Mean 24-h Systolic Blood Pressure Research Articles

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial

BackgroundCombined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown.Methods/designA randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140–179/90–109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model.DiscussionThis statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial.Trial registrationClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203.

Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study

BackgroundA fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP. MethodsThis randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population. ResultsParticipants were mostly female (73.5 ​%) and White (81.6 ​%), with a mean age of 53.4 years; 32.4 ​% had no hypertension diagnosis or treatment, 62.5 ​% had hypertension using 0 to 2 antihypertensive medications, and 5.1 ​% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 ​mmHg. At week 8, mean SBP change was −0.1 ​mmHg (placebo), +1.4 ​mmHg (phentermine 30 ​mg), and −3.3 ​mmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was −3.2 ​mmHg (95 ​% CI: -5.48, -0.93 ​mmHg; p ​= ​0.0059). The between-group difference for PHEN/TPM versus phentermine 30 ​mg was −4.7 ​mmHg (95 ​% CI: −6.96, −2.45 ​mmHg; p ​< ​0.0001). Common (>2 ​% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate. ConclusionsIn this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).

Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

Effect of initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy on ambulatory blood pressure indices

Abstract Background The QUARTET trial showed that a combination of four ultra-low-dose blood pressure (BP) medications lowered mean unattended office BP more effectively than initial monotherapy. Purpose To investigate the effects of a combination of four ultra-low-dose blood pressure (BP) medications on ambulatory BP changes. Methods Australian adults (≥18 years) with hypertension who were untreated or on monotherapy were eligible for participation in the QUARTET study. Overall, 591 participants were randomly assigned to receive either the quadpill (containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). The difference in 24-hour, daytime and night-time systolic and diastolic ambulatory BP at 12 and 52 weeks were pre-defined secondary outcomes. Reported parameters for this analysis were derived from ambulatory BP recordings of 576 participants that fulfilled pre-defined validation criteria. Results Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At baseline, 24-h systolic/diastolic BP was 139.2/81.0 mmHg in the monotherapy vs. 139.8/81.3 in the quadpill group, daytime BP was 142.5/83.5 vs 143.4/84.0 mmHg, and night-time BP was 125.1/70.7 vs. 125.4/70.7 mmHg. At 12 weeks, mean 24-h ambulatory systolic and diastolic BP were 7.7 (95%CI: 9.6, 5.8) and 5.3 (95%CI: 6.5, 4.1) mmHg lower in the quadpill versus monotherapy group (p&amp;lt;0.001 for both). Similar reductions were observed for daytime (8.1/5.7 mmHg lower in quadpill compared to montherapy group) and night-time (6.3/4.0 mmHg lower in quadpill compared to monotherapy group) BP (all p&amp;lt;0.001) at 12 weeks. The reduction in systolic and diastolic ambulatory BP variability were more pronounced in the quadpill group at 12 weeks, the 24-h standard deviation was reduced by -1.2 (-1.8, -0.5) mmHg for systolic and -0.9 (-1.5, -0.4) mmHg diastolic BP. The rate of BP control (24 hours BP ≥130 and/or ≥80 mmHg) at 12 weeks was higher in the quadpill group (77% vs 50%; p&amp;lt;0.001). These effects were maintained at 52 weeks. Conclusion A quadruple quarter-dose combination compared to monotherapy resulted in greater ambulatory BP lowering across the entire 24-hour period with higher ambulatory BP control rates at both 12 and 52 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy – which has been previously shown not to increase the rate of side effects - and extends it to ambulatory BP measurements.

Does COVID-19 Cause Non-Dıpper Hypertension?

Coronavirus disease 2019 (COVID-19) remains a health problem worldwide. The present study aimed to investigate the effect of blood pressure (BP) on the circadian pattern and prevalence of new-onset non-dipper hypertension in the post-COVID period in patients with known hypertension. This prospective single-center study included 722 patients hospitalized for COVID-19 infection. Ambulatory BP (ABP) data were collected during their initial hospitalization. The ABP data were reassessed 1month after the patients were discharged. The results were compared with a healthy control group with known hypertension but without COVID-19 infection. After exclusion criteria were applied, the study included 187 patients with COVID-19 and 136 healthy hypertensive controls. Post-COVID ABP showed that patients with COVID-19 had significantly higher mean 24-h systolic and diastolic BP, mean nighttime systolic and diastolic BP, and mean daytime diastolic BP than the control group. In addition, new-onset non-dipper hypertension was significantly higher in patients with COVID-19. This study demonstrated for the first time that the circadian pattern is disturbed and a non-dipper pattern develops in individuals with known hypertension during the post-COVID period.

The Association between Diverticular Rebleeding and Early-Morning Blood Pressure and Surge: A Prospective Observational Trial

Introduction: Colonic diverticular bleeding is the major cause of lower gastrointestinal bleeding. Hypertension is a major risk factor for diverticular rebleeding. Direct evidence of an association between actual 24-h blood pressure (BP) and rebleeding is lacking. Therefore, we analyzed the association between 24-h BP and diverticular rebleeding. Methods: We performed a prospective observational cohort trial involving hospitalized patients with colonic diverticular bleeding. We performed 24-h BP measurements (ambulatory BP monitoring [ABPM]) in the patients. The primary outcome was diverticular rebleeding. We evaluated the 24-h BP difference and the morning and pre-awaking BP surge between rebleeding and non-rebleeding patients. Morning BP surge was defined as early-morning systolic BP minus the lowest night systolic BP >45 mm Hg (highest quartile of morning BP surge). The pre-awaking BP surge was defined as the difference between morning BP and pre-awaking BP. Results: Of 47 patients, 17 were excluded, leaving 30 who underwent ABPM. Of the 30 patients, 4 (13.33%) had rebleeding. The mean 24-h systolic and diastolic BP were 125.05 and 76.19 mm Hg in rebleeding patients and 129.98 and 81.77 mm Hg in non-rebleeding patients, respectively. Systolic BP at 5:00 (difference −23.53 mm Hg, p = 0.031) and 11:30 (difference −31.48 mm Hg, p = 0.006) was significantly lower in rebleeding patients than in non-rebleeding patients. Diastolic BP at 2:30 (difference −17.75 mm Hg, p = 0.023) and 5:00 (difference −16.12 mm Hg, p = 0.043) was significantly lower in rebleeding patients than in non-rebleeding patients. A morning surge was observed in one rebleeding patient and no non-rebleeding patients. The pre-awaking surge was significantly higher in rebleeding patients (28.44 mm Hg) than in non-rebleeding patients (9.30 mm Hg) (p = 0.015). Conclusion: Lower BP in the early-morning and a higher pre-awaking surge were risk factors for diverticular rebleeding. A 24-h ABPM can identify these BP findings and reduce the risk of rebleeding by enabling interventions in patients with diverticular bleeding.

Blood pressure, arterial stiffness, and cardiovascular risk profiles in 8-12-year-old children following preeclampsia (FINNCARE-study).

The aim was to study if children following preeclampsia (PE) develop alterations in blood pressure (BP) and arterial stiffness already early in life, and how this is associated with gestational, perinatal and child cardiovascular risk profiles. One hundred eighty-two PE (46 early-onset with diagnosis before 34 gestational weeks, and 136 late-onset) and 85 non-PE children were assessed 8-12 years from delivery. Office and 24-h ambulatory BP, body composition, anthropometrics, lipids, glucose, inflammatory markers, and tonometry-derived pulse wave velocity (PWV) and central BPs were assessed. Office BP, central BPs, 24-h systolic BP (SBP) and pulse pressure (PP) were higher in PE compared with non-PE. Early-onset PE children had the highest SBP, SBP-loads, and PP. SBP nondipping during night-time was common among PE. The higher child 24-h mean SBP among PE was explained by maternal SBP at first antenatal visit and prematurity (birth weight or gestational weeks), but child 24-h mean PP remained related with PE and child adiposity after adjustments. Central and peripheral PWVs were elevated in late-onset PE subgroup only and attributed to child age and anthropometrics, child and maternal office SBP at follow-up, but relations with maternal antenatal SBPs and prematurity were not found. There were no differences in body anthropometrics, composition, or blood parameters. PE children develop an adverse BP profile and arterial stiffness early in life. PE-related BP is related with maternal gestational BP and prematurity, whereas arterial stiffness is determined by child characteristics at follow-up. The alterations in BP are pronounced in early-onset PE.Clinical Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT04676295ClinicalTrials.gov Identifier: NCT04676295.

Long-term safety and efficacy of renal sympathetic denervation in atrial fibrillation: 3-year results of the AFFORD study

BackgroundAtrial fibrillation (AF) is the most common sustained arrhythmia which has been associated with increased sympathetic nervous system activity and hypertension. Recent evidence indicated that renal sympathetic denervation (RDN) could safely contribute to an improvement in AF burden.ObjectiveTo investigate the long-term safety and efficacy of radiofrequency RDN in hypertensive patients with symptomatic AF.MethodsThis pilot study included patients with symptomatic paroxysmal or persistent AF (European Hearth Rhythm Association class ≥ II) despite optimal medical therapy, office systolic blood pressure (BP) ≥ 140 mmHg and ≥ 2 antihypertensive drugs. AF burden was measured using an implantable cardiac monitor (ICM), implanted 3 months prior to RDN. ICM interrogation and 24-h ambulatory BP monitoring were performed at baseline and at 3/6/12/24/36 months post RDN. The primary efficacy outcome was daily AF burden. Statistical analyses were performed using Poisson and negative binomial models.ResultsA total of 20 patients with a median age [25th–75th percentiles] of 66.2 [61.2–70.8] years (55% female) were included. At baseline, office BP ± standard deviation (SD) was 153.8/87.5 ± 15.2/10.4 mmHg, while mean 24-h ambulatory BP was 129.5/77.3 ± 15.5/9.3 mmHg. Baseline daily AF burden was 1.4 [0.0–10.9] minutes/day and throughout a 3-year follow-up period, no significant change was observed (− 15.4%/year; 95% confidence interval (CI) − 50.2%, + 43.7%; p = 0.54). The number of defined daily doses of antiarrhythmic drugs and antihypertensive drugs remained stable over time, while mean 24-h ambulatory systolic BP decreased with − 2.2 (95% CI − 3.9, − 0.6; p = 0.01) mmHg/year.ConclusionsIn patients with hypertension and symptomatic AF, stand-alone RDN reduced BP but did not significantly reduce AF burden up until 3 years of follow-up.Graphical abstract

Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study

BackgroundPerirenal fat plays a key role in sustaining pathological high blood pressure. We aim to investigate the efficacy of intervention for perirenal fat mediated by focused power ultrasound (FPU) on primary hypertension.MethodsA multicenter, randomized, sham-controlled, double-blinded trial will be implemented in 200 participants with mild to moderate hypertension. All enrolled participants will be randomly allocated to perirenal fat modification (PFM) intervention using FPU or sham-procedure at a ratio of 1:1 and will be followed up at 24 h, 14 days, 30 days, and 90 days after the intervention. The primary endpoint is changes in office systolic blood pressure (SBP) at 30 days compared with baseline. The secondary endpoints include the changes in office SBP from baseline to 90 days, changes in 24-h mean SBP from baseline to 30 days and 90 days, and changes in heart rate from baseline to 30 days. Safety endpoint is defined as any severe adverse events related to the intervention.DiscussionThe present study is the first to use noninvasive FPU to intervene in perirenal fat to achieve the goal of reducing blood pressure for patients with essential hypertension. Our study is expected to provide a new treatment strategy to control high blood pressure.Trial registrationClinicalTrials.gov. NCT05049096. Registered on September 7, 2021.Protocol version: Version 1.3.1, data 23 August 2021.Sponsor: Prof. Xiangqing Kong is the principal investigator of this trial.

Association between renal sympathetic denervation and arterial stiffness: the ASORAS study.

Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the association between noninvasive vascular stiffness indices and RDN-mediated BP reduction. In this prospective, single-arm pilot study, patients with systolic office BP at least 140 mmHg, mean 24-h systolic ambulatory blood pressure (ABP) at least 130 mmHg and at least three prescribed antihypertensive drugs underwent radiofrequency RDN. The primary efficacy endpoint was temporal evolution of mean 24-h systolic ABP throughout 1-year post RDN (measured at baseline and 3-6-12 months). Effect modification was studied for baseline ultrasound carotid-femoral and magnetic resonance (MR) pulse wave velocity (PWV), MR aortic distensibility, cardiac MR left ventricular parameters and clinical variables. Statistical analyses were performed using linear mixed-effects models, and effect modification was assessed using interaction terms. Thirty patients (mean age 62.5 ± 10.7 years, 50% women) with mean 24-h ABP 146.7/80.8 ± 13.7/12.0 mmHg were enrolled. Following RDN, mean 24-h systolic ABP changed with -8.4 (95% CI: -14.5 to -2.3) mmHg/year ( P = 0.007). Independent effect modifiers were CF-PWV [+2.7 (0.3 to 5.1) mmHg/year change in outcome for every m/s increase in CF-PWV; P = 0.03], daytime diastolic ABP [-0.4 (-0.8 to 0.0) mmHg/year per mmHg; P = 0.03], age [+0.6 (0.2 to 1.0) mmHg/year per year of age; P = 0.006], female sex [-14.0 (-23.1 to -5.0) mmHg/year as compared with men; P = 0.003] and BMI [+1.2 (0.1 to 2.2) mmHg/year per kg/m 2 ; P = 0.04]. Higher CF-PWV at baseline was associated with a smaller reduction in systolic ABP following RDN. These findings could contribute to improve identification of RDN responders.

Stepwise treatment of uncontrolled HyperTensioN (Stepwise-HTN): Study design of a cluster randomised controlled trial in primary care

BackgroundUncontrolled hypertension is a major health problem, and a key risk factor for cardiovascular disease. Most patients are detected and managed in primary care, but approximately 50% remains uncontrolled.Our aim is to assess whether a guided stepwise work-up management strategy for patients with uncontrolled hypertension in primary care would result in better blood pressure control in these patients compared to usual care. MethodsA cluster randomised controlled trial aiming at randomizing 40 general practices to either “a protocolised stepwise work-up” or to “usual care”.Uncontrolled hypertension is defined as an office blood pressure (BP) >140/90 mmHg while being prescribed three or more antihypertensive drugs simultaneously from different therapeutic classes for three or more months in an adequate dose. In the intervention arm, patients with uncontrolled hypertension will receive the stepwise approach, consisting of (i) excluding a white coat effect, (ii) re-evaluation of lifestyle, (iii) re-evaluation of drug adherence, (iv) optimalisation of antihypertensive treatment and (v) referral if the office BP is still >140/90 mmHg. The control group receives usual care in a regular program for cardiovascular risk management.The primary outcome is the absolute difference in the mean 24-h systolic BP between intervention and control arm after 8 months. Secondary outcomes include differences in the percentage of patients achieving a controlled BP, and time to reach a controlled BP. ConclusionIf stepwise treatment of uncontrolled hypertension is proven effective, the strategy could be implemented by blending the approach to the cardiovascular risk management already applied in general practice.Trial registrationNTR7304, https://www.trialregister.nl/trial/7099

Abstract 10370: Effects of Tirzepatide on 24-Hour Ambulatory Blood Pressure and Heart Rate in Adults With Obesity - Results From the SURMOUNT-1 Ambulatory Blood Pressure Monitoring Sub-Study

Background: Tirzepatide has demonstrated substantial reductions in body weight and in-office blood pressure (BP) in people with obesity with and without type 2 diabetes (T2D). The effects of tirzepatide on ambulatory BP and heart rate (HR) have not been evaluated. We sought to assess the effect of tirzepatide on 24-hour (24h) mean systolic BP (SBP), diastolic BP (DBP) and HR, as measured during 24h ambulatory BP monitoring (ABPM) in people living with obesity without T2D. Methods: In the SURMOUNT-1 ABPM sub-study, participants with a body mass index ≥30, or ≥27 kg/m 2 and at least one weight-related complication (excluding diabetes), with SBP/DBP &lt;140/90 mmHg (and stable antihypertensive therapy if used), were randomly assigned 1:1:1:1 to once-weekly subcutaneous tirzepatide 5, 10, or 15 mg or placebo. The randomization was stratified by pre-diabetes status, country, sex, and use of heart rate controlling medicines at baseline. Participants underwent 24h ABPM at baseline and after 36 weeks of treatment. Results: Among participants randomized in the SURMOUNT-1 trial, 600 were enrolled in the ABPM substudy (69% female; mean age 46 y, BMI 37 kg/m 2 ). No clinically significant between-treatment differences were observed in baseline characteristics. Overall, 494 participants had evaluable ABPM data at baseline and post-baseline. Treatment with all tirzepatide doses was associated with significant reductions in 24h SBP at 36 weeks compared with placebo. Participants who received tirzepatide 5 and 10 mg, but not 15 mg, had significantly reduced 24h DBP at 36 weeks versus placebo. An increase in 24h HR was observed with each tirzepatide dose relative to placebo. Conclusion: After 36 weeks of treatment, tirzepatide was associated with statistically significant and clinically meaningful reductions in mean 24h SBP at all doses and of DBP at the two lower doses. Tirzepatide treatment was associated with a dose-dependent increase in the mean 24h HR.

A parallel evaluation of short- and mid-term changes of ambulatory blood pressure in kidney transplant recipients and kidney donors.

Kidney transplantation (KTx) is associated with improved blood pressure (BP) levels for kidney transplant recipients (KTRs) without evoking significant changes in donors. However, there is a paucity of studies offering simultaneous detailed evaluation of BP profiles over time in transplant donor-recipient pairs. The aim of the present study was the parallel evaluation of ambulatory BP levels and trajectories in KTRs and their respective living kidney donors in the short and mid-term following KTx. The study enrolled 40 prospective adult KTRs and their 40 respective donors. All participants were evaluated with 24-h ambulatory BP monitoring (Mobil-O-Graph NG device) at three time points: baseline (1 month before KTx), 3 months and 12 months after KTx. In KTRs, 3-month 24-h systolic BP (SBP) was marginally reduced and 12-month 24-h SBP significantly reduced compared with baseline [131.9±13.3versus126.4±11.9 mmHg (P=.075) and 123.9±10.3 mmHg (P=.009), respectively]. At both the 3- and 12-month time points, 24-h diastolic BP (DBP) was significantly reduced [86.7±11.5versus82.2±8.1 mmHg (P=.043) and 80.3±8.5 mmHg (P=.009)]. Similar observations were made for day- and night time SBP and DBP. Repeated-measures analysis of variance (ANOVA) showed a significant gradual decrease over time in mean 24-h SBP [F(1.463, 39.505) = 3.616; P=.049, partial η 2=0.118] and DBP [F(1.374, 37.089) = 11.34; P=.055, partial η 2=0.116]. In contrast, in kidney donors, 24-h SBP [118.5±11.6versus118.2±12.8 mmHg (P= .626) and 119.2±11.4 mmHg (P=.748)] and DBP did not change at 3 or 12 months compared with baseline; repeated measures ANOVA showed no differences in the mean 24-h SBP and DBP levels over time. The number of antihypertensive agents decreas in KTRs and remained stable in donors. KTx reduces ambulatory BP levels and trajectories in KTRs at 3 months and further so at 12 months post-surgery. Kidney donation does not affect the ambulatory BP levels and trajectories of donors at the same intervals.

Impact of drug adherence on blood pressure response to alcohol-mediated renal denervation

Purpose While poor drug adherence is frequent in patients with resistant hypertension, detailed analyses of the impact of drug adherence on the success of renal denervation are scarce. We report drug adherence at baseline, changes in drug adherence, and the influence of these parameters on blood pressure changes at 6 and 12 months in patients treated with alcohol-mediated renal denervation as part of the Peregrine study. Materials and methods Urinary detection of antihypertensive drugs was performed using high-performance liquid chromatography-tandem mass spectrometry. Full adherence, partial adherence, and complete non-adherence were defined as 0, 1, or ≥2 drugs not detected, respectively. Results Renal denervation was performed in 45 patients with uncontrolled hypertension on ≥3 antihypertensive medications (62% men, age 55 ± 10 years). At baseline, the proportion of fully, partially, and non-adherent patients was 62% (n = 28), 16% (n = 7), and 22% (n = 10), respectively. At 6 months, adherence improved by 21% (n = 9), remained unchanged at 49% (n = 21), and worsened by 30% (n = 13). Mean 24-h systolic blood pressure decreased by 10 ± 13, 10 ± 4, and 14 ± 19 mmHg in fully, partially, and non-adherent patients (p = 0.77), and by 14 ± 14, 8 ± 11, and 14 ± 18 mmHg in patients who improved, maintained, or decreased adherence, respectively (p = 0.35). The results at 12 months were similar. Conclusion About 40% of patients with apparently treatment-resistant hypertension were not fully adherent at baseline, and adherence decreased further in 30%. Nevertheless, mean blood pressure changes after renal denervation were similar irrespective of drug adherence. Our results suggest that such patients may benefit from alcohol-mediated renal denervation, irrespective of drug adherence. These findings are hypothesis-generating and need to be confirmed in ongoing sham-controlled trials.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. Medtronic.

Effects of isometric leg training on ambulatory blood pressure and morning blood pressure surge in young normotensive men and women

Despite the reported association between diurnal variations in ambulatory blood pressure (BP) and elevated cardiovascular disease risk, little is known regarding the effects of isometric resistance training (IRT), a practical BP-lowering intervention, on ambulatory BP and morning BP surge (MBPS). Thus, we investigated whether (i) IRT causes reductions in ambulatory BP and MBPS, in young normotensives, and (ii) if there are any sex differences in these changes. Twenty normotensive individuals (mean 24-h SBP = 121 ± 7, DBP = 67 ± 6 mmHg) undertook 10-weeks of bilateral-leg IRT (4 × 2-min/2-min rest, at 20% maximum voluntary contraction (MVC) 3 days/week). Ambulatory BP and MBPS (mean systolic BP (SBP) 2 h after waking minus the lowest sleeping 1 h mean SBP) was measures pre- and post-training. There were significant reductions in 24-h ambulatory SBP in men (− 4 ± 2 mmHg, P = 0.0001) and women (− 4 ± 2 mmHg, P = 0.0001) following IRT. Significant reductions were also observed in MBPS (− 6 ± 8 mmHg, p = 0.044; − 6 ± 7 mmHg, P = 0.019), yet there were no significant differences between men and women in these changes, and 24-h ambulatory diastolic BP remained unchanged. Furthermore, a significant correlation was identified between the magnitude of the change in MBPS and the magnitude of changes in the mean 2-h SBP after waking for both men and women (men, r = 0.89, P = 0.001; women, r = 0.74, P = 0.014). These findings add further support to the idea that IRT, as practical lifestyle intervention, is effective in significantly lowering ambulatory SBP and MBPS and might reduce the incidence of adverse cardiovascular events that often occur in the morning.

Herbs and spices at a relatively high culinary dosage improves 24-hour ambulatory blood pressure in adults at risk of cardiometabolic diseases: a randomized, crossover, controlled-feeding study

ABSTRACTBackgroundIntake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases.ObjectivesThe objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d−1 · 2100 kcal−1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults.MethodsA 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period.ResultsNo between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P = 0.02) and diastolic (P = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (−1.9 mm Hg; 95% CI: −3.6, −0.2 mm Hg; P = 0.02); the difference between the HSD and LSD was not statistically significant (−1.6 mm Hg; 95% CI: −3.3, 0.04 mm Hg; P = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (−1.5 mm Hg; 95% CI: −2.5, −0.4 mm Hg; P = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function.ConclusionsIn the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d−1 · 2100 kcal−1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d−1 · 2100 kcal−1), in adults at elevated risk of cardiometabolic diseases.This trial was registered at clinicaltrials.gov as NCT03064932.

Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind, placebo-controlled trial.

To characterize the blood pressure (BP) profile of the new β3-adrenergic receptor agonist, vibegron, in patients with overactive bladder. Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days and underwent ambulatory BP monitoring. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime ambulatory systolic BP (SBP). Secondary endpoints were CFB in mean 24-h SBP and in mean daytime and mean 24-h ambulatory diastolic BP (DBP) and heart rate (HR). Safety was assessed through adverse event reporting. Of 214 patients randomized, 96 receiving vibegron and 101 receiving placebo had evaluable baseline and day 28 measurements. Overall, 39.6 and 30.7% of patients receiving vibegron and placebo, respectively, had preexisting hypertension. The least squares mean difference (LSMD; 90% confidence interval) between vibegron and placebo in CFB in mean daytime SBP was 0.8 (-0.9, 2.5) mmHg. LSMD in CFB in mean daytime DBP and HR was 0.0 mmHg and 0.9 bpm, respectively. No significant differences between treatments were seen in CFB in mean 24-h SBP (LSMD, 0.6 mmHg), DBP (-0.2 mmHg) or HR (1.0 bpm). The most common treatment-emergent adverse event was hypertension, with rates comparable between groups [vibegron: n = 5 (4.7%); placebo: n = 4 (3.7%)]. One patient receiving vibegron took a prohibited medication (phentermine) known to increase BP. Once-daily vibegron had no statistically significant or clinically relevant effects on BP or HR.

Renal nerve stimulation: complete versus incomplete renal sympathetic denervation

Purpose Blood pressure (BP) reduction after renal sympathetic denervation (RDN) is highly variable. Renal nerve stimulation (RNS) can localize sympathetic nerves. The RNS trial aimed to investigate the medium-term BP-lowering effects of the use of RNS during RDN, and explore if RNS can check the completeness of the denervation. Material and methods Forty-four treatment-resistant hypertensive patients were included in the prospective, single-center RNS trial. The primary study endpoint was change in 24-h BP at 6- to 12-month follow-up after RDN. The secondary study endpoints were the acute procedural RNS-induced BP response before and after RDN; number of antihypertensive drugs at follow-up; and the correlation between the RNS-induced BP increase before versus after RDN (delta [Δ] RNS-induced BP). Results Before RDN, the RNS-induced systolic BP rise was 43(±21) mmHg, and decreased to 9(±12) mmHg after RDN (p < 0.001). Mean 24-h systolic/diastolic BP decreased from 147(±12)/82(±11) mmHg at baseline to 135(±11)/76(±10) mmHg (p < 0.001/<0.001) at follow-up (10 [6–12] months), with 1 antihypertensive drug less compared to baseline. The Δ RNS-induced BP and the 24-h BP decrease at follow-up were correlated for systolic (R = 0.44, p = 0.004) and diastolic (R = 0.48, p = 0.003) BP. Patients with ≤0 mmHg residual RNS-induced BP response after RDN had a significant lower mean 24-h systolic BP at follow-up compared to the patients with >0 mmHg residual RNS-induced BP response (126 ± 4 mmHg versus 135 ± 10 mmHg, p = 0.04). 83% of the patients with ≤0 mmHg residual RNS-induced BP response had normal 24-h BP at follow-up, compared to 33% in the patients with >0 mmHg residual RNS-induced BP response (p = 0.023). Conclusion The use of RNS during RDN leads to clinically significant and sustained lowering of 24-h BP with fewer antihypertensive drugs at follow-up. RNS-induced BP changes were correlated with 24-h BP changes at follow-up. Moreover, patients with complete denervation had significant lower BP compared to the patients with incomplete denervation.

Impact of changes in weight and haematocrit on the reduction in systolic office and ambulatory blood pressure with empagliflozin in patients with type 2 diabetes

Abstract Background There is uncertainty on how empagliflozin (EMPA) reduces blood pressure (BP), and in particular the potential role for changes in weight and haematocrit in mediating these effects. Purpose To assess the contributions of changes in weight and haematocrit on EMPA induced changes in BP in patients with type 2 diabetes mellitus (T2DM) in the EMPA-BP and EMPA-REG OUTCOME trials. Methods Patients received placebo (PBO), EMPA 10 mg or EMPA 25 mg. In EMPA-BP (12-week study), 823 patients with T2DM and hypertension (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, BMI 32.6 [5.1] kg/m2) were studied. In EMPA-REG OUTCOME, of the 7,020 treated patients with T2DM and cardiovascular disease (mean [SD] age 63.1 [8.6] years, HbA1c 8.07 [0.85] %, BMI 30.6 [5.3] kg/m2), 95.0% were on anti-hypertensive treatment at baseline. ANCOVA/MMRM models were applied to assess changes in systolic BP (SBP) at week 12 associated with, and independent of, changes in weight and haematocrit (Hct). SBP measurements are based on mean 24-h measurements from an ambulatory blood pressure monitoring (ABPM) device in EMPA-BP and seated office measurements in EMPA-REG OUTCOME. Results Mean (SD) baseline SBP was 131.7 (11.8), 131.3 (13.0) and 131.2 (12.1) mmHg in the PBO, EMPA 10 mg and EMPA 25 mg groups, respectively in EMPA-BP (mean 24-h SBP) and 135.8 (17.2), 134.9 (16.8) and 135.6 (17.0) mmHg (office SBP), respectively in EMPA-REG OUTCOME. In these relatively young patients with T2DM and mildly elevated mean SBP, EMPA reduced mean SBP by 3.4–4.2 mmHg compared with PBO (table) at week 12. Mean (SE) weight was reduced with EMPA (10 and 25mg) vs PBO treatment by −1.5 (0.2) kg and −2.0 (0.2) kg in EMPA-BP and by −1.2 (0.1) kg and −1.5 (0.1) kg in EMPA-REG OUTCOME at week 12. Mean (SE) haematocrit was increased by 2.1 (0.2) % and 1.8 (0.2) % versus placebo in EMPA-BP and by 2.2 (0.1) % and 2.5 (0.1) % in EMPA-REG OUTCOME with EMPA 10 mg and EMPA 25 mg, respectively. Weight loss accounted for 21–24% of the SBP reduction with EMPA treatment in EMPA-BP and 9–11% in EMPA-REG OUTCOME. Changes in Hct accounted for negligible (between −10% to 1%) SBP reduction with EMPA. Conclusion The reduction in SBP is modestly mediated through a reduction in weight. There was no meaningful effect of EMPA induced changes in Hct on SBP. Results were consistent using ABPM or office SBP. These findings suggest that EMPA's effects on SBP are likely mediated through other mechanisms such as natriuresis or reduction in arterial stiffness. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company. Table 1