Mintz Gabrielle E, Marcantonio Edward R, Walston Jeremy D, Dillon Simon T, Jung Yoojin, Trivedi Shrunjal, Gu Xuesong, Fong Tamara G, Cavallari Michele, Touroutoglou Alexandra, Dickerson Bradford C, Jones Richard N, Shafi Mouhsin M, Pascual-Leone Alvaro, Travison Thomas G, Inouye Sharon K, Libermann Towia A, Ngo Long H, Vasunilashorn Sarinnapha M
Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA.
Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
J Gerontol A Biol Sci Med Sci. 2024 Dec 11;80(1). doi: 10.1093/gerona/glae285.
Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (eg, mortality); however, inflammatory indices have not yet been examined in delirium.
Four inflammatory markers, C-reactive protein, interleukin-6, soluble tumor necrosis factor alpha receptor-1, and chitinase-3 like protein-1, were measured preoperatively and on postoperative day 2 in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, 4 inflammatory indices were considered: (i) quartile summary score, (ii) weighted summary score, (iii) principal component score, and (iv) a well-established inflammatory (least absolute shrinkage and selection operator-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method, supplemented by chart review. Generalized linear models with a log-link term were used to determine the association between each inflammatory index and delirium incidence.
Among the inflammatory indices, the weighted summary score demonstrated the strongest association with delirium: participants in the weighted summary score quartile (Q)4 had a higher risk of delirium versus participants in Q1, after clinical variable adjustment (relative risk, 95% confidence interval for preoperatively: 3.07, 1.80-5.22; and postoperative day 2: 2.65, 1.63-4.30). The weighted summary score was more strongly associated with delirium than the strongest associated individual inflammatory marker (preoperatively chitinase-3 like protein-1 [relative risk 2.45, 95% confidence interval 1.53-3.92]; postoperative day 2 interleukin-6 [relative risk 2.39, 95% confidence interval 1.50-3.82]).
A multi-protein inflammatory index using a weighted summary score provides a slight advantage over individual inflammatory markers in their association with delirium.
尽管谵妄的发病机制尚不清楚，但越来越多的证据支持炎症在其中发挥作用。此前，个别炎症生物标志物已被证明与谵妄有关。将生物标志物汇总成一个指数，在预测某些健康结局（如死亡率）方面可能比单个生物标志物提供更多信息；然而，炎症指数尚未在谵妄中进行研究。
对548名70岁及以上接受非心脏大手术的成年人（平均年龄76.7岁[标准差5.2]，58%为女性，24%发生谵妄）在术前和术后第2天测量了四种炎症标志物，即C反应蛋白、白细胞介素-6、可溶性肿瘤坏死因子α受体-1和几丁质酶-3样蛋白-1。从这些标志物中，考虑了4种炎症指数：（i）四分位数汇总评分，（ii）加权汇总评分，（iii）主成分评分，以及（iv）一个与死亡率相关的成熟炎症（最小绝对收缩和选择算子衍生）指数。使用意识模糊评估法评估谵妄，并辅以病历审查。采用带有对数链接项的广义线性模型来确定每个炎症指数与谵妄发生率之间的关联。
在炎症指数中，加权汇总评分与谵妄的关联最强：在临床变量调整后，加权汇总评分四分位数（Q）4的参与者发生谵妄的风险高于Q1的参与者（术前相对风险，95%置信区间：3.07，1.80 - 5.22；术后第2天：2.65，1.63 - 4.30）。加权汇总评分与谵妄的关联比最强的单个炎症标志物更强（术前为几丁质酶-3样蛋白-1[相对风险2.45，95%置信区间1.53 - 3.92]；术后第2天为白细胞介素-6[相对风险2.39，95%置信区间1.50 - 3.82]）。
使用加权汇总评分的多蛋白炎症指数在与谵妄的关联方面比单个炎症标志物略有优势。
