Medical Research Council Centre for Epidemiology of Child Health and Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, UK.
PLoS One. 2010 May 24;5(5):e10801. doi: 10.1371/journal.pone.0010801.
Vitamin D deficiency has been suggested as a cardiovascular risk factor, but little is known about underlying mechanisms or associations with inflammatory or hemostatic markers. Our aim was to investigate the association between 25-hydroxyvitamin D [25(OH)D, a measure for vitamin D status] concentrations with pre-clinical variations in markers of inflammation and hemostasis.
METHODOLOGY/PRINCIPAL FINDINGS: Serum concentrations of 25(OH)D, C-reactive protein (CRP), fibrinogen, D-dimer, tissue plasminogen activator (tPA) antigen, and von Willebrand factor (vWF) were measured in a large population based study of British whites (aged 45 y). Participants for the current investigation were restricted to individuals free of drug treated cardiovascular disease (n = 6538). Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p < or =0.015 for all), but associations with CRP, fibrinogen, and vWF were explained by adiposity. Association with tPA persisted after full adjustment (body mass index, waist circumference, physical activity, TV watching, smoking, alcohol consumption, social class, sex, and month), and average concentrations were 18.44% (95% CI 8.13, 28.75) lower for 25(OH)D > or =75 nmol/l compared to < 25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/l compared to others (quadratic term p = 0.01). We also examined seasonal variation in hemostatic and inflammatory markers, and evaluated 25(OH)D contribution to the observed patterns using mediation models. TPA concentrations varied by season (p = 0.02), and much of this pattern was related to fluctuations in 25(OH)D concentrations (p < or =0.001). Some evidence of a seasonal variation was observed also for fibrinogen, D-dimer and vWF (p < 0.05 for all), with 25(OH)D mediating some of the pattern for fibrinogen and D-dimer, but not vWF.
Current vitamin D status was associated with tPA concentrations, and to a lesser degree with fibrinogen and D-dimer, suggesting that vitamin D status/intake may be important for maintaining antithrombotic homeostasis.
维生素 D 缺乏被认为是心血管疾病的一个风险因素，但关于其潜在机制或与炎症和止血标志物的关系知之甚少。我们的目的是研究 25-羟维生素 D [25(OH)D，衡量维生素 D 状态的指标]浓度与炎症和止血标志物的临床前变化之间的关系。
方法/主要发现：在一项英国白人的大型人群基础研究中（年龄 45 岁），测量了血清 25(OH)D、C 反应蛋白（CRP）、纤维蛋白原、D-二聚体、组织型纤溶酶原激活物（tPA）抗原和血管性血友病因子（vWF）的浓度。目前的研究对象仅限于无药物治疗的心血管疾病的个体（n=6538）。校正性别和月份后，25(OH)D 与所有结果呈负相关（p<0.015），但与 CRP、纤维蛋白原和 vWF 的相关性可通过肥胖来解释。在充分调整后，与 tPA 的关联仍然存在（体重指数、腰围、体力活动、看电视、吸烟、饮酒、社会阶层、性别和月份），与 25(OH)D>或=75 nmol/l 相比，25(OH)D<25 nmol/l 时，平均浓度低 18.44%（95%CI 8.13，28.75）。与 25(OH)D50-90 nmol/l 的参与者相比，D-二聚体浓度较低（二次项 p=0.01）。我们还检查了止血和炎症标志物的季节性变化，并使用中介模型评估了 25(OH)D 对观察到的模式的贡献。tPA 浓度随季节而变化（p=0.02），而这种模式的大部分与 25(OH)D 浓度的波动有关（p<0.001）。还观察到纤维蛋白原、D-二聚体和 vWF 存在季节性变化的一些证据（p<0.05），25(OH)D 对纤维蛋白原和 D-二聚体的模式有一定的中介作用，但对 vWF 没有。
目前的维生素 D 状态与 tPA 浓度有关，与纤维蛋白原和 D-二聚体的关系较小，这表明维生素 D 状态/摄入可能对维持抗血栓形成的体内平衡很重要。
