Stress Hyperglycemia Ratio and the Risk of Sepsis in Patients With Heart Failure: Retrospective Cohort Study From Medical Information Mart for Intensive Care-IV

Background: The occurrence of sepsis in patients with heart failure (HF) has received less attention in research; yet, it poses a significant clinical challenge due to the complex interplay between chronic cardiac dysfunction and acute systemic inflammation. The stress hyperglycemia ratio (SHR) has emerged as an independent risk factor in various cardiovascular diseases and patients with sepsis, but its role in predicting sepsis risk in patients with HF remains underexplored. Objective: This study investigates the association between SHR and sepsis occurrence in patients with HF and explores the potential mediating role of inflammatory indicators. Methods: This retrospective cohort study used data from the Medical Information Mart for Intensive Care-IV (version 3.0) database, encompassing patients with HF from critical care units. SHR was calculated based on initial blood glucose and glycated hemoglobin A1c levels. The analysis population was divided into 4 groups based on the quartiles of the SHR. The primary end point was 7-day sepsis incidence, which was diagnosed following Sepsis-3 criteria. Results: Within the 1205-patient cohort (male: 764/1205, 63.4%; median 71.51, IQR 62.45-79.47), a total of 162 (13.4%) patients with HF experienced sepsis within 7 days. In the fully adjusted model, a per-unit SHR increase was linked to an 18% higher sepsis risk (hazard ratio 1.18, 95% CI 1.01-1.38; P=.04). Restricted cubic splines analysis showed a nonlinear saturation effect association (P for nonlinearity=.02), which was consistent in the diabetic subgroup (P for nonlinearity=.01). After adjusting for 7-day mortality as a competing event using the Fine-Gray model, SHR was independently associated with an increased risk of sepsis (P=.01). The association between SHR and sepsis was significantly modified by diabetes mellitus, BMI, and insulin use (all P for interaction<.05). Furthermore, mediation analysis indicated that several inflammatory indices, including the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-neutrophil ratio, systemic inflammation response index, and monocyte-neutrophil-to-lymphocyte ratio, significantly mediated the association in critically ill patients with HF. Conclusions: In critically ill patients with HF, an elevated SHR was associated with heightened 7-day sepsis risk, especially for those combined with diabetes. Furthermore, systemic inflammatory indices partially mediated this association in the overall population, implicating inflammation as a potential mechanistic link between SHR and sepsis.