Plasma Markers of Procoagulant Activity Among Individuals with Coronary Artery Disease

Background: There is compelling evidence that coronary atherosclerosis represents a chronic active process characterized by inflammation, impaired fibrinolysis, intermittent plaque rupture, and luminal thrombosis. Identifying readily measurable plasma markers of procoagulant activity may have an important role in both tracking and understanding the natural history, as well as in defining the ideal treatment, of patients with coronary artery disease. Methods/Results: A total of 30 men and women with suspected coronary artery disease who underwent outpatient cardiac catheterization were sampled for evidence of thrombin generation and fibrin formation in plasma. Compared with healthy controls, patients had significantly increased concentrations of fibrinopeptide A (18.8 +/- 10.8 ng/ml vs. 2.5 +/- 2.3, p < 0.001), thrombin-antithrombin complexes (8.13 +/- 4.56 ng/ml vs. 3.4 +/- 3.0, p < 0.001), and prothrombin activation fragment 1.2 (0.15 +/- 0.09 ng/ml vs. 0.12 +/- 0.19, p = 0.01). There was a statistically insignificant trend toward increased thrombin-antithrombin complex concentrations in patients with hypercholesterolemia (p = 0.10). Patients with angiographically defined coronary artery disease involving two or more vessels were found to have heightened thrombin generation and fibrin formation compared with those with single vessel disease. Conclusions: Patients with atherosclerotic coronary artery disease exhibit evidence of heightened procoagulant activity, including thrombin generation and fibrin formation. This observation, coupled with those derived from other recent studies, support the hypothesis that coronary atherosclerosis represents a chronic active process typified by vessel wall inflammation and recurrent thrombosis. Future efforts in disease prevention and treatment must consider these fundamental pathobiologic properties.