AUTHOR=Giudici Alessandro , Palombo Carlo , Kozakova Michaela , Morizzo Carmela , Cruickshank J. Kennedy , Khir Ashraf W. TITLE=Subject-Specific Pressure Normalization of Local Pulse Wave Velocity: Separating Intrinsic From Acute Load-Dependent Stiffening in Hypertensive Patients JOURNAL=Frontiers in Physiology VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.783457 DOI=10.3389/fphys.2021.783457 ISSN=1664-042X ABSTRACT=Pulse wave velocity (PWV) is a powerful predictor of cardiovascular events. However, its intrinsic blood pressure (BP)-dependency complicates distinguishing between acute and chronic effects of increased BP on arterial stiffness. Based on the assumption that arteries exhibit a nearly exponential pressure-area relationship, this study proposes a method to assess inter-subject differences in local PWV independently from BP. The method was then used to analyse differences in local carotid PWV (cPWV) between hypertensives and healthy normotensives people before and after BP normalisation. Pressure (P) and diameter (D) waveforms were simultaneously acquired via tonometer at the left and ultrasound scanning at right common carotid artery (CCA), respectively, in 22 patients with Grade 1 or 2 hypertension and 22 age- and sex-matched controls. cPWV was determined using the D2P-loop method. Then, exponential modelling of the P-area (A = πD2/4) relationships allowed defining a mathematical formulation to compute subject-specific changes in cPWV associated with BP changes, thus enabling the normalisation of cPWV against inter-subject differences in BP at the time of measurement. Carotid systolic (S)BP and diastolic (D)BP were, on average, 17.7 (p<0.001) and 8.9 mmHg (p<0.01) higher in hypertensives than controls, respectively. cPWV was 5.56±0.86 m/s in controls and 6.24±1.22 m/s in hypertensives. BP alone accounted for 68% of the cPWV difference between the two groups: 5.80±0.84 vs 6.03±1.07 m/s after BP-normalisation (p=0.47). Mechanistic normalisation of cPWV was in agreement with that estimated by ANCOVA. In conclusion, the proposed method, that could be easily implemented in the clinical setting, allows to assess inter-subject differences in PWV independently of BP. Our results suggested that mild hypertension in middle age subjects without target organ damage does not significantly alter the stiffness of the CCA wall independently of acute differences in BP. The results warrant further clinical investigations to establish the method potential clinical utility.