Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis

Abstract

Objective

To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. Methods: We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women’s Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Results: Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18–2.69, p trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07–2.73, p trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Conclusions: Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.

Keywords:

• Amyotrophic lateral sclerosis
• risk factors in epidemiology
• cohort studies

Acknowledgments

We would like to thank the participants and staff of the NHS, HPFS, MEC, CPS-II, and WHI for their valuable contributions.

Short list of WHI Investigators: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg. Investigators and Academic Centers: (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Jennifer Robinson; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (University of Nevada, Reno, NV) Robert Brunner. Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Mark Espeland.

Declaration of interest

Dr. Kjetil Bjornevik reports no disclosures; Dr. Éilis J. O’Reilly reports no disclosures; Dr. Marianna Cortese reports no disclosures; Dr. Jeremy D. Furtado reports no disclosures; Dr. Laurence N. Kolonel reports no disclosures; Dr. Loic Le Marchand reports no disclosures; Dr. Marjorie L. McCullough reports no disclosures; Dr. Sabrina Paganoni reports research grants from Amylyx Pharmaceuticals, Revalesio Corporation, the ALS Association, ALS Finding a Cure, the American Academy of Neurology, the Salah Foundation, the Spastic Paraplegia Foundation; Dr. Michael A. Schwarzschild reports no disclosures; Dr. Aladdin H. Shadyab reports being a consultant for Rancho BioSciences, LLC; Dr. JoAnn E. Manson reports no disclosures; Dr. Alberto Ascherio reports no disclosures. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Additional information

Funding

This study was supported by a grant from the National Institute of Neurological Diseases and Stroke (R01 NS045893) awarded to Alberto Ascherio. The NHS is funded by the National Institutes of Health through grants UM1 CA186107 and R01 CA49449. The HPFS cohort is funded by the National Institutes of Health through grant U01 CA167552. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohorts. The MEC cohort is funded by the National Institutes of Health through U01 CA164973. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.