Decreased circulating microRNA-223 level predicts high on-treatment platelet reactivity in patients with troponin-negative non-ST elevation acute coronary syndrome

• Published in: Journal of thrombosis and thrombolysis Vol. 38; no. 1; pp. 65 - 72
• Main Authors: Zhang, Ying-Ying, Zhou, Xin, Ji, Wen-Jie, Shi, Rui, Lu, Rui-Yi, Li, Jin-Long, Yang, Guo-Hong, Luo, Tao, Zhang, Jian-Qi, Zhao, Ji-Hong, Jiang, Tie-Min, Li, Yu-Ming
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2014; Springer Nature B.V
• Subjects: Acute Coronary Syndrome - blood; Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - genetics; Aged; Aspirin - administration & dosage; Biomarkers - blood; Blood Platelets - metabolism; Cardiology; Cytochrome P-450 CYP2C19 - blood; Cytochrome P-450 CYP2C19 - genetics; Female; Hematology; Humans; Male; Medicine; Medicine & Public Health; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Platelet Aggregation Inhibitors - administration & dosage; Real-Time Polymerase Chain Reaction; Retrospective Studies; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Troponin - genetics; Troponin - metabolism; Clopidogrel; High on-treatment platelet reactivity; Platelet function test; MicroRNAs; Vasodilator-stimulated phosphoprotein
• ISSN: 0929-5305; 1573-742X; 1573-742X
• DOI: 10.1007/s11239-013-1022-9

To investigate the relationship between circulating microRNA 223 (miR-223) levels and clopidogrel responsiveness in patients with coronary heart disease. A total of 62 consecutive patients with troponin-negative non-ST elevation acute coronary syndrome (NSTE-ACS) scheduled for elective percutaneous coronary intervention were enrolled. The plasma circulating miR-223 levels were quantified by real-time PCR, and platelet reactivity was determined by platelet reactivity index (PRI), measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry after 300 mg (for at least 24 h) or 75 mg clopidogel (for at least 5 days) plus aspirin treatment. All subjects were dichotomized according to PRI median (normal-responders: PRI ≤ 56.3 %, n = 31 and low-responders: PRI > 56.3 %, n = 31). Compared with normal-responders, circulating miR-223 level was significantly decreased in low-responders ( P  = 0.007). In addition, miR-223 level was statistically correlated with PRI (Spearman r  = −0.379, P  = 0.002). Stepwise binary logistic regression analysis revealed that among factors that potentially influence platelet reactivity ( CYP2C19*2 / *3 loss-of-function genotypes, use of calcium channel blockers/proton-pump inhibitors, age, diabetes and smoking), decreased circulating miR-223 level was the only independent predictor for the presence of PRI-determined lower responders (OR 0.111, 95 % CI 0.018–0.692, P  = 0.019). Our data suggest that circulating miR-223 may serve as a novel biomarker for assessment of clopidogrel responsiveness in troponin-negative NSTE-ACS patients.