Fibrinolytic Proteins and Progression of Coronary Artery Disease in Relation to Gemfibrozil Therapy

Anders Hamsten; Mikko Syvänne; Angela Silveira; Le-Anh Luong; Markku S. Nieminen; Steve Humphries; M. Heikki Frick; Marja-Riitta Taskinen

doi:10.1055/s-0037-1613826

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(03): 397-403
DOI: 10.1055/s-0037-1613826

Review Article

Schattauer GmbH

Fibrinolytic Proteins and Progression of Coronary Artery Disease in Relation to Gemfibrozil Therapy

Anders Hamsten

¹From the King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden

,

Mikko Syvänne

²From the Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

,

Angela Silveira

¹From the King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden

,

Le-Anh Luong

³From the Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London, United Kingdom

,

Markku S. Nieminen

²From the Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

,

Steve Humphries

³From the Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London, United Kingdom

,

M. Heikki Frick

²From the Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

,

Marja-Riitta Taskinen

³From the Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London, United Kingdom

› Author Affiliations

Abstract

Summary

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.

Key words

Atherosclerosis - thrombosis - gemfibrozil - coronary artery disease - angiography - fibrinolysis - lipoproteins

Full Text

References

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