Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

Wave reflections affect the proximal aortic pressure and flow waves and play a role in systolic hypertension. A measure of wave reflection, receiving much attention, is the augmentation index (AI), the ratio of the secondary rise in pressure and pulse pressure. AI can be limiting, because it depends not only on the magnitude of wave reflection but also on wave shapes and timing of incident and reflected waves. More accurate measures are obtainable after separation of pressure in its forward (P f ) and reflected (P b ) components. However, this calculation requires measurement of aortic flow. We explore the possibility of replacing the unknown flow by a triangular wave, with duration equal to ejection time, and peak flow at the inflection point of pressure (F tΙP ) and, for a second analysis, at 30% of ejection time (F t30 ). Wave form analysis gave forward and backward pressure waves. Reflection magnitude (RM) and reflection index (RI) were defined as RM=P b /P f and RI=P b (P f +P b ), respectively. Healthy subjects, including interventions such as exercise and Valsalva maneuvers, and patients with ischemic heart disease and failure were analyzed. RMs and RIs using F tIP and F t30 were compared with those using measured flow (F m ). Pressure and flow were recorded with high fidelity pressure and velocity sensors. Relations are: RM tIP =0.82RM mf +0.06 (R 2 =0.79; n=24), RM t30 =0.79RM mf +0.08 (R 2 =0.85; n=29) and RI tIP =0.89RI mf +0.02 (R 2 =0.81; n=24), RI t30 =0.83RI mf +0.05 (R 2 =0.88; n=29). We suggest that wave reflection can be derived from uncalibrated aortic pressure alone, even when no clear inflection point is distinguishable and AI cannot be obtained. Epidemiological studies should establish its clinical value.

Quantification of wave reflection in the human aorta from pressure alone a proof of principle. Commentary

A review of machine learning in hypertension detection and blood pressure estimation based on clinical and physiological data

Objective: We investigate the field feasibility of carotid stiffness measurement using ARTSENS® Touch and report the first community-level data from India. Method: In an analytical cross-sectional survey among 1074 adults, we measured specific stiffness index ( $\beta $ ), pressure-strain elastic modulus ( $\text{E}_{\text {p}}$ ), arterial compliance (AC), and one-point pulse wave velocity (PWV $_{\beta }$ ) from the left common carotid artery. Data for established risk factors (waist circumference, blood pressure, plasma glucose, triglycerides, and HDL-C) were also collected. The association of carotid stiffness with age, gender, hypertension/diabetes, smoking, and clustering of risk factors was studied. Results: Measurements were repeatable with a relative difference (RD) between consecutive readings of $\sim 80$ % of arterial diameter values. The average RDs for $\beta $ , $\text{E}_{\text {p}}$ , AC, and PWV $_{\beta }$ , were 20.51%, 22.31%, 25.10%, and 14.13%, respectively. Typical range for stiffness indices among females and males were $\beta $ : 8.12 ± 3.59 vs 6.51 ± 2.78, $\text{E}_{\text {p}}$ : 113.24 ± 56.12 kPa vs 92.33 ± 40.65 kPa, PWV $_{\beta }$ : 6.32 ± 1.38 ms−1 vs 5.81 ± 1.16 ms−1, and AC: 0.54 ± 0.36 mm2 kPa−1 vs 0.72 ± 0.38 mm2 kPa−1. Mean $\beta $ , $\text{E}_{\text {p}}$ , and PWV $_{\beta }$ increased (and mean AC decreased) across decades of age; the trend persisted even after excluding hypertensives and subjects with diabetes. The odds ratio of presence of multiple risk factors for $\text{E}_{\text {p}} \ge93.71$ kPa and/or PWV $_{\beta } \ge6.56$ ms−1 was ≥ 2.12 or above in males. In females, it was just above 2.00 for $\text{E}_{\text {p}} \ge91.21$ kPa and/or PWV $_{\beta } \ge5.10$ ms−1 and increased to ≥ 3.33 for $\text{E}_{\text {p}} \ge143.50$ kPa and ≥ 3.25 for PWV $_{\beta } \ge7.31$ ms−1. Conclusion: The study demonstrated the feasibility of carotid stiffness measurement in a community setting. A positive association between the risk factors and carotid artery stiffness provides evidence for the device’s use in resource-constrained settings. Clinical Impact: The device paves the way for epidemiological and clinical studies that are essential for establishing population-level nomograms for wide-spread use of carotid stiffness in clinical practice and field screening of ‘at-risk’ subjects.

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Assessment of Carotid Arterial Stiffness in Community Settings With ARTSENS

Noninvasive continuous blood pressure estimation is a promising alternative to minimally invasive blood pressure measurement using cuff and invasive catheter measurement, because it opens the way to both long-term and continuous blood pressure monitoring in ecological situation. The most current estimation algorithm is based on pulse transit time measurement where at least two measured signals need to be acquired. From the pulse transit time values, it is possible to estimate the continuous blood pressure for each cardiac cycle. This measurement highly depends on arterial properties which are not easily accessible with common measurement techniques; but these properties are needed as input for the estimation algorithm. With every change of input arterial properties, the error in the blood pressure estimation rises, thus a periodic calibration procedure is needed for error minimization. Recent research is focused on simplified constant arterial properties which are not constant over time and uses only linear model based on initial measurement. The elaboration of continuous calibration procedures, independent of recalibration measurement, is the key to improving the accuracy and robustness of noninvasive continuous blood pressure estimation. However, most models in literature are based on linear approximation and we discuss here the need for more complete calibration models. 

Noninvasive Continuous Blood Pressure Estimation From Pulse Transit Time: A Review of the Calibration Models

Local pulse wave velocity (PWV) is evolving as one of the important determinants of arterial hemodynamics, localized vessel stiffening associated with several pathologies, and a host of other cardiovascular events. Although PWV was introduced over a century ago, only in recent decades, due to various technological advancements, has emphasis been directed toward its measurement from a single arterial section or from piecewise segments of a target arterial section. This emerging worldwide trend in the exploration of instrumental solutions for local PWV measurement has produced several invasive and noninvasive methods. As of yet, however, a univocal opinion on the ideal measurement method has not emerged. Neither have there been extensive comparative studies on the accuracy of the available methods. Recognizing this reality, makes apparent the need to establish guideline-recommended standards for the measurement methods and reference values, without which clinical application cannot be pursued. This paper enumerates all major local PWV measurement methods while pinpointing their salient methodological considerations and emphasizing the necessity of global standardization. Further, a summary of the advancements in measuring modalities and clinical applications is provided. Additionally, a detailed discussion on the minimally explored concept of incremental local PWV is presented along with suggestions of future research questions.

Local Pulse Wave Velocity: Theory, Methods, Advancements, and Clinical Applications

The stiffness of large arteries, measured locally from a small segment or regionally over a long trajectory, has a highly clinically relevant role in cardiovascular hemodynamics. A comprehensive measure of vascular stiffness accounting for both the local and regional stiffness indices has strong potential in stratifying risks of future events. Existing technologies are not amenable for such combined measurements, especially with provisions for easy-to-use, minimal operator dependency, portability, and field deployability. In this work, we report a novel device with these features that perform simultaneous measurement of local and regional stiffness indices. The device uses a single-element ultrasound transducer to measure carotid diameter waveforms in an image-free manner. It estimates the carotid local stiffness indices such as stiffness index (β), pressure-strain elastic modulus (EP), and one-point local pulse wave velocity (PWV β ). A bladder-type thigh cuff enabled the synchronized acquisition of femoral pressure pulse wave, and was used to measure the carotid-femoral pulse wave velocity (cfPWV) – the gold-standard regional aortic stiffness index. An in-vivo study on 35 subjects verified the functionality and measurement reliability of the ARTSENS®. The measured beat-by-beat carotid β (range: 2.71 – 11.15), EP (range: 32.31 – 153.65 kPa), and PWV β (range: 3.50 – 7.72 m/s) were repeatable with variability < 8.7%. The cfPWV measurements were in agreement with that provided by SphygmoCor device (R = 0.93, p < 0.001, and mean absolute error = 4.82%). The association between local and regional stiffness indices was further investigated. This study demonstrated a strong potential of using ARTSENS® to easily evaluate local and regional stiffness for screening in clinical and resource-constrained settings.

An Image-Free Ultrasound Device for Simultaneous Measurement of Local and Regional Arterial Stiffness Indices

Non-invasive evaluation of vascular stiffness has established utility in cardiovascular risk and stroke prediction. This work presents an accelerometric sensor-based system with an integrated hydrostatic pressure correction unit for arterial luminal diameter measurement and local vascular stiffness assessment. A custom-designed accelerometric patch for continuous monitoring of percutaneous acceleration plethysmogram (APG) from the common carotid artery, which could estimate the arterial wall displacement, was developed. A calibration model was established to estimate the true carotid luminal diameter waveform from the accelerometer-based arterial wall displacement signals. The system’s accuracy for carotid stiffness measurement was validated by multiple in-vivo human subject studies and compared against a clinical-grade B-mode ultrasound imaging system. Accelerometric-derived carotid diameter waveform morphologically replicated the anachrotic, and dicrotic limb of the true carotid diameter recorded using reference devices. The group-average baseline value of measured carotid end-diastolic diameter and distension was 5.81 ± 0.53 mm and 0.51 ± 0.15 mm with a maximum observed beat-by-beat variation of 6.5% and 9%, respectively. Accelerometer-based vascular stiffness measures showed a significant correlation (R2 > 0.88, P < 0.0001), and clinically acceptable agreement with a reference standard imaging system. APG derived carotid stiffness indices demonstrated the capability to detect expected age-associated changes in stiffness. The study revealed that the accelerometric sensor system offers a reliable, cost-effective method for long-term non-invasive monitoring of location-specific vascular stiffness measures with potential applications in ambulatory healthcare monitors.

V. V. Abhidev

Papers

Local Pulse Wave Velocity: Theory, Methods, Advancements, and Clinical Applications

An Image-Free Ultrasound Device for Simultaneous Measurement of Local and Regional Arterial Stiffness Indices

An Accelerometric Sensor System With Integrated Hydrostatic Pressure Correction to Assess Carotid Arterial Stiffness