Diagnostic and prognostic micro-RNAs in ischaemic stroke due to carotid artery stenosis and in acute coronary syndrome: a four-year prospective study

Background: Circulating microRNAs (miRs) levels are potentially important diagnostic and prognostic biomarkers in acute coronary syndrome (ACS) or cerebral ischaemic events (CIE) resulting from internal carotid artery stenosis (ICAS). Aim: This four-year prospective study aimed to compare the levels of circulating miRs in ACS vs. CIE patients, and investigate miRs potentially associated with risk of recurrent cardiovascular events. Methods: The circulating miRs levels (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375, and miR-499-5p) were compared in 43 (34 men, 57.6 +/- 10.1 years) patients with ACS, and in 71 (47 men, 69.5 +/- 9.6 years) with CIE due to ICAS. A four-year prospective evaluation of miRs associated with risk of cardiovascular death (CVD), myocardial infarction (MI), CIE, or all (CVD/MI/CIE) was performed. Results: In ACS vs. CIE patients, the levels of miR-124-3p (p < 0.001), miR-134-5p (p = 0.012), miR-208b-3p (p < 0.001), miR-34a-5p (p < 0.001), and miR-499-5p (p < 0.001) were higher, while levels of miR-16-5p (p < 0.001) and miR-122-5p (p < 0.001) were lower. Levels of miR-1-3p (p = 0.195), miR-133a-3p (p = 0.333), miR-133b (p = 0.056), and miR-375 (p = 0.055) were non-statistically different. During follow-up (median 57 months, Q1-Q3: 54-60), CVD/MI/CIE occurred in 23 subjects, including eight CVDs, five non-fatal CIEs, and 10 non-fatal MIs. The multivariate Cox proportional hazard analysis (relative risk [RR]; 95% confidence interval [CI]) revealed that miR-208b-3p (1.225; 1.092-1.375), miR-34a-5p (0.963; 0.935-0.992), and miR-499-5p (0.077; 0.025-0.239) were independently associated with risk of CVD/MI/CIE, as well as risk of each event. Furthermore, miR-133b (1.009; 1.003-1.015) was associated with risk of CVD. Conclusions: This study shows that although most investigated miRs levels differ significantly between patients with ACS and CIE, similar levels of circulating miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we identified several common miRs as possible risk factors for recurrent cardiovascular events.