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March 07, 2023; 100 (10) Research ArticleOpen Access

Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis

A Meta-analysis and Population-Based Study

View ORCID ProfileMark R. Janse van Mantgem, View ORCID ProfileWouter van Rheenen, Anemone V. Hackeng, Michael A. van Es, View ORCID ProfileJan H. Veldink, Leonard H. van den Berg, View ORCID ProfileRuben P.A. van Eijk
First published December 2, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201657
Mark R. Janse van Mantgem
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Wouter van Rheenen
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Anemone V. Hackeng
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Michael A. van Es
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Jan H. Veldink
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Leonard H. van den Berg
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Ruben P.A. van Eijk
From the Department of Neurology (M.R.J.M., W.R., A.V.H., M.A.E., J.H.V., L.H.B., R.P.A.E.), UMC Utrecht Brain Center, and Biostatistics & Research Support (R.P.A.E.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
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Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis
A Meta-analysis and Population-Based Study
Mark R. Janse van Mantgem, Wouter van Rheenen, Anemone V. Hackeng, Michael A. van Es, Jan H. Veldink, Leonard H. van den Berg, Ruben P.A. van Eijk
Neurology Mar 2023, 100 (10) e1062-e1071; DOI: 10.1212/WNL.0000000000201657

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Abstract

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.

Glossary

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

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Submitted and externally peer reviewed. The handling editor was Associate Editor Anthony Amato, MD, FAAN.

  • ↵* These authors contributed equally to this work as senior authors.

  • Received March 3, 2022.
  • Accepted in final form October 20, 2022.
  • Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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