Circulating miRNAs Related to Long-term Adverse Cardiovascular Events in STEMI Patients: A Nested Case-Control Study

Background: Long-term morbidity and mortality of patients with ST-segment-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI) remain substantial. Circulating microRNAs (miRNAs) play an important role in cardiovascular disease development. We aimed to identify circulating miRNAs associated with adverse cardiovascular events after acute myocardial infarction (AMI). Methods: We performed a prospective, nested, case-control study of 932 patients with STEMI who underwent primary PCI. A 3-phase approach was conducted to screen candidate circulating miRNAs in 70 patients who subsequently experienced cardiac death, hospitalization for heart failure, or recurrent AMI (major adverse cardiovascular events [MACE] group) and in 140 patients matched for age, sex, time from symptom onset to blood collection and dual-antiplatelet therapy who did not report adverse cardiovascular events during 2-year follow-up (non-MACE group). Results: We found that miR-26a-5p, miR-21-5p, and miR-191-5p levels were lower in the MACE group than in the non-MACE group (all P < 0.001). Multivariate conditional logistic regression analysis revealed that miR-26a-5p, miR-21-5p, and miR-191-5p levels were significantly inversely associated with incident primary composite outcomes (all adjusted P < 0.01). Importantly, the combination of these 3 miRNAs plus B-type natriuretic peptide clearly improved the risk scores recommended in the current guidelines, as determined with the use of C-statistics, net reclassification, and integrated discrimination. Conclusions: Our study provides proof-of-concept in humans that circulating miRNAs are associated with increased rates of distinct cardiovascular events, suggesting that they can serve as effective prognostic biomarkers and therapeutic targets for patients with AMI.