MiR-223 and MiR-186 Are Associated with Long-Term Mortality after Myocardial Infarction

Abstract

Background-The identification and stratification of patients at risk of fatal outcomes after myocardial infarction (MI) is of considerable interest to guide secondary prevention therapies. Currently, no accurate biomarkers are available to identify subjects who are at risk of suffering acute manifestations of coronary heart disease as well as to predict adverse events after MI. Non-coding circulating microRNAs (miRNAs) have been proposed as novel diagnostic and prognostic biomarkers in cardiovascular diseases. The aims of the study were to investigate the clinical value of a panel of circulating miRNAs as accurate biomarkers associated with MI and mortality risk prediction in patients with documented MI. Methods and Results-seven circulating plasma miRNAs were analyzed in 67 MI patients and 80 control subjects at a high cardiovascular risk but without known coronary diseases. Multivariate logistic regression analyses demonstrated that six miRNAs were independently associated with MI occurrence. Among them, miR-223 and miR-186 reliably predicted long-term mortality in MI patients, in particular miR-223 (HR 1.57 per one-unit increase, p = 0.02), after left ventricular ejection fraction (LVEF) adjustment. Kaplan-Meier survival analyses provided a predictive threshold value of miR-223 expression (p = 0.028) for long-term mortality. Conclusions-Circulating miR-223 and miR-186 are promising predictive biomarkers for long-term mortality after MI.

Keywords: biomarker; cardiovascular disease; microRNA; myocardial infarction.

Figure 1

Relative expression of plasma miRNA levels in MI and control populations. The ΔΔCt method was used to quantify the relative miRNA expression of miR-122, miR-150, miR-16, miR-186, miR-195, miR-223 and miR-92a. Ct values were normalized to cel-miR-39-3p and cel-miR-39-5p and the relative expression of the miRNAs was calculated by the 2^−ΔΔCt, ^{−[Ct(miRNA target) − (meanCt(miRNA control))]} method. Data are presented as means with 95% CI (CI; confidence interval). p values were calculated with the Wilcoxon–Mann–Whitney test.

Figure 2

Kaplan–Meier survival estimate according to the median of miR-223 (A) and miR-186 (B). χ², Chi-squared test.