Premorbid lipid levels and long-term risk of ALS—a population-based cohort study

Abstract

Objective

To assess the temporal relationship between premorbid lipid levels and long-term amyotrophic lateral sclerosis (ALS) risk.

Methods

From Norwegian cardiovascular health surveys (1974–2003), we collected information on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, and other cardiovascular risk factors. ALS incidence and mortality were identified through validated Norwegian health registries. The relation between premorbid lipid levels and ALS risk was assessed by Cox regression models.

Results

Out of 640,066 study participants (51.5% females), 974 individuals (43.5% females) developed ALS. Mean follow-up time was 23.7 (SD 7.1) years among ALS cases. One mmol/l increase in LDL-C was associated with 6% increase in risk for ALS (hazard ratio 1.06 [95% CI: 1.01–1.09]). Higher levels of TC and TG were also associated with increased ALS risk, but only within the last 6–7 years prior to ALS diagnosis or death. No association between HDL-C and ALS risk was found. Adjusting for body mass index, birth cohort, smoking, and physical activity did not alter the results.

Conclusions

Higher levels of LDL-C are associated with increased ALS risk over 40 years later, compatible with a causal relationship. The temporal relationship between TG, TC, and ALS risk suggests that increased levels of these lipid biomarkers represent consequences of ALS.

Keywords:

• Amyotrophic lateral sclerosis
• lipids
• low-density lipoprotein cholesterol
• epidemiology
• risk factors

Acknowledgments

We are grateful for data supplied from the Norwegian Patient Registry, the Norwegian Cause of Death Registry, and the Norwegian Institute of Public Health, and for financial support from the patient organization ALS Norway.

Data availability

The authors do not have permission to share data.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

The study was funded by grants from the patient organization ALS Norway (AMV, TH, and ON), and by grants from South-Eastern Norway Regional Health Authority (grant number 2022050) (ON).