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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose To examine associations between cardiovascular risk factors and age-related macular degeneration ( AMD). Methods A population-based, cross-sectional study of Caucasians aged 65-87 years was conducted in Norway in 2007/2008. Retinal photographs were graded for AMD. Multivariable logistic regression analyses were performed based on questionnaires addressing habits of smoking, alcohol consumption, physical activity, health and medication; and physical examination comprising anthropometric measurements, blood pressure and blood sampling. Cardiovascular disease status was obtained from a validated end-point registry. Results Gradable photographs were available for 2631 participants, of whom 92 (3.5%) subjects had late AMD. In the multivariable analysis of late AMD, significant interactions were found between sex and the variables age, triglyceride level, use of lipid-lowering drugs and physical exercise. Current daily smoking was significantly related to late AMD in both sexes (odds ratio ( OR) 4.06, 95% confidence interval ( CI) 1.69-9.76 and OR 3.59, 95% CI 1.17-11.04, women and men, respectively) compared with never smokers. Higher number of pack years was associated with the presence of large drusen (>125 μm) ( OR 1.04, 95% CI 1.01-1.09 per 5 years). Higher systolic blood pressure ( OR 1.06, 95% CI 1.01-1.12 per 5 mmHg), overweight ( OR 2.87, 95% CI 1.13-7.29) and obesity ( OR 2.92, 95% CI 1.06-8.03), physical exercise duration ( OR 0.41, 95% 0.18-0.96 for 30 min or more compared with less) and frequency ( OR 0.46, 95% CI 0.23-0.92 for weekly or more often compared to less) were associated with late AMD in women only. Conclusions Smoking was strongly associated with AMD, in line with results from other populations. Also, late AMD was related to higher systolic blood pressure, physical inactivity, overweight and obesity in women. [ABSTRACT FROM AUTHOR]

Background The Rose Angina Questionnaire (RAQ) was constructed in the 1960s for assessing the population burden of angina. Studies have found that screening positivity by RAQ conferred an elevated risk of coronary heart disease (CHD). It is, however, not clear to what extent Rose angina represents early CHD in relatively young adults who are free of known CHD. If representing CHD, Rose angina is expected to carry prognostic information in addition to the risk conferred by other risk factors. Methods The Tromsø Study is a population-based cohort study in Northern Norway. All men aged 20–54 years (n=8238) and women aged 20–49 years (n=8001), free of known cardiovascular disease (CVD), who participated in a survey 1979–1980, were followed throughout 2010 for incident myocardial infarction (MI), and for incident MI or stroke used as proxy for incident CVD. HRs were estimated using a Cox proportional hazard regression model. Results In age-adjusted analyses, Rose angina predicted MI and CVD in both sexes. The excess risk was substantially accounted for by CVD risk factors, leaving no significantly elevated MI risk above the risk explained by these factors (adjusted HR 1.31; 95% CI 0.95 to 1.80 in men, HR 1.20; 95% CI 0.69 to 2.10 in women). A similar pattern was seen for CVD (adjusted HR 1.16; 95% CI 0.87 to 1.55 in men and 1.30; 95% CI 0.82 to 2.06 in women). Conclusions Rose angina predicted MI and CVD in a 29-years’ follow-up of a relatively young population. Established CVD risk factors were important mediators. [ABSTRACT FROM AUTHOR]

Background: Seasonal changes in cardiovascular disease (CVD) risk factors may be due to exposure to seasonal environmental variables like temperature and acute infections or seasonal behavioural patterns in physical activity and diet. Investigating the seasonal pattern of risk factors should help determine the causes of the seasonal pattern in CVD. Few studies have investigated the seasonal variation in risk factors using repeated measurements from the same individual, which is important as individual and population seasonal patterns may differ. Methods: The authors investigated the seasonal pattern in systolic and diastolic blood pressure, heart rate, body weight, total cholesterol, triglycerides, high-density lipoprotein cholesterol, C reactive protein and fibrinogen. Measurements came from 38 037 participants in the population-based cohort, the Tromsø Study, examined up to eight times from 1979 to 2008. Individual and population seasonal patterns were estimated using a cosinor in a mixed model. Results: All risk factors had a highly statistically significant seasonal pattern with a peak time in winter, except for triglycerides (peak in autumn), C reactive protein and fibrinogen (peak in spring). The sizes of the seasonal variations were clinically modest. Conclusions: Although the authors found highly statistically significant individual seasonal patterns for all risk factors, the sizes of the changes were modest, probably because this subarctic population is well adapted to a harsh climate. Better protection against seasonal risk factors like cold weather could help reduce the winter excess in CVD observed in milder climates. [ABSTRACT FROM AUTHOR]

Aim: The aim was to determine the prevalence of overweight and obesity among 6-year-old children in Finnmark, the northernmost county of Norway. Methods: This is a survey of 1774 children born during 1999 and 2000 from 18 of 19 child healthcare centres in Finnmark. Body mass index data extracted retrospectively in 2007 from health records at the age of 6 years were compared with international definitions of over- and underweight. The prevalence figures were further compared with socio-demographic figures on municipality level. Results: Overall, 19% of the children were classified as overweight or obese; 5% were classified as obese. The prevalence of overweight and obesity was higher among girls (22%) than among boys (16%) (p < 0.01). The prevalence of underweight was 8% among both girls and boys. Despite large variations in the prevalence of overweight and obesity between municipalities (9-35%), no association was found with municipality figures on socio-demographic factors. Conclusion: In the northernmost county Finnmark, the prevalence of overweight including obesity among 6-year-old children was somewhat higher than in previous surveys from Norway, especially among girls. [ABSTRACT FROM AUTHOR]

Background: Meteorological factors like cold temperatures and heavy snowfalls have been reported to increase myocardial infarction (MI) incidence, but there are inconsistencies in results as well as in methodology in previous studies. The objective of this study was to examine the impact of meteorological factors on incidence of MI in a population-based study in Tromsø,Norway (698399N).Methods: A total of 32 110 participants from the Tromsø Study enrolled between 1974 and 2001 were followed throughout 2004. Each incident case of MI was validated by the review of medical records and death certificates.Meteorological data from the Tromsø Weather Station were collected from the Norwegian MeteorologicalInstitute database. Poisson regression models were applied to analyse the impact of meteorological factors on MI incidence. All analyses were stratified by sex and age.Results: A total of 1882 first-ever MIs were registered. The main finding was an increase in MI incidence among persons older than 65 years with decreasing temperatures (p=0.016) and increasing snowfall (p=0.030). When comparing the lowe and upper limits of the temperature distribution (−10°C with 20°C), the MI risk increased by 47% (RR=1.47, 95% CI 1.09 to 2.13). Comparing limits of the snowfall distribution (10 with 0 mm), the MI risk increased by 44% (rr=1.44, 95% CI 1.07 to 1.94).Conclusions: In this subarctic population, MI incidence was little affected by the weather, probably due to behavioural protection. However, cold weather and heavy snowfall may be associated with increased risk of MI among older people. [ABSTRACT FROM AUTHOR]

Objective. To develop a cardiovascular risk model simulating different clinical settings using a staged approach. Design. Using data from 27 477 men and women from the Norwegian Tromsø Study in 1986–1987 and 1994–1995, Cox regression models for either myocardial infarction (MI) or stroke combined with a similar model for the competing event a risk model that assess ten-year risk of MI and stroke was developed. Explanatory variables (questions, simple examinations and blood samples) were added gradually. The model was validated using Hosmer-Lemeshow test, the Brier score, c-index, integrated discrimination improvement (IDI) and Net Reclassification Improvement (NRI). Results. In total, 1 298 events of MI and 769 events of stroke were registered. For MI the model showed excellent discrimination in each step with c-index from 0.833 to 0.946. For stroke the c-index ranged between 0.817 and 0.898. IDI showed significant increases in discrimination. The Brier scores and goodness of fit test showed well calibrated models in all steps for all sex- and end-point specific models (p>0.05). Conclusions. Although the predictive and discriminative ability of the models increased with each step, even the simplest model containing only data from questions or blood samples alone yielded valid estimates of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results. Methods: Data were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143). 1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day. Results: The high-consumption county had higher prevalence of statin use in all age groups. Atorvastatin and simvastatin were dispensed in 79-87% of all statin users, and the proportion was significantly higher in the high-consumption county. The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The high-consumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties. Conclusion: Although differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county. [ABSTRACT FROM AUTHOR]

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

Introduction: The prevalence of type 2 diabetes is increasing worldwide. In Norway, register-based studies have reported an increased prevalence of type 2 diabetes and, recently, a decrease in incidence of type 2 diabetes. Aim: To investigate long-term trends in self-reported diabetes, HbA1c levels and medication use in a population-based study. Methods: We used self-report and laboratory data from adult women and men participating in one or more of four consecutive surveys of the population-based Tromsø Study; Tromsø 4 1994-95 (n=27158), Tromsø 5 2001 (n=8130), Tromsø 6 2007-08 (n=12984) and Tromsø 7 2015-16 (n=21083). Participants answered questionnaires including questions on diabetes and medication use. Non-fasting blood samples were collected and analysed for HbA1c at Department of Laboratory Medicine University Hospital North Norway. We included participants aged 40-89 years at each survey without missing values on the diabetes question in Tromsø 4 (n=16830), Tromsø 5 (n=7206), Tromsø 6 (n=12200), Tromsø 7 (n=20434) to study trends in diabetes prevalence. Moreover, we used HbA1c levels in Tromsø 4 (n=6720), Tromsø 5 (n=5833), Tromsø 6 (n=12003) and Tromsø 7 (n=20174) to study trends in diabetes unawareness (HbA1c =6.5% & no self-reported diabetes), and to study treatment target achievement (HbA1c=7.0% & self-reported diabetes). We used generalized estimating equation models to study overall and group-specific age-adjusted trends in women and men in 10-year age-groups. Results: In preliminary analyses, we found a statistically significant increase in prevalence of selfreported diabetes in both sexes and all age-groups. More results will be available. Conclusion: In these preliminary analyses, using self-report and laboratory data from repeated crosssectional surveys of an adult general population, we found an increase in prevalence of self-reported diabetes over the last two decades. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood.Methods: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years.Results: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90 versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index.Conclusions: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors.Methods and Results: We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48-97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively.Conclusions: We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events. [ABSTRACT FROM AUTHOR]

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.)

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.

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.

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.)

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.)

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: 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.)

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: 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.)

Background: Atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS). Emerging evidence also indicates an association between AF and pulmonary embolism (PE). Because IS may potentially mediate the observed risk of PE in AF, we aimed to assess the impact of AF on the cause-specific risks of PE and IS in a large cohort recruited from the general population., Methods and Results: We observed 29 842 participants from 3 surveys of the Tromsø study (inclusion in 1994-1995, 2001-2002, and 2007-2008) to the end of 2012. Incident events of AF, IS, and PE during follow-up were recorded, and information on potential confounders was obtained at baseline. Cox regression models, with AF as a time-dependent variable, were used to calculate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for PE and IS. There were 2067 participants diagnosed as having AF, 296 with PE and 1164 with IS, during a median of 17.6 years of follow-up. The risks of PE (HR, 10.88; 95% CI, 6.23-18.89) and IS (HR, 6.16; 95% CI, 4.47-8.48) were substantially increased during the first 6 months after AF diagnosis, with crude incidence rates of 18.5 per 1000 person-years for PE and 52.8 per 1000 person-years for IS. The risk estimates remained elevated for both PE (HR, 1.72; 95% CI, 1.10-2.71) and IS (HR, 2.45; 95% CI, 2.05-2.92) throughout the study period., Conclusions: AF was associated with increased cause-specific risks of both PE and IS. Our findings infer that the risk of PE in AF is not explained by intermediate IS., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Red cell distribution width (RDW), a measure of the variability in size of the circulating erythrocytes, is associated with cardiovascular morbidity and mortality. We aimed to investigate whether RDW was associated with incident stroke and case fatality in subjects recruited from the general population. Baseline characteristics were obtained from 25,992 subjects participating in the fourth survey of the Tromsø Study, conducted in 1994/95. Incident stroke was registered from inclusion until December 31, 2010. Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (95% CI) for stroke, adjusted for age, sex, body mass index, smoking, haemoglobin level, white blood cell count, thrombocyte count, hypertension, total cholesterol, triglycerides, self-reported diabetes, and red blood cell count. During a median follow-up of 15.8 years, 1152 participants experienced a first-ever stroke. A 1% increment in RDW yielded a 13% higher risk of stroke (multivariable HR: 1.13, 95% CI: 1.07-1.20). Subjects with RDW in the highest quintile compared to the lowest had a 37% higher risk of stroke in multivariable analysis (HR: 1.37, 95% CI: 1.11-1.69). Subjects with RDW above the 95-percentile had 55% higher risk of stroke compared to those in the lowest quintile (HR: 1.55, 95% CI: 1.16-2.06). All risk estimates remained unchanged after exclusion of subjects with anaemia (n=1102). RDW was not associated with increased risk of death within one year or during the entire follow-up after an incident stroke. RDW is associated with incident stroke in a general population, independent of anaemia and traditional atherosclerotic risk factors.

Background: Though the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population., Methods and Findings: Measurements and DNA were obtained from the participants in the Tromsø Study in 1994-1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05-1.49) for T2D and 1.14 (1.02-1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints., Conclusions: The VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.

Objective: To investigate the association between echocardiographic measurements with emphasis on diastolic dysfunction and risk of atrial fibrillation (AF) in a population-based cohort study., Methods: We followed 2406 participants from the Tromsø Study from 1994 to 2010. Left atrial (LA) size and mitral Doppler indices as measured by echocardiography were used for evaluating diastolic dysfunction. Information concerning age, systolic blood pressure, height, heart rate, body mass index, total and high-density lipoprotein cholesterol, self-reported use of alcohol, smoking, coffee, physical activity, antihypertensive treatment, prevalent coronary heart disease, valvular heart disease, heart failure, hypertrophy, diabetes and palpitations were obtained at baseline. The outcome measure was clinical AF, documented by an ECG., Results: AF was detected in 462 subjects (193 women). Mean age at baseline was 62.6 years. Incidence rate of clinical AF was 12.6 per 1000 person-years. In multivariable Cox proportional hazards regression analysis, moderately enlarged LA was associated with 60% (95% CI 1.2 to 2.0) increased risk of AF. Severely enlarged LA had HR for AF of 4.2 (95% CI 2.7 to 6.5) with p value for linear trend <0.001, and the association was similar in both sexes. Abnormal mitral Doppler flow adjusted for predictor variables did not show a statistically significant association with AF risk. However, when LA size was also adjusted for, the risk of AF increased by 30% (95% CI 1.0 to 1.6)., Conclusions: Our findings suggest that enlarged LA as a measure for diastolic dysfunction is a significant risk factor for AF in both sexes, and adding measures of abnormal diastolic flow increased the predictive ability significantly., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Identification of individuals with high risk for first-ever myocardial infarction (MI) can be improved. The objectives of the study were to survey multiple protein biomarkers for association with the 10-year risk of incident MI and identify a clinically significant risk model that adds information to current common risk models., Methods and Results: We used an immunoassay platform that uses a sensitive, sample-efficient molecular counting technology to measure 51 proteins in samples from the fourth survey (1994) in the Tromsø Study, a longitudinal study of men and women in Tromsø, Norway. A case control design was used with 419 first-ever MI cases (169 females/250 males) and 398 controls (244 females/154 males). Of the proteins measured, 17 were predictors of MI when considered individually after adjustment for traditional risk factors either in men, women, or both. The 6 biomarkers adjusted for traditional risk factors that were selected in a multivariable model (odds ratios [OR] per standard deviation) using a stepwise procedure were apolipoprotein B/apolipoprotein A1 ratio (1.40), kallikrein (0.73), lipoprotein a (1.29), matrix metalloproteinase 9 (1.30), the interaction term IP-10/CXCL10×women (0.69), and the interaction term thrombospondin 4×men (1.38). The composite risk of these biomarkers added significantly to the traditional risk factor model with a net reclassification improvement of 14% (P=0.0002), whereas the receiver operating characteristic area increased from 0.757 to 0.791, P=0.0004., Conclusions: Novel protein biomarker models improve identification of 10-year MI risk above and beyond traditional risk factors with 14% better allocation to either high or low risk group., (© 2015 American Heart Association, Inc.)

Background/aims: Estimated glomerular filtration rate (eGFR) is used extensively in epidemiological research. Validations of eGFR have demonstrated acceptable performance, but the dependence of creatinine and cystatin C on non-GFR factors could confound associations with disease. Few studies have investigated this issue in direct comparison with measured GFR (mGFR). We compared the associations between eGFR and mGFR and retinal vasculopathy, a marker of systemic microvasculopathy., Methods: Iohexol clearance and retinal photography were examined in the Renal Iohexol Clearance Survey in Tromsø 6, which consists of a representative sample of middle-aged persons from the general population. A total of 1,553 persons without self-reported kidney disease, cardiovascular disease or diabetes were investigated. Three eGFR equations based on creatinine and/or cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated regression methods., Results: mGFR in the lowest quartile was associated with an increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16-2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C (eGFRcys) was consistently biased relative to mGFR in its associations with retinal vessel diameters across different models. eGFR based on creatinine (eGFRcrea) and eGFR based on both creatinine and cystatin C were also biased in several of these models (p < 0.05). For retinopathy, the differences between the 3 eGFR and mGFR measurements were not statistically significant., Conclusions: Low mGFR is associated with retinopathy in the general population. eGFR based on creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the relationship between the retina and kidney function in healthy persons., (© 2015 S. Karger AG, Basel.)

Obesity is a risk factor for arterial and venous thromboembolism. However, it is not known whether obesity mediates risk through shared mechanisms. In a population-based cohort, we aimed to compare the impact of obesity measures on risk of venous thromboembolism (VTE) and myocardial infarction (MI), and explore how obesity-related atherosclerotic risk factors influenced these relationships. Measures of body composition including body mass index , waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR) and waist-to-height ratio (WHtR) were registered in 6,708 subjects aged 25-84 years, who participated in the Tromsø Study (1994-1995). Incident VTE- and MI-events were registered until January 1, 2011. There were 288 VTEs and 925 MIs during a median of 15.7 years of follow-up. All obesity measures were related to risk of VTE. In linear models, WC showed the highest risk estimates in both genders. In categorized models (highest versus lowest quintile), WC showed highest risk in men (HR 3.59; 95 % CI 1.82-7.06) and HC in women (HR 2.27; 95 % CI 1.54-4.92). Contrary, WHR and WHtR yielded the highest risk estimates for MI. The HR of MI (highest vs. lowest quintile) for WHR was 2.11 (95 % CI 1.59-2.81) in men and 1.62 (95 % CI 1.13-2.31) in women. The risk estimates for MI were substantially attenuated after adjustment for atherosclerotic risk factors, whereas the estimates for VTE remained unchanged. Our findings suggest that the impact of body fat distribution, and the causal pathway, differs for the association between obesity and arterial and venous thrombosis.

Background: A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort., Methods and Results: The study included 21 624 subjects recruited from the Tromsø Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35-1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02-1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12-2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE., Conclusions: FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors., (© 2014 American Heart Association, Inc.)

Background: Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is associated with mortality and adverse outcome in selected populations with cardiovascular disease. It is scarcely known whether RDW is associated with incident myocardial infarction (MI). We aimed to investigate whether RDW was associated with risk of first-ever MI in a large cohort study with participants recruited from a general population., Methods and Results: Baseline characteristics, including RDW, were collected for 25 612 participants in the Tromsø Study in 1994-1995. Incident MI during follow-up was registered from inclusion through December 31, 2010. Cox regression models were used to calculate hazard ratios with 95% confidence intervals for MI, adjusted for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets, and other traditional cardiovascular risk factors. A total of 1779 participants experienced a first-ever MI during a median follow-up time of 15.8 years. There was a linear association between RDW and risk of MI, for which a 1% increment in RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to 1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI, 1.34 to 2.20). All effect estimates were essentially similar after exclusion of participants with anemia (n=1297) from the analyses., Conclusion: RDW is associated with incident MI in a general population independent of anemia and cardiovascular risk factors., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: To describe trends in cardiovascular risk factors and change over time across education levels, and study the influence from medicine use and gender., Methods: Data from participants (30-74 years) of the Tromsø Study in 1994-1995 (n=22 108) and in 2007-2008 (n=11 565). Blood samples, measurements and self-reported educational level and medicine use were collected., Results: Differences in risk factor levels across education groups were persistent for all risk factors over time, with a more unfavourable pattern in the lowest education group. The exception was cholesterol, with the reduction being largest in the lowest educated, resulting in weakened educational trends over time. While a significant educational trend in cholesterol persisted among the non-users of lipid-lowering drugs (LLD), no educational trend in cholesterol was found among the LLD users in 2007-2008. The strongest educational trends were found for daily smoking and Body Mass Index (BMI). In 2007-2008 the odds for being a smoker were five times higher among the lowest educated compared to the highest educated. In men, the odds for being in the highest quintile of the BMI distribution were, in 2007-2008, almost doubled in the lowest compared to the highest educated. The lowest educated women had 6.2 mm Hg higher mean systolic blood pressure than the highly educated, mean BMI of 26.4 kg/m 2 and smoking prevalence of 37.7%., Conclusions: The difference across education groups for cholesterol levels decreased, while the educational gap persisted over time for the other risk factors. Use of LLD seemed to contribute to the reduction of social differences in cholesterol levels., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 × 10(-8)). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.

Aims: Serum uric acid (SUA) has been associated with cardiovascular disease in population studies, but its relation to atrial fibrillation (AF) is largely unknown. The aim of this study was to investigate the association between baseline SUA and future AF in a large population-based cohort., Methods and Results: A total of 6308 men and women from a population survey in Tromsø, Norway in 1994-95 were followed-up for 10.8 years. The mean age at baseline was 60 years. Information on angina, myocardial infarction, diabetes, anti-hypertensive and diuretic treatment, physical activity, smoking and alcohol, and measurements of height, weight, blood pressure, SUA, total cholesterol, and high density lipoprotein-cholesterol were obtained at baseline. The outcome measure was first-ever AF, documented on an electrocardiogram. We identified 572 cases of incident AF. In multivariable Cox proportional hazards regression analysis adjusted for cardiovascular risk factors and concomitant diseases, SUA was associated with AF in both sexes. Hazard ratio per 1 SD increase in SUA (91 μmol/L) was 1.40 [95% confidence intervals (CI), 1.14-1.72] in women and 1.17 (95% CI, 1.02-1.36) in men. The upper quartile of SUA conferred a 76% increased risk for AF in women and 49% in men as compared with the lowest quartile., Conclusion: This prospective population-based cohort study showed that baseline SUA was associated with an increased risk for future AF in both sexes.

Background: Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population., Methods and Results: In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69-6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32-3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients., Conclusions: Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE.

Background: Pulmonary embolism (PE) may trigger atrial fibrillation through increased right atrial pressure and subsequent atrial strain, but the degree of evidence is low. In this study, we wanted to investigate the impact of incident venous thromboembolism (VTE) on future risk of atrial fibrillation in a prospective population-based study., Methods and Results: The study included 29 974 subjects recruited from the Tromsø study (1994-1995, 2001-2002, 2007-2008). Incident VTE and atrial fibrillation events were registered from date of enrolment to end of follow-up, December 31, 2010. Cox proportional hazard regression models using age as time-scale and VTE as a time-dependent variable were used to estimate crude and multivariable hazard ratios (HRs) for atrial fibrillation with 95% confidence intervals (CIs). During 16 years of follow up, 540 (1.8%) subjects had an incident VTE event, and 1662 (5.54%) were diagnosed with atrial fibrillation. Among those with VTE, 50 (9.3%) developed subsequent atrial fibrillation. Patients with VTE had 63% higher risk of atrial fibrillation compared to subjects without VTE (multivariable-adjusted HR: 1.63, 95% CI: 1.22 to 2.17). The risk of atrial fibrillation was particularly high during the first 6 months after the VTE event (HR 4.00, 95% CI: 2.21 to 7.25) and among those with PE (HR 1.78, 95% CI: 1.13 to 2.80)., Conclusions: We found that incident VTE was associated with future risk of atrial fibrillation. Our findings support the hypothesis that PE may lead to cardiac dysfunctions that, in turn, could trigger atrial fibrillation.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia which increases morbidity and mortality. Identification of risk factors is therefore important. We examined the impact of palpitations and cardiovascular risk factors in prediction of AF (all types) and lone AF in a large population-based cohort., Design: We carried out a prospective population-based cohort study., Methods: A total of 22,815 participants from a population survey in 1994-1995 were followed-up for a mean of 11.1 years. Mean age at baseline was 46 years. Measurements of height, weight, blood pressure, heart rate, total cholesterol and high-density lipoprotein (HDL)-cholesterol, and information on palpitations, diabetes, angina, myocardial infarction, and antihypertensive treatment were obtained at baseline. The outcome measure was first-ever AF, documented on an electrocardiogram. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for AF., Results: Palpitations were associated with increased risk of AF in both women (HR 1.62, 95% confidence interval [CI] 1.29-2.02) and men (HR 1.91, 95% CI 1.54-2.35). For hypertension the HR for AF was 1.98 (1.46-2.69) in women and 1.40 (1.13-1.74) in men. The HR for 1 SD increase in body mass index (BMI) was 1.16 (1.06-1.27) in women and 1.47 (1.32-1.63) in men. Body height and BMI were associated with increased risk for lone AF in men., Conclusion: Palpitations, hypertension and BMI were predictive of future atrial fibrillation in both sexes.

Background: Inflammatory biomarkers are reported as risk factors for atrial fibrillation (AF), but their impact is uncertain., Objective: We investigated the associations between inflammatory biomarkers and future AF in a large general cohort., Methods: Available markers were white blood cells (WBCs) with subgroups, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and osteoprotegerin (OPG). A total of 6315 men and women from a population survey in Tromsø, Norway in 1994 to 1995 were followed for a mean of 10.9 years. Mean age at baseline was 60 years. Measurements of height, weight, blood pressure, heart rate, total cholesterol, high-density lipoprotein (HDL) cholesterol, WBC count, and information on diabetes, angina, myocardial infarction, and antihypertensive treatment, were obtained at baseline. Fibrinogen, hs-CRP, and OPG were obtained at a follow-up visit. The outcome measure was first-ever AF, documented on an electrocardiogram. The Cox proportional hazards regression model was used to estimate hazard ratios of AF., Results: In the multivariable analysis, adjusted for traditional cardiovascular risk factors and other inflammatory biomarkers, hs-CRP was associated with AF in men only (hazard ratio = 1.14 for a 1 SD increase; 95% CI, 1.02-1.28). There was a significant increase in AF across quartiles of WBCs in men (P = 0.007) and in the total study population (P = 0.004). OPG was associated with AF in patients free of coronary heart disease at baseline. Fibrinogen and subgroups of WBCs showed no significant association with AF., Conclusion: This population-based cohort study showed that hs-CRP was independently associated with AF in men, but apparently not in women, and that patients with WBCs in the upper quartile had increased risk of AF., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

Background: Although the mortality of coronary heart disease (CHD) has declined in Western countries during the last decades, studies have suggested that the prevention and treatment of CHD may not have been as effective in women as in men. We examined gender- and age-specific trends in incidence, case fatality and the severity of first myocardial infarction (MI) in a large Norwegian population-based study., Design: Prospective population-based cohort study., Methods: A total of 31,323 participants enrolled between 1974 and 2001 were followed throughout 2004 for a total of 400,572 person-years. Suspected coronary events were adjudicated by a review of hospital records and death certificates. A total of 1669 events fulfilled standardized criteria of first-ever fatal or non-fatal MI., Results: In the age group 35-79 years, the age-adjusted incidence of MI declined significantly in men, whereas an increase was observed in women. For men and women ≥ 80 years the incidence rates remained unchanged. The severity of MI and the 28-day and 1-year case fatality rates declined significantly and similarly in men and women., Conclusion: Trends in MI incidence differed by sex and age; in the age group 35-79 years a marked decrease was observed among men but an increase was observed among women, while no change was observed among older patients. MI severity and case fatality were clearly reduced for both sexes. These data suggest that the burden of CHD is shifting from middle-aged men toward middle-aged women and elderly patients.