Fibrinolytic proteins and progression of coronary artery disease in relation to gemfibrozil therapy

Impaired fibrinolytic function, mainly due to increased plasma plasminogen activator inhibitor-1 (PAI-1) activity, is common in patients with manifest coronary artery disease (CAD) and a predictor of recurrent cardiovascular events, We investigated the relationships of plasma tissue-type plasminogen activator (tPA) and PAI-1 antigen levels, plasma PAI-1 activity and PAI 4/ 5-guanosine (4G/5G) genotype to CAD progression in 203 middle-aged men part icipating in the Lopid Coronary Angiography Trial (LOCAT). A higher tPA antigen concentration, whether baseline or on-trial, was assoc iated with a more severe global angiographic response (p < 0.05), an associ ation mainly accounted for by progression of diffuse lesions in graft-affec ted segments (change in per-patient means of average diameters of segments haemodynamically related to bypass grafts). Plasma PAI-1 activity and mass concentration and 4G/5G PAI-1 genotype were unrelated to angiographic outco me measurements. tPA and PAI-1 antigen increased significantly in the gemfi brozil group (+11.3% and + 16.4%, respectively, p < 0.001), whereas there w as no treatment effect on PAI-I activity (median change 0.0%). It is concluded that fibrinolytic function does not substantially influence progression of CAD as assessed by angiography in middle-aged men. Furtherm ore, pronounced long-term lowering of serum triglycerides by gemfibrozil tr eatment does not significantly affect the plasma PAI-1 activity level but i ncreases the plasma tPA and PAI-1 antigen concentrations.