Carricarte Naranjo Claudia, Marras Connie, Visanji Naomi P, Cornforth David J, Sanchez-Rodriguez Lazaro, Schüle Birgitt, Goldman Samuel M, Estévez Mario, Stein Phyllis K, Jelinek Herbert F, Lang Anthony E, Machado Andrés
Facultad de Biología, Universidad de La Habana, La Habana, Cuba.
Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, ON, Canada.
Clin Auton Res. 2025 Feb 19. doi: 10.1007/s10286-024-01104-6.
Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis.
HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate.
Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls.
Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.
逐搏心率变异性（HRV）增加是携带亮氨酸重复激酶2基因（LRRK2）G2019S突变的帕金森病（PD）患者（LRRK2-PD）的一个特征。由于LRRK2突变具有不完全外显率，因此可能仅在一部分LRRK2非显性携带者（NMC）中观察到PD转化前的HRV变化。我们旨在评估通过聚类分析确定的具有LRRK2-PD独特特征的NMC亚组中的HRV。
分析了从25名NMC、32名相关非携带者（RNC）、27名无关健康对照和14名LRRK2-PD患者的心电图中提取的300个正常心跳间期的HRV测量值。使用问卷和量表评估临床症状，并基于心率减速能力（DC）和雷尼熵，通过k均值聚类分析确定三个NMC亚组。使用多元回归分析比较标准和高级HRV测量值，并控制年龄、性别和平均心率。
与RNC和对照相比，7名NMC（NMC2，28%）亚组的逐搏HRV标志物显著增加。与对照相比，NMC2中的不规则性增加和DC也得到了验证，并且是NMC2和RNC中的典型特征。总体而言，NMC2的HRV特征与LRRK2-PD患者相当。与其他NMC、RNC和对照相比，NMC2进一步表现出更大的运动和非运动特征。
我们的结果证实，在表现出LRRK2-PD临床特征的NMC亚组中也发现了LRRK2-PD的HRV特征。需要进一步研究以阐明较高的HRV是否代表LRRK2-PD前驱表现。
