Normal Pregnancy Is Associated with Changes in Central Hemodynamics and Enhanced Recruitable, but Not Resting, Endothelial Function.

Introduction. Flow-mediated dilation (FMD), low flow-mediated constriction (L-FMC), and reactive hyperemia-related changes in carotid-to-radial pulse wave velocity (ΔPWVcr%) could offer complementary information about both "recruitability" and "resting" endothelial function (EF). Carotid-to-femoral pulse wave velocity (PWVcf) and pulse wave analysis-derived parameters (i.e., AIx@75) are the gold standard methods for noninvasive evaluation of aortic stiffness and central hemodynamics. If healthy pregnancy is associated with both changes in resting and recruitable EF, as well as in several arterial parameters, it remains unknown and/or controversial. Objectives. To simultaneously and noninvasively assess in healthy pregnant (HP) and nonpregnant (NP) women central parameters in conjunction with "basal and recruitable" EF, employing new complementary approaches. Methods. HP (n = 11, 34.2 ± 3.3 weeks of gestation) and age- and cardiovascular risk factors-matched NP (n = 22) were included. Aortic blood pressure (BP), AIx@75, PWVcf, common carotid stiffness, and intima-media thickness, as well as FMD, L-FMC, and ΔPWVcr %, were measured. Results. Aortic BP, stiffness, and AIx@75 were reduced in HP. ΔPWVcr% and FMD were enhanced in HP in comparison to NP. No differences were found in L-FMC between groups. Conclusion. HP is associated with reduced aortic stiffness, central BP, wave reflections, and enhanced recruitable, but not resting, EF.

Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction.

Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about "recruitability" of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with "basal and recruitable" EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both "resting and recruitable" endothelial dysfunctions.

Composición y biomecánica de placas de ateroma carotídeas / Composition and biomechanics of carotid atheroma plaques

Introducción: la enfermedad aterosclerótica y sus complicaciones constituyen la causa más frecuente de muerte en el mundo. Un análisis de la relación entre parámetros estructurales y mecánicos de las placas de ateroma carotídea (PAC) es mandatorio a la hora de aumentar nuestros conocimientos en torno a los mecanismos que favorecerían la fatiga mecánica del material de la placa y su complicación. Objetivos: analizar la distensibilidad carotídea en sujetos sanos y con PAC según su composición estructural. Métodos: se estudiaron 100 sujetos asintomáticos con PAC (n=36) y sin PAC (n=64). Se clasificaron las PAC según la mediana de niveles de grises y mapeo por color en lipídicas (L), fibrolipídicas (FL) y fibrosas/calcificadas (FC). Se combinó ultrasonido modo-B con tonometría de aplanamiento y se cuantificó la distensibilidad a lo largo del eje longitudinal en cinco sectores a nivel de la PAC y de la arteria carótida normal. Resultados: se clasificaron 71 PAC (35 L, 16 FL y 20 FC), todas se encontraron en segmentos arteriales con menores niveles de distensibilidad comparado con las arterias sanas. Las PAC FC mostraron mayor rigidez a nivel del hombro proximal en comparación con las L y FL que se comportan de manera más homogénea en todos sus sectores. Conclusión: las PAC L y FL (consideradas de mayor riesgo) no presentaron el cambio significativo de rigidez parietal observado en las PAC FC, consideradas de menor riesgo de complicación. Estas diferencias biomecánicas relacionadas con la composición global de la PAC podrían tener una implicancia en la patogenia de la complicación de placa.

Introduction: the aterosclerotic disease and its complications are the most frequent cause of death in the world. An analysis of the relationship between structural and mechanic parameters of the carotid aterome plaque (CAP) is mandatory in the need of improving our knowledge concerning the mechanisms that would favor the mechanic fatigue of the plaque material and its complication. Objectives: analize the carotid distensibility in healthy persons and with patients with CAP according to their structural composition. Methods: 100 asymptomatic individuals were studied, with CAP (n=36) and without CAP (n=64). CAP persons were classified according to the standard levels of greys and color mapping in lipidic (L), fibrolipidic (FL) and fibrous/calcified (FC). B-mode Ultrasound with applanation tonometry were combined and the distensibility was quantified along the longitudinal axis in five sectors to the level of the CAP and in the normal carotid artery. Results: 71 CAP (35 L, 16 FL y 20 FC) were classified all in low-level distensibility arterial segments compared to healthy arteries. The FC CAP showed more rigidity in the proximal shoulder compared to the L and FL that behave more homogeneously in all their sectors. Conclusion: the L and FL CAPs (considered of major risk) did not present the parietal rigidity significant change observed in the FC CAP, considered of low complication risk. These biomechanic differences related to the global composition of the CAP could have an implication in the pathogenesis of the plaque complication.

Función endotelial y estados hipertensivos del embarazo: Velocidad de la onda del pulso carótido-radial como método alternativo para detectar disfunción endotelial en embarazadas

Resumen La preeclampsia constituye una causa mayor de morbimortalidad materno-fetal que cursa con una disfunción endotelial (DFE) generalizada. Detectar la DFE subclínica durante el embarazo contribuiría en su identificación precoz y anticiparía su tratamiento. Se ha propuesto utilizar los cambios en la velocidad de la onda del pulso carótido-radial (VOPcr) para evaluar la DFE en pacientes con enfermedad arterial. Sin embargo, se desconocen los alcances de dicha técnica en la evaluación de la DFE durante el embarazo. Objetivo: evaluar y comparar los cambios de la VOPcr en embarazadas y mujeres no embarazadas. Material y método: participaron embarazadas sanas (ES; n = 13), preeclámpticas (PE; n = 7), hipertensas sin proteinuria (HNP; n = 6) y mujeres no embarazadas (NE; n = 32). Se cuantificó la VOPcr (mecanotransductores), el diámetro arterial braquial (ultrasonido) y la velocidad sanguínea braquial (Doppler) antes (basal) y después de realizar un estímulo isquémico (esfigmomanometría). Resultados: la VOPcr disminuyó en ES (6,9 ± 1,5 a 6,0 ± 0,9 m/s, p < 0,001) y en NE (8,1 ± 0,9 a 7,4 ± 0,9 m/s; p < 0,001); no se obtuvieron cambios en HNP (6,6 ± 1,4 a 6,7 ± 1,0 m/s; p = 0,91) y en PE se observó una tendencia al aumento (6,0 ± 0,7 a 6,4 ± 0,8 m/s; p = 0,10). El DVOPcr% (porcentaje de cambio de la VOPCr basal versus postisquemia) fue distinto comparando ES con HNP (-11,9% versus +2,2%; p < 0,01), con NE (-11,9% versus -8,5%; p < 0,05) y con PE (-11,9 versus +6,2%; p < 0,01), respectivamente, sin encontrar diferencias entre HNP y PE (p = 1,00). Conclusión: las ES mostraron una reactividad vascular aumentada respecto a NE y HNP/PE evaluada por DVOPcr%, evidenciando en HNP/PE una respuesta vascular alterada. La VOPcr podría desempeñar un importante rol en el estudio de la DFE durante el embarazo, con una potencial aplicación clínica en la predicción de la preeclampsia.

Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment.

Carotid-to-radial pulse wave velocity (PWV(cr)) has been proposed to evaluate endothelial function. However, the measurement of PWV(cr) is not without limitations. A new simple approach could have wide application. Stiffness index (SI) is obtained by analysis of the peripheral pulse wave and gives reproducible information about stiffness of large arteries. This study assessed the effects of hyperemia on SI and compared it with PWV(cr) in 14 healthy subjects. Both were measured at rest and during 8 minutes after ischemia. SI temporal course was determined. At 1 minute, SI and PWV(cr) decreased (5.58 ± 0.24 to 5.34 ± 0.23 m/s, P < 0.05; 7.8 ± 1.0 to 7.2 ± 0.9 m/s; P < 0.05, resp.). SI was positively related to PWV(cr) in baseline (r = 0.62 , P < 0.05), at 1 minute (r = 0.79, P < 0.05), and during the whole experimental session (r = 0.52, P < 0.05). Conclusion. Hyperemia significantly decreases SI in healthy subjects. SI was related to PWV(cr) and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness.

Pulse wave velocity as marker of preclinical arterial disease: reference levels in a uruguayan population considering wave detection algorithms, path lengths, aging, and blood pressure.

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the "reference population"; the group of subjects with optimal/normal blood pressures levels at study time represented the "normal population." Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes.

Carotid-radial pulse wave velocity as an alternative tool for the evaluation of endothelial function during pregnancy: potential role in identifying hypertensive disorders of pregnancy.

UNLABELLED: Preeclampsia/eclampsia syndrome, a major cause of maternal mortality and morbidity, has been recognized as a condition with a globally impaired endothelial function (EF). The possibility of identifying early subclinical endothelial damage during pregnancy could be of value in classifying the different hypertensive states of pregnancy, and have a positive impact in the understanding of this syndrome, as well as on the appropriate treatment of these patients. Reactive hyperemia-related changes in carotid-radial pulse wave velocity (PWVcr) were proposed as an alternative tool for the evaluation of EF in patients with cardiovascular risk factors. If impaired EF, which follows hypertensive disorders of pregnancy can be assessed using PWVcr changes remains still unknown. AIMS: To assess and compare reactive hyperemia-related changes in PWVcr and FMD in pregnant women (healthy and with hypertensive disorders) and non pregnant women. METHODS: Healthy pregnant (HP; n=13), preeclamptic (PE; n=7), non-proteinuric hypertensive (NPH; n=6) and non-pregnant (NP; n=32) women were included. Left PWVcr (strain gauge mechano-transducers), left brachial arterial diameter (B-Mode ultrasound) and blood flow velocity (Doppler ultrasound) were measured before (baseline) and after the transient ischemia of the left forearm were determined. RESULTS: One minute after the cuff deflation, PWVcr decreased in HP (6.9 ± 1.5 to 6.0 ± 0.9 m/s, p<0.001) and in NP (8.1 ± 0.9 to 7.4 ± 0.9 m/s; p<0.001). NPH showed a blunted hyperemic PWVcr response (6.6 ± 1.4 to 6.7 ± 1.0 m/s; p=0.91), whereas PE showed a tendency to increase (6.0 ± 0.7 to 6.4 ± 0.8 m/s; p=0.10). Reactive hyperemia PWVcr response (ΔPWVcr in %) differed comparing HP with NPH (-12% vs. +2%; p<0.01) and with PE (-12 vs. +6%; p <0.01), whereas no differences were found between NHP and PE (p=1.00). CONCLUSION: HP showed an enhanced PWVcr reduction, whereas PE and NPH showed a blunted hyperemic PWVcr response. Carotid-radial PWVcr analysis could have a potential role in the assessment of pregnancy to study EF with a potential clinical application in predicting pregnancy induced hypertension and preeclampsia.

Aging-related changes and reference values for the carotid intima-media thickness in a Uruguayan population.

UNLABELLED: Carotid intima-media thickness (CIMT) is a well-established subclinical marker of atherosclerosis. Non-invasive vascular evaluation has emerged as a useful tool to aid in individual cardiovascular (CV) risk stratification and diagnose. The use of CIMT in CV risk stratification requires knowing the expected reference values for the population studied. Our aim were: a) to evaluate the relationship between aging and CIMT, b) to analyze gender and side (right vs left) related-differences in CIMT and c) to determine the CIMT reference values for an Uruguayan population taking into account aging-related CIMT changes. METHODS: 367 asymptomatic subjects without known CV disease or risk factors were included in the study. Subjects were divided into six age groups. High-resolution B-mode ultrasound images of both (right and left) common carotid arteries were obtained based on the techniques and recommendations described in international consensus. RESULTS: No significant age-related differences in CIMT between men and women were observed. The mean left CIMT was thicker compared with right CIMT in groups 4, 5 and 6. However, there were no significant differences in those groups. The nomogram model was constructed from data base, in which the 95% confidence interval was considered. Diagnosis thresholds were determined as well. CONCLUSION: We define reference values of CIMT for our population using gold standard techniques which contributes to standard techniques which contributes to an improved insight into clinical practice and can be used routinely for evaluation.

Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

Age-related changes in reservoir and excess components of central aortic pressure in asymptomatic adults.

Study of humans aging has presented difficulties in separating the aging process from concomitant disease and/or in defining normality and abnormality during its development. In accordance with this, aging associates structural and functional changes evidenced in variations in vascular parameters witch suffer alterations during atherosclerosis and have been proposed as early markers of the disease. The absence of adequate tools to differentiate the expected (normal) vascular changes due to aging from those related with a vascular disease is not a minor issue. For an individual, an early diagnosis of a vascular disease should be as important as the diagnosis of a healthy vascular aging. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The arterial pressure waveform can be explained in terms of a reservoir pressure, related to the arterial system compliance, and an "excess" or wave-related pressure, associated with the traveling waves. The aim of this study was to evaluate, by means of a mathematical approach, age-related changes in measured, reservoir and excess central aortic pressure in order to determine if age-related changes are concentrated in particular decades of life. Central aortic pressure waveform was non-invasively obtained in healthy subjects (age range: 20-69 years old). Age-related profiles in measured, reservoir and excess pressure were calculated.

Pulse wave velocity normal levels in a Uruguayan population: differences between 'adjusted' and measured values vary depending on age and the calculation algorithm used.

UNLABELLED: Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness. However, the absence of standardized methodologies of study and lack of normal and references values have limited wider implementation of PWV in clinical practice. In this work normal PWV levels were determined in a Uruguayan population and the obtained values were analyzed taking into account data from other populations. The differences between the 'real' PWV levels and the PWV calculated using different wave detection algorithms and path lengths were assessed, and compared the taking into account the changes in PWV with aging. RESULTS: The Uruguayan population showed a rate of PWV increase comparable to that reported previously in non-hypertensive European subjects, although overall, PWV values were approximately 2 m/s higher in the Uruguayan population. The different approaches used to calculate the PWV showed differences in their availability to follow aging-variations in 'adjusted' (or 'real') PWV.

Gender-related differences in the excess pressure component of central aortic pressure waveform of healthy young.

Gender-related difference in cardiovascular diseases is one of the most investigated and still unsolved issues. Finding an explanation to this topic might have important implications for the understanding of the differences between men and women in diseases and possibly lead to the development of gender-specific strategies for its management. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The pressure waveform can be explained in terms of a reservoir pressure related to arterial compliance and an "excess" or wave-related pressure associated with traveling waves. Gender-differences in the ascending aorta pressure waveform reservoir and excess components are to be characterized. The aim of this study was to evaluate, by means of a mathematical approach, gender-related differences in the central aortic pressure waveform components. Central aortic pressure waveform was non-invasively obtained in 22 healthy subjects (Age: 20 years old; 11 female). Males and females showed differences in the level and time to maximal excess pressure component, but no gender-related differences were found in the reservoir one.

Uruguay eHealth initiative: preliminary studies regarding an integrated approach to evaluate vascular age and preclinical atherosclerosis (CUiiDARTE project).

In this work we present an initiative to develop a national (Uruguayan) program to evaluate vascular age and to detect pre-clinical atherosclerosis using: gold-standard technologies; complimentary and integrative approaches to asses arterial functional and structural indexes; data bases systems to process, analyze and determine normal and reference values and to identify the most sensitive markers of vascular changes for different ages. We evaluated, in a Uruguayan population complementary structural and functional vascular parameters that associate aging-related changes and are considered markers of sub-clinical atherosclerosis. Traditional CV risk factors were assessed. The subjects (n=281) were submitted to non-invasive vascular studies to evaluate: 1) Common carotid artery (CCA) intima-media thickness and diameter waveforms, 2) CCA stiffness, 3) aortic stiffness (pulse wave velocity) and 4) peripheral and central pressure pulse wave derived parameters. Age groups: 21-30, 31-40, 41-50, 51-60, and 61-70 years-old. Age-related profiles were obtained for the different vascular parameters, and their utility to assess vascular changes in young, middle-aged and old subjects was evaluated. The work has the strength of being the first that uses, in Latin-America an integrative approach to characterize vascular aging-related changes.