Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis
Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis
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DOI：
10.1210/jc.2016-1368
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发表时间：
2016-06-01
影响因子：
5.8
通讯作者：
de Boer, Ian H.
中科院分区：
文献类型：
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作者：
Blondon, Marc;Cushman, Mary;de Boer, Ian H.
背景：解释已记录的 25-羟基维生素 D [25(OH)D] 缺乏与心血管疾病 (CVD) 和静脉血栓栓塞风险增加之间关联的机制，可能与不良止血和炎症反应有关。目的：评估 25(OH)D 缺乏是否与促血栓和促炎症生物学特征相关。设计：横断面分析。背景：动脉粥样硬化的多种族研究，多中心美国成年人前瞻性队列。参与者：最多 6554 名没有 CVD 的成年人。主要结果指标：10 种止血生物标志物（D-二聚体、纤维蛋白原、因子 VIII、纤溶酶抗纤溶酶和同型半胱氨酸 [n = 6443]；von Willebrand 因子、可溶性组织因子、纤溶酶原激活物抑制剂-1 (PAI-1)、总组织因子途径抑制剂 (TFPI) 和可溶性血栓调节蛋白 [n = 814]）和三种炎症生物标志物（IL-6、C 反应蛋白 [n = 6443] 和 TNF-α 可溶性受体 [n = 3802]）。结果：在 6443 名受试者中（46.6% 男性；平均年龄 62.1 岁；平均体重指数 28.3 kg/m(2)），白人 (37.8%)、黑人(27.2%)、华人 (12.2%) 和西班牙裔 (21.8%) 种族/民族，平均 25(OH)D 为 25.3 ng/mL。多重调整后，25(OH)D 浓度与 IL-6 和同型半胱氨酸浓度以及 PAI-1 和 TFPI 浓度相关：25(OH)D 每减少 10 ng/mL，IL-6 增加 5.1%（95% 置信区间 [CI]，3.4-6.9；P = .001）；同型半胱氨酸升高 3.7%（95% CI，3.0-4.3；P = .001）； PAI-1 升高 7.0%（95% CI，0.9 - 13.6；P = .025）； TFPI 高 2.1%（95% CI，0.0-4.2；P = .047），无种族/民族异质性。其他止血和炎症生物标志物没有观察到显着关联。结论：循环中 IL-6 升高和同型半胱氨酸浓度升高所反映的炎症增加可能代表了 25(OH)D 缺乏与 CVD 和静脉血栓栓塞风险增加之间的联系机制。低浓度的 25(OH)D 也与 PAI-1 和 TFPI 浓度相关，但与其他止血生物标志物无关。
Context: Mechanisms explaining documented associations of 25-hydroxyvitamin D [25(OH)D] deficiency with increased risks of cardiovascular disease (CVD) and venous thromboembolism may relate to adverse hemostatic and inflammatory responses.Objective: To evaluate whether 25(OH)D deficiency is associated with a prothrombotic and proinflammatory biological profile.Design: Cross-sectional analyses.Setting: The Multi-Ethnic Study of Atherosclerosis, a multicenter prospective cohort of American adults.Participants: Up to 6554 adults free of CVD.Main Outcome Measures: Ten hemostatic biomarkers (D-dimer, fibrinogen, factor VIII, plasmin-antiplasmin, and homocysteine [n = 6443]; von Willebrand factor, soluble tissue factor, plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin [n = 814]), and three inflammatory biomarkers (IL-6, C-reactive protein [n = 6443], and TNF-alpha soluble receptor [n = 3802]).Results: Among 6443 subjects (46.6% men; mean age, 62.1 years; mean body mass index, 28.3 kg/m(2)) of White (37.8%), Black (27.2%), Chinese (12.2%), and Hispanic (21.8%) race/ethnicity, mean 25(OH)D was 25.3 ng/mL. After multiple adjustment, 25(OH)D concentrations were associated with concentrations of IL-6 and homocysteine and also with concentrations of PAI-1 and TFPI: per 10 ng/mL decrement in 25(OH)D, 5.1% higher IL-6 (95% confidence interval [CI], 3.4-6.9; P = .001); 3.7% higher homocysteine (95% CI, 3.0-4.3; P = .001); 7.0% higher PAI-1 (95% CI, 0.9 - 13.6; P = .025); and 2.1% higher TFPI (95% CI, 0.0-4.2; P = .047), without racial/ethnic heterogeneity. No significant associations were observed for other hemostatic and inflammatory biomarkers.Conclusions: Increased inflammation as reflected by higher circulating IL-6 and increased homocysteine concentrations may represent mechanisms linking 25(OH)D deficiency to greater risks of CVD and perhaps venous thromboembolism. Low concentrations of 25(OH)D were also associated with PAI-1 and TFPI concentrations, but not with other hemostatic biomarkers.