Association of Heart Rate Variability and Acceleration Plethysmography with Systemic Comorbidity Burden in Patients with Glaucoma

<b>Background</b>: Autonomic nervous system (ANS) and vascular factors are associated with glaucoma. However, the association between systemic comorbidity burden and ANS and hemodynamic function in patients with glaucoma remains unclear. This study aimed to examine the association between heart rate variability (HRV) and acceleration plethysmography (APG) parameters and the age-adjusted Charlson Comorbidity Index (ACCI) in patients with glaucoma. <b>Methods</b>: A total of 260 subjects (260 eyes), including 186 with primary open-angle glaucoma (PG) and 74 with exfoliation glaucoma (EG), were enrolled at Shimane University Hospital from June 2023 to July 2024. HRV and APG were assessed using a sphygmograph (TAS9 Pulse Analyzer Plus View). HRV parameters included time-domain measures (SDNN, RMSSD, CVRR) and frequency-domain measures (TP, VLF, LF, HF, LF/HF). APG parameters included the a, b, c, d, and e components of the accelerated pulse wave, and the following vascular types: Type A, Type B, and Type C. The association between ACCI and HRV and APG parameters was evaluated using Spearman's rank correlation and multivariate regression adjusted for sex, body mass index, pulse rate, systolic and diastolic blood pressure, intraocular pressure, medication score, mean deviation, and glaucoma type. <b>Results</b>: By univariate analysis, against ACCI, significant inverse correlations were observed for several parameters: LnLF (R = -0.17, <i>p</i> = 0.0062); LnLF/LnHF (R = -0.24, <i>p</i> = 0.00012); b peak (R = -0.14, <i>p</i> = 0.031); d peak (R = -0.17, <i>p</i> = 0.0072); and e peak (R = -0.15, <i>p</i> = 0.015). Regarding HRV parameters, multivariate linear regression models showed that ACCI was significantly positively associated with RMSSD (coefficient: 2.861; 95% CI: 0.447 to 5.274) and significantly negatively associated with the frequency-domain parameters LnLF (coefficient: -0.127; 95% CI: -0.245 to -0.009) and LnLF/LnHF (coefficient: -0.038; 95% CI: -0.062 to -0.014). In APG parameters, the c peak was significant associated with ACCI (coefficient: -12.6; 95% CI: -22.5 to -2.69). ACCI was significantly associated with Type B (coefficient: 0.305; 95% CI: 0.057 to 0.552). <b>Conclusions</b>: Greater systemic comorbidity burden may be related to impaired ANS regulation and increased vascular stiffness in glaucoma patients.