Abstract
Increasing evidence points out at vascular stiffness (and in particular aortic stiffness measured by pulse wave velocity) as a reliable biomarker of vascular aging, able to integrate in a ...single measure the overall burden of cardiovascular (CV) risk factors on the vasculature over time; furthermore, it may be per se a mechanism of disease, by inducing microcirculatory damage and favoring CV events. Increased aortic stiffness has been shown to predict future CV events and improve risk reclassification in those at intermediate risk. However, several questions in this field are still open, limiting the wide use of these tools in the clinical practice. This article will review the basic aspects of physiology of large artery stiffness, as well as current evidence about its possible clinical applications.
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and ...structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of ...the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing direct structural damage and by causing further ROS production. Despite this sound biological rationale and a number of pre-clinical and clinical lines of evidence, studies testing the effects of classical antioxidants such as vitamin C, vitamin E, or folic acid in combination with vitamin E have been disappointing. Rather, substances such as statins, angiotensin-converting enzyme inhibitors, or AT1-receptor blockers, which possess indirect antioxidant properties mediated by the stimulation of NO production and simultaneous inhibition of superoxide production (e.g. from the NADPH oxidase), have been shown to improve vascular function in pre-clinical and clinical studies and to reduce the incidence of cardiovascular events in patients with cardiovascular disease. Today, oxidative stress remains an attractive target for cardiovascular prevention and therapy. However, a deeper understanding of its source, and of its role in vascular pathology, is necessary before new trials are attempted.
Hypertension and insomnia are very common and often coexist. There is evidence to suggest that the increasing prevalence of arterial hypertension in the past decade might be related both to an ...increased prevalence of insomnia and to the decline of sleep duration due to modern lifestyle. The aim of this paper is to reconsider both the clinical evidence of the relationship between conditions of sleep loss and of perceived impairment in sleep quality with hypertension and the potential pathophysiological mechanisms underlying the biological plausibility of their relationship. Through a systematic search from MEDLINE, EMBASE, PsychINFO we selected articles, which reported experimental sleep deprivation designs, or studied sleep duration or insomnia and their relationship with blood pressure or hypertension in participants over 18 years. This analysis shows that experimental sleep deprivation, short sleep duration, and persistent insomnia are associated with increased blood pressure and increased risk of hypertension, even after controlling for other risk factors. Pathophysiological mechanisms underlying this association might be related to inappropriate arousal ("hyperarousal") due to an overactivation of stress system functions. According this hypothesis, prolonged sleep loss or alterations of sleep quality might act as a neurobiological and physiologic stressor that impair brain functions and contribute to allostatic load, compromising stress resilience and somatic health.
In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor ...blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes.
We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures.
On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio OR, 3.35, 95% confidence interval CI, 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05-11.96).
Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.
Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease ...(CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.
Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study ...was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms.
Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used.
Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals.
An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.
Obesity is reaching epidemic proportions globally and represents a major cause of comorbidities, mostly related to cardiovascular disease. The autonomic nervous system (ANS) dysfunction has a two-way ...relationship with obesity. Indeed, alterations of the ANS might be involved in the pathogenesis of obesity, acting on different pathways. On the other hand, the excess weight induces ANS dysfunction, which may be involved in the haemodynamic and metabolic alterations that increase the cardiovascular risk of obese individuals, i.e., hypertension, insulin resistance and dyslipidemia. This article will review current evidence about the role of the ANS in short-term and long-term regulation of energy homeostasis. Furthermore, an increased sympathetic activity has been demonstrated in obese patients, particularly in the muscle vasculature and in the kidneys, possibily contributing to increased cardiovascular risk. Selective leptin resistance, obstructive sleep apnea syndrome, hyperinsulinemia and low ghrelin levels are possible mechanisms underlying sympathetic activation in obesity. Weight loss is able to reverse metabolic and autonomic alterations associated with obesity. Given the crucial role of autonomic dysfunction in the pathophysiology of obesity and its cardiovascular complications, vagal nerve modulation and sympathetic inhibition may serve as therapeutic targets in this condition.
In the context of home confinement during the coronavirus disease (COVID-19) pandemic, objective, real-time data are needed to assess populations' adherence to home confinement to adapt policies and ...control measures accordingly.
The aim of this study was to determine whether wearable activity trackers could provide information regarding users' adherence to home confinement policies because of their capacity for seamless and continuous monitoring of individuals' natural activity patterns regardless of their location.
We analyzed big data from individuals using activity trackers (Withings) that count the wearer's average daily number of steps in a number of representative nations that adopted different modalities of restriction of citizens' activities.
Data on the number of steps per day from over 740,000 individuals around the world were analyzed. We demonstrate the physical activity patterns in several representative countries with total, partial, or no home confinement. The decrease in steps per day in regions with strict total home confinement ranged from 25% to 54%. Partial lockdown (characterized by social distancing measures such as school closures, bar and restaurant closures, and cancellation of public meetings but without strict home confinement) does not appear to have a significant impact on people's activity compared to the pre-pandemic period. The absolute level of physical activity under total home confinement in European countries is around twofold that in China. In some countries, such as France and Spain, physical activity started to gradually decrease even before official commitment to lockdown as a result of initial less stringent restriction orders or self-quarantine. However, physical activity began to increase again in the last 2 weeks, suggesting a decrease in compliance with confinement orders.
Aggregate analysis of activity tracker data with the potential for daily updates can provide information regarding adherence to home confinement policies.
Venturia inaequalis is an ascomycete fungus responsible for apple scab, a disease that has invaded almost all apple growing regions worldwide, with the corresponding adverse effects on apple ...production. Monitoring and predicting the effectiveness of intervention strategies require knowledge of the origin, introduction pathways, and population biology of pathogen populations. Analysis of the variation of genetic markers using the inferential framework of population genetics offers the potential to retrieve this information.
Here, we present a population genetic analysis of microsatellite variation in 1,273 strains of V. inaequalis representing 28 orchard samples from seven regions in five continents. Analysis of molecular variance revealed that most of the variation (88%) was distributed within localities, which is consistent with extensive historical migrations of the fungus among and within regions. Despite this shallow population structure, clustering analyses partitioned the data set into separate groups corresponding roughly to geography, indicating that each region hosts a distinct population of the fungus. Comparison of the levels of variability among populations, along with coalescent analyses of migration models and estimates of genetic distances, was consistent with a scenario in which the fungus emerged in Central Asia, where apple was domesticated, before its introduction into Europe and, more recently, into other continents with the expansion of apple growing. Across the novel range, levels of variability pointed to multiple introductions and all populations displayed signatures of significant post-introduction increases in population size. Most populations exhibited high genotypic diversity and random association of alleles across loci, indicating recombination both in native and introduced areas.
Venturia inaequalis is a model of invasive phytopathogenic fungus that has now reached the ultimate stage of the invasion process with a broad geographic distribution and well-established populations displaying high genetic variability, regular sexual reproduction, and demographic expansion.
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