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Published on: November 23, 2017

Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction

James P Corsetti1, Dan Ryan, Arthur J Moss

  • 1Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. James_Corsetti@urmc.rochester.edu

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 22, 2007
PubMed

Insights

In nonhyperlipidemic postinfarction patients, the plasminogen-activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism is linked to recurrent coronary events. This genetic marker, not blood markers, identified high-risk individuals for further study.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Translational Medicine

Background:

  • Nonhyperlipidemic patients post-myocardial infarction (MI) face high recurrent coronary event risk.
  • Existing risk assessments often focus on incident MI, with limited evaluation of other factors.
  • Identifying novel risk predictors beyond traditional markers is crucial for this patient group.

Purpose of the Study:

  • To investigate the association of genetic polymorphisms and blood markers with recurrent coronary events in nonhyperlipidemic post-MI patients.
  • To identify specific genetic variants and biomarkers that predict future cardiovascular events in this population.
  • To assess risk beyond incident MI by examining a comprehensive set of genetic and blood variables.

Main Methods:

  • Screening of 37 atherosclerosis-associated genetic polymorphisms and 17 blood marker variables in nonhyperlipidemic post-MI patients.
  • Application of Outcome Event Mapping to identify a subgroup with maximal dependence of risk on a specific polymorphism.
  • Multivariable Cox regression analyses within the identified subgroup, adjusting for clinical covariates and medications.

Main Results:

  • The 4G/5G insertion/deletion polymorphism in the plasminogen-activator inhibitor-1 (PAI-1) gene promoter was the only significant genetic predictor identified.
  • Outcome Event Mapping identified a subgroup of 182 patients (out of 846) showing maximal risk dependence on the PAI-1 polymorphism.
  • Within this subgroup, homozygosity for the PAI-1 4G allele significantly increased risk (HR 4.30), while no blood markers showed significant association.

Conclusions:

  • The PAI-1 4G/5G polymorphism is a significant predictor of recurrent coronary events in a subgroup of normolipidemic post-MI patients.
  • Genetic risk assessment, specifically the PAI-1 genotype, appears more critical than the studied blood markers in this population.
  • These findings highlight the potential of targeted genetic screening for personalized risk stratification in post-MI patients.
Abstract

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