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Background  Platelet activation is involved in acute coronary syndromes ( ACS ). Incomplete suppression by low‐dose aspirin treatment of thromboxane ( TX ) metabolite excretion (urinary 11‐dehydro‐ TXB  2 ) is predictive of vascular events in high‐risk patients. Myeloid‐related protein ( MRP )‐8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts,  MRP ‐14 has emerged as a powerful predictor of  ACS .    Methods and Results  We enrolled 68 stable ischemic heart disease ( IHD ) and 63  ACS  patients, undergoing coronary angiography, to evaluate whether  MRP ‐8/14 release in the circulation is related to  TX ‐dependent platelet activation in  ACS  and  IHD  patients and to residual  TX  biosynthesis in low‐dose aspirin–treated  ACS  patients. In  ACS  patients, plasma  MRP ‐8/14 and urinary 11‐dehydro‐ TXB  2  levels were linearly correlated ( r =0.651,  P <0.001) but significantly higher than those in  IHD  patients ( P =0.012,  P =0.044) only among subjects not receiving aspirin. In aspirin‐treated  ACS  patients,  MRP ‐8/14 and 11‐dehydro‐ TXB  2  were lower versus those not receiving aspirin ( P <0.001) and still significantly correlated ( r =0.528,  P <0.001). Higher 11‐dehydro‐ TXB  2  significantly predicted higher  MRP ‐8/14 in both all  ACS  patients and  ACS  receiving aspirin ( P <0.001, adj  R  2 =0.463 and adj  R  2 =0.497) after multivariable adjustment. Conversely, plasma  MRP ‐8/14 ( P <0.001) and higher urinary 8‐iso‐prostaglandin F 2α  ( P =0.050) levels were significant predictors of residual, on‐aspirin,  TX  biosynthesis in  ACS  (adjusted  R  2 =0.384).    Conclusions  Circulating  MRP ‐8/14 is associated with  TX ‐dependent platelet activation in  ACS , even during low‐dose aspirin treatment, suggesting a contribution of residual  TX  to  MRP ‐8/14 shedding, which may further amplify platelet activation. Circulating  MRP ‐8/14 may be a target to test different antiplatelet strategies in  ACS .

journal of the american heart association

Circulating  Myeloid‐Related Protein –8/14 is Related to Thromboxane‐Dependent Platelet Activation in Patients With Acute Coronary Syndrome, With and Without Ongoing Low‐Dose Aspirin Treatment