Use of Circulating MicroRNAs to Diagnose Acute Myocardial Infarction

Abstract

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 (>105-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.