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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:605-610.)
© 1999 American Heart Association, Inc.

Original Contributions

Low-Density Lipoprotein Particle Size Is Inversely Related to Plasminogen Activator Inhibitor-1 Levels

The Insulin Resistance Atherosclerosis Study

Andreas Festa; Ralph D'Agostino, Jr; Leena Mykkänen; Russell Tracy; Barbara V. Howard; Steven M. Haffner

From the Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, TX (A.F., L.M., S.M.H.); Department of Public Health Sciences, Bowman Gray School of Medicine, Winston Salem, NC (R.D'A.); Department of Pathology, University of Vermont School of Medicine, VT (R.T.); and Medlantic Research Institute, Washington, DC (B.V.H.).

Correspondence to Andreas Festa, MD, Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7873. E-mail festa{at}uthscsa.edu

Abstract—High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=-0.21, P<0.0001), independent of gender and ethnicity. However, the authors found a significant interaction with glucose tolerance status (P=0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT (P=0.023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles.

Key Words: plasminogen activator inhibitor-1 • low-density lipoprotein particle size • glucose tolerance • insulin resistance

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