Abstract P178: Association of Plasminogen Activator Inhibitor-1 with Prevalence and Progression of Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Background: Elevated circulating levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with myocardial infarction and cardiovascular mortality. Since the fibrinolytic system plays an integral role in the pathogenesis of coronary artery disease, we sought to examine the association of PAI-1 with subclinical atherosclerosis.
Hypothesis: PAI-1 is associated with prevalent CAC and predicts progression of CAC, independent of traditional cardiovascular risk factors and inflammatory markers.
Methods: We studied the cross-sectional association of PAI-1 and CAC, as well as the prospective association with progression of CAC in a random sample from MESA who had PAI-1 measured at baseline and computed tomography at baseline and follow-up. Multivariable ordinal logistic regression was used to estimate associations of PAI-1 levels with baseline categories of CAC defined as 0, 1-99, 100-299, and ≥300 Agatston units. Multivariable logistic regression analyses examined CAC progression (defined using a previously published algorithm as incident CAC, increase of ≥10 Agatston units for baseline CAC 1-99, or increase of ≥10% in CAC score for baseline CAC ≥100). Adjustment covariates included demographics, risk factors, and inflammatory markers.
Results: In 839 participants mean age was 59 years old; 59% and 47% were female and white, respectively. At baseline, the highest (vs. the lowest) tertile of PAI-1 was associated with an odds ratio (OR) for being in a higher CAC category of 1.50 (95% CI: 1.01 - 2.27, p < 0.05) after multivariable adjustment. Over a median follow-up of 8.5 years, the highest tertile of PAI-1 was associated with a multivariable-adjusted OR of 1.67 (95% CI 1.09-2.55, p<0.01) for CAC progression (Table).
Conclusions: Higher levels of PAI-1 in middle-age are associated with prevalent CAC and with progression of CAC, independent of traditional risk factors and inflammatory markers. These data suggest a role for PAI-1 in the pathogenesis of subclinical atherosclerosis independent of inflammation.
Author Disclosures: S. Khan: None. D.E. Vaughan: None. C. Chan: None. K. Liu: None. M. Cushman: None. D. Lloyd-Jones: None.
- © 2015 by American Heart Association, Inc.