Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM U1018, Team «Exposome, Heredity, Cancer and Health», CESP, Villejuif, France.
Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM U1018, Team «High-Dimensional Biostatistics for Drug Safety and Genomics», CESP, Villejuif, France.
Mov Disord. 2023 May;38(5):854-865. doi: 10.1002/mds.29349. Epub 2023 Feb 14.
Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures.
We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation.
We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation.
The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins.
Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
他汀类药物是帕金森病（PD）药物再利用的候选药物。很少有研究基于时间变化的暴露来检查反向因果关系、他汀类药物亚组和剂量反应关系。
我们研究了他汀类药物的使用是否与 PD 的发病率有关，同时试图克服之前描述的局限性，特别是反向因果关系。
我们使用了法国女性 E3N 队列研究的数据（随访时间为 2004 年至 2018 年）。通过多个来源确定新诊断的 PD，并由专家进行验证。新的他汀类药物使用者通过相关药物索赔确定。我们建立了一个嵌套病例对照研究，以描述诊断前的他汀类药物处方和医疗咨询轨迹。我们使用时间变化的多变量 Cox 比例风险回归模型来研究他汀类药物与 PD 的关系。暴露指数包括既往使用、累积时间/剂量、平均日剂量，并滞后 5 年以解决反向因果关系。
病例对照研究（693 例病例，13784 例对照）显示病例对照轨迹存在差异，病例组在诊断前 5 年内发生变化。在 73925 名女性（年龄 54-79 岁）中，524 人患有 PD，11552 人在滞后分析中开始使用他汀类药物。任何他汀类药物的既往使用与 PD 无关（风险比 [HR] = 0.87，95%置信区间 [CI] = 0.67-1.11）。相反，亲脂性他汀类药物的既往使用与较低的 PD 发病率显著相关（HR = 0.70，95%CI = 0.51-0.98），且平均日剂量存在剂量反应关系（P 线性趋势 = 0.02）。亲水性他汀类药物则没有关联。
至少 5 年前使用亲脂性他汀类药物与女性 PD 发病率降低相关，且与平均日剂量存在剂量反应关系。
