Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease

Abstract

Background: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD.

Objective: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications.

Methods: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX).

Results: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001).

Conclusions: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Keywords: Exercise; Parkinson’s disease; autonomic nervous system; chronotropic incompetence; heart rate.

Fig. 1

Association between age and maximal heart rate during CPET in SPARX by chronotropic group. PDnon-chrono (n = 90), PDchrono (n = 13), and PDchronomed (n = 25).

Fig. 2

Maximal heart rate in each study group. Data are median, interquartile range, and 95% confidence interval. PDnon-chrono (n = 90), PDchrono (n = 13), and PDchronomed (n = 25). p < 0.001 for PDnon-chrono vs. PDchrono, p < 0.001 for PDnon-chrono vs. PDchronomed, p = 0.010 for PDchrono vs. PDchronomed.

Fig. 3

Association between systolic orthostatic blood pressure response (i.e., standing-lying SBP) and deviation from APMHR in study participants. PDnon-chrono (n = 87), PDchrono (n = 13), and PDchronomed (n = 25).

Fig. 4

A) Cardiorespiratory fitness as measured by VO2peak, p = 0.027 for PDnon-chrono vs. PDchrono (PDnon-chrono (n = 89), PDchrono (n = 13), and PDchronomed (n = 25)). B) peak respiratory exchange ratio, p = 0.448 (PDnon-chrono (n = 90), PDchrono (n = 13), and PDchronomed (n = 25). Data are median, interquartile range, and 95% confidence interval.