RT Journal Article
SR Electronic
T1 Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1062
OP e1071
DO 10.1212/WNL.0000000000201657
VO 100
IS 10
A1 Mark R. Janse van Mantgem
A1 Wouter van Rheenen
A1 Anemone V. Hackeng
A1 Michael A. van Es
A1 Jan H. Veldink
A1 Leonard H. van den Berg
A1 Ruben P.A. van Eijk
YR 2023
UL http://n.neurology.org/content/100/10/e1062.abstract
AB Background and Objective To explore the association between lipids, polygenic profile scores (PPS) for biomarkers of lipid metabolism, markers of disease severity, and survival in patients with amyotrophic lateral sclerosis (ALS).Methods We meta-analyzed the current literature on the prognostic value of lipids in patients with ALS. Subsequently, we evaluated the relationship between lipid levels at diagnosis, clinical disease stage, and survival in all consecutive patients diagnosed in the Netherlands. We determined the hazard ratio (HR) of each lipid for overall survival, defined as death from any cause. A subset of patients was matched to a previous genome-wide association study; data were used to calculate PPS for biomarkers of lipid metabolism and to determine the association between observed lipid levels at diagnosis and survival.Results Meta-analysis of 4 studies indicated that none of the biomarkers of the lipid metabolism were statistically significantly associated with overall survival; there was, however, considerable heterogeneity between study results. Using individual patient data (N = 1,324), we found that increased high-density lipoprotein (HDL) cholesterol was associated with poorer survival (HR of 1.33 (95% CI 1.14–1.55, p < 0.001)). The correlation between BMI and HDL cholesterol (Pearson r −0.26, 95% CI −0.32 to −0.20) was negative and between BMI and triglycerides (TG) positive (Pearson r 0.18, 95% CI 0.12–0.24). Serum concentrations of total cholesterol and LDL cholesterol were lower in more advanced clinical stages (both p < 0.001). PPS for biomarkers of lipid metabolism explained 1.2%–13.1% of their variance at diagnosis. None of the PPS was significantly associated with survival (all p > 0.50).Discussion Lipids may contain valuable information about disease severity and prognosis, but their main value may be driven as a consequence of disease progression. Our results underscore that gaining further insight into lipid metabolism and longitudinal data on serum concentrations of the lipid profile could improve the monitoring of patients and potentially further disentangle ALS pathogenesis.ALS=amyotrophic lateral sclerosis; ALSFRS=ALS functional rating scale; BMI=body mass index; EEC=El Escorial criteria; ENCALS=European Network to Cure ALS; FTD=frontotemporal dementia; HDL=high-density lipoprotein; HDL-C=HDL cholesterol; HR=hazard ratio; LDL-C=low-density lipoprotein cholesterol; PPS=polygenic profile score; TC=total cholesterol; TG=triglycerides