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.

中文翻译：

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诊断前血浆脂质水平和肌萎缩侧索硬化症的风险

摘要

客观的

评估诊断前血脂水平是否与肌萎缩侧索硬化症 (ALS) 风险相关。方法：我们在五个大型前瞻性美国队列（护士健康研究、卫生专业人员随访研究、癌症预防研究 II 营养队列、多民族队列研究和妇女健康倡议）中进行了匹配的病例对照研究，并确定了 275 名在随访期间发展为 ALS 并在疾病诊断前提供了血液样本的人。对于每个 ALS 病例，我们随机选择了两名在病例诊断时还活着并在队列、出生年份（±1 年）、性别、种族/民族、禁食状态和抽血时间上匹配的对照。我们测量了血浆样本中的总胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL-C)、高密度脂蛋白胆固醇 (HDL-C) 和甘油三酯 (TG) 水平，结果：在针对匹配因素调整的分析中，较高水平的 HDL-C 与较高的 ALS 风险相关（风险比 [RR] Q4 与 Q1：1.78，95% 置信区间 [CI]：1.18-2.69，p趋势： 0.007)。在另外调整体重指数、体力活动、吸烟、饮酒、血浆尿酸盐水平和降胆固醇药物使用的多变量分析中，估计值仍然相似（RR Q4 vs. Q1：1.71，95% CI：1.07-2.73 , p趋势：0.02)。TC、LDL-C 和 TG 的血浆水平与 ALS 风险无关。结论：更高的诊断前 HDL-C 水平，但与其他脂质水平无关，与更高的 ALS 风险相关。