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

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

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.

Background Unrecognized myocardial infarction (MI) is a frequent and intriguing entity associated with a similar risk of death as recognized MI. Previous studies have not fully addressed whether the poor prognosis is explained by traditional cardiovascular risk factors. We investigated whether electrocardiographically detected unrecognized MI was independently associated with cardiovascular events and death and whether it improved prediction for future MI in a general population. Design Prospective cohort study. Methods We studied 5686 women and men without clinically recognized MI at baseline in 2007-2008. We assessed the risk of future MI, stroke and all-cause mortality in persons with unrecognized MI compared with persons with no MI during 31,051 person-years of follow-up. Results In the unadjusted analyses, unrecognized MI was associated with increased risk of future recognized MI (hazard ratio 1.84, 95% confidence interval (CI) 1.15-2.96) and all-cause mortality (hazard ratio 1.78, 95% CI 1.21-2.61), but not stroke (hazard ratio 1.09, 95% CI 0.56-2.17). The associations did not remain significant after adjustment for traditional risk factors (hazard ratio 1.25, 95% CI 0.76-2.06 and hazard ratio 1.38, 95% CI 0.93-2.05) for MI and all-cause mortality respectively. Unrecognized MI did not improve risk prediction for future recognized MI using the Framingham Risk Score ( p = 0.96) or the European Systematic COronary Risk Evaluation ( p = 0.65). There was no significant sex interaction regarding any of the endpoints. Conclusion Electrocardiographic unrecognized MI was not significantly associated with future risk of MI, stroke or all-cause mortality in the general population after adjustment for the traditional cardiovascular risk factors, and it did not improve prediction of future MI.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background Guidelines for the prevention of cardiovascular disease recommend the estimation of an individual's total risk. We have developed a new model for the prediction of the 10-year risk of incident acute myocardial infarction or cerebral stroke based on Norwegian data, NORRISK 2. Design The model was based on 10-year follow-up of a large population-based cohort (CONOR) through linkage to the CVDNOR project, a database of cardiovascular disease hospital discharge diagnoses and mortality in Norway in 1994-2009. Methods We used the Fine and Gray regression model to estimate the 10-year risk adjusting for competing risk. The model population consisted of participants in 1994-1999 and the external validation population of participants in 2000-2003. We validated the model by area under the receiver operating characteristic curves, calibration plots and analyses of sensitivity and specificity. Results The model population consisted of 31,445 men and 35,267 women aged 40-79 years with 3658 endpoints in men and 2459 in women. The external validation population consisted of 19,980 men and 19,309 women, of whom 1858 men and 874 women had an endpoint during follow-up. The area under the curve was 0.79 (0.79-0.80) in men and 0.84 (0.83-0.85) in women in the model population and was slightly lower in the external validation population. Calibration plots showed good agreement between observed and predicted risk. The sum of sensitivity and specificity was greatest around the suggested risk thresholds. Conclusion The NORRISK 2 model showed good validity in an external dataset and will be a valuable tool to guide decisions about preventive interventions in people without known previous cardiovascular disease.

Background Resting heart rate is an established risk factor for cardiovascular disease, but long-term individual resting heart rate trajectories and their effect on cardiovascular disease morbidity and mortality have not yet been described. Methods This large population-based longitudinal study included 14,208 men and women aged 20 years or older, not pregnant and not using blood pressure medications, who attended at least two of the three Tromsø Study surveys conducted between 1986-2001. Resting heart rate was measured using an automated Dinamap device. Participants were followed up from 2001 to 2012 with respect to myocardial infarction, atrial fibrillation, ischaemic stroke, cardiovascular disease death and total death. The Proc Traj statistical procedure was used to identify resting heart rate trajectories. Results Five common long-term resting heart rate trajectories were identified: low, moderate, decreasing, increasing and elevated. In men, an elevated resting heart rate trajectory was independently associated with an increased risk of myocardial infarction when low resting heart rate trajectory was used as a reference (hazard ratio 1.83, 95% confidence interval 1.11-3.02). Risk of total death in men was lowest in the low resting heart rate trajectory group and highest in the increasing and elevated resting heart rate trajectory groups. In women, the association between resting heart rate trajectories and myocardial infarction was similar to that in men, but it was not significant. Conclusions Among the five long-term resting heart rate trajectories we identified, increasing and elevated trajectories were associated with an increased risk of myocardial infarction and total death in men. Our results suggest that changes in long-term individual resting heart rate in the general population may provide additional prognostic information.

Background: Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population., Methods: We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR., Results: In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ) eGFR increased by 0.35 mL/min/1.73 m 2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m 2 ), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG., Conclusions: OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substantial morbidity and mortality with a major worldwide public health impact. It is increasingly recognized as a highly heritable condition. This study aimed to determine genetic risk factors for early-onset AF., Methods and Results: We sequenced the whole genomes of 8453 Icelanders and imputed genotypes of the 25.5 million sequence variants we discovered into 1799 Icelanders with early-onset AF (diagnosed before 60 years of age) and 337 453 controls. Each sequence variant was tested for association based on multiplicative and recessive inheritance models. We discovered a rare frameshift deletion in the myosin MYL4 gene (c.234delC) that associates with early-onset AF under a recessive mode of inheritance (allelic frequency = 0.58%). We found eight homozygous carriers of the mutation, all of whom had early-onset AF. Six of the homozygotes were diagnosed by the age of 30 and the remaining two in their 50s. Three of the homozygotes had received pacemaker implantations due to sick sinus syndrome, three had suffered an ischemic stroke, and one suffered sudden cardiac death., Conclusions: Through a population approach we found a loss of function mutation in the myosin gene MYL4 that, in the homozygous state, is completely penetrant for early-onset AF. The finding may provide novel mechanistic insight into the pathophysiology of this complex arrhythmia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Background: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium., Methods: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes., Results: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%)., Conclusions: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Context: Vitamin D deficiency is associated with insulin resistance and risk of future diabetes., Objective: The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus (T2DM)., Design: This was a randomized controlled trial performed in 2008 through 2015., Setting: The study was conducted at the clinical research unit at a teaching hospital., Patients: Five hundred eleven subjects (mean age 62 y, 314 males) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included. A total of 256 were randomized to vitamin D and 255 to placebo. Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events., Interventions: Interventions included vitamin D (cholecalciferol) 20 000 IU/wk vs placebo for 5 years. Annual oral glucose tolerance tests were performed., Main Outcome Measure: Progression to T2DM was the main outcome measure. Secondary outcomes were change in glucose levels, insulin resistance, serum lipids, and blood pressure., Results: The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L (24 ng/mL). One hundred three in the vitamin D and 112 in the placebo group developed T2DM (hazard risk 0.90; 95% confidence interval 0.69–1.18, Cox regression, P = .45, intention to treat analysis). No consistent significant effects on the other outcomes were seen. Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results. No serious side effects related to the intervention were recorded., Conclusions: In subjects without vitamin D deficiency, vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes. Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect. This study tested if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes (T2DM).

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: 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: 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.

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.

Aims: To investigate changes in cardiovascular risk factors over 14 years in relation to diabetes status., Methods: The study is based on 10,327 subjects who attended the Tromsø Study in 1994 and were screened again in 2007-8. At baseline there were 79 prevalent cases, and 397 incident cases of type 2 diabetes mellitus (DM2) were diagnosed between 1994 and 2008., Results: Cases with DM2 had decreasing levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol and blood pressure (BP) and increasing levels of triglycerides, body mass index (BMI), and anti-hypertensive treatment during 14 years of follow-up. Despite decreasing BP, more than 75% of the treated cases had BP above 135/80 at the end of follow-up. Similarly, less than 35% of incident cases using statins had low-density lipoprotein cholesterol (LDL-C) below the recommended threshold value of 2.6 mmol/l., Conclusions: Despite greater relative reduction in cardiovascular risk factors among people with DM2 compared to those without, treatment targets were met in less than 50% of subjects with DM2. Thirteen percent reached the combined targets for glucose, BP and LDL-C control. This indicates a need for more effective strategies to control cardiovascular risk factors especially among individuals with DM2.

An association between body height and venous thromboembolism (VTE) has been suggested by previous studies including males only. The aim of this prospective cohort study was to investigate the sex-specific impact of body height on risk of VTE in a general population. Risk factors, including body height and weight, were registered for 26,727 subjects aged 25-96 years who participated in the Tromsø Study (Norway) in 1994-1995. Incident VTE events were registered through September 1, 2007. There were 462 VTE events during a median 12.5 years of follow-up. Body height was a risk factor for VTE in men, but not in women. Multivariable hazard ratios per 10 cm, adjusted for age, body mass index, diabetes, smoking, and hormone therapy (women), were 1.34 (95% confidence interval: 1.09, 1.64) for men and 1.13 (95% confidence interval: 0.91, 1.40) for women. Hazard ratios by quartiles of body height revealed that men in the upper quartile (>181 cm) had a 1.99-fold (95% confidence interval: 1.35, 2.92) increased risk of VTE compared with men in the lowest quartile (<173 cm) (P for trend across quartiles = 0.002). There was no significant trend (P = 0.2) across quartiles of body height for women. Study findings revealed that body height is a sex-specific risk factor for VTE in men.

Objective: To study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes., Design: Population-based prospective cohort study., Methods: For the analyses, 1454 men who participated in the fourth Tromsø study (1994-1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments., Results: There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54-0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33-0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39-0.79) and when comparing the third (HR 0.38, CI 0.18-0.81) and the fourth quartile (HR 0.37, CI 0.17-0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E(2)) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26-0.93) and the third (HR 0.51, CI 0.27-0.96) quartile to the highest quartile., Conclusion: Men with higher E(2) levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.

Objective: To study the impact of endogenous testosterone levels in community-dwelling men on later risk for myocardial infarction (MI) and all-cause, cardiovascular disease (CVD), and ischemic heart disease (IHD) mortality., Design: Population-based prospective cohort study., Methods: For the analyses, we used a cohort of 1568 randomly selected men, with sex-hormone data participating in the fourth Tromsø Study (1994-1995). Defined end points were first-ever MI (fatal or nonfatal), all-cause, CVD, and IHD mortality. A committee performed thorough ascertainment of end points, following a detailed protocol. Complete ascertainment of end points was until 30 September 2007 for all-cause mortality, until 31 December 2005 for CVD/IHD mortality, and until 31 December 2004 for first-ever MI. The prospective association between total and free testosterone and end points were examined using Cox proportional hazard regression, allowing for multivariate adjustment for age and cardiovascular risk factors., Results: During follow-up, there were 395 deaths from all causes, 130 deaths from CVD and 80 deaths from IHD, while 144 men experienced a first-ever MI. There was a significant increase in all-cause mortality risk for men with free testosterone in the lowest quartile (<158 pmol/l) compared with the higher quartiles after age adjustment hazard ratios (HR 1.24, 95% confidence interval, CI 1.01-1.53) and after multivariate adjustments (HR 1.24, 95% CI 1.01-1.54). Total testosterone was not associated with mortality risk. Likewise, there were no significant changes in risk for first-ever MI across different total or free testosterone levels., Conclusion: Men with free testosterone levels in the lowest quartile had a 24% increased risk of all-cause mortality.

Background: Chronic kidney disease is associated with increased cardiovascular mortality, and even mild impairment of renal function is a cardiovascular risk factor. Several studies have investigated the risk factors for the development of end-stage renal disease, but little is known about predictors of change in renal function in the general population., Methods: The present study included 2249 men and 2192 women without signs of kidney disease at baseline who were followed for 7 years from 1994 to 1995 in the Tromsø Study. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease study equation. Gender-specific multiple linear regression analyses were used to assess predictors of change in eGFR (DeltaGFR)., Results: Change in eGFR, measured in ml/min/1.73 m(2)/year, was associated with systolic blood pressure (SBP) [beta-value for a 10-mmHg increase in SBP, men = -0.14, 95% confidence interval (CI) = -0.18 to -0.09; women = -0.07, 95% CI = -0.11 to -0.03] and fibrinogen [beta-value for 1 SD increase in fibrinogen, men (1 SD: 0.85 g/L) = -0.12, 95% CI -0.20 to -0.03; women (1 SD: 0.80) = -0.11, 95% CI -0.20 to -0.02]. High alcohol consumption in men and high physical activity in women predicted an increase in eGFR. Higher albumin/creatinine ratio was associated with a decline in eGFR in men only., Conclusions: Some risk factors for change in GFR seem to be gender specific but both high SBP and high levels of fibrinogen contribute to a more rapid decline in GFR for both men and women.

Aims: To study the implications of European guidelines on the use of antihypertensives and/or lipid-lowering drugs (LLDs) for primary prevention in a Norwegian population., Methods and Results: The Tromsø study is a population-based study in the municipality Tromsø, Norway (from 1974 to till now). This analysis includes 45-79-year-old participants in 2001 (n = 6362, attendance rate 86%). From the age of 60 years in men and 70 years in women, almost all participants were defined as high-risk individuals according to the European guidelines, with established cardiovascular disease, diabetes, or a 10-year risk score of > or =5%. In the primary prevention subgroup of the 45-64-year-olds, recommended antihypertensive and/or LLD use would be higher in men only, 42% compared with 12% on current medication. Among the 65-79-year-olds, >90% would be eligible for antihypertensives and/or LLDs in both sexes when compared with current treatment rates of <30%. In total, 40% of all participants aged 45-79 would be candidates for primary prevention, compared with 15% on current medication., Conclusion: The implementation of the European guidelines could imply a doubling of the numbers of Norwegian adults on cardiovascular medication for primary prevention. Contributors to the increase would be more frequent drug use in men and elderly people, particularly for LLD use.