Qi Mengmeng, Wei Jin, Zhang Meng, Jiao Chucheng, He Chang, Sui Liutao, Ma Shiyin, Mao Zhi, Pan Xudong, Zhu Xiaoyan
Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Shock. 2025 Apr 1;63(4):579-586. doi: 10.1097/SHK.0000000000002538. Epub 2025 Feb 17.
Objective: The causality between cardiometabolic disease (CMD) and sepsis has remained largely unknown. To elucidate this, we conducted a Mendelian randomization (MR) and population study. Methods: First, we used univariable and multivariable MR analyses to investigate causal associations between CMD and sepsis-related outcomes. We obtained genome-wide association study summary from both the MRC Integrative Epidemiology Unit and the FinnGen consortium. Subsequently, a two-step mediation MR analysis was performed to explore mediators. Afterward, we conducted an observational study using the Medical Information Mart for Intensive Care IV database, in which multivariable logistic regression models were utilized to examine the relationship between CMD and sepsis-related outcomes. Results: In the MR study, type 2 diabetes mellitus (OR = 1.058, 95% CI = 1.017-1.100, P = 0.005), obesity (OR = 1.113, 95% CI = 1.057-1.172, P < 0.001), and heart failure (HF) (OR = 1.178, 95% CI = 1.063-1.305, P = 0.002) were independently causally related to sepsis. Obesity (OR = 1.215, 95% CI = 1.027-1.437, P = 0.023) and HF (OR = 1.494, 95% CI = 1.080-2.065, P = 0.015) also showed independent causal associations with sepsis critical care admission. Mediation MR analysis identified 23 blood metabolites potentially causally linked to sepsis ( P < 0.05), yet none mediated the relationship between CMD and sepsis. In the observational study, we found associations between sepsis and several conditions including type 2 diabetes mellitus, obesity, hypertension, stroke, HF, and hyperlipidemia after adjusting for confounding factors. Moreover, hypertension, stroke, HF, coronary artery disease, and hyperlipidemia were linked to sepsis critical care admission. Conclusion: This study has, for the first time, revealed indicative evidence of a causal relationship between CMD and sepsis through observational and genetic evidence. Taken together, clinical attention to sepsis may be warranted among patients with CMD.
心脏代谢疾病（CMD）与脓毒症之间的因果关系在很大程度上仍不清楚。为阐明这一点，我们进行了一项孟德尔随机化（MR）和人群研究。方法：首先，我们使用单变量和多变量MR分析来研究CMD与脓毒症相关结局之间的因果关联。我们从医学研究委员会综合流行病学单位和芬兰基因联盟获得了全基因组关联研究汇总数据。随后，进行了两步中介MR分析以探索中介因素。之后，我们使用重症监护医学信息数据库IV进行了一项观察性研究，其中使用多变量逻辑回归模型来检验CMD与脓毒症相关结局之间的关系。结果：在MR研究中，2型糖尿病（OR = 1.058，95%CI = 1.017 - 1.100，P = 0.005）、肥胖（OR = 1.113，95%CI = 1.057 - 1.172，P < 0.001）和心力衰竭（HF）（OR = 1.178，95%CI = 1.063 - 1.305，P = 0.002）与脓毒症独立存在因果关系。肥胖（OR = 1.215，95%CI = 1.027 - 1.437，P = 0.023）和HF（OR = 1.494，95%CI = 1.080 - 2.065，P = 0.015）也与脓毒症重症监护入院存在独立因果关联。中介MR分析确定了23种血液代谢物可能与脓毒症存在因果联系（P < 0.05），但没有一种介导CMD与脓毒症之间的关系。在观察性研究中，我们发现调整混杂因素后，脓毒症与包括2型糖尿病、肥胖、高血压、中风、HF和高脂血症在内的几种疾病之间存在关联。此外，高血压、中风、HF、冠状动脉疾病和高脂血症与脓毒症重症监护入院有关。结论：本研究首次通过观察性和基因证据揭示了CMD与脓毒症之间因果关系的指示性证据。综上所述，对于患有CMD的患者，可能有必要对脓毒症给予临床关注。
