Use of circulating microRNAs to diagnose acute myocardial infarction.

ABSTRACT

BACKGROUND: Rapid and correct diagnosis of acute myocardial infarction (MI) has an important impact on patient treatment and prognosis. We compared the diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) and cardiac enriched microRNAs (miRNAs) in patients with MI. METHODS: Circulating concentrations of cardiac-enriched miR-208b and miR-499 were measured by quantitative PCR in a case-control study of 510 MI patients referred for primary mechanical reperfusion and 87 healthy controls. RESULTS: miRNA-208b and miR-499 were highly increased in MI patients (>10(5)-fold, P < 0.001) and nearly undetectable in healthy controls. Patients with ST-elevation MI (n= 397) had higher miRNA concentrations than patients with non-ST-elevation MI (n = 113) (P < 0.001). Both miRNAs correlated with peak concentrations of creatine kinase and cTnT (P < 10(-9)). miRNAs and hs-cTnT were already detectable in the plasma 1 h after onset of chest pain. In patients who presented <3 h after onset of pain, miR-499 was positive in 93% of patients and hs-cTnT in 88% of patients (P= 0.78). Overall, miR-499 and hs-cTnT provided comparable diagnostic value with areas under the ROC curves of 0.97. The reclassification index of miR-499 to a clinical model including several risk factors and hs-cTnT was not significant (P = 0.15). CONCLUSION: Circulating miRNAs are powerful markers of acute MI. Their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain.