Background: The development of heart failure (HF) following an acute myocardial infarction (AMI) remains a significant clinical problem. However the early prediction of left ventricular (LV) remodelling that ultimately leads to HF remains challenging, with current biomarkers only elevated once there is a change in LV function. Plasma microRNAs (miRs) have been recently proposed as functional biomarkers in this context. As fibrotic and inflammatory processes are implicated in pathogenic LV remodelling, and miR-30d and miR-146a are reported to have regulatory functions in these processes, this study aimed to determine if circulating levels of these miRs could be early predictors of HF development at the time of an AMI.
Methods: We conducted a case-control study with 40 AMI patients who developed new HF within 1 year (cases) matched for age, gender, hypertension, and diabetes 2:1 with control AMI patients who did not develop HF. We measured miR-30d and miR-146a using qPCR (2-ΔΔCq method against ‘spiked’ cel-miR-39), and IL-6 and CRP using ELISA from plasma samples taken prior to angiography during the index admission.
Results: We observed a modest correlation between IL-6 and CRP levels (r=0.65, p<0.0001), and between IL-6 and miR-30d (r=0.29, p<0.05), but not between CRP and miR-30d (r=0.2, p=0.2), suggesting miR-30d is only modestly associated with traditional measures of inflammation. Neither CRP nor IL-6 correlated significantly with miR-146a (r=0.07, p=0.6 and r=0.2, p=0.2 respectively). miR-30d levels were significantly elevated in HF cases compared to controls (1.6 AU (0.8-5.7) vs 0.82 AU (0.53-1.4, p<0.05), however miR146a levels were not significantly different between cases and control (1.5 AU (0.7-2.8) vs 0.8 AU (0.5-1.6), p=0.12). Additionally, both inflammatory markers IL-6 and CRP were significantly higher in the HF cases compared to controls (3.3 (1.1-6.5) vs 2.2 (1.4-4.4) pg/ml, p<0.01 and 3.8 (1.8-16.3) vs 1.9 (0.9-5.0) mg/ml, p<0.01 respectively).
Conclusion: Patients who develop new HF post-AMI had significantly higher levels of circulating miR-30d and inflammatory markers IL-6 and CRP at time of index admission compared to controls. Further work evaluating the utility of miR-30d as an early marker of LV remodelling is warranted.