Sandra Wray

Arterial Stiffness and Renal Replacement Therapy: A Controversial Topic

The increase of arterial stiffness has been to have a significant impact on predicting mortality in end-stage renal disease patients. Pulse wave velocity (PWV) is a noninvasive, reliable parameter of regional arterial stiffness that integrates the vascular geometry and arterial wall intrinsic elasticity and is capable of predicting cardiovascular mortality in this patient population. Nevertheless, reports on PWV in dialyzed patients are contradictory and sometimes inconsistent: some reports claim the arterial wall stiffness increases (i.e., PWV increase), others claim that it is reduced, and some even state that it augments in the aorta while it simultaneously decreases in the brachial artery pathway. The purpose of this study was to analyze the literature in which longitudinal or transversal studies were performed in hemodialysis and/or peritoneal dialysis patients, in order to characterize arterial stiffness and the responsiveness to renal replacement therapy.

Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients

Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP). Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels. Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV) in a central arterial pathway (carotid-femoral) and in a peripheral pathway (carotid-brachial). A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups. Results. Only carotid-femoral stiffness was positively associated (P < 0.05) with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration. Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP.

The effects of age on pulse wave velocity in untreated hypertension

Increased arterial stiffness is an important determinant of cardiovascular risk, able to predict morbidity and mortality, and closely associated with ageing and blood pressure. The aims of this study were: (1) To determine the age‐dependent reference pulse wave velocity (PWV), and compare it with values from hypertensive patients, and (2) to evaluate the impact of isolated and untreated hypertension on arterial stiffness. A total of 1079 patients were enrolled and divided into a control group (NT) of asymptomatic normotensive patients and a group of asymptomatic hypertensive patients (HT). Blood pressure, carotid‐femoral PWV, and body mass index were measured in each subject, whose blood was drawn for laboratory tests. Aortic mean PWV in the NT group was 6.85 ± 1.66 m/s, which increased linearly (R2 = 0.62; P < .05) with age. In patients over 50 years of age, PWV was significantly higher than in younger patients (8.35 vs 5.92 m/s, respectively, P < .001). This significant difference persisted when observing male and female patients separately. In the hypertensive group, mean PWV value was 8.04 ± 1.8 m/s (range 4.5‐15.8 m/s) and increased (R2 = 0.243; P < .05) with age. The PWV increase in HT was significantly higher (0.93 m/s per decade, P < .001) than in NT (0.44 m/s per decade). Our study provides normal values of PVW per decade, and shows that these values increase with age, especially after 50 years of age, particularly in HT patients. This stiffness growth rate may be responsible for increased cardiovascular risk in both groups.

Structural and Functional Properties of Venous Wall: Relationship between Elastin, Collagen, and Smooth Muscle Components and Viscoelastic Properties

The aims of this work were (1) to analyze the viscoelastic behavior of different venous segments and their differences, considering the structural characteristics (elastin, collagen, and smooth muscle content) of the venous wall; (2) to analyze the venous biomechanical behavior by means of the histological characteristics of the veins. Nine healthy male Corriedale sheep were included. One vein was selected from each animal to evaluate its biomechanical properties: (a) anterior vena cava, (b) right jugular vein, and (c) right femoral vein. Each selected vein was instrumented with pressure and diameter sensors. After excision, a small ring-shaped sample was set apart from each segment for histological analysis. The amounts of elastin, collagen and smooth muscle were correlated to calculated biomechanical parameters (high- and low-pressure compliance and viscosity). Conclusions are the following: (1) the viscoelastic behavior of the venous wall varies depending on the vascular territory, and it is associated with the variation of the histological structure. These differences involve muscle (both smooth and striated), elastin, and collagen contents. (2) In addition, the quantity of collagen was negatively correlated with high- and low-pressure compliances, and (3) the smooth muscle content was higher in peripheral veins and is positively correlated with venous wall viscosity.

Reference intervals and percentiles for carotid-femoral pulse wave velocity in a healthy population aged between 9 and 87 years

There is little information regarding age‐related reference intervals (RIs) of carotid‐femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year‐to‐year percentile curves and body‐height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9–87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age‐related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age‐specific (year‐to‐year) percentile curves that were defined using the standard normal distribution. Age‐specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height‐related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years.

Hemodialysis Decreases the Etiologically-Related Early Vascular Aging Observed in End-Stage Renal Disease: A 5-Year Follow-Up Study

Aims: To analyze the early vascular aging (EVA) in end-stage renal disease (ESRD) patients, attempting to determine a potential association between EVA and the etiology of ESRD, and to investigate the association of hemodialysis and EVA in ESRD patients during a 5-year follow-up period. Methods: Carotid-femoral pulse wave velocity (cfPWV) was obtained in 151 chronically hemodialyzed patients (CHP) and 283 control subjects, and in 25 CHP, who were followed-up after a 5-year lapse. Results: cfPWV increased in ESRD patients compared to control subjects. The cfPWV-age relationship was found to have a steeper increase in ESRD patients. The highest cfPWV and EVA values were observed in patients with diabetic nephropathy. Regression analysis demonstrated a significant reduction of the EVA in HD patients on a 5-year follow-up. Conclusion: Patients in ESRD showed higher levels of EVA. cfPWV and EVA differed in ESRD patients depending on their renal failure etiology. CHP showed an EVA reduction after a 5-year follow-up period.

Quantitative Analysis of the Relationship between Blood Vessel Wall Constituents and Viscoelastic Properties: Dynamic Biomechanical and Structural In Vitro Studies in Aorta and Carotid Arteries

The purposes of this work were to perform in sheep a quantification of the elastic, viscous, and inertial moduli obtained in carotid and aortic artery segments during in vitro dynamic studies that mimic the normal circulatory function; a quantitative determination of collagen, elastin, and vascular smooth muscle of the carotid and aortic segments analyzed in vitro; the correlation between the amounts of each arterial wall constituent and the viscoelastic properties. To this end, nine healthy sheep were included. One artery was selected from each animal to evaluate its biomechanical properties: (a) in three sheep the ascending aorta, (b) in three the thoracic descending aorta, and (c) in the remaining three the proximal segments of the carotid artery. Each selected artery was instrumented with pressure and diameter sensors. After excision, a small ring-shaped sample was set apart from each segment for histological analysis. In conclusion, (a) the arterial compliance showed a positive association with the absolute and relative amount of the parietal elastin, and (b) arterial viscosity was positively associated with the relative amount of smooth muscle, and this association was increased when the correlation was calculated considering the amount of collagen as well as the amount of smooth muscle.

Experimental assessment of a myocyte-based multiscale model of cardiac contractile dysfunction

Cardiac contractile dysfunction (CD) is a multifactorial syndrome caused by different acute or progressive diseases which hamper assessing the role of the underlying mechanisms characterizing a defined pathological condition. Mathematical modeling can help to understand the processes involved in CD and analyze their relative impact in the overall response. The aim of this study was thus to use a myocyte-based multiscale model of the circulatory system to simulate the effects of halothane, a volatile anesthetic which at high doses elicits significant acute CD both in isolated myocytes and intact animals. Ventricular chambers built using a human myocyte model were incorporated into a whole circulatory system represented by resistances and capacitances. Halothane-induced decreased sarco(endo)plasmic reticulum Ca2+ (SERCA2a) reuptake pump, transient outward K+ (Ito), Na+-Ca2+ exchanger (INCX) and L-type Ca2+ channel (ICaL) currents, together with ryanodine receptor (RyR2) increased open probability (Po) and reduced myofilament Ca2+ sensitivity, reproduced equivalent decreased action potential duration at 90% repolarization and intracellular Ca2+ concentration at the myocyte level reported in the literature. In the whole circulatory system, model reduction in mean arterial pressure, cardiac output and regional wall thickening fraction was similar to experimental results in open-chest sheep subjected to acute halothane overdose. Effective model performance indicates that the model structure could be used to study other changes in myocyte targets eliciting CD.

Arterial Stiffness in Haemodialyzed Patients: Findings and Controversies

Vascular research in end-stage renal diseases is an interesting field in which the characterization of arterial stiffness proved to be valuable to predict morbidity and mortality. Particularly, patients on renal replacement therapy have been reported to have significant increases in arterial stiffness and cardiovascular mortality. The clinical relevance of the measurement of arterial stiffness is linked to therapeutical and preventive interventions. The purpose of this work is to analyze the results of the scientific research in the field of arterial stiffness, in which hemodialyzed patients were involved, emphasizing on clinical and in-vitro research carried out by our group compared to contributions previously reported in the specialized literature. These investigations are necessary to improve diagnostic strategies and monitor the arterial response to therapeutical interventions in chronic kidney disease.

Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients Depends on the Location of the Upper-limb Vascular Access

BACKGROUND Pulse wave velocity ratio (PWV-ratio), a measure of central-to-peripheral arterial stiffness gradient, is calculated as a quotient between carotid-femoral and carotid-radial PWV (cf-PWV/cr-PWV). This new index has been reported to be significantly associated with increased mortality in hemodialyzed patients. Since several reports showed differences in arterial stiffness regarding the pathway where the vascular access (VA) is, the purpose of this research was: a) to compare arterial stiffness values obtained in the left and right sides of the body in hemodialyzed and non-hemodialyzed patients, and b) to analyze PWV-ratio values obtained on the side of the body where the VA was placed and compare them to its contralateral intact side. Since it is difficult to adequately measure cr-PWV in patients with a VA in the forearm, we measured the carotid- brachial PWV (cb-PWV) and used it to calculate PWV-ratio (cf-PWV/cb-PWV). METHODS A Pearsons correlation and Bland & Altman analysis were performed in hemodialyzed (n=135) and non-hemodialyzed (n=77) patients, to quantify the equivalence between arterial stiffness parameters (cf-PWV, cb-PWV, PWV-ratio) obtained on each side of the body with respect to its contralateral side. RESULTS We conclude that PWV-ratio values measured on the side where the VA is placed were significantly higher than those obtained in its contralateral side, in hemodialyzed patients included in this research. Moreover, cf-PWV, cb-PWV and PWV-ratio values obtained on one side of the body were always highly correlated with its contralateral side. CONCLUSION According to this research, any research involving PWV-ratio should always consider the observed territory.