De Biase N; University of Pisa, Pisa, Italy.
Del Punta L; Moura-Ferreira S; De Schutter S; et al

Journal of Hypertension. 44(12):2227-2237, 2026 Dec 01.

OBJECTIVES: Conventional definitions of hypertensive response to exercise
(HRE) rely on absolute systolic blood pressure (SBP) thresholds, which do
not account for the metabolic demand driving the pressor response and show
inconsistent association with pathophysiology and prognosis. Whether
indexing SBP to oxygen consumption (VO 2 ) provides independent
pathophysiological information along the continuum from arterial
hypertension (AH) to heart failure (HF) remains unclear. We investigated
the haemodynamic and prognostic implications of the SBP/VO 2 slope in
patients with AH and preserved left ventricular ejection fraction.

METHODS: We enrolled 970 participants with AH, including 34% with
established HF. All subjects underwent baseline echocardiography and
cardiopulmonary exercise testing with stress echocardiography. We
categorized patients into tertiles of the slope of SBP relative to peak VO
2 from rest to peak exercise; the highest tertile was used to define HRE
for descriptive analyses. Patients were followed for all-cause mortality
or HF-related hospitalisation.

RESULTS: Patients with HRE (SBP/VO 2 slope >5.7 mmHg/ml/kg/min) displayed
adverse cardiac remodelling (higher left ventricular mass index, left
atrium dilation), systemic exercise-induced vascular dysfunction (elevated
peak systemic vascular resistance, reduced total arterial compliance), and
reduced peripheral oxygen extraction (lower peak arteriovenous oxygen
difference), despite well controlled resting BP. Over a 24-month median
follow-up, a steeper SBP/VO 2 slope was associated with a higher risk of
death or HF-related hospitalisation, independent of peak VO 2 (hazard
ratio per 1-standard deviation increase: 1.21; P = 0.041).

CONCLUSIONS: In patients with AH, a steeper SBP/VO 2 slope identifies a
high-risk haemodynamic phenotype and may repre