Changes In Systolic Blood Pressure Research Articles

Rationale and Design of a Randomized, Open-Label, Parallel-Group Study of Esaxerenone Versus Angiotensin Receptor Blockers in Older Patients With Uncontrolled Hypertension on Calcium Channel Blocker Monotherapy (ESCORT-HT).

Angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are commonly prescribed as first- and second-line treatments for older Japanese patients with hypertension. However, due to age-related decline in renin activity, the effectiveness of ARBs may decrease. This highlights the need for other antihypertensive agents to be used in combination with CCBs to replace ARBs for more effective blood pressure (BP) control. The ESCORT-HT study is a multicenter, randomized, controlled, open-label, parallel-group study with a 4-week run-in period and 12-week treatment period. This study aims to evaluate the efficacy of esaxerenone as a second-line treatment for hypertension and to determine whether its BP-lowering effect is noninferior to that of ARBs in older patients with uncontrolled hypertension on CCB monotherapy. The safety profiles of esaxerenone and ARBs will also be evaluated. Patients will be randomly assigned in a 1:1 ratio to receive either esaxerenone or an ARB. The primary efficacy endpoint will be the change from baseline in morning home systolic BP at the end of the treatment period. The BP-lowering effect of esaxerenone will be considered noninferior to that of ARBs if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic BP change between esaxerenone and ARB is <3.8mmHg, and will be considered superior if the upper limit of the two-sided 95% CI is <0. The findings may elucidate the possible benefits of earlier use of mineralocorticoid receptor blockers in combination with CCBs in older patients with essential hypertension.

Self-measurement of blood pressure at home using a cuff device for change in blood pressure levels: systematic review and meta-analysis.

The effect of self-measurement of blood pressure (BP) at home (home BP measurement, HBPM) has been evaluated over the past decade. This meta-analysis included the latest studies to determine whether HBPM reduced BP (PROSPERO ID: CRD42023442225). PubMed, Cochrane Library Database, and IchuShi-Web were searched for randomized controlled trials after the year 2000 which demonstrated the effect of HBPM on BP change compared with usual care (UC). Overall, 65 articles (n = 21,053; 63 based on patients with hypertension) were included. The systolic/diastolic BP reduction was significantly greater in the HBPM than in the UC group by 3.27/1.61 mmHg (95% confidence intervals: 2.40-4.15/1.14-2.07) at the end of the intervention, and I2 values ≥ 46.7% suggested moderate-to-high heterogeneity. The funnel plots exhibited no notable publication bias (Egger's test p ≥ 0.16). HBPM with co-interventions (such as telemonitoring) showed a stronger BP-lowering effect than without co-interventions whilethe effect of HBPM on BP change remained significant in the absence of co-interventions. HBPM was not associated with systolic BP changes when we combined the four studies that used a wrist cuff device for HBPM. The number of antihypertensive medications increased by 0.17 medications in the HBPM group compared with that in the UC group. There were no significant differences in body mass index changes or risk of severe adverse outcomes between the groups. Our results demonstrated a beneficial effect of HBPM in reducing BP, particularly when used in conjunction with telemonitoring or additional medical support and when employing upper-arm cuff devices.

Selecting Transfemoral Access or Upper Extremity Access for Renal Denervation Based on Vascular Morphology: Long‐term Results

ABSTRACTTo evaluate the long‐term efficacy and safety of transfemoral access (TFA) versus upper extremity access (UEA) for renal denervation (RDN) based on vascular morphology. This study retrospectively enrolled patients with resistant hypertension who underwent RDN treatment via TFA and UEA (brachial, radial, and ulnar artery) at the Fuwai Hospital between February 2012 and November 2019. Follow‐up was conducted at 6 months, 1 year, and 3 years after RDN, and the last visit was June 2023. A total of 85 patients were enrolled, 58 (68.2%) of them were treated via TFA, and 27 patients (31.8%) via UEA. The fluoroscopy time was less in the TFA group (12.2 ± 5.7 min vs. 15.2 ± 7.2 min; p = 0.038). The procedure time (TFA group: 40.8 ± 14.9 min vs. UEA group: 38.6 ± 11.6 min; p = 0.506), contrast volume (TFA group: 78.2 ± 25.9 mL vs. UEA group: 91.9 ± 39.7 mL; p = 0.061) were similar between two groups, without procedure‐related complications. Fifty‐eight participants completed the last visit with a 3–12 year of follow‐up (9.5 ± 1.3 years). Compared with baseline, there were no significant differences in the change of office systolic blood pressure (−12.6 ± 21.6 mmHg vs. −13.1 ± 22.8 mmHg; p = 0.933), 24‐h mean systolic blood pressure (−11.9 ± 14.2 mmHg vs. −11.3 ± 15.3 mmHg; p = 0.899), the number of antihypertensive drugs, and renal function between two groups. There were three adverse events in the TFA group (3 of 58 patients, 5.2%) versus one (1 of 27 patients, 3.7%) in the UEA group, without a significant difference between the two groups. The study showed RDN via UEA was feasible using a special‐designed catheter, particularly in patients with illegal vascular morphology via TFA.

High-intensity interval training is an effective exercise mode to maintain normal blood pressure during pregnancy: a randomized control trial

Pregnant women are more susceptible to high blood pressure (BP) than the general adult population; therefore, all means of preventing this condition should be considered. High-intensity interval training (HIIT) is effective in this regard in the general population, but there is a lack of evidence of its effectiveness during pregnancy. This study aimed to compare an 8-week HIIT program to self-performed moderate-to-vigorous physical activity among pregnant women by evaluating changes in BP after a maximal progressive cardiorespiratory exercise test (CPET) performed at pre-intervention and post-intervention time points. A total of 54 Caucasian women in uncomplicated, singleton pregnancies (age 32 ± 4 years, 22 ± 4 weeks of gestation; M ± SD) with normal BP values completed the interventions. The experimental (HIIT) group (n = 34) completed an online supervised HIIT program consisting of three sessions per week and supplemented by an educational class once per week. Participants in the education (EDU) group (n = 20) attended an educational class once per week and were encouraged to perform moderate-to-vigorous physical activity (PA) on their own. Pre- and post-intervention, all women underwent a CPET on a cycle ergometer with a respiratory gas analyzer. On the day of the CPET, maternal systolic and diastolic BP (mmHg) was measured at rest (before the CPET) and approximately 60 min after the CPET using an electronic BP monitor. Identical CPET and BP measurement protocols were employed for both the HIIT and EDU groups at the pre- and post-intervention time points. Pre-intervention, the HIIT and EDU groups both showed a decrease in systolic and diastolic BP after the CPET, though only the change in systolic BP was statistically significant (HIIT group: p = 0.01; EDU group: p = 0.001). Post-intervention, there were no significant differences in either group between resting and post-CPET BP. There were significant post-intervention differences in VO2peak (p < 0.001) and HRmax (p = 0.002) between the HIIT and EDU groups. From pre- to post-intervention, the EDU and HIIT groups both showed decreases in resting systolic or diastolic BP; there was a significant difference in systolic BP in the EDU group (p = 0.005) and a significant difference in diastolic BP in the HIIT group (p = 0.03). Both groups maintained normal BP values throughout the experiment. However, HIIT, in addition to maintaining normotension, improved cardiorespiratory fitness in pregnant women. It seems that both supervised HIIT and self-performed moderate-to-vigorous PA can be recommended as strategies to prevent BP disorders during pregnancy. More studies are needed to confirm our findings.Trial registration The full study protocol was registered in ClinicalTrials.gov (NCT05009433).

Antihypertensive effects and changes in extracellular water content by mineralocorticoid receptor antagonists in patients with primary aldosteronism.

In primary aldosteronism (PA), non-suppressible excessive aldosterone secretion due to dietary salt intake significantly contributes to hypertension and cardiovascular complications. Blocking the overactivation of mineralocorticoid receptors (MRs) with mineralocorticoid receptor antagonists (MRAs) is a cornerstone for the medical treatment of PA. However, the role of MRAs in controlling hypertension remains unclear. This study aimed to explore the relationship between changes in body composition parameters (determined by bioelectrical impedance analysis), blood pressure (BP) levels, serum potassium (K+) levels and Study 36-Item Short-Form Health Survey (SF-36) scores after MRA treatment in 50 patients with PA. Treatment with MRAs significantly decreased the systolic BP (SBP) and diastolic BP (DBP) levels and extracellular water (ECW) volume, while it increased the serum K+ levels, active renin concentrations (ARCs), and scores on several SF-36-based quality of life (QOL) subscales. ECW change (ΔECW) and serum K+ change were not significantly associated with changes in SBP and DBP levels. ΔECW showed a significant inverse correlation with ΔARC, suggesting that ARC increases with decreasing ECW volume due to renal MR activity blockade and that ARC is a highly sensitive indicator of ECW volume. In the stratified analysis of patients with PA, ECW volume was significantly decreased in those aged ≥60 years and those with a body mass index of ≥25 kg/m2. In conclusion, MRA treatment showed antihypertensive, biochemical, and QOL improvement effects in patients with PA. The antihypertensive effect may not be related to the decrease in ECW volume due to renal MR activity blockade. Evaluation of ECW using BIA in patients with PA treated with MRAs. Abbreviations: ARC, active renin concentration; BIA, bioelectrical impedance analysis; BMI, body mass index; BP, blood pressure; ECW, extracellular water; K+, serum potassium; MRA, mineralocorticoid receptor antagonist; PA, primary aldosteronism; QOL; quality of life; Δ, parameter changes after MRA treatment.

Abstract 4136812: Optimal Pacing for Cerebral Perfusion: Elucidating Relationship Between Resting Pacemaker Heart Rate and Pulse Pressure

Background: Cognitive decline and dementia are significant global health concerns, with hypertension being a major risk factor. Increasingly, the elderly population is receiving pacemakers, and the pacing rates are set as low as 50bpm. Moreover, the relationship between blood pressure (BP) components, particularly diastolic BP (DBP) and pulse pressure (PP), and the risk of cognitive decline or dementia remains complex. The highest risk is observed in patients with low DBP and concurrently increased PP, likely indicating vascular stiffness. To our knowledge, no studies have assessed the programming of pacemakers to increase heart rates to target DBP and PP improving cerebral perfusion. Objectives: In patients with permanent pacemakers, resting heart rate (HR) can be artificially increased, and its consequence on hemodynamics, including PP, can be easily measured. This study aims to investigate the impact of increasing resting HR on PP in patients with poor vascular compliance. Secondary outcomes include evaluating changes in DBP, SBP, and cardiac output, as well as assessing patient tolerance to higher-paced heart rates through recording subjective symptoms. Methods: The study will employ a prospective cross-sectional interventional design. Digital plethysmography will be utilized to measure hemodynamic parameters, including systolic blood pressure (SBP), DBP, PP, and cardiac output, at baseline resting-paced heart rates. Subsequently, the pacemaker resting heart rate will be incrementally increased to a final rate of 100 beats per minute (bpm), with measurements taken 2-5 minutes after each change. Results: Ten out of twenty patients were recruited, with a mean age of 75.3 years old. The median change in PP from baseline HR of 70 to 100 was -8.7% (IQR -18.8 - +2.8, p= 0.114), SBP 4.2% (IQR 0 – 11.9, p=0.059), and DBP 20.1% (IQR 12.9 -23, p=0.005). There were no adverse outcomes and no patient-reported symptoms during higher pacing rates. Conclusion: This study provides the basis for proof of concept. Since an increased HR decreases PP, this will be subsequently tested against improvement in cerebral perfusion by cerebral Doppler studies, and its impact on cognitive function will be tested. This has the potential to change the standard of practice for patients with pacemakers and allow for collaboration across multiple specialties such as neurology, geriatric medicine and cardiology.

Scleroderma Renal Crisis and Musculoskeletal Corticosteroid Injections.

Inflammatory arthritis frequently affects patients with systemic sclerosis (SSc) but musculoskeletal corticosteroid (MSKC) injections are often avoided due to concerns of scleroderma renal crisis (SRC). This study investigated the incidence of SRC following MSKC injections. In a 136-SSc cohort, 46 subjects underwent a total of 330 MSKC injections each receiving a significant dosage of triamcinolone acetonide (mean, 95.2 ± 44.2 mg per injection session). Blood pressure (BP), serum creatinine and glucose, urine protein, and complications were retrospectively reviewed before and after injection. MSKC and control subjects were similar in age (MSKC: 58.9 ± 12.1 vs. 55.5 ± 14.9 years), female (MSKC: 97.8% [45/46] vs. 89.9% [81/90]), antinuclear antibody (MSKC: 71.7% [33/46] vs. 81.1% [73/90]), anti-centromere antibody (MSKC: 47.8% [22/46] vs. 37.8% [34/90]), anti-topoisomerase antibody (MSKC: 26.1% [12/46] vs. 26.7% [24/90]), and anti-RNA polymerase III antibody (MSKC: 17.4.1% [8/46] vs. 24.4% [22/90]) (all p > 0.05). Pre- and post-MSKC demonstrated nonsignificant changes in systolic BP (pre: 127 ± 22 vs. post: 127 ± 21 mm Hg, p = 1.0), diastolic BP (pre: 71 ± 13 vs. post: 71 ± 11 mm Hg, p = 1.0), creatinine (pre: 0.78 ± 0.56 vs. post: 0.76 ± 0.20 mg/dL, p = 0.64), glucose (pre: 100 ± 21 vs. post: 99 ± 24 mg/dL, p = 0.67), and urine protein-creatinine ratio (pre: 0.14 ± 0.12 vs. post: 0.12 ± 0.11 mg/mg, p = 0.41). One case of SRC with mortality occurred in the controls and none in the MSKC group. No infections, hematologic abnormalities, or tendon rupture were noted. MSKC injections in established SSc are generally safe with low incidences of SRC and complications. However, it is still prudent to monitor high-risk individuals and recent-onset SSc post-MSKC injection.

Addressing Hypertension and Diabetes through Community-Engaged Systems (ANDES) in Puno, Peru: rationale and study protocol for a hybrid type 2 effectiveness and implementation randomized controlled trial

BackgroundHypertension is the most common cardiovascular disease in Peru despite the availability of cost-effective, evidence-based treatment. Here we describe the rationale and study design for a hybrid type 2 randomized controlled trial to test the implementation and effectiveness of a community health worker (CHW)-led hypertension control program within the national primary care system in Puno, Peru.MethodsWe will recruit 1068 adult participants with hypertension aged ≥ 18 years in Puno, Peru, via facility-based enrollment and community health fairs. Participants will be individually randomized (1:1) to either continue with usual care or participate in a 12-month CHW-led home-based hypertension control program consisting of blood pressure monitoring, medication adherence support, and healthy lifestyle counseling. Outcome development and reporting are guided by the Consolidated Framework for Implementation Research (CFIR), the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, and the Proctor et al. framework. Clinical effectiveness outcomes include mean change in systolic blood pressure (primary outcome), diastolic blood pressure, and HbA1C. Implementation outcomes include fidelity (i.e., CHW protocol adherence and dose), reach, adoption, sustainability, acceptability, and cost-effectiveness.DiscussionThe ANDES trial is testing the first CHW-led multicomponent strategy for hypertension and type 2 diabetes management in Peru. This type 2 hybrid trial will provide critical insights into the individual, community, and system-level factors necessary for successful implementation and effectiveness. These data can inform the future adaptation and scaling of the ANDES strategy in Peru and other LMICs, as well as influence policies at the system level to support this transition. Furthermore, by addressing both hypertension and diabetes, the ANDES strategy supports integrated care approaches advocated by the WHO HEARTS technical package, ultimately enhancing health outcomes and reducing morbidity and mortality in the region.Trial registrationClinicalTrials.gov, ID: NCT05524987, Addressing Hypertension and Diabetes through Community-Engaged Systems in Puno, Peru (ANDES study), prospectively registered on September 1, 2021.

Pharmacist interventions in the control of hypertension and adherence to anti-hypertensive treatment: A systematic review and meta-analysis of randomised controlled trials

Abstract Introduction Non-adherence to antihypertensive therapy is one of the major barriers for the achievement of blood pressure (BP) control and has a significant cost burden1. Non-adherence is also thought to be one of the leading factors leading to ethnic disparities in hypertension control in the UK2. Pharmacists have an important role in the management of hypertension and non-adherence due to their ideal position to promote optimal use of medication3. Many have advocated for pharmacist involvement in team-based hypertension management, however which pharmaceutical care interventions are most effective remains unclear. There have been many new studies in recent years exploring the effect of pharmacist interventions in hypertension and this meta-analysis provides an update of the current literature and quantification of the results. Aim This study aimed to systematically evaluate the efficacy of pharmacist-delivered interventions for adults with hypertension and examine the intervention characteristics associated with greater BP-lowering efficacy. The primary outcome was the change in BP and secondary outcomes were % achieving BP control. Methods Systematic review and meta-analysis of randomized controlled trials (RCTs). This review was registered on PROSPERO. Embase, CENTRAL, MedLine, Psychinfo and CINAHL were searched until February 2024. Eligible studies included adult patients with a diagnosis of essential hypertension where a pharmacist intervention (alone or collaborative care) targeting BP control was compared with control (usual care). Exclusion criteria included secondary hypertension, pregnancy, children and review articles/case studies. The risk of bias was assessed by the Cochrane risk-of-bias tool for RCTs. The primary outcome was change in BP. We extracted data on sample and intervention characteristics. Meta-analysis was performed using Comprehensive Meta-Analysis Software v4. Moderator analyses examined the association between intervention effects and intervention features. This study was a systematic review and meta-analysis of already completed trials and so ethical approval was not required. Results 2402 articles were retrieved. After removal of duplicates, 1538 were screened by title and abstract against the inclusion criteria. 88 studies with 25,516 participants were included. Mean intervention duration was 7.2 months (range 1-14 months). The overall pooled mean differences in systolic BP (SBP) and diastolic BP (DBP) between pharmacist intervention and control were -7.39 (-8.56, -6.23) mmHg and -3.99 (-4.61, -3.37) mmHg respectively, both P&amp;lt;0.001. With BP control, pharmacist interventions caused a significant increase in those achieving BP control compared to usual care (+21 (16.88, 25.27) %, P&amp;lt;0.001). Duration of intervention had no influence on change in SBP or DBP (both P&amp;gt;0.05). Discussion Pharmacists can make a significant impact in the management of hypertension in respect to increasing treatment adherence and improving BP control and this study highlights the importance of including them as part of the multidisciplinary team responsible for patient care. Limitations of the present study include the inability to extract individual patient data and stratification by ethnicity, socioeconomic status and gender. However, pharmacist interventions in hypertension significantly reduced SBP and DBP and improved BP control. Identifying the characteristics of the most effective interventions can lead to better treatment adherence and BP-lowering in patients with hypertension.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2). In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.6 or 6.0 mg, and dose flexibility is permitted. Participants (n = 726) in SYNCHRONIZE-1 (NCT06066515) have a baseline BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one obesity-related complication but without T2D; participants (n = 755) in SYNCHRONIZE-2 (NCT06066528) have a baseline BMI ≥ 27 kg/m2 and T2D. The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76. Secondary endpoints include change in systolic blood pressure and measures of glycemia. A SYNCHRONIZE-1 substudy is evaluating changes in body composition and liver fat content using magnetic resonance imaging. These trials are designed to provide robust evaluation of the efficacy, safety, and tolerability of survodutide for the treatment of obesity in the presence or absence of T2D.

Effectiveness and Safety of the Telmisartan and Amlodipine Fixed-dose Combination in Managing Hypertension among Indian Patients (TACT India Study): Rationale and Study Design.

Background: The prevalence of hypertension is on the rise, with approximately 200 million individuals affected by this condition in India. Epidemiological studies suggest that one in every three adults in India has hypertension. Fixed-dose combinations (FDCs) present a potential strategy to address the challenge of effective blood pressure control. They are now recommended for the initiation in most hypertensive patients by the guidelines. However, studies evaluating the safety and effectiveness of FDCs in large Indian populations with hypertension are few. Aim: The aim of this real-world study is to evaluate the safety and effectiveness of the fixed-dose combination of telmisartan and amlodipine in managing hypertension in Indian patients. Materials and methods: This prospective, multicenter, observational, real-world evidence study is designed to enroll 10,000 eligible participants from 1,000 study sites across India. Adult patients with newly diagnosed or uncontrolled hypertension on monotherapy would be eligible for enrollment in the study. The study participants would be administered the study treatment per the treating physician's routine clinical practice and followed up after 8 weeks. The primary endpoint is to measure the change in systolic blood pressure (SBP) from baseline to week 8, while secondary endpoints include determining the percentage of patients who reach their blood pressure targets., description of demographic characteristics of the Indian hypertensive population, and reporting of safety outcomes. Conclusion: The TACT India study will provide longitudinal, real-world data on the effectiveness and safety of telmisartan and amlodipine FDC among a large cohort of the Indian population with hypertension.

The modified Baveno classification for obstructive sleep apnoea - Development and evaluation based on the ESADA database.

The "Baveno classification" replaced the apnoea hypopnoea index (AHI) with symptoms and comorbidities for treatment indication in obstructive sleep apnoea (OSA). This study evaluates a modified Baveno classification which adds a validated cardiovascular disease (CVD) risk score and acknowledges severe breathing disturbances. OSA patients from the European Sleep Apnoea Data Base (ESADA) were retrospectively allocated into CVD risk groups 1-3 based on SCORE-2 and the ESC guidelines. AHI ≥30 /h conferred strong treatment indication. When AHI was <30/h, symptoms and CVD risk dictated allocation to weak, intermediate or strong treatment indication group. Change in Epworth Sleepiness Scale (ESS) and office systolic blood pressure (SBP) at follow-up (12-24 months) under positive airway pressure (PAP) were assessed. 8625 patients were analysed (29% female, age 56 [49;64] years, BMI 31.9 [28.4;36.3] kg·m-2). Treatment indication was weak in 501 (6%), intermediate in 2085 (24%) and strong in 6039 (70%). There was a continuous increase in age, SBP, C-reactive protein and glycosylated haemoglobin from weak to strong (p<0.001). PAP prescription increased from 52% to 64% to 93% (weak to strong, p<0.001). The change in ESS score was -2, -4 and -5, respectively (p<0.001). Reductions of ≥3 mmHg of median SBP occurred when AHI was ≥30/h and in symptomatic patients with CVD risk levels>1 when AHI was <30/h. This analysis provides supporting evidence for the key role of CVD risk assessment and severe breathing disturbances in the identification of OSA patients most likely to benefit from treatment.

Effects of Sedentary Behavior Reduction on Blood Pressure in Desk Workers: Results From the RESET-BP Randomized Clinical Trial.

Sedentary behavior (SB) is observationally associated with cardiovascular disease risk. However, randomized clinical trials testing causation are limited. We hypothesized that reducing SB would decrease blood pressure (BP) and pulse wave velocity (PWV) in sedentary adults. This parallel-arm, 3-month randomized clinical trial recruited desk workers, age 18 to 65 years, with systolic BP 120 to 159 or diastolic BP (DBP) 80 to 99 mm Hg, off antihypertensive medications, and reporting <150 min/wk of moderate to vigorous intensity physical activity. Participants were randomized to a SB reduction intervention or a no-contact control group. The intervention sought to replace 2 to 4 h/d of SB with standing and stepping through coaching, a wrist-worn activity prompter, and a sit-stand desk. SB and physical activity were measured with a thigh-worn accelerometer and quantified during all waking hours and separately during work and nonwork times. Clinic-based resting systolic BP (primary outcome) and DBP, 24-hour ambulatory BP, and PWV were assessed by blinded technicians at baseline and 3 months. Participants (n=271) had a mean age of 45 years and systolic BP/DBP 129/83 mm Hg. Compared with controls, intervention participants reduced SB (-1.15±0.17 h/d), increased standing (0.94±0.14 h/d), and increased stepping (5.4±2.4 min/d; all P<0.05). SB and activity changes mainly occurred during work time and were below the goal. The intervention did not reduce BP or PWV in the intervention group compared with controls. Between-group differences in resting systolic BP and DBP changes were -0.22±0.90 (P=0.808) and 0.13±0.61 mm Hg (P=0.827), respectively. The findings were similarly null for ambulatory BP and PWV. Decreases in work-time SB were associated with favorable reductions in resting DBP (r=0.15, P=0.017). Contrary to our hypotheses, reductions in work-time SB (r=-0.19, P=0.006) and increases in work-time standing (r=0.17, P=0.011) were associated with unfavorable increases in carotid-femoral PWV. As expected, increases in nonwork-time standing were favorably associated with carotid-femoral PWV (r=-0.14, P=0.038). A 3-month intervention that decreased SB and increased standing by ≈1 hour during the work day was not effective for reducing BP. Future directions include examining effects of interventions reducing SB through activity other than work-time standing and clarifying association between standing and PWV in opposite directions for work and nonwork time. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03307343.

Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial

Abstract Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (&amp;lt;120 mm Hg) and standard (&amp;lt;140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP &amp;lt;110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (&amp;gt;-4 mm Hg to &amp;lt;6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of &amp;gt;-4 mm Hg to &amp;lt;6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

Injectable angiotensinogen inhibition therapy for hypertension: a systematic review and meta-analysis

Abstract Introduction Hypertension is the leading risk factor worldwide for cardiovascular mortality, and the development of kidney disease. Management of hypertension involves multiple approaches that involve daily tablet ingestion, with high rates of non-adherence. There is an unmet need for innovative interventions to improve adherence to treatment. Purpose We aimed to perform a systematic review and meta-analysis to investigate the role of injectable angiotensinogen (AGT) inhibitors, such as Zilebesiran and IONIS-AGT-LRx, in the treatment of hypertension. Methods PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled clinical trials (RCTs) comparing injectable AGT inhibitors versus placebo. Efficacy was assessed through mean changes in angiotensinogen, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We also examined safety endpoints. We computed pooled mean differences (MD) or risk ratios (RR) for continuous and binary outcomes, respectively, under a random-effects model with a 95% confidence interval (CI). Results Four studies were included for a total of 512 patients, of whom 279 (54.5%) were male, with a mean age of 57 years old; 349 (68.2%) were white. The mean baseline SBP was 142 ± 19.9 mmHg. In a pooled analysis, mean change of AGT decreased significantly with injectable AGT inhibitor compared with placebo (MD -77.86 %; 95% CI -107.49 to -48.23; p&amp;lt;0.01). Similarly, mean change in SBP (MD -14.15 mmHg; 95% CI -19.53 to -8.78; p=0.30) and DBP (MD -8.49 mmHg; 95% CI -9.98 to -7.00; p=0.78) were also significantly lower in the injectable AGT inhibitor group compared with placebo. AGT inhibitors were well tolerated, without associations with serious adverse events, adverse events related to discontinuation, death, hyperkalaemia, or hypotension. However, there was an increase in injection site reaction with these agents compared with placebo (RR 5.86; 95% CI 1.14 to 30.17; p=0.83). Conclusions In this meta-analysis of RCTs, injectable AGT inhibitors were associated with a significant decrease in mean AGT, SBP, and DBP as compared with placebo. There were no significant differences between groups in serious adverse events, although injection site reaction was more common in patients treated with injectable AGT inhibitors.Forest plot of mean change in SBP

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with &amp;gt;10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p&amp;lt;0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Safety, tolerability and blood pressure lowering of the innovative guanylyl cyclase a-receptor activator MANP in an ethnically diverse resistant hypertension population: a phase 1B clinical trial

Abstract Background/Introduction MANP is a novel atrial natriuretic peptide (ANP) analog bioengineered as a particulate guanylyl cyclase A receptor (GC-A) activator with superior receptor binding, resistance to neprilysin degradation, natriuretic, aldosterone suppressing and blood pressure (BP) lowering properties than native ANP. MANP is now under clinical development for resistant hypertension (RH). The rationale for its design was the fundamental role of the ANP/GC-A system in BP homeostasis through which GC-A activation with MANP leads to BP reduction through renal, vascular, and hormonal mechanisms mediated by the second messenger cGMP. Purpose We investigated the safety, tolerability, cGMP activation and BP reductions of MANP compared to placebo in subjects with RH. Methods We performed a double-blind, placebo controlled randomized trial in 36 RH patients comprised of approximately 50% non-African Americans (NAA) and 50% AA. MANP was administered in 6 cohorts receiving ascending subcutaneous (SQ) doses of MANP once daily from 3 ug/kg to a maximal dose of 7 ug/kg or placebo for 5 days and then followed for 21 days after dosing. Endpoints included safety, cGMP activation and changes in systolic BP (SBP), aldosterone (Aldo) levels and glomerular filtration rate (GFR). Results MANP was safe and well tolerated. One patient in the 7 ug/kg cohort was discontinued due to symptomatic hypotension. Compared to baseline, plasma cGMP increased in all MANP groups on Day 1 and Day 5 with no change in the placebo group. The maximal SBP reduction in the MANP group on Days 1 (D1) and 5 (D5) was -17.5 (D1) and -16 mmHg (D5) with 3 ug/kg (lowest dose) and -39.5 (D1) and -36.3 mmHg (D5) with 7 ug/kg (highest dose); Changes in the Placebo group were -6.3 (D1) and -16.7 mmHg (D5). Notably, the SBP reductions in AA were greater than NAA in the 4 and 7 ug/kg cohorts. After the 1-hour timepoint on both the first and fifth days, Aldo and percentage of Aldo reduction generally remained suppressed compared to baseline. Twenty-one days after MANP dosing, SBP remained lower in three groups receiving SQ MANP (4, 4.5 and 7 ug/kg) compared to placebo in association with a preservation of GFR. There were no reported drug related serious adverse events. Conclusions This clinical trial demonstrates that once a day SQ administration of MANP in RH subjects activates cGMP, without attenuation over 5 days, and reduces SBP and preserves GFR. At higher doses of MANP, SBP reductions were greater in AA compared to NAA. MANP also demonstrated Aldo inhibiting actions compared to placebo. Importantly, MANP was overall safe and well-tolerated. Our findings support the continued clinical development of MANP as a novel GC-A activating peptide for the treatment of RH.

Comparing the cardiorespiratory safety of parenteral olanzapine and benzodiazepines to parenteral haloperidol/droperidol and benzodiazepines in emergency department patients

IntroductionThis study sought to assess the cardiorespiratory safety of parenteral olanzapine and benzodiazepine combination treatment compared to parenteral droperidol or haloperidol and benzodiazepine combination treatment. Materials and methodsThis was a retrospective chart review conducted in adult emergency department patients who received intramuscular (IM) or intravenous (IV) droperidol, haloperidol, or olanzapine within one hour of IM or IV benzodiazepine. Patients were stratified into groups based on whether they received either olanzapine in combination with a benzodiazepine (n = 48) or droperidol or haloperidol in combination with a benzodiazepine (n = 48). ResultsPatients in each group had a decrease in their systolic blood pressure (SBP) after IM/IV olanzapine and IM/IV droperidol or haloperidol when used in combination with an IM/IV benzodiazepine ((Olanzapine + benzodiazepine (mmHg), median (IQR): Pre-SBP: 132 (117–151) vs. Post-SBP: 117 (99–131), p < 0.01) (Droperidol or haloperidol + benzodiazepine (mmHg), median (IQR): Pre-SBP: 138 (122–149) vs. Post-SBP: 106 (98–127), p < 0.01)). Both groups had similar percent SBP decreases post-combination treatment (Olanzapine + benzodiazepine (15.6 %) vs. Droperidol or haloperidol + benzodiazepine (15.2 %); p = 0.55). We did not observe any statistically significant between group differences for hypotension (Olanzapine + benzodiazepine: 1/48, 2.1 % vs. Droperidol or haloperidol + benzodiazepine: 3/48, 6.3 %; p = 0.62)), escalation in oxygen requirements (Olanzapine + benzodiazepine: 7/48, 14.6 %) vs. Droperidol or haloperidol + benzodiazepine: 5/48, 10.4 %; p = 0.76)), or intubation due to cardiorespiratory depression (Olanzapine + benzodiazepine: 0/0, 0 % vs. Droperidol or haloperidol + benzodiazepine: 0/0, 0 %; p = 1.00)). ConclusionThis study found decreases in SBP after administering parenteral olanzapine and parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine. The percent change in SBP and the frequency of hypotensive episodes post-combination treatment were not different between groups. There were also no differences between groups in need of increased oxygen requirements post-combination treatment or need for intubation due to cardiorespiratory depression. This study suggests parenteral olanzapine in combination with a parenteral benzodiazepine may have comparable cardiorespiratory safety versus parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine when treating agitation in the adult ED.

Systolic plood pressure response to ASi BI 690517 with and without empagliflozin in CKD

Abstract Background and Aims: BI 690517 is a highly selective aldosterone synthase inhibitor (ASi) in clinical development for CKD treatment. Coadministration of BI 690517 with a sodium-glucose cotransporter-2 inhibitor may provide additive efficacy and also mitigate risk of hyperkalaemia. This multinational, randomised, dose-finding, Phase II trial (NCT05182840) investigated the efficacy and safety of BI 690517, given alone or in combination with empagliflozin (EMPA), for albuminuria reduction in people with CKD and with or without type 2 diabetes.1 Here, we present a secondary analysis for effects on systolic blood pressure (SBP). Method Adults with CKD receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were randomised (R1) 1:1 to receive background EMPA 10 mg or placebo (PBO-EMPA) during an 8-week run-in. They were then re-randomised (R2) 1:1:1:1 to receive BI 690517 (3 mg, 10 mg, or 20 mg) or PBO-ASI for 14 weeks, in addition to their assigned EMPA or PBO-EMPA therapy. Participants had mean baseline SBP ≥110 and ≤160 mmHg. Elevated blood pressure (BP) was defined as SBP ≥140 mmHg or DBP ≥90 mmHg and receiving ≥2 classes of anti-HTN medication. Changes in SBP from R2 baseline to Week 14 were analysed to assess BI 690517 effects with and without EMPA use. Results Of 714 people randomised at R1, 586 were randomised at R2, and the treated set consisted of 583 people. Demographics and clinical characteristics were similar between dose groups.1 At R2 baseline, 169 (29.0%) people had elevated BP. Mean SBP was 142.7 mmHg in the elevated BP group versus 129.2 mmHg in the non-elevated BP group. Treatment with BI 690517 consistently reduced SBP with reductions that were comparable in people with and without elevated BP (p-value for interaction not significant) (Table). Conclusions In people with CKD, BI 690517 reduced SBP in people with and without elevated BP.(Table)

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.