Juan Torrado

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.

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.

Reactive hyperemia-related changes in carotid-radial pulse wave velocity as a potential tool to characterize the endothelial dynamics

Current methods used to evaluate the endothelial function have limitations. The analysis of the pulse wave velocity (PWV) response to transient ischaemia could be an alternative to evaluate the endothelial dynamics. Aims: To analyze (a) the carotid-radial PWV temporal profile during flow mediated dilatation test, and (b) the PWV changes considering its main vascular geometrical (diameter) and intrinsic (elastic modulus) determinants. Methods: Sixteen healthy young adults were included. The carotid-radial PWV (strain gauge mechano-transducers), wall thickness and brachial diameter (B-Mode ultrasound) were measured before (basal state), during a forearm cuff inflation (5 minutes) and after its deflation (10 minutes). The PWV, brachial diameter and elastic modulus changes and temporal profile were analyzed (basal state, 15, 30, 45, and 60 seconds after cuff deflation). Results: Transient ischaemia was associated with arterial stiffness changes, evidenced by carotid-radial PWV variations. The PWV and diastolic diameter changes, and temporal profiles differed. The arterial stiffness changes could not be explained only by geometrical (diameter) changes. Conclusion: The carotid-radial PWV analysis, evaluated using robust and simple available techniques, could be used in the clinical practice to study the vascular response to transient ischaemia and the endothelial function.

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

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, <;0.001) and in NP (8.1 ± 0.9 to 7.4 ± 0.9 m/s; <;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%; <;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.

Carotid-radial pulse wave velocity as a discriminator of intrinsic wall alterations during evaluation of endothelial function by flow-mediated dilatation

Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. Aims: a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects “FMD responders” or “non-responders” behave regards to PWVcr changes. Methods: 34 healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10th percentiles FMD and PWVcr changes in the population were used for the definition of the subjects (“responders and non-responders”). Results: Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p<0.05). There were differences in the PWV and FMD temporal profiles. Within “FMD responders” there were “PWV responders and non-responders”. Conclusion: Assessing RHT-related changes in PWVcr in the context of a FMD evaluation, could be useful as a discriminator of intrinsic wall alterations giving additional information of vascular dynamics.

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.

Levels and rates of change in carotid-radial pulse wave velocity associated with reactive hyperaemia: Analysis of the dependence on transient ischemia length

The analysis of carotid-radial pulse wave velocity (PWVcr) changes in response to forearm transient ischemia (TI) has been proposed as an alternative approach to evaluate endothelial function. Consider flow mediated dilatation tests, PWVcr changes are characterized after 5 minutes of TI. It is unknown if lower TI times could be used and if different TI times would result in different PWVcr responses (levels and/or kinetics). Objective: To determine PWVcr changes associated with the reactive hyperemia in response to 1, 3 or 5 minutes of forearm TI. Methods: We measured left PWVcr change using mechano-transducers in healthy volunteers (22±2 years old) before (basal) and after 1 (n=14), 3 (n=14) and 5 (n=15) minutes of TI (forearm cuff inflation), respectively. The change of level and rate in PWVcr were recorded at 15, 30, 45 and 60 seconds after cuff release. Right brachial pressure was measured. Results: There were no changes in heart rate or blood pressure during the studies. Regardless of the occlusion length, TI resulted in PWVcr reduction (p<0.05). The groups showed similar maximum PWVcr reduction. However, there were differences in the immediate PWVcr changes (−4.9±0.2%; −6.8±0.3% and −8.3±0.5% for 1, 3 and 5 minutes of TI, respectively) (p<0.05). Then, the immediate rate of PWVcr change differed (p<0.05) among the different ischemia times considered. Thereafter, the differences diminished and a minute after TI the groups showed similar levels and mean rate of PWVcr reduction. Conclusion: Similar maximum PWVcr responses can be obtained after 1, 3, or 5 minutes of TI. Different TI times resulted in dissimilar immediate, but not later, PWVcr changes.

Cardiac resynchronization results in aortic blood flow-associated changes in the arterial load components: Basal biomechanical conditions determine the load changes

The cardiac resynchronization therapy (CRT) effects on the arterial load components, the mechanisms (i.e. haemodynamic changes-dependence) involved in the load reduction and the factors (i.e. basal load conditions) associated with the load changes after CRT, are to be evaluated. Aims: a) to analyze the potential changes in the arterial load components (peripheral resistances, arterial compliance and impedance) associated with the CRT, b) to determine if the load components changes are associated with variations in haemodynamic variables (pressure, heart rate or blood flow), c) to analyze the relationship between the load components basal state and their changes after CRT. To fulfill these aims cardiac and arterial structural and mechanical parameters were non-invasively evaluated in 8 heart failure patients, pre- and post-CRT (23±8 days). The main results were that short-term after CRT: 1) there were changes in the static and dynamic determinants of the arterial load; 2) the changes in the load components were not associated with heart rate or pressure variations, but with blood flow changes, and 3) the load components basal levels and their changes after CRT were associated.

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 (PWVcr) has been proposed to evaluate endothelial function. However, the measurement of PWVcr 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 PWVcr 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 PWVcr 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 PWVcr 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 PWVcr and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness.

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.