van Duijvenboden Stefan, Ramírez Julia, Scheurink Job, Darweesh Sirwan K L, Orini Michele, Tinker Andrew, Munroe Patricia B, Thannhauser Jos, Evers Luc, IntHout Joanna, Lambiase Pier D, Bloem Bastiaan R, Doherty Aiden, Brouwer Marc A
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Institute of Cardiovascular Science, UCL, London, UK.
Ann Neurol. 2025 Nov;98(5):1004-1013. doi: 10.1002/ana.70010. Epub 2025 Aug 2.
To determine whether established heart rate parameters of exercise, related to cardiac autonomic function, are associated with incident Parkinson's disease, independent of both clinical and autonomic prodromal features.
A study of UK Biobank participants who performed a standardized bicycle exercise test (2009-2013), followed until November 2022, and analyzed in January 2024, was carried out. Heart rate increase from rest to exercise, and heart rate decrease from peak exercise to recovery were associated with incident Parkinson's disease. Multivariable adjustment was performed both for clinical characteristics and for prodromal non-cardiac autonomic features.
A total of 69,288 eligible participants (men 48%, mean age 56.8 years [SD 8.2 years]) were followed for 12.5 years: among the 319 (0.5%) who developed Parkinson's disease, recognized prodromal markers (constipation, bladder dysfunction) were more common at baseline. The median lag time to diagnosis was 9.3 years (interquartile range 4.4). Both heart rate increase (37.5 [SD 11.5] vs 40.8 [SD 12.4] b.p.m., p < 0.001) and recovery (23.4 [SD 8.8] vs. 27.8 [SD 10.3] b.p.m., p < 0.001) were significantly lower in incident cases compared with controls. Heart rate recovery was independently associated with incident Parkinson's disease, whereas heart rate increase was not. Specifically, a blunted heart rate lowering during recovery was associated with a 30% higher risk of incident Parkinson's disease (HR 1.3; 95% CI 1.1-1.4; p < 0.001 per 10 beats less recovery).
Collectively, this suggests that cardiac autonomic involvement precedes clinically manifest Parkinson's disease, and that heart rate recovery might serve as a quantitative prodromal marker. ANN NEUROL 2025;98:1004-1013.
确定与心脏自主神经功能相关的既定运动心率参数是否与帕金森病的发病相关，且独立于临床和自主神经前驱特征。
对英国生物银行中进行标准化自行车运动测试（2009 - 2013年）的参与者进行研究，随访至2022年11月，并于2024年1月进行分析。从静息到运动时的心率增加以及从运动峰值到恢复时的心率降低与帕金森病的发病相关。对临床特征和前驱非心脏自主神经特征均进行了多变量调整。
共有69288名符合条件的参与者（男性占48%，平均年龄56.8岁[标准差8.2岁]）被随访了12.5年：在319名（0.5%）患帕金森病的参与者中，公认的前驱标志物（便秘、膀胱功能障碍）在基线时更为常见。诊断的中位延迟时间为9.3年（四分位间距4.4年）。与对照组相比，发病病例的心率增加（37.5[标准差11.5]次/分钟对40.8[标准差12.4]次/分钟，p < 0.001）和恢复（23.4[标准差8.8]次/分钟对27.8[标准差10.3]次/分钟，p < 0.001）均显著降低。心率恢复与帕金森病的发病独立相关，而心率增加则不然。具体而言，恢复过程中心率降低不明显与帕金森病发病风险高30%相关（风险比1.3；95%置信区间1.1 - 1.4；每少恢复10次心跳，p < 0.001）。
总体而言，这表明心脏自主神经受累先于临床明显的帕金森病，且心率恢复可能作为一种定量的前驱标志物。《神经病学年鉴》2025年；98：1004 - 1013。
