Abstract
Previous studies investigating the role of circulating microRNAs in acute coronary syndrome (ACS) were based on small patient numbers, performed no comparison with established markers of cardiac injury and did not have appropriate controls. We determined the potential diagnostic value of circulating microRNAs as novel early biomarkers in 332 suspected ACS patients on presentation to the emergency department (ED) in a prospective single-centre study including cardiac miRNAs (miR-1, -208a and -499), miR-21 and miR-146a. Levels of all miRs studied were significantly increased in 106 patients diagnosed with ACS, even in patients with initially negative high-sensitive (hs) troponin or symptom onset <3 h. MiR-1, miR-499 and miR-21 significantly increased the diagnostic value in all suspected ACS patients when added to hs-troponin T (AUC 0.90). These three miRs were strong predictors of ACS independent of clinical co-variates including patient history and cardiovascular risk factors. Interestingly, the combination of these three miRs resulted in a significantly higher AUC of 0.94 than hs-troponin T (0.89). Circulating microRNAs hold great potential as novel early biomarkers for the management of suspected ACS patients.
Highlights
Acute coronary syndrome (ACS) remains one of the leading causes of morbidity and mortality in the Western world
We selected three miRNAs – miR-1, miR-499 and miR-208 – because of their known high expression in cardiac tissue to determine their diagnostic value in suspected acute coronary syndrome (ACS) patients upon first presentation in the emergency department (ED)
Our results demonstrate that the levels of miR-1 and miR-499 are markedly elevated in patients with ACS compared to non-ACS patients (Fig 1A and C)
Summary
Acute coronary syndrome (ACS) remains one of the leading causes of morbidity and mortality in the Western world. MiRNAs were found to be present in human serum and plasma and altered expression profiles were observed in cancer and other diseases like diabetes (Chen et al, 2008; Mitchell et al, 2008; Zampetaki et al, 2010) This led to the hypothesis that miRNAs might be released upon cardiac injury and that the detection of cell-free miRNAs – including cardiac-related miR-1, miR-499 and miR-208a – could be used for the diagnosis of ACS (Adachi et al, 2010; Ai et al, 2010; Cheng et al, 2010; Corsten et al, 2010; D’Alessandra et al, 2010; Gidlof et al, 2011; Ji et al, 2009; Kuwabara et al, 2011; Olivieri et al, 2012; Wang et al, 2010a,b; Widera et al, 2011). Several studies used samples taken at the time of reperfusion to determine miRNAs, rather than samples taken upon initial presentation to the ED, when diagnostic uncertainty is most evident
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