Esporta Transcoronary Concentration Gradients Of Mir133a and Clinical Outcome in Patients With CAD

Introduction: Circulating microRNAs (miR) have been proposed as useful biomarkers. miR133a is a muscle-specific miR, previously shown to be released from the heart. In order to establish a potential prognostic role for the cardiac release of miR133a, we measured transcoronary concentration gradients of miR133a. Methods: In 111 patients (29 with ACS, 82 with stable CAD) undergoing coronary angiography, circulating levels of miR-133a were measured by TaqMan PCR in EDTA-plasma simultaneously obtained from the aortic bulb (Ao) and the coronary venous sinus (CVS). Transcoronary concentration gradients were calculated by subtracting plasma miRs levels in Ao from miRs levels in CVS. Major adverse cardiac events (MACE: death, non-fatal-myocardial infarction, revascularization) were recorded during 30±18 months (mean ± SD) of follow-up. Results: The release of miR133a into the coronary circulation was significantly associated with the overall MACE rate in both stable CAD and ACS patients (p=0.011 and p=0.002, respectively). Single end-point-analysis revealed that cardiac release of miR133a was significantly associated with increased rate of death in patients with ACS (p=0.017). Kaplan-Meier curves demonstrated a significantly worse event-free survival in patients with higher (> median) transcoronary gradients of miR133a (p=0.026 in stable CAD group, p=0.007 for ACS group, see fig.). However, by multivariate testing including hs-troponin levels, transcoronary concentration gradients of miR133a did not longer independently predict clinical outcome. Conclusions: The cardiac release of miR133a, as measured by its transcoronary concentration gradient, is associated with significantly higher incidence of MACE in patients with CAD. However, when corrected for the release of troponin, miR133a concentrations do no longer predict clinical outcome, indicating that increased miR133a release is secondary to myocardial cell necrosis.