Angiotensin Receptor Blockers May Reduce PD Risk in Patients With Hypertension

A statistically significant reduction of Parkinson disease (PD) risk in patients with newly diagnosed hypertension was seen following treatment with angiotensin receptor blockers (ARBs), according to the findings of a retrospective cohort study published in The American Journal of Medicine.

As the second-most common neurodegenerative disease after Alzheimer disease, PD has several approved symptom-alleviating medications, but no disease modification treatments are yet available. As a commonly used antihypertensive, ARBs have been shown to reduce oxidative stress in prior animal and in vitro studies, a key factor implicated in the pathogenesis and progression of PD.

“The renin-angiotensin system (RAS) has long been known for its role in blood pressure regulation and sodium and water homeostasis. ARBs have been proven to control blood pressure effectively and safely by blocking the main RAS effector, the type I angiotensin receptor,” explained the study authors.

“Recent studies have revealed the existence of local RAS in the brain, containing the same components as the classic RAS, and may be crucial in the process of dopaminergic neuron loss in PD.”

They enrolled 107,207 patients with newly diagnosed hypertension from the Taiwan National Health Insurance Research Dataset between 2001 and 2013 to compare the PD risk with ARB treatment users (n = 49,572) and nonusers (n =  57,635), as well as assess the dose effect of ARBs on PD risk reduction.

Treatment users were stratified into 4 subgroups according to cumulative ARB defined daily doses (DDD) of 91 to 180, 181 to 360, 361 to 720, and more than 720, and then these users were compared with nonusers based on PD risk reduction. Information was also collected on 5 related comorbidities to examine whether these diseases affected the risk of PD during the study period: diabetes, stroke, chronic kidney disease (CKD), liver cirrhosis, and chronic obstructive pulmonary disease (COPD) and related lung diseases.

Among the study cohort, ARB-treated patients were more likely to be men and exhibited significantly higher rates of diabetes, stroke, CKD, liver cirrhosis, and COPD than patients without ARB treatment. Rates of statin use and use of all classes of antihypertensive drugs were also significantly higher in the ARB-treated group.

A total of 527 (1.1%) PD cases were identified among patients with ARB treatment in a median observation period of 8.4 years vs 1255 (2.2%) PD cases in those without ARB treatment in a median observation period of 6.8 years.

After adjusting for age, sex, and other confounding variables, including the 5 related comorbidities, the risk for developing PD was found to be statistically lower in ARB users vs nonusers (adjusted HR [aHR], 0.56; 95% CI, 0.51-0.63). Kaplan-Meier survival analysis for patients with and without ARB treatment showed a significant difference between the 2 groups regarding PD risk (log-rank test, P < .001).

A consistent risk reduction was shown in adjusted models for PD among subgroups with different DDDs vs nonusers, in which the greatest reduction was observed among those receiving the most doses of ARBs:

• DDD of 91 to 180 (aHR, 0.62; 95% CI, 0.50-0.75)
• DDD of 181 to 360 (aHR, 0.64; 95% CI, 0.53-0.77)
• DDD of 361 to 720 (aHR, 0.62; 95% CI, 0.51-0.74)
• DDD above 720 (aHR, 0.44; 95% CI, 0.37-0.53)

“This study proposes that reduced brain RAS by ARB treatment may constitute an effective neuroprotective strategy for reducing PD risk in patients with newly diagnosed hypertension,” concluded researchers. “Further clinical trials focusing on ARB treatment are needed to confirm its neuroprotective effects in PD.”

Reference

Lin HC, Tseng YF, Shen AL, Chao JCJ, Hsu CY, Lin HL. Association of angiotensin receptor blockers with incident Parkinson disease in patients with hypertension: A retrospective cohort study. Am J Med. 2022 May 14;S0002-9343(22)00351-5. doi:10.1016/j.amjmed.2022.04.029