The interaction of macro- and microvascular function underlies brachial artery flow-mediated dilation in humans.

Brachial artery flow-mediated dilation (BAFMD) is induced by hyperemic wall shear rate (WSR) following forearm ischemia. In older adults, there appears to be a reduced hyperemic WSR and altered stimulus-response relationship occurring at the brachial artery compared to young adults. However, it is unclear if an altered forearm microvascular response to ischemia influences brachial hyperemic WSR in older adults. We determined the association between brachial hyperemic WSR and forearm skeletal muscle oxygen saturation in young and older adults. Healthy young (n=17, 29±7 yrs) and older (n=32, 65±4 yrs) adults participated in the study. BAFMD by a multi-gate spectral Doppler system and forearm skeletal muscle oxygen saturation by near infrared spectroscopy were concurrently measured. Compared to the young, older adults showed reduced oxygen extraction kinetics [OE: 0.15 (0.12-0.17) vs 0.09 (0.05-0.12) %s-1] and magnitude (SO2deficit: 3810±1420 vs 2723±1240 %s) during ischemia, and oxygen re-saturation kinetics (SO2slope: 2.5±0.7 vs 1.7±0.7 %s-1) upon reperfusion (all p<0.05). When OE in the young and SO2slope in older adults were stratified by their median values, young adults with OE above median had greater hyperemic WSR parameters compared to those with OE below median (p<0.05), but SO2slope in older adults did not show clear differences in hyperemic WSR parameters between those with above/below median. This study demonstrates that, additionally to a reduced microvascular response to ischemia, there may be a possible dissociation of microvascular response to ischemia to brachial hyperemic WSR in older adults, which may result in a further impairment of BAFMD in this cohort.

Type 2 diabetes exacerbates changes in blood pressure-independent arterial stiffness: cross-sectional and longitudinal evidence from the SUMMIT study.

Greater central artery stiffness is observed in people with type 2 diabetes (T2DM). Elevated blood pressure (BP) and altered arterial wall structure/composition in T2DM are generally considered as main drivers for this alteration. However, because conventional arterial stiffness measures are BP-dependent and as such an influence of BP remains in a measure, it is unclear if greater central artery stiffness is a function of greater BP, or due to changes in the structure and composition of the arterial wall. We aimed to measure BP-independent arterial stiffness (ß0) cross-sectionally and longitudinally in T2DM. We studied 753 adults with T2DM (DM+) and 436 adults without (DM-) at baseline (Phase 1), and 310 DM+ and 210 DM- adults at 3-yr follow-up (Phase 2). We measured carotid-femoral pulse wave velocity and used it to calculate ß0. In Phase 1, ß0 was significantly greater in DM+ than DM- after adjusting for age and sex [27.5 (26.6-28.3) vs. 23.6 (22.4-24.8) au, P < 0.001]. Partial correlation analyses after controlling for age and sex showed that ß0 was significantly associated with hemoglobin A1c (r = 0.15 P < 0.001) and heart rate [(HR): r = 0.23 P < 0.001)] in DM+. In Phase 2, percentage-change in ß0 was significantly greater in DM+ than DM- [19.5 (14.9-24.0) vs. 5.0 (-0.6 to 10.6) %, P < 0.001] after adjusting for age, sex, and baseline ß0. ß0 was greater in DM+ than DM- and increased much more in DM+ than in DM- over 3 yr. This suggests that T2DM exacerbates BP-independent arterial stiffness and may have a complemental utility to existing arterial stiffness indices.NEW & NOTEWORTHY We demonstrate in this study a greater BP-independent arterial stiffness ß0 in people with type 2 diabetes (T2DM) compared to those without, and also a greater change in ß0 over 3 yr in people with T2DM than those without. These findings suggest that the intrinsic properties of the arterial wall may change in a different and more detrimental way in people with T2DM and likely represents accumulation of cardiovascular risk.

Association between Low-Density Lipoprotein Cholesterol and Vascular Biomarkers in Primary Prevention.

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.

Heart rate variability, serum cortisol levels and temperament in a sample of workers exposed to occupational stress: a preliminary report.

Work-related stress is an emerging risk for psychiatric occupational disorders including Adjustment Disorders (AD). The aim of this study was to investigate in workers exposed to occupational stress suffering from AD about putative indices of stress and mental health resilience such as serum cortisol (seC) levels, Heart Rate Variability (HRV) and affective temperaments. We consecutively recruited 15 male and 15 female AD patients between workers evaluated for occupational stress at an Italian Occupational Medicine Unit. SeC levels were measured by specific immunoassay. HRV indices were recorded using Task Force® Monitor system (CNSystems, Graz, Austria). Specific questionnaires were used to measure perceived and occupational stress, psychopathological symptoms and temperament. Women presented higher levels of occupational stress, higher High-Frequency HRV (HF-HRV) and lower Low-Frequency HRV (LF-HRV) than men. SeC levels were positively correlated with LF-HRV values and negatively with HF-HRV values. The LF/HF ratio resulted to be inversely correlated with the score of Harm Avoidance temperament dimension and directly with the score of Reward Dependence temperament dimension. In conclusion, in AD patients exposed to occupational stress high seC levels and reward dependence appear to be associated with a pattern of HRV reflecting less mental health resilience.

Corrigendum: Carotid reservoir pressure decrease after prolonged head down tilt bed rest in young healthy subjects is associated with reduction in left ventricular ejection time and diastolic length.

[This corrects the article DOI: 10.3389/fphys.2022.866045.].

Reservoir Pressure Integral Is Independently Associated With the Reduction in Renal Function in Older Adults.

BACKGROUND: Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.4±7.9 years, 194 females) at baseline and after 3 years. METHODS: Reservoir-excess pressure parameters, including reservoir pressure integral, excess pressure integral, systolic, and diastolic rate constants, were obtained by radial artery tonometry. RESULTS: After 3 years, and in a group of 94 individuals (72.4±7.6 years, 26 females), there was an estimated glomerular filtration rate reduction of >5% per year (median reduction of 20.5% over 3 years). A multivariable logistic regression analysis revealed that higher baseline reservoir pressure integral was independently associated with a smaller reduction in estimated glomerular filtration rate after accounting for conventional cardiovascular risk factors and study centers (odds ratio: 0.660 [95% CIs, 0.494-0.883]; P=0.005). The association remained unchanged after further adjustments for potential confounders and baseline renal function (odds ratio: 0.528 [95% CIs, 0.351-0.794]; P=0.002). No other reservoir-excess pressure parameters exhibited associations with the reduction in renal function. CONCLUSIONS: This study demonstrates that baseline reservoir pressure integral was associated with the decline in renal function in older adults at 3-year follow-up, independently of conventional cardiovascular risk factors. This suggests that reservoir pressure integral may play a role in the functional decline of the kidneys.

Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Progressive Additive Benefits of Prehabilitation and Subsequent Bariatric Surgery on Cardiac Autonomic Regulation as Assessed by Means of a Simple Unitary Composite Index: Preliminary Data from an Observational Study.

Obesity is associated with an increased risk of several chronic comorbidities, which may also be determined by dysfunctional autonomic nervous system (ANS). The influence of bariatric surgery (BS) on ANS balance was explored in previous studies, but with high heterogeneity in both the assessment timing and methods employed. In the present observational study, we applied a clinical protocol which considers two subsequent phases. Twenty-nine non-diabetic obese subjects were studied at baseline (T0), after one month of lifestyle modification (prehabilitation) (phase 1-T1), and after eight months following BS (phase 2-T2). ANS regulation was assessed across the three study epochs by means of ANSI, a single composite percent-ranked proxy of autonomic balance, being free of gender and age bias, economical and simple to apply in a clinical setting. The aim of the present study was to investigate the effects of the clinical protocol based on prehabilitation and subsequent BS on the ANS regulation by means of ANSI. Potential intertwined correlations with metabolic parameters were also investigated. Notably, we observed a progressive improvement in ANS control, even by employing ANSI. Moreover, the reduction in the markers of sympathetic overactivity was found to significantly correlate with the amelioration in some metabolic parameters (fasting glucose, insulin levels, and waist circumference), as well as in stress and tiredness perception. In conclusion, this study provides convincing evidence that a unitary proxy of cardiac autonomic regulation (CAR) may reflect the progressive improvement in autonomic regulation following behavioral and surgical interventions in obese patients. Intriguingly, this might contribute to reducing cardiovascular and metabolic risk.

Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis.

The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb. Progression of bulb IMT demonstrates independent associations with baseline bulb IMT, the plaque gray scale median (GSM), and the plasma level of platelet-derived growth factor (PDGF) (standardized ß-coefficients and 95% confidence interval [CI] -0.14 [-0.06 to -0.02] p = 0.001, 0.15 [0.02-0.07] p = 0.001, and 0.20 [0.03-0.07] p < 0.001, respectively). Plasma PDGF correlates with the plaque GSM (0.23 [0.15-0.29] p < 0.001). These observations provide insight into the atherosclerotic process in high-risk subjects by showing that progression primarily occurs in fibrotic plaques and is associated with increased levels of PDGF.

Detecting the vulnerable carotid plaque: the Carotid Artery Multimodality imaging Prognostic study design.

BACKGROUND: Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography. OBJECTIVES: The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques. STUDY DESIGN: We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).

Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length.

Background: The arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted 'wave transmission model', the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the 'Windkessel function' of the elastic arteries. Recently, a 'reservoir-excess pressure' model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related 'reservoir' pressure and a wave-related 'excess' pressure. Methods: In this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis. Results: Compared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP. Conclusion: This is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

Hemodynamic variations in arterial wave reflection associated with the application of increasing levels of PEEP in healthy subjects.

Positive end-expiratory pressure (PEEP) may affect arterial wave propagation and reflection, thus influencing ventricular loading conditions. The aim of the study was to investigate the hemodynamic variations in arterial wave reflection (i.e., wave reflection time, augmentation index, left ventricular ejection time, diastolic time, SEVR) associated with the application of increasing levels of PEEP in healthy subjects. We conducted a prospective observational study. Study population was selected from students and staff. Pulse contour wave analysis was performed from the right carotid artery during stepwise increase in PEEP levels (from 0 cmH2O, 5 cmH20, 10 cmH2O) with applanation tonometry. Sixty-two healthy volunteers were recruited. There were no significant changes in heart rate, augmentation index (AIx), left ventricular ejection time, Diastolic time (DT) among all of the different steps. A significant increase of time to the inflection point (Ti) was observed during all steps of the study. Diastolic area under the curve (AUC) divided by systolic-AUC (SEVR) increased from baseline to PEEP = 5 cmH2O, and from baseline to PEEP = 10 cmH2O. AIx and Ti were significantly correlated (directly) at the baseline and during PEEP = 10 cmH2O. Ti and DT were significantly correlated at the baseline and during PEEP = 5 cmH2O. In our preliminary results, low levels of PEEP played a role in the interaction between the heart and the vascular system, apparently mediated by a prolongation of the diastolic phase and a reduction in the systolic work of the heart.Clinical trials registration number: NCT03294928, 19/09/2017.

Noninvasive carotid pressure-diameter loops to identify viscoelastic properties in ageing, hypertension and type 2 diabetes.

OBJECTIVES: Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). METHODS: We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (n = 69), combined hypertension/T2DM (H-T2DM, n = 99), normotensive (N-T2DM, n = 25) and healthy controls (n = 114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D2P-loop method, and wall viscosity from hysteresis, the area (HA) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. RESULTS: Controls' hysteresis fell quadratically with age (R2 = 0.23, P < 0.001). Yet mean HA in hypertensive patients (0.95, 95% CI 0.65-1.23) was six-fold higher than in age-matched controls (0.14, -0.20 to 0.49, P < 0.001) with a 2.5× difference between diastolic (dDs) to systolic (sDs) distensibility (P < 0.05) in hypertensive patients. HA was higher in hypertensive patients and H-T2DMs (0.80, 0.58-1.04) than N-T2DMs (0.20, -0.17 to 0.54, P < 0.05), but similar between controls and N-T2DMs. BP-adjusted carotid diameters in all T2DM were significantly greater compared with controls and hypertensive patients. CONCLUSION: Higher BP increased wall viscosity, hysteresis and relative difference between systolic and diastolic distensibility across groups. Carotid diameters were increased in all T2DMs, more in H-T2DM, probably altering BP-flow dynamics in T2DM.

Vascular Ageing and Aerobic Exercise.

Impairment of vascular function, in particular endothelial dysfunction and large elastic artery stiffening, represents a major link between ageing and cardiovascular risk. Clinical and experimental studies identified numerous mechanisms responsible for age-related decline of endothelial function and arterial compliance. Since most of these mechanisms are related to oxidative stress or low-grade inflammation, strategies that suppress oxidative stress and inflammation could be effective for preventing age-related changes in arterial function. Indeed, aerobic physical activity, which has been shown to improve intracellular redox balance and mitochondrial health and reduce levels of systemic inflammatory markers, also improves endothelial function and arterial distensibility and reduces risk of cardiovascular diseases. The present paper provides a brief overview of processes underlying age-related changes in arterial function, as well as the mechanisms through which aerobic exercise might prevent or interrupt these processes, and thus attenuate vascular ageing.

Transfer-function-free technique for the noninvasive determination of the human arterial pressure waveform.

The estimation of central aortic blood pressure is a cardinal measurement, carrying effective physiological, and prognostic data beyond routine peripheral blood pressure. Transfer function-based devices effectively estimate aortic systolic and diastolic blood pressure from peripheral pressure waveforms, but the reconstructed pressure waveform seems to preserve features of the peripheral waveform. We sought to develop a new method for converting the local diameter distension waveform into a pressure waveform, through an exponential function whose parameters depend on the local wave speed. The proposed method was then tested at the common carotid artery. Diameter and blood velocity waveforms were acquired via ultrasound at the right common carotid artery while simultaneously recording pressure at the left common carotid artery via tonometer in 203 people (122 men, 50 ± 18 years). The wave speed was noninvasively estimated via the lnDU-loop method and then used to define the exponential function to convert the diameter into pressure. Noninvasive systolic and mean pressures estimated by the new technique were 3.8 ± 21.8 (p = 0.015) and 2.3 ± 9.6 mmHg (p = 0.011) higher than those obtained using tonometery. However, differences were much reduced and not significant in people >35 years (0.6 ± 18.7 and 0.8 ± 8.3 mmHg, respectively). This proof of concept study demonstrated that local wave speed, estimated from noninvasive local measurement of diameter and flow velocity, can be used to determine an exponential function that describes the relationship between local pressure and diameter. This pressure-diameter function can then be used for the noninvasive estimation of local arterial pressure.

A pandemic recap: lessons we have learned.

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

Interaction between Autonomic Regulation, Adiposity Indexes and Metabolic Profile in Children and Adolescents with Overweight and Obesity.

Early obesity predicts initial modifications in cardiac and vascular autonomic regulation. The aim of this study was to assess the possible interaction between non-invasive measures of autonomic cardiovascular control and peripheral endothelium regulation in children with overweight and obesity. We involved 114 young subjects (77M/37F, 12.7 ± 2.2 years) with normal weight (NW, n = 46) to overweight or obesity (OB, n = 68). Multivariate statistical techniques utilizing a collection of modern indices of autonomic regulation, adiposity indexes and metabolic profile were employed. Resting values show substantial equivalence of data. Conversely, blood pressure variance is greater in NW/OB groups. The correlation matrix between major autonomic and metabolic/hemodynamic variables shows a clustered significant correlation between homogeneous indices. A significant correlation between metabolic indices and endothelial and autonomic control, mostly in its vascular end, was recorded. Particularly, the alpha index is significantly correlated with triglycerides (r = -0.261) and endothelial indices (RHI, r = 0.276). Children with obesity show a link between indices of autonomic and endothelial function, fat distribution and metabolic profile. The optimization of autonomic control, for instance by exercise/nutrition interventions, could potentially prevent/delay the occurrence of structural vascular damage leading to reduced cardiovascular health.

Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals With Type 2 Diabetes.

[Figure: see text].

Subject-Specific Pressure Normalization of Local Pulse Wave Velocity: Separating Intrinsic From Acute Load-Dependent Stiffening in Hypertensive Patients.

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 D 2 P-loop method. Then, the exponential modeling of the P-area (A = πD 2/4) 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.