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

Abstract

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; cohort studies; risk factors in epidemiology.

Figure 1.

The association of prediagnostic lipid levels with ALS risk using penalized splines (P-splines). * The red lines represent the risk ratio for ALS according to changes in prediagnostic lipid levels relative to the median level in controls. The shaded regions represent 95% confidence intervals. The vertical lines correspond to the fifth, 25^th, 50^th, 75^th, and 95^th percentile for each type of lipid among the controls. The figures are adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, use of cholesterol lowering drugs, and matching factors (age, sex, fasting status, and time of blood draw).