Louise Keehn

Central Aortic Blood Pressure From Ultrasound Wall-Tracking of the Carotid Artery in Children Comparison With Invasive Measurements and Radial Tonometry

Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP (r=0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods (r=0.95; P<0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements.Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP ( r =0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods ( r =0.95; P <0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements. # Novelty and Significance {#article-title-25}

Decreased arterial elasticity in children with nondialysis chronic kidney disease is related to blood pressure and not to glomerular filtration rate.

We compared large artery mechanical properties in children with nondialysis stages of chronic kidney disease with those in children with normal renal function, examining the potential effect of blood pressure (BP) components and level of renal dysfunction. Common carotid artery mechanical properties, carotid-femoral pulse wave velocity, and carotid and peripheral BP were measured in children (n=226) with nondialysis chronic kidney disease (n=188; 11.9±3.7 years; 26%, 25%, 30%, 16%, and 3% in stages 1, 2, 3, 4 and 5, respectively) and healthy controls (n=38; 11.5±3.3 years). In children with nondialysis chronic kidney disease when compared with healthy controls, at similar levels of peripheral and carotid BP, carotid artery diastolic diameter and wall thickness were similar. In those with suboptimal BP (≥75th percentile), indices of arterial elasticity indicated greater stiffness than in healthy normotensive controls (distensibility: 92±31 versus 114±33 kPa−1×10−3, P=0.03; compliance: 2.1±0.7 versus 2.6±0.7 m2 kPa−1×10−6, P=0.02; Young elastic modulus: 0.151±0.068 versus 0.109±0.049 kPa×103, P=0.02; and wall stress: 83.6±23.5 versus 68.7±14.9 kPa, P=0.02). In all children, mechanical properties were independently related to carotid and peripheral BP components but not to estimated glomerular filtration rate. In children with nondialysis chronic kidney disease, changes in elastic properties of the carotid artery are primarily related to BP and not to glomerular renal function.

Altered dependence of aortic pulse wave velocity on transmural pressure in hypertension revealing structural change in the aortic wall.

Aortic pulse wave velocity (aPWV), a major prognostic indicator of cardiovascular events, may be augmented in hypertension as a result of the aorta being stretched by a higher distending blood pressure or by a structural change. We used a novel technique to modulate intrathoracic pressure and thus aortic transmural pressure (TMP) to examine the variation of intrathoracic aPWV with TMP in hypertensive (n=20; mean±SD age, 52.1±15.3 years; blood pressure, 159.6±21.2/92.0±15.9 mm Hg) and normotensive (n=20; age, 55.5±11.1 years; blood pressure, 124.5±11.9/72.6±9.1 mm Hg) subjects. aPWV was measured using dual Doppler probes to insonate the right brachiocephalic artery and aorta at the level of the diaphragm. Resting aPWV was greater in hypertensive compared with normotensive subjects (897±50 cm/s versus 784±43 cm/s; P<0.05). aPWV was equal in hypertensive and normotensive subjects when measured at a TMP of 96 mm Hg. However, dependence of aPWV on TMP in normotensive subjects was greater than that in hypertensive subjects (9.6±1.6 versus 3.8±0.7 cm/s per mm Hg increase in TMP, respectively, means±SEM; P<0.01). This experimental behavior was best explained by a theoretical model incorporating strain-induced recruitment of stiffer fibers in normotensive subjects and fully recruited stiffer fibers in hypertensive subjects. These results explain previous contradictory findings with respect to isobaric aPWV in hypertensive compared with normotensive subjects. They suggest that hypertension is associated with a profound change in aortic wall mechanical properties possibly because of destruction of elastin leading to less strain-induced stiffening and predisposition to aortic dissection.

Measurement of pulse wave velocity in children: comparison of volumetric and tonometric sensors, brachial-femoral and carotid-femoral pathways

Background: Pulse wave velocity (PWV), a measure of arterial stiffness strongly predictive of cardiovascular risk in adults, is usually measured by sequential ECG-referenced carotid and femoral tonometry. A simplified technique, more suitable for use in children, employs simultaneous volumetric recording from a sensor applied over the carotid artery and a cuff applied over the femoral artery or arm and thigh pressure cuffs applied over the brachial and femoral arteries. The purpose of this study was to compare PWV computed over the carotid-femoral path (PWVcf) with that over the brachial-femoral path (PWVbf) using a volumetric system (Vicorder) and to compare values of PWVcf obtained by the volumetric and a tonometric method (SphygmoCor) in children. Method: Vicorder PWVcf and PWVbf were compared in 156 children (3–18 years, 110 with chronic kidney disease), and PWVcf by Vicorder was compared to PWVcf by SphygmoCor in a subset of 122 patients. Results: PWVcf by Vicorder was moderately correlated with PWVcf by SphygmoCor (R = 0.50, P < 0.000). PWVbf and PWVcf Vicorder were more closely correlated (R = 0.75, P < 0.0001), but with a significant systematic difference. Applying a correction factor to PWVbf measurements gave results similar to those obtained over the carotid-femoral path. Within-patient coefficients of variation for repeated measures were 5.9, 7.8, and 8.5% for PWVbf (Vicorder), PWVcf (Vicorder) and PWVcf (SphygmoCor), respectively. All PWV values showed a similar relation to age. Conclusion: Volumetric methods appear reproducible and are easy to use in children, but values obtained by Vicorder and SphygmoCor are not interchangeable even when measured over the same pathway.

Gut microbial diversity is associated with lower arterial stiffness in women

Abstract Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= −0.25(0.07), P = 1 × 10−4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing—two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3–12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.

Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort

Aims Vascular ageing is characterized by arterial stiffening, dilation, and arterial wall thickening. We investigated the extent to which these changes are related and their heritability during 5 year follow-up in the Twins UK cohort. Methods and results Carotid-femoral pulse wave velocity (PWVcf), carotid diameter, carotid distensibility, and carotid intima-media thickness (IMT) were measured in 762 female twins (mean age 57.9 ± 8.6 years) at two time-points over an average follow-up of 4.9 ± 1.5 years. Magnetic resonance imaging (MRI) was performed in a sub-sample of 38 women to measure aortic pulse wave velocity (PWVaorta), diameter, and wall thickness. Heritability of changes in arterial wall properties was estimated using structural equation modelling. Annual increases in PWVcf, carotid diameter, distensibility, and IMT were 0.139 m/s, 0.028 mm, -0.4 kPa-1, and 0.011 mm per year, respectively. In regression analysis, predictors of progression in PWVcf included age, mean arterial pressure (MAP), and heart rate (HR) at baseline, and progression in MAP, HR, and body mass index (BMI). Predictors of progression in IMT included progression in MAP, BMI, and triglyceride levels. Progression of PWV and distensibility correlated with progression in carotid diameter but not with IMT. Heritability of progression of PWVcf, diameter, and IMT was 55%, 21%, and 8%, respectively. In a sub-sample of women that underwent MRI, aortic wall thickness increased by 0.19 mm/year, but aortic wall thickening was not correlated with an increase in lumen diameter or PWVaorta. Conclusion Arterial stiffening, as measured by PWVcf, and dilation are heritable but independent of arterial wall thickening. Genetic and cardiovascular risk factors contribute differently to progression of PWV and IMT.

[PP.03.08] THE HAEMODYNAMIC MECHANISM OF THE AGE-RELATED INCREASE IN PULSE PRESSURE IN WOMEN

Objective: An age-related increase in pulse pressure is the major cause of morbidity and mortality in the ageing population and is more marked in women than in men. The haemodynamic determinants of increased pulse pressure remain incompletely understood. The aim of this study is was to examine the contribution of ventricular dynamics, large artery stiffness, and pressure wave reflection to central pulse pressure. Design and method: A total of 2162 women aged 18 to 91 years (mean ± SD, age 57 ± 13 years) from the Twins UK cohort were studied. Non-invasive aortic flow velocity and blood pressure were measured by Doppler sonography and carotid tonometry system respectively. Carotid-femoral PWV was measured using the SphygmoCor system. Reflection index (the ratio of the peak of the backward pressure wave over that of the forward pressure wave) was computed from the pressure and flow waves. Results: Central pulse pressure increased with age, from 29.5 ± 0.46 mmHg for those aged below 40 years to 52.6 ± 0.85 mmHg for those over 70 years (means ± SE, P < 0.001). PWV increased approximately 13.2% per decade. Maximum flow velocity tended to increase (from 1.11 ± 0.01 to 1.16 ± 0.01 m/s over the 5 decades, P < 0.01), and ejection volume at the time of peak pulse pressure increased from 63.3 ± 1.41 to 72.3 ± 1.92 ml (P < 0.001) but reflection index decreased from 0.28 ± 0.01 to 0.25 ± 0.01 (P < 0.001). Conclusions: These results suggest that the age-related increase in central pulse pressure is driven mainly by an increase in arterial stiffening and increased ventricular ejection.

Response to Validation of Devices and Methods for Noninvasive Estimation of Central Aortic Blood Pressure in Children

We thank Papaioannou and colleagues for their interest in our study.1 They raise several related concerns regarding the influence of errors in the determination of peripheral blood pressure (BP; which our study did not address) on estimates of central blood pressure.2 We agree that this is a most important point. All of the current noninvasive methods for measuring central blood pressure require calibration from peripheral BP measurements. However, errors in peripheral BP are transferred to central blood pressure, so that the difference between central and peripheral systolic blood pressure is affected little by peripheral calibration3 and the ratio of central to peripheral pulse pressure is not affected by calibration. Thus, if relative differences (eg, effects of treatment on central versus peripheral BP) are of interest, the issue of calibration is less critical. For absolute measurements …

Central Aortic Blood Pressure From Ultrasound Wall-Tracking of the Carotid Artery in Children

Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP (r=0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods (r=0.95; P<0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements.Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP ( r =0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods ( r =0.95; P <0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements. # Novelty and Significance {#article-title-25}

Central Aortic Blood Pressure From Ultrasound Wall-Tracking of the Carotid Artery in ChildrenNovelty and Significance

Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP (r=0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods (r=0.95; P<0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements.Differences between central aortic root (c) and peripheral (p) systolic blood pressure (SBP) may be particularly marked in children, but noninvasive methods for assessing cSBP in children have not been validated. We compared estimates of cSBP obtained from radiofrequency ultrasound wall tracking of the carotid artery (ART.LAB system) with that measured directly by a catheter in the aortic root at the time of arterial cannulation. Carotid waveforms were calibrated from invasive measurements of mean and diastolic pressures. In 9 children aged 10.5±5.0 years (mean±SD), cSBP obtained from carotid wall tracking was highly correlated with invasive measures of cSBP ( r =0.99) with mean (±SD) difference 3.9±2.5 mm Hg. Second, we compared values of cSBP obtained from the carotid with those obtained using noninvasive applanation tonometry at the radial artery and a radial-to-aortic transfer function (SphygmoCor). Both carotid and radial tonometric measurements were calibrated from the same peripheral mean and diastolic measurements of blood pressure obtained by sphygmomanometry. In 84 children aged 13.2±3.2 years, there was excellent agreement between the 2 methods ( r =0.95; P <0.001) with mean difference 0.71±3.7 mm Hg (95% confidence interval =−1.53 to 1.01). This invasive validation study confirms that cSBP as estimated by carotid wall tracking provides an acceptable measurement of true cSBP when calibration is from true mean and diastolic pressures. Close agreement of cSBP obtained by carotid wall tracking and radial tonometry suggests that these provide similar results when calibrated from the same peripheral blood pressure measurements. # Novelty and Significance {#article-title-25}