Hypertension and 28-day mortality in sepsis patients: An observational and mendelian randomization study

• Published in: Heart & lung 2025-03, Vol.70, p.147-156
• Main Authors: Sun, Lichang, Zhang, Cong, Song, Ping, Zhong, Xiaoni, Xie, Biao, Huang, Yingzhu, Hu, Yuanjia, Xu, Ximing, Lei, Xun
• Format: Article
• Language: English
• Subjects: 28-day mortality; Hypertension; Intensive care unit; Mendelian randomization; Sepsis
• ISSN: 0147-9563; 1527-3288; 1527-3288
• DOI: 10.1016/j.hrtlng.2024.11.020

•Mendelian randomization leverages genetic variants as instrumental variables to simulate random allocation, thereby exploring the causal effects of genetic factors on phenotypes and effectively mitigating confounding factors.•Mendelian randomization analysis reveals a causal association between hypertension and 28-day mortality in sepsis patients.•The results of the observational study not only support the findings from the Mendelian randomization analysis but also reveal a significant positive correlation between hypertension and the 28-day mortality rate in sepsis patients. Predicting and reducing the 28-day mortality in sepsis remains a challenge in this research field. This study aimed to explore the association between hypertension and 28-day mortality in sepsis. This study is a cross-sectional approach with Mendelian Randomization (MR). We used GWAS data for hypertension as the exposure and 28-day mortality in sepsis as the outcome and employed the main inverse variance weighted method along with other supplementary MR techniques to verify the causal association between hypertension and 28-day mortality in sepsis. We used sensitivity analyses to ensure the robustness of the research findings. Finally, we utilized clinical data from the Medical Information Mart for Intensive Care-IV database to assess the risk association between hypertension and 28-day mortality in sepsis using difference analysis and multivariate logistic regression analysis. According to MR, hypertension increased the 28-day mortality in sepsis in both two datasets (FinnGen: odds ratio [OR] = 1.61, 95 % confidence interval [CI] = 1.15–2.26, p = 0.006; Medical Research Council-Integrative Epidemiological Unit: OR = 160, 95 % CI = 2.76–9250, p = 0.014). In our observational study, we included a total of 2012 sepsis patients, of which 60.5 % were male, and the average age was 55.4 years. By applying univariate and multivariate logistic regression models (univariate analysis p = 0.02, multivariate analysis p = 0.02), we observed a significantly increased risk of 28-day mortality due to hypertension in sepsis patients. This study confirmed the causal relationship between hypertension and the 28-day mortality in sepsis.