk irrespective of sedentary time, for example, HR for 10 versus 0 daily min of MVPA was 0.85 (95% CI 0.74 to 0.96) in those accumulating <10.5 daily sedentary hours and 0.65 (95% CI 0.53 to 0.79) in those accumulating ≥10.5 daily sedentary hours. Joint association analyses confirmed that higher MVPA was superior to lower sedentary time in lowering mortality risk, for example, 10 versus 0 daily min of MVPA was associated with 28-55% lower mortality risk across the sedentary time spectrum (lowest risk, 10 daily sedentary hours: HR 0.45, 95% CI 0.31 to 0.65). CONCLUSIONS: Sedentary time was associated with higher mortality risk but only in individuals accumulating less than 22 min of MVPA per day. Higher MVPA levels were associated with lower mortality risk irrespective of the amount of sedentary time.

Obesity Does Not Protect From Subarachnoid Hemorrhage: Pooled Analyses of 3 Large Prospective Nordic Cohorts.

BACKGROUND: Several population-based cohort studies have related higher body mass index (BMI) to a decreased risk of subarachnoid hemorrhage (SAH). The main objective of our study was to investigate whether the previously reported inverse association can be explained by modifying effects of the most important risk factors of SAH-smoking and hypertension. METHODS: We conducted a collaborative study of three prospective population-based Nordic cohorts by combining comprehensive baseline data from 211 972 adult participants collected between 1972 and 2012, with follow-up until the end of 2018. Primarily, we compared the risk of SAH between three BMI categories: (1) low (BMI<22.5), (2) moderate (BMI: 22.5-29.9), and (3) high (BMI≥30) BMI and evaluated the modifying effects of smoking and hypertension on the associations. RESULTS: We identified 831 SAH events (mean age 62 years, 55% women) during the total follow-up of 4.7 million person-years. Compared with the moderate BMI category, persons with low BMI had an elevated risk for SAH (adjusted hazard ratio [HR], 1.30 [1.09-1.55]), whereas no significant risk difference was found in high BMI category (HR, 0.91 [0.73-1.13]). However, we only found the increased risk of low BMI in smokers (HR, 1.49 [1.19-1.88]) and in hypertensive men (HR, 1.72 [1.18-2.50]), but not in nonsmokers (HR, 1.02 [0.76-1.37]) or in men with normal blood pressure values (HR, 0.98 [0.63-1.54]; interaction HRs, 1.68 [1.18-2.41], P=0.004 between low BMI and smoking and 1.76 [0.98-3.13], P=0.06 between low BMI and hypertension in men). CONCLUSIONS: Smoking and hypertension appear to explain, at least partly, the previously reported inverse association between BMI and the risk of SAH. Therefore, the independent role of BMI in the risk of SAH is likely modest.

Drug-Eluting versus Bare-Metal Stents in Saphenous Vein Grafts Compared to Native Coronary Vessels: The Norwegian Coronary Stent Trial Study.

BACKGROUND: Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare-metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The Norwegian Coronary Stent Trial study is the first to randomize lesions to percutaneous coronary intervention in native vessels and SVG. AIMS: The aim of this study was to compare the rate of mortality, MI, and TLR across stent and vessel types. METHODS: In this substudy, 6,087 patients with a single lesion in native vessels and 164 in SVG were followed for 5 years. RESULTS: MI was more frequent in SVG (subdistributional hazard ratio [SHR] 4.95 (3.75-6.54, p < 0.001), but not affected by stent type. In the first 500 days, DES reduced TLR in native vessels (SHR 0.21 (0.15-0.30) p < 0.001) and SVG (SHR 0.18 (0.04-0.80) p = 0.02). Thereafter, DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23-8.94) p = 0.02). After 5 years, the TLR rate was still significantly lower for DES in native vessels (3.2% vs. 7.8%, p < 0.001) but not in SVG (21.4% vs. 18. 4%). CONCLUSION: In SVG, no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and MI in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted.

Longitudinal changes in concentrations of persistent organic pollutants (1986-2016) and their associations with type 2 diabetes mellitus.

BACKGROUND: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality. OBJECTIVES: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases. METHODS: We conducted a longitudinal, nested case-control study (1986-2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points. RESULTS: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p'-DDE, and p,p'-DDT declined more slowly in cases than controls, whereas ß-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide. DISCUSSION: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.

The seventh survey of the Tromsø Study (Tromsø7) 2015-2016: study design, data collection, attendance, and prevalence of risk factors and disease in a multipurpose population-based health survey.

AIMS: The Tromsø Study is an ongoing population-based health study in Tromsø, Norway, initiated in 1974. The purpose of the seventh survey (Tromsø7) 2015-2016 was to advance the population risk factor surveillance and to collect new types of data. We present the study design, data collection, attendance, and prevalence of risk factors and disease. METHODS: All inhabitants in Tromsø municipality, Norway, aged 40 years and older (N=32,591) were invited to a health screening including extensive questionnaires, face-to-face interviews, biological sampling (blood, urine, saliva, nasal/throat swabs, faeces), measurements (anthropometry, blood pressure, pulse, pulse oximetry) and clinical examinations (pain sensitivity, echocardiography, cognitive, physical, and lung function, accelerometer measurements, eye examinations, carotid ultrasound, electrocardiography, dual-energy X-ray absorptiometry, and heart, lung and carotid auscultation). New research areas in this round were dental and oral health examinations, collection of faecal samples for studies of normal bacterial flora and antibiotic resistance, and 24-hour urine samples for examination of sodium and iodine intakes. RESULTS: Attendance was 65% (N=21,083), and was higher in women, age group 50-79 years, previous attenders, and Norwegian-born individuals. Cardiovascular risk factor levels and prevalence of chronic obstructive lung disease decreased since the last survey, while the prevalence of obesity and diabetes increased. CONCLUSIONS: Attendance was stable from the sixth survey. Interaction with participants might be key to maintain participation. Favourable trends in risk factors continue, except for a continued increase in obesity. Both new data collection technology and traditional physical examinations will be crucial for the impact of future population studies.

Long-Term Survival, Causes of Death, and Trends in 5-Year Mortality After Intracerebral Hemorrhage: The Tromsø Study.

BACKGROUND AND PURPOSE: Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades. METHODS: We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression. RESULTS: Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27-2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%; P<0.001). Smoking increased the risk of 5-year mortality in cases and controls (HR, 1.59 [95% CI, 1.15-2.19]), whereas serum cholesterol was associated with 5-year mortality in cases only (HR, 1.39 [95% CI, 1.04-1.86]). Use of anticoagulants at ICH onset increased the risk of death (HR, 2.09 [95% CI, 1.09-4.00]). There was no difference according to ICH location (HR, 1.15 [95% CI, 0.56-2.37]). Five-year mortality did not change during the study period (odds ratio per calendar year, 1.01 [95% CI, 0.93-1.09]). CONCLUSIONS: Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.

Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

BACKGROUND: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity. METHODS: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis. RESULTS: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity. CONCLUSIONS: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development.

Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10-18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10-11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

The bidirectional associations between leisure time physical activity change and body mass index gain. The Tromsø Study 1974-2016.

OBJECTIVES: To examine whether leisure time physical activity changes predict subsequent body mass index (BMI) changes, and conversely, whether BMI changes predict subsequent leisure time physical activity changes. METHODS: This prospective cohort study included adults attending ≥3 consecutive Tromsø Study surveys (time: T1, T2, T3) during 1974-2016 (n = 10779). If participants attended >3 surveys, we used the three most recent surveys. We computed physical activity change (assessed by the Saltin-Grimby Physical Activity Level Scale) from T1 to T2, categorized as Persistently Inactive (n = 992), Persistently Active (n = 7314), Active to Inactive (n = 1167) and Inactive to Active (n = 1306). We computed BMI change from T2 to T3, which regressed on preceding physical activity changes using analyses of covariance. The reverse association (BMI change from T1 to T2 and physical activity change from T2 to T3; n = 4385) was assessed using multinomial regression. RESULTS: Average BMI increase was 0.86 kg/m2 (95% CI: 0.82-0.90) from T2 to T3. With adjustment for sex, birth year, education, smoking and BMI at T2, there was no association between physical activity change from T1 to T2 and BMI change from T2 to T3 (Persistently Inactive: 0.89 kg/m2 (95% CI: 0.77-1.00), Persistently Active: 0.85 kg/m2 (95% CI: 0.81-0.89), Active to Inactive: 0.90 kg/m2 (95% CI: 0.79-1.00), Inactive to Active 0.85 kg/m2 (95% CI: 0.75-0.95), p = 0.84). Conversely, increasing BMI was associated with Persistently Inactive (odds ratio (OR): 1.17, 95% CI: 1.08-1.27, p < 0.001) and changing from Active to Inactive (OR: 1.16, 95% CI: 1.07-1.25, p < 0.001) compared with being Persistently Active. CONCLUSIONS: We found no association between leisure time physical activity changes and subsequent BMI changes, whereas BMI change predicted subsequent physical activity change. These findings indicate that BMI change predicts subsequent physical activity change at population level and not vice versa.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

BACKGROUND: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS: Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

Is the ongoing obesity epidemic partly explained by concurrent decline in cigarette smoking? Insights from a longitudinal population study. The Tromsø Study 1994-2016.

The increase of obesity coincides with a substantial decrease in cigarette smoking. We assessed post-cessation weight change and its contribution to the obesity epidemic in a general population in Norway. A total of 14,453 participants (52.6% women), aged 25-54 years in 1994, who attended at least two of four surveys in the Tromsø Study between 1994 and 2016, were included in the analysis. Hereof 77% participated in both the first and the last survey. Temporal trends in mean body mass index (BMI), prevalence of obesity (BMI ≥ 30 kg/m2) and daily smoking were estimated with generalized estimation equations. We assessed BMI change by smoking status (ex-smoker, quitter, never smoker, daily smoker), and also under a scenario where none quit smoking. In total, the prevalence of daily smoking was reduced over the 21 years between Tromsø 4 (1994-1995) and Tromsø 7 (2015-2016) by 22 percentage points. Prevalence of obesity increased from 5 - 12% in 1994-1995 to 21-26% in 2015-2016, where obesity in the youngest (age 25-44 in 1994) increased more than in the oldest (p < 0.0001). Those who quit smoking had a larger BMI gain compared to the other three smoking subgroups over the 21 years (p < 0.0001). The scenario where none quit smoking would imply a 13% reduction in BMI gain in the population, though substantial age-related differences were noted. We conclude that smoking cessation contributed to the increase in obesity in the population, but was probably not the most important factor. Public health interventions should continue to target smoking cessation, and also target obesity prevention.