bluuebunny/crossref_metadata_2025 huggingface dataset:
PHARMACOLOGIC ACTIVATION OF THE ALTERNATIVE RAS ATTENUATES DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION IN MONOCROTALINE TREATED RATS
Authors: Vigl Benjamin , Trubacova Simona , Poglitsch Marko , Domenig Oliver , Balis Peter , Barta Andrej , Valovic Pavol , Liskova Silvia , Simko Fedor , Paulis Ludovit
Published: April 2021

Objective:

Pulmonary arterial hypertension (PAH) is a rare, chronic and debilitating disease characterized by increased pulmonary arterial pressure leading to right heart failure and – eventually death. Several drugs are approved for the treatment of PAH, but due to ongoing disease progression only half of the patients survive more than 7 years after diagnosis. A novel therapeutic approach based on pharmacologic activation of the alternative RAS was investigated in monocrotaline induced PAH in rats.

Design and method:

PAH was induced in 12 week-old Wistar rats by an injection of monocrotaline (60 mg/kg). Immediately after PAH induction, the rats (n = 11-12 in each group) were treated for 4 weeks with either a) vehicle, b) the novel peptidase inhibitor ALT001, or c) the endothelin receptor antagonist bosentan – representing the standard of care. Vehicle-treated sham rats served as healthy controls. Analysis included tissue and plasma equilibrium levels of angiotensin metabolites, echocardiography determined right ventricular function and structure, pulmonary arterial pressure, systemic blood pressure and histomorphometrical evaluations.

Results:

Ang II was significantly increased in lungs of monocrotaline treated animals concomitant with a profound increase in pulmonary arterial pressure (mPAP), reduced fractional shortening, dilated pulmonary valve diameter and a thickened and enlarged right ventricle. ALT001 treatment resulted in increased Ang 1–7 levels while Ang II levels were normalized. Bosentan treatment did not affect angiotensin peptide levels. The PAH induced increase in mPAP was almost completely abolished by ALT001 treatment, while systemic blood pressure remained unaffected. Right ventricular structure and function was effectively preserved under ALT001 treatment and pathological changes in fractional shortening (FS) were significantly reduced.

Conclusions:

Small molecule based modulation of the RAS might represent a promising novel therapeutic approach in treating RAS-related diseases, including PAH.

(Partly supported by VEGA 1/0127/17, FFG 872313)
ROLE OF VASCULAR NOX5 IN ANG II-MEDIATED PRO-FIBROTIC AND PRO-INFLAMMATORY SIGNALLING IN THE KIDNEY
Authors: Montezano Augusto , Rios Francisco , Camargo Livia De Lucca , Palacios-Ramirez Roberto , Tarjus Antoine , Sagan Agnieszka , Guzik Tomasz J. , Jaisser Frederic , Graham Delyth , Touyz Rhian M.
Published: April 2021

Objective:

Mice expressing human Nox5 (hNox5) in vascular smooth muscle cells (VSMC) exhibit increased contraction, ROS generation, cardiac fibrosis and increased pulse pressure. In kidneys, hNox5 in podocytes is associated with albuminuria, hypertension and inflammation. Here we questioned whether VSMC Nox5 influences kidney function and damage in Ang II-induced hypertension.

Design and method:

Wildtype (WT) and mice expressing hNOX5 in SMC (Nox5+SM22+) were studied. Mice were infused with Ang II (600 ng/Kg/day) for 28 days. Blood pressure was assessed by tail-cuff, kidney damage by histology, and mRNA and protein expression by qPCR and western-blotting, respectively. Inflammatory infiltrate was assessed by FACS.

Results:

Ang II increased blood pressure (mmHg) in WT (162.7 ± 9) and Nox5+SM22+ (162.3 ± 10). Albuminuria was increased in Nox5+SM22+ versus WT mice (10.2 ± 6 vs 1.27 ± 0.3 mg/mmol, p < 0.05) and by Ang II in both groups (Nox5: 44.8 ± 18; WT: 58.7 ± 12 mg/mmol). Kidneys from Ang II-infused Nox5+SM22+ mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT. Kidney expression of vimentin (AU: 1.01 ± 0.05 vs WT 0.85 ± 0.03) and aSMA (AU: 0.44 ± 0.03 vs WT 0.33 ± 0.01), markers of myofibroblast differentiation, was increased in Nox5 mice (p < 0.05), an effect that was augmented by Ang II. In kidneys from Nox5+SM22+ mice, levels of macrophage F4/80+ cells were increased (%: 24 ± 2 vs WT 18 ± 1, p < 0.05). Ang II increased macrophage homing in kidneys from WT mice (34 ± 3%, p < 0.05 vs non-treated), but did not further increase it in Nox5 mice (35 ± 5%). Levels of cytotoxic CD8+ T cells and expression of IL-1b and IRAK were increased by Ang II in Nox5 mice.

Conclusions:

Our study suggests that Nox5 in VSMCs induces renal fibrosis and pro-inflammatory signalling by Ang II, likely through increased ROS generation.
ANGIOTENSIN II MODULATES VASCULAR EXTRACELLULAR MATRIX TROUGH AT1R ACTIVATION IN NORMOTENSIVE MICE
Authors: Viegas Katia Aparecida da Silva , Souza Thais Cristina de , Lima Cintia Taniguti , Silva Juliane Cristina de Souza , Alves Tatiana Pereira , Lacchini Silvia
Published: April 2021

Objective:

To study the effect of angiotensin II on extracellular matrix (ECM) in cardiac arteries of normotensive mice and identify ECM components involved in this vascular remodeling.

Design and method:

Male C57Bl6 mice were treated for 7 and 14 days with low dose of Ang II (ANG, 100ng/kg/min), AT1R blocker (Losartan, LOS 20 mg/kg), combination LOS+ANG or Water (CONT). Blood pressure was measured by tail plethysmography. Histologic cuts (5 micrometers) were used to quantify perivascular collagen (COL - Picrosirius). The expression of COL types IV and VII, Fibronectin (FBN), Tenascin-C (TN-C), MMP-2 and 9 was made by immunohistochemistry, in a semi-quantitative score from 0 to 4. Results were compared by two-way ANOVA.

Results:

No changes in SBP and HR were observed in all groups. ANG increased thick collagen fibers (3.29 ± 0.76au) compared to CONT group (2.83 ± 0.98au) and LOS+ANG (2.5 ± 0.55au); LOS reduced the presence of these (1.5 ± 0.58au) compared to other groups. Thin collagen fibers did not change due to treatments. We found that Ang II increased COL IV (+166% after 7 days and +100% after 14 days) and VII (7d:+125% and 14d:+100%). Concomitant treatment with LOS did not reverse the effect of Ang II on COV IV (7d:+166% and 14d:+125%), but the combination of LOS+ANG II abolished the increase in COL VII observed both after 7 to 14 d. Tenascin-C, on the other hand, showed an intriguing result: it was not expressed in the CONT, ANG II and LOS treatments, but had an intense staining after LOS+ANG II treatment. Similarly, LOS+ANG induced an important increase in FBN (7d:+116% and 14d:183%y). Ang II did not change MMP-2 expression while MMP-9 increased after 7 and 14days.

Conclusions:

Ang II modulates vascular extracellular matrix independently of hypertension. Ang II modifies collagen fibers, COL VII and MMP-2 through AT1 receptor. Results suggest that COL IV, FBN, TN-C and MMP-9 are modulated possibly by AT2R. The understanding of mechanisms by which Ang II induces vascular extracellular remodeling may be important to determine the reversible and irreversible vascular remodeling, as observed in hypertension.
SOLUBLE (PRO)RENIN RECEPTOR ASSOCIATES ADVERSELY WITH LEFT VENTRICULAR STRUCTURE AND FUNCTION IN YOUNG ADULTS
Authors: Gafane-Matemane Lebo , Kruger Ruan , Schutte Aletta
Published: April 2021

Objective:

Most of the evidence on the role of (pro)renin receptor in blood pressure regulation and target organ damage emanate from animal models. Recent, though limited studies in humans confirm the contribution of soluble (pro)renin receptor (s(P)RR) to renin-angiotensin system (RAS) activation, volume retention and renal damage, with an apparent ethnic difference. This study aimed to compare levels of s(P)RR between black and white ethnicities and explore for the first time in a normotensive young bi-ethnic population the associations of s(P)RR with relative wall thickness (RWT), left ventricular mass index (LVMi), left ventricular ejection fraction (LVEF), stroke volume (SV), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI).

Design and method:

The study population included 1175 apparently healthy young black (N = 588) and white (N = 587) participants aged 20–30 years old. We recorded ambulatory blood pressure. Echocardiography measurements were performed to determine RWT, LVMi, LVEF, SV (standardized for body height), EDVI and ESVI (both standardized for body surface area). s(P)RR was analyzed from serum, while plasma renin activity-surrogate (PRA-S) and angiotensin II were determined using the RAS™ Fingerprint.

Results:

s(P)RR, PRA-S, angiotensin II, SV, EDVI and ESVI were higher in the white group as compared to the black group (all P < 0.001). RWT and LVEF were higher in the black group (both P< = 0.012), while LVMi was similar between the two groups (P = 0.66). Using forward stepwise multiple regression analyses, we observed independent associations of s(P)RR with RWT (β=0.13; P = 0.009), LVEF (β=-0.12; P = 0.008), SV (β=-0.17; P < 0.001) and EDVI (β=-0.13; P = 0.006) only in white adults. The associations were independent of angiotensin II, which did not enter any of the models when included as a covariate. No associations were observed in the total or black group.

Conclusions:

s(P)RR associated with an increase in RWT and adversely with left ventricular function in normotensive young white adults and not in their black counterparts. These results suggest that s(P)RR has the potential to be an early marker of cardiac remodeling and dysfunction independent of hypertension and systemic renin-angiotensin activity in white populations.
ELASTASE-2 KNOCKOUT IS ASSOCIATED WITH LESS SUSCEPTIBLE AORTA DILATION IN RESPONSE TO ANGIOTENSIN II STIMULATION IN THE MICE MODEL
Authors: Mestriner Fabiola , Ribeiro Mauricio Serra , Mesquita Carolina D’ Avila , Couto Ariel Emiliano Souza do , Campos Ligia Borges , Barbosa Jessyca Michelon , Corsi Carlos A. Curylofo , Nakagi Vanessa Souza , Joviliano Edwaldo , Evora Paulo , Polonis Kataryzina , Becari Christiane
Published: April 2021

Objective:

Elastase-2 (ELA-2), a chymotrypsyn-serine protease elastase family member 2A, is expressed in several tissues such as the lungs, heart, liver, kidneys, brain, and vessels. ELA-2 was found to generate angiotensin II (AngII) in arteries and contribute to resistance arteries and vascular remodeling in animal models. It has also been shown that continuous infusion of AngII induces abdominal aortic aneurysm (AAA) in mice. Therefore, we sought to investigate the role of ELA-2 in an aortic dilation, which is a risk factor to AAA development, in a mouse model.

Design and method:

Male wild type (C57bl/6, WT) and ELA-2 knockout (CELA-2aTm1Bdr; ELA-2 KO) mice were treated with saline or angiotensin II (AngII, 2.28 g/g/min) for twenty-eight days by subcutaneously mini-pumps infusion. To evaluate the role of elastase-2 in a AAA development, mice were divided into four groups: WT treated with saline (WT+SAL), ELA-2KO treated with saline (ELA-2KO+SAL), WT treated with AngII (WT+AngII), and ELA-2KO treated with Ang II (ELA-2KO+AngII). The vascular ultrasound (US) was done before treatment and once a week during 28 days of treatment. The abdominal aorta measurements such as maximum aortic diameter, aortic para-renal diameter, aortic infra-renal diameter, and aortic supra-renal diameter were collected. A dilated aorta is a risk factor aortic rupture/aneurysm. Statistical analyses were performed by the Shapiro Wilk Normality test, two-way ANOVA with Sidak's multiple comparisons test. This study is approved by the Ethics Committee (CEUA-131/2019).

Results:

The most dilated aorta as measured by the maximum aorta diameter was detected in WT+AngII group and was 60% higher than in the WT+Saline (p = 0.01). There was no significant difference in the maximum aorta diameter between ELA-KO+SAL vs. ELA-2KO+AngII (p = 0.8). The measurement of dilation in aortic para-renal and aortic infra-renal showed that AngII induced a dilation in WT+AngII (p < 0.05), while not modified these parameters in ELA-2KO+AngII group. The aortic supra-renal diameter parameters and weight showed no differences between groups.

Conclusions:

These results suggest that ELA-2KO mice might be less susceptible to develop an aorta dilation. Therefore, Elastase-2 is a candidate factor that contributes to the formation and/or development of abdominal aortic aneurysm.
ROLE OF ALDOSTERONE AND P66SHC PROTEIN ON EXPRESSION OF THE SODIUM-GLUCOSE TRANSPORTER SGLT2 IN THE VASCULAR SYSTEM
Authors: Battistoni Allegra , Ucci Sarassunta , Nicoletti Carmine , Montezano Augusto C. , Filippini Antonio , Volpe Massimo , Touyz Rhian M. , Savoia Carmine
Published: April 2021

Objective:

SGLT2 is a transporter involved in sodium and glucose reabsorption in the kidney. SGLT2 inhibitors are a novel class of antidiabetic drugs which inhibit sodium and glucose reabsorption in the tubule, and they have shown a significant protective effect on cardiovascular outcomes in clinical trials. However the role of SGLT2 in the cardiovascular system is not fully elucidated.

The aim of this study was to investigate the modulation of SGLT2 expression in the vascular system and kidney in a mouse model of aldosterone-induced hypertension and to explore the role of p66shc, through which aldosterone/MR signals.

Design and method:

Wild type mice (WT) and p66shc mice -/- (14 weeks, 6 per group) were treated or not with aldosterone (300 μg/kg/day) for 4 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method. The expression of SGLT2 and the mineralocorticoid receptor (MR) in the kidney and aorta was evaluated by immuno-blotting.

Results:

At the beginning of study SBP was similar in WT and p66shc-/-. Aldosterone increased SBP in both WT (192.3 ± 4.522 vs 103.3 ± 2.996; p < 0.05) and p66shc-/- mice (176.8 ± 5.313 vs 105.3 ± 1.542; p < 0.05), although at significant less extent in p66shc-/-. SGLT2 expression was significantly lower in p66shc -/- compared to WT in both kidney and aorta (-50%, for both tissues, p < 0.05). Aldosterone increased SGLT2 expression by 3-fold only in WT (p < 0.05) in aorta but not in the kidney. MR expression was similar in all groups.

Conclusions:

SGLT2 is expressed in vascular tissue as well as in the kidney. Aldosterone modulates its expression only in the vascular tissue, suggesting a tissue specific effect. The p66shc protein may be involved in the modulation of SGLT2 expression in both tissues. These findings suggest that aldosterone and p66shc adaptor protein may contribute to the modulation of SGLT2 expression in the vascular system. Thus SGLT2 may play a role in the vascular homeostatic functions of aldosterone-induced hypertension.
THE PSYCHOLOGICAL COMPONENT OF THE QUALITY OF LIFE WAS RELATED TO COMPOSITE ENDPOINT IN TREATED PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Yana Koshelyaevskaya , Andreeva Galiya , Smirnova Marina , Gorbunov Vladimir , Kurekhyan Armine
Published: April 2021

Objective:

The aim of our study was to determine association between composite endpoint and quality of life (QL) scale scores in treated patients with arterial hypertension (AH).

Design and method:

We analyzed database of treated AH patients (n = 125) with concomitant chronic diseases without exacerbation. We assessed relationships between the initial ambulatory blood pressure monitoring (ABPM) data, socio-demographic indicators, QL scale scores, Asthma Control Questionnaire (ACQ) indices and composite endpoint (death for any reason, angina pectoris, transient ischemic attack, development of chronic heart failure, arterial revascularization, frequent ventricular extrasystoles, atrial fibrillation) after 30.1 ± 7.6 months from the inclusion visit. QL questionnaires (J.Siegrist et al.), ACQ (45 patients had asthma) was completed initially, after 6 months and after 12 months, the ABPM session was performed initially and after 12 months, antihypertensive therapy was corrected at all visits. We analyzed the following QL scale scores: 0 scale: mood at the doctor's visit, I scale: physical well-being; II scale: physical performance; III scale: positive psychological well-being; IV scale: negative psychological well-being; V scale: psychological performance; VI scale: social well-being; VII scale: social performance. We used ANOVA for statistical analysis.

Results:

The baseline mean daytime systolic BP (SBP) was 125.1 ± 10.5; diastolic (DBP) - 76.1 ± 7.3 mm Hg. We found negative correlations between composite endpoint and: III scale scores (positive psychological well-being) (F = -5.3, p < 0.05); 0 scale (mood at the doctor's visit) (F = -5.6, p < 0.05).

We identified a positive correlation between endpoint data and V scale scores (psychological performance) (F = 12.2, p < 0.001). The composite endpoint was not correlated with sex, age, BMI, smoking, ambulatory and clinical blood pressure, the number of drugs in concomitant therapy, pulmonary forced vital capacity. At the end of the study, we registered 21 cases included in the composite endpoint: death (2), transient ischemic attack (1), arterial revascularization (4), frequent ventricular extrasystole (3), atrial fibrillation (8), angina pectoris (3).

Conclusions:

Thus, psychological QL component such as good mood at the doctor's visit (scale 0), positive psychological well-being (scale III) had negative relationship with composite endpoint, at the same time the psychological performance (scale V) had positive correlation with composite endpoint results.
IMPLEMENTATION OF A STRUCTURED CARE PATHWAY FOR RESISTANT HYPERTENSION: PATIENT PROFILE AFTER 1 YEAR
Authors: Vanparys Joris , Deblaton Maite , Van Frachen Beatrice , Derwa Axel
Published: April 2021

Objective:

Cardiovascular diseases remain a major cause of death. Arterial hypertension is an important risk factor, and although it is frequently screened for, it is often suboptimally treated. By implementing a structured care pathway for treatment-resistant hypertension, we aimed to improve diagnosis and treatment of these patients and identify patients at high risk for developing cardiovascular and renal complications.

Design and method:

Patients were referred to the hypertension clinic because of treatment-resistant hypertension despite 3 classes of antihypertensive drugs, or for hypertension diagnosed before the age of 40. All patients received 24 h ambulatory blood pressure monitoring (ABPM) and screening lab tests. Patients with inadequately treated hypertension (>130/80 mmHg/24 h) were evaluated via a structured pathway with a multidisciplinary approach including cardiac and renal ultrasound, nutritional education and additional screening for secondary causes of hypertension.

Results:

In the first year after implementing our structured care pathway, 51 patients were referred: 28 for hypertension diagnosed before the age of 40 and 23 for treatment-resistant hypertension.

Mean age was 51 (range 17–81). 55% were overweight or obese, 16% smoked, 25% had diabetes and 22% used lipid-lowering drugs.

ABPM identified 45 patients (88%) with inadequately treated hypertension. Their treatment regimen was intensified.

Screening for secondary hypertension suggested primary hyperaldosteronism in 3 patients.

Fibromuscular dysplasia was diagnosed in 1 patient.

Patients with treatment-resistant hypertension were on average taking 3,3 different classes of antihypertensive drugs, with ACEi/ARB being used by 96% of patients, and calcium-antagonist by 78%.

Cardiac ultrasound revealed left ventricular hypertrophy in 17 patients (33%). 4 patients had renal insufficiency (eGFR<45 ml/min/1,73m2), 3 had proteinuria.

In patients with treatment-resistant hypertension, the median 10 year risk of cardiovascular death (SCORE risk charts) was 4,25% (range 1–30%). The median 10 year risk of cardiovascular morbidity (Framingham general CVD risk score) was 26,18% (range 7,12–62,6%).

Conclusions:

Implementing a structured care pathway for treatment-resistant hypertension including ABPM is an important tool to identify patients requiring antihypertensive treatment optimization and to diagnose patients with secondary hypertension. Furthermore, it can identify patients with end-organ damage and a high cardiovascular disease risk.
FEATURES OF METABOLIC AND HEMODYNAMIC INDICATORS IN OBESE PATIENTS WITH RESISTANT HYPERTENSION
Authors: Shalimova Anna , Psarova V. , Kochuieva M.
Published: April 2021

Objective:

To establish the features of metabolic and hemodynamic parameters in obese patients with true and pseudo-resistant arterial hypertension (AH).

Design and method:

The study included 200 patients with AH grade II and obesity I-II classes (age 45–55 years). Patients were initially prescribed dual antihypertensive therapy (ACEI and CCB). Those patients who did not reach target blood pressure (BP) levels after 3 months on dual therapy were additionally assigned a third antihypertensive drug (indapamide). Of the 98 patients who were assigned triple therapy, 48 patients did not reach target BP levels: 27 patients had pseudo-resistant AH (due to low compliance with treatment and insufficient adherence to the physician's instructions to ensure adequate levels of physical activity), and 21 patients had true resistant AH (did not have target BP levels with triple antihypertensive therapy and sufficient physical activity). These patients were additionally prescribed spironolactone. The effectiveness of the treatment in all groups was evaluated 6 months after the start of antihypertensive therapy.

Results:

Comparative assessment of obese patients in the presence and absence of resistant AH after 6 months of therapy showed that, unlike patients without resistance, individuals with resistant AH differed more pronounced cardiovascular remodeling and metabolic disorders, greater dysbalance of oxidative stress-antioxidant protection, greater proinflammatory activity and higher activity of the RAAS. When performing a comparative evaluation of the indicators in patients with pseudo-resistant and true resistant AH, it was found that patients with true resistance differed from pseudo-resistant patients with significantly lower (p = 0.0229) body mass index (BMI). In addition, in the absence of differences in BP levels, cardiovascular remodeling, lipid and carbohydrate profiles, patients with true resistance had significantly higher levels of aldosterone (p = 0.0449), higher activity of oxidative stress system (malondialdehyde, p = 0.0055 and diene conjugates, p = 0.0299), lower levels of general antioxidant protection (p = 0.0004), higher adiponectin levels (p = 0.0000), and lower leptin level (p = 0.0001), compared to pseudo-resistant patients

Conclusions:

Obese patients with true resistance differed from pseudo-resistant patients with significantly lower BMI, higher aldosterone level, higher activity of the oxidative stress system, lower activity of the antioxidant protection system, higher adiponectin level, and lower leptin level.
DRUG-RESISTANT HYPERTENSION IN PRIMARY ALDOSTERONISM
Authors: Rossi Gian Paolo , Rossitto Giacomo , Maiolino Giuseppe , Lenzini Livia
Published: April 2021

Objective:

Drug-resistant arterial hypertension can derive from unrecognized forms of secondary hypertension of which primary aldosteronism (PA) is one of the most common. While available data suggest a high prevalence of PA in patients with resistant hypertension (RH), its rate in such population is unclear. This study sought to establish the rate of RH in patients with PA and the blood pressure outcome and resistance to treatment after adrenalectomy PA-RH patients subtyped by adrenal vein sampling (AVS).

Design and method:

Data from consecutive patients with unambiguous diagnosis of PA and seeking surgical cure, submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America, were collected in an observational prospective registry from 2000 to 2015. Blood pressure outcome and resistance to treatment by the American Heart Association 2018 criteria or a local clinical definition were the main study outcomes. Inclusion criteria were age > 18 years, indication to perform AVS following current guidelines, center's agreement to participate and approval of the local Ethics Committee.

Results:

Of 1625 enrolled PA patients, 73.7% had conclusive information on presence or absence of resistant hypertension. Of these, 20.1% were judged to have RH, a rate that raised to 49.5% according to the clinical definition of each center lead investigator. RH was about twice as common in men as in women (p < 1x10-4). Fifty-three percent of the PA patients with RH underwent surgery, which resolved resistance to drug treatment in all.

Conclusions:

RH is a common presentation of PA in consecutive patients seeking surgical cure; AVS-guided adrenalectomy allowed to resolve resistance of high blood pressure to treatment. Hence, the optimal management of patients with PA and RH requires subtyping with adrenal vein sampling.
ARE SUBJECTIVE MEASURES THE ANSWER TO ASSESS PHYSICAL ACTIVITY ON A DAILY BASIS CLINICAL PRACTICE IN PATIENTS WITH RESISTANT HYPERTENSION?
Authors: Ribeiro Fernando , Lopes Susana , Garcia Catarina , Oliveira José , Figueiredo Daniela , Bertoquini Susana , Polónia Jorge , Alves Alberto , Mesquita-Bastos José
Published: April 2021

Objective:

Physical activity is a vital sign for cardiovascular health. However, several factors, such as the duration of the protocol, equipment cost, and need for qualified professionals make the assessment of physical activity with objective measures impractical on a daily basis in a clinical practice. Hence, this study aims to examine the association between subjective and objective physical activity levels in patients with resistant hypertension.

Design and method:

Sixty-six patients (age: 59 ± 1.0 yrs; gender: 50.7% men; BMI: 29.8 ± 0.6 kg/m2; number of antihypertensive medications: 4.6 ± 0.1) were recruited. Outcome measures included clinical data, blood pressure, daily physical activity (questionnaire and accelerometry). Physical activity was objectively measured over a 7-day period with an accelerometer and sedentary time, and time spent at light and moderate-to-vigorous physical activity (MVPA) was computed. Physical activity was also subjectively (self-assessment) assessed from 2 questions regarding moderate and vigorous physical activity. The association between the objective and subjective physical activity measurement was tested, and the McNemar test was employed to examine differences between measures.

Results:

The proportion of patients reporting at least 20 min of continuous, moderate intensity physical activity per week was 60.9% (n = 39) compared to the 27% (n = 17) that were actually registered by the accelerometer (p < 0.05). The difference was also higher in the category of vigorous physical activity, where 1 patient (1.6%) did at least 20 minutes of vigorous activity, while 22 patients (34.4%) actually reported to have done it (p < 0.05). Self-reported moderate and vigorous physical activity were not correlated with objectively measured moderate and vigorous activity (rho = 0.116, p = 0.379; rho = -0.087, p = 0.508, respectively).

Conclusions:

Our findings highlight that despite being a valid, easy and inexpensive solution for assessing physical activity levels in adults with resistant hypertension, the subjectively (self- reported) measures are overestimating the physical activity levels. Findings suggest that self-reported physical activity should be interpreted with caution in adults with resistant hypertension and complemented by accelerometry data when possible.
CHRONIC KIDNEY DISEASE IN PATIENTS WITH RESISTANCE HYPERTENSION AND ACHIEVEMENT OF TARGET BLOOD PRESSURE
Authors: Rekovets Oksana , Torbas Olena , Kushnir Svitlana , Primak Galina , Krushynska Nina , Granich Vladimir , Sirenko Yuriy
Published: April 2021

Objective:

Glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how different factors can affect on achievement of target blood pressure in patients with resistant hypertension and chronic kidney disease (CKD). To evaluate factors related with achievement of target blood pressure in patients with resistant hypertension and CKD.

Design and method:

We included 1134 patients who taken 3 or more antihypertensive drugs: first group (n = 877) patients with RH and eGFR (CKD-EPI) > = 60 ml/min/1.73 m2 a mean age of 53.5 ± 7.1 years, and second group (n = 257) patients with RH and eGFR (CKD-EPI) < 60 ml/min/1.73 m2 a mean age 66.1 ± 8.5 years, SBP 172.8 ± 8.2 and DBP 101.2 ± 6.3mmHg. Patients with secondary arterial hypertension was excluded.

Results:

513 patients (58.5%) with eGFR > = 60 ml/min/1.73 m2 and achievement target office BP and 233 patients (41.5%) not achievement target office BP. 140 patients (54.5%) with eGFR < 60 ml/min/1.73 m2 and achievement target office BP and 117 patients (45.5%) not achievement target office BP. Patients with CKD-EPI > = 60 ml/min/1.73 m2 and achievement BP had higher blood renin (324.5 ± 23.3) ng/l vs not achievement BP (23.2 ± 3.5) ng/l (p < 0.05). Patients with CKD-EPI > = 60 ml/min/1.73 m2 and achievement BP had low blood cortisol level (47.8 ± 3.4) mkg/dl vs patients not achievement BP (163.7 ± 7.8) mkg/dl (p < 0.05). Aldosterone blood level was similar in both group 26.7 ng/dl vs 28.1 ng/dl respectively. Patients with CKD-EPI < 60 ml/min/1.73 m2 and achievement BP had low blood renin (34.1 ± 3.6) ng/l as patients not achievement BP (26.8 ± 2.5) ng/l (p > 0.05). Patients with CKD-EPI < 60 ml/min/1.73 m2 and achievement BP had low blood cortisol (6.0 ± 0.6) mkg/dl vs patients not achievement BP (127.7 ± 8.6) mkg/dl (p < 0.05).

Conclusions:

In patients with RH and CKD-EPI < 60 ml/min/1.73 m2 factors related with not achievement target BP was higher blood cortisol. In patients with RH and CKD-EPI > = 60 ml/min/1.73 m2 factors related with not achievement target BP was low blood renin level and higher blood cortisol.
IMPACT OF POLYPHARMACY AND COMORBIDITIES TO CLINICAL OUTCOMES IN RESISTANT HYPERTENSION RENAL DENERVATION GROUP
Authors: Juknevicius Vytautas , Berukstis Andrius , Jukneviciene Renata , Saule Ieva Marija , Laucevicius Aleksandras
Published: April 2021

Objective:

To analyse impact of polypharmacy to blood pressure control in resistant hypertension renal denervation group.

Design and method:

This prospective study included 73 selected patients with resistant hypertension and RDN (Sympathetic Renal Denervation) performed. Routine follow up was performed subsequently 1, 3, 6, 12, 24 and 48 months after the RDN. Total numbers of pills, prescibed for all diseases was registered. Two groups of patients were defined: A group- patient whom less than 7 pills prescribed and group B -more than 7 pills. Number of antihypertensive medications was analysed separately Also various characteristics were registered: age, sex, comorbidities, 24h-ABPM, arterial stiffness etc. Statistical analysis was performed using SPSS 23.0 Statistical Software.

Results:

A total cases of 73 patients were included. 6 patients died, 18 failed to remain in the follow up during 4 years. Remaining 49 patients data were analyzed. Median age was 55 (33–72) years old with 53,1 % (n = 26) patients being male. Two groups were similar, acoording to age, weight, office blood pressure, heart rate (p > 0,05), but there was higher numbers of diabetes melitus and coronary artery disease in group B. Mean prescribed antihypertensive drugs (A- 4,75; B- 6,52; p > 0,05). In A group we observed significantly reduced BP (sABP 162,6mmHg to 149,6mmHg, p < 0,01; dABP 100,8mmHg to 90,24mmHg, p = 0,01) during 48 months. In B group: sABP 163,76 mmHg to 152,1mmHg, p = 0,13; dABP 89,7 mmHg to 85,1 mmHg, p = 0,54). In A group we observed significantly reduced carotid-femoral aortic pulse wave velocity (AoPWV) from 11.2 m/s to 10.0 m/s in 4 years (p = 0,01). In second group AoPWV increased from 11,8 m/s to 12,8 m/s, but not significantly (p = 0.34).

Conclusions:

Patients with more comorbidities and receiving more pills are at higher cardiovascular risk and their blood pressure is more difficult to control, even after renal denervation procedure.
THE DEVELOPMENT OF RESISTANT HYPERTENSION INDEPENDENT OF THE PRECEDING PERIOD OF THE BLOOD PRESSURE CONTROL IS ASSOCIATED WITH THE INCREASED RISK OF CARDIOVASCULAR EVENTS AND DEATH
Authors: Gupta Ajay , Rostamian Somayeh , Mackay Judith , Godec Thomas , Whitehouse Andrew , Poulter Neil , Sever Peter
Published: April 2021

Objective:

Resistant hypertension (RH) is associated with the increased risk of cardiovascular events (CVEs); that excess risk is often attributed to the legacy of the previous period of uncontrolled blood pressures (BPs). We used the database of the ASCOT trial to evaluate the risk of CVEs (non-fatal myocardial infarction, fatal coronary heart disease, and fatal/non-fatal stroke) and death, after controlling for the cumulative mean of BPs for a preceding period of 2-years (using area-under-curve [AUC]).

Design and method:

18,926 hypertensive patients were initially followed up for the development of RH or not for a period of 2-years. During that period, we calculated the AUC of the cumulative mean BPs (AUCcmBPs) until the RH diagnosis or the end of the 2-year period if no-RH. These patients were then followed up from this new baseline for the risk of CVEs or death. We estimated incidence rates and developed a multivariable Cox regression model after adjusting for a-priori confounders (age, sex, socio-economic status, BMI, total cholesterol, HDL-cholesterol, systolic-BP at baseline, randomized treatment allocation, diabetes, other vascular diseases) and the AUCcmBPs. Interaction tests were done for those who were taking antihypertensive medications prior to the randomization or not.

Results:

About one-third (n = 5,660) developed RH by the end of 2-years. During the further median follow-up of 3.9 years, there were 1113 CVEs and 745 deaths. The incidence rate of CVE and death was higher in those with RH vs those without (34.8 and 18.9 per 1,000 person-years vs 24.0 and 15.4, respectively). In the multivariable model after controlling for the AUCcmBPs, those with RH, as compared to those without, had a significantly higher risk of CVE and death (HR: 1.15 [95% CI 1.03–1.27], p-value = 0.010, and 1.16 [1.02–1.33], p-value = 0.028, respectively). This excess in the risk didn’t differ significantly between those who were on prior antihypertensive therapy or not (interaction test p-value = 0.430 and p-value = 0.310, respectively).

Conclusions:

After accounting for prior BPs, the presence of RH is associated with the increased risk of CVEs and death; which could be because of the additional risk due to associated genotypical or phenotypical factors.
DIRECTLY OBSERVED ADMINISTRATION OF ANTI-HYPERTENSIVE MEDICATION PRIOR TO AMBULATORY BLOOD PRESSURE MONITORING – A USEFUL TOOL FOR INVESTIGATING ‘RESISTANT HYPERTENSION’
Authors: Lawson Gwyneth , Fish Richard
Published: April 2021

Objective:

Non-adherence to anti-hypertensive medication is a well-recognized cause of apparent ‘resistant hypertension’. We investigated whether directly observed administration (DOA) of anti-hypertensive medications, immediately prior to 24-hour ambulatory blood pressure monitoring (ABPM), would help exclude ‘treatment resistance’ potentially caused by medication non-adherence.

Design and method:

Resistant hypertension was defined (as per UK guidelines) as a mean daytime blood pressure (BP) of 135/85 or more despite the use of three or more anti-hypertensives. All patients had 24-hour ABPM immediately after a morning clinic appointment. Patients attending our nurse-led hypertension clinic were requested in advance to not take their prescribed anti-hypertensives on the morning of their appointment, but to bring their medications with. Patients were then observed taking their medications prior to ABPM. Patients that did not follow these instructions or who had ABPM organised from a different clinic (without DOA) formed the control group. Proportions were compared with Chi-squares tests. Data analysis was performed using Microsoft EXCEL 2010.

Results:

From November 2018 – October 2019, 53 patients had DOA before ABPM and were compared with 136 controls (see Table 1 for characteristics of each group). In the DOA group the average daytime BP was 138/83 with 38% having BP <135/85. In the control group average daytime BP was 141/86 with 27% having BP < 135/85.

In total 54 patients were taking three or more anti-hypertensive medications. Table 2 compares the characteristics of these patients that underwent DOA (n = 14) compared with those that did not (n = 40). Of these patients, 50% that underwent DOA had a mean daytime BP of <135/85 compared with 20% in the control group (p = 0.03).

Conclusions:

Eliminating any effect of medication non-adherence by directly observed administration of prescribed anti-hypertensives immediately prior to ABPM leads to a lower rate of ‘resistant hypertension’ diagnoses. This strategy may therefore negate the need for further treatment and/or investigation in some patients.
THE RELATIONSHIP AMONG BRACHIAL SYSTOLIC BLOOD PRESSURE, MICROALBUMINURIA, AND 24-H URINARY EXCRETION ON CENTRAL SYSTOLIC PRESSURE IN RESISTANT HYPERTENSIVE PATIENTS
Authors: Cestario Elizabeth , Rubio Tatiane de Azevedo , Souza Maira Regina de , Mello Priscilla Gaisteu de , Gonsalez Elizangela Gianini , Costa Larissa Morete Caieiro da , Martin Jose Fernando Vilela , Toledo Juan Carlos Yugar
Published: April 2021

Objective:

Resistant hypertensive patients have a high prevalence of target organ damage. Increased central systolic blood pressure (cSBP) is more relevant than the peripheral one in these patients, because heart, brain and kidneys are directly exposed to high cSBP levels. Moreover, it is directly related to left ventricular hypertrophy, left atrial size, ischemic heart disease, brain injury, and kidney dysfunction. Currently, assessing cSBP and Augmentation Index (Aix) can be helpful to stratify cardiovascular risk and there is evidence that an improvement on cSBP leads to reduction of cardiovascular events and guides the antihypertensive treatment with drugs that more effective on cSBP reduction.An open prospective study was conducted, to identify markers associated with high cSBP values in resistant hypertensive patients on antihypertensive treatment.

Design and method:

Seventy-two hypertensive patients were recruited in the Hypertension Outpatient Clinic of FAMERP (44 women/ 28 men). Clinical characteristics and biochemical data collected are shown in the Table 1. The central systolic arterial pressure (cSBP) and the augmentation index (AIx) were measured using Tonometry HEM 9000-A validated OMRON equipment (JAPAN).

Results:

Multiple regression (cSBP) showed positive correlation between cSBP and brachial SBP (p = 0,0243) and microalbuminuria (p = 0,0325) and negative correlation with 24-h urinary sodium (p = 0,0277). Table2 and Figures.

Conclusions:

In Resistant hypertensive patientes the microalbuminuria can be useful as a marker to Increased central systolic blood pressure (cSBP)
HYPERTENSIVE PATIENTS WITH GREATER GENETIC RISK RESPOND LESS EFFECTIVELY TO TREATMENT AND ARE MORE LIKELY TO BE TREATMENT RESISTANT
Authors: Warren Helen , Traylor Matthew , Garofalidou Tatiana , Ng Fu Liang , Gupta Ajay , Sever Peter , Caulfield Mark , Munroe Patricia
Published: April 2021

Objective:

Patients with resistant hypertension (RHTN) have increased cardiovascular disease risk. It is believed there may be genetic causes, although robust associations remain to be validated.

Over 1,000 genetic loci have been discovered for BP from genome-wide association studies (GWAS), with application of genetic risk scores (GRS) enabling population risk stratification. However it is unknown whether genetic risk influences treatment response.

We investigated whether BP associated loci: (i) are associated with RHTN; (ii) mediate the effect of antihypertensives on BP lowering response.

Design and method:

We analysed 6,266 patients of European ancestry with genetic data from ASCOT.

BP-GRSs were constructed for systolic (SBP), diastolic BP (DBP) and pulse pressure (PP) using all available 1,167 pairwise-independent published BP-associated genetic variants, weighted by their effect estimates from our recent BP-GWAS in N∼750k individuals.

We tested the BP-GRS for association with: (i) RHTN, adjusted for known non-genetic predictors: sex, age, BMI, diabetes, randomization treatment arm and left ventricular hypertrophy; (ii) BP response to monotherapy treatment, adjusted for sex, age, baseline-BP, dose and baseline antihypertensive use. All analyses adjusted for 10 principal components of ancestry.

Results:

Each BP-GRS is significantly associated with RHTN (P = 1.13 × 10-13, 1.96 × 10-5, 1.21 × 10-14 for SBP, DBP, PP) with increased genetic risk leading to increased odds of RHTN. Patients in the top 20% of SBP-GRS have 1.74 times greater odds of RHTN than the lowest 20% (P = 6.96 × 10-10). Additional adjustment for baseline-BP does not change conclusions. The association even remains significant (P = 5.11 × 10-4) with stronger effect (OR = 2.52) when restricted only to 1,037 patients untreated at baseline.

The BP-GRS is also significantly associated with SBP and DBP response to amlodipine (N = 1,780): patients in the lowest 20% genetic risk group achieve better lowering response by 3.77mmHg mean difference between SBP pre and post treatment (P = 8.27 × 10-4).

Conclusions:

Our results confirm the hypothesis for a genetic contribution to RHTN, indicating RHTN patients are likely to be those with highest genetic risk of hypertension, which helps to explain the clinical challenge. We show that those with greater BP genetic risk respond less effectively to treatment and provide evidence that BP genes also influence treatment response.
ASSESSMENT OF RENAL DENERVATION IN THE TREATMENT OF RESISTANT HYPERTENSION IN A SPECIALIZED UNIT
Authors: Águila Fernando Jaén , Chamorro Ricardo Roa , Bustos Pablo González , García Juan Diego Mediavilla
Published: April 2021

Objective:

Renal denervation (RDN) is indicated in patients despite the use of three or more anti-hypertensive drugs including a diuretic, which, having ruled out secondary causes of hypertension (HT), are not controlled and are classified as resistant hypertension (RHT). The approximate prevalence is 10% -20% of the hypertensive population and represents a high incidence of adverse cardiovascular events in these patients.

RND is a minimally invasive method, but the effectiveness of this technique has shown some contradictory data due to a heterogeneity in the design of these studies.

Our objective is to evaluate the clinical experience in patients undergoing RDN in our unit.

Design and method:

Retrospective record of the 2009–2019 period. 16 patients with RHT treated by RDN with Symplicity-Flex or Spyral devices have been included. The statistical study was made with Spss program.

Results:

56.3% were male. Mean age of 53 ± 8 years. The average preRDN clinical SBP 169 ± 19 mmHg; DBP clinical preRDN mean 101 ± 17 mmHg; Mean postRDN clinical SBP 149 ± 26 mmHg; DBP clinical postRDN mean 88 ± 11 mmHg; Average number of preRDN drugs 5.88 ± 0.8; Average number of postRDN drugs of 4.67 ± 1.4. 75% of the procedures were done with the spiral symplicity method. Average number of ablations 24 ± 9 per procedure. There was no deterioration of renal function or complications.

Conclusions:

Our data provide a decrease in clinical BP after RDN, with a decrease in the number of drugs used to control their BP, and there seems to be a better response to the spiral symplicity method with greater number of ablations. The RDN technique has been proven safe, with no relevant complications and preserved renal function. The data therefore guarantee the safety and efficacy of this technique, which coincide with the recent national registries published in real life and that support its use in selected patients and in experienced centers.
ESSENTIAL HYPERTENSION OR A MISSING CAUSE FOR SECONDAY HYPERTENSION?
Authors: Munteanu Alice Elena , Ionita Iulia Theodora , Casian Mihnea , Gurzun Maria Magdalena , Diaconescu Corina
Published: April 2021

Objective:

The case highlights the importance of diagnosing secondary hypertension and adequate treatment in the setting of a patient with classical cardiovascular risk factors which would otherwise make primary hypertension the most likely diagnosis.

Design and method:

Clinical Case

Results:

A 57 year-old male with cardiovascular risk factors (smoking, dislypidemia), grade 2 essential hypertension (ESC/ESH) and G3a stage chronic kidney disease (CKD) presents to our clinic with fatigue and persistent high blood pressure values despite treatment with ACEi. Clinical exam was unremarkable except for a 10mmHg difference between the arm and foot systolic blood pressure. The 24-hour ambulatory blood pressure monitoring revealed a non-dipping profile, with a mean blood pressure value of 150/100mmHg. TTE was performed and the following were observed: bicuspid aortic valve with tight aortic stenosis (mean AV PG > 40mmHg, AVA = 1.12cm2) and LV systolic dysfunction (LVEF = 35%). TEE was also performed and confirmed the bicuspid aortic valve. Given the context of the patient, computed tomography angiography (CTA) was the investigation of choice in order to visualize the aorta. Postductal coarctation was detected with a hypoplastic thoracic aorta and multiple collateral vessels. The coronary angiogram was normal. The ACEi was stopped and the patient received a dihydropyridine calcium channel blocker in combination with an adolsterone receptor antagonist with a favourable course. Aortic valve replacement surgery with mechanical valve implantation was recommended. Considering the multiple collateral vessels and complex vascular morphology, surgical correction of the coarctation was considered no longer feasible

Conclusions:

CoA was the actual cause for the persistent high blood pressure values in an adult male with cardiovascular risk factors who was believed to have essential hypertension. In the setting of aortic stenosis with impaired LV systolic function, high blood pressure values are not typical. Taking into account the BAV, the clinical suspicion of CoA was high and prompted further investigations. The CKD is the result of the the underperfusion of the kidneys secondary to the CoA and the use of ACEi.