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

NCT07231731 | Completed

• 1 other identifier: microRNA-POCD
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biomarkers; Coronary Artery Bypass Surgery; Interleukin-6; MicroRNAs; Postoperative Cognitive Complications; Systemic Inflammatory Response Syndrome

Keywords

Anesthesia, General; Blood-Brain Barrier; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cholinesterases; Cognitive Disorders; Cognitive Dysfunction; Coronary Artery Bypass; Coronary Artery Disease; Critical Care; Extracorporeal Circulation; Gene Expression; Inflammation; Interleukins; Mental Disorders; Myocardial Revascularization; Nervous System Diseases; Neurocognitive Disorders; Neuroinflammatory Diseases; Neuropsychological Tests; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Perioperative Period; Postoperative Care; Postoperative Cognitive Complications; Postoperative Complications; S100B protein, human; Thoracic Surgery; Treatment Outcome

Outcome Measures

Primary Outcomes (2)

• Perioperative changes in microRNA 151-5p expression.

  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).

  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 Outcomes (7)

• Perioperative changes in levels of white blood cells.

  Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission.

• Perioperative changes in levels of C-reactive protein.

  Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

• Perioperative changes in levels of procalcitonin.

  Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

• Perioperative changes in levels of interleukin-6.

  Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

• Perioperative changes in levels of cholinesterase.

  Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

Study Arms (1)

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.

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Osijek University Hospital: lead
• Josip Juraj Strossmayer University of Osijek: collaborator

Study Sites (1)

University Hospital Osijek

Osijek, 31000, Croatia

Location

Related Publications (7)

• van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012 Mar;67(3):280-93. doi: 10.1111/j.1365-2044.2011.07008.x.

  PMID: 22321085 BACKGROUND

• Kok WF, Koerts J, Tucha O, Scheeren TW, Absalom AR. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery. Anaesthesia. 2017 Mar;72(3):359-369. doi: 10.1111/anae.13712. Epub 2016 Dec 17.

  PMID: 27987229 BACKGROUND

• Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194.

  PMID: 29621031 BACKGROUND

• Greaves D, Psaltis PJ, Ross TJ, Davis D, Smith AE, Boord MS, Keage HAD. Cognitive outcomes following coronary artery bypass grafting: A systematic review and meta-analysis of 91,829 patients. Int J Cardiol. 2019 Aug 15;289:43-49. doi: 10.1016/j.ijcard.2019.04.065. Epub 2019 Apr 24.

  PMID: 31078353 BACKGROUND

• Kapoor MC. Neurological dysfunction after cardiac surgery and cardiac intensive care admission: A narrative review part 1: The problem; nomenclature; delirium and postoperative neurocognitive disorder; and the role of cardiac surgery and anesthesia. Ann Card Anaesth. 2020 Oct-Dec;23(4):383-390. doi: 10.4103/aca.ACA_138_19.

  PMID: 33109792 BACKGROUND

• Polito F, Fama F, Oteri R, Raffa G, Vita G, Conti A, Daniele S, Macaione V, Passalacqua M, Cardali S, Di Giorgio RM, Gioffre M, Angileri FF, Germano A, Aguennouz M. Circulating miRNAs expression as potential biomarkers of mild traumatic brain injury. Mol Biol Rep. 2020 Apr;47(4):2941-2949. doi: 10.1007/s11033-020-05386-7. Epub 2020 Mar 26.

  PMID: 32219772 BACKGROUND

• Pozniak T, Shcharbin D, Bryszewska M. Circulating microRNAs in Medicine. Int J Mol Sci. 2022 Apr 3;23(7):3996. doi: 10.3390/ijms23073996.

  PMID: 35409354 BACKGROUND

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

MicroRNA expression will be determined from serum isolated from a venous blood sample.

MeSH Terms

Conditions

Postoperative Cognitive Complications; Systemic Inflammatory Response Syndrome; Cognitive Dysfunction; Coronary Artery Disease; Inflammation; Mental Disorders; Nervous System Diseases; Neurocognitive Disorders; Neuroinflammatory Diseases; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Postoperative Complications

Condition Hierarchy (Ancestors)

Cognition Disorders; Shock; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Slavica Kvolik, Professor

  University Hospital Osijek

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 7 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of medicine, Specialist in anaesthesiology, reanimatology and intensive care medicine, Subspecialist in intensive care medicine

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 17, 2025
• Study Start: May 31, 2022
• Primary Completion: June 23, 2023
• Study Completion: October 26, 2023
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

CR (1)