Drs. Ernst and Resch [1] present a comprehensive review of the role of fibrinogen as a cardiovascular risk factor. They delineate possible mechanisms by which fibrinogen may promote atherosclerosis and thrombosis. In one study [2] of fibrin gel network characteristics and plasma fibrinogen in patients who had a myocardial infarction before the age of 45 years, those with an increased plasma fibrinogen concentration had a lower fibrin gel porosity than either patients with normal plasma fibrinogen levels or controls. This suggests that a propensity to form tight, rigid, and space-filling fibrin network structures with small pores may be associated with premature coronary artery disease. Munkvad and coworkers [3] found that the plasma concentrations of clottable fibrinogen and high-molecular-weight fibrinogen were related to the development of myocardial infarction in patients with coronary disease. A positive correlation of clottable fibrinogen and high-molecular-weight fibrinogen was shown (r = 0.58, P < 0.001), implying that high-molecular-weight fibrinogen represents a major percentage of the clottable fibrinogen concentration in patients with coronary ischemia.

As pointed out by Drs. Ernst and Resch, several medications may affect fibrinogen levels. The differing effects of antithrombotic agents are noteworthy in this regard. One group of researchers [4] investigated fibrinogen levels in 64 patients who had aorto-coronary bypass surgery and who were randomly assigned to receive either warfarin (international normalized ratio, 2.5 to 4.2) or aspirin (300 mg/d). Whereas patients treated with warfarin had increased fibrinogen levels 9 months after surgery compared with baseline, the patients treated with aspirin showed no significant change. Engelberg [5] studied 29 patients with ischemic heart disease who received intermittent subcutaneous heparin therapy (10 000 units three times a week or 15 000 units twice a week). Coagulable plasma fibrinogen decreased in 22 of the 29 patients in a gradual, continuous, and highly significant (P = 0.0006) fashion.

Finally, a recent study [6] showed that an increase of 1 mg of fibrinogen in patients with stable intermittent claudication correlated with a nearly two-fold increase in the probability of death within the next 6 years. This indicates that fibrinogen may not only be involved in the pathogenesis of arterial disease but may also be the strongest independent predictor of death in this clinical setting.