Apolipoprotein E genotype and the association between C-reactive protein and postoperative delirium: Importance of gene-protein interactions

Introduction: Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation. Methods: We tested whether APOE modifies the established association between Creactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (>= 234.12 mg/L) was defined by the highest sample-based quartile. Delirium was determined using the Confusion Assessment Method and chart review, and severity was determined by the Confusion AssessmentMethod-Severity score. Results: APOE epsilon 4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by epsilon 4 status. Among..4 carriers, there was a strong relationship between highCRP (vs. low CRP) and delirium incidence (relative risk [95% confidence interval], 3.0 [1.4-6.7]); however, no significant association was observed among non-epsilon 4 carriers (relative risk [95% CI], 1.2 [0.8-1.7]). Discussion: Our findings raise the possibility that APOE..4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.