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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.

Aims To study change over 8 years in cardiovascular risk, achievement of national guideline-based treatment targets of lipids, blood pressure (BP) and smoking in primary prevention of cardiovascular disease (CVD), medication use, and characteristics associated with target achievement among individuals with high CVD risk in a general population. Methods and results We followed 2524 women and men aged 40–79 years with high risk of CVD attending the population-based Tromsø study in 2007–08 (Tromsø6) to their participation in the next survey in 2015–16 (Tromsø7). We used descriptive statistics and regression models to study change in CVD risk and medication use, and characteristics associated with treatment target achievement. In total, 71.4% reported use of BP- and/or lipid-lowering medication at second screening. Overall, CVD risk decreased during follow-up, with a larger decrease among medication users compared with non-users. Treatment target achievement was 31.0% for total cholesterol Conclusion We found an overall improvement in CVD risk factors among high-risk individuals over 8 years. However, guideline-based treatment target achievement was relatively low for all risk factors except smoking. Medication use was the strongest characteristic associated with achieving treatment targets. This study has demonstrated that primary prevention of CVD continues to remain a major challenge.

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA

Purpose To describe medication adherence to lipid-lowering drugs (LLDs), antihypertensive drugs, and acetylsalicylic acid (ASA) among persons with coronary heart disease (CHD) and explore its association with low-density-lipoprotein (LDL)-cholesterol, and systolic and diastolic blood pressure. Methods Based on record linkage between the seventh wave of the Tromsø Study and the Norwegian Prescription Database, medication adherence was calculated as the proportion of days covered (PDC) for persistent prevalent users in the period of 365 days before the attendance date. Multivariable linear regression models were used to assess the association between systolic and diastolic blood pressure and medication nonadherence to antihypertensive drugs, age, sex, lifestyle, body mass index (BMI), current and previous diabetes, and between LDL-cholesterol and medication nonadherence to LLDs, age, sex, lifestyle, BMI, and current and previous diabetes. Results Mean PDC was 0.94 for LLDs and antihypertensive drugs and 0.97 for ASA. Among persons with PDC ≥ 0.80 for LLDs, 12.0% had an LDL-cholesterol Conclusion Adherence to antihypertensive drugs, LLDs, and ASA among persons with CHD were high despite low achievement of treatment goals for blood pressure and LDL-cholesterol. There was a statistically significant association between adherence to LLDs and LDL-cholesterol, but not between adherence to antihypertensive drugs and blood pressure.

AimsTo compare the population proportion at high risk of cardiovascular disease (CVD) using the Norwegian NORRISK 1 that predicts 10-year risk of CVD mortality and the Norwegian national guidelines from 2009, with the updated NORRISK 2 that predicts 10-year risk of both fatal and non-fatal risk of CVD and the Norwegian national guidelines from 2017.MethodsWe included participants from the Norwegian population-based Tromsø Study (2015–2016) aged 40–69 years without a history of CVD (n=16 566). The total proportion eligible for intervention was identified by NORRISK 1 and the 2009 guidelines (serum total cholesterol ≥8 mmol/L, systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg) and NORRISK 2 and the 2017 guidelines (serum total cholesterol ≥7 mmol/L, low density lipoprotein (LDL) cholesterol ≥5 mmol/L, systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg).ResultsThe total proportion at high risk as defined by a risk score was 12.0% using NORRISK 1 and 9.8% using NORRISK 2. When including single risk factors specified by the guidelines, the total proportion eligible for intervention was 15.5% using NORRISK 1 and the 2009 guidelines and 18.9% using NORRISK 2 and the 2017 guidelines. The lowered threshold for total cholesterol and specified cut-off for LDL cholesterol stand for a large proportion of the increase in population at risk.ConclusionThe population proportion eligible for intervention increased by 3.4 percentage points from 2009 to 2017 using the revised NORRISK 2 score and guidelines.

Funding Acknowledgements Type of funding sources: None. Background Although the use of guidelines in clinical practice is emphasised, large multi-center studies of patients with cardiovascular disease have shown secondary prevention to be suboptimal, which increase the risk of recurrent events. Purpose To examine ESC guideline treatment target achievement after myocardial infarction for cardiovascular risk factors, medication use and a broad range of lifestyle factors in women and men from a Norwegian general population. Methods In a population-based study conducted 2015-2016 (65% attendance), 637 participants 40-95 years (23% women, 70% ≥65 years) had validated myocardial infarction. Cross-sectionally, we investigated target achievement for blood pressure (sedentary, accelerometer-measured moderate-to-vigorous ≥150 min/week), diet (intake of fruits ≥200 g/day, vegetables ≥200 g/day, fish ≥200 g/week, saturated fat Results Proportion of target achievement was for blood pressure 55.8%, LDL cholesterol 9.3%, HbA1c 42.7%, BMI 19.5%, waist circumference 15.6%, non-smoking 86.2%, self-reported physical activity 79.5%, objectively measured physical activity 9.1%, intake of fruits 66.7%, vegetables 38.4%, fish 96.8%, saturated fat 25.4%, fiber 29.5%, and alcohol 78.5%, use of antidiabetics 84.3%, lipid-lowering drugs 86.8%, antihypertensives 78.5% and antithrombotics 77.9%. In total, 0.8% achieved all cardiovascular risk factor targets (blood pressure, LDL cholesterol, BMI and waist circumference combined). Compared to men, a lower proportion of women achieved the target for waist circumference (6.9% vs 18.1%, p = 0.002). Compared to participants 65 years or older, a higher proportion of those 40-64 years achieved the target for blood pressure (71.2% vs 49.0%, p Conclusion Secondary prevention after myocardial infarction was suboptimal in both women and men. A negligible proportion achieved the treatment target for all risk factors. Improvement in follow-up care after myocardial infarction is needed.

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive‐CRP (hs‐CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA‐life), a prospective population‐based cohort study, 7,356 men were included. Prediagnostic WBC and hs‐CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow‐up. During a mean 11.8 years follow‐up, 509 men developed prostate cancer (mean age at diagnosis 71.7 years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs‐CRP), a combined score based on analyte tertiles (score range 2–6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose–response relationship between hs‐CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00–1.07. Men with an increase in hs‐CRP between two measurements (Δhs‐CRP) of ≥1.00 mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02–1.82), compared to men with no change or decrease in hs‐CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04–2.73) compared to men with lower scores. Our study supports that hs‐CRP including repeated measurements alone or in combination with WBC may be a useful inflammation‐related biomarker for prostate cancer risk and prognosis.

ObjectiveTo examine the association between area-level education and the local growth trajectories in antibacterial dispensing rates in Norwegian municipalities among children under 3 years old.DesignRetrospective, longitudinal study using individual primary care prescription data from the Norwegian Prescription Database for the period 2006–2016. Data were collected on the date of dispensing, the type and amount of antibiotic, the patient’s age, sex and municipality of residence and linked to municipality-level statistics on education available from Statistics Norway. We used multilevel growth curve modelling, with a linear trend variable modelled as a random effect and a cross-level interaction between linear trends and the proportion of the population in the municipality having received a university or college education.SettingThe local government level in Norway. The sample includes all municipalities over the study period.Outcome measureNumber of dispensed antibacterial prescriptions per 100 children in individual primary care by municipality and year.ResultsWe identified a significant negative linear trend in the square root of the dispensing rate for children under 3 years old during the period. This trend varied between municipalities. A negative cross-level interaction term between population education levels and random trends showed that municipalities with an average level of population education saw a reduction in their square root dispensing rates of −0.053 (95% CI −0.066 to −0.039) prescriptions per 100 children. Each additional percentage point in population education contributed a further −0.0034 (95% CI −0.006 to –0.001) reduction to the square root dispensing rate.ConclusionsMunicipalities in which a larger proportion of the local population have high educational achievements have been more successful in reducing antibacterial dispensing rates in children under 3 years old. Adopting area-level strategies and addressing local community disadvantages may help to optimise practices and prescribing patterns across local communities.

Introduction We aimed to investigate whether the proportion of undiagnosed diabetes varies by socioeconomic status and healthcare consumption, in a Norwegian population screened with glycated hemoglobin (HbA1c). Research design and methods In this cohort study, we studied age-standardized diabetes prevalence using data from men and women aged 40–89 years participating in four surveys of the Tromsø Study with available data on HbA1c and self-reported diabetes: 1994–1995 (n=6720), 2001 (n=5831), 2007–2008 (n=11 987), and 2015–2016 (n=20 170). We defined undiagnosed diabetes as HbA1c ≥6.5% (48 mmol/mol) and no self-reported diabetes. We studied the association of education, income and contact with a general practitioner on undiagnosed diabetes and estimated adjusted prevalence ratio (aPR) from multivariable adjusted (age, sex, body mass index) log-binomial regression. Results Higher education was associated with lower prevalence of diagnosed and undiagnosed diabetes. Those with secondary and tertiary education had lower prevalence of undiagnosed diabetes (aPR for tertiary vs primary: 0.54, 95% CI: 0.44 to 0.66). Undiagnosed as a proportion of all diabetes was also significantly lower in those with tertiary education (aPR:0.78, 95% CI: 0.65 to 0.93). Household income was also negatively associated with prevalence of undiagnosed diabetes. Across the surveys, approximately 80% of those with undiagnosed diabetes had been in contact with a general practitioner the last year, similar to those without diabetes. Conclusions Undiagnosed diabetes was lower among participants with higher education. The hypothesis that those with undiagnosed diabetes had been less in contact with a general practitioner was not supported.

Aims To investigate European guideline treatment target achievement in cardiovascular risk factors, medication use, and lifestyle, after myocardial infarction (MI) or ischaemic stroke, in women and men living in Norway. Methods and results In the population-based Tromsø Study 2015–16 (attendance 65%), 904 participants had previous validated MI and/or stroke. Cross-sectionally, we investigated target achievement for blood pressure (sedentary, accelerometer-measured moderate-to-vigorous ≥150 min/week), diet (intake of fruits ≥200 g/day, vegetables ≥200 g/day, fish ≥200 g/week, saturated fat Conclusion Secondary prevention of cardiovascular disease was suboptimal. A negligible proportion achieved the treatment target for all risk factors. Improvement in follow-up care and treatment after MI and stroke is needed.

Sarah Cook,1– 3 Anne Elise Eggen,1 Laila A Hopstock,1 Sofia Malyutina,4,5 Marina Shapkina,4 Alexander V Kudryavtsev,1,6 Hasse Melbye,1,* Jennifer K Quint3,* 1Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway; 2Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK; 3National Heart and Lung Institute, Imperial College London, London, UK; 4Research Institute of Internal and Preventive Medicine, Branch of Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation; 5Novosibirsk State Medical University, Russian Ministry of Health, Novosibirsk, Russian Federation; 6Northern State Medical University, Arkhangelsk, Russian Federation*These authors contributed equally to this workCorrespondence: Sarah Cook Email sarah.cook@lshtm.ac.ukBackground: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Despite a high prevalence of smoking and respiratory symptoms, two recent population-based studies in Russia found a relatively low prevalence of obstructive lung function. Here, we investigated the prevalence of both obstructive lung disease and respiratory symptoms in a population-based study conducted in two Russian cities and compared the findings with a similar study from Norway conducted in the same time period.Methods: The study population was a sub-sample of participants aged 40– 69 years participating in the Know Your Heart (KYH) study in Russia in 2015– 18 (n=1883) and in the 7th survey of the Tromsø Study (n=5271) carried out in Norway in 2015– 16 (Tromsø 7) who participated in spirometry examinations. The main outcome was obstructive lung function (FEV1/FVC ratio< lower limit of normal on pre-bronchodilator spirometry examination) with and without respiratory symptoms (chronic cough and breathlessness). In those with obstructive lung function, awareness (known diagnosis) and management (use of medications, smoking cessation) were compared.Results: The age-standardized prevalence of obstructive lung function was similar among men in both studies (KYH 11.0% vs Tromsø 7 9.8%, p=0.21) and higher in the Norwegian (9.4%) than Russian (6.8%) women (p=0.006). In contrast, the prevalence of obstructive lung function plus respiratory symptoms was higher in Russian men (KYH 8.3% vs Tromsø 7 4.7%, p< 0.001) but similar in women (KYH 5.9% vs Tromsø 7 6.4%, p=0.18). There was a much higher prevalence of respiratory symptoms in Russian than Norwegian participants of both sexes regardless of presence of obstructive lung function.Conclusion: The prevalence of respiratory symptoms was strikingly high among Russian participants but this was not explained by a higher burden of obstructive lung function on spirometry testing in comparison with Norwegian participants. Further work is needed to understand the reasons and health implications of this high prevalence of cough and breathlessness.Keywords: COPD, Russian Federation, Norway, respiratory symptoms

IntroductionCompared with many other countries Russia has a high prevalence of diabetes in men and women. However, contrary to what is found in most other populations, the risk is greater among women than men. The reasons for this are unclear.Research design and methodsPrevalence and risk factors for diabetes at ages 40–69 years were compared in two population-based studies: Know Your Heart (KYH) (Russia, 2015–2018, n=4121) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015–2016, n=17 649). Diabetes was defined by the level of glycated hemoglobin and/or self-reported diabetes and/or diabetes medication use. Marginal structural models were used to estimate the role of key risk factors for diabetes in differences between the studies.ResultsAge-standardized prevalence of diabetes was higher in KYH compared with Tromsø 7 in men (11.6% vs 6.2%) and in women (13.2% vs 4.3%). Age-adjusted ORs for diabetes in KYH compared with Tromsø 7 were 2.01 (95% CI 1.68 to 2.40) for men and 3.66 (95% CI 3.13 to 4.26) for women. Adiposity (body mass index and waist circumference) explained none of this effect for men but explained 46.0% (39.6, 53.8) for women. Addition of smoking and C reactive protein, as further mediators, slightly increased the percentage explained of the difference between studies to 55.5% (46.5, 66.0) for women but only to 9.9% (−0.6, 20.8) for men.ConclusionsAdiposity is a key modifiable risk factor that appears to explain half of the almost threefold higher female prevalence of diabetes in Russia compared with Norway, but none of the twofold male difference.

Tinnitus and pain have many similarities. Both are subjective sensations that may turn chronic, they are often accompanied by hypersensitivity in their respective sensory system, and overlapping brain changes have been observed. Since no population study has examined the empirical association between chronic pain and tinnitus, the present study aimed to explore the relationship in a general adult population. We used data from the seventh survey of the Tromsø Study (2015–2016). Participants (aged ≥40) responded to questions about pain and tinnitus. Using multiple logistic regression, we analysed the adjusted relationship between chronic pain and tinnitus in the full sample (n = 19,039), using several tinnitus definitions ranging from tinnitus >5 minutes within the past 12 months (broadest definition) to at least weekly and highly bothersome tinnitus (strictest definition). We also analysed relationships between number of body regions with pain, pain intensity and bothering, and tinnitus >5 minutes, among participants with chronic pain (n = 11,589). We found an association between chronic pain and tinnitus that was present irrespective of tinnitus definition, but was stronger with more bothersome tinnitus. With chronic pain, the odds of tinnitus >5 minutes was 64% higher, while odds of at least weekly, highly bothersome tinnitus was 144% higher than without chronic pain. Among participants with chronic pain, the number of pain regions was the pain variable most strongly associated with tinnitus >5 minutes (OR = 1.17 (95% CI: 1.14–1.20) for an increase of one region), whereas the other pain variables (intensity and bothering) showed weaker associations. All chronic pain variables had significant interactions with age, with the strongest associations for the youngest individuals (40–54 years). Our findings support the existence of an association between chronic pain and tinnitus and emphasises the importance of examining for comorbid pain in tinnitus patients to provide a more comprehensive treatment of tinnitus.

Introduction Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). Purpose We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). Materials and methods NORSTENT was a randomized, double blind, pragmatic randomized trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008–11. The patients (N=9,013) were randomized to receive either a drug eluting stent or a bare metal stent, and were treated with at least 9 months of DAPT. The patients were followed for a median of five years, with BARC 3–5 major bleeding as one of the safety endpoints. We estimated cumulative incidence by a competing risks model and risk factors through cause-specific Cox models. Results The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease (CKD), underweight (80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.7, 95% CI 1–3-2.2). Conclusions The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of CKD, advanced age, and underweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Northern Norway Regional Health Authority (Helse Nord RHF)

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 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.

Objective - To validate self-reported use of medications for secondary prevention of coronary heart disease (CHD) in a population-based health study by comparing self-report with pharmacy dispensing data, and explore different methods for defining medication use in prescription databases. Study design and setting - Self-reported medication use among participants with CHD (n = 1483) from the seventh wave of the Tromsø Study was linked with the Norwegian Prescription Database (NorPD). Cohen’s kappa, sensitivity, specificity, and positive and negative predictive values were calculated, using NorPD as the reference standard. Medication use in NorPD was defined in three ways; fixed-time window of 180 days, and legend-time method assuming a daily dose of one dosage unit or one defined daily dose (DDD). Results - Kappa-values for antihypertensive drugs, lipid-lowering drugs and acetylsalicylic acid all showed substantial agreement (kappa ≥0.61). Validity varied depending on the method used for defining medication use in NorPD. Applying a fixed-time window gave higher agreement, positive predictive values and specificity compared with the legend-time methods. Conclusion - Self-reported use of medication for secondary prevention of CHD shows high validity when compared with pharmacy dispensing data. For CHD medications, fixed-time window appears to be the most appropriate method for defining medication use in prescription databases.

Background Cardiovascular disease (CVD) mortality is substantially higher in Russia than in neighbouring Norway. We aimed to compare blood pressure- and lipid-lowering medication use and proportion meeting treatment targets between general population samples in the two countries in those with CVD and diabetes. Methods The study population was adults aged 40–69 years reporting a diagnosis of myocardial infarction (MI), stroke and/or diabetes participating in cross-sectional population-based studies in Russia (Know Your Heart (KYH) 2015–18 N = 626) and Norway (The Tromsø Study 2015–16 (Tromsø 7) N = 1353). Reported medications were coded according to the 2016 WHO Anatomical Therapeutic Chemical Classification system. Treatment targets were defined using the Joint European Societies guidelines for CVD prevention in clinical practice (2016). Results Age- and sex-standardized prevalence of use of lipid-lowering medications was higher in Tromsø 7 for all three conditions with a disproportionately large difference in those reporting MI (+ 48% (95% CI 39, 57%)). Proportion meeting treatment targets for LDL cholesterol was poor in both studies (age- and sex-standardized prevalence of control KYH vs Tromsø 7: MI 5.1% vs 10.1%; stroke 11.6% vs 5.8%; diabetes 24.9% vs 23.3%). Use of antihypertensive medication was higher in KYH for stroke (+ 40% (95% CI 30, 50%)) and diabetes (+ 27% (95% CI 19, 34%)) groups but approximately equal for the MI group (− 1% (95% CI -1, 1%)). Proportion meeting blood pressure targets was lower in KYH vs Tromsø 7 (MI 51.8% vs 76.3%; stroke 49.5% vs 69.6%; diabetes 51.9% vs 63.9%). Conclusions We identified different patterns of medication use in people with CVD and diabetes. However despite higher use of lipid-lowering medication in the Norwegian study treatment to target for total cholesterol was poor in both Russian and Norwegian studies. In contrast we found higher levels of use of antihypertensive medications in the Russian study but also that less participants met treatment targets for blood pressure. Further work should investigate what factors are responsible for this seeming paradox and how management of modifiable risk factors for secondary prevention could be improved.

Background The leukotriene receptor antagonist montelukast has been shown to rejuvenate aged brains in rats; however, data on humans are still scarce. Objective To investigate if montelukast may alleviate degenerative neurological changes using a register data. Setting Norwegian registry data analyses. Method The present observational study was based on data from the Norwegian Prescription Database and the Tromsø Study. The former has information regarding the use of prescription medicine; the latter includes tests for brain function such as subjective memory and finger-tapping. Multivariate linear regression analyses were performed to see how the use of various medications correlated with the test results, correcting for likely confounders. Main outcome measure Results on seven different tests considered relevant for neurological health were used as outcome. Results Previous use of montelukast correlated with improved scores on cognitive or neurological functioning (F = 2.20, p = 0.03 in a multivariate test). A range of other medications were tested with the same algorithm, including drugs acting on the immune system, but none of them correlated with (overall) significantly improved test results. Conclusion The present data suggest that montelukast may alleviate degenerative neurological changes associated with human aging.

Purpose Whether an unfavorable lifestyle not only affects breast cancer risk, but also influences age at onset of breast cancer and survival, is under debate. Methods In a population-based cohort, the Energy Balance and Breast Cancer Aspects throughout life (EBBA-Life) study, a total of 17,145 women were included. During follow-up, 574 women developed invasive breast cancer. Breast cancer cases were followed for an additional 9.1 years. Detailed medical records were obtained. Cox’s proportional hazard regression models were used to study the association between pre-diagnostic lifestyle factors (weight, physical activity, alcohol use, smoking, and hypertension), breast cancer risk, age at diagnosis, and survival. Results At study entry, 34.3% of the participating women were overweight and 30.7% were physically inactive. Mean age at breast cancer diagnosis was 58.0 years, and 78.9% of the tumors were estrogen receptor positive. Among menopausal women who did not use hormone therapy and had an unfavorable lifestyle (3–5 unfavorable factors), compared with women who had a favorable lifestyle, we observed a twofold higher risk for postmenopausal breast cancer (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.23–3.69), and they were 3.4 years younger at diagnosis (64.8 versus 68.2 years, P = 0.032). Breast cancer patients with an unfavorable lifestyle, compared with patients with a favorable lifestyle, had almost a two times higher overall mortality risk (HR 1.96, 95% CI 1.01–3.80). Conclusions Our study supports a healthy lifestyle improving breast cancer prevention, postponing onset of disease, and extending life expectancy among breast cancer patients.

BackgroundRussia has one of the highest rates of mortality from cardiovascular disease (CVD). At age 35–69 years, they are eight times higher than in neighbouring Norway. Comparing profiles of blood-based CVD biomarkers between these two populations can help identify reasons for this substantial difference in risk.MethodsWe compared age-standardised mean levels of CVD biomarkers for men and women aged 40–69 years measured in two cross-sectional population-based studies: Know Your Heart (KYH) (Russia, 2015–2018; n=4046) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015–2018; n=17 646). A laboratory calibration study was performed to account for inter-laboratory differences.ResultsLevels of total, low-density lipoprotein-, high-density lipoprotein-cholesterol and triglycerides were comparable in KYH and Tromsø 7 studies. N-terminal pro-b-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hsCRP) were higher in KYH compared with Tromsø 7 (NT-proBNP was higher by 54.1% (95% CI 41.5% to 67.8%) in men and by 30.8% (95% CI 22.9% to 39.2%) in women; hs-cTnT—by 42.4% (95% CI 36.1% to 49.0%) in men and by 68.1% (95% CI 62.4% to 73.9%) in women; hsCRP—by 33.3% (95% CI 26.1% to 40.8%) in men and by 35.6% (95% CI 29.0% to 42.6%) in women). Exclusion of participants with pre-existing coronary heart disease (279 men and 282 women) had no substantive effect.ConclusionsDifferences in cholesterol fractions cannot explain the difference in CVD mortality rate between Russia and Norway. A non-ischemic pathway to the cardiac damage reflected by raised NT-proBNP and hs-cTnT is likely to contribute to high CVD mortality in Russia.

ObjectivesTo describe the prevalence of general (body mass index (BMI) ≥30 kg/m2) and abdominal (waist circumference women >88 cm, men >102 cm) obesity in Tromsø 7 (2015–2016), and the secular change from Tromsø 6 (2007–2008). Furthermore, to study longitudinal changes in body weight and waist circumference from Tromsø 6 to Tromsø 7.SettingA population study in Tromsø, Norway.ParticipantsThe cross-sectional analyses included 20 855 participants in Tromsø 7 (aged ≥40 years) and 12 868 in Tromsø 6 (aged ≥30 years). The longitudinal analyses included 8592 participants with repeated measurements, aged 35–79 in Tromsø 6.Outcome measuresMean age-specific and sex-specific BMI, waist circumference, prevalence of general and abdominal overweight and obesity, as well as longitudinal changes in body weight and waist circumference according to sex and birth cohort.ResultsOver 8 years, the age-adjusted prevalence of general obesity increased (pConclusionsRepeated cross-sectional analyses showed that the prevalence of general obesity increased, whereas the increase in abdominal obesity was less marked. Longitudinal analyses showed increases in both body weight and waist circumference. The youngest age groups have the largest increase.

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), all men had a general health examination at study entry and were followed between 1994 and 2016. Patients with available tissue samples after a prostatectomy with curative intent were identified (n = 189). The tissue expression of miR-24-1-5p in prostate cancer was examined by in situ hybridization (ISH) in tissue microarray (TMA) blocks by semi-quantitative scoring by two independent investigators. Multivariable Cox regression models were used to study the associations between miR-24-1-5p expression and prostate cancer recurrence. The prostate cancer patients had a median age of 65.0 years (range 47–75 years). The Cancer of the Prostate Risk Assessment Postsurgical Score, International Society of Urological Pathology grade group, and European Association of Urology Risk group were all significant prognostic factors for five-year recurrence-free survival (p < 0.001). Prostate cancer patients with a high miR-24-1-5p expression (≥1.57) in the tissue had a doubled risk of recurrence compared to patients with low expression (HR 1.99, 95% CI 1.13–3.51). Our study suggests that a high expression of miR-24-1-5p is associated with an increased risk of recurrence of prostate cancer after radical prostatectomy, which points to the potential diagnostic and therapeutic value of detecting miR-24-1-5p in prostate cancer cases.

Publisher's version (útgefin grein), Background The Nordic countries have commonalities in gender equality, economy, welfare, and health care, but differ in culture and lifestyle, which might create country-wise health differences. This study compared life expectancy, disease burden, and risk factors in the Nordic region.Methods Life expectancy in years and age-standardised rates of overall, cause-specific, and risk factor-specific estimates of disability-adjusted life-years (DALYs) were analysed in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Data were extracted for Denmark, Finland, Iceland, Norway, and Sweden (ie, the Nordic countries), and Greenland, an autonomous area of Denmark. Estimates were compared with global, high-income region, and Nordic regional estimates, including Greenland.Findings All Nordic countries exceeded the global life expectancy; in 2017, the highest life expectancy was in Iceland among females (85·9 years [95% uncertainty interval [UI] 85·5–86·4] vs 75·6 years [75·3–75·9] globally) and Sweden among males (80·8 years [80·2–81·4] vs 70·5 years [70·1–70·8] globally). Females (82·7 years [81·9–83·4]) and males (78·8 years [78·1–79·5]) in Denmark and males in Finland (78·6 years [77·8–79·2]) had lower life expectancy than in the other Nordic countries. The lowest life expectancy in the Nordic region was in Greenland (females 77·2 years [76·2–78·0], males 70·8 years [70·3–71·4]). Overall disease burden was lower in the Nordic countries than globally, with the lowest age-standardised DALY rates among Swedish males (18 555·7 DALYs [95% UI 15 968·6–21 426·8] per 100 000 population vs 35 834·3 DALYs [33 218·2–38 740·7] globally) and Icelandic females (16 074·1 DALYs [13 216·4–19 240·8] vs 29 934·6 DALYs [26 981·9–33 211·2] globally). Greenland had substantially higher DALY rates (26 666·6 DALYs [23 478·4–30 218·8] among females, 33 101·3 DALYs [30 182·3–36 218·6] among males) than the Nordic countries. Country variation was primarily due to differences in causes that largely contributed to DALYs through mortality, such as ischaemic heart disease. These causes dominated male disease burden, whereas non-fatal causes such as low back pain were important for female disease burden. Smoking and metabolic risk factors were high-ranking risk factors across all countries. DALYs attributable to alcohol use and smoking were particularly high among the Danes, as was alcohol use among Finnish males.Interpretation Risk factor differences might drive differences in life expectancy and disease burden that merit attention also in high-income settings such as the Nordic countries. Special attention should be given to the high disease burden in Greenland., This study was funded by the Bill & Melinda Gates Foundation. The authors wish to thank Jonas Minet Kinge (Norwegian Institute of Public Health, Oslo, Norway) for valuable input regarding socioeconomic differences in life expectancy in the Nordic countries. CRC has received research funding from Svenska Läkaresällskapet (SLS-779681), Tysta Skolan, Hörselforskningsfonden (#503), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 72204655 and the GENDERNET Co-Plus Fund (GNP-182). JJC acknowledges grant support from the Swedish Research Council (grant number 2019-01059). JMcG is supported by the Danish National Research Foundation (Niels Bohr Professorship), and is employed by The Queensland Centre for Mental Health Research which receives core funding from the Queensland Health. STS is currently funded by a grant from Region Zealand and a grant from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 801790). OP-R has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 837180. TL is supported by the Academy of Finland (Grant #319200). Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this Article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/WHO., "Peer Reviewed"

Background Primary prevention guidelines promote the use of risk assessment tools to estimate total cardiovascular risk. We aimed to study trends in cardiovascular risk and contribution of single risk factors, using the newly developed NORRISK 2 risk score, which estimates 10-year risk of fatal and non-fatal cardiovascular events. Design Prospective population-based study. Methods We included women and men aged 45–74 years attending the sixth and seventh survey of the Tromsø Study (Tromsø 6, 2007–2008, n = 7284 and Tromsø 7, 2015–2016, n = 14,858) to study secular trends in NORRISK 2 score. To study longitudinal trends, we followed participants born 1941–1962 attending both surveys ( n = 4534). We calculated NORRISK 2 score and used linear regression models to study the relative contribution (% R2) of each single risk factor to the total score. Results Mean NORRISK 2 score decreased and distribution in risk categories moved from higher to lower risk in both sexes and all age-groups between the first and second surveys ( p Conclusion We found significant favourable secular and longitudinal trends in total cardiovascular risk and single risk factors during the last decade. Change in systolic blood pressure, smoking and cholesterol were the main contributors to risk score change; however, the impact of single risk factors on the total score differed by sex, age and birth cohort.

Background The relationship between high sensitivity C-reactive protein and migraine is unclear. The aim of this cross-sectional population-based study was to investigate the association between high sensitivity C-reactive protein and types of headache, and to evaluate the impact of insomnia on this association. Methods A total of 20,486 (63%) out of 32,591 invited, aged ≥40 years or older, participated in the seventh wave of the Tromsø study conducted in 2015–2016 and had valid information on headache, insomnia and high sensitivity C-reactive protein. The influence of insomnia on the association between questionnaire-based diagnoses of headache and elevated high sensitivity C-reactive protein defined as >3.0 mg/L was assessed using multiple logistic regression, estimating prevalence odds ratio with 95% confidence intervals. Results A total of 6290 participants (30.7%) suffered from headache during the last year. Among these, 1736 (8.5%) fulfilled the criteria of migraine, 991 (4.8%) had migraine with aura, 746 (3.6%) migraine without aura (3.8%), and 4554 (22.2%) had non-migrainous headache. In the final multi-adjusted analysis, elevated high sensitivity C-reactive protein was associated with headache (odds ratio 1.10, 95% confidence interval 1.01–1.20), migraine (odds ratio 1.17, 95% confidence interval 1.01–1.35), and migraine with aura (odds ratio 1.23, 95% confidence interval 1.01–1.53). No association was found between elevated high sensitivity C-reactive protein and migraine without aura or non-migrainous headache. The association between high sensitivity C-reactive protein and migraine was strongly dependent on insomnia status. Among individuals with insomnia, elevated high sensitivity C-reactive protein was associated with migraine (odds ratio 1.49, 95% confidence interval 1.02–2.17), and migraine with aura (odds ratio 1.59, 95% confidence interval 1.03–2.45), whereas no such relationship was found among those without insomnia. Conclusions In this cross-sectional study, participants with migraine, in particular migraine with aura, were more likely to have elevated high sensitivity C-reactive protein, evident only among those with insomnia.

Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. The Lancet Publishing Group