Does arterial hypertension influence the onset of Huntington's disease?

Abstract

Huntington’s disease (HD) age of onset (AO) is mainly determined by the length of the CAG repeat expansion in the huntingtin gene. The remaining AO variability has been attributed to other little-known factors. A factor that has been associated with other neurodegenerative diseases is arterial hypertension (AHT). The aim of this study is to evaluate the contribution of AHT to the AO of HD. We used data from a cohort of 630 European HD patients with adult onset collected by the REGISTRY project of the European Huntington’s Disease Network. Multiple linear regression and ANOVA, controlling for the CAG repeat number of the expanded allele (CAGexp) of each patient, were performed to assess the association between the AHT condition and the AO of the motor symptoms (mAO). The results showed a significant association between AHT and mAO, especially when we only considered the patients diagnosed with AHT prior to manifesting any HD signs (pre-HD AHT). Remarkably, despite the low number of cases, those patients developed motor symptoms 5–8 years later than normotensive patients in the most frequent CAGexp range (40–44). AHT is an age-related condition and consequently, the age of the patient at the time of data collection could be a confounder variable. However, given that most pre-HD AHT patients included in our study had started treatment with antihypertensive drugs prior to the onset of HD, and that antihypertensive drugs have been suggested to confer a neuroprotective effect in other neurodegenerative diseases, raises the interest in elucidating the impact of AHT and/or AHT treatment in HD age of onset in further studies. A confirmation of our results in a larger sample set would open the possibility to significantly improve HD management.

Hypertension Is Associated With an Earlier Age of Onset of Huntington's Disease

“…The aforementioned analyses were performed based on the assumption that treating the diagnosis of HTN as a time‐dependent covariate was important. To ensure that this assumption was accurate, we analyzed the Enroll dataset using similar methods as described in the previous report in an effort to replicate those results . In addition, we repeated our primary analysis, but did not include age as a covariate and did not treat the diagnosis of HTN as a time‐dependent covariate.…”

“…These findings do contradict a recently published study that queried the role of blood pressure on the ADx of HD and suggested that the presence of HTN was associated with a later ADx, thus implying a protective effect of HTN in HD. 19 The authors of that study noted that their findings may have been influenced by the fact that the prevalence of HTN increases with age. We have addressed that possibility and uncovered an opposite effect of HTN on the ADx.…”

“…In fact, we employed the same methods used in the previous study and replicated those results. 19 In addition, we repeated our survival analysis but did not control for age and did not treat HTN as a time-dependent covariate, which resulted in findings suggestive of a protective effect of HTN in HD. These analyses demonstrate the importance of accounting for the fact that the risk of developing HTN increases with age, as we have done.…”

“…A recent study using the REGISTRY database suggested that a concomitant diagnosis of HTN and HD was associated with a significantly later ADx compared with normotensive patients with HD . Unfortunately, this study did not seem to account for the fact that the incidence of HTN increases with age, which could mistakenly demonstrate a protective effect of HTN.…”

“…To ensure that this assumption was accurate, we analyzed the Enroll dataset using similar methods as described in the previous report in an effort to replicate those results. 19 In addition, we repeated our primary analysis, but did not include age as a covariate and did not treat the diagnosis of HTN as a time-dependent covariate. In both instances, we spuriously induced a significant protective effect of HTN in HD.…”