The prevalence and impact of orthostatic intolerance in young women across the hypermobility spectrum.

Orthostatic intolerance (OI) is frequently reported in young women with generalized hypermobility spectrum disorder (G-HSD) and hypermobile EDS (hEDS). However, it remains currently unclear whether OI is a comorbidity or fundamental part of the pathophysiology of G-HSD or hEDS. This study investigated the prevalence and impact of OI in young women across the hypermobility spectrum. Forty-five women (14-30 years, 15 controls, 15 G-HSD, and 15 hEDS) undertook a head-up tilt (HUT) and active stand test. Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH) were assessed using age-related criteria. Autonomic dysfunction and quality-of-life questionnaires were also completed. The prevalence of POTS was higher in women with G-HSD than hEDS and control groups during HUT (43% vs. 7% and 7%, respectively, p < 0.05), but similar between groups during the active stand (47%, 27%, and 13% for G-HSD, hEDS, and control, respectively). No participants had OH. hEDS and G-HSD participants reported more severe orthostatic symptoms and poorer quality of life than controls. Although POTS was observed in hypermobile participants, there is no conclusive evidence that its prevalence differed between groups due to differences between the HUT and active stand assessments. Nevertheless, OI and broader autonomic dysfunction impacted on their quality of life.

Measuring Arterial Stiffness in Animal Experimental Studies.

The arterial wall is a composite material of elastin, collagen, and extracellular matrix with acutely modifiable material properties through the action of smooth muscle cells. Therefore, arterial stiffness is a complex parameter that changes not only with long-term remodeling of the wall constituents but also with acute contraction or relaxation of smooth muscle or with changes in the acute distending pressure to which the artery is exposed. It is not possible to test all these aspects using noninvasive or even invasive techniques in humans. Full characterization of the mechanical properties of the artery and the specific arterial factors causing changes to stiffness with disease or modified lifestyle currently require animal studies. This article summarizes the major in vivo and ex vivo techniques to measure the different aspects of arterial stiffness in animal studies.

The effect of interval sprinting exercise on vascular function and aerobic fitness of post-menopausal women.

Menopausal transition accelerates an age-associated decrease in vascular function and a decline in aerobic fitness. The purpose of this study was to examine the effect of 8 weeks of interval sprinting cycle ergometer exercise on arterial stiffness, basal forearm blood flow, and aerobic fitness of post-menopausal women. Sixty overweight post-menopausal women were randomized into either exercise (Ex, n = 30) or control (C, n = 30) groups. Ex participants completed 24 interval sprinting exercise (ISE) sessions over 8 weeks. Each 20-minute ISE session comprised of alternating 8 seconds sprints and 12 seconds of light pedaling. Arterial stiffness assessed through ankle-brachial pulse wave velocity (baPWV) and augmentation index (AIx), basal forearm blood flow (FBF) assessed using venous occlusion, and aerobic fitness were assessed before and after the intervention. baPWV was significantly decreased in the Ex group by 7.2%, P = .03, whereas AIx demonstrated a 10% decrease, P = .002. No changes were found in basal FBF. Aerobic fitness was significantly increased, P = .002, in the Ex group (14%) with no change occurring in the control group.ISE training, despite minimal exercise commitment time (8 hours over 8 weeks), significantly lowered the arterial stiffness and increased the aerobic fitness of post-menopausal women. These results suggest that ISE positively influences the negative change in arterial stiffness and aerobic fitness that typically accompanies menopause.

Central aortic pressure improves prediction of cardiovascular events compared to peripheral blood pressure in short-term follow-up of a hypertensive cohort.

Objective: The aim of this study was to assess indices of a comprehensive panel of central aortic pressure and arterial stiffness for prediction of cardiovascular events in a hypertensive cohort.Methods: Noninvasive measurements of central aortic blood pressure, brachial pressure, wave reflection augmentation index, pressure amplification, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) were obtained in 675 hypertensive patients (age 61 ± 9 years, 425 males) for a mean follow-up period 25 ± 4 months. The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD.Results: After adjusting for confounding factors, central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events (CV) compared to peripheral pressure indices (pSBP, pPP) at age >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 central augmented pressure (cAP) entailed a 1.4 times higher risk of increased total events in elderly patients (age >60 years). For males, each SD increase in cAP was associated with 1.36 times higher risk of increased total events. For females, each SD increase in cAIx and cAP was associated with 0.4 and 0.5 times lower risk of increased total and major CV, respectively. This sex difference is most likely due to lack of age-related increase of cAIx in females after age >60 years compared to males.Conclusions: Central pressure improved prediction of CVD compared to peripheral pressure during a relatively short-term follow up of approximately 2 years at age >60 years.

Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γnorm) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γnorm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γnorm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γnorm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and reflection index as wave reflection indexes.

Cerebral Haemodynamics: Effects of Systemic Arterial Pulsatile Function and Hypertension.

PURPOSE OF REVIEW: Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion. RECENT FINDINGS: Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries.

Experimental investigations have established that the stiffness of large arteries has a dependency on acute heart rate (HR) changes. However, the possible underlying mechanisms inherent in this HR dependency have not been well established. This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWVTan) and by phase velocity from the transfer function (afPWVTF) in the time and frequency domain, respectively. PWV was significantly and positively associated with HR for α ≥ 0.6; for α = 0.6, 0.8, and 1, HR-dependent changes in afPWVTan were 0.01 ± 0.02, 0.07 ± 0.04, and 0.22 ± 0.09 m/s per 5 beats/min; HR-dependent changes in afPWVTF were 0.02 ± 0.01, 0.12 ± 0.00, and 0.34 ± 0.01 m/s per 5 beats/min, respectively. This crosses the range of previous physiological studies where the dependence of PWV on HR was found to be between 0.08 and 0.10 m/s per 5 beats/min. Therefore, viscoelasticity of the arterial wall could contribute to mechanisms through which large artery stiffness changes with changing HR. Physiological studies are required to confirm this mechanism.NEW & NOTEWORTHY This study used a transmission line model to elucidate the role of arterial viscoelasticity in the dependency of pulse wave velocity on heart rate. The model uses fractional viscoelasticity concepts, which provided novel insights into arterial hemodynamics. This study also provides a means of assessing the clinical manifestation of the association of pulse wave velocity and heart rate.

Improved assessment of arterial stiffness using corrected cardio-ankle vascular index (CAVI0) in overweight adolescents with white-coat and essential hypertension.

Arterial stiffness is a marker of vascular damage. Although adiposity increases cardiovascular risk, the relationship between paediatric overweight and arterial stiffness is unclear. The study aimed to evaluate the simultaneous effect of hypertension and overweight on arterial stiffness using cardio-ankle vascular index (CAVI) and related novel, theoretically blood pressure (BP)-independent, index CAVI0. CAVI and CAVI0 were measured in 140 adolescent boys (16.0 ± 1.9 years) divided into age-matched groups: normal-weight normotensives, overweight normotensives, overweight white-coat hypertensives, and overweight essential hypertensives. Overweight normotensives had significantly lower CAVI and CAVI0 compared to normal-weight normotensives (4.81 ± 0.64 vs. 5.33 ± 0.66, p < .01; 7.10 ± 0.99 vs. 7.81 ± 1.00, p < .01, respectively). CAVI and CAVI0 in overweight essential hypertensives showed no significant difference compared to normal-weight normotensives and were significantly higher compared to overweight normotensives (5.32 ± 0.77 vs. 4.81 ± 0.64, p < .01; 7.77 ± 1.19 vs. 7.10 ± 0.99, p < .01, respectively). CAVI, but not CAVI0, was associated positively with diastolic pressure (0.022 mmHg-1, p = .002) and negatively with pulse pressure (-0.022 mmHg-1, p = .001), and it was significantly higher in overweight white-coat hypertensives compared to overweight normotensives (5.20 ± 0.63 vs. 4.81 ± 0.64, p < .05). The lowering effect of overweight on arterial stiffness indexed by CAVI and CAVI0 in hypertensive adolescents seems to counterbalance the early arteriosclerotic effect of essential hypertension. The increase in CAVI, but not CAVI0, in overweight white-coat hypertensives could be attributable to residual BP dependence of CAVI, which is not present in CAVI0. Under certain conditions, CAVI0 may offer a clinically relevant improved assessment of arterial stiffness superior to CAVI.

Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic Dysfunction, and Structural Remodeling in a Rat Model of Chronic Kidney Disease.

BACKGROUND/AIMS: Chronic kidney disease (CKD) is associated with large artery remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang II) a known driver of these pathologies. We investigated long-term Ang II type 1 receptor inhibition with valsartan on aortic function and structure in the Lewis polycystic kidney (LPK) rat model of CKD. METHODS: Mixed sex LPK and Lewis control (total n = 28) treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups were studied. Functional responses to noradrenaline (NA), potassium chloride and endothelium-dependent and independent relaxations were investigated in vitro using acetylcholine hydrochloride (ACh) and sodium nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS) substrate L-arginine, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin on ACh responses were examined. RESULTS: In the LPK, valsartan reduced systolic blood pressure and urinary protein, ameliorated exaggerated sensitivity to NA, and normalized endothelium-dependent (ACh-Rmax; 91 ± 7 vs. 59 ± 6%, p = 0.0001) and independent dysfunction (SNP-Rmax; 99 ± 1 vs. 82 ± 7%, p = 0.040), as well as improving NO-dependent relaxation (Rmax; -51 ± 6 vs. -26 ± 9%, p = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin disruption/fragmentation, calcification, media cystic degeneration, and levels of matrix metalloproteinase 9. CONCLUSIONS: This study highlights the role of Ang II in driving vascular manifestations of CKD and indicates that early treatment can significantly limit pathological changes.

Pressure dependency of aortic pulse wave velocity in vivo is not affected by vasoactive substances that alter aortic wall tension ex vivo.

Aortic stiffness, a predictive parameter in cardiovascular medicine, is blood pressure dependent and experimentally requires isobaric measurement for meaningful comparison. Vasoactive drug administration to change peripheral resistance and blood pressure allows such isobaric comparison but may alter large conduit artery wall tension, directly changing aortic stiffness. This study quantifies effects of sodium nitroprusside (SNP, vasodilator) and phenylephrine (PE, vasoconstrictor) on aortic stiffness measured by aortic pulse wave velocity (aPWV) assessed by invasive pressure catheterization in anaesthetized Sprague-Dawley rats (n = 7). This was compared with nondrug-dependent alteration of blood pressure through reduced venous return induced by partial vena cava occlusion. In vivo drug concentration was estimated by modeling clearance rates. Ex vivo responses of excised thoracic and abdominal aortic rings to drugs was measured using myography. SNP administration did not alter aPWV compared with venous occlusion (P = 0.21-0.87). There was a 5% difference in aPWV with PE administration compared with venous occlusion (P < 0.05). The estimated in vivo maximum concentration of PE (7.0 ± 1.8 ×10(-7) M) and SNP (4.2 ± 0.6 ×10(-7) M) caused ex vivo equivalent contraction of 52 mmHg (thoracic) and 112 mmHg (abdominal) and relaxation of 96% (both abdominal and thoracic), respectively, despite having a negligible effect on aPWV in vivo. This study demonstrates that vasoactive drugs administered to alter systemic blood pressure have a negligible effect on aPWV and provide a useful tool to study pressure-normalized and pressure-dependent aPWV in large conduit arteries in vivo. However, similar drug concentrations affect aortic ring wall tension ex vivo. Future studies investigating in vivo and ex vivo kinetics will need to elucidate mechanisms for this marked difference.

Opposing changes in thoracic and abdominal aortic biomechanical properties in rodent models of vascular calcification and hypertension.

This study investigated the effects of hypertension on regional aortic biomechanical and structural properties in three rat models of vascular calcification: the hypertensive Lewis polycystic kidney (LPK; n = 13) model of chronic kidney disease, spontaneously hypertensive rats (SHRs; n = 12), and calcification in normotensive Lewis rats induced by vitamin D3 and nicotine (VDN; n = 8). Lewis and Wistar-Kyoto rats were controls. Thoracic and abdominal aortic stiffness parameters were assessed by tensile testing. In models where aortic stiffness differences compared with controls existed in both thoracic and abdominal segments, an additional cohort was quantified by histology for thoracic and abdominal aortic elastin, collagen, and calcification. LPK and VDN animals had higher thoracic breaking strain than control animals (P < 0.01 and P < 0.05, respectively) and lower energy absorption within the tensile curve of the abdominal aorta (P < 0.05). SHRs had a lower abdominal breaking stress than Wistar-Kyoto rats. LPK and VDN rats had more elastic lamellae fractures than control rats (P < 0.001), which were associated with calcium deposition (thoracic R = 0.37, P = 0.048; abdominal: R = 0.40, P = 0.046). LPK rats had higher nuclear density than control rats (P < 0.01), which was also evident in the thoracic but not abdominal aorta of VDN rats (P < 0.01). In LPK and VDN rats, but not in control rats, media thickness and cross-sectional area were at least 1.5-fold greater in thoracic than abdominal regions. The calcification models chronic kidney disease and induced calcification in normotension caused differences in regional aortic stiffness not seen in a genetic form of hypertension. Detrimental abdominal aortic remodeling but lower stiffness in the thoracic aorta with disease indicates possible compensatory mechanisms in the proximal aorta.

Characterizing dynamic properties of retinal vessels in the rat eye using high speed imaging.

PURPOSE: The dynamic properties of retinal vessels including pulse wave propagation and pulsatility index provide new perspective in retinal hemodynamic analysis. In this study we utilize a high speed imaging system to capture these characteristics in the rat eye for the first time. METHODS: Retinal video images of 9 Wistar-Kyoto (WKY) rats were captured at a rate of 250 frames per second for 10s with a 50° field of view using a high speed camera (Optronis, Kehl, Germany). Two recordings were taken from each rat at the same sites for repeatability analysis. The electrocardiogram (ECG) was measured simultaneously with retinal images. Arterial retinal pulse wave velocity (rPWV) and arterial/venous pulse amplitude were calculated from recorded images. Arterial measurements were repeated in another normotensive strain of the same age (Sprague-Dawley, n=4). RESULTS: The average WKY rPWV was 11.4 ± 6.1 cm/s. The differences between repeated measures were not significant (-2.8 ± 2.9 cm/s, p=0.2). Sprague-Dawley animals had a similar rPWV (9.8 ± 2.2 cm/s, p=0.61). The average arterial and venous pulse amplitude was 7.1 ± 1.5 µm and 8.2 ± 2.0 µm respectively. There was a positive correlation between rPWV and heart rate in the WKY groups (r(2)=0.32). A positive correlation was also obtained between arterial and venous diameter and their pulse amplitude (r(2)=0.67 and r(2)=0.37 respectively). CONCLUSION: rPWV was associated with heart rate. Higher pulsation amplitude was also correlated with larger vessel diameter. High speed imaging of retinal vessels in the rat eye provides an accurate and robust method to study dynamic characteristics of these vessels and their relationship with ocular and systemic abnormalities.

Validation of oscillometric ratio and maximum gradient methods for non-invasive blood pressure measurement with intra-arterial blood pressure measurements as reference.

Most non-invasive blood pressure (BP) measurements are carried out using instruments which implement either the Ratio or the Maximum Gradient oscillometric method, mostly during cuff deflation, but more rarely during cuff inflation. Yet, there is little published literature on the relative advantages and accuracy of these two methods. In this study of 40 lightly sedated individuals aged 64.1 ± 9.6 years, we evaluate and compare the performance of the oscillometric ratio (K) and gradient (Grad) methods for the non-invasive estimation of mean pressure, SBP and DBP with reference to invasive intra-arterial values. There was no significant difference between intra-arterial estimates of mean pressure made via Korotkoff sounds (MP-OWE) or the gradient method (MP-Grad). However, 17.7% of MP-OWE and 15% of MP-Grad were in error by more than 10 mmHg. SBP-K and SBP-Grad underestimated SBP by 14 and 18 mmHg, whilst accurately estimating DBP with mean errors of 0.4 ±â€Š5.0 and 1.7 ±â€Š6.1 mmHg, respectively. Relative to the reference standard SBP-K, SBP-Grad and DBP-Grad were estimated with a mean error of -4.5 ±â€Š6.6 and 1.4 ±â€Š5.6 mmHg, respectively, noting that using the full range of recommended ratios introduces errors of 12 and 7 mmHg in SBP and DBP, respectively. We also show that it is possible to find ratios which minimize the root mean square error (RMSE) and the mean error for any particular individual cohort. We developed linear models for estimating SBP and SBP-K from a range of demographic and non-invasive OWE variables with resulting mean errors of 0.15 ±â€Š5.6 and 0.3 ±â€Š5.7 mmHg, acceptable according to the Universal standard.

Evaluation of the oscillometric method for noninvasive blood pressure measurement during cuff deflation and cuff inflation with reference to intra-arterial blood pressure.

There is little quantitative clinical data available to support blood pressure measurement accuracy during cuff inflation. In this study of 35 male and 5 female lightly anaesthetized subjects aged 64.1 ±â€Š9.6 years, we evaluate and compare the performance of both the oscillometric ratio and gradient methods during cuff deflation and cuff inflation with reference to intra-arterial measurements. We show that the oscillometric waveform envelopes (OWE), which are key to both methods, exhibit significant variability in both shape and smoothness leading to at least 15% error in the determination of mean pressure (MP). We confirm the observation from our previous studies that K1 Korotkoff sounds underestimate systolic blood pressure (SBP) and note that this underestimation is increased during cuff inflation. The estimation of diastolic blood pressure (DBP) is generally accurate for both the ratio and the gradient method, with the latter showing a significant increase during inflation. Since the gradient method estimates SBP and DBP from points of maximum gradient on each OWE recorded, it may offer significant benefits over the ratio method. However, we have shown that the ratio method can be optimized for any data set to achieve either a minimum mean error (ME) of close to 0 mmHg or minimum root mean square error (RMSE) with standard deviation (SD) of <5.0 mmHg. We conclude that whilst cuff inflation may offer some advantages, these are neither significant nor substantial, leaving as the only benefit, the potential for more rapid measurement and less patient discomfort.

Comparison of cuff inflation and cuff deflation brachial sphygmomanometry with intra-arterial blood pressure as reference.

Conventional sphygmomanometry with cuff deflation is used to calibrate all noninvasive BP (NIBP) instruments and the International Standard makes no mention of calibrating methods specifically for NIBP instruments, which estimate systolic and diastolic pressure during cuff inflation rather than cuff deflation. There is however increasing interest in inflation-based NIBP (iNIBP) instruments on the basis of shorter measurement time, reduction in maximal inflation pressure and improvement in patient comfort and outcomes. However, we have previously demonstrated that SBP estimates based on the occurrence of the first K1 Korotkoff sounds during cuff deflation can underestimate intra-arterial SBP (IA-SBP) by an average of 14 ±â€Š10 mmHg. In this study, we compare the dynamics of intra-arterial blood pressure (IABP) measurements with sequential measurement of Korotkoff sounds during both cuff inflation and cuff deflation in the same individual. In 40 individuals aged 64.1 ±â€Š9.6 years (range 36-86 years), the overall dynamic responses below the cuff were similar, but the underestimation error was significantly larger during inflation than deflation, increasing from 14 ±â€Š10 to 19 ±â€Š12 mmHg ( P  < 0.0001). No statistical models were found which could compensate for this error as were found for cuff deflation. The statistically significant BP differences between inflation and deflation protocols reported in this study suggest different behaviour of the arterial and venous vasculature between arterial opening and closing which warrant further investigation, particularly for iNIBP devices reporting estimates during cuff inflation. In addition, measuring Korotkoff sounds during cuff inflation represents significant technical difficulties because of increasing pump motor noise.

Accurate detection of Korotkoff sounds reveals large discrepancy between intra-arterial systolic pressure and simultaneous noninvasive measurement of blood pressure with brachial cuff sphygmomanometry.

Cardiovascular disease is the number 1 cause of death globally, with elevated blood pressure (BP) being the single largest risk factor. Hence, BP is an important physiological parameter used as an indicator of cardiovascular health. Noninvasive cuff-based automated monitoring is now the dominant method for BP measurement and irrespective of whether the oscillometric or the auscultatory method is used, all are calibrated according to the Universal Standard (ISO 81060-2:2019), which requires two trained operators to listen to Korotkoff K1 sounds for SBP and K4/K5 sounds for DBP. Hence, Korotkoff sounds are fundamental to the calibration of all NIBP devices. In this study of 40 lightly sedated patients, aged 64.1 ±â€Š9.6 years, we compare SBP and DBP recorded directly by intra-arterial fluid filled catheters to values recorded from the onset (SBP-K) and cessation (DBP-K) of Korotkoff sounds. We demonstrate that whilst DBP-K measurements are in good agreement, with a mean difference of -0.3 ±â€Š5.2 mmHg, SBP-K underestimates true intra-arterial SBP (IA-SBP) by an average of 14 ±â€Š9.6 mmHg. The underestimation arises from delays in the re-opening of the brachial artery following deflation of the brachial cuff to below SBP. The reasons for this delay are not known but appear related to the difference between SBP and the pressure under the cuff as blood first begins to flow, as the cuff deflates. Linear models are presented that can correct the underestimation in SBP resulting in estimates with a mean difference of 0.2 ±â€Š7.1 mmHg with respect to intra-arterial SBP.

Association of 24-h central hemodynamics and stiffness with cardiovascular events and all-cause mortality. The VASOTENS Registry.

OBJECTIVES: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients. METHODS: In 591 hypertensive patients (mean age 58 ±â€Š14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years. RESULTS: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P  = 0.0001], female sex [1.57 (1.05, 2.33), P  = 0.027], CV disease [2.22 (1.50, 3.29), P  = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P  = 0.027], PWV [1.59 (1.07, 2.36), P  = 0.022], or AIx [1.59 (1.08, 2.36), P  = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P  = 0.924], AIx [1.06 (0.66, 1.69), P  = 0.823], and central PP [1.18 (0.76, 1.82), P  = 0.471], were not significant predictors in multivariate analyses. CONCLUSIONS: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice.

Nitric oxide (NO) can modulate arterial stiffness by regulating both functional and structural changes in the arterial wall. Tissue transglutaminase (TG2) has been shown to contribute to increased central aortic stiffness by catalyzing the cross-linking of matrix proteins. NO S-nitrosylates and constrains TG2 to the cytosolic compartment and thereby holds its cross-linking function latent. In the present study, the role of endothelial NO synthase (eNOS)-derived NO in regulating TG2 function was studied using eNOS knockout mice. Matrix-associated TG2 and TG2 cross-linking function were higher, whereas TG2 S-nitrosylation was lower in the eNOS(-/-) compared with wild-type (WT) mice. Pulse-wave velocity (PWV) and blood pressure measured noninvasively were elevated in the eNOS(-/-) compared with WT mice. Intact aortas and decellularized aortic tissue scaffolds of eNOS(-/-) mice were significantly stiffer, as determined by tensile testing. The carotid arteries of the eNOS(-/-) mice were also stiffer, as determined by pressure-dimension analysis. Invasive methods to determine the PWV-mean arterial pressure relationship showed that PWV in eNOS(-/-) and WT diverge at higher mean arterial pressure. Thus eNOS-derived NO regulates TG2 localization and function and contributes to vascular stiffness.

Comparison of effects of peripheral vasculature on tonometric radial pulse and cuff-based brachial pulse waveform as used in estimation of central aortic pressures.

OBJECTIVE: Aortic pressure estimation requires reliable peripheral pulse waveform acquisition. The peripheral waveform can change with local vascular effects that can be independent of aortic pressure. This study quantifies the effects of peripheral vasculature changes on radial and brachial waveforms. DESIGN AND METHOD: In 20 subjects (37± 15 years, 7 female), brachial volumetric displacement (cuff-based) and radial tonometry waveforms were simultaneously measured whilst a cuff around the hand on the same arm was inflated to induce transmural pressures of -60, -30, -15, 0, 15 and 30 mmHg, altering local peripheral resistance and compliance by graded arterial wall unloading. Aortic blood pressure (BP), augmentation index (AIx) and ejection duration were calculated from the measurements using a generalized transfer function. The parameters under unloaded conditions were compared to baseline measurements. RESULTS: Brachial systolic and diastolic BP did not change throughout the experiment. Altering peripheral resistance and compliance did not significantly change calculated aortic BP values, although changes were nominally greater for radial (maximum +8±1 mmHg) compared to brachial (maximum +2±1 mmHg) waveforms. AIx at 0 mmHg transmural pressure (maximum arterial wall unloading) was higher when derived from radial waveforms (+24±3%, p<0.001) but not when derived from brachial waveforms. CONCLUSIONS: Localized changes in peripheral resistance and compliance affect tonometer acquired radial waveforms but not volumetric displacement acquired brachial pressure waveforms, as judged by computed central aortic augmentation pressure parameters. This suggests aortic pressure estimation from the brachial cuff waveform is less sensitive to peripheral vasculature disturbances that alter the peripheral arterial pulse morphology.

From peripheral finger-derived pulse waveforms to aortic pressure waveform features: an application of a generalized transfer function.

OBJECTIVE: Aortic (central) pressure features are associated with cardiovascular complications and can be algorithmically derived from non-invasive peripheral arterial waveforms. This has conventionally been performed with a pressure waveform (i.e., tonometry or oscillometry) rather than with the optical-based sensor (photoplethysmography (PPG)) that is predominantly used in wearable health devices. Extraction of aortic features from a peripheral PPG waveform has yet to be investigated. This study aims to compare aortic features extracted from peripheral arterial waveforms acquired with different sensor modalities using the same transfer function. DESIGN AND METHOD: Radial tonometry (reference), finger volume-clamped PPG (Penáz) and fingertip PPG waveforms were measured in participants (n=29, 36±16 years, 15 female) under baseline conditions. Waveforms were converted into an aortic pressure waveform using the transfer function. Waveform features were extracted from the converted waveform. Extracted features were compared with correlation plots and a Bland-Altman analysis. RESULTS: Aortic pressure features extracted from a finger using the Penáz technique were comparable to radial tonometry derived features. Aortic features extracted from a fingertip waveform were more variable in comparison to radial tonometry-derived features. CONCLUSIONS: Aortic (central) pressure waveform features contain valuable haemodynamic information and have the capacity to be easily and conveniently implemented in wearable health devices. Future use of these features in wearable health devices incorporating PPG requires the development, and/or, optimization of a unique transfer function to more accurately represent the aortic pressure waveform for cardiovascular assessment.Clinical Relevance- Aortic pressure features might be used in wearable health devices following the development of a unique transfer function for optical-transduced peripheral vascular signals.