[Clinical significance of the cardiovascular risk factor fibrinogen in secondary prevention]

Abstract

Seven prospective, epidemiological studies indicate plasma fibrinogen levels (over 300-350 mg/dl) as an important, independent cardiovascular risk factor for subsequent myocardial infarction and stroke. Furthermore, several clinical studies revealed an association between fibrinogen and both the angiographic and clinical degree of coronary heart disease. In addition, a significant relation of fibrinogen with the number of occluded coronary vessels was found. The following pathophysiologic mechanism are of particular importance: Fibrinogen is a main determinant of plasma viscosity and red cell aggregation. Both phenomena deteriorate blood fluidity especially in the microcirculation. Fibrinogen plays a central role in platelet aggregation and performs an essential substrate in the coagulation cascade. Thus, high fibrinogen levels may favor a hypercoagulable state resulting in final thrombotic events of cardiovascular disease. Fibrinogen is also involved in atherogenesis by stimulating proliferation and migration of smooth muscle cells. Several determinants of fibrinogen levels are known. Smoking is the strongest one in healthy persons. This clinically important effect is dose related. Consequently, cessation of smoking is a major step to lower fibrinogen and subsequently the individual cardiovascular risk. Reduction of overweight and maintenance of regular physical activity are further nonpharmacologic means. Fibrates decrease fibrinogen about 10-30% on an average. Finally, intermittent low-dose Urokinase for end-stages of coronary artery disease and LDL-apheresis (HELP) represent additional approaches to reduce fibrinogen.