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

Abstract

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.

Adipose Tissue and Atherothrombosis

“…Most of the studies have described a deleterious effect of high plasma PAI-1 levels which may predict restenosis [80][81][82][83][84]. The same effect was obtained in a group of 251 consecutive patients who underwent femoro-popliteal percutaneous transluminal angioplasty [85]. However, in two studies decreased PAI-1 antigen (and not increased) levels exhibited a high predictive power of deleterious events [86,87].…”