Pulse pressure—a review of mechanisms and clinical relevance

AbstractThe goal of this study was to review the origin, clinical relevance and treatment of pulse pressure (PP). Elevated PP is increasingly being recognized as a risk factor for cardiovascular, particularly coronary, disease. Pulse pressure is discussed in terms of both Windkessel and distributive models of the arterial circulation. Pulse pressure arises from the interaction of cardiac ejection (stroke volume) and the properties of the arterial circulation. An increased stiffness of the aorta and large arteries leads to an increase in PP through a reduction in arterial compliance and effects on wave reflection. A number of factors are known to influence arterial wall behavior and, therefore, PP. In addition to the effects of aging and blood pressure on arterial wall elasticity, there is some evidence that atherosclerosis, per se, amplifies these effects. Thus, the relationship between PP and coronary disease may be bidirectional. A number of dietary and lifestyle interventions have been shown to modify large artery behavior. These include aerobic exercise training and consumption of n-3 fatty acids. Conversely, strength training is associated with an increase in arterial stiffness and a higher PP. The effects of antihypertensive medication have been extensively studied, but many studies are difficult to interpret because of concomitant change in blood pressure, and to a lesser degree, heart rate. However a number of studies do suggest direct arterial wall effects, particularly for angiotensin-converting enzyme inhibitors. A distributed compliance model of the arterial circulation provides a framework for understanding the causes, effects and potential treatment of elevations in PP

“True fan = watch match”? In Search of the ‘Authentic’ Soccer Fan.

Academics have created typologies to divide association football (soccer) fans into categories based upon the assumed ‘authenticity’ of their fandom practices. One of the main requirements of ‘authentic’ fandom has been assumed to be match attendance. The goal of this paper was to critically assess this assumption through considering how fans themselves talk about the significance of match attendance as evidence of ‘authentic’ fandom. In light of the fact that the voices of English non-league fans on the ‘authenticity’ debate have so far been overshadowed by the overbearing focus of much previous research on the upper echelons of English soccer, an e-survey was conducted with 151 members of an online community of fans of English Northern League (NL) clubs (a semi-professional / amateur league based in North East England). Findings revealed that opinion was divided on the constituents of ‘authentic’ fandom and match attendance was not deemed to be the core evidence of support for a club by 42% of the sample. Elias (1978) suggested that dichotomous thinking hinders sociological understanding and it is concluded that fan typologies are not sufficient for assessing the ‘authenticity’ of fan activities

Numerical and in vitro experimental study of arterial deformation and buckling under hypertension and atherosclerotic conditions

Cardiovascular diseases remain the major cause of mortality worldwide. Pathologies of the vasculature such as atherosclerosis are often related to biochemical and genetic factors as well as mechanical effects that strongly change the function and shape of arteries. The present work is part of a general research project which aims to better understand the mechanical mechanisms responsible for atherosclerotic plaque formation and rupture. The chosen approach is to use numerical fluidstructure interaction (FSI) methods to study the relative influence of hemodynamic parameters on the structural stresses generated on plaques. To this aim, a numerical study of a simplified straight vessel exposed to lumen pressure was investigated under quiescent and steady flow conditions. As the internal pressure or the steady velocity increases, the vessel buckles lead-ing to a non-linear large deformation behaviour. The results have been validated using theoretical predictions for the buckling thresholds. Further studies on idealised cardiovascular conditions such as stenosis (i.e., lumen constriction) or aneurysm like (i.e., arterial wall expansion) formation have also been performed

Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression

Asymptomatic people with well-controlled HIV do not have abnormal left ventricular global longitudinal strain

BackgroundPrevious studies have reported impairment in systolic and diastolic function in people with HIV (PWHIV). Our aim was to determine if echocardiographically measured left ventricular (LV) global longitudinal strain (GLS) is abnormal in asymptomatic PWHIV.MethodsA cross-sectional study of PWHIV (n = 98, 89% male, median age 53 years) and HIV-negative people (n = 50, median age 53 years) without known cardiovascular disease were recruited from a single centre. All participants completed a health/lifestyle questionnaire, provided a fasting blood sample, and underwent a comprehensive echocardiogram for assessment of diastolic and systolic LV function, including measurement of GLS.ResultsAll PWHIV were receiving antiretroviral therapy (ART) for a median of 12 years (IQR: 6.9, 22.4), the majority with good virological control (87% suppressed) and without immunological compromise (median CD4 598 cells/µl, IQR: 388, 841). Compared with controls of similar age and gender, there was no difference in GLS [mean GLS −20.3% (SD 2.5%) vs. −21.0% (SD 2.5%), p = 0.14] or left ventricular ejection fractions [65.3% (SD 6.3) vs. 64.8% (SD 4.8), p = 0.62]. Following adjustment for covariates (gender, heart rate, systolic and diastolic blood pressure, and fasting glucose), the difference in GLS remained non-significant. There were no differences in LV diastolic function between the groups. Exposure to at least one mitochondrially toxic ART drug (didanosine, stavudine, zidovudine, or zalcitabine) was not associated with impairment of LV systolic function.ConclusionNo clinically significant impairment of myocardial systolic function, as measured by LV GLS, was detected in this predominantly Caucasian male population of PWHIV on long-term ART, with no history of cardiovascular disease

Three-dimensional numerical simulation of blood flow in mouse aortic arch around atherosclerotic plaques

Atherosclerosis is a progressive disease, involving the build-up of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is critically important since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those likely to rupture (vulnerable) or less likely to rupture (stable). In the last decade, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces and structural stress) on the plaque formation, progression and rupture processes but no general agreement has been found. The purpose of the present work is to include more realistic conditions for the numerical calculations of the blood flow by implementing real geometries with plaques in the numerical model. Hemodynamical parameters are studied in both diseased and healthy configurations. The healthy configuration is obtained by removing numerically the plaques from three dimensional geometries obtained by micro-computed tomography. A new hemodynamical parameter is also introduced to relate the location of plaques to the characteristics of the flow in the healthy configuration

Mechanism of Beraprost Effects on Pulmonary Hypertension: Contribution of Cross-Binding to PGE2 Receptor 4 and Modulation of O2 Sensitive Voltage-Gated K+ Channels

Background: The purpose of this study is to elucidate mechanism(s) by which the orally active PGI2 analog, Beraprost (BPS), ameliorates pulmonary hypertension (PH). Prostaglandins are an important treatment for PH. Mechanisms of their action are not fully elucidated in relation to receptor subtype and effects on O2 sensitive Kv channels.Methods: Distal (3rd order and beyond) pulmonary arteries from chronically hypoxic rats and from humans with established PH were studied. Measurements included pulmonary haemodynamics and histology, vascular reactivity, prostanoid receptor expression and activity of the O2 sensitive Kv channels.Results: Prostacyclin receptor (IP), prostaglandin receptor E3 (EP3) and prostaglandin receptor E4 (EP4) are the main pulmonary artery receptor subtypes in both rat and human pulmonary arteries. Circulating levels of PGI2 and PGE2 were reduced in PH. PH was also associated with reduced receptor expression of IP but not of EP4. The effects on IP expression were overcome with BPS. Dilatory responses in PH to BPS were reduced in the presence of EP4 blockade. Expression and activity of oxygen sensitive Kv channels were reduced in pulmonary artery smooth muscle cell from rats with PH and humans with PAH and were also overcome by administration of BPS. Effects of BPS on oxygen sensitive Kv channels were reduced in the presence of EP4 blockade implicating the EP4 receptor, as well as the IP receptor, in mediating BPS effects.Conclusion: Reduced expression of pulmonary IP receptors and reduced activity of O2 sensitive Kv channels are found in PH in both humans and rats. The orally active prostacyclin analogue, BPS, is able to reverse these changes, partly through binding to the EP4 receptor