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

Abstract 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 C-reactive 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 Assessment Method––Severity score. Results APOE e4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by e4 status. Among e4 carriers, there was a strong relationship between high CRP (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-e4 carriers (relative risk [95% CI], 1.2 [0.8–1.7]). Discussion Our findings raise the possibility that APOE e4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.