Circulating miRNA levels differ with respect to carotid plaque characteristics and symptom occurrence in patients with carotid artery stenosis and provide information on future cardiovascular events

Rafal Badacz; Tadeusz Przewłocki; Jacek Gacoń; Ewa Stępień; Francisco J Enguita; Izabela Karch; Krzysztof Żmudka; Anna Kabłak-Ziembicka

doi:10.5114/aic.2018.74358

Circulating miRNA levels differ with respect to carotid plaque characteristics and symptom occurrence in patients with carotid artery stenosis and provide information on future cardiovascular events

Postepy Kardiol Interwencyjnej. 2018;14(1):75-84. doi: 10.5114/aic.2018.74358. Epub 2018 Mar 22.

Authors

Rafal Badacz¹, Tadeusz Przewłocki¹, Jacek Gacoń², Ewa Stępień³, Francisco J Enguita⁴, Izabela Karch¹, Krzysztof Żmudka¹, Anna Kabłak-Ziembicka¹

Affiliations

¹ Department of Interventional Cardiology, School of Medicine, Jagiellonian University, John Paul II Hospital, Krakow, Poland.
² Department of Invasive Cardiology, E. Szczeklik's Hospital, Tarnow, Poland.
³ Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland.
⁴ Institute of Molecular Medicine, Faculty of Medicine of Lisbon, Lisbon, Portugal.

Abstract

Introduction: Circulating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS).

Aim: This prospective study investigated associations between circulating miRNAs and symptomatic and asymptomatic ICAS, carotid plaque morphology and future cardiovascular events.

Material and methods: Circulating miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were analyzed in 92 consecutive patients with significant ICAS referred for revascularization. Group I comprised 65 subjects (41 males, age 69.3 ±9.7 years) with a recent CIE. Group II comprised 27 patients (15 males, age 68.2 ±8.4 years) with asymptomatic ICAS. The ICAS degree and plaque morphology was assessed by ultrasonography. The incidences of cardiovascular death (CVD), myocardial infarction (MI) and recurrent CIE (CVD/MI/CIE) were recorded prospectively (mean: 38.7 ±3.8 months).

Results: Groups II and I differed significantly in levels of miR-124-3p (p = 0.036), miR-133a-3p (p = 0.043) and miR-134-5p (p = 0.02). Hypoechogenic, as compared to echogenic, plaques differed in levels of miR-124-3p (p = 0.038), miR-34a-5p (p = 0.006), miR-133b (p = 0.048), miR-134-5p (p = 0.045), and miR-375 (p = 0.016), while calcified plaques differed in miR-16-5p (p = 0.023). Ulcerated plaques showed higher levels of miR-1-3p (p = 0.04) and miR-16-5p (p = 0.003), while thrombotic plaques showed lower levels of miR-1-3p (p = 0.032). CVD/MI/CIE occurred in 14 (15.5%) out of 90 follow-up patients. Multivariate Cox and ROC analysis showed associations between miR-1-3p and CVD (AUC = 0.634; HR = 4.84; 95% CI: 1.62-14.5; p = 0.005), MI (AUC = 0.743; HR = 7.8; 95% CI: 2.01-30.0; p = 0.003), and CVD/MI/CIE (AUC = 0.560; HR = 4.6; 95% CI: 1.61-13.1; p = 0.004), while miR-133b was associated with recurrent CIE (AUC = 0.581; HR = 2.25; 95% CI: 1.01-5.02; p = 0.047).

Conclusions: A significant difference in levels of selected miRNAs is observed in symptomatic vs. asymptomatic ICAS. Plaque morphology and structure is associated with change of miRNA levels. The expression of miR-1-3p may be a potential prognostic factor for future cardiovascular events.

Keywords: biomarkers; carotid plaque morphology; internal carotid artery stenosis; ischemic stroke; miRNAs; prognosis.