Jo Youngkwon, Kim Seungyeon, Ye Byoung Seok, Lee Euni, Yu Yun Mi
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, South Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Front Pharmacol. 2022 Mar 3;13:837890. doi: 10.3389/fphar.2022.837890. eCollection 2022.
Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson's disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the development of PD is inconsistent. To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability. This was a propensity score-matched retrospective cohort study using 2008-2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66-0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53-0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors. The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.
肾素-血管紧张素系统（RAS）抑制剂已被认为是帕金森病（PD）的保护剂。然而，关于RAS抑制剂与PD发生之间关联的流行病学证据并不一致。本研究旨在通过RAS抑制剂的类型、累积使用时长及其血脑屏障（BBB）穿透能力的程度，探讨RAS抑制剂对缺血性心脏病（IHD）患者发生PD风险的影响。这是一项倾向评分匹配的回顾性队列研究，使用了来自韩国健康保险审查与评估数据库的2008 - 2019年医疗理赔数据。采用多变量Cox比例风险回归分析评估IHD患者使用RAS抑制剂与PD之间的关联。风险以调整后的风险比（aHRs）和95%置信区间（CIs）表示。在10年的随访中，62228例IHD患者中有1086例发生了PD。Cox回归模型显示，与未使用RAS抑制剂相比，使用RAS抑制剂与较低的PD风险显著相关（aHR = 0.75；95% CI 0.66 - 0.85）。具体而言，仅在使用可穿越血脑屏障的血管紧张素II受体阻滞剂（ARBs）时，这种降低的PD风险仍然存在（aHR = 0.62；95% CI = 0.53 - 0.74），并且随着累积使用时长的增加，这种关联更加明确。使用可穿越血脑屏障的血管紧张素转换酶抑制剂未观察到PD风险显著降低。使用具有血脑屏障穿透特性且累积使用时长较长的ARBs可显著降低IHD患者发生PD的风险。这种保护作用可为PD的疾病修饰候选药物提供见解。
Zotero 插件