Plasma levels of miR-143 and miR-145 are associated with coronary in-stent restenosis within 1 year of follow-up after drug-eluting stent implantation

Background: ISR remains the major adverse outcome after percutaneous coronary intervention (PCI). MicroRNAs have been demonstrated to be associated with coronary plaque and stable in the blood and can be used as biomarkers/predictors. This study aimed to investigate whether circulating microRNAs could predict in-stent restenosis (ISR). Methods: MicroRNA array was used to detect differently expressed microRNAs between 30 ISR patients and 30 non-ISR patients in the derivation cohort. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the microRNA array results and to detect levels of target microRNAs in the validation cohort. All patients were followed up for at least 1 year, and major adverse cardiac events (MACEs) were recorded. Univariate and multivariate logistic regression analysis were applied to find factors associated with ISR. Receiver operating characteristics (ROC) and Kaplan-Meier survival curves were used to analyze the predictive ability of the microRNA score for ISR. Results: MicroRNA array and qRT-PCR showed that miR-143, 145, 425, 208, and let-7g were differently expressed between ISR patients and non-ISR patients. Multivariate analysis demonstrated that lower levels of mir-143 (OR =2.36, 95% CI: 1.43-3.67) and mir-145 (OR =2.12, 95% CI: 1.56-3.48) were associated with ISR. MicroRNA scores differed statistically between ISR patients and non-ISR patients (49.18 +/- 2.05 vs. 52.10 +/- 2.41, P<0.01) and has predictive ability for ISR with an area under the curve (AUC) of 0.8206 (95% CI: 0.7155-0.9256, P<0.01). In the validation cohort, Kaplan-Meier survival curves demonstrated that patients with higher microRNA scores have better prognosis in 1 year of follow-up. Conclusions: A lower plasma level of mir-143/145 predicts a higher risk of ISR and a worse outcome.