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 participating in the Lopid Coronary Angiography Trial (LOCAT). A higher tPA antigen concentration, whether baseline or on-trial, was associated with a more severe global angiographic response (p < 0.05), an association mainly accounted for by progression of diffuse lesions in graft-affected 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 outcome measurements. tPA and PAI-1 antigen increased significantly in the gemfibrozil group (+11.3% and + 16.4%, respectively, p < 0.001), whereas there was no treatment effect on PAI-1 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. Furthermore, pronounced long-term lowering of serum triglycerides by gemfibrozil treatment does not significantly affect the plasma PAI-1 activity level but increases the plasma tPA and PAI-1 antigen concentrations.
Hamsten
A
A
King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden. hamsten@instmed.ks.se
Syvänne
M
M
Silveira
A
A
Luong
L A
LA
Nieminen
M S
MS
Humphries
S
S
Frick
M H
MH
Taskinen
M R
MR
D000368:Aged; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D005342:Fibrinolysis / Q000187:drug effects*; D015248:Gemfibrozil / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D010959:Tissue Plasminogen Activator / Q000097:blood
D000960:Hypolipidemic Agents; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D015248:Gemfibrozil