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

Joseph P. Mathew, Mihai V. Podgoreanu, Hilary P. Grocott, William D. White, Richard W. Morris, Mark Stafford-Smith, G. Burkhard Mackensen, Christine S. Rinder, James A. Blumenthal, Debra A. Schwinn, Mark F. Newman

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


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.

Original languageEnglish
Pages (from-to)1934-1942
Number of pages9
JournalJournal of the American College of Cardiology
Issue number19
StatePublished - May 15 2007

Bibliographical note

Funding Information:
Supported in part by grants AG09663 (to Dr. Newman), HL54316 (to Dr. Newman), AG17556 (to Dr. Schwinn), HL075273 (to Dr. Schwinn), and M01-RR-30 (Duke Clinical Research Centers Program) from the National Institutes of Health and grants 0256342U (to Dr. Mathew), 9951185U (to Dr. Mathew), 9970128N (to Dr. Newman), and 0120492U (to Dr. Podgoreanu) from the American Heart Association. Measurement of C-reactive protein levels was supported by Biosite Diagnostics. The first two authors contributed equally to this work. Members of the PEGASUS Investigative Team are acknowledged in the Appendix .

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Genetic Variants in P-Selectin and C-Reactive Protein Influence Susceptibility to Cognitive Decline After Cardiac Surgery'. Together they form a unique fingerprint.

Cite this