Autonomic predictors of orthostatic hypertension during head-up tilt testing in syncope patients

Background/Introduction Syncope is a common clinical condition most frequently related to reflex mechanisms characterised by transient hypotension and/or bradycardia. In contrast, orthostatic hypertension (OHT) is an often overlooked condition, despite evidence linking it to increased cardiovascular risk and cerebrovascular events. Excessive pressor responses during orthostasis may represent a distinct haemodynamic phenotype contributing to orthostatic intolerance. Purpose To assess autonomic nervous system function in patients with syncope according to the presence of OHT during head-up tilt testing (HUTT) and to identify autonomic and haemodynamic predictors of this response. Methods We studied 723 patients, who had at least one syncope in the last 12 months; 90 (12.4%) developed OHT during HUTT. Syncope was defined according to ESC guidelines, and OHT as a sustained blood pressure increase to ≥140/90 mmHg lasting at least 1 minute during HUTT. Patients with cardiogenic syncope, epilepsy, primary autonomic neuropathies, orthostatic hypotension during HUTT, resting blood pressure ≥140/90 mmHg, significant left ventricular outflow tract obstruction, significant carotid stenosis, or non-sinus rhythm were excluded. All patients underwent Valsalva maneuver, handgrip test (HGT), and deep breathing test (HRB). Autonomic assessment included 5-minute resting heart rate variability analysis (HRV), resting blood pressure variability patterns, and baseline heart rate behaviour. Groups were compared according to OHT status, and binary logistic regression was used to identify independent predictors. Results Patients with OHT were older than those without OHT (48.7 ± 15.4 vs 45.1 ± 15.5 years, p = 0.038) and more frequently male. OHT group was associated with normal/borderline HGT responses, abnormal HRB, and extreme or low resting blood pressure variability. Resting HRV indices (PNN50, Total power, very low and high frequency) were lower in the OHT group. In multivariable analysis, OHT was independently associated with abnormal HRB (OR 2.517, p = 0.005), extreme resting blood pressure variability (OR 20.839, p = 0.009), and low resting blood pressure variability (OR 3.629, p = 0.005), while abnormal HGT (OR 0.134, p = 0.016) and female sex (OR 0.518, p = 0.012) were inversely associated. Conclusion Although syncope is typically associated with hypotension and/or bradycardia, a subset of patients develops orthostatic hypertension during orthostatic challenge. This phenotype is more common in men and is characterised by abnormal resting blood pressure regulation, preserved sympathetic reactivity, and impaired cardiovagal modulation.