Abstract 3205: Elevated Plasma Plasminogen Activator Inhibitor Type-1 Activity is an Independent Novel Determinant of Coronary Microvascular Dysfunction in Hypertension: The First Direct Demonstration Using 15O-Water Positron Emission Tomography
Background: Elevated plasma levels of plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of fibrinolysis and a regulator of vasoactivity, predispose to cardiovascular events. Although coronary flow reserve (CFR) is impaired in hypertensive patients, the relationship between CFR and hypofibrinolysis is not elucidated. We, thus, investigated whether elevated PAI-1 activity is associated with blunted CFR in hypertensive patients.
Methods: Untreated and uncomplicated essential hypertensive patients (n=29) and age-matched healthy controls (n=10) were studied. Myocardial blood flow (MBF) was measured at rest and during adenosine triphosphate (ATP) infusion using 15O-water and positron emission tomography (PET). CFR was calculated by dividing ATP-induced hyperemic MBF by resting MBF as a marker of coronary microvascular function. Furthermore, plasma PAI-1 activity was measured to assess its contribution to the severity of coronary microvascular dysfunction.
Results: Blood pressure was significantly higher in hypertensives compared with controls (150±13/100±12 vs.118±11/ 66±8 mmHg). ATP-induced MBF and CFR were attenuated in hypertensives (ATP-MBF: 2.77±0.15 vs. 3.49±0.71 ml/g/min; p<0.02, CFR: 2.95±1.06 vs. 4.25±0.69; p<0.001). In univariate analysis, CFR in hypertensive patients was significantly correlated with HDL (r=0.46, p<0.05), homeostasis model assessment (HOMA-IR, r=−0.39, p<0.05) and PAI-1 activity (r=−0.61, p<0.001). In multivariate analysis including biomarkers related to atherogenecity (age, sex, smoking, BMI, LDL, HDL, triglyceride, HOMA-IR, high-sensitive CRP, IL-6, TNF-α, and PAI-1 activity), elevated PAI-1 activity remained a significant independent determinant of blunted CFR.
Conclusions: Elevated plasma PAI-1 activity is an independent marker for identifying coronary microvascular dysfunction in hypertensive patients as assessed by using PET. PAI-1 levels may be useful to predict the development of atherosclerotic events in high-risk hypertensives with coronary microvascular dysfunction.