Resistant Hypertension Research Articles

In these cases, I treat hypertension with renal ablation.

Systemic arterial hypertension is one of the leading causes of mortality and morbidity worldwide. Despite therapeutic advancements, a significant proportion of hypertensive patients fail to achieve adequate blood pressure control. Renal denervation (RDN) is emerging as an innovative and minimally invasive procedure to treat hypertension by modulating the renal sympathetic nervous system. Recent clinical trials, including SYMPLICITY HTN-3, SPYRAL HTN-OFF MED, and RADIANCE-HTN SOLO, have shown variable results, influenced by patient selection and study design. The latest 2024 ESC guidelines on systemic arterial hypertension recommend RDN as a therapeutic option in selected cases, especially in patients with resistant hypertension not adequately controlled by pharmacological therapy. However, the response to this approach varies according to individual pathophysiology and the level of sympathetic activation. This article highlights how RDN, performed using ultrasound or radiofrequency technologies, may represent a breakthrough for difficult-to-treat patients, bridging current therapeutic gaps and reducing long-term cardiovascular risk. Finally, it emphasizes the importance of a multi-disciplinary assessment to maximize the benefits of the procedure.

Cost-Effectiveness of Ultrasound Renal Denervation for Resistant Hypertension in Belgium, France and The Netherlands.

Endovascular ultrasound renal denervation (uRDN) with the Paradise System has emerged as an adjunctive treatment option for the management of uncontrolled resistant hypertension (rHTN). This study assesses the cost-effectiveness of uRDN for rHTN across three European countries-Belgium, France and the Netherlands. On the basis of a previously developed state-transition Markov model, we projected costs, life years (LYs) and quality adjusted life years (QALYs) with the addition of uRDN to standard of care (SoC) compared with SoC alone over patient lifetime. Analyses were based on the RADIANCE-HTN TRIO trial, which demonstrated a mean reduction in office systolic blood pressure from a baseline of 8.5 mmHg at 2 months post-uRDN among patients with rHTN. Mortality and costs data were separately sourced and applied for each country independently. Country-specific discount rates were applied to both cost and outcomes. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). The base-case analyses of the models for all three countries show uRDN plus SoC results in improvement in both LYs and QALYs per patient and higher costs compared with SoC alone. The mean ICERs for each country model fall well below the respective country-specific willingness-to-pay thresholds (WTPs)-Belgium: WTP €40,000 and ICER €4426/QALY gained; France: WTP €50,000 and ICER €6261/QALY gained; and the Netherlands: WTP €20,000 and ICER €1654/QALY gained. Results were robust across scenarios and sensitivity analyses. The addition of endovascular uRDN offers clinicians and payers a cost-effective adjunctive treatment approach alongside hypertensive medication for the management of rHTN in the healthcare systems of Belgium, France and the Netherlands.

Renal dysfunction in patients with resistant hypertension: association with clinical profile and fat depots

Introduction. Chronic kidney disease (CKD) and arterial hypertension (AH), especially its resistant forms, are two closely related and mutually aggravating diseases. The pathophysiology of CKD development in patients with resistant AH is complex and is not limited to the negative impact of hemodynamic, metabolic, neurohormonal and proinflammatory factors. The common pathophysiological mechanism of development of both diseases is visceral obesity, which has both systemic and local negative effects. However, aspects of kidney damage in patients with resistant AH (RAH) require further study, and their understanding may open up new possibilities in a comprehensive approach to nephroprotection.Aim: To study the relationship between a decrease in the functional state of the kidneys in patients with resistant hypertension and clinical data, the size of systemic and local fat depots, as well as markers of sympathetic activity.Material and Methods. Sixty-three patients with RAH were included in comparative cross-sectional study. CKD C3 was documented in 19 patients (30%). Magnetic resonance imaging (MRI) (1.5 Tesla) was used to assess the sizes of kidney and abdominal fat depots (thickness and area of subcutaneous and visceral adipose tissue (S SAT and VAT), paranephral adipose tissue thickness (PRAT). In addition to routine examinations, patients underwent measurement of cystatin C levels in the blood and 24-hour blood pressure monitoring. Activity of sympathetic nervous system was assessed by catecholamine’s measuring in urine and blood tests, beta-adrenergic membrane reactivity (β-ARM) of erythrocytes, and systolic BP variability.Results. Patients with CKD compared to patients without CKD were older, higher pulse BP levels (p = 0.005), fasting glucose (p = 0,007), had smaller kidney sizes (p = 0.046), S VAT (p = 0.025) and PRAT thickness (p = 0.013), and lower kidney diameter/PRAT ratio (p = 0.022). No intergroup differences were found in anthropometric indices, SAT thickness and markers of sympathetic activity. Decreased estimated glomerular filtration rate (eGFR) had quantitative associations with increased PRAT thickness and percent adipose tissue (AT) (r = –0.27, p < 0.05 for both)). High uric acid levels correlated with increased S VAT, PRAT thickness and a set of anthropometric parameters.Conclusions. The presence of CKD in patients with RAH is associated not only with age, an increase in pulse BP and fasting glucose, but also with an increase in the size of visceral fat depots, and a decrease in the functional state of the kidneys is directly related to an increase in adipose tissue in the perirenal region, the percentage of adipose tissue and an increase in vascular stiffness.

Aldosterone-targeted therapies: early implementation in resistant hypertension and chronic kidney disease.

Aldosterone-targeted therapies: early implementation in resistant hypertension and chronic kidney disease.

Aprocitentan for Treatment-Resistant Hypertension: Pharmacology Concepts and Clinical Insights.

Treatment resistant hypertension (TRH) occurs in nearly 20% of patients with a diagnosis of hypertension despite receiving three or more antihypertensives and places individuals at an increased risk of morbidity and mortality compared to essential hypertension. Numerous pathophysiological factors underlie TRH, including endothelin-1, which until recently no approved treatments targeted. Endothelin-1 exhibits multiple actions through binding to ETA and ETB receptors. Vasoconstriction of the vascular smooth muscle occurs when endothelin-1 binds ETA and ETB, however; vasodilation of endothelial cells also occurs through activation of ETB. Currently available endothelin receptor antagonists (ERA) were only approved for pulmonary hypertension until 2024 when the Food and Drug Administration approved aprocitentan as the first ERA for hypertension treatment in combination with other antihypertensives. The approval of aprocitentan occurred following the publication of the phase 3 PRECISION trial that compared aprocitentan versus placebo for patients with "true" TRH. Aprocitentan 12.5 mg exhibited a placebo-adjusted reduction in sitting systolic and diastolic blood pressure of 3.8/3.9 mmHg at 4 weeks of treatment. A dose-dependent increase in peripheral edema and a small reduction in hemoglobin due to hemodilution were greater in the aprocitentan-treated patients. Animal study data from past endothelin receptor antagonists showed this class of agents may lead to birth defects and was the basis for aprocitentan's black-box warning. Overall, clinical trial data supports aprocitentan's use as an effective agent for the TRH, but clinicians will need to individualize patient treatment selection and consider the safest and most efficacious options currently available.

Renal denervation plus cardiac ablation vs. cardiac ablation alone for patients with atrial fibrillation and uncontrolled arterial hypertension : Asystematic review and updated meta-analysis of randomized controlled trials.

Atrial fibrillation (AF) is acomplex arrhythmia often worsened by hypertension (HTN). Pharmacological treatments frequently underperform, and the best approach, particularly combining renal denervation (RDN) with cardiac ablation (CA), remains unclear. We conducted an updated meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of RDN combined with CA versus CA alone in patients with AF and uncontrolled HTN. We performed asystematic review and meta-analysis of RCTs retrieved from PubMed, Embase, and the Cochrane Library up to July 2024. Primary outcomes included AF recurrence, periprocedural complications, blood pressure changes, and estimated glomerular filtration rate (eGFR). Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed using arandom-effects model. Eight RCTs were included, involving 689 patients (37% female). Of these, 355 underwent RDN + CA, and 334 underwent CA alone, with amean follow-up of at least 12months. The RDN + CA group exhibited asignificant reduction in AF recurrence (RR: 0.77; 95% CI: 0.61-0.97). There were no significant differences in periprocedural complications (RR: 1.06; 95% CI: 0.60-1.89), systolic blood pressure (MD: -6.79; 95% CI: -14.71-1.14), diastolic blood pressure (MD: -2.47; 95% CI: -8.13-3.20), or eGFR (MD: 1.14; 95% CI: -11.95-14.23). Our findings show that RDN combined with CA significantly reduces AF recurrence compared to CA alone, presenting apromising approach for patients with resistant HTN and AF.

The New Drugs in the Treatment of Hypertension and Resistant Hypertension: A Review of Therapies

Advancements in pharmacotherapy for hypertension (HTN) have led to the development of new drug classes and innovative supportive treatments. Aprocitentan, an endothelin receptor antagonist, has demonstrated promising effects in managing resistant hypertension, as evidenced by the PRECISION study [1]. Another notable innovation is firibastat, an aminopeptidase A inhibitor, which reduces the activity of the renin-angiotensin system by modulating angiotensin II conversion in the brain. Studies on firibastat suggest its potential in reducing blood pressure in primary hypertensive patients [2]. In the treatment of resistant HTN, newer forms of aldosterone inhibitors, such as esaxerenone, have shown greater selectivity compared to spironolactone, reducing the risk of side effects [3]. Additionally, baxdrostat, a potassium salt of aldosterone synthase inhibitor, decreases aldosterone production and improves blood pressure control [1]. Adjunctive therapies, including renal denervation and baroreceptor stimulation, are being investigated for their efficacy in reducing resistance to medication in patients with resistant HTN. Research suggests that these interventions may be particularly beneficial for patients who do not respond to standard pharmacological treatments [4]. Further research into these pharmacological and procedural therapies is crucial for optimizing hypertension management strategies.

Translating physiology of the arterial chemoreflex into novel therapeutic interventions targeting carotid bodies in cardiometabolic disorders

AbstractThis review resulted from a conference on the pathological role of arterial chemoreflex and carotid bodies in cardiometabolic diseases held at the 27th Congress of the Polish Cardiac Society in September 2023 in Poznan, Poland. It reflects the contribution of Polish researchers and their international collaborations, which have been fundamental in the development of the field. Aberrant activity of the carotid bodies leads to both high tonicity and increased sensitivity of the arterial chemoreflex with resultant sympathoexcitation in chronic heart failure, resistant hypertension and obstructive sleep apnoea. This observation has led to several successful attempts of removing or denervating the carotid bodies as a therapeutic option in humans. Regrettably, such interventions are accompanied by serious respiratory and acid–base balance side‐effects. Rather than a single stereotyped reaction, arterial chemoreflex comprises an integrative multi‐system response to a variety of stimulants and its specific reflex components may be individually conveyed at varying intensities. Recent research has revealed that carotid bodies express diverse receptors, synthesize a cocktail of mediators, and respond to a plethora of metabolic, hormonal and autonomic nervous stimuli. This state‐of‐the‐art summary discusses exciting new discoveries regarding GLP‐1 receptors, purinergic receptors, the glutamate–GABA system, efferent innervation and regulation of blood flow in the carotid body and how they open new avenues for novel pharmacological treatments selectively targeting specific receptors, mediators and neural pathways to correct distinct responses of the carotid body‐evoked arterial chemoreflex in cardiometabolic diseases. The carotid body offers novel and advantageous therapeutic opportunities for future consideration by trialists. image

Hypertension management in patients with advanced chronic kidney disease with and without dialysis

Purpose of review Hypertension is a common comorbidity in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on dialysis, contributing significantly to cardiovascular disease and increased mortality. Managing hypertension in this population is complex due to the frequent occurrence of resistant hypertension. This review highlights the recent updates in hypertension management for these patients, especially considering new guidelines and therapeutic options. Recent findings Recent literature emphasizes updated KDIGO guidelines, which have lowered blood pressure targets to decrease cardiovascular risks in patients with advanced CKD and ESKD. First-line therapies include diuretics, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers. New pharmacological treatments, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, endothelin receptor antagonists, RNA interference therapeutics, and aldosterone synthase inhibitors, offer promising options for resistant hypertension. Additionally, lifestyle modifications, including a low-salt diet and aerobic exercise, and volume control through ultrafiltration in dialysis patients, are crucial for blood pressure management. Summary The findings suggest that individualized treatment strategies, incorporating both pharmacologic and nonpharmacologic approaches, are essential for optimizing blood pressure control in patients with advanced CKD and ESKD. These strategies can improve cardiovascular outcomes and enhance patient quality of life, with important implications for clinical practice.

The role of insomnia in the development of resistant hypertension in uncontrolled hypertensive patients with obstructive sleep apnea: A prospective study.

The role of insomnia in the development of resistant hypertension in uncontrolled hypertensive patients with obstructive sleep apnea: A prospective study.

Correlational Analysis of Resistant Hypertension with Diabetes Mellitus, Chronic Kidney Disease, and the Interplay of Sodium, Calcium, Magnesium, and Phosphorus.

To analyze the relationship between resistant hypertension (RH) and hypertension, diabetes mellitus, chronic kidney disease, sodium, calcium, magnesium, phosphorus. A total of 475 patients with hypertension admitted to Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2021 to December 2023 were divided into hypertension group (HT group) and resistant hypertension group (RH group). We compared the differences between these two groups, and analyzed the influencing factors of RH, as well as the correlation between RH and the course of hypertension, diabetes mellitus, chronic kidney disease, and levels of sodium, calcium, magnesium and phosphorus. Compared with HT group, RH group had a significantly higher blood pressure (P < 0.05), longer duration of hypertension, diabetes mellitus, and chronic kidney disease (P < 0.01) and a higher proportion of combined chronic kidney disease (P = 0.006). The duration of hypertension, serum sodium ion concentration (≥142.00mmol/L), calcium ion concentration (2.19 to < 2.30mmol/L), and 24h urinary phosphorus ion level were independent influencing factors of RH (P < 0.05). For hypertension patients with diabetes mellitus or chronic kidney disease, the risk of RH is significantly higher. The risk of RH may be lower in patients with blood sodium <142.00mmol/L, blood calcium >2.29mmol/L, 24h urine sodium and magnesium ions of 116.52 and 2.69mmol, respectively, and higher 24h urine phosphorus ions.

G-296 Role of 24-Hour Urinary Cortisol-to-Cortisone Ratio in Black and White Patients With Resistant Hypertension and Chronic Kidney Disease

G-296 Role of 24-Hour Urinary Cortisol-to-Cortisone Ratio in Black and White Patients With Resistant Hypertension and Chronic Kidney Disease

G-515 Role of Endothelin-1 in patients with Resistant Hypertension With and Without Chronic Kidney Disease

G-515 Role of Endothelin-1 in patients with Resistant Hypertension With and Without Chronic Kidney Disease

Value of multi-modal ultrasound in evaluation of the accessory renal artery.

The evaluation of the accessory renal artery (ARA) holds clinical significance in the effective intervention of resistant hypertension and renal vascular-related surgical procedures. Multi-modal ultrasound is a non-invasive, secure, and real-time imaging modality, especially useful in patients with renal impairment. Nevertheless, few studies have focused on the value of multi-modal ultrasound in the assessment of the ARA. This study aimed to explore the diagnostic performances of multi-modal ultrasound in the assessment of the ARA. A retrospective data collection (clinical and imaging information) was conducted on patients who underwent renal artery conventional ultrasound and contrast-enhanced ultrasound (CEUS) examinations between August 2019 and November 2023 in Beijing Hospital. A total of 73 patients with a unilateral or bilateral ARA based on their computed tomography angiography (CTA) results were included. Compared with CTA results, the accuracy of multi-modal ultrasound for the assessment of the ARA was evaluated, and underlying reasons for misdiagnosis and missed diagnosis were analyzed. Among the 73 patients (144 kidneys), CTA identified 85 ARAs, whereas multi-modal ultrasound detected 70 ARAs. Although multi-modal ultrasound failed to detect 15 ARAs, it did not result in any false-positive diagnoses. When CTA did not detect any ARAs in a kidney, multi-modal ultrasound also did not find any ARA. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of multi-modal ultrasound in diagnosing ARA were calculated as 82.4%, 100%, 100%, 81.0%, and 90.9%, respectively. The receiver operating characteristic (ROC) analysis demonstrated an area under the curve (AUC) of 0.906 (P<0.001). The consistency analysis yielded a kappa value of 0.806 (P<0.01). Comparisons were conducted between patients with detected ARAs and those with missed ARAs. The age and body mass index (BMI) between the two groups were found to be statistically significant (P<0.05). Multi-modal ultrasound, characterized by its non-invasive, safe, and reproducible nature, demonstrates a high level of diagnostic accuracy in detecting the ARA. Thus, multi-modal ultrasound holds promise as a valuable tool for evaluating the ARA.

Contemporary Use of an Old Drug: Minoxidil for Resistant Hypertension.

Contemporary Use of an Old Drug: Minoxidil for Resistant Hypertension.

Cost-effectiveness analysis of radiofrequency renal denervation for uncontrolled hypertension in Sweden

Introduction Radiofrequency renal denervation (RF RDN) is a catheter-based therapy for uncontrolled hypertension. This model-based analysis examined the cost-effectiveness of RF RDN in Sweden. Methods Clinical events, costs, quality-adjusted life-years (QALYs) were projected over 10-year and lifetime horizons with a decision-analytic Markov model. The model accounted for seven primary health states, including hypertension alone, myocardial infarction (MI), stroke, other symptomatic coronary heart disease (CHD), heart failure (HF), end-stage renal disease (ESRD), and death; health state transitions were informed by multivariate risk equations. Clinical evidence from the SPYRAL HTN-ON MED trial informed the treatment effect modeled (-4.9 mmHg reduction in office systolic blood pressure (SBP) vs. sham). Costs, utilities, and post-event mortality were obtained from Swedish literature where possible, with the base case conducted from the healthcare payer perspective. The primary outcome of the analysis was the incremental cost-effectiveness ratio (ICER), with the cost-effectiveness of RF RDN vs. standard of care (SoC) evaluated against an assumed willingness-to-pay threshold of SEK 500,000 per QALY gained. Extensive sensitivity analyses were performed. Results At 10-years, the relative risks for RF RDN were 0.80 for stroke, 0.88 for MI, 0.89 for CHD, 0.72 for HF, 0.96 for ESRD, 0.86 for cardiovascular death and 0.93 for all-cause death. Over lifetime, RF RDN led to incremental costs and QALYs of SEK 63,136 (total costs SEK 497,498 for RF RDN vs. SEK 434,362 for SoC) and 0.45 (total QALYs 14.79 for RF RDN vs. 14.34 for SoC), yielding an ICER of SEK 139,280 per QALY gained. RF RDN was cost-effective across all scenarios and sensitivity analyses. Conclusion Model projections suggest RF RDN to be a cost-effective therapy for uncontrolled including resistant hypertension in Sweden based on contemporary clinical evidence.

Bilateral Renal Artery Stenosis Due to Fibromuscular Dysplasia Presenting as Resistant Hypertension in a Young Adult: A Case Report and Literature Review

Background: Fibromuscular dysplasia (FMD) is a rare, non-atherosclerotic, non-inflammatory vascular disease that predominantly affects young individuals, especially women. It is an important but underrecognized cause of secondary hypertension. Case Presentation: We report the case of a 28-year-old man with no prior medical history who presented with severe hypertension discovered incidentally during evaluation for headaches. Despite triple antihypertensive therapy, blood pressure remained poorly controlled. Laboratory tests were unremarkable, and there was no evidence of end-organ damage. Renal Doppler ultrasound and CT angiography revealed bilateral renal artery stenosis consistent with fibromuscular dysplasia. The patient underwent successful percutaneous transluminal balloon angioplasty of both renal arteries without stent placement. Post-procedural follow-up showed significant blood pressure improvement, allowing reduction to monotherapy. Doppler ultrasound controls at 1, 3, 6 months, and annually thereafter confirmed sustained patency without restenosis. Conclusion: This case highlights the importance of considering FMD in young patients with resistant hypertension. Early diagnosis and intervention can result in excellent clinical outcomes without the need for stenting.

Emerging Pharmacological Approaches for the Treatment of Arterial Hypertension

Despite the availability of several drug classes for the treatment of hypertension, the current approaches to high blood pressure (BP) are not fully satisfying the needs of this patient population. As a result, in recent years, many clinical trials have investigated novel pharmacological approaches for lowering high BP. As overactivity of the renin–angiotensin–aldosterone system is often present in hypertensive patients, especially those with resistant hypertension, several studies have focused on novel strategies to counteract this phenomenon by the use of non-steroidal inhibitors of the mineralocorticoid receptors, aldosterone synthase inhibitors or RNA-targeting therapies to inhibit the hepatic synthesis of angiotensinogen. The latter approach in particular might offer the additional advantage of reducing the daily pill burden of these patients, hence mitigating the common occurrence of non-adherence to treatment. Because obesity and diabetes are common risk factors for hypertension (a high percentage of individuals with resistant hypertension being obese), numerous investigations have analyzed the BP-lowering effects of those agents, such as glucagon-like peptide-1 receptor agonists and sodium–glucose co-transporter-2 inhibitors, which have been shown to reduce body weight and improve cardiovascular outcomes in these patients. Available evidence suggests that these drug classes can indeed afford a clinically meaningful BP decrease and, potentially, reduce the treatment burden. In conclusion, even though the rates of uncontrolled hypertension remain high, several novel therapeutic options are in the offing. As these emerging treatments will compound with many already available agents, future efforts should be directed at better phenotyping patients to tailor the most suitable approach for each one.

Hypertension Rounds: Successful treatment with evocalcet for resistant hypertension induced by asymptomatic primary hyperparathyroidism.

Hypertension Rounds: Successful treatment with evocalcet for resistant hypertension induced by asymptomatic primary hyperparathyroidism.

The Journey of Resistant Hypertension: From the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure to American Heart Association/American College of Cardiology Guidelines

The Journey of Resistant Hypertension: From the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure to American Heart Association/American College of Cardiology Guidelines