Genetic Variants in P-Selectin and C-Reactive Protein Influence Susceptibility to Cognitive Decline After Cardiac Surgery

Objectives: We hypothesized that candidate gene polymorphisms in biologic pathways regulating inflammation, cell matrix adhesion/interaction, coagulation-thrombosis, lipid metabolism, and vascular reactivity are associated with postoperative cognitive deficit (POCD). Background: Cognitive decline is a common complication of coronary artery bypass graft (CABG) surgery and is associated with a reduced quality of life. Methods: In a prospective cohort study of 513 patients (86% European American) undergoing CABG surgery with cardiopulmonary bypass, a panel of 37 single-nucleotide polymorphisms (SNPs) was genotyped by mass spectrometry. Association between these SNPs and cognitive deficit at 6 weeks after surgery was tested using multiple logistic regression accounting for age, level of education, baseline cognition, and population structure. Permutation analysis was used to account for multiple testing. Results: We found that minor alleles of the CRP 1059G/C SNP (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.16 to 0.78; p = 0.013) and the SELP 1087G/A SNP (OR 0.51, 95% CI 0.30 to 0.85; p = 0.011) were associated with a reduction in cognitive deficit in European Americans (n = 443). The absolute risk reduction in the observed incidence of POCD was 20.6% for carriers of the CRP 1059C allele and 15.2% for carriers of the SELP 1087A allele. Perioperative serum C-reactive protein (CRP) and degree of platelet activation were also significantly lower in patients with a copy of the minor alleles, providing biologic support for the observed allelic association. Conclusions: The results suggest a contribution of P-selectin and CRP genes in modulating susceptibility to cognitive decline after cardiac surgery, with potential implications for identifying populations at risk who might benefit from targeted perioperative antiinflammatory strategies.