Reduction In 24-hour Systolic Blood Pressure Research Articles

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 the first 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; AngioCare, 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://clinicaltrials.gov; Unique identifier: NCT02901704.

Reduction in systolic blood pressure following dietary fibre intervention is dependent on baseline gut microbiota composition

Uncontrolled hypertension is a primary cause of non-communicable diseases and death globally(1). The gut microbiota plays a role in hypertension and dietary interventions high in fibre have been shown to lower blood pressure (BP)(2). Not all participants respond to dietary fibre interventions, for reasons which are unclear. Here we aimed to identify responders of a high fibre intervention based on their baseline gut microbiome. Twenty treatment-naive participants with hypertension received either placebo or 40g per day of prebiotic acetylated and butyrylated high amylose maize starch (HAMSAB) supplementation for 3 weeks in a phase II randomised cross-over double-blind placebo-controlled trial. Blood pressure was monitored at baseline and each endpoint by 24-hour ambulatory BP monitoring, with those experiencing a reduction between timepoints of ≥ 2 mmHg classified as responders. Baseline stool samples were collected and the V4-V5 region of the 16S gene sequenced. Taxonomy was assigned by reference to the SILVA database. The MaAsLin2 package was used for assessing the relationship between baseline gut microbiota and response to dietary intervention. Overall participants had significant reduction in 24-hour systolic BP (–6.1 mmHg, p = 0.03), with 14 individuals classified as responders and six individuals as non-responders. 13 genera were found to be differentially abundant between responders and non-responders. Genera significantly enriched in responders included Dialister (β = 1.29, q = 1.921x10-134), Coprococcus (β = 1.26, q = 3.282x10-121), Bifidobacterium (β = 1.67, q = 1.11x10-81), Ruminococcus (β = 0.161, q = 1.11x10-8) and Roseburia (β = 0.82, q = 4.275x10-2). Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased level of bacterial genera known to contain species that produce short-chain fatty acids (e.g. Bifidobacterium, Roseburia and Ruminococcus) at baseline. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension.

S-57-3: GUT MICROBIAL METABOLITES LOWER 24-HOUR SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS

Objective: Clinical evidence supports that dietary fibre intake lowers blood pressure (BP). Dietary fibres remain intact until they reach the colon. There, they are fermented by gut microbial communities to produce metabolites, particularly short-chain fatty acids (SCFAs). Previous studies, including our own, have demonstrated that supplementation with the SCFAs acetate and butyrate lower BP in experimental models. However, whether dietary supplementation with SCFAs in humans elicits the same reduction in BP is undetermined. We aimed to establish whether a SCFAs-enriched dietary supplement lowers 24-hour BP in participants with essential hypertension. Design and method: Twenty untreated hypertensive participants, diagnosed by 24-hour BP using a Mobil-O-Graph device, were recruited for a phase II randomized placebo-controlled double-blind crossover trial. Participants were randomized to receive a daily intervention of 40 g/day of acetylated and butyrylated high amylose maize starch (HAMSAB) or 40 g/day of regular flour or cornflour (placebo). The dietary intervention lasted three weeks, with a three-week washout period following completion. The primary endpoint was a change in 24-hour systolic BP. Secondary endpoints included SCFA levels and changes in gut microbiome. Results: Participants were on average 55.8 ± 11.2 (mean ± SD) years of age, had a body mass index (BMI) of 25.7 ± 2.5km2/m, and 30% were female. The baseline 24-hour systolic BP was 136 ± 6mmHg. The dietary intervention was well-tolerated and had high acceptability with 93% compliance. There was no difference in 24-hour systolic BP between the baseline visits (P = 0.55) and the placebo (P = 0.18). After 3-weeks on the HAMSAB diet, the placebo-subtracted treatment 24-hour systolic BP difference was 6.1 ± 9.9mmHg (P = 0.027). These observations were independent of age, sex, BMI and study arm. Day and night systolic BP were reduced by 6.5 ± 12.3mmHg (P = 0.01) and 5.7 ± 9.8mmHg (P = 0.02), respectively, and 24-h central BP by 7.2 ± 14.7 mmHg (P = 0.005). There was no change in stroke volume, cardiac output or heart rate; however, HAMSAB reduced total vascular resistance (P = 0.049). Compared to the placebo, the HAMSAB diet elevated acetic and butyric acid levels by 7.8-fold (P = 0.016). HAMSAB also shifted the gut microbial ecosystem (P = 0.037) and increased the prevalence of the acetate and butyrate producers Parabacteroides distasonis and Ruminococcus gauvreauii (q-value &lt; 0.05). Conclusions: We observed a clinically relevant reduction in 24-hour systolic BP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP. Low fibre diets and reduced gut microbial metabolites may be one of the principal reasons for the hypertension epidemic in Western countries.

JS-HR-10: ADVANCES IN RENAL DENERVATION FOR TREATING HYPERTENSION

Excessive activation of sympathetic nervous system is closely related to the onset and progression of hypertension. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure (BP) and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the cardiovascular center in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. Renal denervation (RDN) is a neuromodulation therapy that partially interrupts both the efferent outputs from the brain to the kidney and the afferent inputs from the kidney to the brain and has attracted attention as a novel device therapy for hypertension. In clinical practice, denervation is performed through the lumen of the renal artery using a catheter. Radiofrequency, ultrasound, and alcohol-based RDN devices are being developed as new second-generation devices. A randomized sham-controlled trials using 24-hour ambulatory BP measurement is required for approval of clinical use of RDN. The SPYRAL HTN OFF-MED pivotal trial showed the superiority of RDN using radiofrequency-based catheter compared with a sham procedure to safely lower 24-hour systolic BP in the absence of antihypertensive medications. The RADIANCE-HTN TRIO trials showed the superiority of RDN using ultrasound-based catheter compared with a sham procedure to safely lower daytime BP in patients with resistant hypertension. The REQUIRE trial is the first trial of ultrasound RDN in Asian patients from Japan and South Korea with resistant hypertension. The study findings were neutral for the primary endpoint, with similar reductions in 24-hour systolic BP in the RDN and sham control groups. Although BP reduction after RDN was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. Japanese Society of Hypertension performed the meta-analysis of nine randomized sham-controlled trials of RDN including these three trials mentioned above. The results showed that RDN significantly reduced a range of office, home and 24-hour BP parameters in patients with resistant, uncontrolled, and drug-naïve hypertension. There were no significant differences in magnitude of BP reduction between radiofrequency-based and ultrasound-based devices. Recently, the efficacy and safety of RDN in the SPYRAL HTN OFF-MED pivotal trial up to 36 months have been reported. In this session, the latest basic and clinical evidence/aspects of RDN will be summarized and discussed, which is about to be introduced into the clinical practice.

The role of continuous positive airway pressure in blood pressure control for patients with obstructive sleep apnea and hypertension: a meta-analysis of randomized controlled trials.

The aim of this study was to review the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and hypertension. Biomedical databases were searched for randomized controlled trials (RCTs) comparing CPAP with control among these patients. Seven RCTs reporting 24-hour ambulatory BP were identified for meta-analysis. CPAP was associated with significant reductions in 24-hour ambulatory systolic blood pressure (SBP) (-2.32 mm Hg; 95% confidence interval [CI], -3.65 to -1.00) and diastolic blood pressure (DBP) (-1.98 mm Hg; 95% CI, -2.82 to -1.14). CPAP led to more significant improvement in nocturnal SBP than that in diurnal SBP. Subgroup analysis showed that patients with resistant hypertension or receiving antihypertensive drugs benefited most from CPAP. Meta-regression indicated that CPAP compliance, age, and baseline SBP were positively correlated with decrease in 24-hour DBP, but not reduction in 24-hour SBP.

Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.

Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified.

Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product

Background Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early morning period, a time when both morbid and mortal cardiovascular events are increased compared to other times of the day. Methods We studied the effects of a graded-release delivery system of diltiazem (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime, on blood pressure (BP), heart rate, and the heart rate-systolic BP product during the first 4 hours after awakening in a double-blind, titration-to-effect trial. There were 261 men and women enrolled in the trial with an untreated sitting diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109 mm Hg. Patients were randomized to either diltiazem extended release (ER) tablets each evening (240 mg titrated to 360 mg and to 540 mg) or ramipril each evening (5 mg titrated to 10 mg and to 20 mg). Early morning assessments of BP, heart rate, and the heart rate-systolic BP product were performed using 24-hour ambulatory recordings after 10 weeks of therapy. Results In each therapeutic group, 76% of patients were titrated to the highest possible dose. After 10 weeks of treatment, reductions in early morning BP by diltiazem ER tablets were significantly greater (−18/−15 mm Hg) than reductions by ramipril (−13/−8 mmHg , P < .005 for systolic BP and P < .001 for diastolic BP). Diltiazem ER tablets also led to greater reductions in morning heart rate and the heart rate-pressure product compared to ramipril. Reductions in mean 24-hour diastolic BP, heart rate, and the rate-pressure product were greater in patients treated with diltiazem ER tablets compared to ramipril, while reductions in 24-hour systolic BP were similar in each group. The observed adverse effects were not serious and incidences were similar for the 2 treatment groups. Conclusions These data demonstrate that bedtime administration of diltiazem ER, an agent designed to parallel the circadian rhythm of BP and heart rate, led to significantly greater early morning hemodynamic effects compared to the angiotensin-converting enzyme inhibitor ramipril, also dosed in the evening.