Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients With Coronary Artery Disease

      Circulating levels of microRNA (miR)-133a are increased in patients with coronary atherosclerotic disease (CAD). Whether the cardiac release of this miR provides any prognostic information in patients with CAD is currently unknown. We aimed to investigate if changes in concentration of miR-133a trough the coronary circulation may be associated with patients' cardiovascular outcome. We enrolled 111 patients (82 with stable CAD and 29 with acute coronary syndromes [ACS]) who underwent coronary angiography. Circulating levels of miR-133a were measured across the transcoronary circulation. Major adverse cardiac events (MACE: death, nonfatal myocardial infarction, and need for revascularization) were recorded through a median follow-up of 32 months. An increased transcoronary concentration gradient of miR133a showed a significant association with overall rate of MACE at follow-up in patients with both stable CAD and ACS (p = 0.011 and p = 0.002, respectively). At the single end point-analysis, increased transcoronary concentration gradients of miR133a were significantly associated with increased rate of death in patients with ACS (p = 0.017) and with increased incidence of new revascularization because of in-stent restenosis in patients with stable CAD (p = 0.026). Kaplan-Meier curves showed a significantly worse event-free survival in patients with greater transcoronary gradients of miR133a (p = 0.026 in stable CAD group and p = 0.007 for ACS group). Nevertheless, these findings lost their significance after adjustment for common cardiovascular risk factor and high-sensitivity troponin-T. In conclusions, the release of miR133a, as measured by its transcoronary concentration gradient, is associated with a higher incidence of MACE in patients with CAD, but it does not add significant prognostic information compared with traditional prognostic biomarkers, therefore limiting its potential usefulness in the clinical practice. Nevertheless, the differential modulation of miR-133a release in the coronary circulation may reflect pathophysiological mechanism involved in CAD progression and complications and suggest a novel potential role for this miR in the development of in-stent restenosis.
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