Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice.

Aging is a major risk factor of atherosclerosis through different complex pathways including replicative cellular senescence and age-related clonal hematopoiesis. In addition to aging, extracellular stress factors, such as mechanical and oxidative stress, can induce cellular senescence, defined as premature cellular senescence. Senescent cells can accumulate within atherosclerotic plaques over time and contribute to plaque instability. This review summarizes the role of cellular senescence in the complex pathophysiology of atherosclerosis and highlights the most important senotherapeutics tested in cardiovascular studies targeting senescence. Continued bench-to-bedside research in cellular senescence might allow the future implementation of new effective anti-atherosclerotic preventive and treatment strategies in clinical practice.

Left Ventricular Systolic Function Has Strong Independent Genetic Background from Diastolic Function: A Classical Twin Study.

Background and Objectives: No data are available on whether the heritability of left ventricle (LV) systolic and diastolic parameters are independent of each other. Therefore, our aim was to assess the magnitude of common and independent genetic and environmental factors defining LV systolic and diastolic function. Materials and Methods: We analyzed 184 asymptomatic twins (65% female, mean age: 56 ± 9 years). Transthoracic echocardiography was performed to measure LV systolic (global longitudinal and circumferential strain; basal and apical rotation) and diastolic (early diastolic velocity of mitral inflow and lateral mitral annulus tissue; deceleration time and early diastolic strain rate) parameters using conventional and speckle-tracking echocardiography. Genetic structural equation models were evaluated to quantify the proportion of common and specific genetic (Ac, As) and environmental factors (Ec, Es) contributing to the phenotypes. Results: LV systolic parameters had no common genetic or environmental heritability (Ac range: 0-0%; Ec range: 0-0%; As range: 57-77%; Es range: 24-43%). Diastolic LV parameters were mainly determined by common genetic and environmental effects (Ac range: 9-40%; Ec range: 11-49%; As range: 0-29%; Es range: 0-51%). Systolic parameters had no common genetic or environmental factors (Ac = 0%; Ec = 0%) with diastolic metrics. Conclusions: Systolic LV parameters have a strong genetic predisposition to any impact. They share no common genetic or environmental factors with each other or with diastolic parameters, indicating that they may deteriorate specifically to given effects. However, diastolic functional parameters are mainly affected by common environmental influences, suggesting that pathological conditions may deteriorate them equally. Estimation of the genetic and environmental influence and interdependence on systolic and diastolic LV function may help the understanding of the pathomechanism of different heart failure classification types.

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study.

OBJECTIVES: Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. METHODS: In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). RESULTS: Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CONCLUSION: CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. KEY POINTS: • Aortic root dimensions are determined by genetic and environmental effects. • Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions. • Computed tomography angiography might provide more accurate heritability estimates compared to TTE. • Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions.

Environmental Factors Responsible for Variability of Hepatic Vein Flow: A Doppler Assessment in Healthy Twins.

Doppler interrogation studies of the liver blood flow indicate altered hepatic vein waveforms in association with impaired hepatocellular function. However, little is known about the mechanisms responsible for variations of these parameters in the absence of disease. We aimed to investigate the contribution of heritable and environmental factors to the physiological variability of hepatic vein flow in a twin cohort. Two hundred twenty-eight healthy adult Hungarian twins (69 monozygotic, 45 same-sex dizygotic pairs) underwent Doppler sonography of the hepatic vein. Age- and sex-adjusted heritability of the highest velocity (amplitude of S wave) of hepatic vein flow was negligible. Shared environment contributed to 33% (95% CI, 16%-51%), and unshared environment was responsible for the largest portion (67%; 95% CI, 49%-84%) of the variance. Duration of sports activities was significantly (P < 0.05) related to the magnitude of hepatic vein flow, while other risk factors and lifestyle characteristics had no significant influence. The data suggest that genetic factors have little impact on the parameters of hepatic venous blood flow. The variability observed in healthy twins by the Doppler interrogation can be explained by the effect of unshared environmental components primarily related to regular physical activity. These findings underscore the importance of unique environments in physiological variations of hepatic venous blood flow.

Heritability of venous biomechanics.

OBJECTIVE: Altered venous biomechanics may contribute to the pathogenesis of venous diseases, and their heritability is less known. METHODS AND RESULTS: Seventy-eight monozygotic twin pairs (aged 42.4 ± 16.8 years) and 24 same-sex dizygotic twin pairs (aged 50.5 ± 16.1 years) were examined. Anteroposterior and mediolateral diameters of the common femoral vein were measured by ultrasonography. Measurements were made both in supine and in standing body positions, with or without controlled forced expiration (Valsalva test). High correlation of diameter, capacity, and distensibility values was found between twin pairs. The univariate heritability (A), shared (C), and unshared (E) environmental effects model has shown 39.3% genetic component of the variance of low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal capacity changes, even after elimination of sex, age, and body weight effects. Bivariate Cholesky analysis revealed substantial covariance of inherited body weight and venous capacity components (57.0%-81.4%). CONCLUSIONS: Femoral vein capacity and elasticity depend ≈30% to 40% on genetic factors, and this value in the standing body position can reach 50%. A relatively high genetic covariance was found between weight and femoral vein capacity and elasticity. Our work might yield some new insights into the inheritance of venous diseases that are associated with altered venous biomechanics and help elucidate the involved genes.

Echocardiography Imaging of the Right Ventricle: Focus on Three-Dimensional Echocardiography.

Right ventricular function strongly predicts cardiac death and adverse cardiac events in patients with cardiac diseases. However, the accurate right ventricular assessment by two-dimensional echocardiography is limited due to its complex anatomy, shape, and load dependence. Advances in cardiac imaging and three-dimensional echocardiography provided more reliable information on right ventricular volumes and function without geometrical assumptions. Furthermore, the pathophysiology of right ventricular dysfunction and tricuspid regurgitation is frequently connected. Three-dimensional echocardiography allows a more in-depth structural and functional evaluation of the tricuspid valve. Understanding the anatomy and pathophysiology of the right side of the heart may help in diagnosing and managing the disease by using reliable imaging tools. The present review describes the challenging echocardiographic assessment of the right ventricle and tricuspid valve apparatus in clinical practice with a focus on three-dimensional echocardiography.

Atrial Cardiomyopathy in Valvular Heart Disease: From Molecular Biology to Clinical Perspectives.

This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.

Evidence for a strong genetic influence on carotid plaque characteristics: an international twin study.

BACKGROUND AND PURPOSE: Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. METHODS: One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. RESULTS: Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%-90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%-87%), 69% for plaque size (area in mm2 in longitudinal plane; 50 percentile; 95% CI, 16%-86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%-90%), 74% for plaque numerosity (95% CI, 26%-86%), 68% (95% CI, 40%-84%), and 66% (95% CI, 32%-90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%-34%). Controlling for relevant covariates did not change the results significantly. CONCLUSIONS: The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.

[Characteristics of smoking and secondhand smoke exposure in monozygotic and dizygotic twins: results from an international twin study]. / Egy- és kétpetéju ikrek aktív és passzív dohányzási szokásai: nemzetközi ikervizsgálat eredményei.

INTRODUCTION: Zygosity differences in smoking exposure are unclear in twins. AIMS: To assess smoking and secondhand smoke exposure characteristics in twins. METHODS: 151 monozygotic and 62 dizygotic Hungarian and American adult twin pairs (age 43.8±16.5 years, mean±SD) participated in the study. RESULTS: Monozygotic twins started smoking 1.8 years earlier compared to dizygotic twins (p = 0.08). Dizygotic twins smoked longer (p<0.01) and suffered more parental smoke exposure during childhood (p<0.05). Monozygotic twins reported stricter smoking restrictions at home and workplaces (p<0.005) and less smoke exposure in indoor public places (p<0.01). 85.7% of monozygotic twins were ex or active smokers, while only 69.5% of the dizygotics (p<0.01). Lesser difference was observed in the self-reported smoke exposure rate in monozygotic compared to dizygotic pairs concerning restaurants and cafés (p<0.05) which was not present regarding bars, pubs and transportation facilities. CONCLUSIONS: Different psychological family orientation may be present across zygosity. Preventive parental care is warranted in twin families exposed to smoking.

The Added Value of Atrial Strain Assessment in Clinical Practice.

Speckle tracking echocardiography has emerged as a sensitive tool to analyze myocardial function with improved diagnostic accuracy and prognostic value. Left atrial strain assessment has become a novel imaging method in cardiology with superior prognostic value compared to conventional left atrial volume indices. Left atrial function is divided into three phases, reservoir function being the most important. This review summarizes the added value of speckle tracking echocardiography derived left atrial strain assessment in clinical practice. Recently published data suggest the prognostic value of left atrial reservoir function in heart failure, atrial fibrillation, stroke and valvular heart disease. Furthermore, left atrial reservoir strain proved to be a predictor of cardiovascular morbidity and mortality in the general population. Thus, routine assessment of left atrial function can be an optimal strategy to improve cardiovascular risk prediction and supplement the current risk prediction models.

Cellular Senescence, Aging and Non-Aging Processes in Calcified Aortic Valve Stenosis: From Bench-Side to Bedside.

Aortic valve stenosis (AS) is the most common valvular heart disease. The incidence of AS increases with age, however, a significant proportion of elderly people have no significant AS, indicating that both aging and nonaging pathways are involved in the pathomechanism of AS. Age-related and stress-induced cellular senescence accompanied by further active processes represent the key elements of AS pathomechanism. The early stage of aortic valve degeneration involves dysfunction and disruption of the valvular endothelium due to cellular senescence and mechanical stress on blood flow. These cells are replaced by circulating progenitor cells, but in an age-dependent decelerating manner. When endothelial denudation is no longer replaced by progenitor cells, the path opens for focal lipid deposition, initiating subsequent oxidation, inflammation and micromineralisation. Later stages of AS feature a complex active process with extracellular matrix remodeling, fibrosis and calcification. Echocardiography is the gold standard method for diagnosing aortic valve disease, although computed tomography and cardiac magnetic resonance are useful additional imaging methods. To date, no medical treatment has been proven to halt the progression of AS. Elucidation of differences and similarities between vascular and valvular calcification pathomechanisms may help to find effective medical therapy and reduce the increasing health burden of the disease.

Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure.

Transthoracic (TTE) and transesophageal echocardiography (TEE) is the standard imaging method for atrial septal defect (ASD) and patent foramen ovale (PFO) detection, for patient selection for transcatheter ASD/PFO closure, for intraoperative guidance and for long-term follow-up. The size, shape, location and the number of the atrial communications schould be determined. The accuracy of PFO detection can be improved by using agitated saline together with maneuvers to transiently increase the right atrial (RA) pressure. The appearance of microbubbles in the left atrium (LA) within 3 cardiac cycles after opacification of the RA is considered positive for the presence of an intracardiac shunt. Three dimensional TEE identifies further septal fenestrations and describes the dynamic morphology of ASD/PFO and atrial septal aneurysm. Follow-up evaluations with TTE is recommended at 1, 6, and 12 months after the procedure, with a subsequent evaluation every year. Previous studies showed an increased incidence of atrial arrhythmias early after device closure. Speckle tracking analysis may help to understand functional left atrial remodeling following percutaneous closure and its impact on atrial arrhythmias.

The aging venous system: from varicosities to vascular cognitive impairment.

Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima-media thickness: A longitudinal twin study.

BACKGROUND: Heart rate (HR), mean arterial pressure (MAP) and carotid intima-media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. METHODS: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. RESULTS: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33-0.51) for HR, 0.34 (95% CI: 0.24-0.43) for MAP, and 0.23 (95% CI: 0.12-0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29-0.71) for HR, 0.56 (95% CI: 0.31-0.81) for MAP, and 0.36 (95% CI: 0.07-0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. CONCLUSIONS: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Relationship between Cardiac Remodeling and Exercise Capacity in Elite Athletes: Incremental Value of Left Atrial Morphology and Function Assessed by Three-Dimensional Echocardiography.

BACKGROUND: Data are scarce regarding left atrial (LA) adaptation to regular physical exercise. The aim of this study was to examine left ventricular (LV) and also LA morphologic and functional remodeling in elite athletes using three-dimensional (3D) echocardiography. METHODS: In this retrospective analysis, the study group consisted of 138 elite athletes (mean age, 20 ± 4 years; 62% men) and 50 sedentary control subjects. Electrocardiographically gated full-volume 3D data sets were obtained for offline analysis using dedicated software for 3D LA and LV measurements. Body surface area-indexed LA maximal volume (LAVmax) and LV end-diastolic volume were determined. LA total emptying fraction, LA passive and LA active emptying fraction, and LV global longitudinal strain were also calculated. Athletes also underwent cardiopulmonary exercise testing to determine peak oxygen uptake. RESULTS: Athletes demonstrated higher 3D LAVmax (32 ± 6 vs 26 ± 8 mL/m2) and indexed LV end-diastolic volume (85 ± 12 vs 62 ± 10 mL/m2) compared with control subjects (P < .001 for both). Functional measures of the left ventricle and left atrium, such as the absolute value of 3D LV global longitudinal strain (19 ± 2% vs 22 ± 2%), LA total emptying fraction (58 ± 6% vs 64 ± 6%), and active emptying fraction (24 ± 10% vs 32 ± 10%) were lower in athletes (P < .001 for all). Male athletes had higher indexed LV end-diastolic volume compared with female athletes (89 ± 13 vs 80 ± 8 mL/m2, P < .001), but LAVmax did not differ between genders (32 ± 6 vs 33 ± 5 mL/m2, P = .18). Besides heart rate, gender, and body surface area, 3D LAVmax, LV global longitudinal strain, and LA passive emptying fraction were independent predictors of peak oxygen uptake. CONCLUSIONS: Regular physical exercise results in marked LA and LV remodeling with considerable gender differences as explored by 3D echocardiography. In contrast with various cardiovascular diseases, more pronounced LA dilation and lower resting functional measures are associated with better exercise performance.

[New results in the research of the biomechanics of the venous system]. / Ujabb eredmények a vénás rendszer biomechanikájának kutatásában.

The upright posture of man had been a major evolutional challenge. The mechanisms responsible for orthostatic tolerance mostly affect the venous system. In this paper, we discuss new results regarding the biomechanics of the venous system highlighting a rather neglected field, the biomechanical properties of the vein wall. These properties change according to localization of veins, age, gender and body mass. The anti-gravitational adaptation of veins is a complex process involving all three layers of the venous wall. Local myogenic and humoral mechanisms as well as systemic hormonal and nervous influences control the adaptive processes in the veins. Long term adaptation involves structural and functional remodeling of the venous wall. Disorders of the veins mostly cause pathological remodeling. Hemodynamic factors (pressure and flow) together with inflammatory processes may lead to pathological alterations, changing the biomechanical properties of the vein wall, which further contribute to the reservation and progression of venous dysfunction. Appropriate testing of venous function can reveal biomechanical disorders even in clinically asymptomatic patients. Thus, biomechanical investigation of veins not only helps to understand the underlying pathomechanism but it also can contribute to early diagnosis and follow-up of venous disorders. When recognized in time, pathological remodeling can be prevented or treated. In this way, the incidence of venous disorder could be cut back reducing both human suffering and material loss.

Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall.

AIMS: The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. METHODS: 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. RESULTS: Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). CONCLUSIONS: Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.

Genetically determined pattern of left ventricular function in normal and hypertensive hearts.

We sought to assess the inheritance of left ventricular (LV) function using speckle-tracking echocardiography and the impact of hypertension on modifying the genetically determined pattern of contraction in a population of twins. We recruited 92 Caucasian twin pairs, including 74 hypertensive (HTN) siblings. Beyond standard echocardiographic protocol, a speckle-tracking analysis was performed, including global longitudinal strain (GLS). Systolic function, as assessed by ejection fraction, showed moderate heritability (61%); however, GLS showed higher and dominant heritability (75%). Heterogeneity models revealed that there were no differences between the HTN and non-HTN subjects regarding the heritability of GLS. However, the heritability estimates of diastolic function parameters, including early diastolic strain rate, were low. LV systolic biomechanics is highly heritable. GLS shows dominant heritability, despite the presence of early-stage hypertensive heart disease. Early diastolic parameters are rather determined by environmental factors. These findings suggest the presence of a genetic framework that conserves systolic function despite the expression of diastolic dysfunction and may underlie the phenotypic progression towards heart failure with preserved ejection fraction.

Correction: Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall.

[This corrects the article DOI: 10.1371/journal.pone.0192948.].

Generalized changes in venous distensibility in postthrombotic patients.

INTRODUCTION: In situ biomechanical properties of peripheral large veins were compared between asymptomatic young patients who had previously unilateral femoro-popliteal deep venous thrombosis (DVT) and age-matched, healthy controls; the aim of this study was to assess local or generalized alterations of venous wall biomechanics in postthrombotic patients. PATIENTS AND METHODS: Inner diameters of both common femoral veins, right axillary vein, and right internal jugular veins were measured in two directions by ultrasonography. Venous pressure was altered by posture changes (standing and lying) and by application of graded and controlled Valsalva. Ten postthrombotic young patients without any symptoms and 11 age-matched control subjects were included. RESULTS: In postthrombotic patients, both the affected and unaffected common femoral vein diameters and capacities were larger at low transmural pressures than those for the control group, but they demonstrated significantly less distensibility when higher pressures were applied. Similarly, in the internal jugular vein, capacity without Valsalva was significantly higher in postthrombotic patients and distensibility was reduced (statistically significant in the erect position). Pressure-induced changes in axillary vein diameter were negligible. CONCLUSIONS: In situ diameter and capacity changes, and in situ distensibility of the femoral veins on both sides (i.e., the side of previous thrombosis as well as the disease-free side) and of the jugular veins are reduced in the young DVT patients compared to veins of the age-matched, healthy controls. The pathophysiological mechanism of generalized venous wall changes in these young DVT patients remains unknown.