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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 ?4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by ?4 status. Among ?4 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-?4 carriers (relative risk [95% CI], 1.2 [0.8-1.7]). DISCUSSION:Our findings raise the possibility that APOE ?4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.

SUBMITTER: Vasunilashorn SM

PROVIDER: S-EPMC7086383 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Vasunilashorn Sarinnapha M SM Ngo Long H LH Inouye Sharon K SK Fong Tamara G TG Jones Richard N RN Dillon Simon T ST Libermann Towia A TA O'Connor Margaret M Arnold Steven E SE Xie Zhongcong Z Marcantonio Edward R ER

Alzheimer's & dementia : the journal of the Alzheimer's Association 20200104 3

<h4>Introduction</h4>Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation.<h4>Methods</h4>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 char ...[more]

PMID: 31761478

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Project description:ObjectiveCatechol-O-methyltransferase (COMT), a key enzyme in degrading catecholamines associated with the stress response, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated "warriors") withstand the onset of neuropsychiatric disorders and cognitive decline, whereas individuals with Met/Met and Val/Met genotypes ("nonwarriors") are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium.MethodsThis was a prospective cohort study conducted at two academic medical centers. The study involved 547 patients aged 70 or older undergoing major noncardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele-specific polymerase chain reaction assays, considering warriors versus nonwarriors. High plasma CRP, measured on postoperative day 2 using enzyme-linked immunosorbent assay, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and race/ethnicity, stratified by COMT genotype, to determine whether the association between CRP and delirium differed by COMT.ResultsPrevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk [RR] 1.0, 95% confidence interval [CI] 0.4-2.6). In contrast, among nonwarriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1-2.2).ConclusionCOMT warriors may be protected against the increased risk of delirium associated with high CRP on postoperative day 2. With further confirmation, COMT genotype may help target interventions for delirium prevention in the vulnerable nonwarrior group.

Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Project description:ObjectiveThis study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with the goal of offering novel insights for clinical interventions targeting POD.MethodsA retrospective analysis was conducted on the medical records of patients who underwent hip fracture surgery in a tertiary medical institution from January 2013 to November 2023. The patients were classified based on hypoalbuminemia (defined as a serum albumin level < 35 g/L) and clinical threshold. Multivariable logistic regression and propensity score matching analysis (PSM) were employed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for POD to eliminate potential confounding factors. Additionally, subgroup analysis was performed to explore the interaction effect.ResultsThe retrospective cohort study included 1,440 patients, with an incidence of POD found to be 19.1%. In a multivariable logistic regression analysis, patients with hypoalbuminemia had an adjusted OR of 2.99 (95%CI: 2.14-4.18) compared to those with normal albumin levels (≥ 35 g/L). Furthermore, a significant trend was observed across different severity categories, including mild hypoalbuminemia (34.9-30.0 g/L; adjusted OR = 2.71, 95%CI: 1.84-3.99), moderate hypoalbuminemia (29.9-25.0 g/L, adjusted OR = 3.44, 95%CI: 1.88-6.28), and severe hypoalbuminemia (<25.0 g/L; adjusted OR = 3.97, 95%CI: 1.78-8.86), with a trend value of p <0.001. Similar results were observed in the PSM analysis. Additionally, treating preoperative serum albumin level as a continuous variable, the risk of POD increased by 11% (95% CI, 1.08-1.15) with each 1 g/L decrease in preoperative serum albumin level.ConclusionLow preoperative levels of albumin are strongly associated with POD in geriatric patients with hip fractures, and a significant dose-response relationship exists between them.

Dataset Information

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

Publications

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

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