Plasminogen activator inhibitor-1 and outcome after femoropopliteal angioplasty: analysis of genotype and plasma levels

• Published in: Thrombosis and haemostasis Vol. 90; no. 4; p. 717
• Main Authors: Mlekusch, Wolfgang, Schillinger, Martin, Exner, Markus, Sabeti, Schila, Mannhalter, Christine, Minar, Erich, Wagner, Oswald
• Format: Journal Article
• Language: English
• Published: Germany 01-10-2003
• Subjects: Aged; Angioplasty, Balloon, Coronary; Constriction, Pathologic - genetics; Female; Genotype; Humans; Male; Middle Aged; Peripheral Vascular Diseases - genetics; Peripheral Vascular Diseases - therapy; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Single Nucleotide; Popliteal Artery; Promoter Regions, Genetic - genetics; Proportional Hazards Models; Prospective Studies; Thrombosis - genetics; Treatment Failure; Treatment Outcome; Vascular Patency - genetics
• ISSN: 0340-6245
• DOI: 10.1160/th03-03-0159

Plasminogen activator inhibitor-1 (PAI-1) is suggested to be involved in the pathophysiology of early thrombosis and late restenosis after percutaneous transluminal angioplasty (PTA). The role of the PAI-1 promoter genotype in this context is indeterminate. We investigated the association of the (4G/5G) polymorphism at nucleotide position (-675) in the PAI-1 gene promoter, PAI-1 plasma levels, and postangioplasty outcome after femoropopliteal PTA. We studied 251 consecutive patients who underwent femoro-popliteal PTA. In a subgroup of 86 patients PAI-1 plasma levels at baseline, 8, 24 and 48 hours postintervention were measured and correlated to the genotype. Patients were followed for early thrombosis and the late restenosis (> or =50%) within 12 months. Multivariate Cox proportional hazards analysis was performed to assess the association between the PAI-1 genotype and PTA failure. Results show that the PAI-1 genotype was neither associated with PAI-1 plasma levels (p=0.40) nor the change of PAI-1 from baseline to 8 (p=0.39), 24 (p=0.86) and 48 hours (p=0.89). Three out of 35 homozygous (4G/4G) patients (9%) had early thrombotic reocclusions, compared to two out of 153 heterozygous (4G/5G) patients (1%) and none of the 63 homozygous (5G/5G) patients (p=0.007). Restenosis after median 5 months (interquartile range 3 to 9) was found in 117 patients (42%), without significant association between the PAI-1 genotype and late postangioplasty failure (Log Rank p=0.95). We can conclude that carriers of the 4G allele exhibited a higher frequency of early thrombotic reocclusions after percutaneous angioplasty. However, the PAI-1 gene promoter polymorphism (4G/5G) was not associated with PAI-1 plasma levels or late postangioplasty restenosis.