Department of Medicine, University of Vermont, Burlington, VT 05446, USA.
J Thromb Haemost. 2013 Jun;11(6):1078-84. doi: 10.1111/jth.12223.
HMG-CoA reductase inhibitors (statins) reduce the risk of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers; however, the mechanism for the reduction in VTE risk is unknown.
In a large cohort of healthy people, we studied associations of statin use with plasma hemostatic factors related to VTE risk.
Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 healthy men and women aged 45-84 years, free of clinical cardiovascular disease at baseline; 1001 were using statins at baseline. Twenty-three warfarin users were excluded. Age, race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users, and multivariable linear regression models were used to assess associations of statin use with hemostatic factors, adjusted for age, race/ethnicity, education, income, aspirin use, hormone replacement therapy (in women), and major cardiovascular risk factors.
Participants using statins had lower adjusted levels of D-dimer (- 9%), C-reactive protein (- 21%) and factor VIII (- 3%) than non-users (P < 0.05). Homocysteine and von Willebrand factor levels were non-significantly lower with statin use. Higher fibrinogen (2%) and plasminogen activator inhibitor-1 (22%) levels were observed among statin users than among non-users (P < 0.05). Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use.
Findings of lower D-dimer, FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk. A prospective study or clinical trial linking these biochemical differences to VTE outcomes in statin users and non-users is warranted.
羟甲基戊二酰辅酶 A 还原酶抑制剂(他汀类药物)可降低健康人群静脉血栓栓塞(VTE)的风险。他汀类药物可降低炎症生物标志物水平;然而,降低 VTE 风险的机制尚不清楚。
在一项大型健康人群队列研究中,我们研究了他汀类药物的使用与与 VTE 风险相关的血浆止血因子之间的关联。
对动脉粥样硬化多民族研究(MESA)进行了横断面分析,该研究是一项 6814 名年龄在 45-84 岁之间、基线时无临床心血管疾病的健康男性和女性的队列研究;1001 人在基线时使用他汀类药物。排除了 23 名华法林使用者。比较了他汀类药物使用者和非使用者之间的年龄、种族和性别调整后止血因子水平,并使用多变量线性回归模型评估了他汀类药物使用与止血因子的相关性,调整了年龄、种族/民族、教育、收入、阿司匹林使用、激素替代疗法(女性)和主要心血管危险因素。
与非使用者相比,使用他汀类药物的参与者的 D-二聚体(-9%)、C 反应蛋白(-21%)和因子 VIII(-3%)的调整后水平较低(P<0.05)。使用他汀类药物时,同型半胱氨酸和血管性血友病因子水平略有降低。与非使用者相比,他汀类药物使用者的纤维蛋白原(2%)和纤溶酶原激活物抑制剂-1(22%)水平较高(P<0.05)。进一步调整 LDL 和甘油三酯水平并不能减轻他汀类药物使用与这些因子之间观察到的差异。
他汀类药物使用时 D-二聚体、因子 VIII 和 C 反应蛋白水平降低的发现表明了他汀类药物可能降低 VTE 风险的机制假说。有必要进行一项前瞻性研究或临床试验,将这些生化差异与他汀类药物使用者和非使用者的 VTE 结局联系起来。