Plasminogen activator inhibitor-1 and outcome after femoropopliteal angioplasty: analysis of genotype and plasma levels.
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.
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003251:Constriction, Pathologic / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000235:genetics / Q000628:therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011150:Popliteal Artery; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013927:Thrombosis / Q000235:genetics; D017211:Treatment Failure; D016896:Treatment Outcome; D014654:Vascular Patency / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1