Daytime Ambulatory Systolic Blood Pressure Research Articles

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

TEN YEAR FOLLOW-UP OF PATIENTS WITH RESISTANT HYPERTENSION RANDOMIZED TO RENAL DENERVATION OR ANTIHYPERTENSIVE DRUG TREATMENT

Objective: Renal denervation (RDN) is a treatment option in resistant hypertension. The procedure is considered safe, although randomized trials only demonstrate a moderate blood pressure (BP) lowering effect, when considering medication adherence. Some observational studies describe reduction in BP several years after the procedure. The aim of the study was to describe long-term safety and potential benefits of RDN after ten years, compared to optimized drug treatment, measuring serum concentration of antihypertensive drugs to ensure adherence. Design and method: We report data from ten year follow-up of patients randomized to RDN (n=9) or drug adjustment (n=10). Initially the patients had treatment-resistant hypertension, defined as daytime systolic ambulatory BP >= 135 mmHg after witnessed intake (directly observed therapy, DOT) of >= 3 antihypertensive drugs including a diuretic and therefore considered as adherent. One year after RDN or drug adjustment, we optimized antihypertensive medication for all patients. Thereafter, patients received appropriate antihypertensive treatment in primary or secondary care, according to their BPs. Patients were informed of serum concentration measurements performed at the 7-year visit. At the 10-year visit, serum drug measurements before DOT and ambulatory BP measurement (ABPM) were used for evaluation of adherence. Antihypertensive agents were registered, glomerular filtration rate (eGFR) was estimated by the CKD-EPI formula using creatinine and Cystatin C, and renal arteries were examined by CT or MRI. Results: All living patients (n=18) attended the 10-year visit, now mean age 69 years, using 4±2 antihypertensive agents, with no difference between groups. Serum concentrations confirmed that all patients were adherent to reported medication. There were significant and similar BP reductions in both groups compared to baseline; daytime ABPM -22±15/9±8 mmHg in the RDN group, and -20±15/13±7 mmHg in the control group (figure). No patients developed renal artery stenosis. The decrease in eGFR was similar in both groups. Conclusions: To our knowledge this is the RCT with the longest follow-up supporting long-term safety of RDN in patients with resistant hypertension. Daytime ABPM improved during 10 years of follow-up, not explained by RDN, but due to adjustments in antihypertensive regimens and probably better adherence to medication.

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage

Introduction Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. Design and methods Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. Results Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05–2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34–0.95), p = 0.03). Conclusions None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

Agreement Between Guideline Thresholds Using an "All-in-One" Device to Measure Office, Home, and Ambulatory Blood Pressures.

Blood pressure (BP) thresholds for diagnosing and managing hypertension vary for office, home, and ambulatory readings, and between guideline documents. This analysis determined corresponding office, home, and ambulatory BP thresholds using baseline data from the HI-JAMP (Home-Activity Information and Communication Technology-Based Japan Ambulatory Blood Pressure Monitoring Prospective) study, which used a validated "all-in-one" BP monitoring device. Data from 2322 treated patients with hypertension who underwent office BP measurement, then 24-hour ambulatory BP monitoring, then home BP monitoring for 5 days were analyzed. Corresponding BP thresholds for office, home, and ambulatory measurements were determined using Deming regression. Values equivalent to office systolic BP (SBP) of 120 and 140 mm Hg were as follows: 115.9 and 127.7 mm Hg for 24-hour ambulatory SBP; 120.8 and 134.0 mm Hg for daytime ambulatory SBP; 104.9 and 117.9 mm Hg for nighttime ambulatory SBP; and 122.0 and 134.2 mm Hg for morning-evening average home SBP. Deming regression showed that morning-evening average home SBP and daytime ambulatory SBP were almost the same (home SBP=0.99×daytime ambulatory SBP+0.27 mm Hg; r=0.627). Morning-evening average home SBP values of 120 and 135 mm Hg were equivalent to daytime ambulatory SBP values of 119.1 and 133.9 mm Hg, respectively. A home SBP threshold of 130 mm Hg corresponded to 24-hour and nighttime ambulatory SBP values of 123.5 and 113.6 mm Hg, whereas a home SBP threshold of 135 mm Hg corresponded to 24-hour and nighttime ambulatory SBP values of 128.0 and 119.2 mm Hg. Ambulatory and home BP thresholds in this analysis were similar to those proposed by existing guidelines. The similarity between the home BP and daytime ambulatory BP thresholds was a clinically relevant finding.

EFFECT OF BAROREFLEX ACTIVATION THERAPY ON BLOOD PRESSURE: THE BAT-STUDY – A RANDOMIZED SHAM CLINICAL PILOT TRIAL

Objective: To explore the effects of baroreflex activation therapy (BAT) on blood pressure in individuals with refractory hypertension. Design and method: This investigator-initiated randomized, double-blinded sham-controlled pilot trial included five Finnish patients with refractory hypertension. Participants were found eligible if they were 18 - 70 years old with a daytime systolic ambulatory blood pressure (ABP) of 145 mmHg or higher, and/or a daytime diastolic ABP of 95 mm Hg or higher. Patients were on 3 or more antihypertensive drugs including a diuretic. A witnessed drug intake prior to ABPM was implemented. The Barostim Neo System was implanted for modulation of the autonomic nervous system by direct electrical stimulation of the carotid baroreceptors. After 1 month following implantation, all participants were randomized to either 8 months of baroreflex activation therapy (BAT-system on) or continuous pharmacotherapy (BAT-system off) followed by continuous BAT-therapy for all participants for 8 months. The complete design is outlined in the Figure. 24-hour ABP-measurements were performed per protocol. The primary outcome was defined as a change in ambulatory systolic blood pressure after 8 months of BAT, compared to pharmacotherapy. Results and conclusions: After 8 months of follow-up BAT decreased mean systolic daytime blood pressure by 11.8 mmHg in three participants randomized to BAT, while in the two remaining participants randomized to continuous pharmacotherapy mean systolic daytime blood pressure increased by 8.7 mmHg. When pooling all daytime systolic 24-hour ABP-measurements across the entire follow-up, BAT-therapy was associated with a 9.2 mmHg lower mean blood pressure as compared to continuous pharmacotherapy (143.5 mmHg [95% CI:142.2 - 144.9] vs 152.7 mmHg [151.1 - 154.2], P &lt; 0.0001). In linear mixed models with the BAT-system's status as a fixed effect, day-time systolic blood pressure recordings from 24-hour ABP-measurements at baseline and after 8 months of follow-up were compared between individuals on BAT and continuous pharmacotherapy. Here, BAT-therapy was associated with a reduction in mean systolic day-time blood pressure of -11.7 mmHg (P &lt; 0.0001). In conclusion, BAT-therapy may be a promising tool in lowering systolic blood pressure in individuals with refractory hypertension. Figure. Study design. ABPM = ambulatory blood pressure measurement. Device = Control of Device.

GENETIC VARIATION AND PREDICTED PHENOTYPES IN CYP2C9, CYP2C19, CYP3A4, CYP3A5 AND CYP2D6 GENES AMONG 552 PATIENTS WITH UNCONTROLLED TREATED HYPERTENSION

Objective: Altered drug metabolism may be a contributing factor to uncontrolled hypertension. Beta-blockers, alpha-blockers, calcium antagonists and angiotensin receptor blockers undergo hepatic metabolism by cytochrome P450 (CYP) enzymes. Genetic variation can contribute to interindividual variation, lack of treatment response or side effects with discontinuation of treatment. We aimed to determine common CYP gene variations in patients with treated but uncontrolled hypertension and to compare the distribution with the prevalence in the overall Caucasian population. Design and method: In this national multicenter study we mapped CYP2D6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in 552 patients prescribed &gt; = 2 antihypertensive agents and with systolic daytime ambulatory blood pressure (ABPM) &gt; = 135 mmHg. On the (MALDI-TOF) MassARRAY analyzer, single nucleotide variants and small insertions/deletions (indels) were investigated with the VeriDose Core Panel and CYP2D6 copy-number variation with the VeriDose CYP2D6 CNV Panel (Agena Biosciences). Each allele is associated with either normal, decreased, absent, increased or unknown enzyme function based on activity scores defined by the The Clinical Pharmacogenetics Implementation Consortium (CPIC) and describe function and phenotypes for genes (IM = Intermediate metabolizer, PM = poor metabolizer, RM = rapid metabolizer and UM = ultra-rapid metabolizer). Results: 94% of patients were Caucasian. Mean daytime ABPM was 146/84 mmHg (135-190/55-106 mmHg), median age 63 (26-86) years and 35% were female. The distributions of the predicted phenotypes (illustrated in colors in Figure) for each enzyme did not differ from that reported in Caucasian population by The Pharmacogenomics Knowledgebase (PharmGK) (gray). 11% had normal phenotype in all five enzymes whereas 49% had &gt; = 2 enzymes affected by gene variants. Conclusions: The phenotype distribution of five relevant CYP genes in patients with uncontrolled hypertension did not differ from the general Caucasian population. Dosing guidelines based on CYP2D6 genotype currently exist for metoprolol, but for other antihypertensive drugs further investigation is needed. The low proportion of patients with five normal enzymes and the high proportion with &gt; = 2 enzymes affected suggest that pharmacogenetic CYP-testing may be useful for individualizing drug treatment in patients with uncontrolled hypertension.

CAN SERUM CONSENTRATION MEASUREMENTS OF ANTIHYPERTENSIVE DRUGS IMPROVE BLOOD PRESSURE CONTROL? A MULTICENTER DOUBLE BLINDED RANDOMIZED CONTROLLED TRIAL

Objective: Drug concentration in urine or serum using liquid chromatography coupled to mass-spectrometry (UHPLC-MS/MS) may disclose non-adherence. Whether this direct method will improve adherence is still unknown. In this multicenter randomized controlled trial with a double-blinded approach, we aimed to investigate if measurements and standardized information about serum concentrations of antihypertensive drugs (therapeutic drug monitoring (TDM)), could improve blood pressure (BP) control in documented non-adherent hypertensive patients. Design and method: Patients were &gt; = 18 years old with eGFR &gt;30 mL/min/1.73m2, prescribed &gt; = 2 antihypertensive agents and on a stable treatment regimen for at least 4 weeks. Experienced pharmacologists assessed adherence status based on serum drug concentrations, dose and patient-reported time since last intake of the drugs. Patients received no information regarding use of blood samples to screen for non-adherence. The ethics committee approved the study. All patients signed written informed consent. Non-adherent patients with a systolic daytime ambulatory BP (ABPM) &gt; = 135 mmHg were randomized 1:1 to TDM-intervention or not. The number of visits during 6 months follow-up were equal in both groups and antihypertensive medication regimens remained unchanged. Standardized TDM-information was given to the intervention-group at baseline and after 1 and 3 months. The control group remained uninformed about serum drug measurements until after completion of the study. Life style advice and information on necessity of BP treatment, how to remember to take medications and potential hypertension mediated end-organ damage were given to both groups. Investigators and patients were masked for BPs, and separate personnel measuring BPs were blinded to randomization group. Results: From 2017 to 2022, 606 patients (52.3%) of 1159 patients investigated had uncontrolled HT. The non-adherent patients were younger (57.8 vs 64.0 years, p &lt; 0.001), duration of hypertension was shorter (12 vs 16 years, p = 0.024) and daytime diastolic ABPM (90 vs 84 mmHg, p &lt; 0.001) and heart rate (76 vs 70 bpm, p &lt; 0.001) were higher. Uncontrolled and non-adherent patients were enrolled into the subsequent randomized study performed with a double-blinded approach. Conclusions: There was no difference in the primary end-point, daytime systolic ABPM at 3 months, between TDM and control group (-6.7 vs -7.3 mmHg, p = 0.897).

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.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

OR20-3 Characterization of the Pathophysiologic Spectrum of Subclinical Primary Aldosteronism in Normotension

Abstract Context Accumulating evidence suggests that primary aldosteronism can manifest across a broad phenotypic spectrum and that its origins can at times be detected among normotensive individuals. Herein, we conducted deep-phenotyping studies to interrogate the pathophysiologic continuum of the primary aldosteronism phenotype among normotensive participants. Methods Normotensive participants with obesity, metabolic syndrome, and/or high-normal untreated blood pressure underwent dietary sodium loading and restriction protocols (to maximally suppress and stimulate angiotensin II-mediated aldosterone production), dexamethasone suppression and cosyntropin stimulation protocols (to maximally suppress and stimulate ACTH-mediated aldosterone production), and 24h ambulatory blood pressure monitoring. Measurement of aldosterone and 18-hybrid steroids via LC-MS/MS was conducted to quantify the degree of dysregulated CYP11B2 expression. Urinary extracellular vesicles (uEV) were isolated to measure renal tubular protein content associated with mineralocorticoid receptor activation. In order to characterize parameters across the severity spectrum of non-suppressible and renin-independent aldosterone production, participants with suppressed renin activity were categorized by tertile of 24h urinary aldosterone production following oral sodium suppression testing. Repeated measures linear mixed models were used to analyze trends for each parameter across tertiles of autonomous aldosterone production; for ease of presentation, the mean [SD] of the first vs. third tertile are presented for selected parameters. Results Following oral sodium loading, greater non-suppressible renin-independent aldosterone production was associated with greater kaliuresis, higher daytime ambulatory systolic blood pressure within the normal range, and a progressive impairment in the ability to suppress production of serum aldosterone (P-trend=0.009), 18-hydroxycorticosterone (9.3 [5.0] vs. 19.6 [6.5] ng/dL, P-trend=0.004), 18-hydroxycortisol (45.0 [25.4] vs. 70.9 [29.9] ng/dL, P-trend=0.03), and 18-oxocortisol (1.2 [0.03] vs. 3.4 [7.2], P-trend=0.01). Similarly, following dexamethasone suppression testing, there was a progressive inability to suppress 18-hydroxycorticosterone (8.3 [5.0] vs. 15.4 [8.2] ng/dL, P-trend=0.004), 18-hydroxycortisol (6.6 [3.8] vs. 10.2 [3.6] ng/dL, P-trend=0.03), and 18-oxocortisol (1.2 [0.01] vs. 1.4 [0.6] ng/dL, P-trend=0.01) in parallel with greater renin-independent aldosterone production. In contrast, following stimulation with cosyntropin, greater non-suppressible and renin-independent aldosterone production was associated with progressively enhanced production of 18-hydroxycorticosterone (77.6 [25.4] vs. 121.1 [31.1] ng/dL, P-trend=0.004), 18-hydroxycortisol (68.5 [28.4] vs. 86.2 [26.3] ng/dL, P-trend=0.03), and 18-oxocortisol (3.2 [2.8] vs. 7.3 [3.5] ng/dL, P-trend=0.01). Excretion of uEV's of pendrin (P=0.002) and aquaporin 2 (P=0.002) all increased with greater non-suppressible aldosterone production. Conclusions Dynamic phenotyping studies in normotensive individuals demonstrate a continuum of non-suppressible and renin-independent aldosterone production that parallels higher blood pressure, greater kaliuresis, increased 18-hybrid steroid production indicative of dysregulated CYP11B2 expression, and increased uEV excretion indicative of renal mineralocorticoid receptor activation. This pathophysiologic continuum of normotensive primary aldosteronism provides phenotypic support for histopathology studies showing ectopic CYP11B2 expression within adrenal glands of normotensive humans, and for epidemiologic studies demonstrating renin-independent aldosterone production in normotensive populations increases risk for developing hypertension. Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 a.m.

Association between nocturnal blood pressure dipping and chronic kidney disease

Abstract Introduction Management of blood pressure (BP) in chronic kidney disease (CKD) is critical for preventing cardio-renal complications. While increasing attention has been given to discrepancies between office and ambulatory BP control in this population, information on nocturnal BP decrease patterns (dipping) in CKD is still scarce. Purpose We aimed at describing nocturnal BP dipping patterns and its predictors in patients with CKD. Methods We analysed data from patients with CKD stages 1 to 5 referred for kidney function testing from September 2006 to January 2022, including 24-hour urine collection, gold-standard measurement of glomerular filtration rate (GFR) using clearance of a radioisotopic tracer, as well as ambulatory BP measurement (ABPM) in a single tertiary hospital in Paris, France. A total of 1177 ABPM were available in 642 participants. The magnitude of dipping was calculated as the difference between day- and night-time systolic BP (SBP), in percentage of daytime SBP. Participants were then categorized as extreme-dippers (≥20%), dippers (10% to &amp;lt;20%), non-dippers (0% to &amp;lt;10%), or reverse-dippers (&amp;lt;0%). Factors associated with a less than 10% dipping were analysed with crude and adjusted logistic regression models including a random intercept to deal with clustering of measurements within patients. Results Participants (mean age 56±15 years; 35% female, mean GFR 49±21 mL/min per 1.73 m2) consisted of 8% extreme-dippers, 37% dippers, 40% non-dippers, and 15% reverse-dippers. The prevalence of non- or reverse-dipping increased with CKD severity, from 36% in CKD stage 1 to 65% in CKD stages 4–5 (Figure). In crude analyses, African origin, a lower measured GFR, a higher daytime SBP, diabetes, a higher number of antihypertensive medications and a higher 24-hour urinary sodium to potassium ratio (24h Na/K) were associated with abnormal dipping status. In the multivariable adjusted regression, non or reverse dipping was independently associated with measured GFR (odds ratio [OR, 95% confidence interval] per 10 ml/min/1.73 m2 decrease = 1.16 [1.06–1.26], p=0.001), daytime ambulatory SBP (OR per 10 mmHg decrease = 1.17 [1.06–1.28], p=0.001), African origin (OR= 1.56 [1.04–2.34], p=0.03) and 24h Na/K (OR per 1-unit increase = 1.20 [1.06–1.37], p=0.006). Conclusions The prevalence of nocturnal non-or reverse dipping BP profiles increases substantially across the spectrum of CKD. Measured GFR, ambulatory daytime SBP, African origin and 24-hour urinary sodium to potassium ratio are independent predictors of abnormal nocturnal BP decrease and thus may help in cardiovascular risk stratification in this population. More research is needed on whether nocturnal dipping may be a treatment target to reduce cardiorenal complications. Funding Acknowledgement Type of funding sources: None.

Long-term follow-up of patients undergoing renal sympathetic denervation

ObjectivesRenal denervation (RDN) proved to significantly lower blood pressure (BP) at 2–6 months in patients on and off antihypertensive drugs. Given a lack of longer-term follow-up data, our aim was to assess the safety and efficacy of RDN up to five years taking into account antihypertensive drug regimen changes over time.MethodsIn the present single-center study, patients underwent RDN for (therapy resistant) hypertension. Patients underwent protocolized yearly follow-up out to five years. Data were collected on 24-h ambulatory BP and office BP monitoring, renal function, antihypertensive drug regimen, and safety events, including non-invasive renal artery imaging at 6/12 months. Efficacy analyses were performed using linear mixed-effects models.ResultsSeventy-two patients with mean age 63.3 ± 9.5 (SD) years (51% female) were included. Median follow-up time was 3.5 years and Clark’s Completeness Index was 72%. Baseline ambulatory daytime BP was 146.1/83.7 ± 17.4/12.2 mmHg under a mean number of 4.9 ± 2.7 defined daily doses (DDD). At five years, ambulatory daytime systolic BP as calculated from the mixed model was 120.8 (95% CI 114.2–127.5) mmHg and diastolic BP was 73.3 (95% CI 69.4–77.3) mmHg, implying a reduction of -20.9/-8.3 mmHg as compared to baseline estimates (p < 0.0001). The number of DDDs remained stable over time (p = 0.87). No procedure-related major adverse events resulting in long-term consequences were observed.ConclusionsThe BP-lowering effect of RDN was safely maintained at least five years post-procedure as reflected by a significant decrease in ambulatory daytime BP in the absence of escalating antihypertensive drug therapy over time.Graphical abstract

PREVALENCE AND PREDICTORS OF NOCTURNAL BLOOD PRESSURE DIPPING IN CHRONIC KIDNEY DISEASE

Objective: Management of blood pressure (BP) in chronic kidney disease (CKD) is critical for preventing cardio-renal complications. Information on nocturnal BP decrease patterns (dipping) in CKD is still scarce. We aimed at describing nocturnal BP dipping patterns and its predictors in patients with CKD. Design and method: We analysed data from patients with CKD stages 1 to 5 referred for kidney function testing from September 2006 to January 2022, including 24-hour urine collection, gold-standard measurement of glomerular filtration rate (GFR) using clearance of a radioisotopic tracer, as well as ambulatory BP measurement (ABPM) in a single tertiary hospital in Paris, France. A total of 1177 ABPM were available in 642 participants. The magnitude of dipping was calculated as the difference between day- and night-time systolic BP (SBP), in percentage of daytime SBP. Factors associated with a less than 10% dipping were analysed with adjusted logistic regression models including a random intercept to deal with clustering of measurements within patients. Results: Participants (mean age 56 ± 15 years; 35% female, mean GFR 49 ± 21 mL/min per 1.73 m2) consisted of 8% extreme-dippers (&gt; = 20%), 37% dippers (10% to &lt; 20%), 40% non-dippers (0% to &lt; 10%), and 15% reverse-dippers (&lt;0%). The prevalence of non- or reverse- dipping increased with CKD severity, from 36% in CKD stage 1 to 65% in CKD stages 4–5 (Figure). Non or reverse dipping was independently associated with measured GFR (odds ratio [OR, 95% confidence interval] per 10 ml/min/1.73m2 decrease = 1.16 [1.06 – 1.26], p = 0.001), daytime ambulatory SBP (OR per 10 mmHg decrease = 1.17 [1.06–1.28], p = 0.001), African origin (OR = 1.56 [1.04 – 2.34], p = 0.03) and 24 h Na/K (OR per 1-unit increase = 1.20 [1.06 – 1.37], p = 0.006). Conclusions: The prevalence of nocturnal non-or reverse dipping BP profiles increases substantially across the spectrum of CKD. Measured GFR, African origin, ambulatory daytime SBP and 24-hour urinary sodium to potassium ratio are independent predictors of abnormal nocturnal BP decrease and thus may help in cardiovascular risk stratification in this population. More research is needed on whether nocturnal dipping may be a treatment target to reduce cardiorenal complications.

REVERSE WHITE-COAT EFFECTS ACCORDING TO THE ACHIEVED BLOOD PRESSURES BELOW THE TARGET BLOOD PRESSURES FOR INTENSIVE BLOOD PRESSURE CONTROL

Objective: In the application of nalysedd controlled trial data for intensive blood pressure (BP) control into clinical practice, the corresponding BPs among office, home, and ambulatory BPs were suggested to be similar if achieved clinic systolic BP (SBP) become 130 mmHg or lower. But the magnitude and its clinical implication of reversed white-coat effect (WCE) was not clearly reported. Design and method: From the 1843 data of treated hypertension patients in Korean ambulatory blood pressure monitoring (Kor-ABP) registry, WCE were calculated according to the range of achieved clinic SBPs, &lt; 120 mmHg (group1), 120~130 mmHg (group2), 130–140 mmHg (group3), and &gt; = 140 mmHg (group4). The factors related to WCE were nalysed using multivariable regression analysis. WCE was defined by clinic SBP minus daytime ambulatory SBP. Results: Mean age was 59 years and the proportion of female was 55%. Significant factors for the WCE were BMI (beta = -0.342), smoking (beta = -3.394), good sleep quality (beta = 0.872 per each 4 point likert scale), and clinic SBP(beta = 0.578). Mean SBPs for group 1 to 4 were 111.4 mmHg, 124.0 mmHg, 134.1 mmHg, and 157.5 mmHg, respectively. WCEs for the group were -8.3 mmHg for group1, -4.5 mmHg for group2, -1.9 mmHg for group3, and 9.9 mmHg for group4. The difference in WCEs between the group 4 and untreated hypertension patients (SBP, 155.6 +/-13.6) was not statistically significant (9.9 +/- 16.1 mmHg 9.0 +/-16.8, p = 0.2). Conclusions: Reverse WCE should be considered to estimate the safety of intensive BP control when SBP lowered below 120 mmHg. The presence of reverse WCE instead of WCE highlights more reassuring aspect than previously thought when the patient is asymptomatic or tolerable.

THE PERSONAL TRAIT CORRELATED WITH THE NIGHT BLOOD PRESSURE LEVEL IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: The aim of our study was to determine associations between the personal trait of patients and the night blood pressure (BP) level in untreated arterial hypertension (AH) patients. Design and method: We nalysed database of several studies (200 AH patients without serious concomitant diseases). Ambulatory blood pressure monitoring (ABPM) (Spacelabs 90207) was performed after the washout period (3–7 days). After ABPM each patient completed the Russian version of the psychological questionnaire Minnesota Multiphasis Personality Inventory (MMPI) and the emotional intelligence questionnaire (EmIn, by Lyusin D.) (only 90 patients). We nalysed the following MMPI scales: L – lie scale, F – aggravation scale, K – correction scale, 1 (Hs) – hypochondria, 2 (D) – depression, 3 (Hy) – hysteria, 4 (Pd) – psychopathy, 6 (Pa) – rigidity of affect, 7 (Pt) – psychasthenia, 8 (Sc) – schrizothemia, 9 (Ma) – hypomania. We assessed the following EmIn scale scores: I - emotion self-awareness; II - management of one’s own emotions; III - control of emotional expression; IV - understanding others’ emotions; V- management of others’ emotions. We used Pearson correlation coefficient ®. Results: The initial mean ambulatory daytime systolic BP (SBP) was 142.1 ± 14.2, diastolic (DBP) - 89.5 ± 10.1 mm Hg), age - 52,7 ± 12.2 years.(M ± SD). We found the following significant correlations: 1) 9 scale scores of MMPI (optimism, good mood, cheerfulness level) had negative relationships with the night DBP (r = -0,17, p &lt; 0,05) and night SBP (r = -0,16, p &lt; 0,05) levels; 2) IV scale scores of EmIn (understanding others’ emotions) had relations with the night DBP (r = -0,28, p &lt; 0,05) and night SBP (r = -0,30, p &lt; 0,05) levels; 3) V scale scores of EmIn (management of others’ emotions) had correlations with the night DBP (r = -0,26, p &lt; 0,05) and night SBP (r = -0,26, p &lt; 0,05) parameters. Optimism, cheerfulness, good mood (9 scale scores of MMPI) was associated with the night BP decrease, but intensification of the interpersonal emotional interactions (IV, V scale - management or understanding others’ emotions) can lead to the night BP increase. Conclusions: Optimism, cheerfulness, good mood was related with the night BP decrease. But intensification of the interpersonal emotional interactions can lead to the night BP increase.

Twenty-Four Hour Blood Pressure Response to Empagliflozin and Its Determinants in Normotensive Non-diabetic Subjects.

BackgroundSodium–glucose co-transport 2 inhibitors (SGLT2i) lower blood pressure (BP) in normotensive subjects and in hypertensive and normotensive diabetic and non-diabetic patients. However, the mechanisms of these BP changes are not fully understood. Therefore, we examined the clinical and biochemical determinants of the BP response to empagliflozin based on 24-h ambulatory BP monitoring.MethodsIn this post-hoc analysis of a double-blind, randomized, placebo-controlled study examining the renal effects of empagliflozin 10 mg vs. placebo in untreated normotensive non-diabetic subjects, the 1-month changes in 24 h ambulatory BP were analyzed in 39 subjects (13 placebo/26 empagliflozin) in regard to changes in biochemical and hormonal parameters.ResultsAt 1 month, empagliflozin 10 mg decreased 24-h systolic (SBP) and diastolic (DBP) BP significantly by −5 ± 7 mmHg (p < 0.001) and −2 ± 6 mmHg (p = 0.03). The effect on SBP and DBP was more pronounced during nighttime (resp. −6 ± 11 mmHg, p = 0.004; −4 ± 7 mmHg, p = 0.007). The main determinants of daytime and nighttime SBP and DBP responses were baseline BP levels (for daytime SBP: coefficient −0.5; adj. R2: 0.36; p = 0.0007; for night-time SBP: coefficient −0.6; adj. R2: 0.33; p = 0.001). Although empaglifozin induced significant biochemical changes, none correlated with blood pressure changes including urinary sodium, lithium, glucose and urate excretion and free water clearance. Plasma renin activity and plasma aldosterone levels increased significantly at 1 month suggesting plasma volume contraction, while plasma metanephrine and copeptin levels remained the same. Renal resistive indexes did not change with empagliflozin.ConclusionSGLT2 inhibition lowers daytime and nighttime ambulatory systolic and diastolic BP in normotensive non-diabetic subjects. Twenty-four jour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Baseline ambulatory BP was the only identified determinant of systolic and diastolic BP response. This suggests that still other factors than sustained glycosuria or proximal sodium excretion may contribute to the resetting to lower blood pressure levels with SGLT2 inhibition.Clinical Trial Registration:[https://www.clinicaltrials.gov], identifier [NCT03093103].

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.

Unattended automated office blood pressure in living donor kidney transplant recipients

Purpose Hypertension is common in kidney transplant recipients (KTRs). For the evaluation of blood pressure (BP), 24-h ambulatory BP measurements (ABPM) are considered superior to usual office measurements but are also resource demanding and troublesome to many patients. We therefore evaluated the use of unattended automated office BP (AOBP) during the first year following living donor kidney transplantation and compared AOBP with ABPM as obtained 12 months after transplantation. Materials and methods Data were retrieved from a cohort of 57 KTRs (mean age 45 ± 14 years, 75% males) who all received kidneys from living donors and had a good graft function (estimated glomerular filtration rate (eGFR) 52 ± 16 ml/min/1.73 m2 at 12 months). Unattended AOBP was measured at each visit to the outpatient clinic using the BpTru® device, while ABPM was obtained by Spacelabs® equipment before and 12 months after transplantation. Results AOBP remained stable from month 2 (130.2 ± 10.8/82.2 ± 7.8 mmHg) to month 12 (129.0 ± 12.8/83.1 ± 9.6 mmHg) post-transplantation. At 12 months follow-up, ambulatory daytime systolic BP was slightly higher than AOBP (132.7 ± 10.7 vs. 129.4 ± 12.2 mmHg, p = 0.04), while diastolic BP was similar (82.7 ± 7.7 vs. 82.0 ± 10.2 mmHg). Using Bland–Altman plots, 95% limits of agreements were −17.9 to 24.5 mmHg for systolic and −16.5 to 15.1 mmHg for diastolic BP. When considering a target BP of ≤130/<80 mmHg, 62% had sustained hypertension, 9% white coat hypertension and 11% masked hypertension. Using multiple linear regression analysis, only urine albumin-creatinine ratio tended to predict a higher systolic AOBP (p = 0.07). Conclusion In a cohort of stable living donor KTRs, mean values of unattended AOBP using BpTru® are comparable to daytime ABPM with a misclassification rate of approximately 20%.

Paradoxical increase in ambulatory systolic blood pressure in coarctation of aorta as compared to idiopathic hypertension

Abstract Background The relationship between office vs ambulatory blood pressure (BP) indices is well-studied in patients with idiopathic hypertension, and based on these data, it is known that average 24-hour ambulatory BP is typically lower than office BP. However, emerging data show that office systolic BP (SBP) underestimates arterial afterload in patients with coarctation of aorta (COA), and minimal increase in stroke volume during low intensity exercise results in exaggerated rise in SBP as compared to those with idiopathic hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with idiopathic hypertension. Methods Case-control study of 118 COA patients and 118 patients with idiopathic hypertension matched by age, sex, body mass index and office SBP. Results Although both groups had similar office SBP (132±17 mmHg) by design, the COA group had paradoxical increases in 24-hour ambulatory SBP (135±14 vs 126±13, p&amp;lt;0.001) and daytime ambulatory SBP (142±16 vs 130±13, p&amp;lt;0.001), and less nocturnal dipping (−3±5 vs −9±4, p&amp;lt;0.001). The COA group also had a higher prevalence of masked hypertension (36 [31%] vs 14 [12%], p&amp;lt;0.001), and worse arterial function indices. Conclusion These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating idiopathic hypertension guidelines recommendations to the treatment of COA. It also provides rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population. Funding Acknowledgement Type of funding sources: None.

PD66-11 EFFECTS OF VIBEGRON ON AMBULATORY BLOOD PRESSURE IN PATIENTS WITH OVERACTIVE BLADDER: RESULTS FROM A DOUBLE-BLIND STUDY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III (PD66)1 Sep 2021PD66-11 EFFECTS OF VIBEGRON ON AMBULATORY BLOOD PRESSURE IN PATIENTS WITH OVERACTIVE BLADDER: RESULTS FROM A DOUBLE-BLIND STUDY Michael A. Weber, William B. White, Jennifer King, Ann Walker, Paul N. Mudd, and Cornelia Haag-Molkenteller Michael A. WeberMichael A. Weber More articles by this author , William B. WhiteWilliam B. White More articles by this author , Jennifer KingJennifer King More articles by this author , Ann WalkerAnn Walker More articles by this author , Paul N. MuddPaul N. Mudd More articles by this author , and Cornelia Haag-MolkentellerCornelia Haag-Molkenteller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002110.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ambulatory blood pressure monitoring (ABPM) is a sensitive method used to determine whether small changes in blood pressure (BP) and heart rate (HR) are induced by new drugs. This randomized, double-blind, placebo-controlled ABPM trial was used to characterize the BP and HR profile of the novel β3-adrenergic receptor agonist vibegron in patients with OAB. METHODS: Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime (waking hours) ambulatory systolic BP (SBP). Key secondary endpoints were CFB to day 28 in mean daytime ambulatory diastolic BP (DBP) and HR and in mean 24-hour ambulatory SBP, DBP, and HR. Point estimates for treatment group means and treatment differences were presented with a 2-sided 90% confidence interval (CI). For the primary endpoint, the upper limit of the CI was evaluated against a criterion of 3.5 mmHg. RESULTS: A total of 214 patients with OAB were randomized; of these, 96 in the vibegron group and 101 in the placebo group had evaluable ABPM measurements at baseline and day 28. Mean age was 59.3 years and 74.6% were female; 39.6% and 30.7% of patients receiving vibegron or placebo, respectively, had pre-existing hypertension. The least squares mean difference (LSMD; 90% CI) CFB to day 28 in daytime SBP was 0.81 (‒0.88, 2.49) mmHg for vibegron vs placebo (Table). Changes in daytime DBP and HR were comparable for vibegron and placebo (Table). The 90% CIs include 0, implying no statistically significant differences were seen in mean 24-hour SBP (Figure), DBP, or HR (Table). The most commonly reported treatment-emergent adverse event was hypertension (vibegron: n=5 [4.7%, 95% CI=1.6%‒10.7%]; placebo: n=4 [3.7%, 95% CI=1.0%‒9.2%]); no event of hypertension with vibegron was considered treatment related. CONCLUSIONS: In patients with OAB, once-daily vibegron was not associated with clinically meaningful or statistically significant effects on BP or HR and had a safety profile comparable with placebo. Source of Funding: Urovant Sciences © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1163-e1163 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael A. Weber More articles by this author William B. White More articles by this author Jennifer King More articles by this author Ann Walker More articles by this author Paul N. Mudd More articles by this author Cornelia Haag-Molkenteller More articles by this author Expand All Advertisement Loading ...