Although blood viscosity is an important component in determining vascular function, it is often assumed constant. Emerging evidence linking individual differences in viscosity to cardiovascular disease casts doubt on this assumption. The purpose of this study was to determine the contribution of whole blood viscosity to key measures of vascular function. To address this aim as comprehensively as possible, first, whole blood viscosity was compared with traditional risk factors for cardiovascular disease. Then flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), and carotid artery compliance were calculated either with or without blood viscosity taken into account. Lastly, we tested whether the removal of blood viscosity could influence well-established associations between age and vascular function. Blood viscosity and vascular function were measured in 97 adults ranging in age from 18-63 years. No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Whole blood viscosity was not significantly correlated with FMD, cfPWV, and carotid compliance. As expected, age was positively correlated with cfPWV (r=0.65, p<0.001) and negatively correlated with FMD (r=-0.21, p<0.05) and carotid compliance (r=-0.45, p<0.01). Even after controlling for viscosity, these relationships remained statistically significant (cfPWV r=0.65, p<0.001; FMD r=-0.24, p<0.05; carotid compliance r=-0.44, p<0.05). These results indicate that whole blood viscosity does not appear to significantly impact measures of vascular function and that the rationale for including whole blood viscosity in the calculation of vascular function remains weak. / text

Vascular stiffening is defined as the reduced ability of the blood vessels to expand in response to an increase in blood pressure. Vascular stiffening is often not appreciated as a disease in and of itself but is important to recognize because it is considered a predictor of many cardiovascular disease states. Mechanisms of vascular stiffening remain largely unknown; however the immune system has been found to play major roles in cardiovascular disease and arterial remodeling. This dissertation therefore seeks to illustrate the role of the adaptive immune system in vascular stiffening. This has been done by modeling vascular stiffness in transgenic mice lacking an adaptive immune system as well as immunosuppression in normal mice using a novel method to stimulate regulatory T cells with a cytokine immune complex. We have found that inhibition of the immune system by the use of a genetic knockout (RAG 1 ⁻/⁻ mice) or suppression of an existing immune system with an IL-2/anti-IL-2 complex reduces the development of angiotensin II-induced vascular stiffening. This dissertation supports the role of the adaptive immune system, and particularly CD4⁺T cells, in the development of vascular stiffening as well as the protective roles of Tregs in the disease. It also highlights the use of the IL-2/anti-IL-2 complex as a new potential therapy for vascular stiffness. Therapeutics that suppress adaptive immune function may be beneficial in the treatment of vascular stiffening.

To assess the relationships of body mass index (BMI) on arterial stiffness at rest and post-maximal treadmill graded exercise testing (GXT). Forty-four apparently healthy, young adult males (22.1 ± 0.48 years) were recruited and divided into either a healthy weight (H, ≤24.9 kg/m2), overweight (OV, 24.9-29.9 kg/m2) or obese (OB, ≥29.9 kg/m2) group based on BMI. All subjects underwent arterial stiffness (carotid-femoral pulse wave velocity, cfPWV), blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP) and body composition (bioelectrical impedance analysis, BIA) measurements at rest. Following the GXT, measures of arterial stiffness (cfPWV) and BP were acquired. Resting measures of cfPWV, BMI, systolic BP, diastolic BP, MAP, and PP were significantly (p <0.05) greater in OV and OB compared with H. Compared with OV, OB had a greater BMI. Relative peak oxygen consumption (VP2peak) was greater in H compared with OV and OB (p<0.05). systolic BP was positively associated, whereas VO2peak was inversely related to cfPWV (p<0.05). No significant inter-group interactions were observed with cfPWV after the GXT. However, interactions were observed for SBP, DBP and PP (p<0.05). In young men with varying BMI, SBP and VO2peak were associated with resting cfPWV. However, similar cardiovascular responses were observed between groups after a maximal GXT.

Background/objectives There are few studies investigating the long-term association between childhood blood pressure (BP) and adult cardiovascular remodeling. We seek to examine the effect of elevated childhood BP on cardiovascular remodeling in early or middle adulthood.Methods We used the "Beijing BP Cohort Study", where 1259 subjects aged 6-18 years old were followed over 24 years from childhood (1987) to early or middle adulthood (2011). Anthropometric measures and BP were obtained at baseline and follow-up examinations. Carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured to assess cardiovascular remodeling in early or middle adulthood. Multiple logistic regression models were used to assess the odds ratio (OR) and 95% confidence interval (CI) for cardiovascular remodeling.Results 82 out of 384 children with elevated BP (21.4%) had adult hypertension. Compared to those with normal BP, children with elevated BP were at 2.1 times (95% CI: 1.4-3.1) likely to develop hypertension in early or middle adulthood. Compared to those with normal BP, children with elevated BP were at higher OR of developing high cfPWV (OR = 1.8, 95% CI = 1.3-2.4), high cIMT (1.4, 1.0-1.9), or high LVMI (1.4, 1.0-1.9) in early or middle adulthood. The ORs for remodeling (for any measures) were 1.4 (0.9-2.0) in early adulthood for children age 6-11 years, and 1.6 (1.1-2.4) in middle adulthood for those aged 12-18 years.Conclusions Children with elevated BP from 6 years old have accelerated remodeling on both cardiac and arterial system in early or middle adulthood.

Pulse wave velocity (PWV) and augmentation index (AI) are independent predictors of cardiovascular health. However, the comparability of multiple oscillometric modalities currently available for their assessment was not studied in detail. In the present study, we aimed to evaluate the relationship between indices of arterial stiffness assessed by diastolic and suprasystolic oscillometry. In total, 56 volunteers from the general population (23 males; median age 70 years [interquartile range: 65–72 years]) were recruited into observational feasibility study to evaluate the carotid-femoral/aortic PWV (cf/aoPWV), brachial-ankle PWV (baPWV), and AI assessed by 2 devices: Vicorder (VI) applying diastolic, right-sided oscillometry for the determination of all 3 indices, and Vascular explorer (VE) implementing single-point, suprasystolic brachial oscillometry (SSBO) pulse wave analysis for the assessment of cfPWV and AI. Within- and between-device correlations of measured parameters were analyzed. Furthermore, agreement of repeated measurements, intra- and inter-observer concordances were determined and compared for both devices. In VI, both baPWVand cfPWVinter-correlatedwell and showed good level of agreement with bilateral baPWVmeasured byVE (baPWV[VI]– baPWV[VE]R: overall concordance correlation coefficient [OCCC]¼0.484, mean difference¼1.94 m/s; cfPWV[VI]–baPWV[- VE]R: OCCC¼0.493, mean difference¼1.0m/s). In contrast, SSBO derived aortic PWA (cf/aoPWA[VE]) displayed only weak correlation with cfPWV(VI) (r¼0.196; P¼0.04) and ipsilateral baPWV (cf/ aoPWV[VE]R–baPWV[VE]R: r¼0.166; P¼0.08). cf/aoPWA(VE) correlated strongly with AI(VE) (right-sided: r¼0.725, P<0.001). AI exhibited marginal between-device agreement (right-sided: OCCC¼ 0.298, mean difference: 6.12%). All considered parameters showed good-to-excellent repeatability giving OCCC > 0.9 for 2-point-PWV modes and right-sided AI(VE). Intra- and inter-observer concordances were similarly high except for AI yielding a trend toward better reproducibility in VE (interobserver–OCCC[VI] vs [VE]¼0.774 vs 0.844; intraobserver OCCC[VI] vs [VE]¼0.613 vs 0.769). Both diastolic oscillometry-derived PWV modes, and AI measured either with VI or VE, are comparable and reliable alternatives for the assessment of arterial stiffness. Aortic PWV assessed by SSBO in VE is not related to the corresponding indices determined by traditional diastolic oscillometry.

Rationnel : La vitesse d'onde de pouls (VOP) est une méthode non invasive d'estimation de la rigidité artérielle. Les recommandations internationales établissent que la VOP est un marqueur puissant du risque cardiovasculaire (CV). La corrélation entre la pression artérielle périphérique et la VOP et leurs influences respectives sur la mortalité ont été peu étudiés chez les sujets âgés. Notre objectif était d'analyser cette corrélation chez les sujets institutionnalisés de plus de 80 ans. Méthodes : PARTAGE (valeur prédictive de la pression artérielle et de la rigidité artérielle chez institutionnalisé la population très âgée) est une étude de cohorte suivant pendant 2 ans 1130 sujets de plus de 80 ans institutionnalisés dans 72 centres en France et en Italie. La corrélation entre pression artérielle systolique et diastolique (PAS et la PAD) et la VOP (mesuré avec un tonomètre PulsePen ®) a été étudié chez 1071 sujets ayant des données de VOP. Résultats : La corrélation entre la PA et la VOP dans notre étude est significative mais faible. Les coefficients de corrélation sont de 0,24 pour la corrélation PAS clinique-VOP, 0,26 pour la corrélation PP-VOP, et 0,30 pour la corrélation PA automesure-VOP. La corrélation est systématiquement plus élevée chez les femmes mais sans atteindre la significativité. Le niveau de corrélation est inversement proportionnel à l'âge : les corrélations les plus fortes sont retrouvées dans la population la plus jeune. Le traitement antihypertenseur n'a pas d'impact sur la corrélation. Conclusion : La faiblesse de la corrélation montre que la PA et la VOP expriment différents phénomènes physiopathologiques de la rigidité artérielle. L'analyse longitudinale de l'étude PARTAGE, mise en perspective avec ceux trouvés dans nos travaux, pourraient permettre de proposer la VOP comme une méthode complémentaire, voire alternative, à la mesure de la PA dans l'évaluation du risque CV dans la population des sujets très âgés / Background: Carotid-femoral pulse wave velocity (PWV) provides a comprehensive non-invasive assessment of arterial stiffness. PWV is now established as a strong marker of cardiovascular disease. The correlation between peripheral blood pressure and PWV and their respective influences on mortality have been poorly studied in the elderly. Our objective was to analyze this correlation in nursing home residents over 80 years of age. Results could ultimately be helpful in implementing strategies for diagnosis and long-term follow-up of the very elderly population. Methods: The PARTAGE (Predictive value of blood pressure and ARTerial stiffness in institutionalized very AGEd population) study is a 2-year cohort study of 1130 subjects living in 72 nursing homes in France and Italy. The correlation between baseline systolic and diastolic blood pressure (SBP and DBP) and baseline PWV (measured with a PulsePen® tonometer) was studied in 1071 subjects with available PWV measurements. Results: Correlations between peripheral blood pressure and PWV were significant but weak: r=0.24 for self-measured SBP, r=0.30 for casual SBP, r=0.11 for self measured DBP, r=0.14 for casual DBP and r=0.26 for casual pulse pressure (PP). A trend for a weaker correlation was observed in the higher age group for self measured SBP and in the lower ADL group for self measured SBP and DBP. The correlations were systematically higher in women compared to men (but did not reach statistical significance) and lower with advanced age group. The correlation was not impacted by antihypertensive. Conclusion: These findings suggest that SBP, DBP and PWV provide different information in the very elderly. The prospective, longitudinal, long term PARTAGE study results will allow further insight; provide additional in-depth information regarding the respective prognostic value of these two measurement methods. NCT00901355

African Americans have increased risk for cardiovascular and cerebral vascular disease relative to Caucasian Americans. While it is generally accepted that arteries become stiffer at a younger age in African Americans; less is known regarding cerebral vascular function / reactivity (CVMR) to hypercapnia in African Americans. Furthermore, little is known regarding the relationship between arterial stiffness and CVMR, particularly in young healthy adults. We hypothesized that African Americans have stiffer arteries (i.e. arterial stiffness) and reduced CVMR during hypercapnia relative to Caucasian Americans. We also hypothesized that there would be a negative relationship between arterial stiffness and CVMR. Lastly, we hypothesized that these responses would be related to a decrease in Vitamin D status in this population and there would be correlation between Vitamin D status and CVMR. In 11 African American and 19 Caucasian American subjects central arterial stiffness was indexed from carotid-femoral pulse wave velocity (PWV). CVMR was assessed by the cerebral vascular conductance (CVC) response to rebreathing-induced hypercapnia. Vitamin D status was assessed from plasma 25(OH) Vitamin D. PWV was elevated in the African Americans (African American: 581.16 ± 27.7 cm/sec vs. Caucasian American: 502.98 ± 17.6 cm/sec; P < 0.01). CVMR was significantly reduced during hypercapnic rebreathing in the African Americans (African American: 3.05 ± 0.38% of baseline/mmHg vs. Caucasian American: 5.09 ± 0.29% of baseline/mmHg; P < 0.001). When data from all subjects was included there was a trend towards a negative relationship (R = 0.32, P = 0.10) between PWV and CVMR. Vitamin D status was significantly lower in African Americans (African American: 14.96 ± 0.97 ng/ml vs. Caucasian American: 32.73 ± 0.99 ng/ml; P < 0.001); however, there was no significant relationship between Vitamin D status and CVMR (R = 0.23 P = 0.23). In conclusion, these data indicate that African Americans have impaired cerebral vascular responses to hypercapnia, stiffer arteries, and lower Vitamin D status when compared with Caucasian Americans. In addition, there may be a negative relationship between CVMR and PWV; however, no significant correlation between Vitamin D status and vascular function including PWV or CVMR was observed in this study. / text

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-12T15:21:22Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese de Zoraya versão definitiva 131015 aceita.pdf: 2706371 bytes, checksum: 83da3cf5bbbffb2d66214831901498f3 (MD5) / Made available in DSpace on 2016-04-12T15:21:22Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese de Zoraya versão definitiva 131015 aceita.pdf: 2706371 bytes, checksum: 83da3cf5bbbffb2d66214831901498f3 (MD5) Previous issue date: 2015-02-27 / Esta tese teve como objetivo estudar um marcador de aterosclerose subclínica, a rigidez aórtica, medida através da velocidade de onda de pulso aórtica, diante da importância de se identificar os pacientes com risco maior de desenvolver doenças cardiovasculares (DCV), hoje, uma das principais causas de morbidade e mortalidade, não relacionada à síndrome da imunodeficiência adquirida (AIDS) em pessoas vivendo com o vírus da imunodeficiência humana (PVHIV). Entre setembro de 2011 e janeiro de 2013, a população do estudo composta por homens e mulheres vivendo com o vírus da imunodeficiência humana (HIV), participantes da coorte HIV/AIDS-PE, no nordeste do Brasil, iniciada em 2007, foi submetida a dois desenhos de estudos visando identificar os fatores de risco cardiovasculares tradicionais e emergentes associados com a rigidez aórtica e sua progressão.Visando identificar fatores de riscos cardiovasculares emergentes, incluindo a perda de massa óssea, realizamos um estudo transversal em mulheres vivendo com HIV que haviam realizado densitometria mineral óssea, no período entre Outubro de 2010 a Novembro de 2011. A densidade mineral óssea (DMO), foi medida pela absorciometria de energia dupla de raio-x de (DXA) nas regiões da coluna lombar, colo de fêmur e fêmur total e a rigidez aórtica, foi medida pela velocidade de onda de pulso aórtica (VOPa). O resultado principal deste estudo foi a correlação negativa significante entre a DMO do colo de fêmur e do fêmur total com a VOPa mesmo ajustada para idade, síndrome metabólica e pressão arterial média. Sugerindo que mulheres vivendo com HIV com perda de massa óssea deverão ser avaliadas para doença cardiovascular aterosclerótica. Para investigar a progressão da rigidez aórtica, foram acompanhados por uma média de 2,9 anos, homens e mulheres vivendo com HIV que haviam realizado a primeira avaliação da rigidez aórtica entre Abril e Novembro de 2009. O achado mais importante deste estudo foi a verificação de uma acelerada progressão da rigidez aórtica associada a fatores de risco tradicionais, idade, sexo masculino e hipertensão arterial e uma correlação negativa com a duração da infecção em uma população sob bom controle virológico. Os dados favorecem intensificar medidas para melhor controle da hipertensão arterial e da imunodeficiência. / This thesis aimed to study a marker of Subclinical Atherosclerosis, aortic stiffness measured by aortic pulse wave velocity, given the importance of identifying the patient with higher risk of developing cardiovascular diseases, today, one of the leading causes of morbidity and mortality, not related to AIDS. Between September 2011 and January 2013, the study population comprised of men and women living with human immunodeficiency virus (HIV), HIV/AIDS cohort participants-PE, in northeastern Brazil, initiated in 2007, have undergone two designs of studies aimed at identifying the factors of traditional and emerging cardiovascular risk associated with aortic stiffness and its progression. Aiming to identify emerging cardiovascular risk factors, including the loss of bone mass, we performed a cross-sectional study in women living with HIV who had performed bone mineral densitometry in the period between October 2010 to November 2011. Bone mineral density was measured by dual-energy x-ray absorptiometry (DXA) in regions of the lumbar spine, neck femur and total femur and aortic stiffness was measured by aortic pulse wave velocity (aPWV). The main result of this study was the significant negative correlation between the BMD of the femoral neck and total femur aPWV even adjusted for age, metabolic syndrome and mean arterial pressure. Suggesting that women living with HIV with low of bone mass should be assessed for atherosclerotic cardiovascular disease. To investigate the progression of aortic stiffness, were accompanied by an average of 2.9 years, men and women living with HIV who had carried out the initial evaluation of aortic stiffness between April and November 2009 .The most important finding of this study was the verification of an accelerated progression of aortic stiffness associated with traditional risk factors, age, male and hypertension and a negative correlation with duration of infection in a population under good viral control. The data favor the aggressive measures of intensify and immunodeficiency hypertension.

The aim of this diploma thesis is to assess the applicability of pulse wave propagation monitoring in the cardiovascular system in the field of prediction and early diagnosis of abdominal aortic aneurysm (AAA). The very first part is focused on description of heart and blood vessels with its pathological changes in presence of aneurysm. For this reason, current methods of monitoring and surgical treating of AAA were mentioned. Due to their difficult clinical use widely in the population, new methods based on pulse wave monitoring were presented. Using an analytical approach we estimated the difference in the arrival of the pulse wave at measurable locations between healthy and pathological aorta in the order of miliseconds. By experimental monitoring using photoplethysmographic sensors, we observed significant changes of pulse wave velocity with respect to the mechanical properties of the artery wall (mainly associated with age), which we tried to implement by hyperelastic material models used in computational simulations of pulse wave proagation on simplified geometries by fluid structure interaction method. These analyzes should verify applicability of FSI simulations in further development of diagnostic methods of AAA.

This thesis deals with the methodology of use of whole-body impedance cardiography for evaluation of pulse wave velocity. The first three chapters explain selected hemodynamic properties of the arterial system related to the issue of pulse wave propagation. At the same time the ordinary methods for estimation, its disadvantages and merits has been summarized. Points at issue of whole-body impedance evaluation methodology for pulse wave velocity are researched in second part of this thesis. In order that analysis the procedure for correct methodology has been determined. Particularly determination of reference proximal point for calculation of transit time towards aortic valve, and design and accuracy of transit distance measurement were discussed. Based on the obtained data, a calculation of representative pulse wave velocity to eight limb locations was performed.