Ambulatory Systolic Blood Pressure Research Articles

Isometric handgrip versus aerobic exercise: a randomized trial evaluating central and ambulatory blood pressure outcomes in older hypertensive participants.

It remains unclear whether the hemodynamic effects of isometric handgrip exercise (IHG) are comparable to those of aerobic exercise (AE). This study investigated the efficacy of IHG in reducing central and ambulatory blood pressure in older hypertensive participants and compared its effects with AE. In a three-arm randomized controlled trial, 54 older hypertensive participants (age range: ≥60; mean age: 69 years) underwent 12 weeks of either IHG training (n = 17), AE training (n = 19), or were part of a no-exercise control group (n = 18). IHG participants engaged in bilateral handgrips using a digital device, four times for 2 min each at 30% of maximal voluntary contraction. AE participants undertook brisk walking and cycling exercises at moderate intensity for 30 min, thrice weekly. Baseline and postintervention measurements included resting office, central, and 24-h ambulatory blood pressures. Both IHG and AE interventions led to significant reductions in office and ambulatory systolic blood pressure compared to control group (P < 0.05 for both), with no marked difference in the magnitude of systolic blood pressure reductions between the two groups. Notably, the IHG group exhibited greater reductions in office, central, and ambulatory diastolic blood pressure compared to the AE group and control group. While both IHG and AE effectively lowered ambulatory systolic blood pressure, IHG demonstrated superior efficacy in reducing central and ambulatory diastolic blood pressure. Consequently, IHG training presents a promising alternative antihypertensive therapy for hypertensive participants over the age of 60.

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): &amp;lt;45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups &amp;lt;45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group &amp;lt;45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p&amp;lt;0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p&amp;lt;0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p&amp;lt;0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p&amp;lt;0.001). Between group differences in eGFR changes were statistically significant (adjusted p&amp;lt;0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR &amp;lt;45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive

Abstract Background Zilebesiran is an investigational RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In KARDIA-1, a single subcutaneous (SC) dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The Phase 2 KARDIA-2 study assessed efficacy and safety of zilebesiran with a standard oral antihypertensive in patients with uncontrolled hypertension. Purpose Uncontrolled hypertension is a leading cause of cardiovascular morbidity and mortality, and medication non-adherence affects blood pressure control. Developing effective, long-lasting treatments is crucial for patients with hypertension uncontrolled by standard therapy. Methods KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with ≤2 antihypertensives. Patients discontinued prior antihypertensive medication and were randomized 10:7:4 to open-label, once-daily oral treatment with 40 mg olmesartan, 5 mg amlodipine, or 2.5 mg indapamide. After ≥4 weeks on protocol-specified medication, patients with a 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 in a double-blind manner to a single SC dose of zilebesiran 600 mg or placebo as add-on therapy. The primary endpoint was change from baseline to Month 3 in 24-hr mean ambulatory SBP versus placebo for each group. Efficacy and safety were also assessed in pre-specified subgroups: age (&amp;lt;65; ≥65 years), sex, race (Black; other), baseline 24-hr mean ambulatory SBP (&amp;lt;145; ≥145 mmHg), and baseline estimated glomerular filtration rate (≥60; &amp;lt;60 mL/min/1.73m2). Results The primary analysis included 667 patients (median age [range] 59 [27–75] years; 57% male, 28% Black). At Month 3, least-squares mean differences (LSMD) (95% confidence interval [CI]) between zilebesiran and placebo for the olmesartan, amlodipine, and indapamide groups were −4.0 (−7.6, −0.3), −9.7 (−12.9, −6.6), and −12.1 (−16.5, −7.6) mmHg, respectively, for 24-hr mean ambulatory SBP (all p&amp;lt;0.05). LSMD (95% CI) in office SBP for the same groups were −7.0 (−10.4, −3.6), −10.2 (−13.5, −6.9), and −18.5 (−22.8, −14.2) mmHg, respectively, (all p&amp;lt;0.001). SBP reductions were consistent across subgroups, except for a trend towards an attenuated response observed in Black patients (Figs 1, 2). More patients receiving zilebesiran (49–58%) than placebo (39–48%) experienced ≥1 adverse event through Month 6, with low rates of hyperkalaemia, hypotension, or acute kidney injury reported across all groups. Conclusion In KARDIA-2, a single dose of zilebesiran significantly reduced SBP versus placebo at Month 3 on top of a standard oral antihypertensive, with encouraging safety data. SBP reduction was consistent across most subgroups. Treatment with zilebesiran combined with standard antihypertensives may be effective for a broad population of patients with hypertension uncontrolled on monotherapy.

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.

Treatment optimisation for blood pressure with single-pill combinations in India (TOPSPIN) – Protocol design and baseline characteristics

BackgroundThe burden of over 300 million individuals living with hypertension in India is increasing steadily. Most current guidelines recommend initial combination therapy for effective blood pressure (BP) control. However, there is no randomised evidence to inform which combinations to use in the South Asian population, who account for over one-quarter of the world's population. MethodsThis multi-centre, single-blind, randomised, three-arm trial recruited men and women aged 30–79 years with hypertension. The trial compares the efficacy of commonly recommended single pill combinations (SPCs) of three drug classes – calcium channel blocker (amlodipine), ACE inhibitor (perindopril), and a thiazide-like diuretic (indapamide). The primary objective is to determine the most effective two-drug combination, initially at starting doses with forced up-titration at 2 months, in reducing 24-h ambulatory systolic blood pressure (ASBP) at 6 months. The trial has 85 % power to detect a difference of 3 mmHg in 24-h ASBP amongst the groups.Participant recruitment took place from August 2022 to February 2024. Baseline resultsThe 1981 participants (42.0 % women) enrolled had a mean age of 52.1 (SD 11.3) years and a mean body mass index of 26.5 (SD 4.2) kg/m2. 58.1 % of participants had a previous diagnosis of hypertension and 18.6 % of participants were known to diabetes. The mean ASBP was 135.6 (SD 17.0) mmHg, and the mean ambulatory diastolic BP was 84.5 (SD 10.9) mmHg. ConclusionThe TOPSPIN trial is the first randomised evaluation of commonly used BP-lowering combination therapies in a South Asian population. The results have potentially significant implications for choosing first-line antihypertensive agents among Indians and the South Asian diaspora.

Effects of probiotics and fibers on markers of nephropathy, inflammation, intestinal barrier dysfunction and endothelial dysfunction in individuals with type 1 diabetes and albuminuria. The ProFOS Study

AimsTo estimate whether a mix of pre- and probiotics would strengthen the gut barrier and protect the kidneys in individuals with type 1 diabetes and albuminuria. MethodsRandomized, placebo-controlled, crossover study. Forty-one participants received synbiotic (pre- and probiotics) mix or placebo for 12 weeks with 6 weeks washout. Primary endpoint was change from baseline to end-of-period in UACR. Secondary endpoints were changes in endothelial glycocalyx thickness, inflammatory and intestinal barrier dysfunction markers, glomerular filtration rate (GFR) and ambulatory systolic blood pressure. ResultsThirty-five participants completed the study. Mean age was 58 (SD 10) years, 73 % (n = 30) were male, median UACR was 134 (IQR 63–293) mg/g, estimated GFR was 75 (30) ml/min/1.73m2. There was no significant difference in UACR with a mean relative change (CI 95 %) from baseline to end-of-treatment of −3.0 (−18.4; 15.5) % in the synbiotic group and −12.0 (−29.6; 9.6) % in the placebo group with no significant difference between treatment periods (9.37 (−25.2; 44.0) percentage points; p = 0.60). No significant beneficial difference in the secondary end points was demonstrated. ConclusionTwelve weeks treatment with synbiotic mix had no effect on UACR or on any of the secondary endpoints in subjects with type 1 diabetes and albuminuria.

Long-term safety and efficacy of endovascular ultrasound renal denervation in resistant hypertension: 8-year results from the ACHIEVE study.

Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2months. Beyond 3years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN. This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24h ambulatory SBP ≥130mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m2 undergoing uRDN. The primary efficacy outcome was 24h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting. A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6-8.9]years. Mean age was 62.6±9.3years (37.0% female). Preprocedural 24h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3-7.0]. At 8years after uRDN, the change in 24h ambulatory SBP was -19.5 [95%CI -26.7,-12.4] mmHg (p<0.001). The 8-year change in the number of DDDs was -1.7 [-2.8,-0.6] (p = 0.003). The 8-year decline in eGFR was -8.9 [-13.2,-4.7] ml/min/1.73m2 (p<0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0-8.0]years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected. A significant BP reduction was observed up until 8years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events.

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy. This multicenter prospective study evaluates the changes in ABP after 12weeks of dapagliflozin 10mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25mL/min/1.73 m2. Primary endpoint was the change of nighttime systolic blood pressure (SBP). Changes of daytime SBP, prevalence of normal dipping (day/night SBP ratio <0.9) and changes in ABP patterns, that is, sustained uncontrolled hypertension (SUCH), white coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and controlled hypertension (CH) were secondary endpoints. Eighty-three of 96 patients completed the study [age 68.7±8.9 years, 73.5% males, GFR 49±17mL/min/1.73 m2, median albuminuria: 0.18 (interquartile range 0.10-0.38) g/24h]. After 12weeks of dapagliflozin, nighttime SBP declined by -3.0mmHg (95% confidence interval -5.2/-0.8mmHg; P=.010) with an improvement of nighttime SBP goal (<110mmHg) from 18.0% to 27.0% (P<.001). Similarly, the prevalence of normal dipping increased (from 31.3% to 50.6%, P=.005). A decrease in daytime (-2.4mmHg; P=.046) and office (-7.9mmHg; P=.009) SBP was also found. The decline of ambulatory and office SBP was associated with increased prevalence of CH (from 6.0% to 18.0%) and significant improvement of SUCH, WUCH and MUCH (P=.009). Albuminuria decreased (P<.001), whereas eGFR did not change (P=.297). Urinary tract infection (4.2%) and acute kidney injury (3.6%) were the main causes of drop-out. Only one patient showed a drop of nighttime SBP below 90mmHg. Dapagliflozin is associated with improvement in circadian blood pressure rhythm with no major safety signal related to excessive blood pressure decrease.

Systematic Review and Meta-Analysis of Second-Generation Sham-Controlled Randomized Trials of Renal Denervation Therapy for Patients with Hypertension.

Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

The association of obesity and hyperuricemia with ambulatory blood pressure in children.

Primary hypertension (HTN) in children is on the rise and linked to the childhood obesity epidemic. Recent studies support the role of hyperuricemia in the pathogenesis of HTN. With this study we intend to evaluate the effect of body mass index (BMI) and uric acid levels on daily blood pressure (BP) parameters/phenotypes and target organ damage (TOD). A mean ambulatory systolic and/or diastolic BP ≥ 95th percentile or above the adolescent cut points was defined as 'HTN'. Patients were grouped as group 1 normal weight, and group 2 overweight/obese. Of the 140 children (89 male/51 female) with a mean age of 13.9 ± 2.6years, 21 were overweight and 86 were obese. Mean 24-h systolic BP (SBP) and daytime SBP were higher in group 2 (p = 0.015, p = 0.011). BMI was positively correlated with 24-h SBP (r = 0.272, p = 0.001) and daytime SBP (r = 0.280, p = 0.001). Uric acid level showed a moderate correlation with daytime SBP (r = 0.311, p < 0.01). Logistical regression analysis showed that daytime SBP is independently associated with obesity (OR 7.44, 95%CI 2.7-20.6, p < 0.001) and male sex (OR 4.60, 95%CI 2.0-10.2, p < 0.001), but not uric acid. Left ventricular hypertrophy was more common in non-dippers (p = 0.044). Male sex and BMI are independently associated risk factors for systolic BP. The association between non-dipping pattern and TOD suggests the widespread use of ambulatory blood pressure monitoring (ABPM) in childhood HT. In this paper, we could not demonstrate an independent association between uric acid and SBP. The effect of uric acid on SBP seems to be regulated by other metabolic factors in addition to uric acid.

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.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is a sham-controlled trial investigating the safety and efficacy of RDN in China. This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; Shanghai Angiocare Medical Technology, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02901704.

O89 POOLED, LONG-TERM ANALYSIS OF THE GLOBAL SYMPLICITY CLINICAL TRIAL PROGRAM OF RADIOFREQUENCY RENAL DENERVATION FOR THE TREATMENT OF UNCONTROLLED HYPERTENSION

Background/Objective: The Global Symplicity Clinical program is the largest investigation of radiofrequency renal denervation (RDN) to treat uncontrolled hypertension (HTN) to date. Over 4,000 patients enrolled into Spyral First-in-Man, Global SYMPLICITY Registry DEFINE, and multiple randomized, controlled and sham controlled trials including HTN-Japan, Symplicity HTN-3, SPYRAL HTN-OFF and -ON MED studies. We leveraged the entire Symplicity Global Clinical program dataset to develop a multivariate, patient-level, mixed model assessing (1) long-term BP reductions after RDN, and (2) whether specific patient characteristics correlate with future BP reductions after the procedure. Methods: Repeated BP measurements from each patient in the Global Symplicity Clinical program were analyzed using linear mixed models fitted with 24-h ambulatory systolic (S)BP and office SBP as outcome variables. Baseline SBP, baseline number of antihypertensive (AH) medications, and AH medications over time were included as fixed effects. Additional patient characteristics were included as potential significant fixed effects. To account for multiple BP measurements per patient and multiple studies, nested random effects were included using an auto-regressive correlation structure. Results: Data from 4156 patients treated with either the first-generation Symplicity Flex or the next-generation Symplicity Spyral catheter. Estimated, office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic with a steep reduction after RDN through the first 6 months (Figure), followed by a steady reduction in SBP afterward through 36 months. Higher baseline SBP was correlated with greater BP reductions. AF history (-3.7 mmHg compared to no AF, p=0.0048) and increasing eGFR at baseline (-0.039 mmHg for every 1 ml/min increase in baseline eGFR, p=0.040) significantly correlated with lower 24-h ambulatory SBP. Conclusion: This is the most comprehensive analysis of radiofrequency RDN to date. Higher baseline SBP was strongly correlated with greater BP reductions. The results demonstrate the durability of RDN as an adjunctive therapy to treat HTN. Prospective studies need to validate whether certain patient characteristics are associated with improved response to RDN.

Changes in blood pressure after catheter-based renal denervation in South Africa.

Renal denervation (RDN) is an interventional treatment for patients with uncontrolled hypertension. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, world-wide registry designed to assess the safety and efficacy of RDN. We evaluated the outcomes in South African patients in the GSR over 12 months. Eligible patients with hypertension had a daytime mean blood pressure (BP) > 135/85 mmHg or night-time mean BP > 120/70 mmHg. Office and 24-hour ambulatory systolic BP reduction and adverse events over 12 months were evaluated. South African patients (n = 36) in the GSR had a mean age of 54.4 ± 9.9 years with a median of four prescribed antihypertensive medication classes. At 12 months, mean changes in office and 24-hour ambulatory systolic BP were -16.9 ± 24.2 and -15.3 ± 18.5 mmHg, respectively, with only one adverse event recorded. RDN safety and efficacy in South African patients were consistent with world-wide GSR results.

Abstract P442: Impact of arterial stiffness on the blood pressure lowering effect of the dual endothelin antagonist aprocitentan in patients with resistant hypertension

Background: The phase-3 PRECISION study demonstrated the efficacy of aprocitentan to lower both office and ambulatory blood pressure (BP) in patients with resistant hypertension. Increased arterial stiffness has been associated with less favorable responses to pharmacologic BP lowering therapies. In this post-hoc analysis, we investigated the impact of arterial stiffness, assessed by the ambulatory arterial stiffness index (AASI), on the BP lowering effect of aprocitentan. Methods: The study included a 4-week double blind period (aprocitentan 12.5 mg, 25 mg, or placebo) and a 32-week single blind period (aprocitentan 25 mg). A total of 730 patients with resistant hypertension were randomized and 633 had available ambulatory BP monitoring (ABPM) results at baseline. The AASI was calculated from ABPM data as 1 minus the regression slope of diastolic on systolic BP. The patient population was dichotomized into two groups according to the baseline median AASI. Results: Patients with higher baseline AASI (≥0.54) tended to be older (63±11 versus 60±10) and to have a higher 24-hour ambulatory systolic BP (140±14 versus 135±14 mmHg) than patients with lower AASI (&lt;0.54). These patients with higher baseline AASI were also more likely to have chronic kidney disease stage 3-4 corresponding to an estimated glomerular filtration rate in the 15 to 60 mL/min/1.73 m 2 range (27% versus 18%). The BP lowering effect of aprocitentan at Week 4 was similar for both the patients with stiffer vasculature who have a higher baseline AASI (≥0.54) and for those with a lower AASI (&lt;0.54) (Table 1). No relevant change in AASI was reported with aprocitentan treatment at Week 4 (end of the double-blind period) or Week 36 (end of the single-blind period). Conclusion: Aprocitentan is an effective BP lowering therapy across the arterial stiffness continuum observed in patients with resistant hypertension. Longer observation times are needed to fully assess the impact of treatment on this structural and functional parameter.

Abstract P386: Predictors of Home Blood Pressure Response to Ultrasound Renal Denervation

Background: Out-of-office blood pressure measurements are recommended for hypertension (HTN) management. The RADIANCE clinical trial program showed that ultrasound renal denervation (uRDN) significantly reduces daytime ambulatory systolic blood pressure (SBP) in patients with mild-to-moderate HTN (RADIANCE-HTN SOLO, RADIANCE II) and resistant HTN (RADIANCE-HTN TRIO). Previous analyses have assessed predictors of daytime ambulatory SBP response at 2-months. This analysis assessed predictors of home SBP (HSBP) at 2-months. Method: This analysis included 250 patients who were randomized to and received uRDN and were treated per-protocol. Separate linear regression models were used to assess predictors of the change in HSBP at 2-months. Multivariable regression analysis was conducted including variables with p-value&lt;0.20. Backward selection with a stay criterion of 0.20 was used to select the predictors for the final multivariable analysis. Study was pre-defined as a covariate in the final model. Results: Patients were 69% male and 76% white; average age was 53.9 years and baseline office BP 155.5/101.5 mmHg. The only significant predictor (p&lt; 0.05) resulting from the separate linear regression models adjusting for cohort was baseline HSBP. Other predictors included in the multivariable analyses (p&lt;0.20) were sex, black race, screening medications(Y/N), orthostatic HTN, and right renal artery diameter. In the multivariable analyses, baseline HSBP was the only significant predictor of change in HSBP at 2-months (p=0.009, See Table). Conclusions: In this analysis of response to treatment with uRDN using home BPs, baseline HSBP was the only consistent significant predictor of response. Baseline BP value as a predictor of RDN response is consistent with prior analyses.

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 &gt;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&lt;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.

Associations of 24-Hour Central Systolic Blood Pressure With Multiorgan Damage in Nondialysis Patients With Chronic Kidney Disease.

Multiple target-organ damages (TODs) in the same patient are common and further increase the risk of cardiovascular disease. However, the relationship between ambulatory central systolic blood pressure (SBP) and multiple TODs has yet to be explored. MobilO-Graph PWA was used to monitor the participants' ambulatory blood pressure, and the presence of left ventricular hypertrophy, carotid hypertrophy, and kidney injury were used to define TOD. Logistic regression analyses and receiver operating characteristic analyses were used to explore the correlation between SBP and TOD. Overall, 2018 nondialysis patients with chronic kidney disease were included and 580 (28.74%) had multiple TODs. Twenty-four-hour central SBP with c2 calibration exhibited a stronger correlation with the increasing number of TOD compared with 24-hour brachial SBP in ordinal logistic regression analyses. In the multivariable analyses with the presence of multiple TODs, the odds ratios were 1.786 (95% CI, 1.474-2.165; P<0.001) for 24-hour brachial SBP and 1.949 (95% CI, 1.605-2.366; P<0.001) for 24-hour central SBP with c2 calibration. The receiver operating characteristic analyses also showed that 24-hour central SBP with c2 calibration had higher discrimination than 24-hour brachial SBP regarding multiple TODs (P<0.001). In addition, using 130/135 mm Hg as the threshold for 24-hour brachial SBP/central SBP with c2 calibration to cross-classify, the prevalence of multiple TODs was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension, with no difference between the latter 2 conditions. Twenty-four-hour central SBP with c2 calibration was more associated with the presence of multiple TODs compared with 24-hour brachial SBP and was helpful in risk classification of multiple TODs among nondialysis patients with chronic kidney disease.

Randomized Trials of Renal Denervation for Uncontrolled Hypertension: An Updated Meta-Analysis.

Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter-based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta-analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications. Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham-controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24-hour ambulatory (-3.70 [95% CI, -5.41 to -2.00] mm Hg), office (-4.76 [95% CI, -7.57 to -1.94] mm Hg), and home (-3.28 [95% CI, -5.96 to -0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24-hour ambulatory (-2.23 [95% CI, -3.56 to -0.90] mm Hg), office (-6.39 [95% CI, -11.49 to -1.30]), home (-6.08 [95% CI, -11.54 to -0.61] mm Hg), daytime (-2.62 [95% CI, -4.14 to -1.11]), and nighttime (-2.70 [95% CI, -5.13 to -0.27]) systolic blood pressures, as well as 24-hour ambulatory (-1.16 [95% CI, -1.96 to -0.35]), office (-3.17 [95% CI, -5.54 to -0.80]), and daytime (-1.47 [95% CI, -2.50 to -0.27]) diastolic blood pressures. RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham-controlled trials and contemporary trials using US Food and Drug Administration-approved devices.

Cardiovascular effects of dog appeasing pheromone in the hospital environment

Recent research has emphasized the health implications of acute or chronic stress in animals. Hospitalized dogs are susceptible to stress due to various factors, including exposure to a novel environment, invasive procedures, and separation from their primary caregiver. The clinical significance of stress in these animals underscores the importance of stress management from the moment of admission. However, there remains a lack of universal qualitative and quantitative indicators of stress in small animals, necessitating reliance on behavioral analysis and stress marker assessment for accurate diagnosis. Among these markers, cardiovascular parameters such as heart rate and systolic blood pressure are commonly used, although their interpretation can be influenced by various factors. The aim of the study was to assess the impact of appeasing pheromone on cardiovascular parameters in hospitalized dogs. Ten healthy dogs were selected for a prospective, paired, randomized, and double-blinded. The dogs were submitted to two experimental protocols: pheromone administration and placebo. The cardiovascular parameters were evaluated at baseline until the end of a 24-hour hospitalization period. The study evaluated ambulatory electrocardiography and systolic non-invasive blood pressure using a doppler. Analysis of cardiovascular parameters revealed no significant difference in systolic blood pressure between groups, despite its elevation in both treatment conditions. In the placebo group, the maximum heart rate of the placebo group at time baseline (T0) was lower compared to subsequent time points (T6, T12, T20), indicative of stress upon arrival in the hospital environment. Conversely, the pheromone group showed a higher mean heart rate at T20 compared to the placebo group. Additionally, the placebo group displayed a higher minimum heart rate at time baseline (T0) compared to later time points (T6, T12, T20, T24). At time T6, a higher minimum heart rate was observed in the pheromone group. Even though fluctuations were observed in mean and minimum heart rates during monitoring, they indicated no clinically relevant deviations. There was no difference in heart rate variability over time between the analyzed substances. Exposure to dog appeasing pheromone through a diffuser presentation, therefore, did not lead to significant changes in cardiovascular parameters related to stress reduction in hospitalized dogs.