Next generation MicroRNA sequencing to identify coronary artery disease patients at risk of recurrent myocardial infarction

Abstract

Background and aims: Variation in micro-RNA (miRNA) levels in blood has been associated with alterations of physiological functions of the cardiovascular system. Circulating miRNA have the potential to become reliable biomarkers for risk stratification and early detection of cardiovascular events. Recurrent thrombotic events in patients with established coronary artery disease (CAD) demonstrate the need for personalized approaches to secondary prevention, especially in light of recent novel treatment approaches.

Methods: In a single center cohort study, whole blood samples were collected from 437 subjects undergoing cardiac catheterization, who were followed for recurrent cardiovascular events during a mean follow up of 1.5 years. We selected a case cohort (n = 22) with recurrent thrombotic events on standard medical therapy (stent thrombosis (n = 6) or spontaneous myocardial infarction (MI) (n = 16)) and a matched cohort with CAD, but uneventful clinical follow up (n = 26), as well as a control group with cardiovascular risk factors, but without angiographic CAD (n = 24). We performed complete miRNA next generation sequencing of RNA extracted from whole blood samples (including leukocytes and platelets).

Results: A differential pattern of miRNA expression was found among controls, CAD patients with no events, and CAD patients with recurrent events. MiRNA previously associated with MI, CAD, endothelial function, vascular smooth muscle cells, platelets, angiogenesis, heart failure, cardiac hypertrophy, arrhythmia, and stroke were found variably expressed in our case-control cohorts. Seventy miRNA (FDR <0.05) were linked to the risk of recurrent myocardial infarction and future stent thrombosis, as compared to CAD patients with subsequently uneventful follow up.

Conclusions: MiRNA next generation sequencing demonstrates altered fingerprint profile of whole blood miRNA expression among subjects with subsequent recurrent thrombotic events on standard medical therapy ('non-responders'), as compared to subjects with no recurrent cardiovascular events. MiRNA profiling may be useful to identify high risk subjects and provide additional insights into disease mechanisms not currently attenuated with standard medical therapy used in CAD treatment.

Keywords: Coronary artery disease; Myocardial infarction; Stent thrombosis; microRNA.