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Plasma hepcidin is associated with future risk of venous thromboembolism.

ABSTRACT: Red cell distribution width (RDW) is associated with venous thromboembolism (VTE), but the underlying mechanism(s) is unclear. Iron deficiency is associated with high RDW, and studies suggest an association between iron deficiency and VTE. To assess whether iron deficiency is a risk factor for VTE that explains the association between RDW and VTE, we conducted a nested case-control study of 390 patients with VTE and 802 age- and sex-matched controls selected from the population-based cohort of the Tromsø Study. Physical measurements and blood samples were collected from 1994 to 1995. Logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE by RDW, hepcidin, and ferritin light chain (FtL). RDW was inversely associated with hepcidin, FtL, and hemoglobin. The risk of VTE increased linearly across categories of higher plasma hepcidin levels. Participants with hepcidin in the highest quartile had an OR for VTE of 1.32 (95% CI, 1.00-2.42), and those in the >90% percentile had an OR for VTE of 1.66 (95% CI, 1.14-2.42) compared with the reference group (quartiles 2 and 3). The risk estimates remained similar after adjustment for C-reactive protein. The risk of VTE increased by categories of higher RDW and was strengthened after inclusion of hepcidin and FtL in the multivariable model. Our findings reject the hypothesis that iron deficiency explains the association between RDW and VTE and suggest, in contrast, that high body iron levels might increase the risk of VTE.

SUBMITTER: Ellingsen TS

PROVIDER: S-EPMC5998931 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Plasma hepcidin is associated with future risk of venous thromboembolism.

Ellingsen Trygve S TS Lappegård Jostein J Ueland Thor T Aukrust Pål P Brækkan Sigrid K SK Hansen John-Bjarne JB

Blood advances 20180601 11

Red cell distribution width (RDW) is associated with venous thromboembolism (VTE), but the underlying mechanism(s) is unclear. Iron deficiency is associated with high RDW, and studies suggest an association between iron deficiency and VTE. To assess whether iron deficiency is a risk factor for VTE that explains the association between RDW and VTE, we conducted a nested case-control study of 390 patients with VTE and 802 age- and sex-matched controls selected from the population-based cohort of t ...[more]

PMID: 29844204

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Project description:ImportanceIt is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).ObjectiveTo estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.Design, setting, and participantsThis study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.ExposuresA panel of several established cardiovascular risk factors.Main outcomes and measuresHazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).ResultsOf the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.Conclusions and relevanceOlder age, smoking, and adiposity were consistently associated with higher VTE risk.

Project description:ImportanceThe size of the risk of recurrent venous thromboembolism (VTE) after surgery in patients with a history of VTE is not well known.ObjectivesTo estimate the risk of and to identify the factors associated with recurrent VTE in patients undergoing surgery who have a history of VTE.Design, setting, and participantsThis population-based, follow-up cohort study includes patients with VTE who participated in the Multiple Environment and Genetic Assessment (MEGA) study. Original data were collected from March 1999 to April 2010. Data analysis began in June 1999 and ended in April 2010.ExposuresSurgery following a first VTE.Main outcomes and measurementsKaplan-Meier analyses were used to estimate cumulative incidences of recurrent VTE. Cox regression with a time-dependent covariate (surgery) was used to calculate the hazard ratio (HR) for developing recurrent VTE after surgery compared with no surgery.ResultsOverall, 3741 patients (mean [SD] age, 48.4 [12.8] years; 2020 [54.0%] women) with a history of VTE were included in the analysis, amounting to 18 899 person-years, with a median (interquartile range) follow-up of 5.7 (3.0-7.2) years. Of the 3741 patients, 580 (15.5%) underwent surgery and 601 (16.1%) developed a recurrent thrombotic event. The 1-month cumulative incidence of recurrent VTE for all surgery types was 2.1% (95% CI, 1.2%-3.6%), which increased to 3.3% (95% CI, 2.1%-5.1%) at 3 months and 4.6% (95% CI, 3.1%-6.6%) at 6 months. At 6 months, risk of recurrent VTE ranged from 2.3% to 9.3%, depending on surgery type. In addition to surgery type, factor V Leiden mutation (HR, 3.4; 95% CI, 1.6-7.4) and male sex (HR, 2.7; 95% CI, 1.3-5.8) were associated with increased risk of recurrent VTE.Conclusions and relevanceSurgery was associated with an increased risk of recurrent VTE in patients with a history of VTE; risk remained high for up to 6 months after the procedure. This study suggests that high-risk individuals may be identified based on surgery type, sex, and the presence of factor V Leiden mutation. These findings stress the need for revision of the current thromboprophylactic approach to prevent recurrence in these patients.

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Plasma hepcidin is associated with future risk of venous thromboembolism.

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Plasma hepcidin is associated with future risk of venous thromboembolism.

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