Aortic Wave Research Articles

Biological sex influences aortic hemodynamic responses to maximal exercise in healthy older adults

Aging is associated with stiffening of large elastic arteries resulting in early wave reflection, which increases aortic systolic blood pressure (BP) and left ventricular afterload. These age-related alterations predispose older adults to cardiovascular disease (CVD). Exercise is recommended for reducing CVD risk in older adults, but the acute aortic hemodynamic responses to exercise have not been fully described. We have previously shown that exercise intensity influences acute aortic hemodynamic responses to submaximal exercise in older adults, however, the responses to maximal exercise have not been investigated. In young adults, the influence of maximal exercise on aortic wave characteristics is impacted by sex. Therefore, the objective of this study was to investigate the acute effects of maximal exercise on aortic wave characteristics in healthy older adults and to test the hypothesis that the acute aortic hemodynamic responses to maximal exercise will be influenced by sex. Twenty-two older men and postmenopausal women (66.4±1.0 yrs, mean±SE, 11M/11W) completed the study. Research participants were free of major clinical disease, were not using hormone replacement therapy or participating in endurance exercise training. Aortic wave characteristics were assessed using wave separation analysis (SphygmoCor XCEL) before and immediately after maximal exercise, based on a modified Balke treadmill test. We found that wave reflection, assessed as augmentation index (AIx) at heart rate of 75 bpm (AIx@75), was not different between older men and women prior to maximal exercise ( P=0.2). Following maximal exercise, AIx@75 increased in older men (21.1±2.6 vs. 28.2±2.4 %, pre- vs. post-exercise, P=0.02) and women (27.4±3.3 vs. 33.9±3.2 %, P=0.03), but the response was not influenced by sex ( P=0.9 for sex × time interaction). Aortic systolic and diastolic BP (AoSBP and AoDBP) were not different in older men compared with women prior to maximal exercise ( P≥0.4). In response to maximal exercise, AoSBP and AoDBP significantly increased in older men (AoSBP: 113±3 vs. 118±2 mmHg, P=0.01 and AoDBP: 75±2 vs. 80±2 mmHg, P<0.01), but not in women (AoSBP: 113±4 vs. 113±4 mmHg, P=0.9; P=0.04 for sex × time interaction and AoDBP: 73±2 vs. 74±2 mmHg, P=0.054; P=0.02 for sex × time interaction). In conclusion, sex influences the aortic BP response to maximal exercise, but not the wave reflection response in older adults. This finding suggests that left ventricular afterload remains elevated during recovery from maximal exercise in older men which may differentially expose them to a transient risk of experiencing a cardiac complication. This work was supported by National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Wave reflection quantification analysis and personalized flow wave estimation based on the central aortic pressure waveform.

Pulse wave reflections reflect cardiac afterload and perfusion, which yield valid indicators for monitoring cardiovascular status. Accurate quantification of pressure wave reflections requires the measurement of aortic flow wave. However, direct flow measurement involves extra equipment and well-trained operator. In this study, the personalized aortic flow waveform was estimated from the individual central aortic pressure waveform (CAPW) based on pressure-flow relations. The separated forward and backward pressure waves were used to calculate wave reflection indices such as reflection index (RI) and reflection magnitude (RM), as well as the central aortic pulse transit time (PTT). The effectiveness and feasibility of the method were validated by a set of clinical data (13 participants) and the Nektar1D Pulse Wave Database (4,374 subjects). The performance of the proposed personalized flow waveform method was compared with the traditional triangular flow waveform method and the recently proposed lognormal flow waveform method by statistical analyses. Results show that the root mean square error calculated by the personalized flow waveform approach is smaller than that of the typical triangular and lognormal flow methods, and the correlation coefficient with the measured flow waveform is higher. The estimated personalized flow waveform based on the characteristics of the CAPW can estimate wave reflection indices more accurately than the other two methods. The proposed personalized flow waveform method can be potentially used as a convenient alternative for the measurement of aortic flow waveform.

The influence of electrocardiogram-gated computed tomography reconstruction into 8 or 10 cardiac phases on cardiac-pulsatility-induced motion quantification of stent grafts in the aorta

ObjectiveThe goal of this study was to determine to what extent aortic stent graft motion quantification is comparable between electrocardiogram (ECG)-gated computed tomography (CT) scans with reconstructions into 8 and 10 cardiac phases on CT scanners from two different vendors. MethodsAn experimental setup that induces motion of an aortic stent graft, according to a predefined aortic blood pressure wave, was placed in two CT scanners of different vendors. The stent graft motion was captured using an ECG-gated CT technique and quantified using dedicated analysis algorithms. The calculated motion amplitudes and total traveled path lengths of stent segmentations were compared between scans reconstructed into 8 and 10 phases and between the scanners, after validation with sensor measurements and repeated measurements. ResultsNo difference in motion amplitudes in z-direction (craniocaudal direction) was observed between the reconstructions into 8 and 10 phases (0.02 mm; 95% confidence interval [CI], –0.01 to 0.05 mm; P = .358). The z-amplitudes differed by 0.04 mm (95% CI, 0.01-0.07 mm; P = .003) between the different CT scanners. Path lengths differed 0.07 mm (95% CI, 0.01-to 0.13 mm; P = .013) between the reconstructions into 8 and 10 phases and 0.13 mm (95% CI, 0.06-0.17 mm; P < .001) between the different scanners. ConclusionsThe motion amplitudes can accurately be compared between 8 and 10 phases and between the two scanners, without differences larger than the voxel size of 0.3 × 0.3 × 0.5 mm. Clinical motion analysis results of different ECG-gated CT scans and CT scanners can be compared up to the accuracy of the CT scan.

146 AORTIC ACCELERATION TIME/EJECTION TIME RATIO AND BI-VENTRICULAR PERFORMANCE IN SEVERE AORTIC STENOSIS

Abstract Introduction Echocardiographic evaluation of severe aortic stenosis (SAS) is is important to guide the therapeutic approach but often challenging. Recent studies have demonstrated that the ratio of acceleration time/ejection time (AT/ET) is a simple and reproducible echocardiographic parameter that integrates aortic stenosis severity evaluation and adds information on patient's prognosis. Aim The aim of the study is to investigate the role of the ratio of acceleration time (AT) and ejection time (ET) and its major determinants in severe aortic stenosis . Methods Consecutive echocardiograms of patients with severe AS referred to our center were analyzed offline using Tomtec Arena (Tomtec, Untershlei heim, Germany). AT was measured from the start of the CW Doppler aortic wave, to the peak of the aortic jet. ET was calculated from the same starting point, to the end of the CW Doppler aortic wave. Results A total of 135 patients with severe aortic stenosis formed the study cohort: patients with AT/ET below the median value of 0.35 (vs. higher) presented lower LVEDV (60 vs. 71 ml/mq; p 0.014), left ventricle mass index (116 vs 130 g/m2; p 0.035) and higher LVEF (58 vs 50%; p 0.001), GLS (- 14 vs - 12%; p 0.025), FAC (46 vs 41%; p 0.01), SBP (141 vs 131 mmHg; p 0.003). At multivariable analysis the major AT/ET determinants were systolic arterial pressure and bi-ventricular performance parameters. The following nested regression were created: the first inclusive of systolic arterial pressure (PAS), fractional area change (FAC), left ventricular mass indexed (LVMI), global longitudinal strain (GLS) (R2=0.48 p&amp;lt;0.001), the second inclusive of PAS, FAC, LVMI, GLS, AVA (R2=0.57, p&amp;lt;0.001), the third inclusive of PAS, FAC, LVMI, LVEF, AVA (R2=0.64, p&amp;lt;0.001). Conclusion Our study demonstrated that AT/ET ratio relates quite well with LV performance in the context of SAS. An high ACT/ET ratio tends to be associated with a poor bi-ventricular performance and LV negative remodeling. It is possible that this simple parameter in the next future could help in staging the disease among SAS patients.

Abstract 13430: Arterial Health After Preeclampsia: Role of Chronic Hypertension

Introduction: Preeclampsia (PE) is associated with an increased cardiovascular (CV) risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). To improve our understanding of CV risk after PE, we evaluated the contribution of persistent HTN on arterial health. Methods: We recruited 40 women with PE history and 40 age-matched women with normotensive pregnancies (6 months - 6 years post-partum). We comprehensively evaluated measures of arterial health and hemodynamics with validated technique combining applanation tonometry and transthoracic echocardiography. We compared 3 groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls. Associations of PE-HTN with arterial health measures were assessed with multivariable linear regression adjusted for age, BSA, heart rate, diabetes, smoking history, serum creatinine and parity. Results: Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, number of pregnancies was 2.4 ± 1.4, and time since last pregnancy was 2.6 ± 1.2 years, and not different across the 3 groups (P&lt;0.05 for each). Results of the multivariable linear regression models are summarized in the Figure, demonstrating that women with PE-HTN had significantly higher aortic stiffness, wave reflections, pulsatile and steady arterial load than controls. Among women with previous PE whose blood pressure normalized postpartum, arterial stiffness, wave reflections and steady arterial load were also worse compared to controls, albeit with smaller effect size (p&lt;0.05). Conclusions: This is the first study to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with CV events in the population, women with PE-HTN may represent a higher risk subgroup who could benefit from targeted primary prevention strategies.

Abstract 14300: Arterial Stiffness is Associated With Intermediate-Term Home Blood Pressure Variability: The Electronic Framingham Heart Study

Introduction: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies examined associations between arterial stiffness and digital home BPV over an intermediate time span. Objective: We investigated if antecedent arterial stiffness was associated with home BPV among participants in the electronic Framingham Heart Study (eFHS). We hypothesize that higher arterial stiffness predicts higher intermediate-term home BPV over one-year follow-up. Methods: At an FHS research exam (2016-2019), participants underwent arterial tonometry to acquire mean arterial pressure (MAP) and measures of arterial stiffness (carotid femoral pulse wave velocity, CFPWV; forward pressure wave amplitude, FWA) and wave reflection (reflection coefficient, RC). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly. Participants with &lt; 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with home average real variability (ARV) of systolic (SBP) and diastolic (DBP) BP adjusting for covariates. We obtained ARV as an average of the absolute differences of consecutive BP measurements. ARV considers not only the dispersion of the BP readings around the mean, but also the order of BP readings. We used p&lt;0.05 for significance. Results: Among 857 eFHS participants (mean age 54 years, 59% women, mean BP 119/76, 47% hypertension, mean ARV of DBP 5.50, mean ARV of SBP 8.61), higher FWA and RC were associated with higher ARV of SBP ( Table ). Higher CFPWV was associated with lower ARV of DBP ( Table ). Conclusion: In eFHS, higher FWA and RC were associated with higher intermediate-term home BPV of SBP while higher CFPWV was associated with blunted BPV of DBP. Our findings suggest that higher aortic stiffness and wave reflection may affect day-to-day modulation of blood pressure in a home-based setting.

Relationship between Pulmonary Regurgitation and Ventriculo-Arterial Interactions in Patients with Post-Early Repair of Tetralogy of Fallot: Insights from Wave-Intensity Analysis.

This study aimed to investigate the effect of pulmonary regurgitation (PR) on left ventricular ventriculo–arterial (VA) coupling in patients with repaired tetralogy of Fallot (ToF). It was hypothesised that increasing PR severity results in a smaller forward compression wave (FCW) peak in the aortic wave intensity, because of right-to-left ventricular interactions. The use of cardiovascular magnetic resonance (CMR)-derived wave-intensity analysis provided a non-invasive comparison between patients with varying PR degrees. A total of n = 201 patients were studied and both hemodynamic and wave-intensity data were compared. Wave-intensity peaks and areas of the forward compression and forward expansion waves were calculated as surrogates of ventricular function. Any extent of PR resulted in a significant reduction in the FCW peak. A correlation was found between aortic distensibility and the FCW peak, suggesting unfavourable (VA) coupling in patients that also present stiffer ascending aortas. Data suggest that VA coupling is affected by increased impedance.

Menopause influences aortic pulse pressure and pressure wave responses to metaboreflex activation in women.

Postmenopausal women (post-MW) have greater risk of heart failure due to aortic pulsatile overload on the left ventricle associated with increased backward wave pressure (Pb). Post-MW have exaggerated peripheral blood pressure (BP) response to exercise mediated by metaboreflex (postexercise muscle ischemia [PEMI]) overactivation. Increased forward wave pressure (Pf) and Pb are determinants of aortic pulse pressure (PP) during isometric handgrip exercis (IHG) in young adults. We hypothesized that aortic PP and pressure wave responses to PEMI are augmented in nonhypertensive post-MW compared with premenopausal women (pre-MW). Aortic BP, Pf, Pb, and reflection magnitude were assessed at rest and during IHG and PEMI by applanation tonometry in 15 pre-MW and 16 post-MW. Aortic systolic BP during PEMI similarly increased in both groups. The increase in diastolic BP was lower in post-MW (post-MW Δ6 ± 2 vs pre-MW Δ11 ± 2 mm Hg, P < 0.05). Aortic PP (post-MW Δ8 ± 2 vs pre-MW Δ3 ± 2), Pf (post-MW Δ6 ± 1 vs pre-MW Δ0 ± 1), and Pb (post-MW Δ5 ± 1 vs pre-MW Δ2 ± 1) augmented during PEMI in post-MW ( P < 0.05 for all), but not in pre-MW. Reflection magnitude increased during PEMI only in pre-MW (pre-MW Δ7 ± 2 vs post-MW Δ-1 ± 2, P < 0.05) due to concurrent increases in Pf and Pb in post-MW. Even in nonhypertensive postmenopausal women, increases in Pf and Pb and decrease in aortic DBP are important factors that contribute to the augmented aortic PP response to PEMI.

Aortic pressure-only wave separation analysis in adolescents: accuracy and associations with left ventricular mass index.

Early-life exposure to high blood pressure (BP) is associated with cardiovascular target organ damage but not all BP-related risk is attributable to systolic and diastolic BP alone. In adolescence, aortic wave separation (WS) parameters are associated with increased left ventricular mass index (LVMI) but this approach is limited by the requirement for aortic flow measurements. Several methods for estimating the aortic flow waveform from pressure waveforms have emerged, but their accuracy and associations with LVMI have never been tested in adolescents, which was the aim of our study. Carotid pressure waveforms were acquired by tonometry from 58 adolescents (age 16 ± 1.5 years, 59% female). Measured (aortic) flow and LVMI were acquired via 2D echocardiography. Three pressure-only approximations of aortic flow were synthesized, including triangular, excess, and individualized-physiologic flow. A 4th aortic flow (average flow) was approximated from the average of all 58 measured flow waveforms. Forward (Pf) and backward (Pb) pressure and reflection magnitude (Rm) were derived from WS analysis. The individualized-physiologic flow produced the best approximations of Pf (mean difference ± SD, -0.15 ± 2.38 mmHg), Pb (0.14 ± 0.25 mmHg), and Rm (0.01 ± 0.02 mmHg). Pf derived using measured, individualized-physiologic, and average flow, was similarly associated with LVMI adjusting for age, brachial systolic BP, cardiac output, and BMI (P ≤ 0.03 all). Pb derived using all flow waveforms was associated with LVMI and all associations yielded similar effect estimates. Of the estimated flow waveforms, individualized-physiologic flow yielded the best approximation of WS parameters and may provide important physiological and clinical insight among adolescents.

Surface Recording of Aortic Pressure Wave from Aortic Area of Auscultation in Women with Hypertension: A New Idea to Indirectly Monitor Aortic Pressure

Objectives: Blood pressure recording from the peripheral artery is subject to variations. While blood pressure is said to a modifiable risk factor for many cardiovascular and neurological diseases, the diagnosis of hypertension using Sphygmomanometry must be complemented with other tests to find central blood pressures. A newer, non-invasive method to indirectly record the aortic pressures is required. Aim of the study is to record surface aortic pressure waves (SAP) from aortic area of auscultation during breath holding and to compare the wave characteristics in hypertensive and normotensive women at rest and after mild exercise. Materials and Methods: 128 women were recruited in the study. Piezoelectric sensor placed in the aortic area was used for getting the SAP waves during breath holding for 30 seconds. ECG was taken to show temporal association of these waves to R waves. Mean arterial pressures from arm (map-a) and from SAP waves (map-s) were calculated. Powerlab 8/35 and Labchart Pro software by AD Instruments were used in the study. Results: R waves were followed by the SAP waves by about 31±2.2 ms at rest and 11±2.4 ms after mild exercise in all subjects. In hypertensive women, the map-s values were significantly (p &lt; 0.05) lower in magnitude than in normotensive women both at rest and after exercise. There was no significant correlation between the map-a and map-s in any of the groups at rest or after exercise. Conclusion: This new method, with some refinement could prove as a better alternative to blood pressure recording.

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

BackgroundWaveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown.Methods and ResultsWe analyzed participants aged between 40 and 69 from the population‐based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10‐year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c‐index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow‐up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores.ConclusionsSome waveform parameters are independently associated with MACEs in a population‐based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Impact Of Age On Aortic Pressure And Pressure Waves Responses To Metaboreflex Activation In Women

INTRODUCTION: Aging and hypertension are related to exaggerated peripheral blood pressure (BP) responses to exercise and metaboreflex activation (post-exercise muscle ischemia, PEMI). Postmenopausal (POST) women have greater risk of heart failure with preserved ejection fraction due to increased aortic pulsatile load on the left ventricle induced by increased systolic BP (SBP) and decreased diastolic BP (DBP) at rest. Age-related aortic stiffening augments pressures of the forward (Pf) and the reflected wave (Pb) traveling from peripheral arteries to the aorta. Increases in Pf and Pb contribute to elevated aortic SBP and pulse pressure (PP) responses to exercise, increasing the risk for cardiovascular events. However, the influence of Pf and Pb on aortic pulsatile load during isometric handgrip (IHG) and PEMI in normotensive premenopausal (PRE) and POST women have not been examined. PURPOSE: To investigate the effect of age on aortic BP, Pf, and Pb during IHG and PEMI in normotensive PRE and POST women. METHODS: Fifteen PRE (age: 24 ± 1 years) and 16 POST women (age: 59 ± 1 years) participated in this study. Brachial BP was obtained using an automated device and radial arterial tonometry was used to capture aortic waveforms to estimate aortic BP and pressure waves at rest, during a 2-min IHG at 30% of maximal force, and during a 3-min PEMI. RESULTS: BP responses to IHG were similar in both groups. Brachial PP (POST: Δ9 ± 1 mmHg vs PRE: Δ0 ± 2 mmHg, P < 0.01), aortic PP (POST: Δ8 ± 1 mmHg vs PRE: Δ3 ± 2 mmHg, P = 0.03), Pf (POST: Δ6 ± 1 mmHg vs PRE: Δ0 ± 1 mmHg, P < 0.01), and Pb (POST: Δ5 ± 1 mmHg vs PRE: Δ2 ± 1 mmHg, P = 0.02) responses to PEMI were significantly increased in POST compared to PRE women. Aortic DBP (POST: Δ6 ± 1 mmHg vs PRE: Δ11 ± 2 mmHg, P = 0.04) responses to PEMI was significantly lower in POST than PRE women. Brachial and aortic SBP significantly (P < 0.001) increased during PEMI in both PRE and POST women, but there was no difference (P > 0.05) between groups. CONCLUSION: Normotensive POST women have augmented aortic PP response to PEMI compared to PRE women due to increases in pressure of the forward and backward waves and a decrease in DBP. Our findings suggest that the age-related increase in muscle metaboreflex activation does not induce a systolic overload and the increase in aortic PP is attributed to reduced DBP in normotensive POST women.

Cine magnetic resonance imaging sagittal plane, slow-motion postoperative. The countermovement of the upward systolic blood ejection of the left ventricle led to a downward impulse on the tightly coupled oesophagus. This impulse led to a considerable compression of the lumen and a deflection of the oesophagus backwards. Dorsal support for the oesophagus had been provided by the systolic aortic wave,

Cine magnetic resonance imaging sagittal plane, slow-motion postoperative. The countermovement of the upward systolic blood ejection of the left ventricle led to a downward impulse on the tightly coupled oesophagus. This impulse led to a considerable compression of the lumen and a deflection of the oesophagus backwards. Dorsal support for the oesophagus had been provided by the systolic aortic wave,

ARTERIAL HAEMODYNAMIC PARAMETERS LINKED TO ARTERIAL PULSATILITY, EXCESS WAVE PROPAGATION AND COGNITIVE FUNCTION

Objective: Hypertension is associated with the development of cognitive impairment and dementia in an ageing population. Aortic stiffness and alterations in central artery haemodynamics could intensify the penetration of excess wave energy into the cerebral circulation, damaging the microvasculature in addition to age-associated vascular changes. We aimed to determine whether haemodynamic parameters linked to arterial pulsatility and excess wave propagation was associated with cognitive function in a sample of normotensive and hypertensive individuals. Design and method: We studied 35 treatment-naïve patients with stage II/III hypertension (HT: 63.8 ± 7.4yrs, 19F, SBP 175.6 ± 16.8 mmHg) and 35 age-, sex- and body mass index-matched normotensive individuals (NT: SBP 127.2 ± 8.2 mmHg). Indices of excess pressure including excess pressure integral (INTXSP) and peak excess pressure (MAXXSP) were obtained by radial artery tonometry. Aortic forward compression wave intensity (FCWI) and aortic pulse wave velocity (aPWV) were estimated as proposed by Hughes et al (Front Physiol. 2020). A battery of cognitive examination tests was administered including Addenbrooke’s Cognitive Examination-III (ACE), Mini-Mental State Examination (MMSE), Trail making test part A (TMT-A) and B (TMT-B). Results: Both INTXSP (9.2 ± 2.7 vs 5.4 ± 1.2 mmHg s) and MAXXSP (54.1 ± 12.8 vs 33.4 ± 5.9 mmHg) were significantly higher in HT compared to NT (p &lt; 0.001). Additionally, FCWI [14.9 (12.0–20.0) vs 8.0 (6.8–9.3) x105 W/m2] and aPWV (7.2 ± 1.7 vs 4.5 ± 0.8 m/s) were significantly greater in HT compared with NT (p &lt; 0.001). Higher INTXSP was associated with poorer ACE (rs = -0.310, p = 0.009), longer TMT-A (r = 0.409, p &lt; 0.001) and TMT-B (r = 0.380, p = 0.001). Similarly, higher MAXXSP was associated with poorer ACE (rs = -0.343, p = 0.004), longer TMT-A (r = 0.397, p = 0.001) and TMT-B (r = 0.330, p = 0.006), and greater aPWV was associated with poorer ACE (rs = -0.331, p = 0.005), longer TMT-A (r = 0.397, p = 0.001) and TMT-B (r = 0.324, p = 0.007). Higher FCWI was associated with longer TMT-A (rs = 0.378, p = 0.002) and TMT-B (rs = 0.260, p = 0.038), and showed a trend to be associated with poorer ACE (rs = -0.238, p = 0.054). None of the haemodynamic indices was associated with MMSE. Conclusions: Haemodynamic parameters linked to excess arterial wave propagation are associated with poorer cognitive function. These observations reveal a potential mechanism linking hypertension and cognitive impairment, and reinforce the importance of blood pressure control to reduce cognitive impairment risk.

Feasibility of waveform separation of central aortic pressure pulse based on lognormal flow wave approximation

Wave reflections affect the aortic pressure and flow waves and may yield effective indices for monitoring cardiovascular health and disease. More accurate measures of wave reflection are obtainable after separation of aortic pressure waveform into its forward and backwards components. This paper presents a novel method for waveform separation of aortic pressure using a single pressure pulse measurement together with a lognormal flow wave approximation. The separated forward and backward waves were used to calculate the wave reflection parameters including reflection amplitude (RM) and reflection index (RI), and derive the aortic pulse transit time (PTT). The feasibility of the proposed method was verified using the central aortic pressure estimated from a measured radial pressure pulse by an aortic pulse analyzer and aortic flow waveform (39 data sets). Wave separation analysis (WSA) was assessed using the pressure and approximated flow waveforms based on two methods respectively, the proposed lognormal flow wave and the existing triangular flow wave. The results were compared with that of the measured flow wave. In time domain, for RM, RI, and PTT, the relations between the values calculated from the estimated flow and that from the measured flows can be characterized accurately by the linear regression models with the following coefficients of determination: R2 = 0.87 (RM), 0.86 (RI), 0.79 (PTT) using the lognormal flow; R2 = 0.84 (RM), 0.83 (RI), 0.77 (PTT) using the triangular flow. Agreement between reference and approximated values was increased when the approximated flow waveform was obtained using lognormal approximation rather than triangular estimation. The lognormal flow wave, a more physiological waveform, for approximating the flow improved the results of WSA in both time and frequency domains.

Sex Differences in Vascular Endothelial Function After Liver Transplant

INTRODUCTIONLiver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. Sex differences may be a significant determinant in the pathophysiology of CVD. However, sex‐differences in vascular dysfunction, an established precursor to CVD, have not been explored in LT recipients. The purpose of this study was to investigate the sex differences in vascular function and cardiometabolic risk‐factors to CVD among LT patients.METHODSConduit artery endothelial function was measured via flow‐mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 23 age‐matched LT patients (11 Male, 12 Female; Mean ± SEM: Age 55 ± 2 years). Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Novel plasma based cardiometabolic risk factors were assessed with nuclear magnetic resonance spectroscopy. Lipoprotein insulin resistance index (LPIR) was calculated as a weighted combination of concentrations and particle sizes of very low‐density, low‐density, and high‐density lipoproteins. Diabetes risk index (DRI) factors LPIR and branched‐chain amino acid levels to predict the risk of type 2 diabetes. Metabolic inflammation index (INFX) combines concentrations of the inflammation biomarker GlycA and high‐density lipoprotein particle subspecies.RESULTSMales had lower FMDBA than females (3.98 ± 0.63 vs 6.27 ± 0.43%, p &lt; 0.01). There were no sex differences in aortic systolic pressure (Male vs Female; 129 ± 3 vs 118 ± 5 mmHg, p = 0.09), body mass index (38 ± 2 vs 36 ± 2 kg/m2, p = 0.61), LPIR (57 ± 7 vs 55 ± 7, p = 0.89), DRI (53 ± 7 vs 44 ± 6, p = 0.38), or INFX (47 ± 2 vs 54 ± 3, p = 0.13).CONCLUSIONSMales had poorer vascular endothelial function compared to females following LT, suggesting that males may be more susceptible to the development of CVD after LT. However, this increased risk cannot be explained by differences in traditional cardiometabolic risk factors. Future research should identify non‐traditional CVD risk factors that contribute to sex differences in vascular function towards implementing precision medicine for the prevention and management of CVD in LT patients.

Weight Gain, Fibroblast Growth Factor‐23, and Vascular Function in Liver Transplant Recipients

INTRODUCTIONLiver transplant (LT) recipients experience significant weight gain and an increased risk of cardiovascular disease (CVD) after transplant. The pathophysiology of this cardiometabolic burden is not fully understood. In the general population, weight gain and increased adiposity are associated with elevated circulating levels of fibroblast growth factor‐23 (FGF‐23). Increased FGF‐23 has been linked with CVD in other disease populations. This study tested the working hypothesis that weight gain after LT is associated withincreased levels of FGF‐23, that subsequently contribute to vascular dysfunction, an established precursor of CVD.METHODSWe enrolled 21 LT patients (M/F: 9/12; Mean ± SEM, Age: 55 ± 2 yrs) and 8 age matched healthy controls (HC; M/F: 2/6; 47 ± 6 yrs). Vascular endothelial function was assessed with flow‐mediated dilation (FMD) of the brachial artery using duplex ultrasound. Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Serum levels of FGF‐23 were assessed by enzyme linked immunosorbent assay (ELISA).RESULTSHigher body mass index (BMI) values were reported in LT patients (37 ± 1 kg/m2) compared to HC (26 ± 1 kg/m2, p = &lt;0.001). Weight gain (BMI) was positively associated with serum FGF‐23 values (r = 0.5, p = 0.01). Central systolic pressures (125 ± 3 vs. 110 ± 6 mmHg, p = 0.01) and central pulse pressures (51 ± 4 vs. 39 ± 4 mmHg, p = 0.05) were higher in LT patients compared with controls. There was no difference in endothelial function (FMD) in LT patients (4.59 ± 0.55%) compared to their HC counterparts (6.08 ± 0.48%, p = 0.12). FGF‐23 values were not associated with measures of vascular function.CONCLUSIONWeight gain is evident in LT patients and is correlated with higher serum FGF‐23 values. However, our findings do not suggest a relationship between serum levels of FGF‐23 and vascular function in LT recipients.

Mental Stress Pressor Response and Post‐Stress Aortic Wave Reflection

Reactivity to mental stress has been linked to cardiovascular risk, and is shown to negatively influence aortic wave reflection for up to an hour after acute mental arithmetic. It has been postulated that sympathetic catecholamine release during the stressful task drives the sustained elevation in wave reflection. In the present study we sought to determine how muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) reactivity influence post mental stress aortic augmentation index (AIx). Twenty‐seven volunteers (25±1 years) with resting blood pressure ≥120/80 mmHg participated in the present study. Baseline pulse wave analysis and pulse wave velocity recordings were assessed on participants after 10 minutes of supine rest. Participants were then instrumented for measurements of MSNA (microneurography), beat‐to‐beat blood pressure (finger plethysmography), and heart rate (3‐lead ECG). Subsequently MSNA, blood pressure, and heart rate were measured during a 5‐minute baseline, 5‐minute mental stress task (serial subtraction), and 5‐minute recovery. Finally, aortic wave reflection (i.e. AIx) was reassessed 10 minutes after completion of mental stress. Statistical analyses included paired t‐tests to compare MSNA, MAP, heart rate (HR), and perceived stress during baseline and mental stress. We used standard multiple regression with change in AIx as the dependent variable and changes in MSNA, MAP, and perceived stress as the independent variables. Means were considered significantly different when p&lt;0.05. The mental stress task significantly increased HR (Δ15±2 beats/minute), MAP (Δ14±1 mmHg), and perceived stress (Δ1.9±0.1 a.u.), while MSNA was not significantly increased. There was however a range of changes in MSNA from ‐13 to +20 bursts/minute. The change in MAP during mental stress was a significant predictor (ꞵ=0.47; p=0.03) of the change in AIx (post‐stress vs. baseline). Changes in MSNA and perceived stress were not predictors of mental stress‐related changes in AIx. Our results indicate that the aortic wave reflection responses to mental stress appear to be linked to the pressor response, but not sympathetic or perceived stress responses. This is novel preliminary data that suggests there may not be a direct link between sympathetic activation and aortic wave reflection following cognitive stress.

Pressure Only Wave Separation Pulsatile Hemodynamics in Adolescents: Accuracy and Associations with Left Ventricular Mass Index

IntroductionEarly‐life exposure to cardiovascular disease (CVD) risk factors, such as high blood pressure (BP), is associated with cardiovascular target organ damage in later life. However, not all BP‐related risk is explained by higher systolic and diastolic BP alone. In adolescence, aortic wave separation (WS) pulsatile hemodynamic parameters are associated with adverse left ventricular (LV) structure but are limited by the requirement for measured aortic flow. Several methods for estimating aortic flow from pressure waveforms have emerged, but their accuracy and associations with LV structure have never been tested in adolescents. We hypothesized that pressure‐only estimated flow waveforms would: 1) accurately approximate measured flow hemodynamic WS parameters and 2) be similarly associated with LV mass as measured flow hemodynamics among healthy adolescents.Methods. BP waveforms were acquired via carotid tonometry in 58 adolescents (age 16±1.5 years, 59% females). Measured (aortic) flow and LV mass index (LVMI) were measured via 2D echocardiography. Three pressure‐only approximations of aortic flow waveforms were synthesized from analysis of the BP waveform, including triangular, excess, and individualized physiologic flow. A 4th aortic flow waveform (average flow) was approximated from the average of all 58 measured flow waveforms. Forward (Pf) and backward (Pb) pressure and reflection magnitude (Rm) were derived from WS analysis.Results. Compared to measured flow, individualized physiologic and average flow produced the best approximations of Pf (mean difference ± SD, ‐0.15±2.38 and 1.23±2.84 mmHg respectively), Pb (0.14±0.25 and 0.67±0.10 mmHg), and Rm (0.01±0.02 and ‐0.01±0.02 mmHg). Pf derived using all flow waveforms, measured, and estimated, was associated with LVMI (R &gt;0.44, P &lt;0.001 for all), and these associations yielded similar effect estimates in all instances (z‐score &lt;1.1, P &gt;0.28). All associations persisted after adjusting for age, systolic BP, heart rate, and aortic diameter (P &lt;0.05 all).Conclusion. Of the estimated flow waveforms, individualized physiologic flow yielded the best approximation of WS hemodynamic parameters. It may provide important physiological and clinical insight related to cardiovascular target organ damage among adolescents.

L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults

Augmented aortic systolic blood pressure (SBP) and wave reflection via sympathetic-mediated vasoconstriction elevates the risk for adverse cardiovascular events in older adults. L-citrulline (L-CIT) supplementation has shown to reduce aortic SBP and pulse pressure (PP) responses to cold pressor test (CPT) induced sympathoactivation in young men. The aim of this study was to elucidate the efficacy of L-CIT supplementation to attenuate aortic hemodynamic responses to CPT in older adults. Sixteen older adults were randomly assigned to placebo or L-CIT (6g/day) for 14-days in a crossover, double-blind, placebo-controlled design. Brachial SBP and aortic SBP, PP, augmented pressure (AP), augmentation index standardized at 75bpm (AIx@75), and pressure of the forward (Pf) and reflected (Pb) waves were evaluated at rest and during CPT pre- and post-intervention. Although no hemodynamic changes at rest, brachial SBP (Δ-12±18 vs. Δ4±14mmHg; P=0.008) and aortic SBP (Δ-10±14 vs. Δ4±12mmHg; P=0.005), PP (Δ-10±12 vs. Δ4±11mmHg; P=0.002), AP (Δ-4±4 vs. Δ2±7mmHg; P=0.004), AIx@75 (Δ-3.2±7.2 vs. Δ2.2±6.9%; P=0.038), Pf (Δ-6±10 vs. Δ3±9mmHg; P=0.019), and Pb (Δ-4±6 vs. Δ2±6mmHg; P=0.008) responses to the CPT were significantly attenuated following L-CIT supplementation vs. placebo. L-CIT supplementation attenuated aortic pulsatile pressure and pressure wave reflection responses to CPT in older adults, providing possible cardioprotection during cold-induced sympathoactivation in older adults.