Supplementary Material for: Cardiovascular Diseases, Medications, and ALS: A Population-Based Case-Control Study

<b><i>Introduction:</i></b> We investigated the associations between antecedent all-cause CVD diagnoses, cause-specific CVD diagnosis, and CVD medication prescriptions with the risk of developing amyotrophic lateral sclerosis (ALS). <b><i>Materials and Methods:</i></b> We conducted a population-based case-control study of U.S. Medicare enrollees from 2006 to 2013. The final sample included 3,714 incident ALS cases and 18,570 controls (matched on age, sex, enrollment length, and county). Information was collected from Medicare Parts A, B, and D administrative claims data on hypertension, ischemic heart disease, heart failure, acute myocardial infarction, atrial fibrillation, prescriptions of angiotensin-converting enzyme inhibitors, angiotensin II receptors blockers, calcium channel blockers, beta blockers, and antiarrhythmics. Associations were evaluated using conditional logistic regression adjusting for age, sex, race/ethnicity, geographical location, alcohol and tobacco use, and socioeconomic status. <b><i>Results:</i></b> The odds ratio (OR) for having one or more ICD-9 codes for any cardiovascular disease diagnosis at least 24 months prior to the date of ALS diagnosis was 0.85 (95% confidence interval [CI]: 0.78–0.92). Cardiovascular conditions that were inversely associated with ALS included heart failure (OR = 0.79; 95% CI 0.70–0.89), atrial fibrillation (OR = 0.81; 95% CI 0.77–0.92), and hypertension (OR = 0.91; 95% CI 0.84–0.98). Exposures to several classes of cardiovascular medications were inversely associated with ALS risk even after adjusting for confounding by indication, including ACE inhibitors (OR = 0.84, 95% CI 0.77–0.91), calcium channel blockers (OR = 0.64, 95% CI 0.59–0.70), and beta blockers (OR = 0.76, 95% CI 0.71–0.83). <b><i>Discussion/Conclusion:</i></b> These findings merit additional research, including animal studies and pilot clinical trials, to further evaluate and evidence the effects of ACEIs, CCBs, and BBs on the risk of developing and clinical expression of ALS.

<b><i>引言：</i></b> 本研究探讨了前驱性全因心血管疾病（cardiovascular disease, CVD）诊断、特异性病因心血管疾病诊断以及心血管疾病用药处方与肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）发病风险之间的关联。<b><i>材料与方法：</i></b> 本研究针对2006至2013年美国医疗保险参保人群开展了一项基于人群的病例对照研究。最终样本纳入3714例新发ALS病例与18570例对照（按年龄、性别、参保时长及县域进行匹配）。研究数据取自医疗保险A、B、D部分的行政索赔数据，涵盖高血压、缺血性心脏病、心力衰竭、急性心肌梗死、心房颤动，以及血管紧张素转换酶抑制剂（angiotensin-converting enzyme inhibitors, ACEI）、血管紧张素Ⅱ受体阻滞剂、钙通道阻滞剂（calcium channel blockers, CCB）、β受体阻滞剂（beta blockers, BB）和抗心律失常药物的处方信息。采用条件logistic回归模型进行关联分析，校正因素包括年龄、性别、种族/族裔、地理位置、烟酒使用情况及社会经济地位。<b><i>结果：</i></b> 在ALS诊断至少24个月前即存在一项或多项心血管疾病诊断的ICD-9编码的受试者，其发病优势比（odds ratio, OR）为0.85（95%置信区间[CI]：0.78~0.92）。与ALS发病风险呈负相关的心血管疾病包括心力衰竭（OR=0.79；95%CI 0.70~0.89）、心房颤动（OR=0.81；95%CI 0.77~0.92）及高血压（OR=0.91；95%CI 0.84~0.98）。在校正指征混杂因素后，数类心血管药物的暴露仍与ALS发病风险呈负相关，包括ACEI（OR=0.84，95%CI 0.77~0.91）、CCB（OR=0.64，95%CI 0.59~0.70）及BB（OR=0.76，95%CI 0.71~0.83）。<b><i>讨论/结论：</i></b> 本研究结果有待进一步研究验证，包括动物实验与先导性临床试验，以深入评估ACEI、CCB及BB对ALS发病风险及临床表型表达的影响。