Jaeger Beate Roxane, Labarrere Carlos Alberto
Institut für Klinische Chemie, Klinikum der Universität München, München.
Herz. 2003 Sep;28(6):530-8. doi: 10.1007/s00059-003-2497-5.
Fibrinogen is far more important as a risk factor for acute cardiovascular syndromes than generally recognized. Evidence from a recent metaanalysis (including 22 studies of 63,736 subjects and 5,717 events [1] suggests that the risk for myocardial infarction and stroke almost doubles if the fibrinogen level exceeds 3.03 g/l (measured according to Clauss) with an odds ratio of 1.99 and a 95% confidence interval of 1.85-2.13. The predictive value of fibrinogen levels equally applies to men and women, young and old, primary and secondary prevention. Repeated fibrinogen measurements are particularly helpful with emphasis on high risk patients: concentrations of the upper tertile indicate a 92% higher risk of impending acute cardiovascular syndromes, as evidenced by a metaanalysis evaluating five prospective studies with 9,639 participants and 671 events [1]. Together with other risk factors such as hypertension, hypercholesterolemia, or diabetes, the risk of fatal and nonfatal acute cardiovascular syndromes may further increase by 6-12- fold, while fibrinogen remains an independent risk factor for both cardiac and extracardiac atherothrombotic complications, as well as for iatrogenic complications like restenosis following PTCA or stenting. Fibrin(ogen) and his effector thrombin substantially determine the extent and outcome of atherothrombotic complications, because they are the molecules linking the mutually dependent events of atherogenesis, coagulation/fibrinolysis, rheology/vasotonus, and inflammation. Interventional studies on fibrinolytic and defibrinating substances, as well as GpIIb/IIIa-inhibitors for treatment of acute cardiovascular syndromes have confirmed the benefit of fibrinogen reduction and extended the experimental evidence for the relevance of fibrin(ogen) in the pathogenesis of these syndromes. Accordingly, the preventive use of fibrates leading to moderate reductions in plasma cholesterol and fibrinogen diminished significantly the rate of reinfarction. The emerging possibilities from a more than 50% fibrinogen reduction (by studies using H.E.L.P. apheresis) strengthened the therapeutic concept to free the blood from all risk factors-as effective as it can be-in order to achieve an optimal plaque regression, since changes in the blood composition strongly affect the fragility and stability of the atherosclerotic plaques.
纤维蛋白原作为急性心血管综合征的危险因素，其重要性远超过普遍认知。最近一项荟萃分析（涵盖22项研究，共63736名受试者和5717例事件[1]）的证据表明，如果纤维蛋白原水平超过3.03g/l（根据克劳斯法测量），心肌梗死和中风的风险几乎会翻倍，优势比为1.99，95%置信区间为1.85 - 2.13。纤维蛋白原水平的预测价值同样适用于男性和女性、年轻人和老年人、一级预防和二级预防。反复测量纤维蛋白原对高危患者尤为有用：一项荟萃分析评估了五项有9639名参与者和671例事件的前瞻性研究，结果表明，处于上三分位数浓度的患者即将发生急性心血管综合征的风险要高92%[1]。与高血压、高胆固醇血症或糖尿病等其他危险因素一起，致命和非致命急性心血管综合征的风险可能会进一步增加6至12倍，而纤维蛋白原仍然是心脏和心脏外动脉粥样硬化血栓形成并发症以及诸如PTCA或支架置入术后再狭窄等医源性并发症的独立危险因素。纤维蛋白（原）及其效应分子凝血酶在很大程度上决定了动脉粥样硬化血栓形成并发症的程度和结果，因为它们是连接动脉粥样硬化、凝血/纤维蛋白溶解、流变学/血管张力和炎症这些相互依存事件的分子。针对急性心血管综合征治疗的纤维蛋白溶解和去纤维蛋白物质以及糖蛋白IIb/IIIa抑制剂的干预性研究证实了降低纤维蛋白原的益处，并扩展了关于纤维蛋白（原）在这些综合征发病机制中相关性的实验证据。因此，使用贝特类药物进行预防性治疗可适度降低血浆胆固醇和纤维蛋白原，显著降低再梗死率。（通过使用H.E.L.P.血液分离术的研究）实现纤维蛋白原降低超过50%所带来的新可能性，强化了从血液中尽可能清除所有危险因素以实现最佳斑块消退的治疗理念，因为血液成分的变化会强烈影响动脉粥样硬化斑块的脆弱性和稳定性。
