Abstract 16789: Plasminogen Activator Inhibitor-1 is Predictive of Endothelial Dysfunction Measured as Digital Reactive Hyperemia

Abstract

Background: Local hemostasis is regulated by the endothelium, and plasminogen activator inhibitor-1 (PAI-1) acts as the main inhibitor of the fibrinolytic system. Production of PAI-1 is upregulated in chronic inflammatory states such as cardiovascular disease (CVD), and may reflect endothelial dysfunction. Digital reactive hyperemia (RHI) is a convenient test of microvascular and endothelial function. Lower RHI is associated with worse long term outcome. Whether levels of PAI-1 reflect microvascular function measured by RHI has not been studied. Methods: We measured CVD risk factors in 682 participants (mean age 51±9 years, 57% female) enrolled in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study. Levels of PAI-1 were examined as continuous, log-transformed values. Digital pulse wave amplitude during reactive hyperemia was assessed using the Endo-PAT 2000 device (Itamar Medical, Israel). Briefly, a reactive hyperemia index (RHI) was calculated as the ratio of baseline to post-hyperemic pulse wave after 5 minutes of forearm cuff inflation. RHI was used as both a continuous and dichotomous variable. Results: Median levels of PAI-1 were 13.3 (IQR 7.2, 26.3) ng/mL. Levels of PAI-1 correlated inversely with the RHI (r=-0.112, p=0.005). Participants with PAI-1 levels in the highest tertile had lower RHI compared to those in the lowest tertile (2.1±0.6 vs. 2.3±0.7, p=0.004). Furthermore, levels of PAI-1 in the highest tertile increased the odds of a RHI <1.35, a value indicative of coronary endothelial dysfunction, by 3.7 (95% CI 1.2, 11.3). After adjustment for age, gender, race, smoking, hypertension, diabetes, waist circumference, mean arterial pressure, glucose, and lipid profile, PAI-1 remained a significant predictor of lower RHI (p=0.02). Conclusion: PAI-1 predicts lower RHI, indicating reduced digital microvascular reactivity that may be due to endothelial dysfunction. Since impaired RHI has been associated with worse long-term outcomes, this may be a useful tool for monitoring risk and following response to therapeutic PAI-1 antagonists