Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain

Abstract

Objectives. To address the diagnostic value of circulating microRNAs (miRNAs) in patients presenting with acute chest pain.Design. In a prospective, international, multicentre study, six miRNAs (miR-133a, miR-208b, miR-223, miR-320a, miR-451 and miR-499) were simultaneously measured in a blinded fashion in 1155 unselected patients presenting with acute chest pain to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. The clinical follow-up period was 2 years.Results. Acute myocardial infarction (AMI) was the adjudicated final diagnosis in 224 patients (19%). Levels of miR-208b, miR-499 and miR-320a were significantly higher in patients with AMI compared to those with other final diagnoses. MiR-208b provided the highest diagnostic accuracy for AMI (area under the receiver operating characteristic curve 0.76, 95% confidence interval 0.72-0.80). This diagnostic value was lower than that of the fourth-generation cardiac troponin T (cTnT; 0.84) or the high-sensitivity cTnT (hs-cTnT; 0.94; both P < 0.001 for comparison). None of the six miRNAs provided added diagnostic value when combined with cTnT or hs-cTnT (ns for the comparison of combinations vs. cTnT or hs-cTnT alone). During follow-up, 102 (9%) patients died. Levels of MiR208b were higher in patients who died within 30 days, but the prognostic accuracy was low to moderate. None of the miRNAs predicted long-term mortality.Conclusion. The miRNAs investigated in this study do not seem to provide incremental diagnostic or prognostic value in patients presenting with suspected AMI.

The role of circulating microRNAs in acute coronary syndromes: ready for prime time?

“…Furthermore, the area under the receiver operating curves were low (AUC: 0.53-0.76) compared to high sensitive troponin (AUC: 0.94). The miR-133a, miR-208b and miR-499 levels were significantly higher in STEMI patients than in NSTEMI patients (16). These findings are in line with the findings of Widera et al on miR-133a and miR-208a (15), although both studies failed to demonstrate an independent prognostic value of all miRs studied.…”

“…The largest study included in this review was performed by Devaux et al (16). It prospectively investigated the use of six different miRs in n=1,155 patients with acute chest pain and suspected acute myocardial infarction.…”

Which future for circulating microRNAs as biomarkers of acute myocardial infarction?

“…In patients with hypertrophic obstructive cardiomyopathy, circulating levels of muscle-enriched miR-1 and miR-133a were significantly increased 15 mins after transcoronary ablation of septal hypertrophy (4), supporting the hypothesis that heart-derived miRNAs may constitute early diagnostic biomarkers of AMI. The excitement around the diagnostic potential of miRNAs for AMI was tempered by large-scale studies in AMI patients and patients with chest pain reporting that circulating miRNAs fail to provide an incremental diagnostic value over traditional markers including cTns (2,5). This disappointing result was nevertheless limited by the fact that patients in these retrospective studies were initially diagnosed with cTns.…”

MicroRNAs as biomarkers for acute myocardial infarction: Small molecules with a huge potential

“…From all studied miRNAs, miRNA-208b provided the highest diagnostic accuracy for AMI (AUC miRNA-208b = 0.76; 95%CI: 0.72-0.80), but was lower than cTnT (AUC cTnT = 0.84) or high sensitivity cardiac troponin T (hs-cTnT) (AUC hs-cTnT = 0.94). Furthermore, miRNA-208b levels were higher in patients who died within 30 days, but its prognostic value for predicting long-term mortality has been lost (37). The explanation of lower accuracy of miRNA-208b lies in the fact that miRNA-208b, contrarily to miRNA-208a, is not cardiac-specific with high expression in skeletal muscle (27,38).…”