Canseco-Avila Luis M, Jerjes-Sánchez Carlos, Ortiz-López Rocío, Rojas-Martínez Augusto, Guzmán-Ramírez Denisse
Dpto. Bioquímica, Facultad de Medicina del Hospital Universitario, UANL, México.
Arch Cardiol Mex. 2006 Oct-Dec;76 Suppl 4:S158-72.
Endothelial dysfunction and inflammation play a crucial role in all stages of atherosclerosis, from the beginning, during progression, and, finally, in its highest clinical expression: acute coronary syndromes. In this process, fibrinogen, an acute phase reactant with active participation in endothelial function, thrombosis and inflammation has proved to be an independent variable to cardiovascular risk together with its participation in resistance phenomena to different antithrombotic approaches. The reasons by which fibrinogen is elevated in cardiovascular disease and atherosclerosis are, in general, only incompletely understood; but all cells involved in the atherogenetic process are able to produce cytokines, which induce an acute phase reaction that increases fibrinogen levels in plasma. The potential pathophysiological mechanisms by which elevated fibrinogen levels mediate cardiovascular risk are multiple. Fibrinogen forms the substrate for thrombin an represents the final step in the coagulation cascade, it is essential for platelet aggregation, it modulates endothelial function, it promotes smooth muscle cell proliferation and migration, it interacts with the binding of plasmin with its receptor and, finally, it represents a major acute phase protein. Epidemiological studies have established sufficient evidence to consider fibrinogen as a strong, consistent, and independent cardiovascular risk marker or factor. Based on all these implications, the target of this review is an analysis of physiopathogenic and epidemiologic evidence searching for guidelines to establish whether fibrinogen as a risk factor or marker is the lost link between cardiovascular disease and classic risk factors.
Analyses of the respective studies suggest that fibrinogen is an important and independent cardiovascular risk factor, clearly associated with conventional risk factors and genetic polymorphisms. Whether or not fibrinogen is causally involved in atherothrombogenesis still remains to be determined and despite of unsolved issues that are waiting conclusive answers, fibrinogen has emerged as an important additional marker of cardiovascular risk.
内皮功能障碍和炎症在动脉粥样硬化的各个阶段都起着至关重要的作用,从起始阶段、进展过程,直至其最严重的临床表型:急性冠状动脉综合征。在这个过程中,纤维蛋白原作为一种急性期反应物,积极参与内皮功能、血栓形成和炎症反应,已被证明是心血管风险的一个独立变量,同时它还参与了对不同抗血栓治疗方法的抵抗现象。心血管疾病和动脉粥样硬化中纤维蛋白原升高的原因,总体而言,目前仍未完全明确;但参与动脉粥样硬化形成过程的所有细胞都能够产生细胞因子,这些细胞因子会引发急性期反应,从而使血浆中纤维蛋白原水平升高。纤维蛋白原水平升高介导心血管风险的潜在病理生理机制是多方面的。纤维蛋白原是凝血酶的底物,代表凝血级联反应的最后一步,它对血小板聚集至关重要,可调节内皮功能,促进平滑肌细胞增殖和迁移,与纤溶酶与其受体的结合相互作用,并且,它还是一种主要的急性期蛋白。流行病学研究已经积累了充分的证据,足以将纤维蛋白原视为一个强大、一致且独立的心血管风险标志物或因素。基于所有这些影响,本综述的目标是分析病理生理和流行病学证据,以寻找相关指南,来确定纤维蛋白原作为风险因素或标志物是否是心血管疾病与经典风险因素之间缺失的环节。
对各项研究的分析表明,纤维蛋白原是一个重要且独立的心血管风险因素,与传统风险因素及基因多态性明显相关。纤维蛋白原是否因果性地参与动脉粥样硬化血栓形成仍有待确定,尽管仍有一些未解决的问题等待最终答案,但纤维蛋白原已成为心血管风险的一个重要附加标志物。