Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study

Simon T. Dillon, Sarinnapha M. Vasunilashorn, Long Ngo, Hasan H. Otu, Sharon K. Inouye, Richard N. Jones, David C. Alsop, George A. Kuchel, Eran D. Metzger, Steven E. Arnold, Edward R. Marcantonio, Towia A. Libermann

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation–based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p <.05], 0.29 mg/L, 1.56 mg/L [p <.01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p <.05], 2.53 mg/L [p <.01]) and postoperative day 2 (MPD 71.97 mg/L [p <.01], 35.18 mg/L [p <.05], 63.76 mg/L [p <.01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, −0.66 mg/L, 1.10 mg/L). Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalBiological Psychiatry
Volume81
Issue number2
DOIs
StatePublished - Jan 15 2017

Fingerprint

Delirium
C-Reactive Protein
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Proteomics
Preoperative Care
Proteins
Dementia
Mass Spectrometry

Keywords

  • C-reactive protein
  • Case-control study
  • Delirium
  • Inflammation
  • Postoperative
  • Proteomics

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery : A Longitudinal Nested Case-Control Study. / Dillon, Simon T.; Vasunilashorn, Sarinnapha M.; Ngo, Long; Otu, Hasan H.; Inouye, Sharon K.; Jones, Richard N.; Alsop, David C.; Kuchel, George A.; Metzger, Eran D.; Arnold, Steven E.; Marcantonio, Edward R.; Libermann, Towia A.

In: Biological Psychiatry, Vol. 81, No. 2, 15.01.2017, p. 145-153.

Research output: Contribution to journalArticle

Dillon, ST, Vasunilashorn, SM, Ngo, L, Otu, HH, Inouye, SK, Jones, RN, Alsop, DC, Kuchel, GA, Metzger, ED, Arnold, SE, Marcantonio, ER & Libermann, TA 2017, 'Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study', Biological Psychiatry, vol. 81, no. 2, pp. 145-153. https://doi.org/10.1016/j.biopsych.2016.03.2098
Dillon, Simon T. ; Vasunilashorn, Sarinnapha M. ; Ngo, Long ; Otu, Hasan H. ; Inouye, Sharon K. ; Jones, Richard N. ; Alsop, David C. ; Kuchel, George A. ; Metzger, Eran D. ; Arnold, Steven E. ; Marcantonio, Edward R. ; Libermann, Towia A. / Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery : A Longitudinal Nested Case-Control Study. In: Biological Psychiatry. 2017 ; Vol. 81, No. 2. pp. 145-153.
@article{bf03f2cc80884bf897d02ab7c5bc88ea,
title = "Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study",
abstract = "Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24{\%} delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation–based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p <.05], 0.29 mg/L, 1.56 mg/L [p <.01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p <.05], 2.53 mg/L [p <.01]) and postoperative day 2 (MPD 71.97 mg/L [p <.01], 35.18 mg/L [p <.05], 63.76 mg/L [p <.01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, −0.66 mg/L, 1.10 mg/L). Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.",
keywords = "C-reactive protein, Case-control study, Delirium, Inflammation, Postoperative, Proteomics",
author = "Dillon, {Simon T.} and Vasunilashorn, {Sarinnapha M.} and Long Ngo and Otu, {Hasan H.} and Inouye, {Sharon K.} and Jones, {Richard N.} and Alsop, {David C.} and Kuchel, {George A.} and Metzger, {Eran D.} and Arnold, {Steven E.} and Marcantonio, {Edward R.} and Libermann, {Towia A.}",
year = "2017",
month = "1",
day = "15",
doi = "10.1016/j.biopsych.2016.03.2098",
language = "English (US)",
volume = "81",
pages = "145--153",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "2",

}

TY - JOUR

T1 - Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery

T2 - A Longitudinal Nested Case-Control Study

AU - Dillon, Simon T.

AU - Vasunilashorn, Sarinnapha M.

AU - Ngo, Long

AU - Otu, Hasan H.

AU - Inouye, Sharon K.

AU - Jones, Richard N.

AU - Alsop, David C.

AU - Kuchel, George A.

AU - Metzger, Eran D.

AU - Arnold, Steven E.

AU - Marcantonio, Edward R.

AU - Libermann, Towia A.

PY - 2017/1/15

Y1 - 2017/1/15

N2 - Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation–based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p <.05], 0.29 mg/L, 1.56 mg/L [p <.01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p <.05], 2.53 mg/L [p <.01]) and postoperative day 2 (MPD 71.97 mg/L [p <.01], 35.18 mg/L [p <.05], 63.76 mg/L [p <.01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, −0.66 mg/L, 1.10 mg/L). Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.

AB - Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation–based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p <.05], 0.29 mg/L, 1.56 mg/L [p <.01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p <.05], 2.53 mg/L [p <.01]) and postoperative day 2 (MPD 71.97 mg/L [p <.01], 35.18 mg/L [p <.05], 63.76 mg/L [p <.01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, −0.66 mg/L, 1.10 mg/L). Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.

KW - C-reactive protein

KW - Case-control study

KW - Delirium

KW - Inflammation

KW - Postoperative

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=84965029201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84965029201&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2016.03.2098

DO - 10.1016/j.biopsych.2016.03.2098

M3 - Article

C2 - 27160518

AN - SCOPUS:84965029201

VL - 81

SP - 145

EP - 153

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 2

ER -