Abstract
BACKGROUND: Lactate dehydrogenase (LDH) is a vital metabolic enzyme with significant prognostic value in various diseases. However, the association between LDH levels and mortality risk in cancer patients remains insufficiently characterized. METHODS: This retrospective cohort study included 4,337 cancer patients from the National Health and Nutrition Examination Survey (NHANES) (1999-2018). The exposure variable was serum LDH levels, and the outcome was all-cause mortality. Covariates included demographic characteristics, anthropometric measures, metabolic indicators, and comorbidities. Multivariable Cox proportional hazard models were used to evaluate the association between LDH and mortality. The nonlinear relationship was further investigated using generalized additive models with penalized splines and two-piecewise Cox models. All statistical analyses were performed using EmpowerStats software. RESULTS: During a follow-up of 39,217.58 person-years, 1,779 deaths occurred. After full adjustment, each 10 U/L increase in LDH was associated with a 5.0% increased mortality risk (Hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.03-1.07). A U-shaped relationship between LDH levels and mortality was observed, with an inflection point at 128 U/L, with mortality risk reduced by 7% below this threshold (HR = 0.93, 95% CI: 0.89-0.97) and increasing by 8% above this threshold (HR = 1.08, 95% CI: 1.06-1.10). This pattern was consistent across sexes, with optimal thresholds of 121 U/L for males and 136 U/L for females. CONCLUSION: LDH demonstrates a U-shaped association with all-cause mortality in cancer patients, with sex-specific optimal ranges identified. These findings suggest that LDH levels within the identified ranges are associated with improved survival outcomes in patients with cancer.