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Objective: Associations between occupational physical activity (OPA) and mortality risks are inconclusive. We aimed to examine associations between (1) OPA separately and (2) jointly with leisure time physical activity (LTPA), and risk of all-cause, cardiovascular disease (CVD) and cancer mortality, over four decades with updated exposure and covariates every 6-8 years., Methods: Adults aged 20-65 years from the Tromsø Study surveys Tromsø3-Tromsø7 (1986-2016) were included. We categorised OPA as low (sedentary), moderate (walking work), high (walking+lifting work) or very high (heavy manual labour) and LTPA as inactive, moderate and vigorous. We used Cox/Fine and Gray regressions to examine associations, adjusted for age, body mass index, smoking, education, diet, alcohol and LTPA (aim 1 only)., Results: Of 29 605 participants with 44 140 total observations, 4131 (14.0%) died, 1057 (25.6%) from CVD and 1660 (40.4%) from cancer, during follow-up (median: 29.1 years, 25th-75th: 16.5.1-35.3). In men, compared with low OPA, high OPA was associated with lower all-cause (HR 0.83, 95% CI 0.74 to 0.92) and CVD (subdistributed HR (SHR) 0.68, 95% CI 0.54 to 0.84) but not cancer mortality (SHR 0.99, 95% CI 0.84 to 1.19), while no association was observed for moderate or very high OPA. In joint analyses using inactive LTPA and low OPA as reference, vigorous LTPA was associated with lower all-cause mortality combined with low (HR 0.75, 95% CI 0.64 to 0.89), high (HR 0.67, 95% CI 0.54 to 0.82) and very high OPA (HR 0.74, 95% CI 0.58 to 0.94), but not with moderate OPA. In women, there were no associations between OPA, or combined OPA and LTPA, with mortality., Conclusion: High OPA, but not moderate and very high OPA, was associated with lower all-cause and CVD mortality risk in men but not in women. Vigorous LTPA was associated with lower mortality risk in men with low, high and very high OPA, but not moderate OPA., Competing Interests: Competing interests: M-LL has received lecture fees from Bayer, Sanofi and BMS/Pfizer not related to this study. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

There is an immediate need to optimize cardiovascular (CV) risk management and primary prevention of childhood obesity to timely and more effectively combat the health hazard and socioeconomic burden of CV disease from childhood development to adulthood manifestation. Optimizing screening programs and risk management strategies for obesity-related CV risk in childhood has high potential to change disease trajectories into adulthood. Building on a holistic view on the aetiology of childhood obesity, this document reviews current concepts in primary prevention and risk management strategies by lifestyle interventions. As an additional objective, this scientific statement addresses the high potential for reversibility of CV risk in childhood and comments on the use of modern surrogate markers beyond monitoring weight and body composition. This scientific statement also highlights the clinical importance of quantifying CV risk trajectories and discusses the remaining research gaps and challenges to better promote childhood health in a population-based approach. Finally, this document provides an overview on the lessons to be learned from the presented evidence and identifies key barriers to be targeted by researchers, clinicians, and policymakers to put into practice more effective primary prevention strategies for childhood obesity early in life to combat the burden of CV disease later in life., Competing Interests: Conflict of interest: G.B.Z. has consulted for Cardionovum, Crannmedical, Innovheart, Guidotti, Meditrial, Opsens Medical, Replycare, Teleflex, and Terumo. D.W. has received consulting and lecturing fees from Novo Nordisk A/S. M.L.L. has received lecture fees from Bayer, Sanofi and BMS/Pfizer., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Background: Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless., Discussion: The rapid evolution of the e-cigarette market has outpaced the legislator's regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence., Conclusion: This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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: 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.

Aims: This study examined the association of leisure time physical activity, occupational physical activity, and resting heart rate with all-cause and cardiovascular disease mortality in Sami and non-Sami populations., Study Design: This was a longitudinal, observational population-based study., Methods: The Finnmark 3 study cohort was examined in 1987-1988 and followed for all-cause and cardiovascular disease mortality for 26 years. The cohort included 17,697 men and women with a mean age of 47.2 years at baseline. Leisure time physical activity and occupational physical activity were assessed with a validated questionnaire at baseline, whereas cause of death was obtained from the Norwegian Cause of Death Registry., Results: A total of 1983 women and 3147 men died during follow-up. Leisure time physical activity was linearly and inversely associated with all-cause mortality, but not coronary heart disease mortality. Compared to inactive subjects, all-cause mortality was significantly reduced by 16% in the active leisure time physical activity group (hazard ratio 0.84; 95% confidence interval 0.76-0.92). Both for all-cause and cardiovascular disease mortality, we observed a U-shaped relationship with occupational physical activity, as participants in the walking and lifting group had significantly lower mortality than both the mostly sedentary and the heavy manual labour group ( p  < 0.05). An increase in resting heart rate by one beat per minute was associated with a 1.1% increase in all-cause mortality (hazard ratio 1.011; 95% confidence interval 1.009-1.013). The associations were similar in Sami and non-Sami subjects., Conclusion: In this population-based study, leisure time physical activity was inversely associated with all-cause mortality, whereas resting heart rate was positively associated with all-cause and cardiovascular disease mortality. There was a U-shaped association between occupational physical activity and cardiovascular disease and all-cause mortality.

Albuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetyl-β-D-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994-1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%-80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group., (Copyright © 2016 by the American Society of Nephrology.)

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., (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.)

A reduced glomerular filtration rate (GFR) in chronic kidney disease is a risk factor for cardiovascular disease. However, evidence indicates that a high GFR may also be a cardiovascular risk factor. This issue remains unresolved due to a lack of longitudinal studies of manifest cardiovascular disease with precise GFR measurements. Here, we performed a cross-sectional study of the relationship between high GFR measured as iohexol clearance and subclinical cardiovascular disease in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6), a representative sample of the middle-aged general population. A total of 1521 persons without cardiovascular disease, chronic kidney disease, diabetes, or micro- or macroalbuminuria were examined with carotid ultrasonography and electrocardiography. The GFR in the highest quartile was associated with an increased odds ratio of having total carotid plaque area greater than the median of non-zero values (odds ratio 1.56, 95% confidence interval 1.02-2.39) or electrocardiographic signs of left ventricular hypertrophy (odds ratio 1.62, 95% confidence interval 1.10-2.38) compared to the lowest quartile. The analyses were adjusted for cardiovascular risk factors, urinary albumin excretion, and fasting serum glucose. Thus, high GFR is associated with carotid atherosclerosis and left ventricular hypertrophy and should be investigated as a possible risk factor for manifest cardiovascular disease in longitudinal studies.

Importance: Identification of structural heart disease in asymptomatic individuals could allow early disease-modifying treatment., Objective: To examine whether echocardiographic screening in the general population improves long-term survival or reduces the risk of cardiovascular disease., Design, Setting, and Participants: We studied 6861 middle-aged participants from the population-based Tromsø Study in Norway., Intervention: Participants were randomly allocated to an echocardiographic screening group (n = 3272) or a control group (n = 3589)., Main Outcomes and Measures: Using the as-treated approach, the data were analyzed for mortality and incidence of fatal and nonfatal myocardial infarction and stroke., Results: During 15 follow-up years, 880 persons (26.9%) in the screening group and 989 persons (27.6%) in the control group died (hazard ratio, 0.97; 95% CI, 0.89-1.06). No significant differences between the groups were observed in the secondary outcome measures (sudden death, mortality from any heart disease, or incidence of fatal and nonfatal myocardial infarction and stroke)., Conclusions and Relevance: Echocardiographic screening for structural and valvular heart disease in the general population provided no benefit for mortality or for the risk of myocardial infarction or stroke.

Background: Glomerular filtration rate<60 mL/min/1.73 m2 is associated with increased cardiovascular risk. Cystatin C is believed to be a better tool than creatinine for detection of mild renal dysfunction (>60 mL/min/1.73 m2) and possibly a more sensitive marker for cardiovascular risk and all-cause mortality. We examined the association of cystatin C with cardiovascular morbidity and all-cause mortality in a prospective population-based study., Methods: Cystatin C was measured in 2852 men and 3153 women in the Tromsø Study 1994/95. Gender-specific associations during 12 years of follow-up for all-cause mortality and 9.5 years for myocardial infarction (MI) and ischaemic stroke were assessed (Cox proportional hazard ratios, HRs)., Results: During follow-up, 591 MIs, 293 ischaemic strokes and 1262 deaths occurred. In women, HR for all-cause mortality was increased in the upper cystatin C quartile (≥0.93 mg/L) compared with the lowest quartile (≤0.73 mg/L); 1.38, 95% confidence interval 1.04-1.84. A significant interaction with gender was observed. One SD (0.17 mg/L) increase in cystatin C was associated with 9% higher risk of death in women, also when persons with a cancer history were excluded. Crude HRs for MI and ischaemic stroke were increased in both genders, but the associations did not persist after multivariable adjustments. No independent associations with end points were observed in non-gender-specific analyses., Conclusions: Cystatin C was not independently associated with fatal and non-fatal MI or ischaemic stroke in the general population. However, cystatin C was a risk factor for all-cause mortality in women.

In the western world, cardiovascular disease is the leading cause of death for both sexes. These diseases show substantial differences between the sexes with respect to epidemiology, biology and clinical aspects. In recent years, more attention has been directed towards sex differences in pharmacological effects. Although both sexes are included in most pharmacological trials, the proportion of women is often too low to enable sex-specific analyses.

Machine Learning (ML) methods have become important for enhancing the performance of decision-support predictive models. However, class imbalance is one of the main challenges for developing ML models, because it may bias the learning process and the model generalization ability. In this paper, we consider oversampling methods for generating synthetic categorical clinical data aiming to improve the predictive performance in ML models, and the identification of risk factors for cardiovascular diseases (CVDs). We performed a comparative study of several categorical synthetic data generation methods, including Synthetic Minority Oversampling Technique Nominal (SMOTEN), Tabular Variational Autoencoder (TVAE) and Conditional Tabular Generative Adversarial Networks (CTGANs). Then, we assessed the impact of combining oversampling strategies and linear and nonlinear supervised ML methods. Lastly, we conducted a post-hoc model interpretability based on the importance of the risk factors. Experimental results show the potential of GAN-based models for generating high-quality categorical synthetic data, yielding probability mass functions that are very close to those provided by real data, maintaining relevant insights, and contributing to increasing the predictive performance. The GAN-based model and a linear classifier outperform other oversampling techniques, improving the area under the curve by 2%. These results demonstrate the capability of synthetic data to help with both determining risk factors and building models for CVD prediction. [ABSTRACT FROM AUTHOR]

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. [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: Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods: In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings: We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00–1.29), 1.33 (1.16–1.51), and 1.67 (1.44–1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. Interpretation: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths. [ABSTRACT FROM AUTHOR]

High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies showing a blood pressure decline in recent decades lack data to follow individuals born in different decades from early and middle adulthood to older age. We investigated changes in age-specific blood pressure by repeated measurements in 37 973 women and men born 1905 to 1977 (aged 20–89 years) examined ≤5× between 1979 and 2008 in the population-based Tromsø Study. Mixed models were used to estimate time trends. Mean systolic and diastolic blood pressure decreased from 1979 to 2008 in both genders in the age groups 30 to 89 years. The decrease was similar in the 80th percentile and the 20th percentile of the population blood pressure distribution. The decrease in systolic blood pressure in age group 40 to 49 years was 10.6 mm Hg in women and 4.5 mm Hg in men. Systolic blood pressure increased with age in women and men born 1920 to 1949, whereas a decrease or flattening of curve was observed in the younger birth cohorts. Thus, we found both time periodic and cohort effects, and trends were more pronounced in women than in men. The findings suggest changes in blood pressure in the population rather than an effect of treatment of high-risk individuals. [ABSTRACT FROM AUTHOR]

Background: The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovascular health by 20%. The objectives of the study were to assess the association between the proposed cardiovascular health metric score and incident myocardial infarction (MI) and to estimate the generalized impact fraction (GIF). Methods: The health metric score was derived from ideal levels of six cardiovascular risk factors from the population-based Tromsø Study of 22,121 residents of Tromsø, Norway aged 30 to 79 years, examined in 1994-95, 2001, and 2007-08. Incident events of MI were recorded from the date of enrollment in 1994-95 to the end of 2010. Adjudication of hospitalized and out-of hospital events was performed by an independent endpoints committee based on data from hospital and out-of hospital journals, autopsy records and death certificates. Cox proportional hazard regression was used to estimate hazard ratios (HR). GIF was calculated from age stratified analysis using a case-load weighted-sum method. Bootstrapping was used to estimate 95% simulation intervals. Results: A total of 1652 MIs accrued over an average of 14.7 person-years of follow-up. Few men (0.96%) and women (3.6%) had ideal levels in all 6 metrics. 64.7% (men) and 55.7% (women) had ideal levels in 2 or 3 metrics. The age-adjusted HR per point increase in health score was 0.65 (95% confidence interval: 0.61, 0.70) in men and 0.59 (0.54, 0.64) in women. A shift of 30% of subjects from low score levels ⩽3 to scores ⩾4 was estimated to prevent 13.7% (11.2, 16.2) of incident MI in men and 15.9% (12.1, 19.4) in women. Conclusions: The association between the health metric score and MI indicate that close to 15% of incident MIs could be prevented by attainable and realistic improvements in the health metrics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. To assess the population burden of angina pectoris symptoms (APS), self-reported angina and a combination of these, and explore potential ethnic disparity in their patterns. If differences in APS were found between Sami and non-Sami populations, we aimed at evaluating the role of established cardiovascular risk factors as mediating factors. Design. Cross-sectional population-based study. Methods. A health survey was conducted in 2003-2004 in areas with Sami and non-Sami populations (SAMINOR). The response rate was 60.9%. The total number for the subsequent analysis was 15,206 men and women aged 36-79 years (born 1925-1968). Information concerning lifestyle was collected by 2 self-administrated questionnaires, and clinical examinations provided data on waist circumference, blood pressure and lipid levels. Results. This study revealed an excess of APS, self-reported angina and a combination of these in Sami relative to non-Sami women and men. After controlling for age, the odds ratio (OR) for APS was 1.42 (p <0.001) in Sami women and 1.62 (p <0.001) for men. When including relevant biomarkers and conventional risk factors, little change was observed. When also controlling for moderate alcohol consumption and leisure-time physical activity, the OR in women was reduced to 1.24 (p =0.06). Little change was observed in men. Conclusion. This study revealed an excess of APS, self-reported angina and a combination of these in Sami women and men relative to non-Sami women and men. Established risk factors explained little or none of the ethnic variation in APS. In women, however, less moderate alcohol consumption and leisure-time physical activity in Sami may explain the entire ethnic difference. [ABSTRACT FROM AUTHOR]

Objective: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B ( PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general. Methods: DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer, or death, as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (fT4), and free T3 (fT3) were measured. Results: From the Tromsø Study, 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer, and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level that was 0.29 mIU/L higher than in the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 [1.00-1.29], hazard ratio [confidence interval], Cox regression with adjustment for age, sex, and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5 cm). In 584 subjects with serum TSH, fT4, and fT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and nonsignificantly lower serum fT3 (mean difference 0.15 pmol/L) levels than subjects with the G:G genotype. Conclusion: rs4704397 is associated with thyroid function, risk of MI, and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn. [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]

Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 × 10−7). We identified one locus for heart rate (MYH6), four for PR interval (TBX5, SCN10A, CAV1 and ARHGAP24) and four for QRS duration (TBX5, SCN10A, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between TBX5 and CAV1 and atrial fibrillation (P = 4.0 × 10−5 and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval. [ABSTRACT FROM AUTHOR]

Tracking of cardiovascular risk factors (blood pressure, body mass index (BMI), and serum lipids) has not been studied much in a general, adult population. No known study has compared tracking of these factors for both sexes. In the present study, 17,710 men and women aged 20-61 years at baseline attended two or three population-based health surveys in Tromsø, Norway, over 16 years (between 1979-1980 and 1994-1995). Tracking coefficients were estimated by using different methods, and possible predictors of tracking were found. There was a high degree of tracking for BMI (overall tracking coefficients: 0.85 for men, 0.80 for women). Relatively high (or moderate) tracking was found for systolic blood pressure (respective sex-specific coefficients: 0.52, 0.54), diastolic blood pressure (0.48, 0.48), high density lipoprotein cholesterol (0.55, 0.64), and total cholesterol (0.77, 0.65). The lowest coefficients were for triglycerides (0.43, 0.39). Analysis of tracking in the upper sextile confirmed these results. Although some baseline predictors were associated with tracking, the effects were relatively weak. When predictors for tracking in the upper sextile were assessed, significant associations were found with relatively strong effects. No major sex differences were observed in tracking. However, women were more likely than men to remain in the upper sextile of systolic and diastolic blood pressures and of BMI. [ABSTRACT FROM AUTHOR]