25-hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18,791 participants.
Brøndum-Jacobsen P, Benn M, Tybjaerg-Hansen A, Nordestgaard BG.
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; The Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Vitamin D has potential antithrombotic effects suggesting that vitamin D analogs could be used as adjunctive antithrombotic agents. However, epidemiological evidence of an association between reduced 25-hydroxyvitamin D concentrations and risk of venous thromboembolism is lacking.
We tested the hypothesis that reduced plasma 25-hydroxyvitamin D concentrations associate with increased risk of venous thromboembolism in the general population.
We prospectively studied 18,791 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study. During up to 30 years of follow-up, 950 participants were diagnosed with venous thromboembolism. Plasma 25-hydroxyvitamin D concentrations were adjusted for seasonal variation.
Cumulative incidence of venous thromboembolism as a function of age increased with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D (log-rank trend:p= 4×10(-4) ). Comparing participants in the lowest versus the highest tertile of plasma 25-hydroxyvitamin D concentrations, the crude risk estimates in an age and sex adjusted model was a 37% (95% confidence interval: 15%-64%) increased risk of venous thromboembolism. Corresponding risk increases in an age, sex, body mass index, smoking, and cancer adjusted model was 26% (5%-51%), and in a multivariable adjusted model further including physical activity, hormone replacement therapy, menopausal status, oral contraception use, and lipid lowering therapy 28% (6%-53%). Furthermore, corresponding risk increases with attempts to correct for regression dilution bias were 103% (37%-202%), 70%(14%-155%), and 73%(15%-160%) in the three models, respectively.
In these large general population studies, we observed stepwise increasing risk of venous thromboembolism with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D concentrations.
© 2012 International Society on Thrombosis and Haemostasis.
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