AIMS:Radiofrequency (RF) renal denervation (RDN) safely lowers office and 24-h blood pressure (BP). This meta-analysis examined the long-term durability of RF RDN based on randomized trials and observational studies. METHODS AND RESULTS:Patients with uncontrolled hypertension undergoing RF RDN using the Symplicity Flex™ or Spyral™ device and a minimum follow-up of 3 years were included. Key outcomes included office and 24-h BP change from baseline as well as changes in anti-hypertensive drugs. A random effects meta-analysis was conducted over 3 years, or the last reported follow-up beyond 3 years. A total of 2212 patients identified among 18 reports were evaluated for BP. The mean duration of follow-up was 4.4 years (range 3-9.4). The long-term reduction in office systolic BP from baseline in 15 reports (n = 2040) was -23.0 mmHg (95% confidence interval: -26.8 to -19.1, P < 0.05) for the random effects model and -20.5 (-21.6 to -19.4) for the fixed effect model. Twenty-four-hour ambulatory systolic BP was available in 11 reports (n = 1018) and decreased significantly by -13.6 mmHg (-16.5 to -10.8, P < 0.05). Fixed effect model results were similar. Diastolic office and 24-h BP paralleled these findings in both models. Nighttime systolic BP also decreased significantly by -14.2 mmHg (-27.6 to -0.8, P < 0.05). The number of prescribed anti-hypertensive drugs and eGFR also decreased. Heart rate remained unchanged through the final follow-up in both models. Safety events were rare, with a mean rate of renal artery complications of 0.14% (0.08-0.20%). CONCLUSION:This meta-analysis comprising 18 studies demonstrated sustained and significant office and ambulatory BP reductions following Symplicity RDN through at least 3 years without an increase in anti-hypertensive medication.

Complement activation is an early event in ischemia–reperfusion injury during ST-elevation myocardial infarction (STEMI) and drives endothelial dysfunction via glycocalyx (eGC) degradation. While downstream fragments such as C5a contribute to vascular injury, the role of the early anaphylatoxin C3a remains unclear. This study delineates the effects of the C3a:C3a-Receptor-axis on endothelial function, cytoskeletal dynamics, and eGC integrity. Sixty-four first-time STEMI patients and sixty-four age- and sex-matched healthy controls were enrolled. Patients were stratified into quartiles based on serum C3a concentrations, and comparisons were performed between the lowest vs. highest quartiles as well as between all STEMI patients vs. controls. Inflammatory and glycocalyx parameters were assessed via ELISA, AFM nanoindentation, and monocyte adhesion assays. NO bioavailability was measured chemiluminescence-based. C3a-receptor-antagonists (SB290157 and JR14a), C5a-Receptor1-antagonism (PMX53), as well as Rac1-Inhibition (NSC23766) were used to verify pathway specificity and downstream signaling involvement. High C3a levels were associated with marked endothelial injury: eGC height was reduced (− 44

Blood pressure (BP) control often remains suboptimal despite patients receiving multiple antihypertensives. Recent clinical trials of novel antihypertensives have included patients with hypertension receiving ≥ 2 antihypertensives; however, evidence of hypertension prevalence, patient characteristics, and adverse outcomes risk in this population are limited. This study aimed to assess the prevalence of uncontrolled (uHTN) and controlled hypertension (cHTN) in patients receiving ≥ 2 antihypertensives and to describe patient characteristics and adverse outcomes risk. EnligHTN is a multinational, observational, longitudinal, cohort study of adults with hypertension. Data from 2018 to 2023 were extracted from electronic medical records and claims data sources from the US, UK, Spain, Germany, and Israel. Adults with a hypertension diagnosis after 2018 and a BP measurement after receiving ≥ 2 antihypertensives for ≥ 30 days (index date) were included. uHTN was defined based on index BP according to national guidelines (US: ≥ 130/80 mmHg; other countries: ≥ 140/90 mmHg). Data were summarized by country. Overall, data from 340,000 patients were included. Across countries, mean age of patients was 57‒70 years, 50–63

Hypertension (HTN) and in particular, uncontrolled and resistant hypertension, is common in patients with chronic kidney disease (CKD), yet large-scale data on the characteristics of patients with CKD and inadequately controlled HTN are sparse. This study aims to analyze and compare the clinical profiles of patients with CKD who exhibit inadequately controlled blood pressure (BP) while on treatment with at least two antihypertensive medications, against those whose BP is well-controlled under similar treatment conditions. The EnligHTN study is an observational database study using data from claims and health registries to assess the burden of inadequately controlled HTN. This analysis included data from IQVIA Ambulatory EMR linked with IQVIA PharMetrics® Plus in US (data from other countries will be added later). A total of 8,397 patients diagnosed with CKD and HTN and treated with ≥2 antihypertensive drugs between 2018–2023 were included. CKD was defined as either ≥2 eGFR measures ≥90 days apart, both <60 mL/min/1.73 m2, or a recorded diagnosis of: CKD; end-stage renal disease; hypertensive CKD; diabetic CKD; glomerular diseases; or renal tubulo-interstitial diseases. Patients were considered inadequately controlled if their first office BP (oBP) measurement was above BP target (130/80 mmHg) while being treated with ≥2 antihypertensive drugs for at least 30 days (index). Patient characteristics at index were summarized by oBP control status. Among patients with CKD treated with ≥2 antihypertensive drugs, 65% had inadequately controlled HTN. Patients with inadequately controlled HTN had a mean oBP of 139/82 mmHg, mean age of 60 (standard deviation (SD): 11) years and 56% were male. Patients with controlled HTN had a mean oBP of 116/69 mmHg, mean age of 62 (SD: 11) years and 54% were male. The average number of antihypertensive drugs was similar in both groups (2.4 vs. 2.5). The most prevalent comorbidities in patients with inadequately controlled and controlled HTN were dyslipidemia (63% and 66%, respectively), obesity (62% and 54%, respectively) and type 2 diabetes (44% and 49%, respectively). A higher proportion of patients whose HTN was controlled were taking sodium-glucose cotransporter 2 inhibitors (8% vs 5%) and statin (52% vs 45%) medications at index, compared to CKD patients with inadequately controlled HTN. Two thirds of the patients with CKD who were treated with at least 2 antihypertensive drugs had inadequately controlled BP. Comorbidities were commonly present in both those with and without BP at target level. This indicates a significant burden of uncontrolled BP in patients with CKD and comorbid HTN.

Die arterielle Hypertonie ist weltweit weiterhin einer der häufigsten Risikofaktoren für Morbidität und Sterblichkeit. Für eine effektive kardiovaskuläre Prävention ist daher die kontinuierliche Verbesserung des klinischen Managements der arteriellen Hypertonie notwendig. Den 2024 Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) für das Management des erhöhten Blutdruckes und der Hypertonie kommt hierbei eine besondere Bedeutung zu. In den neuen Leitlinien wurde die Bedeutung der häuslichen Blutdruckmessung unter standardisierten Bedingungen für Diagnostik und Therapiekontrolle weiter gestärkt. Es wurde eine neue strengere Blutdruckklassifikation eingeführt mit neuen Kategorien für „nicht erhöhten“ Blutdruck (< 120/70 mm Hg) und „erhöhten“ Blutdruck (120/70–139/89 mm Hg). In der Kategorie des „erhöhten“ Blutdruckes soll eine Therapieentscheidung, basierend auf dem kardiovaskulären Gesamtrisiko, erfolgen. Neue Empfehlungen zu Lebensstilinterventionen umfassen neben dem bekannten aeroben Bewegungstraining jetzt auch Empfehlungen für ein dynamisches oder isometrisches Widerstandstraining, sowie zur Kaliumzufuhr und Zuckerreduktion. Die medikamentöse Therapie soll vorzugsweise in Kombinationstherapie als Single-Pill-Kombination erfolgen. Hierbei wird zu Beginn der Therapie die Verwendung von niedrig dosierten Zwei- bzw. Dreifachkombinationen empfohlen. Die renale Denervierung kann zur Blutdrucksenkung bei Patienten mit therapieresistenter Hypertonie erwogen werden, wenn die Behandlung in einem spezialisierten Zentrum durchgeführt wird. In diesem Kommentar werden die wesentlichen Neuerungen der Leitlinien kompakt zusammengefasst, kritisch beleuchtet, und deren praktische Umsetzung im Kontext des deutschen Gesundheitswesens wird diskutiert.

Our aim was a sex-specific analysis to characterize the phenotype for women with resistant hypertension (rHTN), an understudied population, referred for renal denervation (RDN) from the Global SYMPLICITY Registry DEFINE (N = 3332 patients). For this analysis, 2502 patients with uncontrolled hypertension (office systolic blood pressure (SBP) ≥140 mmHg, ≥3 antihypertensive drugs) were referred for RDN. Age at baseline was 18–88 years for men and 21–89 years for women. We used propensity score matching to account for demographic differences at baseline identified by multivariate regression analysis. Changes in BP, outcomes (all-cause death, cardiac death, stroke, myocardial infarction), and quality of life (QoL) after 36 months were assessed. Women had fewer comorbidities at baseline but had higher BP and worse QoL, anxiety, and depression compared to men. After propensity matching to minimize bias, BP changes were comparable by sex, and BP was significantly reduced from baseline following RDN. Women ≥55 years of age with resistant hypertension had a greater reduction in BP compared with women <55 years. At 36 months after RDN, there was a significant 12% reduction in anxiety/depression compared to baseline for women with resistant hypertension. When baseline office SBP was in the highest tertile (>178 mmHg), cardiac death was more prevalent in women (6.1%) than men (1.7%). Our sex-stratified analysis of the global registry allowed a longitudinal assessment, providing important insights into the phenotype of resistant hypertension in women. We identified sex-specific differences that highlight the need for early detection and management of hypertension in women.

Background: Despite the availability of various treatment options, uncontrolled hypertension (HTN) remains prevalent, significantly increasing risks of cardiorenal disease and mortality, and underscores the urgency of greater engagement from healthcare providers and burden for healthcare systems. We aimed to characterize healthcare resource utilization (HCRU) among patients with uncontrolled HTN across several countries. Methods: In this multi-country database cohort study, data from Telotròn (Spain (ESP)), IQVIA Ambulatory EMR linked with IQVIA PharMetrics® Plus claims (US), Clinical Practice Research Datalink (UK) and Meuhedet (Israel (ISR)) from 2018 to 2023 were used, with data anticipated from additional countries. Patients were included if they had a diagnosis of HTN and their first blood pressure (BP) measurement; were being treated with ≥2 antihypertensive medications for ≥30 days (index date) and were above the BP target (US: ≥130/80 mmHg; UK, ESP, and ISR: ≥140/90 mmHg), indicating uncontrolled HTN. Patient characteristics and all-cause HCRU were analyzed descriptively. Results: A total of 199,167 patients with uncontrolled HTN were included (Table 1). The mean age ranged from 56.9 – 67.2 years and 40.6% – 46.9% were female. Mean age was the highest in ISR (67.2 years; standard deviation (SD) 11.9) and lowest in the US (56.9 years; SD 11.5). General practice visit rates were highest in ISR, followed by the UK, ESP and the US. The number of outpatient specialist visits ranged from 2.31 (95%CI 2.28, 2.35) in ESP to 7.11 (6.92, 7.30) per person per year (PPPY) in ISR. The number of hospital admissions ranged between 0.56 (95%CI; 0.53, 0.59) in ESP and 1.52 in the UK (95%CI; 1.51, 1.53) PPPY with mean number of days hospitalized between 3.58 (95%CI; 3.57, 3.59) and 8.85 (95%CI; 8.63, 9.07) PPPY. Lastly, the number of emergency department visits varied the most between the US (1.20 (95%CI; 1.15, 1.26)) and ISR (0.48 (95%CI; 0.46, 0.50)). Conclusions: Uncontrolled HTN is associated with a substantial burden on healthcare resources. Patterns of HCRU varied across countries, likely reflecting differences in healthcare systems, clinical practice, definitions of uncontrolled HTN and patient demographics.

Although metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, has become the most common chronic liver disorder, its complex pathophysiology has not been fully elucidated up to date. A correlation between elevated sympathetic activation and MASLD has been highlighted in recent preclinical and clinical studies. Furthermore, increased sympathetic activity has been associated with the main mechanisms involved in MASLD, such as lipid accumulation in the liver, insulin resistance, and metabolic dysregulation, while it has been also correlated with the progression of MASLD, leading to liver fibrosis. Preclinical studies demonstrated that therapies which ameliorate the activation of the sympathetic nervous system, such as renal and liver sympathetic denervation, reduce hepatic insulin resistance, decrease hepatic glucose production, and reverse hepatic steatosis in high-fat-diet models. However, data from clinical trials regarding the effect of renal denervation on metabolic parameters are conflicting, since several trials reported a favorable effect, while other trials stated no significant difference, with the profound limitation of the lack of originally designed denervation trials in this setting. Thus, a thorough review of the role of the sympathetic nervous system in the pathophysiology of MASLD, as well as the results of recent sympathetic denervation studies and trials regarding metabolic regulation and MASLD treatment would be of great importance.

Background: About 50% of patients are nonadherent to antihypertensive medications (AHM), impairing blood pressure (BP) management. The RADIANCE-HTN TRIO trial screened patients with resistant hypertension by first placing them on a fixed-dose combination triple pill (ARB+amlodipine+HCTZ). Ambulatory BP measurement 4 weeks later found 43% had controlled BP and were thus ineligible for enrollment. A total of 136 patients with uncontrolled BP were randomized to ultrasound renal denervation (uRDN) or sham-control. This analysis assessed adherence characteristics among patients in the trial. Method: TRIO patients consented to have chemical adherence testing that detected AHM or their metabolites in spot urine samples at baseline, 2 and 6 months. Full adherence (FA) was defined by all prescribed drugs detected in the sample. Results: Adherence data were available at any timepoint for 129 and all timepoints for 91 patients. Among patients with data at all timepoints, 66% (60/91) were FA and 34% (31/91) were partially- or fully nonadherent (PA/NA) to any of their prescribed medications. Adherence rates did not differ between treatment groups or geographies. Women were less likely to be FA (p<0.001) (Table). PA/NA patients had higher rates of peripheral and cerebrovascular disease, and higher BP before and after triple pill. Adherence to triple pill was 81% at baseline, 85% at 2-months, and 83% at 6-months. Medications were titrated after 2-months. At 6-months, adherence to additional medication classes prescribed was: aldosterone antagonist 71%, beta blockers 62%, and centrally-acting alpha-2 agonists 60%. Conclusions: The stringent TRIO study design uncovered significant medication nonadherence that translated into a high rate of apparent resistant HTN. It also showed high adherence to a fixed-dose triple pill. One third of enrolled patients were not fully adherent to medications, and these patients had higher BP and higher rates of vascular disease. Understanding clinical features associated with medication adherence may improve hypertension management.

Radiofrequency renal denervation (RF RDN) safely reduces office and 24-hour blood pressure (BP) in patients with uncontrolled hypertension. We performed a meta-analysis to assess long-term durability of RF RDN to at least 3 years based on published reports of outcomes including the Symplicity Flex and Spyral catheters, inclusive of the largest RF RDN registry to date: Global Symplicity Registry (GSR) DEFINE. A PRISMA guided search was performed to identify clinical reports of RF RDN using the Symplicity Flex or Spyral device in patients with uncontrolled hypertension with a minimum of 3 years follow up. Data from the GSR DEFINE registry were updated from the trial database. Key outcomes included office and 24-hour BP change from baseline as well as changes in antihypertensive drugs. A random effects meta-analysis was conducted at 3 years, or the last reported follow-up beyond 3 years and effect size was weighted by the inverse variance. Following screening of 217 records, 18 reports were included in the meta-analysis. Mean time of follow up was 4.3 years (range: 3-9.4). The long-term reduction in office systolic (S)BP from baseline in 13 reports (n=1779) was -22.8 mmHg (95%CI: -27.5, -18.1 p<0.001; Figure). 24-hour SBP was available in 10 reports (n=912) and also decreased significantly (-13.3 mmHg; 95%CI: -17.4, -9.2 p<0.001). Diastolic BP data and safety event rates will also be reported. Number of antihypertensive drugs changed by +0.29 (95%: -0.2, 0.8) through final follow-up. Meta-analysis of 18 reports indicates substantial BP reduction following RF RDN sustained to at least 3 years.