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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]

Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixedeffects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden. [ABSTRACT FROM AUTHOR]

A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort.The study included 21 624 subjects recruited from the Troms⊘ Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35-1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02-1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12-2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE.FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors. [ABSTRACT FROM AUTHOR]

Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (i.e., a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant. [ABSTRACT FROM AUTHOR]

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.