Dynamics of microRNA Expression and Systemic Inflammatory Response in POCD After Cardiac Surgery

November 15, 2025 updated by: Visnja Ikic, MD, Osijek University Hospital

Association of MicroRNA-151-5p Expression With Systemic Inflammatory Response and Cognitive Status in Patients After Coronary Artery Bypass Surgery (MiRNACOG)

Postoperative cognitive decline (POCD) is one of the most common complications after cardiac surgery. It is characterized by impaired memory, attention, and executive functions and can have long-term consequences. The goal of this observational study was to investigate the mechanisms of cognitive decline after cardiac surgery and potential biomarkers that could aid in the diagnosis, prevention, and treatment of POCD. The investigators focused on the role of microRNAs (miRNAs) and systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia as potential factors involved in the development of the neuroinflammatory response and subsequent POCD. The main question this study aims to answer is whether perioperative miRNA 151-5p expression is associated with POCD after surgery. The second aim is to examine the association between miRNA-151-5p and systemic inflammation. The investigators measured circulating miRNA-151-5p levels and plasma levels of inflammatory biomarkers in patients undergoing surgical myocardial revascularization. To assess cognitive function, participants completed the Montreal Cognitive Assessment (MoCA Test). Changes in the measured values of miRNA-151-5p expression and inflammatory markers, as well as changes in cognitive status after surgery, were assessed in relation to the preoperative state.

Study Overview

Status

Completed

Conditions

Detailed Description

Surgical myocardial revascularization is a procedure used in patients with ischemic heart disease to bypass atherosclerotic narrowings or blockages of the coronary arteries using an arterial or venous graft (Coronary Artery Bypass Grafting - CABG). One of the most common complications after cardiac surgery is postoperative cognitive decline (POCD). It is characterized by impaired memory, attention, and executive functions and can have long-term consequences, such as delayed physical therapy and mobilization, prolonged stay in the intensive care unit and hospital, more frequent discharge to nursing homes, reduced quality of life, and increased mortality.

The causes of POCD are multifactorial. The systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia is considered a factor in the development of the neuroinflammatory response and subsequent POCD. Neuroinflammation can cause dysfunction or death of brain cells and damage to the blood-brain barrier, leading to an increase in the level of biochemical markers of brain injury in the blood. Studies indicate that numerous microRNAs (miRNAs) play a role in controlling the inflammatory response. MiRNAs are small, endogenous, non-coding RNA molecules, typically 18-25 nucleotides long, that regulate gene expression at the post-transcriptional level. They are central mediators of cellular proliferation, differentiation, and apoptosis. MiRNA levels in tissues and peripheral blood are similar, and circulating miRNAs are stable and suitable for measurement. Specific miRNAs (miRNA 151-5p, 505, 499, 625, and others) may be potential early biomarkers of brain damage after a mild traumatic brain injury. Anesthesia and surgery also, through complex mechanisms, can cause changes in brain cells that can lead to the release of specific miRNAs, and these miRNAs can be detected in blood and various biological fluids.

Hypothesis: Higher levels of perioperative miRNA-151-5p expression are associated with the systemic inflammatory response and with the development of POCD.

Aim of this study is:

To investigate the association between miRNA-151-5p expression levels and biochemical parameters of systemic inflammation, as well as the association of both with cognitive status in patient undergoing CABG surgery.
To investigate the association between patients' demographic and clinical characteristics and miRNA-151-5p expression levels, the level of biochemical parameters of systemic inflammation, and patients' cognitive status.

Research plan:

The research was carried out at the Clinical Hospital Centre Osijek. Respecting the inclusion and exclusion criteria for participation in the study, the research included patients aged 65 to 80 years who, according to the American Society of Anesthesiologists (ASA) classification, are classified into groups III and IV, and who are undergoing CABG surgery with the use of extracorporeal circulation. Surgeries were performed according to the standard protocol for balanced anesthesia, cardiac surgery, and extracorporeal circulation. All participants underwent the same anesthetic procedure and anesthesia based on midazolam, propofol, sufentanyl, rocuronium and sevoflurane. The depth of anesthesia was monitored using Patient State Index (PSI). All surgeries were performed using extracorporeal circulation with the maintenance of normothermia (36 °C).

Blood samples for determination of levels of cholinesterase, interleukin-6, protein S100B, miRNA-151-5p expression and routine laboratory parameters (complete blood count, levels of troponin I, C-reactive protein, procalcitonin, glucose, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, albumin, electrolytes, lactate, coagulation tests, and arterial blood gas analysis) were taken at three time points: before surgery prior to induction of anesthesia, immediately after the procedure upon admission to the intensive care unit, and 48 hours after the surgical procedure.

Cognitive function testing was performed the day before surgery and postoperatively, once daily every day until the 6th postoperative day. The investigators used a validated scoring scale for assessing cognitive functions, the Montreal Cognitive Assessment - MoCA Test. Demographic and clinical data were recorded for all subjects. Subjects were followed up 7 days.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Croatia
- - Osijek, Croatia, 31000
    - University Hospital Osijek

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Older Adult

Accepts Healthy Volunteers

Sampling Method

Probability Sample

Study Population

Patients undergoing coronary artery bypass grafting surgery at the Department of Cardiac and Thoracic Surgery of the Clinic for Surgery, Clinical Hospital Center Osijek.

Description

Inclusion Criteria:

patients undergoing coronary artery bypass graft surgery to treat coronary artery disease
two or more coronary bypass surgery with the use of extracorporeal circulation
patients between the ages of 65 and 80
patients according to the classification of the American Society of Anesthesiologists (ASA) classified in groups III and IV
patients who agreed to participate in the research and signed an informed consent

Exclusion Criteria:

patients with communication difficulties (severe visual, hearing and speech impairment)
illiterate patients
patients with a history of dementia, schizophrenia, Parkinson's disease, Alzheimer's disease, alcoholism
patients with previously known liver failure of any grade according to the Child-Pough classification
patients with previously known renal failure greater than grade 2
patients taking immunosuppressive, corticosteroid and anticholinergic therapy
intraoperatively used cell-saver and/or hemofilter
patients in whom the planned procedure is not performed
patients in whom it is not possible to assess cognitive functions postoperatively (patients sedated due to intra- or postoperative surgical complications)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Coronary Artery Bypass Graft (CABG) group The study include a cohort of patients, between the ages of 65 and 80, who undergo coronary artery bypass graft surgery to treat coronary artery disease, receiving 2 or more coronary artery bypass grafts with the use of extracorporeal circulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative changes in microRNA 151-5p expression. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	MicroRNA-151-5p expression levels will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU. Levels of microRNA expression will be calculated relative to reference microRNA-16-5p using 2-∆∆cT method.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Perioperative changes in cognitive function measured by Montreal Cognitive Assessment (MoCA Test). Time Frame: 1 day before surgery and once daily postoperatively, up to the 6th postoperative day.	Cognitive function will be assessed in all patients at enrollment one day before surgery, and daily for the following six postoperative days using the Montreal Cognitive Assessment (MoCA test). Montreal Cognitive Assessment scale: minimum score is 0 and maximum score is 30 points, a score of 26 or above is considered normal, while scores below this may indicate cognitive impairment. A score of 18-25 suggests mild cognitive impairment, 10-17 suggests moderate impairment, and a score 0-9 suggests severe impairment.	1 day before surgery and once daily postoperatively, up to the 6th postoperative day.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative changes in levels of white blood cells. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission.	Levels of white blood cells will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission.
Perioperative changes in levels of C-reactive protein. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	Levels of C-reactive protein will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Perioperative changes in levels of procalcitonin. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	Levels of procalcitonin will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Perioperative changes in levels of interleukin-6. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	Levels of interleukin-6 will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Perioperative changes in levels of cholinesterase. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	Levels of cholinesterase will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Perioperative changes in levels of protein S-100B. Time Frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission	Levels of protein S-100B will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.	Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
Patient demographic data. Time Frame: From enrollment to the end of cognitive testing at 6th postoperative day.	Patient demographic data: age, gender, education, and previous medical history will be recorded and correlated with microRNA expression levels, inflammatory biomarkers and the Montreal Cognitive Assessment (MoCA test) scores. Montreal Cognitive Assessment scale: minimum score is 0 and maximum score is 30 points, a score of 26 or above is considered normal, while scores below this may indicate cognitive impairment. A score of 18-25 suggests mild cognitive impairment, 10-17 suggests moderate impairment, and a score 0-9 suggests severe impairment.	From enrollment to the end of cognitive testing at 6th postoperative day.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Osijek University Hospital

Collaborators

Josip Juraj Strossmayer University of Osijek

Investigators

Study Chair: Slavica Kvolik, Professor, University Hospital Osijek

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

MoCA - Cognitive Assessment [Internet]. [cited 2022 Feb 9]. MoCA - Cognitive Assessment. Available from: https://www.mocatest.org/.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2022

Primary Completion (Actual)

June 23, 2023

Study Completion (Actual)

October 26, 2023

Study Registration Dates

First Submitted

November 13, 2025

First Submitted That Met QC Criteria

November 14, 2025

First Posted (Estimated)

November 17, 2025

Study Record Updates

Last Update Posted (Actual)

November 19, 2025

Last Update Submitted That Met QC Criteria

November 15, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

microRNA-POCD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

After study completion, upon reasonable request, data may be shared with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

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