β-Blocker Use and Delayed Onset and Progression of Huntington Disease

危险系数 医学 观察研究 亨廷顿病 内科学 析因分析 物理疗法 疾病 置信区间
作者
Jordan L. Schultz,Amy C. Ogilvie,Lyndsay A. Harshman,Peg Nopoulos
出处
期刊:JAMA Neurology [American Medical Association]
卷期号:82 (1): 85-85
标识
DOI:10.1001/jamaneurol.2024.4108
摘要

Importance Huntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD. Objective To evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms. Design, Setting, and Participants This observational, longitudinal multicenter study used the Enroll-HD platform database (initiated September 2011 to present), including propensity score–matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) who were either users or nonusers of β-blockers. Participants included patients with genetically confirmed preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) who were taking a β-blocker and were matched to similar non–β-blocker users. Exposure Uninterrupted use of a β-blocker for more than 1 year. Main Outcomes and Measures For PreHD: risk of receiving a motor diagnosis of HD over time. For mmHD: progression rate of total motor score, total functional capacity score, and the symbol digit modalities test. Post hoc analyses were performed to test additional clarifying hypotheses after the primary analyses were completed. Results This study included 174 preHD β-blocker users (59 males; 115 females) with a mean age of 46.4 (SD, 13.1) years and a mean cytosine-adenine guanine repeat length of 41.1 (SD, 2.4) who were well matched to 174 preHD non–β-blocker users. The preHD β-blocker users showed a statistically significant reduction in the annualized hazard of receiving a motor diagnosis compared with nonusers (n = 174) (hazard ratio, 0.66; 95% CI, 0.46-0.94; P = .02). There were 149 mmHD β-blocker users (86 males; 60 females) with a mean age of 58.9 (SD, 11.3) years and a mean cytosine-adenine guanine repeat length of 42.0 (SD, 2.3) matched to 149 mmHD non–β-blocker users. The β-blocker users had a slower mean annualized worsening in total motor score (mean difference [MD], −0.45; 95% CI, −0.85 to −0.06; q = 0.025), total functional capacity score (MD, 0.10; 95% CI, 0.02-0.18; q = 0.025), and symbol digit modalities test (MD, 0.33; 95% CI, 0.10-0.56; q = 0.017) compared with matched nonusers. Conclusions and Relevance In this study, β-blocker use was associated with delayed motor onset in preHD and reduced the rate of worsening of symptoms in mmHD. These findings demonstrated that β-blockers may have a therapeutic role in HD but further studies are required.

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