MiRNAs as Biomarkers of Myocardial Infarction: A Meta-Analysis

Abstract

BackgroundRecent studies have demonstrated that acute myocardial infarction induces a distinctive miRNA signature, suggesting that miRNAs may serve as diagnostic markers. Although many studies have investigated the use of miRNAs in the detection of cardiac injury, some had small sample sizes (<100 patients) or reported different results for the same miRNA. Here, the role of circulating miRNAs for use as biomarkers of myocardial infarction is summarized and analyzed.Methods and ResultsMedline, SCI, Embase, and Cochrane databases were searched up to January 2013 for studies that evaluated associations between miRNAs and myocardial infarction. Relevant publications were identified by searching for combinations of “myocardial infarction,” “miRNAs,” and their synonyms. Methodological quality was scored using a standardized list of criteria, and diagnostic performance was assessed using estimates of test sensitivity and specificity. These values were summarized using summary receiver-operating characteristic curves. Nineteen studies met the inclusion criteria: 15 studies reported sensitivity, specificity, and AUC, but 4 studies did not. Total miRNAs: sensitivity: 0.78 (95%CI: 0.77–0.80; P = 0.0000); specificity: 0.82 (95%CI: 0.80–0.83; P = 0.0000). miR-499: sensitivity: 0.88 (95%CI:0.86–0.90; P = 0.0000); specificity: 0.87 (95%CI:0.84–0.90; P = 0.0000). miR-1: sensitivity: 0.63 (95%CI:0.59–0.66; P = 0.0000); specificity: 0.76 (95%CI:0.71–0.80; P = 0.0000). miR-133a: sensitivity: 0.89 (95%CI:0.83–0.94; P = 0.0047); specificity: 0.87 (95%CI:0.79–0.92; P = 0.0262). miR-208b: sensitivity: 0.78 (95%CI:0.76–0.81; P = 0.0581); specificity: 0.88 (95%CI:0.84–0.91; P = 0.0000). The correlation between miRNAs and other diagnostic biomarkers of myocardial infarction was obvious.ConclusionMiRNAs, especially miR-499 and miR-133a, may be suitable for use as diagnostic biomarkers of myocardial infarction.

microRNAs in cardiovascular disease – clinical application

“…On the basis of these findings, a meta-analysis including 15 studies of diagnostic miRNA quantification for MI discovered an overall sensitivity of 0.78, specificity of 0.82, and an AUC for overall miRNA analysis regarding discrimination of MI [85], comparable with cTNT. At the same time, a high correlation between miRNAs and cTnT, high sensitive (hs-) cTnT as well as CK and CK-MB was identified [85]. Finally, miR-1, miR-499, and miR-21 were identified to significantly increase the diagnostic value in combination with hs-TnT in ACS patients [24], and the combinatory utilization of these three miRNAs improved the AUC to significantly higher values (0.94) than hs-TnT alone (0.89) [24].…”

“…Even more important is the observation that the accuracy to differentiate NSTEMI from acute heart failure (AHF) was higher for miR-499-5p compared with cT [23]. On the basis of these findings, a meta-analysis including 15 studies of diagnostic miRNA quantification for MI discovered an overall sensitivity of 0.78, specificity of 0.82, and an AUC for overall miRNA analysis regarding discrimination of MI [85], comparable with cTNT. At the same time, a high correlation between miRNAs and cTnT, high sensitive (hs-) cTnT as well as CK and CK-MB was identified [85].…”

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

“…In summary, they have also shown that miRNA-208b had the quite high sensitivity (78%; 95%CI: 76-81%) and the highest specificity (88%; 95%CI: 84-91%) from all cardiac miRNAs included into the study. The authors found strong correlations between studied miRNAs and other classic biomarkers of AMI such as cTnT, hs-cTnT, CK and CK-MB (40).…”

“…In their previously mentioned meta-analysis Cheng et al indicated that from all studied miRNAs (miRNA-1, miRNA-133a, miRNA-208a, miR-NA-499) -miRNA-499 is most significantly associated with myocardial infarction, and has the highest sensitivity (88%; 95%CI: 86-90%) and specificity (87%; 95%CI: 84-90%) for AMI diagnosis (40).…”

Feedback Mechanisms for Cardiac-Specific MicroRNAs and cAMP Signaling in Electrical Remodeling

“…12,15,16 In the acute phase of MI, levels of miR-1 and miR-133a increase and can be detected in the circulation. 17 However, these miRs quickly decline, 18,19 and lead to chronically depressed levels. 20 Myocardia from patients with ischemic heart failure exhibited decreased levels of miR-1 and miR-133a which were restored after implantation of a left ventricular assist device (LVAD).…”