Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction patients.
OBJECTIVE
Nonhyperlipidemic postinfarction patients are at high risk for recurrent coronary events by virtue of incident myocardial infarction (MI); however, few studies assess risk beyond incident MI. The aim of this study was to assess such risk as a function of 37 atherosclerosis-associated genetic polymorphisms and 17 blood marker variables.


RESULTS
Screening of polymorphisms in nonhyperlipidemic postinfarction patients revealed significant risk only for the 4G/5G insertion/deletion polymorphism in the promoter of the plasminogen-activator inhibitor-1 (PAI-1) gene. Outcome event mapping, an exploratory data analysis tool, was then applied to define a subgroup (182 patients from total study population of 846 nondiabetic patients) exhibiting maximal functional dependence of risk on the PAI-1 polymorphism. Cox multivariable regression analyses within the subgroup adjusted for significant clinical covariates and medication use as a function of the PAI-1 polymorphism and 17 atherosclerosis-associated blood markers revealed significant risk for patients homozygous for the 4G allele (hazard ratio 4.30, 95% CI 1.98 to 9.33, P=0.00023), and lack of significant risk-association with any blood marker.


CONCLUSIONS
In a subgroup of normolipidemic postinfarction patients, only the PAI-1 4G/5G polymorphism was associated with recurrent risk from a set of atherosclerosis-associated genetic polymorphisms and blood markers.
Corsetti
James P
JP
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. James_Corsetti@urmc.rochester.edu
Ryan
Dan
D
Moss
Arthur J
AJ
Rainwater
David L
DL
Zareba
Wojciech
W
Sparks
Charles E
CE
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000401:mortality; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics* / Q000401:mortality; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011336:Probability; D016016:Proportional Hazards Models; D012008:Recurrence; D012016:Reference Values; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D005819:Genetic Markers; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1