Background: The microRNAs (miRs) are small non-coding RNA molecules regulating expression of multiple genes, which can be quantified using reverse transcription quantitative PCR methods. Some studies reported their utility in ST elevation myocardial infarction (STEMI) diagnostic process, whereas their diagnostic value in non-ST elevation acute coronary syndrome (NSTE-ACS) remains unclear.
Purpose: We sought to evaluate the expression of 5 free circulating miRs (miR-1, miR-21, miR-133a, miR-208a, miR-499) and their diagnostic value for distinguishing NSTE-ACS from stable coronary artery disease (SCAD).
Material and methods: Our study was daesigned as prospective, single-center observational study. The study group was composed of 72 patients (pts) with NSTE-ACS (mean age 66.1±11.6, 28% female) with symptoms onset <24 hours before the hospital admission and 34 pts with confirmed SCAD (mean age 65.3±10.5, 32% female) as controls. Blood was sampled twice in the NSTE-ACS group (at admission and 4 h after) and once in SCAD. Unstable angina (UA) vs non-STEMI diagnosis was based on the troponin 99th percentile rule, according to the current guidelines. Relative expression of miRs were calculated using the ΔΔCt method after normalization to the cel-miR-39 spiked-in control. The mean value of miRs' relative expression from two time samples in NSTE-ACS pts were used for further analysis.
Results: Free circulating miRs (except mir-21) were significantly elevated in pts with diagnosed NSTEMI: miR-1 levels were increased 6.5-fold (p<0.001), miR-133a 23.6-fold (p<0.001), miR-208a 4.0-fold (p=0.033) and miR-499 8.2-fold as compared to controls with SCAD. Moreover, miR-1 levels were increased 7.5-fold (p<0.001), miR-133a 5.8-fold (p=0.033) and miR-499 7.0-fold (p=0.003) when comparing NSTEMI to UA patients, and additionally two of them were able to discriminate between UA and SCAD patients: miR-133a (p=0.005) and miR-208a (p=0.035). Three of analyzed miRs were able to differentiate any NSTEMI individuals from other patients: miR-1 [area under the curve (AUC) 0.863, 95% CI 0.761–0.933, p<0.001], miR-133a (AUC 0.799, 95% CI 0.687–0.885, p<0.001) and miR-499 (AUC 0.766, 95% CI 0.651–0.858, p<0.001). MiR-1 elevation >12.2 fold yielded a sensitivity of 74.4% and specificity of 90.6%, miR-21 elevation >23.8 fold 74.4% and 84.4%, miR-499 elevation >4.7 fold 64.1% and 93.8% for distinguishing NSTEMI vs others.
Conclusions: The present study describes a unique signature of three circulating miRNAs as a robust biomarker to distinguish not only NSTEMI patients from other individuals (miR-1, miR-208a, miR-133a, miR-499), but also NSTEMI from UA patients (miR-1, miR-133a, miR-499) and UA from SCAD (miR-133a and miR-208a).