Central-to-peripheral blood pressure amplification: role of the recording site, technology, analysis approach, and calibration scheme in invasive and non-invasive data agreement.

Background: Systolic blood pressure amplification (SBPA) and pulse pressure amplification (PPA) can independently predict cardiovascular damage and mortality. A wide range of methods are used for the non-invasive estimation of SBPA and PPA. The most accurate non-invasive method for obtaining SBPA and/or PPA remains unknown. Aim: This study aims to evaluate the agreement between the SBPA and PPA values that are invasively and non-invasively obtained using different (1) measurement sites (radial, brachial, carotid), (2) measuring techniques (tonometry, oscillometry/plethysmography, ultrasound), (3) pulse waveform analysis approaches, and (4) calibration methods [systo-diastolic vs. approaches using brachial diastolic and mean blood pressure (BP)], with the latter calculated using different equations or measured by oscillometry. Methods: Invasive aortic and brachial pressure (catheterism) and non-invasive aortic and peripheral (brachial, radial) BP were simultaneously obtained from 34 subjects using different methodologies, analysis methods, measuring sites, and calibration methods. SBPA and PPA were quantified. Concordance correlation and the Bland-Altman analysis were performed. Results: (1) In general, SBPA and PPA levels obtained with non-invasive approaches were not associated with those recorded invasively. (2) The different non-invasive approaches led to (extremely) dissimilar results. In general, non-invasive measurements underestimated SBPA and PPA; the higher the invasive SBPA (or PPA), the greater the underestimation. (3) None of the calibration schemes, which considered non-invasive brachial BP to estimate SBPA or PPA, were better than the others. (4) SBPA and PPA levels obtained from radial artery waveform analysis (tonometry) (5) and common carotid artery ultrasound recordings and brachial artery waveform analysis, respectively, minimized the mean errors. Conclusions: Overall, the findings showed that (i) SBPA and PPA indices are not "synonymous" and (ii) non-invasive approaches would fail to accurately determine invasive SBPA or PPA levels, regardless of the recording site, analysis, and calibration methods. Non-invasive measurements generally underestimated SBPA and PPA, and the higher the invasive SBPA or PPA, the higher the underestimation. There was not a calibration scheme better than the others. Consequently, our study emphasizes the strong need to be critical of measurement techniques, to have methodological transparency, and to have expert consensus for non-invasive assessment of SBPA and PPA.

Aortic systolic and pulse pressure invasively and non-invasively obtained: Comparative analysis of recording techniques, arterial sites of measurement, waveform analysis algorithms and calibration methods.

Background: The non-invasive estimation of aortic systolic (aoSBP) and pulse pressure (aoPP) is achieved by a great variety of devices, which differ markedly in the: 1) principles of recording (applied technology), 2) arterial recording site, 3) model and mathematical analysis applied to signals, and/or 4) calibration scheme. The most reliable non-invasive procedure to obtain aoSBP and aoPP is not well established. Aim: To evaluate the agreement between aoSBP and aoPP values invasively and non-invasively obtained using different: 1) recording techniques (tonometry, oscilometry/plethysmography, ultrasound), 2) recording sites [radial, brachial (BA) and carotid artery (CCA)], 3) waveform analysis algorithms (e.g., direct analysis of the CCA pulse waveform vs. peripheral waveform analysis using general transfer functions, N-point moving average filters, etc.), 4) calibration schemes (systolic-diastolic calibration vs. methods using BA diastolic and mean blood pressure (bMBP); the latter calculated using different equations vs. measured directly by oscillometry, and 5) different equations to estimate bMBP (i.e., using a form factor of 33% ("033"), 41.2% ("0412") or 33% corrected for heart rate ("033HR"). Methods: The invasive aortic (aoBP) and brachial pressure (bBP) (catheterization), and the non-invasive aoBP and bBP were simultaneously obtained in 34 subjects. Non-invasive aoBP levels were obtained using different techniques, analysis methods, recording sites, and calibration schemes. Results: 1) Overall, non-invasive approaches yielded lower aoSBP and aoPP levels than those recorded invasively. 2) aoSBP and aoPP determinations based on CCA recordings, followed by BA recordings, were those that yielded values closest to those recorded invasively. 3) The "033HR" and "0412" calibration schemes ensured the lowest mean error, and the "033" method determined aoBP levels furthest from those recorded invasively. 4) Most of the non-invasive approaches considered overestimated and underestimated aoSBP at low (i.e., 80 mmHg) and high (i.e., 180 mmHg) invasive aoSBP values, respectively. 5) The higher the invasively measured aoPP, the higher the level of underestimation provided by the non-invasive methods. Conclusion: The recording method and site, the mathematical method/model used to quantify aoSBP and aoPP, and to calibrate waveforms, are essential when estimating aoBP. Our study strongly emphasizes the need for methodological transparency and consensus for the non-invasive aoBP assessment.

Brachial Blood Pressure Invasively and Non-Invasively Obtained Using Oscillometry and Applanation Tonometry: Impact of Mean Blood Pressure Equations and Calibration Schemes on Agreement Levels.

The use of oscillometric methods to determine brachial blood pressure (bBP) can lead to a systematic underestimation of the invasively measured systolic (bSBP) and pulse (bPP) pressure levels, together with a significant overestimation of diastolic pressure (bDBP). Similarly, the agreement between brachial mean blood pressure (bMBP), invasively and non-invasively measured, can be affected by inaccurate estimations/assumptions. Despite several methodologies that can be applied to estimate bMBP non-invasively, there is no consensus on which approach leads to the most accurate estimation. Aims: to evaluate the association and agreement between: (1) non-invasive (oscillometry) and invasive bBP; (2) invasive bMBP, and bMBP (i) measured by oscillometry and (ii) calculated using six different equations; and (3) bSBP and bPP invasively and non-invasively obtained by applanation tonometry and employing different calibration methods. To this end, invasive aortic blood pressure and bBP (catheterization), and non-invasive bBP (oscillometry [Mobil-O-Graph] and brachial artery applanation tonometry [SphygmoCor]) were simultaneously obtained (34 subjects, 193 records). bMBP was calculated using different approaches. Results: (i) the agreement between invasive bBP and their respective non-invasive measurements (oscillometry) showed dependence on bBP levels (proportional error); (ii) among the different approaches used to obtain bMBP, the equation that includes a form factor equal to 33% (bMBP = bDBP + bPP/3) showed the best association with the invasive bMBP; (iii) the best approach to estimate invasive bSBP and bPP from tonometry recordings is based on the calibration scheme that employs oscillometric bMBP. On the contrary, the worst association between invasive and applanation tonometry-derived bBP levels was observed when the brachial pulse waveform was calibrated to bMBP quantified as bMBP = bDBP + bPP/3. Our study strongly emphasizes the need for methodological transparency and consensus for non-invasive bMBP assessment.

Relationship between Augmentation Index and Wall Thickening Fraction during Hypotension in an Animal Model of Myocardial Ischemia-Reperfusion and Heart Failure.

AIMS: Non-invasive indices to evaluate left ventricular changes during ischemic heart failure are needed to quantify the myocardial impairment and the effectiveness of therapeutic manoeuvres. The aims of this work were to calculate the Wall Thickening Fraction (WTF) and the Augmentation Index (AIx) and to assess the relationship between WTF and AIx using data obtained from an animal model with heart failure followed by a myocardial ischemia stage and a reperfusion stage. METHODS: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage. RESULTS: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage. CONCLUSION: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Characteristics and Determinants of Pulse Pressure-Age Relationship in Healthy and Non-treated Hypertensive Subjects of Argentinean Population.

BACKGROUND: The relationship between the increases in pulse pressure (PP) and arterial stiffness determined by aging or systemic hypertension has been widely reported. These findings are supported by large-cohort analyzes conducted in well-known populations, such as Framingham Study. However, there is evidence that an age-PP curvilinear relationship may exist in hypertensive subjects. This study aimed to evaluate the age-related change in pulse pressure and arterial stiffness in a population-based study. METHODS: Carotid-femoral Pulse Wave Velocity (cfPWV) were obtained in 2075 subjects. RESULTS: Age-related changes of PP showed a curvilinear relationship (R=0.39, p<0.0001) in normotensive subjects, with a nadir at around 50 years of age. On the other hand, the age-cfPWV relationship showed a linear and positive correlation (R=0.72, p<0.0001). PP also showed a curvilinear relationship with age (R=0.36, p<0.0001) in hypertensive subjects, with a nadir around 50 years of age. The age-cfPWV relationship showed a linear and positive correlation (R=0.55, p<0.0001). Similar results were observed in the adult population (age≥16 years). Multivariate analysis showed that age, sex, cfPWV, and mean arterial pressure are determinants of PP values in the entire population; however, this result was not uniform when different subgroups were analyzed. CONCLUSION: In conclusion, age-related changes in PP showed a curvilinear relationship and no parallelism with the age-cfPWV relationship for both normotensive and hypertensive subjects. The determinants of PP impact it differently depending on age and the pathological condition of the subject.

Central Blood Pressure Waves Assessment: A Validation Study of Non-invasive Aortic Pressure Measurement in Human Beings.

INTRODUCTION: Measurement of central (aortic) systolic blood pressure has been shown to provide reliable information to evaluate target organ damage. However, non-invasive central blood pressure measurement procedures are still under analysis. AIM: To compare human pressure waveforms invasively obtained in the aorta, with the corresponding waveforms non-invasively recorded using an oscillometric device (Mobil-O-Graph). METHODS: In this research were included 20 subjects in which invasive percutaneous coronary interventions were performed. They were 10 males (68 ± 12 y. o. , BMI: 27.4 ± 4.6 kg/m2) and 10 females (77 ± 8 y. o. , BMI: 28.5 ± 5.3 kg/m2). During the invasive aortic pressure recording, a synchronized non-invasive Mobil-O-Graph acquisition beat by beat and reconstructed central pressure wave was performed. Both, invasive and non-invasive pressure waves were digitized and stored for subsequent analysis and calculations. A computerized interpolation procedure was developed in our laboratory to compare these pressure waves. RESULTS: A significant correlation between Mobil-O-Graph central blood pressure measurements and the corresponding invasive values was found in males (r < 0.81; p < 0.01) and females (r < 0.93; p < 0.01). However, in both genders, the slope of the regression lines was lesser than 1 (males: y = 0.7354x + 18.998; females: y = 0.9835x + 2.8432). In the whole population (n = 20), a significant correlation between Mobil-O-Graph central blood pressure measurements and the corresponding invasive values was found (r < 0.89; p < 0.01) and the regression line was lesser than 1 (y = 0.9774x + 1.7603). CONCLUSIONS: In this research, a high correlation between invasive central blood pressure values and those measured with the Mobil-O-Graph device was found in males, females and the whole population. However, a sub estimation of Mobil-O-Graph central blood pressure values was observed.

Reference intervals of aortic pulse wave velocity assessed with an oscillometric device in healthy children and adolescents from Argentina.

Age-related reference intervals (RIs) of aortic pulse wave velocity (Ao-PWV) obtained from a large healthy population are lacking in South America. The aims of this study were to determine Ao-PWV RIs in a cohort of healthy children and adolescents from Argentina and to generate year-to-year percentile curves. Ao-PWV was measured in 1000 healthy subjects non-exposed to traditional cardiovascular risk factors (Age: 10-22 y. o., 56% males). First, we evaluated if RIs for males and females were necessaries (correlation and covariate analysis). Second, mean (M) and standard deviation (SD) age-related equations were obtained for cf-PWV, using parametric regression methods based on fractional polynomials. Third, age-specific (year to year) percentiles curves (for all, males and females children and adolescents) were generated using the standard normal distribution. They were, age-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th and 99th percentile curves and values. After covariate analysis (i.e., adjusting by age, jugulum-symphysis distance, body weight and height), specific RIs for males and females of children and adolescents were evidenced as necessaries. The equations were For all subjects: Ao-PWV_Mean = 4.98 + 12.86x10-5 Age3. Ao-PWV_SD = 0.47 + 21.00x10-6Age3. For girls: Ao-PWV_Mean = 5.07 + 10.23x10-5Age3. Ao-PWV_SD = 0.50 + 10.00x10-6Age3. For boys: Ao-PWV_Mean = 4.87 + 15.81x10-5Age3. Ao-PWV_SD = 0.46 + 22.34x10-6Age3. Our study provides the largest database to-date concerning Ao-PWV in healthy children and adolescents in Argentina. Age-related equations (M and SD values) for Ao-PWV are reported by the first time. Specific RIs and percentiles of Ao-PWV are now available according to age and sex for an Argentinian population.

Assessment of Intra-Aortic Counterpulsation in an Animal Model of Heart Failure and Myocardial Ischemia.

The effectiveness of intra-aortic balloon pumping (IABP) is currently evaluated using indirect indexes. The diastolic pressure augmentation is quantified using the subendocardial viability ratio (SEVR) and the DABAC/SABAC index (areas beneath the aortic pressure-time signals during the diastolic and systolic periods, respectively). The SEVR requires invasive recordings of left ventricular pressure; the DABAC/SABAC index may represent an alternative, since it only requires an aortic pressure signal. Nonetheless, it has never been used in an animal model of counterpulsated heart failure and ischemia-reperfusion episode. The aims of this work were: (i) to develop an animal model of heart failure, with a myocardial ischemia-reperfusion episode, treated with IABP during the reperfusion period; (ii) to evaluate the effects of the IABP using the SEVR and DABAC/SABAC indices; and (iii) to assess the relationship between both ratios. Cardiovascular parameters were obtained in anesthetized sheep, in which induced heart failure and ischemia-reperfusion episodes were monitored with and without IABP 1:2. Systolic and diastolic blood pressure signals were assessed in the aorta and in the left ventricle. Values of cardiac output and left ventricular wall thickness signals were obtained. Induction of ischemia and heart failure determined decreases in SEVR and DABAC/SABAC indices with respect to their basal stage (0.807 ± 0.118 vs. 0.601 ± 0.107, P < 0.05 and 1.062 ± 0.136 vs. 0.902 ± 0.161, P < 0.05, respectively). Counterpulsated animals whose myocardial reperfusion was accompanied by heart failure showed a significant improvement of wall thickening fraction along time (R2  = 0.7627, P < 0.001). During counterpulsated heart failure accompanied by myocardial reperfusion, the SEVR was positively correlated with DABAC/SABAC index.

Reference intervals and percentile curve for left ventricular outflow tract (LVOT), velocity time integral (VTI), and LVOT-VTI-derived hemodynamic parameters in healthy children and adolescents: Analysis of echocardiographic methods association and agreement.

BACKGROUND: Echocardiographic reference intervals (RIs) for left ventricular outflow tract (LVOT) and velocity time integral (VTI) are scarce in pediatrics. AIMS: (a) to generate RIs and percentiles for LVOT, VTI, and hemodynamic variables in healthy children and adolescents from Argentina; (b) to analyze the equivalence between stroke volume (SV), cardiac output (CO), and cardiac index (CI) obtained from two-dimensional echocardiography (2D) and LVOT-VTI analysis with pulsed wave Doppler (PWD); and (c) to analyze the association between subjects' characteristics and VTI and LVOT-VTI-derived parameters. METHODS: Two-dimensional and PWD studies were done in 385 subjects (5-24 years). Mean and standard deviation age-related and body surface area (BSA)-related equations were obtained for VTI and LVOT-VTI-derived parameters (parametric regression methods based on fractional polynomials). BSA- and age-specific percentiles were determined. RESULTS: Pulsed wave Doppler- and 2D-derived parameters were positively correlated. However, PWD values were always lower than those from 2D. Specific RIs for PWD and 2D data were necessary. Covariance analysis showed that sex-specific RIs were required for LVOT, but not for VTI, VTI-derived CO and CI. Age-related RIs were obtained for LVOT, LVOT-VTI, and VTI-derived CO and CI. BSA-related RIs for VTI-derived CO and CI were obtained. CONCLUSIONS: Stroke volume, CO, and CI data from 2D and PWD are not equivalent. An accurate analysis of LVOT-VTI-derived parameters requires considering age and BSA. In this study, age- and BSA-related RIs and percentiles for LVOT, VTI, and hemodynamic parameters in healthy children and adolescents were determined, discriminating data according to the methodological approach (2D or PWD).

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.

Carotid Intima Media Thickness Reference Intervals for a Healthy Argentinean Population Aged 11-81 Years.

Reference intervals (RIs) of carotid intima media thickness (CIMT) from large healthy population are still lacking in Latin America. The aim of this study was to determine CIMT RIs in a cohort of 1012 healthy subjects from Argentina. We evaluated if RIs for males and females and for left and right carotids were necessary. Second, mean and standard deviation (SD) age-related equations were obtained for left, right, and average (left + right)/2) CIMT using parametric regression methods based on fractional polynomials, in order to obtain age-specific percentiles curves. Age-specific percentile curves were obtained. Males showed higher A-CIMT (0.577 ± 0.003 mm versus 0.566 ± 0.004 mm, P = 0.039) in comparison with females. For males, the equations were as follows: A-CIMT mean = 0.42 + 8.14 × 10-5⁎Age2; A-CIMT SD = 5.9 × 10-2 + 1.09 × 10-5⁎Age2. For females, they were as follows: A-CIMT mean = 0.40 + 8.20 × 10-5⁎Age2; A-CIMT SD = 4.67 × 10-2 + 1.63 × 10-5⁎Age2. Our study provides the largest database concerning RIs of CIMT in healthy people in Argentina. Specific RIs and percentiles of CIMT for children, adolescents, and adults are now available according to age and gender, for right and left common carotid arteries.

Reference Intervals of Central Aortic Blood Pressure and Augmentation Index Assessed with an Oscillometric Device in Healthy Children, Adolescents, and Young Adults from Argentina.

Age-related reference intervals (RIs) of central (aortic) systolic blood pressure (cSBP) and augmentation index (cAIx) obtained from large healthy population are lacking in Argentina (South America). Aims. To analyze the existence of associations among cSBP and cAIx with demographic, anthropometric, and hemodynamic parameters and to generate percentile curves and RIs adjusted to each level of age and gender and/or body height. cSBP and cAIx were measured in 1038 healthy children, adolescents, and young adults. First, we evaluated if RIs for males and females were necessary using correlation and covariate analysis. Second, mean (M) and standard deviation (SD) age-related equations were obtained for cSBP and cAIx, using parametric regression methods based on fractional polynomials. Third, age specific percentiles curves were generated. Fourth, body height specific percentiles curves were generated using a similar procedure. The obtained equations (considering age as independent variable) for all subjects (cSBP0.26 and (cAIx + 12.001)0.5) were as follows: cSBP Mean = 3.0581 + 0.2189 log(Age) - 0.001044Age; cSBP SD = -0.03919 + 0.1535 log(Age) - 0.004564Age; cAIx mean = 9.5226 - 6.1599 log(Age) + 0.1450Age; cAIx SD = 1.3880 - 0.8468 log(Age) + 0.03212Age. This study, performed in Argentinean healthy children, adolescents, and young adults with ages of 5 to 22 years, provides the first RIs and percentile curves of cSBP and cAIx. Additionally, specific body height-related cAIx percentiles are reported for the analyzed population. The RIs and percentiles contribute to the knowledge of arterial dynamic evolution along the normal aging process and the interpretation of data obtained in clinical research and daily clinical practice.

Forward and Backward Aortic Components and Reflection Indexes in Children and Adolescents: Determinants and Role in High Pressure States.

BACKGROUND: High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. The study aims: 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand the main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. METHODS: Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. EVALUATIONS: central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters; the main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). RESULTS AND CONCLUSION: There were systematic and proportional differences between the data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations), showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with the major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. Evaluating wave components and reflection parameters could contribute to improve the comprehension and management of HBP states.

Increases in Peripheral Systolic Pressure Levels and Z-score Associate Gradual Aortic Pressure Increase and Functional Arterial Impairment in Children and Adolescents.

BACKGROUND: Arterial changes associated with children and adolescents high blood pressure (HBP) states would vary depending on the arterial type, arterial indexes considered and/or on blood pressure (BP) levels. AIMS: To determine in children and adolescents: 1) if there is gradual structural-functional arterial impairment associated with gradual peripheral (brachial) systolic BP (pSBP) level or z-score increases, and 2) whether subjects with HBP levels and those with normal BP differ in the profiles of arterial changes associated with pSBP deviations. METHODS: 1005 asymptomatic children and adolescents were included. Clinical, anthropometric and arterial non-invasive evaluations were performed. Heart rate, brachial BP, aortic BP and wavederived parameters (i.e. augmentation index), carotid and femoral diameters, blood velocities and elastic modulus, carotid intima-media thickness and aortic pulse wave velocity, were obtained. Two groups were assembled: Reference (without cardiovascular risk factors (CVRFs); n=379) and HBP (n=175). Additionally, subjects were ascribed to groups according to their pSBP z-scores (z-score ≤ 0, 0< z-score < 1 or z-score ≥ 1). Age and sex-related mean and standard deviation equations were obtained for each variable (Reference group). Using those equations, data (entire population) were converted into z-scores. Groups were compared (absolute and z-scored variables) before and after adjusting for cofactors (ANOVA/ANCOVA). Linear regression analyses were done considering: pSBP and z-pSBP (independent) and absolute levels and z-scores for hemodynamic and arterial indexes (dependent variables). Differences in hemodynamic and arterial levels and z-scores variations (dependent) associated with variations in pSBP and z-pSBP (independent variable) were assessed. The slopes of the models for Reference and HBP groups were compared. CONCLUSION: HBP states associate hemodynamic and arterial changes not explained by exposure to other CVRFs, anthropometric or demographic factors. The higher the pSBP deviations from ageand sex-expected mean value in the Reference group, the higher the hemodynamic and arterial indexes deviation. The pSBP-related variations in hemodynamic and arterial indexes would not differ depending on whether HBP states are present or not.

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 Pearson's 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.

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.

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.

Comparative in vivo analysis of the role of the adventitia and the endothelium on arterial mechanical function: relevance for aortic counterpulsation.

PURPOSE: The comparative effect of the intimal and adventitial layers on arterial biomechanics control, in basal and altered conditions, remains to be elucidated. This study aimed (1) to characterize the arterial conduit (CF) and buffering (distensibility) function of the iliac arteries in in vivo animals, in which the intimal and adventitial layers were removed; (2) to determine the effects of intra-aortic ballon pumping (IABP) on simultaneously de-adventitialized (DA) and de-endothelialized (DE) iliac arteries before and after induced heart failure. METHODS: Pressure and diameter signals were measured in the iliac arteries of sheep (n = 7) in which the adventitial and intima layer were removed. Intra-aortic balloon pump (IABP) assistance was used in a control state and after heart failure induction. RESULTS: Both DE and DA determined significant changes in arterial diameter, distensibility and CF. Changes were higher after DA than after DE in terms of distensibility and CF (p<0.05). DA followed by DE (DA + DE) showed significant increases in arterial diameter and CF, accompanied by a decrease in distensibility (p<0.05) with respect to intact arteries. Heart failure induction caused significant hemodynamic changes without modifying the already impaired local biomechanical parameters. Nonsignificant improvements in the biomechanical parameters of DA + DE iliac arteries were observed during IABP before and after heart failure induction. CONCLUSIONS: Biomechanical changes caused by DA of iliac arteries were more important than those observed after DE. The DA + DE arteries showed significant differences with respect to intact arteries and with DA or DE arteries. IABP-related effects on arterial mechanics were absent in DA + DE arteries.