Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
J Neurol Neurosurg Psychiatry. 2011 Jun;82(6):638-42. doi: 10.1136/jnnp.2010.236752. Epub 2011 Apr 6.
Reports of increased amyotrophic lateral sclerosis (ALS) with hyperlipidaemia and elevated plasma homocysteine levels as well as cigarette-smoking and polymorphisms in angiogenic genes suggest a role for altered vascular homeostasis in ALS pathogenesis. The authors assessed the association between vascular risk factors and ALS.
Traditional cardiovascular risk factors (smoking, hypertension, hypercholesterolaemia, diabetes and body mass index (BMI)) and cardiovascular disease prior to ALS onset established by a questionnaire were compared in 334 patients and 538 age- and sex-matched controls. Biochemical assessments (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and homocysteine) at diagnosis were measured in blood samples of 303 patients with ALS and compared with prospectively collected data from 2100 population-based controls.
Patients with ALS used cholesterol-lowering agents less frequently (OR=0.6, p=0.008) and had a lower BMI (OR=0.9, p=0.001), a lower LDL/HDL ratio (women: OR=0.5, p<0.001; men: OR=0.4, p<0.001) and lower homocysteine levels (women: OR=0.9, p=0.02; men: OR=0.9, p<0.001). The mean LDL and TC levels were significantly lower among patients with a lower functional vital capacity percentage of predicted (FVC). In the univariate analysis, a higher LDL/HDL ratio correlated with increased survival (HR=0.9, p=0.04); after adjusting for the confounders age, site and FVC, no difference was observed.
Vascular risk factors, measured clinically and biochemically, were not associated with increased ALS. Instead, patients reported less use of cholesterol-lowering medication and had a lower premorbid BMI and favourable lipid profile-all findings consistent with the hypothesis that a higher metabolic rate plays a role in ALS.
有报道称，脂代谢异常、同型半胱氨酸水平升高、吸烟以及血管生成基因多态性与肌萎缩侧索硬化症（ALS）的发生有关，这表明血管内环境稳态的改变可能与 ALS 的发病机制有关。作者评估了血管危险因素与 ALS 之间的相关性。
通过问卷调查，比较了 334 例 ALS 患者和 538 名年龄和性别匹配的对照组中传统心血管危险因素（吸烟、高血压、高胆固醇血症、糖尿病和体重指数（BMI））和 ALS 发病前的心血管疾病。对 303 例 ALS 患者的血液样本进行了生化评估（总胆固醇（TC）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、hs-CRP 和同型半胱氨酸），并与前瞻性收集的 2100 名基于人群的对照组数据进行了比较。
与对照组相比，ALS 患者使用降脂药物的频率较低（OR=0.6，p=0.008），BMI 较低（OR=0.9，p=0.001），LDL/HDL 比值较低（女性：OR=0.5，p<0.001；男性：OR=0.4，p<0.001），同型半胱氨酸水平较低（女性：OR=0.9，p=0.02；男性：OR=0.9，p<0.001）。在预测肺活量（FVC）百分比较低的患者中，平均 LDL 和 TC 水平显著较低。在单因素分析中，较高的 LDL/HDL 比值与生存时间延长相关（HR=0.9，p=0.04）；在调整年龄、部位和 FVC 等混杂因素后，差异无统计学意义。
临床和生化测量的血管危险因素与 ALS 无关。相反，患者报告降脂药物的使用率较低，且发病前 BMI 较低，血脂谱较好——所有这些发现都与代谢率较高在 ALS 中发挥作用的假说一致。
