Arterial stiffness index beta and cardio-ankle vascular index inherently depend on blood pressure but can be readily corrected

Objectives: Arterial stiffness index beta and cardio-ankle vascular index (CAVI) are widely accepted to quantify the intrinsic exponent (beta(0)) of the blood pressure (BP)-diameter relationship. CAVI and b assume an exponential relationship between pressure (P) and diameter (d). We aim to demonstrate that, under this assumption, beta and CAVI as currently implemented are inherently BP-dependent and to provide corrected, BP-independent forms of CAVI and beta.Methods and results: In P = P(ref)e(beta 0[(d/dref)-1)], usually reference pressure (P-ref) and reference diameter (d(ref)) are substituted with DBP and diastolic diameter to accommodate measurements. Consequently, the resulting exponent is not equal to the pressure-independent beta(0). CAVI does not only suffer from this 'reference pressure' effect, but also from the linear approximation of (dP=dd). For example, assuming beta(0) = 7, an increase of SBP/DBP from 110/70 to 170/120mmHg increased beta by 8.1% and CAVI by 14.3%. We derived corrected forms of b and of CAVI (CAVI(0)) that indeed did not change with BP and represent the pressure-independent beta(0). To substantiate the BP effect on CAVI in a typical follow-up study, we realistically simulated patients (n = 161) before and following BP-lowering 'treatment' (assuming no follow-up change in intrinsic beta(0) and therefore in actual P-d relationship). Lowering BP from 160 +/- 14/111 +/- 11 to 120 +/- 15/79 +/- 11 mmHg (p &lt;0.001) resulted in a significant CAVI decrease (from 8.1 +/- 2.0 to 7.7 +/- 2.1, p = 0.008); CAVI(0) did not change (9.8 +/- 2.4 and 9.9 +/- 2.6, p = 0.499).Conclusion: beta and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness trials. BP-independent forms are presented to readily overcome this problem.</p

Pediatric reference values for arterial stiffness parameters cardio-ankle vascular index and CAVI0

The process of arteriosclerosis begins early in life, and cardiovascular risk factors identified in childhood tend to persist into adulthood. Cardio-ankle vascular index (CAVI), a recent parameter of arterial stiffness, is considered an independent predictor of cardiovascular risk. However, there are no studies reporting sex- and age-specific physiological values of CAVI in childhood. We aimed to establish reference values for CAVI and its blood pressure-corrected variant (CAVI0) in 500 healthy children and adolescents aged 7 to 19 years and to study potential relationships with anthropometric indices. Sex- and age-specific distributions of CAVI and CAVI0 values in healthy children and adolescents are presented. Boys aged 15-19 years had lower CAVI than girls, which could result from CAVI's slight blood pressure dependence. CAVI0 did not show such sex difference. Body roundness index-a novel parameter to quantify abdominal fat-was a strong anthropometric predictor of both CAVI and CAVI0. This is the first study providing pediatric age- and sex-specific reference values for arterial stiffness parameters CAVI and CAVI0. The presented data can contribute to the understanding of the evolution of these indices during childhood and adolescence. Under specific conditions, CAVI0 may offer more robust information about arterial stiffness than standard CAVI

Principles of cerebral hemodynamics when intracranial pressure is raised: lessons from the peripheral circulation.

BACKGROUND: The brain is highly vascular and richly perfused, and dependent on continuous flow for normal function. Although confined within the skull, pressure within the brain is usually less than 15 mmHg, and shows small pulsations related to arterial pulse under normal circumstances. Pulsatile arterial hemodynamics in the brain have been studied before, but are still inadequately understood, especially during changes of intracranial pressure (ICP) after head injury. METHOD: In seeking cohesive explanations, we measured ICP and radial artery pressure (RAP) invasively with high-fidelity manometer systems, together with middle cerebral artery flow velocity (MCAFV) (transcranial Doppler) and central aortic pressure (CAP) generated from RAP, using a generalized transfer function technique, in eight young unconscious, ventilated adults following closed head trauma. We focused on vascular effects of spontaneous rises of ICP ('plateau waves'). RESULTS: A rise in mean ICP from 29 to 53 mmHg caused no consistent change in pressure outside the cranium, or in heart rate, but ICP pulsations increased in amplitude from 8 to 20 mmHg, and ICP waveform came to resemble that in the aorta. Cerebral perfusion pressure (=central aortic pressure - ICP), which equates with transmural pressure, fell from 61 to 36 mmHg. Mean MCAFV fell from 53 to 40 cm/s, whereas pulsatile MCAFV increased from 77 to 98 cm/s. These significant changes (all P < 0.01) may be explained using the Monro-Kellie doctrine, because of compression of the brain, as occurs in a limb when external pressure is applied. CONCLUSION: The findings emphasize importance of reducing ICP, when raised, and on the additional benefits of reducing wave reflection from the lower body.This study was supported by the National Institute of Health Research, the Biomedical Research Centre (Neuroscience Theme), and the Medical Research Council (Grants G0600986 and G9439390). J.D.P. has received the NIHR Investigator Awards. M.O.K. is sponsored by an Australian Postgraduate Awards Industrial Linkage Grant from the Australian Research Council (LP0884094), with AtCor Medical Australia as the collaborating organization.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1097/HJH.000000000000053

17β-estradiol changes the human cerebral endothelial cell proteome upon exposure to cyclic stretch

Hypertension and estrogen deficiency in women have been identified as significant risk factors for cerebrovascular diseases. Hypertension causes excessive vascular stretch and contributes to the initiation of cellular injury in blood vessels while estrogen has been demonstrated to exert beneficial protective effects on the vascular system. Although the specific biological outcomes exerted by either excessive stretch or estrogen exposure are well established, the combined biochemical effects of both stimuli remain unclear. Therefore, this study was conducted for quantitative proteomics study on human cerebral microvascular endothelial cells (HCMECs) subjected to 20% “pathological” cyclic stretch for a period of 18 hour in the presence or absence of 17β-estradiol by isobaric Taqs for Relative and Absolute Quantification. The results showed that only some proteins responded to 17β-estradiol (e.g., thioredoxin reductase-1), stretch (e.g., 14-3-3 protein epsilon or acidic leucine-rich nuclear phosphoprotein 32 family member B) and interestingly, some proteins returned to control pre-treatment levels when exposed to both (e.g., d-dopachrome decarboxylase, thrombospondin-1). In addition, HCMECs that exposed only to estrogen had a very similar proteomic profile (i.e., up-regulation of structural, cellular adhesion and proliferation proteins) as to those exposed to estrogen with 20% stretching for 18 hour, suggesting that estrogen ablated the detrimental effects by the stretch alone. These findings sheds light on the molecular mechanisms by which the cerebrovascular protective actions of estrogen on HCMEC exposed to pathological levels of cyclic stretch which could provide a platform for future research in therapeutic approach

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences +/- SD= 44 +/- 11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences +/- SD= 0 +/- 8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered

Blood Pressure and Arterial Stiffness

Background—The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index β-transformed value (β-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results—In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions—Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects

Age-Specific Acute Changes in Carotid-Femoral Pulse Wave Velocity With Head-up Tilt

BACKGROUND: Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age. METHODS: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP. RESULTS: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04). CONCLUSIONS: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson