Serum total lactate dehydrogenase-to-high-density lipoprotein ratio as a predictor of 28-day mortality risk in patients with sepsis: a retrospective cohort study

Background Sepsis remains a major cause of global mortality and is characterized by dysregulated inflammation, metabolic reprogramming, and organ dysfunction. Total lactate dehydrogenase (LDH) and high-density lipoprotein (HDL) reflect complementary aspects of cellular injury and host inflammatory response. This study evaluated the prognostic value of the serum LDH/HDL ratio in patients with sepsis. Methods This multicenter, retrospective cohort study included 1020 patients with sepsis. Baseline total LDH and HDL were measured within 24 h after admission or meeting sepsis criteria, and LDH/HDL was calculated from the first recorded values. Patients were grouped according to empirical LDH/HDL quartiles. Kaplan–Meier survival analysis and Cox proportional hazards models were used to evaluate the association between LDH/HDL and 28-day all-cause mortality. Restricted cubic spline analysis, subgroup analyses, ROC analysis, calibration assessment, and decision curve analysis were performed to assess dose–response patterns and predictive utility. Results The 28-day mortality event count was 304 among 1020 patients. Kaplan–Meier analysis showed significant survival differences across LDH/HDL quartiles (log-rank P < 0.001). In the fully adjusted Cox model, each 1-unit increase in Ln (LDH/HDL) was associated with higher 28-day mortality risk (HR = 1.629, 95% CI 1.418–1.872, P < 0.001). The association was approximately linear in spline analysis. The apparent AUCs were 0.693 for LDH/HDL, 0.715 for SOFA, and 0.758 for SOFA plus Ln (LDH/HDL). Conclusions Higher baseline LDH/HDL was independently associated with increased short-term mortality among patients with sepsis. LDH/HDL may provide additional prognostic information alongside established severity scores, but its incremental clinical value was modest and requires prospective external validation before clinical implementation.