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1 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet 2 unknown 3 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet 4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
BACKGROUND: 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. OBJECTIVES: We tested the hypothesis that reduced plasma 25-hydroxyvitamin D concentrations associate with increased risk of venous thromboembolism in the general population. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Journal of Thrombosis and Haemostasis, 2013, Vol 11, Issue 3, p. 423-431
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