心脏代谢疾病与败血症相关结果的因果关系：一项孟德尔随机和人群研究

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE

SHOCK Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI:10.1097/SHK.0000000000002538

Mengmeng Qi, Jin Wei, Meng Zhang, Chucheng Jiao, Chang He, Liutao Sui, Shiyin Ma, Zhi Mao, Xudong Pan, Xiaoyan Zhu

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引用次数: 0

摘要

目的：CMD与脓毒症之间的因果关系在很大程度上仍然未知。为了阐明这一点，我们进行了孟德尔随机化（MR）和人口研究。方法：首先，我们使用单变量和多变量MR分析来研究CMD与败血症相关结果之间的因果关系。我们从MRC综合流行病学单位和FinnGen联盟获得了全基因组关联研究摘要。随后，进行了两步中介MR分析以探索中介。随后，我们使用MIMIC-IV数据库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查CMD与败血症相关结果之间的关系。结果：在磁共振研究中，2型糖尿病（T2DM）（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）与败血症有独立的因果关系。肥胖（OR = 1.215, 95% CI = 1.027 ~ 1.437, p = 0.023）和心衰（OR = 1.494, 95% CI = 1.080 ~ 2.065, p = 0.015）也与脓毒症重症住院有独立的因果关系。介导性磁共振分析发现23种血液代谢物与败血症有潜在的因果关系（p < 0.05），但没有一种代谢物介导CMD与败血症之间的关系。在观察性研究中，我们发现脓毒症与T2DM、肥胖、高血压、中风、心衰和高脂血症等几种疾病之间存在关联。此外，高血压、中风、心衰、冠状动脉疾病和高脂血症与脓毒症重症监护住院有关。结论：本研究首次通过观察和遗传证据揭示了CMD与败血症之间因果关系的指示性证据。综上所述，在CMD患者中，对败血症的临床关注可能是必要的。

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THE CAUSAL ASSOCIATION OF CARDIOMETABOLIC DISEASES AND SEPSIS-RELATED OUTCOMES: A MENDELIAN RANDOMIZATION AND POPULATION STUDY.

Abstract: 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.

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来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.