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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:548.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Plasminogen Activator Inhibitor-1 Polymorphism (4G/5G) Predicts Recurrence in Nonhyperlipidemic Postinfarction Patients

James P. Corsetti; Dan Ryan; Arthur J. Moss; David L. Rainwater; Wojciech Zareba; Charles E. Sparks

From the Department of Pathology and Laboratory Medicine (J.P.C., D.R., C.E.S.), the Department of Medicine - Cardiology Unit (A.J.M., W.Z.), University of Rochester School of Medicine and Dentistry, Rochester, NY; and the Department of Genetics (D.L.R.), Southwest Foundation for Biomedical Research, San Antonio, Tex.

Correspondence to James P. Corsetti, MD, PhD, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Box 626, 601 Elmwood Avenue, Rochester, NY 14642. E-mail James_Corsetti{at}urmc.rochester.edu

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.

Methods and 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.

To provide information generally not available regarding recurrent risk beyond incident myocardial infarction in nonhyperlipidemic postinfarction patients, 37 genetic markers and 17 blood markers associated with CVD were assessed for risk using multivariable modeling. Only the 4G/5G polymorphism in the PAI-1 promoter region was associated with risk.

Key Words: plasminogen activator inhibitor-1 (PAI-1), 4G/5G polymorphism • postinfarction • risk factors • multivariable analysis