Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock.

Mikko Hänninen,Tuukka Tarvasmäki,Päivi Lakkisto,Heli Segersvärd,Toni Jäntti,Mélanie Vausort,Ilkka Tikkanen,Heli Tolppanen,Johan Lassus,For The Cardshock Study Group ,Veli-Pekka Harjola,Alessandro Sionis,Yvan Devaux

doi:10.3390/ijms21217925

Abstract

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.

Highlights

Cardiogenic shock (CS) is an acute state of inadequate cardiac output, resulting in end-organ hypoperfusion, multisystem organ failure, and high in-hospital mortality [1,2,3,4]
With regard to specific miRNAs that could be involved in the pathophysiology of CS, we considered miR-21-5p, miR-122-5p, and miR-320a-3p as possible candidates. miR-21-5p is expressed broadly in different human tissues and changes in its expression have been shown in various diseases, including cardiovascular diseases (CVD) [12,13]
In the pprreesseennttssttuuddyy,wweeshshoowwththatatcicricruclualtaintignglelveevleslosfomf miRi-R2‐12-15‐p5,pm, imRi-R12‐122-52p‐5,pa,nadnmd imR-i3R2‐03a2-03ap‐ a3rpeaerleevealetvedateind ninonnsounrsvuirvvoirvsorosf oCfSCcSocmopmapreadredtotosusruvriviovrosr.s.AAbboovvee mmeeddiiaann lleevvels of miR‐-21‐-5pp, miR-‐122‐-5p and miR‐-320a‐-3p were associated with known markers of hypoperfusion

Summary

Introduction

Cardiogenic shock (CS) is an acute state of inadequate cardiac output, resulting in end-organ hypoperfusion, multisystem organ failure, and high in-hospital mortality [1,2,3,4]. The etiology of CS is most often acute coronary syndrome (ACS) (i.e., shock caused by acute myocardial infarction (AMI)), but several other cardiac emergencies (e.g., end-stage heart failure, acute severe mitral regurgitation, cardiac tamponade or rupture, isolated right ventricular failure, or prior severe valvular disease) can cause CS [5,6]. MiRNAs have been found to be present in human plasma and serum. They have been shown to have remarkable resilience against degradation caused by endogenous plasma ribonuclease (RNase) activity or multiple freeze–thaw cycles [8]. The presence of stable extracellular miRNAs has sparked theorization of their possible role as potential novel biomarkers in various diseases, with promising findings already described in different cardiovascular diseases (CVD) and cancer types [9,10,11]

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