BACKGROUND: Predicting and reducing the 28-day mortality in sepsis remains a challenge in this research field. OBJECTIVE: This study aimed to explore the association between hypertension and 28-day mortality in sepsis. METHODS: 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. RESULTS: 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. CONCLUSION: This study confirmed the causal relationship between hypertension and the 28-day mortality in sepsis.