Aortic Stiffness Research Articles

Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension.

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.

Estimated versus measured aortic stiffness: implications of diabetes, chronic kidney disease, sex and height.

Aortic stiffness is measured by carotid-femoral pulse wave velocity (PWV), but it can also be estimated (ePWV) based on age and brachial mean arterial pressure (MAP). However, diabetes mellitus and/or chronic kidney disease (DM/CKD) may cause more pronounced damage to the arterial wall, changing the pressure and PWV relationship. Furthermore, sex and height could affect PWV through their relationship to the arterial diameter and path length. The aim of the present study was to quantify the extent to which DM/CKD, sex and height affect the validity of ePWV in predicting PWV. This cross-sectional study evaluated PWV in adult participants at high risk of aortic stiffness, using Complior and the second derivative transit time algorithm (PWV 2nd ). PWV 2nd was converted into intersecting tangent PWV (PWV ITc ), and ePWV was calculated using the Reference Values for Arterial Stiffness Collaboration formulas. Among 825 patients (62% males), the mean age was 60 ± 17 years, 34% had diabetes mellitus, 69% had CKD, and 24% did not have DM/CKD. MAP, ePWV, PWV 2nd , and PWV ITc were, respectively, 96 ± 14 mmHg, 9.8 (8.1-11.8) m/s, 9.5 (7.8-11.9) m/s and 11.3 (8.8-15.9) m/s. There was a significant interaction between DM/CKD, sex, and the predictive value of ePWV. Increasing height lowered the intercept but did not affect the slope of the relationship between estimated and measured PWVs. These findings suggest that the current ePWV equations do not accurately predict PWV in patients with DM/CKD, and that sex and height should also be considered in the future ePWV equations.

Dialysate Sodium Levels, Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients.

Dialysate Sodium Levels, Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients.

Patient-specific compliant simulation framework informed by 4DMRI-extracted pulse wave Velocity: Application post-TEVAR

We introduce a new computational framework that utilises Pulse Wave Velocity (PWV) extracted directly from 4D flow MRI (4DMRI) to inform patient-specific compliant computational fluid dynamics (CFD) simulations of a Type-B aortic dissection (TBAD), post-thoracic endovascular aortic repair (TEVAR). The thoracic aortic geometry, a 3D inlet velocity profile (IVP) and dynamic outlet boundary conditions are derived from 4DMRI and brachial pressure patient data. A moving boundary method (MBM) is applied to simulate aortic wall displacement. The aortic wall stiffness is estimated through two methods: one relying on area-based distensibility and the other utilising regional pulse wave velocity (RPWV) distensibility, further fine-tuned to align with in vivo values. Predicted pressures and outlet flow rates were within 2.3 % of target values. RPWV-based simulations were more accurate in replicating in vivo hemodynamics than the area-based ones. RPWVs were closely predicted in most regions, except the endograft. Systolic flow reversal ratios (SFRR) were accurately captured, while differences above 60 % in in-plane rotational flow (IRF) between the simulations were observed. Significant disparities in predicted wall shear stress (WSS)-based indices were observed between the two approaches, especially the endothelial cell activation potential (ECAP). At the isthmus, the RPWV-driven simulation indicated a mean ECAP>1.4 Pa-1 (critical threshold), indicating areas potentially prone to thrombosis, not captured by the area-based simulation.RPWV-driven simulation results agree well with 4DMRI measurements, validating the proposed pipeline and facilitating a comprehensive assessment of surgical decision-making scenarios and potential complications, such as thrombosis and aortic growth.

Increased Aortic Stiffness With Acute Exercise in Heart Failure: Assessment by Cardiovascular Magnetic Resonance

This study aimed to investigate the acute changes in proximal aortic distensibility, a measure of aortic stiffness, induced by acute exercise in participants with and without heart failure (HF). Participants with HF (n = 24) and without HF (n = 26) underwent cardiovascular magnetic resonance (CMR) (1.5 T) imaging at rest and after submaximal supine bicycle ergometry. The participants were further categorized into HF with reduced ejection fraction (HFrEF) (n = 14) and HF with preserved ejection fraction (n = 10) based on the left ventricular ejection fraction. At rest and immediately after exercise, cine CMR images of the cross-sectional ascending and descending aorta at the pulmonary artery bifurcation level were obtained to determine aortic distensibility (AoD), with lower AoD indicating greater aortic stiffness. Differences in means of values at rest and before and after exercise were compared using the nonparametric Wilcoxon sign test. There was no significant difference in AoD at rest between subjects with HF and controls. However, immediately after exercise, participants with HF but not controls exhibited a significant reduction in AoD, indicating higher aortic stiffness related to exercise (median [interquartile range] for the ascending aorta: 3.16 (1.26) × 10-3 mm Hg-1 to 2.39 (1.57) × 10-3 mm Hg-1 and the descending aorta: 4.19 (2.58) × 10-3 mm Hg-1 to 2.96 (1.79) × 10-3 mm Hg-1) (both p = 0.023). This decrease was particularly observed in participants with HFrEF but not in those with HF with preserved ejection fraction. Exercise-induced aortic stiffness, detectable by noninvasive CMR, may contribute to unfavorable ventricular-vascular interactions during exercise in participants with HF, especially HFrEF.

Heart Stiffening in Pediatric Dilated Cardiomyopathy: Causes of Severity

Background: Cardiomyopathy, characterized by heart stiffness, can lead to heart failure. This study aimed to investigate aortic stiffness in children with dilated cardiomyopathy (DCM) to better understand its contribution to disease severity. Methods: This case-control study compared 48 children with DCM with 96 healthy children over a 10-year period starting in 2011. Aortic strain, aortic stiffness index, aortic distensibility, and pressure strain elastic modulus were measured. These parameters, along with several echocardiographic measures, were compared between the DCM and control groups. Statistical analyses were performed using SPSS 18, with a significance threshold set at a P value below 0.05. Results: The participants included 57.6% boys, with 58.3% in the DCM group and 57.35% in the control group (χ2=0.014, P=0.905). The age range was 2 to 18 years, with mean ages of 11.08±4.63 years for the DCM group and 10.77±2.82 years for the control group (P=0.691). Significant differences between groups were observed in aortic distensibility (P=0.004), aortic stiffness β index (P=0.001), and pressure strain elastic modulus (P=0.004). Post-treatment analyses based on ejection fraction and fractional shortening cutoffs indicated no changes in elasticity parameters except for the aortic stiffness β index, which varied according to the Ross classification. Conclusion: Children with DCM exhibited reduced aortic strain and aortic distensibility, as well as elevated aortic stiffness β index and pressure strain elastic modulus

Dialysate Sodium Levels, Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients.

Increased aortic blood-pressure(BP) and arterial stiffness are associated with higher cardiovascular risk in hemodialysis. Previous works showed that lower dialysate sodium is associated with lower brachial-BP; data on aortic-BP and arterial stiffness are limited. This study aimed to investigate the effects of different dialysate sodium concentrations on 72-h aortic-BP and arterial stiffness parameters in hemodialysis patients. This analysis is part of a prospective, non-randomized interventional study. Twenty-five hemodialysis patients underwent a set of three periods of different dialysate sodium concentrations; six sessions with dialysate sodium of 137meq/L, followed consecutively by six sessions with 139meq/L and, finally, six sessions with 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM (Mobil-O-Graph) was performed to evaluate aortic-BP and arterial stiffness indices during the overall 72-h, different 24-h, day-time and night-time periods. Mean 72-h aortic SBP/DBP were higher with increasing dialysate sodium concentrations (137meq/L: 114.2±15.3/77.0±11.8mmHg vs 139meq/L: 115.4±17.3/77.9±14.0mmHg vs 141meq/L: 120.5±18.4/80.5±14.7mmHg, p=0.002/p=0.057, respectively). Wave-reflections parameters (AIx, AIx(75), AP) were not significantly different between the three dialysate sodium concentrations. Ambulatory PWV was significantly higher with increasing dialysate sodium concentrations (137meq/L: 8.5±1.7m/s vs 139meq/L: 8.6±1.6m/s vs 141meq/L: 8.8±1.6m/s, p<0.001). In generalized linear-mixed-models including 72-h brachial SBP as random covariate, the adjusted marginal-means of 72-h PWV were not significantly different between-groups. This study showed that lower dialysate sodium concentrations are associated with significant decreases in ambulatory aortic BP and PWV. This study showed that higher dialysate sodium concentrations are associated with significant increases in ambulatory aortic BP and PWV. These findings further support the need for modification of dialysate sodium concentration in hemodialysis.

Association of Cardiac MRI-derived Aortic Stiffness with Early Stages and Progression of Heart Failure with Preserved Ejection Fraction.

Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, n = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, n = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, n = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], P = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], P = .01). Increased PWV correlated with higher PCWP (P = .006), left atrial and left ventricular long-axis strain (all P < .02), and N-terminal pro-brain natriuretic peptide levels (P < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], P = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; P = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; P = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; P < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; P < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. Keywords: MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 Supplemental material is available for this article. © RSNA, 2024.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease

Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Prognostic impact of peripheral artery disease-related parameters in patients with acute coronary syndrome.

Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. Among 270 patients admitted for ACS (mean age 67 years, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61-10.08, P < 0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.

Cardiovascular effects of long-duration space flight.

Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

A Characterization of the Cardiac Physiology and Aortic Pulse Wave Properties of Artistic Swimmers Across Competitive Levels.

The distinct physical and environmental stressors of artistic swimming (previously termed synchronized swimming) result in unique hemodynamic stimuli. Given that the hemodynamic stress associated with participation in an exercise modality drives adaptation of the heart and central vasculature, artistic swimming may produce a distinct cardiovascular phenotype. Presumably, athletes competing at the highest levels also have greater training exposure and, thus, exhibit more adaptation. The purpose of this study was to characterize cardiovascular form and function across the competitive spectrum of artistic swimmers. Cardiovascular structure and function were compared in a cross-sectional study of healthy controls, varsity, and elite artistic swimmers, using pulse wave analysis, pulse wave velocity, and echocardiographic images both at rest and during isometric handgrip exercise. Aortic stiffness was similar across all groups, as were characteristics of the decomposed aortic pressure waveform. At rest, both varsity and elite swimmers demonstrated similar systolic function compared to controls. However, peak left ventricular twist was greater in varsity and elites (controls: 8.0 ± 3.9, varsity: 12.8 ± 8.6, elites: 13.4 ± 3.9; both p < 0.02). Furthermore, elites demonstrated greater peak left ventricular radial strain (controls: 29.2 ± 9.9, varsity: 32.5 ± 10.3, elites: 53.9 ± 15.1; both p < 0.001) and longitudinal strain (controls: -16.9 ± 1.6, varsity: -16.5 ± 1.8, elites: -19.5 ± 3.2; both p < 0.04). In contrast to controls, both varsity and elite artistic swimmers demonstrated no change in peak late diastolic transmitral filling velocity (controls: Δ0.2 ± 0.04 m/s, varsity: Δ0.06 ± 0.04 m/s, elites: Δ0.05 ± 0.04 m/s) during isometric handgrip exercise (both p > 0.05), with elites demonstrating lower peak velocity than varsity swimmers, (p = 0.048) indicating preservation of diastolic function. Artistic swimmers demonstrate distinct cardiac physiology at rest and during isometric handgrip, with a greater extent of distinguishing features observed in those competing at the highest level of competition.

Are aortic biomechanical properties early markers of dilatation in patients with Marfan syndrome? A systematic review and meta-analysis

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta $$\\end{document}-stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta $$\\end{document}-SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta $$\\end{document}-stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta $$\\end{document}-SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery.

Decreased Aortic Elasticity in Rheumatoid Arthritis: An Early Sign of Atherosclerosis and Predictive Factors.

Atherosclerosis is increased in patients with rheumatoid arthritis (RA) and early diagnosis of vascular disease leads to better outcome. Our aim was to evaluate whether aortic elasticity decreases in the subclinical stage of atherosclerosis in RA patients without any cardiovascular disease and to determine disease-related risk factors. One hundred fourteen patients with RA, 50 patients with spondyloarthritis, and 50 healthy control were included in this study. Aortic elasticity was evaluated by echocardiography (ECHO). The relationship between atherosclerosis and vascular risk factors, including age, disease activity, C-reactive protein, and serum tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) levels was investigated. In ECHO evaluation, aortic stiffness was increased (P=.01), and aortic strain and elasticity were decreased (P < .01, P=.01) in RA patients compared to control groups. Serum tumor necrosis factor-like weak inducer of apoptosis levels were also significantly lower (P < .01) in RA, but no significant correlation was found with aortic strain measurement (P > .05). Aortic elasticity was shown to decrease significantly with age in all groups (P < .05). In this study, we observed deterioration of aortic parameters indicating early atherosclerosis in RA. Aging was found to be the single predictive factor for vascular disease. Although a decrease in sTWEAK level was detected in the RA group, no statistically significant relationship could be demonstrated between sTWEAK level and aortic elasticity parameters. However, the cross-sectional design of the study and possible fluctuations in serum markers depending on disease activity make it difficult to draw a clear conclusion on this subject.

Neonatal hyperoxia exposure leads to developmental programming of cardiovascular and renal disease in adult rats

Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-β1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.

SPECTRUM AND CHARACTERISTICS OF THE ELECTROCARDIOGRAPHIC CHANGES IN CHILDREN WITH TYPE I DIABETES MELLITUS

Introduction. Type I diabetes mellitus (T1D) is one of the most widespread and socially significant diseases. Well-known as a co-occurring condition with youth-onset type 1 diabetes mellitus, cardiovascular disease manifests early after initial diagnosis as signs of cardiovascular remodeling. Growing data indicates that type 1 diabetic children and young adults experience subclinical heart dysfunction, central aortic stiffening, and accelerated peripheral vascular disease. Increased morbidity and mortality in adults have been linked to peripheral artery, heart, and cerebrovascular diseases, and early vascular alterations have been demonstrated to exist since childhood. Little is known to date concerning the development of early cardiac structural and functional problems in children with T1D. Early diagnostic is of high importance. Aim. To assess the frequency and spectrum of electrocardiography (ECG) abnormalities in children with type 1 diabetes. Materials and methods. Records of 60 patients with type I diabetes included into the analysis. ECG data, main anamnestic, clinical and laboratory data analyzed. Results. So-called "small ECG abnormalities" were found. Incomplete left/right blockade bundle branch block found in 22.5% of children, shortened PQ interval in 15%, extrasystoles, tachycardia, bradycardia in 52.5%, T wave amplitude decrease in 60%. 87.5% of the examinees have a combination of 2–3 of the above changes on the ECG. Only 12% of the examined children had an ECG without pathological changes. All children with newly diagnosed type 1 DM had at least 1 of the described ECG abnormalities. Correlation analysis done. Substantial positive correlations between Hb1Ac levels and number of ECG changes, serum cholesterol levels and number of ECG changes were found. Conclusions. The results of the study indicate that the majority of children with type I diabetes have so-called "small ECG abnormalities." According to the type of disturbances, they can be classified as rhythm and conduction disturbances and combined changes. These findings are promising in terms of management tactics for children with type I diabetes, early detection and timely therapeutic correction of ECG abnormalities.

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism

Introduction Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. Material and Methods The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. Results There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). Conclusion Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

Changes in the cardiovascular risk profile in children approaching kidney replacement therapy

Despite significant cardiovascular (CV) morbidity in children on dialysis and after kidney transplantation, data on the evolution of CV damage in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) is unknown. The burden, progression, and predictors of CV damage before KRT onset were explored in two prospective multicenter cohorts from Europe and Canada: Cardiovascular Comorbidity in Children with CKD (4C) and Haemodiafiltration, Heart and Height (3H) studies, conducted from 2009-19 and 2013-16, respectively. CV damage and risk factors were evaluated (i) cross sectionally at KRT-start (n=248), and (ii) longitudinally over the 2-years preceding KRT start (n=157; 331 patient-visits). Longitudinal analyses with mixed-effects models estimated associations of modifiable CV risk factors with change in carotid intima-media thickness (cIMT) standard deviation score (SDS), pulse wave velocity (PWV-SDS), left ventricular (LV) mass and systolic dysfunction. 248 patients, age 14.3 (12.2, 16.2) years were evaluated at median 35 (28-114) days before KRT start. Elevated cIMT-SDS and PWV-SDS were present in 43% and 25%, and LV hypertrophy and systolic dysfunction in 49% and 33%. Aortic stiffness and LV hypertrophy significantly increased, especially in the year before KRT start (adjusted odds ratio, OR 0.33, P=0.002 and OR 0.54, P=0.01, respectively). 79% of children had >3 modifiable CV risk factors at KRT onset. Diastolic BP and BMI were strongly associated with a linear increase in all CV measures. After controlling for CV risk factors, the time to KRT onset no longer predicted the burden of CV damage. This comprehensive CV evaluation shows the progressive accrual of modifiable risk factors and a high burden of CV damage in the years preceding KRT onset. CV damage in the pre-KRT period is preventable. Supported by EU4Health Programme (101085068) and Kidney Research UK (RP39/2013).

Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs.

Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia. Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA. Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content. Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.

Aortic tissue stiffness and tensile strength are correlated with density changes following proteolytic treatment

Introduction: Dissection or rupture of the aorta is accompanied by high mortality rates, and there is a pressing need for better prediction of these events for improved patient management and clinical outcomes. Biomechanically, these events represent a situation wherein the locally acting wall stress exceed the local tissue strength. Based on recent reports for polymers, we hypothesized that aortic tissue failure strength and stiffness are directly associated with tissue mass density. The objective of this work was to test this novel hypothesis for porcine thoracic aorta.Methods: Three tissue specimens from freshly harvested porcine thoracic aorta were treated with either collagenase or elastase to selectively degrade structural proteins in the tissue, or with phosphate buffer saline (control). The tissue mass and volume of each specimen were measured before and after treatment to allow for density calculation, then mechanically tested to failure under uniaxial extension.Results: Protease treatments resulted in statistically significant tissue density reduction (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.003), which in turn was significantly and directly correlated with both ultimate tensile strength (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.03) and tangent modulus (sham vs. collagenase p = 0.007 and sham vs elastase p = 0.03).Conclusions: This work demonstrates for the first time that tissue stiffness and tensile strength are directly correlated with tissue density in proteolytically-treated aorta. These findings constitute an important step towards understanding aortic tissue failure mechanisms and could potentially be leveraged for non-invasive aortic strength assessment through density measurements, which could have implications to clinical care.