24-h Systolic Blood Pressure Research Articles

An Underlying Mechanism by which Hepatic Steatosis Drives the Development of Hypertension

Hepatic steatosis, a consequence of obesity, is closely associated with metabolic and cardiovascular diseases, including hypertension. Even in patients that are not hypertensive, the amount of fat in the liver is positively associated with blood pressure. We hypothesized there was an underlying mechanism linking excess fat in the liver with increased blood pressure. We have previously established that liver lipid content is positively associated with hepatic production and release of the inhibitory neurotransmitter GABA, a process dependent on both the GABA shunt and electrogenic GABA transporters. Because GABA is co‐transported with 1‐2 net positive charges, hepatocyte depolarization, common in obesity, encourages hepatocyte GABA release. To investigate the effect of hepatocyte depolarization, we used an adeno‐associated virus to induce hepatocyte specific expression of an artificial chimeric channel that opens in the presence of an exogenous ligand causing depolarization. Inducing hepatocyte depolarization increases release of GABA and decreases hepatic vagal afferent nerve activity. We established that administering the depolarizing ligand acutely (15‐40 minutes after IP administration) increased systolic (30.08 ± 5.6 mmHg), diastolic (16.47 + 4.3 mmHg), and mean blood pressure (17.85 + 4.4 mmHg) measured via telemetry devices. In hepatic vagotomized mice hepatocyte depolarization had no effect on blood pressure, establishing the key role of afferent hepatic vagal signals in regulating blood pressure. Pharmacological inhibition of the GABA shunt by daily administration of ethanolamine‐O‐sulfate (4 days; 8 mg/mouse/day) limited liver slice GABA release and decreased systolic, diastolic, and mean (10 ± 3.07 mmHg; P < 0.05) blood pressure in diet‐induced obese mice during the first hour of the dark cycle. We subsequently knocked down GABA‐transaminase with bi‐weekly IP deliver of an anti‐sense oligonucleotide targeted to GABA‐transaminase (12.5 mg/kg). We have previously established that this decreases liver GABA‐transaminase mRNA expression by 97% without affecting mRNA expression in the pancreas or brain. GABA‐transaminase knockdown decreased 24h mean, systolic, and diastolic blood pressure (17 + 3, 20 +2, and 14 + 4 mmHg respectively) in obese, angiotensin II induced hypertensive (continuous delivery of angiotensin II 800 ng/kg/min by Alzet® osmotic minipump) male mice. Together this data supports a role of hepatocyte GABA production and release in the hypertension that accompanies obesity. Moreover, our results provide a mechanism by which hepatic lipid content can affect blood pressure, identifying potential targets for the treatment and prevention of obesity‐induced hypertension.

Influence of family history of hypertension on blood pressure and heart rate variability in young adults: a meta-analysis.

This meta-analysis evaluates the impact of family history of hypertension (FHH + ) on blood pressure (BP) and heart rate variability (HRV) in young adults. Observational studies that evaluated adults (aged between 18 and 40 years) of both sexes, are without cardiometabolic disease diagnosis, are published in English, and are reporting on the influence of FHH + (father, mother, or both) on BP and HRV were included. In June 2021, we made a search of the electronic database MEDLINE (accessed by PubMed). Random-effects models were used, and data are reported as standardized mean difference and 95% confidence limits. Thirty-eight studies with a total of 2025 individuals were included. Clinic systolic [3.13 mmHg (1.75-4.51)] and diastolic [2.85 mmHg (1.65-4.04)] BPs were higher ( P < 0.001) in individuals with an FHH + . Only 24-h systolic BP was higher [1.76 mmHg (0.05-3.47); P = 0.04] in individuals with an FHH + . As for HRV indices in time-domain, RMSSD: -7.00 ms (-10.75 to -3.26), SDNN: -13.93 ms (-23.56 to -4.30), and HF [-6.82 n. u. (-9.76 to -3.89)] were lower ( P < 0.05), and LF [4.78 ms (2.52-7.03)] and LF/HF ratio [0.32 (0.14-0.50)] were higher ( P < 0.001) in individuals with an FHH + . FHH + negatively impacts BP and HRV in young adults.

Controlled-release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta-analysis.

Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high‐quality and relevant meta‐analyses are lacking. This meta‐analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well‐tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out‐of‐office (including 24‐h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random‐effect meta‐analyses. A risk of bias assessment was performed using the Cochrane risk‐of‐bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled‐release melatonin (not an immediate‐release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: –7.88 to .73; I2 = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well‐tolerated. Due to the limited number of high‐quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. Medtronic.

Harmonic Distortion of Blood Pressure Waveform as a Measure of Arterial Stiffness.

Aging and disease alter the composition and elastic properties of the aortic wall resulting in shape changes in blood pressure waveform (BPW). Here, we propose a new index, harmonic distortion (HD), to characterize BPW and its relationship with other in vitro and in vivo measures. Using a Fourier transform of the BPW, HD is calculated as the ratio of energy above the fundamental frequency to that at the fundamental frequency. Male mice fed either a normal diet (ND) or a high fat, high sucrose (HFHS) diet for 2–10 months were used to study BPWs in diet-induced metabolic syndrome. BPWs were recorded for 20 s hourly for 24 h, using radiotelemetry. Pulse wave velocity (PWV), an in vivo measure of arterial stiffness, was measured in the abdominal aorta via ultrasound sonography. Common carotid arteries were excised from a subset of mice to determine the tangent modulus using biaxial tension-inflation test. Over a 24-h period, both HD and systolic blood pressure (SBP) show a large variability, however HD linearly decreases with increasing SBP. HD is also linearly related to tangent modulus and PWV with slopes significantly different between the two diet groups. Overall, our study suggests that HD is sensitive to changes in blood pressure and arterial stiffness and has a potential to be used as a noninvasive measure of arterial stiffness in aging and disease.

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].

Early morning hemodynamic changes and left ventricular hypertrophy and mortality in hemodialysis patients.

An exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The early morning changes in these parameters have not been investigated in the hemodialysis population. In a pilot, single center study including a series of 58 patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40months. The pre-awakening HR surge (r = -0.46, P = 0.001) but not the corresponding BP surge (r = -0.1, P = 0.98) was associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% CI 0.83-0.96, P = 0.001]. The link between the pre-awakening HR surge with these outcome measures was robust and largely independent of established risk factors in the hemodialysis population, including the nocturnal dipping of BP. Weighted 24h systolic BP and HR variability did not correlate with LVMI (all P > 0.11) nor with the risk of death (P > 0.11) and were also independent of the nocturnal dipping of systolic BP and HR. This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for left ventricular hypertrophy (LVH) and mortality in the hemodialysis population.

Incremento matutino de la presión arterial en pacientes con ictus isquémico reciente: el factor olvidado

IntroductionHigh morning BP surge (MBPS) has been associated with an increased risk of cardiovascular events. We evaluated the presence of a high MBPS in patients with recent ischaemic stroke. Material and methodsA case-control study was carried out. One hundred patients with an ischaemic stroke in the previous 6 months and fifty hypertensive patients without cardiovascular disease were included as controls. Results61 lacunar (LAC) and 39 non-lacunar (NLAC) strokes were studied. The mean age was 65±11 years, and 60 (40%) patients were women. High MBPS was present in 9% of strokes (in 5 LAC and 4 NLAC) and in 8% of controls (p not significant [NS]), with a similar mean value of MBPS in both groups: 23.9±14mmHg and 24.9±15mmHg respectively (p=NS), although the control patients had a higher office BP (systolic [p=.008] and diastolic [p=.0001]), 24h systolic BP (p=.028) and daytime systolic BP (p=.022). Among the stroke patients, high MBPS was associated with previous coronary heart disease (p=.005), circadian BP pattern (p=.029), but not with the type of antihypertensive treatment prescribed. In multivariate analysis, elevated MBPS was only associated with previous coronary artery disease (p=.001). ConclusionsApproximately one in ten patients with recent ischaemic stroke has a high MBPS. Strategies to detect and treat high MBPS after a stroke are needed.

Effects of Bushen-Jiangya granules on blood pressure and pharmacogenomic evaluation in low-to-medium-risk hypertensive patients: study protocol for a randomized double-blind controlled trial

IntroductionHypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension.Methods and analysisThis trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0.Ethics and disseminationThis study has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences.DiscussionWe hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians.Trial registrationChinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019

Effects of isometric leg training on ambulatory blood pressure and morning blood pressure surge in young normotensive men and women

Despite the reported association between diurnal variations in ambulatory blood pressure (BP) and elevated cardiovascular disease risk, little is known regarding the effects of isometric resistance training (IRT), a practical BP-lowering intervention, on ambulatory BP and morning BP surge (MBPS). Thus, we investigated whether (i) IRT causes reductions in ambulatory BP and MBPS, in young normotensives, and (ii) if there are any sex differences in these changes. Twenty normotensive individuals (mean 24-h SBP = 121 ± 7, DBP = 67 ± 6 mmHg) undertook 10-weeks of bilateral-leg IRT (4 × 2-min/2-min rest, at 20% maximum voluntary contraction (MVC) 3 days/week). Ambulatory BP and MBPS (mean systolic BP (SBP) 2 h after waking minus the lowest sleeping 1 h mean SBP) was measures pre- and post-training. There were significant reductions in 24-h ambulatory SBP in men (− 4 ± 2 mmHg, P = 0.0001) and women (− 4 ± 2 mmHg, P = 0.0001) following IRT. Significant reductions were also observed in MBPS (− 6 ± 8 mmHg, p = 0.044; − 6 ± 7 mmHg, P = 0.019), yet there were no significant differences between men and women in these changes, and 24-h ambulatory diastolic BP remained unchanged. Furthermore, a significant correlation was identified between the magnitude of the change in MBPS and the magnitude of changes in the mean 2-h SBP after waking for both men and women (men, r = 0.89, P = 0.001; women, r = 0.74, P = 0.014). These findings add further support to the idea that IRT, as practical lifestyle intervention, is effective in significantly lowering ambulatory SBP and MBPS and might reduce the incidence of adverse cardiovascular events that often occur in the morning.

Intravascular Renal Denervation Reduces Ambulatory and Office Blood Pressure in Patients with Essential Hypertension: A Meta-Analysis of Randomized Sham-Controlled Trials

Background: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. Methods: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-h ambulatory BP or office BP. This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I² index was <50%. A fixed-effects model was used when the I² index was ≥50%. Results: A total of 1,297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) −3.02 (WMD, 95% CI: −4.95, −1.10, p < 0.01) and diastolic BP (DBP) −1.66 (WMD, 95% CI: −2.44, −0.88, p < 0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −2.67 (95% CI: −5.08, −0.27; p < 0.05; I² = 0%, p = 0.53) and −0.82 (95% CI: −2.19, 0.56; p > 0.05; I² = 0%, p = 0.64) mm Hg. In the studies using second-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −3.14 (95% CI: −5.94, −0.33, p < 0.05; I² = 71%, p = 0.008) and −2.06 (95% CI: −3.02, −1.11, p < 0.001; I² = 50%, p = 0.09) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP −6.30 (WMD, 95% CI: −7.67, −4.93, p < 0.001; I² = 43%, p = 0.14) and DBP −3.88 (WMD, 95% CI: −4.44, −3.33, p < 0.001; I² = 42%, p = 0.14) mm Hg, respectively. Conclusions: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice.

Physical Activity in Renal Disease and the Effect on Hypertension: A Randomized Controlled Trial

Introduction: Exercise is an effective strategy for blood pressure (BP) reduction in the general population, but its efficacy for the management of hypertension in chronic kidney disease (CKD) is not known. We evaluated the difference in 24-h ambulatory systolic BP (SBP) with exercise training in people with moderate to severe CKD. Methods: Participants with an estimated glomerular filtration rate (eGFR) of 15–44 mL/min per 1.73 m² and SBP >120 mm Hg were randomized to receive thrice-weekly moderate-intensity aerobic-based exercise over 24 weeks, or usual care. Phase 1 included supervised in-center and home-based sessions for 8 weeks. Phase 2 was 16 weeks of home-based sessions. BP, arterial stiffness, cardiorespiratory fitness, and markers of cardiovascular (CV) risk were analyzed using mixed linear regression. Results: We randomized 44 people; 36% were female, the median age was 69 years, 55% had diabetes, and the median eGFR was 28 mL/min per 1.73 m². Compared with usual care, there was no significant change in 24-ambulatory SBP at 8 weeks (2.96 mm Hg; 95% confidence interval (CI): −2.56, 8.49) or 24 weeks. Peak oxygen uptake improved by 1.9 mL/kg/min in the exercise group (95% CI: 0.03, 3.79) at 8 weeks with a trend toward higher body mass index 1.84 kg/m² (95% CI: −0.10, 3.78) and fat free mass, but this was not sustained at 24 weeks. Markers of CV risk were unchanged. Conclusions: Despite an improvement in peak aerobic capacity and body composition, we did not detect a change in 24-h ambulatory SBP in people with moderate-to-severe CKD.

24-hour central blood pressure and immune system activation in adolescents with primary hypertension - a preliminary study.

Adult and pediatric data suggest a positive relationship between the extent of subclinical inflammation, blood pressure, and hypertension-mediated organ damage (HMOD) in primary hypertension (PH). 24-hour (24-h) ambulatory blood pressure (ABPM) and central blood pressure (CBP) are strong predictors of HMOD. Our study aimed to analyze the relationship between 24-h central ABPM, subclinical inflammation, and clinical data in adolescents with PH. In 28 untreated adolescents with PH (14.50 ±2.27 years) and 25 healthy peers (14.76 ±2.83 years), we analyzed 24-h peripheral and central ABPM, markers of subclinical inflammation (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, mean platelet volume - MPV), and clinical and biochemical data. Patients with PH had higher 24-h peripheral and central blood pressure than healthy peers. In all 53 patients, we found significant (p < 0.05) positive correlations between NLR, PLR and 24-h central systolic, diastolic, and mean blood pressure (24-h cSBP, 24-h cDBP, 24-h cMAP), between 24-h central augmentation index corrected for heart rate 75 (24-h cAIx75HR) and platelet count. In 28 patients with PH, 24-h cAIx75HR correlated with low-density lipoprotein (LDL) cholesterol (R = 0.442), and ambulatory arterial stiffness index with body mass index (BMI) (R = 0.487), uric acid (R = 0.430), and high-density lipoprotein (HDL) cholesterol (R = -0.428). Increased central 24-h blood pressure may be associated with immune system activation in adolescents with primary hypertension. In adolescents with primary hypertension, dyslipidemia and hyperuricemia are risk factors for increased arterial stiffness. Further studies on central and peripheral blood pressure in terms of their relationship with inflammation in these patients are needed.

Durable strong efficacy and favorable long-term renal safety of the anatomically optimized distal renal denervation according to the 3 year follow-up extension of the double-blind randomized controlled trial

BackgroundHistorical reports on surgical renal denervation consistently describe renal plexus as a triangle or fan-like structure converging at the kidney gate. Following that anatomy, we developed a distal mode of radiofrequency renal denervation (RDN) mainly in segmental branches of the renal artery and confirmed its superior efficacy over the conventional main trunk procedure in a 6-months double-blind randomized controlled trial (NCT02667912). To assess the long-term effects of distal RDN we extended the follow-up of our study to three years. MethodsBP, serum creatinine, eGFR were measured one and three years after randomization; major adverse renal events were assessed over the entire study period. The blinding was maintained over the entire three-year study period. FindingsOf 55 randomized patients, 47 (23/24, distal/main trunk RDN, respectively) were assessed at one year and 39 (21/18) at three years post-procedure. Twenty-four-hour ambulatory systolic BP remained powerfully lowered after distal RDN both at one- and three-years assessments(mean change from baseline: -18.0, 95% CI -27.6 to -8.5; p<0.05 and -16·9, 95% CI -27·3 to -6·5; p<0·05, mmHg, respectively. This was accompanied by a moderate drop in eGFR at one year: -8·9 ml/min/m2, 95% CI -14·8 to -3·1; p<0·05, which, however, subsequently decreased in size at three years: -6·5, 95% CI -13·2 to 0·3; p>0·05. After main trunk RDN, the decrease of 24h systolic BP was quite moderate at one year: -12·1, 95% CI -19·2 to -5·0; p<0·05, and further weakened at three-year assessment: -8·5, 95% CI -19·7 to 2·2; p>0.05. eGFR was almost unchanged at one year: -1·3, 95% CI -6·6 to 4·0; p>0·05, but significantly decreased at three years: -5·0, 95% CI -9·6 to -0·3; p<0·05. InterpretationOur data demonstrate the durable strong BP-lowering efficacy and favorable long-term renal safety of distal RDN.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against haemodialysis patients.

ABSTRACTBackgroundHypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients.MethodsA total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed.ResultsKTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P < 0.001); no significant differences were noted for diastolic blood pressure levels with the exception of the second nighttime. Repeated measurements ANOVA showed a significant effect of renal replacement therapy modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between them; the greatest between-group difference in BP (KTRs–HD in mmHg) was observed at the end of the second 24 h [–13.9 mmHg (95% confidence interval –21.5 to –6.2); P < 0.001]. Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD patients during all periods studied (24-h SBP average real variability: KTRs: 9.6 ± 2.3 mmHg; HD first 24 h: 10.3 ± 3.0 mmHg; P = 0.032; second 24 h: 11.5 ± 3.0 mmHg; P < 0.001). No differences were noted in dipping pattern between the two groups.ConclusionsSBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Herbs and spices at a relatively high culinary dosage improves 24-hour ambulatory blood pressure in adults at risk of cardiometabolic diseases: a randomized, crossover, controlled-feeding study

ABSTRACTBackgroundIntake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases.ObjectivesThe objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d−1 · 2100 kcal−1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults.MethodsA 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period.ResultsNo between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P = 0.02) and diastolic (P = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (−1.9 mm Hg; 95% CI: −3.6, −0.2 mm Hg; P = 0.02); the difference between the HSD and LSD was not statistically significant (−1.6 mm Hg; 95% CI: −3.3, 0.04 mm Hg; P = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (−1.5 mm Hg; 95% CI: −2.5, −0.4 mm Hg; P = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function.ConclusionsIn the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d−1 · 2100 kcal−1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d−1 · 2100 kcal−1), in adults at elevated risk of cardiometabolic diseases.This trial was registered at clinicaltrials.gov as NCT03064932.

Considering Psychosocial Factors When Investigating Blood Pressure in Patients with Short Sleep Duration: A Propensity Score Matched Analysis.

Few studies have considered psychosocial characteristics when investigating the associations between sleep duration and blood pressure (BP). In this study, we took propensity score matching (PSM) to adjust for psychosocial characteristics when comparing BP between individuals with short sleep duration and those with normal sleep duration. A total of 429 participants were included. 72 participants with sleep duration ≤6 h and 65 participants with sleep duration >6 h were matched after PSM. We compared office BP, 24-hour BP, and prevalence of hypertension in the populations before and after PSM, respectively. In the unmatched population, participants with sleep duration ≤6 h were observed with higher office diastolic BP (DBP) and 24-h systolic BP (SBP)/DBP (all P < 0.05). In the matched populations, the differences between the two groups (sleep duration ≤6 h vs. sleep duration >6 h) in office DBP (88.4 ± 10.9 vs. 82.5 ± 11.1 mm Hg; P=0.002), 24-h SBP (134.7 ± 12.0 vs. 129.3 ± 11.6 mm Hg; P=0.009), and 24-h DBP (83.4 ± 9.9 vs. 78.1 ± 10.1 mm Hg; P=0.002) become more significant. Participants with sleep duration ≤6 h only show higher prevalence of hypertension based on 24-h BP data, while analysis after PSM further revealed that these with sleep duration ≤6 h presented about 20% higher prevalence of elevated BP up to office diagnosed hypertension threshold. Therefore, psychosocial characteristics accompanied with short sleep duration should be fully valued in individuals at risks for elevated BP. This trial is registered with NCT03866226.

Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS.

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration.Methods: Young and middle-aged adults (18–65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction.Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (−9.9 vs −9.9 mmHg, P > 0.05) or daytime (−11.5 vs. −10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (−10.8 vs. −10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups.Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

Six Months of Inspiratory Muscle Training to Lower Blood Pressure and Improve Endothelial Function in Middle-Aged and Older Adults With Above-Normal Blood Pressure and Obstructive Sleep Apnea: Protocol for the CHART Clinical Trial.

Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance—due to poor sleep quality and nocturnal hypoxemia—and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA.Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50–80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living.Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously.Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).

Association between Short-Term Blood Pressure Variability and Intracranial Atherosclerotic Plaque Vulnerability: A High-Resolution Magnetic Resonance Imaging Study.

Aim: short-term blood pressure variability (BPV) as a risk factor of atherosclerosis and cardiovascular events has been investigated. However, its association with atherosclerotic plaque vulnerability remains unknown. The objective of this study was to determine the association between short-term BPV and intracranial atherosclerotic plaque vulnerability. Methods: this is a cross-sectional analysis of 267 ischemic stroke patients with symptomatic intracranial atherosclerosis (mean age, 65±12 years old; 60.3% male), which were prospectively recruited in a comprehensive stroke center. Systolic and diastolic BP SD, CV, and BP variability ratio (BPVR) from 24 hours, daytime, and nighttime were calculated from 24-h ambulatory blood pressure monitoring, intracranial atherosclerotic plaque burden and vulnerability were evaluated by high-resolution magnetic resonance vessel wall imaging. Logistic regression analysis was used to locate the correlation between short-term BPV and plaque vulnerability. Results: a total of 36.3% subjects presented with intraplaque hemorrhage (IPH) in this study. Multivariate logistic regression suggested that nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently after adjusted for cardiovascular risk factors, odds ratio (OR) and 95% confidence interval (CI) for per SD BPV changes were 1.418 (1.051, 1.914) and 0.731 (0.548, 0.976), respectively, and this association also independent of atherosclerosis burden and 24-h mean systolic BP level. Further subgroup analysis by age and hypertension history demonstrated that the statistical correlation could only establish in the elder, and subjects with hypertension. Conclusion: nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently, especially in the elderly and subjects with hypertension.