Sebastian Vermeersch

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'Establishing normal and reference values'

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.

Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity

Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis)

OBJECTIVES This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample. BACKGROUND Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. METHODS Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] × 100), augmentation index ([Second/First systolic peak] × 100) and pulse pressure amplification ([Radial/aortic pulse pressure] × 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years. RESULTS After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p < 0.0001), comparing favorably to other risk factors for CHF as per various measures of model performance, reclassification, and discrimination. In a fully adjusted model, compared to nonhypertensive subjects with low RM, the HRs (95% CI) for hypertensive subjects with low RM, nonhypertensive subjects with high RM, and hypertensive subjects with high RM were 1.81 (0.85 to 3.86), 2.16 (1.07 to 5.01), and 3.98 (1.96 to 8.05), respectively. CONCLUSIONS Arterial wave reflections represent a novel strong risk factor for CHF in the general population.

Noninvasive (Input) Impedance, Pulse Wave Velocity, and Wave Reflection in Healthy Middle-Aged Men and Women

The relation between arterial function indices, such as pulse wave velocity and augmentation index with parameters derived from input impedance analysis, is still incompletely understood. Carotid pressure, central flow waveforms, and pulse wave velocity were noninvasively acquired in 2026 apparently healthy, middle-aged subjects (1052 women and 974 men) 35 to 55 years old at inclusion. Input and characteristic impedance, reflection coefficient, the ratio of backward-to-forward pressure amplitude (reflection magnitude), and augmentation index were derived. Pulse wave velocity increased by 15% (from 6.1 to 7.0 m/s) both in men and women. In qualitative terms, input impedance evolved from a pattern indicative of wave transmission and reflection to a pattern more compatible with a windkessel-like system. In women, a decrease in total arterial compliance led to an increased input impedance in the low frequency range, whereas few changes were observed in men. Characteristic impedance did not change with age in women and even decreased in men (P<0.001) and could not be identified as the primary determinant of central pulse pressure. Augmentation index increased with age, as was expected, and was systematically higher in women (P<0.001). Reflection coefficient and reflection magnitude increased with age (P<0.001) without gender differences. We conclude that, in healthy middle-aged subjects, the age-related increase in arterial stiffness (pulse wave velocity) is not fully paralleled by an increase in arterial impedance, suggesting a role for age-dependent modulation of aortic cross-sectional area. Wave reflection increases with age and is not higher in women than in men.

Age and gender related patterns in carotid-femoral PWV and carotid and femoral stiffness in a large healthy, middle-aged population.

Background The relationship between aortic (carotid–femoral) pulse wave velocity and stiffness measures based on local diameter and pressure readings is not yet fully understood. Methods We compared the relationship with age and gender of aortic pulse wave velocity to stiffness indices (compliance and distensibility coefficient) evaluated at the common carotid and femoral arteries in 2195 (1131 women) apparently healthy subjects, aged 35–55 years participating in the Asklepios study. Aortic pulse wave velocity was further compared with previously reported central arterial stiffness parameters on the same population. Subjects were divided into four age groups for analysis. Results Femoral arterial stiffness was higher in men than in women (P < 0.001) but did not change with age and no age–gender interaction was evident. Carotid arterial stiffness increased with age (P < 0.001) and showed a significant (P < 0.001) age–gender interaction, with carotid stiffness increasing more rapidly in women than in men, crossing over around the age of 45. Aortic pulse wave velocity did not differ between men and women, but did increase with age (P < 0.001). No age–gender interaction was evident. Conclusion The relation with age and gender of local and central stiffness measures is not the same over the age range 35–55 in apparently healthy men and women. Depending on the central stiffness parameter used, age–gender effects evident at the carotid artery are or are not found centrally. Though the relevance of these differences requires further evaluation in a longitudinal study with outcome data, they need to be kept in mind when designing or interpreting results from arterial stiffness evaluation studies.

Carotid to femoral pulse wave velocity: a comparison of real travelled aortic path lengths determined by MRI and superficial measurements.

Objectives Carotid–femoral pulse wave velocity (PWV) is the gold standard method for determination of arterial stiffness. PWV is assessed by dividing travelled distance by travel time. Standardization and validation of the methodology for travelled distance measurement is of crucial importance. The aim of the current investigation was to standardize and validate the methodology for travelled distance measurement. Methods Real travelled carotid–femoral path lengths were measured with MRI in 98 healthy men/women (50% men, age 21–76 years) and are used as reference distance. This reference distance was compared with 11 estimates of aortic path length from body surface distances commonly used in PWV measurement, nine of them based on tape measures and two based on body height. Determinants of the difference between reference distance and the best body surface distance were determined. Additionally, the influence of body contours was identified. Results The tape measure distance from carotid to femoral artery (CA-FA), multiplied by 0.8, yielded the best agreement with the reference aortic path length [difference 0.26 cm (SD 3.8), not statistically significant]. Thirty percent of the variation in difference between the reference distance and tape measure distance (CA-FA × 0.8) was explained by age. Adding BMI increased this number to 34%. Conclusion The tape measure distance from CA-FA, multiplied by 0.8, corresponds best with the real travelled aortic path length. This distance is moderately (yet statistically significantly) influenced by age and minimally by BMI.

Distance measurements for the assessment of carotid to femoral pulse wave velocity

Background Carotid–femoral pulse wave velocity can be determined using different distances – either direct carotid–femoral distance or subtracted [(sternal–femoral) − (carotid–sternal)] distance – resulting in pulse wave velocity differences of up to 30%. The present study aims to present and validate a population-based model for the conversion between distances. Method Three thousand one hundred and sixteen participants from the Asklepios study (n = 2510) and Hôpital Européen Georges Pompidou (n = 606) databases, in which all distance measurements were available, were randomly distributed in a model (n = 311) and validation (n = 2805) population. Model parameters for the conversion equations were selected and evaluated using multiple linear regression with stepwise selection of covariates (age, sex, weight, height, BMI and waist circumference). The proposed model was evaluated on the validation population. Results The difference between direct and subtracted distances was found to be partially dependent on body height, and its inclusion in the multivariate model improved model performance by over 20%. Other combinations of adjustments did not improve model prediction. Conversion equations derived in the model population were: Estimated Direct_distance = 0.45*Subtracted_distance + 0.21*height + 0.08 and Estimated Subtracted_distance = 1.04*Direct_distance − 0.11*height − 0.02, respectively. Applying these equations for estimation of direct and subtracted distances in the validation population yielded good correspondence to measured results (r2 = 0.73 and 0.57, respectively), with nonsignificant mean differences between estimated and measured values. Increasing the size of the model population did not significantly change the model validity. Conclusion In cases in which not all distance measurements are available for exact conversion, the presented equations can be used to convert between distance definitions.

Determining carotid artery pressure from scaled diameter waveforms: comparison and validation of calibration techniques in 2026 subjects

Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation.

Comparison of central pressure estimates obtained from SphygmoCor, Omron HEM-9000AI and carotid applanation tonometry

Background The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor.

Noninvasive determination of local pulse wave velocity and wave intensity: changes with age and gender in the carotid and femoral arteries of healthy human

We recently introduced noninvasive methods to assess local pulse wave velocity (PWV) and wave intensity ((n)dI) in arteries based on measurements of flow velocity (U) and diameter (D). Although the methods were validated in an experimental setting, clinical application remains lacking. The aim of this study was therefore to investigate the effect of age and gender on PWV and (n)dI in the carotid and femoral arteries of an existing population. We measured D and U in the carotid and femoral arteries of 1,774 healthy subjects aged 35-55 yr, a subgroup of the Asklepios population. With the use of the lnDU-loop method, we calculated local PWV, which was used to determine arterial distensibility ((n)Ds). We then used the new algorithm to determine maximum forward and backward wave intensities ((n)dI(+max) and (n)dI(-min), respectively) and the reflection index ((n)RI). On average, PWV was higher, and (n)Ds was lower in the femoral than at the carotid arteries. At the carotid artery, PWV increased with age, but (n)Ds, (n)dI(+max), and (n)dI(-min) decreased; (n)RI did not change with age. At the femoral artery, PWV was higher, and (n)Ds was lower in male, but all parameters did not change significantly with age in both women and men. We conclude that the carotid artery is more affected by the aging process than the femoral artery, even in healthy subjects. The new techniques provide mechanical and hemodynamic parameters, requiring only D and U measurements, both of which can be acquired using ultrasound equipment widely available today, hence their advantage for potential use in the clinical setting.