24-h Ambulatory Systolic Blood Pressure Research Articles

O91 SIGNIFICANT NIGHTTIME BLOOD PRESSURE REDUCTIONS FOLLOWING RENAL DENERVATION IN PATIENTS WITH UNCONTROLLED HYPERTENSION: POOLED ANALYSIS FROM THE SPYRAL HTN TRIALS

Objective: Elevated nighttime systolic blood pressure (SBP) is more strongly associated with risk for cardiovascular events than daytime or office SBP. We assessed whether radiofrequency renal denervation (RF RDN) reduces nighttime SBP, in addition to other times of the day. Design and Method: We pooled data from patients with uncontrolled hypertension undergoing RF RDN using the latest-generation SpyralTM multi-electrode catheter, from the published, SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-ambulatory SBP were evaluated at baseline and at 12 months. Different time ranges were evaluated including nighttime (1am-6am), morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urinary drug testing, where available, was assessed at baseline and at 12 months. Results: Data from 388 patients undergoing RDN were pooled. Patients were 54±10yrs old, 26.8% female, BMI 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% type 2 diabetes, 9.8% obstructive sleep apnea, 47.7% history of smoking. The baseline nighttime SBP was 139±11mmHg, and 92.5% had nocturnal hypertension (BP ≥120/70 mmHg). Patients took 1.0±1.2 antihypertensive drugs with drug burden of 1.6±3.1 at baseline. 12 months after RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The overall 24-h ambulatory SBP reduced by -11.9±12.4mmHg, nighttime -10.8±15.4mmHg, morning -12.8±20.4mmHg, daytime -12.2±13.6mmHg, and office -17.7±15.4mmHg (Figure). Patients took 1.8±1.1 antihypertensive drugs with drug burden of 2.9±3.0 at 12 months. Results from 24 months, not currently available, will also be presented. Conclusions: In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. RF RDN achieved clinically meaningful reductions throughout the 24-hr circadian cycle including the nighttime SBP, when CV risk is highest. RF RDN, in addition to pharmacotherapy, may help to reduce this risk.

Impacts of renal denervation on blood pressure in patients with obstructive sleep apnea.

Sympathetic nerve activation followed by obstructive sleep apnea (OSA) accounts for blood pressure elevation. The effectiveness of renal denervation (RDN) in controlling blood pressure in patients with OSA remains controversial. In this systematic review, we tried to pool currently available data to assess the effects of RDN therapy on blood pressure in OSA patients. We retrieved Pubmed, EMbase and Cochrane Library through 17 May 2023, using the following key words: "renal denervation" and"obstructive sleep apnea". Full articles reporting the change of blood pressure after RDN procedure were included. A total of five studies were included in the meta-analysis. Pooled analysis showed that RDN markedly reduced both 24-h ambulatory systolic blood pressure (24h-SBP) (Mean difference (MD): -7.54mmHg; 95%Cl: -10.16 to -4.91mmHg; I2 = 0%) and 24-h ambulatory diastolic blood pressure (24h-DBP) (MD: -5.28mmHg; 95%Cl: -7.35 to -3.22mmHg; I2=0%). Daytime systolic blood pressure (dSBP) was reduced after RDN (MD: -7.54mmHg; 95%Cl: -10.82 to -4.57mmHg; I2 = 54%). With regards to nocturnal blood pressure, we found that RDN resulted in a significant reduction in nighttime systolic blood pressure (nSBP) (MD: -6.91mmHg; 95%Cl: -10.69 to -2.85mmHg; I2=0%). Subgroup analysis showed that dSBP was reduced by 12.00 mmHg, 12.00 mmHg, and 7.25 mmHg at 1 month, 3 months and 6 months, respectively. Our pooled analysis showed that AHI was not significantly changed by RDN. No major compilations were associated with RDN. RDN exerts a considerable blood pressure-lowering effect in hypertensive patients with OSA, which was sustained at least 6 months.

Comparative efficacy and safety of six angiotensin IIreceptor blockers in hypertensive patients: a network meta-analysis.

The antihypertensive effects of angiotensin II receptor blockers (ARBs) are well recognized. However, conventional meta-analyses have reported inconsistent results on their efficacy and safety. This study aimed to evaluate the efficacy and safety of six ARBs (losartan, valsartan, irbesartan, telmisartan, candesartan, and olmesartan) commonly used to treat hypertension, using anetwork meta-analysis. We retrieved randomized controlled trials on hypertension treatment using ARBs from the PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases. The efficacy outcomes included absolute changes in office systolic and diastolic blood pressure from baseline, and 24-h ambulatory blood pressure. Safety outcomes were assessed by the total number of adverse events (AEs) during treatment. We conducted the network meta-analysis using the 'bugsnet' and 'gemtc' packages in R. A total of 193 studieswere included. Olmesartan had the highest surface under the cumulative ranking in reducing office systolic (91.4%) and diastolic blood pressure (87.2%). Candesartan has the highest ranking in lowering 24h ambulatory systolic blood pressure (95.4%), while telmisartan reduced 24h ambulatory diastolic blood pressure (83.4%). Olmesartan also ranked highest in safety (70.8%). Valsartan and losartan were less effective in lowering blood pressure than other drugs, with no significant differences. Olmesartan and telmisartan were associated with fewer AEs than losartan, although the incidence of adverse events was similar between the other blockers. Olmesartan and telmisartan demonstrated the best balance of antihypertensive efficacy and minimal adverse events.More research is needed to confirm whether telmisartan and olmesartan are optimal choices for controlling blood pressure in patients.

HIGHER BASELINE SYSTOLIC BLOOD PRESSURE IS ASSOCIATED WITH GREATER BLOOD PRESSURE REDUCTIONS FOLLOWING RADIOFREQUENCY RENAL DENERVATION IN A POOLED COHORT OF OVER 3900 PATIENTS

Objective: Uncontrolled hypertension (HTN) is the leading global risk factor for cardiovascular disease, and higher systolic blood pressure (SBP) increases this risk. Radiofrequency renal denervation (RF RDN) has been shown to reduce BP effectively in patients with uncontrolled HTN. We investigated the relationship between increasing baseline SBP and its change after RF RDN. Design and method: Patients undergoing RF RDN (N=3974) were pooled from global clinical trials in patients on antihypertensive drugs: SPYRAL First-In-Man, SYMPLICITY HTN-3, HTN-Japan, SPYRAL HTN ON-MED, and the Global SYMPLICITY Registry DEFINE. Office and 24-h ambulatory SBP at baseline and 6 months after RF RDN were evaluated. Linear regression analysis was performed to evaluate the correlation between baseline and SBP change after 6 months (SBP change=intercept+slope∗baseline SBP). Results: The baseline SBP for office and 24-h ambulatory BP were 167±24mmHg and 154±18mmHg, respectively. Patients were prescribed 4.4±1.5 antihypertensive drugs at baseline. After 6 months, prescribed antihypertensive drugs decreased to 4.3±1.5 (p<0.0001). In both office and 24-h ambulatory SBP, baseline SBP correlation with SBP change after 6 months was statistically significant; every 1mmHg increase in baseline office SBP was associated with a 0.59mmHg (r2=0.30; p<0.001) reduction in SBP, and every 1mmHg increase in baseline 24-h ambulatory SBP was associated with a 0.45mmHg (r2=0.19; p<0.001) reduction in SBP at 6 months. According to this linear regression, a baseline office SBP of 160mmHg, 170mmHg and 180mmHg were associated with 6 months office SBP reduction by -9.2mmHg, -15.1mmHg and -21.0mmHg, respectively (Figure). Reductions in SBP of this magnitude have previously been shown to correspond with substantial reductions in the risk of cardiovascular events. Conclusions: A continuous and inverse relationship was observed between baseline SBP and 6 months SBP change in patients with uncontrolled HTN undergoing RF RDN. Higher baseline SBP led to a greater reduction in SBP and may derive greater benefit from an RDN procedure. These findings may help clinicians and patients in their shared decision making regarding their BP management. However, this is a retrospective analysis which needs further prospective validation.

BLOOD PRESSURE RESPONDERS TO RENAL DENERVATION BASED ON A NEW DEFINITION

Objective: Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is an unmet need for patient selection. Any antihypertensive intervention follows the law of the inital value, which means that the baseline BP predicts the BP change, a phenomenon known as Wilder‘s Principle (European Heart Journal, 2015, 36, 576-579). Thus, any observed change in BP after renal denervation is the sum of the change in BP depending on the baseline BP and the specific BP reduction related to RDN. Based on this concept, we propose a new definition of BP responders. Design and method: In our center, a total of 127 patients with uncontrolled hypertension underwent RDN and 24h ambulatory BP was measured at baseline, 6- and 12 months after the procedure. According to the Wilder's principle, the decrease in the 24h ambulatory systolic BP (SBP) was related to the baseline 24h SBP (p=<0.001, r=-0.466, y=69.28–0.52∗x). Subsequently, we calculated the predicated decrease in 24h SBP and subtracted this from the the observed decrease in 24h SBP, thereby getting the specific or residual effect of SBP decrease. According to this RDN specific change of 24h SBP, the study cohort was divided into tertials: RDN responders, neutral responders and non-responders. Results: Our study population with mean of age of 59 years consisted of 74% males and 55% with type 2 Diabetes (T2D). The RDN specific (residual) 24-hour ambulatory blood pressure decreased by -14.4/-8.8mHg (responder group), 1.4/0.4mmHg (neutral group) und 15.7/8.5 mmHg (non-responder group) twelve months after RDN (see table). According to our new definition of BP-responders to RDN, the RDN responder group was characterized only by lower number of antihypertensive medication (p=0.002), low BMI (p<0.001), and the absence of T2D (p=0.013). Conclusions: We propose a new definition of responders to RDN, separating the BP- changes related to the baseline BP from those related to the reduction of the sympathetic nerve activity after RDN. Following this approach, we identified low BMI, less antihypertensive medication and absence of T2D as positive predictors for BP response to renal denervation.

RENAL DENERVATION RESULTS IN SUBSTANTIAL NOCTURNAL BP REDUCTION IN PATIENTS WITH A REVERSED DIPPING PATTERN

Objective: We characterized patients with reverse blood pressure (BP) dipping pattern and uncontrolled hypertension (HTN) at baseline referred for radiofrequency renal denervation (RF RDN), and their subsequent BP changes. Design and method: Patients with HTN were enrolled into the Global SYMPLICITY Registry (GSR) DEFINE and underwent RF RDN. Patients were grouped into different BP dipping patterns defined by night/daytime BP ratio: dippers (ratio 0.9 or below), non-dippers (ratio 0.9 to 1.0 or below), reverse dippers (ratio >1.0). Baseline characteristics and BP changes through 3yrs were compared between groups based on dipper patterns. Statistical significance was defined as p<0.05. Results: As of March 2023, 3331 patients with uncontrolled BP were enrolled, 2276 of whom had 24-h BP measures and could be categorized by dipping patterns. Majority of the patients were non-dippers (44.3%), followed by dippers (34.6%) and reverse dippers (21.1%). Reverse dippers (n=480) were the oldest (62±12yrs; p=0.0024), more likely to have cardiac disease (54.2%; p<0.0001), diabetes (48.1%; p<0.0001) and renal disease (38.9%; p<0.0001). Reverse dippers had the highest baseline 24-h ambulatory systolic BP (SBP) (156±19mmHg; p<0.0001) and nighttime SBP (163±21; p<0.0001). In contrast, they had the lowest daytime SBP (153±19mmHg; p<0.0001) and heart rate (66±11bpm; p<0.0001). Reverse dippers were prescribed the most antihypertensive drugs (5.2±1.7; p=0.0058). 3yrs after RF RDN, significant overall 24-h ambulatory SBP reduction from baseline was observed within all dipping patterns, and the largest reduction was observed within reverse dippers (-11.8±25.1mmHg; Figure), particularly in the nighttime (-21.1±23.8mmHg). Conclusions: Reverse dippers with uncontrolled HTN referred for RDN were prescribed more antihypertensive drugs and had more comorbidities compared to patients with other dipping patterns. After RF RDN, significant SBP changes from baseline were observed irrespective of dipping status. The largest BP reduction was observed in nighttime BP in patients with reverse dipping pattern. RF RDN may offer an effective adjunctive therapy to drugs to lower nighttime BP patients with a reverse dipping pattern, who have the highest risk of cardiovascular events.

SIGNIFICANT NIGHTTIME BLOOD PRESSURE REDUCTIONS AFTER RADIOFREQUENCY RENAL DENERVATION IN PATIENTS WITH UNCONTROLLED HYPERTENSION: POOLED ANALYSIS OF THE SPYRAL HTN TRIALS

Objective: Elevated nighttime systolic blood pressure (SBP) is more strongly associated with risk for cardiovascular events than daytime or office SBP. We assessed whether radiofrequency renal denervation (RF RDN) reduces nighttime SBP, in addition to other times of the day. Design and method: We pooled data from patients with uncontrolled hypertension undergoing RF RDN using the latest-generation Spyral multi-electrode catheter, from the published, SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-ambulatory SBP were evaluated at baseline and at 12 months. Different time ranges were evaluated including nighttime (1am-6am), morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urinary drug testing, where available, was assessed at baseline and at 12 months. Results: Data from 388 patients undergoing RDN were pooled. Patients were 54±10yrs old, 26.8% female, BMI 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% type 2 diabetes, 9.8% obstructive sleep apnea, 16.2% current smoker. The baseline nighttime SBP was 139±11mmHg, and 92.5% had nocturnal hypertension (BP greater than or equal to 120/70 mmHg). Patients took 1.0±1.2 antihypertensive drugs with drug burden of 1.6±3.1 at baseline. 12 months after RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The overall 24-h ambulatory SBP reduced by -11.9±12.4mmHg, nighttime -10.8±15.4mmHg, morning -12.8±20.4mmHg, daytime -12.2±13.6mmHg, and office -17.7±15.4mmHg (Figure). Patients took 1.8±1.1 antihypertensive drugs with drug burden of 2.9±3.0 at 12 months. Conclusions: In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. RF RDN achieved clinically meaningful reductions throughout the 24-hr circadian cycle including the nighttime SBP, when CV risk is highest. RF RDN, in addition to pharmacotherapy, may help to reduce this risk.

DETERMINANTS AND ASSOCIATIONS OF COMMON CAROTID INTIMA-MEDIA ROUGHNESS IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES

Objective: Carotid atherosclerosis, including increased intima-media thickness (IMT) and plaque, is associated with increased cardiovascular (CV) risk. The role of the irregularity of the carotid intima-media surface in terms of total CV risk has been insufficiently investigated. This study investigated determinants and associations of common carotid intima-media roughness in patients with type 2 diabetes and hypertension. Design and method: Adults with type-2 diabetes and hypertension were evaluated with (i) 24h ambulatory blood pressure (ABP) monitoring (20 min intervals, Microlife WatchBPO3), (ii) carotid ultrasonography for the calculation of the common carotid IMT (use of automated software that allows the calculation of the average value of multiple measurements), carotid plaque score (CPS), and standard deviation (SD) of the common carotid intima-media (derived for the multiple measurements performed for the calculation of the IMT), and (iii) ultrasound estimation of left ventricular mass index (LVMI). Results: Ninety-five individuals were analyzed [age 66.3±8.9 years, 61 men, body mass index (BMI) 30.8±4.8 kg/m2, HbA1c 6.6±0.8%, 24-hour ABP (systolic/diastolic) 123±13/69.4±7.3 mmHg, IMT 0.83±0.16 mm, SD IMT 0.07±0.03 mm, CPS 5.5±4.8 mm]. SD IMT was correlated with IMT (r=0.49, p<0.001), nighttime systolic ABP (r=0.21, p<0.05), 24h weighted SD of systolic ABP (r=0.26, p<0.05), CPS (r=0.30, p<0.01) and LVMI (r=0.39, p<0.001). In stepwise multivariable regression analysis with age, nighttime systolic ABP, 24h weighted SD of systolic ABP, total number of IMT measurements and IMT as independent variables, the SD IMT was determined by IMT (β=0.08, p<0.001) and 24h weighted SD of systolic ABP (β=0.003, p<0.05). Conclusions: These preliminary data suggest that in patients with type-2 diabetes and hypertension, carotid intima-media roughness is determined by IMT and the variability of 24h systolic ABP, and is associated with the severity of carotid atherosclerosis and left ventricular hypertrophy.

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

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

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

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

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

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

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

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

Improved health-related quality of life after renal denervation in patients with resistant hypertension: 3-year outcomes in the global symplicity registry

Abstract Background Hypertension is associated with increased mental anxiety and depression. Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled, resistant hypertension (rHTN). The Global SYMPLICITY Registry (GSR) DEFINE is a prospective, open-label, single-arm, all-comer worldwide study, enrolling patients to undergo RDN. Whether BP reductions after RDN improve patients’ self-reported health and quality of life through long-term follow-up remains elusive. Purpose To evaluate changes in self-reported health and quality of life of rHTN patients following radiofrequency RDN. Methods GSR DEFINE patients completed the EuroQoL five-dimensions three-level (EQ-5D) questionnaire to assess their own health state on a visual analog scale (VAS: 0 to 100, with 0 being ‘worst possible’ and 100 being ‘best possible'). Patients were also asked to assess five dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, anxiety/depression at 3 levels: no problems (score: 0), some problems (1), severe problems (2). Patients answered the questionnaire at 6, 12, 24, and 36-month follow-up after the RDN procedure. Categorical measures from the pooled results of the questionnaire between subgroups were compared using the Kruskal-Wallis test. Here we assess the self-reported health state and quality of life measures among patients with rHTN (office systolic BP ≥150 mmHg and on ≥3 antihypertensive drugs) at baseline through 36 months. Results At baseline, GSR patients with rHTN (n=2051) had an office systolic blood pressure (OSBP) of 175.2 ± 19.8 mmHg and a 24-h ambulatory systolic blood pressure (ASBP) of 157.4 ± 18.6 mmHg. At 36 months after RDN, rHTN patients had significant reductions in OSBP (-23.5 ± 27.0 mmHg; n=906; p&amp;lt;0.001) and ASBP (-10.3 ± 20.9 mmHg; n=329; p&amp;lt;0.001), respectively. Antihypertensive medication remained unchanged through 36 months. Correspondingly, patients with rHTN reported a significant improvement in the self-reported health state from baseline after RDN at each follow-up through 36 months (Figure). At baseline (n=1813), patients with rHTN reported a 0.86 ± 0.20 EQ-5D quality of life score. At 36 months (n=839), patients with rHTN reported an improved quality of life with a 0.85 ± 0.21 score which was a statistically significant change from baseline (p=0.0024). Conclusion Following RDN, self-reported health state and quality of life data from a large population of rHTN patients improved from baseline through 36-months. These results suggest that BP reductions following radiofrequency RDN may alleviate mental anxiety and depression associated with hypertension.

Skin sodium content as a predictor of blood pressure response to renal denervation

Patients with treatment resistant hypertension (TRH) are known to have elevated sodium (Na) content in muscle and skin. Renal denervation (RDN) emerged as an adjacent therapeutic option in this group of patients. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN in patients with TRH. Radiofrequency-device based RDN was performed in 58 patients with uncontrolled TRH. Office and 24-h ambulatory BP were measured at baseline and after 6 months. To assess tissue Na content Na magnetic resonance imaging (Na-MRI) was performed at baseline prior to RDN. We splitted the study cohort into responders and non-responders based on the median of systolic 24-h ambulatory blood pressure (ABP) reduction after 6 months and evaluated the association between BP response to RDN and tissue Na content in skin and muscle. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Six months after RDN 24-h ABP decreased by −8.6/−4.7 mmHg. BP-Responders were characterized by the following parameters: low tissue sodium content in the skin (p = 0.040), female gender (p = 0.027), intake of aldosterone antagonists (p = 0.032), high baseline 24-h night-time heart rate (p = 0.045) and high LDL cholesterol (p < 0.001). These results remained significant after adjustment for baseline 24-h systolic BP. Similar results were obtained when the median of day-time and night-time ABP reduction after 6 months were used as cut-off criteria for defining BP response to RDN. We conclude that in addition to clinical factors including baseline 24-h ABP Na-MRI may assist to select patients with uncontrolled TRH for RDN treatment.

The effects of extra virgin olive oil or butter on cardiovascular biomarkers in European and Chinese males in the UK: A pilot randomised crossover trial.

Purpose: No dietary interventional studies have reported the impact of olive oil on cardiovascular risk markers in groups of different ethnic origins. We report a pilot randomised controlled trial of an intervention supplementing extra virgin olive oil (EVOO) on markers of cardiovascular risk among East Asian Chinese, and European Caucasian individuals. Methods: A cross-over, randomised controlled dietary intervention for 2 weeks was undertaken. Thirty-two adults, healthy, individuals of Chinese and European origin took part in this study. 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), and blood lipids, were assessed. Results: Positive benefits of EVOO consumption were observed in all participants. Lower 24-h ambulatory SBP (-4.3 mmHg; p = 0.020), and day-time SBP (5.528 mmHg; p = 0.008), night-time DBP (-3.784 mmHg; p = 0.008) and night-time MAP (-3.747 mmHg; p = 0.007) were seen in all participants independently of covariates. In addition, total cholesterol (7.9 mg/dL; p = 0.017) and LDL-cholesterol (6.5 mg/dL; p = 0.028) were increased with butter but not with olive oil. No significant difference in other cardiovascular risk factors were observed. However, differences were observed between Caucasians and East Asian individuals in the absence of significant differences in lifestyle. Conclusion: This pilot study suggests that consumption of EVOO should be advocated as a healthier dietary fat and recommended to replace butter as a dietary strategy to improve cardiovascular health in both Caucasians and East Asian individuals.

OFFICE BLOOD PRESSURE VARIABILITY AND INSTABILITY IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS: ASSOCIATION WITH PRECLINICAL ORGAN DAMAGE

Objective: To evaluate the association of systolic blood pressure (SBP) variability and instability within a single office visit with preclinical target organ damage in young individuals. Design and method: Apparently healthy individuals aged 6-25 years referred for elevated blood pressure (BP) were subjected to triplicate office BP measurements in a single visit and 24h ambulatory BP monitoring. SBP variability and instability were quantified using (i) standard deviation (SD) (ii) coefficient of variation (CV) (iii) average real variability (ARV) (iv) maximum office SBP (v) maximum-minimum office SBP difference (MMD) (vi) ratio of difference between 1st-3rd measurement to the average office SBP (Relative change). Preclinical organ damage was evaluated by (i) carotid intima-media thickness (cIMT), (ii) carotid-femoral pulse wave velocity (PWV; Complior device), and (iii) echocardiographic left ventricular mass index (LVMI). Results: 301 individuals were analyzed (mean age 13.8±3.7 years, 66.8% males, BMI z-score 1.12±0.95, average office BP 122.6±16.9/72.5±10.7 mmHg, 24h ambulatory BP 119.1±11.4/67.8±6.8 mmHg). LVMI measurements were available in 258 participants, IMT in 208 and PWV in 60. LVMI, IMT and PWV were associated with office SBP (r = 0.30/0.23/0.42, respectively, p&lt; = 0.001), 24h ambulatory SBP (r = 0.35/0.33/0.48, p&lt; = 0.001) and maximum office SBP (r = 0.31/0.30/0.41, p&lt; = 0.001). LVMI and IMT were associated with SD (r = 0.14/0.15, p&lt;0.05) and MMD (r = 0.13/0.15, p&lt;0.05), while IMT and PWV with age (r = 0.31/0.38, p&lt;0.001). Other indices of variability were not associated with indices of organ damage. In stepwise multivariable linear regression models (independent variables: age, sex, BMI z-score, office SBP, 24h ambulatory SBP, maximum office SBP, SD, MMD), LVMI was determined by BMI z-score and 24h ambulatory SBP, IMT by age, male sex and 24h ambulatory SBP, and PWV by 24h ambulatory SBP. Conclusions: These results suggest that in young individuals the variability and instability of office SBP within a single visit are not associated with preclinical organ damage.

NOCTURNAL BLOOD PRESSURE DIPPING AND PRECLINICAL TARGET ORGAN DAMAGE IN YOUNG INDIVIDUALS

Objective: A blunted nighttime blood pressure (BP) decrease (non-dipping) has been linked to increased cardiovascular risk. Relevant research data in children and adolescents are scarce with most studies conducted in young individuals with medical conditions, e.g., diabetes. This study investigated the relationship of nighttime dipping with indices of preclinical target organ damage (TOD) in young individuals. Design and method: Individuals referred for suspected hypertension and healthy volunteers aged 6-25 years were evaluated with 24h ambulatory BP (ABP) monitoring. The nighttime BP dip was quantified as the percentage BP decline as compared to the daytime value. Non-dippers were defined as those with systolic and/or diastolic nighttime dip &lt;10%. TOD was assessed by echocardiographic left ventricular mass index (LVMI) and ultrasonographic determination of intima-media thickness of the common carotid artery (IMT). Results: 276 individuals were included (13.8±3.8 years, 67% males, 31.2% children, 56.1% adolescents, 12.7% adults, 3.3% healthy volunteers, BMI z-score 1.18±0.96, 37.4% obese, 25.7% with elevated 24h ABP, 27.9% with elevated nighttime BP). LVMI measurements were available in 257 and IMT in 205. The average systolic/diastolic dip was 12.1±4.7/19.6±6.3% and 30.4% of participants were classified as non-dippers. TOD indices were higher in non-dippers than in dippers (LVMI 30.5±8.2 versus 28.4±5.9 g/m2.7; IMT 0.517±0.054 versus 0.500±0.053 mm, p&lt;0.05 for both). In linear regression analysis, non-dipping was independently associated with LVMI (↓ = 2.14, p = 0.01) and IMT (↓ = 0.02, p = 0.02), after adjustment for sex, age, BMI z-score and 24h systolic ABP. However, after adjustment for the nighttime BP levels (instead of 24h ABP) this association lost its statistical significance. Conclusions: These data suggest that in young individuals nocturnal non-dipping is associated with TOD, but not after accounting for the nighttime BP levels.

RELATIONSHIPS OF OFFICE, AMBULATORY, AND HOME BLOOD PRESSURE WITH ORGAN INJURY BIOMARKERS

Objective: International guidelines recommend out-of-office blood pressure (BP) monitoring including ambulatory and home BP. Although the superiority of ambulatory and home BP is controversial, home BP is more prevalent in plactice and there is a gap with the guidelines. We assessed this issue by conducting the analysis of relationship of BP with clinical biomarkers. Design and method: We analyzed the relationship of office, ambulatory, and home BP with organ injury biomarkers including urine-albumin creatinine ratio (UACR), serum b-type natriuretic peptide (BNP), serum high-sensitive troponin T (hsTnT), echocardiographic left ventricular mass index (LVMI), and brachial-ankle pulse wave velocity (baPWV) in 1,172 outpatients who underwent both ambulatory and home BP measurements and examined serum and urine tests and others. Results: In the univariate analysis of Pearson's correlation, average of morning and evening home systolic BP (SBP) was strongly related with log-transformed BNP, log-transformed hsCRP, LVMI, and baPWV compared with 24-h ambulatory systolic BP (log-transformed UACR [n = 1432], r = 0.24 in home SBP versus r = 0.18 in ambulatory SBP, P = 0.17 in z-test for comparison of these correlations; log-transformed BNP [n = 1432], r = 0.17 vs. r = -0.04, P&lt;0.01; log-transformed hsTnT [n = 1092], r = 0.19 vs. r = -0.03, P&lt;0.01; LVMI [n = 1036], r = 0.23 vs. r = 0.10, P&lt;0.01; baPWV [n = 1361], r = 0.31 vs. r = 0.08, P&lt;0.01). In the multivariable linear regression models for log-transformed BNP, log-transformed hsTnT, and LVMI, the model-fit were improved when adding home SBP to the model including 24-h ambulatory SBP, but these relationships were not shown in vice versa. In addition, we also used Structural Equation Modeling for assessment of relationship of office, ambulatory, and home SBP with clinical biomarkers. Conclusions: Our findings suggested the superiority of home BP in the relationship with several biomarkers for hypertensive organ damage compared with ambulatory BP, which may provide a rationale for the management on hypertension using home BP monitoring in clinical practice conducted in many countries including Japan.

EXERCISE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION: A SYSTEMATIC REVIEW WITH META-ANALYSIS

Objective: High grade evidence supports exercise as a key therapy in the prevention and management of hypertension. Yet, the lack of a meta-analysis on the effects of exercise on ambulatory blood pressure monitoring (ABPM) in patients with hypertension was identified as an important research gap in the 2022 consensus document from the European Association of Preventive Cardiology and the ESC council on Hypertension. Therefore, we performed a meta-analysis to investigate the effects of exercise on blood pressures measured by means of ABPM, in patients with arterial hypertension or high-normal blood pressure (BP). Design and method: A systematic literature search was performed in three databases from inception to October 2021. Randomized controlled trials involving exercise training of at least 4 weeks, in adults with a high-normal BP or arterial hypertension, were included. Trials had to report data on daytime, nighttime or 24-h ambulatory systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Primary outcomes were changes in 24h, daytime and nighttime ABP. Pooled effect sizes are reported as weighted mean with 95% confidence intervals (CI). Results: We included 24 trials, involving 23 aerobic training interventions and 4 resistance exercise interventions. A total of 1668 participants were included: 942 in exercise groups, 726 as controls. Table 1: Pooled effect size, 95% CI and p-value of different exercise types on 24h, daytime and nighttime BP: Only 67 participants and 35 controls were included in resistance exercise protocols. In this subpopulation, results for 24h, daytime or nighttime BP were insignificant (p&gt;0.05). Funnel plots for 24h, daytime and nighttime BP did not show any significant publication bias. Conclusions: Exercise therapy reduces 24h BP in patients with arterial hypertension or high normal blood pressure. The effect is more pronounced on daytime than on nighttime BP. The results of this meta-analysis are mostly driven by trials examining aerobic exercise. More trials are needed on the effect of resistance exercise on ABPM.

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