Assessment of indirect effects of apolipoprotein Eε4 carrier status on postoperative delirium incidence in cardiac surgery – A preplanned secondary analysis of a prospective cohort study

Background Although postoperative delirium is a frequent complication, its pathophysiological mechanisms have not been completely elucidated yet. Recent studies suggested indirect influences of apolipoprotein Eε4 (APOEε4) allele, a genetic risk factor of Alzheimer’s disease, on the association between postoperative delirium and some known risk factors. Objectives This preplanned secondary analysis (ClinicalTrials.gov NCT03706989) aimed to determine whether APOEε4 carrier status played an indirect role on postoperative delirium incidence related to (1) preoperative cognitive impairment and to (2) postoperative inflammation in cardiac surgery. Methods 220 adult patients undergoing elective cardiac surgery were included in the study. Preoperative cognitive assessment was performed the day before surgery using both a battery of five neuropsychological tests and the Mini-Mental State Examination. Postoperative inflammation was evaluated by C-reactive protein (CRP) concentrations in blood. Patients were screened for postoperative delirium from the Intensive Care Unit until discharge from the hospital using CAM-ICU (3 times a day in the ICU), CAM (2 times a day at the ward) and a chart review. Comparisons between groups were performed using a χ 2 test for dichotomous variables and a Student t-test for continuous variables. Association between the studied exposure (preoperative cognition or postoperative systemic inflammation) and the incidence of postoperative delirium, as well as their respective interactions with APOEε4 carrier status, were assessed using multivariable logistic regression models. Results Among 220 cardiac surgery patients, 65 (29.5%) developed delirium. Fifty-three patients (24%) carried at least one allele ε4. Multivariable logistic regression models showed that (1) interactions between APOEε4 carrier status and preoperative cognitive status or between APOEε4 carrier status and postoperative CRP concentrations were negligible, and (2) extensive preoperative cognitive testing remained a key predictor of postoperative delirium. Discussion APOEε4 carrier status did not modify the effect of preoperative cognitive impairment or the effect of higher postoperative systemic inflammation on postoperative delirium occurrence in our clinical series.