Abstract 11775: Change in Circulating Mir-652 Predicts Mortality in Patients with Acute Coronary Syndromes
Background: MicroRNAs, small RNAs that regulate gene expression, are stable in plasma and may have clinical utility as diagnostic or prognostic markers in disease. We previously identified elevated levels of miR-323-3p, miR-652 and miR-27b in plasma from patients incurring recent acute coronary syndrome (ACS, ∼1 month after admission) compared with controls. Aim and
Methods: This study investigated whether levels of these microRNAs remained elevated in the same patients (unstable angina, n=100; ST-elevation or non-ST-elevation myocardial infarction, n=100) at follow-up clinics ∼4 months and ∼12 months after admission compared with controls (n=100), and examined associations with neurohormones, echocardiography markers and survival over 5 years follow-up.
Results: At ∼4 months follow-up, miR-323-3p and miR-652 levels remained elevated in patients compared with controls (323-3p: 57-fold, p<0.001; 652: 2-fold, p<0.01) and miR-27b had returned to control levels. There was little or no difference in levels between the first and second follow-up clinics for any of the microRNAs. The change in miR-652 from baseline to first follow-up was significantly associated with mortality: patients who maintained elevated levels at first follow-up survived better than patients in whom levels decreased from post-ACS baseline (p=0.018). The change in miR-652, in combination with the established prognostic marker, NT-proBNP, improved stratification of high-risk individuals. Survival was higher in patients in whom NT-proBNP decreased from baseline to first follow-up and miR-652 increased from baseline to first follow-up (n=47, 6% died), compared with all other groups (p≤0.001, NT-proBNP and miR-652 both decreased, n=63, 37% died; or NT-proBNP increased and miR-652 decreased, n=39, 33% died; or NT-proBNP and miR-652 both increased, n=25, 40% died). Neither levels of miR-27b and miR-323-3p, nor changes in these microRNAs over time, were strongly correlated with survival, neurohormones or echocardiography measurements.
Conclusions: These data suggest that dynamic changes in miR-652 level are prognostic and that inhibition of miR-652 gene targets forms part of the compensatory response to cardiac dysfunction that promotes survival in ACS patients.
- © 2012 by American Heart Association, Inc.