bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREVALENCE OF PATIENT WITH TREATMENT-RESISTANT HYPERTENSION AND SCREENING RATE FOR PRIMARY HYPERALDOSTERONISM IN THAI AMBULATORY CARE SETTING
Authors: Suksiriworaboot Tanawin , Yacharad Arun , Sunthornyothin Yongkasem Vorasettakarnkij Sarat , Chattranukulchai Pairoj 
Published: June 2023

Objective:
Patients with treatment-resistant hypertension (TRH) have significantly higher mortality outcomes when compared with controlled hypertension. Primary hyperaldosteronism (PA) is one of the common treatable causes of this condition. Although the practice guidelines recommend testing for PA among those with TRH, the screening rates in Thailand's ambulatory care setting are unknown.

Design and method:
This is a single-center cross-sectional study. All hypertensive adults followed at ambulatory clinics of a tertiary care hospital between January 2020, and May 2022 were screened. Patients who met one of two following criteria were diagnosed as TRH: 1) uncontrolled blood pressure (BP) despite the use of 3 antihypertensive drug classes, including diuretics 2) concurrent use of greater than or equal to 4 antihypertensive drug classes, regardless of BP control. Patients without data of consecutive office BP records at least one month apart or lack of laboratory results were excluded. Hypokalemia was defined as a low serum potassium level identified on at least 2 visits.

Results:
Among 2,047 patients diagnosed with hypertension, the prevalence of TRH was 9.4% (192 patients) with a mean (±SD) age of 74 (±10) years, 59% were women, and the mean number of antihypertensive agents was 3.8±0.7. The screening rate for PA in TRH and non-TRH groups were 3.1% and 0.8%, respectively (p = 0.001). Among those with TRH, the screened PA group significantly had more prevalence of hypokalemia than the non-screened group (33.3% vs 2.7%, p<0.001). From subgroup analysis of all patients with hypokalemia and without hypokalemia, the testing rates for PA were 18.2% and 0.6%, respectively (p<0.001). The average duration from first hypokalemia detection to receiving testing for PA was 19 months. Five of the 20 patients received screening were diagnosed with PA and had better BP control after receiving appropriate treatment.

Conclusions:
This is the first study in Thailand to examine a PA screening rate in a real-life, ambulatory care setting. The low screening rate reflects the unawareness and inertia of physicians to adhere to guideline-recommended practices. Initiatives to encourage PA screening should be more emphasized and barriers that caused low screening rate should be further explored.
POOR ACHIEVEMENT OF THE TARGET BLOOD PRESSURE LEVELS ASSOCIATED WITH DIASTOLIC HEART FAILURE IN PATIENTS WITH RESISTANT HYPERTENSION
Authors: Rekovets Oksana , Sirenko Yuriy , Torbas Olena , Kushnir Svitlana , Primak Galina 
Published: June 2023

Objective:
Aim of this study was to assess the impact of not achievement of the target blood pressure levels on the presence of the diastolic heart failure in patient with resistant hypertension (RH).

Design and method:
The study included patients with arterial hypertension who received 3 and more AH drugs and had BP > 140/90 mm Hg and were admitted to the department of secondary hypertension. In all patients we performed the following examinations: anthropometry, office blood pressure, electrocardiography (ECG), echocardiography, ABPM, sleep apnea determination, blood biochemical analysis, determination of levels of TTH, T3, T4, blood renin, blood aldosterone levels, blood cortisol level and metanephrine in the urine.

Results:
The study included 1146 patients with RH who received 3 or more antihypertensive drugs with the level of office blood pressure at admission > = 140/90 mm Hg. The mean age was 57,9 ± 0,37 years. The average body weight is 87,7 ± 0,61 kg, body mass index - 31,0 ± 0,19 kg/m2. Baseline office SBP/DBP - 174,6 ± 0,64/100,5 ± 0,38 mmHg. Half of the patients (51.4%) received 3 antihypertensive drugs, four drugs - 37.1%, five drugs - 9.1%, and six drugs - 2.4% respectively. Our data showed that after correction of the therapy only 31% of patients who received 3 or more antihypertensive drugs had true resistant hypertension. Fixed combinations were taken by 71.9% of patients. Patients who did not achieve target BP had significantly higher cortisol level (155.0 ± 44.0 vs 35.9 ± 20.8 ng/l) and the highest left ventricular mass index (147.5 ± 3.46 vs 135.3 ± 1.74 g/m2), obesity (42.9 vs 37.5 %), kidney function abnormalities (2.7 vs 0.8 %), and also we noted the higher prevalence of the diastolic heart failure in comparison with patients who achieved target BP (16.9 vs 8.5 %).

Conclusions:
Not achievement of the target blood pressure levels was associated with the presence of the diastolic heart failure in patients with resistant hypertension
RENAL DENERVATION REDUCES RETINAL ARTERIAL REMODELING IN PATIENTS WITH TREATMENT RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS
Authors: Bosch Agnes , Schmid Axel , Kannenkeril Dennis , Ott Christian , Harazny Joanna , Striepe Kristina , Guenes-Altan Merve , Schiffer Mario , Uder Michael , Schmieder Roland E. 
Published: June 2023

Objective:
Renal denervation has been shown to be a safe and effective method to lower blood pressure (BP) in patients with uncontrolled treatment resistant hypertension (TRH). Patients with TRH and T2DM typically show hypertrophic arteriolar remodeling, which is associated with the development of early target end-organ damage. By using the retinal vasculature as a mirror of vascular remodeling in the systemic circulation, arteriolar remodeling can be non-invasively assessed with Scanning Laser Doppler Flowmetry (SLDF). In this analysis we assessed the impact of RDN on retinal arteriolar remodeling in patients with TRH and T2DM.

Design and method:
Retinal arteriolar remodeling was assessed using SLDF together with office and 24-hour ambulatory BP before and 6 as well as 12 months after renal denervation in 22 patients with TRH and T2DM. All patients participated in the investigator initiated study program “Renal Denervation in Treatment Resistant Hypertension” (NCT01687725). SLDF allows confocal measurement of the retinal arteriolar parameters, such as outer (OD) and inner (ID) diameter. Based on ID and OD the following parameters of arteriolar remodeling are derived: retinal arteriolar wall thickness (WT), wall-to-lumen ratio (WLR), and retinal arteriolar crosssectional area (CA).

Results:
Retinal arteriolar parameters were analysed in 18 male and 4 female patients with 6.5 antihypertensive medications on average. There was a significant reduction of systolic and diastolic 24-hour ambulatory as well office BP 6 as well as 12 months after RDN (table 1). In 77.3% of the patients number of antihypertensive medications was reduced. We found a reduction of hypertrophic retinal arteriolar remodeling and also a reduction of WLR 12 months after RDN (table 1). Of note, no significant changes of retinal arteriolar remodeling were found 6 months after RDN.

Conclusions:
In very high-risk patients with TRH and T2DM endovascular RDN reduced retinal arteriolar remodeling and retinal wall-to-lumen ratio, a prognostic marker of further end-organ damage. Whereas BP-changes already occurred 6 months after RDN, changes in retinal arteriolar remodelling were observed 12 months after RDN. We conclude that after RDN reversal of arteriolar remodeling happens slowly and requires long-term effective BP control.
RENAL SYMPATHETIC DENERVATION AND NEURO-HORMONAL EVALUATION BY SELECTIVE VENOUS CATHETERIZATION: THE RESIDENCY STUDY
Authors: Bagordo Domenico , Rossitto Giacomo , Crimì Filippo , Ceolotto Giulio , Antonelli Giorgia , Battistel Michele , Barbiero Giulio , Tarantini Giuseppe , Basso Daniela , Rossi Gian Paolo 
Published: June 2023

Objective:
Renal denervation (RD) is effective in reducing blood pressure (BP) in hypertensive patients, but the pathophysiologic mechanisms underlying the variable individual response are unclear and early markers of procedural success are lacking. The aim of the study was to evaluate intra-/peri-operative effects of RD on the renin-angiotensin-aldosterone system (RAAS) either as determinants and markers of efficacy.

Design and method:
Patients with resistant hypertension and eGFR>45 ml/min underwent radiofrequency-RD (Medtronic Symplicity-Spyral) with simultaneous sampling of the renal veins (RV), left adrenal vein and pre-renal inferior vena cava (IVC). Samples were collected before (t0) and 15’ after RD from each sequentially-approached side. Additional peripheral blood samples collected on the morning before RD and 3h, 24h and 7 days after the procedure were tested for renin, aldosterone and cortisol. During this timeframe, antihypertensive therapy remained unchanged.

Results:
Ten patients were recruited (61±11yo; 30%F; BP = 149/84 ±11/12 mmHg on 4 (range 3-6) antihypertensive drugs). Peripheral renin concentration showed no significant changes during/immediately after RD and up to 7 days after, in spite of the observed BP reduction (136/78 ±17/15 mmHg; p<0.05). Similarly, RV renin was unaffected by ipsilateral RD compared to the corresponding t0 values (p = 0.899). Aldosterone and cortisol increased in the adrenal vein during RD (p<0.001), but their IVC-corrected ratio and their peripheral plasma concentrations at follow-up did not, likely reflecting a self-limiting stress reaction.

Conclusions:
These results do not suggest any direct blunting effect of RD on RAAS, and do not support the contention of monitoring acute RAAS changes as proxies for procedural effectiveness.
RENAL DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION: FOLLOW UP 2011-2021 OF THE SERIES OF THE ESH CENTER OF EXCELLENCE IN TURIN
Authors: Fasano Chiara , Ponsa Lara , Fanelli Elvira , Rabbia Franco , Rossato Denis , Pappaccogli Marco , Eula Elisabetta , Mangeruga Martina , Bertello Chiara , Veglio Franco 
Published: June 2023

Objective:
Renal denervation (DRN) is one of the invasive therapeutic approaches of resistant arterial hypertension. The aim of this study was to re-evaluate patients undergoing DRN, in terms of safety and efficacy.

Design and method:
A retrospective evaluation of patients undergoing DRN between 01/01/2011 and 31/12/2021 in the Arterial Hypertension Center of Turin.

Results:
The series included 14 subjects, of which 8 (57%) were female and with an average age 54±10 years. The number of antihypertensive drugs before renal denervation was 5.7±1.0 and at baseline the blood pressure was 188/113±22±18 mmHg. 28% of subjects had a history of ischemic heart disease and 27% of previous stroke and/or transient ischemic event. 9 subjects were denervated with Symplicity device, 1 with Vessix, 4 with Symplicity Spyral. The mean duration of follow-up was 5.2 years. From a safety point of view, there were no short-term or long-term complications. In terms of efficacy, the number of responders at 6 months, defined as a reduction of at least 10 mmHg in systolic blood pressure (PAS) at 24h Blood Pressure Monitoring, was 9 subjects (64%). Two subjects reported systolic blood pressure values below 135 mmHg.
Regarding the type of device used, 75% of subjects treated with Spiral devices were responders, compared with 60% of subjects treated with other catheters. Among the non-responders, 2 presented events one year after the DRN. Only 1 responder had high level of renin at baseline.

Conclusions:
The data relating to the case studies of the Arterial Hypertension Center of Turin highlight the safety of the renal denervation procedure and a blood pressure response in 60% of patients. The latest generation catheters seems to be more effective. However, the small number of cases did not allow to identify predictive factors of response to DRN.
EXERCISE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION: A SYSTEMATIC REVIEW WITH META-ANALYSIS
Authors: Vanparys Joris , Decorte Elise , Cornelissen Veronique 
Published: June 2023

Objective:
High grade evidence supports exercise as a key therapy in the prevention and management of hypertension. Yet, the lack of a meta-analysis on the effects of exercise on ambulatory blood pressure monitoring (ABPM) in patients with hypertension was identified as an important research gap in the 2022 consensus document from the European Association of Preventive Cardiology and the ESC council on Hypertension. Therefore, we performed a meta-analysis to investigate the effects of exercise on blood pressures measured by means of ABPM, in patients with arterial hypertension or high-normal blood pressure (BP).

Design and method:
A systematic literature search was performed in three databases from inception to October 2021. Randomized controlled trials involving exercise training of at least 4 weeks, in adults with a high-normal BP or arterial hypertension, were included. Trials had to report data on daytime, nighttime or 24-h ambulatory systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Primary outcomes were changes in 24h, daytime and nighttime ABP. Pooled effect sizes are reported as weighted mean with 95% confidence intervals (CI).

Results:
We included 24 trials, involving 23 aerobic training interventions and 4 resistance exercise interventions. A total of 1668 participants were included: 942 in exercise groups, 726 as controls.
Table 1: Pooled effect size, 95% CI and p-value of different exercise types on 24h, daytime and nighttime BP:
Only 67 participants and 35 controls were included in resistance exercise protocols. In this subpopulation, results for 24h, daytime or nighttime BP were insignificant (p>0.05).
Funnel plots for 24h, daytime and nighttime BP did not show any significant publication bias.

Conclusions:
Exercise therapy reduces 24h BP in patients with arterial hypertension or high normal blood pressure. The effect is more pronounced on daytime than on nighttime BP. The results of this meta-analysis are mostly driven by trials examining aerobic exercise. More trials are needed on the effect of resistance exercise on ABPM.
WARBURG EFFECT CHARACTERIZES THE SKELETAL MUSCLE IN FABRY DISEASE: EXPERIMENTAL EVIDENCE AND CLINICAL IMPLICATIONS
Authors: Gambardella Jessica , Fiordelisi Antonella , Cerasuolo Federica Andrea , Buonaiuto Antonietta , Avvisato Roberta , Viti Alessandro , Sommella Eduardo , Merciai Fabrizio , Salviati Emanuela , Campiglia Pietro , D’Argenio Valeria , Parisi Silvia , Bianco Antonio , Spinelli Letizia , Riccio Eleonora , Pisani Antonio , Ciccarelli Michele , Santulli Gaetano , Sorriento Daniela , Iaccarino Guido 
Published: June 2023

Objective:
Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD), and strongly impact the patient's quality of life. Still, the SM in FD is poorly investigated. Although energetic alterations are reported in cells from FD patients, they have never been related to fatigue and pain. Given the pivotal relevance of energetics for SM health, we undertook the investigation of the SM.

Design and method:
We consistently observed a reduced tolerance to aerobic activity and lactate accumulation in FD-humanized mouse model and patients. Accordingly, in sedentary mouse FD SM we detected an increase in fast/glycolytic-fibers, mirrored by an upregulation of glycolytic enzymes and glucose-transporters

Results:
In fibroblasts derived from FD patients, we confirmed a high glycolytic-rate and accordingly, metabolomic/lipidomic-analysis revealed that lipids are underutilized as energetic fuel in FD-patients. In the quest for a tentative mechanism, we explored analogies with genetic myopathies, that show altered expression of energetic metabolism. Specifically, we explored HIF-1 upregulation and found it increased in FD mice and patients. Consistent with our previous screening of miRNAs associated with metabolic stress in FD, we observed a significant upregulation of miR-17 in FD patients and mice. Of note, miR-17 has been associated with cellular metabolic remodeling and HIF-1 up-regulation in different contexts. In our experimental setting, a specific antagomir targeting miR-17 was able to inhibit HIF-1 accumulation and revert metabolic-remodeling in FD-cells.

Conclusions:
Our findings unveil an anaerobic glycolytic-switch under normoxia, known as Warburg Effect, which is induced by miR-17-mediated-upregulation of HIF-1. The miR-17/HIF-1 pathway can be a new therapeutic target in FD, and Exercise-testing and blood lactate may become a new diagnostic and monitoring-tool in FD.
EXERCISE RELATED HYPOTENSIVE EFFECT IN A CARDIAC REHABILITATION PROGRAM AS A POSSIBLE PROGNOSTIC MARKER OF CARDIOVASCULAR RISK
Authors: Carvalho Simão Almeida , Costa Carlos , Fernandes Andreia , Adrega Tiago , Albuquerque Nelson , Briosa Ana , Gome Ana , Bastos Mesquita 
Published: June 2023

Objective:
There are some studies that analyze the correlation between the magnitude of the hypotensive effect after exercise and the long-term cardiovascular benefit. However, this same effect in a cardiac rehabilitation program (CRP) is unknown.
The aim was meausuring the benefit of this effect in patients undergoing a cardiac rehabilitation program.

Design and method:
We analyzed 19 patients who completed a CRP for 3 months (2 weekly sessions of cardiovascular and resistance exercise), in the period between September 2021 and September 2022, after an Acute Coronary Syndrome or hospitalization for Decompensated Heart Failure.
In each rehabilitation session, the blood pressure values were evaluated before the beginning of the exercise and after (1st minute and 5th minute of recovery).
The effect was compared in two different moments of the program - 1st and 12th session - having defined as main “outcome” a magnitude of higher systolic blood pressure drop in the 12th compared to the 1st session.
After completion of the CRP, all patients included in the study were given two validated questionnaires to assess insomnia (“Insomnia Severity Index – ISI”) and the impact of the current illness on quality of life (EQ-5D).

Results:
Regarding the patients included, the clinical and sociodemographic characteristics are described in table 1.
Comparing males and females, using a T-student analysis, there was a statistically significant difference in relation to a greater systolic hypotensive effect in the male group compared to the female group (91.7% vs 40.0%, p < 0.05) – table 2.
Regarding the analysis of the impact on quality of life, the total number of patients with improvement in the hypotensive effect of systolic blood pressure showed statistically significant lower values in the questionnaire (EQ5D) – 6.8±1.3 vs 9.0±1.0 (p<0.05) and higher in the score of insomnia 10.7 ± 9.0 vs. 3.9 ± 4.1 - table 2.

Conclusions:
The systolic hypotensive effect of exercise, observed in the rehabilitation program of the current study, is associated with better rates of insomnia and impact on quality of life. The authors intend to confirm this hypothesis in the longitudinal evaluation of future events.
EXPRESSION OF MICRO-RNA 221 AND 223 IN ISCHEMIC STROKE DUE HYPERTENSIVE EMERGENCY
Authors: Martin Jose F Vilela , Andrade Days Oliveira De , Cosenso-Martin Luciana N , Yugar-Toledo Juan C , Silva-Souza Doroteia 
Published: June 2023

Objective:
Hypertensive crisis can account for damage on target organs characterizing hypertensive emergencies (HE). Ischemic Stroke (IS) is among these injuries. Expression of microRNAs (miRNAs) is considered the possible factors related to HE. This study evaluated the association of expression of miRNAs 221 and 223 in patients suffering ischemic stroke due to HE.

Design and method:
Thirty and four patients with IS due to hypertensive emergency (IS-HE), 33 individuals with IS without HE (IS), 31 controlled hypertensive (CHT) and 33 normotensive (NT) individuals were studied. The expression of miRNAs 221 and 223 was performed by RT-q PCR (real-time quantitative polymerase chain reaction).

Results:
Systolic and diastolic blood pressure were significantly higher in the IS-HE compared to IS, CHT and NT groups (162/99 mmHg vs 140/87, 128/69 and 129/82 mmHg, respectively; p <0.05). The miRNA-221 expression was higher in the IS-HE group compared to the IS, CHT and NT groups (4.23 vs 2.44, 1.35 and 1.05, respectively; p<0.0001). There was overexpression of miR-223 in the IS-HE and IS groups compared to CHT and NT groups (1.56 and 1.73 vs 0.13 and 0.66; p < 0.001).

Conclusions:
This study provides evidence of the miRNAs participation in the pathophysiology of ischemic stroke due hypertensive emergency, thus assuring that the increased expression of miR-221 and miR-223 determines a greater chance of the individual presenting IS due HE. The miRNAs 221 and 223 are related to endothelial damage; thus, their overexpression shows the participation of endothelial dysfunction in cases of acute blood pressure elevation.
FAPESP 2016/08203-6.
DIFFERENCES IN SYMPATHETIC OUTFLOW PROFILES AMONG CANDIDATES TO RENAL DENERVATION
Authors: Sciarrone Paolo , D’alesio Giacomo , Borrelli Chiara , Navari Alessandro , Filidei Francesco , Carrasco Adrian , Mazzoni Alberto , Oddo Calogero M. , Emdin Michele , Passino Claudio , Taddei Stefano , Masi Stefano , Bacca Alessandra V. , Giannoni Alberto 
Published: June 2023

Objective:
Renal denervation (RDN) is increasingly used to reduce sympathetic outflow and improve blood pressure (BP) control in patients with resistant or difficult-to-treat arterial hypertension. However, the BP response to the procedure is variable, and factors influencing this variability remain largely unknown. Sympathetic outflow recorded before the procedure might predict the BP response to RDN, although results from different studies remain conflicting. These discrepancies might depend on the limited characterization of the sympathetic outflow before RDN, making its better definition an important goal to refine the patient selection.

Design and method:
We prospectively enrolled patients with difficult-to-treat arterial hypertension undergoing RDN. Patients underwent an extensive clinical evaluation, and the muscle sympathetic nerve activity (MSNA) in resting conditions and during respiratory maneuvers (controlled inspiratory apneas, evaluation of chemoreflex sensitivity to hypoxia and hypercapnia with the rebreathing technique) was recorded through microneurography. Sympathetic burst frequency, incidence, amplitude, duration and integral, as well as inter-burst interval, were calculated with a semi-automated in-house software.

Results:
Table 1 reports the clinical characteristics of the 10 patients that were enrolled and underwent MSNA recording before RDN. Only in 6 patients the MSNA signal was clearly interpretable and, of these, 5 subjects (Figure 1) completed the whole battery of the respiratory stimuli (2 patients couldn’t perform chemoreflex testing due to panic attack and loss of neural signal). Apnea increased the burst frequency and incidence in all patients, although the magnitude of the changes from the resting acquisition was variable. The MSNA responses to the other respiratory maneuvers were jeopardized. Burst duration remained stable, whereas an increased MSNA could be observed (subjects 1 and 3) in terms of risen burst integral and reduced inter-burst interval compared to baseline. The sympathetic response to inspiratory apneas seems mediated by chemoreflex responses in these patients. The other subjects did not show such variations.

Conclusions:
Respiratory maneuvers are feasible during MSNA acquisitions and unveil different patterns of sympathetic responses in patients with hypertension undergoing RDN. Such differences might be missed at rest but could represent novel predictors of the BP response to the procedure.