Statin use and delayed onset of Huntington's disease

Abstract

Background There is evidence to suggest that 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase inhibitors (statins) may be beneficial in Huntington's disease (HD). Objective This study aimed to determine if statin use was associated with delayed motor diagnosis in participants with premotor HD. Methods Among premotor HD participants from the Enroll‐HD database, statin users were propensity score matched with statin nonusers based on cytosine‐adenine‐guanine–age product score, cytosine‐adenine‐guanine repeat length, baseline age, sex, and region. A Cox regression survival analysis compared the annualized hazard ratio (HR) of receiving a motor diagnosis between the 2 groups. Results The annualized HR of progressing to an HD motor diagnosis was lower in the statin users (n = 89) when compared with the statin nonusers (n = 89; HR = 0.27 [95% CI 0.18‐0.50], P < .0001). Conclusions In patients with premotor HD, statin use was associated with a delayed motor diagnosis of HD. Further studies are warranted to investigate if statins would be an effective disease‐modifying therapy for HD. © 2018 International Parkinson and Movement Disorder Society

Author response to Dr. Aziz—“Statin use and delayed onset of Huntington disease”

“…Although we agree with these concerns, the lipid profiles of participants is not immediately available within the Enroll‐HD database, making it difficult to comment on the association between hyperlipidemia and disease progression. This limitation is outlined in more detail in the discussion section of our article . Overall, we agree with Dr. Aziz that the results of our study should be interpreted with caution until further follow‐up studies are conducted to help us better understand the mechanisms underlying these findings …”

“…This limitation is outlined in more detail in the discussion section of our article . Overall, we agree with Dr. Aziz that the results of our study should be interpreted with caution until further follow‐up studies are conducted to help us better understand the mechanisms underlying these findings …”

“…In addition, the inclusion of all variables that were used for the original matching procedure in the survival analysis (Cytosine‐Adenine‐Guanine repeats, baseline age, baseline CAG‐Age Product score, baseline BMI, sex, region, and history of tobacco abuse) did not alter the results of the statin analysis (hazard ratio = 0.18; 95% confidence interval, 0.10‐0.36; P < .0001), and baseline BMI did not significantly contribute to this enhanced model (ß = −0.030, P = .238), nor did any other included covariates. Again, we agree that body weight is an important consideration when modeling the disease progression of Huntington's disease (HD), but the mean difference in baseline BMI that is observed between the groups did not seem to significantly confound the results of this study . It is also important to consider that the participants included in our study differed from participants in the study cited by Dr. Aziz, in which their group demonstrated that body weight was a predictor of disease progression.…”

“…We greatly appreciate the thoughtful commentary and review provided by Dr. Aziz and agree that confounders, such as body mass index (BMI), are very important to consider when interpreting the results of this study . First, the propensity score matching procedures implemented utilized maximum execution performance with a maximum difference in propensity scores of 0.005 (0.5%).…”

“…In that study, the participants from the Enroll‐HD study were included who had already received a motor diagnosis and were being followed after their clinical diagnosis. However, in our study, only participants who had a diagnostic confidence level of less than 4 at their baseline visit were included . This is important because the relationship between BMI and disease progression prior to motor diagnosis of HD is not well established.…”