Alberto Avolio

Role of Pulse Pressure Amplification in Arterial Hypertension Experts’ Opinion and Review of the Data

Arterial hypertension is a major modifiable cardiovascular (CV) risk factor worldwide based on observational studies of brachial artery blood pressure (BP). In the latest guidelines of the European Society of Hypertension1 for the management of arterial hypertension, aortic stiffness was introduced as an index of target organ damage. Three additional cardinal features of BP were also acknowledged: (1) systolic BP and pulse pressure (PP) may differ between the brachial artery and central arteries (ie, the aorta and its proximal branches), (2) the effects of antihypertensive drug treatment on brachial BP does not invariably reflect those seen on central BP, and (3) central BP is significantly related to CV events. Moreover, the guidelines acknowledged that noninvasive methods exist for the assessment of central hemodynamic parameters, such as central PP, and highlighted the need for large scale interventional studies that will further confirm the prognostic importance of central BP. Two years ago, coincident with the 6th International Workshop on the “Structure and Function of the Vascular System,” in Paris, a consensus document on the role of central BP in arterial hypertension was published.2 It concluded that there is “mounting evidence suggesting that central BP and indices correlate more closely with intermediate markers of CV risk than brachial BP”. It was also suggested that clinicians and researchers need to become familiarized with the disparity between peripheral and central BPs, ie, the phenomenon of pressure wave amplification. The present document is designed to address this need. The left ventricle consumes energy by ejecting blood into the arterial system, thereby creating arterial blood flow and pressure. This phenomenon is easily conceived as a propagating pulse along the arterial bed. In daily clinical practice the arterial pulse, at a distinct site of the arterial tree (eg, at the brachial artery), is quantified as the …

Methods and devices for measuring arterial compliance in humans

This review analyses methods and devices used worldwide to evaluate the arterial stiffness. Three main methodologies are based upon analysis of pulse transit time, of wave contour of the arterial pulse, and of direct measurement of arterial geometry and pressure, corresponding to regional, systemic and local determination of stiffness. They are used in clinical laboratory and/or in clinical departments. Particular attention is given to the reproducibility data in literature for each device. This article summarizes the discussion of the dedicated Task Force during the first Conference of Consensus on Arterial Stiffness held in June 2000 (Paris, France).

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association.

Much has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as “cf” is used when speaking of specific segments of the arterial circulation. The ability to measure arterial stiffness has been present for many years, but the measurement was invasive in the early times. The improvement in technologies to enable repeated, minimal-risk, reproducible measures of this aspect of circulatory physiology led to its incorporation into longitudinal cohort studies spanning a variety of clinical populations, including those at extreme cardiovascular risk (patients on dialysis), those with comorbidities such as diabetes mellitus (DM) and hypertension, healthy elders, and general populations. In the ≈3 decades of clinical use of PWV measures in humans, we have learned much about the importance of this parameter. PWV has proven to have independent predictive utility when evaluated in conjunction with standard risk factors for death and cardiovascular disease (CVD). However, the field of arterial stiffness investigation, which has exploded over the past 20 years, has proliferated without logistical guidance for clinical and …

Improved arterial distensibility in normotensive subjects on a low salt diet.

Arterial pulse wave velocity (PWV), a noninvasive index of arterial distensibility, was measured in 57 normotensive subjects who followed a voluntary low salt diet for a period ranging from 8 months to 5 years (mean, 24.8 months). Subjects who followed a regular diet were matched for age and mean arterial pressure with the low salt (LS) sample and were used as controls (C). For both samples, subjects were divided into three age groups: Group 1 (aged 2 to 19 years, n = 16), Group 2 (29 to 44 years, n = 26), and Group 3 (45 to 66 years, n = 15). There was a marked increase in aortic PWV with age in the control sample but not in the LS sample. There was no significant difference in aortic PWV for Group 1, but in Groups 2 and 3, the LS subjects showed a decrease of 21.8% and 22.7%, respectively, compared to C subjects. Aortic PWV (cm/sec) was: Group 1: C =581 (SE 44), LS =614 (SE 31); Group 2: C =942 (SE 46); LS =737 (SE 27) (p < 0.001); Group 3: C =958 (SE 77), LS =741 (SE 25) (p < 0.05)). Arm and leg PWV were also significantly lower in the older age groups. These findings suggest that normotensive adult subjects who follow a low salt diet (mean intake, 44 mmol Na/24 hours) have reduced arterial stiffness and that the effect is independent of blood pressure. This is prima facie evidence that reduced salt intake has a beneficial effect in improving distensibility of the central aorta and large peripheral arteries, which is independent of its antihypertensive action.

Quantification of Alterations in Structure and Function of Elastin in the Arterial Media

The structure of medial elastin determines arterial function and affects wall mechanical properties. The aim of this study was to (1) characterize the structure of elastin in terms of textural features, (2) relate structural parameters to total number of cardiac cycles (TC), and (3) determine the contribution of medial elastin to lumen mechanical stress. Images of pressure-fixed aortic sections stained for elastin were obtained from specimens collected postmortem from 35 animals of different species with a wide range of age, heart rate, and TC and divided into 2 groups: TClow=3.69+/-0.38x10(8) (n=17) and TChigh=15.8+/-2.38x10(8) (n=18) (P<0.001). A directional fractal curve was generated for each image, and image texture was characterized by directional fractal curve parameters. Elastin volume fraction and interlamellar distance were obtained by image analysis. Wall stress distribution was determined from a finite element model of the arterial wall with multiple layers simulating elastin lamellae. DFC amplitude was related to elastin volume fraction. Increased TC (TClow versus TChigh) was associated with lower directional fractal curve amplitude (0.23+/-0.02 versus 0.14+/-0.02; P<0.001), reduced elastin volume fraction (36.5+2.6% versus 25.7+2.1%; P<0.01), and increased interlamellar distance (8.5+/-0.5 versus 11.5+/-1.0 microm; P<0.05). Loss of medial elastic function increased pressure-dependent maximal circumferential stress. Structural alterations of medial elastin, quantified by fractal parameters, are associated with cumulative effects of repeated pulsations due to the combined contribution of age and heart rate. Loss of medial functional elasticity increases luminal wall stress, increasing the possibility of endothelial damage and predisposition to atherosclerosis.

Quantification of Wave Reflection in the Human Aorta From Pressure Alone: A Proof of Principle

Wave reflections affect the proximal aortic pressure and flow waves and play a role in systolic hypertension. A measure of wave reflection, receiving much attention, is the augmentation index (AI), the ratio of the secondary rise in pressure and pulse pressure. AI can be limiting, because it depends not only on the magnitude of wave reflection but also on wave shapes and timing of incident and reflected waves. More accurate measures are obtainable after separation of pressure in its forward (Pf) and reflected (Pb) components. However, this calculation requires measurement of aortic flow. We explore the possibility of replacing the unknown flow by a triangular wave, with duration equal to ejection time, and peak flow at the inflection point of pressure (FtIP) and, for a second analysis, at 30% of ejection time (Ft30). Wave form analysis gave forward and backward pressure waves. Reflection magnitude (RM) and reflection index (RI) were defined as RM=Pb/Pf and RI=Pb/(Pf+Pb), respectively. Healthy subjects, including interventions such as exercise and Valsalva maneuvers, and patients with ischemic heart disease and failure were analyzed. RMs and RIs using FtIP and Ft30 were compared with those using measured flow (Fm). Pressure and flow were recorded with high fidelity pressure and velocity sensors. Relations are: RMtIP=0.82RMmf+0.06 (R2=0.79; n=24), RMt30=0.79RMmf+0.08 (R2=0.85; n=29) and RItIP=0.89RImf+0.02 (R2=0.81; n=24), RIt30=0.83RImf+0.05 (R2=0.88; n=29). We suggest that wave reflection can be derived from uncalibrated aortic pressure alone, even when no clear inflection point is distinguishable and AI cannot be obtained. Epidemiological studies should establish its clinical value.

Age, hypertension and arterial function

1 Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross‐sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age‐related changes observed in peripheral arteries appear to be less marked. 2 The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3 Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4 Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end‐product cross‐links between proteins, such as collagen and elastin, hold substantial promise.

Arterial blood pressure measurement and pulse wave analysis—their role in enhancing cardiovascular assessment

The most common method of clinical measurement of arterial blood pressure is by means of the cuff sphygmomanometer. This instrument has provided fundamental quantitative information on arterial pressure in individual subjects and in populations and facilitated estimation of cardiovascular risk related to levels of blood pressure obtained from the brachial cuff. Although the measurement is taken in a peripheral limb, the values are generally assumed to reflect the pressure throughout the arterial tree in large conduit arteries. Since the arterial pressure pulse becomes modified as it travels away from the heart towards the periphery, this is generally true for mean and diastolic pressure, but not for systolic pressure, and so pulse pressure. The relationship between central and peripheral pulse pressure depends on propagation characteristics of arteries. Hence, while the sphygmomanometer gives values of two single points on the pressure wave (systolic and diastolic pressure), there is additional information that can be obtained from the time-varying pulse waveform that enables an improved quantification of the systolic load on the heart and other central organs. This topical review will assess techniques of pressure measurement that relate to the use of the cuff sphygmomanometer and to the non-invasive registration and analysis of the peripheral and central arterial pressure waveform. Improved assessment of cardiovascular function in relation to treatment and management of high blood pressure will result from future developments in the indirect measurement of arterial blood pressure that involve the conventional cuff sphygmomanometer with the addition of information derived from the peripheral arterial pulse.

The Relationship of Age With Regional Aortic Stiffness and Diameter

OBJECTIVES The purpose of this study was to determine the impact of age on regional aortic pulse wave velocity (aPWV). BACKGROUND aPWV is an independent predictor of cardiovascular risk and increases exponentially with age. However, it is unclear whether such changes occur uniformly along the length of the aorta or vary by region. METHODS A total of 162 subjects, aged 18 to 77 years and free of cardiovascular disease and medication, were recruited from the Anglo-Cardiff Collaborative Trial. Cine phase contrast magnetic resonance imaging was performed at 5 aortic levels. Systolic diameter and average blood flow were measured at each level and regional aPWV (regional aPWV measured by cine phase contrast magnetic resonance imaging) determined in 4 aortic segments: the arch (R1), the thoracic-descending aorta (R2), mid-descending aorta (R3), and the abdominal aorta (R4) and across the entire aorta. RESULTS Regional PWV measured by cine phase contrast magnetic resonance imaging values increased from the valve to the bifurcation in the 4 segments (PWV-R1- PWV-R4: 4.6 ± 1.5 m/s, 5.5 ± 2.0 m/s, 5.7 ± 2.3 m/s, 6.1 ± 2.9 m/s, respectively) and did not differ between genders. The greatest age-related difference in stiffness occurred in the abdominal aorta (+0.9 m/s per decade, p < 0.001) followed by the thoracic-descending region (+0.7 m/s, p < 0.001), the mid-descending region (+0.6 m/s, p < 0.001) and aortic arch (+0.4 m/s, p < 0.001). The average systolic diameters decreased moving distally (L1-5: 3.1 ± 0.4 cm, 2.3 ± 0.3 cm, 2.1 ± 0.3 cm, 1.9 ± 0.2 cm, and 1.7 ± 0.2 cm, respectively). The greatest variation in systolic diameter as a function of age occurred in the ascending region (+0.96 mm/decade, p < 0.001). Values of aPWV measured across the entire aorta were strongly correlated with PWV-tonometry (R = 0.71, p < 0.001), although they were significantly lower (mean difference 1.7 ± 1.6 m/s, p < 0.001). CONCLUSIONS The greatest difference in aortic stiffness occurs in the abdominal region, whereas the greatest difference in diameter occurs in the ascending aorta, which may help offset an increase in wall stiffness.

Nebivolol Increases Arterial Distensibility In Vivo

Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. &bgr;-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that &bgr;-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of &bgr;-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating &bgr;-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6±3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of −1±3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of −5±3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of NG-monomethyl-l-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a &bgr;2 adrenoceptor–dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.