Session Information
Date: Monday, June 5, 2017
Session Title: Epidemiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To test the association between Parkinson’s disease (PD) and calcium channel blocker CCB use in individuals carrying LRRK2 mutations.
Background: LRRK2 mutation penetrance is incomplete for PD. Environment and/or other genes may influence penetrance. CCB use, particularly dihydropyridine calcium channel blocker use (diCCB), may lower PD risk, and their possible disease-modifying effects are being studied in a Phase 3 clinical trial. The relationship between CCB use and LRRK2-associated PD has not been studied.
Methods: Symptomatic (“PD”) and asymptomatic (“nonPD”) people who all carried pathogenic G2019S, R1441, or I2020T LRRK2 variants provided information on regular CCB use (defined as > 1 pill per day for > 6 months) prior to index date (onset date in PD, interview date in nonPD). 16 sites from the international LRRK2 study PD-Genetic and Environmental Modifiers (PD GEM) participated. The relationship between regular CCB use and age at onset of PD was determined for any CCB, and separately for diCCB, using a Cox proportional hazards model, adjusted for gender and cigarette smoking.
Results: 169 PD (51% men, mean age 55 years) and 121 nonPD (38% men, mean age 54 years) were enrolled and provided information on CCB use. CCB use was reported in 9.5% of PD and 7.4% of nonPD participants. CCB use was associated with a lower hazard of PD after adjusting for sex and smoking. HR for any CCB use =0.56 (0.33-0.95) and for diCCB use HR=0.53 (0.27-1.04) and non-diCCB HR=0.67 (0.32-1.44). After adjusting for geographic region the hazard ratio estimates were similar: any CCB use HR=0.62 (0.36-1.05), diCCB HR=0.60 (0.30-1.18) and non-diCCB HR=0.71 (0.33-1.53). Results were similar in men and women.
Conclusions: Regular CCB use is associated with reduced penetrance/later age at onset in LRRK2 associated PD for both dihydropyridine and non-dihydropyridine CCBs. After adjusting for region this was not significant but this may be due to being underpowered. CCBs may be useful as disease-modifying treatments in LRRK2-associated PD. A non-specific effect secondary to a reduction in blood pressure cannot be ruled out.
To cite this abstract in AMA style:
C. Marras, K. Marder, R. Alcalay, R. Saunders-Pullman, C. Meng, S. Goldman, A. Lang, M. Korell, M. San Luciano, E. Tolosa, B. Schuele, A. Brice, S. Goldwurm, G. Riboldazzi, C. Klein, G. Mellick, C. Sue, E.K. Tan, K. Brockmann, K. Hasegawa, S. Bressman, J. Ferreira, M. Tazir, W. Langston, D. Berg, C. Tanner. Calcium Channel Blocking Drugs and Risk of LRRK2 Parkinson’s Disease [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/calcium-channel-blocking-drugs-and-risk-of-lrrk2-parkinsons-disease/. Accessed November 22, 2024.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/calcium-channel-blocking-drugs-and-risk-of-lrrk2-parkinsons-disease/