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Background In-vivo assessment of aortic characteristic impedance (Z ao ) and total arterial compliance (C T ) has been hampered by the need for invasive methods to access simultaneous recordings of aortic pressure and flow, wall thickness, and cross-sectional area. In contrast, regional pulse wave velocity (PWV) measurements are noninvasive and clinically available. Given that PWV is strongly related to aortic stiffness (1), we assume that carotid-to-femoral PWV (cfPWV) and carotid-to-radial PWV (crPWV) may contain sufficient information to evaluate the elasticity of the ascending aorta. Concretely, here, we present a noninvasive regression method for estimating Z ao and C T using cuf pressure, cfPWV, and crPWV. Methods Gradient Boosting is employed for predicting Z ao , and C T . The regressors are trained/tested using a pool of virtual subjects ( n = 4833) generated from a previously validated in-silico model (2). The cross validation is performed using a 10-fold cross-validation (3).The population used has been previously generated (4) and reflects a wide range of hemodynamical properties and states. Results Predictions had a high accuracy (Figure) achieving a normalized-RMSE equal to 6.24 ± 1.19% ( r = 0.85, p < 0.001) for Z ao , and 4.38 ± 0.36% ( r = 0.97, p < 0.001) for C T , respectively. High errors were reported for high values of Z ao due to the limited amount of similar data. Conclusion The proposed approach constitutes a step forward to noninvasive screening of elastic vascular properties in human by exploiting easily obtained measurements. This study could introduce a valuable tool for assessing aortic stiffness reducing the cost and the complexity of the required measuring techniques. Clinical evaluation is required to validate the method in-vivo . Figure Comparison of the estimated values with the reference values. Scatterplot and Bland-Altman plot for the predicted Z ao (left panel). Scatterplot and Bland-Altman plot for the predicted C T (right panel). Solid line represents equality. Limits of agreement (LoA), within which 95% of errors are expected to lie, are defined by the two horizontal dashed lines.

Recently, many promising indices of micro- and macrocirculation have been widely used to promptly detect target organ damage before major cardiovascular events occur. More specifically, nailfold capillaroscopy, fundoscopy, near-infrared spectroscopy, ultrasound, laser speckle contrast analysis and central arterial pressure waveform analysis have been used to reveal capillary rarefaction, retinal vessel alterations, reduced brain and muscle oxygenation, endothelial dysfunction and arterial stiffness respectively. Additionally, the cross-talk between macro- and microvascular alterations has been a topic intensively discussed during the last years. Contrary to what someone might expect, i.e. that different microvascular target organ damage will coexist and occur at the same time in different tissues of the human body, in most studies the different types of microangiopathy seem not to synchronize or follow a specific order of appearance but rather to affect the different tissues randomly. On the other hand, arterial stiffening of the large arteries seems consistently to co-exist and correlate with almost all microvascular lesions. Nevertheless, many questions arise: When do the above lesions coexist? In which individuals? In which diseases? What can they predict when identified in apparently healthy people? In the present paper, the results of the study of the above indices, all applied in the same individuals at the same time, will be presented in a variable spectrum of diseases (naïve hypertensives, diabetics, rheumatologic patients, women with gestational diabetes, obese people, as well as healthy controls) to explore not only the interactions between them but mostly their importance for the amelioration of cardiovascular risk classification.

Background Daily assessment of vascular health may predict cardiovascular incidence. Vascular aging index (VAI) calculated from second derivative of photoplethysmogram (SDPTG) is a simple, non-invasive measure possibly reflecting vascular stiffness. However, the effects of daily life events such as mental stress and day-to-day variability as well as its relation to other indices of vascular stiffness remain unclear. Purpose To determine whether VAI measured by finger SDPTG is 1) correlated with peripheral augmentation index (pAI), 2) altered by acute mental stress, and 3) affected by day-to-day variability. Methods Simultaneous measurements of finger photoplethysmogram and radial artery tonometry were performed in 68 healthy subjects (age = 22–64 years) of whom 31 subjects were further tested during a 30-second mental arithmetic and 10 subjects underwent day-to-day variability assessment for 5 consecutive days. VAI was calculated from a 20-second segment of photoplethysmogram data [ 1 ]. Results At rest, VAI was positively correlated with pAI ( r = 0.62, p < 0.001). During mental arithmetic, VAI increased when compared with the control condition ( p = 0.032) whereas pAI did not show significant change. Five day measurements of VAI demonstrated the overall coefficient of variation of 21.1 ± 13.7% across all subjects. Conclusion VAI calculated from the finger SDPTG is related to a measure of vascular stiffness and sensitive to mental stress with fair day-to-day variability. These findings suggest that VAI assessment needs to be performed at the quiet resting condition.

Introduction Chronic increases in aldosterone (Aldo) levels (hyperaldosteronism) increases blood pressure and induces hypertension. In the cardiovascular system, Aldo stimulates reactive oxygen species (ROS) generation. ROS contribute to vascular dysfunction by increasing vascular smooth muscle contractile tone, among other effects. Nuclear factor erythroid 2–related factor 2 (Nrf2), it’s one of the main factors in the adaptive response to oxidative stress. Hypothesis Aldo negatively regulates the antioxidant system Nrf2, favoring ROS accumulation and subsequent vascular dysfunction. Methods Vascular function was evaluated in mice aortic conductance arteries, by performing concentration-effect curves to phenylephrine (PE) and acetylcholine (ACh). ROS production, determined by lucigenin and AmplexRed chemiluminescence, and Nrf2 activity by a nuclear translocation assay, were determined in endothelial cells (EA.hy926). Results Aldo increased PE contractions and decreased the relaxation response to ACh. L-sulforaphane, a Nrf2 activator, prevented Aldo-induced vascular dysfunction. In endothelial cells, Aldo increased ROS generation, i.e. superoxide anion and hydrogen peroxide, in a time-dependent manner. In addition, Aldo increased Nrf2 translocation at 30 min, 1 and 3 hours. However, after 3 hours, Aldo decreased Nrf2 translocation. Conclusion These data indicate that Aldo increases ROS in endothelial cells and causes impairment in vascular reactivity, events associated with decreased Nrf2 activity. Financial support: FAPESP (Process Number: 2018/05298-1), CAPES, CNPq. This study was approved by the Ethics Committee on Animal Experimentation of the Ribeirao Preto Medical School (030/2018).

Objectives High levels of aldosterone may contribute to early development of hypertension. The aim was to evaluate the influence of high serum aldosterone on cardiovascular function in healthy black and white South Africans. Methods This study was embedded in the African-PREDICT study, included 233 black and 217 white participants aged 20–30 years. Cardiovascular-and biochemical variables were measured with known methods. Results The ABPM night DBP is significantly higher in the black high aldosterone participants (58 vs 60 mmHg). The ABPM day SBP is significantly lower (125 vs 122 mmHg) in the white participants. The SV in the white participants is significantly lower (95 vs 90 ml) compared to the low aldosterone group. The vascular compliance is also significantly lower (2.4 vs 2.5 ml/mmHg) in the white participants. The angiotensin II are significantly higher in the black (47.6 vs 87.5 pmol/l) and white (85.6 vs 145.2 pmol/l) high aldosterone groups. NT-proBNP (36.4 vs 24.8 pmol/l) is significantly lower in the black high aldosterone group. Partial correlations in the black high aldosterone group revealed positive associations with vascular compliance ( r = 0.22; p = 0.004), angiotensin II ( r = 0.49; p = <0.001) as well as with CRP ( r = 0.16; p = 0.031) and in the whites with angiotensin II ( r = 0.27; p = <0.001) and CRP ( r = 0.15; p = 0.041). Regression analysis revealed that the angiotensin II contributes to aldosterone in the blacks and ROS only in whites. Conclusion The lower NT-proBNP in the blacks has a stabilizing role against volume overload while in the white participants ROS may contribute to early vascular changes.

Background Hemodynamic optimization of unstable patients by means of fluid resuscitation improves patient outcome, but choosing the correct amount of fluid can be difficult. Too little fluid may not ensure adequate perfusion whereas too much fluid is associated with increased mortality. Static parameters are not sufficiently sensitive to detect a reduction in preload, and dynamic parameters rely on changes induced by mechanical ventilation. We hypothesized that the arterial wave form contains parameters that can be used as model input to identify patients that benefit from fluid administration. Methods Radial artery waveform parameters were extracted in patients after they had undergone a coronary artery bypass graft surgery ( n = 20, all male). Three classes were defined: unchanged preload, preload reduction induced by positive end-expiratory breath holds (PEEP), and preload increase following fluid administration. A leave-one-out multinomial logistic regression was performed to train and evaluate the model. Model performance is reported as accuracy, sensitivity and specificity. Results In univariate analysis, left ventricular ejection time, augmentation index, dPdtmax and stroke volume showed the largest variation between the classes and were selected as model inputs. Following leave-one-out cross-validation the final model detected decreased preload with an accuracy, sensitivity and specificity of 87.5%, 85% and 90% respectively. Fluid administration did not give enough stimulus for modelling. Conclusion Arterial waveform parameters adequately distinguish unchanged from artificially reduced preload; preload increase could not be reliably detected. Since PEEP influences arterial compliance, future studies need to evaluate this effect, and also the applicability of the model in other populations.

It has been proven that aortic pulse wave velocity (aoPWV), the measure of arterial stiffness is a strong and independent predictor of both cardiovascular events and all-cause mortality. Beyond the “gold standard” cfPWV (carotid-femoral) a plenty of methods are available for measuring PWV but the interpretation of their results are problematic and not interchangeable. Patients and Methods Our aim was to assess the association and agreement of two oscillometric methods; the upper armcuffed invasively validated Arteriograph system and the brachial-ankle PWV (baPVW) measurement employed by the automatic BOSO-ABI system which operates simultaneous cuff-measurements on both extremities. 157 apparently healthy individuals of both sexes (mean age was 44.3 + 9.3 ys; 54 male and 103 female) were examined in this study. Results Mean PWV was significantly higher with BOSO (11.76 + 1.52 m/s) than Arteriograph (8.45 + 1.71 m/s). The two different measurement modalities demonstrated moderate linear correlation (The Pearson’s test of correlation coefficient r = 0.391, p < 0.001). The lack of agreement between the two methods is confirmed also by the Bland-Altman plot. Conclusion Both methods are simple and easy to use and offer a user independent automatic assessment of PWV. The difference of the measured values derived from the different path length the two methods use.

Background Calibration of carotid artery tonometry waveforms needs to account for pulse pressure augmentation [ 1 ]. Due to its location nearer to the heart, carotid pulse pressure (carPP) is about 10 mmHg lower than brachial (brachPP) [ 1 ]. In practice, perfect applanation is hard to achieve with tonometry and thus tracking-errors may occur, leading to an exaggerated fall in the diastolic limb of the tonometry waveform. Consequently, the mean-to-diastolic difference of the waveform is underestimated, leading to an overestimation of carPP after calibration. We assessed the relationship between brachPP and carPP in 100 subjects, aged 18–80 yrs. Methods and Results Brachial pressure (Omron) and carotid tonometry (Sphygmocor) measurements were performed by a single, highly skilled vascular technician, according to Artery Society methodological standards. CarPP was 5 ± 13 mmHg lower than brachPP. Bland-Altman analysis revealed a positive trend ( r = 0.695, p < 0.0001) between the carPP–brachPP difference and their mean, with carPP being 20 mmHg lower than brachPP at a mean 40 mmHg which extended to carPP being 20 mmHg higher(!) than brachPP at a mean 80 mmHg. Accordingly, 30% of the study population showed unphysiological carPP, indicating an unrealistic i.e. reverse amplification. Even with a tolerance of +5 mmHg, still 20% of cases showed unrealistic values. Conclusion In practice, calibrated carotid tonometry waveforms may yield unphysiological overestimations of carotid pulse pressure. This finding implies (potential) estimation errors in regression model studies on central pressure and local stiffness, suggesting brachial pulse pressure would be a valid compromise.

Background Aortic valve stenosis (AS) is the most common valve disease in an elderly population, therefore, simple screening examination for AS is needed. Although a prolonged carotid upstroke time (UT), and prolonged ejection time (ET) of a brachial pulse wave (BPW) have been observed in severe AS patients, it has been unclear which BPW parameters have a better correlation with the severity of AS. The aim of this study was to examine which BPW parameters are most relevant to the severity of AS. Methods Sixty-five Consecutive moderate and severe AS patients who were evaluated by trans-thoracic echocardiography were enrolled in this study. Control patients who were adjusted for age, gender, and blood pressure among outpatients were enrolled ( N = 110). UT, ET, initial upstroke time (iUT), and half rise time of upstroke (1/2 hrUT) were evaluated correlations between mean pressure gradient (mPG) among AS patients. Results iUT and 1/2 hrUT have significant correlations with mPG among AS patients (iUT: R = 0.50, 95% CI = 0.29–0.67, p < 0.0001; 1/2 hrUT: R = 0.41, 95% CI = 0.19–0.60, p < 0.001), whereas UT and ET did not. Multivariate logistic regression analysis showed area under curve (AUC) of iUT and 1/2 hrUT were higher than UT and ET to predict mPG >40 mmHg (AUC: iUT vs 1/2 hrUT vs UT vs ET = 0.90 vs 0.89 vs 0.69 vs 0.77). Conclusion The severity of AS appeared strongly in the first half of the BPW upstroke. iUT and 1/2 hrUT may be a simple and useful screening test to assess the severity of AS.

Introduction Acute, gravity-induced blood pressure (BP) changes during head-up tilt may generate concomitant variations in carotid-femoral pulse wave velocity (cf-PWV). We aimed to separate the pressure-dependent and -independent components of cf-PWV changes observed during head-up tilt. Methods 30 healthy individuals (age 48 ± 18 years (mean ± SD), 38% males, BP 130/74 ± 12/8 mmHg) underwent head-up passive tilting at a = 0°, 30°, and 60°. BP was taken at the upper arm, constantly kept at heart level. Aortic BP was reconstructed from radial tonometry (SphygmoCor). Stiffness index b0 was estimated at 0°. 1 Assumptions: [ 1 ] from MRI2, the effective cf-PWV travel distance (ETD, 80% of straight carotid-to-femoral distance) begins at heart level; [ 2 ] the change in DBP along the aorta is predictable from the hydrostatic pressure gradient (0.73 mmHg/cm) 3; [ 3 ] cf-PWV and hydrostatic pressure relate linearly, hence predicted cf-PWV can be calculated as the average of aortic (PWVaorta, using b0 and aortic DBP) and femoral (PWVfem, using b0 and femoral DBP, corresponding to aortic DBP + (ETD × sin(a) * 0.73)) PWVs. Results Both young (24–48 years) and old (48–82 years) individuals showed increasing trends for peripheral SBP, DBP, PP, and central DBP with tilting; central SBP remained unchanged. Heart rate (HR) and cf-PWV increased with body tilt in both groups (Figure, left). b0 linearly correlated with age ( R = 0.70, p < 0.01). After adjustment for HR4, observed-vs-predicted cf-PWV exponentially increased as a function of age ( R 2 = 0.38, p < 0.01 for quadratic equation, p = 0.04, vs. linear; Figure, right). Conclusion With aging, the acute relationship between BP and cf-PWV becomes progressively nonlinear.