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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Circulating miRNAs Related to Long-term Adverse Cardiovascular Events in STEMI Patients: A Nested Case-Control Study
Xinying Yang1, Xiaoyu Du2, Ke Ma1
1Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Insights
Lower levels of specific circulating microRNAs (miRNAs) like miR-26a-5p, miR-21-5p, and miR-191-5p are linked to adverse cardiovascular events in ST-segment-elevation myocardial infarction (STEMI) patients post-PCI.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- Long-term outcomes for ST-segment-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) remain a significant clinical challenge.
- Circulating microRNAs (miRNAs) are increasingly recognized for their role in the pathogenesis of cardiovascular diseases.
- Identifying reliable biomarkers for predicting adverse events after acute myocardial infarction (AMI) is crucial for patient management.
Purpose of the Study:
- To identify circulating microRNAs (miRNAs) that can predict major adverse cardiovascular events (MACE) in patients with STEMI treated with primary PCI.
- To evaluate the prognostic value of specific miRNAs in conjunction with established clinical risk scores.
Main Methods:
- A prospective, nested case-control study involving 932 STEMI patients who underwent primary PCI.
- A three-phase approach was used to screen candidate miRNAs in patients who experienced MACE (cardiac death, heart failure hospitalization, or recurrent AMI) versus a matched control group without MACE over a 2-year follow-up.
- Multivariate conditional logistic regression was employed to assess the association between miRNA levels and MACE.
Main Results:
- Lower levels of miR-26a-5p, miR-21-5p, and miR-191-5p were significantly associated with an increased risk of MACE in STEMI patients (P < 0.001).
- These three miRNAs were inversely correlated with primary composite outcomes (adjusted P < 0.01).
- Combining these miRNAs with B-type natriuretic peptide significantly improved the predictive performance of current guideline-recommended risk scores.
Conclusions:
- Circulating miRNAs, specifically miR-26a-5p, miR-21-5p, and miR-191-5p, serve as promising prognostic biomarkers for cardiovascular events in AMI patients.
- These miRNAs represent potential therapeutic targets for mitigating adverse outcomes following acute myocardial infarction.
- The findings support the clinical utility of miRNAs in refining risk stratification beyond current standards.
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.

