Patients with Huntington disease who received antihypertensive medication had slower disease progression less cognitive impairment compared with patients with untreated hypertension.
Data from Enroll-HD, the largest observational study of patients with Huntington disease (HD) demonstrate a novel association between hypertension and the use of antihypertensive medication with alterations to HD onset, severity and progression. Hypertensive patients taking antihypertensive medication experienced less cognitive, motor, and functional impairment than patients with HD with untreated hypertension.
Enroll-HD was a multicenter, longitudinal, observational study that included data from 15,301 participants (55.6% female, 3539 premanifest HD, 8043 manifest HD, 3629 gene negative and/or family controls at baseline; 50,452 visits in total). Additionally, investigators collected longitudinal data from 5355 individuals who participated in the Registry study.
Investigators used the International Classification of Diseases (10th revision) to diagnose essential hypertension. That excluded patients with hypertension complicating pregnancy, neonatal hypertension, primary pulmonary hypertension, and primary and secondary hypertension involving vessels of the brain or eye and those with comorbid heart or kidney disease.
The main clinical outcome measures observed in the study included the total motor score (TMS), depression and anxiety score on the Hospital Anxiety and Depression Scale, total functional capacity (TFC), and all of the Unified Huntington’s Disease Rating Scale cognitive subdomains. Disease severity and progression were based on performances on motor, functional, behavioral, and cognitive subdomains.
Each patient was assessed on 4 cognitive subtests including Stroop, Verbal Fluency, Trail Making, and the Symbol Digit Modalities Test.
At baseline, 2248 participants (15.5%) had a diagnosis of hypertension, 1697 of which were currently prescribed antihypertensive medication. Hypertension was observed in 13.85% of patients with HD (premanifest and manifest) compared to 19.34% of patients in the control group. In terms of risk factors for hypertension, patients with HD consumed more alcohol, smoked more cigarettes, and smoked for more years than controls.
Notably, clinical onset of HD was diagnosed 1.5 years earlier in normotensive patients compared with hypertensive patients with HD. Those who received treatment for hypertension were diagnosed with clinical onset 2.04±0.41 years later than normotensive patients (P <.001) and 2.25±0.71 years later than those with untreated hypertension (P=.004). The investigators pointed out that age at diagnosis did not differ between untreated hypertensives and normotensive patients.
The study authors observed a longitudinal connection between time and hypertension status between the normotensive and hypertensive groups (95% CI, 0.00015—0.0011; P = .011).
Untreated hypertensives (n = 372) experienced a greater change in TMS over time compared with treated hypertensives (n = 1144; 2.88 ± 1.09, P = .02) and normotensives (n = 3032, 2.47 ± 0.99, P = .03). Additionally, the TMS did not differentiate between normotensive and treated hypertensive HD patients (P = .79). Antihypertensive medication duration use did not predict motor score in treated hypertensive participants (F1,1558 = 0.16; 95% CI, −0.01 to 0.008; P = 069).
When comparing antihypertensive medications, including angiotensin-converting enzyme inhibitors (31.0%), angiotensin receptor blockers (15.7%), beta-blocking agents (18.0%), calcium channel blockers (17.2%), and diuretics (11.7%), there was no observed effect on motor score (P = .68), TFC (P = .10), depression score (P = .78), anxiety score (P = .32), age at onset (P = .26), or performance on any cognitive test (all P > 0.05 FDR-adjusted) based on class.
“Crucially, these results identified an association between hypertension, antihypertensives, and HD disease severity, progression, and onset yet did not allow inference about causality,” the investigators wrote. “Further work should focus on establishing if a causal relationship exists, given the current lack of disease‐modifying therapies currently available for HD.”
Steventon JJ, Rosser AE, Hart E, Murphy K. Hypertension, antihypertensive use and the delayed-onset of Huntington’s disease. Movement Disord. Published online February 4, 2020. doi:10.1002/mds.27976.