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Cerebral small vessel disease (CSVD) is one of the most common nervous system diseases. Hypertension and neuroinflammation are considered important risk factors for the development of CSVD and white matter (WM) lesions. We used the spontaneously hypertensive rat (SHR) as a model of early-onset CSVD and administered epimedium flavonoids (EF) for three months. The learning and memorization abilities were tested by new object recognition test. The pathological changes of WM were assessed using magnetic resonance imaging, transmission electron microscopy (TEM), Luxol fast blue and Black Gold staining. Oligodendrocytes (OLs) and myelin basic protein were detected by immunohistochemistry. The ultrastructure of the tight junctions was examined using TEM. Microglia and astrocytes were detected by immunofluorescence. RNA-seq was performed on the corpus callosum of rats. The results revealed that EF could significantly improve the learning and memory impairments in SHR, alleviate the injury and demyelination of WM nerve fibers, promote the differentiation of oligodendrocyte precursor cells (OPCs) into mature OLs, inhibit the activation of microglia and astrocytes, inhibit the expression of p38 MAPK/NF-κB p65/NLRP3 and inflammatory cytokines, and increase the expression of tight-junction related proteins ZO-1, occludin, and claudin-5. RNA-seq analysis showed that the neurotrophin signaling pathway played an important role in the disease. RT-qPCR and WB results showed that EF could regulate the expression of nerve growth factor and brain-derived neurotrophic factor and their downstream related proteins in the neurotrophin signaling pathway, which might explain the potential mechanism of EF's effects on the cognitive impairment and WM damage caused by hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Hypertension causes platelet activation and adhesion in the brain resulting in glial activation and neuroinflammation. Further, activation of Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor (ACE2/Ang (1-7)/MasR) axis of central Renin-Angiotensin System (RAS), is known to reduce glial activation and neuroinflammation, thereby exhibiting anti-hypertensive and anti-neuroinflammatory properties. Therefore, in the present study, the role of ACE2/Ang (1-7)/MasR axis was studied on platelet-induced glial activation and neuroinflammation using Diminazene Aceturate (DIZE), an ACE2 activator, in astrocytes and microglial cells as well as in rat model of hypertension. We found that the ACE2 activator DIZE, independently of its BP-lowering properties, efficiently prevented hypertension-induced glial activation, neuroinflammation, and platelet CD40-CD40L signaling via upregulation of ACE2/Ang (1-7)/MasR axis. Further, DIZE decreased platelet deposition in the brain by reducing the expression of adhesion molecules on the brain endothelium. Activation of ACE2 also reduced hypertension-induced endothelial dysfunction by increasing eNOS bioavailability. Interestingly, platelets isolated from hypertensive rats or activated with ADP had significantly increased sCD40L levels and induced significantly more glial activation than platelets from DIZE treated group. Therefore, injection of DIZE pre-treated ADP-activated platelets into normotensive rats strongly reduced glial activation compared to ADP-treated platelets. Moreover, CD40L-induced glial activation, CD40 expression, and NFкB-NLRP3 inflammatory signaling are reversed by DIZE. Furthermore, the beneficial effects of ACE2 activation, DIZE was found to be significantly blocked by MLN4760 (ACE2 inhibitor) as well as A779 (MasR antagonist) treatments. Hence, our study demonstrated that ACE2 activation reduced the platelet CD40-CD40L induced glial activation and neuroinflammation, hence imparted neuroprotection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Several agents are emerging from five different novel classes of antihypertensive medications. We will focus on endothelin antagonists and non-steroidal mineralocorticoid receptor antagonists. While several agents exist in this later class, only a couple have demonstrated superior efficacy in resistant hypertension management. Endothelin receptor antagonists are effective therapy for primary and resistant hypertension, but they are not widely used. This is due to side effects demonstrated in large clinical trials, specifically increased peripheral edema and worsening heart failure in some cases, as well as the availability of many alternative agents to manage blood pressure effectively. However, the relationship between endothelin and its close ties to hypertension is evolving. Recent pre-clinical work explores new applications of more selective endothelin receptor antagonists. They suggest that specific subtypes of hypertension may benefit more from endothelin receptor blockade than simply those with primary hypertension. We review this topic and other related data. Lastly, we also provide a brief overview of non-steroidal mineralocorticoid receptor antagonists as some in the class show promise as antihypertensive agents., Competing Interests: Declaration of competing interest No financial conflicts or competing interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

In this study, we synthesized a series of seven benzimidazole derivatives incorporating the structural acidic framework of angiotensin II (Ang II) type 1 receptor (AT 1 R) antagonists (ARA-II) employing a three-step reaction sequence. The chemical structures were confirmed by 1 H NMR, 13 C NMR and mass spectral data. Through biosimulation, compounds 1-7 were identified as computational safe hits, thus, best candidates underwent ex vivo testing against two distinct mechanisms implicated in hypertension: antagonism of the Ang II type 1 receptor and the blockade of calcium channel. Molecular docking studies helped to understand at the molecular level the dual vasorelaxant effects with the recognition sites of the AT 1 R and the L-type calcium channel. In an in vivo spontaneously hypertensive rat model (SHR), intraperitoneally administration of compound 1 at 20 mg/kg resulted in a 25 % reduction in systolic blood pressure, demonstrating both ex vivo vasorelaxant action and in vivo antihypertensive multitarget efficacy. ©2024 Elsevier., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies., Methods: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age 2 , sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group., Results: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship ( p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk., Discussion: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.

Transient receptor potential canonical 5 (TRPC5) is a calcium-permeable non-selective cation channel involved in various pathophysiological processes, including renal injury. Recently, GFB-887, an investigational pyridazinone TRPC5 inhibitor, demonstrated significant therapeutic potential in a Phase II clinical trial for focal segmental glomerulosclerosis (FSGS), a rare and severe form of chronic kidney disease (CKD). In the current study, based on the structure of GFB-887, we conducted extensive structural modification to explore novel TRPC5 inhibitors with desirable drug-like properties and robust nephroprotective efficacy. A series of pyridazinone derivatives featuring a novel tetrahydroimidazo[1,2-a]pyrazine scaffold were synthesized and their activities were evaluated in HEK-293 cells stably expressing TRPC5 using a fluorescence-based Ca 2+ mobilization assay. Among these compounds, compound 12 is turned out to be a potent TRPC5 inhibitor with apparent affinity comparable to the parent compound GBF-887. Compound 12 is highly selective on TRPC4/5 over TRPC3/6/7 and hERG channels, along with acceptable pharmacokinetic properties and a favorable safety profile. More importantly, in a rat model of hypertension-induced renal injury, oral administration of compound 12 (10 mg/kg, BID) efficaciously reduced mean blood pressure, inhibited proteinuria, and protected podocyte damage. These findings further confirmed the potential of TRPC5 inhibitors on the CKD treatment and provided compound 12 to be a valuable tool for exploring TRPC4/5 pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Poststroke epilepsy (PSE) is a common complication after ischemic stroke. This study investigates the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the risk of PSE in patients with ischemic stroke., Methods and Results: A population-based retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database between 2000 and 2015. Patients with hypertension with a history of ischemic stroke were classified into prevalent, new, and nonusers according to their use of ACEIs/ARBs. Prevalent ACEI/ARB users were further classified into continuing or discontinued users, based on their poststroke medication adherence. We used multivariate Cox regression models, adjusted for demographics and comorbidities, to assess the risk of PSE among different ACEI/ARB user groups. There were 182 983 ACEI/ARB users and 38 365 nonusers included. There were 7387 patients diagnosed with PSE, whereas 213 961 were not. Nonusers exhibited a higher risk of PSE (adjusted hazard ratio [aHR], 1.72 [95% CI, 1.63-1.82]). Both prevalent and nonusers had higher risks compared with new ACEI/ARB users, with respective aHRs of 1.33 (95% CI, 1.25-1.41) and 2.00 (95% CI, 1.87-2.14). Discontinued ACEI/ARB users showed the highest risk of PSE (aHR, 2.34 [95% CI, 2.15-2.54]), suggesting the importance of continuing ACEI/ARB use after stroke. Treatment-by-age interaction was significant among patients with or without ACEI/ARB use before stroke ( P value for interaction 0.004 and <0.001, respectively), suggesting a stronger beneficial association in younger patients., Conclusions: The use of ACEIs/ARBs after ischemic stroke in patients with hypertension is associated with a reduced risk of PSE, especially among younger patients.

Background: It is unknown how blood pressure (BP) relates to stroke risk across levels of hypertension daily dose (HDD)-quantified antihypertensive medication intensity., Methods and Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study enrolled 30 239 participants from the 48 contiguous US states in 2003 to 2007 with in-person follow-up in 2013 to 2016 (Visit 2). We included those without prior stroke at Visit 2, treating this visit as T 0 . Biannual phone calls and medical record review ascertained incident stroke events. Cox proportional hazard models estimated the hazard ratio (HR) of incident stroke by treatment intensity defined by systolic BP stages and HDD groupings. There were 344 stroke events over a median 5.5 years. Relative to systolic BP <120 mm Hg and no antihypertensive medications, the stroke HR was 2.86 (95% CI, 1.68-4.85) for systolic BP 140 to 159 mm Hg and HDD tertile 2, 2.33 (1.37-3.97) for systolic BP 140 to 159 mm Hg and HDD tertile 3, 3.08 (1.20-7.88) for systolic BP ≥160 mm Hg and HDD tertile 2, and 3.66 (1.61-8.30) for systolic BP ≥160 mm Hg and HDD tertile 3. Stroke risk was similar across HDD levels for people with systolic BP <140 mm Hg., Conclusions: Among adults without prior stroke, systolic BP ≥140 mm Hg and HDD tertile ≥2 was associated with greater stroke risk. For adults with BP <140 mm Hg, stroke risk was similar despite cumulative dose of antihypertensive medications used. These findings support the practice of BP-lowering medications to mitigate stroke risk.

Competing Interests: Conflict of interest: Professor Webb’s employer, the University of Edinburgh, has been paid by Alnylam for his contributions to the zilebesiran programme in hypertension. He has undertaken recent consultancy roles with Idorsia, Janssen, and Silence pharmaceuticals in the field of cardiovascular research.

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study, patients completed the Protocol for Responding to & Assessing Patients' Assets, Risks & Experiences questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as systolic blood pressure greater than or equal to 140 mm Hg and/or diastolic blood pressure greater than or equal to 90 mm Hg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (adjusted hazards ratio = 1.77; 95% confidence interval = 1.10 to 2.83, P = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics., (© The Author(s) 2024. Published by Oxford University Press.)

Aims: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations., Methods and Results: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%)., Conclusion: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic., Methods: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population., Results: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less., Conclusion: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Background: Regular physical activity is associated with a reduced stroke risk. However, this relationship might be attenuated in the presence of hypertension and antihypertensive medication use. We examined the dose-response relationship between physical activity and stroke in normotensive and hypertensive individuals., Methods: A Dutch population-based cohort including 139 930 individuals (41% men; mean age, 44±13) was performed (median follow-up, 6.75 years). Participants were stratified at baseline as hypertensive (44%) or normotensive (56%) and categorized into quartiles of the lowest (Q1) to the highest (Q4) moderate-to-vigorous, self-reported physical activity. The primary outcome was incident stroke (fatal and nonfatal). Cox regression estimated hazard ratios and 95% CIs. The main analyses were stratified on baseline blood pressure and adjusted for confounders. Hypertensives were stratified into medicated (21%) or non-medicated (79%)., Results: Compared with Q1, adjusted hazard ratios were 0.87 (0.69-1.10; P =0.23), 0.75 (0.59-0.95; P =0.02), and 0.94 (0.74-1.20; P =0.64) for Q2 to Q4, respectively in the total population. Hazard ratios for normotensives were 0.79 (0.50-1.25; P =0.32), 0.75 (0.48-1.18; P =0.22), 0.97 (0.62-1.51; P =0.90) for Q2 to Q4, respectively. In hypertensives, hazard ratios were 0.89 (0.68-1.17; P =0.41), 0.74 (0.56-0.98; P =0.03), 0.92 (0.69-1.23; P =0.56) for Q2 to Q4, respectively. There was no significant interaction between hypertension status for the relation between physical activity and stroke risk. The stratified analysis revealed a smaller benefit of moderate-to-vigorous physical activity in medicated hypertensives compared with nonmedicated hypertensives, but no significant interaction effect was found., Conclusions: Regular moderate-to-vigorous physical activity is beneficial for stroke risk reduction (Q3 compared with Q1), which is not affected by hypertension. Antihypertensive medication may be associated with a smaller benefit of moderate-to-vigorous physical activity on the risk of stroke, but further research is warranted., Competing Interests: None.

Over the last decade, randomized clinical trials of several pharmacologic agents have demonstrated a reduction in cardiovascular mortality and other important secondary outcomes. Angiotensin-Neprilysin Inhibitors and Sodium-Glucose Co-transporter 2 inhibitors have now become pillars in the treatment of heart failure. Ivabradine is a negative chronotropic agent used as an adjunctive therapy in patients with heart failure. Two new hypertension therapies, zilebresiran and aprocitentan, are currently in investigational stages. Finally, mavacamten has emerged as a pharmacologic treatment for hypertrophic obstructive cardiomyopathy. Practitioners must be familiar with the indications and side effects of newer therapies as they are now frequently prescribed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon., Methods: A systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity., Results: The available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements., Conclusion: In this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis., Competing Interests: Declaration of competing interest The named authors have no conflict of interest, financial or otherwise., (Copyright © 2024. Published by Elsevier GmbH.)

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available., Competing Interests: None.

Objective: Evaluate a cardiovascular care intervention intended to increase access to comprehensive medication management (CMM) pharmacy care and improve vascular health goals among socially disadvantaged patients., Design: Retrospective electronic health records-based evaluation., Setting: Thirteen health care clinics serving socially vulnerable neighborhoods within a large health system., Participants: Hypertensive and hyperlipidemic adult patients., Intervention: CMM pharmacists increased recruitment among patients who met clinical criteria in clinics serving more diverse and socially vulnerable communities. CMM pharmacists partnered with patients to work toward meeting health goals through medication management and lifestyle modification., Main Outcome Measures: Changes in the engagement of socially disadvantaged patients between preintervention and intervention time periods; vascular health goals (ie, controlled blood pressure, appropriate statin and aspirin therapies, and tobacco nonuse); and the use of health system resources by CMM care group., Results: The intervention indicated an overall shift in sociodemographics among patients receiving CMM care (fewer non-Hispanic Whites: N = 1988, 55.81% vs N = 2264, 59.97%, P < .001; greater place-based social vulnerability: N = 1354, 38.01% vs N = 1309, 34.68%, P = .03; more patients requiring interpreters: N = 776, 21.79% vs N = 698, 18.49%, P < .001) compared to the preintervention period. Among patients meeting intervention criteria, those who partnered with CMM pharmacists (N = 439) were more likely to connect with system resources (social work: N = 47, 10.71% vs 163, 3.74%, P < .001; medical specialists: N = 249, 56.72% vs N = 1989, 45.66%; P < .001) compared to those without CMM care (N = 4356). Intervention patients who partnered with CMM pharmacists were also more likely to meet blood pressure (N = 357, 81.32% vs N = 3317, 76.15%, P < .001) and statin goals (N = 397, 90.43% vs N = 3509, 80.56%, P < .001) compared to non-CMM patients., Conclusions: The demographics of patients receiving CMM became more diverse with the intervention, indicating improved access to CMM pharmacists. Cultivating relationships among patients with greater social disadvantage and cardiovascular disease and CMM pharmacists may improve health outcomes and connect patients to essential resources, thus potentially improving long-term cardiovascular outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment., Methods: From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model., Results: The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively ( P >0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group ( P interaction =0.05)., Conclusions: Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311., Competing Interests: None.

Background: Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management., Objective: To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era., Methods: Design: Retrospective population-based cohort study., Setting: Ontario, Canada., Participants: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017., Exposure: Sex (female vs. male)., Outcomes and Measures: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression., Results: Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997])., Conclusions: Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Hypertension, a risk factor for developing cardiovascular disease, is becoming increasingly prevalent worldwide. Digital health is now widely utilized for hypertension management, and numerous studies have assessed its effectiveness., Objective: The review aims to analyse the effectiveness of digital health (i.e., mobile health (mHealth), telehealth, and the combination of mHealth & telehealth) on hypertensive patients, concerning three key areas: clinical outcomes, medication adherence, and adherence to lifestyle changes, as compared to standard care., Methods: The review followed the PRISMA framework. Eight electronic databases were scanned for randomized control trials focusing on the effects of mHealth or telehealth on hypertensive patients, published between 2010 and 2023. All processes were conducted by the first two authors independently. A meta-analysis was conducted for quantitative data, while a narrative synthesis was conducted for qualitative data., Results: In total, 74 studies involving 92 686 participants were identified. The meta-analysis favoured the interventions, revealing a significant decrease in systolic blood pressure and diastolic blood pressure for mHealth, telehealth and mHealth & telehealth groups. Nevertheless, medication adherence showed improvement only in the mHealth group, while blood pressure control showed improvement in both mHealth and mHealth & telehealth groups, and BMI showed improvement only in the mHealth group. Evidence for adherence to physical activity and DASH diet/salt intake remained inconclusive., Conclusion: In general, mHealth and telehealth have demonstrated their merits in improving the clinical outcomes of hypertensive patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans., Aim: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension., Methods: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F 2 -isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets., Results: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14 + CD16 - ) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo., Conclusions: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods., Clinical Trial Registry Number: NCT04584372 (ClinicialTrials.gov)., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypertension remains a major problem worldwide, especially across the Asia-Pacific region, which reports high prevalence rates and slow improvements in treatment rate and blood pressure (BP) control rate. Asian patients with hypertension may also vary with regard to phenotype and the epidemiology of the complications of hypertension, especially when compared with Western patients. Given these differences, Western guidelines may not necessarily be applicable to countries in the Asia Pacific. This narrative review aims to provide a critical comparison between the recently published European Society of Hypertension (ESH) 2023 guidelines and existing local guidelines in select Asian countries, offer expert opinion on how to fill gaps in the ESH 2023 guidelines for hypertension in the Asian context, and examine the need for harmonisation of hypertension guidelines worldwide. This review focuses on the definition and diagnosis of hypertension, the treatment thresholds and targets, and recommendations on the use of pharmacotherapy., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets., Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories., Results: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; P interaction =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively., Conclusions: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar., Competing Interests: J.A. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Ortho Clinical Diagnostics, Quidel Cardiovascular Inc, and Siemen’s Health Care Diagnostics. He has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” C.M. Ballantyne reports consulting and research support from Abbott and Roche Diagnostics. J.D. Berry reports grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics, consulting fees from Roche Diagnostics, and the Cooper Institute. The other authors report no conflicts.

Objectives: Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors., Design: Retrospective cohort study., Setting and Participants: A total of 24,870 Department of Veterans Affairs (VA) nursing home residents aged ≥65 years with long-term stays (≥180 days) from 2006 to 2019., Methods: We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission., Results: More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years)., Conclusions and Implications: Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes., Competing Interests: Disclosures M.A.S. and S.J.L. receive honoraria as authors on UpToDate. The other authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. All rights reserved.)

Background: Medication nonadherence is a barrier to hypertension control. The Centers for Disease Control and Prevention recommends prescribing 90-day fills for maintenance medications yet antihypertensives are often dispensed as 30-day fills. Our objectives were to examine how often patients receive 30-day supplies of medication despite prescriptions for longer duration and to examine the effect of medication fill duration on adherence and hypertension control., Methods: We conducted a retrospective cohort study of pediatric patients with hypertension over a 3-year period. For each patient, days prescribed per fill were compared to days dispensed per fill using pharmacy reports and insurance claim data. Proportion of Days Covered (PDC) was calculated to estimate adherence. Hypertension control was determined by provider assessment of control and blood pressure measurement at the final visit., Results: Final cohort included 449 patients. A total of 70% had at least one prescription for ≥ 90 days but only 37% had at least one dispense for ≥ 90 days. There was no difference in the likelihood of being prescribed a 90-day fill by insurance type (public vs. private); however, patients with public insurance were less likely to be dispensed a 90-day fill (OR = 0.068, p < 0.001). Patients who received 90-day fills had better adherence (median PDC 77.5% vs. 58.1%, p < 0.001) and were more likely to have hypertension control based on provider assessment., Conclusions: Longer fill duration is associated with improved adherence and hypertension control. Patients with public insurance are markedly less likely to be dispensed 90-day fills, a modifiable barrier to improving adherence., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Suboptimal medication adherence is common among patients with cardiovascular diseases. We sought evidence on non-pharmacological interventions used to support adherence for patients with hypertension and/or dyslipidemia., Methods: We searched MEDLINE, EMBASE, MEDLINE In-Process, ClinicalTrials.gov, EUCTR, and conference proceedings from July 2011 to July 2021 to identify trials evaluating effects of health education, phone reminders, or digital interventions on medication adherence or persistence of adult patients with hypertension and/or dyslipidemia. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool v2., Results: Of 64 studies, 62 used health education approaches (e.g. educational interviews, motivational meetings, advice from physicians, and mobile health content), 16 phone reminders (e.g. text reminders, electronic pill-box linked reminders, bi-directional text messaging), and 10 digital applications as interventions (e.g., various self-management applications). All studies assessed medication adherence; only two persistence. Overall, 30 studies (83%) assessing health education approaches alone and 25 (78%) combined with other strategies, 12 (75%) phone reminders and eight studies (80%) digital applications combined with other strategies reported improved medication adherence. Two studies assessing health education approaches reported improved persistence., Conclusions: Our findings indicate non-pharmacological interventions may positively impact adherence. Therefore, 'beyond the pill' approaches could play a role in preventing cardiovascular diseases.

We have previously observed that prolonged administration of rapamycin, an inhibitor targeting the mammalian target of rapamycin complex (mTORC)1, partially reduced hypertension and alleviated kidney inflammation in Dahl salt-sensitive (SS) rats. In contrast, treatment with PP242, an inhibitor affecting both mTORC1/mTORC2, not only completely prevented hypertension but also provided substantial protection against kidney injury. Notably, PP242 exhibited potent natriuretic effects that were not evident with rapamycin. The primary objective of this study was to pinpoint the specific tubular sites responsible for the natriuretic effect of PP242 in SS rats subjected to either 0.4% NaCl (normal salt) or 4.0% NaCl (high salt) diet. Acute effects of PP242 on natriuretic, diuretic, and kaliuretic responses were determined in unanesthetized SS rats utilizing benzamil, furosemide, or hydrochlorothiazide [inhibitors of epithelial Na + channel (ENaC), Na-K-2Cl cotransporter (NKCC2), or Na-Cl cotransporter (NCC), respectively] either administered alone or in combination. The findings indicate that the natriuretic effects of PP242 in SS rats stem predominantly from the inhibition of NCC and a reduction of ENaC open probability. Molecular analysis revealed that mTORC2 regulates NCC activity through protein phosphorylation and ENaC activity through proteolytic cleavage in vivo. Evidence also indicated that PP242 also prevents the loss of K + associated with the inhibition of NCC. These findings suggest that PP242 may represent an improved therapeutic approach for antihypertensive intervention, potentially controlling blood pressure and mitigating kidney injury in salt-sensitive human subjects. NEW & NOTEWORTHY This study explored mechanisms underlying the natriuretic effects of mammalian target of rapamycin protein complex 2 inhibition using PP242 and revealed both epithelial Na + channel and Na-Cl cotransporter in the distal tubular segments were potentially inhibited. These observations, with prior lab evidence, indicate that PP242 prevents hypertension via its potent inhibitory effects on these specific sodium transporters and by reducing renal immune responses. This dual action, coupled with potassium sparing effects, suggests an improved approach for managing hypertension and associated kidney damage.

Purpose of Review: As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined., Recent Findings: Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD., Summary: This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Enalapril is an orally administered angiotensin-converting enzyme inhibitor which is widely prescribed to treat hypertension, chronic kidney disease, and heart failure. It is an ester prodrug that needs to be activated by carboxylesterase 1 (CES1). CES1 is a hepatic hydrolase that in vivo biotransforms enalapril to its active form enalaprilat in order to produce its desired pharmacological impact. Several single nucleotide polymorphisms in CES1 gene are reported to alter the catalytic activity of CES1 enzyme and influence enalapril metabolism. G143E, L40T, G142E, G147C, Y170D, and R171C can completely block the enalapril metabolism. Some polymorphisms like Q169P, E220G, and D269fs do not completely block the CES1 function; however, they reduce the catalytic activity of CES1 enzyme. The prevalence of these polymorphisms is not the same among all populations which necessitate to consider the genetic panel of respective population before prescribing enalapril. These genetic variations are also responsible for interindividual variability of CES1 enzyme activity which ultimately affects the pharmacokinetics and pharmacodynamics of enalapril. The current review summarizes the CES1 polymorphisms which influence the enalapril metabolism and efficacy. The structure of CES1 catalytic domain and important amino acids impacting the catalytic activity of CES1 enzyme are also discussed. This review also highlights the importance of pharmacogenomics in personalized medicine., (© 2024. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

Background: Hypertension is a global health concern that is best managed at the primary care level. In low- and middle-income countries (LMICs) facing resource constraints, collaboration between well-prepared entry-level advanced practice nurses (APNs) and physicians (medical doctors [MDs]) can enhance the care of patients with primary hypertension., Objective: The purpose of this study was to evaluate the effectiveness of collaborative entry-level APNs in primary hypertension management, including patient knowledge, physiological and behavioral outcomes, consultation length, and patient satisfaction., Methods: Sixty-three eligible patients were randomly assigned to either an entry-level APN intervention group or a control group with MDs. Three master's-prepared nurses, trained in hypertension management, acted as entry-level APNs, following the Joint National Committee guidelines in collaboration with a physician. The control group underwent standard clinic consultations. After 1 month, a mixed analysis of variance was used to assess intervention effectiveness, examining both between-groups and within-groups outcomes., Results: Both groups shared similar sociodemographic and baseline characteristics. Significant improvements in blood pressure, body mass index, knowledge, self-management, and medication adherence were found at the 1-month follow-up, with no significant differences in outcomes or patient satisfaction between the entry-level APN and MD groups. However, clinical consultation time was significantly longer for entry-level APNs than for MDs., Conclusions: Collaborative entry-level APNs managing primary hypertension are comparable with MD care; however, larger, longer trials are essential for a thorough assessment. Strengthening the development of entry-level advanced practice nursing roles in low- and middle-income countries is crucial for addressing service gaps in primary hypertension and other chronic diseases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Addressing disparities in blood pressure control must include supporting antihypertensive medication adherence (MA). Developing effective MA interventions requires identifying the most important factors influencing MA., Objective: In this review, the authors aimed to meta-analyze the results of research testing associations between factors potentially influencing antihypertensive MA and assessed antihypertensive MA in historically underrepresented populations. Additional exploratory analyses focused on system-level factors, which have been understudied and may particularly impact disparities in MA., Methods: A health sciences librarian assisted with searching across 10 databases. Inclusion criteria included (1) published in English, (2) sample of adults with hypertension, (3) ≥50% of participants having self-identified as a race/ethnicity underrepresented in the country where the study was conducted, and (4) reporting sufficient data to calculate effect size(s)., Results: Fifty-eight studies were eligible for inclusion. Nine factors met criteria for planned analyses. Older age ( r = 0.08, P < .01; k = 26 studies) and higher income ( r = 0.11, P = .01; k = 15) were significantly correlated with better MA. Having depressive symptoms was significantly correlated with worse MA ( r = -0.18, P < .01; k = 11). Effect sizes for sex, education level, marital status, number of medications, comorbidities, and perceived social support were not significant. System-level factors examined included insurance coverage, access to healthcare, perceived barriers, having a primary care provider, perceptions of their healthcare provider, and experiences of discrimination in healthcare., Conclusions: Understanding the impact of factors associated with antihypertensive MA in historically underrepresented adults can support development of targeted, culturally relevant MA interventions. Future research should examine the impact of system-level factors on antihypertensive MA among historically underrepresented populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately., Design and Setting: The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden., Patients: Participants ( n  = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate., Main Outcome Measures: Association between self-reported BP and 10 self-report lifestyle-related variables., Results: Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP ( p  < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p  < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women., Conclusion: In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.

Background: Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients., Objectives: To investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following BS in Korean patients with morbid obesity., Setting: This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021)., Methods: We included patients who underwent BS between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission., Results: A total of 3810 patients were included in this study. For 1-year following BS, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their BS showed a relatively higher incidence of remission than other groups., Conclusions: BS was associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear., Methods: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality., Results: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries., Conclusions: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension., Experimental Approach: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks., Key Results: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects., Conclusions and Implications: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Primary aldosteronism is the most common cause of secondary hypertension, which is caused by increased aldosterone secretion in the adrenal cortex and contains many subtypes, among which familial hyperaldosteronism is relatively rare. Familial hyperaldosteronism can be divided into four subtypes based on its clinical manifestations and mutated genes: FH-I , FH-II , FH-III , and FH-IV . This article reports on three patients with FH-IV: a mother and her two sons. They were diagnosed with hypertension in other hospitals, and hypokalemia was found during hospitalization in our department. Diltiazem and terazosin were used for elution for 1 month. Renin and aldosterone levels in standing or supine positions improved, and the aldosterone-to-renin ratio was positive. Primary aldosteronism was diagnosed based on improved saline and captopril inhibition tests. As the three patients were blood-related immediate family members, gene screening was performed, diagnosing them with FH-IV . This article reports the clinical characteristics of the three cases in combination with related literature to improve the understanding of FH-IV ., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings., Methods: This was a retrospective cross-sectional analysis of patients 5-22 years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2 weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action., Results: 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0 years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action., Conclusions: While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Adherence to antihypertension medications has been explored in previous studies; however, these studies generally focus on individuals who reside in urban areas. Improved understanding is needed regarding rural older adults who are self-managing medications for hypertension and the motivational factors that may influence adherence., Objectives: The purpose of this study was to examine medication adherence among rural older adults with hypertension and the association with motivational factors as defined in self-determination theory, including quality of motivation (autonomous vs controlled), perceived competence, perceived autonomy support, and basic psychological needs satisfaction. Rural nursing theory was also used to explore the concept of resilience., Methods: This cross-sectional study involved 80 older adults (≥65 years old) self-managing at least 1 prescribed medication for managing their hypertension. Participants ranged in age from 65 to 89 (mean [SD], 74.04 [6.18]) years from rural areas in the northwest. Participants completed a demographic questionnaire, a measure of medication adherence, and questionnaires to assess perceived autonomy support, basic needs satisfaction, autonomous and controlled motivation, perceived competence, and resilience., Results: Correlational analysis and multiple regression were used to examine associations and predict adherence. Perceived autonomy support, resilience, cost of medication, and medication regimen complexity were the only variables significantly associated with medication adherence and predicted adherence. Resilience mediated the relationship between perceived autonomy support and medication adherence., Conclusions: Overall, findings indicate high levels of adherence. Interventions that enhance perceptions of autonomy support and resilience may be useful in managing hypertension., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertensive patients with high-risk comorbidities require medications for each condition, leading to greater burden. The number of chronic conditions can affect patients' concurrent medication adherence., Objective: We aimed to compare the characteristics of groups based on their concurrent medication adherence and investigate the association between the number of high-risk comorbidities and concurrent medication adherence for patients with hypertension and high-risk comorbidities., Methods: A secondary data analysis was performed with the 2018 Korea Health Panel Survey, including 2230 patients with hypertension and at least 1 high-risk comorbidity who were prescribed medications for at least 2 conditions. Using medication adherence for each condition, we identified 3 concurrent medication adherence groups: adherent, suboptimal, and nonadherent groups. Multinominal logistic regression was used to determine the association between the number of high-risk comorbidities and the concurrent medication adherence groups., Results: Adherent, suboptimal, and nonadherent groups included 85%, 11%, and 4% of the patients, respectively. Whereas having more high-risk comorbidities was associated with belonging to the suboptimal group compared with the adherent group (adjusted odds ratio, 1.46), having fewer high-risk comorbidities was associated with belonging to the nonadherent group compared with the adherent group (adjusted odds ratio, 0.52)., Conclusions: We identified 3 groups based on their concurrent medication adherence. Our results indicated that the relationship of the number of high-risk comorbidities with the concurrent medication adherence group was inconsistent., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Hypertension is a leading cause of death and disease burden followed by dyslipidemia. Their asymptomatic nature leads to low adherence and persistence to treatments. A systematic literature review (SLR) investigated the impact of single-pill-combinations (SPC) compared to free-equivalent combination (FEC) on adherence, persistence, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes, in patients with hypertension, dyslipidemia, or both., Methods: MEDLINE, MEDLINE-IN-PROCESS, Embase, and Cochrane were searched from inception until 11 May 2021, for studies comparing SPC against FEC in patients with hypertension and/or dyslipidemia. Patient characteristics, study design, therapies, measures of adherence or persistence, clinical outcomes, and follow-up were extracted., Results: Among 52 studies identified in the SLR, 27 ( n  = 346,030 patients) were included in the meta-analysis. SPCs were associated with significantly improved adherence compared with FEC, as assessed through medication-possession-ratio ≥80% (odds ratio (OR) 0.42, p  < 0.01) and proportion of days covered ≥80% (OR 0.45, p  < 0.01). SPC also improved persistence (OR 0.44, p  < 0.01) and systolic blood pressure (SBP) reduction (mean difference -1.50, p  < 0.01) compared with the FEC., Conclusions: SPC use resulted in significantly improved adherence, persistence, and SBP levels compared with FEC in patients with hypertension. The findings support SPC use in reducing the burden of hypertension and dyslipidemia.

Background: Hypertension is the chronic disease that most affects the elderly population worldwide and is the main modifiable risk factor for cardiovascular diseases. In hypertensive elderly patients, health literacy emerges as a key component for achieving better clinical outcomes., Objective: This study aims to describe the health literacy strategies used for elderly patients with arterial hypertension., Methods: A review of the scientific literature was conducted in accordance with recommendations from the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Three databases were used to identify relevant studies which were then assessed for eligibility, extracted, and categorized., Results: A total of 6442 articles were identified in the databases, out of which 1486 were duplicates and were removed. Based on titles and abstracts, 4887 articles were excluded, and 59 were eliminated through full-text analysis for not meeting the eligibility criteria. Ten studies were included in this scoping review. The identified strategies included face-to-face group educational sessions, face-to-face individual educational sessions, use of written educational materials, educational sessions through electronic devices and/or computers, individual counseling, physical exercise, and personal health diary. The most addressed topics were the nature of hypertension, nutrition, and physical exercise. The study environments highlighted the importance of involving a multidisciplinary team in health literacy strategies for elderly individuals whith hypertension., Conclusions: Interventions with mixed measures were commonly used by the authors and encouraged disease self-management. Access to information and the promotion of critical thinking allowed patients to have better disease control. However, studies linking health literacy and elderly individuals with arterial hypertension are still scarce, indicating the need for further research., Competing Interests: Declarations of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To determine if individuals chronically (>1 yr) prescribed antihypertensive medications have a normal BP response to peak exercise compared with unmedicated individuals., Methods: Participants included 2555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 yr were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the American Heart Association., Results: The unmedicated group had a greater prevalence ( P < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence ( P < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher ( P < 0.01) in medicated compared with unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP ( P = 0.613), risk factors ( P = 0.104), or cardiorespiratory fitness ( P = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP ( P = 0.039), but not for men ( P = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors, and cardiorespiratory fitness ( P = 0.022)., Conclusions: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension., (Copyright © 2024 by the American College of Sports Medicine.)