25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18 791 participants
Article first published online: 13 MAR 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 3, pages 423–431, March 2013
How to Cite
25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18 791 participants. J Thromb Haemost 2012; 11: 423–31. DOI:10.1111/jth.12118., , , .
- Issue published online: 13 MAR 2013
- Article first published online: 13 MAR 2013
- Accepted manuscript online: 29 DEC 2012 09:48AM EST
- Manuscript Accepted: 13 DEC 2012
- Manuscript Received: 27 JUL 2012
- 25-hydroxyvitamin D;
- population study;
- prospective study;
- venous thromboembolism;
- vitamin D;
- vitamin D deficiency
Vitamin D has potential antithrombotic effects, suggesting that vitamin D analogs could be used as adjunctive antithrombotic agents. However, epidemiologic evidence of an association between reduced 25-hydroxyvitamin D concentrations and the risk of venous thromboembolism is lacking.
To test the hypothesis that reduced plasma 25-hydroxyvitamin D concentrations are associated with an 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.
The 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). On comparison of participants in the lowest and the highest tertile of plasma 25-hydroxyvitamin D concentrations, the crude risk estimate in a model adjusted for age and sex was a 37% (95% confidence interval [CI] 15–64%) increased risk of venous thromboembolism. The corresponding risk increase in a model adjusted for age, sex, body mass index, smoking and cancer was 26% (95% CI 5–51%), and in a multivariable-adjusted model also including physical activity, hormone replacement therapy, menopausal status, oral contraception use and lipid-lowering therapy it was 28% (95% CI 6–53%). Furthermore, corresponding risk increases with attempts to correct for regression dilution bias were 103% (95% CI 37–202%), 70% (95% CI 14–155%) and 73% (95% CI 15–160%) in the three models, respectively.
In these large general population studies, we observed a stepwise increasing risk of venous thromboembolism with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D concentrations.