The aim of the Lancet Commission on hypertension is to identify key actions to improve the management of blood pressure both at the population and the individual level, and to generate a campaign to ...adopt the suggested actions at national levels to reduce the impact of elevated blood pressure globally. The first task of the Commission is this report, which briefly reviews the available evidence for prevention, identification, and treatment of elevated blood pressure, hypertension, and its cardiovascular complications.
Uncontrolled hypertension drives the global burden of increased cardiovascular disease (CVD) morbidity and mortality. Although high blood pressure (BP) is treatable and preventable, only half of the ...patients with hypertension undergoing treatment have their BP controlled. The failure of polypharmacy to attain adequate BP control may be due to a lack of physiological response, however, medication non-adherence and clinician inertia to increase treatment intensity are critical factors associated with poor hypertension management. The long-time medication titration, lifelong drug therapy, and often multi-drug treatment strategy are frustrating when the BP goal is not achieved, leading to increased CVD risk and a substantial burden on the healthcare system. Growing evidence indicates that neurohumoral activation is critical in initiating and maintaining elevated BP and its adverse consequences. Over the past decades, device-based therapies targeting the mechanisms underlying hypertension pathophysiology have been extensively studied. Among these, robust clinical experience for hypertension management exists for renal denervation (RDN) and baroreflex activation therapy (BAT), carotid body denervation (CBD), central arteriovenous anastomosis, and to a lesser extent, deep brain stimulation. Future studies are warranted to define the role of device-based approaches as an alternative or adjunctive treatment option to treat hypertension.
Systemic hypertension is a growing contributor to global disease burden and premature cause of death worldwide.
The percentage of patients achieving target BP levels remains largely inadequate.
Hypertension is characterised by activation of the sympathetic nervous system, with the magnitude depending on age and the disease severity.
Device-based interventions have been extensively studied to directly target the relevant sympathetic neural pathophysiological mechanisms involved in BP control.
Modulation of the chronic sympathetic outflow with CBD or BAT shows promise for the treatment of poorly controlled hypertension in addition to antihypertensive medicines.
The BP response to device-based therapies appears variable and cannot be predicted before the procedure.
Until more robust evidence related to patient selection, procedural and technical aspects is available, chemoreflex and baroreflex neuromodulation therapy should be restricted to randomised sham-controlled trials performed in experienced centres.
There is growing recognition of cardiovascular consequences of obstructive sleep apnea (OSA). Recurrent episodes of airway obstructions result in hypoxia and hypercapnia increasing sympathetic neural ...tone, which in turn causes vasoconstriction and marked increases in blood pressure (BP). BP response to OSA may be important in understanding the absence of nocturnal BP fall in the subgroup of hypertensive patients termed 'non-dippers'. Even mild sleep apnea can increase nocturnal BP through different mechanisms including hypoxemia, sympathetic activation, mechanical changes and disruption of normal sleep. Sleep apnea may be an important factor in determining the increased cardiovascular risk in hypertensive non-dippers. Effective treatment of sleep apnea may attenuate neurohumoral and metabolic abnormalities, improve diurnal BP control and conceivably reduce cardiovascular risk. This review examines the evidence linking OSA to non-dipping pattern of hypertension, and discusses potential mechanisms underlying this link. We will review first, prognostic value of nighttime BP; second, the cardiovascular consequences of sleep apnea; third, the evidence for altered diurnal BP profile in sleep apnea; fourth, the mechanisms contributing to both nocturnal and daytime hypertension in sleep apnea; fifth, the benefits of sleep apnea treatment and finally implications for hypertension management.
A high incidence of acute cardiovascular events and sudden cardiac death following unexpected acute emotional stress or a natural catastrophic disaster has been well-documented over the past decades. ...Chronic psychosocial factors have been shown to be directly linked to the development of hypertension, cardiovascular disease and stroke. Activation of various neurogenic pathways is an important mediator of acute and chronic stress-induced hypertension and heart disease. Heightened sympathetic activation has been shown to be a critical contributor linking psychogenic effects on cardiovascular regulation to serious and often fatal CV outcomes. Accordingly, several therapeutic approaches that attenuate autonomic imbalance via modulation of increased sympathetic outflow by either non-pharmacological or interventional means have been shown to alleviate clinical symptoms. Likewise stress reduction per se achieved with transcendental medicine has been linked to improved patient outcomes. Therapies that oppose adrenergic activity and/or have the potential to attenuate negative emotions are likely to reduce cardiovascular risk and its adverse consequences attributable to chronic mental stress.
Renal Denervation in Moderate to Severe CKD HERING, Dagmara; MAHFOUD, Felix; SCHLAICH, Markus P ...
Journal of the American Society of Nephrology,
07/2012, Letnik:
23, Številka:
7
Journal Article
Arterial hypertension remains a primary global health problem with significant impact on cardiovascular morbidity and mortality. The low rate of hypertension control and failure to achieve target ...blood pressure levels particularly among high-risk patients with resistant hypertension has triggered renewed interest in unravelling the underlying mechanisms to implement therapeutic approaches for better patient management. Here, we summarize the crucial role of neurogenic mechanisms in drug-resistant hypertension, with a specific focus on central control of blood pressure, the factors involved in central integration of afferent signalling to increase sympathetic drive in resistant hypertension, and briefly review recently introduced interventional strategies distinctively targeting sympathetic activation.
Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO ...precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (
< 0.001) and a trend towards higher plasma TMAO (
= 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR,
= 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk.
Summary
Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid‐base homeostasis. ...The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin‐angiotensin‐aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti‐inflammatory effects and modulation of centrally‐mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti‐inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre‐clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented.
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