bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RISKS AND BENEFITS OF RENAL ARTERY STENTING IN FIBROMUSCULAR DYSPLASIA. LESSONS FROM ARCADIA-POL STUDY
Authors: Kadziela Jacek , Jozwik-Plebanek Katarzyna , Pappaccogli Marco , Niepen Patricia Van Der , Prejbisz Aleksander , Dobrowolski Piotr , Michalowska Ilona , Talarowska Paulina , Warchol-Celinska Ewa , Strzyczynski Lukasz , Krekora Jan , Andziak Piotr , Maciag Rafal , Sterlinski Ignacy , Witkowski Adam , Januszewicz Andrzej , Adlam David , Januszewicz Magdalena , Persu Alexandre
Published: June 2023

Objective:

Percutaneous transluminal angioplasty (PTA) is the recommended revascularization strategy in patients with renal artery stenosis (RAS) caused by fibromuscular dysplasia (FMD), limiting stenting to complications management. However this recommendation is based on cases reports and small series.

The main aim of the study was to retrospectively analyze immediate and long-term results of renal stenting and PTA in FMD patients. The second aim was to evaluate the results of stenting as support of renal artery aneurysm (RAA) closure.

Design and method:

The study group consisted of 58 patients percutaneously treated due to significant RAS (70 arteries) and 9 patients (10 RAAs) with a history of stent implantation before aneurysm embolization, derived from 343 ARCADIA-POL registry patients. PTA was performed as initial treatment in 61 arteries (PTA-group), whereas primary stenting was done in 9 arteries (STENT-group). Stent-related complications(SRC) were defined as: in-stent restenosis (>50%) or occlusion (ISR/O); stent fracture; stent underexpansion (SU) or migration.

Results:

In PTA-group, the first restenosis rate was 50.8%. Subsequently, 22 arteries underwent a second procedure: re-PTA(12 arteries) or stent implantation(10 arteries) . The incidence of recurrent restenosis after re-PTA was 41.7%. In the 10 arteries initially treated with PTA that underwent stenting for restenosis, complications occurred in 7 of them (70%), including 2 SUs and 5 ISR/Os .

In STENT-group, SU occurred in one case (11.1%) and in-stent restenosis in 33.3% (3 of 9 stents).

In combined analysis, SRC occurred following 11/19 stenting procedures (57.9%) including 3 periprocedural (SUs) and 8 late complications (ISR/Os). Finally, despite several subsequent revascularization attempts, 4 of 19 (21%) stented arteries were totally occluded and one remained significantly stenosed at follow-up imaging (Figure).

In contrast to FMD-RAS procedures, there was only one intraprocedural complication (partial stent migration) and no late SRC in RAA patients.

Conclusions:

Renal artery stenting in FMD provides modest benefit in terms of restenosis prevention but poses high risk of immediate and late complications, including stent occlusion. Our study supports recommendations limiting stenting to the management of complications. In contrast, renal artery stenting in FMD RAA closure is associated with favorable long-term outcomes.
A PROSPECTIVE MULTICENTER RANDOMIZED SHAM-CONTROLLED CLINICAL TRIAL TO EVALUATE THE SAFETY AND EFFECTIVENESS OF NETRODTM RADIOFREQUENCY RENAL DENERVATION SYSTEM FOR HYPERTENSION
Authors: Gao Fei , Li Yue Ping , Zhou Yu Jie
Published: June 2023

Objective:

To evaluate the safety and effectiveness of a novel basket-like six-electrode radiofrequency renal denervation (RDN) system (NetrodTM RDN System) in treating patients with uncontrolled hypertension.

Design and method:

This is a prospective, multicenter, randomized sham-controlled trial. Patients with uncontrolled hypertension (office BP > = 150/90 and <180/110mmHg, and average SBP > = 135mmHg by 24-hour ambulatory BP monitoring (ABPM), after taking > = 2 antihypertensive drugs with stable dose for > = 4 weeks) were screened after informed consent. All eligible patients first entered a lead-in period for > = 4 weeks of standardized medication (Nifedipine + hydrochlorothiazide), and those continued to meet definition of uncontrolled hypertension were randomized 2:1 to RDN group (using NetrodTM RDN System) and sham control group (renal artery angiography only). All continued with the 2-drug regimen and were evaluated at 7 days or discharge (whichever comes first), 1, 2, 3 and 6 months post procedure. Both patients and site investigators who evaluate the patients were blinded to treatment assignment. The primary endpoint is office SBP change from baseline at 6 months post procedure. Secondary endpoints include changes from baseline of office DBP. 24-hour ABPM at 6 months post procedure and safety events.

Results:

A total of 205 patients from 25 centers were enrolled and 139 randomized to RDN group and 66 to sham control group, with no statistical difference of baseline clinical characteristics between the 2 groups including baseline BP. Compared to baseline, at 6 months post procedure RDN group has a significantly greater office SBP reduction than sham group (25.53 ± 12.62mmHg vs 8.39 ± 11.89mmHg, p < 0.001). Office DBP change was -13.49 ± 8.09mmHg (RDN) vs -3.93 ± 9.04mmHg (sham), p < 0.001. For 24-hour ABPM, the average SBP and DBP reduction were also significantly greater in the RDN vs sham group (11.91 ± 12.23 vs 3.87 ± 12.45mmHg, p < 0.001; 6.03 ± 7.50 vs 1.68 ± 7.30mmHg, p < 0.001, respectively). Device or procedure related serious adverse events were rare throughout the trial.

Conclusions:

The novel NetrodTM RDN System is safe and effective in treating uncontrolled hypertension with significant reduction in both office and 24-hour ambulatory BP.
RESPONSE OF BLOOD PRESSURE TO RENAL DENERVATION IS NOT ASSOCIATED WITH GENETIC VARIANTS
Authors: Delles Christian , Schmieder Roland E. , Daly Ronan , Hamilton Graham , Schmid Axel , Herzyk Pawel , Mahfoud Felix
Published: June 2023

Objective:

Renal denervation (RDN) is an evidence-based therapeutic option in patients with hypertension. However, the blood pressure (BP) responses to RDN in individual patients is currently impossible to predict. We conducted an unbiased genomic screen to identify genetic variants that are associated with response to RDN.

Design and method:

We included 268 patients (34.7% female, mean age 62 ± 10 years, BMI 30.5 ± 5.1 kg/m2) with uncontrolled treatment resistant hypertension (baseline BP 166 ± 21 / 90 ± 15 mmHg) who underwent endovascular RDN using the Symplicity™ catheter (Medtronic Inc, USA). Response to 24 hour ambulatory BP was assessed after 6 months and divided into two groups, above and below the median response of 6.0 mmHg, taking pre-intervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249,669 variants was conducted using Illumina NovaSeq technology read on a Nova Seq S4 Flow Cell device. Read quality was overall excellent with the eight poorest performing samples still covering 30 reads per base for 80% of the exome. Reads were analysed by a standardised variant calling pipeline, using principal component analysis followed by individual logistic regressions to model association of variants with phenotype where appropriate.

Results:

There has been no linkage found between individual gene variants and the response variable. These neutral findings were further confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in AGT, ADD1, ADRB1, ADRB2 and SCNN1A that have been proposed as potential candidate genes for response of BP to RDN and again found no association (all p>0.13). Gene ontology analysis of variants across the two responder groups highlighted differences in biological processes such as cell adhesion and molecular function such as protein tyrosine kinase activity.

Conclusions:

Response to RDN is not robustly associated with the genetic make-up of patients with uncontrolled treatment resistant hypertension. Our data do not support the use of a genetic score to predict BP response. We found, however, different regulation of biological processes and cellular/molecular function that could provide insights into the mechanisms of RDN.
CHANGES ON RIGHT VENTRICULAR DIMENSIONS, FUNCTION, AND PULMONARY CIRCULATION LOADING ACCORDING TO THE DEGREE OF INTERDIALYTIC WEIGHT GAIN IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Anastasiou Vasileios , Alexandrou Maria Eleni , Kamperidis Vasileios , Daios Stylianos , Tsilonis Konstantinos , Theodorakopoulou Marieta , Moysidis Dimitrios , Iatridi Fotini , Giannakoulas George , Ziakas Antonios , Sarafidis Pantelis
Published: June 2023

Objective:

The right ventricle (RV) is a thin-walled cardiac chamber, whose sizing and pressure characteristics are susceptible to altered loading conditions. This study aimed to investigate changes in RV's function, right heart's dimensions, and pulmonary pressures in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%).

Design and method:

Forty-one patients receiving standard thrice-weekly hemodialysis were divided into a higher (> 4.5%) and a lower ( <  4.5%) IDWG% group for the present analysis, according to the recommended higher threshold of IDWG%. All participants underwent a 2-dimensional echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval in a crossover design.

Results:

RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs 14.11 ± 13.38 mmHg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, assessed by RV E/Em did not differ significantly between the two groups (p = 0.84). Significant right heart chambers’ enlargement was observed in both groups and during both intervals, but a more prominent dilatation of inferior vena cava was noted in patients with higher IDWG% (0.44 ± 0.25 vs 0.2 ± 0.31cm, p = 0.014) over the 2-day interval.

Conclusions:

During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher that the recommended thresholds, as evidenced by higher RVSP elevations. This finding may add another plausible mechanism for increased cardiovascular morbidity and mortality during the long interval.
CARDIOVASCULAR AND ALL-CAUSE MORTALITY ARE NOT CLOSER ASSOCIATED WITH CENTRAL THAN PERIPHERAL BLOOD PRESSURE IN AN ELDERLY CHINESE POPULATION: THE NORTHERN SHANGHAI STUDY
Authors: Yu Shikai , Zhao Song , Tang Jiamin , Zhao Yifan , Xu Yawei , Zhang Yi
Published: June 2023

Objective:

Controversy exists in the comparison between central and peripheral blood pressure (BP) in prediction of cardiovascular and all-cause mortality. To examine whether central BP predicts cardiovascular and all-cause mortality better than brachial BP in a large cohort of elderly Chinese.

Design and method:

A total of 3050 participants enrolled in the Northern Shanghai Study, a prospective cohort study focusing on the cardiovascular risk of community-dwelling elderly Chinese living in the north of Shanghai, China between 2014 and 2019, were included. Central BP was estimated tonometrically from the redial pulse waveform. Vital status of all participants was confirmed by reviewing the regional morality record system in October 2020. Cox proportional hazards models were conducted to evaluated the predictive value of central and peripheral systolic BP (SBP) and pulse pressure (PP).

Results:

During the median follow-up of 5.6 years, 203 deaths, 77 of which were cardiovascular, occurred. When central and peripheral SBP were analyzed separately, both central and peripheral SBP predicted all-causes mortality (Peripheral: HR 1.040, 95% CI 1.002 to 1.080; Central: HR 1.038, 95%CI 1.000 to 1.078; Per 5 mm Hg), but not cardiovascular mortality, after adjusting age, sex, BMI, current smoking, lipid, cerebrocardiovascular disease, diabetes, antihypertensive treatment, statin treatment, hypoglycemic treatment and estimated glomerular filtration rate. When central and peripheral SBP were included in the same stepwise regression of all-cause mortality, only peripheral SBP were stayed in the final model (HR 1.037, 95%CI 1.000 to 1.074, per 5 mm Hg), after adjustment for covariates. Neither central nor peripheral PP predicted mortality after adjusted covariates.

Conclusions:

Central BP was not superior than peripheral BP in predicting cardiovascular and all-cause mortality in the elderly Chinese.
EFFECTS OF 2-WEEK DIETARY NITRATE SUPPLEMENTATION AND ANTIBACTERIAL MOUTHWASH TREATMENT ON RESERVOIR-EXCESS PRESSURE PARAMETERS IN HEALTHY OLDER ADULTS
Authors: Aizawa Kunihiko , Thompson Christopher , Hughes Alun D. , Parker Kim H. , Shore Angela C. , Vanhatalo Anni , Jones Andrew M.
Published: June 2023

Objective:

The nitrate-nitrite-nitric oxide pathway contributes to blood pressure (BP) regulation in humans. However, it is unknown if the pathway alters arterial haemodynamic parameters derived from reservoir-excess pressure analysis. We therefore determined whether an enhancement/disruption of nitrate-nitrite-nitric oxide pathway by dietary nitrate and antibacterial mouthwash, respectively, would alter reservoir-excess pressure parameters in older adults.

Design and method:

Healthy older adults (n = 30, 71.0 ± 2.6 yrs, 19F, 133 ± 11 mmHg for systolic BP and 70 ± 6 mmHg for diastolic BP) participated in this study. Participants were randomised to either a 2-week active nitrate treatment (BR: ∼12.4 mmol beetroot juice daily as a nitrate source) or 2-week placebo treatment (PL: nitrate-depleted beetroot juice) followed by 2-week washout. They then crossed-over to the alternate treatment which was followed by another 2-week washout. Thereafter, they completed a twice-daily antibacterial mouthwash treatment (MW) for two weeks with the aim of disrupting enterosalivary nitrate circulation. Prior to and following each 2-week treatment, reservoir-excess pressure parameters including reservoir pressure integral, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant were obtained through radial artery tonometry along with brachial systolic and diastolic BP. Aortic pulse wave velocity (aPWV) was estimated as previously described (Hughes et al., Front Physiol 2020;11:550).

Results:

Circulating plasma nitrate [614 (95%CI: 545, 683) microM] and nitrite [0.51 (95%CI: 0.30, 0.72) microM] increased with BR, and decreased with MW [nitrate, -17.1 (95%CI: -28.1, -6.1) microM; nitrite, -0.03 (95%CI:-0.05, -0.01) microM]. Relative to PL, BR reduced brachial systolic BP [-2.0 (95%CI: -3.9, -0.1) mmHg], INTXSP [-0.4 (95%CI: -0.7, -0.1) mmHg·s], and aPWV [-0.2 (95%CI: -0.4, 0.0) m/s]. MW increased brachial systolic [2.0 (95%CI: 0.0, 3.9) mmHg], diastolic [1.2 (95%CI: 0.4, 2.0) mmHg] BP, and decreased SRC [-0.2 (95%CI: -0.3, 0.0) 1/s] relative to PL.

Conclusions:

Favourable (INTXSP with BR) and unfavourable (SRC with MW) alterations in reservoir-excess pressure parameters were observed with 2-week dietary nitrate and antibacterial mouthwash treatments, which was accompanied by a small change in brachial systolic BP. These observations may suggest a potential link between enhancing/disrupting nitrate-nitrite-nitric oxide pathway and cardiovascular health in older adults.
THE EFFECT OF POTASSIUM SUPPLEMENTATION ON ALDOSTERONE AND BLOOD PRESSURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: McNally Ryan , Chowienczyk Phil , Farukh Bushra , Faconti Luca
Published: June 2023

Objective:

Increased potassium intake can reduce blood pressure (BP) particularly in subjects with hypertension by favouring sodium excretion and promoting vasorelaxation. However, potassium intake also stimulates the activity of the renin-angiotensin-aldosterone system (RAAS) which is one of the main homeostatic pathways for BP regulation. This interaction however has not been extensively investigated. Here we perform a systematic review and meta-analysis of clinical trials to assess the effect of subacute potassium supplementation on plasma aldosterone concentration (PAC) and BP in adult individuals.

Design and method:

This systematic review and meta-analysis was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL). Medical subject headings (MeSH) and non-MeSH terms were used to search the databases for relevant publications. Titles were firstly screened by title and abstract for relevance before full-text articles were assessed for eligibility according to a pre-defined inclusion and exclusion criterion. The keywords used included “aldosterone”, “potassium” and “RAAS”. The review protocol was registered on the PROSPERO database.

Results:

A total of 6395 articles were retrieved (after removal of duplicates) and after title/abstract screening, 124 full-text articles were assessed for eligibility. 38 met the pre-specified inclusion/exclusion criteria of including potassium and PAC (of which 17/38 also reported systolic BP (SBP)). Potassium supplementation caused a significant decrease in SBP (mean difference [95% CI] -3.48mmHg [-4.8, -2.1], P < 0.001) and an increase in both urinary potassium excretion (75.5mEq/day [59.6, 65.5], P < 0.001) and serum potassium (+0.43 [0.22, 0.64] mmol/L, P < 0.001). There was also an increase in PAC (standardised 0.395 [0.271, 0.519], P < 0.001). Meta-regression showed a significant positive correlation between change in PAC and change in urinary potassium (P < 0.001) but not with SBP (P = 0.93).

Conclusions:

In adult individuals, potassium supplementation lead to decrease in BP and increase in serum/urinary potassium and PAC. There is no correlation between the BP-lowering effect and rise in aldosterone.
PROGNOSTIC SIGNIFICANCE OF THE WALL TO LUMEN RATIO OF RETINAL ARTERIOLES EVALUATED BY ADAPTIVE OPTICS IN HUMAN HYPERTENSION
Authors: Ciuceis Carolina De , Rosei Claudia Agabiti , Malerba Paolo , Brami Valeria , Chiarini Giulia , Fama’ Francesca , Rossini Claudia , Gaggero Andrea , Lemoli Matteo , Nardin Matteo , Petelca Alina , Bortoluzzi Chiara , Baresi Mattia , Porteri Enzo , Muiesan Maria Lorenza , Rosei Enrico Agabiti , Rizzoni Damiano
Published: June 2023

Objective:

Structural alterations in the microcirculation may be considered an important mechanism of hypertension-mediated organ damage. An increased media to lumen ratio of subcutaneous small resistance arteries evaluated with locally invasive techniques (biopsies of subcutaneous fat, micromyography) may predict the subsequent development of cardiovascular events. However, it is not presently known whether structural alterations of retinal arterioles evaluated with a non-invasive approach (adaptive optics) may have a prognostic meaning.

Design and method:

Two-hundred and thirty-seven subjects were included in the present study. They were normotensive subjects (n = 65, 27,4%) and patients with essential hypertension (n = 163, 68,8%) or primary aldosteronism (n = 9, 3,8%). All subjects were submitted to a non-invasive evaluation or retinal arteriolar morphology (evaluation of the wall/lumen ratio: WLR) by adaptive optics. The subjects were re-evaluated after an average follow-up time of 5.5 years on order to assess the occurrence of death or cardio-cerebrovascular events.

Results:

Fifty-four total events occurred in the population enrolled, of which 29 were cardio-cerebrovascular event (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, including aneurism requiring intervention, cardiac valvular disease) while the remaining were events or deaths for any cause, including neoplastic disease. The event-free survival was significantly less in those with a WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (p < 0.001 by both the Mantel-Cox test and the Breslow test). Subjects with events had a WLR of retinal arterioles significantly greater than those without events. The evidence was confirmed after restricting the analysis to cardiovascular events, excluding events or deaths of neoplastic origin. The average follow-up time of our subjects was 4.6 ± 1.6 years for a total of 1090 patients-years. Patients with cardiovascular events were older and with more elevated levels of circulating glucose.

Conclusions:

Structural alterations of retinal arterioles evaluated by adaptive optics may predict cardio-cerebral events and total mortality.
THE CLINICAL RELEVANCE OF ADOPTING DIFFERENT DEFINITIONS OF NIGHT-TIME WHEN ASSESSING NOCTURNAL BLOOD PRESSURE
Authors: Hofmann Elisabeth , Küchler Gert , Parati Gianfranco , Bothe Tomas L. , Patzak Andreas , Pilz Niklas
Published: June 2023

Objective:

For hypertension diagnosis, the current European guidelines recommend to combine repeated office readings with use of out-of-office blood pressure (BP) measurements, like ambulatory blood pressure monitoring (ABPM). The drop of systolic BP during night (dipping behaviour) is one of the most important information offered by 24h ABPM. Night-time is most defined as the time period between 22 and 6 h. However, ambulatory sleep studies have shown that individual sleep behaviour is heterogenous. Shifted, shortened, or prolonged time-in-bed (TIB) may lead to changes in classification of dipping behaviour. Additionally, 20% of the population suffers from insomnia, meaning that during TIB patients are partially awake. We investigated nocturnal BP and dipping classification based on actual sleep time vs. individual TIB vs. 22 - 6 h.

Design and method:

Thirty adults (9 women, mean age 65.1 ± 9.5 years) underwent ABPM via a validated Boso TM- 2430 device. Simultaneously, motor activity and body position were recorded (SOMNOtouch™ NIBP, SOMNOmedics) allowing determination of individual TIB and actual sleep time.

Results:

In nine patients (30%), individual TIB was shifted by more than two hours, usually being shifted towards later hours. Mean duration of TIB was 7:18h (2:13h to 10:08h). Mean sleep efficiency in individual TIB was 85.6% compared to 72.4% in standard 22 - 6 h.

When defining TIB as 22 - 6 h, prevalence of non-dippers was 63% (n = 19). After analysing the corrected TIB, only 37% (n = 11) remained non-dippers. Individual adoption of TIB led to a change in dipping classification in 27% (n = 8) of patients (in all cases from non-dipper to dipper). Considering only BP values during actual sleep, dipping classification changed in another four patients, two patients changing from non-dipper to dipper while two patients changed from dipper to extreme dipper.

Conclusions:

In 12 out of 30 patients (40%), BP dipping classification changed when adjusting TIB individually and considering BP values during actual sleep. This study highlights that individually determined TIB and exclusion of wake phases during night is of critical importance for a correct assessment of dipping behaviour and may play an important role in optimizing the clinical management of arterial hypertension.
MONOCYTE DERIVED CYTOKINES INDUCE ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Kantauskaite Marta , Wieners Rebecca , Knipping Anika , Rahman Masudur , Duvnjak Blanka , Schmidt Claudia , Srugies Fabian , Rump Lars C. , Stegbauer Johannes
Published: June 2023

Objective:

Due to aldosterone excess and its pleotropic effects patients with primary aldosteronism (PA) are exposed to high rates of cardiovascular events. Endothelial dysfunction, as a part of vascular disease, is one of the earliest changes related to high cardiovascular risk and monocytes are the main immune cells participating in the development of vascular wall damage. Therefore, we ought to compare endothelial function between PA patients and healthy controls. Next, we wanted to estimate, if monocytes are able to induce endothelial dysfunction solely by their secretome.

Design and method:

13 healthy controls and 42 PA patients received flow mediated dilation measurements (FMD). Later, monocytes were isolated from 8 PA patients and 6 healthy individuals and placed in cell culture. 24 hours later supernatants were collected for cytokine measurements using Human Cytokine 17-plex Assay (Bio-rad). Effects of monocyte derived cytokines on endothelial function were assessed using wire Myograph (Danish Myo Technology). Pre-contraction was induced by norepinephrine (1μM) (Sigma) followed by cumulative concentration response curve to carbachol (0.3μM-300μM) (Sigma).

Results:

FMD was significantly lower among PA patients (6.3(3.8-8.1)% vs 10.5 ± 3%, p < 0.05). Furthermore, monocytes from patients with PA secreted significantly higher concentrations of following cytokines and growth factors than healthy controls: G-CSF, IFN-gamma, TNF-alfa, IL-6, IL-10, IL-8, IL-17, and MCP-1. Especially concentrations of IL-6 (388 (351-580)pg/ml vs 36(4-268)pg/ml, p < 0.05) and TNF-alfa (95(48-135)pg/ml vs 17(5-41)pg/ml, p < 0.05) were much higher among PA patients. Incubation of mouse thoracic aorta with this monocyte secretome for 24 hours revealed stronger vascular contraction than using supernatant from healthy controls. In pre-constricted murine aortas, maximal dilation of 87.9 ± 11% was reached using aortas incubated in PA monocyte secretome whereas a dilation of 90.9 ± 9.1% was reached in controls. Indeed, carbachol EC50 for aortas incubated in monocyte secretome derived from healthy controls was 1.0mkM and 1.9mkM for PA patients.

Conclusions:

PA patients demonstrate endothelial dysfunction measured by FMD. Moreover, monocytes isolated from these patients are characterized by high secretion of pro-inflammatory cytokines which induce endothelial dysfunction, one of mechanisms triggering vascular dysfunction among these patients.
GENETIC DELETION OR PHARMACOLOGICAL INHIBITION OF THE SODIUM AND HYDROGEN EXCHANGER 3 IN THE PROXIMAL TUBULES OF THE KIDNEY ATTENUATES ANGIOTENSIN II AND SALT-INDUCED HYPERTENSION
Authors: Zhuo Jia Long , Li Xiao
Published: June 2023

Objective:

According to American Heart Association, ∼46% of American adults have hypertension and ∼13 of these patients develop poorly controlled hypertension even treated with >3 - 4 different classes of antihypertensive drugs. The mechanisms underlying poorly controlled hypertension remain incompletely understood. The present study tested the proof of concept hypothesis that the sodium and hydrogen exchanger 3 (NHE3) in the proximal tubules of the kidney may be a therapeutic target of angiotensin II (Ang II) and salt-induced hypertension in mice.

Design and method:

To test the hypothesis, we generated a new mouse model with deletion of NHE3 selectively in the proximal tubules of the kidney using the iL-Sglt2-Cre and Nhe3-floxed approach (PT-Nhe3-/-). Adult male wildtype (WT) and PT-Nhe3-/- mice were infused without or with a low dose of Ang II (0.5 mg/kg/day, i.p., via minipump) and maintained on 2% high salt diet for 2 weeks to induce Ang II- and salt-dependent hypertension. Animals were then treated without or with an absorbable NHE3 inhibitor AVE-0657 for 2 weeks (20 mg/kg/day, p.o., a gift of Sanofi-Aventis).

Results:

Under basal conditions, deletion of NHE3 selectively in the proximal tubules of the kidney decreased basal systolic and mean blood pressure by ∼13 ± 3 mmHg in PT-Nhe3-/- mice (P < 0.01 vs. WT), whereas inhibition of NHE3 primarily in the proximal tubules with AVE-0657 lowered basal blood pressure by ∼7  ± 2 mmHg in WT mice (P < 0.05 vs. control WT). Ang II and high salt treatment significantly increased blood pressure by 26  ± 5 mmHg in WT mice (P < 0.01), which was significantly attenuated in PT-Nhe3-/- mice (P < 0.01). Ang II and salt-induced hypertension in WT mice was also significantly attenuated by NHE3 inhibition in the kidney proximal tubules with AVE-0657 (P < 0.01). Concurrent treatment with losartan, an AT1 receptor blocker (20 mg/kg/day, p.o.), completely lowered blood pressure to control level in WT mice (P < 0.05). AVE-0657 had no further effect on blood pressure in PT-Nhe3-/- mice.

Conclusions:

In conclusion, our results support the proof of concept hypothesis that NHE3 in the proximal tubules of the kidney may be a therapeutic target of Ang II and salt-induced hypertension.
PROGNOSIS OF RESISTANT HYPERTENSION, WHITE-COAT RESISTANT HYPERTENSION, AND REFRACTORY HYPERTENSION
Authors: Sierra Alejandro De La , Ruilope Luis , Gorostidi Manuel , Vinyoles Ernest , Segura Julian , Armario Pedro , Oliveras Anna , Williams Bryan
Published: June 2023

Objective:

To evaluate total and cardiovascular mortality in different forms of Resistant Hypertension (RH).

Design and method:

A total of 35129 treated patients were included from the Spanish ABPM Registry. Mean follow-up was 10 years. Total and cardiovascular mortality were compared in Cox models adjusted for clinical confounders. The following groups were compared:

- Controlled Hypertension (CH; N = 8146; 23.2%): normal office BP treated with 3 or less antihypertensive drugs vs. RH (N = 9408; 26.8%): elevated office BP treated with 3 or more drugs or normal office BP treated with 4 or more drugs.

- Controlled RH (CRH; N = 831; 8.8%): normal office BP treated with 4 or more drugs vs. Uncontrolled RH (UCRH; 8577; 91.2%): elevated office BP treated with 3 or more drugs.

- Among patients with UCRH, the following groups were compared: True RH (TRH; 5288; 61.7%): elevated (>130/80 mmHg) 24-h BP vs. White-coat RH (WCRH; 3289; 38.3%): normal 24-h BP.

- Refractory hypertension (RefrH; 823; 8.7%): elevated office BP while treated with 5 or more drugs vs. Non-refractory RH (the remaining RH patients).

Results:

Compared to CH, RH was associated with an increased risk in total mortality (HR: 1.22; 95%CI: 1.13 - 1.31) and cardiovascular mortality (1.37; 1.21 - 1.55). Compared with CRH, UCRH was not associated with a significant increased risk in total or cardiovascular mortality. Compared to WCRH, TRH increased the risk of mortality (1.45; 1.32 - 1.60) and cardiovascular mortality (1.68 (1.43 - 1.98). Finally, RefrH also increased the risk of total mortality (1.16; 1.01 - 1.34) and cardiovascular mortality (1.30; 1.05 - 1.62) in comparison to non-refractory RH. Either total or cardiovascular mortality was not increased in WCRH, compared to CH.

Conclusions:

RH increased the risk of total and mortality with respect to CH. Among RH, office BP control does not modify such prognosis, while 24-h BP is a powerful determinant, with a clear increased risk in those with elevated 24-h BP (TRH), compared to those with normal 24-h BP (WCRH). The study confirms the clinical importance of RH, as well as the usefulness of ABPM in stratifying those patients, in order to improve therapeutical efforts to reduce the global risk.
AVERAGE ACHIEVED BP <130/80 MMHG IN HIGH-RISK MIDDLE-AGED AND OLDER HYPERTENSIVE PATIENTS PROVIDES STRONG CARDIOVASCULAR PROTECTION EXCEPT IN LEFT VENTRICULAR HYPERTROPHY
Authors: Heimark Sondre , Mehlum Maria H. , Mancia Giuseppe , Søraas Camilla L. , Liestöl Knut , Kjeldsen Sverre E. , Larstorp Anne C. K. , Rostrup Morten , Mariampillai Julian E. , Wachtell Kristian , Julius Stevo , Weber Michael A.
Published: June 2023

Objective:

Evidence that reducing blood pressure (BP) to <130/80 mmHg rather than to <140/90 mmHg by antihypertensive treatment in hypertensive patients is conflicting. Left ventricular hypertrophy (LVH) is common in hypertension, and low perfusion pressure may result in ischemia in patients with LVH. We investigated whether average achieved BP <130/80 mmHg implied cardiovascular benefits in high-risk middle-aged and older hypertensive patients who participated in the VALUE Trial. Considering a previous report of excess mortality in LVH patients with in-treatment systolic BP (SBP) <130 mmHg, we paid special attention to whether the average achieved SBP <130 mmHg may cause harm in similar patients with LVH.

Design and method:

Of the 15,245 participants, we identified 13,803 patients without cardiovascular events during the first six months after randomization during which previous medications were discontinued and study drugs up-titrated. Of these, 2,458 patients had LVH on an electrocardiogram (ECG). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other pre-specified endpoints for patients who achieved average SBP 130 - 139 mmHg (No LVH group n = 4,863, ECG LVH group n = 929) and <130 mmHg (No LVH group n = 2,107, ECG LVH group n = 305). Reference groups were patients who achieved an average SBP > = 140 mmHg following the first excluded six months (No LVH group n = 4,375, ECG LVH group n = 1,224).

Results:

The No LVH group with average achieved BP <130/80 mmHg had a significantly lower incidence of all endpoints except for myocardial infarction. The ECG LVH group with average achieved SBP <130 mmHg had increased cardiac mortality (HR = 1.98, p = 0.032) and all-cause mortality (HR = 1.74, p = 0.007), and SBP <130 mmHg was not associated with a reduction in any endpoint. However, as in those without LVH, the ECG-LVH group had fewer strokes and heart failure with an average achieved diastolic BP <80 mmHg.

Conclusions:

Our data suggest that target SBP <130 mmHg may cause harm and needs further investigation in middle-aged and older patients with LVH detected by ECG. Otherwise, the average achieved BP <130/80 mmHg prevents most cardiovascular endpoints in middle-aged and older hypertensive patients with high cardiovascular risk but without LVH.
ROLE OF NATRIURESIS AND FRAILTY IN BLOOD PRESSURE REGULATION IN ELDERLY PEOPLE
Authors: Zagato Laura , Citterio Lorena , Simonini Marco , Tunesi Francesca , Rovere-Querini Patrizia , Manfredi Angelo , Concas Maria Pina , Manunta Paolo , Lanzani Chiara
Published: June 2023

Objective:

The objective of the study is to investigate, in elderly people, the relationship between natriuresis, frailty and blood pressure (BP).

Design and method:

The FRASNET geriatric population (1204 subjects) is an Italian observational cohort that includes frail (35%), pre-frail (37.3%) and robust (27.7%) subjects. They have been characterised for BP, renal function, sodium intake (by Kawasaki formula), anthropometric data, cognitive status, quality of life, comorbidities, and chronic therapies.

ANOVA and conditional inference tree analyses have been carried out.

Results:

745 participants out of 1203 (60%) were under anti-hypertensive treatment. Increased visceral fat, male sex and lower number of medications taken are risk factors for suboptimal control of BP (71.4%).

An inferential analysis evidenced (Fig. 1) a first node between male and female, a second one according to age (75 y), a third with natriuresis (217 mEq/24h).

Non-frail subjects presented the highest values for both systolic and diastolic BP; the frail group presents systolic BP values below the threshold of 140 mmHg. BPs are negatively correlated with frailty status (systolic p = 0.048, diastolic p <0.001, Figure 2).

Conclusions:

Frailty and blood pressure follow an inverse tendency: the higher the severity of the frail status, the lower the blood pressure.

The relationship between BP and natriuresis is preserved only in young women whereas in very old people (>75 y) is no more present.

This evidence is supported by physiological explanations and suggest to be cautious in salt reduction intake in elderly people.
STABILIZATION OF TELOMERE BY THE ANTI-AGING PROPERTY OF METFORMIN MITIGATES OLEIC ACID-INDUCED ATHEROSCLEROTIC PATHOGENESIS
Authors: Sung Jin Young , Kim Seul Gi , Kang Young Jin , Choi Hyoung Chul
Published: June 2023

Objective:

Factors associated with the atherosclerotic process, including inflammation, senescence-associated secretory phenotypes and telomere dysfunction are closely linked to senescence in VSMCs. However, whether senescent VSMCs are sufficient to cause atherosclerotic process and whether the phenotypes and risk factors of senescent VSMCs affect atherosclerotic pathogenesis are unclear. We investigated the mechanism of inhibition of atherosclerosis by the anti-aging agent metformin and whether attenuating risk factors senescent VSMCs affects atherogenesis.

Design and method:

We performed in vitro studies including western blot, immunoprecipitation, RT-PCR, flow cytometry, immunofluorescence, FISH analysis, MMP zymography, and transfection of TERT siRNA. In vivo, to test the effect metformin on atherosclerotic lesion formation in ApoE-/- mice, male mice were divided into three groups (each, n = 5). After feeding the high-fat diet for 16 weeks, mice were sacrificed and the formation of atherosclerotic lesions in the aortas and the aortic sinuses were analyzed.

Results:

Oleic acid (OA)-induced atherosclerotic pathogenesis in normal VSMCs showed marked senescence-associated features, manifested as increased b-gal positive cells and phenotypic switching of VSMCs in vitro; however, these phenomena were shown to be reversed by metformin. To determine what mechanism by metformin alleviates atherogenesis and senescent VSMC, we studied in the enhancement of telomere function by phosphorylating AMPK (Ser485) and PGC1 alpha. In our results, metformin showed increased the expression of p-AMPK (Ser485) as well as the phosphorylation of PGC1 alpha-dependent TERT expression and telomerase activity. Importantly, the depletion of TERT did not reduce risk factors for atherosclerosis and aged VSMCs despites metformin treatment in OA-induced atherosclerotic pathogenesis. We also found in the aortas of high-fat diet ApoE-/- mice, metformin treatment significantly attenuated atherosclerotic plaques and senescent VSMCs, and upregulated the expression of p-AMPK (Ser485)/p-PGC1 alpha and the enhancement of telomere function.

Conclusions:

The reduction of atherosclerotic pathogenesis in VSMCs and ApoE-/- mice is associated with significantly inhibited senescent phenotypes and risk factors. Increasing p-AMPK (Ser485)/p-PGC1 alpha by metformin the enhancement of telomere function mitigates senescent risk factors and may be a promising therapeutic strategy in atherosclerosis.
ARTERIAL STIFFNESS ESTIMATED BY BRACHIAL OSCILLOMETRY PREDICTS PROGRESSION TO HYPERTENSION IN PATIENTS WITH NORMAL AMBULATORY BLOOD PRESSURE
Authors: Rodilla Enrique , Mendizabal Andrea , Jimenez Iratxe , Canales Sergio , Roldan Alicia , Perez Leticia , Catalan Marta , Saez Maria Carmen , Ferrer Anna , Pintos Santiago , Fernandez Monica , Morro Santiago , Chorda Jose , Costa Jose Antonio
Published: June 2023

Objective:

There is growing evidence that arterial stiffness can precede hypertension (HTN). This study aimed to assess the predictive value of Pulse Wave Velocity, estimated by brachial oscillometry (ePWV), for incident HTN in patients with initially normal ambulatory BP measurement (ABPM) after one year of follow-up.

Design and method:

This retrospective, observational, longitudinal study included all consecutive patients referred to a HTN Unit with suspected naïve HTN, without prior pharmacological treatment. EVA was defined according to ePWV exceeding the 90th percentile of its age group (Mobil-O-Graph, IEM®). Incident HTN was defined as ABPM at follow-up > 130/80 mmHg or prescription of antihypertensive medication. Standard clinical tests and ABPM were performed at baseline and after 12 months.

Results:

223 consecutive patients with ABPM <130/80 mmHg entered the study, with 155 women (69.5%), a mean age of 47.9 years (±13.5), mean office BP of 128/73 (±13/8), mean ABPM of 118/73 (±7/5) mmHg and mean estimated PWV of 7.74 m/s (±1.7). At baseline, 51.1% of patients showed EVA. At follow-up, after a mean time of 1,1 years, 114 participants presented elevated ABPM. After adjustment for age, gender and ambulatory BP, presence of EVA at baseline was associated with progression to HTN at follow-up (OR:2,5;IC:1,4-4,6;p = 0.003). Furthermore, the pattern of PWV-EVA and incident HTA according to age were superimposable (Image). Arterial stiffness defined as ePWV > 10 m/s was also significantly associated with incident HTN, but showed a completely different distribution in age compared with incident HTN. Of note, arterial stiffness at follow-up was mainly determined by EVA at baseline (OR:6.1;IC:3.2-11.6;p = 0.001), but not by BP traits.

Conclusions:

Arterial damage, characterized as early vascular aging according to estimated PWV by brachial oscillometry, doubles the probability of sustained HTN one year after initial assessment in naïve patients with normal ABPM at baseline, independently of ambulatory and or office blood pressure at baseline. On the other hand, the main determinant of arterial stiffness at follow-up was elevated ePWV at baseline, but not blood pressure traits.
FISETIN ENHANCES PPAR GAMMA EXPRESSION TO PREVENT VASCULAR SMOOTH MUSCLE CELL SENESCENCE VIA MTORC2-AKT-FOXO3A SIGNALING PATHWAY
Authors: Kim Seul Gi , Sung Jin Young , Kang Young Jin , Choi Hyoung Chul
Published: June 2023

Objective:

Cellular senescence is caused by diverse stimuli and is contributed to cardiovascular diseases such as atherosclerosis, coronary heart disease, and hypertension. Several studies have indicated that PPAR gamma is mainly a key mediator in lipid metabolism and adipocyte differentiation. In addition, PPAR gamma has a protective effect in vascular biology and regulates the inflammation and reactive oxygen species (ROS). Nevertheless, the anti-aging mechanism of PPAR gamma has not been elucidated in vascular smooth muscle cell (VSMC). Although mTORC2 is involved in the cellular senescence and autophagy, there are significantly fewer studies than mTORC1. Therefore, we focused on mTORC2 function and then aimed to investigate the correlation between PPAR gamma and mTORC2, and to identify the anti-aging mechanism in VSMC.

Design and method:

To generate the oxidative stress-induced VSMC senescence, we treated with hydrogen peroxide (H2O2). The anti-aging effect and underlying mechanism of fisetin were evaluated by Western blot analysis, senescence-associated beta-galactosidase (SA-beta-gal) staining, flow cytometry, immunofluorescence analysis, and immunoprecipitation analysis.

Results:

We found hydrogen peroxide (H2O2) induced not only PPAR gamma translocation from nuclear to cytosol but also mTORC2 activation with VSMC senescence. We determined mTORC2 activation contributed to the senescence by suppressing FoxO3a-autophagy signaling pathway. Furthermore, the double knockdown of mTORC1 and mTORC2 decreased the cellular senescence and increased the autophagy activation more than single knockdown. However, fisetin acted as a PPAR gamma activator, leading to the inhibition of VSMC senescence through mTORC2-Akt (Ser473)-FoxO3a signaling pathway which is related to autophagy.

Conclusions:

These results demonstrate PPAR gamma is associated with cellular senescence and fisetin has anti-aging effect via PPAR gamma activation and mTORC2 inhibition. Moreover, mTORC2 signaling pathway could regulate autophagy, which suggests mTORC2 is considered a significant target for preventing cellular senescence and aging-related disease.
ASSOCIATION BETWEEN HOUSEHOLD SOLID FUEL USE AND RISK OF SARCOPENIA: DATA FROM THE CHINA HEALTH AND RETIREMENT LONGITUDINAL STUDY
Authors: Chen Chao-Lei
Published: June 2023

Objective:

Few studies have examined the effects of air pollutants on the risk of sarcopenia, especially air pollution from indoor settings. We aimed to explore the cross-sectional and longitudinal associations of household solid fuel use for cooking and heating, separately and simultaneously, with risk of sarcopenia.

Design and method:

Cross-sectional and follow-up data from the China Health and Retirement Longitudinal Study (CHARLS) were used. Multivariable-adjusted generalized linear models and Cox proportional hazards regression models were performed to estimate the odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CI), respectively. We also calculated the extent of interaction or joint relations of sociodemographic and behavioral factors and household fuel use with sarcopenia.

Results:

11,494 (median age: 57.0 years; 47.4% males) and 7,483 (median age: 57.0 years; 46.9% males) participants were included in the cross-sectional and follow-up study, respectively. After fully adjusting for covariates, both using solid fuels for cooking and heating were positively associated with incident sarcopenia in the longitudinal analyses, with hazard ratio (HR) (95% CI) of 1.56 (1.28-1.89) and 1.26 (1.04-1.52), respectively. When comparing to those using clean fuels for both cooking and heating, participants using solid fuels for both cooking and heating were more likely to have incident sarcopenia [HR (95% CI):1.52 (1.19-1.93)]. In addition, compared with those persistently used clean fuel for cooking, significantly higher risk of new-onset sarcopenia was found in participants persistently used solid fuels [HR (95% CI):2.05 (1.55-2.71)]. Moreover, significant multiplicative and/or additive interactions were observed between age, smoking status and solid fuel use for cooking with risk of sarcopenia (all P for interaction < 0.05). Similar results were found in the cross-sectional analyses.

Conclusions:

Household solid fuel use was significantly associated with higher risk of sarcopenia. In addition, ageing and smoking had synergetic effects with burning solid fuels for increasing the risk of sarcopenia. Our results highlighted the importance of taking multi-pronged measures from both aspects of air pollution and health behavior to prevent sarcopenia and promote healthy ageing.
ATRIAL FIBRILLATION AND MORTALITY RISK IN HYPERTENSIVE PATIENTS ACCORDING TO CARDIORESPIRATORY FITNESS
Authors: Pittaras Andreas , Grassos Charalampos , Faselis Charles , Tsimploulis Apostolos , Doumas Michael , Lovic Dragan , Papavasiliou Maria , Manolis Athanasios J. , Kokkinos Peter
Published: June 2023

Objective:

Atrial fibrillation (AF) is associated with increased risk of mortality. Epidemiologic evidence strongly supports an inverse and graded association between cardiorespiratory fitness (CRF) and mortality risk. The impact of CRF status on mortality risk in hypertensive patients with AF has not been assessed. The aim of the study was to evaluate the association between CRF and mortality risk in hypertensive patients with AF.

Design and method:

We identified 24,171 hypertensive patients (mean age 67.5±9.0 yrs), with documented AF who completed an exercise treadmill test (ETT) between years 1999 to 2020, with no evidence of ischemia. We established 5 fitness categories (quintiles) based on age-specific peak metabolic equivalents (METs) achieved: Least-fit (4.0±1.1 METs; n = 8,857); Low-fit (6.4±1.1 METs; n = 6,103); Moderate-fit (7.8±1.1 METs; n = 4,256); Fit (10.0±0.9 METs; n = 3,803) and High-fit (12.6±1.6 METs; n = 1,152). We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals [CI] for mortality across CRF categories. The models were adjusted for age race, gender, resting blood pressure, comorbidities, and medications.

Results:

During follow-up (median = 8.8 years; 224,138 person-years), 10,499 individuals died (46.8 events per 1,000 person-years). The risk for stroke was 14% lower for each 1-MET increase in exercise capacity (HR = 0.86, CI: 0.85-0.87; p<0.001). When considering CRF categories, mortality risk was 27% lower for the Least-Fit individuals (HR = 0.73; CI: 0.70-0.77) and declined progressively with increased CRF to approximately 45% t0 60% for Moderate-fit and Fit, and 67% (HR = 0.33; CI: 0.29-0.37) for High-Fit individuals.

Conclusions:

Increased CRF was inversely related to mortality in hypertensive patients with AF. The association was independent of comorbidities and graded.