Abstract

Background and PurposeHypertension has been associated with Parkinson's disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients.MethodsHypertensive patients who were free of PD, dementia and stroke were recruited from 2005–2006 using Taiwan National Health Insurance Database. We examined the association between the use of calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and the incidence of PD using beta-blockers as the reference. Cox regression model with time-varying medication use was applied.ResultsAmong 65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a reduced risk of PD (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.57–0.90). Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was associated with a decreased risk of PD (aHR = .69 [55–0.87]. Further decreased association was observed for higher cumulative doses of felodipine (aHR = 0.54 [0.36–0.80]) and amlodipine (aHR = 0.60 [0.45–0.79]). There was no association between the use of ACEIs (aHR = 0.80 [0.64–1.00]) or ARBs (aHR = 0.86 [0.69–1.08]) with PD. A potentially decreased association was only found for higher cumulative use of ACEIs (HR = 0.52 [0.34–0.80]) and ARBs (HR = 0.52 [0.33–0.80]).ConclusionsOur study suggests centrally-acting dihydropyridine CCB use and high cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD in hypertensive patients. Further long-term follow-up studies are needed to confirm the potential beneficial effects of antihypertensive agents in PD.

Highlights

  • Parkinson’s disease (PD) is a common neurodegenerative disorder which underlying mechanism leading to dopaminergic neuron death remains elusive and current therapies remain purely symptomatic [1,2,3,4]

  • These in vitro studies form the bases of hypothesis that antihypertensive agents, especially angiotensin receptor blockers (ARBs), inhibitors of angiotensin converting enzyme (ACEIs), and calcium channel blockers (CCBs), may have possible neuroprotective effects in PD [11,12,13,14,15]

  • Compared with BBs, the use of CCBs was associated with a significantly reduced risk of PD

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Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder which underlying mechanism leading to dopaminergic neuron death remains elusive and current therapies remain purely symptomatic [1,2,3,4]. Data from one population-based cohort study of Finland shows that, as compared with normotensive subjects, women with hypertension are associated with a 60% increased risk of PD [6]. Angiotensin II, the effector peptide of the central renin-angiotensin system (RAS) in substantia nigra, is a pro-inflammatory compound that can activate the oxidative cascades with resulting neuronal death [10]. These in vitro studies form the bases of hypothesis that antihypertensive agents, especially angiotensin receptor blockers (ARBs), inhibitors of angiotensin converting enzyme (ACEIs), and calcium channel blockers (CCBs), may have possible neuroprotective effects in PD [11,12,13,14,15]. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients

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