Predictive value of the haptoglobin-to-lactate ratio for mortality in patients with sepsis-associated myocardial injury: a retrospective cohort study

Background Sepsis-induced myocardial injury (SIMI) is a frequent and life-threatening complication among critically ill patients with sepsis. While lactate is a classic marker of tissue hypoperfusion and metabolic stress, haptoglobin (Hp) serves as a vital scavenger of toxic cell-free hemoglobin, reflecting the host's antioxidative defense capacity. Consequently, the haptoglobin-to-lactate ratio (HLR) may represent a novel composite index capturing the balance between physiological reserve and pathological insult. However, the prognostic value of HLR has not been systematically evaluated in the high-risk population of patients with SIMI.This study aimed to examine the association between the HLR and both short- and long-term all-cause mortality in patients with SIMI, and to assess its prognostic value in this high-risk population. Methods This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 3.1) database. Adult patients who met Sepsis-3 criteria and were admitted to the intensive care unit (ICU) were included. SIMI was defined as an elevated serum troponin T (> 0.01 ng/mL) within the first 24 hours of ICU admission in the absence of acute coronary syndrome or other non-septic causes. The HLR was calculated as Hp (mg/dL) divided by serum lactate (mmol/L) on the first ICU day and analyzed both as a continuous variable and in quartiles. Baseline characteristics were compared across HLR quartiles. Survival differences were estimated using Kaplan–Meier curves. Cox proportional hazards regression models were applied to assess the independent association between HLR and 28-day and 90-day all-cause mortality. Non-linear relationships were explored using restricted cubic splines (RCS). Subgroup analyses were performed to test the consistency of associations across clinical strata. Results A total of 609 patients with SIMI were included. Patients in higher HLR quartiles had lower SOFA scores and significantly lower lactate levels compared with those in lower quartiles. Kaplan–Meier analysis demonstrated significantly improved survival with increasing HLR quartiles (log-rank P  < 0.001). In multivariable Cox regression models, a higher HLR was independently associated with reduced 28-day all-cause mortality (Q4 vs. Q1: adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.43–0.95, P  = 0.025) and 90-day all-cause mortality (Q4 vs. Q1: adjusted HR 0.67, 95% CI 0.46–0.96, P  = 0.027). RCS analysis revealed an L-shaped non-linear relationship between HLR and mortality risk, with optimal breakpoints identified at 7.864 for 28-day mortality and 2.125 for 90-day mortality. Subgroup analysis indicated that the prognostic value of HLR was particularly pronounced in elderly patients aged ≥ 65 years ( P for interaction = 0.035). Conclusions The HLR is a novel and reliable biomarker for predicting short- and long-term mortality in septic patients with myocardial injury. This simple, inflammation–metabolism–based index may serve as a convenient tool for risk stratification and prognostic assessment in critical care settings.