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

2003 ◽  
Vol 90 (10) ◽  
pp. 717-723 ◽  
Author(s):  
Martin Schillinger ◽  
Markus Exner ◽  
Schila Sabeti ◽  
Christine Mannhalter ◽  
Erich Minar ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Gene Promoter ◽  
Plasminogen Activator Inhibitor ◽  
Cox Proportional Hazards ◽  
Nucleotide Position ◽  
Plasminogen Activator Inhibitor 1 ◽  
Late Restenosis ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen 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 femoropopliteal 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 (≥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.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke

2011 ◽  
Vol 38 (8) ◽  
pp. 5355-5360 ◽  
Author(s):  
Adriano de Paula Sabino ◽  
Daniel Dias Ribeiro ◽  
Caroline Pereira Domingueti ◽  
Mariana Silva dos Santos ◽  
Telma Gadelha ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Young Patients ◽  
Plasminogen Activator Inhibitor ◽  
Promoter Polymorphism ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Abstract 43: Association of Plasminogen Activator Inhibitor-1 with Prevalent and Incident Obesity is Independent of Inflammatory Markers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Donald M Lloyd-Jones ◽  
Cheelin Chan ◽  
Kiang Liu ◽  
Mary Cushman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Inflammatory Markers ◽  
Smoking Status ◽  
Plasminogen Activator Inhibitor ◽  
Cox Proportional Hazards ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ethnic Study ◽  
Activator Inhibitor ◽  
Pai 1

Background: In experimental animal models, deficiency of plasminogen activator inhibitor-1 (PAI-1) protects against development of obesity. In addition, elevated circulating levels of PAI-1 are associated in cross-sectional studies with prevalent obesity in humans. However, no studies have investigated the prospective association between PAI-1 and incident obesity. Methods: Plasma PAI-1 levels were measured in a random sample of men and women at baseline (2000-2002) in the Multi-Ethnic Study of Atherosclerosis. Obesity was defined as body mass index (BMI) > 30kg/m2. Incident obesity was identified at four follow-up exams (2002-2011) among those who were not obese at baseline. Logistic regression was used to examine the odds ratios (OR) and 95% confidence intervals (CI) of prevalent obesity at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) for time to incident obesity. The covariates used for adjustment included baseline demographics (age, race, sex, center), lifestyle risk factors (physical activity, dietary energy intake, smoking status, alcohol consumption, education), and inflammatory markers (CRP and IL-6). Results: In 839 participants mean age was 59 years old; 59% and 47% of the cohort were female and white, respectively. At baseline, each standard deviation (SD) increase in log(PAI-1) level was associated with an odds ratio (OR) for adjusted prevalent obesity of 2.70 (95% CI: 2.21 - 3.30, p<0.001. This association remained significant after further adjustment for IL-6 and CRP with OR 2.39 (95% CI: 1.94-2.94, p<0.001). Over a median follow-up of 8.5 years, 16% of participants developed obesity. The multivariable adjusted hazard ratio for incident obesity was 1.36 (95% CI 1.09-1.69, p<0.001) per 1 SD increase in log(PAI-1). (Table). Conclusions: Elevated PAI-1 levels are associated with prevalent and incident obesity. These findings are consistent with results from murine studies and provide evidence suggesting a potential role of PAI-1 in the pathogenesis of obesity.

W1490: Association Between Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Colorectal Adenomas

2010 ◽  
Vol 71 (5) ◽  
pp. AB341
Author(s):  
Eun Ran Kim ◽  
Moon Hee Yang ◽  
Yeun Jung Lim ◽  
Jin Hee Lee ◽  
Byung-Hoon Min ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Plasminogen Activator Inhibitor ◽  
Colorectal Adenomas ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1

2016 ◽  
Vol 116 (07) ◽  
pp. 162-171 ◽  
Author(s):  
Amirhossein Sahebkar ◽  
Cristiana Catena ◽  
Kausik Ray ◽  
Antonio Vallejo-Vaz ◽  
Željko Reiner ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Plasminogen Activator ◽  
Publication Bias ◽  
Plasma Levels ◽  
Meta Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Lipid Lowering ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryElevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I2 test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and “trim and fill” tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: –15.72 ng/ml, 95 % confidence interval [CI]: –25.01, –6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: –21.32 ng/ml, 95 % CI: –32.73, –9.91, I2=99 %) and particularly atorvastatin (WMD: –20.88 ng/mL, 95 % CI: –28.79, –12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.

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