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Purpose/Background/Objectives: According to reservoir-wave theory, excess pressure (XSP) is analogous to flow and related to excess cardiac workload. In end-stage renal disease (ESRD) patients, we have shown that XSPI is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). Recently AVF has been proposed treatment for treatment of resistant hypertension. However, this benefit may be mitigated through an increase in cardiac output. Therefore, we examine whether XSPI increases after creation of an AVF in ESRD patients. Methods: Hemodynamic assessments were performed within 1 month before and 6 months after creation of AVF in ESRD patients. Carotid pressure waves were recorded using arterial tonometry, calibrated using brachial diastolic and mean arterial pressure. Using pressure only approach, reservoir-wave analysis was used to derive reservoir pressure (RP), XSP and their integrals (RPI, XSPI). Results: 38 patients (63% male, mean age 59 ± 15 years) were assessed 3.9 ± 1.2 months Post-AVF. Carotid RP decreased slightly (115 ± 18 vs 109 ± 24, p = 0.060), due to the reduction of diastolic BP (79 ± 10 vs 73 ± 12 mm Hg, p = 0.003). While, carotid systolic BP (123 ± 20 vs 119 ± 27 mm Hg, p = 0.380) remained unchanged, XSP and XSPI increased (XSP: 14 [12–19] to 17 [12–22] mmHg, p = 0.031; XSPI: 275 [212–335] to 334 [241–349] kPa.s, p = 0.015). Conclusion: While AVF creation reduced diastolic BP, it resulted in higher XSPI, which has been associated with increased mortality. Therefore, the long-term efficacy of AVF in reducing clinical outcomes should be specifically addressed.

Purpose/Background/Objective: According to reservoir-wave approach (RWA) arterial pressure is the sum of a reservoir pressure (RP) accounting for dynamic storage and release of blood from arteries, and an excess pressure (XSP) analogous to flow. RP is the minimal left ventricular work required to generate aortic flow, while XSP corresponds to surplus cardiac workload. We have previously shown that kidney transplantation (KTx) improves aortic stiffness [1], however, by adding renal vessels to existing vascular network, KTx may increase cardiac output. Thus, we aimed to examine whether XSP increases after KTx. Methods: Before and 3 months after KTx, carotid pressure waves were recorded using arterial tonometry, calibrated using brachial diastolic and mean blood pressure. Using pressure only approach, reservoir-wave analysis was used to derive RP, XSP and their integrals (RPI, XSPI). RWA parameters were compared with Wilcoxon non-parametric test using SPSS 26.0. Results: 75 patients (69% male, mean age 51 ± 13 years) were assessed. Three months after KTx, both carotid RP (121.2 ± 20.7 vs 103.5 ± 15.7, p < 0.001) and RPI (11192.52 ± 2763.11 vs 9531 ± 1978, p < 0.001) decreased significantly, but carotid XSP and XSPI remained unchanged. Carotid systolic (131.0 ± 23.2 vs 114.1 ± 15.5, p < 0.001) and diastolic (83.4 ± 11.9 vs 72.8 ± 9.93, p < 0.001) blood pressures were also reduced. Conclusion: KTx decreased reservoir pressure, suggesting a decrease in minimal cardiac workload. However, we did not see an increase in excess pressure or its integral, suggesting that addition of a donor renal artery does not significantly alter cardiac outflow and excess workload 3 months after KTx.

Background: Estimating aortic blood pressure (BP) non-invasively requires peripheral waveform calibration using cuff systolic (SBP) and diastolic (DBP). Accuracy of estimated aortic BP has never been determined when peripheral waveforms are precision calibrated using peripheral intra-arterial SBP/DBP. This is relevant to understanding the best methods to estimate aortic BP accurately and was the aim of this study. We also determined how other calibrations influence estimated aortic BP accuracy. Methods: Ascending aortic, brachial and radial artery intra-arterial BP was measured among 104 patients (61.8±10 years, 66% male) undergoing coronary angiography. Intra- arterial aortic SBP was compared with estimated aortic SBP by generalised transfer function (SphygmoCor) using: (1) intra-arterial brachial pressure waveforms calibrated with intra-arterial brachial SBP/DBP; (2) intra-arterial radial pressure waveforms calibrated with intra-arterial brachial SBP/DBP and (3) radial SBP/DBP and; (4) intra-arterial aortic mean arterial pressure (MAP)/DBP. Results: All intra-arterial SBP/DBP peripheral waveform calibrations significantly underestimated intra-arterial aortic SBP ((1) −4.5±7.0 mmHg; (2) −8.8±8.0 mmHg and (3) −5.4±7.6 mmHg; p < 0.0001 all). Conversely, intra-arterial aortic MAP/DBP calibration (4) accurately estimated aortic SBP (0.03±4.6 mmHg, p = 0.95). Underestimation of intra-arterial aortic SBP was related to lower aortic-to-brachial SBP amplification (r > 0.25, p < 0.009 all calibrations). Conclusion: Even when using accurate (intra-arterial) SBP/DBP for precision peripheral waveform calibration, aortic SBP was significantly underestimated. Intra-arterial aortic MAP/DBP was the most accurate calibration, but is not feasible for non-invasive use. These findings highlight the need for improved ways to accurately estimate aortic SBP.

Accurate measurement of blood pressure (BP) is a critical goal for appropriate diagnosis and management of high BP. The measurement reference standard is brachial cuff BP, but recent large-scale meta-analyses show major deficiencies in the accuracy of this method. Indeed, irrespective of cuff technique (e.g. mercury auscultation or oscillometry) brachial cuff BP measures lack precision for representing the BP within both the brachial artery and the central aorta. These data clearly indicate the need to refine and improve methods to measure BP accurately, whether at the brachial or central aortic level, with preference towards the latter as the best representation of pressure loading experienced by the organs at risk from hypertension. The current focus to improve measurement of central aortic BP is on better calibration methods, with mean arterial pressure (MAP) and diastolic BP (DBP) proposed as the best solution. However, the ability to accurately estimate central aortic BP using this calibration method appears to be device-specific and related to the capacity of different devices to accurately measure MAP/DBP using conventional cuff BP. Beyond this, even if we can accurately measure MAP/DBP using non-invasive cuff methods, this does not necessarily provide a final solution because characteristic waveform features and the level of systolic BP amplification still influence accuracy. Thus, altogether, manufacturers of devices purporting to measure central aortic BP need to provide robust evidence about accuracy performance; preferably according to ARTERY Society recommendations.

Introduction: Aortic stiffness predicts cardiovascular mortality but is limited as a risk marker because it is dependent on blood pressure (BP). A potential solution is provided from the ratio of aortic-to-brachial artery stiffness (ab-ratio), which is purported to be a BP-independent risk marker among patients with renal dysfunction (RD). We sought to determine the BP-independence of the ab-ratio in patients with disease (including RD) and healthy populations. Methods: The ab-ratio (aortic/brachial pulse wave velocity; PWV) and mean arterial pressure (MAP) were recorded in patients with RD (n = 119, aged 65 ± 7 years), hypertension (n = 140, aged 62 ± 9 years), type 2 diabetes (n = 77, aged 60 ± 9 years) and healthy individuals (n = 99, aged 51 ± 8 years). Multiple-regression analysis was performed to test the independent association of MAP with the ab-ratio adjusted for age, sex, body-mass index and blood glucose. Results: There was no significant relationship between the ab-ratio and MAP in patients with RD (β = 0.002, 95% CI 0.002, 0.006, p = 0.34), hypertension (β = 0.001, 95% CI 0.003, 0.006, p = 0.62) or diabetes (β = 0.006, 95% CI 0.002, 0.014, p = 0.11). However, in healthy individuals the ab-ratio was significantly and independently associated with MAP (β = 0.008, 95% CI 0.003, 0.013, p = 0.003). There was a significant difference in the strength of association between the ab-ratio and MAP between patients with disease and healthy individuals (z > 2.2, p < 0.05 for all). Conclusion: Although ab-ratio is purported to be a risk marker that is independent of BP, this was observed only among patient populations, and not in healthy individuals. Therefore, the ab-ratio is influenced by disease status and may have restricted value as a BP-independent risk marker.

Brachial cuff blood pressure (BP) is clinically important, but may be an inaccurate substitute for central BP. Many non-invasive devices have been developed that purport to estimate central BP from peripheral artery sites, yet with no standardized guidelines; the accuracy testing of these new devices has not been undertaken in a uniform fashion with comparable protocols. This is an abridged paper describing the recommendations reached by an international task force convened to identify issues that need to be addressed and reach consensus relating to methods for assessing and reporting the accuracy (validation) of central BP devices. The recommendations are endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society, as well as the European Society of Hypertension (ESH) Working Group on Arterial Structure and Function, and the ESH Working Group on Blood Pressure Monitoring and Cardiovascular Variability. Researchers interested in validating central BP monitors should read the full version of the statement.

Background: Aortic reservoir function is associated with increased cardiovascular events. Patients with chronic kidney disease in need of dialysis have increased aortic stiffness and reversal of the aortic-to-brachial stiffness gradient, which could impair aortic reservoir function. The aim of this study was to determine the relationship between the aortic-to-brachial stiffness gradient and aortic reservoir function. Methods: Among 310 patients with chronic kidney disease on dialysis, aortic and brachial stiffness were measured by pulse wave velocity (PWV), with the aortic-to-brachial stiffness gradient calculated by the ratio of aortic and brachial PWV (PWV ratio). Aortic reservoir function was measured by radial tonometry-derived reservoir pressure (RP) and excess pressure (XSP) integrals. Results: RP was significantly and positively associated with PWV ratio (Standardized β=0.168 p

Background: There is anecdotal belief that clinic blood pressure (BP) drops over consecutive measurements. This has led to guideline recommendations to discard the first BP reading, or take only one reading if systolic BP (SBP)

The original purpose for recording brachial blood pressure (BP) more than 100 years ago was to estimate central (aortic) BP. While high brachial BP is an important cardiovascular risk factor, it is clear that major differences in central systolic BP (SBP; e.g. >30 mmHg) can occur among people with similar brachial SBP. It is also proven that central SBP responses to antihypertensive therapy can differ substantially from brachial SBP responses, such that true treatment effects cannot be gauged from conventional brachial BP. Importantly, assessment of central BP results in: 1) improved predictive accuracy of future cardiovascular events beyond brachial BP and other cardiovascular risk factors; 2) superior diagnostic accuracy over brachial BP and; 3) different patient management than usual care guided by brachial BP. Collectively, the above illustrates that central BP is a better cardiovascular risk biomarker than brachial BP. As with all medical advances there are areas of research need and international consensus is required on issues such as standardization of techniques. However, central BP can now be accurately estimated (with appropriate waveform calibration) using brachial cuff methods in an approach that is familiar to clinicians, acceptable to patients and amenable to widespread use. In other words, this modern BP technique can finally satisfy the original purpose for measuring central aortic BP as intended more than 100 years ago. Although the tipping point towards routine use is yet to be reached, the body of evidence continues to favour the view that central BP should be used in clinical practice.

Background: Augmentation index (AIx) is regarded as a marker of systemic arterial stiffness. Patients with type 2 diabetes mellitus (T2DM) have increased arterial stiffness, but not AIx, which suggests that mechanisms contributing to AIx in T2DM may differ from healthy individuals and be unrelated to arterial stiffness. The aim of this study was to examine the cardiovascular and clinical determinates of AIx (including arterial stiffness) in patients with T2DM compared with controls. Methods: Clinical characteristics and haemodynamic variables (including aortic and brachial pulse wave velocity [stiffness], cardiac output, systemic vascular resistance and heart rate) and AIx (by radial tonometry) were recorded in 53 T2DM and 53 matched controls. Correlates of AIx unadjusted for heart rate were assessed by uni- and multi-variable analysis. Results: Compared with controls, T2DM patients had significantly higher aortic stiffness (7.6 ± 1.6 vs 6.7 ± 1.9 m/s p = 0.016), cardiac output, heart rate, brachial and central BP; lower brachial stiffness and systemic vascular resistance, but no significant difference in AIx (27 ± 9 vs 24 ± 11% p = 0.184). AIx (adjusted or unadjusted) was not significantly related to aortic or brachial stiffness in either group (p > 0.198 all). Independent predictors of AIx in T2DM patients were height and heart rate, whereas in controls, AIx was independently related to height. Conclusions: Determinants of AIx in patients with T2DM differ from healthy individuals. Moreover, AIx is not significantly related to regional large artery stiffness and should not be regarded as indicative of systemic arterial stiffness.

Background: Evaluation of cardiac output (CO) and other haemodynamic parameters may aid in understanding factors involved in arterial blood pressure (BP) changes with exercise and postural stress. Impedance cardiography offers a rapid, non-invasive means to acquire this information, however there is limited data assessing the reproducibility of this technique during haemodynamic perturbation. This study aimed to assess reproducibility of CO and other haemodynamic parameters derived from impedance cardiography during exercise and in different postures. Methods: 51 participants (mean age 57 ± 9 years, 57% male) had CO and other haemodynamic variables (including end diastolic volume, left ventricular work, ejection fraction and systemic vascular resistance) measured via impedance cardiography (Physio Flow) at two visits separated by 12 ± 7 days. Measures were recorded at rest in three postures (supine, seated and standing), during upright cycle ergometry at a fixed workload (40 W), and also during steady state exercise at an intensity of 60% and 70% of age-predicted maximum heart rate (HRmax). Results: CO reproducibility was assessed over a wide range (5.27 ± 1.00–12.09 ± 2.02 l/min). There was good agreement between CO measured at each visit in all postures and exercise conditions (intra-class correlation coefficient [ICC] range 0.729–0.888, P < 0.05 for all) with a small difference between visits (mean difference 0.06 ± 1.10 l/min). All other haemodynamic variables showed good agreement between visits (ICC range 0.714–0.970, P < 0.05 for all). Conclusions: Non-invasive impedance cardiography provides an acceptably reproducible means to evaluate CO and other haemodynamic variables relevant to arterial BP regulation during different postures and light-to-moderate intensity exercise.

Background: Estimated central blood pressure (BP) predicts cardiovascular mortality independent of brachial BP, but whether central BP may be useful in clinical practice is unknown. This study aimed to test the value of central BP as a management tool for physicians treating patients with essential hypertension. Methods: Patients with hypertension (n=84; 61±8 years) were randomised to 12 months of treatment decisions guided by usual care (UC, n=39) or, in addition, by central BP (CBP, n=45; based on age and gender-specific normal central systolic BP [SBP] values). Titration recommendations were provided to each patient’s general practitioner, as well as the patient themselves. Relevant clinical information (eg left ventricular [LV] mass, blood biochemistry and symptoms) were considered when making titration recommendations in all patients. Central BP was estimated by SphygmoCor 8.0. Primary outcome measures were; 1) change in LV mass 2) use of medication and 3) quality of life. We hypothesized that there will be no significant difference in LV mass between groups (study powered for equivalence). However, it was expected that there will be significantly less use of medication and improved quality of life in the CBP group because more appropriate titration choices will be made to maintain normal central SBP. Results: Baseline LV mass index (CBP, 27.6±5.7 v±UC, 29.7±5.9g/m2.7), brachial SBP (CBP, 130±14 v UC 130±14 mmHg) and central SBP (CBP, 118±13 v UC 118±15 mmHg) were similar between groups (P>0.05 for all). However, in the CBP group, 33% (n=15) received a recommendation to reduce medication, whilst there were 3% (n=1) in the UC group (P=0.001). Moreover, 8 CBP patients were recommended to cease antihypertensive medication but maintained normal BP, indicating that they may have been incorrectly diagnosed with hypertension and unnecessarily taking medication based on brachial BP assessments. Conclusion: Therapeutic decisions based on CBP are different from those based on standard BP. Follow up data and final results (N=312) are expected in 2011.

Numerous studies in healthy individuals with normal office blood pressure (BP) have shown that a hypertensive response to exercise predicts the future onset of hypertension, as well as cardiovascular morbidity and mortality, independent of office BP. The mechanisms underlying the predictive value of exercise BP are incompletely understood. However, it has been proposed that the additional cardiovascular stress imposed by exercise may unmask the presence of concealed hypertension. A new non-invasive method of exercise arterial pressure waveform analysis (and central BP estimation) may provide additional clinical information, as well as insight into mechanisms, beyond the BP obtained by traditional upper arm cuff methods.