Background:
Orthostatic hypotension (
OH) is a major sign of cardiovascular autonomic failure leading to
orthostatic intolerance and
syncope.
Orthostatic hypotension is traditionally divided into classical
OH (cOH) and delayed
OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of
OH patients in a tertiary
syncope unit. Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained
syncope and severe
orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of
epinephrine,
norepinephrine, C-terminal-pro-
arginine-vasopressin (CT-
proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-
atrial-natriuretic-peptide and pro-
adrenomedullin in the supine position and at 3-min HUT. Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated
arrhythmia (5 vs. 2%, p = 0.04),
Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before
syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-
proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing
norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in
epinephrine (p < 0.001) and CT-
proAVP (p = 0.001) were greater in cOH, whereas
norepinephrine increased more in dOH (p = 0.045). Conclusions: One-quarter of patients with unexplained
syncope and severe
orthostatic intolerance present
orthostatic hypotension. Classical
OH patients are older, more often have supine
hypertension, pathologic Valsalva maneuver,
Parkinson's disease, pacemaker-treated
arrhythmia, and lower glomerular filtration rate. Classical
OH is associated with increased
vasopressin and
epinephrine during HUT, but blunted increase in
norepinephrine.