Differential Cardiac and Peripheral Vascular Low-Frequency Oscillation Responses to Voluntary Breath-Hold

Objective. This study performed a comparative analysis of autonomic responses during voluntary breath-holds at inspiration and expiration by assessing low-frequency (LF) oscillations in heart rate (HR) and photoplethysmogram (PPG) signals. Methods. Eleven healthy volunteers underwent a modified head-up tilt test with breath-holds at inspiration and expiration in supine and standing positions. Electrocardiogram, finger PPG, and respiratory signals were recorded simultaneously. LF oscillation (0.04-0.15 Hz) amplitudes were assessed during spontaneous breathing and breath-hold phases. Relative changes in LF amplitudes (ΔLFA) were calculated for each signal, and the ΔLFA ratio (ΔLFA_PPG/ΔLFA_HR) was derived. Results. Cardiac and vascular signals showed divergent responses in LF oscillation amplitude during breath-holds. While PPG signals demonstrated a significant increase during expiration-holds (ΔLFA_PPG = +71.56%, p = 0.003), HR signals showed a non-significant overall decrease (ΔLFA_HR = -25.28%, p = 0.481). In this exploratory study (n = 11), comparative analysis showed that the vascular response (ΔLFA_PPG) was significantly greater than the cardiac response (ΔLFA_HR) during expiration-holds (p = 0.005) and across all stages (p = 0.012). However, expiration holds were systematically shorter than inspiration holds by approximately 24 s (median 32.1 s vs. 56.3 s). Because breath-hold duration was self-determined and not standardized, the observed differences between inspiration and expiration conditions may reflect either respiratory phase, cumulative apnea duration, or their interaction (our design cannot disentangle these effects). The ΔLFA ratio showed a negative median value overall (-0.25), indicating a complex and often inverse relationship between vascular and cardiac responses. However, due to the small sample size (n = 11), these results are strictly hypothesis-generating and cannot be generalized beyond the studied cohort. The study was powered only to detect large effect sizes (Cohen's d > 1.2), and the wide bootstrap confidence intervals indicate substantial estimation uncertainty. Independent replication in larger, more diverse populations is essential before any clinical or physiological generalization can be made. Conclusions. This study documents opposing directional changes in cardiac and peripheral vascular LF oscillations during shorter expiration and longer inspiration breath-hold. Because respiratory phase and apnea duration are confounded in our design, we cannot determine whether these differential responses are phase-dependent, duration-dependent, or driven by both factors. The findings highlight the necessity of multi-signal analysis incorporating both ECG and PPG for a more comprehensive autonomic assessment of local and systemic autonomic influences and underscore that future studies must employ standardized breath-hold durations across both respiratory phases to isolate the specific contribution of respiratory phase. The ΔLFA ratio is explored here as a descriptive metric of the direction and magnitude of cardiac-vascular response differences, but its mathematical stability and physiological interpretation remain limited and require validation with direct sympathetic nerve recordings.