Variables of the fibrinolytic system: Risk indicators for CHD

The impairment of the fibrinolytic system, which leads to fibrin deposit and is involved in proliferation and migration of vascular cells, as shown in animal models, seems to play a role in the development of atherosclerotic lesions. Recent results of several prospective studies are in favour of this hypothesis. A decreased plasma fibrinolytic activity (FA) is predictive of coronary events in young men (Northwick Park Heart Study). An increased plasma concentration of PAI-1 is predictive of myocardial infarction (MI) in patients with angina (ECAT Angina Pectoris Study). An increased t-PA antigen concentration (which reflect mainly PA1-1/t-PA complexes) is predictive of MI in healthy subjects (Physicians' Health Study) and in angina patients (ECAT). Moreover there is a relationship between plasma concentration of PAI-1 or t-PA antigen and carotid thickness in apparently healthy subjects (ARIC Study). The impairment of the fibrinolytic system is mainly related to the plurimetabolic syndrome called insulin resistance (IR). Many studies have shown that FA, PAI-1 or t-PA antigen levels are strongly correlated to the multiple components of this syndrome (ponderal index, waist on hip ratio, triglyceride, HDL cholesterol, insulin, blood pressure ...). The mechanisms responsible for the alterations of fibrinolytic system in IR are not fully understood. Are mainly proposed the role of hormones/growth factors (insulin, proinsulin, IgF1), cytokines (TNF), lipoproteins (natives or oxydized, VLDL-LDL) on PAI-1 synthesis by vascular cells (SMC-endothelial cells), hepatocytes or adipocytes. In addition t-PA antigen plasma levels reflect the inflammatory status (ECAT Study). Modulation of the parameters of fibrinolysis is obtained with prescription of hygiene-dietetic rules (hypocaloric diet, physical exercise), with drugs such as oral antidiabetic drugs (Metformin), lipid lowering agents (Niacin, Gimfibrozil), or ACE inhibitor (Captopril).