High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies show... more High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies showing a blood pressure decline in recent decades lack data to follow individuals born in different decades from early and middle adulthood to older age. We investigated changes in age-specific blood pressure by repeated measurements in 37973 women and men born 1905 to 1977 (aged 20–89 years) examined ≤5× between 1979 and 2008 in the population-based Tromsø Study. Mixed models were used to estimate time trends. Mean systolic and diastolic blood pressure decreased from 1979 to 2008 in both genders in the age groups 30 to 89 years. The decrease was similar in the 80th percentile and the 20th percentile of the population blood pressure distribution. The decrease in systolic blood pressure in age group 40 to 49 years was 10.6 mm Hg in women and 4.5 mm Hg in men. Systolic blood pressure increased with age in women and men born 1920 to 1949, whereas a decrease or flattening of curve was observed ...
A number of large population-based cardiovascular surveys have been conducted in Norway since the... more A number of large population-based cardiovascular surveys have been conducted in Norway since the beginning of the 1970s. The surveys were carried out by the National Health Screening Service in cooperation with the universities and local health authorities. All surveys comprised a common set of questions, standardized anthropometric and blood pressure measurements and non-fasting blood samples that were analysed for serum lipids at the Ulleva ˚l Hospital Laboratory. These surveys provided considerable experience in conducting large-scale population-based surveys, thus an important background for the Cohort of Norway (CONOR). In the late 1980s the Research Council of Norway established a programme in epidemiology. This also gave stimulus to the idea of establishing a cohort including both core survey data and stored blood samples.
ObjectivesThe aim of this study was to investigate time trends in known and undiagnosed diabetes,... more ObjectivesThe aim of this study was to investigate time trends in known and undiagnosed diabetes, HbA1c levels, and other cardio-metabolic risk factors in the general population as well as treatment target achievement among those with diabetes.Design and settingRepeated cross-sectional surveys in the population-based Tromsø Study.MethodsWe used age-adjusted generalized estimating equation models to study trends in self-reported and undiagnosed (HbA1c ≥6.5%) diabetes, cardio-metabolic risk factors and the metabolic syndrome in 27281 women and men aged 40-84 years examined in up to four surveys of the Tromsø Study between 1994 and 2016. Further, we analyzed trends in diabetes treatment target achievement.ResultsDuring 1994-2016 diabetes prevalence increased in women (2.3% to 3.9%) and men (2.4% to 5.3%) and in all age-groups, while the proportion of undiagnosed diabetes in women (33% to 20%) and men (37% to 27%) decreased. Blood pressure and total cholesterol decreased, while waist ci...
The association between myocardial infarction (MI) and future risk of incident cancer is scarcely... more The association between myocardial infarction (MI) and future risk of incident cancer is scarcely investigated. Therefore, we aimed to study the risk of cancer after a first time MI in a large cohort recruited from a general population. Participants in a large population-based study without a previous history of MI or cancer (n = 28,763) were included and followed from baseline to date of cancer, death, migration or study end. Crude incidence rates (IRs) and hazard ratios (HRs) for cancer after MI were calculated. During a median follow-up of 15.7 years, 1747 subjects developed incident MI, and of these, 146 suffered from a subsequent cancer. In the multivariable-adjusted model (adjusted for age, sex, BMI, systolic blood pressure, diabetes mellitus, HDL cholesterol, smoking, physical activity and education level), MI patients had 46% (HR 1.46; 95% CI: 1.21-1.77) higher hazard ratio of cancer compared to those without MI. The increased cancer incidence was highest during the first 6 ...
Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standar... more 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. 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. 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 ...
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substant... more 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. 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 ...
IMPORTANCE It is not clear to what extent the higher incidence of coronary heart disease (CHD) in... more IMPORTANCE It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce. OBJECTIVE To quantify the difference in risk of incident myocardial infarction (MI) between men and women. DESIGN, SETTING AND PARTICIPANTS Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015.
C oronary heart disease (CHD) mortality rates have decreased in many countries during the last de... more C oronary heart disease (CHD) mortality rates have decreased in many countries during the last decades. 1,2 Both changes in the rates of out-of-hospital CHD deaths and hospitalization rates and the outcome of myocardial infarction (MI) with ST-segment elevation (STEMI) and non-ST-segment elevation (non-STEMI) will affect mortality. 3 Editorial see p 8 Clinical Perspective on p 81 It has been suggested that 45% to 75% of the decrease in deaths from CHD can be attributed to decreases in smoking, blood pressure, and cholesterol. 4-8 These studies based their estimates on ecological data or mathematical modeling of aggregate data. Few studies used individual person data, 9,10 and the studies were limited to population subgroups and did not study out-of-hospital CHD or subtypes of MI. We used individual person data from repeated surveys of a general population to study the rates of out-of-hospital CHD; the incidence, treatment, and outcome of hospitalized STEMI and non-STEMI; and the impact of changes in coronary risk factor levels during the years 1995 to 2010. Methods Study Population The Tromsø Study is a population-based, prospective study of various health issues and chronic diseases. It consists of 6 surveys of both sexes conducted in the municipality of Tromsø, Norway, from 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-STsegment-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.
Background and Objective In addition to its role as a transport protein, the vitamin D binding pr... more 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 PLOS ONE |
The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovas... more 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). 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...
Identification of structural heart disease in asymptomatic individuals could allow early disease-... more Identification of structural heart disease in asymptomatic individuals could allow early disease-modifying treatment. To examine whether echocardiographic screening in the general population improves long-term survival or reduces the risk of cardiovascular disease. We studied 6861 middle-aged participants from the population-based Tromsø Study in Norway. Participants were randomly allocated to an echocardiographic screening group (n = 3272) or a control group (n = 3589). Using the as-treated approach, the data were analyzed for mortality and incidence of fatal and nonfatal myocardial infarction and stroke. During 15 follow-up years, 880 persons (26.9%) in the screening group and 989 persons (27.6%) in the control group died (hazard ratio, 0.97; 95% CI, 0.89-1.06). No significant differences between the groups were observed in the secondary outcome measures (sudden death, mortality from any heart disease, or incidence of fatal and nonfatal myocardial infarction and stroke). Echocardi...
Objective: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently sev... more 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.
Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thicknes... more Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). Methods— IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. Results— During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a highe...
Background and Purpose— Carotid plaque and intima-media thickness (IMT) are recognized as risk fa... more Background and Purpose— Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery. Methods— IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005. Results— Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09–1.38; P =0.0009) in men and 1.19 (95% CI, 1.01–1.41; P =0.04) in women when adjusted for other cardiova...
Aims: To determine the gender-specific incidence and risk factors of type-2 diabetes mellitus (T2... more Aims: To determine the gender-specific incidence and risk factors of type-2 diabetes mellitus (T2DM) in a general population. Methods: The study is based on 12,431 men and 13,737 women aged 25-98 years, attending the Tromsø Study in 1994 and followed through 2005, who did not have diabetes when entering the study. Sex-specific hazard ratios were estimated from Cox proportional hazard models. Results: A total of 522 cases of T2DM were registered, 308 among men and 214 among women. The age-standardised incidence rate was higher in men than in women, 2.6 (95% CI 2.32—2.90) and 1.6 (95% CI 1.40—1.83) per 1000 person-years, respectively. In multivariate survival analysis, age, body mass index (BMI), triglycerides, high-density lipoprotein (HDL) cholesterol, hypertension, family history of diabetes, low education and smoking were independent predictors of T2DM in both genders (p>0.05). Total cholesterol and lack of leisure-time physical activity were independent predictors in men only....
Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins aft... more Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA.
Purpose To examine the cross-sectional relationship between drusen, late age-related macular dege... more Purpose To examine the cross-sectional relationship between drusen, late age-related macular degeneration (AMD), and cognitive function. Methods We included 2149 stroke-free participants from the population-based Tromsø Study in Norway. Retinal photographs were graded for presence of drusen and AMD. Cognitive function was assessed using the verbal memory test (short verbal memory), digit-symbol coding test (processing speed), and the tapping test (psychomotor tempo). We assessed the relationship between drusen, late AMD, and cognitive test scores, adjusted for potential confounders. Results Late AMD was associated with decreased performance in the verbal memory test (standardized b ¼ À 0.23, 95% confidence interval (CI): À 0.51 to À 0.01). Intermediate and large drusen were associated with decreased performance in the digit-symbol coding test (standardized b ¼ À 0.14 and-0.19, 95% CIs: À 0.23 to À 0.05 and À 0.29 to À 0.09, respectively). Participants with large drusen were more likely to have test scores in the lowest quartile of the digit-symbol coding test (odds ratio (OR) ¼ 1.9, 95% CI: 1.1-3.5) and the tapping test (OR ¼ 1.6, 95% CI: 1.0-2.6), but not in the verbal memory test (OR ¼ 1.0, 95% CI: 0.6-1.6). Conclusions The findings suggest a relationship between drusen deposition and reduced cognitive function. Although the relationships between drusen, late AMD, and the cognitive test results varied in strength and significance across the types of cognitive test, and may partly have been caused by residual confounding, it is not unlikely that a genuine but weaker relationship exists between drusen deposition and cognitive decline.
Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome, which accordingly ha... more Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome, which accordingly has been questioned both as a research and clinical tool. The aim of this study was to determine differences in risk factors for type 2 diabetes between groups with high or low metabolic score. The study population were 26,093 men and women attending the Tromsø Study in 1994, followed through 2005, and who did not have diabetes when entering the study. A total of 492 incident cases of type 2 diabetes were registered. A metabolic score was defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III. For those fulfilling C 3 metabolic score criteria, increasing age, body mass index (BMI), triglycerides and a family history of diabetes were independent predictors. Age, BMI, and triglycerides predicted type 2 diabetes more strongly in subjects with low metabolic score, whereas high HDL cholesterol was not protective in this low risk group. The risk associated with a positive family history was unaffected by level of metabolic score. In addition smoking, low education and in men also physical inactivity were independent risk factors only in those with low metabolic score. Adding these nonmetabolic risk factors increased correct classification from an ROC area of 77.2 to 87.1% (P value \ 0.0001). One half of the incident cases of type 2 diabetes were missed by using high metabolic score for risk prediction. Keywords Type 2 diabetes Á Metabolic syndrome Á Low metabolic score Á High metabolic score Á Non-metabolic risk factors Á Receiver operating characteristics
ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later ... more ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes.DesignPopulation-based prospective cohort study.MethodsFor 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.ResultsThere 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 p...
High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies show... more High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies showing a blood pressure decline in recent decades lack data to follow individuals born in different decades from early and middle adulthood to older age. We investigated changes in age-specific blood pressure by repeated measurements in 37973 women and men born 1905 to 1977 (aged 20–89 years) examined ≤5× between 1979 and 2008 in the population-based Tromsø Study. Mixed models were used to estimate time trends. Mean systolic and diastolic blood pressure decreased from 1979 to 2008 in both genders in the age groups 30 to 89 years. The decrease was similar in the 80th percentile and the 20th percentile of the population blood pressure distribution. The decrease in systolic blood pressure in age group 40 to 49 years was 10.6 mm Hg in women and 4.5 mm Hg in men. Systolic blood pressure increased with age in women and men born 1920 to 1949, whereas a decrease or flattening of curve was observed ...
A number of large population-based cardiovascular surveys have been conducted in Norway since the... more A number of large population-based cardiovascular surveys have been conducted in Norway since the beginning of the 1970s. The surveys were carried out by the National Health Screening Service in cooperation with the universities and local health authorities. All surveys comprised a common set of questions, standardized anthropometric and blood pressure measurements and non-fasting blood samples that were analysed for serum lipids at the Ulleva ˚l Hospital Laboratory. These surveys provided considerable experience in conducting large-scale population-based surveys, thus an important background for the Cohort of Norway (CONOR). In the late 1980s the Research Council of Norway established a programme in epidemiology. This also gave stimulus to the idea of establishing a cohort including both core survey data and stored blood samples.
ObjectivesThe aim of this study was to investigate time trends in known and undiagnosed diabetes,... more ObjectivesThe aim of this study was to investigate time trends in known and undiagnosed diabetes, HbA1c levels, and other cardio-metabolic risk factors in the general population as well as treatment target achievement among those with diabetes.Design and settingRepeated cross-sectional surveys in the population-based Tromsø Study.MethodsWe used age-adjusted generalized estimating equation models to study trends in self-reported and undiagnosed (HbA1c ≥6.5%) diabetes, cardio-metabolic risk factors and the metabolic syndrome in 27281 women and men aged 40-84 years examined in up to four surveys of the Tromsø Study between 1994 and 2016. Further, we analyzed trends in diabetes treatment target achievement.ResultsDuring 1994-2016 diabetes prevalence increased in women (2.3% to 3.9%) and men (2.4% to 5.3%) and in all age-groups, while the proportion of undiagnosed diabetes in women (33% to 20%) and men (37% to 27%) decreased. Blood pressure and total cholesterol decreased, while waist ci...
The association between myocardial infarction (MI) and future risk of incident cancer is scarcely... more The association between myocardial infarction (MI) and future risk of incident cancer is scarcely investigated. Therefore, we aimed to study the risk of cancer after a first time MI in a large cohort recruited from a general population. Participants in a large population-based study without a previous history of MI or cancer (n = 28,763) were included and followed from baseline to date of cancer, death, migration or study end. Crude incidence rates (IRs) and hazard ratios (HRs) for cancer after MI were calculated. During a median follow-up of 15.7 years, 1747 subjects developed incident MI, and of these, 146 suffered from a subsequent cancer. In the multivariable-adjusted model (adjusted for age, sex, BMI, systolic blood pressure, diabetes mellitus, HDL cholesterol, smoking, physical activity and education level), MI patients had 46% (HR 1.46; 95% CI: 1.21-1.77) higher hazard ratio of cancer compared to those without MI. The increased cancer incidence was highest during the first 6 ...
Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standar... more 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. 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. 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 ...
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substant... more 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. 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 ...
IMPORTANCE It is not clear to what extent the higher incidence of coronary heart disease (CHD) in... more IMPORTANCE It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce. OBJECTIVE To quantify the difference in risk of incident myocardial infarction (MI) between men and women. DESIGN, SETTING AND PARTICIPANTS Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015.
C oronary heart disease (CHD) mortality rates have decreased in many countries during the last de... more C oronary heart disease (CHD) mortality rates have decreased in many countries during the last decades. 1,2 Both changes in the rates of out-of-hospital CHD deaths and hospitalization rates and the outcome of myocardial infarction (MI) with ST-segment elevation (STEMI) and non-ST-segment elevation (non-STEMI) will affect mortality. 3 Editorial see p 8 Clinical Perspective on p 81 It has been suggested that 45% to 75% of the decrease in deaths from CHD can be attributed to decreases in smoking, blood pressure, and cholesterol. 4-8 These studies based their estimates on ecological data or mathematical modeling of aggregate data. Few studies used individual person data, 9,10 and the studies were limited to population subgroups and did not study out-of-hospital CHD or subtypes of MI. We used individual person data from repeated surveys of a general population to study the rates of out-of-hospital CHD; the incidence, treatment, and outcome of hospitalized STEMI and non-STEMI; and the impact of changes in coronary risk factor levels during the years 1995 to 2010. Methods Study Population The Tromsø Study is a population-based, prospective study of various health issues and chronic diseases. It consists of 6 surveys of both sexes conducted in the municipality of Tromsø, Norway, from 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-STsegment-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.
Background and Objective In addition to its role as a transport protein, the vitamin D binding pr... more 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 PLOS ONE |
The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovas... more 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). 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...
Identification of structural heart disease in asymptomatic individuals could allow early disease-... more Identification of structural heart disease in asymptomatic individuals could allow early disease-modifying treatment. To examine whether echocardiographic screening in the general population improves long-term survival or reduces the risk of cardiovascular disease. We studied 6861 middle-aged participants from the population-based Tromsø Study in Norway. Participants were randomly allocated to an echocardiographic screening group (n = 3272) or a control group (n = 3589). Using the as-treated approach, the data were analyzed for mortality and incidence of fatal and nonfatal myocardial infarction and stroke. During 15 follow-up years, 880 persons (26.9%) in the screening group and 989 persons (27.6%) in the control group died (hazard ratio, 0.97; 95% CI, 0.89-1.06). No significant differences between the groups were observed in the secondary outcome measures (sudden death, mortality from any heart disease, or incidence of fatal and nonfatal myocardial infarction and stroke). Echocardi...
Objective: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently sev... more 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.
Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thicknes... more Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). Methods— IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. Results— During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a highe...
Background and Purpose— Carotid plaque and intima-media thickness (IMT) are recognized as risk fa... more Background and Purpose— Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery. Methods— IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005. Results— Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09–1.38; P =0.0009) in men and 1.19 (95% CI, 1.01–1.41; P =0.04) in women when adjusted for other cardiova...
Aims: To determine the gender-specific incidence and risk factors of type-2 diabetes mellitus (T2... more Aims: To determine the gender-specific incidence and risk factors of type-2 diabetes mellitus (T2DM) in a general population. Methods: The study is based on 12,431 men and 13,737 women aged 25-98 years, attending the Tromsø Study in 1994 and followed through 2005, who did not have diabetes when entering the study. Sex-specific hazard ratios were estimated from Cox proportional hazard models. Results: A total of 522 cases of T2DM were registered, 308 among men and 214 among women. The age-standardised incidence rate was higher in men than in women, 2.6 (95% CI 2.32—2.90) and 1.6 (95% CI 1.40—1.83) per 1000 person-years, respectively. In multivariate survival analysis, age, body mass index (BMI), triglycerides, high-density lipoprotein (HDL) cholesterol, hypertension, family history of diabetes, low education and smoking were independent predictors of T2DM in both genders (p>0.05). Total cholesterol and lack of leisure-time physical activity were independent predictors in men only....
Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins aft... more Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA.
Purpose To examine the cross-sectional relationship between drusen, late age-related macular dege... more Purpose To examine the cross-sectional relationship between drusen, late age-related macular degeneration (AMD), and cognitive function. Methods We included 2149 stroke-free participants from the population-based Tromsø Study in Norway. Retinal photographs were graded for presence of drusen and AMD. Cognitive function was assessed using the verbal memory test (short verbal memory), digit-symbol coding test (processing speed), and the tapping test (psychomotor tempo). We assessed the relationship between drusen, late AMD, and cognitive test scores, adjusted for potential confounders. Results Late AMD was associated with decreased performance in the verbal memory test (standardized b ¼ À 0.23, 95% confidence interval (CI): À 0.51 to À 0.01). Intermediate and large drusen were associated with decreased performance in the digit-symbol coding test (standardized b ¼ À 0.14 and-0.19, 95% CIs: À 0.23 to À 0.05 and À 0.29 to À 0.09, respectively). Participants with large drusen were more likely to have test scores in the lowest quartile of the digit-symbol coding test (odds ratio (OR) ¼ 1.9, 95% CI: 1.1-3.5) and the tapping test (OR ¼ 1.6, 95% CI: 1.0-2.6), but not in the verbal memory test (OR ¼ 1.0, 95% CI: 0.6-1.6). Conclusions The findings suggest a relationship between drusen deposition and reduced cognitive function. Although the relationships between drusen, late AMD, and the cognitive test results varied in strength and significance across the types of cognitive test, and may partly have been caused by residual confounding, it is not unlikely that a genuine but weaker relationship exists between drusen deposition and cognitive decline.
Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome, which accordingly ha... more Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome, which accordingly has been questioned both as a research and clinical tool. The aim of this study was to determine differences in risk factors for type 2 diabetes between groups with high or low metabolic score. The study population were 26,093 men and women attending the Tromsø Study in 1994, followed through 2005, and who did not have diabetes when entering the study. A total of 492 incident cases of type 2 diabetes were registered. A metabolic score was defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III. For those fulfilling C 3 metabolic score criteria, increasing age, body mass index (BMI), triglycerides and a family history of diabetes were independent predictors. Age, BMI, and triglycerides predicted type 2 diabetes more strongly in subjects with low metabolic score, whereas high HDL cholesterol was not protective in this low risk group. The risk associated with a positive family history was unaffected by level of metabolic score. In addition smoking, low education and in men also physical inactivity were independent risk factors only in those with low metabolic score. Adding these nonmetabolic risk factors increased correct classification from an ROC area of 77.2 to 87.1% (P value \ 0.0001). One half of the incident cases of type 2 diabetes were missed by using high metabolic score for risk prediction. Keywords Type 2 diabetes Á Metabolic syndrome Á Low metabolic score Á High metabolic score Á Non-metabolic risk factors Á Receiver operating characteristics
ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later ... more ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes.DesignPopulation-based prospective cohort study.MethodsFor 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.ResultsThere 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 p...
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