Changes in Body Size during Early Growth Are Independently Associated with Arterial Properties in Early Childhood.

Nutritional status in early life stages has been associated with arterial parameters in childhood. However, it is still controversial whether changes in standardized body weight (z-BW), height (z-BH), BW for height (z-BWH) and/or body mass index (z-BMI) in the first three years of life are independently associated with variations in arterial structure, stiffness and hemodynamics in early childhood. In addition, it is unknown if the strength of the associations vary depending on the growth period, nutritional characteristics and/or arterial parameters analyzed. AIMS: First, to compare the strength of association between body size changes (Δz-BW, Δz-BH, Δz-BWH, Δz-BMI) in different time intervals (growth periods: 0-6, 0-12, 0-24, 0-36, 12-24, 12-36, 24-36 months (m)) and variations in arterial structure, stiffness and hemodynamics at age 6 years. Second, to determine whether the associations depend on exposure to cardiovascular risk factors, body size at birth and/or on body size at the time of the evaluation (cofactors). Anthropometric (at birth, 6, 12, 24, 36 m and at age 6 years), hemodynamic (peripheral and central (aortic)) and arterial (elastic (carotid) and muscular (femoral) arteries; both hemi-bodies) parameters were assessed in a child cohort (6 years; n =632). The association between arterial parameters and body size changes (Δz-BW, Δz-BH, Δz-BWH, Δz-BMI) in the different growth periods was compared, before and after adjustment by cofactors. RESULTS: Δz-BW 0-24 m and Δz-BWH 0-24 m allowed us to explain inter-individual variations in structural arterial properties at age 6 years, with independence of cofactors. When the third year of life was included in the analysis (0-36, 12-36, 24-36 m), Δz-BW explained hemodynamic (peripheral and central) variations at age 6 years. Δz-BH and Δz-BMI showed limited associations with arterial properties. CONCLUSION: Δz-BW and Δz-BWH are the anthropometric variables with the greatest association with arterial structure and hemodynamics in early childhood, with independence of cofactors.

Stroke volume and cardiac output non-invasive monitoring based on brachial oscillometry-derived pulse contour analysis: Explanatory variables and reference intervals throughout life (3-88 years).

BACKGROUND: Non-invasive assessment of stroke volume (SV), cardiac output (CO) and cardiac index (CI) has shown to be useful for the evaluation, diagnosis and/or management of different clinical conditions. Through pulse contour analysis (PCA) cuff­based oscillometric devices would enable obtaining ambulatory operator-independent non-invasive hemodynamic monitoring. There are no reference intervals (RIs), when considered as a continuum in childhood, adolescence and adult life, for PCA-derived SV [SV(PCA)], CO [CO(PCA)] and CI [CI(PCA)]. The aim of the study were to analyze the associations of SV(PCA), CO(PCA) and CI(PCA) with demographic, anthropometric, cardiovascular risk factors (CVRFs) and hemodynamic parameters, and to define RIs and percentile curves for SV(PCA), CO(PCA) and CI(PCA), considering the variables that should be considered when expressing them. METHODS: In 1449 healthy subjects (3-88 years) SV(PCA), CO(PCA) and CI(PCA) were non-invasively obtained (Mobil-O-Graph; Germany). ANALYSIS: associations between subject characteristics and SV(PCA), CO(PCA) and CI(PCA) levels (correlations; regression models); RIs and percentiles for SV(PCA), CO(PCA) and CI(PCA) (parametric methods; fractional polynomials). RESULTS: Sex, age, and heart rate would be explanatory variables for SV, CO, and CI levels. SV levels were also examined by body height, while body surface area (BSA) contributing to evaluation of CO and CI. CVRFs exposure did not contribute to independently explain the values of the dependent variables. SV, CO and CI levels were partially explained by the oscillometric-derived signal quality. RIs and percentiles were defined. CONCLUSIONS: Reference intervals and percentile for SV(PCA), CO(PCA) and CI(PCA), were defined for subjects from 3-88 years of age, results are expressed according to sex, age, heart rate, body height and/or BSA.

Aortic pressure and forward and backward wave components in children, adolescents and young-adults: Agreement between brachial oscillometry, radial and carotid tonometry data and analysis of factors associated with their differences.

Non-invasive devices used to estimate central (aortic) systolic pressure (cSBP), pulse pressure (cPP) and forward (Pf) and backward (Pb) wave components from blood pressure (BP) or surrogate signals differ in arteries studied, techniques, data-analysis algorithms and/or calibration schemes (e.g. calibrating to calculated [MBPc] or measured [MBPosc] mean pressure). The aims were to analyze, in children, adolescents and young-adults (1) the agreement between cSBP, cPP, Pf and Pb obtained using carotid (CT) and radial tonometry (RT) and brachial-oscillometry (BOSC); and (2) explanatory factors for the differences between approaches-data and between MBPosc and MBPc.1685 subjects (mean/range age: 14/3-35 y.o.) assigned to three age-related groups (3-12; 12-18; 18-35 y.o.) were included. cSBP, cPP, Pf and Pb were assessed with BOSC (Mobil-O-Graph), CT and RT (SphygmoCor) records. Two calibration schemes were considered: MBPc and MBPosc for calibrations to similar BP levels. Correlation, Bland-Altman tests and multiple regression models were applied. Systematic and proportional errors were observed; errors´ statistical significance and values varied depending on the parameter analyzed, methods compared and group considered. The explanatory factors for the differences between data obtained from the different approaches varied depending on the methods compared. The highest cSBP and cPP were obtained from CT; the lowest from RT. Independently of the technique, parameter or age-group, higher values were obtained calibrating to MBPosc. Age, sex, heart rate, diastolic BP, body weight or height were explanatory factors for the differences in cSBP, cPP, Pf or Pb. Brachial BP levels were explanatory factors for the differences between MBPosc and MBPc.

Arterial Structural and Functional Characteristics at End of Early Childhood and Beginning of Adulthood: Impact of Body Size Gain during Early, Intermediate, Late and Global Growth.

An association between nutritional characteristics in theearlylife stages and the state of the cardiovascular (CV) system in early childhood itself and/or at the beginning of adulthood has been postulated. It is still controversial whether changes in weight, height and/or body mass index (BMI) during childhood or adolescence are independently associated with hemodynamics and/or arterial properties in early childhood and adulthood. AIMS: First, to evaluate and compare the strength of association between CVproperties (at 6 and 18 years (y)) and (a) anthropometric data at specific growth stages (e.g., birth, 6 y, 18 y) and (b) anthropometric changes during early (0-2 y), intermediate (0-6 y), late (6-18 y) and global (0-18 y) growth. Second, to determine whether the associations between CVproperties and growth-related body changes depend on size at birth and/or at the time of CVstudy. Third, to analyze the capacity of growth-related body size changes to explain hemodynamic and arterial properties in early childhood and adulthood before and after adjusting for exposure to CV risk factors. Anthropometric, hemodynamic (central, peripheral) and arterial parameters (structural, functional; elastic, transitional and muscular arteries) were assessed in two cohorts (children, n = 682; adolescents, n = 340). Data wereobtained and analyzed following identical protocols. RESULTS: Body-size changes in infancy (0-2 y) and childhood (0-6 y) showed similar strength of association with CV properties at 6 y. Conversely, 0-6, 6-18 or 0-18 ychanges were not associated with CV parameters at 18 y. The association between CV properties at 6 yand body-size changes during growth showed: equal or greater strength than the observed for body-size at birth, and lower strength compared to that obtained for current z-BMI. Conversely, only z-BMI at 18 y showed associations with CV z-scores at 18 y. Body size at birth showed almost no association with CVproperties at 6 or 18 y. CONCLUSION: current z-BMI showed the greatest capacity to explain variations in CV properties at 6 and 18 y. Variations in some CV parameters were mainly explained by growth-related anthropometric changes and/or by their interaction with current z-BMI. Body size at birth showed almost no association with arterial properties at 6 or 18 y.

Peripheral and Central Aortic Pressure, Wave-Derived Reflection Parameters, Local and Regional Arterial Stiffness and Structural Parameters in Children and Adolescents: Impact of Body Mass Index Variations.

AIM: The aim was to analyze and compare the associations between body mass index (BMI) and structural and functional cardiovascular variables measured in children and adolescents. METHODS: 609 healthy subjects (mean age/range 12/4-18 years, 45% females) were studied. Subjects' BMI and the corresponding z-scores (z-BMI) were determined. Cardiovascular measurements: peripheral and aortic blood pressure (BP), aortic wave-derived parameters, common carotid, femoral and brachial artery diameters and stiffness, carotid intima-media thickness, carotid-radial and carotid-femoral pulse wave velocity (crPWV, cfPWV) and cfPWV/crPWV ratio. Cardiovascular data were standardized (z-scores) using equations (fractional polynomials) obtained from a sub-group (reference population, n = 241) non-exposed to cardiovascular risk factors (CVRFs). Simple and multiple regression models were obtained for the associations between cardiovascular z-scores and z-BMI and/or z-BMI, age, sex and CVRFs. RESULTS: z-BMI was associated with standardized cardiovascular variables, regardless of age, sex and CVRFs. BP (peripheral rather than aortic) was the variable with the greatest variations associated with z-BMI. Systolic (SBP) and pulse pressure (PP; in that order) were the variables with the highest variations associated with z-BMI. Carotid, but not femoral or brachial stiffness showed BP-dependent variations associated with z-BMI. Arterial diameters were associated with z-BMI, without differences among arteries. CONCLUSION: In children and adolescents, z-BMI was gradually and positively associated with haemodynamic (peripheral and central BP) and vascular parameters (structural and functional) with independence of age, sex and other CVRFs (Dyslipidemia, Hypertension, Smoke, Diabetes). There were differences in the associations depending on the arteries studied and on whether central or peripheral haemodynamic parameters were analyzed.

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.

Comparative Analysis of Arterial Parameters Variations Associated with Inter-Individual Variations in Peripheral and Aortic Blood Pressure: Cross-Sectional Study in Healthy Subjects Aged 2-84 years.

INTRODUCTION: The association between arterial parameters and blood pressure (BP) interindividual variations could depend on the arterial segment, BP component (systolic, SBP; diastolic, DBP; pulse pressure, PP) and/or on whether central (cBP) or peripheral (pBP) BP variations are considered. AIM: To assess and compare arterial parameters variations associated with interindividual variations in cBP and pBP. METHODS: Healthy subjects (n = 923; 488 males, 2-84 years) were included. pBP and cBP waves were obtained (Mobil-O-Graph; SphygmoCor). Arterial diameter, intima-media thickness, local elastic modulus (carotid, CEM; brachial, BEM; femoral, FEM) and regional (carotid-radial and carotid-femoral pulse wave velocity; crPWV and cfPWV) arterial stiffness were determined. Associations between BP and arterial parameters interindividual variations were analyzed and compared (correlations; linear regressions; slopes comparisons) considering data transformed into z-scores. RESULTS: Given a variation in z-cSBP or z-pSBP, z-CEM, z-FEM and z-cfPWV (stiffness indexes), were among the parameters with major BP-associated variations. z-crPWV and z-cfPWV, rather than local stiffness indexes were the parameters with major variations associated with z-DBP variations. z-cPP or z-pPP were associated with z-CEM and z-FEM variations, but not with brachial or regional stiffness variations. Most of the arterial parameters-BP slopes did not show significant differences when considering a variation in z-cSBP and z-pSBP. z-CEM and z-FEM were mainly associated with z-cPP and z-pPP variations, respectively. CONCLUSION: Disregard of age and sex, the variations in arterial parameters associated with BP interindividual variations showed differences depending on whether variations were central or peripheral; in SBP, DBP or PP and depending on the arterial segment considered.

Children and Adolescents Macrovascular Reactivity Level and Dynamics, But Not the Microvascular Response, is Associated with Body Mass Index and Arterial Stiffness Levels.

INTRODUCTION: The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Detection of children and adolescents at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying cardiovascular disease. Vascular reactivity (VR) is altered even by early atherosclerosis. Obesity is a main cardiovascular risk factor (CVRF) observed in childhood. If childhood obesity associates impaired macro and/or micro VR is controversial. AIMS: To characterize macro and micro VR analyzing the stimulus and vascular response temporal profiles in children and adolescents considering their body mass index (BMI); and to assess potential associations between subjects' characteristics and the hyperemic stimulus and/or VR. METHODS: Healthy subjects (n = 99, age 5-17 years, female 46%) were included. Considering the BMI, normal, overweight and obese groups were defined. CVRF exposure was assessed. Brachial flow-mediated dilation and reactive hyperemia, associated with transient ischemia (forearm cuff-inflation) were evaluated. Diameter, flow velocities, resistive indexes and shear-stress were determined before, during and after cuff-release. Complimentary VR indexes were computed. Aortic stiffness and aortic and brachial blood pressure were determined. RESULTS: Obese showed the lowest and slowest macrovascular response (p < 0.05). Micro VR was not associated with obesity. Higher aortic stiffness levels were associated with slower macrovascular responses (p < 0.05). CONCLUSION: Childhood obesity associates not only reduced, but also slowed macrovascular reactivity. Microvascular response to transient ischemia is preserved in obese children. Macro and microvascular responses would be non-associated phenomena in childhood. During childhood, VR dynamics would depend on the arterial stiffness.

High Central Aortic Rather than Brachial Blood Pressure is Associated with Carotid Wall Remodeling and Increased Arterial Stiffness in Childhood.

INTRODUCTION: In adults, central blood pressure (cBP) is reported to associate target organ damages (TODs) rather than peripheral blood pressure (pBP). However, data regarding the association of pre-clinical TODs with cBP and pBP in pediatric populations are scarce. AIM: To evaluate in children and adolescents the importance of cBP and pBP levels, in terms of their association with hemodynamic and vascular changes. METHODS: 315 subjects [age (mean/range) 12/8-18 years] were included. MEASUREMENTS: pBP (oscillometry, Omron-HEM433INT and Mobil-O-Graph), cBP levels and waveforms (oscillometry, Mobil-O-Graph; applanation tonometry, SphygmoCor), aortic wave reflection-related parameters, carotid intima-media thickness (CIMT) and carotid (elastic modulus, stiffness-index) and aortic stiffness (carotid-femoral pulse wave velocity, PWV). Four groups were defined considering pBP and cBP percentiles (th): cBP ≥90th, cBP <90th, pBP ≥90th, pBP <90th. In each group, haemodynamic and vascular parameters were compared for subgroups defined considering the level of the remaining blood pressure (cBP or pBP). Subgroups were matched for anthropometric and cardiovascular risk factors (propensity matching-score). RESULTS: Subjects with high cBP showed a worse cardiovascular risk profile in addition to worse peripheral hemodynamic conditions. The CIMT, carotid and aortic stiffness levels were also higher in those subjects. CIMT and carotid stiffness remained statistically higher when subjects were matched for pBP and other cardiovascular risk factors. There were no differences in arterial properties when subjects were analyzed (compared) considering similar pBP levels, during normal and high cBP conditions. CONCLUSION: Compared with pBP, the cBP levels show a greater association with vascular alterations (high CIMT and arterial stiffness), in children and adolescents.

Changes in Central Aortic Pressure Levels, Wave Components and Determinants Associated with High Peripheral Blood Pressure States in Childhood: Analysis of Hypertensive Phenotype.

The aims were to determine whether children's high peripheral blood pressure states (HBP) are associated with increased central aortic blood pressure (BP) and to characterize hemodynamic and vascular changes associated with HBP in terms of changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR) and net and relative contributions of reflected waves to the aortic pulse amplitude. We included 154 subjects (mean age 11; range 4-16 years) assigned to one of two groups: normal peripheral BP (NBP, n = 101), defined as systolic and diastolic BP < 90th percentile, or high BP (HBP, n = 53), defined as average systolic and/or diastolic BP levels ≥90th percentile (curves for sex, age and body height). The HBP group included children with hypertensive and pre-hypertensive BP levels. After a first analysis, groups were compared excluding obese and dyslipidemic children. Peripheral and central aortic BP, PWV and pulse wave-derived parameters (augmentation index, forward and backward wave components' amplitude) were measured using gold-standard techniques, applanation tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). Independent of the presence of dyslipidemia and/or obesity, aortic systolic and pulse BP were higher in HBP than in NBP children. The increase in central BP could not be explained by an increase in the relative contribution of reflections to the aortic pressure wave, higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP would be explained by an increase in the amplitude of both incident and reflected wave components.

Children and Adolescent Obesity Associates with Pressure-Dependent and Age-Related Increase in Carotid and Femoral Arteries' Stiffness and Not in Brachial Artery, Indicative of Nonintrinsic Arterial Wall Alteration.

Aim. To analyze if childhood obesity associates with changes in elastic, transitional, and/or muscular arteries' stiffness. Methods. 221 subjects (4-15 years, 92 females) were assigned to normal weight (NW, n = 137) or obesity (OB, n = 84) groups, considering their body mass index z-score. Age groups were defined: 4-8; 8-12; 12-15 years old. Carotid, femoral, and brachial artery local stiffness was determined through systodiastolic pressure-diameter and stress-strain relationships. To this end, arterial diameter and peripheral and aortic blood pressure (BP) levels and waveforms were recorded. Carotid-femoral, femoropedal, and carotid-radial pulse wave velocities were determined to evaluate aortic, lower-limb, and upper-limb regional arterial stiffness, respectively. Correlation analysis between stiffness parameters and BP was done. Results. Compared to NW, OB subjects showed higher peripheral and central BP and carotid and femoral stiffness, reaching statistical significance in subjects aged 12 and older. Arterial stiffness differences disappeared when levels were normalized for BP. There were no differences in intrinsic arterial wall stiffness (elastic modulus), BP stiffness relationships, and regional stiffness parameters. Conclusion. OB associates with BP-dependent and age-related increase in carotid and femoral (but not brachial) stiffness. Stiffness changes would not be explained by intrinsic arterial wall alterations but could be associated with the higher BP levels observed in obese children.

Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification.

The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5-15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV.