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 (P-A) relationship, this study proposes a method to assess intersubject differences in local PWV independently from BP. The method was then used to analyze differences in local carotid PWV (cPWV) between hypertensive and healthy normotensive people before and after BP-normalization. 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, the exponential modeling 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 normalization of cPWV against intersubject differences in BP at the time of measurement. Carotid systolic BP (SBP) and diastolic BP (DBP) 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-normalization (p = 0.47). The mechanistic normalization of cPWV was in agreement with that estimated by analysis of covariance (ANCOVA). In conclusion, the proposed method, which could be easily implemented in the clinical setting, allows to assess the intersubject differences in PWV independently of BP. Our results suggested that mild hypertension in middle-aged 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 potential clinical utility of the method.
Highlights
Arterial stiffness as pulse wave velocity (PWV) is a powerful predictor of mortality and cardiovascular events in hypertensive patients, above and beyond traditional risk factors (Boutouyrie et al, 2002; Laurent et al, 2003; Cardoso et al, 2019)
Hypertensive and control groups were matched in age and gender, but not heart rate (HR) that was on average 6 bpm higher in hypertensives (p = 0.021)
Average common carotid artery (CCA) diameters at systolic BP (SBP) and diastolic BP (DBP) were slightly higher in hypertensives than controls, but differences were not significant and were reduced further after appropriate SBP and DBP adjustments [7.62 (7.23–8.02) vs. 7.76 (7.37–8.16) mm and 7.15 (6.77–7.53) vs. 7.33 (6.95–7.71) mm]
Summary
Arterial stiffness as pulse wave velocity (PWV) is a powerful predictor of mortality and cardiovascular events in hypertensive patients, above and beyond traditional risk factors (Boutouyrie et al, 2002; Laurent et al, 2003; Cardoso et al, 2019). The heterogeneous microstructure of the arterial wall makes its behavior highly nonlinear (Giudici et al, 2021b) so that arterial stiffness and, PWV are intrinsically blood pressure (BP)-dependent (Spronck et al, 2015b) This fact complicates distinguishing between chronic (i.e., actual BP-induced wall remodeling) and acute effects (i.e., transitional shift to a different working point in the nonlinear behavior of the arterial wall) of increased BP on arterial structure and mechanics. In clinical investigations, statistical adjustments for systolic BP (SBP) (Valbusa et al, 2019), mean BP (MBP) (Desamericq et al, 2015), and pulse pressure (PP) (Brandts et al, 2012) are often made, most regional PWV metrics (e.g., carotid-femoral and brachial-ankle PWV), use the foot of arterial waves as the fiducial point, suggesting that diastolic BP (DBP) likely represent a more appropriate choice for their pressurenormalization (Spronck et al, 2017b). As intergroup differences in SBP are typically larger than those in DBP, widely used SBPand MBP-statistical adjustments likely lead to overcorrections of PWV and potentially limit our understanding of pressureinduced chronic vascular damage (Spronck et al, 2017b)
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