Brief report on a phase I/IIa study to assess the safety, tolerability, and immune response of AGMG0201 in patients with essential hypertension

We have been developing an angiotensin II vaccine for hypertension. We conducted a placebo-controlled dose escalation study to investigate the safety, tolerability, and immunological responses of this angiotensin II vaccine (AGMG0201). AGMG0201 was administered to participants with mild to moderate hypertension between 18 and 79 years of age. Twelve patients each were enrolled in the low-dose and high-dose groups. Within each group, subjects were randomly assigned to receive either the active study drug or a placebo at a ratio of 3:1. Each participant received a single intramuscular injection, followed by a second injection 30 days later, and was monitored for 360 days after the second dose. The results showed that most treatment-related adverse events were classified as mild or moderate in severity, including pain and erythema at the injection site. Anti-angiotensin II antibodies were observed in the AGMG0201 patients, especially in the high-dose group. Overall, AGMG0201 was well tolerated.

Pengaruh terapi musik klasik (mozart) terhadap tekanan darah pada lansia dengan hipertensi

The effect of classic music therapy (mozart) on blood pressure in elderly with hypertensionBackground: Based on the Health Profile of North Lampung Regency in 2018 the number of people with hypertension in the last three years increased to 600 in 2017 and in 2018 the number of sufferers was 741 sufferers.Purpose: To determine the effect of classical music therapy (Mozart) on blood pressure.Method: Quantitative research uses a quasi-experimental approach. The population was patients with hypertension at the Elderly Post health service (Posyandu) at Kalibalangan Health Center, which amounts to 80 people. A sample of 62 participants divided into 2 groups, 31 participants by music therapy + antihypertensive drug (amlodipine), and 31 other participants only take the antihypertensive drug as amlodipine. Data collection techniques by monitoring of blood pressure. The statistical test used is the Independent Test.Results:The average blood pressure of systole before being given Classical Music (Mozart) + Amlodiphine is 164.2 mmHg, diastole 102.7 mmHg. The average blood pressure of systole before being given Amlodipine is 163.5mmHg, diastole 103.9 mmHg. Average blood pressure of systole after given Classical Music (Mozart) + Amlodipine is 147.1mmHg, diastole 89.03mmHg. The mean systole blood pressure after Amlodipine is 152.3mmHg, diastole 95.2 mmHg. There are differences in systolic blood pressure in patients with moderate hypertension between the intervention groups (classical music therapy (mozart) ) and the control group (p-value = 0,000) There is a difference in diastolic blood pressure in patients with moderate hypertension between the intervention group (classical music therapy (mozart) and the control group (p value = 0.016).Conclusion: There is an influence of classical music therapy (mozart) on blood pressure, it is recommended to use the results of this study as an alternative therapy in the treatment of primary hypertension and so that it can be socialized to the communityKeywords: Classical Music Therapy (Mozart); Blood Pressure; Hypertension; ElderlyPendahuluan: Jumlah penderita hipertensi di Kabupaten Lampung Utara dalam tiga tahun terakhir mengalami peningkatan tahun 2015 sebesar 10.743 penderita tahun 2016 sebesar 13.039 penderita dan tahun 2017 sebesar 11.228 penderita. Sementara di Puskesmas Kalibalangan tahun 2015 sejumlah 604 turun menjadi 458 tahun 2016, kemudian meningkat menjadi 600 tahun 2017 dan tahun 2018 sejumlah 741 pasien, musik klasik merupakan salah satu terapi non farmakalogik yang mampu menurunkan tekanan darah.Tujuan: Diketahui pengaruh terapi music klasik (Mozart) terhadap tekanan darah pada lansia.Metode: Penelitian kuantitatif menggunakan pendekatan eksperimen semu. Populasi dalam penelitian ini adalah penderita hipertensi di Posyandu Puskesmas Kalibalangan yang berjumlah 80 orang. Sampel sebanyak 62 partisipan dibagi menjadi 2 kelompok, 31 partisipan dengan terapi musik + obat anti hipertensi (amlodipine), dan 31 partisipan lainnya hanya mengkonsumsi obat anti hipertensi sebagai amlodipine. Teknik pengumpulan data dengan mengamati tekanan darah. Uji statistik yang digunakan adalah Independent Test.Hasil: Rata-rata tekanan darah systole sebelum diberi Musik Klasik (Mozart) + Amlodiphine adalah 164.2 mmHg, diastole 102,7 mmHg, pada kelompok yang diberi Amlodipine adalah 163.5mmHg, diastole 103.9 mmHg. Rata-rata tekanan darah systole sesudah diberi Musik Klasik (Mozart) + Amlodipine adalah 147.1 mmHg, diastole 89.03 mmHg, pada kelompok yang diberi Amlodipine adalah 152.3 mmHg, diastole 95.2 mmHg. Ada perbedaan tekanan darah sistolik pada penderita hipertensi sedang antara kelompok intervensi (terapi music klasik (mozart) dan kelompok control (p-value = 0,000). Ada perbedaan tekanan darah diastolic pada penderita hipertensi sedang antara kelompok intervensi (terapi music klasik (mozart) dan kelompok control (p value =0,016).Simpulan: Ada pengaruh terapimusik klasik (Mozart) terhadap tekanan darah pada lansia, sehingga disarankan agar menggunakan hasil penelitian ini sebagai salah satu terapi alternative dalam pengobatan hipertensi primer dan agar dapat disosialisasikan kepada masyarakat.

Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep

Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.

DESCRIPTION OF HYPERTENSION LEVELS IN PRIMARY HYPERTENSION ADULTS AND ELDERLY IN KARANGBINANGUN LAMONGAN DISTRICT

Introduction: Hypertension is often a silent killer because it is often without symptoms that warn of a problem. Symptoms that appear are often considered as common disorders, so that the victim is too late to realize that the disease is coming. Hypertension is an increase in blood pressure above normal limits with systolic value of 140 mmHg and diastolic value of 90 mmHg. The purpose of this study was to determine the level of hypertension in patients with primary hypertension in Karangbinangun Lamongan District. Method: This research design using descriptive with a population of 70 respondents then sampled using simple random sampling and get a sample of 64 respondents, in accordance with the inclusion criteria, are healthy patients and willing to sign the informed consent The variable in this study is the level of hypertension. The data of this study were taken from the results of blood pressure measurements by standards WHO. The data is tabulated in the form of frequency distribution by categorizing hypertension into mild, moderate and severe. Result: The results showed that half of the respondents (50%) had mild hypertension, 28.1% moderate hypertension and 21.9% severe hypertension. Conclusion: Seeing the results of this study, that there are still many people who have hypertension, so health education by health workers and family is needed to prevent recurrence.

The place of combination of lercanidipine – enalapril in the treatment of hypertension: efficacy, safety, special features

In order to improve the effectiveness of antihypertensive treatment, doctors more often prescribe fixed dose combinations of two or three antihypertensive products. In this case, the concomitant effects of these products contribute to better control of blood pressure, improve patient’s adherence to treatment and reduce the risk of side effects. The fixed dose combination of lercanidipine and enalapril is quite new for Ukrainian physicians; however, there is already a sufficient evidence base for the efficacy and safety of such combination therapy. Lecranidipine – enalapril combination reduce systolic and diastolic blood pressure in patients with moderate hypertension without severe side effects. In addition, this combination is effective and safe in patients with comorbidities.

EVALUATION OF RENOPROTECTIVE EFFECT OF CILNIDIPINE IN PATIENTS WITH MILD TO MODERATE HYPERTENSION AND TYPE 2 DIABETES MELLITUS – A PROSPECTIVE STUDY

Objective: The objective of the study was to evaluate the renoprotective effect of cilnidipine by estimating urinary albumin and creatinine levels in mild-to-moderate hypertension (HTN) with type 2 diabetes mellitus (DM) and also evaluate the adverse drug profile of cilnidipine in the same patients. Methods: This was a single-center, prospective, open-labeled, randomized study. A total of 60 patients of either gender aged between 30 and 60 with mild-to-moderate HTN with type 2 DM were included in the study. Urine albumin and urine creatinine were measured at day 1 and day 181. Blood pressure (BP) was measured in all visits. The drug cilnidipine at a dose of 10–20 mg oral was given and the corresponding improvement in the levels of urine albumin and other parameters was identified. Results: There was a significant reduction in the mean systolic BP from 150.07±5.44 mmHg in visit 0 to 123.03±5.23 mmHg in visit 3. And also, there was a significant reduction in the mean diastolic BP from 95.5±8.15 mmHg in visit 0 to 80.8±2.42 mmHg in visit 3. The mean heart rate at visit zero was 76.71±4.86. At the end of 6 months of treatment, there was a significant reduction to 70.63±2.74. There was a significant reduction in the microalbuminuria from 66.62±8.39 to 38.8±6.45. The mean reduction was 27.56±10.25. There was no change in the creatinine level. Conclusion: The study reveals that the drug cilnidipine is safe and effective in reducing the microalbuminuria and also effectively reduces BP in hypertensive patients. Hence, the drug cilnidipine can be safely administered to the patient with diabetes and HTN.

Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia

Background In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. Methods Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. Discussion This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. Trial registration NCT02531490, registered on 24 August 2015.

Abstract 16361: Effects of Low-dose Triple Combination Therapy on Time at Target Blood Pressure - Results From the TRIUMPH Randomized Controlled Trial

Introduction: Cumulative exposure to hypertension is an adverse prognostic marker. However longitudinal assessments of blood pressure (BP), i.e. TIme at TaRgEt (TITRE), are not routinely assessed in practice. Specifically, the effect of low-dose combination anti-hypertensive therapy on TITRE has not been studied. Hypothesis: Low-dose triple combination antihypertensive medication achieves greater TITRE compared to usual care. Methods: TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients from urban hospital clinics in Sri Lanka were randomised to either once-daily low-dose triple combination polypill (20mg of telmisartan, 2.5mg of amlodipine, and 12.5mg of chlorthalidone) or standard care. This analysis compared TITRE in the intervention and usual care groups over 6 months follow-up, with TITRE defined as percentage of time at target BP. Target BP was defined as <140/90mmHg or <130/80mmHg in patients with diabetes or chronic kidney disease. Results: The trial comprised 700 patients (mean [±SD] age: 56±11 years, 58% women). Patients in the triple pill group (n=349) achieved a higher TITRE compared to those in the standard care group (n=351) at 6 months (64±32% vs 43±34%, risk difference -21%, 95%CI -26% to -6%, p<0.001). Almost twice as many patients in the triple pill group spent the majority of follow-up time at target (TITRE >50%: 64% vs 37%, p<0.001). The effect of the triple pill was seen early, with the majority achieving TITRE >50% by 12 weeks. Those on the triple pill achieved a consistently higher TITRE at all follow-up periods compared to usual care (0-6 weeks: 36±31% vs 21±28%; 6-12 weeks: 74±39% vs 46±43%; 12-24 weeks: 77±37% vs 53±44%, all p<0.001). When predictors of TITRE were examined, only triple pill therapy was predictive of TITRE >75% (odds ratio [OR] 3.41, 95%CI 2.30-5.04, p<0.001). Conclusion: Among patients with mild-moderate hypertension, treatment with a low-dose triple combination pill significantly increased time at target compared to usual care. This study also introduces TITRE as a novel outcome assessing longitudinal BP control in trials.