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Arterial stiffness is a risk factor for cardiovascular and chronic kidney disease. However, the role of arterial stiffness as a predictor of the age-related glomerular filtration rate (GFR) decline in the general population remains unresolved because of difficulty in measuring GFR with sufficient precision in epidemiological studies. The ambulatory arterial stiffness index (AASI) is a proposed indicator of arterial stiffness easily calculated from ambulatory blood pressure. We investigated whether AASI could predict GFR decline measured as iohexol clearance in the general population. We calculated AASI from baseline ambulatory blood pressure and measured the iohexol clearance at baseline and follow-up in the RENIS-FU study (Renal Iohexol Clearance Survey Follow-Up). AASI was defined as 1 minus the regression slope of the diastolic blood pressure measurement over the systolic blood pressure measurement for each patient. The RENIS cohort included a representative sample of the general middle-aged population without baseline diabetes mellitus, cardiovascular disease, or kidney disease (n=1608). The participant age was 50 to 62 years old at baseline, and the median observation time was 5.6 years. The mean (SD) of the GFR decline rate was 0.95 mL/min per year (2.23) and that of the AASI was 0.38 mL/min per year (0.13). Baseline ambulatory blood pressure or the night/day systolic or diastolic ambulatory blood pressure ratios were not associated with GFR decline. In multivariable-adjusted linear mixed regression analysis, 1 SD of increase in the baseline AASI was associated with a 0.14 mL/min per year (95% confidence interval, -0.26 to -0.02) steeper GFR decline. We conclude that the AASI is an independent risk factor for accelerated age-related GFR decline in the general middle-aged population. [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]

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

The article discusses a research which examines the association of multiple protein biomarkers with the 10-year risk of incident first-ever myocardial infarction (MI) and identifies a clinically significant risk model in samples from a longitudinal study of men and women in Tromsø, Norway. The study found several clinically significant biomarkers adjusted for traditional risk factors including apolipoprotein B/apolipoprotein A1 ratio, kallikrein, and matrix metalloproteinase 9.

Background: Genetic variation can be used to study causal relationships between biomarkers and diseases. Here, we identify new common and rare genetic variants associated with cardiovascular-related protein levels (protein quantitative trait loci [pQTLs]). We functionally annotate these pQTLs, predict and experimentally confirm a novel molecular interaction, and determine which pQTLs are associated with diseases and physiological phenotypes., Methods and Results: As part of a larger case-control study of venous thromboembolism, serum levels of 51 proteins implicated in cardiovascular diseases were measured in 330 individuals from the Tromsø Study. Exonic genetic variation near each protein's respective gene (cis) was identified using sequencing and arrays. Using single site and gene-based tests, we identified 27 genetic associations between pQTLs and the serum levels of 20 proteins: 14 associated with common variation in cis, of which 6 are novel (ie, not previously reported); 7 associations with rare variants in cis, of which 4 are novel; and 6 associations in trans. Of the 20 proteins, 15 were associated with single sites and 7 with rare variants. cis-pQTLs for kallikrein and F12 also show trans associations for proteins (uPAR, kininogen) known to be cleaved by kallikrein and with NTproBNP. We experimentally demonstrate that kallikrein can cleave proBNP (NTproBNP precursor) in vitro. Nine of the pQTLs have previously identified associations with 17 disease and physiological phenotypes., Conclusions: We have identified cis and trans genetic variation associated with the serum levels of 20 proteins and utilized these pQTLs to study molecular mechanisms underlying disease and physiological phenotypes., (© 2016 The Authors.)

Objective: Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks., Approach and Results: Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (P for trend <0.001) and with increasing total plaque area (P for trend <0.001), but neither intima-media thickness (P for trend=0.94) nor total plaque area (P for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis., Conclusions: In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.

Objective: The goal of this study was to investigate the combined effect of obesity and body height on the risk of venous thromboembolism (VTE) in a prospective population-based study., Methods and Results: Personal characteristics, including measures of obesity and body height, were collected in 26 714 men and women, aged 25 to 97 years, who participated in the Tromsø Study in 1994 to 1995. Incident VTE events were registered through September 1, 2007. There were 461 incident VTE events during a median of 12.5 years of follow-up. A tall stature was associated with increased risk of VTE in normal-weight (body mass index <25 kg/m(2)) and obese (body mass index ≥30 kg/m(2)) men, but not in women. The combination of obesity and tall stature synergistically increased the risk of VTE in both sexes. Tall (≥182 cm), obese men had a 5-fold (multivariable hazard ratio 5.16; 95% CI 2.39 to 11.14) increased risk of VTE compared with normal-weight men with short (≤172 cm) stature. Tall (≥168 cm), obese women had an almost 3-fold (multivariable hazard ratio 2.89; 95% CI 1.31 to 6.35) increased risk of VTE compared with normal-weight, short (≤159 cm) women., Conclusion: The combination of obesity and a tall stature was associated with a substantially increased risk of VTE, especially in men, suggesting synergistic effects of obesity and height on risk of VTE in both sexes.

Objective: The purpose of this study was to assess the impact of various obesity measures on identification of subjects at risk and their respective risk estimates for VTE in a prospective population-based study., Methods and Results: Measures of body composition such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) were registered in 6708 subjects aged 25 to 84 years, who participated in the Tromsø Study (1994-1995). Incident VTE-events were registered during follow-up until September 1, 2007. There were 222 VTE-events during a median of 12.3 years of follow-up. All measures of obesity exhibited significantly increased HR for VTE in multivariable models with highest risk estimates for WC in both genders. The risk of VTE increased across quartiles of BMI, WC, and HC in both genders, but not for WHR. WC identified more subjects at risk using established criteria for obesity. WC had the highest area under the curve in both genders in ROC analysis, and WC above ROC-derived cut-off values (WC > or =85 cm in women and > or =95 cm in men) were associated with HRs of 1.92 (95% CI: 1.05 to 3.48) in women and 2.78 (95% CI: 1.47 to 5.27) in men., Conclusions: Our findings indicate that WC is the preferable anthropometric measure of obesity to identify subjects at risk and to predict risk of VTE.