Potential Value of Serum Lipid in the Identication of Postoperative Delirium Undergoing Knee/Hip Arthroplasty: The Perioperative Neurocognitive Disorder and Biomarker Lifestyle Study

Abstract

Objective: We aimed to investigate the relationship between preoperative lipid level and postoperative delirium (POD) and explore whether lipid's effect on POD is mediated by POD core protein.

Methods: A total of 635 patients who were planned to undergo knee/hip arthroplasty under combined spinal-epidural anesthesia, regardless of gender, were selected. The patients were aged 40-90 years with American Society of Anesthesiologists physical status I II. The Mini-Mental State Examination (MMSE) was completed 1 day before the operation. Five milliliter elbow venous blood was taken from the patients before anesthesia, and serum levels of total cholesterol (TG), triglyceride (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were detected. Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural combined puncture, and amyloid beta₄₀ (Aβ₄₀), amyloid beta₄₂ (Aβ₄₂), total Tau (t-Tau), and phosphorylated Tau (p-Tau) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). After the operation, the occurrence and severity of POD were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and NPOD group. Logistic regression was used to analyze the relationship between POD and TC, TG, LDL-C, and HDL-C, and the mediating effect was used to analyze the role of POD core proteins in the relationship between lipid and MDAS. We used the receiver operating characteristic (ROC) and the precision-recall curve (PRC) analysis to assess the ability of TC, TG, LDL-C, and HDL-C ability to predict POD. Finally, we performed a sensitivity analysis to assess the stability of the results.

Results: A total of 562 patients were finally enrolled in this study, and 66 patients developed POD, with an incidence of 11.7%. Logistic regression analysis showed that high concentration of TC (OR = 3.148, 95%CI 1.858∼5.333, P < 0.001), TG (OR = 2.483, 95%CI 1.573∼3.918, P < 0.001), and LDL-C (OR = 2.469, 95%CI 1.310∼4.656, P = 0.005) in serum were risk factors for POD. A high concentration of HDL-C (OR = 0.258, 95%CI 0.112∼0.594, P = 0.001) was a protective factor for POD after adjusted for age, sex, education, and MMSE score. ROC curves showed that HDL-C have the highest sensitivity and specificity in predicting POD. For these four lipid markers, the PRC range from 0.602 to 0.731, respectively. The mediating analysis showed that POD core proteins could partially mediate the relationship between lipid and POD (effect value: 16.19∼91.04%). The results were barely changed in the sensitivity analysis, and the sensitivity analysis has shown that the results were stable.

Conclusion: The increase of serum TG, TC, and LDL-C concentration is a risk factor for POD development, while high HDL-C concentration is a protective factor for POD, and the occurrence of POD is caused by hyperlipidemia may be caused by POD core proteins.

Clinical trial registration: [www.ClinicalTrials.gov], identifier [Chictr200033439].

Keywords: cholesterol; delirium; high-density lipoprotein (HDL); low-density lipoprotein (LDL); mediation effect; triglycerides (TG).

FIGURE 1

Flow diagram.

FIGURE 2

The receiver-operator characteristic analyses for TC [0.708 (0.623–0.784)], TG [0.761 (0.679–0.831)], LDL-C [0.607 (0.519–0.691)], HDL-C [0.620 (0.531–0.703)] and CSF biomarkers in predicting delirium.

FIGURE 3

The precision-recall curve of predicting postoperative delirium.

FIGURE 4

Mediation analyses with Memorial Delirium Assessment Scale (MDAS) as outcome. The relationship between triglyceride (TC) and postoperative delirium severity was mediated by amyloid and tau pathology indicated by (1A) amyloid beta₄₂ (Aβ₄₂), (1B) total Tau (t-Tau), (1C) amyloid beta₄₂/t-Tau (Aβ₄₂/t-Tau) ratios, (1D) Aβ₄₂/p-Tau ratios, (1E) Aβ₄₀/p-Tau ratios. The relationship between total cholesterol (TG) and postoperative delirium severity was mediated by amyloid and tau pathology indicated by (2A) t-Tau, (2B) Aβ₄₂/t-Tau ratios, (2C) Aβ₄₀/t-Tau ratios, (2D) Aβ₄₀/p-Tau ratios. The relationship between low-density lipoprotein (LDL-C) and postoperative delirium severity was mediated by amyloid and tau pathology indicated by (3A) Aβ₄₂ and (3B) t-Tau. The relationship between high-density lipoprotein (HDL-C) and postoperative delirium severity was mediated by amyloid and tau pathology indicated by (4A) t-Tau, (4B) Aβ₄₀/t-Tau ratios and (4C) Aβ₄₀/p-Tau ratios. IE, indirect effect.