bluuebunny/crossref_metadata_2025 huggingface dataset:
YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice
Authors: Casso Abigail G , Gioscia-Ryan Rachel A , Sapinsley Zachary J , Van Dongen Nicholas S , Bazzoni Amy E , Neilson Andrew P , Zigler Melanie C , Davy Kevin P , Seals Douglas R , Brunt Vienna E
Published: December 2020

Age-related increases in aortic stiffness, assessed by pulse wave velocity (PWV), predict cardiovascular (CV)-related mortality, but the upstream drivers are incompletely understood.

Purpose

To determine if higher circulating levels of the gut microbiome-derived metabolite trimethylamine-N-oxide (TMAO) contribute to age-related aortic stiffening.

Methods and Results

Plasma TMAO concentrations were higher in healthy middle-aged-to-older (45–79 y; N = 83) vs. young (18–27 y; N = 14) humans (6.3 ± 0.6 vs. 1.8 ± 0.3 μM; p < 0.01) and positively related to carotid-femoral (c-f) PWV (r2 = 0.15, p < 0.0001). To determine the role of TMAO in established age-related aortic stiffness, we supplemented old mice (27 mo; N = 12–16/group) with 1% 3,3-dimethyl-1-butanol (DMB; suppresses microbiota-dependent TMAO production) in drinking water for 8–10 weeks vs. normal drinking water (control). Relative to young mice (3 mo; N = 23), old mice had higher aortic (a) PWV (412 ± 17 vs. 349 ± 11 cm/s; p < 0.01), but DMB had no effect on aPWV (p = 0.58 vs. control) despite suppressing plasma TMAO (control: 8.7 ± 6.3 vs. DMB: 4.3 ± 1.2 µM, p = 0.07) to young levels (3.8 ± 2.6 µM). Next, to determine if TMAO contributes to the development of aortic stiffening, we initiated DMB at mid-life (18 mo; i.e., before the onset of stiffening; N = 8–21/age/treatment). aPWV was similar between young and 18 month-old mice (363 ± 5 cm/s; p = 0.58), but increased progressively with age in control mice (24 mo: 401 ± 13 cm/s, p = 0.03 vs. young; 27 mo: 442 ± 10 cm/s, p < 0.001 vs. young), whereas age-related increases in PWV were considerably attenuated by DMB (24 mo: 359 ± 9 cm/s; 27 mo: 388 ± 10 cm/s, both p < 0.01 vs. control).

Conclusions

Age-related increases in TMAO contribute to the development of aortic stiffness. TMAO-targeted interventions initiated in mid-life may prevent/delay age-related aortic stiffening and reduce CV risk.

Funding

HL134887-02S1, AG060884, HL140875, AG000279.
YI 1.6 Flow Mediated Slowing of Pulse Wave Velocity as a Measure of Endothelial Function
Authors: Sharma Anju , Chandran Dinu S. , Jaryal Ashok , Deepak Kishore K.
Published: December 2020

Purpose

Ultrasonographic measurement of flow mediated dilatation (FMD) of brachial artery is the gold standard non-invasive technique to measure endothelial function. However, measurement of FMD is technically cumbersome, operator dependent and requires trained manpower, all of which limits its clinical utility. Flow mediated slowing (FMS) of regional arterial pulse wave velocity (PWV) has been proposed as a feasible, operator-independent alternative to ultrasonographically measured FMD [1,2]. We investigated the temporal correlation between brachial artery FMD and simultaneously recorded FMS of brachial-radial PWV in healthy volunteers.

Methods

Twenty-three healthy volunteers, involving 15 males and 8 females with age 26.39 ± 4.41 participated in the study. Endothelial function was assessed by measuring FMS of brachial-radial PWV using two-point applanation tonometry and simultaneously performed ultrasonographic imaging of brachial artery to record FMD. After 1-minute of baseline recording, distal supra-systolic arterial occlusion was produced by inflating a sphygmomanometer cuff to 250 mmHg for 5 minutes. During the phase of reactive hyperemia that follows the release of distal arterial occlusion, both the parameters were simultaneously recorded for a period of 6-minutes.

Results

Flow mediated slowing of pulse wave velocity didn’t correlate with simultaneously recorded FMD. Recovery of PWV coinciding with peak FMD showed strong positive correlation with FMD (r = 0.60, p = 0.002). Time averaged recovery of PWV during the period 60–90s post release of occlusion correlated with FMD (r = 0.46, p = 0.0253).

Conclusion

Recovery of brachial-radial PWV during post-occlusive reactive hyperemia could be used as a feasible, imaging independent alternative to ultrasonographically measured FMD.
YI 1.7 Transmural Quantification of Murine Vascular Smooth Muscle Cell Density Distribution from 3D Microscopy Images
Authors: van der Laan Koen W. F. , Reesink Koen D. , van der Bruggen Myrthe M. , Jaminon Armand M. G. , Megens Remco T. A. , Schurgers Leon J. , Delhaas Tammo , Spronck Bart
Published: December 2020

Purpose

Investigating the biomechanical role of smooth muscle cells (SMCs) in arteries requires knowledge of their structural distributions. Compared to histology, 3D microscopy offers non-destructive ex vivo imaging under realistic conditions [1]. Robust 3D segmentation of SMCs, however, is challenging. We propose a method for automatic SMC quantification, and assessed its potential using a murine SMC apoptosis model.

Methods

After euthanasia, carotid arteries (control and with induced SMC apoptosis: SM22α-hDTR [2]) were excised and mounted between micropipettes (Figure A). Nuclei were stained with SYTO41. Arteries were imaged using two-photon microscopy [1], while stretched to in vivo length and pressurised to 100 mmHg (Figure B). Image stacks were processed as follows: 1) deconvolution; 2) nuclei segmentation using vesselness filtering [3,4] (Figure C); 3) cylindrical coordinate system identification; 4) splitting of coincident nuclei, based on cores defined from groups of neighbouring voxels with similar orientations [3] (Figure D and E); 5) cylindrical coordinate system re-identification; and 6) cell density-distribution quantification (Figure F). Segmentation performance was assessed by comparing with manual cell counts.

Results

Figure E demonstrates the method’s ability to split undersegmented coinciding nuclei. Cell counts were lower in SM22α-hDTR than in control; algorithm-derived counts were comparable to manual (Figure F). The control sample showed multiple SMC layers, while the SM22α-hDTR sample showed a single SMC layer (Figure F), which was confirmed visually.

Conclusion

We developed a precise tool to quantify SMC distributions in ex vivo murine arteries, to facilitate quantitative modelling of SMC biomechanics. We intend to expand the current approach to address cell orientation, shape, and size.
YI 2.1 Pulse Wave Velocity Estimation from the Radial Pulse Waveform using Gaussian Process Regression: A Machine Learning Based Study
Authors: Jin Weiwei , Chowienczyk Phil , Alastruey Jordi
Published: December 2020

Objective and Motivation

Pulse wave velocity (PWV) is known to be associated with vascular ageing, a risk factor for cardiovascular disease (CVD) [1]. The European gold standard measurement of PWV requires an experienced operator to measure pulse waveforms at multiple sites, sometimes together with an electrocardiogram [2,3]. This study aims to estimate PWV from the radial pulse waveform using machine learning.

Methods

Radial pulse waveforms and carotid-femoral PWVs were acquired in 3,082 unselected twins (https://twinsuk.ac.uk). 14 fiducial points on each pulse waveform were extracted using an in-house algorithm [4]. LASSO regression and principal component analysis (PCA) were used to identify the key features (timing and magnitude of the fiducial points) associated with PWV and exclude outliers. Finally, Gaussian process regression was used to estimate the PWV based on those key features only.

Results

Results show that PWV can be estimated from the radial pulse waveform only with an overall root mean squared error (RMSE) of 1.82 m/s (Figure A). Most of the measured PWV values were within the 95% confidence interval range of the estimated PWV. The difference between measured and estimated PWV values increased with the increasing PWV. PWV estimation on a subgroup of twins with a healthy range of blood pressure and PWV values [5] was achieved with a RMSE of 1.38 m/s (Figure B).

Conclusion

In this proof-of-concept study we have shown the possibility of estimating PWV from the radial pulse waveform using machine learning. This approach could make CVD detection more accessible to the wider population.
YI 2.4 Neural Baroreflex Sensitivity and Long-Term Effect of Antihypertensive Agents—A Pharmacological Substudy of the Paris Prospective Study III
Authors: Danchin Nicolas , Guibout Catherine , Jouven Xavier , Perier Marie-Cécile , Thomas Frederique , Fortier Catherine , Empana Jean-Philippe , Khettab Hakim , Bruno Rosa-Maria , Boutouyrie Pierre
Published: December 2020

Background/Objectives

The baroreflex is a crucial mechanism acutely modulating vascular tone and heart rate response to maintain blood pressure (BP) in an optimal range. A decrease in baroreflex sensitivity (BRS) is associated with ageing, and pathological conditions such as hypertension and diabetes. Antihypertensive agents are generally known to have beneficial effect on the BRS, however it is still uncertain if the effect is mediated through a more compliant arterial wall or a sympathoinhibitory action.

Methods

In the Paris Prospective Study III [1], spontaneous baroreflex, carotid stiffness and pharmacological drugs intake were available in 7967 adults (aged 55–75 years). The neural component of the baroreflex sensitivity (nBRS) was obtained with a cross-spectral analysis of variations in carotid distention rate and R-R intervals. Pharmacological classes were analysed according to the Anatomical Therapeutic Chemical (ATC) classification. Individuals with a BP lowering medication (BP-treated) were paired to non-BP treated individuals with a similar cardiovascular risk (controls) using a propensity score matching procedure (n = 1182 pairs).

Results

Amongst pharmacological classes of BP lowering agents, only agents acting on the renin-angiotensin system (ACEi-ARB) were associated with nBRS (β = −0.08, p = 0.045). Compared to their matched controls, ACEi-ARB users had lower nBRS (2.79 ± 0.66 vs. 2.90 ± 0.62, p = 0.03). In multivariate analysis, ACEi-ARB remained significant (stdβ = −0.09, p = 0.025) after adjustment for carotid stiffness (stdβ = 0.25, p < 0.001) and systolic pressure (stdβ = −0.20, p < 0.001).

Conclusion

In this epidemiological study, ACEi-ARB were negatively associated with nBRS. This effect is independent of BP and stiffness, which may suggest an inhibition of sympathetic activity by ACEi-ARB.
YI 2.6 Comparison of Cardiovascular Disease Primary Prevention Guidelines between Australia, England and the United States
Authors: Chapman Niamh , Breslin Monique , Lay-Flurrie Sarah , Zhou Zhen , Sharman James , Nelson Mark , McManus Richard
Published: December 2020

Objective

Cardiovascular disease (CVD) primary prevention guidelines recommend absolute CVD risk estimation to guide blood pressure and lipid therapy recommendations but are inconsistent despite relying on similar evidence. This study aimed to compare the populations recommended for treatment according to guidelines in Australia, England and the United States.

Methods

Cross-sectional analysis of national health survey data from Australian, English and United States (n = 4,056; n = 2,994; n = 2,943; respectively) adults aged ≥40 years. Participants were classified as recommended for therapy based on clinical characteristics denoting high risk and absolute CVD risk stratification according to each country’s guidelines [1–6]. Agreement in therapy recommendation assessed by Kappa statistic.

Results

Agreement in therapy recommendation was minimal to weak (κ = 0.35–0.54). Proportions recommended for either blood pressure or lipid lowering treatment ranged between 26–32%, 47–52% and 43–47% in Australia, England and United States. There was minimal to strong agreement in therapy recommendation according to clinical criteria (κ = 0.38–0.83) and minimal to moderate agreement according to absolute CVD risk (κ = 0.28–0.64) across guidelines.

Conclusion

Despite similar evidence apparently underpinning guidance, there is little agreement in the populations targeted for CVD primary prevention with Australia recommending far few people for treatment in comparison to England or the United States. This is due to differences in both clinical characteristics considered high risk and absolute CVD risk stratification. Whilst different countries may adopt different policies on the appropriate level of risk to target, these findings suggest a need to develop international consensus definition for high CVD risk in primary prevention guideline.
P.04 A Transfer-Function-Free Technique for the Non-Invasive Estimation of Central Arterial Pressure
Authors: Giudici Alessandro , Cretu Ioana , Negoita Madalina , Wilkinson Ian B , Khir Ashraf W
Published: December 2020

Background

Central aortic pressure (CAP) is important for the determination of the cardiovascular risk. Transfer function (TF)-based techniques allow for estimating CAP non-invasively from pressure waveforms acquired distally in the circulation. However, TF-based CAP might preserve the high frequencies of the distal waveform [1]. Therefore, we propose a new method where CAP is estimated from local direct non-invasive measurements of diameter (D) and blood velocity (U) waveforms.

Methods

Aortic root D and U were measured using an ultrasound scanner (GE, Vivid E95) in 10 healthy volunteers (46 ± 15 years, 5 men), and used to determine local wave speed (PWV) using the lnDU-loop method [2]. Brachial systolic (Ps) and diastolic blood pressure (Pd), as well as central Ps, were also estimated using a sphygmomanometer (Uscom, BPPLUS-R7). CAP was determined as:

, where, and blood density = 1060 kg/m3.

Results

Mean brachial Ps and Pd were 124.1 ± 9.5 and 77.9 ± 5.4 mmHg, respectively. Mean PWV was 3.07 ± 0.71 m/s, leading to = 1.00 ± 0.46. The average calculated Ps was only –0.4% lower than TF-Ps (116.4 ± 11.2 vs. 116.9 ± 8.9, mmHg). Estimated calculated aortic and measured brachial mean pressure were almost identical with a difference of 0.01% (97.8 ± 6.9 vs. 97.8 ± 6.5, mmHg).

Discussion

This proof-of-concept study shows that the CAP waveform can be estimated non-invasively from measurements of brachial Pd, and aortic D and U obtained using equipment available in almost every cardiovascular clinic. Further studies are warranted to establish the full utility of the new technique.
P.07 The Progression of Left Ventricular Ejection Time in Simulated Microgravity
Authors: Orter Stefan , Möstl Stefan , Bachler Martin , Hoffmann Fabian , Mayer Christopher C. , Kaniusas Eugenijus , Reisinger Michaela , Wassertheurer Siegfried , Tank Jens , Hametner Bernhard
Published: December 2020

Introduction

Microgravity in space is known to cause major alterations in the cardiovascular system. Left ventricular ejection time (LVET) can be measured by the time from the onset point of the pressure wave to the incisura of the dicrotic notch. The aim of this study was to simulate microgravity by head-down tilt bedrest (HDT) to examine changes in LVET in female and male subjects.

Methods

24 healthy subjects (16 males and 8 females, height 176 ± 7 cm, weight 77 ± 6 kg, age 37 ± 10 years) were enrolled in a HDT study. The bed rest study applied strict –6° HDT for 60 days. Pulse wave measurements were taken using an oscillometric pressure cuff on the brachial artery. LVET index (LVETi) was calculated according to Weissler et al [1]. LVETis of different measurement times were compared using repeated measures ANOVA with post-hoc analysis using paired t-tests and Bonferroni correction.

Results

Figure shows a decrease of LVETi during bed rest, followed by a sharp rise of LVETi after bed rest. Repeated measures ANOVA confirmed significant differences between measurement times. The increase of LVETi from each HDT measurement day to 4 days after HDT (R + 4) was significant (p < 0.001). There were no significant differences comparing male and female subjects.

Discussion/Conclusion

Overall, we conclude that LVETi decreased during HDT and reached four days after bed rest a similar level as before for both female and male subjects. As LVETi removes heart rate induced effects on LVET, the change in LVETi might be a result of change in ventricular ejection and afterload.
P.14 Transcranial Colour Duplex Reveals Haemodynamically Significant Venous Flow Alterations Following Resection of Arteriovenous Malformation of the Brain
Authors: Busch Kathryn , Davidson Andrew , Butlin Mark , Avolio Alberto , Kiat Hosen
Published: December 2020

Background

Resection of a brain arteriovenous malformation (bAVM) can impose several post-operative challenges including post- operative haemorrhage (POH) [1]. The mechanism of such complications remains controversial although deliberately inducing hypotension has proven successful for POH prevention [2]. Daily non-invasive monitoring for patients may be useful in predicting POH. Transcranial color duplex (TCCD) and central aortic pressures (CAP) can be derived non-invasively providing pressure and haemodynamic measurements. These techniques may provide valuable insight into the process of vessel remodeling following bAVM resection.

Methods

This prospective study evaluated fifteen patients with bAVMs. CAP and TCCD were studied pre-operatively and then daily for up to 14 days post-operatively. CAP and TCCD parameters were compared with a group of normal volunteers and a control group of participants having craniotomies.

Results

The post-operative venous changes were dramatic and have not been previously studied. In the early post-operative period there was a marked prominence of venous flow adjacent to the middle cerebral artery. The venous signals demonstrated significantly increased velocities and pulsatility. Furthermore, two of the patients with sustained increased venous prominence, velocity, and pulsatility suffered a POH. After the initial period of post-operative venous flow alteration, the venous parameters returned to normal values.

Conclusion

These preliminary findings provide insight into vessel remodeling and elucidate the time frame for venous flow alterations after surgery. If confirmed in future validation studies, the period of increased venous velocity, pulsatility and prominence may correlate to the time at which patients are at risk of POH.
P.15 Isolated Systolic Hypertension and Central Blood Pressure: Implications from the National Nutrition and Health Survey in Taiwan
Authors: Chuang Shao-Yuan , Chang Hsing-Yi , Cheng Hao-Min , Pan Wen-Harn , Chen Chen-Huan
Published: December 2020

Objectives

We aimed to investigate the association between isolated systolic hypertension (ISH) and central blood pressure (BP) in a nationally representative population.

Methods

A total of 2029 adults without anti-hypertensive medicine, aged ≥19 years old participated in the 2013–2016 National Nutrition and Health Survey in Taiwan. Central and brachial BP were simultaneously measured using a cuff-based stand-alone central BP monitor purporting to measure invasive central BP (type II device). Central hypertension [1] was defined by central systolic (SBP)/diastolic BP (DBP) ≥130 or 90 mmHg, and ISH was defined by brachial SBP ≥140 and DBP <90 mmHg.

Results

The prevalence of ISH was 6.51% among adults aged ≥19 years old (2.15% [n = 21] for young adults [aged <50 years] and 10.54% [n = 111] for older adults [aged ≥50 years]). ISH subjects had significantly higher central pulse pressure (PP) (62.8 mmHg for the young and 72.4 mmHg for elders) than those subjects with either isolated diastolic hypertension (brachial SBP <140 and DBP ≥90 mmHg, central PP 44.8 mmHg) or systolic diastolic hypertension (brachial SBP ≥140 and DBP ≥90 mmHg, central PP 60.2 mmHg). There was a U-shaped trend in the association between age and ISH prevalence, and between age and central PP. The ISH prevalence was 2.95%, 1.73% and 10.54%, and the average central PP was 49.5, 47.0, and 54.0 mmHg for subjects aged <30, between 30–50, and ≥50 years, respectively. Moreover, all ISH adults had central hypertension and a higher prevalence of obesity than the normotensives (body mass index ≥27 Kg/m2, 71% vs. 17%, for age <50 years, and 27% vs. 17% for age ≥50 years).

Conclusions

All subjects with ISH, young or older, had central hypertension. Central PP was higher in the young and older age groups in comparison to the middle age group. The U-shaped trend corresponded to the association between age and ISH prevalence.
P.19 Intradialytic Changes in Cerebral Blood Flow and Regional Changes in Arterial Stiffness
Authors: Paré Mathilde , Obeid Hasan , Labrecque Lawrence , Drapeau Audrey , Marquis Karine , Brassard Patrice , Agharazii Mohsen
Published: December 2020

Purpose/Background/Objective

Cognitive decline is highly prevalent amongst end-stage renal disease (ESRD) patients and is accelerated upon initiation of hemodialysis (HD) [1]. ESRD increases aortic stiffness and blood flow pulsatility, which may damage small vessels of target organs like the brain [2]. In this pilot study, we aimed to evaluate the acute effect of HD on cerebral blood flow and its relation to arterial stiffness.

Methods

Before, every hour during and after HD (T0–T4), we measured cerebral flow velocity (FV) using transcranial Doppler, blood pressure (BP) via digital finger cuff (Nexfin), cardiac activity using ECG and aortic pulse wave velocity (PWV) with Mobile-O-Graph. FV pulsatility index (PI) and transit times between ECG peak and the foot of both FV and BP waveforms (cerebral dT; digital dT) were computed using in house MATLAB-based analysis. Changes during HD were evaluated with Generalized Estimating Equation models adjusting for multiple comparisons in SPSS 26.0.

Results

In eight participants aged 63 ± 17 y. old (4 diabetics, 3 women), peak FV decreased from baseline at T1 and T2 (−11.2 cm/s, p = 0.007; −12.2 cm/s, p < 0.001), PI decreased at T1 (0.81 to 0.77, p = 0.005), whilst minimum FV, mean BP and partial pressure of CO2 remained unchanged. Digital dT increased at T3 (0.19 to 0.22, p < 0.001) and cerebral dT increased throughout HD (T1-T4, p < 0.005), whereas aortic PWV did not change.

Conclusions

During hemodialysis, cerebral and digital transit times increased, suggesting decreased stiffness of small peripheral vessels, without significant changes in aortic stiffness. Reduced stiffness of cerebral arteries may partially explain decreased cerebral flow pulsatility.
P.21 Albuminuria Intensifies the Relationship Between Urinary Sodium Excretion and Central Pulse Pressure: The Wakuya Study
Authors: Tagawa Kaname , Tsuru Yusuke , Yokoi Katsumi , Aonuma Takanori , Hashimoto Junichiro
Published: December 2020

Objectives

Central pulse pressure (cPP) is responsible for vital organ hemodynamics [1,2], and its monitoring is important for cardiovascular disease prevention [3]. Excess sodium intake and (micro)albuminuria, a manifestation of renal microvascular damage, are also known as strong predictors of cardiovascular disease [4,5]. We sought to investigate the cross-sectional relationships among dietary sodium consumption, albuminuria and cPP in the general population.

Methods

Subjects were 933 apparently healthy adults in Wakuya town, Miyagi, Japan (mean age, 56 ± 10 years). Radial pressure waveforms were recorded with applanation tonometry to estimate mean arterial pressure (MAP), cPP, forward and backward pressure amplitudes, and augmentation index. Urinary sodium/creatinine ratio (UNaCR) and albumin/creatinine ratio (UACR) were measured in spot urine samples.

Results

Median values of UNaCR, UACR and cPP were 139 (interquartile range, 89–205) mEq/g, 5 (4–11) mg/g and 38 (33–45) mmHg, respectively. Both UACR and UNaCR were positively correlated with cPP, even after adjusted for MAP (p < 0.001). Moreover, UACR and UNaCR had a synergistic influence on increasing cPP, which was independent of age, sex, estimated glomerular filtration rate, hyperlipidemia and diabetes (interaction p < 0.05). A similar synergistic influence between UACR and UNaCR was found on the forward but not backward pressure amplitude or augmentation index. The overall results were not altered on replacement of UACR with the existence of chronic kidney disease.

Conclusions

(Micro)albuminuria strengthens the positive association between urinary sodium excretion and central pulse (and systolic forward) pressure. Excess sodium intake may magnify cardiovascular risk through widening aortic pulsatile pressure, particularly in the presence of concomitant chronic kidney disease.
P.24 Factors Associated with Premature Vascular Aging in Patients with Arterial Hypertension
Authors: Melekhina I. V. Inna , Medvedeva E. G. Elizaveta Georgievna , Ivanova S. V. Svetlana , Yushchuk E. N. Elena , Trush E. Yu. Ekaterina
Published: December 2020

Objectives

Identification of factors associated with premature vascular aging in patients with arterial hypertension (AH).

Methods

The study included 61 patients (29 men, 32 women) with 1–2 grade AH without cardiovascular complications, aged 40 to 60 years, of which 28 (45.9%) had type 2 diabetes. The duration of AH was 5.0 [2.0; 10.0] years, type 2 diabetes - 2.0 [1.0; 4.0] years. The assessment of vascular stiffness using cardio-ankle vascular index (CAVI) and vascular age (VA) was performed by volumetric sphygmography (VaSera-1500). All patients were divided into 2 groups: with normal VA (the passport age corresponds to the VA, n = 35) and premature vascular aging (the VA is higher than the passport age, n = 26).

Results

There were no significant differences in gender, smoking, dyslipidemia, and the presence and duration of type 2 diabetes in the comparison groups. Significantly higher values of blood pressure (BP) were observed in the group of patients with premature vascular aging - 153.7 ± 26.2/95.3 ± 13.2 versus 137.9 ± 18.6/88.4 ± 13.3 mm Hg., higher duration of AH 10.0 [4.0; 13.0] vs. 3.0 [1.0; 8.0] years, higher blood urea level 5.7 [5.3; 6.8] vs. 4.5 [3.8; 5.8] mmol/l, increased CAVI average values on the right and on the left 8.8 [8.4; 9.4] vs. 7.4 [6.7; 7.9], intima-media thickness (IMT) of CCA (0.92 ± 0.13 vs. 0.80 ± 0.09 mm) and LV mass index (LVMI), 96.1 ± 21.8 vs. 86.1 ± 20.7 g/m2.

Conclusion

Premature vascular aging in patients with AH was associated with the degree and duration of hypertension, increased IMT, vascular stiffness [1], blood urea levels and LVMI.
P.25 Radial-Digital Pulse Wave Velocity: A Non-Invasive Method for Assessing Stiffness of Peripheral Small Arteries
Authors: Obeid Hasan , Garneau Charles-Antoine , Fortier Catherine , Pare Mathilde , Boutouyrie Pierre , Agharazii Mohsen
Published: December 2020

Pulse wave velocity (PWV) has been used to evaluate arterial stiffness of large arteries. Here, we examine the feasibility of radialdigital PWV (RD-PWV) as a measure of stiffness of smaller arteries, and its response to changes in local mean arterial pressure. In 29 healthy subjects, we used Complior probes to record arterial pulse wave at radial artery and tip of the index. To determine transit time, we used both second derivative and intersecting tangents of the entire recordings using the device-embedded algorithms, in house Matlab analyses of only reliable waves, and by numerical simulation using arterial tree model. In 15 subjects, we examine the response of RD-PWV to changes in local MAP by vertical displacement of the hand above and below the mid-axillary line. Using second derivative, RD-PWV were 4.68 ± 1.18, 4.69 ± 1.21, 4.32 ± 1.19 m/s respectively for deviceembedded, Matlab-based and numerical simulation analyses, respectively. Using intersecting tangents RD-PWV were 4.73 ± 1.20, 4.45 ± 1.08, 4.50 ± 0.84 m/s, respectively for device-embedded, Matlab-based and numerical simulation analyses, respectively. The strongest correlation (r = 0.92) was seen between device-embedded and Matlab-based second derivatives. The intersession coefficients of variation were 7.0 ± 4.9% and 3.2 ± 1.9% (p = 0.04) for device-embedded and Matlab-based second derivative algorithms. We estimated that each increase of 10 mm Hg in local MAP by vertical displacement of the hand resulted in an increase in RD-PWV of 0.28 m/s. This study shows that RD-PWV can be used for the non-invasive assessment of stiffness of small-sized arteries.
P.26 Liver Transglutaminase 2 Level Comparison Among Different Dietary Interventions
Authors: Oztemiz Elif , Dogan Soner , Tuna Bilge Guvenc
Published: December 2020

Purpose/Background/Objectives

Tissue transglutaminase (TG2) is a highly expressed protein especially in endothelial cells. TG2 has several functions including transamidation activity which is important in several processes such as extracellular matrix remodeling [1]. TG2 activity takes place in aortic stiffness regulation and atherosclerotic plaque formation [2]. One of the most effective implementation for atheroprone state and general cardiovascular health is calorie restriction (CR). In addition, lipid accumulation and subsequent metabolic disorders can be regulated by CR and longer lifespan can be achieved [3]. In this study we aimed to determine the effect of different CR application types on liver TG2 levels of female mice fed up to 82 weeks old age.

Methods

For this purpose, female MMTV-TGF-a mice fed with different dietary regimes; ad libitum (AL), chronic CR (%15 restriction of AL group), intermittent CR (3 weeks AL (ICR-ReFeed)+1 week %60 restriction of AL (ICR-Restricted), between 10-week to 82-week old. Liver tissue was isolated at 10-week old (AL mice as baseline), 50 and 82 weeks. Then, liver tissue samples were homogenized for western blotting. Analysis made by ImageLab software and Glyceraldehyde-3-Phosphate Dehydrogenase used as housekeeping gene.

Results

TG2 levels were increased in CCR and ICR-R groups, decreased in ICR-RF compared to AL group. In addition, 82-week old AL mice had higher level of TG2 than 10-week old.

Conclusion

These results may provide future perspectives about TG2 levels depending on feeding protocols and ageing in kidney. TG2 levels in arteries of the same groups will be examined in further studies.
P.29 Involvement of Cannabinoid Receptors in Regulation of MMPs, Cell Proliferation and Apoptosis in Vascular Smooth Muscle Cells
Authors: Greiner Bettina , Sommerfeld Manuela , Kintscher Ulrich , Kappert Kai , Kaschina Elena
Published: December 2020

Objectives

Cannabinoid receptors CB1R and CB2R are expressed in the vascular smooth muscle cells (VSMCs) and may contribute to vascular remodeling process (O’Sullivan, 2015). This study aimed to investigate the implication of CB1R and CB2R in the regulation of matrix metalloproteases MMP2 and MMP9, cell proliferation and apoptosis.

Methods

Primary VSMCs of contractile type were derived from rat aorta. Following compounds were studied: the CB1R agonist arachidonyl-2-chloroethylamide (ACEA), the CB1R antagonist/inverse agonist rimonabant, the CB2R agonist JWH133, the CB2R antagonist/inverse agonist AM630. The cells were treated with compounds simultaneously with IL1α stimulation. MMP2 and MMP9 were analyzed 48h after treatment via gelatin zymography, Western blotting and immunofluorescence. Apoptotic markers FasL, Caspase-3 and TGFbeta1 were used. This experimental setup was repeated using IncuCyte cell imaging to evaluate cell proliferation and apoptosis.

Results

The CB2R agonist JWH133 decreased the activity of proMMP9 (p < 0.05), abolished IL1α -induced up-regulation of proMMP9/MMP9 proteins, and decreased MMP2 activity by tendency (11%). JWH133 also decreased the number of apoptotic cells (p < 0.05). Accordingly, CB2R antagonist AM630 did not prevent MMP9 release. CB1R antagonist Rimonabant reduced activity of proMMP9 (35%) and MMP2 (4%) and abolished protein up-regulation of proMMP9/MMP9. CB1R stimulation with ACEA had an ambiguous effect. JWH133 and Rimonabant increased cell proliferation (p < 0,05) and decreased expression of apoptosis markers FasL and caspase-3.

Conclusions

The CB2R agonist JWH133 and CB1R antagonist Rimonabant prevented release of MMP9 and cell death of VSMCs. Therefore, stimulation of the CB2R or blockade of the CB1R may be favorable by vascular outward remodeling processes.
P.32 Non-Invasive Measures of Arteriosclerosis Across Childhood and Adolescence: Insights Into the Natural History of Disease
Authors: Nasir Reeja , Cai Tommy Ye , Meroni Alice , Skilton Michael
Published: December 2020

Objectives

Non-invasive methodologies for assessing arteriosclerosis, including carotid intimal-medial thickness (cIMT) for assessing subclinical atherosclerosis and carotid-femoral pulse wave velocity (cfPWV) for measuring arterial stiffness, are well established and validated in adults [1, 2]. However, they are less well-described in children. Alternative methodologies, such as aortic IMT (aIMT), may be more appropriate in children provided the natural history of atherosclerotic disease [3]. Previous studies have predominantly applied these methodologies in a narrow age-range of children; methodological differences between studies make inter-study comparison of absolute values difficult. Therefore, we aimed to assess the severity of arteriosclerosis across childhood and adolescence using standardised application of age-appropriate and established methodologies.

Methods

We prospectively recruited 97 healthy children aged 2 to 20 (mean age = 11.2 ± 5.12 years old; stratified into five sex-balanced age groups). cIMT and aIMT were assessed via high-resolution B-mode ultrasonography. cfPWV was assessed via a semi-automated cuff-based device (Sphygmocor XCEL; AtCor Medical, Australia).

Results

aIMT increased with age (9 μm per year [95% CI: 6, 12], p < 0.0001), whereas cIMT did not meaningfully increase with age (2 μm per year [95% CI: −1, 5], p = 0.14). cfPWV remained relatively stable during early childhood, with an apparent increase from adolescence onwards.

Conclusions

Carotid and aortic atherosclerosis both increase throughout childhood, although this increase is greatest in the aorta. The aorta begins to stiffen during adolescence. Assessment of aortic arteriosclerosis is feasible in childhood and adolescence, and should be prioritised over assessment of carotid atherosclerosis in this age group.
P.35 TASK-1 Channels Play an Anticontractile Role in Rat Septal Coronary Artery Under Pharmacological Blockade of Endothelium
Authors: Lazarenko B. S. Varvara , Shvetsova Anastasia , Gaynullina Dina , Schubert Rudolph
Published: December 2020

Purpose/Background/Objectives

TASK-1 (TWIK-related acid-sensitive potassium) channels conduct background K+ currents in smooth muscle cells of pulmonary arteries suppressing vasocontraction. However, the vasomotor role of TASK-1 channels in systemic arteries as well as their regulation by the endothelium are poorly understood. Therefore, we investigated the impact of TASK-1 channels on the regulation of arterial contraction in the presence or absence of the relaxing influence of the endothelium in the brain and the heart, important regions of the systemic circulation.

Methods

Segments of basilar and septal coronary arteries (2-mm long) were isolated from male Wistar rats and mounted in a wire myograph. The functional impact of TASK-1 channels was assessed by the effect of their blocker AVE1231 (1 µM) on contractile responses to the thromboxane A2 receptor agonist U46619. Experiments were performed first on endothelium-intact arteries and then after combined blockade of NO-synthase (L-NNA, 100 µM), cyclooxygenase (indomethacin, 10 µM) and EDHF (TRAM34, 1 µM and UCL1684, 0.1 µM).

Results

AVE1231 did not change basal tone and contractile responses to U46619 of either basilar or septal coronary arteries with intact endothelium. However, incubation with AVE1231 after pharmacological blockade of the endothelium led to the development of basal tone and augmented contractile responses to U46619 in septal coronary arteries, but not in basilar arteries.

Conclusions

TASK-1 channels may play a protective anticontractile role in the coronary circulation under conditions of endothelial dysfunction.

Supported by RSF (grant N 20-75-00027). We thank Sanofi for the gift of AVE1231.
P.41 Measurement of Pressure-dependent Intra-Beat Changes in Carotid Pulse Wave Velocity using Image-Free Fast Ultrasound
Authors: Raj Kiran V , Nabeel P M , Joseph Jayaraj , Chandran Dinu , Sivaprakasam Mohanasankar
Published: December 2020

Background

The clinical significance of pressure-dependent intra-beat changes in local pulse-wave velocity (C) has recently come to light [1]. While reported methods require arterial pressure and diameter measurements from a single site to assess intra-beat changes in C, we present an image-free fast ultrasound device that performs this by capturing diameter waveforms from two proximal locations on an artery.

Methods

The functionality was assessed on eight normotensive participants (26 ± 4 years). By perturbing blood pressure through a short duration moderate lower body negative pressure intervention [2], CD and CF pulse wave velocities corresponding to diastolic and 80% of peak pressure were measured from the carotid artery. Human NIBP system (ADInstruments, India) was used for monitoring continuous pressure.

Results

The device captured dual-diameter waveforms and evaluated CD and CF, with a beat-to-beat variation <8% during baseline. CD was smaller than CF (p < 0.001), 4.2 ± 0.5 m/s versus 4.6 ± 0.7 m/s during baseline and 3.7 ± 0.6 m/s versus 3.9 ± 0.7 m/s during intervention. Concomitant to the drop in group-average diastolic (17%) and systolic (18%) pressures during the intervention, CD and CF dropped by 14% and 16%, respectively. The statistically significant correlation (r > 0.6, p < 0.001) of CD and CF with the diastolic and systolic pressures for each individual was preserved even after adjusting for heart-rate.

Conclusions

The device demonstrated its functionality and reliably measured the incremental nature of C. Its pressure-dependent intra-beat variations and inter-beat dynamics during the intervention concurred with literature. Further studies are underway to demonstrate the potential use of the device in vascular research and clinical applications.
P.47 Feasibility Evaluation of Imaging-Free Ultrasound Technology to Measure Diameters of Brachial and Radial Arteries for Assessment of Endothelial Function
Authors: Chandran Dinu , Joseph Jayaraj , Sen Sakshi , Raj Kiran , Nabeel P. M. , Deepak Kishore Kumar
Published: December 2020

Background

Ultrasonographic imaging to record changes in peripheral arterial diameter associated with Flow mediated dilatation or Low flow mediated constriction is routinely used to assess various facets of vascular endothelial function. Imaging poses many challenges including requirement of costly ultrasound machines, trained manpower to perform imaging and effort-intensive steps to analyse the images subsequently using manual or automated methods. We tested the feasibility and validity of using an imaging-free technology to record resting arterial diameters of brachial and radial arteries.

Methods

Eight healthy volunteers initially underwent ultrasonographic imaging (M7, Mindray; Shenzhen, P.R. China) of brachial artery and proximal radial artery. The brachial and radial artery ‘zones’ thereby identified through imaging were surface marked on subject’s arm. Imaging-free ARTSENS® Pen device [1] (Healthcare Technology Innovation Centre, IIT Madras, India) consisting of highly integrated hardware for operating a single element broadband ultrasound transducer (centre-frequency = 5 MHz, spatial half angle <1.3 degrees, diameter = 5 mm) in pulse-echo mode was used to track detectable arterial wall motion and measure end-diastolic diameters from previously identified brachial and radial ‘zones’.

Results

End-diastolic diameters measured by ARTSENS® Pen decreased significantly on moving from brachial to radial zone identified by imaging (4.34 ± 1.07 mm vs 2.05 ± 0.43 mm; p < 0.0001) and correlated strongly with imaging-based measurements (r = 0.93; p < 0.0001).

Conclusion

ARTSENS® Pen device offers feasible and valid imaging-free solution to measure peripheral arterial diameters which could potentially be employed for assessment of vascular endothelial function.
P.50 Radial Artery Phenotyping in Fibromuscular Dysplasia Through Ultra-High Frequency Ultrasound: A Radiomic Approach
Authors: Poli Federica , Bruno Rosa Maria , Faita Francesco , Khettab Hakim , Azizi Michel , Vitali Saverio , Cosottini Mirco , Caramella Davide , Ghiadoni Lorenzo , Taddei Stefano , Boutouyrie Pierre , Persu Alexandre , Jeunemaitre Xavier , Lorthioir Aurélien
Published: December 2020

Rationale and Aim

This study is aimed at identifying possible patterns of vascular wall disarray and remodeling in radial arteries of patients with fibromuscular dysplasia (FMD), by means of ultrahigh frequency ultrasound (UHFUS).

Methods

UHFUS scans of the radial arteries and of 30 FMD patients and 30 healthy controls were obtained by VevoMD (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 10 end-diastolic frames for each subject were analyzed. 74 radiomic features and 4 engineered parameters were extracted: intima-media thickness (IMT) and adventitia thickness (AT), an adjunctive acoustic interface for each layer (IMT and AT triple signal). The extracted parameters were used to train classification models, using Support Vector Machine Linear (SVM), K-Nearest Neighbors (KNN), Logistic Regression, Linear Discriminant Analysis (LDA). The models were then tested on an independent validation population (38 FMD patients and 28 healthy subjects).

Results

IMT (185 ± 46 vs 168 ± 37, p =) and AT (104 ± 34 vs 96 ± 35, p = 0.004) were significantly higher in FMD than in controls. IMT and AT triple signal were also more frequent in FMD than in control images (p < for both). The most accurate classification models were LDA (sensitivity = 0.67, specificity = 0.76, accuracy = 0.71, AUC = 0.71) and Logistic Regression (sensitivity = 0.71, specificity = 0.72, accuracy = 0.71, AUC = 0.71). The models showed and accuracy of about 70% when tested on the validation population.

Conclusions

Wall ultrastructure of radial arteries of FMD patients is extensively altered: IMT and AT are thickened and the first and/or second layer of the arterial wall is splitted, showing a triple signal feature. Radiomic descriptors combined with engineered parameters allow to distinguish between radial images from FMD patients and controls with a 70% accuracy.
P.53 Ascending Aorta Diameter and Pulse Wave Velocity are Increased and Local Hemodynamic is Disrupted in Patients with Blunt Traumatic Thoracic Aortic Injury Treated by TEVAR
Authors: Guala Andrea , Sala Daniel Gil , Ruiz-Muñoz Aroa , Garcia-Reyes Marvin , Dux-Santoy Lydia , Teixido-Tura Gisela , Tello Cristina , Valente Filipa , Lopez-Sainz Angela , Galian Laura , Gutierrez Laura , Johnson Kevin , Wieben Oliver , Ferreira Ignacio , Evangelista Arturo , Bellmunt-Montoya Sergi , Rodriguez-Palomares Jose
Published: December 2020

Background

Thoracic endovascular aortic repair (TEVAR) is becoming the preferred treatment option to repair the proximal descending aorta after rupture following blunt traumatic injury. However, hemodynamic and mechanic implications of this intervention are poorly understood. Exploiting the possibilities of 4D flow magnetic resonance imaging, hemodynamics, stiffness and local dilation in the ascending aorta in patients following aortic repair by TEVAR are studied.

Methods

Fifteen apparently healthy individuals who underwent TEVAR implantation after traumatic descending aortic injury and 44 healthy volunteers (HV) underwent 4D flow-MRI. Ascending aorta pulse wave velocity was computed [1]. Moreover, at eight planes equally distributed in the ascending aorta systolic flow reversal ratio, i.e. relative amount of backward flow during systole, and in-plane rotational flow, measuring the strength of helical flow, were computed [2,3].

Results

TEVAR patients and HV did not differ in terms of age, sex, BSA and blood pressure (Table). However, compared to HV, TEVAR patients showed reduced in-plane rotational flow in the distal ascending aorta in patients with TEVAR and increased backward systolic flow in the whole ascending aorta (Figure). Patients with TEVAR had a stiffer ascending aorta, with pulse wave velocity higher compared control (7.8 ± 4.2 vs 5.3 ± 1.9, p = 0.004). Finally, aortic root and ascending aorta diameters were larger in TEVAR patients compared to HV (Table).

Conclusions

The implantation of TEVAR in apparently healthy individuals after traumatic rupture of the proximal descending aorta is associated with altered hemodynamics, higher stiffness and larger aortic diameter in the region proximal to the TEVAR.

Table

Healthy volunteers
TEVAR patients
p

N
44
15

Age [years]
40 ± 12
43 ± 10
0.392

Sex [% male]
66
80
0.075

Years from intervention [years]
N/A
10.3 ± 6.4
N/A

Body surface area [m2]
1.87 ± 0.15
1.96 ± 0.23
0.088

Systolic blood pressure [mmHg]
127 ± 19
131 ± 15
0.389

Diastolic blood pressure [mmHg]
70 ± 11
74 ± 9
0.198

Aortic root diameter [mm]
31 ± 4
34 ± 4
0.026

Ascending aorta diameter [mm]
28 ± 4
32 ± 3
0.003

Ascending aorta PWV [m/s]
5.3 ± 1.9
7.8 ± 4.2
0.004
P.56 Differences in Vascular Effects Between One Session of Moderate-Intensity Continuous Physical Exercise and High-Intensity Interval Physical Exercise in Individuals with High Blood Pressure
Authors: Rodrigues Sara , Verardino Renata G S , Costa Marcel J A , Duenhas-Berger Ana Luíse , Costa-Hong Valéria , Bortolotto Luiz A
Published: December 2020

Purpose

To compare augmentation index (AIx) between one Moderate-intensity continuous physical exercise (MICPE) and one High-intensity interval physical exercise (HIIPE) session in normal/high normal blood pressure (BP) (120–140 for systolic and 80–90 mmHg for diastolic). Additionally, to compare two AIx methods (SphygmoCor® and Arteriograph®) [1].

Methods

Exercise intensity and energy expenditure (equalizing) were according to the cardiopulmonary stress test. Individuals were randomized to exercise sessions, performed as cross-over. AIx were analyzed at baseline, immediately after and 24hours after MICPE and HIIPE session and compared among all times. ΔAIxHIIPE (AIxHIIPE - AIxBaseline) and ΔAIxMICPE were calculated. Correlation and agreement analysis was performed between AIx methods.

Results

Individuals (n = 23; 78% women; 48 ± 1 years; systolic/diastolicBP = 125 ± 2/84 ± 1 mmHg) had lower AIxSphygmoCor® at MICPE compared to baseline and to 24 hours MICPE (27.2 ± 2.2 vs 32.8 ± 1 and 31.0 ± 2.5%; p < 0.01). AIxSphygmoCor® was lower in HIIPE than other times (23.2 ± 2.4 vs baseline 32.8 ± 1.9 p < 0.01; vs MICPE 27.2 ± 2.2; p = 0.039; vs 24 hours MICPE 31.0 ± 2.5; p < 0.01 and vs 24 hours HIIPE 32.2 ± 2.0%; p < 0.01). AIxArteriograph® was lower in HIIPE (16.0 ± 3.7%) than baseline (28.9 ± 3.4%; p = 0.001), 24 hours MICPE (25.7 ± 4.0%; p = 0.008) and 24 hours HIIPE (29.5 ± 3.9%; p = 0.005). ΔAIxHIIPE was greater than ΔAIxMICPE (−9.37 vs −5.15; p = 0.028). AIxArteriograph® showed a positive correlation with AIxSphygmoCor® (r = 0.793; p < 0.01) and showed agreement.

Conclusion

Regardless of intensity, one exercise session improves AIx. The effect seems to be greater after HIIPE than MICPE.