Treatment Of Arterial Hypertension Research Articles

SiRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model.

The aim of this study was to develop a possible treatment for pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is a rare disease characterised by a pulmonary arterial pressure greater than 20 mmHg. One of the factors that contribute to PAH is an increase in the production of endothelin-1, a polypeptide that increases vascular resistance in the pulmonary arteries, leading to increased pulmonary arterial pressure and right ventricular hypertrophy. The objective of this study was to design, synthesize, and evaluate two siRNAs directed against endothelin-1 in a rat model of PAH induced with monocrotaline. Wistar rats were administered monocrotaline (60 mg/kg) to induce a PAH model. Following two weeks of PAH evolution, the siRNAs were administered, and after two weeks, right ventricular hypertrophy was evaluated using the RV/LV+S ratio, blood pressure, weight, and relative expression of ECE-1 (Endothelin-converting enzyme-1) mRNA (messenger RNA) by RT-PCR (real-time PCR). The monocrotaline group showed an increase in the hypertrophy index and in ECE-1 mRNA, as well as a significant decrease in weight compared to the control group, while in the monocrotaline + siRNA group, a significant decrease was observed in the relative expression of ECE-1 mRNA, as well as in right ventricular hypertrophy. Based on the above information, we conclude that the administration of siRNAs directed to ECE-1 decreases the damage associated with PAH.

Treatments for pulmonary arterial hypertension: navigating through a network of choices.

Treatments for pulmonary arterial hypertension: navigating through a network of choices.

Clinical use of macitentan in the treatment of connective tissue disease-associated pulmonary arterial hypertension.

Connective tissue disease (CTD) is the second most common cause of the pulmonary arterial hypertension (PAH). Currently, clinical data concerning CTD-PAH is scarce. Our study aimed to assess the efficacy and safety of macitentan in the treatment of CTD-PAH. In this retrospective study, patients diagnosed with CTD-PAH at The First Affiliated Hospital of Soochow University from April 2020 to November 2021 were included. Of the patients, 9 were switched to macitentan monotherapy whereas 23 received initial combination therapy. The mean follow-up time was 24 weeks. Six-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography parameters before and after medication were assessed. Adverse reactions were also recorded and compared. After 24 weeks of treatment, 6MWD, NT-proBNP, systolic pulmonary artery pressure (sPAP) estimated by ultrasound, tricuspid regurgitation pressure gradient (TRPG) and tricuspid annular plane systolic excursion (TAPSE) in the macitentan monotherapy group revealed significant differences (Z=-2.67, Z=-2.67, t=6.20, t=5.60, t=-3.04, P<0.05). There were no statistically significant differences in right ventricular diameter (RVD), right atrial diameter (RAD), ascending aortic root inner diameter (AAO) and left ventricular end-diastolic diameter (LVEDd) (P>0.05). After 24 weeks of medication, the number of patients with WHO-FC grade III/IV symptoms decreased from 6 to 3, 1 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 2, 2 to 4 respectively(P<0.05). After 24 weeks of treatment, 6MWD, NT-proBNP, LVEDd, sPAP and TRPG in the macitentan combined with sildenafil treatment group revealed statistically significant differences (Z=-4.11, Z=-3.74, Z=-3.83, t=6.88, t=6.54, P<0.001). Significant differences in RVD, RAD, and TAPSE were found (t=3.46, t=3.69, t=-3.12, P<0.05). There were no statistically significant variances in AAO between the groups (P>0.05). The number of patients with WHO-FC grade III/IV symptoms decreased from 16 to 8, 5 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 1, 2 to 14 respectively (P<0.001). There were no statistically significant differences before and after treatment in 6MWD, NT-proBNP, RVD, RAD, AAO, LVEDd, sPAP, TRPG and TAPSE between the two groups (P>0.05). There were no statistically significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr) and hemoglobin (Hb) between 0 and 24 weeks (P>0.05). Exercise tolerance and cardiac function in patients with CTD-PAH were significantly improved after treatment with macitentan, which was well tolerated. Therefore, macitentan may be an effective and safe targeted drug for CTD-PAH.

Changes in Psychological Profile and Cognitive Function in Patients with Arterial Hypertension Who Have Suffered From COVID-19 Under the Influence of Treatment

Today, the issue of treatment and rehabilitation of patients with COVID-19 is extremely relevant. A disease that has shaken the medical community, even after the patient recovers, can have serious consequences for health in the future. The greatest concern in the post-covid period is caused by rather serious and long-term complications (especially in patients who have experienced a severe form of COVID-19), which include: cardiovascular (damage to the heart muscle, exacerbation and progression of hypertension), respiratory, neurological (disturbance of sensation taste and smell, sleep disorders), psychological (depression, anxiety, mood swings) outcomes. In the modern population, there is an increased level of cognitive disorders. They have multifactorial nature, in particular, one of such pathogenetic factors is arterial hypertension (AH) and its complications, the frequency of post-stroke cognitive impairment from mild to severe grade reaches 60% during the first year. On the other hand, according to observations, treatment of AH can reduce the risk of dementia development. The results of the data analysis showed a higher prevalence of cognitive impairment in patients with AH in the post-epidemic period than in patients with elevated blood pressure (BP) who did not suffer from COVID-19. The objective: to analyze the frequency of anxiety-depressive disorders and cognitive function in patients with medically controlled AH who experienced COVID-19, and to evaluate the effectiveness of additional use of a combination of L-carnitine, L-arginine and coenzyme Q10 in the post-covid period. Materials and methods. 53 patients (24 women and 29 men) with a diagnosis of AH who treated with drug antihypertensive therapy and who recovered from COVID-19, were included in a prospective single-center study. Questionnaires (MMSE, SSS-8, PHQ-9) were chosen to assess anxiety-depressive disorders and cognitive function. The study participants were divided into two groups that did not differ in age and gender. In the first group standard treatment was added with a combination of L-arginine, L-carnitine and coenzyme Q10, the patients in the second group received standard therapy. Results. An additional effect on improved BP control only when used drug therapy in a complex with a combination of L-arginine, L-carnitine and coenzyme Q10 was determined, as well as a positive effect on improved the clinical condition of patients with AH, restoration of the psychological state after a recovery from respiratory infection SARS-COV- 2. Conclusions. The patients with AH who have suffered from COVID-19 often have psychological changes and impaired cognitive function under the conditions of medical BP control. The use of a combination of L-arginine, L-carnitine and coenzyme Q10 as part of complex therapy contributed to a more effective recovery of psychological and cognitive disorders, improvement of the subjective condition of patients due to the additional positive effect on the control of BP and heart rate.

Beta-blockers and chronic kidney disease: a literature review

Chronic kidney disease (CKD) and cardiovascular diseases are widespread throughout the world and are closely related to each other. Sympathetic hyperactivity, characteristic of CKD, increases cardiovascular risk and accelerates the progression of kidney disease by activating beta-adrenergic receptors. Beta-blockers play an important role in preventing the negative effects of in creased activity of the sympathetic nervous system on the cardiovascular system and kidneys, can slow the progression of renal disease, and have proven effective in reducing overall and cardiovascular mortality and treatment of coronary heart disease, heart failure, arterial hypertension, and arrhythmias in patients with CKD. Despite this, beta-blockers are still underused in patients with CKD, especially in its later stages, including ESRD. Although there are currently no clear recommendations for the choice of any specific beta blocker in CKD, factors such as the CKD stage, presence of diabetes mellitus or reduced insulin sensitivity, and pharmacodynamics (cardioselectivity, α1-blocking- and vasodilating properties) and pharmacokinetic properties (metabolism, routes of elimination from the body, degree of binding to plasma proteins and dualizability) should be considered. At present, along with ACE inhibitors, AT1-receptor antagonists, and SGLT2 inhibitors, beta-blockers remain indispensable drugs for treating cardiovascular diseases with proven positive effects on the progression of kidney failure in patients with CKD. Their broader use in this population is expected to further reduce cardiovascular mortality and delay the initiation of renal replacement therapy.

Pulmonary arterial hypertension treatment: an individual participant data network meta-analysis.

Effective therapies that target three main signalling pathways are approved to treat pulmonary arterial hypertension (PAH). However, there are few large patient-level studies that compare the effectiveness of these pathways. The aim of this analysis was to compare the effectiveness of the treatment pathways in PAH and to assess treatment heterogeneity. A network meta-analysis was performed using individual participant data of 6811 PAH patients from 20 Phase III randomized clinical trials of therapy for PAH that were submitted to the US Food and Drug Administration. Individual drugs were grouped by the following treatment pathways: endothelin, nitric oxide, and prostacyclin pathways. The mean (±standard deviation) age of the sample was 49.2 (±15.4) years; 78.4% were female, 59.7% had idiopathic PAH, and 36.5% were on background PAH therapy. After covariate adjustment, targeting the endothelin + nitric oxide pathway {β: 43.7 m [95% confidence interval (CI): 32.9, 54.4]}, nitric oxide pathway [β: 29.4 m (95% CI: 22.6, 36.3)], endothelin pathway [β: 25.3 m (95% CI: 19.8, 30.8)], and prostacyclin pathway [oral/inhaled β: 19.1 m (95% CI: 14.2, 24.0), intravenous/subcutaneous β: 24.4 m (95% CI: 15.1, 33.7)] significantly increased 6 min walk distance at 12 or 16 weeks compared with placebo. Treatments also significantly reduced the likelihood of having clinical worsening events. There was significant heterogeneity of treatment effects by age, body mass index, hypertension, diabetes, and coronary artery disease. Drugs targeting the three traditional treatment pathways significantly improve outcomes in PAH, with significant treatment heterogeneity in patients with some comorbidities. Randomized clinical trials are warranted to identify the most effective treatment strategies in a personalized approach.

Analysis of the list of medicines for arterial hypertension therapy during pregnancy

Preserving the pregnant women health is one of the most important task in the health care system. In 2020, more than 21,000 cases of hypertensive disorders were diagnosed during pregnancy in Ukraine. Arterial hypertension during pregnancy is the main risk factor for negative consequences for the child and mother. During pregnancy, antihypertensive therapy reduces the risk of morbidity or premature birth, as well as adverse effects to the fetus/newborn.&#x0D; The purpose of the study was to analyze the list of registered antihypertensive medicines under the INN, which are presented on the domestic pharmaceutical market, and to analyze their socio-economic availability.&#x0D; Research materials and methods. Analysis of antihypertensive medicines in accordance with national recommendations for the arterial hypertension treatment during pregnancy in Ukraine; analysis of the State Register of Medicinal Products of Ukraine, the National List of Essential Medicines, the State Formulary of Medicines (15 issue). Data from the information resource «Tabletki.ua» were used to determine the pharmaceuticals prices. Methods – information search, analysis, generalization, marketing research, «minimization of cost» method, calculation of socio-economic affordability ratios – the liquidity ratio Cliq, the ratio of adequacy solvency Ca.s.&#x0D; The results of the analysis of antihypertensive medicines that are registered and have indications during pregnancy showed that the following medicines with INNs are available on the pharmaceutical market: methyldopa, nifedipine, metoprolol tartrate, esmolol, nicardipine, uradipyl, but the following INNs labetalol, hydralazine, acebutolol, mepindolol, oxprenolol are missing. It was established that the list of antihypertensive medicines used during pregnancy is represented by 33 trade names of various medicinal forms from 10 countries of the world, the specific weight of which is 69% of medicines of foreign production. There is an insufficient amount of methyldopa medicines on the domestic pharmaceutical market, as there is only one name of a foreign manufacturer.&#x0D; It was determined by the «cost minimization» method that the costs for one month of treatment when using nifedipine of a domestic manufacturer compared to a drug of a foreign manufacturer are lower by 90%. For metoprolol of the domestic manufacturer, the costs are 73% lower than for the imported drug.&#x0D; The socio-economic availability of medicines was determined using the price liquidity ratio and the solvency adequacy ratio, which indicated relatively adequate price competition and the high availability of most antihypertensive medicines for the population of Ukraine.

«Назначить нельзя не назначить»: роль β-блокаторов в современном лечении пациента с артериальной гипертонией и сопутствующими заболеваниями

The paper is focused on clarifying the role of using β-blockers in modern treatment of arterial hypertension (AH) in patients with comorbidities. Despite the fact that the majority of clinical guidelines on the treatment tactics for AH consider β-blockers as the drugs prescribed when there are certain additional indications, nowadays an attempt is made to return to the distant past of cardiology, when β-blockers played a role of first line antihypertensive drugs. The paper provides evidence-based arguments in favor of the balanced approach to prescription of β-blockers to patients with AH. At the same time, the paper presents the results of the recent analysis involving the data on the participants of the large randomized trial focused on assessing the effects of dapagliflozin in patients with heart failure and preserved left ventricular ejection fraction suggesting frequent use of β-blockers in clinical practice for patients with AH and concomitant disorders, as well as the β-blockers’ safety and probable efficacy. The paper provides the meta-analysis results allowing one to estimate antihypertensive effect of β-blockers, the use of which makes it possible to reduce systolic blood pressure by almost 8—10 mm Hg. Furthermore, the paper discusses an opportunity to quickly obtain information about the role of certain drugs for treatment of AH using ChatGPT that is considered to be a promising information technology. The paper also provides data on the use of the doses of β-blockers that are not high enough and does not allow to achieve optimal heart rate in clinical practice.

Features of antihypertensive therapy in the Russian population: data from the ESSE-RF3 study

Aim. To evaluate the usage of antihypertensive drugs (AHDs) and their combinations in participants aged 35 to74 years with arterial hypertension (AH) in the population-based study ESSE-RF3.Material and methods. Representative samples of the population aged 35 to 74 years from 15 regions of Russia (n=28731) with a response rate over 70% were examined in the ESSE-RF3 study. Therapy received by 9944 participants with AH (with systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg, or when the subject was taking AHDs) was analyzed. Information about AHDs intake (brand name of the drug) was recorded by questionnaire and coded according to International Nonproprietary Names by classes. Statistical analysis was performed using the open-source R 4.1 environment. Comparison of discrete indicators between groups was performed using Fisher’s exact test. The significance level for all tested hypotheses was taken as.05. The study was approved by the Ethics Committee of FGBI “NMRC TPM” of the Ministry of Health of the Russian Federation, each participant signed an informed consent.Results. Among the patients receiving therapy for AH, angiotensin-converting enzyme inhibitors (ACEIs) were used by 38.8% of participants, angiotensin receptor blockers (ARBs) — 31.6%, betablockers (BBs) — 29.0%, сalcium channel blockers (CCBs) — 21.5%, diuretics — 18.6%, 1.1% — outdated AHDs; 8.6% — other groups of drugs. Monotherapy was used by 53.1% of patients, 33.1% of participants received two, and 13.9% received three AHDs. Among participants taking two or more AHDs (including single-pill combinations (SPC)), males most often received the combination of BB+ ACEI and females — BB+ARBs. SPC AHDs were used by 10.3% of those receiving therapy (males: 9.8%, females: 10.6%). Among SPCs, the top three combinations were CCBs + ACEIs (28%), diuretics + ACEIs (27.5%), and diuretics + ARBs (24.4%).Conclusion. The population study ESSE-RF3, based on the survey of a representative sample of the Russian population aged 35-74 years, showed that more than a half of participants with AH receiving therapy were used the monotherapy, only every tenth of those treated received SPC. The problem of insufficient patients’ literacy was indicated — about 1% of patients received outdated AGPs. In addition, 8.6% of patients used non-AHDs for the treatment of AH. For improving the control of AH treatment, it is necessary to increase the adherence of patients to the prescribed therapy and more strict adherence of doctors to the published guidelines for AH treatment.

Treatment of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review and meta-analysis

The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.

Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study

This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8– < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC. Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8– < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results. Trial registration: NCT01342952, April 27, 2011.What is Known:•The endothelin receptor antagonist, ambrisentan, is indicated for treatment of pulmonary arterial hypertension (PAH). Previous studies have shown similar efficacy and tolerability in pediatric patients as in adults.What is New:• This open-label extension study assessed the long-term use of ambrisentan in pediatric patients (8–<18 years) with PAH, most of whom were also receiving recommended background PAH treatment. • Weight-based dosing of ambrisentan, given alone or in combination with other PAH therapies, was well tolerated with clinical improvements consistent with prior randomized study results.

Применение психотропных препаратов в соматической медицине (Обзор литературы)

In the early stages of the development of psychiatry, all new psychotropic drugs, without any exception, came to it from other areas of medicine. Examples are chlorpromazine (came from anesthesiology, where it was used for so-called potentiated anesthesia), reserpine (came from cardiology, where it was used as a treatment for arterial hypertension), lithium (came from rheumatology, where it was used to treat gout, long before John Cade), iproniazid (originally a promising anti-tuberculosis drug), methylene blue (came from parasitology, where it was used to treat malaria), sulpiride (was discovered in the process of searching for a new antiarrhythmic among procainamide analogues). Now the situation has turned 180 degrees. The arsenal of psychotropic drugs at the disposal of psychiatrists today had expanded unimaginably, compared to the 1950s. And many of these drugs, in addition to their main psychotropic activity, have a number of additional somatotropic properties that are of genuine interest to researchers from various fields of medicine. Within the framework of this article, we decided to focus not on rather banal and already widely known properties of some psychotropic drugs, such as analgesic, antiemetic, prokinetic, antipruritic or antimigraine activity, but on unexpected and sometimes surprising properties, such as their antitumor activity against some tumors of the central nervous system, their antifungal, antibacterial, antiviral activities.

The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP production via a dual mechanism differs from PDE5i, which protects cGMP from degradation by PDE5, rather than increasing its production. sGC stimulators may therefore have the potential to increase cGMP levels under conditions of NO depletion that could limit the effectiveness of PDE5i. Such differences in mode of action between sGC stimulators and PDE5i could lead to differences in treatment efficacy between the classes. In addition to vascular effects, sGC stimulators have the potential to reduce inflammation, angiogenesis, fibrosis and right ventricular hypertrophy and remodelling. In this review we describe the evolution of treatments targeting the NO-sGC-cGMP pathway, with a focus on PH.

Possibilities of Using the National Electronic Data Syetstem in Assessing the Control of Arterial Hypertension at The Primary Health Care Level in the Kyrgyz Republic Using the Example of a Single Family Medicine Center.

To determine the capabilities of the National Electronic System for collecting quantitative data necessary to assess the quality of management and effectiveness of arterial hypertension (AH) control at the primary health care (PHC) level and to develop indicators and possibilities of their use for a standardized report on the quality of AH management and control at the PHC level in the Kyrgyz Republic. Data from electronic outpatient records were processed for all registered patients of a pilot family medicine center (FMC) that was selected randomly. The registered patient group consisted of 91,226 people older than 18 years, including 37,740 men and 53,486 women. The data obtained during contact with a patient was entered by the family doctor into the electronic outpatient record and automatically forwarded to the center that collected and aggregated the data. To monitor AH control, 11 indicators were developed and evaluated. The indicators were divided into 3 groups: indicators for identifying AH, indicators for the quality of AH patient management, and indicators for the effectiveness of AH control. In total, 26,206 patients (7,933 men and 18,273 women) visited the FMC during a year, and blood pressure (BP) was measured in 71.4% of them. In 2022, 5,072 patients (5.6% of the registered group) visited the FMC for AH, including 1,539 men and 3,533 women (4.1 and 6.6% of the registered patient group, respectively; p&lt;0.001). The proportion of patients with AH who, according to the clinical protocol, had their BP measured 2 times a year or more, was 81.4% and was slightly higher for women than for men (82.3% and 79.1%, respectively; p&lt;0.01). 38.7% of AH patients received antihypertensive drugs. Lipid-lowering therapy was prescribed to 23.5% of AH patients. The proportion of AH patients taking acetylsalicylic acid was higher, 36.3% for the whole group, including 34.1% for men and 37.2% for women (p&lt;0.05). The efficacy of AH treatment was 62.8%. Any monitoring system has limitations for the amount of useful data that can be obtained ensuring their proper quality. Taking this into account, two major indicators are suggested to use for evaluating the effectiveness of AH control at the PHC level: 1) the number of AH patients who have achieved the BP goal; 2) the number of AH patients who visited a medical institution (health care facility) during a calendar year relative to the number of registered patients (AH detectability).

Evaluation of the Molecular Mechanism of Chlorogenic Acid in the Treatment of Pulmonary Arterial Hypertension Based on Analysis Network Pharmacology and Molecular Docking

Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by increased pressure in the pulmonary arteries, which can lead to heart failure and death. Chlorogenic acid (CGA) is a natural compound present in several foods and medicinal plants and has been described to exert a therapeutic effect in various diseases. However, its potential therapeutic effect on PAH remains undeciphered. In this study, the potential of CGA for the treatment of PAH was investigated using network pharmacology analysis and molecular docking. Methods: Potential CGA targets were obtained from the SwissTargetPrediction and GeneCards databases. Moreover, potential PAH targets were collected from the GeneCards and DisGNET databases. Then, common targets were selected, and a protein-protein network (PPI) was constructed between common CGA and PAH targets using the STRING database. The common hub targets were selected, and GO enrichment analysis was performed via KEGG using the DAVID 6.8 database. Additionally, molecular docking analysis was performed to investigate the interaction between CGA and these potential therapeutic targets. Results: We obtained 168 potential targets for CGA and 5779 potential targets associated with PAH. Among them, 133 were common to both CGA and PAH. The main hub targets identified through PPI network analysis were TP53, HIF1A, CASP3, IL1B, JUN, MMP9, CCL2, VEGFA, SRC, IKBKB, MMP2, CASP8, NOS3, MMP1, and CASP1. KEGG pathway analysis showed that these hub targets are associated with pathways such as lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. In addition, the molecular docking results showed a high binding affinity between CGA and the 15 hub PAH-associated targets, further supporting its therapeutic potential. Conclusions: This study provides preliminary evidence on the underlying molecular mechanism of CGA in the treatment of PAH. The findings suggest that CGA could be a promising option for the development of new PAH drugs.

Modelling and Docking studies of Endothelin receptors ( PAH Inducing proteins) with Bosenten Monohydrate

Pulmonary arterial hypertension (PAH) is a serious disease of pulmonary arteries. When Pulmonary Arterial Hypertension (PAH) develops, blood flow through the pulmonary arteries is restricted and the right side of the heart is put under increasing strain to pump blood through to the lungs. The different changes in the blood vessels raise the pressure and increase the resistance to blood flow through the lungs, making it harder for the heart to pump blood through the lungs. Over time, due to the additional strain, the heart begins to work less effectively and eventually, the right heart can fail (this is known as 'right ventricular failure'). Pulmonary arterial hypertension (PAH) is relatively rare. It is estimated that there are about 30-50 people with PAH for every million of the population. While Pulmonary Arterial Hypertension (PAH) can occur at any age, it is more common in women in their childbearing years and the average age of diagnosis is 36. The exact cause of pulmonary arterial hypertension (PAH) remains unknown. In recent years research has focused particularly on the role of three specific substances that are produced in these cells: prostacyclin, nitric oxide and endothelin. These three agents work together to help the blood to flow smoothly through the heart and lungs and it is thought that an imbalance in levels of one or more of these substances contributes to the development of conditions such as Pulmonary Arterial Hypertension (PAH). This leads to the progressive changes in the vessels and the subsequent rise in pressure. This area of research has led to the development of specific treatments for Pulmonary Arterial Hypertension (PAH).

Liver injury due to endothelin receptor antagonists: a real-world study based on post-marketing drug monitoring data.

Liver injury is the hallmark adverse reaction of endothelin receptor antagonist (ERA). Since the first drug, bosentan has been widely used in clinical practice, hepatotoxicity has been accompanied by the history of ERA. The new ERA has been proven to have a lower liver risk but the current research findings are inconsistent. ERA-based targeted drug combinations are commonly used in the treatment of pulmonary arterial hypertension, where the risk of liver injury is difficult to estimate. This study aimed to compare the correlation between ERA and different ERA combination regimens with liver injury in the real world. This is a retrospective study using data from the Adverse Event Reporting System (Food and Drug Administration AERS, FAERS). The study used proportional imbalance and Bayesian analysis to mine FAERS data from January 2004 to December 2022 to determine the association of three ERAs with liver injury and to further mine the risk of liver injury due to the combination of ERAs with other targeted drugs. In addition, we analyzed the onset time, mortality, and hospitalization rate of liver injury caused by different ERA combination regimens. We screened out 3581 ERA-related liver injury events, of which bosentan (59.82%) had the largest number of cases. The patients with liver injury were mainly female (60.63%), and the age was concentrated between 61 and 75 years (26.75%). According to different signal mining methods, reporting odds ratio (ROR; 3.38, 95% confidence interval = 3.23-3.53), proportional reporting ratio (PRR; 3.22, χ2 = 37.84), Bayesian confidence propagation neural network (BCPNN; 1.68, 95% confidence interval = 1.61), multi-item gamma Poisson shrinker (MGPS; 3.21, 95% confidence interval = 3.09), bosentan had the strongest association with liver injury compared to ambrisentan and macitentan. Furthermore, bosentan + sildenafil [ROR (2.52, 95% confidence interval = 2.23-2.84), PRR (2.44, χ2 = 15.92), BCPNN (1.29, 95% confidence interval = 1.14), MGPS (2.44, 95% confidence interval = 2.21)], bosentan + epoprostenol [ROR (5.39, 95% confidence interval = 4.29-6.77), PRR (4.94, χ2 = 65.18), BCPNN (2.30, 95% confidence interval = 1.83), MGPS (4.94, 95% confidence interval = 4.08)], bosentan + iloprost [ROR (2.70, 95% confidence interval = 2.11-3.45), PRR (2.61, χ2 = 31.03), BCPNN (1.38, 95% confidence interval = 1.08), MGPS (2.61, 95% confidence interval = 2.12)] had a higher risk of liver injury caused by the three ERA combination regimens. The median time to onset of hepatotoxicity associated with all ERA combination regimens was 259 days (interquartile range: 58-716.5 days). Finally, the hospitalization rate for patients experiencing hepatotoxicity with ERA combination regimens was 47.86% and the mortality rate was 12.67%. By mining the FAERS, we analyzed and compared the risk of liver injury related to different ERA and ERA combination regimens, and the onset time and adverse reaction outcomes of all ERA combination regimens. According to the results of the study, bosentan had the highest risk of liver injury and the combination regimens bosentan + sildenafil, bosentan + epoprostenol, and bosentan + iloprost had a stronger risk of liver injury. From the early stages of treatment, we need to regularly monitor the liver function of patients, especially for females and the elderly, and discontinue the suspected drug as soon as the liver injury occurs.

Sotatercept for Pulmonary Arterial Hypertension in the Inpatient Setting.

Patients with pulmonary arterial hypertension (PAH) who are admitted to the hospital pose a challenge to the multidisciplinary healthcare team due to the complexity of the pathophysiology of their disease state and PAH-specific medication considerations. Pulmonary arterial hypertension is a progressive disease that may lead to death as a result of right ventricular (RV) failure. During acute on chronic RV failure it is critical to decrease the pulmonary vascular resistance with the goal of improving RV function and prognosis; therefore, aggressive PAH-treatment based on disease risk stratification is essential. Pulmonary arterial hypertension treatment for acute on chronic RV failure can be impacted by end-organ damage, hemodynamic instability, drug interactions, and PAH medications dosage and delivery. Sotatercept, a first in class activin signaling inhibitor that works on the bone morphogenetic protein/activin pathway is on track for Food and Drug Administration approval for the treatment of PAH based on results of recent trials in where the medication led to clinical and hemodynamic improvements, even when added to traditional PAH-specific therapies. The purpose of this review is to highlight important considerations when starting or continuing sotatercept in patients admitted to the hospital with PAH.

Factors associated with adherence to antihypertensive agents in the older adult

Introduction: With aging, there is an increased risk of suffering from different chronic diseases, including high blood pressure. Hypertension management must be carried out by health professionals, whether or not treatment involves medication. By controlling drug treatment, especially adherence, serious health problems for older people can be avoided. Objective: To determine the factors associated with adherence to arterial hypertension treatment in older adults who live at home. Materials and Methods: A quantitative and cross-sectional study was conducted in La Libertad Region, Peru, with 342 older adults living at home. For data collection, a sociodemographic profile form, anthropometric measurements, blood pressure measurements, the Mini-mental State Examination (MMSE) test, the Geriatric Depression Scale (GDS), and the Morisky Green Levine (MGL) adherence scale were used. In addition, descriptive and analytical statistics were used. Result: 57.60% of the participants did not adhere to the pharmacological treatment, and, in most of the sociodemographic variables examined, they did not adhere to pharmacological treatment in most cases. Likewise, a relationship between retirement in older adults and the MGL adherence scale score was identified. The study showed evidence linking treatment adherence and age (p=0.01), retirement status (p=0.05), and history of stroke (p=0.004). Discussion: Treatment adherence depends on sociodemographic and health factors for disease control and a healthy lifestyle. Conclusion: Older adults and their caregivers need guidance and education to improve adherence to pharmacological treatments.

Complications of arterial hypertension

Complications of arterial hypertension (AH), beginning to show a direct relationship with the level of blood pressure 145/95 mm Hg. Art., for many decades are the leading cause of death among all causes of death. Arterial hypertension, without a doubt, is the leading medical and social problem of our time, the role of which in mortality and disability of people continues to grow, despite the great attention paid to this problem by the scientific community, practitioners and authorities. Against the backdrop of growing knowledge and progress in the field of pharmacology and therapy of hypertension, the frequency of achieving target blood pressure today in the United States and European countries has stabilized by 25-34%, in Russia in the 1990s. was - in men 5.7%, in women - 17.5%, decreasing with age[2]. According to the National Guidelines for the Prevention, Diagnosis and Treatment of Arterial Hypertension (draft) in Russia in 2006, this indicator slightly improved (21.5%)[2, 4]. Apparently, it is within these limits that one can speak of the limit of population possibilities of the unconditionally dominant drug therapy of hypertensive conditions today.