The Effect of Obstructive Sleep Apnea on Subclinical Target Organ Damage in Patients With Resistant Hypertension.

INTRODUCTION: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients. METHODS: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years. RESULTS: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects. CONCLUSIONS: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR.

Screening of serum markers in patients with resistant hypertension.

Background: This study delves into the intricacies of resistant hypertension (RH), a prevalent yet enigmatic chronic cardiovascular ailment that is linked to a myriad of complications. Although its full pathogenesis is still shrouded in mystery, the field of proteomics offers a beacon of hope, with its potential to shed light on the proteins that orchestrate the tapestry of life. Harnessing the power of proteomics is essential for demystifying the pathogenesis of RH, enabling more precise diagnostics and treatments, and ultimately improving prognostic outcomes. Methods: Our approach was to employ rigorous statistical analyses to home in on proteins with significant expression variances between our two cohorts. We complemented this with bioinformatics tools to unravel the intricate functions and pathways of these proteins. By synthesizing these insights with the clinical profiles of our patients, we were able to distill a set of definitive biomarkers with diagnostic potential. In our quest for clarity, we also embarked on a retrospective journey, amassing and scrutinizing clinical data from both RH and hypertension (HTN) patients. We crafted and rigorously assessed risk factor models to evaluate their diagnostic prowess. Results: Our exploration spanned across 30 blood samples from RH patients and 20 from those grappling with HTN. Our inquiry yielded some compelling revelations: (1) RH patients showcased 29 unique proteins, in contrast to the 59 unique proteins found in HTN patients. A deeper dive into the proteomic data unveiled molecular functions predominantly tied to lipid metabolism, protein networking, and oxidative stress, with a spotlight on pathways such as cholesterol metabolism, coagulation, and the complement cascade. (2) By charting receiver operating characteristic curves and rigorously analyzing the proteomic data, we surfaced 11 proteins with notable diagnostic potential, tightly interwoven with clinical metrics. Conclusion: Our research has pinpointed 11 proteins that stand as promising serum biomarkers, endowed with significant diagnostic value. This discovery marks a stride towards a more nuanced understanding and management of resistant hypertension.

The Efficacy of Renal Denervation in Treating Resistant Hypertension: A Systematic Review.

Resistant hypertension is blood pressure (BP) that is persistently above target in spite of the maximally tolerated usage of at least three anti-hypertensives simultaneously. The sympathetic nervous system is instrumental in blood pressure (BP) regulation. Renal (sympathetic) denervation involves using ablative energy to disrupt the sympathetic nerves in renal arteries. This systematic review examines the efficacy of this treatment modality. Abiding by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted an extensive literature search in five databases, Cochrane Library, Google Scholar, PubMed, PubMed Central (PMC), and ScienceDirect, to retrieve studies that are free, open access, and published in English done within the past four years. Nineteen articles passed critical appraisal. These articles were randomized controlled trials (RCT), a case report, a cross-sectional study, a cohort study, and previous reviews. Renal denervation (RDN) was generally superior to sham control in patients with resistant hypertension for reducing various systolic blood pressure (SBP) measures, including 24-hour ambulatory, daytime, and nighttime SBP. The efficacy was highest in patients whose baseline SBP was higher. BP reduction was sustained for years post-procedure. The procedure had a good safety profile with no severe complications. Future studies should compare the efficacy of different types of renal denervation, such as ethanol ablation versus radiofrequency ablation, and renal denervation against other procedure-based treatment modalities, such as carotid baroreceptor stimulation and transcranial direct current stimulation.

Association of the Triglyceride-Glucose Index With Resistant Hypertension and a Nomogram Model Construction.

BACKGROUND: Resistant hypertension (RH) remains one of the major risk factors for cardiovascular disease. This study aims to investigate the association between the triglyceride-glucose (TyG) index and RH incidence in patients with hypertension and to construct a nomogram for predicting the occurrence of RH. METHODS AND RESULTS: A retrospective cohort study was conducted on 1635 patients initially diagnosed with hypertension at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from August 2019 to August 2021. Patients were followed up for a median of 31 months, with 373 cases (22.81%) developing RH. Least absolute shrinkage and selection operator regression and multivariable Cox regression analysis identified the TyG index as the strongest predictor of RH (hazard ratio, 5.472 [95% CI, 4.028-7.433]; P<0.001). Consistent results were also observed in subgroup analyses across different ages and sexes. In addition to the TyG index, other independent risk factors, including uric acid, age, and the apnea-hypopnea index, were noted. A nomogram model was subsequently developed using these risk factors, and including the TyG index notably enhanced the diagnostic effectiveness of the model in predicting the occurrence of RH. CONCLUSIONS: The TyG index appears to be a potential predictor of RH in patients with hypertension, indicating that insulin resistance might be an important factor in the development and progression of RH.

Renal sympathetic denervation 2024 in Austria: recommendations from the Austrian Society of Hypertension : Endorsed by the Austrian Society of Nephrology and the Working Group of Interventional Cardiology of the Austrian Society of Cardiology.

Renal sympathetic denervation (RDN) is an interventional supplement to medical treatment in patients with arterial hypertension. While the first sham-controlled trial, SYMPLICITY HTN­3 was neutral, with improved procedural details, patient selection and follow-up, recent randomized sham-controlled trials of second-generation devices show a consistent blood pressure lowering effect of RDN, as compared to sham controls. These new data and the recent U.S. Food and Drug Administration (FDA) premarket approval of two RDN devices are the basis for the present recommendations update.This joint position paper from the Austrian Society of Hypertension, together with the Austrian Society of Nephrology and the Working Group of Interventional Cardiology from the Austrian Society of Cardiology includes an overview about the available evidence on RDN and gives specific recommendations for the work-up, patient selection, pretreatment, procedural management and follow-up in patients undergoing RDN in Austria. Specifically, RDN may be used in clinical routine care, together with lifestyle measures and antihypertensive drugs, in patients with resistant hypertension (i.e. uncontrolled blood pressure on 3 antihypertensive drugs) and in those with uncontrolled hypertension, after adequate work-up, if institutional, patient-related and procedural conditions are fulfilled.

GLP-1-based therapies for the treatment of resistant hypertension in individuals with overweight or obesity: a review.

Despite the availability of a wide range of antihypertensive agents, a significant proportion of individuals with resistant hypertension (RHTN) struggle to achieve blood pressure (BP) control. Obesity ranks among the most significant modifiable risk factors for RHTN, with 56-91% of patients with RHTN classified as overweight or obese. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) are a class of anti-obesity medications that have recently demonstrated efficacy in reducing BP and improving cardiovascular (CV) outcomes in individuals with overweight or obesity. Among the available GLP-1-based therapies, liraglutide, semaglutide, and tirzepatide have been approved for chronic weight management in this population. Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, has the greatest effect on weight loss and BP reduction compared to GLP-1 RAs alone. To our knowledge, no trials have directly evaluated the effect of GLP-1 RAs or dual GLP-1/GIP receptor agonists on RHTN management. In this review article, we propose that targeting weight loss through GLP-1-based therapies should be explored as a treatment option for individuals with RHTN who are overweight or obese.

Pressing Update: Aprocitentan for the Treatment of Hypertension.

OBJECTIVE: This article reviews the published data including the pharmacology, efficacy, and safety of aprocitentan, a novel endothelin receptor antagonist developed to treat hypertension in conjunction with additional agents. DATA SOURCES: A literature search was conducted from drug discovery until May 2024 through PubMed, MEDLINE, and National Institutes of Health Clinical Trials Registry utilizing the following search terms: Tryvio, aprocitentan, hypertension, resistant hypertension, endothelin receptor antagonist, and ACT-132577. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language studies, or studies that could be appropriately translated into English, containing the pharmacology, pharmacokinetics, safety, and efficacy of aprocitentan, were selected for review. DATA SYNTHESIS: In the setting of resistant hypertension, aprocitentan has shown significant reductions in blood pressure in both medical office and 24-hour ambulatory settings at 4 weeks with a sustained effect at 40 weeks. Studies evaluating cardiovascular risk reduction have not been conducted at this time. Fluid retention and edema were the most frequent adverse events reported in clinical studies with aprocitentan. As a class, endothelin receptor antagonists may cause fetal harm; aprocitentan should be used with caution to avoid embryo-fetal toxicity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Owing to the existent barriers for the treatment of resistant hypertension, aprocitentan presents itself as an effective option when added to traditional antihypertensives. This single-strength, once-daily regimen may serve as an appealing option to both patients and prescribers. CONCLUSION: Aprocitentan is a safe and effective medication for the treatment of hypertension when added to other pharmacological therapies.

Tackling the Disproportionate Burden of Resistant Hypertension in US Black Adults.

PURPOSE OF REVIEW: Elevated blood pressure is the leading modifiable risk factor for cardiovascular morbidity and mortality in the US. Older individuals, Black adults, and those with comorbidities such as chronic kidney disease, have higher levels of uncontrolled and resistant hypertension. This review focuses on resistant hypertension, specifically in the US Black population, including potential benefits and limitations of current and investigational agents to address the disparate toll. RECENT FINDINGS: There is a necessity to implement public health measures, including early screening, detection, and evidence-based hypertension treatment with lifestyle, approved and investigational agents. The evidence highlights the importance of implementing feasible and cost-effective public health measures to advocate for early screening, detection, and appropriate treatment of hypertension. A team-based approach involving physicians, advanced practice nurses, physician assistants, pharmacists, social workers, and clinic staff to implement proven approaches and the delivery of care within trusted community settings may mitigate existing disparities.

Hyperaldosteronism secondary to renal agenesis: An unusual cause for hypertension in pregnancy.

Literature with regards to pregnancy related outcomes in persons with the presence of a solitary kidney of any cause is scarce. Most of the available information has been extrapolated from persons who have been renal donors. Unilateral renal agenesis affects 1 in 1500 people and can present with resistant hypertension. When a woman with a solitary kidney presents in pregnancy, it may be both a challenging diagnostic and therapeutic problem. Eplerenone, a selective aldosterone blocker has been prescribed for resistant hypertension and in the presence of pregnancy, been useful in persons with primary hyperaldosteronism and resistant hypertension due to obstructive sleep apnoea. We describe the use of Eplerenone in a patient with resistant hypertension in pregnancy, due to secondary hyperaldosteronism precipitated by renal agenesis.

Characterizing apparent treatment resistant hypertension in the United States: insights from the All of Us Research Program.

BACKGROUND: Hypertension (HTN) remains a significant public health concern and the primary modifiable risk factor for cardiovascular disease, which is the leading cause of death in the United States. We applied our validated HTN computable phenotypes within the All of Us Research Program to uncover prevalence and characteristics of HTN and apparent treatment-resistant hypertension (aTRH) in United States. METHODS: Within the All of Us Researcher Workbench, we built a retrospective cohort (January 1, 2008-July 1, 2023), identifying all adults with available age data, at least one blood pressure (BP) measurement, prescribed at least one antihypertensive medication, and with at least one SNOMED "Essential hypertension" diagnosis code. RESULTS: We identified 99 461 participants with HTN who met the eligibility criteria. Following the application of our computable phenotypes, an overall population of 81 462 were further categorized to aTRH (14.4%), stable-controlled HTN (SCH) (39.5%), and Other HTN (46.1%). Compared to participants with SCH, participants with aTRH were older, more likely to be of Black or African American race, had higher levels of social deprivation, and a heightened prevalence of comorbidities such as hyperlipidemia and diabetes. Heart failure, chronic kidney disease, and diabetes were the comorbidities most strongly associated with aTRH. ß-blockers were the most prescribed antihypertensive medication. At index date, the overall BP control rate was 62%. DISCUSSION AND CONCLUSION: All of Us provides a unique opportunity to characterize HTN in the United States. Consistent findings from this study with our prior research highlight the interoperability of our computable phenotypes.

The Current State and Future of Renal Denervation: A Review.

Renal denervation as an option for difficult to treat hypertension has been a concept for several decades, with recent U.S. FDA approval of new, minimally invasive devices. However, while renal denervation has the potential to improve hypertension management, several challenges require consideration prior to widespread adoption. The effect relative to sham control is modest, and generally similar to addition of a single blood pressure lowering medication. It is possible that with additional technique refinement greater effects may be possible. Key factors to consider beyond the direction, strengths, and limitations of the renal denervation technologies themselves, are an understanding of patient groups that derive greatest benefit and phenotypes or biomarkers that predict greater response. This review provides an update on these challenges in addition to the current state and future of renal denervation within the context of hypertension management and treatment.

Cracking the Code: A Case Report on Low-Renin Hypertension.

Low-renin hypertension (LRH) is characterized by hypertension accompanied by low serum renin levels. LRH is a spectrum, including low-renin essential hypertension (LREH), primary hyperaldosteronism, and several acquired or familial secondary forms. Here, we present a case of LRH. A 57-year-old female with resistant hypertension on multiple antihypertensive medications presented for blood pressure management. Workup for secondary causes of hypertension revealed low renin levels with normal aldosterone. The patient was initiated on spironolactone and responded quickly with normal blood pressure on a follow-up visit. LRH is an under-recognized etiology for uncontrolled hypertension. It can be secondary to several different causes. Although treatment of LREH is essentially the same as regular patients, these patients tend to respond well to sodium-volume-depleting diuretics, mineralocorticoid receptor blockers, and epithelial sodium channels (ENaC) blockers.

Hypertension and Device-Based Therapies for Resistant Hypertension: An Up-to-Date Review.

Hypertension is the most prevalent modifiable risk factor associated with cardiovascular mortality. The World Health Organization (WHO) estimates that hypertension directly or indirectly causes the death of at least nine million people globally every year. The number of people living with hypertension (blood pressure (BP) of ≥140 mmHg systolic or ≥90 mmHg diastolic or on medication) doubled between 1990 and 2019, from 650 million to 1.3 billion. Despite a plethora of antihypertensive drugs widely available, a sizable part of the antihypertensive population stays uncontrolled. The unmet need of controlling BP in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. Several device-based approaches have been introduced to lower BP, and most of these strategies aim to modulate autonomic nervous system activity. Importantly, when considering a device-based treatment, each patient's underlying pathophysiology is considered, and the procedural risks are weighed against the cardiovascular risk attributed to the elevated BP. In November 2023, the FDA approved two renal denervation (RDN) devices. This manuscript discusses current interventional devices and procedures recently approved (RDN) and others in the clinical testing stage for arterial hypertension intervention or management. As we list below, all others have shown promising results and are being evaluated on a larger clinical trial. The new device-based classes are as follows: catheter-based RDN, baroreflex amplification, arteriovenous (AV) malformation, carotid body (CB) ablation, pacemaker-based cardiac neuromodulation, electro-acupuncture, and deep brain stimulation. Baroreflex amplification uses peripheral neuromodulation, while AV malformation leverages AV anastomosis. CB ablation modulates chemoreceptors, and pacemaker-based neuromodulation adjusts atrioventricular intervals. Electro-acupuncture proves potential, and deep brain stimulation offers central nervous system intervention.

Primary aldosteronism with postoperative elevation of aldosterone treated effectively by finerenone: A case report.

The authors report a case of primary aldosteronism (PA) with postoperative elevation of aldosterone treated effectively by finerenone. The patient was a hypertensive man with a 30-year history of hypertension and sustained an acute myocardial infarction 5 years ago. Bilateral adrenal nodules with hyperplasia were detected and PA was confirmed. His blood potassium, direct renin concentration, and aldosterone level returned to normal after surgery of right adrenalectomy. However, 1 year after surgery, he experienced a decrease in blood potassium and an increase in aldosterone. A saline infusion test revealed an aldosterone level of 124.47 pg/mL. The patient consented to treatment with finerenone. His aldosterone and potassium levels and blood pressure have been controlled well during follow-up. This case highlights the need to screen for secondary hypertension as early as possible. Finerenone may be effective for patients with PA who are not candidates for surgery and those not relieved after surgery.

High serum levels of reactive nitrogen species and low total antioxidant capacity in patients with resistant hypertension compared to those in age- gender matched healthy controls, controlled hypertension and follow up with propranolol treatment in the extended APPROPRIATE trial.

OBJECTIVES: To perform a comparative analysis of the extended APPROPRIATE trial of measures of reactive nitrogen species and antioxidant capacity in patients having resistant hypertension with controlled hypertension and healthy controls. RESULTS: Mean serum NO2- and NOx levels were significantly lower and mean AOC was significantly higher in patients with controlled hypertension (n = 38) and healthy controls (n = 38) compared to resistant hypertension (RHTN) patients (n = 40) at the pre-intervention stage (p < 0.001). The serum NO2-, NOx and AOC levels of both controlled hypertension and healthy controls were comparable to those of the RHTN patients following treatment with propranolol (n = 18). Considering all samples (n = 114) we noted that there were significant weak and moderate positive correlations between NO2- levels with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.396, p < 0.001 and r = 0.292, p = 0.004) as well as total NOx levels with SBP and DBP (r = 0.636 and r = 0.480 respectively, p < 0.001). Conversely, there was a significant negative correlation between AOC levels with SBP and DBP (r= -0.846 and r = -0.626 respectively, p < 0.001).

Evaluation of aldosterone to direct renin ratio, low renin and related Phenotypes in Afro-Colombian patients with apparent treatment resistant hypertension.

Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle's-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48-60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (ß - 0.15, 95% CI [- 0.27, - 0.03]) and renin concentrations (ß - 0.75, 95% CI [- 1.5, - 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle's-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.

Indications for renal denervation in the treatment of hypertension.

Renal denervation (RDN) is a neuromodulation therapy performed using an intraarterial catheter in patients with hypertension. Recent randomized sham-operated controlled trials have shown that RDN has significant antihypertensive effects in patients with resistant, uncontrolled, and/or drug-naïve hypertension. Based on available evidence, the European Society of Hypertension 2023 guidelines include a Class II recommendation for the use of RDN in individuals with resistant and uncontrolled hypertension. The US Food and Drug Administration approved two devices, the ultrasound-based ReCor ParadiseTM RDN system and the radiofrequency-based Medtronic Symplicity SpyralTM RDN system, as adjunctive therapy for patients with resistant and uncontrolled hypertension. The indications for RDN and incorporation of RDN into clinical practice will grow as clinical evidence accumulates. This mini review summarizes latest findings focusing on the safety and effectiveness of RDN for treating hypertension in the absence and presence of antihypertensive drugs, and discusses the indications for RDN. This mini review focuses on the safety and effectiveness of RDN for treating hypertension in the absence and presence of antihypertensive drugs. The indications for RDN and incorporation of RDN into clinical practice will grow as clinical evidence accumulates and should be reviewed and updated.