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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]

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. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation represents a substantial clinical and public health issue. The definitive impact of body mass index on prognosis of patients with chronic (persistent or permanent) atrial fibrillation remains undetermined. Aim: The purpose of this study was to investigate the association of body mass index with health outcomes (mortality and re-hospitalisation) of patients with chronic atrial fibrillation. Methods: Using data from the Standard versus Atrial Fibrillation spEcific managemenT strategY (SAFETY) trial (a randomised controlled trial of home-based, atrial fibrillation-specific disease management), we performed post-hoc analyses of mortality and re-hospitalisation outcomes during minimum 24-month follow-up according to baseline body mass index profile. Results: Of 297 participants (mean age 71±11 years, 47% female, mean body mass index 29.6±6.7 kg/m2), 35.0% of participants were overweight (body mass index 25.0–29.9 kg/m2) and 43.1% were obese (body mass index≥30 kg/m2). During follow-up, n=42 died including 16/65 (24.6%) classified as normal body mass index, 16/104 (15.4%) classified as overweight and 10/128 (7.8%) classified as obese. Increasing body mass index was not associated with increased mortality but was associated with re-hospitalisation due to cardiovascular disease with greater length-of-stay (odds ratio 1.05; 95% confidence interval 1.00–1.09, p=0.032). Obese individuals experienced increased unplanned admissions compared to overweight individuals (incidence rate ratio 0.71; 95% confidence interval 0.53–0.96, p=0.028), and increased cardiovascular-related (incidence rate ratio 0.58; 95% confidence interval 0.39–0.86, p=0.007) and all-cause admissions (incidence rate ratio 0.63; 95% confidence interval 0.45–0.89, p=0.008) compared to those classified as normal body mass index. Conclusion: Overweight and obesity were not associated with survival in patients with chronic atrial fibrillation but were associated with more frequent hospital care and prolonged stay. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events. Method: This is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N = 79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5. Results: We found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p < 0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p = 0.123). However, we found a significant linear trend (p = 0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased. Conclusion: PTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Print media may influence smoking behaviour through tobacco advertisements and editorial use of tobacco pictures and texts. In Norway tobacco advertising has been banned for many years. The authors studied the coverage of tobacco promotion and tobacco and health in some general Norwegian magazines and newspapers. The findings were related to the publications' policy as stated by their editors. Methods: During three months in 1998–99 all pictures of tobacco and smoking situations were registered, plus the coverage on health aspects of tobacco in all consecutive issues of 7 newspapers and 19 magazines. The editors were asked about their attitudes regarding indirect tobacco advertisement and editorial use of people smoking. Results: All editors for men's magazines and the majority of newspaper editors had no restrictions on displaying both indirect tobacco advertisements and images of people smoking. In total, 610 texts or pictures on tobacco were found in the 624 issues of magazines and newspapers. Only 26 items were indirect tobacco advertisements. Items promoting smoking were more common than coverage of tobacco and health (71% vs 29%), and occurred most frequently in men's magazines (2.1 per issue) and least frequently in local newspapers (0.3 per issue). The proportion of tobacco and health coverage compared with the total tobacco coverage was significantly lower in men's than in family magazines and local newspapers. Conclusion: Editors should be encouraged to increase the coverage of tobacco and health in print media. This may be an important factor in helping their readers to give up or not to take up smoking. [ABSTRACT FROM AUTHOR]

Aims: To (i) define the characteristics of snus users compared with non‐users and smokers and (ii) define the relationship between snus use and self‐reported anxiety and depression and compare it with the relation between smoking and anxiety and depression. Design, setting and participants: A cross‐sectional study based on data from the Norwegian population‐based survey, the Tromsø Study (2015–16). A total of 32 591 people aged 40 years and older in the municipality of Tromsø were invited to attend. There were 21 083 respondents, giving a 65% attendance rate. Measurements: Tobacco use was assessed by current and previous use of snus or cigarettes. Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Findings Snus users were more often male, were younger and had higher income and higher alcohol consumption than smokers and non‐users of snus. In a linear regression analysis, we found no significant association between current snus use and anxiety and depression after adjusting for background variables. However, there was a positive association between previous snus use and anxiety among males [adjusted beta = 0.258; 99% confidence interval (CI) = 0.023–0.492]. Regarding anxiety, the adjusted beta‐coefficients for current smoking were 0.425 (99% CI = 0.184–0.666) for females and 0.303 (99% CI = 0.084–0.522) for males. Concerning depression, the adjusted beta coefficients for current smoking were 0.569 (99% CI = 0.358–0.780) for females and 0.281 (99% CI = 0.060–0.503) for males. Conclusions: In Norway, current snus users differ from current smokers by having a higher socio‐economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding the prevalence of hepatitis C virus (HCV) infection in sporadic porphyria cutanea tarda (S-PCT), membranoproliferative glomerulonephritis (MPGN) and membranous glomerulonephritis (MGN) patients from Northern Norway. It notes that the International Classification of Diseases was used to identify S-PCT patients while micro-particle enzyme immunosorbant assay (MEIA) for anti-HCV. It shows that HCV infection does not occur in patients with S-PCT, MPGN or MGN.

Background: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long‐term endurance training is unclear. Thus, we aimed to examine 10‐year mortality in older male endurance athletes compared with an older male general population. Method: Male athletes (n = 503) participating in an annual long‐distance ski race (median years of participation: 14, range: 1–53) from the Norwegian Birkebeiner Aging study (BiAS), and non‐athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self‐reported leisure‐time PA with all‐cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. Results: After 10 years (median: 10.4, range: 0.5–11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24–0.49) compared with non‐athletes, corresponding to a 15% (95% CI: 12–19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose–response relationship with mortality (p < 0.001). Compared to inactive non‐athletes, PA was associated with lower mortality in both active non‐athletes and athletes. However, the observed benefit among participants reporting moderate‐to‐vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14–0.32) than non‐athletes (HR: 0.43, 95% CI: 0.31–0.59) (p < 0.01). Conclusion: Endurance sport practice was associated with reduced 10‐year mortality, beyond the effect of PA in older men. This study suggests that long‐term endurance sport practice maintained into older adulthood promotes longevity. [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]

Simple Summary: Cervical cancer is the fourth most common cancer in women worldwide. Persistent high-risk human papillomavirus (HPV) can cause invasive cervical cancer through a series of precancerous lesions. Screening women with either cytology examinations or a test detecting HPV infection can prevent cervical cancer. HPV tests are substituting cytology examinations in cervical cancer screening, but more knowledge is needed about the screening performance of HPV tests, especially among younger women. We aimed to determine the long-term performance of a five-type HPV mRNA test to predict CIN3+. These results contribute to the knowledge of the reliability of HPV mRNA testing in cervical cancer screening. Our findings suggest that women with a negative result may extend the screening interval up to 10 years. Background: The study's purpose was to evaluate the performance of a five-type HPV mRNA test to predict cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during up to 12 years of follow-up. Methods: Overall, 19,153 women were recruited by gynecologists and general practitioners in different parts of Norway between 2003 and 2004. The study population comprised 9582 women of these women, aged 25–69 years with normal cytology and a valid five-type HPV mRNA test at baseline. Follow-up for CIN3+ through 2015 was conducted in the Norwegian Cervical Cancer Screening Programme. Results: The cumulative incidence of CIN3+ by baseline status for HPV mRNA-positive and mRNA-negative women were 20.8% and 1.1%, respectively (p < 0.001). Age did not affect the long-term ability of the HPV mRNA test to predict CIN3+ during follow-up. Conclusion: The low long-term risk of CIN3+ among HPV mRNA-negative women and the high long-term risk among HPV mRNA-positive women strengthen the evidence that the five-type HPV mRNA test is an appropriate screening test for women of all ages. Our findings suggest that women with a negative result may extend the screening interval up to 10 years. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood‐based biomarkers reflecting cardiac injury such as high‐sensitivity troponin I (hsTnI) may help close this gap. Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C‐reactive protein, N‐terminal pro B‐type natriuretic peptide). Results: During a median follow‐up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91‐fold (95% confidence interval (CI) 3.30, 4.63; p <.01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable‐adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p =.03). Inclusion of hsTnI did improve model discrimination (C‐index CVRF 0.811 vs. C‐index CVRF and hsTnI 0.813; p <.01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p <.01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p <.01). Conclusion: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT‐proBNP. However, it is associated with the AF‐related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment. [ABSTRACT FROM AUTHOR]

Background and aims Overall, men have roughly twice the risk of myocardial infarction (MI) compared to women, but what causes this contrast is unclear. Identification of subgroups where the gender contrast in risk is particularly low or high, may provide new insight. In the search for such subgroups, we focus on gender-specific effects of established coronary heart disease (CHD) risk factors. Heterogeneity across age groups is also explored. Methods Population-based prospective study from Tromsø, Norway, comprising 33,859 individuals (51% women); 2746 individuals (854 women) received a diagnosis of MI during follow-up at ages 35–94 years. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analyses. Results The association between total cholesterol and risk of MI was stronger for men than women, and IRR for men vs. women accordingly increased with increasing cholesterol, but the risk was higher for men in all subgroups (IRR in range 1.63–3.27), except among older people with low cholesterol levels. The adverse effect of increasing blood pressure (BP) was stronger for women, and IRR for gender diminished with increasing systolic (from 3.90 to 1.38) and diastolic BP (from 2.87 to 1.54). The gender contrast in risk was also substantially reduced in smokers ≥75 years. Associations with high-density lipoprotein cholesterol (HDL-C) did not differ between genders. Conclusions Gender heterogeneity in associations with total cholesterol but not HDL-C indicates gender differences in associations with non-HDL-C. The stronger association with BP in women may relate to more severe hypertension-induced left ventricular hypertrophy. [ABSTRACT FROM AUTHOR]

Objective To investigate the validity of self-reported information about hypertensive disorders in previous pregnancies among women participating in the fourth survey of the Tromsø Study. Design Retrospective cohort study with case-control design. Population Parous women participating in the fourth survey of the Tromsø Study. Methods Medical records including partograms of 200 randomly selected women who had answered positively to whether they had hypertension and/or proteinuria during one or more of their previous pregnancies (cases) and 200 women who had answered negatively (controls) were studied. The cases and controls were matched for age. The investigators were blinded to the allocation of cases and controls until data collection was finished. Main outcome measures Self-reported and actual prevalence of hypertensive pregnancy disorders and predictive value of self-reported hypertension and/or proteinuria in previous pregnancies. Results Clinical data were missing for 23.5% (94/400) of the participants (50 cases and 44 controls). A total of 80% (120/150) of cases and 57.1% (89/156) of controls had answered the question on whether or not they had high blood pressure and/or proteinuria during their pregnancies correctly (positive predictive value 0.800; negative predictive value 0.571). The proportion of false-positive cases declined with increasing age while the proportion of false-negative controls increased until 55 years of age. Conclusions We found good concordance between self-reported hypertension and/or proteinuria during previous pregnancies and actual clinical findings among the cases. However, there was a tendency towards under-reporting among controls. [ABSTRACT FROM AUTHOR]

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

Presents a study which examined the effects which leisure time physical activity can have on the metabolic risk profiles in both men and women. Measurement of body mass index; Importance of serum lipid levels; Definition of biological markers of a metabolic risk profile; Indication of results obtained.

Introduction: Diabetes is associated with increased risk of coronary heart disease (CHD). The relative risk has been found to be higher in women than men, and the more pronounced adverse effect has even been claimed to eliminate the female advantage in risk. However, few previous studies have quantified the difference in risk between men and women among individuals with diabetes. Aims: To evaluate interaction between gender and diabetes in relation to the risk of incident myocardial infarction (MI). Methods: Population-based prospective study of 33,859 individuals (51% women) in Tromsø, Norway. Median follow-up time at ages 35-94 years was 17.6 years; 2,746 individuals (854 women) were diagnosed with MI during follow-up. At their last visit, a total of 1063 individuals (3.1%) reported they had diabetes (530 men, 533 women); 170 (74 women) were later diagnosed with MI. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analysis of person-years at risk. Interaction terms were included in the model to evaluate heterogeneity in risk estimates across subgroups. Results: Adjusted for age, gender and established CHD risk factors, diabetes was associated with a doubling in risk of MI (IRR=2.18, 95% CI=1.86-2.55). The adverse effect was slightly more pronounced for women than men (IRR of 2.55 vs. 1.96, p=0.11, test for interaction). Accordingly, the gender contrast in risk was less pronounced among individuals with diabetes (IRR of 1.63 vs 2.11), but the elevated risk in men remained significant. Considering combined categories of interacting factors, women with diabetes had a risk level close to men without diabetes, but men with diabetes had a risk about four times as high as women without diabetes. Some heterogeneity across age groups was seen, but risk estimates were imprecise. These results are preliminary. Gender heterogeneity in associations with adjustment factors may influence risk estimates. Analyses based on data with 5 year extended follow-up are planned. Conclusions: In terms of relative risk, the association between diabetes and risk of MI was more pronounced for women than men, but the female advantage in risk of MI was not erased in persons with diabetes. [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 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. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage. We hypothesised that increased serum syndecan-1 and -4 were independently associated with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men and women from a general population. Methods Using a case-cohort design, we included 1495 participants from the Tromsø Study 2001-02. Syndecan-1 and -4 were measured in serum. Baseline variables also included age, gender, cardiovascular risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were assessed using multivariable Cox regression models. Results Between baseline in 2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95% confidence interval 1.06–1.63), but not ischaemic stroke and mortality, and the associations were unchanged by adjustment for urinary ACR. Interaction between syndecan-4 and sex was borderline significant, and in gender-specific analysis, syndecan-4 was associated with MI in women only. Syndecan-1 was not associated with any endpoint. Conclusions Syndecan-4 was associated with incident MI, and the association was stronger in women than in men. This suggests a link between endothelial glycocalyx shedding and coronary heart disease in women. Use of syndecan-4 as a risk marker in clinical setting needs further investigation. Highlights • Syndecans shed from the endothelial glycocalyx may reflect early atherosclerosis. • In a general population serum syndecan-4 was associated with myocardial infarction. • The association was found in women only. • Syndecan-1 was not associated with cardiovascular disease after several years. [ABSTRACT FROM AUTHOR]

Background Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. Methods 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12‑lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. Results Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05–2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35–0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37–0.69). No significant sex interaction was present. Conclusions Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ. [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]

Background: Single measurements of modifiable risk factors may underestimate associations with outcomes in cohorts. We aimed to compare risk estimates of myocardial infarction (MI) and venous thromboembolism (VTE) by atherosclerotic risk factors during long follow-up using time-fixed analyses without and with correction for regression dilution and time-varying analyses. Methods: The study included 5970 subjects enrolled in the fourth survey of the Tromsø Study (1994/95). Blood pressure, lipid levels, body mass index (BMI), diabetes and smoking status were measured at baseline, and subjects still alive at the fifth (2001/02, n = 5179) and sixth (2007/08, n = 4391) survey were re-measured. Incident events of MI (n = 714) and VTE (n = 214) were recorded until December 2010. Time-fixed and time-varying Cox regression models were used to estimate hazard ratios (HR) for MI and VTE adjusted for age and sex. Results: Variations in BMI, blood pressure and lipid levels were small, and did not alter the risk estimates when time-varying analyses were compared to time-fixed analyses. For MI, variables that changed considerably over time yielded the greatest changes in risk estimates (HR for smoking changed from 1.80 (95% CI 1.55–2.10) to 2.08 (95% CI 1.78–2.42)). For VTE, only BMI was associated with increased risk in both time-fixed and time-varying analysis, but the risk estimates weakened in the time-varying analysis. Correction of time-fixed HRs with Rosner´s method tended to overestimate risk estimates compared to time-varying analysis. Comment: For MI and VTE, risk estimates based on baseline and repeated measures corresponded well, whereas correction for regression dilution tended to overestimate risks. [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: 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. [ABSTRACT FROM AUTHOR]

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 personyears. 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. [ABSTRACT FROM AUTHOR]

Background and Objective: In addition to its role as a transport protein, the vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f, 1f/2, and 2/2). These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different binding coefficients for the vitamin D metabolites, and accordingly there may be important relations between DBP phenotypes and health. Methods: DNA was prepared from 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. The endpoint registers were complete up to 2010- 2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin D (25(OH)D) was measured. Results: Genotyping for rs7041 and rs4588 was performed successfully in 11 704 subjects. Among these, 1660 were registered with incident MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP phenotype 1f/1f had 23 – 26 % reduced risk of incident cancer compared to the 1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate). Differences in serum 25(OH)D levels could not explain the apparent cancer protective effect of the DBP variant 1f. In addition to cancer and 25(OH)D, there were significant associations between DBP phenotype and body height, hip circumference and serum calcium. Conclusion: There are important biological differences between the common DBP phenotypes. If the relation between the DBP variant 1f and cancer is confirmed in other studies, determination of DBP phenotype may have clinical importance. [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]

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]

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: 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 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]

QT Interval and the Risk of Myocardial Infarction and All-Cause Death. Introduction: The relationship between QT interval and cardiovascular disease is controversial. Methods: All male residents aged 20-61 years and female residents aged 20-56 years were invited to the Tromsø Study in 1986-1987. A total of 15,558 participants free of heart disease were prospectively followed over 20 years for myocardial infarction and death. QT interval at baseline was measured on lead I of the electrocardiogram. Hazard ratios (HRs) with 95% confidence intervals (CIs) per standard deviation change in QT interval were calculated using a Cox regression model. Results: We identified 756 cases of myocardial infarction and 1,183 all-cause deaths. Prolonged QT interval was present in 792 (5%) participants. QT interval was not associated with increased risk of myocardial infarction (HR: 0.95, 95% CI: 0.84-1.07, after adjustment for potential confounders). Heart-rate-corrected QT interval was a significant predictor for all-cause death in men (HR: 1.15, 95% CI: 1.03-1.29), but not in women (HR: 1.04, 95% CI: 0.91-1.18), after adjustment for potential confounders. Conclusions: The findings suggest that the previously observed relationship between QT interval and increased risk of cardiovascular death is not mediated by increased risk of myocardial infarction. The clinical utility of the QT interval to identify individuals at high risk for coronary events is limited in a general population without prior heart disease. (J Cardiovasc Electrophysiol, Vol. 23, pp. 846-852, August 2012) [ABSTRACT FROM AUTHOR]

Background Glomerular filtration rate <60 mL/min/1.73m2 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/1.73m2) 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. [ABSTRACT FROM PUBLISHER]

Objective: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. Methods: DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007-2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level. Results: A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05). Conclusion: Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. [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]

Abstract: Aim: Increased urinary albumin-excretion is a cardiovascular risk-factor. The cardiovascular risk of the metabolic syndrome (MetS) is debated. The aim of the present prospective, population-based study of non-diabetic individuals was to examine the association between low-grade urinary albumin-excretion, MetS, and cardiovascular morbidity and all-cause mortality. Methods: 5215 non-diabetic, non-proteinuric men and women participating in the Tromsø Study 1994–1995 were included. Urinary albumin–creatinine ratio (ACR) was measured in three urine samples. The participants were categorized into four groups by the presence/absence of MetS (the International Diabetes Federation definition) and ACR in the upper tertile (≥0.75mg/mmol). Results: Median follow-up time was 9.6 years for first ever myocardial infarction, 9.7 years for ischemic stroke and 12.4 years for mortality. High ACR (upper tertile)/MetS was associated with increased risk of myocardial infarction (hazard ratio (HR) 1.75; 95% confidence interval (CI): 1.30–2.37, p <0.001), stroke (HR 2.48; 95% CI: 1.66–3.71, p <0.001), and all-cause mortality (HR 1.63; 95% CI: 1.32–2.01, p <0.001) compared to reference (low ACR/no MetS). Similar associations were found for the high ACR/no MetS group. Low ACR/MetS was associated with myocardial infarction only (HR 1.82; 95% CI: 1.39–2.37, p <0.001). MetS predicted neither stroke nor mortality. Adjusted for its individual components, MetS was not associated with any end-point. Conclusions: ACR≥0.75mg/mmol was associated with cardiovascular morbidity and all-cause mortality independently of MetS. MetS was not associated with any end-point beyond what was predicted from its components. Thus, low-grade albuminuria, but not MetS, may be used for risk stratification in non-diabetic subjects. [Copyright &y& Elsevier]

Objective: In this study, we explored airway symptoms and exposure to bioaerosols and exhaust gases in seafood industry plants. Methods: The study details the results from personal and environmental exposure measurements (17 plants), a questionnaire (n = 984), and clinical examinations (n = 225). Results: The workers were exposed to allergens, endotoxins, molds, and exhaust. The 1-year prevalence of work-related airway symptoms was 42.8 % for production workers and 25. 9 % for administrative workers. Mean levels of forced expiratory volume in 1 second and forced vital capacity were less than the predicted values in all exposed nonsmoker groups. A total of 20.5 % had increased levels of total IgE (≥ 100 k U/L). Specific IgE-mediated reactions seemed to be relevant only in the shrimp industry. Conclusions: Seafood industry workers showed a high prevalence of work-related airway symptoms. Further research on the relationship between exposure and effects is necessary. [ABSTRACT FROM AUTHOR]

Skjelbakken T, Langbakk B, Dahl IMS, Løchen M-L. Haemoglobin and anaemia in a gender perspective: The Tromsø Study.Eur J Haematol 2005: 74: 381–388.© Blackwell Munksgaard 2005.Objectives: To examine the gender-specific distribution of haemoglobin (Hb) and the World Health Organization (WHO) criteria for anaemia compared with the 2.5 percentile for Hb.Methods: A population-based study from Tromsø, Northern Norway. All inhabitants above 24 yr were invited. In total, 26 530 (75%) had their Hb analysed.Results: The 2.5–97.5 percentile of Hb was 129–166 and 114–152 g/L for all men and women, respectively. In men, mean Hb decreased from 148 to 137 g/L between 55–64 and 85+ yr. In women, mean Hb increased from 132 to 137 g/L between 35–44 and 65–74 yr and then decreased to 131 g/L among the oldest. Using the WHO criteria for anaemia (Hb:<130 and<120 g/L, men and women respectively), the prevalence of anaemia in men increased with age from 0.6% aged 25–34 to 29.6% aged 85+. For women, the prevalence of anaemia varied from 9.1%, 2.2% and 16.5% in the age groups of 35–44, 55–64 and 85+ yr, respectively. The WHO criteria gave a two to three times higher prevalence of anaemia compared with the 2.5 percentile of Hb in women, but the difference was small in men. Poor self-rated health was not associated with low values of Hb in women. In men, there was an association in some age groups.Conclusion: The WHO criteria for anaemia and the 2.5 percentile for Hb corresponded well for men, but not for women. The WHO criteria of anaemia may result in medicalization of healthy women. [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]