Moderate alcohol consumption has been shown to protect against cardiovascular diseases. The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption was collected by a self-administrated questionnaire in 26,662 subjects, aged 25-97 years, who participated in the Tromsø Study, in 1994-1995. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE. However, subjects consuming = 3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, body mass index, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI: 1.00-2.33). Contrary, subjects with a wine intake of = 3 units/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (= 1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.
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.
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.
Our findings indicate that WC is the preferable anthropometric measure of obesity to identify subjects at risk and to predict risk of VTE.
To disclose risk factors of incident aortic stenosis (AS) and progression of established AS. A prospective cohort study. The Tromsø Study, a population based health survey. Over a 14 years span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3,243 participants. Data from the only hospital serving this population were included in the follow up. Throughout the study 132 participants were diagnosed with incident AS, defined as mean aortic valve gradient =15 mmHg. Cox proportional hazards regression disclosed age (HR 1.11, 95 %CI 1.08-1.14), systolic blood pressure (BP) (HR 1.01, 95 % CI 1.00-1.02), active smoking (HR 1.71, 95 % CI 1.09-2.67), and waist circumference (HR 1.02, 95 % CI 1.00-1.03) as independent predictors of incident AS. Analysis of risk factors for progression of AS disclosed a higher mean aortic gradient at first measurement (p = 0.015), weight (p = 0.015), a low haemoglobin (Hgb) (p = 0.030) and high density lipoprotein (HDL) (p = 0.032) as significant independent predictors. Age, systolic BP, smoking and waist circumference were independent predictors of incident AS, whereas cholesterol was not. Mean aortic gradient at first measurement, weight, an elevated HDL and low Hgb increase the progression rate of the disease. Our data indicate that calcific aortic valve disease is a distinct pathophysiological process, with age, smoking and "wear and tear" of the valve being major contributors to the disease development.
Red cell distribution width (RDW) is a risk marker of venous thromboembolism (VTE), myocardial infarction (MI), stroke, and cancer. Due to interrelations between these diseases, the association between RDW and VTE may be explained by MI, stroke, or cancer.
To investigate whether the effect of RDW on VTE could be explained by intermediate development of MI, stroke, or cancer.
RDW was measured in 24 363 participants of the Tromsø Study in 1994-1995. Incident VTE, MI, stroke, and cancer were registered until December 31, 2010. Conventional and cause-specific Cox-regression models were used to estimate hazard ratios (HR) for VTE with 95% confidence intervals (CI) across categories of RDW.
There were 502 first VTEs during a median follow-up of 16 years. In conventional Cox regression analysis, RDW in the highest quartile was associated with a 71% (HR 1.71, 95% CI 1.09-2.67) and 27% (HR 1.27, 95% CI 0.88-1.85) higher risk of VTE in men and women, respectively, compared to subjects in the lowest quartiles. The risk of VTE among subjects with RDW in the highest quartile was similar for men and women of postmenopausal age. In cause-specific analysis, where each individual contributed with person-time until the first occurring event only, the risk estimates were similar to those of the conventional Cox-regression analysis.
Our findings suggest that the association between RDW and future risk of VTE is not explained by intermediate development of MI, stroke, or cancer.
Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted.
We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR
-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.
-As part of a larger case/control study of VTE, 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 six are novel (i.e. not previously reported); seven associations with rare variants in cis, of which four are novel; and six associations in trans Of the 20 proteins, 15 were associated with single sites and seven with rare variants. cis-pQTLs for kallikrein and F12 also show trans associations for proteins (uPAR, kininogen) known to be cleaved by kallikrein as well as with NTproBNP. We experimentally demonstrate that kallikrein can cleave proBNP (NTproBNP precursor) in vitro Nine of the pQTLs have previously identified associations with 17 diseases and/or physiological phenotypes.
-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 diseases and/or physiological phenotypes.
The relationship between serum levels of calcium, parathyroid hormone (PTH) and risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the associations between serum levels of calcium and PTH, with future risk of VTE in a general adult population.
A total of 27 712 subjects (25-87 years) who participated in Tromsø 4 (1994-1995) and Tromsø 5 (2001-2002) surveys were included in the study, and total calcium and PTH were measured in 27 685 and 8547 subjects respectively. Incident VTE was recorded through December 31, 2012. Cox-regression models with calcium and PTH as time-varying exposures were used to calculate hazard ratios (HR) of VTE by quartiles of calcium and PTH. Quartiles of calcium and PTH were also combined to assess the effect of discordants of both PTH and calcium (e.g. highest and lowest quartiles of both calcium and PTH) on VTE risk using the middle two quartiles as reference.
There were 712 VTEs during 15.0 years of median follow-up. Serum levels of calcium and PTH were not associated with risk of VTE. However, subjects with discordant high serum levels of both calcium and PTH (calcium =2.45?mmol/L and PTH =4.0?pmol/L) had increased risk of VTE compared to those in subjects with normal calcium and PTH (multivariable HR: 1.78, 95% CI: 1.12-2.84).
Serum levels of calcium and PTH separately were not associated with future risk of VTE, but subjects with high levels of both calcium and PTH had increased risk of VTE compared to those in subjects with normal levels.
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.
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.
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.
For MI and VTE, risk estimates based on baseline and repeated measures corresponded well, whereas correction for regression dilution tended to overestimate risks.
Atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS). Emerging evidence also indicates an association between AF and pulmonary embolism (PE). Because IS may potentially mediate the observed risk of PE in AF, we aimed to assess the impact of AF on the cause-specific risks of PE and IS in a large cohort recruited from the general population.
We observed 29 842 participants from 3 surveys of the Tromsø study (inclusion in 1994-1995, 2001-2002, and 2007-2008) to the end of 2012. Incident events of AF, IS, and PE during follow-up were recorded, and information on potential confounders was obtained at baseline. Cox regression models, with AF as a time-dependent variable, were used to calculate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for PE and IS. There were 2067 participants diagnosed as having AF, 296 with PE and 1164 with IS, during a median of 17.6 years of follow-up. The risks of PE (HR, 10.88; 95% CI, 6.23-18.89) and IS (HR, 6.16; 95% CI, 4.47-8.48) were substantially increased during the first 6 months after AF diagnosis, with crude incidence rates of 18.5 per 1000 person-years for PE and 52.8 per 1000 person-years for IS. The risk estimates remained elevated for both PE (HR, 1.72; 95% CI, 1.10-2.71) and IS (HR, 2.45; 95% CI, 2.05-2.92) throughout the study period.
AF was associated with increased cause-specific risks of both PE and IS. Our findings infer that the risk of PE in AF is not explained by intermediate IS.
Cites: Am J Epidemiol. 2010 May 15;171(10):1109-15 PMID 20418276
K.G. Jebsen Thrombosis Research and Expertise Center, Department of Clinical Medicine, University of Tromsø, Norway; Hematological Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Whether atrial fibrillation is related to risk of venous thromboembolism (VTE) is not extensively studied. Therefore, we investigated the association between atrial fibrillation and future risk of VTE in a population-based cohort.
In total, 29 975 subjects were recruited from three surveys of the Tromsø study and followed from enrolment (1994-95, 2001-02 and 2007-08) through 2010. Incident events of atrial fibrillation and VTE during follow-up were recorded. Information on potential confounders was obtained at baseline. Cox-regression models with atrial fibrillation as time-dependent variable were used to calculate hazard ratios (HR) for VTE with 95% confidence intervals (CI).
During 16 years of median follow-up, 1604 subjects were diagnosed with atrial fibrillation and 614 with incident VTE. The risk of VTE was substantially increased during the first 6 months after diagnosis of atrial fibrillation (HR 8.44, 95% CI: 5.61-12.69), and remained increased throughout the study period (HR: 1.43, 95% CI 1.43-1.99) compared to those without atrial fibrillation. Atrial fibrillation displayed higher risk estimates for pulmonary embolism (HR: 11.84, 6.80-20.63) than for deep vein thrombosis (HR: 6.20, 3.37-11.39), during the first 6 months, and was still associated with pulmonary embolism (HR: 1.96, 95% CI: 1.24-3.10) but not with deep vein thrombosis (HR: 1.08, 95% CI: 0.66-1.75) more than 6 months after diagnosis.
Atrial fibrillation was associated with increased risk of VTE, and pulmonary embolism in particular. Our findings support the concept that isolated pulmonary embolism may originate from right atrial thrombi due to atrial fibrillation. This article is protected by copyright. All rights reserved.