Chronic Use of β-Blockers and the Risk of Parkinson’s Disease

Background: Most patients with Parkinson’s disease exhibit intracellular accumulation of the α-synuclein protein encoded by the α-synuclein gene. It was recently shown that β ₂ -adrenoreceptor agonists downregulate this gene, decreasing the apparent risk of Parkinson’s disease by up to 40%. In contrast, exposure to β-blocking drugs increases production of the α-synuclein protein. Objective: The aim of this study was to examine whether chronic exposure to β-blockers is associated with an increased risk for Parkinson’s disease. Patients and Methods: From the electronic charts of Maccabi Health Services, we identified all patients receiving their first β-blocker treatment between 1998 and 2004, and followed them up, for a diagnosis of Parkinson’s disease, between 2005 and 2016. We calculated the morbidity hazard of Parkinson’s disease diagnosis in users of β-blockers compared with non-users, as well as users of angiotensin-converting enzyme (ACE) inhibitors for hypertension, after adjusting for sex, age, weight, smoking status, cholesterol levels and use of statins, employing the Cox proportional hazard model. We also conducted a Kaplan–Meier survival analysis. Results: Overall, 145,098 patients received β-blockers, and 1,187,151 patients did not. The adjusted hazard ratio for Parkinson’s disease among β-blocker users was 1.51 (95% confidence interval 1.28–1.77; p < 0.0001). In contrast, the Parkinson’s disease morbidity hazard for patients receiving ACE inhibitors was no different than for the general population. The morbidity risk showed the effect of cumulative dose response with low threshold levels. Conclusions: Chronic use of β-blockers confers a time- and dose-dependent increased risk for Parkinson’s disease. In view of the available alternatives for β-blockers, their chronic use should be carefully reconsidered.