Abstract 12997: Circulating MRP 8/14 is Associated with Thromboxane-Dependent Platelet Activation in NSTEMI Patients: Effect of Aspirin Treatment
Myeloid related protein (MRP)-8/14 is an heterodimer formed and secreted on activation of platelets, monocytes and neutrophils and regulating vascular inflammation by promoting leukocyte recruitment. A transcriptional platelet profiling approach in ACS patients identified MRP-14 as a novel predictor of MI. Plasma levels of MRP-8/14 are elevated in STEMI patients and predict increased risk of first and recurrent CV events. We aimed to evaluate whether: 1) NSTEMI patients also exhibit higher MRP 8/14 levels as compared to stable CAD patients; 2) MRP 8/14 release in the circulation is related to thromboxane (TX)-dependent platelet activation; 3) MRP 8/14 may be associated with residual TX biosynthesis in low-dose aspirin-treated NSTEMI patients. We enrolled stable CAD and NSTEMI (for reperfusion with primary PCI) patients, undergoing coronary angiography. Plasma levels of MRP 8/14 were significantly higher in NSTEMI (n=38) as compared to stable CAD patients (n=58) [median (IQR) 1.43 (0.94-2.51) vs 0.91 (0.51-1.58) μg/mL, P=0.007]. Patients with NSTEMI not on aspirin treatment had significantly higher plasma MRP 8/14 (2.46 (1.06-2.77) vs 1.09 (0.59-1.85) μg/mL, P=0.007] and urinary 11-dehydro-TXB2 [(1180 (878-1654) vs 607 (449-999) pg/mg cr, P=0.006] as compared to CAD patients not on aspirin. A significant direct correlation was observed between MRP 8/14 and urinary 11-dehydro-TXB2 in all NSTEMI patients (n=38, Rho=0.549, P<0.0001). In NSTEMI patients, both urinary 11-dehydro-TXB2 and plasma MRP 8/14 were significantly lower in aspirin-treated subjects (24 out of 38) as compared to those untreated with aspirin at the time of the cross-sectional evaluation. In aspirin-treated NSTEMI patients, residual TX biosynthesis was significantly related with plasma MRP 8/14 (Rho=0.62, P=0.001). At multivariate analysis, elevated plasma MRP 8/14 (β=0.572, P=0.02) remained the only significant predictor of residual TX biosynthesis. In NSTEMI but not in chronic CAD patients, plasma MRP 8/14 levels are increased and associated with TX-dependent platelet activation. Ongoing low-dose aspirin treatment at the time of the acute event is associated with lower plasma MRP 8/14, whose concentration is associated with residual TX biosynthesis in this setting.
- © 2011 by American Heart Association, Inc.