Different Classes Of Antihypertensive Agents Research Articles

New Potential Treatments for Resistant Hypertension.

To provide an update and review approaches to the treatment of resistant hypertension (RH) with a focus on emerging potential therapies. Resistant hypertension is defined as a blood pressure that remains elevated above a patient's individualized target despite the concurrent use of 3 antihypertensive agents of different classes including a diuretic or use of 4 or more antihypertensive agents. Patients with RH have an increased risk of adverse cardiovascular and renal outcomes. Most RH is attributed to apparent RH and is not true RH. True RH is a diagnosis of exclusion after apparent RH has been excluded. Treatment of RH is challenging, and blood pressure goal is often difficult to achieve. Currently several new therapies have emerged with forthcoming data that provide promise for improved blood pressure control in those with resistant hypertension. Once RH has been diagnosed, patients should be on standardized therapy that includes agents from three different classes including a diuretic with addition in most cases of a mineralocorticoid as a fourth line agent. There are newer agents in development currently being studied in clinical trials including dual endothelin receptor antagonists and aldosterone synthase inhibitors that appear to be efficacious. Other approved medications including SGLT2 inhibitors and non-steroidal mineralocorticoids such as finerenone also need to be incorporated into treatment paradigms. Renal denervation with catheter based devices is another potential promising treatment option in this population.

SEQUENTIAL NEPHRON BLOCKADE VERSUS DUAL RENIN-ANGIOTENSIN SYSTEM BLOCKADE IN TRUE RESISTANT HYPERTENSIVE PATIENTS: A SYSTEMATIC REVIEW

Objective: True resistant hypertension (RHTN) is a challenging medical condition in which the blood pressure remains uncontrolled despite the use of three different classes of antihypertensive agents at maximum tolerated dose. In order to reduce the sodium and volume overload in these patients and bring the blood pressure to acceptable levels, several pharmacologic agents that promote sequential nephron blockade (SNB) or dual renin- angiotensin system blockade (DRASB) can be used. Therefore, this review aims to evaluate the data presented in some clinical trials comparing the SNB to the DRASB. Design and method: A systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was conducted in MEDLINE, Cochrane Library, EMBASE and LILACS, resulting in a total of 123 articles. One abstract and 4 randomized controlled trials were selected to be assessed in this review. Results: Both treatments decreased systolic blood pressure and diastolic blood pressure in ambulatory blood pressure monitoring. In one of the protocols, the decreases in the SNB group were significantly greater than in the DRASB group. A sub-analysis showed that the improvements in blood pressure were significant only in those with acceptable adherence to treatment. The two interventions reduced office blood pressure, with one study indicating that the reduction was superior in SNB. In markers of arterial stiffening and aging, there were no significant improvements. Pulse wave velocity and common carotid artery stiffness were similar in both groups and tended to decrease. One of the studies showed improvement in echocardiographic parameters for diastolic dysfunction. Conclusions: Despite the improvements in blood pressure in both groups, SNB therapy has a higher potential as a treatment for RHTN, especially when there is good adherence to the medication. Also, SNB tended to improve arterial stiffness and diastolic dysfunction. Nonetheless, there is a need for more studies for a better evaluation of these outcomes.

Comparative Efficacy of Antihypertensive Agents in Flow-Mediated Vasodilation of Patients with Hypertension: Network Meta-Analysis of Randomized Controlled Trial

Hypertension induces both structural and functional changes in blood vessels, thereby increasing endothelial dysfunction, which in turn, contributes to an increase in blood pressure. A popular and widely used noninvasive tool, flow-mediated dilation (FMD), is used to examine peripheral artery endothelium-dependent dilation. This study aimed to compare the efficacies of different classes of antihypertensive agents based on their effects on FMD. PubMed, Embase, and Cochrane Library were queried till November 1, 2020. Comparative studies on the efficacies of two or more antihypertensive agents or placebos for hypertensive patients were included. The outcomes were variations in mean systolic and diastolic blood pressure. Two reviewers independently reviewed and filtered the literature and extracted the data; the Cochrane “risk of bias” method was used to evaluate the methodological quality of the randomized controlled trials. A network meta-analysis was performed using Stata 15.0 software with a total of 49 studies. Subgroup analysis based on age and duration of treatments was performed. As compared to the placebo group, patients receiving the antihypertensive drugs exhibited significantly enhanced FMD (ARB + CCB: 4.01%, 95% CI, 0.92–7.11%, p < 0.001; ACEI + ARB: 2.81%, 95% CI, 1.19–4.43%, p < 0.001; ACEI: 2.55%, 95% CI, 1.34–3.77%, p < 0.001; ARB: 2.22%, 95% CI, 1.05–3.38%, p < 0.001; β-blocker: 2.23%, 95% CI, 0.93–3.52%, p < 0.001). In the SUCRA curve for network meta-analysis, the combination of CCB and ARB was found to be the most effective in increasing FMD (SUCRA = 89.0%), followed by ACEI monotherapy (SUCRA = 74.2%). ARB combined with CCB was superior in improving the endothelial function measured as the FMD; ACEI monotherapy was the most effective treatment among the antihypertension medications. There were no significant differences between antihypertensive drug-based monotherapies.

Treatment of Resistant Hypertension in Real Clinical Settings

Background. Current guidelines describe in detail the approaches to the management of patients with resistant hypertension, however, in real clinical settings the number of non-rational and ineffective combinations of antihypertensive drugs used remains high.Aim. To analyze the distribution of different combinations of antihypertensive drugs for the treatment of resistant hypertension and to estimate the proportion of non-rational combinations.Methods. The retrospective analysis includes 117 outpatients with resistant hypertension. Resistant hypertension was defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes. Exclusion criteria was secondary hypertension. We defined rational combination as the standard combination (renin-angiotensin system [RAS] blocker + calcium-channel blocker [CCB] + diuretic) plus one of the group of reserve drugs (mineralocorticoid receptors antagonist [MRA], beta-blocker, alpha-blocker, agonist of imidazoline receptors [AIR]). Non-rational were considered combinations in which reserve drugs were used before the appointment of a triple combination of first-line drugs. Moreover, in a subgroup of non-rational therapy, situations were identified where such a combination was justified.Results. The proportion of rational combinations was 58.9%, reasonably non-rational - 15.5%, unreasonably non-rational - 25.6%. Unreasonably non-rational combinations are distributed as follows: non-appointment of CCB - 12%, non-appointment of RAS-blockers - 8%, non-appointment of diuretics - 6%, use of RAS-blockers for hyperkalemia - 6%, administration of MRA without non-potassium-sparing diuretics - 5%, double blockade of RAS - 3%, other combinations - 7%. In addition to first-line drugs, beta-blockers (93.2%), loop diuretics (22.2%), AIR (21.4) were the most prescribable, while the proportion of MRA is only 15.4% of the entire sample.Limitation: some patient's characteristics could be missed in case histories and some of the combinations could be falsely recognized as malpractice since the analysis was conducted retrospectively.Conclusion. The proportion of the non-rational combinations for the treatment of resistant hypertension is high. Among the drugs of the reserve, the frequent use of beta-blockers and moxonidine and the inadequate administration of spironolactone are noteworthy. The problem of treatment strategy choice remains relevant in real clinical practice.

Hypertension in African Populations: Review and Computational Insights.

Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.

Obstructive sleep apnea is more severe in men but not women with refractory hypertension compared with controlled resistant hypertension.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension (RHTN) and may contribute to refractory hypertension (RfHTN). The objective of the current study was to test the hypothesis that patients with RfHTN have more severe OSA compared with patients with controlled RHTN. Patients (n = 187) referred to the University of Alabama at Birmingham Hypertension Clinic for evaluation and treatment of RHTN, defined as uncontrolled blood pressure (BP) (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg) despite the use of at least three antihypertensive medications including a diuretic, were enrolled following completion of at least three follow-up clinic visits. RfHTN was defined as uncontrolled high BP despite treatment with five or more antihypertensive agents of different classes, including a long-acting thiazide-type diuretic and a mineralocorticoid receptor antagonist. Following enrollment, all patients (n = 130) completed 24-h ambulatory BP measurement and overnight diagnostic polysomnography during normal nightly use of continuous positive airway pressure. Analyses examined the severity of OSA and related sleep characteristics among patients with RfHTN versus controlled RHTN. Of the 130 evaluated patients, 37 (28.5%) had RfHTN and 93 (71.5%) had controlled RHTN. In unadjusted analyses, there was not a significant difference in OSA severity, oxygen saturation, or hypoxemia time in patients with RfHTN versus controlled RHTN (P > 0.05). Men with RfHTN had more severe OSA compared with men with controlled RHTN (P = 0.044). In adjusted analyses, OSA severity was associated with sex (P < 0.0001), but not hypertension phenotype (P = 0.17). The severity of OSA may contribute to RfHTN status in men but not women.

Annals for Educators - 7 July 2020.

Annals for Educators - 7 July 2020.

1-6OBSTRUCTIVE SLEEP APNEA IN RESISTANT HYPERTENSION

Background: HTN is considered resistant when the blood pressure (BP) remains above goal (≥140/90 mmHg) despite lifestyle modification and administration of three antihypertensive agents of different classes, including a diuretic. Obstructive sleep apnea (OSA) is associated with hypoxia, hypercapnia, arousal, and fluctuations of intrathoracic pressure which all contribute to the sympathetic overdrive. The association of resistant hypertension and obstructive sleep apnea are documented in several previous studies. The data from Indonesia are very limited. Aim: Measure the association between obstructive sleep apnea and resistant hypertension. Method: This is a cross-sectional study. The presence of sleep apnea is measured with complete polysomnography (PSG). Resistant hypertension is generally defined as uncontrolled clinic blood pressure (&gt;140/90 mm Hg) after treatment with three or more antihypertensives. The data about medication were obtained from computerized electronic prescription. The data of adherence are measured with the Morisky Adherence scale. We measure the apnea and hypopnea events per hour, which is called the apnea-hypopnea index (AHI), is used to grade OSA. The data presented in a systematic table. Result: The data were obtained from 12 patients with resistant hypertension. The data consist of 8 male and four female. Complete PSG was recorded in all subjects. The result showed that ten patients have obstructive sleep apnea. Severe obstructive sleep apnea (AHI&gt; 30) presence in 7 patients. The data of CPAP/ APAP usage are obtained from 4 subjects. The result showed that blood pressure control is much better after the use of CPAP/ APAP. Conclusion: OSA is very prevalent in resistant hypertension. OSA should be evaluated in patients with resistant hypertension.

P0158RENAL DENERVATION VERSUS SPIRONOLACTONE IN THE TREATMENT OF RESISTANT HYPERTENSION: A META-ANALYSIS

Abstract Background and Aims Resistant hypertension (RH) is defined as blood pressure that remains above guideline-directed goal despite the concurrent use of at least three antihypertensive agents of different classes, one of which is a diuretic. Treatment of RH is focused on the addition of fourth-line therapy. Several studies revealed impressive blood pressure reductions when spironolactone was added to the therapeutic regimen. In the recent years, there has been a growing perception that controlling blood pressure in resistant hypertension is beyond the reach of existing drug therapies, leading to the emergence of device-based therapies, such as renal denervation. Our aim is to do a systematic review of randomized controlled trials that compares the use of Spironolactone and Renal Denervation in patients with RH. Method A comprehensive literature search from the PubMed, Embase, Cochrane Library, and Ovid was performed with the following search terms: Resistant Hypertension, Spironolactone, Renal Denervation. The search was limited to randomized-controlled trials that compared Spironolactone to Renal Denervation in patients with Resistant Hypertension. Three prospective clinical trials were selected and analyzed using Cochrane Revman v5.3. Primary outcome were mean changes in 24-hour Ambulatory Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP). Secondary outcomes include mean changes in Office SBP and DBP. Safety was assessed by changes in eGFR and potassium levels. Results Two trials comprising 130 patients were selected - 63 patients treated with RDN and 67 patients with Spironolactone. Pooled analysis of the 2 trials for 24H SBP and DBP showed an adjusted standardized mean difference of 0.55 mmHg (CI -0.72, 1.82; P = 0.39) and 0.32 mmHg (CI -0.72, 1.35; P = 0.55) with significant heterogeneity. No significant differences were also noted in terms of decline in eGFR (p = 0.07) and changes in serum potassium (p = 0.29) from baseline to 6 months. Conclusion Based on our results, RD appears to be safe and effective treatment for RH. However, additional larger studies should be done including a cost-benefit analysis to explore that possibility of RD as treatment alternative for those intolerant of spironolactone or as a possible 5th line of treatment for those already taking spironolactone.

Therapy Resistant and Refractory Hypertension

Hypertension is defined as resistant to treatment when treatment fails to lower office systolic and diastolic blood pressure values to < 140/90 mmHg. The treatment strategy should include lifestyle measures and appropriate doses of three or more drugs acting by different mechanisms including a diuretic. An updated definition of treatment resistance includes all patients with ≥ 4 antihypertensive agents of different classes irrespective of their on-treatment blood pressure. The term "refractory" hypertension has been suggested for patients with uncontrolled blood pressure on ≥ 5 antihypertensive drugs including the thiazide-like diuretic chlorthalidone and the mineralocorticoid receptor antagonist spironolactone. "Pseudo resistance" especially due to white coat hypertension and non-adherence with the prescribed medication has to be ruled out to be able to identify patients with "true" treatment resistance. Therefore, before distinguishing true from pseudo resistance, the term "apparent" resistance should be used. While the prevalence of apparent resistance may be in the range of 10-15 % of treated patients, the exact prevalence of true resistance remains unknown due to the lack of appropriate studies but is likely to be rather small including a high proportion of patients with secondary forms of hypertension. Once identified most patients with true treatment resistance should receive intensified drug treatment primarily by expanded diuretic usage. Thus, resistant hypertension is primarily a diagnostic challenge: identifying patients with true resistance and those with secondary hypertension.

Is There a Role for Device Therapies in Resistant Hypertension?: The CON Side.

In this piece, I will argue that device-based therapies for resistant hypertension (RH), although interesting and meritorious of further study, do not yet deserve a prominent role in the management of patients with RH. This argument is on the basis of the limited availability of controlled studies using devices, the cost and uncertain long-term effectiveness of device modalities, and the successful track record of medical therapy. First, let me define the demand for advanced therapies in RH. RH is defined as the BP of a hypertensive patient that remains above goal despite the concurrent use of three antihypertensive agents of different classes, preferably including a blocker of the renin-angiotensin system, a calcium channel blocker, and a thiazide-type diuretic (1). The prevalence of RH in the general hypertensive population is 12%–18%, on the basis of office BP measurements >140/90 mm Hg (1), an estimate that is expected to increase by approximately 2% when the 130/80 mm Hg threshold is applied to high-risk patients (2). Approximately one third of these patients have normal 24-hour BP (1), and a sizable portion is nonadherent to prescribed medications; therefore, approximately 5%–10% of hypertensive patients would ultimately qualify as having true RH. The current approach to the treatment of RH calls for adequate dosing of complementary medications, preferential use of long-acting thiazide diuretics ( e.g ., chlorthalidone), and the addition of a mineralocorticoid antagonist ( e.g ., spironolactone) (1). When such a strategy is used, BP goal is achieved in up to 90% of patients (3). Hence, about 0.5%–1% of hypertensive patients (approximately 750,000–1.5 million adults in the United States) would benefit from alternative approaches to treatment, such as referral to hypertension specialists for more advanced drug combinations or the use of device therapies. I acknowledge the importance of treatment nonadherence and medication intolerance in RH. Nonadherence is …

Treatment of Resistant and Refractory Hypertension.

Resistant hypertension (RHTN) is defined as uncontrolled blood pressure despite the use of ≥3 antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin receptor blocker), at maximal or maximally tolerated doses. Antihypertensive medication nonadherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. RHTN is a high-risk phenotype, leading to increased all-cause mortality and cardiovascular disease outcomes. Healthy lifestyle habits are associated with reduced cardiovascular risk in patients with RHTN. Aldosterone excess is common in patients with RHTN, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying RHTN, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.

Renal nerve ablation for resistant hypertension: facts, fictions and future directions.

Hypertension remains a major public health problem and one of the most relevant causes of cardiovascular mortality and morbidity worldwide. Roughly 10% of hypertensive individuals are considered as "resistant" as they are not able to achieve and maintain optimal blood pressure values despite the concurrent use of 3 antihypertensive agents of different classes at optimal doses. As resistant hypertension conveys a higher risk of adverse outcomes, the search for effective treatments to properly manage this condition has progressively surged as a true health priority. The renal nerve plexus plays a central role in regulating arterial blood pressure and renal sympathetic overactivity is a major component in the development and progression of hypertension. On these premises, minimally-invasive catheter based devices for renal nerve ablation have been developed and tested as an alternative treatment for resistant hypertension, but clinical study results have been ambiguous. This review provides a historical perspective on the scientific evidence forming the foundation of renal never ablation from accrued clinical evidence to possible future applications, reaching a tentative conclusion that more research and clinical experience is needed to fully reveal limits and potential indications of this procedure.

The Prevalence of Nonadherence in Patients With Resistant Hypertension: A Systematic Review Protocol.

Background:Resistant hypertension, usually defined as blood pressure remaining above goal despite the concurrent use of 3 or more antihypertensive agents of different classes, is common (about 10% prevalence) and known to be a risk factor for cardiovascular events. These patients also undergo more screening intensity for secondary hypertension. However, not all patients with apparent treatment-resistant hypertension have true resistant hypertension, with some of them being nonadherent to prescribed pharmacotherapy. The prevalence of nonadherence varies from about 5% to 80% in the published literature. However, the relative contributions of intentional and nonintentional nonadherence are not well described. Nonintentional nonadherence refers to occasional forgetfulness and/or carelessness and can sometimes be related to an inability to follow instructions, because of either cognitive or physical limitations. Intentional nonadherence refers to an active process in which a patient may choose to alter the prescribed medication regimen by discontinuing medications, skipping doses, or modifying doses or dosing intervals.Objective:Our objective is to establish the overall prevalence of nonadherence in the apparent treatment-resistant hypertension population and evaluate the relative contributions of nonintentional and intentional nonadherence subtypes.Design:We will conduct a systematic review and meta-analysis.Setting:We will include observational studies and randomized controlled trials where adherence to antihypertensive medications is measured using a test of adherence, either direct or indirect.Patients:We will include adult human participants aged 18 years or older with a diagnosis of resistant hypertension.Measurements:Data extracted from individual studies will include title, first author, design, country, publication year, funding body, method of assessing adherence to antihypertensive medication, prevalence of medication nonadherence, definition of resistant hypertension, sample size, sex, mean age, and coexistent comorbidities.Methods:A librarian will search the databases Medline, EMBASE, Cochrane, CINAHL, and Web of Science for studies meeting criteria for inclusion. Two reviewers will independently screen the titles and abstracts retrieved and assess the methodological quality of eligible full-text articles using the Cochrane Risk of Bias tool for clinical trials and the Newcastle-Ottawa Scale for observational studies. Summary estimates of prevalence will be generated using pooled analysis using the random-effects method. Subgroup analyses, sensitivity analyses, and evaluation of publication bias will also be performed.Results:The outcomes of interest are the pooled prevalence of nonadherence to antihypertensive medication in apparent treatment-resistant hypertension and the prevalence of nonadherence based on different methods of assessing nonadherence (indirect vs direct), which will allow us to estimate the relative proportion of unintentional and intentional nonadherence subtypes in the overall phenomenon of medication nonadherence.Limitations:Possible limitations of this study include the finding of severe heterogeneity, the limitations of the literature search, publication bias, and the lack of granular data in the published studies for a study-level meta-analysis.Conclusions:This systematic review will provide a synthesis of current evidence on the prevalence of medication nonadherence in apparent treatment-resistant hypertension and on the relative contributions of nonintentional and intentional nonadherence subtypes. These findings will provide clinicians with a better understanding of the factors underlying treatment-resistant hypertension and will serve as a strong research base to guide future research on interventions to address medication nonadherence as well as the nonintentional and intentional subtypes.Trial registration:This protocol has been registered with PROSPERO. We will add registration details once available.

A3401 A case report of a 33-year-old man with resistant hypertension and slightly elevated cortisol and aldosterone

Objectives: Describe a unusual case of familial glucocorticoid resistance (FGR). FGR, an autosomal dominant from of monogenic hypertension, is characterized by hypertension, hypokalemia, metabolic alkalosis but no Cushing syndrome. Here, we describe the case of a 33-year-old man patient with resistant hypertension (mean blood pressure above 180/120mmHg after administration six different classes of antihypertensive agents) and slightly elevated cortisol and aldosterone but no hypokalemia, metabolic alkalosis and Cushing syndrome. Our aim was to find the cause and to control the high blood pressure of the patients. Methods: We did a series of checks and excluded primary aldosteronism and hypercortisolism and other diseases. After the DNA sequencing, we found that the patient had a mutation Pro9Arg (c.26C > G) in the NR3C1 gene and the familial glucocorticoid resistance was diagnosed. Results: After taking 0.75 mg dexamethasone at 8 o’clock and 2 kinds of antihypertensive drugs (a calcium-channel blocker plus an angiotensin-II receptor blocker), the average blood pressure of the patient was below 140/90mmHg. Conclusion: The role of genetic testing and genetic counseling in establishing the early diagnosis of FGR is important. FGR can result in resistant hypertension. C.26C > G in the NR3C1 gene that caused p.Pro9Arg is a new mutation of FGR.

RESISTANT ARTERIAL HYPERTENSION

Resistant hypertension is defined as a lack to lower 140 mmHg (systolic blood pressure) and 90 mmHg (diastolic blood pressure) values of ambulatory blood pressure (BP) response using 3 antihypertensive agents of different classes, one of which should be a diuretic in patients fully adherent to antihypertensive therapy. Prevalence of resistant hypertension is ranging from about 5 to 50 % in various cohorts. Initial management requires identification of true treatment resistance by out-of-office BP measurements, assessment of adherence and screening for treatable causes of uncontrolled BP. Recent studies try to indicate possible biomarkers of resistance hypertension. Treatment include lifestyle changes, enhancing treatment adherence and optimization of the doses. An invasive approach to resistant hypertension should be kept for persistently severe cases managed in a specialized hypertension center. This article aims to familiarize readers with the evaluation and management of resistant hypertension by outlining the most recent evidence-based treatment options.

Use of Antihypertensive Agents and Association With Risk of Adverse Outcomes in Chronic Kidney Disease: Focus on Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers.

BackgroundOur objective was to determine patterns of antihypertensive agent use by stage of chronic kidney disease (CKD) and to evaluate the association between different classes of antihypertensive agents with nonrenal outcomes, especially in advanced CKD.Methods and ResultsWe studied 3939 participants of the CRIC (Chronic Renal Insufficiency Cohort) study. Predictors were time‐dependent angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker , β‐blocker, and calcium channel blocker use (versus nonuse of agents in each class). Outcomes were adjudicated heart failure events or death. Adjusted Cox models were used to determine the association between predictors and outcomes. We also examined whether the associations differed based on the severity of CKD (early [stage 2–3 CKD] versus advanced disease [stage 4–5 CKD]). During median follow‐up of 7.5 years, renin‐angiotensin‐aldosterone system inhibitor use plateaued during CKD stage 3 (75%) and declined to 37% by stage 5, while β‐blocker, calcium channel blocker, and diuretic use increased steadily with advancing CKD. Renin‐angiotensin‐aldosterone system inhibitor use was associated with lower risk of heart failure (hazard ratio, 0.79; 95% confidence interval, 0.67–0.97) and death (hazard ratio, 0.78; 95% confidence interval, 0.67–0.90), regardless of severity of CKD. Calcium channel blocker use was not associated with risk of heart failure or death, regardless of the severity of CKD. β‐Blocker use was associated with higher risk of heart failure (hazard ratio, 1.62; 95% confidence interval, 1.29–2.04) and death (hazard ratio, 1.22; 95% confidence interval, 1.03–1.43), especially during early CKD (P<0.05 for interaction).ConclusionsAngiotensin‐converting enzyme inhibitor and angiotensin receptor blocker use decreased, while use of other agents increased with advancing CKD. Use of agents besides angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers may be associated with suboptimal outcomes in patients with CKD.

Does Nordic walking helps to improve exercise capacity and weight control in patients with resistant hypertension?

Resistant high blood hypertension (HBPr) it's defined as arterial pressure that remains above goal in spite of concurrent use of three antihypertensive agents of different classes. HTAR is associated with an increased risk of cardiovascular disease, terminal chronic renal failure and mortality, compared to patients whose hypertension responds to treatment. The currently therapeutic pillar involves multidisciplinary management with pharmacotherapy, health education, nutritional control, psychological support and therapeutic physical exercise. The aim of this study it's to use therapeutic exercise to facilitate the control of the blood pressure to improve the aerobic resistance, the meters walked and the weight control. Prospective, compared quasi-experimental study (pre- and post-intervention). Five cases, all men, with a mean age 58.2 (SD 12.21) years and BMI 32.952 (SD 3.93) kg/m 2 , who were included in a multidisciplinary study entitled: “Study of biomarkers in patients with HBP resistance to antihypertensive treatment”, performed a Nordic walking training program. The principal outcome was the six minutes walking test (6′WT). Other outcomes were the functional capacity (VO 2 peek and VO 2 AT), weight control and the compliance of the program. The improvement of 6′WT was 16.4 meters ( P > 0.05). The initial VO 2 peek was 14.22 ± 2.64 mL/kg/min (64.6%), with an improved of 1.72 mL/kg/min after the program. There was no improvement in VO 2 AT. There was a significant improvement in weight and BMI after the intervention. The compliance of the program was 86.25% ± 9.27. The peak of TA at maximum effort improved in all cases after the program, improving even the hypertensive response of one of the patients. Nordic walking is an excellent therapeutic exercise in patients with HBPr, because improves the blood pressure control, the weight control and the exercise capacity.

Comparative Efficacy of Antihypertensive Agents in Salt-Sensitive Hypertensive Patients: A Network Meta-Analysis.

Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure (BP) in patients with SSH. We used sources as PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), CNKI, and WANFANG database from inception to November 2016. Studies that compared the efficacy of 2 or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure. Twenty-five studies were involved in this meta-analysis. A calcium channel blocker (CCB) with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo (standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60 to 40.16), angiotensin receptor blockers (ARBs) (SMD, 95% CI: 22.94, 5.26 to 40.51), and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, CCB with metformin and moderate salt intake would decrease blood pressure with 17.90 mm Hg. For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake was optimal in reducing BP, while CCB combined with metformin and moderate salt intake was the most efficacious at reducing BP in SSH patients with coexisting obesity.

Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and Calcium Channel Blocker.

In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004-2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051-2.307; p < 0.05) as compared with the A + B + C group. Adding a diuretic may be better than adding a beta-blocker for treating hypertensive patients with prior CVA history who have already received ACEIs/ARBs and CCBs.