[Economic evaluation of Annao Pills combined with antihypertensive drugs in treatment of primary hypertension: a study based on decision tree model].

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.

Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Mechanism and functional substances of Saiga antelope horn in treating hypertension with liver-yang hyperactivity syndrome explored using network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. MATERIALS AND METHODS: The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. RESULTS: SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. CONCLUSIONS: Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.

Enhancing the therapeutic potential of isoliensinine for hypertension through PEG-PLGA nanoparticle delivery: A comprehensive in vivo and in vitro study.

BACKGROUND: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. RESULT: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. CONCLUSION: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. SIGNIFICANCE: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

Effectiveness of herbal drug Terminalia Arjuna in chronic venous insufficiency - A prospective observational study.

INTRODUCTION: Chronic venous insufficiency (CVI) manifests in various clinical presentations ranging from asymptomatic but cosmetic problems to severe symptoms, such as lower limb edema, skin trophic changes, and ulceration. CVI substantially affects the quality of life and work productivity of the patients. Ayurveda, an ancient traditional medicine in India, evaluates the various pathological stages of CVI with a wide range of pathological conditions such as Siragranthi (venous abnormalities), Raktavaritavata (disorders of vata occluded by rakta ∼ blood), ApanaVaigunya (vitiated apanavayu), Arsha (hemorrhoids), VataRakta (rheumatism due to rakta), Kushtha (integumentary disease) and Dushta Vrana (putrefied wound) depending upon the presentations of the patient. Ayurvedic texts mention Terminalia arjuna as a potential herb for treating various conditions related to the circulatory system. The drug is an effective anti-inflammatory, anti-oxidant, and anti-hypertensive and has a definite role in improving cardiovascular hemodynamics and wound healing. These attributes suggest that the potential of Terminalia arjuna needs to be explored as a promising venoactive drug. METHODS: This prospective observational study included 25 patients (31 limbs) with CVI who were treated with Tab Terminalia arjuna (Bark extract of Terminalia arjuna in a dose of 500 mg, given twice a day) and were observed on two visits on day 30 and day 90. Follow-up was carried out for three months to evaluate post-treatment complications or adverse effects. The clinical outcome assessment was done using Venous Clinical Severity Score (VCSS), and clinical grading was performed using clinical classification (C0 - C6) of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification. RESULTS: The median VCSS score (of both limbs) during the third visit was comparatively lower than the first, with a statistically significant improvement at 0.05 level. Further, there was a substantial positive improvement in the clinical classification of CEAP among the patients in pre and post treatment phase. CONCLUSION: The prospective observational study shows that Tab Terminalia arjuna is safe and effective in CVI, reducing the symptoms like pain, edema, inflammation, pigmentation, induration and also expediting ulcer healing.

Study on material basis and anti-hypertensive metabolomics of Zhengan-Xifeng-Tang(ZXT): A comparison between ZXT decoction and granules.

High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients.

Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). AIM OF THE STUDY: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. MATERIALS AND METHODS: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. RESULTS: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. CONCLUSION: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

Acute Effects of Coffee Consumption on Blood Pressure and Endothelial Function in Individuals with Hypertension on Antihypertensive Drug Treatment: A Randomized Crossover Trial.

INTRODUCTION: Coffee is a complex brew that contains several bioactive compounds and some of them can influence blood pressure (BP) and endothelial function (EF), such as caffeine and chlorogenic acids (CGAs). AIM: This study aimed to evaluate the acute effects of coffee on BP and EF in individuals with hypertension on drug treatment who were habitual coffee consumers. METHODS: This randomized crossover trial assigned 16 adults with hypertension to receive three test beverages one week apart: caffeinated coffee (CC; 135 mg caffeine, 61 mg CGAs), decaffeinated coffee (DC; 5 mg caffeine, 68 mg CGAs), and water. BP was continuously evaluated from 15 min before to 90 min after test beverages by digital photoplethysmography. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluated EF before and at 90 min after test beverages. At the same time points, microvascular reactivity was assessed by laser speckle contrast imaging. Repeated-measures-ANOVA evaluated the effect of time, the effect of beverage, and the interaction between time and beverage (treatment effect). RESULTS: Although the intake of CC produced a significant increase in BP and a significant decrease in RHI, these changes were also observed after the intake of DC and were not significantly different from the modifications observed after the consumption of DC and water. Microvascular reactivity did not present significant changes after the 3 beverages. CONCLUSION: CC in comparison with DC and water neither promoted an acute increase in BP nor produced an improvement or deleterious effect on EF in individuals with hypertension on drug treatment who were coffee consumers.

Non-immunosuppressive treatment for IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011. OBJECTIVES: To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events. AUTHORS' CONCLUSIONS: Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.

Renin-angiotensin system mechanism underlying the effect of auricular acupuncture on blood pressure in hypertensive patients with phlegm-dampness constitution: Study protocol for a randomized controlled trial.

BACKGROUND: Phlegm-dampness constitution is a traditional Chinese medicine constitution typically associated with essential hypertension. Previous studies have demonstrated that auricular acupuncture effectively decreases blood pressure and adjusts the constitution. However, the mechanism underlying auricular acupuncture's effect is poorly understood. METHODS: A non-blinded, randomized controlled trial will be undertaken between September 2022 and May 2023. Eighty essential hypertensive patients with a phlegm-dampness constitution will be randomly allocated to one of two groups. The intervention group will receive eight weeks of auricular acupuncture and regular use of antihypertensive drugs, while the control group will only receive antihypertensive drugs. The primary outcome will be any mean differences in office systolic blood pressure. The secondary outcomes investigations will include proteins of the renin-angiotensin system, office blood pressure of different genotypes, and phlegm-dampness constitution scores. DISCUSSION: By demonstrating how auricular acupuncture affects the renin-angiotensin system, this research will offer significant new information on the mechanism underlying the action of auricular acupuncture in hypertension. Moreover, the results will provide crucial clinical information on the associations between renin-angiotensin system gene polymorphisms and the antihypertensive effects of auricular acupuncture. TRIAL REGISTRATION: Registered at the chictr.org.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as ß-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5-60%) and DPP-IV activity (25-100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4-63.2%), and antihypertensive properties through ACE inhibition (24.0-27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions.

Relationship of Blood Pressure, Health Behaviors, and New Diagnosis and Control of Hypertension in the BP-CHECK Study.

BACKGROUND: Undiagnosed hypertension and uncontrolled blood pressure (BP) are common and contribute to excess cardiovascular morbidity and mortality. We examined whether BP control, changes in BP, and patient behaviors and attitudes were associated with a new hypertension diagnosis. METHODS: We performed a post hoc analysis of 323 participants from BP-CHECK (Blood Pressure Checks for Diagnosing Hypertension), a randomized diagnostic study of BP measuring methods in adults without diagnosed hypertension with elevated BP recruited from 12 primary care clinics of an integrated health care system in Washington State during 2017 to 2019. All 323 participants returned a positive diagnostic test for hypertension based on 24-hour ambulatory BP monitoring and were followed for 6 months. We used linear regression to examine the relationships between a new hypertension diagnosis (primary independent variable) and differences in the change in study outcomes from baseline to 6-month. RESULTS: Mean age of study participants was 58.3 years (SD, 13.1), 147 (45%) were women, and 253 (80%) were of non-Hispanic White race. At 6 months, 154 of 323 (48%) participants had a new hypertension diagnosis of whom 88 achieved target BP control. Participants with a new hypertension diagnosis experienced significantly larger declines from baseline in BP (adjusted mean difference: systolic BP, -7.6 mm Hg [95% CI, -10.3 to -4.8]; diastolic BP, -3.8 mm Hg [95% CI, -5.6 to -2.0]) compared with undiagnosed peers. They were also significantly more likely to achieve BP control by 6 months compared with undiagnosed participants (adjusted relative risk, 1.5 [95% CI, 1.1 to 2.0]). At 6 months, 101 of 323 participants (31%) with a positive ambulatory BP monitoring diagnostic test remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications. CONCLUSIONS: Approximately one-third of participants with high BP on screening and ambulatory BP monitoring diagnostic testing remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications after 6 months. New strategies are needed to enhance integration of BP diagnostic testing into clinical practice. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03130257.

Affinin, Isolated from Heliopsis longipes, Induces an Antihypertensive Effect That Involves CB1 Cannabinoid Receptors and TRPA1 and TRPV1 Channel Activation.

In previous studies, we demonstrated that the ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels. However, it has not yet been demonstrated whether the EEH and affinin are capable of lowering high blood pressure. Therefore, the aim of the present study was to determine the effect of the oral administration of the EEH and affinin on the systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats and to explore the participation of cannabinoid receptors and transient receptor potential channels in the mechanism of action of this alkamide. Our results showed that the ethanolic extract of H. longipes and affinin significantly lowered systolic blood pressure and induced an improvement in endothelial function, which is associated with increased serum nitric oxide levels. Inhibition of cannabinoid type 1 receptors by rimonabant (3 mg/kg), transient receptor potential ankyrin 1 channels by HC-030031 (8 mg/kg), and transient receptor potential vanilloid 1 channels by capsazepine (5 mg/kg) significantly decreased the antihypertensive effect induced by affinin, suggesting that the blood pressure-lowering effect of this alkamide involves activation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels.

Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Antihypertensive effects of the combined extract of Sorghum bicolor, Vigna angularis, and Eleusine coracana in spontaneously hypertensive rats.

This study investigated the antihypertensive effects of the combined extract of sorghum, adzuki bean, and finger millet (SAFE) on spontaneously hypertensive rats. The rats were divided into four groups (n = 8): WKY, SHR, SAFE (500 mg/kg SAFE), and CAP (50 mg/kg captopril). SAFE significantly decreased the lean-to-fat mass ratio with no notable changes in body weight, food intake, or food efficiency ratio, and it effectively lowered both systolic and diastolic blood pressures, comparable to CAP. Moreover, it significantly reduced the cardiac mass index and alleviated cardiac fibrosis. SAFE did not induce hepatotoxicity, as indicated by the maintenance of aspartate aminotransferase and alanine aminotransferase levels in the normal range, confirming its safety. Taken together, these findings suggested that SAFE can be used as a dietary supplement for blood pressure regulation and cardiovascular disease prevention.

Xanthan gum and pectin as beverage stabilizers reduce the digestive enzyme hydrolysis of antioxidant and antihypertensive peptides obtained from a brewery byproduct.

An acidic beverage was formulated with xanthan gum (XG), pectin (P) and brewer spent grain (BSG) peptides with antioxidant and antihypertensive properties. The impact of hydrocolloids levels on peptide bioaccessibility was studied. Peptides were obtained from BSG using Purazyme and Flavourzyme enzymes. BSG peptides were fractionated by ultrafiltration (UF) and four fractions were obtained: F1 (>10 kDa), F2 (10-5 kDa), F3 (1-5 kDa), and F4 (<1 kDa). F3 showed the highest protein purity, ferulic acid content, proportion of amphipathic peptides, and bioactive properties (ABTS+ radical scavenging and ACE-I inhibitory activity). The identified peptides from F3 by tandem mass spectrometry were 138. In silico analysis showed that 26 identified peptides had ABTS+ inhibitory activity, while 59 ones presented good antihypertensive properties. The effect of XG and P levels on bioaccessibility of F3 peptides in the formulated beverages was studied by a central composite experimental design. It was observed that F3 peptides interacted with hydrocolloids by electrostatic forces at pH of formulated beverages. The addition of hydrocolloids to formulation modulated the release of the antioxidant peptides and protected the degradation of ACE-I inhibitory peptides from F3 during simulated gastrointestinal digestion. Finally, the level of hydrocolloids that produced intermediate viscosities in the formulated beverages improved the bioaccessibility of the F3 peptides.

Danhong formula alleviates endothelial dysfunction and reduces blood pressure in hypertension by regulating MicroRNA 24 - Phosphatidylinositol 3-Kinase-Serine/Threonine Kinase- Endothelial Nitric Oxide Synthase axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential hypertension (EH) is one of the important risk factors of cardio-cerebrovascular diseases, and it can significantly increase the incidence and mortality of acute myocardial infarction, cerebral infarction and hemorrhage. Danhong Formula (DHF) was consisting of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese) (Plant names have been checked with http://www.the plant list.org on June 28th, 2023) was approved by State Food and Drug Administration of China, that has been used for thousands of years in the treatment of cardiovascular diseases in China with proven safety and efficacy. Though our previous studies have found that DHF improved endothelial dysfunction (ED) and decreased high blood pressure (BP), the underlying mechanisms of its antihypertensive effect still remain unclear. AIM OF THE STUDY: This study investigated whether DHF regulated MicroRNA 24- Phosphatidylinositol 3-Kinase-Serine/Threonine Kinase- Endothelial Nitric Oxide Synthase (miR-24 - PI3K/AKT/eNOS) axis to produce antihypertensive effect and improve endothelial dysfunction. MATERIALS AND METHODS: Firstly, the chemical components of DHF were analyzed by UHPLC-MS. After that, BP was continuously monitored within the 1st, 3rd, and 4th week in SHR to evaluate the antihypertensive effect of DHF intraperitoneal injection. In addition, not only the contents of serum nitric oxide (NO), prostacyclin (PGI2), and angiotensin II (Ang II) were detected, but also the isolated aorta ring experiment was conducted to evaluate the vasomotoricity to evaluate of DHF on improving endothelial dysfunction. Key proteins or mRNA expression associated with miR-24 - PI3K/AKT/eNOS axis in aorta were detected by capillary Western blot, immunohistochemistry or RT-PCR to explore the underlying mechanisms. Index of NO, Ang II PGI2 and key proteins or mRNA expression were also conducted in miR-24-3p over-expression HUVECs model. RESULTS: Compared with SHR control group, DHF (4 mL/kg/day, 2 mL/kg/day, 1 mL/kg/day) treatment significantly reduced high BP in SHR and selectively increased acetylcholine (Ach) induced vasodilation, but not sodium nitroprusside (SNP) in a manner of concentration dependency in isolated aorta ring. DHF (4 mL/kg/day, 1 mL/kg/day) treatment was accompanying an increment of NO and PGI2, and lowering AngII in SHR. Moreover, DHF treatment significantly up-regulated expression of p-PI3K, p-AKT, mTOR, eNOS and p-eNOS, but down-regulated miR-24-3p expression in aorta. Compared with miR-24-3p over-expression HUVECs model group, DHF treatment inhibited miR- 24-3p expression and up-regulated p-PI3K, p-AKT, mTOR and eNOS mRNA expression. Similarly, DHF treatment increased PI3K, AKT, mTOR and eNOS protein expression in HUVECs by Western blot. CONCLUSIONS: These findings suggest that DHF alleviates endothelial dysfunction and reduces high BP in SHR mediated by down-regulating miR-24 via ultimately facilitating up-regulation of PI3K/AKT/eNOS axis. This current study firstly demonstrates a potential direction for antihypertensive mechanism of DHF from microRNA aspect and will promote its clinical applications.

Clinical trial design for assessing hypertension medications: are critical circadian chronopharmacological principles being taking into account?

INTRODUCTION: Clinical hypertension trials typically rely on homeostatic principles, including single time-of-day office blood pressure (BP) measurements (OBPM), rather than circadian chronopharmacological principles, including ambulatory monitoring (ABPM) done around-the-clock to derive the asleep systolic BP (SBP) mean and sleep-time relative SBP decline - jointly the strongest prognosticators of cardiovascular disease (CVD) risk and true definition of hypertension - to qualify participants and assess outcomes. AREAS COVERED: Eight chronopharmacological elements are indispensable for design and conduct of hypertension medication trials, mainly those on ingestion-time differences in effects, and also a means of rating quality of investigations. Accordingly, we highlight the findings and shortcomings of: (i) 155 such ingestion-time trials, 83.9% finding at-bedtime/evening treatment more beneficial than conventional upon-awakening/morning treatment; (ii) HOPE and ONTARGET CVD outcomes investigations assessing in the former add-on ramipril at-bedtime and in the latter telmisartan, ramipril, or both in combination in the morning; and (iii) pragmatic TIME CVD outcomes trial. EXPERT OPINION: Failure to incorporate chronopharmacological principals - including ABPM to derive asleep SBP and SBP dipping to qualify subjects as hypertensive and assess CVD risk - results in deficient study design, dubious findings, and unnecessary medical controversy at the expense of advances in patient care.

Evaluation of antihypertensive activity and molecular docking analysis of Padina boergesenii extract.

INTRODUCTION: Antihypertensive drugs that are chemically synthesized usually tend to initiate different health complications. The quest for bioactive molecules to create novel medicines has focused on Marine resources like seaweeds. These molecules can furnish a positive probability for patients to gain benefits from these natural substances. METHODS: This study aims to identify phytoconstituents present in brown seaweed-Padina boergesenii. Five different solvents were used to prepare extracts and their antioxidant activity as well as antihypertensive activity was evaluated. Phytoconstituents were identified using LC-MS/MS, and subjected to molecular interaction against ACE enzyme. RESULTS: The 70% ethanolic extract exhibited the highest total phenolic content (TPC), significant radical scavenging activity and concentration dependent Angiotensin Converting Enzyme (ACE) inhibition activity. LC-MS/MS analysis confirmed the presence of bioactive compounds from which 7,8 dihydroxycoumarin had the highest affinity against ACE enzyme in molecular docking study. CONCLUSION: These findings advocate that Padina boergesenii can be a potential source for developing novel antihypertensive therapeutic drug(s) and could pave the way for evolving effective and safe remedies from natural resources.