Antihypertensives Linked to Later Onset, Milder Disease in Huntington’s Patients, Large Study Finds

Use of antihypertensives — medications used to treat high blood pressure — is associated with milder disease, slower progression, and delayed clinical onset in people with Huntington’s disease, a study found.

The findings suggest an “exciting future avenue to explore the repurposing of specific antihypertensive medications for the treatment of neurodegenerative disease,” the researchers said.

The study, “Hypertension, Antihypertensive Use and the Delayed‐Onset of Huntington’s Disease,” was published in the journal Movement Disorders.

In addition to the characteristic cognitive, behavioral, and movement deficits, some symptoms associated with Huntington’s disease suggest problems in the autonomic nervous system, the part of the nervous system that acts largely automatically and unconsciously to regulate bodily functions.  These symptoms include excessive sweating, urination difficulties, sexual dysfunction, gastrointestinal problems, and a faster than normal heart rate (tachycardia).

The autonomic nervous system also plays a role in modulating cardiovascular functions, including the control of blood pressure. Problems with blood pressure, including high blood pressure (hypertension), have been associated with neurodegenerative diseases.

While cardiovascular dysfunctions are increasingly recognized as contributors to Huntington’s, little is known about the prevalence and effects of cardiovascular risk factors, including hypertension.

Because hypertension can be treated and controlled, it is important to understand its role in Huntington’s, since disease onset and course are likely influenced by modifiable environmental factors.

Researchers analyzed data from the disease’s largest observational study — a global follow‐on study called Enroll‐HD — to investigate the relationship between hypertension, disease severity, and clinical rates of disease progression in Huntington’s mutation carriers.

The study used data from 14,534 participants in Enroll‐HD: some 3,503 with premanifest disease (those who carried gene mutations but had not yet shown symptoms) 7,409 with manifest disease, and 3,622 controls who were negative for Huntington’s mutations. Follow-up data from 5,355 individuals were also included.

Among the Enroll‐HD participants, 2,248 (15.5%) were hypertensive, and of these, 1,697 (75.5%) were taking antihypertension medication.

Those with hypertension tended to be older, with higher body mass index and lower CAG repeat length. This group also included relatively fewer females, compared with those with normal blood pressure.

Hypertension was less prevalent in Huntington’s patients compared with age‐matched controls. It affected 13.85% of premanifest  and manifest patients combined, and was present in 19.34% of subjects without the disease.

Smoking and alcohol consumption were among risk factors for hypertension in Huntington’s patients.

Those with hypertension who did not receive antihypertensive treatment scored worse on measures of cognitive skills, depression, and total functional capacity, and saw a more marked decline in motor skills over time, than patients with normal blood pressure.

Hypertensive patients who were taking antihypertensive medication had fewer motor, cognitive, and functional impairments than patients not taking those medications.

Moreover, hypertensive patients taking medications had a later onset of Huntington’s disease compared to both untreated hypertensive and patients with normal blood pressure: an average of 2.25 and 2.04 years later, respectively.

The results are supported by a prior study that found a link between delay in disease onset and antihypertensive medication.

“One interpretation of these results is that either antihypertensive medication or the lowering of blood pressure is driving the delay in onset age, with a currently unknown mechanism and implications for HD management,” the researchers said.

Previous work in Alzheimer’s and Parkinson’s support the first hypothesis, suggesting that antihypertensive medication may protect against neurodegeneration.

“Antihypertensive medication was associated with reduced disease severity for all clinical measures in hypertensive HD patients,” the researchers said. “Further investigation into the therapeutic efficacy of antihypertensive medication in cases of prehypertension in HD and in premanifest HD is warranted, along with the combinatorial effect with other HD symptom management therapeutics.”