Aortic aneurysm and dissection (AAD) are vascular disorders with high mortality. Previous evidence has suggested an elevated risk of AAD associated with the use of phosphodiesterase 5A (PDE5A) inhibitors. PDE5A, a cGMP-hydrolyzing enzyme, is enriched in vascular smooth muscle cells (SMCs), but the role of SMC-specific PDE5A in the pathogenesis of AAD is still unclear. In this study, PDE5A expression in human and mouse aortic tissues was analyzed by single-cell RNA sequencing (scRNA-seq), western blotting, immunofluorescence, and immunohistochemistry staining. SMC-specific PDE5A knockout (PDE5ASMC-/-) and PDE5A-overexpressing (PDE5ASMC-OE) mice were constructed and utilized, along with an AAD mouse model induced by a high-fat diet and angiotensin II (Ang II) infusion. In vivo imaging and histological analyses were performed to assess aortic pathologies. PDE5A expression was reduced in human and mouse AAD aortic tissues, primarily in SMCs. Pharmacological inhibition or genetic knockout of PDE5A in SMCs exacerbated aortic wall dilatation and elastin fiber degradation, increasing AAD incidence. In contrast, the AAD phenotype was rescued in challenged PDE5ASMC-OE mice. Mechanistically, PDE5A expression influenced myosin light chain (MLC) phosphorylation, a key regulator of SMC contractility. In AAD tissues from PDE5ASMC-/- mice, increased cGMP-dependent protein kinase (PKG) activation and decreased MLC phosphorylation indicate enhanced aortic relaxation. In conclusion, our findings suggest that PDE5A downregulation or inhibition plays a causative role in exacerbating AAD likely by potentiating cGMP/PKG-mediated aortic SMC relaxation. Our findings highlight the need for caution in the clinical use of PDE5 inhibitors in patients at risk of aortic diseases. © 2025 The Pathological Society of Great Britain and Ireland.

Central artery stiffening increases the haemodynamic pulsations transmitted downstream towards target organs, including the brain. While recent evidence suggests that long duration spaceflight is associated with reduced common carotid artery (CCA) distensibility, cerebrovascular pulsatility has not been extensively characterized in astronauts. This study investigated changes in pulsatility from pre-flight to after 6 months in space, using a secondary analysis of data from four separate experiments. Middle cerebral artery blood velocity (MCAv) was measured during supine rest in 27 astronauts (20 men, 7 women). In subsets of this cohort, we measured CCA distensibility and β stiffness (n = 20), and CCA wave intensity (n = 12). The overall increase in MCAv pulsatility index (PImca) from pre-flight to post-flight was not significant (0.73 ± 0.12 vs. 0.77 ± 0.11, P = 0.060, partial η2 = 0.13). However, individual changes in PImca were directly associated with changes in estimated aortic pulse pressure (r = 0.51, P = 0.007) and β stiffness (r = 0.54, P = 0.015), and inversely associated with changes in distensibility (r = -0.62, P = 0.003), in separate bivariate analyses. Wave intensity analysis suggested a reduction in normalized wave reflection (P = 0.07), and that forward compression wave amplitude was directly related to PImca (r = 0.64, P = 0.025). These findings suggest that PImca in the days immediately following spaceflight is a function of lower carotid distensibility, highlighting the interplay between arterial stiffness and cerebrovascular pulsatility.

Chest radiograph can independently predict adverse outcomes in outpatients. We examined the associations of aortic knob width (AKW), ascending aortic length (AAL), and ascending aortic width (AAW) from chest x-ray with death and cardiovascular events in adults aged 50 and above.

Participants without cardiovascular disease were included from the Guangzhou Biobank Cohort Study (2003-2008). AKW, AAL, and AAW were indexed by body surface area. Aortic enlargement was defined using sex- and age-specific thresholds, calculated as the average value plus 1.96 multiplied by the standard deviation (SD). The associations of AKW, AAL, and AAW indices with all-cause and cause-specific mortality (cardiovascular and cancer), and incident nonfatal and fatal cardiovascular events, were examined through multivariate Cox regressions. Logistic regressions were performed to determine risk factors for aortic enlargement.

Among 27,047 participants (mean age 62 years ± 7 years SD), there were 6977 deaths and 6478 cardiovascular events over an average follow-up period of 16.3 years. Each SD increase in AKW index was associated with a higher risk of all-cause mortality, cardiovascular mortality, and cardiovascular events, with hazard ratios (95% confidence interval [CI]) of 1.13 (1.11-1.16), 1.20 (1.15-1.25), and 1.11 (1.08-1.14), respectively. Similar findings were observed regarding the AAL and AAW indices. Hypertension was a strong risk factor for enlarged AKW (odds ratio 2.52, 95% CI 2.17-2.93), AAL (1.95, 1.63-2.32), and AAW (1.80, 1.56-2.09), respectively.

Thoracic aortic parameters measured through an accessible, cheap, and safe chest radiograph were associated with higher risks of death and cardiovascular events. Hypertension should be managed.

Intracranial pulse wave velocity (PWV) offers the potential to enhance neurovascular care when evaluating cerebrovascular disease. Using 4D flow MRI, we measured PWV in the intracranial vasculature stemming from the internal carotids and basilar arteries using three popular techniques: cross-correlation, waveform optimization and time-to-upstroke which have all been used intracranially, but never compared. Near-perfect agreement between cross-correlation and waveform optimization methods was observed, while the time-to-upstroke method estimated a significantly larger PWV and was more prone to non-physiological values in a cohort of 21 healthy individuals aged 48 ± 18 years. We then analysed our cohort PWV using an ensemble approach given the current lack of methodological consensus. This analysis identified two consistent findings. First, internal carotids measure significantly higher PWV than basilar vascular networks (3.64 ± 1.47 versus 2.53 ± 1.39 m s-1). Second, in our cohort, intracranial PWV was age-independent. We hypothesize that age independence is a healthy physiological trait to minimize microvascular strain, protecting the integrity of the peripheral bed throughout ageing and cardiac pulsatile deformation. The cause for apparent age independence remains unknown. We also identified that previous work on intracranial PWV is likely biased towards the extracranial vasculature, which may explain the study differences in PWV magnitude and the age-dependent nature.

We investigated the impact of hypertension and high pulse wave velocity (PWV), each assessed in a single measurement, on target organ damage, proteinuria, and left ventricular hypertrophy (LVH). This observational cross-sectional study included 13,186 patients who underwent brachial-ankle PWV (baPWV) measurement, urinalysis, and electrocardiography during a health check-up. Blood pressure (BP) was measured at the time of baPWV measurement. Proteinuria and LVH were evaluated using a urine dipstick test and electrocardiography, respectively. Participants were categorized into four groups based on their hypertension (yes/no, defined as BP ≥ 140/90 mmHg) and baPWV (high/low, cutoff value of 14.0 m/s) statuses. The mean age of the participants was 53 ± 11 years, and the prevalence of proteinuria and LVH was 594 (4.5%) and 1716 (13.0%), respectively. Compared with the non-hypertension with low baPWV group, the non-hypertension with high baPWV (odds ratio [OR] 1.41 [95% confidence interval (CI), 1.07-1.86]), hypertension with low baPWV (OR 2.66 [95% CI, 1.78-3.97]), and hypertension with high baPWV groups (OR 2.80 [95% CI, 2.18-3.61]) exhibited a higher multivariate-adjusted risk for proteinuria. The hypertension with low baPWV group had a significantly higher risk of proteinuria than the non-hypertension with high baPWV group. Similar results were obtained for LVH. Hypertension and a high baPWV were independently associated with the prevalence of proteinuria and LVH. Hypertension assessed in a single BP measurement is likely to be a more important risk factor for proteinuria and LVH than high baPWV. Hypertension and high brachial-ankle pulse wave velocity were independently associated with the prevalence of proteinuria and left ventricular hypertrophy. Hypertension assessed in a single blood pressure measurement is likely to be a more important risk factor for proteinuria and left ventricular hypertrophy than high brachial-ankle pulse wave velocity.

The arterial stiffening is attributed to the intrinsic structural stiffening and/or load-dependent stiffening by increased blood pressure (BP). The respective lifetime alterations and major determinants of the two components with normal aging are not clear.

A total of 3053 healthy adults (1922 women) aged 18-79 years were enrolled. The carotid intima-media thickness, diameter, and local BPs were automatically determined by the radio frequency ultrasound system. The Peterson and Young elastic moduli were then calculated to represent total arterial stiffness. Structural stiffness was recalculated at a reference BP of 120/80 mmHg with established models. Load-dependent stiffness was the difference between total and structural stiffness.

Both structural and load-dependent stiffness increased with aging, with much larger changes in the structural components. The age-related increasing rates were higher in women for the structural stiffness than men ( P  < 0.05), but similar for the load-dependent stiffness. The clinical characteristics and arterial stiffness were widely correlated, but most correlations were quite weak ( r  < 0.3) other than BPs. Multiple regression analyses adjusted for sex, age and other clinical correlates showed that structural stiffness increased with pulse pressure (PP) and load-dependent stiffness increased with mean arterial pressure (MAP), respectively.

The age-related arterial stiffening is mainly caused by the intrinsic structural stiffening, which demonstrated significant age-sex interaction. BPs were the major clinical determinants of arterial stiffness, with PP and MAP associated with different arterial stiffness components. The differentiation of the structural and load-dependent arterial stiffness should be highlighted for the optimal vascular health management.

Arterial stiffness can be separated into two main mechanisms: 1) load-dependent stiffening from higher blood pressure and 2) structural stiffening due to remodeling of the vessel wall. The relationship of stiffness mechanisms with heart failure (HF) and atrial fibrillation (AF) is unknown. MESA (multi-ethnic study of atherosclerosis) participants with baseline carotid ultrasound images were included in this study (HF n = 6,278; AF n = 5,292). Carotid pulse wave velocity (cPWV) was calculated from B-mode carotid ultrasound to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mmHg blood pressure with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Associations with incident heart failure events and atrial fibrillation diagnosis were assessed with adjusted Cox hazard models. Four hundred-seven HF events and 1,157 AF diagnoses occurred during a median 17.7 and 16.8 years of follow-up. The associations of carotid artery stiffness mechanisms with HF events were: total cPWV adjusted HR per 1 SD 1.09 [0.98-1.22], P = 0.11; structural cPWV adjusted HR 1.06 [0.94-1.18], P = 0.33; and load-dependent PWV adjusted HR 1.23 [1.05-1.44] per 1 m/s, P = 0.009. The associations of carotid artery stiffness mechanisms with AF diagnoses were: total cPWV adjusted HR 1.11 (1.04-1.20), P = 0.004; structural cPWV adjusted HR 1.10 [1.02-1.16], P = 0.017; load-dependent cPWV adjusted HR 1.12 [1.02-1.23], P = 0.020. Both structural and load-dependent cPWV were associated with the development of AF, and load-dependent cPWV was associated with HF events. These findings indicate that load-dependent cPWV may be a potential treatment target to reduce the incidence of both HF and AF.NEW & NOTEWORTHY We evaluated associations between novel components of arterial stiffness: 1) load-dependent stiffening from higher blood pressure and 2) structural stiffening due to remodeling of the vessel wall and their associations with incident heart failure (n = 6,278) and atrial fibrillation (n = 5,292) over ∼17 years of follow-up. We found that both baseline structural and load-dependent stiffness were associated with the development of atrial fibrillation and load-dependent stiffness was associated with heart failure events.

A previous study reported an increase in carotid-femoral pulse wave velocity (cfPWV) during an upright posture compared to the supine position, partly due to sympathetic activation. However, given that cfPWV is influenced by the transmural pressure (TMP) of the artery, which is elevated in the abdominal aorta in the seated posture due to the increased hydrostatic pressure. Thus, it remains unclear whether this increased cfPWV reflects a true rise in arterial stiffness or is simply a result of the elevated TMP. To assess the validity of cfPWV in the seated posture for arterial stiffness assessment, 20 young healthy subjects underwent arterial stiffness measurements in both the supine and seated positions. There were no significant differences in carotid artery compliance, β-stiffness index, and aortic characteristic impedance between the two positions (P = 0.209-0.380). However, cfPWV was higher in the seated posture than the supine posture (5.4 ± 0.6 vs. 6.2 ± 0.8 m/s, P < 0.0001), showing a high intraclass correlation coefficient (ICC) between positions (r = 0.841, P < 0.0001) and a parallel upward shift by 14% (y = 1.01x + 0.54). Moreover, cfPWV was correlated with TMP at the groin level (r = 0.532, P = 0.0004), and after adjusting for TMP at the groin level using analysis of covariance (ANCOVA), the posture-related difference in cfPWV was no longer significant (P = 0.867). These findings suggest that the increase in cfPWV observed in the seated posture is primarily due to elevated TMP caused by increased hydrostatic pressure, rather than a genuine rise in arterial stiffness. Consequently, cfPWV measurements taken in the seated posture may overestimate arterial stiffness unless they are appropriately adjusted for TMP.NEW & NOTEWORTHY This study demonstrated for the first time that the increase in carotid-femoral pulse wave velocity (cfPWV) observed in the seated posture is likely due to elevated transmural pressure (TMP) caused by increased hydrostatic pressure, rather than an actual rise in central arterial stiffness. Intraclass correlation analysis also showed a parallel upward shift in the regression line between supine and seated postures. This suggests that cfPWV values obtained in the seated position should be adjusted for hydrostatic pressure and TMP.

In this review, we review the current status of biomarkers for aging and possible perspectives on anti-aging or rejuvenation from the standpoint of biomarkers. Aging is observed in all cells and organs, and we focused on research into senescence in the skin, musculoskeletal system, immune system, and cardiovascular system. Commonly used biomarkers include SA-βgal, cell-cycle markers, senescence-associated secretory phenotype (SASP) factors, damage-associated molecular patterns (DAMPs), and DNA-damage-related markers. In addition, each organ or cell has its specific markers. Generally speaking, a combination of biomarkers is required to define age-related changes. When considering the translation of basic research, biomarkers that are highly sensitive, highly specific, with validation and reliability as well as being non-invasive are optimal; however, currently reported markers do not fulfill the prerequisite for biomarkers. In addition, rodent models of aging do not necessarily represent human aging, and markers in rodent or cell models are not applicable in clinical settings. The prerequisite of clinically applicable biomarkers is that they provide useful information for clinical decision-making, such as predicting disease risk, diagnosing disease, monitoring disease progression, or guiding treatment decisions. Therefore, the development of non-invasive robust, reliable, and useful biomarkers in humans is necessary to develop anti-aging therapy for humans. Geriatr Gerontol Int 2025; 25: 139-147.

Blood flow velocity in the cerebral perforating arteries can be quantified in a two-dimensional plane with phase contrast magnetic imaging (2D PC-MRI). The velocity pulsatility index (PI) can inform on the stiffness of these perforating arteries, which is related to several cerebrovascular diseases. Currently, there is no open-source analysis tool for 2D PC-MRI data from these small vessels, impeding the usage of these measurements. In this study we present the Small vessEL MArker (SELMA) analysis software as a novel, user-friendly, open-source tool for velocity analysis in cerebral perforating arteries. The implementation of the analysis algorithm in SELMA was validated against previously published data with a Bland-Altman analysis. The inter-rater reliability of SELMA was assessed on PC-MRI data of sixty participants from three MRI vendors between eight different sites. The mean velocity (vmean) and velocity PI of SELMA was very similar to the original results (vmean: mean difference ± standard deviation: 0.1 ± 0.8 cm/s; velocity PI: mean difference ± standard deviation: 0.01 ± 0.1) despite the slightly higher number of detected vessels in SELMA (Ndetected: mean difference ± standard deviation: 4 ± 9 vessels), which can be explained by the vessel selection paradigm of SELMA. The Dice Similarity Coefficient of drawn regions of interest between two operators using SELMA was 0.91 (range 0.69-0.95) and the overall intra-class coefficient for Ndetected, vmean, and velocity PI were 0.92, 0.84, and 0.85, respectively. The differences in the outcome measures was higher between sites than vendors, indicating the challenges in harmonizing the 2D PC-MRI sequence even across sites with the same vendor. We show that SELMA is a consistent and user-friendly analysis tool for small cerebral vessels.

In part one of this two-part series, we performed a detailed analysis of the hemodynamic signature produced during resistance exercise (RE) and discussed the subacute effects on short-term modulation of large artery stiffness and central pulsatile hemodynamics. In this second part of our two-part series, we consider the subacute recovery window as the driver of resistance exercise training (RET) adaptations. We then discuss the results of RET interventions and corroborate these findings against the information gleaned from cross-sectional studies in habitually strength-trained athletes. Finally, we explore associations between muscular strength and arterial stiffness.

Our reanalysis of key studies assessing arterial stiffness in the hour post-RE suggests changes in both load-dependent and load-independent indices of arterial (aortic) stiffness. Regarding adaptations to habitual RET, a growing body of evidence contradicts earlier findings that suggested RET increases large artery stiffness. Recent meta-analyses conclude that longitudinal RET has no effect or may even reduce large artery stiffness. However, cross-sectional studies continue to support early RET intervention studies and note that habitual RET may increase large artery stiffness and central pulsatile hemodynamics. Complex interactions between vascular smooth muscle cells and the extracellular matrix may offer insight into inter-individual heterogeneity in subacute responses and chronic adaptations to acute RE and habitual RET.

Habitual RET is fundamentally important for skeletal muscle quality and quantity as well as cardiovascular function. Recent literature suggests that habitual RET has negligible effects on large artery stiffness and central hemodynamic pressure pulsatility, but cross-sectional observations still raise questions about the chronic large artery effects of habitual RET.

The incidence of arterial variations in the upper limb is variable among ethnic groups. However, there are only a few studies on the Asian population, particularly in China.

This research provided the first large data series on arterial variations in the upper limb of Chinese adults.

In this observational study, the arteries in the upper limb of consecutive patients were analyzed between July 2020 and June 2021, and the hemodynamic variables of each patient were collected.

The brachial artery deviated in 6.60% of upper limbs (11.89% of patients), and the brachioradial artery (BRA) was the most frequent variation. In the wrists of all patients, the volume flow (VF) of the BRA was lower than that of the radial artery (RA). Besides, the VF of the BRA in patients with end-stage renal disease (ESRD) was lower than that in those without ESRD in the wrist. Additionally, in the forearms of patients without ESRD, the VF of the BRA was lower than that of the RA. In the upper arm of patients with ESRD, the VF of the brachial artery in patients with BRA was significantly lower than that in patients with RA.

The incidence of arterial variations in the upper limb of Chinese adults was 6.60% (limbs) or 11.89% (patients) in this study. In our investigation, the BRA was the most common high bifurcation of the brachial artery type. Furthermore, the Chi-squared test revealed significant differences in the distribution, which was common in the right upper limb but not in sex.

The accessibility of the retina with the use of non-invasive and relatively low-cost ophthalmic imaging techniques and analytics provides a unique opportunity to improve the detection, diagnosis and monitoring of systemic diseases. The National Heart, Lung, and Blood Institute conducted a workshop in October 2022 to examine this concept. On the basis of the discussions at that workshop, this Roadmap describes current knowledge gaps and new research opportunities to evaluate the relationships between the eye (in particular, retinal biomarkers) and the risk of cardiovascular diseases, including coronary artery disease, heart failure, stroke, hypertension and vascular dementia. Identified gaps include the need to simplify and standardize the capture of high-quality images of the eye by non-ophthalmic health workers and to conduct longitudinal studies using multidisciplinary networks of diverse at-risk populations with improved implementation and methods to protect participant and dataset privacy. Other gaps include improving the measurement of structural and functional retinal biomarkers, determining the relationship between microvascular and macrovascular risk factors, improving multimodal imaging 'pipelines', and integrating advanced imaging with 'omics', lifestyle factors, primary care data and radiological reports, by using artificial intelligence technology to improve the identification of individual-level risk. Future research on retinal microvascular disease and retinal biomarkers might additionally provide insights into the temporal development of microvascular disease across other systemic vascular beds.

Arterial compliance (AC) is an important cardiovascular parameter characterizing mechanical properties of arteries. AC is significantly influenced by arterial wall structure and vasomotion, and it markedly influences cardiac load. A new method, based on a two-element Windkessel model, has been recently proposed for estimating AC as the ratio of the time constant T of the diastolic blood pressure decay and peripheral vascular resistance derived from clinically available stroke volume measurements and selected peripheral blood pressure parameters which are less prone to peripheral distortions. The aim of this study was to validate AC estimation using a virtual population generated by in silico model of the systemic arterial tree. In the second part of study, we analysed causal coupling between AC oscillations and variability of its potential determinants - systolic blood pressure and heart rate in healthy young human subjects. The pool of virtual subjects (n=3818) represented an extensive AC distribution. AC was estimated from the peripheral blood pressure curve and by the standard method from the aortic blood pressure curve. The proposed method slightly overestimated AC set in the model but both ACs were strongly correlated (r=0.94, p<0.001). In real data, we observed that AC dynamics was coupled with basic cardiovascular parameters variability independently of the autonomic nervous system state. In silico analysis suggests that AC can be reliably estimated by noninvasive method. The analysis of short-term AC variability together with its determinants could improve our understanding of factors involved in AC dynamics potentially improving assessment of AC changes associated with atherosclerosis process. Key words Arterial compliance, Cardiovascular model, Arterial blood pressure, Causal analysis, Volume-clamp photoplethysmography.

Hypertension is a recognized risk factor for the development of cognitive impairment and dementia in older adults. Aortic stiffness and altered haemodynamics could promote the transmission of detrimental high pressure pulsatility into the cerebral circulation, potentially damaging brain microvasculature and leading to cognitive impairment. We determined whether reservoir-excess pressure parameters were associated with cognitive function in people with hypertension (HT) and normotension (NT).

We studied 35 middle-aged and older treatment-naïve stage II/III HT (office systolic BP 176 ± 17 mmHg) and 35 age-, sex- and body mass index-matched NT (office systolic BP 127 ± 8 mmHg). Parameters derived from reservoir-excess pressure analysis including reservoir pressure integral (INTPR), excess pressure integral (INTXSP), systolic rate constant (SRC), diastolic rate constant (DRC) and pulse wave velocity (PWV) were calculated from an ensemble-averaged aortic pressure waveform derived from radial artery tonometry. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R), Trail Making Test Part A (TMT-A) and Part B (TMT-B).

All reservoir-excess pressure parameters were greater in HT than NT (all P  < 0.05). Greater INTXSP was associated with lower ACE-R score ( rs  = -0.31), longer TMT-A ( r  = 0.31) and TMT-B ( r  = 0.38). Likewise, greater DRC and PWV were also associated with lower ACE-R score ( rs  = -0.27 and rs  = -0.33), longer TMT-A ( r  = 0.51 and r  = 0.40) and TMT-B ( r  = 0.38 and r  = 0.32). Greater INTXSP, DRC and PWV are consistently associated with worse cognitive function in this study.

These observations support a potential mechanistic link between adverse haemodynamics and a heightened risk of cognitive impairment in older adults with hypertension.

Aging-induced aortic stiffness has been associated with altered fatty acid metabolism. We studied aortic stiffness using cardiac magnetic resonance (CMR)-assessed ventriculo-arterial coupling (VAC) and novel aortic (AO) global longitudinal strain (GLS) combined with targeted metabolomic profiling. Among community older adults without cardiovascular disease, VAC was calculated as aortic pulse wave velocity (PWV), a marker of arterial stiffness, divided by left ventricular (LV) GLS. AOGLS was the maximum absolute strain measured by tracking the phasic distance between brachiocephalic artery origin and aortic annulus. In 194 subjects (71 ± 8.6 years; 88 women), AOGLS (mean 5.6 ± 2.1%) was associated with PWV (R = -0.3644, p < 0.0001), LVGLS (R = 0.2756, p = 0.0001) and VAC (R = -0.3742, p <0.0001). Stiff aorta denoted by low AOGLS <4.26% (25th percentile) was associated with age (OR 1.13, 95% CI 1.04-1.24, p = 0.007), body mass index (OR 1.12, 95% CI 1.01-1.25, p = 0.03), heart rate (OR 1.04, 95% CI 1.01-1.06, p = 0.011) and metabolites of medium-chain fatty acid oxidation: C8 (OR 1.005, p = 0.026), C10 (OR 1.003, p = 0.036), C12 (OR 1.013, p = 0.028), C12:2-OH/C10:2-DC (OR 1.084, p = 0.032) and C16-OH (OR 0.82, p = 0.006). VAC was associated with changes in long-chain hydroxyl and dicarboxyl carnitines. Multivariable models that included acyl-carnitine metabolites, but not amino acids, significantly increased the discrimination over clinical risk factors for prediction of AOGLS (AUC [area-under-curve] 0.73 to 0.81, p = 0.037) and VAC (AUC 0.78 to 0.87, p = 0.0044). Low AO GLS and high VAC were associated with altered medium-chain and long-chain fatty acid oxidation, respectively, which may identify early metabolic perturbations in aging-associated aortic stiffening. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

This biomechanical pre-clinical study aimed to assess the consequences on mechanical properties of long term cold storage (+2 to +8 °C) of arterial allografts.

Femoropopliteal arterial segments were collected from multiorgan donors and stored at +2 to +8 °C for twelve months in saline solution with added antibiotics. Mechanical characterisation was carried out using two different tests, with the aim of defining the physiological modulus and the maximum stress and strain borne by the sample before rupture. These characterisations were carried out after zero, six, and twelve months of storage for each sample (T0, T6, and T12, respectively). For comparison, the same tests were performed on cryopreserved femoropopliteal segments after thawing.

Twelve refrigerated allografts (RAs), each divided into three segments, and 10 cryopreserved allografts (CAs) were characterised. The median (interquartile range [IQR]) Young's modulus was not statistically significantly different between the storage times for cold stored allografts: RAT0, 164 (150, 188) kPa; RAT6, 178 (141, 185) kPa; RAT12, 177 (149, 185) kPa. The median (IQR) Young's modulus of the CA group (153; 130, 170 kPa) showed no significant differences from the RA groups, irrespective of storage time. Furthermore, median (IQR) maximum stress and strain values were not significantly different between the different groups: for maximum stress: RAT0, 1.58 (1.08, 2.09) MPa; RAT6, 1.74 (1.55, 2.36) MPa; RAT12, 2.25 (1.87, 2.53) MPa; CA, 2.25 (1.77, 2.61) MPa; and for maximum strain: RAT0, 64% (50, 90); RAT6, 79% (63, 84); RAT12, 72% (65, 86); CA, 67% (50, 95).

Cold storage for up to twelve months appears to have no impact on the mechanical characteristics of human arterial allografts. Therefore, this preservation method, which would greatly simplify routine care, seems feasible. Other indicators are being studied to verify the safety of this preservation process before considering its use in vivo.

To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing.

In the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV.

A total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291).

In our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome.

Stroke induces brain injury, especially severe in hypertensive patients, and elevates mortality rates through non-neurological complications. However, the potential effects of a transient ischaemic episode on the peripheral vasculature of hypertensive individuals remain unclear. We investigated whether transient cerebral ischaemia (90 min)/reperfusion (1 or 8 days) induces alterations in mesenteric resistance artery (MRA) properties in adult male spontaneously hypertensive rats (SHR). In addition, we assessed whether the reported cerebroprotective effects of suberoylanilide hydroxamic acid (SAHA; 50 mg/kg; administered intraperitoneally at 1, 4, or 6 h after reperfusion onset) extend over several days and include beneficial effects on MRAs. Functional and structural properties of MRAs were examined at 1- and 8-days post-stroke. Nuclei distribution, collagen content, and oxidative stress were assessed. Ischaemic brain damage was evaluated longitudinally using magnetic resonance imaging. Following stroke, MRAs from SHR exhibited non-reversible impaired contractile responses to the thromboxane A2 receptor agonist U46619. Stroke increased the MRA cross-sectional area, wall thickness, and wall/lm ratio due to augmented collagen deposition. These changes were partially sustained 8 days later. SAHA did not improve U46619-induced contractions but mitigated stroke-induced oxidative stress and collagen deposition, preventing MRA remodelling at 24 h of reperfusion. Furthermore, SAHA induced sustained cerebroprotective effects over 8 days, including reduced brain infarct and oedema, and improved neurological scores. However, SAHA had minimal impact on chronic MRA contractile impairments and remodelling. These findings suggest that stroke causes MRA changes in hypertensive subjects. While SAHA treatment offers sustained protection against brain damage, it cannot fully restore MRA alterations.

Various studies have correlated the mechanical properties of the aortic wall with its biochemical parameters and inner structure. Very few studies have addressed correlations with the cohesive properties, which are crucial for understanding fracture phenomena such as aortic dissection, i.e. a life-threatening process. Aimed at filling this gap, we conducted a comprehensive biochemical and histological analysis of human aortas (the ascending and descending thoracic and infrarenal abdominal aorta) from 34 cadavers obtained post-mortem during regular autopsies. The pentosidine, hydroxyproline and calcium contents, calcium/phosphorus molar ratio, degree of atherosclerosis, area fraction of elastin, collagen type I and III, alpha smooth muscle actin, vasa vasorum, vasa vasorum density, aortic wall thickness, thicknesses of the adventitia, media and intima were determined and correlated with the delamination forces in the longitudinal and circumferential directions of the vessel as determined from identical cadavers. The majority of the parameters determined did not indicate significant correlation with age, except for the calcium content and collagen maturation (enzymatic crosslinking). The main results concern differences between enzymatic and non-enzymatic crosslinking and those caused by the presence of atherosclerosis. The enzymatic crosslinking of collagen increased with age and was accompanied by a decrease in the delamination strength, while non-enzymatic crosslinking tended to decrease with age and was accompanied by an increase in the delamination strength. As the rate of calcification increased, the presence of atherosclerosis led to the formation of calcium phosphate plaques with higher solubility than the tissue without or with only mild signs of atherosclerosis. STATEMENT OF SIGNIFICANCE: This study presents a detailed biochemical and histological analysis of human aortic samples (ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta) taken from 34 cadavers. The contribution of this scientific study lies in the detailed biochemical comparison of the enzymatic and non-enzymatic glycosylation-derived crosslinks of vascular tissues and their influence on the delamination strength of the human aorta since, to the best of our knowledge, no such comprehensive studies exist in the literature. A further benefit concerns the notification of the limitations of the various analytical methods applied; an important factor that must be taken into account in such studies.

Brain hypoperfusion is associated with cognitive impairment. Higher cerebrovascular impedance modulus (Z) may contribute to brain hypoperfusion. We tested hypotheses that patients with amnestic mild cognitive impairment (aMCI) (i.e., those who have a high risk of developing Alzheimer's disease) have higher Z than age-matched cognitively normal individuals, and that high Z is correlated with brain hypoperfusion. Fifty-eight patients with aMCI (67 ± 7 yr) and 25 cognitively normal subjects (CN, 65 ± 6 yr) underwent simultaneous measurements of carotid artery pressure (CAP, via applanation tonometry) and middle cerebral arterial blood velocity (CBV, via transcranial Doppler). Z was quantified using cross-spectral and transfer function analyses between dynamic changes in CBV and CAP. Patients with aMCI exhibited higher Z than NC (1.18 ± 0.34 vs. 1.01 ± 0.35 mmHg/cm/s, P = 0.044) in the frequency range from 0.78 to 4.29 Hz. The averaged Z in the frequency range (0.78-3.13 Hz) of high coherence (>0.9) was inversely correlated with total cerebral blood flow measured with 2-D Doppler ultrasonography normalized by the brain tissue mass (via structural MRI) across both patients with aMCI and NC (r = -0.311, P = 0.007), and in patients with aMCI alone (r = -0.306, P = 0.007). Our findings suggest that patients with aMCI have higher cerebrovascular impedance than cognitively normal older adults and that increased cerebrovascular impedance is associated with brain hypoperfusion.NEW & NOTEWORTHY This is the first study to compare cerebrovascular impedance between patients with amnestic mild cognitive impairment (aMCI) and age-matched cognitively normal individuals. Patients with aMCI had higher cerebrovascular impedance modulus than age-matched cognitively normal individuals, which was correlated with brain hypoperfusion. These results suggest the presence of cerebrovascular dysfunction in the dynamic regulation of cerebral blood flow in older adults who have high risks of Alzheimer's disease.

Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients.

A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data.

The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium-glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass.

The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.

Aging affects the cardiovascular system, and this process may be accelerated in individuals with cardiovascular risk factors. The main vascular changes include arterial wall thickening, calcification, and stiffening, together with aortic dilatation and elongation. With aging, we can observe left ventricular hypertrophy with myocardial fibrosis and left atrial dilatation. These changes may lead to heart failure and atrial fibrillation. Using multimodality imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging, it is possible to detect these changes. Additionally, multimodality imaging, mainly via CT measurements of coronary artery calcium or ultrasound carotid intima-media thickness, enables advanced cardiovascular risk stratification and helps in decision-making about preventive strategies. The focus of this manuscript is to briefly review cardiovascular changes that occur with aging, as well as to describe how multimodality imaging may be used for the assessment of these changes and risk stratification of asymptomatic individuals.

In breast reconstruction, arterial coupling has been reported to be more favorable in the thoracodorsal artery (TDA) than the internal mammary artery (IMA). This technique may help overcome anastomosis in a small, deep space. Understanding the arteries' mechanical properties is crucial for breast reconstruction's safety and success.

Abdominal-based free flap breast reconstructions performed by a single surgeon between 2020 and 2022 were retrospectively analyzed. The patients were classified by microanastomosis technique (handsewn and coupler device) to compare the rate of vascular revision. Histomorphometric analysis of arterial coupling in TDA and IMA was performed in 10 fresh cadavers for comparing wall thickness and composition, including densities of elastic fiber, smooth muscle, and collagen.

A total of 309 patients (339 reconstructed breasts) were included. There were 29 patients in the TDA handsewn group (A), 38 patients in the TDA coupler group (B), and 242 patients in the IMA handsewn group (C). The rates of arterial revision in groups A, B, and C were 0.00% (95%CI: 0.00%-11.03%), 2.5% (95%CI: 0.44%-12.88%), and 1.49% (95%CI: 0.58%-3.77%), respectively, with no statistically significant differences (p-value = .694). Histologically, the thickness of the tunica media and adventitia between IMA and TDA showed no significant difference. The density of elastic fiber was significantly higher in IMA (16.70%) than in TDA (0.79%) (p-value <.001).

The histologic characteristics of TDA are more favorable for arterial coupling than those of IMA. Arterial coupling is a safe option in situations where TDA anastomosis must be performed through a narrow and deep incision.

To investigate the association of arterial stiffness with brain perfusion, brain tissue volume and cognitive impairment in the general adult population.

This prospective study included 1488 adult participants (age range: 22.8-83.9 years) from the Kailuan study. All participants underwent brachial-ankle pulse wave velocity (PWV) measurement, brain MRI, and Montreal Cognitive Assessment (MoCA). The association of PWV with cerebral blood flow (CBF), brain tissue volume and MoCA score was investigated. Mediation analysis was used to determine whether CBF and brain tissue volume changes mediated the associations between PWV and MoCA score.

A 1 standard deviation (SD) increase in PWV was associated with lower total brain CBF [ β (95% CI) -0.67 (-1.2 to -0.14)], total gray matter CBF [β (95% CI) -0.7 [-1.27 to -0.13)], frontal lobe CBF [ β (95% CI) -0.59 (-1.17 to -0.01)], parietal lobe CBF [ β (95% CI) -0.8 (-1.43 to -0.18)], and temporal lobe CBF [ β (95% CI) -0.68 (-1.24 to -0.12)]. Negative associations were found for PWV and total brain volume [ β (95% CI) -4.8 (-7.61 to -1.99)] and hippocampus volume [ β (95% CI) -0.08 (-0.13 to -0.04)]. A 1 SD increase PWV was significantly associated with elevated odds of developing cognitive impairment [odds ratio (95% CI) 1.21 (1.01-1.45)]. Mediation analysis showed that hippocampal volume partially mediated the negative association between PWV and MoCA scores (proportion: 14.173%).

High arterial stiffness was associated with decreased total and regional CBF, brain tissue volume, and cognitive impairment. Hippocampal volume partially mediated the effects of arterial stiffness on cognitive impairment.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

Bedrest as an experimental paradigm or as an in-patient stay for medical reasons has negative consequences for cardiovascular health. The effects of severe inactivity parallel many of the changes experienced with natural aging but over a much shorter duration. Cardiac function is reduced, arteries stiffen, neural reflex responses are impaired, and metabolic and oxidative stress responses impose burden on the heart and vascular systems. The effect of these changes is revealed in studies of integrative function. Aerobic fitness progressively deteriorates with bedrest and tolerance of upright posture is rapidly impaired. In this review we consider the similarities of aging and bedrest-induced cardiovascular deconditioning. We concur with many recent clinical recommendations that early and regular mobility with upright posture will reduce likelihood of hospital-associated disability related to bedrest.

Advanced age is the major risk factor for dementia including Alzheimer's disease. The clinical effects of recently developed anti-amyloid therapy for Alzheimer's disease were modest and the long-term outcome is unknown. Thus, an in-depth understanding of the mechanisms of brain aging is essential to develop preventive interventions to maintain cognitive health in late life. Mounting evidence suggests that arterial aging manifested as increases in central arterial stiffness is associated closely with cerebrovascular dysfunction and brain aging while improvement of cerebrovascular function with aerobic exercise training contributes to brain health in older adults. We summarized evidence in this brief review that 1) increases in central arterial stiffness and arterial pulsation with age are associated with increases in cerebrovascular resistance, reduction in cerebral blood flow, and cerebrovascular dysfunction, 2) aerobic exercise training improves cerebral blood flow by modifying arterial aging as indicated by reductions in cerebrovascular resistance, central arterial stiffness, arterial pulsation, and improvement in cerebrovascular function, and 3) improvement in cerebral blood flow and cerebrovascular function with aerobic exercise training may lead to improvement in cognitive function. These findings highlight the associations between arterial aging and cerebrovascular function and the importance of aerobic exercise in maintaining brain health in older adults.

The cardio-ankle vascular index (CAVI) is a noninvasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a noninvasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the older adults.. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand between 2017 and 2018. A total of 1 640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into 3 groups based on their CAVI values as high (CAVI ≥ 9), moderate (9 > CAVI ≥ 8), and low (CAVI < 8), in which each group comprised 702, 507, and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.

Heart failure with preserved ejection fraction (HFpEF) is prevalent and associated with a poor prognosis, imposing a significant burden on society. Arterial stiffness is increasingly recognized as a crucial factor in the pathophysiology of HFpEF, affecting diagnosis, management, and prognosis. As a hallmark of vascular aging, arterial stiffness contributes to increased afterload on the left ventricle (LV), leading to diastolic dysfunction, a key feature of HFpEF. Elevated arterial stiffness is linked with common cardiovascular risk factors in HFpEF, such as hypertension, diabetes and obesity, exacerbating the progression of disease. Studies have demonstrated that patients with HFpEF exhibit significantly higher levels of arterial stiffness compared to those without HFpEF, highlighting the value of arterial stiffness measurements as both diagnostic and prognostic tools. Moreover, interventions aimed at reducing arterial stiffness, whether through pharmacological therapies or lifestyle modifications, have shown potential in improving LV diastolic function and patient outcomes. Despite these advancements, the precise mechanisms by which arterial stiffness contributes to HFpEF are still not fully understood, necessitating the need for further research.

Age-associated cardiovascular diseases (CVDs), predominantly resulting from artery-related disorders such as atherosclerosis, stand as a leading cause of morbidity and mortality among the elderly population. Consequently, there is a growing interest in the development of clinically relevant bioengineered models of CVDs. Recent developments in bioengineering and material sciences have paved the way for the creation of intricate models that closely mimic the structure and surroundings of native cardiac tissues and blood vessels. These models can be utilized for basic research purposes and for identifying pharmaceutical interventions and facilitating drug discovery. The advancement of vessel-on-a-chip technologies and the development of bioengineered and humanized in vitro models of the cardiovascular system have the potential to revolutionize CVD disease modelling. These technologies offer pathophysiologically relevant models at a fraction of the cost and time required for traditional experimentation required in vivo. This progress signifies a significant advancement in the field, transitioning from conventional 2D cell culture models to advanced 3D organoid and vessel-on-a-chip models. These innovative models are specifically designed to explore the complexities of vascular aging and stiffening, crucial factors in the development of cardiovascular diseases. This review summarizes the recent progress of various bioengineered in vitro platforms developed for investigating the pathophysiology of human cardiovascular system with more focus on advanced 3D vascular platforms.

Pulse wave encephalopathy (PWE) is hypothesised to initiate many forms of dementia, motivating its identification and risk assessment. As candidate pulsatility based biomarkers for PWE, pulsatility index and pulsatility damping have been studied and, currently, do not adequately stratify risk due to variability in pulsatility and spatial bias. Here, we propose a locus-independent pulsatility transmission coefficient computed by spatially tracking pulsatility along vessels to characterise the brain pulse dynamics at a whole-organ level. Our preliminary analyses in a cohort of 20 subjects indicate that this measurement agrees with clinical observations relating blood pulsatility with age, heart rate, and sex, making it a suitable candidate to study the risk of PWE. We identified transmission differences between vascular regions perfused by the basilar and internal carotid arteries attributed to the identified dependence on cerebral blood flow, and some participants presented differences between the internal carotid perfused regions that were not related to flow or pulsatility burden, suggesting underlying mechanical differences. Large populational studies would benefit from retrospective pulsatility transmission analyses, providing a new comprehensive arterial description of the hemodynamic state in the brain. We provide a publicly available implementation of our tools to derive this coefficient, built into pre-existing open-source software.

Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes.

From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out.

The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p<0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176-0.276, p<0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19-1.33, p<0.001), and 1.16 (1.08-1.25, p<0.001) respectively in diabetic patients before and after adjusting for potential confounders.

The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

In vitro assessment is mandatory for artificial heart valve development. This study aims to investigate the effects of pulse duplicator features on valve responsiveness, conduct a sensitivity analysis across valve prosthesis types, and contribute on the development of versatile pulse duplicator systems able to perform reliable prosthetic aortic valve assessment under physiologic hemodynamic conditions.

A reference pulse duplicator was established based on literature. Further optimization process led to new designs that underwent a parametric study, also involving different aortic valve prostheses. These designs were evaluated on criteria such as mean pressure differential and pulse pressure (assessed from high-fidelity pressure measurements), valve opening and closing behavior, flow, and regurgitation. Finally, the resulting optimized setup was tested under five different hemodynamic settings simulating a range of physiologic and pathologic conditions.

The results show that both, pulse duplicator design and valve type significantly influence aortic and ventricular pressure, flow, and valve kinematic response. The optimal design comprised key features such as a compliance chamber and restrictor for diastolic pressure maintenance and narrow pulse pressure. Additionally, an atrial reservoir was included to prevent atrial-aortic interference, and a bioprosthetic valve was used in mitral position to avoid delayed valve closing effects.

This study showed that individual pulse duplicator features can have a significant effect on valve's responsiveness. The optimized versatile pulse duplicator replicated physiologic and pathologic aortic valve hemodynamic conditions, serving as a reliable characterization tool for assessing and optimizing aortic valve performance.

Coronary artery disease (CAD) risk and plaque scores are often subjective and biased, particularly in mid-age asymptomatic women, whose CAD risk assessment has been historically underestimated. In this study, a new automatic ascending aorta time-to-peak-distention (TPD) analysis was developed for fast screening and as an independent surrogate for subclinical atherosclerosis in asymptomatic women. CCTA was obtained in 50 asymptomatic adults. Plaque burden segment involvement score (SIS) and automatic TPD were obtained from all subjects. Logistic regression analyses were performed to investigate the association between CAD risk scores and TPD with severe coronary plaque burden (SIS>5). TPD, individually, was found to be a significant predictor of SIS>5. Additionally, sex was a significant effect modifier of TPD, with a stronger statistically significant association with women. Four-dimensional aortic time-to-peak distention could supplement conventional CCTA analysis and offer a quick objective screening tool for plaque burden severity and CAD risk stratification, especially in women.