Abstract 9379: Higher Levels of Plasminogen-Activator Inhibitor 1 Are Associated with Progression of Coronary Artery Calcification in Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study

Abstract

Introduction: Relationships of inflammatory and hemostatic biomarkers with progression of coronary artery calcification (CAC) in asymptomatic women are unknown. Hypothesis: We assessed the hypothesis that C-reactive protein (CRP), fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), and tissue plasminogen activator antigen (tPA-ag) were associated with CAC progression in women free of known coronary heart disease (CHD) and stroke. Methods: CRP, fibrinogen, PAI-1, and tPA-ag were measured in SWAN Heart participants from the Pittsburgh and Chicago sites at baseline. CAC was obtained by CT scans and quantified by the Agatston score at baseline and after 2.3±0.5 years of follow-up. Significant CAC progression was defined as present if 1) CAC score was >0 at follow-up in subjects with CAC score = 0 at baseline, 2) annualized change in CAC score was ≥10 in subjects with 0<CAC score<100 at baseline, and 3) annualized percent change in CAC score was ≥10% in subjects with CAC score ≥100 at baseline. Univariable and multivariable logistic regression were used for statistical analyses. The novel biomarkers were log-transformed. Baseline CAC was transformed as log(CAC+1). Results: The study included 252 women (32.5% black, 67.5% white; 56.4% pre- and early perimenopausal, 30.6% late peri- and postmenopausal, and 13.1% hormone therapy users) with a mean age of 51.2±2.6 years at baseline. In unadjusted analyses, log(PAI-1) and log(tPA-ag) were positively and significantly associated with CAC progression (p<0.05), but log(CRP) and log(fibrinogen) were not. Adjusted analyses included the following covariates: baseline CAC, age, site, race, menopausal status, income, education, systolic blood pressure, body mass index, Homeostasis Model Assessment insulin resistance index, family history of cardiovascular (CV) disease, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, CV medication use, and current smoking. Only log(PAI-1) was significantly associated with CAC progression (OR: 1.91; 95% CI: 1.24-2.93; p=0.003). Conclusions: In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CHD risk factors.