Ambulatory Systolic Blood Pressure Research Articles

Ambulatory blood pressure in patients with rheumatoid arthritis: association with immune activation.

The prevalence of hypertension, a major cardiovascular risk factor, is increased in patients with rheumatoid arthritis (RA) and may be driven by immune activation. The purpose of this study was to determine if ambulatory 24-hour blood pressure (BP) is elevated in RA versus control participants and associated with immune activation. We conducted a cross-sectional study of 46 patients with RA and 23 control participants. Participants wore an ambulatory BP monitor which obtained diurnal BP every 15-30 minutes and nocturnal BP every 30 minutes. Inflammatory mediators in plasma were measured using an inflammation proteomics panel. Differences in BP measurements were assessed by Mann-Whitney U, and association with inflammatory mediators was assessed by Spearman correlation. Patients with RA and control participants had similar office BP, but ambulatory systolic BP measurements: 24-hour (median RA =121 mmHg versus control =116 mmHg, P=0.007), diurnal (RA =128 mmHg versus control =120 mmHg, P=0.003), and nocturnal (RA =112 mmHg versus control =103 mmHg, P=0.002) were higher in patients with RA. Patients with RA also had higher nocturnal diastolic BP (RA =63 mmHg versus control =57 mmHg, P=0.02), but other diastolic BP measurements were similar. Nocturnal BP dipping was less in RA (12%) compared to control participants (16%, P=0.02). In RA, higher 24-hour and nocturnal systolic BPs and less nocturnal dipping were strongly correlated with a wide range of inflammatory mediators. Despite similar office measurements, 24-hour and nocturnal systolic BP measurements were higher in RA than control participants and were strongly associated with inflammation.

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Safety and efficacy of once-daily dexfadrostat phosphate in patients with primary aldosteronism: a randomised, parallel group, multicentre, phase 2 trial

Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that targetaldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA. This multi-centre, randomised, phase 2 trial was conducted between November 2019 and May 2022 (NCT04007406; EudraCT code 2019-000919-85). Adults with PA and an office systolic blood pressure of 145-190mmHg were included. After a 2-week single-blind placebo run-in period, participants were randomised 1:1:1 to receive oral dexfadrostat phosphate 4, 8, or 12mg once daily for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo withdrawal period. Randomisation was conducted centrally and stratified by centre and sex. At the beginning and end of the treatment period, 24h ambulatory systolic blood pressure (aSBP) was recorded. Blood samples were taken every 2 weeks. Primary endpoints were the change in aldosterone-to-renin ratio (ARR) and mean 24h aSBP from baseline to the end of the treatment period in the combined dose group of all participants receiving any dose of dexfadrostat phosphate. Safety endpoints were the occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events over the entire study in all randomised participants who received at least one dose of dexfadrostat phosphate. In total, 35 participants received dexfadrostat phosphate and all participants completed the study. Twenty-six participants (74.3%) were male, the mean age was 51.9 years (SD 8.7), and most were White (n=32, 91.4%). The median ARR and the mean 24h aSBP significantly decreased from the beginning to the end of the treatment period in the combined dose group (ARR: 15.3 vs 0.6, least-squares mean [LSM] change in log-normal values-2.5, p<0.0001; aSBP: 142.6 vs 131.9mmHg, LSM change-10.7mmHg, p<0.0001). There were no safety concerns; all TEAEs were mild or moderate and there were no serious TEAEs. Dexfadrostat phosphate corrected the ARR and aSBP and was well tolerated in patients with PA, demonstrating the benefit of pharmacologically targeting the source of hyperaldosteronism. DAMIAN Pharma AG.

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage

Introduction Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. Design and methods Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. Results Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05–2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34–0.95), p = 0.03). Conclusions None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

Design and rationale of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study: A cluster randomized controlled trial for hypertension management in primary care

BackgroundHypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multi-faceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. Materials and MethodsThe CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. 41 primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1600 patients aged 35-80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants’ characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12-month. DiscussionThe CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. Trial registrationhttps://www.clinicaltrials.gov, NCT05605418

A novel, proof-of-concept radiofrequency renal denervation strategy to improve procedural efficiency: 12-month results from the SPYRAL DYSTAL pilot study

BackgroundCatheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure. MethodsThe SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150–180/>90 mmHg and with an ambulatory systolic BP of 140–170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months. ResultsThe SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were −9.0 and −1.4 mmHg at 3 months, −20.3 and −13.9 mmHg at 6 months, and −20.3 and −16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported. ConclusionIn this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study.

Prognostic impact of hypertension grading

BackgroundMost Hypertension Guidelines grade hypertension according to various cut-off values. We sought to investigate the prognostic impact of Grades 1 (140–159 and/or 90–99 mmHg), 2 (160–179 and/or 100–109 mmHg) and 3 (≥180 and/or ≥110 mmHg). MethodsWe followed for an average of 10 years a cohort of 3,150 initially untreated hypertensive patients (mean age 50 years, 44 % women) with no previous cardiovascular disease at entry. All patients underwent diagnostic tests including 24-hour ambulatory blood pressure (BP) monitoring. ResultsAt entry, average clinic BP was 156/97 mmHg and average 24-hour BP was 137/87 mmHg. During follow-up, 314 patients experienced a first major cardiovascular event (composite of non-fatal myocardial infarction or stroke, cardiovascular death, or hospitalization for heart failure). Event rate was not formally dissimilar between Grade 1 and Grade 2 (0.73 vs 0.95 per 100 patient-years, respectively; p = 0.06). It was higher in Grade 3 (1.93 per 100 patient-years; p < 0.01 vs Grade 1 and Grade 2). After adjustment for a robust set of covariables, the hazard ratio was not dissimilar between Grade 1 and Grade 2 (p = 0.27), and higher in Grade 3 than in Grade 1 (p < 0.01), but the excess risk in Grade 3 was no longer significant (hazard ratio: 1.25, 95 % CI 0.87–1.78; p = 0.22) after adjustment for 24-hour ambulatory systolic BP. ConclusionsWe were unable to find a significant difference in the relative hazard of cardiovascular events tied to hypertension Grades 1 and 2. Conversely, Grade 3 (clinic BP ≥180/110 mmHg) portends a higher cardiovascular risk, which is associated with higher levels of 24-hour ambulatory BP.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in eGFR across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Abstract P202: The Effects of Sodium (Na) Reduction and the Dash Diet on Ambulatory Blood Pressure in Black and Non-Black Individuals: Results From the DASH-Na Trial

Background: Black individuals compared to White individuals tend to have higher nighttime BP. It has been hypothesized that lifestyle changes will reduce and potentially eliminate this disparity. Objectives: To determine the effect of reduced Na and the DASH diet, alone and combined, on ambulatory blood pressure (ABP) in Blacks (B) and Non-Blacks (NB, mostly white). Methods: Participants (n=335, 58% B) were randomly assigned to eat a control diet or the DASH diet. On their assigned diet, each participant had three, randomly ordered, 30d feeding periods with different Na levels (low, medium, and high). ABP was measured at the end of each period. Results: Before feeding, mean office SBP was similar in B and NB (135.5 and 134.5 mmHg, respectively). On the reference diet (control diet with high Na), daytime and nighttime SBP were higher in B than NB adults (Table). Compared to the ref diet, reducing Na and consuming the DASH diet, alone and combined, substantially lowered daytime and nighttime systolic ABP in Black and Non-Black individuals. The DASH diet combined with low Na reduced daytime SBP in B and NB with no significant B-NB difference, i.e. no racial disparity in daytime SBP; otherwise, B-NB differences were present in daytime SBP for Na reduction alone and DASH diet alone. For nighttime SBP, there was a consistent pattern such that Na reduction alone, DASH diet alone, and the DASH diet with low Na reduced nighttime SBP in B and NB, but in each case, B had significantly higher nighttime SBP levels than NB. For DBP, Na reduction alone, DASH diet alone, and combined DASH with low Na reduced daytime and nighttime BP in B and NB, but significant B-NB differences persisted (data not shown). Conclusions: Reducing dietary Na and consuming the DASH diet, alone and combined, substantially lowered ABP in Black and Non-Black individuals. However, racial disparities in ABP mostly persisted. These results highlight the importance of implementing both the DASH diet and Na reduction as a means to reduce BP throughout the day, regardless of racial background.

Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce. This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension. This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years. Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23mmHg and 153 ± 16mmHg, respectively. After 10years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17mmHg (P < 0.001) and 14 ± 23mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up. Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10years in patients with resistant hypertension.

Cardio-Ankle Vascular Index as a Marker of Left Ventricular Hypertrophy in Treated Hypertensives: Findings From the Pamela Study.

Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study. The study included 239 out of 562 participants who attended the second and third surveys of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP), blood examinations, echocardiography, and CAVI measurements. In the whole study sample (age 69 ± 9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index, and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with the LVM index (P < 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6 ± 2.8 vs. 9.2 ± 1.8 m/s P < 0.001), larger left atrial diameter, and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/s was the best cut-off for prediction of LVH in the whole sample. Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH.

Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication.

A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail. Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes. Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P < 0.001). The reduction in BP load was also more pronounced with the quadpill. A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.

The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study

Abstract Background Hypertension is associated with increased morbidity and mortality in hemodialysis patients. Existing recommendations suggest reduction of sodium load, but the effect of dialysate sodium on blood pressure (BP) is not fully elucidated. The aim of the present study is to investigate the effect of different dialysate sodium concentrations on 72-h ambulatory BP in hemodialysis patients. Methods This prospective study included patients on standard thrice-weekly hemodialysis. All patients initially underwent six sessions with dialysate sodium concentration of 137meq/L, followed consecutively by another six sessions with dialysate sodium of 139meq/L and, finally, six sessions with dialysate sodium of 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM was performed over the long interdialytic interval to evaluate ambulatory systolic and diastolic BP (SBP and DBP) during the overall 72-h, different 24-h, day-time and night-time periods. Results 25 patients were included in the final analysis. A significant increase in the mean 72-h SBP was observed with higher dialysate sodium concentrations (124.8 ± 16.6 mmHg with 137meq/L vs 126.3 ± 17.5 mmHg with 139meq/L vs 132.3 ± 19.31 mmHg with 141meq/L, P = 0.002). Similar differences were noted for DBP; 72-h DBP was significantly higher with increasing dialysate sodium concentrations (75.1 ± 11.3 mmHg with 137meq/L vs 76.3 ± 13.7 mmHg with 139meq/L vs 79.5 ± 13.9 mmHg with 141meq/L dialysate sodium, P = 0.01). Ambulatory BP during the different 24-h intervals, day-time and night-time periods was also progressively increasing with increasing dialysate sodium concentration. Conclusions This pilot study showed a progressive increase in ambulatory BP with higher dialysate sodium concentrations. These findings support that lower dialysate sodium concentration may help towards better BP control in hemodialysis patients.

RNA Interference With Zilebesiran for Mild to Moderate Hypertension

Angiotensinogen is the most upstream precursor of the renin-angiotensin-aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic, targets hepatic angiotensinogen synthesis. To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens. This phase 2, randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries. Screening initiation occurred in July 2021 and the last patient visit of the 6-month study occurred in June 2023. Adults with mild to moderate hypertension, defined as daytime mean ambulatory systolic BP (SBP) of 135 to 160 mm Hg following antihypertensive washout, were randomized. Randomization to 1 of 4 subcutaneous zilebesiran regimens (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo (once every 3 months) for 6 months. The primary end point was between-group difference in least-squares mean (LSM) change from baseline to month 3 in 24-hour mean ambulatory SBP. Of 394 randomized patients, 377 (302 receiving zilebesiran and 75 receiving placebo) comprised the full analysis set (93 Black patients [24.7%]; 167 [44.3%] women; mean [SD] age, 57 [11] years). At 3 months, 24-hour mean ambulatory SBP changes from baseline were -7.3 mm Hg (95% CI, -10.3 to -4.4) with zilebesiran, 150 mg, once every 6 months; -10.0 mm Hg (95% CI, -12.0 to -7.9) with zilebesiran, 300 mg, once every 3 months or every 6 months; -8.9 mm Hg (95% CI, -11.9 to -6.0) with zilebesiran, 600 mg, once every 6 months; and 6.8 mm Hg (95% CI, 3.6-9.9) with placebo. LSM differences vs placebo in change from baseline to month 3 were -14.1 mm Hg (95% CI, -19.2 to -9.0; P < .001) with zilebesiran, 150 mg, once every 6 months; -16.7 mm Hg (95% CI, -21.2 to -12.3; P < .001) with zilebesiran, 300 mg, once every 3 months or every 6 months; and -15.7 mm Hg (95% CI, -20.8 to -10.6; P < .001) with zilebesiran, 600 mg, once every 6 months. Over 6 months, 60.9% of patients receiving zilebesiran had adverse events vs 50.7% patients receiving placebo and 3.6% had serious adverse events vs 6.7% receiving placebo. Nonserious drug-related adverse events occurred in 16.9% of zilebesiran-treated patients (principally injection site reactions and mild hyperkalemia) and 8.0% of placebo-treated patients. In adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3. ClinicalTrials.gov Identifier: NCT04936035.

Effect of Tai Chi vs Aerobic Exercise on Blood Pressure in Patients With Prehypertension

Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial

BackgroundCurrent hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients.MethodsIn a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis.ResultsIn the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was − 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and − 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of − 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were − 1.47 (p = 0.18) in 24-h diastolic BP, − 2.86 (p = 0.13) and − 2.74 (p = 0.03) in daytime systolic and diastolic BP, and − 0.45 (p = 0.82) and − 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04).ConclusionsThe amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough.Trial registrationClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

The Association between Urinary Sodium-Potassium Ratio, Kidney Function, and Blood Pressure in a Cohort from the General Population.

Subclinical kidney dysfunction may contribute to salt-sensitive hypertension. We assessed the association between the urinary sodium-potassium ratio (Na/K ratio) and blood pressure (BP) in a general population cohort without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension. We investigated whether any such association was mediated by the kidney function markers measured glomerular filtration rate (mGFR), urinary albumin-creatinine ratio (ACR), and urinary epidermal growth factor-creatinine ratio (EGF-Cr). The Tromsø Study is a population-based study of inhabitants of the municipality of Tromsø, Northern Norway. Participants aged 50-62 years, without diabetes, chronic kidney disease, or cardiovascular disease, were invited to the substudy Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6; 2007-09). For the present study, we excluded participants reporting the use of 1 or more antihypertensive agents, leaving 1,311 RENIS-T6 participants for a cross-sectional analysis. We measured office BP, 24-h ambulatory blood pressure (ABP), and mGFR using iohexol clearance. Na/K ratio, ACR, and EGF-Cr were measured in morning urine samples. Urinary Na/K ratio was significantly associated with systolic office BP and ABP independently of cardiovascular risk factors and kidney function markers. A one-standard deviation unit increase in the Na/K ratio was associated with increased systolic ABP by 1.0 (0.3-1.6) mm Hg. Urinary Na/K ratio showed a stronger association with office BP than ABP. EGF-Cr, ACR, and mGFR did not mediate the relationship between urinary Na/K ratio and systolic BP. In a representative sample of the middle-aged North-European population without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension, there was a consistent association between urinary Na/K ratio and BP. The association with BP was not mediated through kidney function measures, suggesting a relationship between a diet with high sodium and low potassium and higher BP regardless of kidney function.

Influence of the Antimycotic Drug Itraconazole on Plasma Cortisol Levels and Blood Pressure in a Patient with Burnout Syndrome

Burnout is a syndrome that is increasingly common nowadays. It is associated with reduced work efficiency and chronic exhaustion. The main cause of burnout is continuous stress at work and not enough rest. The main system involved in the pathogenesis of burnout is the hypothalamic–pituitary–adrenocortical axis with the final substrate of the glucocorticoid hormone cortisol. Therefore, in patients with burnout syndrome, the morning plasma cortisol levels are elevated, but there is no significant change in its evening values. This correlates with an increase in blood pressure, weight gain, muscle weakness, low immunity, etc. The following case report is about the unusual effect of the antifungal drug itraconazole on the circadian rhythm of the plasma cortisol levels, as well as on the blood pressure in patient with burnout syndrome. One month of peroral application of 100 mg itraconazole every day reduces the morning plasma cortisol levels to the greatest extent (by approximately 37%) rather than the evening cortisol levels (by circa 17.5%). The decrease in the mean ambulatory systolic and diastolic blood pressure is also not uniform (it is stronger in diastolic – 27% than in systolic – 17%).

Effect of vitamin B2, vitamin C, vitamin D, vitamin E and folic acid in adults with essential hypertension: a systematic review and network meta-analysis

ObjectivesThe objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.DesignSystematic review and network...