Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Abstract

MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.

Keywords: MACEs; antiplatelet therapy; coronary artery disease; miR-142; plasma miRNAs.

Fig. 1

Flowchart of the technological process. CAD, coronary artery disease; PCI, percutaneous coronary intervention; ARU, aspirin reaction unit; PRU, P2Y12 reaction unit

Fig. 2

Correlations between PRU and plasma miR-126 (a), miR-142 (b), miR-130a (c), miR-27a (d), miR-21 (e), and miR-106a (f) expression levels in 115 CAD patients

Fig. 3

Plasma miR-126 (a), miR-130a (b), miR-142 (c), miR-27a (d), miR-106a (e), and miR-21 (f) levels in individual patients sensitive or resistant to clopidogrel treatment. ****P < 0.0001, ***P < 0.001, *P < 0.05 versus low PRU

Fig. 4

Patients were grouped by sensitivity to aspirin to determine the expression levels of plasma miR-126 (a), miR-130a (b), miR-27a (c), miR-21 (d), miR-106a (e), and miR-142 (f) between patients sensitive and resistant to clopidogrel. *P < 0.05 versus low ARU and low PRU

Fig. 5

Patients were grouped by resistance to aspirin to determine the expression levels of plasma miR-126 (a), miR-142 (b), miR-130a (c), miR-27a (d), miR-21 (e), and miR-106a (f) between patients sensitive and resistant to clopidogrel. ^**P < 0.01, ^*P < 0.05 versus high ARU and low PRU