Development of a Dynamic Multi-Protein Signature of Postoperative Delirium.

Abstract

Background:

Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2).

Methods:

We used the Successful Aging after Elective Surgery (SAGES) Study of adults age ≥70 undergoing major noncardiac surgery (N = 560; 24% delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzyme-linked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the "best" PREOP and POD2 models for delirium.

Results:

We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The "best" multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84).

Conclusion:

The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.

• Authors: Sarinnapha M Vasunilashorn, Long H Ngo, Noel Y Chan, Wenxiao Zhou, Simon T Dillon, Hasan H Otu, Sharon K Inouye, Iris Wyrobnik, George A Kuchel, Janet E McElhaney, Zhongcong Xie, David C Alsop, Richard N Jones, Towia A Libermann, Edward R Marcantonio
• Journal: The journals of gerontology. Series A, Biological sciences and medical sciences (J Gerontol A Biol Sci Med Sci) Vol. 74 Issue 2 Pg. 261-268 (01 16 2019) ISSN: 1758-535X [Electronic] United States
• PMID: 29529166 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• C-Reactive Protein

Topics

• Aged
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Cytokines (blood)
• Delirium (blood, etiology)
• Disease Progression
• Elective Surgical Procedures (adverse effects)
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• Humans
• Male
• Postoperative Complications (blood)
• Prospective Studies
• Proteomics (methods)