Orthostatic Changes in Hemodynamics and Cardiovascular Biomarkers in Dysautonomic Patients

Background Impaired autonomic control of postural homeostasis results in orthostatic intolerance. However, the role of neurohormones in orthostatic intolerance has not been explained. Methods Six-hundred-and-seventy-one patients (299 males; 55 +/- 22 years) with unexplained syncope underwent head-up tilt (HUT) with serial blood sampling. Systolic blood pressure (SBP) and heart rate (HR) supine, after 3min, and lowest BP/highest HR during HUT were recorded. Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 (CT-proET-1), and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were determined at supine and 3min of HUT. Multivariate-adjusted logistic regression model was applied to compare 1st (reference) with 4th quartile of 3 min and maximal Delta SBP/Delta HR (i.e. pronounced hypotension or tachycardia) vs. changes in neuroendocrine biomarkers, respectively. Results Higher resting CT-proET-1 predicted BP fall at 3min (Odds ratio (OR) per 1 SD: 1.62, 95% CI 1.18-2.22; p = 0.003), and max BP fall during HUT (1.82, 1.28-2.61; p = 0.001). Higher resting CT-proAVP predicted BP fall at 3min (1.33, 1.03-1.73; p = 0.03), which was also associated with increase in CT-proAVP (1.86, 1.38-2.51; p = 0.00005) and epinephrine (1.47, 1.12-1.92; p = 0.05) during HUT. Lower resting MR-proANP predicted tachycardia at 3min (0.37, 0.24-0.59; p = 0.00003), and max tachycardia during HUT (0.47, 0.29-0.77; p = 0.002). Further, tachycardia during HUT was associated with increase in epinephrine (1.60, 1.15-2.21; p = 0.005), and norepinephrine (1.87, 1.38-2.53; p = 0.005). Conclusions Resting CT-proET-1 and CT-proAVP are increased in orthostatic hypotension, while resting MR-proANP is decreased in postural tachycardia. Moreover, early BP fall during orthostasis evokes increase in CT-proAVP and epinephrine, while postural tachycardia is associated with increase in norepinephrine and epinephrine.