Mean 24-h Ambulatory Blood Pressure Research Articles

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

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

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

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

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

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus.

To assess the effect of renal denervation (RDN) on renal vascular resistance and renal function in patients with drug-resistant hypertension (HTN) and type 2 diabetes mellitus (T2DM). Fifty-nine patients (mean age 60.3 ± 7.9 years, 25 men) with resistant HTN [mean 24-h ambulatory blood pressure (BP) 158.0 ± 16.3/82.5 ± 12.7 mmHg, systolic/diastolic] and T2DM (mean HbA1c 7.5 ± 1.5%) were included in the single-arm prospective study and underwent RDN. Renal resistive index (RRI) derived from ultrasound Doppler; estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula), office and 24-h ambulatory BP were measured at baseline, 6, and 12 months after RDN to evaluate the respective changes in renal vascular resistance, renal function, and BP during treatment. Forty-three patients completed 12 months follow-up. The RRI changed depending on the baseline value. Specifically, the RRI decreased significantly in patients with elevated baseline RRI values ≥ 0.7 {n = 23; -0.024 [95% confidence interval (CI): -0.046, -0.002], p = 0.035} and did not change in those with baseline RRI < 0.7 [n = 36; 0.024 (95% CI: -0.002, 0.050), p = 0.069]. No significant change was observed in eGFR whereas BP was significantly reduced at 12 months after RDN by -10.9 (95% CI: -16.7, -5.0)/-5.5 (95% CI: -8.7, -2.4) mmHg, systolic/diastolic. No relationship was found between the changes in RRI and BP. Our study shows that RDN can decrease elevated renal vascular resistance (RRI > 0.7) and stabilize kidney function in patients with RHTN and T2DM independently of its BP-lowering effect.

Adequacy of blood pressure control in high-risk hypertensive patients: The DEGREE study

IntroductionHypertension is a modifiable risk factor in patients at the highest risk for cardiovascular events. New invasive treatment options are becoming available that might be particularly appealing for high-risk patients. Therefore, the aim of this study was to determine the prevalence of high-risk patients on routine therapy that do not meet guideline recommended ambulatory blood pressure (ABP) targets. MethodsThis single-center, cross-sectional study was conducted at the Erasmus University Medical Center (Rotterdam, The Netherlands). Inclusion criteria were: (1) age 18–80 years, (2) drugs prescribed for hypertension or history of hypertension and (3) high cardiovascular risk as defined according to the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines. Patients underwent standardized office blood pressure (OBP) and same-day 24-h ABP measurements. Blood pressure (BP) control was defined according to the 2018 ESC/ESH and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. ResultsA total of 100 patients were enrolled (median age 71 years, 35% female). Mean OBP was 142.2/81.9 ± 18.6/12.6 mmHg and mean 24-h ABP was 126.1/70.1 ± 14.3/9.2 mmHg. Patients were on 2.0 [25th–75th percentile: 1.0–3.3] Defined Daily Doses of antihypertensive drugs. ESC/ESH guideline 24-h ABP and OBP targets were not met in 41.8% (95%CI: 31.5–52.6%) and 52.7% (95%CI: 42.0–63.3%), respectively. ACC/AHA guideline 24-h ABP and OBP targets were not met in 59.3% (95%CI: 48.5–69.5%) and 79.1% (95%CI: 69.3–86.9%), respectively. ConclusionsBP remains uncontrolled in 40–60% of high-risk hypertensive patients despite routine use of guideline-recommended therapy. Our findings support the search towards novel invasive BP lowering treatment options.

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.

A simple score to screen for isolated ambulatory hypertension in older adults. Development and validation

Introduction and objectivesMasked or isolated ambulatory hypertension (IAH), a poor-prognosis condition, can be diagnosed with ambulatory blood pressure monitoring (ABPM), but ABPM is not available in many clinical practices. We developed and validated a score to screen for IAH among older adults, where limited information is available. MethodsA total of 645 community-dwelling adults≥65 years from the Seniors-ENRICA-2 cohort (derivation sample) and 327 from the Seniors-ENRICA-1 cohort (external-validation sample), with untreated casual BP<140/90mmHg (mean of the last 2 of 3 BP) were examined. Probabilities of having IAH (mean 24-h ambulatory BP≥130/80mmHg) were calculated with a multivariable model (with sex, age, and clinical variables). Beta coefficients were used to allocate points to each variable in an IAH score (range, 0–12). ResultsParticipants’ mean age was 70.8 years (46.7% men); 19.7% had IAH. Allocated score-points were: male sex (1 point), age≥80 (2 points), body-mass index (2 points if 25–29; 3 if ≥30kg/m2), the first BP measurement (2 points if ≥140/90mmHg), and the mean of the second and third BP (2 points if 120–129/80–84; 4 if 130–139/85–89). Probabilities of having IAH for scores of 6, 7, 8, 9, or ≥10 points were 25%, 35%, 47%, 59%, and 72%, respectively. Area-under-the-ROC curve was 0.80 for the derivation and 0.73 for the validation-sample. Two subjects at high risk of IAH (>8 points) and 3 at middle risk (≥6) needed to undergo ABPM to detect 1 IAH case. ConclusionsA simple score with 4 routine variables performed well identifying IAH in older adults. For high scores, using ABPM for diagnosing IAH was very size-efficient.

Renal Denervation for Uncontrolled and Resistant Hypertension: Systematic Review and Network Meta-Analysis of Randomized Trials.

Comparative efficacy and safety of renal denervation (RDN) interventions for uncontrolled (UH) and resistant hypertension (RH) is unknown. We assessed the comparative efficacy and safety of existing RDN interventions for UH and RH. Six search engines were searched up to 1 May 2020. Primary outcomes were mean 24-h ambulatory and office systolic blood pressure (SBP). Secondary outcomes were mean 24-h ambulatory and office diastolic blood pressure (DBP), clinical outcomes, and serious adverse events. Frequentist random-effects network meta-analyses were used to evaluate effects of RDN interventions. Twenty randomized controlled trials (RCTs) (n = 2152) were included, 15 in RH (n = 1544) and five in UH (n = 608). Intervention arms included radiofrequency (RF) in main renal artery (MRA) (n = 10), RF in MRA and branches (n = 4), RF in MRA+ antihypertensive therapy (AHT) (n = 5), ultrasound (US) in MRA (n = 3), sham (n = 8), and AHT (n = 9). RF in MRA and branches ranked as the best treatment to reduce 24-h ambulatory, daytime, and nighttime SBP and DBP versus other interventions (p-scores: 0.83 to 0.97); significant blood pressure effects were found versus sham or AHT. RF in MRA+AHT was the best treatment to reduce office SBP and DBP (p-scores: 0.84 and 0.90, respectively). RF in MRA and branches was the most efficacious versus other interventions to reduce 24-h ambulatory SBP and DBP in UH or RH.

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension

ObjectivesThe aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space. BackgroundThe number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably high. The renal sympathetic nervous system has been identified as an attractive therapeutic target. MethodsForty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery. ResultsAll patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was −11 mm Hg (95% confidence interval [CI]: −15 to −7 mm Hg) for systolic BP and −7 mm Hg (95% CI: −9 to −4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by −18/−10 mm Hg (95% CI: −25 to −12/−13 to −6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment. ConclusionsPrimary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension.

Differential blood pressure response tocontinuous positive airway pressure treatment according to the circadian pattern in hypertensive patients with obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) has a heterogeneous effect on blood pressure (BP) in hypertensive patients. However, the effect of CPAP on BP in hypertensive subjects regarding circadian BP pattern has never been explored. This study aimed to assess the effect of CPAP on BP, taking into consideration the circadian BP pattern in untreated hypertensive patients.This study is a post hoc analysis of the Spanish Cohort for the Study of the Effect of CPAP in Hypertension (CEPECTA), a multicentre, randomised trial of CPAP versus sham-CPAP in patients with new-onset systemic hypertension and an apnoea-hypopnoea index >15 events·h-1 We included patients for whom 24-h ambulatory BP monitoring (ABPM) data were available at baseline and 12 weeks after the intervention. Subjects were classified based on the dipping ratio (dipper/non-dipper). We evaluated the effect of CPAP on ABPM parameters after 12 weeks of treatment.Overall, 272 hypertensive subjects were included in the analysis (113 dippers and 159 non-dippers). Baseline clinical and polysomnographic variables were similar between the groups. CPAP treatment in non-dipper patients was associated with reductions in 24-h ambulatory BP variables and night-time ambulatory BP measurements. However, a nonsignificant effect was reported in the dipper group. The differential effects of CPAP between the groups were -2.99 mmHg (95% CI -5.92-- -0.06 mmHg) for the mean 24-h ambulatory BP and -5.35 mmHg (95% CI -9.01- -1.69 mmHg) for the mean night-time ambulatory BP.Our results show a differential effect of CPAP treatment on BP in hypertensive patients depending on the circadian pattern. Only non-dipper patients benefited from CPAP treatment in terms of BP reduction.

Normotensive patients with obstructive sleep apnoea: changes in 24-h ambulatory blood pressure monitoring with continuous positive airway pressure treatment.

Continuous positive airway pressure (CPAP) treatment reduces blood pressure (BP) in obstructive sleep apnoea (OSA) and hypertensive patients, but there is a lack of data about the effects of CPAP on the BP in normotensive patients. The aim of the study was to evaluate BP changes in normotensive OSA individuals receiving CPAP treatment. We selected 131 normotensive outpatients with an apnoea/hypopnoea index (AHI) greater than 15 events/hour who required CPAP treatment. All patients underwent a sleep study and 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. In addition, the patients were assessed for the presence of baseline masked hypertension, defined as office BP less than 140/90 mmHg and increased BP on 24-h ABPM (mean 24-h BP ≥130/80 mmHg). After 6 months of CPAP treatment, a mild reduction in all 24-h ABPM variables was observed, but only the mean 24-h DBP [-1.39 mmHg, 95% confidence interval (95% CI), -2.50 to -0.27], mean daytime DBP (-1.39 mmHg, 95% CI -2.56 to -0.22) and the mean 24-h ambulatory BP (-1.80 mmHg, 95% CI, -3.16 to -0.44) reached statistical significance. The reduction was primarily due to BP changes in individuals with masked hypertension who displayed a mean BP reduction of -4.78 mmHg (-7.25 to -2.30 mmHg). Consistent with a circadian BP pattern, a reduction in mean nocturnal BP of -4.73 mmHg (-7.39 to -2.06 mmHg) was observed at 6 months in nondippers; in contrast, the mean nocturnal BP in dippers increased by 2.61 mmHg (0.60-4.62 mmHg). Our findings suggest that the CPAP effects may be different in normotensive outpatients depending on the presence of undiagnosed masked hypertension and the dipping pattern. Therefore, it is important to consider measuring ABPM in this type of patient.

Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: study design for a multicenter, double-blinded, active-controlled, phase 4, randomized trial

BackgroundHypertension is a risk factor for coronary heart disease and stroke, and is one of the leading causes of death. Although over a billion people are affected worldwide, only half of them receive adequate treatment. Current guidelines on antihypertensive treatment recommend combination therapy for patients not responding to monotherapy, but as the number of pills increase, patient compliance tends to decrease. As a result, fixed-dose combination drugs with different antihypertensive agents have been developed and widely used in recent years. CCBs have been shown to be better at reducing central blood pressure and arterial stiffness than diuretics. Recent studies have reported that central blood pressure and arterial stiffness are associated with cardiovascular outcomes. This trial aims to compare the efficacy of combination of calcium channel blocker (CCB) or thiazide diuretic with an angiotensin receptor blocker (ARB).MethodsThis is a multicenter, double-blinded, active-controlled, phase 4, randomized trial, comparing the antihypertensive effects of losartan/amlodipine and losartan/hydrochlorothiazide in patients unresponsive to treatment with losartan. The primary endpoint is changes in mean sitting systolic blood pressure (msSBP) after 4 weeks of treatment. Secondary endpoints are changes in msSBP, mean 24-h ambulatory mobile blood pressure, mean 24-h ambulatory mobile central SBP, mean 24-h ambulatory carotid-femoral pulse wave velocity, ambulatory augmentation index, and microalbuminuria/proteinuria after 20 weeks of treatment. The sample size will be 119 patients for each group in order to confer enough power to test for non-inferiority regarding the primary outcome.ConclusionThe investigators aim to prove that combination of a CCB with ARB shows non-inferiority in lowering blood pressure compared with a combination of thiazide diuretic and ARB. We also hope to distinguish the subset of patients that are more responsive to certain types of combination drugs. The results of this study should aid physicians in selecting appropriate combination regimens to treat hypertension in certain populations.Trial registrationClinicalTrials.gov NCT02294539. Registered 12 November 2014.

Prognostic Importance of Ambulatory Blood Pressure Monitoring in Resistant Hypertension: Is It All that Matters?

This article reviews the current knowledge on the prognostic importance of ambulatory blood pressure (BP) monitoring parameters in patients with apparent treatment-resistant hypertension. Although mean 24-h ambulatory BPs have been consistently established as better cardiovascular risk predictors than clinic (office) BPs in several clinical settings, and ambulatory BP monitoring is generally indicated in patients with resistant hypertension; there were only five previous longitudinal prospective studies that specifically evaluated the prognostic importance of ambulatory BP monitoring parameters in resistant hypertensive patients. These studies are carefully reviewed here. In conjunction, they demonstrated that office BP levels have little, if any, prognostic value in resistant hypertensive patients. Otherwise, several ambulatory BP monitoring parameters are strong cardiovascular risk predictors, particularly nighttime sleep BPs and the non-dipping pattern. Most relevant, the ambulatory BP monitoring diagnosis of true resistant hypertension (i.e., patients with uncontrolled ambulatory BPs, either daytime or nighttime) doubled the risk of future occurrence of major cardiovascular events in contrast to patients with white-coat resistant hypertension (i.e., with controlled ambulatory BPs despite uncontrolled office BPs). This review reinforces the pivotal role of serial ambulatory BP monitoring examinations in the clinical management of patients with resistant hypertension.

Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry.

Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2–6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested.

Short-term effects of the DASH diet in adults with moderate chronic kidney disease: a pilot feeding study

BackgroundAlthough the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) for adults with normal kidney function, evidence is lacking regarding its safety and efficacy in chronic kidney disease (CKD). We aimed to test the effects of the DASH diet on serum electrolytes and BP in adults with moderate CKD.MethodsIn a prospective before–after feeding study, 11 adults with an estimated glomerular filtration rate of 30–59 mL/min/1.73 m2 and medication-treated hypertension were provided a reduced-sodium, run-in diet for 1 week followed by a reduced-sodium, DASH diet for 2 weeks. Changes in serum electrolytes and BP were compared pre–post DASH.ResultsEleven participants underwent feeding; 1 completed 1 week and 10 completed 2 weeks of DASH. Compared with baseline, DASH modestly increased serum potassium at 1 week (mean ± standard deviation, +0.28 ± 0.4 mg/dL; P = 0.043) but had no significant effect on potassium at 2 weeks (+0.15 ± 0.28 mg/dL; P = 0.13). Serum bicarbonate was reduced (−2.5 ± 3.0 mg/dL; P = 0.03) at 2 weeks. Neither incident hyperkalemia nor new onset metabolic acidosis was observed. Clinic BP and mean 24-h ambulatory BP was unchanged. DASH significantly reduced mean nighttime BP (−5.3 ± 5.8 mmHg; P = 0.018), and enhanced percent declines in both nocturnal systolic BP (−2.1% to −5.1%; P = 0.004) and diastolic BP (−3.7% to −10.0%; P = 0.008).ConclusionsThese pilot data suggest that a reduced-sodium DASH dietary pattern does not cause acute metabolic events in adults with moderate CKD and may improve nocturnal BP. Definitive studies are needed to determine long-term effects of DASH in CKD.

Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring

BackgroundThiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. ObjectivesThis study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. MethodsThis 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. ResultsAll 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. ConclusionsTreatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793)

Impact of sympathetic renal denervation: a randomized study in patients after renal transplantation (ISAR-denerve).

Sympathetic overactivity is frequently observed following renal transplantation (RTx), and post-transplant hypertension is a major contributing factor to graft failure and cardiovascular morbidity. This process is perpetuated by preservation of sympathetic afferent activity from the native non-functional kidneys, in the absence of efferent feedback to the renal transplant, which would otherwise modulate neurohumoral activity. We investigated the feasibility and efficacy of renal sympathetic denervation (RDN) in renal transplant recipients. Patients (n = 18) with post-transplant hypertension were randomized 1:1 to receive RDN or medical treatment alone. The primary efficacy end point was change in office systolic blood pressure (SBP) and mean 24-h ambulatory blood pressure monitoring (ABPM) at 6 months. Safety end points were changes in renal function or renovascular complications. After 6 months, patients in the RDN group had a significant reduction in office SBP of 23.3 ± 14.5 mmHg (P = 0.001 for change difference between the groups). In ABPM, nocturnal blood pressure was reduced in the RDN group by -10.38 ± 12.8 mmHg (P = 0.06), whereas no change was measured during the day. In the RDN group, significantly more patients converted from non-dippers to dippers (P = 0.035). There were no adverse safety events in either group. RDN is feasible and safe in renal transplant recipients. However, larger sham-controlled studies will be necessary to clarify the potential role of RDN in this population. NCT01899456.

Non-adherence to antihypertensive medication is very common among resistant hypertensives: results of a directly observed therapy clinic.

Resistant hypertension is common among the hypertensive population with reported prevalence of 12 to 15%. These patients have a higher cardiovascular risk and consequently a poorer cardiovascular prognosis. Suboptimal adherence with antihypertensive medication is a common contributing factor in apparent treatment-resistant hypertension. Patients were observed taking their medications under direct supervision at our directly observed therapy (DOT) clinic. At the DOT clinic visit, patients were fitted with a 24-h ambulatory blood pressure (ABP) monitor and each drug, at currently prescribed dose, was administered by a nurse; at an hourly interval and patient observed for 7 h. ABP readings between pre and post DOT clinic were compared. Fifty out of 56 patients had complete data on the ABP. Twenty four were female and the mean (s.d.) age was 62.0 (11.0) years. On the basis of the study methods that differentiated patients according to their BP response during the DOT clinic, twenty-five (50.0%) patients were deemed to be truly resistant (24-h ambulatory systolic blood pressure (SBP) fall <5 mm Hg) and the remaining 25 were deemed to have clinically significant non-adherence (24-h ambulatory SBP fall ⩾5 mm Hg) to prescribed therapy. In non-adherent patients, the mean 24-h ambulatory BP drop observed was 19.5/9.4 mm Hg (P<0.001 for both). Our results suggest that non-adherence is very common among patients considered to have apparent treatment-resistant hypertension. DOT clinic can be an effective method of identifying the truly resistant hypertensive patients.

Potential future denervation targets

The human sympathetic nervous system has an important regulatory role. In its dysfunctional hyperexcitatory state, it can lead to multiple pathologies. The renal sympathetic nerves play a significant role in these pathological states. Percutaneous renal sympathetic denervation (RSDN) allows for safe minimally invasive selective denervation of the renal sympathetic nerves. RSDN has been shown to be safe and efficacious in blood pressure reduction in earlier nonblinded SYMPLICITY HTN-1 and -2 trials. In Europe, it is approved for a select group of truly resistant severe essential hypertension. However, its real efficacy is now in doubt with the blinded SYMPLICITY HTN-3 trial that showed no significant difference in change in office and mean 24-h ambulatory systolic blood pressure between RSDN and sham-procedure arms. This review will look at the potential targets for percutaneous RSDN-heart failure, cardiac arrhythmias and kidney disease, sleep-disordered breathing and insulin resistance.

Impact of Renal Denervation on 24-Hour Ambulatory Blood Pressure: Results From SYMPLICITY HTN-3

BackgroundPrior studies of catheter-based renal artery denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. ObjectivesSYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal denervation or a sham procedure on ABPM measurements 6 months post-randomization. MethodsPatients with resistant hypertension were randomized 2:1 to renal denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. ResultsThe 24-h ambulatory SBP changed −6.8 ± 15.1 mm Hg in the denervation group and −4.8 ± 17.3 mm Hg in the sham group: difference of −2.0 mm Hg (95% confidence interval [CI]: −5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was −1.1 (95% CI: −4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was −3.3 (95 CI: −6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the denervation group and 15.0% in the sham group (95% CI: −3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was −1.4 ± 7.4 in the denervation group and −1.3 ± 7.3 in the sham group; (95% CI: −1.5 to 1.4; p = 0.94). ConclusionsThis trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261)