bluuebunny/crossref_metadata_2025_split huggingface dataset:
THERAPEUTIC APPROACH FOR HYPERTENSION MANAGEMENT AND CONTROL IN PATIENTS RECEIVING OLMESARTAN-BASED TREATMENT: THE “FAMILY” NON-INTERVENTIONAL STUDY IN PRIMARY CARE IN GREECE
Authors: Kollias Anastasios , Katsimagklis Georgios , Mastrokostopoulos Antonios , Stergiou George S. 
Published: April 2021

Objective:
To evaluate the characteristics, office blood pressure (OBP) levels and usual treatment strategies of hypertensive patients receiving olmesartan-based therapy in general practice.

Design and method:
A nationwide non-interventional survey was performed by primary-care doctors who assessed consecutive hypertensives on stable (> = 4 weeks) olmesartan-based therapy. Patients’ characteristics, OBP levels and treatment changes were reported.

Results:
A total of 4,883 hypertensives on olmesartan-based therapy (age 66.5 ± 11.2 years, men 54%, diabetics 26%, smokers 23%) were assessed by 491 doctors (48% cardiologists, 39% internists, 12% general practitioners, 1% others). Average OBP was 137.6 ± 16.0/82.4 ± 9.8 mmHg (systolic/diastolic) and 56% had controlled OBP (<140/90 mmHg). Participants were receiving 2.2 ± 0.8 antihypertensive drugs (olmesartan monotherapy 21%; 2 drugs 44%; 3 drugs 30%; > = 4 drugs 5%). Of subjects on olmesartan combinations (79%), 89% used fixed-dose pills (37% olmesartan-amlodipine; 28% olmesartan-hydrochlorothiazide; 35% olmesartan-amlodipine-hydrochlorothiazide). Cardiologists prescribed fixed-dose combinations more frequently than general practitioners or internists (77/75/72% respectively, p < 0.01). 13% of patients reported missing at least one dose per week, with most common reported cause the complexity of treatment regimen (75%). OBP control was (i) higher in nondiabetics than diabetics (58% vs. 52%, p < 0.01), despite using fewer drugs (2.2 ± 0.8 vs. 2.4 ± 0.8 drugs, p < 0.01), (ii) lower in patients on monotherapy compared to 2, 3 or > = 4 drugs (53/56/59/57% respectively, p < 0.05) and (iii) higher in patients on fixed-dose than free combinations (58% vs. 53%, p < 0.01). In cases with uncontrolled OBP the following actions were decided: dose increase 18%; drug addition 17%; drug substitution 3%; treatment simplification using fixed-dose combination 7%; no change 55%.

Conclusions:
Combination therapy and particularly fixed-dose combinations are widely prescribed in primary care. However, uncontrolled OBP is common, even in patients on monotherapy, and is worse in diabetics. Physicians’ inertia and complexity of regimen are major barriers in achieving optimal control. More intense and simpler therapy, with wider use of triple fixed-dose combinations and second-line drugs, are necessary to improve the control of hypertension in primary care.
PRIMARY HEALTH CARE PHYSICIANS’ KNOWLEDGE AND ADHERENCE TO HYPERTENSION MANAGEMENT GUIDELINES IN SOUTHWEST OF SAUDI ARABIA
Authors: Shnaimer Jubran , Gosadi Ibrahim 
Published: April 2021

Objective:
Aim of the study: to measure adherence of primary health care (PHC) physicians in Jazan to Saudi guidelines for the management of hypertension (SHMGs).

Specific Objectives:
-To assess the source of guidelines PHC physicians in Jazan is using for management of hypertension cases.
-To measure knowledge of PHC physicians in Jazan about Saudi hypertension guidelines.

Design and method:
This cross-sectional study was conducted in 170 PHC centers in Jazan region, southwest of Saudi Arabia. A self-administered questionnaire was distributed and collected from 316 PHC physicians working in Jazan from June until September 2019. Data were analyzed using descriptive statistics and chi-square test, with a significance level of P < 0.05.

Results:
316 PHC physicians in Jazan participated in the present study; their mean of age (SD) was 38.17 ± 9. More than half of the participants were males (53%). The majority of PHC physicians were non-Saudi (72.47%). Most of the participants were General practice (61.7%). The results revealed that the total Knowledge score of PHC physicians was 7.96 ± 2.55, and the total practice score 7.29 ± 1.69 concerning HTN Saudi hypertension management guidelines. An average number of patients seen daily at the clinic (P = 0.015) and Attendance of training sessions for HTN management (P = 0.020) were the significant factors associated with the level of knowledge and adherence concerning the SHMGs in our study.

Conclusions:
The present study concluded that PHC physicians in Jazan did not fully adhere to all Saudi Hypertension Management Guidelines. The total mean score of the physician's knowledge and practice showed undesirable results. The reason could be explained through low levels of work experience and not having attended any training courses; the study suggested an urgent need for performing continuous education courses on high Blood Pressure levels.
THE HYPERTENSION CANADA PROFESSIONAL CERTIFICATION PROGRAM: A NOVEL IMPLEMENTATION STRATEGY FOR HYPERTENSION GUIDELINES
Authors: Watson Kaitlyn , Tsuyuki Ross , Beahm Nathan , Sedore Rebecca , Bell Alan 
Published: April 2021

Objective:
The uptake of clinical practice guidelines into practice is poor for many chronic conditions, including hypertension. What is missing is an implementation strategy for incorporating guidelines into primary care practice. Herein, we describe the development of the Hypertension Canada Professional Certification Program (HC-PCP), a novel approach to guidelines implementation.

Design and method:
First, we identified 15 competencies believed to be important for primary care professionals to master when providing hypertension care. These competencies were surveyed for consensus by front-line clinicians through the Hypertension Canada e-newsletter. Clinicians were asked to rank the importance (on a Likert scale from 1 = not important to 5 = very important) of each competency for a primary care provider when undertaking a certification in hypertension management.

Results:
A total of 121 clinicians responded to the survey. Of these, 38% were pharmacists, 31.4% were registered nurses, 10.7% were physicians, and 7% were nurse practitioners. There was at least one respondent from each Canadian province and territory, except for the Northwest Territories. All 15 competencies received a mean rank of at least 4. The competencies with the lowest rank was “Demonstrates a sound knowledge of the epidemiology of hypertension” (mean 4.07 (SD 0.85)) and the highest was “Ability to screen and identify hypertension” (mean 4.83 (SD 0.04)). We then used these competencies to develop an online certification program, the HC-PCP. Some features include regular quizzes, submission of a video outlining the learner's blood pressure measurement technique, and submission of 3 patient cases for expert review. The program was launched recently: www.hypertension.ca/professional-certification-program/.

Conclusions:
We have developed a novel online hypertension certification program based upon the Hypertension Canada guidelines. The HC-PCP has been launched to pharmacists first, and is also being tested in a stepped wedge randomized trial called RxPATH (www.epicore.ualberta.ca/home/rxpath/).
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.