PLASMA-FIBRINOGEN AND FACTOR-VII AS RISK-FACTORS FOR CARDIOVASCULAR-DISEASE

The importance of the thrombotic component of coronary heart disease is increasing recognised, and in particular the role of the coagulation system in this process. The Northwick Park Heart study was the first major prospective study to identify both fibrinogen and factor VII(c) as risk factors, as powerful as total cholesterol in predicting ischaemic events. Since then, a number of epidemiological studies have confirmed the importance of fibrinogen, not just in CHD but in stroke as well. A variety of environmental factors are known to influence levels of factor VII and fibrinogen and therefore support their role in the development of coronary thrombosis. Both are known to increase with age and body weight and are relatively elevated in diabetes. Fibrinogen is strongly related to smoking habit and a substantial proportion of the IHD risk associated with smoking is mediated through this relationship. There is a dose response effect between number of cigarettes smoked and level of fibrinogen and an inverse relationship with time since cessation of the habit. Factor VII is known to correlate with total cholesterol level, and there is a relationship between dietary variability of fat intake and factor VII, which is likely to play an important role in the risk of CHD. The case for using either anticoagulation or anti platelet agents in secondary prevention of myocardial infarction is now clear, but there are still uncertainties in primary prevention which relate to the ideal dose intensity of either aspirin or anti-coagulation and the type of patient most likely to benefit. The ongoing Thrombosis Prevention Trial identifies middle-aged males at high risk of a myocardial infarction. These are then randomised in a double blind placebo controlled factorial design to receive one of four treatments: 75 mg of aspirin and warfarin at a low intensity level of anticoagulation titrated to achieve an international normalised ratio of 1.5, either agent singly, or two types of placebo. The progress of this trial is discussed.