Changes In Systolic Blood Pressure Research Articles

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.

Effectiveness and safety of hydrogen inhalation therapy as an additional treatment for hypertension in real-world practice: a retrospective, observational study in China

AimTo evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension.MethodsThis observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups.ResultsIn total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of −4.63 mm Hg (95% CI, −6.51 to −2.74) at week 8, −6.69 mm Hg (95% CI, −8.54 to −4.85) at week 16, −7.81 mm Hg (95% CI, −9.57 to −6.04) at week 24 for SBP, and −1.83 mm Hg (95% CI, −3.21 to −0.45) at week 8, −2.57 mm Hg (95% CI, −3.97 to −1.17) at week 16, −2.89 mm Hg (95% CI, −4.24 to −1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21–1.72) at week 8, 1.90 (95% CI, 1.59–2.27) at week 16, and 2.24 (95% CI, 1.87–2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p-value >0.05.ConclusionThe HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI therapy.

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<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<0.001). Duration of intervention had no influence on change in SBP or DBP (both P>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.

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.

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.

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.

Influence of orthostatic blood pressure changes on the effects of intensive blood pressure control in patients with type 2 diabetes

Abstract Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Semaglutide for the treatment of resistant hypertension

Abstract Background Treatment options for resistant hypertension (RH) are often limited by medication intolerance and adverse effects. Novel approaches to treatment are required. The disease of obesity affects 70% of patients with RH. Purpose To determine if a weight centric approach using semaglutide improved BP control in patients with RH. Methods Individual participant data from three randomised placebo-controlled trials (STEP 1, 3 and 4) examining the effect of semaglutide 2.4mg on body weight over 68 weeks were included. Participants on &amp;gt;4 anti-hypertensive medications or those with systolic BP (SBP) &amp;gt;130mmHg at baseline and 3 anti-hypertensive medications including a diuretic were considered to have RH. Firstly, the change in SBP comparing those on semaglutide to placebo was analysed with baseline systolic BP as a covariate in an ANCOVA model. Then, the RH group was subdivided into those with SBP above or below 130mmHg at baseline and BP response to semaglutide assessed. Analyses were performed using R Software version 4.0.3. Results In the pooled analysis of 3136 trial participants, 111 met the criteria for RH. Compared to placebo, participants on semaglutide had a SBP reduction of -4.93mmHg, adjusted for SBP baseline to -3.16mmHg (95%CI -8.69 to 2.37). For those with RH and a baseline SBP &amp;gt; 130mmHg on semaglutide, the SBP change was -10.94mmHg. This change was 4.54mmHg for those with a SBP &amp;lt; 130mmHg. The diastolic BP changes were -3.62 and 2.79mmHg respectively (Figure 1). At trial completion, 36% of those on semaglutide did not meet the criteria for RH. Conclusions The effect of semaglutide on BP for patients with RH is modest. A greater BP reduction is evident for those with a higher baseline SBP. Targeting excess body weight with semaglutide is a viable treatment option for patients with RH and uncontrolled BP.

Nutritional management, skipping breakfast, glycemic control, and cardiovascular risk on type 2 diabetes mellitus

Abstract Background Meal timing is an emerging field that investigates the influence of eating patterns on circadian rhythm and general health. There is still disagreement in the literature as to whether eating windows could impact weight gain and biochemical markers. Purpose 1- Evaluate the impact of nutritional interventions on weight, body mass index (BMI), waist circumference (WC), fasting blood glucose (FG), glycated hemoglobin (HbA1c), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP), between 0th and 12th month in Type 2 Diabetes Mellitus (T2D); 2-Observe breakfast skipping and sleep disorders, and also analyze the influence of these data with possible changes in anthropometric and biochemical markers. Methods This experimental and observational study recruited 44 participants with T2D. The assessments were carried out in October 2022 and 2023. The nutritional assessment consisted of prescribing a personalized eating plan (Mediterranean diet and DASH). Statistical analysis: For the variables "breakfast habits", "nocturnal awakenings", and "sleep duration", the numbers of participants were converted into percentages of the total number of individuals. Parametric variables were compared using the paired t-test and non-parametric variables were compared by the Wilcoxon test. To evaluate the influence of the habit of eating breakfast and sleep disorders on quantitative variables, variations were calculated between the 0th and 12th month between participants who had or did not have the habit of eating breakfast and had or did not have sleep disorders. Parametric variables were compared using the unpaired t test and non-parametric variables using the Mann-Whitney test. Parametric data were presented as mean ± standard deviation and non-parametric data as median ± interquartile range, both accompanied by the dispersion of all repetitions. α&amp;lt;0.05 and P&amp;lt;0.05 were adopted. Results Significant reductions were found between the 0th and 12th month of FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight (p&amp;lt;0.0001). Regarding breakfast habits, in the 1st month, 77.3% of participants skipped this meal, reducing to 13.6% in the 12th month. For sleep duration, in the 1st month, 90.9% of participants slept less than 6 hours, reducing to 40.9% in the 12th month. For nocturnal awakenings, 70.5% of participants had at least 1 awakening in the 1st month, reducing to 54.5% in the 12th month. For influence analysis, no significant differences were found between changes in FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight on breakfast habit or sleep disorders, except for HDL-C and sleep disorders (p&amp;lt;0.005). Conclusion Nutritional management improved biochemical markers, reduced anthropometric data, regulated the eating window, reduced nocturnal awakenings, and optimized sleep duration in patients with T2D.

Pharmacist care for hypertension management among patients with diabetes: a systematic review

Abstract Background Improving blood pressure (BP) control is of major importance among patients with diabetes, due to their high risk of micro- and macrovascular complications. Community-based models of care with the involvement of pharmacists and other nonphysician healthcare providers can help manage hypertension. We aimed to estimate the effectiveness of pharmacist interventions, alone or in collaboration, on BP among outpatients with diabetes and hypertension. Methods We conducted systematic searches of randomized controlled trials assessing the effect of pharmacist interventions on BP among outpatients with hypertension and diabetes compared to usual care. The outcome was the systolic and diastolic BP change or BP control. We performed a meta-analysis with random effects models and results are presented by mean difference along with relative 95% CI.We will perform subgroup analyses for the types and intensity (duration, frequeny) of pharmacist interventions, patients’ characteristics, and healthcare settings. The protocol was registered in PROSPERO (CRD42021279751) and published in an open-access peer-reviewed journal. Results Out of 2048 study records identified by electronic database searching, we included 9 studies, with 5067 participants, published between 2008 and 2022. These studies were conducted mainly in North America (n = 5; other regions: n = 4). The intervention was led by the pharmacist in 78% of the studies and in collaboration with other healthcare providers in 22%. Pharmacist intervention included patient education in 67%, healthcare providers education in 11% of studies and feedback to healthcare providers in 44% of the studies. Systolic and diastolic BP were reduced after pharmacist intervention by -5.6 mmHg (95% CI: -10.6 to -0.6) and -4.1 mmHg (95% CI: -7.1 to -1.2) respectively. Additional analyses will be presented at the congress. Conclusions Pharmacist interventions improve blood pressure control in hypertensive diabetic outpatients. Key messages • Recent hypertension guidelines recommend pharmacist involvement in hypertension care management. • This systematic review provide updated evidence on the effect of pharmacist interventions on hypertension management of patients with diabetes.

Predialysis central arterial waveform and blood pressure changes during hemodialysis

To investigate the predictive value of the central arterial waveform for intradialytic blood pressure (BP) change, a total of 152 hemodialysis patients (mean age 68 years) on a thrice-weekly hemodialysis schedule were enrolled, and at both the first and second session of the week, BP and central arterial waveform were measured every 30 min during hemodialysis. In both sessions, a 1-standard deviation increase in baseline subendocardial viability ratio (SEVR), an index of subendocardial perfusion, as well as in baseline systolic BP (SBP) was an independent predictor of maximum SBP decrease ≥ 30 mmHg during hemodialysis. When divided into four groups based on the respective median level of SEVR in the SBP ≥ median and SBP < median groups, intradialytic SBP change was different among the subgroups. Multiple logistic regression analysis revealed that, compared with the SBP < median; low SEVR group, the SBP < median; high SEVR group had lower risk, and the SBP ≥ median; low SEVR group had higher risk of SBP decrease ≥ 30 mmHg, but the risk did not differ from that in the SBP ≥ median; high SEVR group. Predialysis subendocardial perfusion evaluated by SEVR was associated with the maximum intradialytic BP decrease, and evaluation of the central arterial waveform could be used as complementary screening for intradialytic BP change.

Association Between Changes in Central Blood Pressure and Peripheral Blood Pressure With New-Onset Hypertension in a Chinese Community-Based Population.

Spot central and peripheral blood pressure are predictors for future hypertension, but the associations between central or peripheral systolic blood pressure (SBP) changes and new-onset hypertension are unclear. Annual changes in central and peripheral SBP over a mean interval of 2.36 years were calculated for 815 Chinese community residents without cardiovascular disease and hypertension at the first two visits, with the formula: ([2nd SBP-1st SBP]/1st SBP) × 100%/time interval (years). The independent and joint associations of these SBP changes with new-onset hypertension at the third visit were assessed with multivariable logistic regression models. During a mean follow-up interval of 4.37 years since the second visit, 171 new cases of hypertension were observed. Central and peripheral SBP changes were significantly associated with new-onset hypertension (central SBP change rate: odds ratio [OR]: 1.19 [95% confidence intervals (CI) 1.13, 1.26]; peripheral SBP change rate: OR: 1.25 [95% CI 1.17, 1.33]), even after adjusting for each other. Compared to the group with neither SBP increased, the group with both SBPs increased showed asignificantly higher risk of new-onset hypertension (OR: 4.52 [95% CI 2.54, 8.04]). The model including both SBP changes had a higher area under the curve (AUC) for predicting hypertension in receiver operating characteristic (ROC) analyses than those with either change alone. Central and peripheral SBP changes are independently and jointly associated with new-onset hypertension. It is recommended to regularly monitor both central and peripheral blood pressures.

Effect of transcutaneous electrical acupoint stimulation at different frequencies on mild hypertension: A randomized controlled trial

BackgroundTranscutaneous electrical acupoint stimulation (TEAS) may contribute to blood pressure (BP) control, but the evidence remains insufficient. Our objectives were to evaluate the impact of TEAS on hypertension and determine the optimal frequency. MethodsA total of 120 hypertensive patients were randomly allocated to the TEAS-2Hz group, TEAS-10Hz group, or usual care control group in a 1:1:1 ratio. All patients were advised to continue their usual antihypertensive regimen. Additionally, patients in the TEAS groups received TEAS therapy 3 times per week for 4 weeks, with a 4-week follow-up. ResultsThe primary outcome was the change in systolic BP (SBP) from baseline to week 4. Secondary outcomes included changes in diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), heart rate variability (HRV), and 12-item health survey (SF-12) at different time points. Both TEAS groups showed reductions in SBP relative to control (TEAS-2Hz group vs. control, −4.70 mmHg [95 % CI, −7.00 to −2.40 mmHg]; P < 0.001; TEAS-10Hz group vs. control, −8.66 mmHg [95 % CI, −10.97 to −6.36 mmHg]; P < 0.001). TEAS-10Hz provided a significant decrease in SBP than TEAS-2Hz (-3.96 mmHg [95 % CI, −1.66 to −6.26 mmHg]; P< 0.001). TEAS groups also exhibited reductions in DBP, MAP, HR, LF/HF ratio（LF/HF）, very low frequency (VLF), and normalized low frequency (LF norm), and an increase in normalized high frequency (HF norm) than control. No differences were observed among groups in low frequency (LF), high frequency (HF), total power (TP), very low frequency (VLF), and SF-12. ConclusionTEAS might be a promising adjunctive therapy for hypertension, and the recommended frequency is 10 Hz, which should be confirmed in larger trials.

The effect of digital therapeutics intervention on improving hypertension management in adults: a meta-analysis of randomized controlled trial.

Digital therapeutics (DTx) intervention is an emerging therapy for the treatment and long-term management of hypertension. We aim to systematically evaluate the overall effect of DTx intervention on improving hypertension management. The systematic review and meta-analysis of RCTs was conducted and the PubMed, EMBASE, Web of Science, and Cochrane Library were searched to identify eligible RCTs published between Jan 1, 1982 and Sep 10, 2023. Random-effect models were utilized to pool estimates of net changes in systolic blood pressure (BP), diastolic BP, BP control rate, body mass index, weight, waist circumference, and physical activity between the DTx group and control group. 15 RCTs were included with a total of 3789 participants. Compared with the control group, DTx intervention was associated with significant changes in systolic BP, diastolic BP, and BP control rate of -3.75 mmHg(95% CI -5.74 to 1.77), -1.79 mmHg (95% CI -2.81 to -0.77) and 1.47% (95% CI 1.10 to 1.95), respectively. In addition, DTx intervention was statistically significant for improving other risk factors such as lower BMI (-0.5 kg/m2, 95% CI -0.86 to -0.15), increased physical activity (66.73 min/week, 95%CI 49.64 to 83.81), and reduced waist circumference (-2.91 cm, 95% CI -5.15 to -0.66). No difference between groups was demonstrated in weight (P = 0.30). Subgroup analyses revealed consistent effects of the change in SBP and DBP across study duration, age, sample size, patient baseline status, and intervention scenario settings(P > 0.05). DTx intervention may be useful for lowering BP and long-term management of hypertension. More large-size trials providing evidence on the same product are needed.