Persistent Elevation Of Blood Pressure Research Articles

The role of macrophages in hypertension and its complications.

Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent disease associated with catastrophic cardiovascular morbidity. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines induce endothelial and epithelial dysfunction, respectively, resulting in vascular oxidative stress and impairment of sodium excretion. By contrast, VEGF-C-expressing macrophages in the skin can facilitate the removal of excess interstitial stores of sodium by stimulating lymphangiogenesis. Inappropriate activation of the renin-angiotensin system (RAS) contributes to essential hypertension in a majority of patients, and macrophages express the type 1 (AT1) receptor for angiotensin II (Ang II). While proinflammatory macrophages clearly contribute to RAS-dependent hypertension, activation of the AT1 receptor directly on macrophages suppresses their M1 polarization and limits tubular and interstitial damage to the kidney during hypertension. Thus, stimulating the macrophage AT1 receptor ameliorates the target organ damage and immune stimulation provoked by AT1 receptor activation in intrinsic renal and vascular cells. The proinflammatory cytokines TNF-α and IL-1β produced by M1 macrophages drive blood pressure elevation and consequent target organ damage. However, additional studies are needed to identify the tissues in which these cytokines act and the signaling pathways they stimulate during hypertension. Moreover, identifying the precise myeloid cell subsets that contribute to hypertension should guide the development of more precise immunomodulatory therapies for patients with persistent blood pressure elevation and progressive end-organ injury.

A placebo‐controlled trial of ‘one‐minute qigong exercise' on the reduction of blood pressure among patients with essential hypertension

AbstractBackgroundHypertension, defined as the persistent elevation of both systolic and diastolic blood pressure (SBP and DBP), and can lead to cardiovascular, cerebrovascular and renal morbidity and mortality if untreated. In Malaysia, primary hypertension among adults is relatively high and a large proportion of cases remains undiagnosed. Qigong is a traditional Chinese exercise that has been shown to have positive health effects.ObjectiveThis study aimed to evaluate the effectiveness of a 5‐day ‘one‐minute qigong exercise’ programme on the reduction of blood pressure among patients with primary hypertension.MethodsAn open‐label, parallel‐group, controlled trial was conducted among participants with essential hypertension who were staff of Universiti Sains Malaysia (USM). The participants were assigned to either the ‘one‐minute qigong exercise’ programme or control, and underwent respective sessions for 5 consecutive days. The outcomes – SBP and DBP – were measured by standardised assessors using manual mercury sphygmomanometers. Repeated measures ANCOVA was performed to compare groups over time.ResultsAt the end of the study, 21 (56.8%) and 25 (92.6%) participants remained in the qigong and control groups, respectively. Overall, there was no significant within‐ or between‐group effect for mean SBP, while there was a marginally significant difference in mean DBP at the DBP×Group interaction level (P=0.049). Mean DBP on day 2 was statistically significantly different between groups (P=0.041).ConclusionOur study showed that the ‘one‐minute qigong exercise’ programme, carried out over a period of 5 consecutive days, offers no additional benefit to control in reducing blood pressure in persons with primary hypertension.

PREVALENSI HIPERTENSI PADA MASYARAKAT DI DESA TEMBUKU KABUPATEN BANGLI BULAN SEPTEMBER 2014

Hypertension define as persistent elevation of blood pressure above normal range. Hypertension is chronic disease of cardiovascular system that can occur several severe complication including heart disease and stroke. About 40% of world population is suffering from hypertension. People who live in the rural area is very vulnerable to suffering more from hypertension due to lack of understanding and statistical information of hypertension. The shift from infectious disease to metabolic disease is happening in rural area and that should be considered as a problem and information of the real situation in rural area of hypertension should be done and to determine the risk factors of hypertension to decrease incidence of hypertension. This research is using descriptive quantitative method. Research is conducted with measurement of blood pressure from the randomly chosen 96 samples and investigation of hypertension risk factors. Risk factors such as gender, family history of hypertension, smoking habit, BMI (body mass index), physical activity, coffee consumption, and average of daily salt intake are questioned to the samples. This research found that 43% of people in Tembuku village is suffering from hypertension. Smoking and coffee consumption is considered as major risk factors in developing hypertension of people in Tembuku villageÂ

Abstract 18353: A Real-world Study Evaluating the Utility of an Innovative Digital Health Feedback Device in Patients With Uncontrolled Hypertension

Introduction: For patients with uncontrolled blood pressure (BP), differentiation of pharmacological resistance from inadequate or improper medication use is key to clinical management. A digital health feedback device (DHFD) has been developed, utilizing an Ingestible Sensor (IS) and Wearable Sensor (WS) to passively record medication taking and timing, and measure physiological and behavioral metrics such as heart rate, step count, activity and rest patterns. This study evaluated DHFD use in diagnosing the cause of persistent BP elevation. Methods: Patients with a history of BP (≥140/90) on ≥2 anti-hypertensives (AHs) at 6 primary care centers in the United Kingdom were prescribed the DHFD for 14 days. Patients co-ingested the IS along with their prescribed BP medications while continuously wearing the WS. BP was assessed on days 1 and 14. Results: A total of 151 patients were enrolled; 38% were taking ≥3 AHs at baseline; 144 patients (95%) completed the 2 planned weeks of DHFD use. Root cause of treatment unresponsiveness was identified by DHFD in 100% of completers; 58% had pharmacological resistance, and 42% had inadequate AH use. During DHFD use, mean systolic BP decreased significantly by -10±17 (p<0.001) and mean diastolic BP decreased significantly by -5±9 mmHg (p<0.001); 38% of subjects achieved BP control on their current therapy. Subsequent management included: medicines reviews and/or adherence counselling with no AH changes in 81%, medication changes in 13%, referrals to specialists in 1%, and no additional actions were taken in 6%. Majority of practices (75%) found the DHFD added value, and 83% of patients expressed a positive experience. Side effects were minimal, consisting of mainly minor skin irritation (8%), or gastrointestinal symptoms (3%). Two patients withdrew due to possibly-related adverse events. Conclusions: In subjects using the DHFD for uncontrolled BP while prescribed AHs, all received a more informed therapeutic intervention from their providers following DHFD use. BP control was achieved in 38% within 2 weeks. DHFD can facilitate evidence-based progression through the BP treatment pathway by differentiating which patients can achieve treatment goals with prescribed therapy from those who may require AH changes.

O60. Treatment of hypertension in pregnancy

Several international (2013 ESH/ESC guidelines, AHA/ISH guidelines, JNC-8) and national (NICE, French, Canadian, Hungarian, Chinese) guidelines have been published recently with recommendations for management of hypertension in pregnancy. Data-based opinions onantihypertensive treatment initiation and target blood pressure (BP), and drugs of choice are not similarly described in these guidelines. Main objectives of the presentation are to summarise data of the relevant literature. Review of the recently published guidelines. Treatment initiation: in addition to life-style changes, there is consensus that drug treatment of severe hypertension (⩾160/110 mmHg) in pregnancy is indicated and beneficial. The suggestion, in the 2007 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) Guidelines, for considering treatment in all pregnant women with persistent elevation of BP ⩾150/95 mmHg is supported by recent US data, showing an increasing trend in the rate of pregnancy-related hospitalizations with stroke — especially during the postpartum period — and by an analysis of stroke victims with severe pre-eclampsia and eclampsia. However, the benefits of antihypertensive therapy are uncertain in pregnant women with mildly to moderately elevated blood pressure (⩽160/110 mmHg), either pre-existing or pregnancy-induced, except for a lower risk of developing severe hypertension. Despite lack of evidence, the Task Force of 2013 ESH/ESC Guidelines reconfirms that physicians should consider early initiation of antihypertensive treatment at values of BP ⩾140/90 mmHg in women with (i) gestational hypertension (with or without proteinuria), (ii) pre-existing hypertension with the superimposition of gestational hypertension or (iii) hypertension with asymptomatic organ damage (OD) or symptoms at any time during pregnancy. Target blood pressure: Guidelines mostly agree on that BP should be normalised (to <140/90 mmHg) in pregnant women with hypertension. Drug treatment: Drug treatment can be considered in pregnant women with persistent elevation of BP ⩾150/95 mmHg, and in those with BP ⩾140/90 mmHg in the presence of gestational hypertension, subclinical OD or symptoms due to increased BP. The recommendations to use methyldopa, labetalol and nifedipine as the only calcium antagonist really tested in pregnancy was confirmed in recent European and US guidelines. Beta-blockers (possibly causing foetal growth retardation if given in early pregnancy) anddiuretics (in pre-existing reduction of plasma volume) should be used with caution, only if other indications exist (e.g. ischemic heart disease, severe tachycardia, excess fluid retention). All agents interfering with the renin-angiotensin system (ACE inhibitors, angiotensin AT-1 receptor blockers, renin inhibitors) should absolutely be avoided. In emergency (pre-eclampsia), intravenous labetalol is the drug of choice with sodium nitroprusside (only for short term) or nitroglycerin in intravenous infusion being other options. According to recent guidelines, in the absence of randomised clinical trials recommendations how hypertension should be treated in pregnant women, can only be guided by experts’ opinion based on case reports and their meta-analyses.

8B.01

Objective: Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with treatment resistant hypertension (TRH), a condition defined as persistent blood pressure (BP) elevation despite prescription of at least 3 antihypertensive drugs, including a diuretic. However, the randomized controlled evidence that RDN effectively lowers BP is scarce and contradictory. This study investigated the current effectiveness of RDN for TRH. Design and method: We performed a systematic review and meta-analysis of the randomized controlled trials (RCT) that reported office and ambulatory systolic BP in RDN and control (sham control or drug adjustment) groups at 6 months of follow-up in patients with TRH. Pooled effect sizes were derived, using a random-effects model. Results: The literature search identified five RCTs with 867 randomized patients. In the pooled analysis, RDN was not associated with a significant decrease, either in office systolic BP (weighted mean difference (WMD): - 4.21 mmHg, 95% confidence interval: -17.12 to 8.69, p = 0.52), or in 24-h ambulatory systolic BP (WMD: -1.94 mmHg, 95% confidence interval: -6.05 to 2.17 mmHg, p = 0.36) compared to control at 6-months of follow-up.Conclusions: In patients with TRH, the overall BP lowering effect of RDN is not superior to control. Accordingly, RDN should not be considered as a treatment modality of RHT in clinical practice. Future research should identify the characteristics of patients who might respond to RDN, effective ablation dose and measure that could confirm that RDN do occur.

Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia

Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B, IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach (APSampler), we found genotype and allelic combinations associated with EH. The most significant associations were observed for SELE rs2076059*C–SELP rs6131*A–VEGFA –2549*I–IL1B rs16944*C (p = 3.42 × 10−5, FDR q = 0.035) and SELE rs2076059*C–SELP rs6131*A–IL12B rs3212227*C–IL1B rs16944*C (p = 323 × 10−4, FDR q = 0.035).

Renal sympathetic denervation after Symplicity HTN-3 and therapeutic drug monitoring in severe hypertension.

Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with apparently treatment resistant hypertension (TRH), a condition defined as persistent blood pressure elevation despite prescription of at least 3 antihypertensive drugs including a diuretic. However, the large fall in blood pressure after RDN reported in the first randomized study, Symplicity HTN-2 and multiple observational studies has not been confirmed in five subsequent prospective randomized studies and may be largely explained by non-specific effects such as improvement of drug adherence in initially poorly adherent patients (the Hawthorne effect), placebo effect and regression to the mean. The overall blood-pressure lowering effect of RDN seems rather limited and the characteristics of true responders are largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with apparently TRH, drug monitoring and improvement of drug adherence may prove more effective and cost-beneficial to achieve blood pressure control. In the meantime, research should aim at identifying characteristics of those patients with truly TRH who may respond to RDN.

Renal sympathetic denervation after Symplicity HTN-3 and therapeutic drug monitoring in patients with resistant hypertension to improve patients' adherence.

Renal sympathetic denervation (RDN) has been proposed as a new treatment modality in patients with apparent treatment-resistant hypertension (TRH), a condition defined as persistent blood pressure (BP) elevation despite prescription of at least three anti-hypertensive drugs including a diuretic. However, the large fall in BP reported after RDN in Symplicity HTN-2, the first randomized study, and in multiple observational studies has not been confirmed in five subsequent prospective randomized studies. The reduction in BP may be mostly due to non-specific effects, such as improvement of drug adherence in initially poorly adherent patients (the Hawthorne effect), placebo effect and regression to the mean. The overall BP lowering effect of RDN seems rather limited and the characteristics of the true responders remain largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with TRH, drug monitoring and subsequent improvement of drug adherence may prove more effective and cost-effective to achieve BP control. In the meantime, research should aim at identifying characteristics of those few patients adherent to drug treatment who has TRH and may respond to RDN.

Contribution of the MnPO Angiotensin Receptors to Brain Stem Activity and Hypertension (LB734)

Repeated bouts of hypoxia during sleep apnea and chronic intermittent hypoxia (CIH) are associated with persistent blood pressure elevation. Neurological mechanisms that drive this maladaptive blood pressure increase are not well understood. Knockdown of the Angiotensin type 1a (AT1a) receptor in a forebrain nucleus, the median preoptic nucleus (MnPO), prevents normoxic hypertension during CIH. In the current study, adult male rats were exposed to CIH after MnPO injections with adeno‐associated viruses containing shRNA‐AT1a or scrambled shRNA. We examined the activity of downstream nuclei by performing immunohistochemistry for ∆FosB, a marker for neuronal activity. We hypothesize that knockdown of AT1a in MnPO results in decreased ∆FosB expression in downstream nuclei such as the rostral ventrolateral medulla (RVLM), and the nucleus tractus solitarius (NTS). ∆FosB staining was significantly lower in the subpostremal region of the NTS and in the RVLM following CIH in AT1a knockdown treated rats versus scramble treated rats. This suggests that CIH mediated ∆FosB staining in the NTS and RVLM is at least partially dependent on AT1a receptors in MnPO. These results, coupled with the prevention of the normoxic hypertension, indicate that angiotensin acting at the MnPO is affecting the activity of neurons in brainstem area that regulate blood pressure.Grant Funding Source: Supported by P01 HL‐88052 and National Institute of Aging, Training in the Neurobiology of Aging, T31 AG020494

Renovascular Hypertension after Laparoscopic Partial Nephrectomy

No AccessJournal of UrologyRadiology Page1 May 2014Renovascular Hypertension after Laparoscopic Partial Nephrectomy Homayoun Zargar, Jonathan Aning, Gerald Legiehn, and Peter Black Homayoun ZargarHomayoun Zargar More articles by this author , Jonathan AningJonathan Aning More articles by this author , Gerald LegiehnGerald Legiehn More articles by this author , and Peter BlackPeter Black More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.01.103AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail References 1 : Blunt renal trauma-induced hypertension: prevalence, presentation, and outcome. Am J Hypertens2006; 19: 500. Google Scholar 2 : Malignant hypertension due to renal artery stenosis after open partial nephrectomy in a solitary kidney. Urology2007; 69: 385. Google Scholar 3 : Intimal injury of ultrasonically skeletonized internal thoracic artery by a vessel clamp: morphological analysis. Interact Cardiovasc Thorac Surg2007; 6: 331. Google Scholar 4 : Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med1934; 59: 347. Crossref, Medline, Google Scholar 5 : Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int1998; 53: 735. Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 191Issue 5May 2014Page: 1418-1420 Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.MetricsAuthor Information Homayoun Zargar More articles by this author Jonathan Aning More articles by this author Gerald Legiehn More articles by this author Peter Black More articles by this author Expand All Advertisement PDF downloadLoading ...

Immune Mechanisms in Hypertension

Low grade inflammation may have a key role in the pathogenesis of hypertension and cardiovascular disease. Several studies showed that both innate and adaptive immune systems may be involved, being T cells the most important players. Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes may be crucial for blood pressure elevation and related organ damage development. In the presence of a mild elevation of blood pressure, neo-antigens are produced. Activated Th1 cells may then contribute to the persistent elevation of blood pressure by affecting vasculature, kidney and perivascular fat. On the other hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role, being their activity crucial for the maintenance of cardiovascular homeostasis. Indeed, Tregs were demonstrated to be able to protect from blood pressure elevation and from the development of organ damage, including micro and macrovascular alterations, in different animal models of genetic or experimental hypertension. In the vasculature, inflammation leads to vascular remodeling through cytokine activity, smooth muscle cell proliferation and oxidative stress. It is also known that a consistent part of ischemia-reperfusion-induced acute kidney injury is mediated by inflammatory infiltration and that Treg cell infusion have a protective role. Also the central nervous system has an important role in the maintenance of cardiovascular homeostasis. In conclusion, hypertension development involves chronic inflammatory process. Knowledge of cellular and molecular players in the progression of hypertension has dramatically improved in the last decade, by assessing the central role of innate and adaptive immunity cells and proinflammatory cytokines driving the development of target organ damage. The new concept of role of immunity, especially implicating T lymphocytes, will eventually allow discovery of new therapeutic targets that may improve outcomes in hypertension and cardiovascular or renal disease in humans and uncover an entirely novel approach in the treatment of hypertension and vascular disease.

Abstract 67: Anti-aging Gene Klotho Deficiency Causes Hypertension Via Upregulation of CYP11B2 Expression and Aldosterone Synthesis

Background - Klotho (KL) is a recently discovered anti-aging gene. Genetic mutation of KL expedites the aging process and shortens lifespan while overexpression of KL slows down the aging process and extends lifespan. The purpose of this experiment is to assess if KL deficiency affects blood pressure (BP). Methods &amp; Results - KL mutant heterozygeous (+/-) mice showed significant and persistent elevation of BP, demonstrating for the first time that half klotho deficiency causes hypertension. It is noticed that plasma level of aldosterone was elevated and that protein expression of CYP11B2 (key enzyme of aldosterone synthesis) in adrenal cortex was increased in KL(+/-) mice, indicating that KL deficiency upregulates aldosterone synthesis. Blockade of aldosterone receptors by eplerenone (6 mg/kg/day) decreased hypertension of KL(+/-) mice to the control level within one week, suggesting that upregulation of aldosterone levels may play a critical role in KL deficiency-induced hypertension. Indeed, the aldosterone signaling (SGK1, NCC and ATP-β) were increased in kidneys of KL(+/-) mice. In addition, half KL deficiency increased renal inflammation as evidenced by upregulated inflammatory factors (IL-6, TNFα, osteopontin and MCP-1) and increased infiltration of T cells and macrophages in kidneys of KL(+/-) mice. Half KL deficiency led to renal functional impairment (increased plasma creatinine and urea and urine albumin) and structural damage (glomerulus collapse, tubule fibrosis). Blockade of aldosterone receptors attenuated KL deficiency-induced renal inflammation and damage. Conclusions - KL is essential to the maintenance of normal BP. KL deficiency caused hypertension and kidney damage via upregulating aldosterone levels and consequently increasing inflammation and SGK1 and NCC signaling in kidneys.

Profile of ambulatory blood pressure in resistant hypertension

Resistant hypertension (HT) is a condition that confers a high cardiovascular risk to the patient due to both persistent blood pressure elevation and the high prevalence of comorbidities and organ damage. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and follow-up of the hypertensive patient, and it is even more important in the evaluation of those with resistant HT. Data from the Spanish ABPM Registry have allowed the comparison between large groups of resistant hypertensive patients seen in daily life and those controlled on antihypertensive treatment, as well as in resistant hypertensive patients who are classified based on ambulatory blood pressure values. In comparison with controlled patients, the cohort of resistant hypertensives has a worse circadian profile with a high proportion of nondipping, but also stark differences between office and ambulatory blood pressures. This enhanced white-coat effect was responsible for more than one-third of resistant hypertensive patients having normal 24-h blood pressures. Clinical data, including comorbidities, organ damage and circadian patterns, suggest a lower cardiovascular risk among white-coat resistant hypertensives. This finding was in agreement with longitudinal studies in smaller cohorts, suggesting fewer cardiovascular events and less mortality. In summary, it seems reasonable to routinely use ABPM in the initial evaluation of all resistant hypertensive patients. In a significant number of these patients, ABPM will also be an essential tool in follow-up, especially regarding the possible effects of all therapeutic maneuvers that are devoted to bringing blood pressure into target ranges.

What are the benefits of renal denervation in patients with resistant hypertension?

Systemic arterial hypertension is one of the most important public health issues, affecting more than one-quarter of the adult population in industrialized countries [1]. It is a major risk factor for cardiovascular disease morbidity and mortality [2,3]. In most patients, hypertension can be effectively managed by a combination of lifestyle interventions and medication [4]. However, a significant portion of patients treated for hypertension are resistant to therapy. Conventionally, resistant hypertension is defined as persistent elevation of blood pressure above goal levels despite the use of at least three hypertensive agents from different classes, including a diuretic, in optimal doses [5]. Current prevalence estimates suggest that 10–30% of patients with hypertension may be resistant to drug therapy [6]. Renal sympathetic overactivity seems to play a crucial role in the development of arterial hypertension and resistance to treatment. Activation of efferent renal sympathetic nerve fibers results in an increased renin secretion rate, increased renal vasoconstriction and enhanced sodium and water retention [7]. In addition, afferent sympathetic activation from the kidneys to the CNS, seems to enhance sympathetic nerve discharge itself again, leading to a vicious circle in the development of arterial hypertension and cardiovascular morbidity [8]. Both effects, the activation of efferent renal sympathetic nerve fibers as well as the afferent ‘feedback’ from the kidneys seem to play a crucial role in the pathogenesis and maintenance of arterial hypertension. The idea of treating arterial hypertension by targeting the autonomic nervous system is decades old. In the predrug era, treatment of malignant hypertension was limited to surgical approaches, such as nephrectomy and surgical lysis of the autonomic nerves. Nonselective surgical sympathectomy (thoracolumbar splanchnicectomy), the so-called Smithwick intervention,

Renal Sympathetic Denervation for Treating Resistant Hypertension

Systemic hypertension represents a significant global concern, because it contributes to vascular and renal morbidity, cardiovascular mortality, and economic burden, hence the impact of hypertension is a major issue in public health worldwide. Improving high blood pressure management is therefore fundamental to influencing clinical outcomes. Despite adherence to multiple available medical therapies, a significant proportion of patients has persistent blood pressure elevation, a condition termed "resistant hypertension". Renal sympathetic innervations contribute to lack of response of anti-hypertensive drugs through an imbalance of regulatory mechanisms. Renal afferent nerve fibers are responsible for sympathetic activation and contribute to blood pressure homeostasis while afferent signals from the kidneys are integrated at the central nervous system and enhance sympathetic nerve discharge. In this regard, a novel strategy that selectively removes these hypertensive contributors represents a new therapeutic opportunity. Recently, a catheter-based method to induce renal sympathetic denervation has been introduced into daily practice. Clinical evaluation of selective renal sympathetic denervation demonstrated a decrease of renal norepinephrine spillover and renin activity, an increase of renal plasma flow, and has confirmed clinically significant, sustained reductions in blood pressure in patients with resistant hypertension. This review summarizes the available data on the role of sympathetic activation in the pathophysiology of hypertension and the current concepts in transcatheter renal artery ablation with radiofrequency delivery for systemic hypertension. Suggestions regarding targets for future systemic hypertension management are also described.

Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial.

Hypertension represents a significant global public health concern, contributing to vascular and renal morbidity, cardiovascular mortality, and economic burden. The opportunity to influence clinical outcomes through hypertension management is therefore paramount. Despite adherence to multiple available medical therapies, a significant proportion of patients have persistent blood pressure elevation, a condition termed resistant hypertension. Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinically meaningful benefit across wide and varied patient populations. Early clinical evaluation with catheter-based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN-3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single-blind trial evaluating the safety and effectiveness of catheter-based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses. The primary effectiveness endpoint is measured as the change in office-based systolic blood pressure from baseline to 6 months. This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy.

Relationship of Childhood Idiopathic Nephrotic Syndrome with Asthma, Hypertension, Complement C&lt;sub&gt;3&lt;/sub&gt;, Urinalysis

A prospective observational study of 43 children with idiopathic nephrotic syndrome (INS) were selected randomly out of 480 children admitted with the disease at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2003 to January 2005. Aim of this study was to correlate the difference in frequency of atopic attack, hypertension, complement c3 level and urinalysis in different types of Idiopathic nephrotic syndrome. Result: Among 43 children with idiopathic nephrotic syndrome (INS), 24 children were steroid sensitive nephrotic syndrome (SSNS) and 19 children having steroid resistant nephrotic syndrome (SRNS) cases, of SSNS group 13 were infrequent relapse nephrotic syndrome (IFRNS) and 11 were frequent relapse steroid dependant nephrotic syndrome (FRNS + SDNS). Bronchial asthma and allergic dermatitis were found in about 63% cases of both steroid resistant nephrotic syndrome (SRNS) and frequent relapse steroid dependant (FRNS+SDNS) group. Hypertension was found in higher number of patient in SRNS compared to SSNS (P&gt; 0.05) It was absent in IFRNS. Steroid contributed more than the disease process in producing hypertension (P&lt; 0.01). Complement C3 comparison among the group could not reach statistically significant level. Similarly, comparison of hematuria showed no difference among the groups but pyuria was higher in SRNS compared to IFRNS (P &gt;0.05). UTI were found equally in all the groups. Conclusion: Higher incidence of asthma, atopic dermatitis were noted in all the groups of idiopathic nephrotic syndrome (INS). C3 was not found significantly low in INS. Persistent elevation of blood pressure is found in higher number of SRNS compared to SSNS and steroid contributed more than the disease process. DOI: http://dx.doi.org/10.3329/bjch.v35i1.10367 BJCH 2011; 35(1): 11-15

Nocturnal dosing and chronic kidney disease progression: new insights

Several studies have identified the presence of altered diurnal blood pressure patterns, specifically elevated nighttime blood pressure in patients with chronic kidney disease. The lack of nocturnal decline in blood pressure is associated with markers of hypertensive target organ damage and predictive of long-term clinical outcomes. The purpose of this review is to summarize the literature in this area and explore the potential for use of nighttime blood pressure for improving risk stratification and as a therapeutic target. The mechanisms of persistent elevation of blood pressure at night in chronic kidney disease are likely to be multifactorial, including altered sodium handling and sympathetic activation among others. Elevated nocturnal blood pressures have been shown to be associated with increased adverse clinical outcomes. Recent studies demonstrate that it is feasible to lower nocturnal blood pressure by modifying the time of administration of antihypertensive medications. Currently, clinical blood pressure measurements are assessed and targeted for drug therapy. This article shows the importance of measuring ambulatory blood pressures, specifically nocturnal blood pressures to improve risk stratification. More research needs to be done to identify interventions that lower nighttime blood pressure, and test their efficacy in improving clinical outcomes.

Hypertension in obstructive sleep apnea: risk and therapy

Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing that occurs due to recurrent collapse of the upper airway with inspiration. Large epidemiologic studies have established that OSA is a risk factor for developing hypertension. The pathophysiologic mechanism of this relationship is due to the distinctive pattern of intermittent hypoxia seen in OSA. This pattern increases sympathetic tone, oxidative stress, inflammation and endothelial dysfunction. These processes can all lead to persistent elevation of blood pressure beyond the obstructive events. OSA should be considered as part of the workup of patients with hypertension. Treatment of OSA with continuous positive airway pressure has an effect on hypertension control and risk reduction of cardiovascular diseases. This review discusses the pathophysiology and causal relationship between OSA and hypertension, along with the cardiovascular effects of treatment of OSA.