Abstract
Aims
Several studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world ...patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function.
Methods and results
The Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (−16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (−8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure.
Conclusion
Long-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.
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.
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.
1 Department of Clinical Medicine and Prevention, University of Milano-Bicocca, and 2 Department of Cardiology, San Luca Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto ...Auxologico, Italiano, Milan, Italy; 3 Hypertension Unit; Department of Hypertension and Diabetology; Medical University of Gdansk, Gdansk, Poland
Several studies have shown the occurrence of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease, including arterial hypertension, ischemic heart disease, and stroke. The pathogenesis of the cardiovascular complications of OSAS is still poorly understood, however. Several mechanisms are likely to be involved, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormality in the process of coagulation, and metabolic dysregulation. The latter may involve insulin resistance and disorders of lipid metabolism. The aim of this review, which reports the data presented at a workshop jointly endorsed by the European Society of Hypertension and by the European Union COST action on OSAS (COST B26), is to critically summarize the evidence available to support an independent association between OSAS and cardiovascular disease.
basic mechanisms; intermittent hypoxia; sleep-disordered breathing; autonomic cardiovascular regulation; obesity
Address for reprint requests and other correspondence: G. Parati, Dept. of Clinical Medicine and Prevention, Univ. of Milano-Bicocca and Ospedale San Luca, IRCCS, Istituto Auxologico Italiano, via Spagnoletto 3, 20149, Milano, Italy (e-mail: gianfranco.parati{at}unimib.it )
The aim of the study was to assess cardiac and respiratory blood pressure (BP) and subarachnoid space (SAS) width oscillations during the resting state for slow and fast breathing and breathing ...against inspiratory resistance. Experiments were performed on a group of 20 healthy volunteers (8 males and 12 females; age 25.3 ± 7.9 years; BMI = 22.1 ± 3.2 kg/m
). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography. SAS signals were recorded using an SAS monitor. Oxyhaemoglobin saturation (SaO
) and end-tidal CO
(EtCO
) were measured using a medical monitoring system. Procedure 1 consisted of breathing spontaneously and at controlled rates of 6 breaths/minute and 6 breaths/minute with inspiratory resistance for 10 minutes. Procedure 2 consisted of breathing spontaneously and at controlled rates of 6, 12 and 18 breaths/minute for 5 minutes. Wavelet analysis with the Morlet mother wavelet was applied for delineation of BP and SAS signals cardiac and respiratory components. Slow breathing diminishes amplitude of cardiac BP and SAS oscillations. The overall increase in BP and SAS oscillations during slow breathing is driven by the respiratory component. Drop in cardiac component of BP amplitude evoked by slow-breathing may be perceived as a cardiovascular protective mechanism to avoid target organ damage. Further studies are warranted to assess long-term effects of slow breathing.
Purpose of Review
Abrupt blood pressure (BP) rise is the most common clinical symptom of acute ischemic stroke (AIS). However, BP alterations during AIS reflect many diverse mechanisms, both ...stroke-related and nonspecific epiphenomena, which change over time and across patients. While extremes of BP as well as high BP variability have been related with worse outcomes in observational studies, optimal BP management after AIS remains challenging.
Recent Findings
This review discusses the complexity of the factors linking BP changes to the clinical outcomes of patients with AIS, depending on the treatment strategy and local vessel status and, in particular, the degree of reperfusion achieved. The evidence for possible additional clinical markers, including the presence of arterial hypertension, and comorbid organ dysfunction in individuals with AIS, as informative and helpful factors in therapeutic decision-making concerning BP will be reviewed, as well as recent data on neurovascular monitoring targeting person-specific local cerebral perfusion and metabolic demand, instead of the global traditional parameters (BP among others) alone.
Summary
The individualization of BP management protocols based on a complex evaluation of the homeostatic response to focal cerebral ischemia, including but not limited to BP changes, may be a valuable novel goal proposed in AIS, but further trials are warranted.
Heart rate variability (hrv) is a physiological phenomenon of the variation in the length of the time interval between consecutive heartbeats. In many cases it could be an indicator of the ...development of pathological states. The classical approach to the analysis of hrv includes time domain methods and frequency domain methods. However, attempts are still being made to define new and more effective hrv assessment tools. Persistent homology is a novel data analysis tool developed in the recent decades that is rooted at algebraic topology. The Topological Data Analysis (TDA) approach focuses on examining the shape of the data in terms of connectedness and holes, and has recently proved to be very effective in various fields of research. In this paper we propose the use of persistent homology to the hrv analysis. We recall selected topological descriptors used in the literature and we introduce some new topological descriptors that reflect the specificity of hrv, and we discuss their relation to the standard hrv measures. In particular, we show that this novel approach provides a collection of indices that might be at least as useful as the classical parameters in differentiating between series of beat-to-beat intervals (RR-intervals) in healthy subjects and patients suffering from a stroke episode.
We tested whether characteristic changes of the plasma lipidome in individuals with comparable total lipids level associate with future cardiovascular disease (CVD) outcome and whether 23 validated ...gene variants associated with coronary artery disease (CAD) affect CVD associated lipid species.
Screening of the fasted plasma lipidome was performed by top-down shotgun analysis and lipidome compositions compared between incident CVD cases (n = 211) and controls (n = 216) from the prospective population-based MDC study using logistic regression adjusting for Framingham risk factors. Associations with incident CVD were seen for eight lipid species (0.21≤q≤0.23). Each standard deviation unit higher baseline levels of two lysophosphatidylcholine species (LPC), LPC16∶0 and LPC20∶4, was associated with a decreased risk for CVD (P = 0.024-0.028). Sphingomyelin (SM) 38∶2 was associated with increased odds of CVD (P = 0.057). Five triglyceride (TAG) species were associated with protection (P = 0.031-0.049). LPC16∶0 was negatively correlated with the carotid intima-media thickness (P = 0.010) and with HbA1c (P = 0.012) whereas SM38∶2 was positively correlated with LDL-cholesterol (P = 0.0*10(-6)) and the q-values were good (q≤0.03). The risk allele of 8 CAD-associated gene variants showed significant association with the plasma level of several lipid species. However, the q-values were high for many of the associations (0.015≤q≤0.75). Risk allele carriers of 3 CAD-loci had reduced level of LPC16∶0 and/or LPC 20∶4 (P≤0.056).
Our study suggests that CVD development is preceded by reduced levels of LPC16∶0, LPC20∶4 and some specific TAG species and by increased levels of SM38∶2. It also indicates that certain lipid species are intermediate phenotypes between genetic susceptibility and overt CVD. But it is a preliminary study that awaits replication in a larger population because statistical significance was lost for the associations between lipid species and future cardiovascular events when correcting for multiple testing.
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