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Diagnostic Potential of miRNAs and their Correlation with High Sensitivity Troponin-I Levels in ACS- NSTEMI Patients

Charan Reddy KV and Nitin S Gokhale

Background: High-sensitivity cardiac troponins (hs-cTns) are used as biomarkers for Acute Myocardial Infarction (AMI). However, hs-cTn levels are not specific and increase in other diseases that are not associated with AMI. Studies have shown that circulating micro RNAs (miRNAs) vary between different types of Acute Coronary Syndrome (ACS) patients. The main objectives of our study are: 1) To measure circulating miRNA-208a (miR-208a) and miRNA-499 (miR-499) in suspected AMI cases in Acute Coronary Syndrome-Non-ST-segment Elevated Myocardial Infarction (ACS-NSTEMI) patients, 2) To determine the time of release of these miRNAs and compare with hs-cTnI, and 3) To evaluate prognostic significance of miR-208a and miR-499 in early prediction of AMI.

Methods: Serum miRNAs were isolated from suspected AMI patients (n=60) and non-ACSNSTEMI chest pain patients (n=10). These AMI patients were divided into 4 groups, very early (≤ 1 hr), early (≥ 1 hr - ≤ 4 hrs), late (≥ 4 hrs - ≤ 8 hrs) and very late (≥ 8 hrs - ≤ 12 hrs) based on the time gap between onset of chest pain and patient presented to hospital Emergency Department (ED). Chemiluminescence Microparticle Immunoassay (CMIA) and Quantitative Real-Time PCR (qRT-PCR) methods were used to determine the expression levels of hs-cTnI and miRNAs respectively.

Results: Plasma levels of hs-cTnI, miR-208a and miR-499 were higher in suspected AMI patients as compared to non-ACS-NSTEMI chest pain patients. Receiver Operating characteristic Curve (ROC) analysis indicated no association between hs-cTnI and miRNA levels between patients presented to ED very early (≤ 1 hr) or early (≥ 1 - ≤ 4 hrs), after onset of chest pain. A positive correlation between miRNAs and hs-cTnI levels in patients presented to ED late (≥ 4-3 ≤ 8 hrs) and very late (≥ 8 - ≤ 12 hrs) after chest pain was observed. Both miRNAs yielded the highest Area Under Curve (AUC) value of 1.000 (95% CI 1.000-1.000) with sensitivity and specificity of 100% in patients presented to ED very early (≤ 1 hr) or early (≥ 1 - ≤ 4 hrs) after onset of chest pain.

Conclusion: Circulating miR-208a and miR-499 are released into the circulation prior to hs-cTnI and appear to be better biomarker for early identification of suspected AMI cases in ACSNSTEMI patients.