Higher total cholesterol and low-density lipoprotein as prognostic indicators of slower progression and prolonged survival in Chinese ALS patients: a cohort study

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with highly heterogeneous progression and limited prognostic biomarkers. Altered lipid metabolism has been implicated in ALS pathogenesis, but its prognostic value remains unclear. This study aimed to evaluate the associations between blood lipid levels and ALS progression and survival in a Chinese patient cohort. A retrospective cohort study was conducted on 1562 ALS patients from Peking University Third Hospital (2007–2016). Propensity score matching and multiple imputation were used to minimize selection bias and address missing data. Baseline lipid profiles were collected, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), LDL/HDL ratio, apolipoprotein A, apolipoprotein B, and lipoprotein a. The primary outcomes were ALS disease progression rate and survival. Associations were assessed using multivariate linear regression, Kaplan–Meier survival analysis, and Cox proportional hazards models. Sex-stratified analyses and mediation analyses for BMI were also performed. A total of 221 patients were ultimately included in the analyses. Higher baseline HDL and LDL levels were associated with delayed symptom onset (6.60 and 1.70 years per 1 mmol/L increase, respectively; P < 0.05). Elevated LDL (β = −0.137; P = 0.037) and LDL/HDL ratio (β = −0.149; P = 0.039) were nominally associated with slower functional decline. In male patients, higher total cholesterol and LDL were nominally associated with a lower risk of death or tracheotomy (HR = 0.573 and 0.495, respectively; P < 0.05), whereas no consistent survival associations were observed in female patients. Mediation analysis found no evidence that blood lipids mediated the relationship between BMI and survival. Higher LDL and TC levels showed potential associations with slower disease progression and longer observed survival in Chinese ALS patients, particularly in men. Blood lipids may serve as accessible prognostic biomarkers for ALS management. Further large-scale, multicenter studies are warranted to validate these findings and explore underlying mechanisms.