Orthostatic Changes in Hemodynamics and Cardiovascular Biomarkers in Dysautonomic Patients

Abstract

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 3 min, 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 3 min of HUT. Multivariate-adjusted logistic regression model was applied to compare 1st (reference) with 4th quartile of 3 min and maximal ΔSBP/ΔHR (i.e. pronounced hypotension or tachycardia) vs. changes in neuroendocrine biomarkers, respectively.

Results: Higher resting CT-proET-1 predicted BP fall at 3 min (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 3 min (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 3 min (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.

Fig 1. Normal hemodynamic response to passive head-up tilt test and nitroglycerin (woman, 32 years).

This patient is representative of lowest (reference) quartiles of both ΔSBP and ΔHR (i.e. Q1).

Fig 2. Normal hemodynamic response to passive head-up tilt test and vasovagal reflex induced by nitroglycerine (man, 50 years).

This patient is representative of lowest (reference) quartiles of both ΔSBP and ΔHR (i.e. Q1).

Fig 3. Pronounced orthostatic tachycardia (≈POTS) and vasovagal reflex syncope (woman, 24 years).

This patient is representative of highest quartiles of ΔHR (i.e. Q4) both after 3 min of HUT and at the maximal heart rate during HUT.

Fig 4. Delayed orthostatic hypotension and syncope probably due to vasovagal reflex activation (woman, 53 years).

This patient is representative of highest quartile of max ΔSBP (i.e. Q4) at the minimal SBP during HUT but not after 3 min of HUT.

Fig 5. Pronounced classical orthostatic hypotension and syncope (man, 65 years).

This patient is representative of highest quartiles of ΔSBP (i.e. Q4) both after 3 min of HUT and at the minimal SBP during HUT.

Fig 6. ORs log regression Q4 vs Q1 adj age sex delta SBP 3min log transformed.

Fig 7. ORs log regression Q4 vs Q1 adj age sex delta SBP max log transformed.

Fig 8. ORs log regression Q4 vs Q1 adj age sex delta HR 3 min log transformed.

Fig 9. ORs log regression Q4 vs Q1 adj age sex delta HR max log transformed.