Abstract 4365098: Immediate/Initial Orthostatic Hypotension: Gravity Triggers Blood Pressure Drop with Upright Posture While Sympathetic Activation Drives Recovery

Background/Introduction: Immediate/Initial orthostatic hypotension (iOH) presents as an abnormal transient blood pressure (BP) decrease immediately upon assuming upright posture, with prompt recovery. The pathophysiology underlying this BP drop and subsequent recovery is incompletely understood. Hypothesis: We hypothesized that the initial BP nadir is determined primarily by gravitational forces and therefore should be similar in healthy subjects (Controls) and individuals exhibiting pure autonomic failure (PAF), whereas recovery time is more likely determined by reflex sympathetic activation, and thus would be expected to be delayed in PAF. Methods: Autonomic testing was undertaken in 116 healthy individuals (age 36±14.3 years) and 35 PAF patients in whom iOH was measurable (age 67±13 years). Continuous non-invasive beat-to-beat BP and ECG recordings were obtained with subjects seated and then during movement to Active Standing (AS). We measured initial systolic BP drop (ΔSBP), time to BP nadir, recovery time (seconds from nadir to 90% of baseline), heart rate increment (ΔHR), and the ΔHR/ΔSBP ratio. Data underwent Shapiro-Wilk normality testing followed by parametric or non-parametric analyses as appropriate. Results: Initial systolic BP decrements with AS were comparable in Controls and PAF patients (-33±14 mmHg vs -36.4±21, p=0.38) despite significantly different baseline SBP values (126±18mmHg vs 142±22, p<0.01). Conversely, compared to Controls, Recovery time was significantly prolonged in PAF (38.6±14.2 vs 18.7±6.3 seconds, p<0.001). Further, compensatory HR response initiated by BP drop was markedly attenuated in PAF (+8±9 vs +19±11 bpm, p<0.01), yielding significantly reduced ΔHR/ΔSBP ratios (0.22±0.25 vs 0.76±0.58 bpm/mmHg, p<0.01). Conclusion: These findings provide physiological evidence that in iOH, BP decrease is driven principally by gravitational hydrostatic effect whereas BP recovery kinetics are importantly determined by autonomic tone, most likely baroreflex-mediated sympathetic activation, and thus are delayed in PAF.