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Background: Patients with ischemic stroke have increased risk of venous thromboembolism (VTE). Obesity is prevalent in stroke patients and a well-established risk factor for VTE. Whether obesity further increases the VTE risk in patients with stroke remains unclear., Objectives: We investigated the joint effect of ischemic stroke and obesity on the risk of incident VTE in a population-based cohort., Methods: Participants ( n  = 29,920) were recruited from the fourth to sixth surveys of the Tromsø Study (1994-1995, 2001, and 2007-2008) and followed through 2014. Incident events of ischemic stroke and VTE during follow-up were recorded. Hazard ratios (HRs) of VTE with 95% CIs were estimated according to combined categories of ischemic stroke and obesity (body mass index ≥ 30 kg/m 2 ), with exposure to neither risk factors as reference., Results: During a median follow-up of 19.6 years, 1388 participants experienced ischemic stroke and 807 participants developed VTE. Among those with stroke, 51 developed VTE, yielding an incidence rate of VTE after stroke of 7.2 per 1000 person-years (95% CI, 5.5-9.5). In subjects without stroke, obesity was associated with a 1.8-fold higher VTE risk (HR, 1.76; 95% CI, 1.47-2.11). In nonobese subjects, stroke was associated with a 1.8-fold higher VTE risk (HR, 1.77; 95% CI, 1.27-2.46). Obese subjects with stroke had a 2-fold increased VTE risk (HR, 2.44; 95% CI, 1.37-4.36)., Conclusion: The combination of obesity and ischemic stroke did not yield an excess risk of VTE. Our findings suggest that obese subjects with ischemic stroke do not have a more than additive risk of VTE., (© 2024 The Authors.)

Objective: To examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI)., Patients and Methods: Adults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255)., Results: Of 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors., Conclusion: Higher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females., Competing Interests: M.L.L. has received lecture fees from 10.13039/100004326Bayer, 10.13039/100004339Sanofi, and 10.13039/100002491BMS/10.13039/100004319Pfizer not related to this study. The remaining authors declare no conflict of interest., (© 2023 The Authors.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: The prevalence of overweight and obesity has risen rapidly worldwide, and the ongoing obesity pandemic is one of the most severe public health concerns in modern society. The average body mass index (BMI) of people living in Northern Norway has also steadily increased since the late 1970s. This study aimed to understand how individuals' health behavior is associated with the general health behavior of the people in their neighborhood., Methods: Using the population-based Tromsø Study, we examined the life course association between average leisure time physical activity at the neighborhood level and the BMI of individuals living in the same neighborhood. We used a longitudinal dataset following 25,604 individuals living in 33 neighborhoods and performed a linear mixed-effects analysis., Results: The results showed that participants living in neighborhoods whose residents were more physically active during their leisure time, were likely to have a significantly lower BMI (-0.9 kg/m², 95% CI -1.5 to -0.4). Also, individuals living in neighborhoods whose residents were doing mainly manual work, had significantly higher BMIs (0.7 kg/m², 95% CI 0.4-1.0)., Conclusions: Our results showed a strong association between the average leisure time physical activity level of neighborhood residents and the higher BMI levels of residents of the same neighborhood., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims/background: Serial blood pressure surveys in cohort studies can inform public health policies to control blood pressure for prevention of cardiovascular diseases., Methods: Mean levels of systolic blood pressure (SBP) were collected in six sequential surveys, involving 38,825 individuals aged 30-79 years (51% female), between 1979 and 2015 in the Tromsø Study in Norway. Mean levels of SBP, prevalence of hypertension and use of blood pressure-lowering treatment were estimated by age, sex and calendar year of survey., Results: Age-specific mean levels of SBP in each decade of age increased by 20-25 mmHg in men and 30-35 mmHg in women and the prevalence of hypertension increased from 25% to 75% among adults aged 30-79 years. Among successive cohorts of adults aged 40-49 years at the time of the six surveys between 1979 and 2015, the mean levels of SBP declined by about 10 mmHg and the prevalence of hypertension declined from 46% to 25% in men and from 30% to 14% in women. The proportion of individuals with hypertension who were treated increased sixfold (from 7% to 42%) between 1979 and 2015, and the proportion of adults with hypertension that were successfully controlled also increased sixfold from 10% to 60% between 1979 and 2015., Conclusions: Although this study demonstrated a halving in the age-specific prevalence of hypertension in men and women and a sixfold increase in treatment and control of hypertension, the burden of hypertension remains high among older people in Norway., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification., (© 2023. The Author(s).)

Background The atherosclerotic effect of an adverse lipid profile is assumed to accumulate throughout life, leading to increased risk of myocardial infarction (MI). Still, little is known about age at onset and duration of unfavorable lipid levels before MI. Methods and Results Longitudinal data on serum lipid levels for 26 130 individuals (50.5% women, aged 20-89 years) were obtained from 7 population-based health surveys in Tromsø, Norway. Diagnoses of MI were obtained from national registers. A linear mixed model was applied to compare age- and sex-specific mean values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentration by MI status (MI versus non-MI). Already from young adulthood, 20 to 35 years before the incident MI, individuals with a subsequent incident MI had on average more adverse lipid levels than individuals of the same age and sex without MI. Analogous to a dose-response relationship, there was a clear trend toward more severe adverse lipid levels the lower the age at incident MI ( P <0.001, test for trend through ordered categories <55, 55-74, ≥75 years). This trend was particularly pronounced for high-density lipoprotein cholesterol in percentage of total cholesterol (both sexes) and for the relative relationship between triglyceride, high-density lipoprotein cholesterol, and total cholesterol level (women). The difference in mean lipid level by MI status was just as large in women as in men, but the age pattern differed ( P ≤0.05, tests of 3-way interaction). Conclusions Compared with general population mean levels, adverse lipid levels were seen 20 to 35 years before the incident MI in both men and women.

Objectives: The objective of our study was to describe time trends in body height according to attained educational level in women and men in Norway., Methods: We used previously collected data from six repeated cross-sectional studies in the population based Tromsø Study 1979-2016. Measured body height in cm and self-reported educational level were the primary outcome measures. We included 31 466 women and men aged 30-49 years, born between 1930 and 1977. Participants were stratified by 10-year birth cohorts and allocated into four groups based on attained levels of education. Descriptive statistics was used to estimate mean body height and calculate height differences between groups with different educational levels., Results: Mean body height increased by 3.4 cm (95% confidence interval (CI) 3.0, 3.8) in women (162.5-165.9 cm) and men (175.9-179.3 cm) between 1930 and 1977. The height difference between groups with primary education compared to long tertiary education was 5.1 cm (95% CI 3.7, 6.5) in women (161.6-166.7 cm) and 4.3 cm (95% CI 3.3, 5.3) in men (175.0-179.3 cm) born in 1930-39. The height differences between these educational groups were reduced to 3.0 cm (95% CI 1.9, 4.1) in women (163.6-166.6 cm) and 2.0 cm (95% CI 0.9, 3.1) in men (178.3-180.3 cm) born in 1970-77., Conclusions: Body height increased in women and men. Women and men with long tertiary education had the highest mean body height, which remained stable across all birth cohorts. Women and men in the three other groups had a gradual increase in height by birth cohort, reducing overall height differences between educational groups in our study population., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2023 Arntsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: To explore sex-specific time trends in atrial fibrillation (AF) incidence and to estimate the impact of changes in risk factor levels using individual participant-level data from the population-based Tromsø Study 1994-2016., Methods and Results: A total of 14 818 women and 13 225 men aged 25 years or older without AF were enrolled in the Tromsø Study between 1994 and 2008 and followed up for incident AF throughout 2016. Poisson regression was used for statistical analyses. During follow-up, age-adjusted AF incidence rates in women decreased from 1.19 to 0.71 per 1000 person-years. In men, AF incidence increased from 1.18 to 2.82 per 1000 person-years in 2004, and then declined to 1.94 per 1000 person-years in 2016. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), physical activity, smoking and alcohol consumption together accounted for 10.9% [95% confidence interval (CI): -2.4 to 28.6] of the AF incidence decline in women and for 44.7% (95% CI: 19.2; 100.0) of the AF incidence increase in men. Reduction in SBP and DBP had the largest contribution to the decrease in AF incidence in women. Increase in BMI had the largest contribution to the increase in AF incidence in men., Conclusion: In the population-based Tromsø Study 1994-2016, AF incidence decreased in women and increased following a reverse U-shape in men. Individual changes in SBP and DBP in women and individual changes in BMI in men were the most important risk factors contributing to the AF incidence trends., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Myocardial infarction (MI) is associated with an increased risk of venous thromboembolism (VTE). Obesity is a recognized risk factor for both MI and VTE. Whether obesity further increases the risk of VTE in MI patients is scarcely investigated., Aim: To study the joint effect of MI and obesity on the risk of VTE., Methods: Study participants (n = 29 410) were recruited from three surveys of the Tromsø Study (conducted in 1994-1995, 2001, and 2007-2008) and followed up through 2014. All incident MI and VTE cases during follow-up were recorded. Cox regression models with MI as a time-dependent variable were used to estimate hazard ratios (HRs) of VTE (adjusted for age and sex) by combinations of MI exposure and obesity status. Joint effects were assessed by calculating relative excess risk and attributable proportion (AP) due to interaction., Results: During a median of 19.6 years of follow-up, 2090 study participants experienced an MI and 784 experienced a VTE. Among those with MI, 55 developed a subsequent VTE, yielding an overall incidence rate (IR) of VTE of 5.3 per 1000 person-years (95% confidence interval [CI]: 4.1-6.9). In the combined exposure group (MI+/Obesity+), the IR was 11.3 per 1000 person-years, and the adjusted HR indicated a 3-fold increased risk of VTE (HR 3.16, 95% CI: 1.99-4.99) compared to the reference group (MI-/Obesity-). The corresponding AP was 0.46 (95% CI: 0.17-0.74)., Conclusions: The combination of MI and obesity yielded a supra-additive effect on VTE risk of which 46% of the VTE events were attributed to the interaction., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Introduction: Cardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of area-level socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously., Aims: To estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES., Methods: In this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) at the geographical subdivision level. Individual-level SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex., Results: ASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects., Conclusions: Living in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants., Competing Interests: None., (© 2022 The Authors.)

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 <5 mmol/L, 27.3% for LDL cholesterol <3 mmol/L, 43.4% for BP <140/90 (<135/85 if diabetes) mmHg, and 85.4% for non-smoking. A total of 9.8% reached all treatment targets combined. Baseline risk factor levels and current medication use had the strongest associations with treatment target achievement., 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 Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The outcomes of real-world unstable angina (UA) in the high-sensitivity troponin era are unclear. We aimed to investigate the outcomes of UA referred to coronary angiography compared to stable angina (SA), non-ST-segment elevation myocardial infarction (NSTEMI), STEMI and a general population., Methods: We included the 9,694 patients with no prior coronary artery disease (CAD) referred to invasive or CT coronary angiography from 2013 to 2018 in Northern Norway (51% SA, 12% UA, 23% NSTEMI and 14% STEMI), and 11,959 asymptomatic individuals recruited from the Tromsø Study. We used Cox models to estimate the hazard ratios (HR) for all-cause mortality and major adverse cardiovascular events (MACE), defined as cardiovascular death, MI or obstructive CAD., Results: The median follow-up time was 2.8 years. The incidence rate of death was 8.5 per 1000 person-years (95 % confidence interval [CI] 8.0-9.0) in the general population, 9.7 (95 % CI 8.3-11.5) in SA, 14.9 (95 % CI 11.4-19.6) in UA, 29.7 (95 % CI 25.6-34.3) in NSTEMI and 36.5 (95 % CI 30.9-43.2) in STEMI. In multivariable adjusted analyses, compared with UA, SA had a 38 % lower risk of death and a non-significant lower risk of MACE (HR 0.62, 95 % CI 0.44-0.89; HR 0.86, 95 % CI 0.66-1.11). NSTEMI had a 2.4-fold higher risk of death (HR 2.39, 95 % CI 1.38-4.14) and a 1.6-fold higher risk of MACE (HR 1.62, 95 % CI 1.11-2.38) compared tox UA during the first year after coronary angiography, but a similar risk thereafter. There was no difference in the risk of death for UA with non-obstructive CAD and obstructive CAD (HR 0.78, 95 % CI 0.39-1.57)., Conclusion: UA had a higher risk of death but a similar risk of MACE compared to SA and a lower 1-year risk of death and MACE compared to NSTEMI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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 (<140/90 mmHg, <130/80 mmHg if diabetes), LDL cholesterol (<1.8 mmol/L), HbA1c (<7.0% if diabetes), overweight (body mass index (BMI) <25 kg/m2, waist circumference women <80 cm, men <94 cm), smoking (non-smoking), physical activity (self-reported >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 <10E%, fibre ≥30 g/day, alcohol women ≤10 g/day, men ≤20 g/day), and medication use (antihypertensives, lipid-lowering drugs, antithrombotics, and antidiabetics), using regression models. Proportion of target achievement was for blood pressure 55.2%, LDL cholesterol 9.0%, HbA1c 42.5%, BMI 21.1%, waist circumference 15.7%, non-smoking 86.7%, self-reported physical activity 79%, objectively measured physical activity 11.8%, intake of fruit 64.4%, vegetables 40.7%, fish 96.7%, saturated fat 24.3%, fibre 29.9%, and alcohol 78.5%, use of antidiabetics 83.6%, lipid-lowering drugs 81.0%, antihypertensives 75.9%, and antithrombotics 74.6%. Only 0.7% achieved all cardiovascular risk factor targets combined. Largely, there was little difference between the sexes, and in characteristics, medication use, and lifestyle among target achievers compared to non-achievers., 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: To test the association of alcohol consumption with total and cause-specific mortality risk., Design: Prospective observational multi-centre population-based study., Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project., Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men)., Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality., Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively., Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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.

Aims: Although absolute (AID) and functional iron deficiency (FID) are known risk factors for patients with cardiovascular (CV) disease, their relevance for the general population is unknown. The aim was to assess the association between AID/FID with incident CV disease and mortality in the general population., Methods and Results: In 12 164 individuals from three European population-based cohorts, AID was defined as ferritin < 100 μg/L or as ferritin < 30 μg/L (severe AID), and FID was defined as ferritin < 100 μg/L or ferritin 100-299 μg/L and transferrin saturation < 20%. The association between iron deficiency and incident coronary heart disease (CHD), CV mortality, and all-cause mortality was evaluated by Cox regression models. Population attributable fraction (PAF) was estimated. Median age was 59 (45-68) years; 45.2% were male. AID, severe AID, and FID were prevalent in 60.0%, 16.4%, and 64.3% of individuals. AID was associated with CHD [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39, P = 0.01], but not with mortality. Severe AID was associated with all-cause mortality (HR 1.28, 95% CI 1.12-1.46, P < 0.01), but not with CV mortality/CHD. FID was associated with CHD (HR 1.24, 95% CI 1.07-1.43, P < 0.01), CV mortality (HR 1.26, 95% CI 1.03-1.54, P = 0.03), and all-cause mortality (HR 1.12, 95% CI 1.01-1.24, P = 0.03). Overall, 5.4% of all deaths, 11.7% of all CV deaths, and 10.7% of CHD were attributable to FID., Conclusions: In the general population, FID was highly prevalent, was associated with incident CHD, CV death, and all-cause death, and had the highest PAF for these events, whereas AID was only associated with CHD and severe AID only with all-cause mortality. This indicates that FID is a relevant risk factor for CV diseases in the general population., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007-2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03-1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01-1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09-2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19-1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A 1c (HbA 1c ) 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 HbA 1c with cardiovascular outcomes in the general population., Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA 1c 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 HbA 1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA 1c (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 HbA 1c . The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA 1c 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. HbA 1c 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: HbA 1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA 1c levels and outcomes. Elevated HbA 1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA 1c levels in the overall population., (© 2021. The Author(s).)

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 (HbA 1c )., 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 HbA 1c 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 HbA 1c ≥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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physical inactivity and obesity are global public health challenges. Older adults are important to target for prevention and management of disease and chronic conditions. However, many individuals struggle with maintaining increased physical activity (PA) and improved diet. This feasibility study provides the foundation for the RESTART trial, a randomized controlled trial (RCT) to test a complex intervention to facilitate favourable lifestyle changes older adults can sustain. The primary objective of this study was to investigate study feasibility (recruitment, adherence, side-effects, and logistics) using an interdisciplinary approach., Methods: This 1-year prospective mixed-method single-arm feasibility study was conducted in Tromsø, Norway, from September 2017. We invited by mail randomly selected participants from the seventh survey of the Tromsø Study (2015-2016) aged 55-75 years with sedentary lifestyle, obesity, and elevated cardiovascular risk. Participants attended a 6-month complex lifestyle intervention program, comprising instructor-led high-intensive exercise and nutritionist- and psychologist-led counselling, followed by a 6-month follow-up. All participants used a Polar activity tracker for daily activity monitoring during the intervention. Participants were interviewed three times throughout the study. Primary outcome was study feasibility measures., Results: We invited potential participants (n=75) by mail of which 27 % (n=20) agreed to participate. Telephone screening excluded four participants, and altogether 16 participants completed baseline screening. The intervention and test procedures of primary and secondary outcomes were feasible and acceptable for the participants. There were no exercise-induced injuries, indicating that the intervention program is safe. Participants experienced that the dietary and psychological counselling were delivered too early in the intervention and in too close proximity to the start of the exercise program. Minor logistic improvements were implemented throughout the intervention period., Conclusion: This study indicates that it is feasible to conduct a full-scale RCT of a multi-component randomized intervention trial, based on the model of the present study. No dropouts due to exercise-induced injury indicates that the exercises were safe. While minor improvements in logistics were implemented during the intervention, we will improve recruitment and adherence strategies, rearrange schedule of intervention contents (exercise, diet, and psychology), as well as improve the content of the dietary and behavioural counselling to maximize outcome effects in the RESTART protocol., Trial Registration: ClinicalTrials.gov Identifier: NCT03807323 Registered 16 January 2019 - retrospectively registered., (© 2021. The Author(s).)

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study., Patients and Methods: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test., Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8-99.2) and a sensitivity of 88.2% (95% CI 82.0-92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6-98.8) and the sensitivity was 85.6% (95% CI 79.0-90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1-98.9) and a sensitivity of 91.5% (95% CI 85.9-95.4)., Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Varmdal et al.)

Aims: To 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., Methods: We 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)., Results: The 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., Conclusion: The population proportion eligible for intervention increased by 3.4 percentage points from 2009 to 2017 using the revised NORRISK 2 score and guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age., Methods: We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF., Results: AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001)., Conclusion: In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life., Competing Interests: Competing interests: RBS has received lecture fees and advisory board fees from BMS/Pfizer outside this work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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/m 2 ) 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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10 -8 ), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994-1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60-2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33-2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46-2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

Objectives: The aim of this study was to investigate time trends in known and undiagnosed diabetes, glycated haemoglobin (HbA1c) levels and other cardiometabolic risk factors in the general population as well as treatment target achievement among those with diabetes., Design and Setting: Repeated cross-sectional surveys in the population-based Tromsø Study., Methods: We used age-adjusted generalised estimating equation models to study trends in self-reported and undiagnosed (HbA1c ≥6.5%) diabetes, cardiometabolic risk factors and the metabolic syndrome in 27 281 women and men aged 40-84 years examined in up to four surveys of the Tromsø Study between 1994 and 2016. Further, we analysed trends in diabetes treatment target achievement., Results: During 1994-2016, diabetes prevalence increased in women (2.3% to 4.6%) and men (2.4% to 5.8%) and in all age groups, while the proportion of undiagnosed diabetes in women (32% to 17%) and men (37% to 24%) decreased. Blood pressure and total cholesterol decreased, while waist circumference increased in participants with and without diabetes, leading to a relatively stable prevalence of the metabolic syndrome throughout the study period. There was a marginal increase in HbA1c levels among participants without diabetes. Only half of those with diabetes achieved the treatment target of HbA1c ≤7.0%., Conclusion: In the last two decades, diabetes prevalence increased, while the proportion of undiagnosed diabetes declined. The prevalence of the metabolic syndrome remained stable throughout, driven by opposing trends with an increase in obesity and a decrease in other cardiometabolic risk factors. HbA1c treatment target achievement did not improve., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the prevalence of general (body mass index (BMI) ≥30 kg/m 2 ) 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., Setting: A population study in Tromsø, Norway., Participants: The 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 Measures: Mean 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., Results: Over 8 years, the age-adjusted prevalence of general obesity increased (p<0.0001) from 20.1% to 23.0% in women and from 20.7% to 25.2% in men. The age-adjusted prevalence of abdominal obesity did not increase in women (from 54.7% to 53.4%), and the increase in men was modest (from 36.8% to 38.6%, p=0.003). Longitudinal analyses showed an increase in body weight, by 1.1 kg (95% CI 0.9 to 1.2) in women and 0.7 kg (95% CI 0.6 to 0.9) in men, and also waist circumference, by 1.3 cm (95% CI 1.0 to 1.5) in women and 1.4 cm (95% CI 1.2 to 1.6) in men. There were inverse relationships (p<0.001) between age at baseline and change in weight and waist circumference., Conclusions: Repeated 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction  Red cell distribution width (RDW) is associated with cardiovascular diseases, including atrial fibrillation (AF) and venous thromboembolism (VTE). Whether RDW is a risk marker for thromboembolic events in AF patients is scarcely known. We aimed to assess the association between RDW and the risk of AF, and AF-related VTE and ischemic stroke, in a population-based cohort. Methods  We measured RDW in 26,111 participants from the Tromsø Study (1994-1995), and registered incident AF cases through December 31, 2013. Among participants with AF, first-ever VTEs and ischemic strokes were registered from the date of AF diagnosis through the end of follow-up. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for AF by quartiles of RDW. Furthermore, we calculated cause-specific HRs for VTE and ischemic stroke by tertiles of RDW for participants with AF. Results  There were 2,081 incident AF cases during a median of 18.8 years of follow-up. Subjects with RDW in the highest quartile (RDW ≥ 13.3%) had 30% higher risk of AF than those in the lowest quartile (RDW ≤ 12.3%). Among those with AF, subjects with RDW in the upper tertile had a doubled risk of ischemic stroke (HR 2.07, 95% CI 1.20-3.57). In contrast, RDW was not associated with incident VTE in subjects with AF. Conclusion  RDW was significantly associated with incident AF in a general population. Among subjects with AF, high RDW was associated with ischemic stroke, but not VTE., Competing Interests: Conflict of Interest None declared.

Background: Atrial fibrillation (AF) is associated with increased risk of ischemic stroke and all-cause mortality. Patients with AF are also at increased risk of venous thromboembolism (VTE), but information on how AF impacts VTE-related mortality is scarce., Objectives: To investigate the impact of AF on all-cause mortality in subjects with and without a thromboembolic event (VTE or ischemic stroke)., Methods: We followed 29 833 participants from the Tromsø study (1994-2008) through 2013 and recorded all deaths during follow-up. Incident AF, VTE, and ischemic stroke were registered as time-dependent exposures. We calculated mortality rates (MRs) by exposure during follow-up and obtained hazard ratios (HRs) for death with 95% confidence intervals (CIs)., Results: A total of 2087 AF cases, 756 VTEs, and 1279 ischemic strokes were registered during a median follow-up of 18.7 years, and 4797 people (16.1%) died. The age-adjusted MR for participants without any event was 1.19 per 100 person-years (PY; 95% CI, 1.15-1.23). Compared to these participants, subjects with the joint AF + VTE exposure had a 3.7-fold increased risk of death (HR, 3.67; 95% CI, 2.77-4.66) in age- and sex-adjusted analyses, similar to the risk observed for VTE alone (HR, 3.76; 95% CI, 3.28-4.30). Participants with stroke had a 2.9-fold increased risk of death (HR, 2.85; 95% CI, 2.56-3.18), and the risk was further increased in participants with both AF and stroke (HR, 4.38; 95% CI, 3.85-4.98)., Conclusions: AF was significantly associated with increased risk of death in participants with incident stroke. In contrast, concomitant AF was not associated with excess mortality risk in VTE patients., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Objectives: The aim of this study was to use the parametric g-formula to estimate the 19-year risk of myocardial infarction (MI) under hypothetical interventions on six cardiovascular risk factors., Design and Setting: A populations-based cohort study with repeated measurements, the Tromsø Study., Primary Outcome Measure: Myocardial infarction., Participants: We estimated the relative and absolute risk reduction under feasible and intensive risk reduction strategies for smoking, physical activity, alcohol drinking, body mass index, total serum cholesterol and systolic blood pressure in 14 965 men and women with 19 years of follow-up (1994-2013)., Results: The estimated 19-year risk of MI under no intervention was 7.5% in individuals with baseline mean age 49.3 years (range 25-69). This risk was reduced by 30% (95% CI 19% to 39%) under joint feasible interventions on all risk factors, and 70% (60%, 78%) under a set of more intensive interventions. The most effective interventions were lowering of total cholesterol to 5.18 mmol/L and lowering of systolic blood pressure to 120 mm Hg (33% and 37% lower MI risk, respectively). The absolute risk reductions were significantly larger in men, in older participants, in smokers and in those with low education., Conclusion: Modification of population levels of cardiovascular risk factors could have prevented close to one-third of the cases of MI in the municipality of Tromsø during 19 years of follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The risk of venous thromboembolism (VTE) is increased after a myocardial infarction (MI). Some prothrombotic genotypes associated with VTE have also been associated with risk of MI. Whether prothrombotic single-nucleotide polymorphisms (SNPs) further increase the risk of VTE in MI patients is scarcely investigated., Aim: To study the combined effect of MI and prothrombotic SNPs on the risk of VTE., Methods: Cases with incident VTE (n = 641) and a randomly sampled subcohort weighted for age (n = 1761) were identified from the 4 to 6 surveys of the Tromsø Study (1994-2012). DNA was genotyped for rs8176719 ( ABO ), rs6025 ( F5 ), rs1799963 ( F2 ), rs2066865 ( FGG ), and rs2036914 ( F11 ). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) were estimated by categories of risk alleles and MI status., Results: Patients with MI had a 1.4-fold increased risk of VTE, and adjustments for the 5 SNPs, either alone or in combination, did not affect this relationship (adjusted HR, 1.52; 95% CI, 1.12-2.07). In subjects without MI, an increased risk of VTE was observed for each of the individual SNPs (≥1 vs. 0 risk alleles), and the risk increased linearly with increasing number of risk alleles in the 5-SNP score. The combination of MI and prothrombotic genotypes, either as individual SNPs or in the 5-SNP score, did not result in an excess risk of VTE., Conclusion: The relationship between MI and VTE was not explained by these 5 prothrombotic genotypes. Prothrombotic genotypes did not yield an excess risk of VTE in patients with MI., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.)

Aim: Long-term evaluations of childhood obesity treatments are needed. We examined changes in weight and cardiometabolic risk 1 year after children completed individual family or group-based weight management interventions., Methods: In 2009-2010, 6- to 12-year-old children with overweight or obesity from Finnmark and Troms (Norway) were recruited after media coverage and randomised to 24 months of individual family (n = 49) or group intervention (n = 48). Individual family intervention included counselling by a paediatric hospital team and a public health nurse in the local community. Group intervention included meetings with other families and a multidisciplinary hospital team, weekly physical activity sessions and a family camp. The primary outcome body mass index (BMI) and cardiometabolic risk factors were analysed 12 months after intervention., Results: From baseline to 36 months, children's BMI increased 3.0 kg/m 2 in individual family and 2.1 kg/m 2 in group intervention (between-group -0.9kg/m 2 , P = 0.096). Data were available from 62 children (64%). Between-group differences in C peptide (P = 0.01) were detected in favour of group intervention. Pooled data from both treatment groups showed continued decrease in BMI standard deviation score (P < 0.001)., Conclusion: No between-group difference in BMI was observed 12 months after intervention. Both groups combined showed sustained decrease in BMI standard deviation score., (©2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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 (% R 2 ) 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  < 0.001). In birth cohorts, when age was set to baseline in NORRISK 2 calculations, risk score decreased during follow-up. Main contributors to NORRISK 2 were systolic blood pressure, smoking and total cholesterol, with some sex, age and birth cohort differences., 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: Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE)., Objectives: To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case-cohort recruited from a general population., Methods: Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were sampled from the Tromsø study (1994-2012) and the Nord-Trøndelag health (HUNT) study (1995-2008). The DNA samples were genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Participants with missing information on risk alleles (n = 175), FHMI (n = 2769), and BMI (n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable-adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk., Results: The FHMI was associated with a 1.3-fold increased risk of VTE (HR 1.32, 95% CI 1.16-1.50) and 1.5-fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22-1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction)., Conclusions: Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk., (© 2019 International Society on Thrombosis and Haemostasis.)

Essentials Prothrombotic genotypes may agument the risk of venous thromboembolism (VTE) after ischemic stroke. We studied this effect in a case-cohort study using a genetic risk score. In stroke patients, a one-category increase in the genetic risk score was associated with a 50% higher relative risk of VTE. The risk of VTE in stroke patients increased with an increasing number of risk alleles. SUMMARY: Background Patients with ischemic stroke have a transiently increased risk of subsequent venous thromboembolism (VTE). Prothrombotic genotypes may augment VTE risk under conditions of high thrombosis risk related to stroke. Aims To investigate the effect of prothrombotic genotypes in patients with ischemic stroke on the risk of VTE in a population-based case-cohort study. Methods Cases with incident VTE (n = 664) and a randomly selected age-weighted subcohort (n = 1817) were sampled from three surveys of the Tromsø Study (1994-2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865) and F11 (rs2036914) single-nucleotide polymorphisms (SNPs). Cox regression models were used to calculate hazard ratios (HRs) for incident VTE according to individual SNPs and categories of risk alleles (5-SNP score; 0-1, 2, 3-4 and ≥ 5) in participants with and without ischemic stroke. Results There were 192 patients with incident stroke, of whom 43 developed VTE during a median of 15.2 years of follow-up. The risk alleles of individual SNPs augmented the elevated VTE risk brought about by ischemic stroke. In stroke patients, a one-category increase in the genetic risk score was associated with a 50% higher relative risk of overall VTE (HR 1.5, 95% confidence interval [CI] 1.3-1.8) and an 80% higher relative risk of provoked VTE (HR 1.8, 95% CI 1.5-2.1). Stroke patients with ≥ 5 risk alleles had a 12-fold (HR 11.7, 95% CI 4.1-33.3) higher relative risk of VTE than stroke-free participants with 0-1 risk alleles. Conclusions Prothrombotic genotypes increased the risk of VTE in stroke patients, and the risk increased with an increasing number of risk alleles., (© 2019 International Society on Thrombosis and Haemostasis.)

Aims: To examine the associations between diastolic dysfunction indices and long-term risk of all-cause mortality in adults over 23-year follow-up., Methods and Results: Participants (n = 2734) of the population-based Tromsø Study of Norway had echocardiography in 1994-1995. Of these 67% were repeated in 2001 and/or 2007-2008. Mortality between 1994 and 2016 was determined by linkage to the national death registry. Cox regression was used to model the hazard of all-cause mortality in relation to left atrial parameters (treated as time-dependent using repeated measurements) adjusted for traditional risk factors and cardiovascular disease. During the follow-up, 1399 participants died. Indexed left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio showed an U-shaped association with all-cause mortality. Combining left atrial diameter with mitral peak E deceleration time increased the prognostic accuracy for all-cause mortality whereas adding mitral peak E to peak A ratio did not increase prognostic value. We estimated new optimal cutoff values of left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio for all-cause mortality outcome. E/e' had a cubic relation to mortality., Conclusion: Both enlarged and small left atrial diameters were associated with increased all-cause mortality risk. A combination of Doppler-based left ventricle filling parameters had an incremental effect on all-cause mortality risk. The cutoff values of diastolic dysfunction indices we determined had similar all-cause mortality prediction ability as those recommended by American Association of Echocardiography and European Association of Cardiovascular Imaging., (© 2019 Wiley Periodicals, Inc.)

Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied., Methods and Results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms., Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE)., Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism., Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018., Exposures: A panel of several established cardiovascular risk factors., Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI)., Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers., Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15⁻1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80⁻2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.

Background: Studies on the relationship between temporal trends in risk factors and incidence rates of intracerebral hemorrhage are scarce., Aims: To analyze temporal trends in risk factors and incidence rates of intracerebral hemorrhage using individual data from a population-based study., Methods: We included 28,167 participants of the Tromsø Study enrolled between 1994 and 2008. First-ever intracerebral hemorrhages were registered through 31 December 2013. Hazard ratios (HRs) for intracerebral hemorrhage were analyzed by Cox proportional hazards models, risk factor levels over time by generalized estimating equations, and incidence rate ratios (IRR) by Poisson regression., Results: We registered 219 intracerebral hemorrhages. Age, male sex, systolic blood pressure (BP), diastolic BP, and hypertension were associated with intracerebral hemorrhage. Hypertension was more strongly associated with non-lobar intracerebral hemorrhage (HR 5.08, 95% CI 2.86-9.01) than lobar intracerebral hemorrhage (HR 1.91, 95% CI 1.12-3.25). In women, incidence decreased significantly (IRR 0.46, 95% CI 0.23-0.90), driven by a decrease in non-lobar intracerebral hemorrhage. Incidence rates in men remained stable (IRR 1.27, 95% CI 0.69-2.31). BP levels were lower and decreased more steeply in women than in men. The majority with hypertension were untreated, and a high proportion of those treated did not reach treatment goals., Conclusions: We observed a significant decrease in intracerebral hemorrhage incidence in women, but not in men. A steeper BP decrease in women may have contributed to the diverging trends. The high proportion of untreated and sub-optimally treated hypertension calls for improved strategies for prevention of intracerebral hemorrhage.

Physical activity and overweight are associated with myocardial infarction (MI). However, their joint association with MI remains unclear. Our objective was to examine the independent and joint association between leisure-time physical activity (LTPA), body mass index (BMI) and MI. This prospective cohort study included 16,572 men and women (47.5% women) aged 20-54 years who took part in the second Tromsø Study. At baseline in 1979-80 LTPA was assessed by questionnaire. Data on MI was collected and adjudicated through hospital and causes of death registries between 1979 and 2013. Cox proportional hazards models were used to examine the independent and joint associations between LTPA, BMI and MI. The final sample included 16,104 individuals. During a median follow up of 34 years, 1613 incident cases of MI were recorded. Physical inactivity and elevated BMI were both independently associated with MI (p for trend 0.02 and <0.001). In joint analyses, normal weight, inactive individuals had a 20% higher risk of MI compared to their active counterparts (hazard ratio (HR) 1.20 (1.02-1.41)). The highest risk of MI was seen in obese, inactive individuals when compared to normal weight, active individuals (HR 3.20 (2.30-4.44)). The risk of MI increased with increasing BMI regardless of the activity level. HRs were lower for active compared to inactive individuals within the same BMI category. The findings suggest that LTPA and BMI are independently associated with risk of MI. LTPA seems to attenuate but not eliminate the risk of MI associated with excess bodyweight., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported., Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study., Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994-1995 and 8483 participants (55% women) attending the Tromsø Study 2007-2008 for first-ever MI up to their participation in 2007-2008 and 2015-2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels., Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994-2008 and 2007-2013, respectively. Mean change in total cholesterol was -2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was -1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was -0.33 (95% confidence interval [CI] -0.51 to -0.14) for total cholesterol and -0.21 (95% CI -0.37 to -0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15-2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II., Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

Red cell distribution width (RDW), a measure of variability in size of circulating erythrocytes, is associated with arterial cardiovascular disease (CVD), but the underlying mechanism remains unclear. We aimed to investigate the impact of chronic inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) on this relationship, and explore whether RDW could be a mediator in the causal pathway between inflammation and arterial CVD. Baseline characteristics, including RDW and hs-CRP, were obtained from 5,765 individuals attending a population-based cohort study. We followed up participants from inclusion in the fourth survey of the Tromsø Study (1994/1995) until December 31, 2012. Multivariable Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for incident myocardial infarction (MI) and ischemic stroke across quintiles of hs-CRP and RDW. Subjects with hs-CRP in the highest quintile had 44% higher risk of MI (HR: 1.44, 95% CI: 1.14-1.80), and 64% higher risk of ischemic stroke (HR: 1.64, 95% CI: 1.20-2.24) compared with subjects in the lowest quintile. RDW mediated 7.2% (95% CI: 4.0-30.8%) of the association between hs-CRP and ischemic stroke. Subjects with RDW in the highest quintile had 22% higher risk of MI (HR: 1.22, 95% CI: 0.98-1.54) and 44% higher risk of ischemic stroke (HR: 1.44, 95% CI: 1.06-1.97) compared with subjects in the lowest quintile. These risk estimates were slightly attenuated after adjustments for hs-CRP. Our findings suggest that chronic inflammation is not a primary mechanism underlying the relationship between RDW and arterial CVD.

Background: Atrial fibrillation (AF) prevalence is increasing, and body mass index (BMI) is a risk factor for AF. However, sex differences in the impact of BMI on AF risk have not been fully elucidated., Methods and Results: Data from the fourth survey (1994-1995) of the Tromsø Study (Norway) were used to investigate the association of single-measurement BMI on future AF risk. To analyze the influence of BMI changes on AF risk, data from individuals who attended the third and fourth study surveys were used. AF diagnosis was derived from record linkage and end point adjudication. Cox regression analysis was conducted using fractional polynomials of BMI and BMI change with models adjusted for age, baseline BMI (change analyses), risk factors, comorbidities, and antihypertensive medications.Data were available for 24 799 individuals from the fourth survey (mean age, 45.5±14.2 years; 52.9% women). Over 15.7±5.5 years, 811 women (6.2%) and 918 men (7.9%) developed AF. In men, lower BMI decreased AF risk and higher BMI increased risk (hazard ratios [95% confidence intervals] for BMI 18 or 40 kg/m 2 compared with 23 kg/m 2 were 0.75 [0.70-0.81] and 4.42 [3.00-6.53], respectively). The same pattern was identified in women. Two surveys were attended by 14 652 individuals. In men and women, a decrease in BMI over time was associated with decreased AF risk and an increase in BMI was associated with increased AF risk., Conclusions: Within a population cohort, BMI was positively associated with AF risk. Change in BMI over time influenced AF risk in both men and women., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)