Tube law parametrization using in vitro data for one-dimensional blood flow in arteries and veins: TUBE LAW PARAMETRIZATION IN ARTERIES AND VEINS.

The deformability of blood vessels in one-dimensional blood flow models is typically described through a pressure-area relation, known as the tube law. The most used tube laws take into account the elastic and viscous components of the tension of the vessel wall. Accurately parametrizing the tube laws is vital for replicating pressure and flow wave propagation phenomena. Here, we present a novel mathematical-property-preserving approach for the estimation of the parameters of the elastic and viscoelastic tube laws. Our goal was to estimate the parameters by using ovine and human in vitro data, while constraining them to meet prescribed mathematical properties. Results show that both elastic and viscoelastic tube laws accurately describe experimental pressure-area data concerning both quantitative and qualitative aspects. Additionally, the viscoelastic tube law can provide a qualitative explanation for the observed hysteresis cycles. The two models were evaluated using two approaches: (i) allowing all parameters to freely vary within their respective ranges and (ii) fixing some of the parameters. The former approach was found to be the most suitable for reproducing pressure-area curves.

Impact of a cuff-based device calibration method on the agreement between invasive and noninvasive aortic and brachial pressure.

INTRODUCTION: Brachial cuff-based methods are increasingly used to estimate aortic systolic blood pressure (aoSBP). However, there are several unresolved issues. AIMS: to determine to what extent the scheme used to calibrate brachial records (1) can affect noninvasive obtained aoSBP levels, and consequently, the level of agreement with the aoSBP recorded invasively, and (2) how different ways of calibrating ultimately impact the relationship between aoSBP and cardiac properties. METHODS: brachial and aortic blood pressure (BP) was simultaneously obtained by invasive (catheterisation) and noninvasive (brachial oscillometric-device) methods (89 subjects). aoSBP was noninvasive obtained using three calibration schemes: 'SD': diastolic and systolic brachial BP, 'C': diastolic and calculated brachial mean BP (bMBP), 'Osc': diastolic and oscillometry-derived bMBP. Agreement between invasive and noninvasive aoSBP, and associations between BP and echocardiographic-derived parameters were analysed. CONCLUSIONS: 'C' and 'SD' schemes generated aoSBP levels lower than those recorded invasively (mean errors: 6.9 and 10.1 mmHg); the opposite was found when considering 'Osc'(mean error: -11.4 mmHg). As individuals had higher invasive aoSBP, the three calibration schemes increasingly underestimated aoSBP levels; and viceversa. The 'range' of invasive aoSBP in which the calibration schemes reach the lowest error level (-5-5 mmHg) is different: 'C': 103-131 mmHg; 'Osc': 159-201 mmHg; 'SD':101-124 mmHg. The calibration methods allowed reaching levels of association between aoSBP and cardiac characteristics, somewhat lower, but very similar to those obtained when considering invasive aoSBP. There is no evidence of a clear superiority of one calibration method over another when considering the association between aoSBP and cardiac characteristics.

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.

Direct estimation of central aortic pressure from measured or quantified mean and diastolic brachial blood pressure: agreement with invasive records.

Background: Recently it has been proposed a new approach to estimate aortic systolic blood pressure (aoSBP) without the need for specific devices, operator-dependent techniques and/or complex wave propagation models/algorithms. The approach proposes aoSBP can be quantified from brachial diastolic and mean blood pressure (bDBP, bMBP) as: aoSBP = bMBP2/bDBP. It remains to be assessed to what extent the method and/or equation used to obtain the bMBP levels considered in aoSBP calculation may affect the estimated aoSBP, and consequently the agreement with aoSBP invasively recorded. Methods: Brachial and aortic pressure were simultaneously obtained invasively (catheterization) and non-invasively (brachial oscillometry) in 89 subjects. aoSBP was quantified in seven different ways, using measured (oscillometry-derived) and calculated (six equations) mean blood pressure (MBP) levels. The agreement between invasive and estimated aoSBP was analyzed (Concordance correlation coefficient; Bland-Altman Test). Conclusions: The ability of the equation "aoSBP = MBP2/DBP" to (accurately) estimate (error <5 mmHg) invasive aoSBP depends on the method and equation considered to determine bMBP, and on the aoSBP levels (proportional error). Oscillometric bMBP and/or approaches that consider adjustments for heart rate or a form factor ∼40% (instead of the usual 33%) would be the best way to obtain the bMBP levels to be used to calculate aoSBP.

Non-invasive central aortic pressure measurement: what limits its application in clinical practice?

The following article highlights the need for methodological transparency and consensus for an accurate and non-invasive assessment of central aortic blood pressure (aoBP), which would contribute to increasing its validity and value in both clinical and physiological research settings. The recording method and site, the mathematical model used to quantify aoBP, and mainly the method applied to calibrate pulse waveforms are essential when estimating aoBP and should be considered when analyzing and/or comparing data from different works, populations and/or obtained with different approaches. Up to now, many questions remain concerning the incremental predictive ability of aoBP over peripheral blood pressure and the possible role of aoBP-guided therapy in everyday practice. In this article, we focus on "putting it on the table" and discussing the main aspects analyzed in the literature as potential determinants of the lack of consensus on the non-invasive measurement of aoBP.

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.

Wave separation analysis-derived indexes obtained from radial and carotid tonometry in healthy pregnancy and pregnancy-associated hypertension: Comparison with pulse wave analysis-derived indexes.

Background: Increased wave reflections assessed by pulse wave analysis (PWA) was proposed as one of the potential culprits of hypertension seen in women with pregnancy-associated hypertension (PAH). However, this statement has never been confirmed with "Wave Separation Analysis" (WSA), a more sophisticated mathematical approach that analyzes the amplitude and interaction between forward and backward aortic pressure waveform components. Objective: To characterize potential changes in pressure wave components of PAH compared to healthy non-pregnant (NP) women and women with normal pregnancies (HP) by using WSA and compared these findings with PWA-derived indexes; secondarily, to evaluate differences in WSA-derived indexes between subgroups of PAH (i.e., preeclampsia [PE] and gestational hypertension [GH]). Methods: Using radial and carotid applanation tonometry, we quantified in HP (n = 10), PAH (n = 16), and NP (n = 401): (i) PWA-derived indexes; (ii) WSA-derived indexes: forward (Pf) and backward (Pb) waveform components, backward component arrival time (PbAT), reflection magnitude (RM = Pb/Pf) and index [RIx = Pb/(Pf + Pb)]. Results: While PAH was associated with a higher Pf compared to HP and NP, Pb and PbAT were similar between the groups. Both GH and PE showed a higher Pf compared to HP, but only PE had a trend of presenting with higher Pb and lower PbAT compared to the other groups. Finally, PAH showed a trend of having lower RM and RIx compared to NP and HP, with no differences between GH and PE. Conclusion: PAH was associated with higher Pf, but not higher Pb, compared to NP and HP, although PE also demonstrated a trend of higher Pb.

Fat-Free Mass Index, Visceral Fat Level, and Muscle Mass Percentage Better Explain Deviations From the Expected Value of Aortic Pressure and Structural and Functional Arterial Properties Than Body Fat Indexes.

Bioelectrical impedance analysis (BIA)-derived indexes [e.g., fat (FMI) and fat-free mass indexes (FFMI), visceral fat level (VFL)] are used to characterize obesity as a cardiovascular risk factor (CRF). The BIA-derived index that better predicts arterial variability is still discussed. Aims: To determine: (1) the association of classical [weight, height, body mass index (BMI), basal metabolic rate (BMR)] and BIA-derived indexes, with arterial properties deviations from expected values (arterial z-scores); (2) maximum arterial variations attributable to BIA-derived indexes; (3) whether the composition of total body, trunk and/or limbs is most closely associated with arterial variations. Methods: Hemodynamic, structural, and functional parameters of different histological types of arteries were assessed (n = 538, 7-85 years). Classical and BIA-derived indexes [fat mass and percentage, FMI, VFL, muscle mass percentage (PMM), FFMI, and percentage] were measured (mono- and multi-segmental devices). Arterial z-scores were obtained using age-related equations derived from individuals not-exposed to CRFs (n = 1,688). Results: First, regardless of the classical index considered, the associations with the arterial properties showed a specific hierarchy order: diameters and local stiffness > aortic and brachial blood pressure (BP) > regional stiffness. Second, all the associations of FMI and FFMI with z-scores were positive. Third, FFMI exceeded the association obtained with BMI and BMR, considering structural z-scores. In contrast, FMI did not exceed the association with z-scores achieved by BMI and BMR. Fourth, regardless of CRFs and classical indexes, arterial z-scores would be mainly explained by FFMI, VFL, and PMM. Fifth, regardless of the body-segment considered, the levels of association between FMI and z-scores did not exceed those found for classic and FFMI. Total fat mass and trunk indexes showed a greater strength of association with z-scores than the FMI of limbs. Sixth, compared to lower limb FFMI indexes, total and upper limbs FFMI showed higher levels of association with z-scores. Conclusions: FFMI (but not FMI) exceeded the strength of association seen between BMI or BMR and structural z-scores. Regardless of the body segment analyzed, the associations between FMI and z-scores did not exceed those found with classic and FFMI. Arterial z-scores could be independently explained by FFMI, VFL, and PMM.

Aging-Related Moderation of the Link Between Compliance With International Physical Activity Recommendations and the Hemodynamic, Structural, and Functional Arterial Status of 3,619 Subjects Aged 3-90 Years.

Background: Compliance with physical activity recommendations (CPARs) is associated with better health indicators. However, there are only few studies to date that have comprehensively analyzed the association between CPARs and cardiovascular status "as a whole" (e.g., analyzing hemodynamic, structural, and functional properties, and different arterial territories). The relationship between CPARs and cardiovascular properties could be strongly influenced by the growth and aging process. Aim: The goal of the study is to investigate the association between CPAR and cardiovascular properties by placing special emphasis on: (i) identifying if there is an independent association, (ii) if the association is "moderated" by age, and (iii) to what extent the association depends on the arterial parameter (hemodynamic vs. structural vs. functional) and/or the arterial segment (e.g., central vs. peripheral; elastic vs. transitional vs. muscular arteries). Methods: A total of 3,619 subjects (3-90 years of age) were studied. Extensive cardiovascular evaluations were performed. Cardiovascular risk factors (CRFs) and physical activity (PA) levels were determined. The subjects were categorized as compliant (n = 1, 969) or non-compliant (n = 1,650) with World Health Organization-related PA recommendations. Correlation and multiple regression models (including CPAR*Age interaction) were obtained, and Johnson-Neyman technique was used to produce regions of significance. Results: The independent association between CPARs and cardiovascular characteristics were strongly moderated by age. The moderation was observed on a wide range of age but particularly notorious on the extremes of life. Certain arterial characteristics demonstrated opposite effects in relation to CPAR status depending on the range of age considered. The association between CPAR and cardiovascular characteristics was independent of CRFs and moderated by age. In subjects younger than 45-55 years, CPAR status was associated with lower central and peripheral blood pressure (i.e., the younger the subject, the higher the reduction). During adult life, as age increases in the subjects, CPARs was associated with a beneficial hemodynamic profile, which is not related with variations in pressure but strongly related with lower levels of waveform-derived indexes and ventricular afterload determinants. Conclusions: The independent associations between CPARs and arterial properties were strongly moderated by age. Data provided by blood pressure levels and waveform-derived indexes would be enough to evaluate the independent association between CPARs and the vascular system in the general population.

Influence of Epoch Length and Recording Site on the Relationship Between Tri-Axial Accelerometry-Derived Physical Activity Levels and Structural, Functional, and Hemodynamic Properties of Central and Peripheral Arteries.

Background: It remains to be established to what extent physical activity (PA) levels among individuals are independently associated with deviations from the "optimal" state of the arterial system. Accelerometers have been proposed as means to obtain reliable, objective, and more comprehensive data of PA. Decisions at the time of data collection/processing could influence the association between accelerometry-derived indices and arterial properties. Objectives: (i) To identify to what extent the strength of association between arterial properties and accelerometer-derived indices depend on the recording site and/or the epoch length; (ii) to determine whether some arterial characteristics (hemodynamic vs. structural vs. functional) or regions (elastic vs. transitional vs. muscular arteries; central vs. peripheral) have higher levels of association with accelerometry-derived indices. Methods: Physical activity (PA), cardiovascular risk factors (CRFs), and cardiovascular properties were evaluated in 60 volunteers (general population; age: 23-62 years; women: 43%). PA was measured daily for 7 days (free-living situation; triaxial-accelerometers ActiGraph-GT3X+; hip and wrist; "Worn-to-wrist" option) and raw data was converted at epoch lengths of 1, 5, 10, 30, and 60-s. PA-related energy expenditure, daily time in moderate-to-vigorous PA, steps/minute, and counts-per-minute for vector magnitude were calculated. The cardiovascular evaluation included hemodynamic (central and peripheral pressure), structural (diameters and intima-media thickness), and functional (local and regional stiffness) parameters of carotids, femoral, and brachial arteries, and carotid-femoral and carotid-radial pathways. Arterial z-scores were obtained using age-related equations derived from healthy participants not exposed to CRFs (n = 1,688; age: 2-84 years; female: 51.2%) to evaluate at which degree each parameter deviates from the "optimal" value. Methods: In general, hip recordings outperformed those obtained on the wrist regarding the strength of association with arterial parameters. Accelerometer-derived indices and their association with arterial properties vary depending on the recording site and epoch length. PA indices are stronger associated with functional (local) than structural variables and with central than peripheral arteries. Conclusions: Regardless of the PA index, there were independent associations with central artery characteristics, which reinforces that these territories would be the most related to PA levels. Differences in data acquisition and processing could lead to differences in conclusions when addressing the association between accelerometer-derived indices and the cardiovascular system.

Shedding Light on the Pathophysiology of Preeclampsia-Syndrome in the Era of Cardio-Obstetrics: Role of Inflammation and Endothelial Dysfunction.

BACKGROUND: Preeclampsia (PE) is a pregnancy complication with serious maternal and neonatal consequences worldwide. Our understanding of PE pathophysiology has significantly evolved over the last decades by recognizing that endothelial dysfunction and systemic inflammation, with an associated angiogenic imbalance, are key pieces of this incomplete puzzle. In the present era, where no single treatment to cure or treat this obstetric condition has been developed so far, PE prevention and early prediction are the most useful clinical approach to reduce the PE burden. INTRODUCTION: Although most PE episodes occur in healthy nulliparous women, the identification of specific clinical conditions that increase the risk of PE dramatically provides a critical opportunity to improve outcomes by acting on potentially reversible factors, and also contributes to better understand this pathophysiologic enigma. METHODS: Pertinent studies were searched in PubMed/Medline and Google Scholar (updated August 2020) using common keywords applied in the field of preeclampsia, inflammation and endothelial dysfunction. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized. CONCLUSION: In this review, we highlight major clinical contributors of PE and shed light on their potential link with endothelial dysfunction and inflammation.

Sex- and Age-Related Physiological Profiles for Brachial, Vertebral, Carotid, and Femoral Arteries Blood Flow Velocity Parameters During Growth and Aging (4-76 Years): Comparison With Clinical Cut-Off Levels.

Ultrasound-derived blood flow velocity (BFV) levels [e.g., peak systolic velocity (PSV)], intrabeat indexes (e.g., resistive), and intersegment ratios [e.g., internal/common carotid artery (ICA/CCA) PSV ratio] are assessed to describe cardiovascular physiology and health status (e.g., disease severity evaluation and/or risk stratification). In this respect, fixed cut-off values (disregard of age or sex) have been proposed to define "significant" vascular disease from BFV-derived data (parameters). However, the use of single fixed cut-off values has limitations. Accurate use of BFV-derived parameters requires knowing their physiological age-related profiles and the expected values for a specific subject. To our knowledge, there are no studies that have characterized BFV profiles in large populations taking into account: (i) data from different age-stages (as a continuous) and transitions (childhood-adolescence-adulthood), (ii) complementary parameters, (iii) data from different arteries, and (iv) potential sex- and hemibody-related differences. Furthermore, (v) there is little information regarding normative data [reference intervals (RIs)] for BFV indexes. Aims: The aims of this study are the following: (a) to determine the need for age-, body side-, and sex-specific profiles for BFV levels and derived parameters (intrabeat indexes and intersegment ratios), and (b) to define RIs for BFV levels and parameters, obtained from CCA, ICA, external carotid, vertebral, femoral, and brachial arteries records. Methods: A total of 3,619 subjects (3-90 years) were included; 1,152 were healthy (without cardiovascular disease and atheroma plaques) and non-exposed to cardiovascular risk factors. BFV data were acquired. The agreement between left and right data was analyzed (Concordance correlation, Bland-Altman). Mean and SD equations and age-related profiles were obtained for BFV levels and parameters (regression methods; fractional polynomials). Results: Left and right body-side derived data were not always equivalent. The need for sex-specific RIs was dependent on the parameter and/or age considered. RIs were defined for each studied artery and parameter. Percentile curves were compared with recommended fixed cut-off points. The equations for sex, body-side, and age-specific BFV physiological profiles obtained in the large population (of children, adolescents, and adults) studied were included (spreadsheet formats), enabling to determine for a particular subject, the expected values and potential data deviations.

Age- and sex-related profiles for macro, macro/micro and microvascular reactivity indexes: Association between indexes and normative data from 2609 healthy subjects (3-85 years).

Vascular reactivity (VR), defined as blood vessels' capability to actively modify the diameter and flow resistances can be non-invasively assessed analyzing vascular response to forearm occlusion. Several VR indexes can be quantified: (i) ´microvascular´, which consider variables that depend almost exclusively on changes in distal resistances, (ii)´ macrovascular´, that evaluate the changes in brachial artery (BA) diameter, adjusting for blood flow stimulus, and (iii) ´macro/micro´, whose values depend on the micro and macrovascular response without discriminating each one´s contribution. VR indexes could not be associated. Many VR indexes have been used without availability of adequate normative data (reference intervals, RIs). AIMS: (1) to evaluate macro, macro/micro and micro VR indexes obtained in a cohort of healthy children, adolescents and adults, (2) to evaluate the association between VR indexes, (3) to determine the need for age and/or sex-specific RIs, and (4) to define RIs for VR indexes. METHODS: Ultrasound (B-mode/Doppler) and automatic computerized analysis were used to assess BA diameter, blood flow velocity and distal resistances, at rest and in conditions of decreased and increased blood flow. Macro, macro/micro and micro VR indexes were quantified (n = 3619). RIs-subgroups were defined according to European Reference Values for Arterial Measurements Collaboration Group (n = 1688, 3-84 years) and HUNT3-Fitness Study Group (n = 2609, 3-85 years) criteria. Mean value and standard deviation equations were obtained for VR indexes. The need for age or sex-specific RIs was analyzed. Percentile curves were defined and data were compared with those obtained in other populations. CONCLUSION: Macro and macro/micro VR indexes showed no association (or it was very weak) with microvascular indexes. Age- and sex-related profiles and RIs for macro, macro/micro and micro VR indexes were defined in a large population of healthy subjects (3-85 y). Equations for mean, standard deviation and percentiles values (year-to-year) were included in text and spreadsheet formats.

Physical Activity, Sedentary Behavior and Sleep Time:Association with Cardiovascular Hemodynamic Parameters, Blood Pressure and Structural and Functional Arterial Properties in Childhood.

An association between movement behavior (MB) components (sleep time (ST), physical activity (PA) and sedentary behavior (SB)) and the state of the cardiovascular (CV) system in children has been postulated. However, it is still controversial whether MB components and/or sub-components (domains) during childhood are independently associated with aortic and peripheral blood pressure (BP), and structural or functional arterial properties. AIMS: (1) to evaluate MB components and subcomponents associations with CV characteristics, (2) to analyze the explanatory capacity of interindividual variations in MB on CV properties inter-individual variations at the beginning of school age. METHODS: Anthropometric, aortic and peripheral BP, hemodynamic levels (cardiac output, systemic vascular resistances), wave reflection indexes, and arterial structural (diameter, intima-media thickness) and functional (blood flow velocities, Doppler-indexes, local and regional arterial stiffness) parameters of elastic (carotids), transitional (brachial) and muscular (femoral) arteries and time spent in MB (PA questionnaires) were assessed in 816 children (5-6 years). Cardiovascular variables were standardized (z-scores), using age- and sex-related mean values and standard deviations obtained from subjects non-exposed to CV risk factors (CRFs) and who complied with 24 h MB recommendations (reference subgroup). Multiple linear regression models were constructed considering the CV z-scores as dependent variables and CRFs and MB components and subcomponents as independent variables. RESULTS: CV variables showed independent association with MB variations. However, their explanatory capacity on CV characteristics was lesser than that of anthropometric indexes, sex and/or high BP. CONCLUSIONS: MB components and sub-components were associated with CV characteristics regardless of other factors, but their capacity to explain variations was lesser than that of anthropometric data, sex or high BP state. MB subcomponents (e.g., sedentary play and screen time in case of SB) showed different (even opposite) associations with CV parameters. ST was associated mainly with indexes of the ventricle ejective function, rather than with CV structural characteristics. SB component and subcomponents were associated with BP, but not with structural parameters. PA component and subcomponents were associated with both BP and structural parameters. The different arterial types, as well central and peripheral parameters showed independent associations with MB components and subcomponents. None of these were independently associated with arterial stiffness.

Role of arterial impairment in preeclampsia: should the paradigm shift?

Preeclampsia is a worldwide pregnancy complication with serious short- and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a large proportion of cases, there is growing evidence that challenges the placental hypothesis in all affected women, since placental histopathology lesions thought to be characteristic are neither sensitive nor specific markers for the disorder. Recent hemodynamic investigations and studies on left ventricular function and structure in women with preeclampsia further challenge this universal paradigm and propose that placental dysfunction could be secondary to a maternal cardiovascular maladaptation to pregnancy in certain patients. Supporting this hypothesis, certain vascular features, which are characteristically enhanced in normal pregnancy allowing a healthy vascular adaptation, are absent in preeclampsia and comparable to the nonpregnant population. However, arterial biomechanics in preeclampsia may only not cope with hemodynamic demands of pregnancy but also impose additional detrimental loads to the maternal heart ("impaired left-ventricle-aorta coupling") and transmit pressure and flow disturbances into the fetoplacental circulation ("impaired large arteries-microcirculation coupling"). In this review, we analyze the major role of the arterial dysfunction in the cardiovascular maladaptation hypothesis of preeclampsia, shed light on its potential etiopathogenic link, and discuss the complementary nature of the placental and cardiovascular theories.

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.

Physiological Age- and Sex-Related Profiles for Local (Aortic) and Regional (Carotid-Femoral, Carotid-Radial) Pulse Wave Velocity and Center-to-Periphery Stiffness Gradient, with and without Blood Pressure Adjustments: Reference Intervals and Agreement between Methods in Healthy Subjects (3-84 Years).

In addition to being a marker of cardiovascular (CV) aging, aortic stiffening has been shown to be independently associated with increased CV risk (directly and/or indirectly due to stiffness-gradient attenuation). Arterial stiffness determines the rate at which the pulse pressure wave propagates (i.e., pulse wave velocity, PWV). Thus, propagated PWV (i.e., the distance between pressure-wave recording sites divided by the pulse transit time) was proposed as an arterial stiffness index. Presently, aortic PWV is considered a gold-standard for non-invasive stiffness evaluation. The limitations ascribed to PWV have hampered its use in clinical practice. To overcome the limitations, different approaches and parameters have been proposed (e.g., local PWV obtained by wave separation and pulse wave analysis). In turn, it has been proposed to determine PWV considering blood pressure (BP) levels (ß-PWV), so as to evaluate intrinsic arterial stiffness. It is unknown whether the different approaches used to assess PWV or ß-PWV are equivalent and there are few data regarding age- and sex-related reference intervals (RIs) for regional and local PWV, ß-PWV and PWV ratio. AIMS: (1) to evaluate agreement between data from different stiffness indexes, (2) to determine the need for sex-specific RIs, and (3) to define RIs for PWV, ß-PWV and PWV ratio in a cohort of healthy children, adolescents and adults. METHODS: 3619 subjects (3-90 y) were included, 1289 were healthy and non-exposed to CV risk factors. Carotid-femoral (cfPWV) and carotid-radial (crPWV) PWV were measured (SphygmoCor System (SCOR)) and PWV ratio (cfPWV/crPWV) was quantified. Local aortic PWV was obtained directly from carotid waves (aoPWV-Carotid; SCOR) and indirectly (generalized transfer function use) from radial (aoPWV-Radial; SCOR) and brachial (aoPWV-Brachial; Mobil-O-Graph system (MOG)) recordings. ß-PWV was assessed by means of cardio-ankle brachial (CAVI) and BP-corrected CAVI (CAVIo) indexes. Analyses were done before and after adjustment for BP. Data agreement was analyzed (correlation, Bland-Altman). Mean and standard deviation (age- and sex-related) equations were obtained for PWV parameters (regression methods based on fractional polynomials). RESULTS: The methods and parameters used to assess aortic stiffness showed different association levels. Stiffness data were not equivalent but showed systematic and proportional errors. The need for sex-specific RIs depended on the parameter and/or age considered. RIs were defined for all the studied parameters. The study provides the largest data set related to agreement and RIs for stiffness parameters obtained in a single population.

Center-To-Periphery Arterial Stiffness Gradient Is Attenuated and/or Reversed in Pregnancy-Associated Hypertension.

Background: Non-pregnant (NP) women have a progressive increase in arterial stiffness from central-to-peripheral arteries ["stiffness gradient" (SG)], which is of physiologic importance since excessive pulsatility is filtered by the creation of wave reflections. If the aorta gets stiff with minimal or no change in the periphery, the SG is dissipated transmitting pressure disturbances to the microcirculation. It remains unknown the status of the SG in both women with healthy pregnancies (HP) and complicated by pregnancy-associated hypertension (PAH). Objective: To determine whether HP and PAH are associated with changes in SG. Secondarily, we aim at identifying potential differences between the subgroups of PAH (pre-eclampsia and gestational hypertension). Methods: HP (n = 10), PAH (n = 16), and healthy NP women (n = 401, to be matched for age, and cardiovascular risk with the pregnant women) were included. Carotid-to-femoral (cfPWV) and carotid-to-radial pulse wave velocity (crPWV), common carotid artery (CCA) and brachial artery (BA) diameters and elastic modulus (EM), and regional (cfPWV/crPWV or "PWV ratio") and local (CCA EM/BA EM or "EM ratio") SG were quantified. Results: HP showed no changes in PWV ratio compared with NP, in the presence of significantly lower cfPWV and crPWV. HP exhibited higher arterial diameters and lower CCA EM/BA EM compared to NP, without differences with PAH. PAH was associated with a significant increase in the PWV ratio that exceeded the levels of both NP and HP, explained by a lower (although significant) reduction of cfPWV with respect to that observed in HP with respect to NP, and a higher reduction in crPWV with respect to that observed between HP and NP. The blunted reduction in cfPWV observed in PAH coincided with an increase in the CCA EM. Conclusions: Compared with NP, HP was associated with unchanged PWV ratio but with a reduction in CCA EM/BA EM, in the setting of a generalized drop in arterial stiffness. Compared with NP and HP, PAH was associated with an "exaggerated rise" in the PWV ratio without changes in CCA EM/BA EM, in the setting of a blunt reduction in cfPWV but exaggerated crPWV drop. The SG attenuation/reversal in PAH was mainly driven by pre-eclampsia.

Aortic Pressure Levels and Waveform Indexes in People Living With Human Immunodeficiency Virus: Impact of Calibration Method on the Differences With Respect to Non-HIV Subjects and Optimal Values.

Background: There are scarce and controversial data on whether human immunodeficiency virus (HIV) infection is associated with changes in aortic pressure (aoBP) and waveform-derived indexes. Moreover, it remains unknown whether potential differences in aoBP and waveform indexes between people living with HIV (PLWHIV) and subjects without HIV (HIV-) would be affected by the calibration method of the pressure waveform. Aims: To determine: (i) whether PLWHIV present differences in aoBP and waveform-derived indexes compared to HIV- subjects; (ii) the relative impact of both HIV infection and cardiovascular risk factors (CRFs) on aoBP and waveform-derived indexes; (iii) whether the results of the first and second aims are affected by the calibration method. Methods: Three groups were included: (i) PLWHIV (n = 86), (ii) HIV- subjects (general population; n = 1,000) and (iii) a Reference Group (healthy, non-exposed to CRFs; n = 398). Haemodynamic parameters, brachial pressure (baBP; systolic: baSBP; diastolic: baDBP; mean oscillometric: baMBPosc) and aoBP and waveform-derived indexes were obtained. Brachial mean calculated (baMBPcalc=baDBP+[baSBP-baDBP]/3) pressure was quantified. Three waveform calibration schemes were used: systolic-diastolic, calculated (baMBPcalc/baDBP) and oscillometric mean (baMBPosc/baDBP). Results: Regardless of CRFs and baBP, PLWHIV presented a tendency of having lower aoBP and waveform-derived indexes which clearly reached statistical significance when using the baMBPosc/baDBP or baMBPcalc/baDBP calibration. HIV status exceeded the relative weight of other CRFs as explanatory variables, being the main explanatory variable for variations in central hemodynamics when using the baMBPosc/baDBP, followed by the baMBPcalc/baDBP calibration. Conclusions: The peripheral waveform calibration approach is an important determinant to reveal differences in central hemodynamics in PLWHIV.