The effect of antihypertensive drugs on arterial stiffness and central hemodynamics: Not all fingers are made the same

Arterial stiffness and central hemodynamics attract increasing scientific interest within the hypertensive community during the last decade. Accumulating evidence indicates that aortic stiffness is a strong and independent predictor of cardiovascular events and all-cause mortality in hypertensive patients, and its predictive value extends beyond traditional risk factors. The role of central hemodynamics and augmentation index (a marker of reflected waves), remains less established and requires further investigation. Several lines of evidence indicate that antihypertensive therapy results in significant reductions of pulse wave velocity and central hemodynamics. However, beta-blockers seem to be the only exception with significant within-class differences. Conventional beta-blockers, although equally effective in reducing pulse wave velocity, seem to be less beneficial on central hemodynamics and augmentation index than the other antihypertensive drug categories, whereas the newer vasodilating beta-blockers seem to share the benefits of the other antihypertensive drugs. In conclusion, aortic stiffness seems ready for ‘prime-time’ in the management of essential hypertension, while further research is needed for central hemodynamics and augmentation index

Carotid Baroreceptor Stimulation for the Treatment of Resistant Hypertension

Interventional activation of the carotid baroreflex has been an appealing idea for the management of resistant hypertension for several decades, yet its clinical application remained elusive and a goal for the future. It is only recently that the profound understanding of the complex anatomy and pathophysiology of the circuit, combined with the accumulation of relevant experimental and clinical data both in animals and in humans, has allowed the development of a more effective and well-promising approach. Indeed, current data support a sustained over a transient reduction of blood pressure through the resetting of baroreceptors, and technical deficits have been minimized with a subsequent recession of adverse events. In addition, clinical outcomes from the application of a new implantable device (Rheos) that induces carotid baroreceptor stimulation point towards a safe and effective blood pressure reduction, but longer experience is needed before its integration in the everyday clinical practice. While accumulating evidence indicates that carotid baroreceptor stimulation exerts its benefits beyond blood pressure reduction, further research is necessary to assess the spectrum of beneficial effects and evaluate potential hazards, before the extraction of secure conclusions

Benefits from Treatment and Control of Patients with Resistant Hypertension

Resistant hypertension is commonly found in everyday clinical practice. However, the risks of resistant hypertension, as well as the benefits of treatment and control of blood pressure in patients with resistant hypertension remain vaguely clarified. Data from small clinical studies and observational cohorts suggest that patients with resistant hypertension are at increased cardiovascular risk, while control of blood pressure offers substantial benefits. It has to be noted however that data from appropriate large randomized studies are missing, and resistant hypertension remains remarkably understudied. Resistant hypertension has attracted significant scientific interest lately, as new therapeutic modalities become available. The interventional management of resistant hypertension either by carotid baroreceptor stimulation or renal sympathetic denervation is currently under investigation with promising preliminary results. This review presents available evidence regarding the benefits of treatment and control of blood pressure in patients with resistant hypertension and offers a critical evaluation of existing data in this field

Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2020.00277/full#supplementary-materialShort-chain fatty acids (SCFAs) are among the main classes of bacterial metabolic products and are mainly synthesized in the colon through bacterial fermentation. Short-chain fatty acids, such as acetate, butyrate, and propionate, reduce endothelial activation induced by proinflammatory mediators, at least in part, by activation of G protein–coupled receptors (GPRs): GPR41 and GPR43. The objective of the study was to analyze the possible protective effects of SCFAs on endothelial dysfunction induced by angiotensin II (AngII). Rat aortic endothelial cells (RAECs) and rat aortas were incubated with AngII (1 μM) for 6 h in the presence or absence of SCFAs (5–10 mM). In RAECs, we found that AngII reduces the production of nitric oxide (NO) stimulated by calcium ionophore A23187; increases the production of reactive oxygen species (ROS), both from the nicotinamide adenine dinucleotide phosphate oxidase system and the mitochondria; diminishes vasodilator-stimulated phosphoprotein (VASP) phosphorylation at Ser239; reduces GPR41 and GPR43 mRNA level; and reduces the endothelium-dependent relaxant response to acetylcholine in aorta. Coincubation with butyrate and acetate, but not with propionate, increases both NO production and pSer239-VASP, reduces the concentration of intracellular ROS, and improves relaxation to acetylcholine. The beneficial effects of butyrate were inhibited by the GPR41 receptor antagonist, β-hydroxybutyrate, and by the GPR43 receptor antagonist, GLPG0794. Butyrate inhibited the down-regulation of GPR41 and GPR43 induced by AngII, being without effect acetate and propionate. Neither β-hydroxybutyrate nor GLPG0794 affects the protective effect of acetate in endothelial dysfunction. In conclusion, acetate and butyrate improve endothelial dysfunction induced by AngII by increasing the bioavailability of NO. The effect of butyrate seems to be related to GPR41/43 activation, whereas acetate effects were independent of GPR41/43.Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF2017-8489-RJunta de Andalucia CTS164European Union (EU)Ministerio de Economia y competitividad, Instituto de Salud Carlos III (CIBER-CV), Spai

The Relationship Between Ambulatory Arterial Stiffness Index and Blood Pressure Variability in Hypertensive Patients

Background and Objectives: Ambulatory arterial stiffness index (AASI) is well known as a predictor of cardiovascular mortality in hypertensive patients. Mathematically, AASI reflect the standard deviation (SD) of blood pressure (BP) variation. AASI is measured higher levels in non-dipper than dipper. Thus, AASI has a possibility of not only reflecting arterial stiffness but also BP variability and/or autonomic nervous dysfunction. Subjects and Methods: Consecutive data from 418 untreated hypertensive patients were analyzed retrospectively. We examined the association between the 24-hour ambulatory BP monitoring (ABPM) parameters and AASI. Results: AASI had a simple correlation with age (R=0.189, p<0.001), relative wall thickness (RWT) (R=0.115, p=0.019), left ventricular mass index (LVMI) (R=0.192, p<0.001), average systolic BP (SBP) (R=0.232, p<0.001), average pulse pressure (PP) (R=0.363, p<0.001), SD of diastolic BP (DBP) (R=-0.352,p<0.001), SD of PP (R=0.330, p<0.001), SD of heart rate (HR) (R=-0.268, p<0.001), and nocturnal dipping (R=-0.137, p=0.005). In multiple linear regression analysis model including clinical parameters and 24 hour-ABPM parameters, independent predictors of AASI were SD of PP (beta=1.246, p<0.001), SD of DBP (beta=-1.067, p<0.001), SD of SBP (beta=-0.197, p<0.001), and non-dipper (beta=0.054, p=0.033). Conclusion: AASI is closely correlated with BP variability. The result of this study shows that AASI is not only a parameter for arterial stiffness, but also a parameter for BP variability

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases

Hyperthymic affective temperament and hypertension are independent determinants of serum brain-derived neurotrophic factor level

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has neuroprotective, proangiogenic and myogenic effects and, therefore, possibly acts as a psychosomatic mediator. Here, we measured serum BDNF (seBDNF) level in hypertensive patients (HT) and healthy controls (CONT) and its relation to affective temperaments, depression and anxiety scales, and arterial stiffness parameters. METHODS: In this cross-sectional study, affective temperaments, anxiety, and depression were studied with questionnaires (TEMPS-A, HAM-A, and BDI, respectively). SeBDNF level and routine laboratory parameters were measured as well. Arterial stiffness was evaluated with a tonometric method. RESULTS: Allover, 151 HT, and 32 CONT subjects were involved in the study. SeBDNF level was significantly higher in HT compared to CONT (24880 +/- 8279 vs 21202.6 +/- 6045.5 pg/mL, p < 0.05). In the final model of regression analysis, hyperthymic temperament score (Beta = 405.8, p = 0.004) and the presence of hypertension (Beta = 6121.2, p = 0.001) were independent determinants of seBDNF. In interaction analysis, it was found that in HT, a unit increase in hyperthymic score was associated with a 533.3 (95 %CI 241.3-825.3) pg/mL higher seBDNF. This interaction was missing in CONT. CONCLUSIONS: Our results suggest a complex psychosomatic involvement of BDNF in the pathophysiology of hypertension, where hyperthymic affective temperament may have a protective role. BDNF is not likely to have an effect on large arteries

Assessment of endothelial function by brachial artery flow mediated dilatation in microvascular disease

<p>Abstract</p> <p>Background</p> <p>Cardiac syndrome X is an important therapeutic and diagnostic challenge to physician. Study of Csx patients may help to understand the pathophysiology of coronary microcirculation and to gain an insight on the management of these group patients.</p> <p>Methods</p> <p>We measured the flow mediated dilation of the brachial artery both endothelium dependent and independent vasodilatation by high resolution ultrasound in 30 cardiac syndrome X patients and matched with 30 healthy control subjects.</p> <p>Results</p> <p>Significantly decreased flow mediated dilatation was observed in patients when compared to control (9.42 ± 7.20 vs 21.11 ± 9.16 p < 0.01) but no significant difference was observed between groups in response to nitroglycerin (25.39 ± 6.82 vs 28.87 ± 8.69). Receiver operator characteristic analysis showed that value of < 11.11 had sensitivity of 80%, specificity 86.67%, positive predictive value 76.66%, negative predictive value 83.33%. In total, 46% of subjects had endothelial dysfunction and of them, CSX subjects had higher prevalence (76% vs 16% p < 0.01) than control subjects. Higher mean values of body mass index, systolic blood pressure and diastolic blood pressure was observed in subjects with FMD < 11.11 than > 11.11(p < 0.01). In logistic regression analysis, FMD was significantly associated with systolic blood pressure (Odds ratio 1.122 95% CI 1.053-1.196 p < 0.01) and body mass index (Odds 1.248 95%CI 0.995-1.56 p < 0.05).</p> <p>Conclusions</p> <p>The study suggests impairment of endothelial function in cardiac syndrome X patients. Increased Systolic blood pressure and body mass index may increase the risk of impairment of endothelial function in this group of patients.</p