Morange P E, Simon C, Alessi M C, Luc G, Arveiler D, Ferrieres J, Amouyel P, Evans A, Ducimetiere P, Juhan-Vague I
Department of Hematology, Faculty of Medicine, INSERM U626, Marseilles, France.
Circulation. 2004 Mar 23;109(11):1343-8. doi: 10.1161/01.CIR.0000120705.55512.EC. Epub 2004 Mar 15.
Tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), and thrombomodulin (TM) are 3 major hemostatic regulatory molecules synthesized by endothelium. Data from epidemiological studies aiming to evaluate the relation between plasma levels of these molecules and the development of coronary heart disease (CHD) are sparse or contradictory.
We examined the association between these endothelial-cell markers and the incidence of fatal or nonfatal myocardial infarction (hard CHD) and stable or unstable angina (angina pectoris) in a prospective cohort (the PRIME Study) of nearly 10 000 healthy men recruited in France and Northern Ireland. We measured baseline plasma concentration of the free form of TFPI (f-TFPI), vWF, and the soluble form of TM (sTM) among 296 participants who subsequently developed CHD over the 5-year follow-up (158 with hard CHD and 142 with angina pectoris) and in 563 control subjects by use of a nested case-control design. Individuals with plasma vWF levels in the highest quartile showed a 3.04-fold increase in the risk of hard CHD compared with those in the lowest quartile (95% CI, 1.59 to 5.80). Individuals with f-TFPI levels below the 10th percentile had a 2.13-fold increased risk of hard CHD compared with those with levels above it (95% CI, 1.08 to 4.18). The risk for both molecules persisted after control for inflammatory parameters. Individuals with vWF levels in the highest quartile and f-TFPI levels below the 10th percentile presented a 6.9-fold increased risk of hard CHD compared with those with vWF levels in the lowest quartile and f-TFPI levels above the 10th percentile (95% CI, 1.3 to 37.8).
vWF and f-TFPI plasma levels were independent risk factors for hard CHD events.
组织因子途径抑制剂（TFPI）、血管性血友病因子（vWF）和血栓调节蛋白（TM）是由内皮细胞合成的3种主要止血调节分子。旨在评估这些分子的血浆水平与冠心病（CHD）发生之间关系的流行病学研究数据稀少或相互矛盾。
我们在法国和北爱尔兰招募的近10000名健康男性的前瞻性队列（PRIME研究）中，研究了这些内皮细胞标志物与致命或非致命性心肌梗死（严重CHD）以及稳定或不稳定型心绞痛（心绞痛）发病率之间的关联。我们采用巢式病例对照设计，测量了296名在5年随访期间随后发生CHD的参与者（158例严重CHD和142例心绞痛）以及563名对照受试者中游离形式的TFPI（f-TFPI）、vWF和可溶性形式的TM（sTM）的基线血浆浓度。血浆vWF水平处于最高四分位数的个体与处于最低四分位数的个体相比，发生严重CHD的风险增加3.04倍（95%CI，1.59至5.80）。f-TFPI水平低于第10百分位数的个体与高于该水平的个体相比，发生严重CHD的风险增加2.13倍（95%CI，1.08至4.18）。在控制炎症参数后，这两种分子的风险仍然存在。vWF水平处于最高四分位数且f-TFPI水平低于第10百分位数的个体与vWF水平处于最低四分位数且f-TFPI水平高于第10百分位数的个体相比，发生严重CHD的风险增加6.9倍（95%CI，1.3至37.8）。
血浆vWF和f-TFPI水平是严重CHD事件的独立危险因素。
