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MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction.

ABSTRACT: Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3-DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3-DNA and Killip-Kimball score. In addition, patients with citH3-DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3-DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3-DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases.

SUBMITTER: de Los Reyes-Garcia AM

PROVIDER: S-EPMC9318357 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Acute ST elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality worldwide despite continuous advances in diagnostic, prognostic and therapeutic methods. Myocardial work (MW) indices and miRNAs have both emerged as potential prognostic markers in acute coronary syndromes in recent years. In this study we aim to assess the prognostic role of myocardial work indices and of a group of miRNAs in young patients with STEMI. We enrolled 50 young patients (<55 years) with STEMI who underwent primary PCI and 10 healthy age-matched controls. We performed standard 2D and 3D echocardiography; we also calculated left ventricular global longitudinal strain (GLS) and the derived myocardial work indices. Using RT-PCR we determined the plasmatic levels of six miRNAs: miR-223-3p, miR-142-3p, miR-146a-5p, miR-125a-5p, miR-486-5p and miR-155-5p. We assessed the occurrence of major adverse cardiac events (MACE) at up to one year after STEMI. Out of 50 patients, 18% experienced MACE at the one-year follow-up. In a Cox univariate logistic regression analysis, myocardial work indices were all significantly associated with MACE. The ROC analysis showed that GWI, GCW and GWE as a group have a better predictive value for MACE than each separately (AUC 0.951, p = 0.000). Patients with higher miRNAs values at baseline (miR-223-3p, miR-142-3p and miR-146a-5p) appear to have a higher probability of developing adverse events at 12 months of follow-up. ROC curves outlined for each variable confirmed their good predictive value (AUC = 0.832, p = 0.002 for miR-223-3p; AUC = 0.732, p = 0.031 for miR-142-3p and AUC = 0.848, p = 0.001 for miR-146a-5p); the group of three miRNAs also proved to have a better predictive value for MACE together than separately (AUC = 0.862). Moreover, adding each of the miRNAs (miR-233, miR-142-3p and miR-146a-5p) or all together over the myocardial work indices in the regression models improved their prognostic value. In conclusion, both myocardial work indices (GWI, GCW and GWE) and three miRNAs (miR-223-3p, miR-142-3p and miR-146a-5p) have the potential to be used as prognostic markers for adverse events after acute myocardial infarction. The combination of miRNAs and MW indices (measured at baseline) rather than each separately has very good predictive value for MACE in young STEMI patients (C-statistic 0.977).

Project description:Background: Young people hold a stable or increasing percentage of patients with acute myocardial infarction (AMI) in many countries. However, data on clinical characteristics and outcomes of young AMI patients were insufficient. This study aimed to analyze clinical characteristics, prognosis, and gender disparities in patients aged ≤45 years with AMI. Methods: A total of 24,125 patients from China Acute Myocardial Infarction registry were included in this study. Clinical characteristics, managements, and in-hospital and 2-year outcomes were compared between patients aged ≤45 years and those aged >45 years. Predictors of all-cause death were obtained using multivariate regression models. Gender disparities of AMI were analyzed among young patients. Results: Of 24,125 patients, 2,042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged >45 years, young patients were more often male, current smokers, and more likely to have medical history of hyperlipidemia. Smoking (72.1%) was the major modifiable risk factor in patients aged ≤45 years. Young patients received more evidence-based medications and had significantly lower risk of both in-hospital and 2-year adverse events than older patients. Education level and left ventricular ejection fraction were independent predictors of 2-year mortality in young patients. Moreover, symptom onset to admission time of young women was significantly longer than that of young men. Young women were less likely to receive percutaneous coronary intervention and suffered higher risk of in-hospital adverse events than young men (adjusted odds ratio for death: 5.767, 95% confidence interval 1.580-21.049, p = 0.0080; adjusted odds ratio for the composite of death, re-infarction, and stroke: 3.981, 95% confidence interval 1.150-13.784, p = 0.0292). Young women who survived at discharge had a higher 2-year cumulative incidence of death (3.8 vs 1.4%, p log-rank = 0.0412). Conclusions: Patients aged ≤45 years constituted a non-negligible proportion of AMI patients, with higher prevalence of smoking and hyperlipidemia but better care and prognosis compared with older patients. There were significant gender disparities of managements and outcomes in young patients. More efforts to improve quality of care in young women are needed.

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MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction.

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