Wang Pangbo, Huang Jing, Xu Liwei, Hu Rong
State Key Laboratory of Trauma, Burn, and Combined Injury, Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Trauma Neurosurgery, NO. 946 Hospital of PLA Land Force, Yining, China.
Front Med (Lausanne). 2025 Jan 6;11:1456742. doi: 10.3389/fmed.2024.1456742. eCollection 2024.
Delirium is a severe neuropsychiatric symptom following acute ischemic stroke (IS) and is associated with poor outcomes. Systemic inflammation and immune dysregulation are believed to contribute to the pathophysiology of delirium. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are widely recognized as convenient and reliable biomarkers of systemic inflammation. However, their association with delirium after IS remains unclear.
In this study, we identified IS patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We employed multivariable logistic regression and restricted cubic splines (RCS) to assess the association between the NLR, PLR, and LMR and delirium. Two-sample Mendelian randomization (MR) analysis was performed to further explore their causal relationship at the genetic level.
A total of 1,436 patients with IS were included in this study, of whom 214 (14.9%) had delirium. In the multivariate logistic regression analysis, after adjustment for confounders, the patients in the highest quartile of the NLR (odds ratio [OR] 2.080, 95% confidence interval [CI], 1.282-3.375) and LMR (OR 0.503, 95% CI 0.317-0.798) and the patients in the second quartile of the PLR (OR 1.574, 95% CI 1.019-2.431) were significantly associated with delirium. The RCS function showed a progressive increase in the risk of delirium with higher NLR and PLR and lower LMR. In the MR analysis, only the PLR was negatively associated with the risk of delirium.
The observational studies found significant associations between the NLR, PLR, and LMR and delirium. However, the MR analysis only demonstrated a potential protective causal relationship between the PLR and delirium. Further prospective studies are needed to validate their association and to elucidate the underlying mechanisms.
谵妄是急性缺血性卒中（IS）后的一种严重神经精神症状，与不良预后相关。全身炎症和免疫失调被认为参与了谵妄的病理生理过程。中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）以及淋巴细胞与单核细胞比值（LMR）被广泛认为是全身炎症方便且可靠的生物标志物。然而，它们与IS后谵妄的关联仍不明确。
在本研究中，我们从重症监护医学信息数据库（MIMIC）-IV中识别出需要入住重症监护病房（ICU）的IS患者。我们采用多变量逻辑回归和受限立方样条（RCS）来评估NLR、PLR和LMR与谵妄之间的关联。进行两样本孟德尔随机化（MR）分析以在基因水平进一步探索它们的因果关系。
本研究共纳入1436例IS患者，其中214例（14.9%）发生谵妄。在多变量逻辑回归分析中，校正混杂因素后，NLR最高四分位数的患者（比值比[OR] 2.080，95%置信区间[CI]，1.282 - 3.375）和LMR最高四分位数的患者（OR 0.503，95% CI 0.317 - 0.798）以及PLR第二四分位数的患者（OR 1.574，95% CI 1.019 - 2.431）与谵妄显著相关。RCS函数显示，随着NLR和PLR升高以及LMR降低，谵妄风险逐渐增加。在MR分析中，只有PLR与谵妄风险呈负相关。
观察性研究发现NLR、PLR和LMR与谵妄之间存在显著关联。然而，MR分析仅表明PLR与谵妄之间存在潜在的保护性因果关系。需要进一步的前瞻性研究来验证它们的关联并阐明潜在机制。
