Department of Epidemiology, University of California at Los Angeles School of Public Health, Los Angeles, CA, USA.
Ann Neurol. 2010 May;67(5):600-6. doi: 10.1002/ana.21937.
This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.
We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis.
Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications.
Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.
本研究旨在探讨二氢吡啶类 L 型钙通道阻滞剂与帕金森病(PD)的相关性,因为这些药物中的一些能够穿透血脑屏障,具有潜在的神经保护作用,并且之前已经评估过其对 PD 风险的影响。
我们在丹麦国家医院/门诊数据库中确定了 1931 名在 2001 年至 2006 年间首次被诊断为 PD 的患者,并根据出生年份和性别与来自人口登记册的 9651 名对照进行了密度匹配。如果病例和他们相应的对照的索引日期早于医院记录中的首次 PD 诊断,则将其提前到首次记录抗帕金森药物处方的日期。处方是从国家药房数据库中确定的。在我们的主要分析中,我们排除了索引日期/PD 诊断前 2 年的所有钙通道阻滞剂处方。
采用逻辑回归分析,调整年龄、性别、慢性阻塞性肺疾病诊断和 Charlson 合并症评分,我们发现,在索引日期前 1995 年至 2 年期间被处方二氢吡啶类药物(不包括氨氯地平)的患者发生 PD 的可能性较低(比值比,0.73;95%置信区间,0.54-0.97);这种 27%的风险降低与使用时间的长短或强度无关。氨氯地平(一种外周作用药物)和其他降压药物的风险估计接近零。
我们的数据表明,二氢吡啶类 L 型钙通道阻滞剂中的中枢作用药物可能具有潜在的神经保护作用,这在能够区分 L 型通道阻滞剂类型的研究中应进一步研究。