Central Aortic Pressure Research Articles

The ghrelin receptor agonist AC01 improves cardiac function in non-human primates and in mice with heart failure by increasing cardiomyocyte contractility

Abstract Background Current therapy for Heart Failure (HF) includes neurohormonal antagonist and modulator drugs that improve remodelling, symptoms and clinical outcomes. However, these drugs do not target the underlying problem of reduced contractility. Improving cardiac contractility without harmful consequences is an unmet need in heart failure therapy. The human peptide hormone ghrelin increases cardiac output in HF patients and increases contractility in murine cardiomyocytes. Purpose We aim to study the cardiovascular effects of a novel oral small molecule ghrelin receptor agonist, AC01, in in vivo and ex vivo mouse models and in non-human primates. Methods HF mice (N=11) underwent pressure-volume loops analysis of cardiac functional and hemodynamic to assess the effects of intravenous AC01 (N=7) or placebo (N=4). Primary cardiomyocytes isolated from HF (N=3) and SHAM (N=5) mice, were treated with combinations of vehicle, AC01, ghrelin receptor antagonist (D-Lys-3-GHRP-6) and pertussis toxin (PTX, a Gαi signalling inhibitor). Live cell imaging was performed to assess cardiomyocyte fractional shortening and Ca2+ signalling, while biochemistry assays were employed to measure PKA activity, and phosphorylation of cardiac Troponin I (cTnI). Cynomolgus monkeys (N=6) were instrumented with devices to measure pulse contour, central aortic blood pressure and ECG devices. Cardiovascular effects of AC01 following single oral dosing were assessed through pulse contour hemodynamic modelling and analysis of autonomic system activation. Results In HF mice, AC01 significantly improved cardiac output (p< 0.01), stroke volume (p< 0.001), and ejection fraction (p< 0.001), and increased nominally the end-systolic pressure-volume curve relationship. In cardiomyocytes, AC01 dose-dependently improved fractional shortening (p< 0.01) without increasing Ca2+ transient amplitudes. AC01 reduced PKA activity (p< 0.05) and reduced phosphorylation of cTnI at Serine 23-24 (p< 0.01). These effects were blocked by pre-treatment with either D-Lys-3-GHRP-6 or PTX. In monkeys, oral AC01 sustainably increased cardiac output (p< 0.05) and stroke volume (p< 0.05) and reduced heart rate without altering central systolic blood pressure or causing tachycardia or arrhythmia. Conclusions AC01 improved CO, SV, and EF in HF mice by increasing contractility in a load-independent fashion. AC01 increased cardiomyocyte contractility without affecting Ca2+ transient amplitudes, through ghrelin receptor Gαi signalling, leading to reduced phosphorylation of cTnI. AC01 improved left ventricle systolic function in monkeys. AC01 is a first in class novel inotrope, which improves contractility in different species without harmful mobilization of Ca2+. AC01 should be explored for the treatment of patients with heart failure.graphical abstract

Invasive validation of central blood pressure measurements using a suprasystolic monitor

Abstract Interest in the assessment of Central Blood Pressure (cBP) is steadily growing since it is a better predictor of myocardial infarction, stroke, or death than Peripheral Blood Pressure (pBP). However, pBP remains the first line for the diagnosis of hypertension (HTN) due to the ease and speed of the measurement. We sought to validate a new method to estimate cBP from brachial sphygmomanometer measurements. We estimated cBP using a sphygmomanometer that can record, after conventional pBP measurements, the pressure in the cuff maintained at a constant suprasystolic pressure. cBP is calculated using a method based on applying a physics-based model of the left subclavian artery to the brachial arterial branch to the suprasystolic brachial artery pressure waveforms. We compared this noninvasive estimated cBP to an invasive gold-standard measurement during cardiac catheterization. After clinically indicated cardiac catheterization requiring a haemodynamic assessment of a moderate coronary artery stenosis by Fractional Flow Reserve (FFR), the wire that incorporates a high fidelity electronic pressure transducer was positioned into the guiding catheter left in the ascending aorta. Simultaneous measurements were performed with a cuff placed on the patient's left arm. The output signals were recorded in a custom-based acquisition system. The comparison was obtained on the same 10 seconds recorded by the cuff and the pressure wire. The goal will be to reach 85 patients as recommended by the ARTERY Society Task Force. It recommends as an accuracy criterion to achieve a mean difference ≤ 5 mmHg with a standard deviation (SD) ≤ 8 mmHg, which are the standards adopted for this study. Patients with aortic stenosis, atrial fibrillation, or frequent (supra)ventricular extrasystoles were excluded. A total of 197 pairs of measured-estimated cBP were analysed in 78 patients with a mean age of 63 ± 8 yo, 75% of whom were men, 70% had hypertension, 26% fdiabetes, 93% dyslipidemia, 41% were tobacco users and 14% suffered from clinical peripheral artery diseases without history of revascularization. The median (InterQuartiles 25-75%) pBP was 123 [112 134] / 70 [64 77] mmHg. Measured cBP was 102 [92 11] / 78 [70 84] mmHg with a central augmentation index of 34 [23 44] %. The mean difference between estimated and measured systolic cBP was 4.9 ± 6.5 mmHg, while it was -3.9 ± 5.8 mmHg for diastolic cBP, meeting the prespecified accuracy criteria. In conclusion, our approach based on an exact matching and comparison of non-invasive suprasystolic arm cuff measurements and high-fidelity aortic BP validates that an estimation of central aortic blood pressure that can be easily carried out in daily practice and might improve HTN management. It remains to be demonstrated that more cardiovascular complications will be avoided by guiding the antihypertensive therapy with cBP instead of pBP measurements.Bland-Altman of estimated - measured cBP

Chronopharmacotherapy and correction of central pressure in the aorta, structural and functional state of the left ventricular in patients with arterial hypertension and ischemic stroke

Objective. To evaluate the dynamics of central aortic pressure and the cardioprotective effect of antihypertensive chronopharmacotherapy in patients with arterial hypertension (AH) and ischemic stroke. Materials and methods. The study included 119 patients with AH who has suffered an ischemic stroke; patients were randomized in 2 groups depending on the chronopharmacotherapy option: group 1 (n = 60) – patients who received indapamide retard 1.5 mg and valsartan 160 mg in the morning; group 2 (n = 59) – indapamide retard 1.5 mg in the morning and valsartan 80 mg each in the morning and before bedtime. After 2 months of pharmacotherapy, the achievement of the target level of blood pressure was assessed. In group 1, blood pressure was recorded in 47 (78.3 %), in group 2 – in 56 (94.9 %) patients (p < 0.05). The rest of the respondents, who did not reach the blood pressure target, underwent correction of antihypertensive therapy and were excluded from further follow-up. Accordingly, further follow-up was carried out in 47 patients of group 1 (group 1a) and 56 patients of group 2 (group 2a). Initially and after 12 months of therapy, echocardiography parameters ("ALOKA SSD 2500", Japan), as well as daily blood pressure monitoring with determination of central aortic pressure (Peter Telegin LLC BPLabVasotens, Russia) were performed. The results of the study were processed using the Statistica 12.0 program (StatSoftInc, USA). Results. At the time of inclusion in the study, the main parameters of the central aortic pressure and echocardiography parameters in both groups of patients were equivalent. After 12 months a statistically more significant decrease in the main parameters of the central aortic pressure (average daily systolic and diastolic pressure in the aorta, pulse pressure in the aorta, augmentation index in the aorta, amplification of pulse pressure, duration of the expulsion period, subendocardial blood flow efficiency index), as well as echocardiography indicators was recorded in group 2a (end-systolic and end-diastolic dimensions, thickness of the interventricular septum, thickness of the posterior wall of the left ventricular myocardium, left ventricular myocardial mass, left ventricular myocardial mass index and ejection fraction) (p < 0.05). The left ventricular myocardial geometry normalized during therapy was recorded significantly more often in group 2a than in group 1a (p < 0.05). Conclusion. Two times a day intake of valsartan with thiazidelike diuretic in the morning facilitated more significant improvement of central aortic pressure, echocardiography parameters and as well as an improvement in the geometry of the left ventricular myocardium comparing to just morning intake.

In silico data-based comparison of the accuracy and error source of various methods for noninvasively estimating central aortic blood pressure

Background and objectivesThe higher clinical significance of central aortic blood pressure (CABP) compared to peripheral blood pressures has been extensively demonstrated. Accordingly, many methods for noninvasively estimating CABP have been proposed. However, there still lacks a systematic comparison of existing methods, especially in terms of how they differ in the ability to tolerate individual differences or measurement errors. The present study was designed to address this gap. MethodsA large-scale ‘virtual subject’ dataset (n = 600) was created using a computational model of the cardiovascular system, and applied to examine several classical CABP estimation methods, including the direct method, generalized transfer function (GTF) method, n-point moving average (NPMA) method, second systolic pressure of periphery (SBP2) method, physical model-based wave analysis (MBWA) method, and suprasystolic cuff-based waveform reconstruction (SCWR) method. The errors of CABP estimation were analyzed and compared among methods with respect to the magnitude/distribution, correlations with physiological/hemodynamic factors, and sensitivities to noninvasive measurement errors. ResultsThe errors of CABP estimation exhibited evident inter-method differences in terms of the mean and standard deviation (SD). Relatively, the estimation errors of the methods adopting pre-trained algorithms (i.e., the GTF and SCWR methods) were overall smaller and less sensitive to variations in physiological/hemodynamic conditions and random errors in noninvasive measurement of brachial arterial blood pressure (used for calibrating peripheral pulse wave). The performances of all the methods worsened following the introduction of random errors to peripheral pulse wave (used for deriving CABP), as characterized by the enlarged SD and/or increased mean of the estimation errors. Notably, the GTF and SCWR methods did not exhibit a better capability of tolerating pulse wave errors in comparison with other methods. ConclusionsClassical noninvasive methods for estimating CABP were found to differ considerably in both the accuracy and error source, which provided theoretical evidence for understanding the specific advantages and disadvantages of each method. Knowledge about the method-specific error source and sensitivities of errors to different physiological/hemodynamic factors may contribute as theoretical references for interpreting clinical observations and exploring factors underlying large estimation errors, or provide guidance for optimizing existing methods or developing new methods.

Retinal Microvascular Changes in Association with Endothelial Glycocalyx Damage and Arterial Stiffness in Patients with Diabetes Mellitus Type 2: A Cross-Sectional Study in a Greek Population.

To evaluate the potential association between endothelial glycocalyx damage, as well as arterial stiffness, and the retinal changes on optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with type 2 diabetes mellitus (DM). Participants in this cross-sectional study were 65 patients with DM type 2 and 42 age- and gender-matched controls without DM. The demographic and clinical characteristics of the participants were recorded. All patients underwent a thorough ophthalmological examination and multimodal imaging, including fundus photography, OCT, and OCT-A. In addition, evaluation of the endothelial glycocalyx thickness by measuring the perfused boundary region (PBR5-25) of the sublingual microvessel, as well as of the arterial stiffness, by measuring the carotid-femoral pulse wave velocity (PWV), the central aortic pressures and the augmentation index (Aix) was performed. Univariate and multivariate logistic regression analysis was performed for the examination of the potential association between the eye imaging variables and the cardiovascular-related variables. The odds ratios (OR) with the respective 95% confidence intervals (CI) were calculated. A p-value < 0.05 was considered statistically significant. Patients with DM presented significantly higher PBR5-25 compared to controls without DM (p = 0.023). At the univariate analysis, increased PBR5-25 (≥2.19 μm vs. <2.19 μm) was associated with decreased peripapillary VD at the superior quadrant (univariate OR (95% CI) = 0.34 (0.12-0.93), p = 0.037). Multivariate logistic regression analysis showed that increased PWV (≥13.7 m/s vs. <13.7 m/s) was associated with an increased foveal avascular zone (FAZ) area on OCT-A (p = 0.044) and increased FAZ perimeter (p = 0.048). Moreover, increased Aix (≥14.745% vs. <14.745%) was associated with diabetic macular edema (DME) presence (p = 0.050) and increased perifoveal and parafoveal superior and temporal thickness on OCT (p < 0.05 for all associations). Markers of endothelial damage and arterial stiffness were associated with structural and microvascular retinal alterations in patients with DM, pointing out that OCT-A could be a useful biomarker for detecting potential cardiovascular risk in such patients.

Accuracy of the WatchBP Office Central as a Type 2 device for non-invasive estimation of central aortic blood pressure in children and adolescents.

High blood pressure (BP) in childhood is a recognised precursor of elevated cardiovascular risk in adulthood. Brachial BP is normally used for clinical decision making, but central BP may be a better marker of pressure load on the heart. There is a paucity of validated non-invasive, automated devices for estimating central BP in children and adolescents. In this study, we compared the WatchBP Office Central (a Type 2 central pressure estimation device) against a high-fidelity micromanometer in the ascending aorta of anaesthetised patients undergoing clinically-indicated catheterisation (n = 15, age 4-16 years). As a secondary aim, central systolic BP (cSBP) was also compared to two non-invasive estimation methods in 34 awake patients undergoing routine cardiac MRI (age 10-18 years). WatchBP substantially overestimated cSBP compared to the intra-arterial gold-standard reference (26.1 ± 7.4mmHg), and recruitment was terminated at n = 11 (included in the analysis) due to high statistical certainty that the device would not pass the validation criteria of 5±8 mmHg. WatchBP cSBP was also substantially higher than values obtained from a phase contrast MRI method (11.8 ± 7.9 mmHg) and the SphygmoCor XCEL (13.5 ± 8.9 mmHg) in the awake patient group, which translate to 21-23 mmHg on average after accounting for known/estimated biases in these non-invasive comparators. Compared with invasive central diastolic and systolic BPs, the brachial measures from WatchBP yielded errors of 0.1 ± 5.6 and 12.5 ± 6.0 mmHg respectively. We conclude that the WatchBP substantially overestimates cSBP in children and adolescents. These findings reinforce the need for central BP-measuring devices to be further developed and validated in this population.

Comparative analysis of central aortic blood pressure, pulse wave velocity & arterial stiffness in patients with obstructive airway disease.

As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

O62 DEGREE OF HYPERTENSION CONTROL IN ABORIGINAL AND NON-ABORIGINE POPULATIONS OF A CITY IN NORTHERN ARGENTINE

High blood pressure is a widely prevalent pathology in the province of Formosa, 52% according to the latest Argentine national survey 2019, so we do not have current data, it was decided to carry out a survey that evaluates blood pressure, arterial stiffness and peripheral resistance. To evaluate how these variables are presented in 2 populations of our city, one of the general population and the other of an indigenous ethnic group of the province called Toba that lives in a neighborhood of this city. Materials and methods: data collection was carried out on patients in 3 institutions, all of which were public, with a prior diagnosis of the disease made by a health professional, in the Central Hospital of Formosa, the interdistrict hospital Evita, and the center of primary care in the Nam Qom neighborhood of Formosa. during a period of 1 month The pressure was taken by validated blood pressure monitors as well as central aortic pressure and peripheral resistance. by a Tel O Graph brand team. The data were analyzed Statistix 10.0. Results: 80 patients, 20 from the ethnic group and 20 from the general population, 62% women, age was 52 years in the general hospital (hg) and 54 in the health center (cs), systolic blood pressure was 129 1/2 and 82 1/2 diastolic, in cs 121 and 83. The central aortic velocity was 7.76 on average and the peripheral resistance 18.62 in the hc - in the cs 6.54 and 18.6. smoking habit, 45 and 25% respectively. The control was 87% in the BP in the hc and 75% in the cs population. Conclusions: Differences were found: a lower prevalence of uncontrolled hypertension than in the general population and in terms of VOP and peripheral resistance we were able to find a difference in favor of the CS population, and also in the degree of control of hypertensive patients in the same trend.

Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial.

Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking. The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay. A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group (P=0.028), and ΔTWV was 1.2±1.7 cm3 in the placebo group and 0.037±1.9 cm3 in the spironolactone group (P=0.022). Change in LV mass was 3.1±8.4 g in the placebo group and -5.8±8.4 g in the spironolactone group (P=0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of -10.1±36.3 ms in the spironolactone group; P=6.33×10-4). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation. Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02169089.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated withvascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

A new methodology for determining the central pressure waveform from peripheral measurement using Fourier-based machine learning

Radial applanation tonometry is a well-established technique for hemodynamic monitoring and is becoming popular in affordable non-invasive wearable healthcare electronics. To assess the central aortic pressure using radial-based measurements, there is an essential need to develop mathematical approaches to estimate the central pressure waveform. In this study, we propose a new Fourier-based machine learning (F-ML) methodology to transfer non-invasive radial pressure measurements to the central pressure waveform. To test the method, collection of tonometry recordings of the radial and carotid pressure measurements are used from the Framingham Heart Study (2640 individuals, 55 % women) with mean (range) age of 66 (40–91) years. Method-derived estimates are significantly correlated with the measured ones for three major features of the pressure waveform (systolic blood pressure, r=0.97, p < 0.001; diastolic blood pressure, r=0.99, p < 0.001; and mean blood pressure, r=0.99, p < 0.001). In all cases, the Bland-Altman analysis shows negligible bias in the estimations and error is bounded to 5.4 mmHg. Findings also suggest that the F-ML approach reconstructs the shape of the central pressure waveform accurately with the average normalized root mean square error of 5.5 % in the testing population which is blinded to all stages of machine learning development. The results show that the F-ML transfer function outperforms the conventional generalized transfer function, particularly in terms of reconstructing the shape of the central pressure waveform morphology. The proposed F-ML transfer function can provide accurate estimates for the central pressure waveform, and ultimately expand the usage of non-invasive devices for central hemodynamic assessment.

Arterial stiffness in non-alcoholic fatty liver disease

Background. The presence of metabolic-associated pathology, namely obesity, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), significantly accelerates the development of the cardiovascular continuum. This is associated with an increased risk of major cardiovascular events (myocardial infarction, stroke). An important organ damage in hypertension (HTN) is the remodeling of small arteries and an increase in stiffness of large arteries. The relationship between NAFLD, dyslipidemia, hypertriglyceridemia, obesity (especially abdominal), diabetes, and HTN is well studied, but there is a lack of clinical studies examining changes in arterial stiffness in NAFLD. Aim of the research was to study the parameters of arterial stiffness in patients with NAFLD. Materials and methods. Eighty-two Caucasian patients with NAFLD (mean age (56.8 ± 1.1) years, 59.8 % men) were enrolled. Participants were divided into two groups: group 1 (n = 44) — NAFLD and concomitant HTN, group 2 (n = 38) — HTN without NAFLD. All patients underwent a standard general clinical examination, laboratory and instrumental work-up. In addition, all patients were assessed for the parameters of arterial stiffness via non-invasive arteriography. Results. Patients with NAFLD had significantly higher office systolic and diastolic blood pressure (by 15.2 and 10.4 %, respectively, p &lt; 0.01) despite comparable drug therapy. The same trends were observed in relation to the central aortic pressure, which was 19.3 % higher in patients with NAFLD (p &lt; 0.01), and central pulse pressure that was 35.9 % higher than in patients without NAFLD (p &lt; 0.01). Brachial artery augmentation index in NAFLD turned to be elevated compared to patients without NAFLD (p &lt; 0.01), but aortic augmentation index was comparable between groups. The return time interval in group 1 was 50.3 % higher than in group 2 (p &lt; 0.01). Finally, patients with NAFLD had a significant increase in pulse wave velocity by 52.3 % compared to those without NAFLD with average value exceeding 12 m/sec (p &lt; 0.01). Conclusions. There is an association between NAFLD and worse indices of arterial stiffness in patients with concomitant HTN.

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy

BackgroundObstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.Methods and resultsForty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.ConclusionsOSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.Trial registrationNCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125.

An FBG-based optical pressure sensor for the measurement of radial artery pulse pressure.

One of the diagnostic tool for clinical evaluation and disease diagnosis is a pulse waveform analysis. High fidelity radial artery pulse waveforms have been investigated in clinical research to compute central aortic pressure, which has been demonstrated to be predictive of cardiovascular diseases. The radial artery must be inspected from several angles in order to obtain the best pulse waveform for estimate and diagnosis. In this study, we present the design and experimental testing of an optical sensor based on Fiber Bragg Gratings (FBG). A 3D printed device along with the FBG is used to measure the radial artery pulses. The proposed sensor is used for the purpose of quantifying the radial artery pulse waveform across major pulse position point. The suggested optical sensing system can measure the pulse signal with good accuracy. The main characteristic parameters of the pulse can then be retrieved from the processed signal for their use in clinical applications. By conducting experiments under the direction of medical experts, the pulse signals are measured. In order to experimentally validate the sensor, we used it to detect the pulse waveforms at Guan position of the wrist's radial artery in accordance with the diagnostic standards. The findings show that combining optical technologies for physiological monitoring and radial artery pulse waveform monitoring using FBG in clinical applications are highly feasible.

CENTRAL AORTIC PRESSURE (CAP) MEASURED IN THE OFFICE WITH SPHYGMOCOR AND DURING 24 HOURS (MOBIL-O-GRAPH AND ARTERIOGRAPH) AND HYPERTENSION MEDIATED ORGAN DAMAGE (HMOD) IN YOUNG PAT

Objective: Central aortic pressure (CAP) is a parameter of central hemodynamics. It can be measured in the office with SphygmoCor, and during 24-hours with Mobil-O-Graph and Arteriograph. Debate is going on whether CAP is more associated with HMOD than brachial blood pressure. The aim of our study is to analyse assocation of office CAP and 24-hour CAP with HMOD in patients with stage 1 hypertension. Design and method: This study included 154 patients with the primary hypertension (69.5% women, mean age 38.5). In all of them we collected various clincial data and antroplogical paramaters. CAP was measured in the office (SphygmoCor) and during regular working days (24h ABPM systems: Mobil-o-Graph and Arteriograph). Results: The increased office CAP was associated with five indicators of HMOD: decrease in eGFR, increase in 24 hours albuminuria, thickness of the intima and carotid media (cIMT), NT pro-BNP, left ventricular hypertrophy- ECG Cornell criteria (LVH). Elevated 24-hour (Mobi-O-Graph) systolic CAP was associated with increased cITM and decreased EF. Higher values of diastolic CAP (Mobi-O-Graph) were accompanied by a greater possibility of LVH. An increase in 24 hours systolic CAP (Arteriograph) was followed with an increase in the cITM. An increase in 24 hours diastolic CAP(Arteriograph) was followed with a decrease in eGFR. Conclusions: CAP could be considered as a indicator of HMOD and total cardiovascular risk especially in young patients, but large longitudinal studies are need in order to confirm this. CAP measured with SphymoCor can be considered a better predictor of HMOD compared to CAP measured over 24 hours. Further investigation is needed to determine clinical value of both office and 24 hours CAP.

COMPARISON OF COMPONENTS OF CENTRAL AORTIC AND PERIPHERAL BLOOD PRESSURE FOR PREDICTION OF CARDIOVASCULAR EVENTS IN A 2-YEAR AND 14-YEAR FOLLOW-UP OF A HYPERTENSIVE COHORT

Objective: The aim of this study was to assess components of central aortic pressure, brachial blood pressure and indices of arterial stiffness for prediction of cardiovascular events in a hypertensive cohort. Design and method: Noninvasive measurements of central aortic blood pressure (SphygmoCor), brachial pressure, central augmentation index (cAIx), augmented pressure (cAP) and carotid intima-media thickness (IMT) were obtained in 681 hypertensive patients (age 61 ± 9 years, 425 males). The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD. An initial analysis was conducted at mean 2-year follow-up and a second analysis is currently being conducted at mean 14-year follow-up. Results: Total events were 59 (8.7%) for the 2-year follow-up and 265 (38.9%) for the 14-year follow-up. Major cardiovascular events were 49 (83.1%) and 178 (67.2%) respectively. The analysis of the 2-year follow-up suggested that central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events compared to peripheral pressure indices (pSBP, pPP) at age &gt;60 years (cSBP: HR = 1.18, pSBP: HR = 1.17, p = 0.034; cPP: HR = 1.28, pPP: HR = 1.2, p = 0.019). Each SD increase in IMT and in cAP was associated with 1.4 times higher risk of increased total events in elderly patients (age &gt;60 years). Males showed that each SD increase in cAP was associated with significantly higher risk of increased total events than females. The complete data for the 14-year follow-up analysis has only recently become available and the analysis will be completed for the conference presentation. Conclusions: Preliminary analysis in a short-term (2-year) follow-up study of a large hypertensive cohort has shown that central aortic pressure and its components can improve prediction of CVD compared to peripheral pressure. The final analysis of the long-term (14-year) follow-up will determine which components are robust predictors and will provide important information on the clinical and epidemiological relevance of central aortic pressure.

Vascular Dysfunction and Inflammation in Liver Transplant Recipients

INTRODUCTION Liver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. The physiological mechanisms driving this risk are not fully understood. Vascular endothelial dysfunction is the initial pathophysiological step in the development of atherosclerosis. The objective of this study was to characterize vascular endothelial function in LT recipients. It was hypothesized that compared to matched healthy controls (HC), LT recipients would have impaired vascular function. METHODS. Conduit artery endothelial function was measured by flow-mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 40 LT patients (18 male, 22 female; mean ± SD: Age, 56±11 years) and 10 age matched HC (4 male, 6 female; Age 51±16 years). Central aortic blood pressures were derived from radial arterial tonometry and the use of the generalized transfer function. A venous blood sample was obtained for nuclear magnetic resonance spectroscopy assessment of the inflammation biomarker GlycA, and high-density lipoprotein (HDL) particle subspecies. A novel metabolic inflammation index was derived from plasma GlycA and HDL subparticle concentrations. RESULTS. LT recipients had higher peripheral (Median [IQR]: HC vs. LT, 119 [111-136] vs. 135 [124-147] mmHg, p=0.01) and central aortic (113 [102-126] vs. 124 [116-139] mmHg, p=0.03) systolic blood pressures. LT recipients had impaired vascular endothelial function (HC vs. LT, FMDBA: 6.08 [5.01-7.61] vs. 4.54 [3.31-6.24] %, p = 0.04). In LT recipients, the inflammation index (55 [45-62] AU) was negatively associated with vascular endothelial function ( r=-0.4, p=0.03). CONCLUSIONS. Despite optimal pharmacological intervention, LT recipients had higher systolic blood pressures and worse vascular endothelial dysfunction compared to HC. In LT recipients, a higher inflammation index was associated with worse endothelial function, suggesting that chronic low-grade inflammation may partly contribute to endothelial dysfunction in this patient population. These findings provide support for the vascular endothelium as a potential therapeutic target to improve cardiovascular health in LT recipients. Supported by CTSA award No. UM1TR004360 from the National Center for Advancing Translational Sciences. This is the full abstract presented at the American Physiology Summit 2024 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.

In silico modelling of stroke volume, cardiac output and systemic vascular resistance in cardiovascular safety pharmacology studies by telemetry

The principle of proportionality of the systolic area of the central aortic pressure to stroke volume (SV) has been long known. The aim of the present work was to evaluate an in silico solution derived from this principle for modelling SV (iSV model) in cardiovascular safety pharmacology studies by telemetry. Blood pressure was measured in the abdominal aorta in accordance with standard practice. Central aortic pressure was modelled from the abdominal aortic pressure waveform using the N-point moving average (NPMA) method for beat-to-beat estimation of SV. First, the iSV was compared to the SV measured by ultrasonic flowmetry in the ascending aorta (uSV) after various pharmacological challenges in beagle dogs anaesthetised with etomidate/fentanyl. The iSV showed minimal bias (0.2 mL i.e. 2%) and excellent agreement with uSV. Then, previous telemetry studies including reference vasoactive and inotropic compounds were retrospectively reanalysed to model drug effects on stroke volume (iSV), cardiac output (iCO) and systemic vascular resistance (iSVR). Among them, the examples of nicardipine and isoprenaline highlight risks of erroneous or biased estimation of drug effects from the abdominal aortic pressure due to pulse pressure amplification. Furthermore, the examples of verapamil, quinidine and moxifloxacin show that iSV, iCO and iSVR are earlier biomarkers than blood pressure itself for predicting drug effect on blood pressure. This in silico modelling approach included in vivo telemetry safety pharmacology studies can be considered as a New Approach Methodology (NAM) that provides valuable additional information and contribute to improving non-clinical translational research to the clinic.

HYPERTENSION AND VASCULAR RIGIDITY MEASUREMENTS IN ABORIGINAL AND NON-ABORIGINE POPULATIONS OF NORTHERN ARGENTINE DURING 2023

Objective: Valuate central aortic pressure and blood pressure in 2 populations in the city of formosa in the year 2023, differences between them, degree of control. It has that one of such populations has its own socio-cultural characteristics.a prospective observational type study was carried out Design and method: taking the central blood and aortic pressure with standardized measurements with a tel or graph tensiometer, The data was taken during 3 months of 2023 in 2 institutions one a primary care center in an aboriginal(a) neighborhood of the toba race and another in the central hospital, both public institutions, have a prior diagnosis of hta. the data was analyzed in the statistix 7.0 Results: study 75 patients, 30 a and 45 non-aborigine (na), the age was 56 in na and 50 in a, the sex of the patients was 25% men (m) in na and 53% h in a. the systolic pressure was 1/2 of 146 in no a and 117 in a, the diastolic pressure 89 in na and 67 in a, the pwv 9.2 in na and 7.3 in a, the increase index 29 in na and 15 in a. Conclusions: found in similar populations, lower values of vop, ta and increase index in the aboriginal population studyed. we should study more population to see if the data are correct and then see the cause

SYSTEMIC DISEASES ARE A GROUP OF INFLAMMATORY ILLNESSES THAT CAN DAMAGE THE ARTERIAL WALL ASSESSED ACCORDING TO NON-INVASIVE ARTERIAL TONOMETRY

Objective: Objective: Hypertensive Cardiovascular Disease is a complex, multifactorial, and chronic illness, frequently beginning during childhood or adolescence, could develop functional and/or structural organ damage by the increase of arterial stiffness and the curve volume/pressure that in turn can raise the stress into the ventricular-arterial coupling and the appearance of arrhythmias. The aim of this study was to assess systemic inflammatory diseases according to non-invasive arterial tonometry and their possible complications. Design and method: Design &amp; Method: This cross-sectional study registered 339 patients, women 77%, both sexes, presented various systemic inflammatory diseases such as Psoriasis (123), Rheumatoid Arthritis (26), Celiac disease (13), Sjögren's disease (9), Crohn's disease (7), Ulcerative colitis (10), Endometriosis (10), Polycystic Ovary Syndrome (141). Anthropological data, Systolic/Diastolic Blood Pressure, and Heart Rate were measured. Central Hemodynamic Parameters (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure) and the difference between the maximum normal level and the observed value of the Augmentation Index (Diff-AIx), the surrogated value of arterial stiffness, were assessed with the SphygmoCor System-PVX, according to established protocols by sex and age. Results: Results: The mean age of women and men was 45-51 years. The mean of Systolic/Diastolic Blood Pressure among women and men was 132.5/81.6-135.2/85.9 mmHg, respectively. The Diff-AIx among women was 4.8 and among men was 5.4. The most important finding of the assessment of the systemic inflammatory diseases was the presence of hypertensive cardiovascular disease, considering the measurements of high systolic and diastolic blood pressure, and the abnormal Central hemodynamic parameters. The most important complication observed was the brief phases of atrial fibrillation during the 24-hour Holter monitoring (7.4%), the mean age of patients was 64.2 years, range of 44-88 years, and the highest percentage of each group were Ulcerative colitis (20.0%), Rheumatoid Arthritis (15.4%), and Crohn's disease (14.3%), Psoriasis (10.6%), Endometriosis (10.0%). Conclusions: Conclusions: The systemic diseases can damage the arterial wall and contribute to the development of Hypertensive Cardiovascular Disease. Cardiologists and clinical physicians, in the anamnesis, should include the search for inflammatory systemic diseases for a more complete clinical evaluation and therapeutic guidance.