BACKGROUND:Indications for pre-emptive aortic surgery are based on ascending aortic diameter. In this study we assessed the diagnostic test properties of novel unadjusted, adjusted, and combined measures of aortic geometry. METHODS:This study comprised an international multicentre analysis of patients undergoing contrast-enhanced computed tomography angiography (CTA) before acute type A aortic dissection (ATAAD). A historical cohort of nonaneurysmal patients and patients with known aneurysmal disease (TAA) were included as a control group. Receiver operating characteristic (ROC) curves were applied to evaluate the aortic measures' diagnostic accuracy (for [un]adjusted aortic diameter, length, and volume), with sensitivity analyses performed in a matched sample. Clinically intuitive measures, such as the number needed to reclassify (NNR) to identify an additional patient at risk of ATAAD, were calculated. RESULTS:Eighty patients underwent CTA before ATAAD occurred, in 5 centres in The Netherlands and Germany. The control group encompassed 333 patients. The specificity of all measures was 98.8%, 97.0%, and 94.9% at contemporary diameter thresholds of 55 mm, 52 mm, and 50 mm. The sensitivity of diameter, length, or volume was 4.1%, 6.8%, and 14.9% at the 98.8% specificity threshold (NNR volume vs diameter: 9.3, P = 0.008). The combination of diameter, length, and volume as a new criterion resulted in an increased sensitivity at the 55-mm and 52-mm thresholds (18.9%, NNR = 6.8, P = 0.001; 23.0%, NNR = 9.3, P = 0.008). Results were consistent in matched samples. CONCLUSIONS:These newly introduced aortic measures seem promising to identify patients at risk of ATAAD, but their net benefit needs to be validated in real-world cohorts.

Background Ex vivo characterization of arterial viscoelastic properties shows arterial stiffness and contractility to depend on both axial stretch and dynamic pressurization. While these arterial properties are the subject of extensive ex vivo research due to their relevance to vascular pathophysiology, only few experimental approaches mimic both physiological axial stretch and dynamic pressurization when characterizing arterial biomechanics, vasoreactivity, and tissue microstructure. To fill this gap, we developed a custom dynamic biaxial pressure myograph compatible with two-photon laser scanning microscopy (TPLSM). Methods We studied five murine carotid artery segments. Sample viscoelastic behaviour was characterized by quasi-static and dynamic pressurization experiments at and around physiological axial stretch, as well as quasi-static stretching at physiological pressures. In addition, vasoconstriction in response to 2 μM phenylephrine was measured during dynamic pressurization and with axial loads that mimicked physiological conditions. Lastly, arterial collagen, elastin, and cell nuclei were imaged using TPLSM with the sample at physiological axial stretch and pressurized at 100 mmHg. Results The setup enabled capture of the non-linear biaxial viscoelastic behaviour of the arterial wall as well as the viscoelastic stiffening with dynamic pressurization. Modulation of these characteristics upon stimulated smooth muscle contraction was also captured well. Moreover, the related ultrastructural properties of the collagen-elastin network as well as the transmural cell distribution, were recordable at corresponding loading conditions by TPLSM. Conclusion The presented multi-modal characterization platform enables comprehensive ex vivo measurements under well-controlled in vivo-like loading conditions, for in-depth studies focusing on arterial stiffening. Our findings emphasize the need for controlling dynamic pressure and axial stretch conditions in investigating mechanistic and constitutive aspects of arterial stiffening. ### Competing Interest Statement The authors have declared no competing interest. European Union’s Horizon 2020 research and innovation programme, 954798, 793805 European Union’s Horizon Europe research and innovation programme, 101081327, 101136728 ARTERY (Association for Research into Arterial Structure and Physiology), 2022 Research Exchange Grant Netherlands Organisation for Scientific Research, Rubicon 452172006

BACKGROUND:Marfan Syndrome (MFS) often leads to thoracic aortic aneurysm (TAA), for which angiotensin (II) receptor blockers (ARBs) are prescribed to reduce aneurysm growth. Although recent pooled analyses demonstrated a statistically significant reduction in aortic growth with ARBs under a frequentist framework, the clinical relevance of this effect remains uncertain. Moreover, ARB therapy is notably burdensome for patients due to significant side-effects. Therefore, this study re-analyses randomised ARB versus comparator trials in MFS patients, under a Bayesian statistical framework. METHODS:The trials included by the Marfan Treatment Trialists' Collaboration were re-analysed using fixed- and random-effects Bayesian models comparing ARBs to controls. The primary outcome was the mean difference in the annual rate of change of aortic root dimension, adjusted for body surface area (z-score). The minimal clinically important difference (MCID) was applied to assess the clinical relevance of the pooled posterior effect, based on previous consensus and available literature (at 0.12 adjusted z-scores/year). RESULTS:Four randomised trials, comprising 626 patients, were included. Under the fixed-effects model, the pooled mean difference was -0.07 z-score/year [95 % CrI, -0.12; -0.01] in favour of ARBs, though with a posterior probability of a clinically relevant treatment effect of only 7.3 %. Using a Bayesian random-effects model, the pooled mean difference was -0.06 z-score/year [95 % CrI, -0.22 to 0.11] in favour of ARBs, with a similarly low probability of achieving the MCID (18.1 %). CONCLUSIONS:The findings of this Bayesian analysis suggest that ARBs are unlikely to achieve clinically meaningful reductions in aortic growth for MFS patients.

Histomorphometric differences in cell-matrix properties were analysed between ascending thoracic aortic aneurysm (ATAA), dissection (ATAAD) and non-aneurysmal patients, as well as across the circumference of the aneurysms in ATAA cases. Fresh anterior aortic wall samples were collected during surgery. A significant radius-to-intima-media thickness (IMT) ratio variation was observed among ATAA patients, indicating patient-specific adaptive responses. The radius-IMT ratio was significantly lower in ATAAD patients. The quantity and quality of elastin and the quantity of collagen were particularly reduced in ATAAD compared to ATAA and non-aneurysmal aortas. Matrix degradation was accompanied by an increase in the density of vascular smooth muscle cells (VSMCs), albeit with reduced expression of VSMC contractile markers (calponin and α-smooth muscle actin (α-SMA)). Concomitantly ATAA and ATAAD samples exhibited increased markers (matrix metalloproteinase (MMP)-2/9) of proteolysis. Based on radius-IMT ratios we roughly identified 'thickening' and 'thinning' (i.e. hypertrophic and hypotrophic) aneurysm variants to capture the substantial variation in the loss of mechanical homeostasis in ATAA. Interestingly we did not find conspicuous differences along the circumference of excised aneurysms in ATAA, except for an increased IMT heterogeneity in 'thinning' aneurysms. We conclude that during aneurysm formation wall stress homeostasis may remain partially intact, particularly in 'thickening' ATAA. Our study underscores the current critique that aneurysm dimensions are poor risk predictors; therefore there is a crucial need for better-informed preventive intervention in ATAAD. KEY POINTS: Ascending thoracic aortic aneurysm (ATAA) variants can be categorised as aortic medial thickening (hypertrophic) or aortic medial thinning (hypotrophic) based on the radius-to-intima-media thickness (IMT) ratio, reflecting distinct disruptions in mechanical homeostasis. Morphological patterns arise from dynamic interactions in the aortic medial layer between vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM). Increased number of synthetic VSMCs in the medial layer of ATAA patients is a compensatory response to maintain vessel elasticity and structural integrity. In acute type A aortic dissection (ATAAD) aortas with medial thinning are characterised by ECM breakdown and maladaptive remodelling. ATAA development is circumferentially homogeneous, despite the occurrence of inter- and intrapatient variability in vascular architecture, composition and VSMC characteristics.

BACKGROUND:Arterial stiffness is a strong predictor of cardiovascular diseases and all-cause mortality. Increased concentrations of highly reactive dicarbonyl compounds-methylglyoxal (MGO), glyoxal (GO), and/or 3-deoxyglucosone (3-DG)-may cause arterial stiffening via formation of advanced glycation end products, triggering maladaptive responses in vascular tissue, e.g., elastin degradation and collagen cross-linking. Therefore, we investigated in the population-based Maastricht study whether plasma MGO, GO, and 3-DG concentrations were cross-sectionally associated with carotid-to-femoral pulse wave velocity (cfPWV) and local carotid stiffness measures: pulse wave velocity (cPWV), and Young's elastic modulus (cYEM) using standardized main variables. METHODS:Fasting dicarbonyl concentrations were determined by ultra-performance liquid chromatography tandem mass spectrometry in EDTA plasma collected from 2,275 participants (age 60 ± 8 years, mean ± SD; 49% women, 605 (27%) with type 2 diabetes mellitus) of the Maastricht Study, an observational, population-based cohort study. Cross-sectional associations were assessed using multivariable linear regression analysis adjusting for age, sex, mean arterial pressure (MAP), heart rate, lifestyle factors, and medication. Since arterial stiffness measures are intrinsically pressure dependent, we additionally assessed the associations with pressure-corrected counterparts, instead of statistically correcting for MAP. RESULTS:Fasting dicarbonyl concentrations were associated with arterial stiffness measures (greater cfPWV, cPWV, and cYEM) in most crude models, but not in adjusted models. The use of pressure-corrected metrics did not materially change the association of interest. CONCLUSIONS:Fasting plasma concentrations of either MGO, GO, or 3-DG are not independently associated with arterial stiffness in this cross-sectional analysis.

Background:Stroke is the second leading cause of death worldwide, with carotid stenosis being a primary contributor. Therefore, stroke prevention would benefit from accessible carotid stenosis screening tools. Historically, acoustic stethoscopes were used to listen to the carotid artery, but this method is now outdated due to its subjectivity and inconsistent sensitivity and specificity in detecting stenosis. In contrast, electronic stethoscopes record audio, enabling precise and objective analysis. To overcome traditional auscultation limitations, our study introduces a signal analysis scheme to evaluate the electronic stethoscope as a potential screening tool for carotid plaques and severe stenosis. Methods:We included 94 patients undergoing duplex ultrasound (DUS) for recent transient ischemic attack (TIA) or pre-operative assessment for carotid endarterectomy. DUS served as the clinical reference for determining plaque presence and estimating carotid stenosis. Participants held their breath during electronic stethoscope measurements at two points along each carotid artery: (I) proximal, on the common carotid; and (II) distal, near the bifurcation. From these recordings, we extracted 10 spectral features and utilized multivariable binary logistic regression for predicting plaques and severe stenosis, applying 10-fold cross-validation for internal validation. We constructed the receiver operating characteristic (ROC) curve by plotting the true positive rate against the false positive rate at various cutoff settings. We reported the area under the curve (AUC), along with sensitivity and specificity, which were determined using a single optimal cutoff point. Results:For detecting >70% stenosis using distal location recordings, the analysis yielded training and testing AUCs of 0.87 and 0.79, sensitivity of 84.9% and 78.6%, and specificity of 73.6% and 72.1%, respectively. Using proximal location recordings, training and testing AUCs were 0.84 and 0.73, with sensitivities of 79.8% and 60.7%, and specificities of 76.0% and 75.6%, respectively. For detecting the presence of plaques, proximal location measurements showed training and testing AUCs of 0.79 and 0.7, sensitivities of 54.9% and 51.9%, and specificities of 91.9% and 78.8%, respectively. Conclusions:Our findings demonstrate that the electronic stethoscope with spectral analysis is promising for identifying severe stenosis but has limited sensitivity for detecting any plaque. The performance obtained with this approach is superior to that attainable with conventional auscultation. This approach could serve as a promising, user-friendly screening tool, particularly in resource-limited settings.

Aging causes changes to arterial contractility and tissue microstructure, resulting in arterial stiffening, a strong risk factor for cardiovascular diseases. Because the interaction between these effects is largely unexplored, this study aims to investigate how aging-induced changes in contractility and wall constituent microstructure impact arterial biomechanics in murine aortas. Vasoreactive responses of thoracic descending aortas of adult (5-mo-old, n = 5) and old (24-mo-old, n = 5) C57Bl/6J mice to phenylephrine, Nω-nitro-l-arginine methyl ester (l-NAME), and sodium nitroprusside were measured under dynamic pressurization conditions. Whole vessel and individual-constituent biaxial viscoelastic properties were characterized during contraction and relaxation while mimicking physiological dynamic loading conditions. In addition, elastin fibers, collagen fibers, and smooth muscle nuclei microstructural organization and morphological properties were quantified in pressurized aortas using two-photon laser scanning microscopy. Compared with adult mice, aortas of old mice displayed thicker walls but similar pressure-diameter behaviors in the absence of contraction. Vasoconstriction in aortas of adult mice 1) significantly increased wall thickness, 2) reduced pulse wave velocity at physiologically high pressure ranges, 3) reduced circumferential and axial stresses and stiffnesses, and 4) altered constituent load bearing. Conversely, aortas of old mice exhibited reduced contractility, altered vasoreactive responses, and reduced cell density. As a result, they were uncapable to alter any of their biomechanical properties through vasoconstriction. In conclusion, vasoconstriction enables modulation of axial and circumferential stresses and stiffnesses in the adult mouse aorta. With aging, this modulatory capacity was impaired.NEW & NOTEWORTHY Using a biaxial pressure myograph that mimics physiological loading conditions, this study demonstrates the capacity of vascular smooth muscle cells in male C57BL/6J mice at 5 mo of age to modulate aortic stiffness through vasoconstriction and dilation. In addition, this capacity is shown to be lost in male C57BL/6J mice at 24 mo of age.

Objectives: Aortic pulse wave velocity (aPWV) predicts cardiovascular risk. Being the reference method for aortic stiffness evaluation, invasive aPWV is also recommended for validation of noninvasive devices. Because of intrinsic haemodynamic variability and processing issues, aPWV shows beat-to-beat variability. We aimed to quantify this variability and evaluate its implications for the reliability and use of aPWV as reference in validation and clinical application studies. Methods: The study included n = 84 patients, in whom two datasets of invasive data were recorded: 1) simultaneous ascending aorta and iliac pressure acquisitions using a dual-tip intra-aortic catheter, and 2) an additional ascending aorta pressure acquisition. By combining the iliac and ascending aorta pressure recordings from the first and second acquisitions, respectively, we evaluated how a sequential acquisition protocol affects variability. We compared three pressure waveform foot identification methods to investigate the effect of data processing on variability. Furthermore, we estimated how averaging over n beats consecutive heartbeats affects the standard deviation (SD) of such n beats-averaged estimate of aPWV. Results: The simultaneously acquired invasive aPWV showed a 5% beat-to-beat SD (variability), with small but significant differences between foot identification methods. The sequential acquisition protocol doubled aPWV variability compared to simultaneous acquisition. However, because averaging had a much stronger effect on sequentially measured aPWV, the two acquisition protocols yielded comparable variabilities at n beats = 10 (2% vs. 3%). Conclusions: Our study suggests that, independently from the acquisition protocol and data processing, the intrinsic beat-to-beat variability of aPWV becomes manageable when aPWV values of at least ten heartbeats are averaged.

The conventional derivation of the pressure pulse wave velocity (PWV) relies on the wave equation for blood flow in a uniform elastic artery, wherein PWV is considered dependent on the linear elasticity of the artery and on the blood density. Arterial elasticity is represented by transverse compliance, i.e., assuming that the artery is fixed lengthwise. However, arteries exhibit a nonlinear and anisotropic stretch–stress behavior, challenging the conventional PWV equation based on a linear stretch–stress relationship. Moreover, the ascending thoracic aorta (ATA) undergoes dynamic axial elongation during the cardiac cycle, which co-determines its biomechanical response. This study establishes a derivation for understanding how this dynamic axial elongation affects local PWV in a hyperelastic ATA. ATA compliance was analytically derived by relating the diameter change to changes in the intraluminal pressure and axial stretch. Synthetic pressure–diameter curves were generated using the Gasser-Ogden-Holzapfel model, assuming a thin-walled cylinder with an axial stretch of 1.2 at diastolic pressure and axial strains of 0, 2, 4, 6, and 8

Diabetes is a leading cause of mortality worldwide, primarily due to cardiovascular diseases (CVD). Arterial stiffness is a CVD predictor and is associated with increased mortality in diabetic individuals. In diabetes, the formation and accumulation of methylglyoxal (MGO), a highly reactive glycolysis by product and a major precursor in advanced glycation endproducts (AGEs) formation, has been implicated in CVD. In this study, we investigated the role of endogenous MGO in arterial stiffening in a mouse model of type 1 diabetes (T1D) overexpressing the MGO-detoxifying enzyme glyoxalase-1 (GLO1). Diabetes was induced in C57BL/6 J mice through 5-day streptozotocin injections. 17-week-old control, diabetic, and GLO1-overexpressing diabetic mice were used. Fasting glucose in diabetes and GLO1/diabetes was higher than control. Plasma, urine, and aortic MGO, AGEs, and cross-links were determined using ultra-performance liquid chromatography tandem mass spectrophotometry. MGO was increased in plasma and urine in diabetic mice, while GLO1 decreased MGO in urine. The AGE cross-link pentosidine in aorta was increased in diabetes and ameliorated by GLO1. Tail-cuff blood pressure and carotid-femoral pulse wave velocity were measured preceding euthanasia, and did not differ between groups. Descending thoracic aorta ex vivo passive biaxial arterial wall biomechanics were measured and diabetes showed elevated ex vivo PWV, which was attenuated by GLO1 overexpression. Material viscoelasticity was decreased in diabetes and normalised by GLO1 overexpression. Second harmonic generation imaging demonstrated a predominant axial orientation of diabetic collagen fibres, while GLO1/diabetes led to a uniform orientation. When comparing GLO1/diabetes and diabetes, bulk RNA sequencing revealed 137 differentially expressed genes affecting extracellular matrix organisation, cell–cell and cell–matrix communication and interaction pathways. In an animal model of T1D, GLO1 overexpression attenuates arterial stiffening at the underlying material levels, by modifying collagen ultrastructure and viscoelastic properties. Targeting MGO may provide a novel approach to prevent arterial T1D stiffening.

Introduction: Arterial stiffening is a hallmark of vascular ageing, and unravelling its underlying mechanisms has become a central theme in the field of cardiovascular disease. While various techniques and experimental setups are accessible for investigating biomechanics of blood vessels both in vivo and ex vivo, comparing findings across diverse methodologies is challenging. Methods: Arterial stiffness in the aorta of adult (5 months) and aged (24 months) wild-type C57Bl/6J mice was measured in vivo, after which ex vivo biomechanical evaluation was performed using the Rodent Oscillatory Tension Setup to study Arterial Compliance (ROTSAC; University of Antwerp, Belgium) and the DynamX setup (Maastricht University, The Netherlands). Stiffness of aortic tissue was measured in both absence and presence of activated smooth muscle cells (i.e., contraction). Measurements in both setups were conducted in parallel with matched protocols and identical buffers and chemicals. Results: Overall, both methods revealed age-related increased aortic stiffness, although parameters of aortic mechanics showed different numerical values, suggesting that results are not directly interchangeable between methods. Surprisingly, smooth muscle cell contraction had opposing effects between the setups. Indeed, smooth muscle cell contraction increased arterial stiffness in the ROTSAC but decreased stiffness in the DynamX. These opposing effects could be attributed to how the two setups differentially load the collagen fibres in the arterial wall, ex vivo. Conclusion: Overall, this study provided critical insights into how different experimental setups can influence the interpretation of aortic biomechanics, emphasizing the need for careful consideration and contextualization of results based on the methodology used.

Local biaxial deformation plays a pivotal role in evaluating the tissue state of the ascending aorta and in driving intramural cell-mediated tissue remodeling. Unfortunately, the absence of anatomical markers on the ascending aorta presents challenges in capturing deformation. Utilizing our established intra-operative biaxial strain measurement method, we delineated local biaxial deformation characteristics in patients undergoing aortic valve replacement and coronary artery bypass graft surgery recipients (n = 20), and Aortic Repair surgery patients (n = 47). Expectedly, mean circumferential strains positively correlated with pulse pressure and negatively correlated with age and diameter. A new observation was that the mean axial strains exhibited the same trend as the mean circumferential strains when correlated with pulse pressure, age and diameter. Interestingly, on analyzing local biaxial strains, our findings revealed higher circumferential strains (by 1 %) proximal to the heart compared to distal regions across the cohorts and within each patient cohort. Furthermore, no discernible regional strain distinctions were noted between the medial and lateral sides of the ascending aorta for the entire patient population and individual cohorts. Patients undergoing Aortic Repair surgery indicated lower strains (ranging from 1 to 3 %) as compared to the other cohort. Our approach holds the potential to establish a foundational framework for the integrated examination of the mechanical and biological conditions and their role in ascending aortic aneurysm development.

Biological tissues decay over time after harvesting, which alters their biomechanical properties. This poses logistical challenges for studies investigating passive arterial biomechanics as tissues need to be characterized shortly after excision. Freezing and cryopreservation methods can help alleviate the need for biomechanical testing of fresh tissue in human ex vivo studies. However, these methods tend to eliminate or reduce arterial cell functionality and affect passive biomechanics. Furthermore, their impact on dynamic arterial biomechanics remains unknown despite arterial viscoelastic properties being an integral component contributing to arterial stiffness under in vivo loading conditions. The present study aims to investigate the impact of rapid cooling and subsequent storage at -80 °C on the passive viscoelastic properties of arterial tissue and aid in ascertaining whether this is a suitable method to delay tissue analysis for studies investigating passive arterial biomechanics. Control and frozen abdominal rat aorta segments were quasi-statically and dynamically tested using a biaxial testing set-up. The results were modeled using a constituent-based quasi-linear viscoelastic modeling framework, yielding directional stiffness parameters, individual constituent biomechanical contributions, and a quantification of viscoelastic stiffening under dynamic pressurization conditions. Frozen samples displayed significantly decreased wall thickness, viscoelastic dissipation, viscoelastic stiffening, and significantly decreased circumferential deformation with changes in luminal pressure. Furthermore, frozen samples displayed significantly increased circumferential stiffness, pulse wave velocity, and collagen load bearing. Consequently, these changes should be considered when utilizing this tissue preservation method to delay biomechanical characterization of rat aortic tissue.

High volumes of sedentary time (ST) may affect arterial stiffness (AS), which precedes the development of cerebrovascular and cardiovascular disease. However, the association between ST and AS remains inconclusive as most previous studies assessed ST with subjective measures and/or focused on relatively small sample sizes. We investigated the associations of objectively measured ST with central and local AS measures in a Dutch cohort, and we determined which factors affected these associations. We recruited adult volunteers from a prospective Dutch cohort study. We collected demographics via annual questionnaires and performed physical examinations at our research centre. ST was measured 24 hrs/day for 8 consecutive days using thigh-worn accelerometery and expressed as daily sitting time (hrs/day). AS was measured using carotid artery ultrasound. Central AS was expressed as carotid-femoral pulse wave velocity (cfPWV, m/s), and local carotid AS was expressed as stiffness index Beta (dimensionless). The associations of ST with AS measures were evaluated using linear regression adjusted for age, sex, employment status, smoking behaviour, cardiovascular health group, body mass index, systolic blood pressure (SBP), total cholesterol and C-reactive protein concentrations, and time spent in moderate-to-vigorous physical activity (MVPA). Interaction terms of these variables with ST were added separately to investigate which factors affected the association of ST with AS. We analysed 666 subjects (64.8±11.0 yrs old, 398 (60%) male) with complete covariate data. ST was 9.1±1.6 hrs/day, and AS levels were 8.6±3.0 m/s for cfPWV and 6.4±3.0 for Beta. The association of ST with cfPWV was not significant (β=0.04 95% confidence interval [-0.11, 0.19], p=0.60) and not moderated by any of the variables (p>0.05 for interactions). The association of ST with Beta was moderated by SBP and time spent in MVPA. Stratified analyses with SBP and time spent in MVPA split at the median revealed a significant association of ST with Beta in subjects who had SBP values greater than 134 mmHg (β=0.29 [0.05, 0.52], p=0.017) or who spent more than 103 min/day in MVPA (β=0.23 [0.03, 0.43], p=0.025). In subjects who had SBP values less than 134 mmHg or who spent less than 103 min/day in MVPA, the association of ST with Beta was not significant. In a cohort of 666 subjects, we found no significant association of ST with central AS. Conversely, we found a significant positive association of ST with local AS in subjects who had the highest SBP or who were most physically active. These findings suggest that in certain subgroups, larger volumes of ST are associated with stiffening of the carotid arteries, which may contribute to the relation between ST and the development of cerebrovascular disease. Further research is needed to understand the underlying physiological processes and their implications.

Contrary to most vessels, the ascending thoracic aorta (ATA) not only distends but also elongates in the axial direction. The purpose of this study is to investigate the biomechanical behavior of the ascending thoracic aorta (ATA) in response to dynamic axial stretching during the cardiac cycle. In addition, the implications of neglecting this dynamic axial stretching when estimating the constitutive model parameters of the ATA are investigated. The investigations were performed through in silico simulations by assuming a Gasser–Ogden–Holzapfel (GOH) constitutive model representative of ATA tissue material. The GOH model parameters were obtained from biaxial tests performed on four human ATA tissues in a previous study. Pressure–diameter curves were simulated as synthetic data to assess the effect of neglecting dynamic axial stretching on estimating constitutive model parameters. Our findings reveal a significant increase in axial stress ( 16

Sedentary behavior (SB) may affect arterial stiffness, preceding the development of cardiovascular disease. We investigated the association of objectively measured SB with arterial stiffness. We also investigated factors that affected this association. We recruited adult volunteers and measured SB with thigh-worn accelerometery for 24 hrs/day for eight consecutive days. Central (carotid-femoral pulse wave velocity, cfPWV, gold standard) and local carotid arterial stiffness (stiffness index Beta and pressure-strain elasticity EP) were measured with ultrasound. Linear regression was used and adjusted for demographics, cardiometabolic factors, and moderate-to-vigorous physical activity (MVPA) volume. Effect modification was studied with interaction terms. Participants (N = 664, 64 (standard deviation: 11, range: 23-89) years, 397 (59.8%) male) demonstrated 9.1 (1.6) hrs/day of SB, and arterial stiffness was 8.6 (3.0) m/s for cfPWV, 6.4 (2.9) for Beta, and 87 (43) kPa for EP. SB was not associated with cfPWV (β = 0.04 95% CI (-0.11, 0.18), p = 0.60). The association of SB with local arterial stiffness was modified by systolic blood pressure (SBP) and MVPA volume. Stratified analyses revealed positive associations of SB with Beta (β = 0.29 (0.05, 0.53), p = 0.016) and EP (β = 4.83 (1.39, 8.27), p = 0.006) in participants with SBP > 134 mmHg or > 103 min/day of MVPA (β = 0.23 (0.03, 0.42), p = 0.024 and β = 3.55 (0.82, 6.29), p = 0.011, respectively). We found no association of objectively measured SB with central arterial stiffness. However, SB was positively associated with local carotid stiffness in participants with higher SBP or MVPA levels. In certain subgroups, SB may affect carotid arterial stiffening, reinforcing the relation between SB and cardiovascular disease.

Stroke is a major cause of morbidity and mortality worldwide with carotid stenosis established as one of its leading culprits. Clinical practice relies primarily on duplex ultrasound (DUS) for the diagnosis of carotid stenosis due to its several advantages over existing modalities. Nevertheless, population-wide screening could benefit from a portable, and user-friendly device. In the context of assessing the potential of Laser Doppler vibrometer (LDV) for stenosis screening, this study aims at exploring and evaluating the performance of several spectral features that best relate to severe stenosis. An in-vitro setup has been employed for the current investigation with stenosis degree determined using a clamp. Progressive clamping and broadening observed in DUS spectra were considered as references indicating the occurrence and increase in flow instability due to the (increasing) stenosis. We recorded 3 cm downstream of the stenosis, inside-tube DUS spectra as well as direct wall vibration spectra by LDV for several graded constrictions. We investigated 10 distinct spectral features to capture spectral broadening. Present findings showed overall broader spectra for stenosis compared to control measurements, with broadening being proportional to stenosis degree. Spectral entropy - reflecting the spectral irregularity and the shift in the frequency content of LDV signal toward higher frequencies - exhibited superior performance over the other spectral features for indicating the presence of severe stenosis.

Abstract Background Conventional measures for assessing arterial stiffness are inherently pressure dependent. Whereas statistical pressure adjustment is feasible in (larger) populations, it is unsuited for the evaluation of an individual patient. Moreover, statistical “correction” for blood pressure may actually correct for: (i) the acute dependence of arterial stiffness on blood pressure at the time of measurement; and/or (ii) the remodeling effect that blood pressure (hypertension) may have on arterial stiffness, but it cannot distinguish between these processes. METHODS We derived—assuming a single-exponential pressure–diameter relationship—3 theoretically pressure-independent carotid stiffness measures suited for individual patient evaluation: (i) stiffness index β0, (ii) pressure-corrected carotid pulse wave velocity (cPWVcorr), and (iii) pressure-corrected Young’s modulus (Ecorr). Using linear regression analysis, we evaluated in a sample of the CATOD study cohort changes in mean arterial pressure (ΔMAP) and comparatively the changes in the novel (Δβ0, ΔcPWVcorr, and ΔEcorr) as well as conventional (ΔcPWV and ΔE) stiffness measures after a 2.9 ± 1.0-year follow-up. RESULTS We found no association between ΔMAP and Δβ0, ΔcPWVcorr, or ΔEcorr. In contrast, we did find a significant association between ΔMAP and conventional measures ΔcPWV and ΔE. Additional adjustments for biomechanical confounders and traditional risk factors did neither materially change these associations nor the lack thereof. Conclusions Our newly proposed pressure-independent carotid stiffness measures avoid the need for statistical correction. Hence, these measures (β0, cPWVcorr, and Ecorr) can be used in a clinical setting for (i) patient-specific risk assessment and (ii) investigation of potential remodeling effects of (changes in) blood pressure on intrinsic arterial stiffness.