BACKGROUND

Patients with unprotected left main coronary artery disease (uLMCAD) have high mortality rate due to sudden heart failure and acute myocardial infarction, for which reliable diagnostic biomarkers to detect this disease at an early stage are in urgent need. Circulating microRNAs (miRNAs) have emerged as a class of novel biomarkers for cardiovascular diseases. The purpose of this study was to investigate utility of miRNAs as biomarkers for early detection of uLMCAD.

METHODS

High-throughput sequencing (NGS) was initially employed to compare circulating miRNA expression profiles in uLMCAD patients to that in patients without coronary artery disease (CAD) to identify candidate miRNA biomarkers. We further validated the expression of candidate miRNAs by quantitative polymerase chain reaction (qPCR) in a larger cohort. Receiver operating characteristic (ROC) analysis with multivariate logistic regression was used to evaluate the diagnostic power of candidate miRNAs individually and combined.

RESULTS

MiR-182-5p, miR-199a-5p and miR-5187-5p were found significantly differentially expressed through NGS (fold changes =1.35, 1.65, 0.5, P values =0.018, 0.046, 0.030, respectively, n=5 for both uLMCAD group and non-CAD control group). In a larger cohort (n=27 for uLMCAD patient and n=38 for non-CAD controls), qPCR confirmed that expression of miR-182-5p was up-regulated (2.57-fold, P=0.011) and expression of miR-5187-5p was down-regulated (0.47-fold, P=0.018) in the plasma of uLMCAD patients. ROC analysis with multivariate logistic regression show that miR-182 and miR-5187 have an AUC score of 0.97 and 0.94 respectively, indicating high diagnostic power as biomarkers for uLMCAD. Interestingly, correlation analysis suggests that the expression of two miRNAs were independent to each other.

CONCLUSIONS

These results suggested that circulating miR-182-5p and miR-5187-5p were suitable diagnostic biomarkers for uLMCAD, both potentially providing diagnostic information for discriminating uLMCAD patients from non-CAD population prior to invasive diagnostic coronary angiography (CAG).