bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOTUM-854 PREVENTS L-NAME-INDUCED ARTERIAL HYPERTENSION IN MICE
Authors: Bolea Gaetan , Ripoche Doriane , Meyer Gregory , Lejoubioux Florian , Michaux Arnaud , Otero Yolanda , Peltier Sebastien , Sirvent Pascal , Reboul Cyril 
Published: April 2021

Objective:
Arterial Hypertension (HTA) is a major cause of premature death worldwide, with an estimated global prevalence of 1.13 billion people. Polyphenolic compounds have been shown promising effects in the context of HTA management. We have developed Totum-854 (T-854), a polyphenol-rich botanical composition to reduce the risk of developing AHT. We assessed the chronic effect of T-854 on preventing the development of N(G)-Nitro-L-arginine-methyl ester (L-NAME)-induced AHT in mice.

Design and method:
Twelve-week-old C57Bl6/J mice were divided into 3 groups: Control (n = 11), L-NAME (n = 11), and L-NAME + T-854 (n = 11). L-NAME (100 mg/kg/day) was dissolved in drinking water. Mice were gavaged once a day for three weeks with either T-854 (450 mg/kg) or vehicle. The arterial pressure was assessed using the CODA® Tail-Cuff System every week for three weeks. Effects of T-854 on in vitro angiotensin-converting enzyme (ACE) activity was also assessed by a HPLC-UV method.

Results:
Body weight evolution was not significantly different between the 3 groups over the study period. As expected, L-NAME increased systolic (SBP; from 105 ± 3 to 130 ± 1 mmHg, p < 0.0001), diastolic (DBP; from 77 ± 3 to 97 ± 2 mmHg, p < 0.0001) and mean (MBP; from 86 ± 3 to 108 ± 2 mmHg, p < 0.0001) blood pressure along the 3 weeks of treatment. Interestingly, in T-854-supplemented mice, SBP was significantly reduced from the first week of supplementation and DBP and MDP from the second week of supplementation. After three weeks of supplementation, T-854 lowered the SBP by 16% (p < 0.0001), the DBP by 20% (p < 0.05) and the MBP by 18 % (p < 0.01), in comparison to L-NAME mice. Moreover, in vitro experiments showed an inhibitory effect of T-854 on ACE activity.

Conclusions:
In conclusion, this study showed that T-854 prevents L-NAME-induced HTA in mice. ACE inhibition may partly explain the preventive effects of T-854 on HTA development in this model. T-854 is a promising new approach for the prevention of HTA.
EARLY ASSESSMENT OF HYPERTENSION MEDIATED ORGAN DAMAGE IS CAPABLE OF PREDICTING CARDIOVASCULAR EVENTS IN FIVE YEARS FOLLOW-UP OF PATIENTS WITH HYPERTENSION AT A CENTER IN MENDOZA
Authors: Renna Nicolás Federico , Williams Bryan , Farez Beder , Repetto Martin , Bernasconi Pablo , Murua Mario , Ramirez Jesica , Miatello Roberto 
Published: April 2021

Objective:
Hypertension-mediated organ damage (HMOD) is a powerful predictor of mortality in hypertensive patients. The objective of the work was to determine the prognostic value of the early detection of HMOD in patients with a recent diagnosis of hypertension.

Design and method:
It is an analytical observational and prospective study that included all patients referred to Hypertension Unit of Hospital Español de Mendoza from January 2015 to December 2019 who met the following criteria: 1- Patients diagnosed with hypertension last 5 years; 2- Has been done a ABPM, 3- That has been done a Colour Doppler Echocardiography (CDE) with preserved ejection fraction and 4- a record of clinical history in the hospital that allowed obtaining the data and personal history. Exclusion criteria: 1- Patients who presented atrial fibrillation at the time of the Doppler echocardiogram study; 2- Any studies had missing or erroneous data, 3- Vital state could not be verified at the end of study, 4-Presence of any valve disease and 5- Ejection fraction of less than 40%, 5- Minor patients 16 years old. Variables and Measurements: ABPM; Colour Doppler Echocardiography (CDE) and patient data features;

Results:
Of the total of patients, 51% were women and 7,8% patients were diagnosed with diabetes mellitus. 196 endpoints were recorded during 60 months of evaluation. Men and patients with diabetes mellitus had a significantly greater number of events using the K-M (Hazard ratio 1.55 CI = 1.17 to 2.0 and Hazard ratio 1.77 CI = 1.04 to 3.0). In CDE, E/A ratio of the transmission flow (HR 1.43 HR CI 1.13–1.81). The nocturnal PP showed a clear association with the occurrence of events (HR 190 HR CI 17.9 to 2022). Evaluation of morning pressure alone did not show associations with cardiovascular risk.

Conclusions:
The most important finding of the study was to find that a population with a diagnosis of arterial hypertension of less than 5 years, with low cardiovascular risk, the pressure of daytime, nighttime and morning surge was a predictor of hard cardiovascular events. So was the E / A ratio of left ventricular transmitral flow.
LEVELS OF IMMUNOGLOBULIN G AND MARKERS OF VASCULAR INFLAMMATORY RESPONSE AS PREDICTORS OF POSSIBLE VASCULAR COMPLICATIONS IN PATIENTS WITH ARTERIAL HYPERTENSION AFTER SARS-COV-2
Authors: Petelina Tatiana , Natalia Musikhina , Elena Yaroslavskaya , Elena Gultyaeva , Ksenia Avdeeva , Elena Gorbatenko , Lyudmila Gapon , Ekaterina Zueva , Anastasia Shcherbinina 
Published: April 2021

Objective:
To investigate the level and relationship of specific immunoglobulin G (IgG) antibodies to SARS-CoV-2 with laboratory parameters of vascular inflammatory response (VIR) during follow-up of patients with arterial hypertension (AH) in 3 months after disease onset.

Design and method:
Retrospective, single-center observational study included 76 confirmed cases of COVID-19 associated with pneumonia (April-May 2020). Gr.1 consisted of 32 patients without AH; Gr.2 involved 44 AH patients, including 18 patients with metabolic disorders (abdominal obesity and impaired carbohydrate metabolism). Complete blood count, biochemical and hemostatic parameters were determined on the day of admission. Comprehensive analysis of clinical instrumental and laboratory parameters, including blood pressure, heart rate, IgG (positivity rate), cytokines, NT-pro BNP, endothelial dysfunction markers, cystatin C, glucose and others was performed in 3 months after discharge.

Results:
In Gr.1, IgG was negatively associated with hemoglobin, red blood cell volume, neutrophils, creatine phosphokinase, homocysteine, those were supplemented by NT-pro BNP, interleukin-6, lactate dehydrogenase, creatinine (p < 0.0001–0.034) in Gr.2 and additionally, D-dimer level, transforming growth factor and P-selectin (p < 0.001–0.036) in metabolic disorders subgroup. Therewith, in patients aged over 40 years, positive association of IgG with levels of SBP and DBP (p < 0.011 and 0.034), MDRD (p < 0.01) was registered. Correlation and regression analysis revealed greater association of IgG level < 12.9 with vascular inflammatory markers, and IgG level > 12.9 with thrombogenic parameters.

Conclusions:
IgG might be a sensitive indicator of VIR and can play a role in predicting possible unwanted vascular complications in AH patients after suffering from SARS-CoV-2.
PLASMA ACE2 ACTIVITY IS INCREASED IN PATIENTS RECOVERED FROM SARS-COV-2 INFECTION: IMPLICATIONS FOR THE PROLONGED CONSEQUENCES OF COVID-19
Authors: Patel Sheila , Juno Jennifer , Lee Wen Shi , Wragg Kathleen , Hogarth P. Mark , Kent Stephen , Burrell Louise 
Published: April 2021

Objective:
COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilises the catalytic site of membrane-bound angiotensin converting enzyme 2 (ACE2) for cell entry. It is thought that endocytosis of ACE2 results in a decrease in membrane bound ACE2 expression, and disruption of the local tissue renin angiotensin system protection. In this study, we hypothesised that SARS-CoV-2 infection would be associated with shedding of ACE2 leading to increased plasma ACE2 activity.

Design and method:
Australians aged > 18 years (n = 66) who had recovered from SARS-CoV-2 infection (positive result by PCR testing) and uninfected controls (n = 70) were recruited. Serial samples were available in 23 recovered SARS-CoV-2 patients. Plasma ACE2 activity was measured using a fluorescent substrate-based assay and levels were compared using the Mann-Whitney or Kruskal–Wallis test. Serial ACE2 activity were analysed using the Friedman test for repeated measures. Post-hoc analysis was performed with a Bonferroni correction. Two-tailed P-values < 0.05 were considered significant.

Results:
Controls and SARS-CoV-2 recovered patients were matched for age (mean ± SD, 54 ± 11 vs. 53 ± 14 years, p = 0.47) and gender (53% vs. 59% male, p = 0.49). There were no significant differences (p > 0.05) in the proportion of hypertension, obesity, diabetes, cardiovascular disease, or use of anti hypertensive, lipid lowering, and anti-platelet medications between the controls and SARS-CoV-2 patients. Plasma ACE2 activity at median 35 days post-infection [interquartile range 30–38 days] was 97-fold higher in SARS-CoV-2 patients compared to controls (5.8 [2–11.3] vs. 0.06 [0.02–2.2] pmol/min/ml, p < 0.0001). Plasma ACE2 activity was significantly different across disease severity (p = 0.033), with severe COVID-19 associated with higher ACE2 activity compared to mild disease (11.2 [8.3–23.2] vs. 5.4 [1.8–9.0] pmol/min/ml, p = 0.027). Men recovered from SARS-CoV-2 had higher ACE2 levels compared to women (9.2 [5.8–15.3] vs. 2.1 [0.2–5.1] pmol/min/ml, p < 0.0001). In 23 patients who had serial blood samples at 63 [56–65] and 114 [111–125] days post infection, median ACE2 activity remained persistently elevated with no differences between time-points (p > 0.05).

Conclusions:
Plasma ACE2 activity is elevated after SARS-CoV-2 infection and remains elevated post-infection. Our findings indicate the need for ongoing investigation to determine if ACE2 levels identify people at risk of prolonged illness following COVID-19.
LOW AWARENESS, TARGET ORGAN DAMAGE AND CARDIOVASCULAR COMPLICATIONS OF HYPERTENSION IN LOW RESOURCE SETTING
Authors: Onwubere Basden , Ejim Emmanuel , Ogah Okechukwu 
Published: April 2021

Objective:
This paper reviews the current picture of low awareness, target organ damage, and cardiovascular complications in Africa using available literature as well as meta-analyses. Sub-Saharan Africa typically consists mostly of a low resource setting.

Design and method:
Meta-analyses of publications on hypertension and related cardiovascular complications in Africa were carried out. An extensive literature search was carried out. Publications were mainly from various locations in Sub-Saharan Africa (SSA).

Results:
A meta-analysis of 37 publications showed the prevalence of hypertension varied extensively between and within studies. Prevalence was higher in urban than in rural populations; it was also higher with increasing age in most studies. Less than 40% were previously diagnosed. Of these less than 30% were on drug treatment, and less than 20% had blood pressure within the defined normal range. Ogah and Rayner identified 38 publications from Sub-Saharan Africa mostly conducted in urban areas: two national surveys (Malawi and Mozambique), 14 in rural settings, 16 in urban communities, one each in semi-urban and semi-urban/rural settings, and four in both rural and urban communities (figure 1)
The treatment status for South African black males with hypertension showed that 20% were aware of their condition, 14% of them were on treatment and only 7% were controlled. ; these figures were respectively 47%, 29%, and 15% for women (Steyn et al) Of 219 hypertensives, in a population in Ghana 104 (47.5%) had evidence of target organ damage. Other studies from Tanzania, Sudan, South Africa, and Nigeria showed a significantly low level of Awareness, significant Target Organ Damage mostly at the time of diagnosis. Generally in Nigeria and most, some other African countries, complications of hypertension contributes significantly to Hospital admissions (Onwubere et al)

Conclusions:
It is observed that in most parts of Africa, hypertension presents with earlier and more severe target organ damage compared to developed country settings. This results from the late presentation, ignorance of the need for regular medical checks, paucity of adequate medical facilities, poverty, sub-standard drugs, and ethnic and genetic factors.
CARDIOVASCULAR OUTCOMES AT RECOMMENDED BLOOD PRESSURE TARGETS IN MIDDLE AGED AND ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS AND HYPERTENSION
Authors: Olsen Eirik , Holzhauer Björn , Julius Stevo , Kjeldsen Sverre , Larstorp Anne , Mancia Giuseppe , Mehlum Maria , Mo Rune , Rostrup Morten , Søraas Camilla , Zappe Dion , Weber Michael 
Published: April 2021

Objective:
The optimal blood pressure (BP) target for patients with type-2 diabetes mellitus (DM) and hypertension has been set at < 130/80 mmHg in guidelines. However, available data of event-based clinical outcomes trials show that little evidence supports these guideline recommendations.

Design and method:
We addressed this issue by post-hoc analyzing the risk of cardiovascular (CV) events in mostly elderly high-risk hypertensive patients with type-2 DM participating in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial.
Patients (n = 5250) were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (< 25%, 25%-49%, 50–74%, 75% -100%) in which BP was reduced to < 140/90 or < 130/80 mmHg.

Results:
After adjustment for baseline demographic differences between groups, a reduction in the proportion of visits in which BP achieved < 140/90 mmHg accompanied a progressive increase in the risk of CV mortality and morbidity as well as of cause-specific events such as stroke, myocardial infarction and heart failure (Figure, upper panel). A progressive reduction in the proportion of visits in which BP was reduced < 130/80 mmHg did not have any effect on CV risks (Figure, lower panel).

Conclusions:
In mostly elderly high-risk hypertensive patients with type-2 diabetes mellitus participating in the VALUE trial, achieving more frequently BP < 140/90 mmHg showed a marked protective effect on overall and all cause specific cardiovascular outcomes. This was not the case for a more frequent achievement of the more intensive BP target, i.e. < 130/80 mmHg.
THE MAIN FACTORS INFLUENCING PHARMACOTHERAPY IN PATIENTS OVER 60 YEARS OLD WITH ARTERIAL HYPERTENSION
Authors: Avdeeva Irina , Borisova Natalia , Burko Nadezhda , Oleynikov Valentin 
Published: April 2021

Objective:
To assess the significance of the main factors influencing the pharmacotherapy performed in patients over 60 years old with arterial hypertension (AH) 1–2 grade.

Design and method:
The study included 50 persons over 60 years old with AH 1–2 grade. Office BP on pharmacotherapy was 136.7 ± 13.5 and 81.8 ± 7.7 mmHg, mean age - 71.7 ± 4.9 years. According to the questionnaires, the following factors were assessed: cost of drugs (less and more than 5 euros), frequency of administration, presence of disease symptoms before taking the drug, influence of awareness of the disease on interest in treatment, self-control over the treatment process, quality of medical care

Results:
The cost of drugs, if it was up to 5 euros, for the majority of patients (64%) had an average significance, while at a cost over 5 euros this factor acquired a high and very high value (50 and 26%, respectively). The frequency of drug intake was of average significance (16%) and higher (high - 22%, very high - 30%). The factors associated with communication with a doctor had a high and very high value for more than 50% of patients: the accuracy of the recommendations was 38 and 30%, the satisfaction from communication with the doctor was 41 and 22%, respectively. The speed of medical care and the doctor's control were predominantly very low (22 and 24%), low (24 and 32%) and medium (24 and 14%) significance. The presence of symptoms for taking drugs increased the significance of receiving treatment by more than 50% (high significance 18%, very high - 46%). The majority of the respondents assessed the disease awareness and interest in treatment as high (34%) and very high (34%). Self-control over the treatment process in half of the patients was rated high (22%) and very high (28%).

Conclusions:
Along with the high cost of drugs, the effectiveness of treatment in patients over 60 years old with hypertension 1–2 grade was significantly influenced by the frequency of drug intake, the presence of symptoms and awareness of the disease, self-control for most people was more important than the doctor's control.
DYNAMICS OF ARTERIAL STIFFNESS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN LONG-TERM EFFECTIVE LIPID-LOWERING THERAPY
Authors: Matrosova Irina , Borisova Natalia , Babina Anastasia , Oleynikov Valentin 
Published: April 2021

Objective:
To assess the dynamics of regional arterial stiffness by volume sphygmography in patients with primary myocardial infarction with ST segment elevation (STEMI) and without ST segment elevation (NSTEMI) on the background of long-term effective lipid-lowering therapy.

Design and method:
A total of 24 people with acute coronary syndrome were examined: 18 men (75%) and 6 women (25%). The diagnosis was confirmed by biomarkers of myocardial necrosis, electrocardiography, coronary angiography. STEMI was diagnosed in 91.6% of individuals. The average age was 52.88 ± 9.55 years; weight - 81.1 ± 12.6 kg; height 169.7 ± 8.9 m; BMI - 28.4 ± 4.1 kg/m2. Office pressure indicators: SBP –116.7 ± 12.23 mm Hg. and DBP –74.94 ± 8.74 mm Hg; heart rate -68.05 ± 5.16 bpm. On 7–9th day from the disease onset and after 48 weeks, the patients underwent an assessment of regional arterial stiffness using volume sphygmography (VaSera-1000, Fukuda Denshi, Japan). The following indicators were determined: the pulse wave velocity in the arteries of muscle type (B-PWV), in the arteries of elastic type on the right and left (R / L-PWV), cardio-ankle vascular index - CAVI1, which characterizes the true arterial stiffness, independent of the blood pressure level and the reflected wave. All patients were prescribed with atorvastatin 80 mg/day during the first 24–96 hours of acute myocardial infarction in addition to standard therapy. The duration of therapy was 48 weeks. If the target LDL-C level of < 1.5 mmol/L was not achieved 5–6 weeks after AMI, patients were additionally prescribed with ezetimibe 10 mg daily.

Results:
Against the background of lipid-lowering therapy, a statistically significant decrease in PWV was observed: R-PWV decreased from 14.3 ± 2.4 to 13.2 ± 1.8 m/s (p = 0.04), L-PWV decreased from 13.8 ± 1.8 to 13.0 ± 1.4 (p = 0.04). Significant dynamics of the average R/L-PWV indicator was from 14.1 ± 2.0 to 13.0 ± 1.6 m/s (p = 0.03). There were no significant changes in CAVI and B-PWV.

Conclusions:
48-week therapy with atorvastatin 80 mg in patients with primary myocardial infarction with ST segment elevation and without ST segment elevation leads to an improvement in the structural and functional properties of elastic type arteries.
ADHERENCE TO 48-WEEK THERAPY WITH ATORVASTATIN AT VARIOUS DOSES IN PATIENTS WITH PREVIOUS MYOCARDIAL INFARCTION
Authors: Oleynikov Valentin , Salyamova Lyudmila , Kvasova Olga , Khromova Angelina , Fadeeva Svatlana , Burko Nadezhda 
Published: April 2021

Objective:
To study adherence to treatment with atorvastatin at various doses for 48 weeks in patients with STEMI.

Design and method:
The study included 117 STEMI patients mean age 52.1 ± 8.4 years in the first 24–96 hours from the disease onset. In accordance with the lipid-lowering therapy, the patients were divided into two groups. The first group included 39 people taking atorvastatin 40 mg/day. The second group consisted of 78 patients who received atorvastatin 80 mg/day. On 7–9th day from the STEMIt, after 24 and 48 weeks of follow-up, treatment adherence was assessed using the Morisky-Green questionnaire. In addition, compliance was determined based on the number of dispensed and returned drugs.

Results:
After 48 weeks of follow-up, pharmacotherapy was continued in the 1st group of 30 people (76.9%), in the 2nd group - 73 (93.6%) patients (p = 0.008); 9 patients (23.1%) from group 1 and 5 people (6.4%) from group 2 (p = 0.008) independently discontinued treatment.
After 48 weeks of follow-up, 17 patients (43.6%) in the 1st group were assigned to the number of compliant patients, and 39 people (50%) in the 2nd subgroup (p = 0.54). Ten patients (25.6%) in group 1 and 15 patients (19.2%) in group 2 (p = 0.39) turned out to be insufficiently adherent. There were 3 people not adhering to treatment in the 1st group (7.7%), in the 2nd group - 19 people (24.4%) (p = 0.03). In group 1, the mean score was initially 4 (4;4) points, after 24 weeks - 4 (3;4) points (p = 0.96), after 48 weeks - 4 (3;4) points (p = 0.87). In the group 2 - 4 (4;4) points, after 24 weeks - 4 (3;4) points (p = 0.99), after 48 weeks - 4 (2;4) points (p = 0.34).
According to the number of issued and returned drugs, the average amount of drugs taken in group 1 was 91.8 (79;99)%, in the 2nd group - 96.9 (82.8; 100)% (p = 0.23). The correct drug intake (>80% compliance) in group 1 was observed in 21 patients (76.7%); in group 2 - 57 (78.1%).

Conclusions:
in STEMI patients, 48-week atorvastatin treatment was characterized by good adherence and did not depend on the dose of the drug taken
STUDY OF THE ECONOMIC EFFICIENCY OF PROJECTS FOR DIGITAL TRANSFORMATION OF THE BP MONITORING MODEL
Authors: Oleynikov Valentin , Dzhazovskaya Irina , Salyamova Lyudmila , Shigotarova Ekaterina , Burko Nadezhda 
Published: April 2021

Objective:
To investigate the economic efficiency of business models for a project for BP monitoring in patients with hypertension in the context of digital transformation of medical services.

Design and method:
Applied functional, structural and business modeling of design options, methods for assessing market capacity, competition analysis, financial modeling, project sensitivity analysis, analysis of regulatory constraints.

Results:
We studied two business models - implemented in commercial medicine and in a budgetary healthcare institution. Common in the models is the patient service scheme (supplying it with a certified tonometer with a built-in GSM or Bluetooth module - measuring BP - transmitting encrypted data to the remote monitoring center - storing it in a cloud database and the patient's electronic medical record - monitoring BP indicators - doctor's response to critical deviations in measurement results — patient feedback through the messenger). The difference in models is related to the sources and form of payment. In a private clinic, it is possible to use the patient's personal funds, voluntary medical insurance schemes, compulsory medical insurance (CMI), in a budgetary healthcare institution - payment at the CMI rate. The considered options turned out to be cost-effective (NPV > 0) with a discounted payback period from 2.8 (option 1) to 3.35 years (option 2). In case of state insurance system, the time for launching a project is lengthened due to the agreeing period on the telemonitoring tariff; the methods of stimulating the medical personnel participating in the RMBP are different. The sensitivity analysis showed that the most critical factor is the tariff level for the service (the acceptable range is 4.84 -8.81 euros for the telemedicine component), investments vary in the range from 225988.7 to 293785.3 euros. IRR of the project - 38% -45%, PI - 1.6 -1.75.

Conclusions:
The use of telemedicine technologies is economically feasible in both commercial and budgetary institutions. An increase in the project's efficiency indicators is possible due to the coverage of large regions. The accumulation and analysis of big data as a result of monitoring will create conditions for the chronopharmacology of antihypertensive drugs.