Antihypertensive Research Articles

Cardiovascular effects of BRAF and MEK inhibitors in patients with melanoma: a prospective study incorporating risk scores, cardiac biomarkers and cardiovascular magnetic resonance imaging

Abstract Background BRAF and MEK inhibitors have revolutionised treatment for patients with BRAF-mutated melanoma. Unfortunately, they are associated with cardiovascular adverse effects including hypertension and cancer-therapy related cardiac dysfunction (CTRCD). The ‘real world’ incidence and risk factors for these adverse effects are poorly described. Purpose To characterise the incidence and risk factors for BRAF and MEK inhibitor-associated hypertension and CTRCD in a prospective ‘real world’ setting. Methods Prospective, observational, cohort study of patients with melanoma treated with BRAF and MEK inhibitors at a regional cancer hospital network (March 2021 - May 2023). Comprehensive assessment was performed at baseline, 4, 12 and 24 weeks following start of treatment, including home and clinic blood pressure assessment, serial echocardiography, stress-perfusion cardiovascular magnetic resonance imaging (CMR) and humoral biomarkers (Figure 1). CTRCD was defined as mild, moderate or severe in line with International Cardio-Oncology Society (IC-OS) definitions. Hypertension was defined as 7 day average home blood pressure of ≥135/85 mmHg or the initiation or escalation of anti-hypertensive therapy. Baseline cardiotoxicity risk stratification was performed using the ESC Cardio-Oncology guideline-recommended tool. Results 61 participants were enrolled. 48% developed BRAF/MEK inhibitor associated hypertension. 46% of participants developed CTRCD and, of these, 24 (86%) were classified as mild, 3 (11%) moderate and 1 (3%) severe. Left ventricular ejection fraction (LVEF) during follow up is shown in Figure 2. All participants with moderate and severe CTRCD also had BRAF/MEK inhibitor associated hypertension. After stratification with the baseline risk assessment tool, no patient in the ‘low risk’ group developed moderate or severe CTRCD. Baseline elevated NT-proBNP (>125pg/mL), history of left ventricular systolic dysfunction and atrial fibrillation were associated with the development of CTRCD. 20 participants underwent stress perfusion CMR at baseline, 4 and 24 weeks. 25% had a drop in LVEF to <50% but only 5% had a co-existing LVEF ≥10% from baseline to fulfil criteria for the diagnosis of moderate CTRCD. Conclusion BRAF and MEK inhibitor-associated hypertension and CTRCD is common, with a higher incidence in this ‘real world’ prospective cohort than observed in clinical trials. The majority of CTRCD was ‘mild’ and the long term sequalae of this remains unknown. No patients considered to be at low baseline risk for CTRCD using the ESC-recommended risk stratification tool developed moderate or severe CTRCD. These findings support the use of routine blood pressure surveillance in this group as well as baseline risk stratification to guide appropriate imaging surveillance of cardiac function.Figure 1.Schedule of study visitsFigure 2.LV function/CTRCD over time

Invasive validation of central blood pressure measurements using a suprasystolic monitor

Abstract Interest in the assessment of Central Blood Pressure (cBP) is steadily growing since it is a better predictor of myocardial infarction, stroke, or death than Peripheral Blood Pressure (pBP). However, pBP remains the first line for the diagnosis of hypertension (HTN) due to the ease and speed of the measurement. We sought to validate a new method to estimate cBP from brachial sphygmomanometer measurements. We estimated cBP using a sphygmomanometer that can record, after conventional pBP measurements, the pressure in the cuff maintained at a constant suprasystolic pressure. cBP is calculated using a method based on applying a physics-based model of the left subclavian artery to the brachial arterial branch to the suprasystolic brachial artery pressure waveforms. We compared this noninvasive estimated cBP to an invasive gold-standard measurement during cardiac catheterization. After clinically indicated cardiac catheterization requiring a haemodynamic assessment of a moderate coronary artery stenosis by Fractional Flow Reserve (FFR), the wire that incorporates a high fidelity electronic pressure transducer was positioned into the guiding catheter left in the ascending aorta. Simultaneous measurements were performed with a cuff placed on the patient's left arm. The output signals were recorded in a custom-based acquisition system. The comparison was obtained on the same 10 seconds recorded by the cuff and the pressure wire. The goal will be to reach 85 patients as recommended by the ARTERY Society Task Force. It recommends as an accuracy criterion to achieve a mean difference ≤ 5 mmHg with a standard deviation (SD) ≤ 8 mmHg, which are the standards adopted for this study. Patients with aortic stenosis, atrial fibrillation, or frequent (supra)ventricular extrasystoles were excluded. A total of 197 pairs of measured-estimated cBP were analysed in 78 patients with a mean age of 63 ± 8 yo, 75% of whom were men, 70% had hypertension, 26% fdiabetes, 93% dyslipidemia, 41% were tobacco users and 14% suffered from clinical peripheral artery diseases without history of revascularization. The median (InterQuartiles 25-75%) pBP was 123 [112 134] / 70 [64 77] mmHg. Measured cBP was 102 [92 11] / 78 [70 84] mmHg with a central augmentation index of 34 [23 44] %. The mean difference between estimated and measured systolic cBP was 4.9 ± 6.5 mmHg, while it was -3.9 ± 5.8 mmHg for diastolic cBP, meeting the prespecified accuracy criteria. In conclusion, our approach based on an exact matching and comparison of non-invasive suprasystolic arm cuff measurements and high-fidelity aortic BP validates that an estimation of central aortic blood pressure that can be easily carried out in daily practice and might improve HTN management. It remains to be demonstrated that more cardiovascular complications will be avoided by guiding the antihypertensive therapy with cBP instead of pBP measurements.Bland-Altman of estimated - measured cBP

Chronopharmacotherapy and correction of central pressure in the aorta, structural and functional state of the left ventricular in patients with arterial hypertension and ischemic stroke

Objective. To evaluate the dynamics of central aortic pressure and the cardioprotective effect of antihypertensive chronopharmacotherapy in patients with arterial hypertension (AH) and ischemic stroke. Materials and methods. The study included 119 patients with AH who has suffered an ischemic stroke; patients were randomized in 2 groups depending on the chronopharmacotherapy option: group 1 (n = 60) – patients who received indapamide retard 1.5 mg and valsartan 160 mg in the morning; group 2 (n = 59) – indapamide retard 1.5 mg in the morning and valsartan 80 mg each in the morning and before bedtime. After 2 months of pharmacotherapy, the achievement of the target level of blood pressure was assessed. In group 1, blood pressure was recorded in 47 (78.3 %), in group 2 – in 56 (94.9 %) patients (p < 0.05). The rest of the respondents, who did not reach the blood pressure target, underwent correction of antihypertensive therapy and were excluded from further follow-up. Accordingly, further follow-up was carried out in 47 patients of group 1 (group 1a) and 56 patients of group 2 (group 2a). Initially and after 12 months of therapy, echocardiography parameters ("ALOKA SSD 2500", Japan), as well as daily blood pressure monitoring with determination of central aortic pressure (Peter Telegin LLC BPLabVasotens, Russia) were performed. The results of the study were processed using the Statistica 12.0 program (StatSoftInc, USA). Results. At the time of inclusion in the study, the main parameters of the central aortic pressure and echocardiography parameters in both groups of patients were equivalent. After 12 months a statistically more significant decrease in the main parameters of the central aortic pressure (average daily systolic and diastolic pressure in the aorta, pulse pressure in the aorta, augmentation index in the aorta, amplification of pulse pressure, duration of the expulsion period, subendocardial blood flow efficiency index), as well as echocardiography indicators was recorded in group 2a (end-systolic and end-diastolic dimensions, thickness of the interventricular septum, thickness of the posterior wall of the left ventricular myocardium, left ventricular myocardial mass, left ventricular myocardial mass index and ejection fraction) (p < 0.05). The left ventricular myocardial geometry normalized during therapy was recorded significantly more often in group 2a than in group 1a (p < 0.05). Conclusion. Two times a day intake of valsartan with thiazidelike diuretic in the morning facilitated more significant improvement of central aortic pressure, echocardiography parameters and as well as an improvement in the geometry of the left ventricular myocardium comparing to just morning intake.

A Case of Moyamoya Disease With Spontaneous Regression of Posterior Choroidal Artery Aneurysm After Improvement in Obesity and Administration of an Antihypertensive Drug

A Case of Moyamoya Disease With Spontaneous Regression of Posterior Choroidal Artery Aneurysm After Improvement in Obesity and Administration of an Antihypertensive Drug

Self-Guided Blood Pressure Screening in the Community, Opportunities, and Challenges.

Community-based health check kiosks provide opportunities to improve the detection and long-term monitoring of hypertension. We describe the sociodemographic and cardiovascular characteristics of first-time and repeat users of these kiosks. This was an observational study. Deidentified data collected from 430 SiSU Health consumer-facing health check stations in pharmacies across Australia between January 2018 and November 2020 were analyzed. Using a logistic regression, we identified factors associated with repeat checks in the overall cohort and in those with possible hypertension presented as adjusted odds ratios (aOR) and 95% CIs. A total of 982 122 unique checks were conducted; 54% (n=530 139) of the health check users were female, and the average age of all users was 38.2 (SD, 16.0) years. Notably, 13% used the kiosks more than once. Overall, 22% met the definition of possible hypertension, 16% (n=136 345) had blood pressure (BP) ≥140/90 mm Hg, 4% (n=34 349) had BP >160/100 mm Hg, and 13% (121 282) reported taking BP medicines. In the adjusted analysis, first-time users who were aged 50 to 69 years (aOR, 0.91 [95% CI, 0.87-0.96]) or ≥70 years (aOR, 0.68 [95% CI, 0.62-0.74]) were less likely than young users (18-29 years) to return for a second health check. Those in very remote areas were 61% (aOR, 0.39 [95% CI, 0.19-0.72]), and smokers were 13% less likely to return (aOR, 0.87 [95% CI, 0.83-0.91]). People taking BP medications were more likely to return (aOR, 1.16 [95% CI, 1.09-1.22]). Community-based health checks may identify people with high BP and could provide an option for self-monitoring. Broader implementation is needed to increase the reach in rural areas and among the elderly population.

Increased Body Mass Index is Independently Associated with Chronic Kidney Disease among People with Type 2 Diabetes

Background The alarming increase in the prevalence of obesity has implications for chronic kidney disease (CKD) progression in type 2 diabetes (T2D). This study aimed to assess if increased body mass index (BMI) can be an independent risk factor for CKD and T2D in the Indian context. Materials and Methods In this cross-sectional study, 602 (M:F = 378:224) participants were screened using Kidney Disease Improving Global Outcomes (KDIGO) from January to October 2023 in Chennai. Demographic, anthropometric, biochemical, clinical details, and comorbidities were recorded. T2D with CKD low risk was taken as control group, and CKD moderate and high risks were the study groups. BMI was classified based on the Asian criteria into normal (18.5–22.9), overweight (23–24.9), and obese (≥25 kg/m2). Results Majority of participants in moderate and high risk categories were obese compared to the low risk category (60.5% and 66.4% vs. 39.1%; p < 0.001). A higher proportion of participants was on antihypertensive drugs in the high risk group and in the obese category (p < 0.001). Comorbidities and diabetic complications were higher in the high risk group (p < 0.001). Multivariate logistic regression revealed that age of ≥ 60 years [OR(95% CI); 6.3(2.2–18); p = 0.009]; increased BMI as overweight [3.6(2.1–6.3); p < 0.001] and obese [5.2(3.3–8.3); p < 0.001]; smoking [4.2(1.7–10.2); p = 0.002]; increased duration of diabetes of 5–15 years [2.3(1.2–4.5); p = 0.013], 16–25 years [4.8(2.2–10.4); p < 0.001], and >25 years [4.2(1.4–13); p = 0.011]; systolic blood pressure [1.01(1.0–1.03); p = 0.02]; and hemoglobin A1c [1.2(1.1–1.3); p < 0.001] were independent risk factors for the progression of CKD. Conclusion Increased BMI was independently associated with CKD in T2D. Overweight and obese individuals are four to five times at risk for CKD progression. Early identification, lifestyle intervention, and weight-lowering drugs may reduce the complications of obesity in T2D and CKD.

Exploring the Chemopreventive Effect of Medication on Gene Expression Linked to Colorectal Cancer: An Observational and Mendelian Randomization Analysis in Healthy Colon Mucosa

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies. Our study aimed to investigate the influence of common medication intake and modifiable risk factors on FE gene expression using a colonic mucosa sample dataset of healthy individuals (BarcUVa-Seq). We applied expression enrichment analysis of the FE genes for each studied medication and factor. Both observational and instrumental (Mendelian randomization) analysis were conducted, and the results were validated using independent datasets. The findings from the observational and instrumental analyses consistently showed that medication intake, especially metformin, considerably downregulated the FE genes. Chemopreventive effects were also noted for antihypertensive drugs targeting the renin–angiotensin system. Conversely, benzodiazepines usage might upregulate FE genes, thus fostering a tumor-promoting microenvironment. In contrast, the findings from the observational and instrumental analyses on modifiable risk factors showed some discrepancies. The instrumental results indicated that obesity and smoking might promote a tumor-favorable microenvironment. These findings offer insights into the biological mechanisms through which risk factors might influence CRC development and highlight the potential chemopreventive roles of metformin and antihypertensive drugs in CRC risk.

Long-term safety and efficacy of endovascular ultrasound renal denervation in resistant hypertension: 8-year results from the ACHIEVE study.

Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2months. Beyond 3years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN. This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24h ambulatory SBP ≥130mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m2 undergoing uRDN. The primary efficacy outcome was 24h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting. A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6-8.9]years. Mean age was 62.6±9.3years (37.0% female). Preprocedural 24h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3-7.0]. At 8years after uRDN, the change in 24h ambulatory SBP was -19.5 [95%CI -26.7,-12.4] mmHg (p<0.001). The 8-year change in the number of DDDs was -1.7 [-2.8,-0.6] (p = 0.003). The 8-year decline in eGFR was -8.9 [-13.2,-4.7] ml/min/1.73m2 (p<0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0-8.0]years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected. A significant BP reduction was observed up until 8years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events.

Pediatric Orally Disintegrating Tablets (ODTs) with Enhanced Palatability Based on Propranolol HCl Coground with Hydroxypropyl-β-Cyclodextrin

Background: Propranolol, largely prescribed as an antihypertensive and antiarrhythmic drug in pediatrics, is characterized by a bitter taste and an astringent aftertaste. Currently, the therapy requires crushing of tablets for adults and their dispersion in water many times a day, leading to loss of dosing accuracy, low palatability, and poor compliance for both patients and caregivers. Objectives: This work aimed to exploit cyclodextrin complexation by cogrinding to develop orally disintegrating tablets (ODTs) endowed with reliable dosing accuracy, good palatability and safety, ease of swallowability, and ultimately better compliance for both pediatric patients and caregivers. Results: Different formulation variables and process parameters were evaluated in preparing ODTs. The technological and morphological characterization and disintegration tests were performed according to official and alternative tests to select the ODT formulation based on the drug Hydroxypropyl-β-cyclodextrin (HPβCD) coground complex form containing Pearlitol® Flash as the diluent and 8% Explotab® as the superdisintegrant, which demonstrated the highest % drug dissolution in simulated saliva and acceptable in vitro palatability assessed by the electronic tongue, confirming the good taste-masking power of HPβCD towards propranolol. Conclusions: Such a new dosage form of propranolol could represent a valid alternative to the common extemporaneous preparations, overcoming the lack of solid formulations of propranolol intended for pediatric use.

Medication Adherence, Blood Pressure Control, Knowledge, Self-care and Self-efficacy among Tunisian Hypertensive Patients

Objectives The aim of this study was to investigate the associated factors with adherence to antihypertensive therapy and to explore the association between medication adherence, blood pressure control, knowledge about hypertension (HTN), self-care, and self-efficacy in hypertensive patients. Methods A cross-sectional study was conducted among 750 hypertensive patients in Tunisia. The data collection tool was a 5-section questionnaire including an information sheet, the Girerd medication adherence scale, the HTN Knowledge Level Scale (HK-LS), the Self-care of HTN Inventory (SC-HI), and the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEM6S). Results A low and moderate level of medication adherence has been observed in 83.2% of the participants. Uncontrolled blood pressure was detected in 73.1% of cases. Only 11.5% have a good level of knowledge about HTN. Concerning Self-care practices, 48.8% of patients have inadequate practices of maintenance, 48.8% have inadequate practices of monitoring, and 83.9% have inadequate practices of management. The self-efficacy for managing HTN was weak in 42.1% of the participants. In multivariate analysis, low medication adherence was associated with the number of antihypertensive pills/day (ORa=2.668; CI95%= (1.447- 4.918) if ≥ 4 pills/day), side effects (ORa=1.834; CI95%= (1.263- 2.665); p=0.001), uncontrolled hypertension (ORa=2.74; CI95%= (1.798- 4.18); p&lt;0.0001), insufficient self-efficacy for managing HTN (ORa=1.773; CI95%=(1.252- 2.512); p&lt;0.0001), and insufficient self-care maintenance (ORa=2.220; CI95%=(1.562- 3.1570); p&lt;0.0001). Conclusion Low medication adherence was associated with uncontrolled blood pressure, more anti-hypertensive pills, side effects, lower self-efficacy, and lower self-care maintenance. Nursing interventions improving the management skills of hypertensive patients may be beneficial in controlling the disease and its subsequent consequences.

Hypertension prevalence among the male population aged 35-74 years in Novosibirsk

Aim. To study the prevalence and risk factors of hypertension (HTN), structure and effectiveness of treatment coverage, as well as disease control indicators among the male population aged 35-74 years in Novosibirsk.Material and methods. This cross-sectional study of the Novosibirsk population was conducted in 2021-2023 at the Research Institute for Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics according to the ESSE-RF3 study protocol. A total of 1200 people aged 35-74 years living in Novosibirsk were examined. The analysis included 600 men. The response rate exceeded 70%. HTN was considered detected in systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or in patients taking antihypertensive agents. Awareness was estimated as the proportion of individuals who had previously been informed by a physician about HTN. Treatment effectiveness was considered the proportion of individuals who achieved target BP values while taking antihypertensive therapy. Hypertension control was considered the proportion of individuals who achieved target values among all those examined with HTN. Statistical processing was performed using the SPSS software package (version 13.0). Associations were assessed using multiple logistic regression analysis. The critical significance level of the null hypothesis (p) was 0,05.Results. The medians of systolic and diastolic BP among men in No­vo­sibirsk were 136,0 [126,5; 149,5] and 89,0 [82,0; 95,5] mm Hg, respectively. The prevalence of HTN among men aged 35-74 in Novo­sibirsk was 68,9%, while 81,1% of men in Novosibirsk were aware of HTN. Among men with HTN, 54,7% take antihypertensive agents. The effectiveness of treatment among men in Novosibirsk is 32,3%, while 19,6% of men control the disease. The odds of hypertension occurrence in men with hypertriglyceridemia increased by 3,5 times, with abdominal obesity — by 2 times, with an positive family history for cardiovascular diseases — by 1,6 times, and with each year of life increased by 1,1 times.Conclusion. The prevalence of HTN among men in Novosibirsk is higher in comparison with the average Russian level. Significant risk factors for HTN include abdominal obesity, hypertriglyceridemia, and decreased physical activity. While awareness, treatment coverage, and HTN control among men aged 35-74 in Novosibirsk correspond to Russian trends, treatment effectiveness turned out to be slightly lower than in the Russian population.

Nitrogen Oxide (NO) in the Pathogenesis of Preeclampsia.

The concentrations of nitric oxide (NO) donors in the plasma of pregnant women with preeclampsia is several times higher than in healthy pregnant women. Antihypertensive drugs acting not through the NO-mediated mechanisms normalized BP in some women with preeclampsia, but did not significantly reduce the levels of NO donors in the plasma. It appears that preeclampsia is associated with insufficient NO availability for the targets, rather than low intensity of NO synthesis. The concentration of NO donor molecules in the plasma can therefore be a useful additional diagnostic marker of preeclampsia.

Pharmacovigilance monitoring and treatment adherence in patients on antihypertensive drugs at a tertiary care centre.

Hypertension is one of the main factors contributing to the global burden of non-communicable diseases. Previous research has revealed that stress, bad lifestyle choices and a lack of knowledge about the disease are the main causes of hypertension that can be controlled. The key cause behind the prevalence of the condition is the lack of medication adherence by patients. This study aims to evaluate medication adherence in patients with hypertension through the Morisky Medication Adherence Scale (MMAS) and to observe any adverse drug reaction leading to non-adherence of medications. A descriptive, cross-sectional study was conducted on 124 patients who attended the outpatient department of medicine. The descriptive tools were MMAS and causality scales for adverse drug reactions. The mean MMAS score was 5.20±1.29. Amongst the demographic profile, age, sex, comorbidities and duration of disease were significantly associated with decreased mean MMAS scores. Forty-two patients experienced drug reactions and only four patients were adherent to their medications. Our study suggests that patients were poorly adherent to their medications. Effective interventions should be considered to improve adherence in patients. Monitoring for adverse drug reactions can lead to improved patient outcomes, whilst interventions to improve adherence can lead to better blood pressure control and reduced risk of cardiovascular events.

Identification of metabolites from the gut microbiota in hypertension via network pharmacology and molecular docking

Hypertension is the most prevalent cardiovascular disease, affecting one-third of adults. All antihypertensive drugs have potential side effects. Gut metabolites influence hypertension. The objective of this study was to identify antihypertensive gut metabolites through network pharmacology and molecular docking techniques and to validate their antihypertensive mechanisms via in vitro experiments. A total of 10 core antihypertensive targets and 18 gut metabolites that act on hypertension were identified. Four groups of protein metabolites, namely, CXCL8-baicalein, CXCL8-baicalin, CYP1A1-urolithin A, and PTGS2-equol, which have binding energies of − 7.7, − 8.5, − 7.2, and − 8.8 kcal-mol−1, respectively, were found to have relatively high affinities. Based on its drug-likeness properties in silico and toxicological properties, equol was identified as a potential antihypertensive metabolite. On the basis of the results of network pharmacology and molecular docking, equol may exert antihypertensive effects by regulating the IL-17 signaling pathway and PTGS2. A phenylephrine-induced H9c2 cell model was subsequently utilized to verify that equol inhibits cell hypertrophy (P < 0.05) by inhibiting the IL-17 signaling pathway and PTGS2 (P < 0.05). This study demonstrated that equol has the potential to be developed as a novel therapeutic agent for the treatment of hypertension.Graphical

Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial

Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety. In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed. The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant. A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice. George Medicines.

Development and Worsening of Hypertension with Age in Male Wistar Rats as a Physiological Model of Age-Related Hypertension: Correction of Hypertension with Taxifolin

To preclinically study the effectiveness of new antihypertensive drugs, various animal hypertension models are used. However, most of them do not correspond to primary hypertension, which develops in people with age. We used male Wistar rats of 4, 10, 12 and 18 months old. The animals were divided according to systolic blood pressure (SBP) into normotensive (SBP ≤ 114 mmHg) or hypertensive (SBP ≥ 115 mmHg). Within hypertensive animals, two cohorts were distinguished—with SBP below and above 125 mmHg. The animals received 100 µg/kg of taxifolin intraperitoneally for 7 days. A significant difference was shown between animals with SBP above and below 115 mmHg, as well as between cohorts of hypertensive animals with SBP above and below 125 mmHg within each age. The number of animals with elevated SBP increased with age both for clusters with an SBP above 115 mmHg and for cohorts with an SBP above 125 mmHg. Administration of taxifolin led to a significant decrease in the SBP only in hypertensive animals. A physiological model of age-related hypertension was obtained in male Wistar rats. It has been shown that hypertension develops and worsens with age. In preclinical studies, it should be taken into account that drugs may have different effects depending on the initial SBP of the animals.

Purtscher-like retinopathy and paracentral acute middle maculopathy associated with improper antihypertensive drug use: a case report

BackgroundPurtscher-like retinopathy (PLR) is a rare retinal microangiopathy with unclear pathogenesis. Paracentral acute middle maculopathy (PAMM) is an optical coherence tomography (OCT) sign proposed in recent years, which is characterized by infarction of the middle layer of the retina. This article reported a rare case of PRL and PAMM probably related to improper antihypertensive drug use in a middle-aged male.Case presentationA 49-year-old man presented with a complaint of sudden-onset vision loss and paracentral scotomas in the right eye for approximately 1 week. At presentation, the best-corrected visual acuity (BCVA) was 20/63 OD and 20/20 OS. Fundus examination showed multiple cotton-wool spots and Purtscher flecken in the posterior segment of the right eye. OCT revealed hyper-reflectivities in the inner nuclear layer (INL), consistent with PAMM. En face OCT showed PAMM’s characteristic “fern-like” perivenular changes. Fluorescein angiography demonstrated prolonged arm-to-retina time, delayed artery and venous filling, and hypofluorescence corresponding to cotton-wool spots. Examinations of the left eye were unremarkable. Many imaging and laboratory tests were performed to detect the possible cause of PLR and PAMM, but no possible explanation was found except improper antihypertensive drug use. The patient was recommended to stop his antihypertensive medication, and prescribed other systemic medicines, including oral prednisolone (40 mg q.d. with gradual tapering), oral cobalamin (0.5 mg t.i.d.), and subcutaneous injections of compound anisodine (2.0 mL q.d.) beside the superficial temporal artery. Two weeks after onset, his BCVA improved to 20/25 in the right eye. During follow-ups, his BCVA recovered to 20/20, accompanied by the regression of fundus lesions. The patient reported no treatment-related adverse effects.ConclusionThis is the first reported case of PLR and PAMM following improper antihypertensive drug use. Our report expands our understanding of the etiology and pathophysiology of PLR and PAMM. We also stress the importance of proper application of medications in clinical practice.

The efficacy of Salvia-ligustrazine and Ligustrazine in treating gestational hypertension: A systematic review and meta-analysis.

Pregnancy-induced hypertension syndrome (PIH), a prevalent and critical condition, has garnered increasing attention due to its significant impact on maternal and fetal health outcomes. The conventional treatment approaches rely on magnesium sulfate and various antihypertensive drugs; however, the clinical efficacy of these treatments is limited, highlighting the need to explore alternative avenues for improvement. Recently, a growing number of clinical studies have investigated the use of Salvia-ligustrazine or Ligustrazine in combination with conventional therapy. A comprehensive synthesis and critical analysis of these studies is necessary to evaluate the efficacy and safety of Salvia-ligustrazine or Ligustrazine in treating PIH. We sought all articles published prior to December 2, 2023, from seven databases to identify randomized controlled trials (RCTs) that involved traditional Chinese medicine Salvia-ligustrazine or Ligustrazine in combination with Western medicines for the conventional treatment of PIH, according to predefined inclusion criteria. The studies were assessed using the Cochrane Risk of Bias tool (ROB2.0), and meta-analyses were conducted using Stata 15.0 statistical software. We analyzed 47 RCTs encompassing 4,517 patients. The results demonstrated that combining Salvia-ligustrazine or Ligustrazine with Western medications was more efficacious than using Western medications alone. This combination improved the overall response rate, reduced the incidence of adverse pregnancy outcomes for mothers and infants, and decreased the occurrence of side effects associated with PIH treatment. While we evaluated the efficacy of traditional Chinese medicine injections of Salvia-ligustrazine or Ligustrazine alongside conventional Western treatments, our conclusions must be considered provisional due to potential bias and the limited availability of RCTs.

Antihypertensive therapy and unplanned maternal postpartum health care utilization in patients with mild chronic hypertension.

To test whether treatment of mild chronic hypertension (CHTN) in pregnancy is associated with lower rates of unplanned maternal healthcare utilization postpartum. This was a secondary analysis of the CHTN and pregnancy (CHAP) study, a prospective, open-label, pragmatic, multicenter, randomized treatment trial of pregnant people with mild chronic hypertension. All patients with a postpartum follow-up assessment were included. The primary outcome was unplanned healthcare utilization, defined as unplanned postpartum clinic visits, Emergency Department or triage visits, or unplanned hospital admissions within six weeks postpartum. Differences in outcomes were compared between study groups (Active Group: blood pressure goal of<140/90 mm Hg, and Control Group: blood pressure goal of <160/105 mm Hg) and factors associated with outcomes were examined using logistic regression. A total of 2,293 patients were included with 1,157 (50.5%) in the active group and 1,136 (49.5%) in the control group. Rates of unplanned maternal postpartum health care utilization did not differ between treatment and control groups, (20.2% vs 23.3%, p=0.07, aOR 0.84, 95% CI 0.69-1.03. However, Emergency Department or triage/maternity evaluation unit visits were significantly lower in the Active group (10.2% vs 13.2%, p=0.03, aOR 0.76, 95% 0.58-0.99). Higher BMI at enrollment and cesarean delivery were associated with higher odds of unplanned postpartum healthcare utilization. While treatment of mild CHTN during pregnancy and postpartum was not significantly associated with overall unplanned healthcare resource utilization, it was associated with lower rates of postpartum Emergency Department and triage visits.

Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness.

There are noticeable sex differences in the treatment response to antihypertensives, with limited data on the response to single pill combinations. The aim of the PRECIOUS trial was to assess the treatment response to perindopril/amlodipine and perindopril/amlodipine/indapamide dual and triple single-pill combination in men and women. Four hundred and forty adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial. Based on the previous antihypertensive therapy, patients were assigned to either perindopril/amlodipine 4/5 mg or perindopril/amlodipine/indapamide 4/5/1.25 mg, with the initial dose up-titrated in 4-week intervals in case of uncontrolled blood pressure. An additional analysis was performed for sex- and age-related differences on the blood pressure response and arterial stiffness in men and women aged 35-74 years. Women achieved better overall blood pressure control in all age groups, except for the 35-44 age group. Women presented higher average 24 h aortic augmentation indexes than men, but had more pronounced decreasing trends. The pulse wave velocity was only age-dependent, with reductions slightly greater in women. Both the aortic augmentation index and pulse wave velocity were significantly decreased in all groups compared to baseline. The results of the PRECIOUS trial contribute significant data to the expanding body of evidence on sex differences in hypertension, including the aspect of age-related changes during the life course of women. The differences between same-aged men and women tend to be smaller with advancing age, but with a greater treatment response in women in all age groups for all observed blood pressure parameters and arterial stiffness. ClinicalTrials.gov identifier NCT03738761.