Serum microRNAs are key predictors of long‐term heart failure and cardiovascular death after myocardial infarction

Abstract

Background Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. Methods and results We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST‐segment elevation MI & median age of 55 years) with long‐term follow‐up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow‐up of 2.1 years miR‐21‐5p, miR‐23a‐3p, miR27b‐3p, miR‐122‐5p, miR210‐3p, and miR‐221‐3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR‐210‐3p [hazard ratio (HR) 2.65 per 1 SD increase, P < 0.001], miR‐23a‐3p (HR 2.11 per 1 SD increase, P < 0.001), and miR‐221‐3p (HR 2.03 per 1 SD increase, P < 0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long‐term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC‐statistic = 0.10 [95% confidence interval (CI), 0.03–0.17], continuous net reclassification index = 34.8% (95%CI, 5.8–57.4%), and integrated discrimination improvement (P < 0.001). Conclusions This is the largest study evaluating the prognostic value of circulating miRNAs for HF‐related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long‐term NYHA status and improve current risk prediction methods.

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

“…Our findings pair well with previous evidence reported in other CV disorders. For instance, low to very low circulating miRNA 30a-5p levels predict sudden cardiac or arrhythmic death in patients with coronary heart disease [ 14 ]; an aberrant miRNA 23a-3p expression reflects the severity of ST-elevated myocardial infarction [ 17 ], predicts heart failure onset [ 39 ], and may help risk stratification for CV mortality and worsening New York Heart Association status in the long-term [ 40 ]. Finally, early deranged miRNA 451a levels anticipate acute coronary plaque rupture after percutaneous coronary intervention [ 26 ] and has prognostic value on the risk of transient or acute stroke in critically ill patients [ 41 ].…”

From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction

“…However, low levels of miRNA-16, miRNA-27a and miRNA-150 appear to predict ventricular remodeling, whereas elevated levels of miRNA-208b, miRNA-34a, miRNA-21 and miRNA-155 correlate negatively with the same myocardial infarction consequences [ 237 , 238 , 239 , 240 ]. A recent study conducted by Rincón et al showed that the main outcome studied could be accurately predicted by miR-21-5p, miR-23a-3p, miR27b-3p, miR-122-5p, miR210-3p and miR-221-3p after a mean follow-up of 2.1 years in 311 consecutive patients hospitalized with MI [ 241 ]. Circulating microRNAs have thus displayed promising results as post-infarction prognostic biomarkers, and further research is needed to develop a risk assessment algorithm based on their levels in blood.…”

MicroRNAs: diagnostic, prognostic and therapeutic role in heart failure—a review

“…26 More recently, Rincón et al demonstrated the strong prognostic value of several miRNAs (miR-210-3p, miR-221-3p, and miR-23a-3p) in predicting long-term hospitalizations for HF and cardiovascular mortality among patients with MI. 27 Circulating miRNAs have also been proposed as useful biomarkers for the diagnosis of atrial fibrillation (AF) that is the most common form of arrhythmia among patients with cardiovascular diseases. The first data regarding the association between miRNAs and AF in the general population come from the Framingham Heart Study.…”

“…More recently, Rincón et al . demonstrated the strong prognostic value of several miRNAs (miR‐210‐3p, miR‐221‐3p, and miR‐23a‐3p) in predicting long‐term hospitalizations for HF and cardiovascular mortality among patients with MI 27 …”