Increased miRNA-related inflammation markers and pro-inflammatory circulating cell profile in patients with poor neurological outcome after out-of-hospital cardiac arrest

Abstract Background Out-of-Hospital Cardiac Arrest (OHCA) supposes a main cause of disability and mortality worldwide. Between patients suffering OHCA, only a 10-20% can be successfully resuscitated and, between them, a 50% suffers of neurological sequelae. Mechanisms underlying brain damage seems to be strongly related with neuroinflammation, mediated by classical (PCR, NLR) and novel (miRNAs) agents at play. Even there are studies suggesting the relevance of miRNA-mediated inflammatory response in ECA, no consistent conclusions about its role in ECA outcomes have been obtained. Purpose The aim of the present investigation is to study the temporal patterns of classical (PCR, NLR) and novel (miRNAs) inflammation markers during hospitalization of ECA patients and to correlate them with neurological outcome. Methods Consecutive OHCA patients were prospectively recruited at the Acute Cardiac Care Unit (ACCU) of the hospital Clinic of Barcelona from March 2019 to December 2023. Serum samples were obtained at 0, 24 and 72 hours after hospital admission. Patients were grouped according to their neurological outcome, measured by Cerebral Performance Category (CPC), at hospital discharge. Classical inflammation markers (PCR and NLR) were measured and in silico pre-targeted serum circulating-miRNAs were analysed by qPCR. Results A total of 120 patients (60 ± 13 years, 20% female) were included for the analysis. At hospital discharge, 55 (45%) patients survived with good NO (GNO; CPC 1-2) and 65 (55%) patients presented a poor NO (PNO; CPC 3-5). Classical inflammation markers such as PCR and NLR were significant higher in PNO than in GNO Group (P-value = 0.0042 and p-ANOVA = 0.0444, respectively) (Figure 1A). 11 inflammation-related miRNAs with strong correlation with OHCA-related conditions such as cardiovascular and coronary artery disease, hypoxic encephalopathy and neuro-inflammation were pre-targeted by in silico analysis. Five of the pre-targetedmiRNAs (miR-21-5p, miR-23a-3p, miR-146-5p, miR-155-5p and miR-181a-5p) presented significant differences between GNO and PNO groups (p-ANOVA = 0.0001, 0.0027, 0.0001, 0.0023 and 0.0002 respectively) in at least one time point, with an reduced expression in all cases in the PNO respect the GNO group (Figure 1B). Conclusions Patients with PNO after OHCA presents a downregulation of inflammation-regulatory miRNAs that leads an increase of clinical inflammation-related mediators such as PCR and NLR, with potential neuro-inflammatory consequences.