Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications.

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

[Secondary hypertension: diagnosis and treatment]. / Ipertensione arteriosa secondaria: diagnosi e trattamento.

Hypertension does not recognize obvious pathogenic causes in the majority of patients (essential hypertension). However, a secondary underlying cause of hypertension can be recognized in 5-10% of unselected hypertensive patients, and this prevalence may increase to more than 20% in patients with hypertension that is difficult to control or frankly resistant to treatment. In children, secondary hypertension is most often due to aortic coarctation, distal thoracic or abdominal aortic stenosis, or specific gene mutations. In adults or elderly individuals, secondary hypertension is most often due to atherosclerotic renal artery stenosis, primary hyperaldosteronism, and Cushing's disease or syndrome. Parenchymal nephropathy and hyperparathyroidism can cause hypertension at all ages, while pheochromocytoma and paraganglioma tend to occur more often in adolescents or young adults. In general, secondary hypertension should be suspected in subjects with: (a) onset of hypertension under 30 years of age especially if in the absence of hypertensive family history or other risk factors for hypertension; (b) treatment-resistant hypertension; c) severe hypertension (>180/110 mmHg), malignancy, or hypertensive emergencies; d) rapid rise in blood pressure values in previously well controlled patients. Any clinical signs suspicious or suggestive of hypertension from endocrine causes, a "reverse dipping" or "non-dipping'" profile at 24 h ambulatory blood pressure monitoring not justified by other factors, signs of obvious organ damage may be helpful clues for diagnosis. Finally, patients snoring or with clear sleep apnea should also be considered for possible secondary hypertension.

Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes.

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

[Accurate determination of three new antihypertensive drugs illegally added to food using ultra-high performance liquid chromatography-tandem mass spectrometry].

Effective strategies are required to address food safety issues related to the illegal addition of antihypertensive drugs to food and claims of antihypertensive function. In this study, a novel ultra-high performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of three antihypertensive drugs (azilsartan, candesartan cilexetil, and lacidipine) in 12 food matrices (pressed candies, solid beverages, alternative teas, tea drinks, biscuits, jellies, mixed liquors, oral liquids, medicinal teas, tablets, hard capsules, and soft capsules). Initially, mass spectrometry parameters, such as the collision energies of the three antihypertensive drugs, were optimized. Subsequently, the response intensities and chromatographic separation conditions of the three drugs in different mobile phases were compared. In addition, to enhance the recoveries, various extraction solvents and purification methods, including solid-phase extraction (SPE) columns and the QuEChERS technique, were investigated. In the developed method, sample determination involved three steps. First, the sample was extracted using 0.2% (v/v) formic acid in acetonitrile and then filtered using high-speed centrifugation, in addition, the extracted solution of alternative tea and medicinal tea was purified using the QuEChERS technique. Second, the supernatant was diluted with water, and filtered through a 0.22 µm polytetrafluoroethylene (PTFE) membrane. Finally, the analytes were separated on an Agilent Eclipse Plus RRHD C18 column (50 mm×2.1 mm, 1.8 µm) using a 5 mmol/L ammonium formate aqueous solution and acetonitrile as the mobile phases under gradient elution conditions and then detected using UHPLC-MS/MS with positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. Methodological validation showed good linear relationships for all three antihypertensive drugs in the investigated concentration ranges, with correlation coefficients (r2) greater than 0.996. The limit of detection (LOD) and limit of quantification (LOQ) of lacidipine were 0.02 mg/kg and 0.04 mg/kg, respectively, whereas those of the other two drugs were 0.01 mg/kg and 0.02 mg/kg, respectively. In the 12 food matrices, the average recoveries of the drugs ranged from 86.6% to 107.5% with relative standard deviations (RSDs) of 1.1%-10.9% (n=6) at low, medium, and high spiked levels. Furthermore, this method was successfully applied to the analysis of real food samples. Overall, the newly developed method is simple, rapid, sensitive, accurate, and suitable for the qualitative and quantitative determination of antihypertensive drugs in different food matrices. This work could provide technical support for food safety agencies in implementing measures against the illegal addition of antihypertensive drugs to food.

Torsemide in the Management of Essential Hypertension.

Torsemide, a loop diuretic, is increasingly recognized for its role in managing essential hypertension. Its mechanism of action involves inhibiting the reabsorption of sodium and chloride ions in the ascending loop of Henle in the kidneys. By doing so, torsemide promotes diuresis, which refers to increased urine production, and subsequently lowers blood pressure. Studies have shown that torsemide is comparably effective to other antihypertensive agents in lowering blood pressure, with the added benefit of potentially improving renal function. However, while torsemide shows promise in hypertensive management, further research is necessary to fully understand its long-term effects and to establish optimal dosing strategies. Future research should focus on clarifying its role in long-term blood pressure control and refining its use in clinical practice to maximize efficacy and minimize adverse effects.

Use of electronic health records to characterize patients with uncontrolled hypertension in two large health system networks.

BACKGROUND: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. METHODS: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension (based on either ICD-10 codes of hypertension or two elevated blood pressure [BP] measurements) receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single BP measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). RESULTS: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). A total of 24.1% of patients at YNHHS and 21.6% at OneFlorida had both diagnosis code for hypertension and elevated blood pressure measurements. Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar incidence rates of deaths, CVD events, and healthcare visits at 3, 6, 12, and 24 months. The two computable definitions generated consistent results. CONCLUSIONS: While the current EHR systems are not fully optimized for disease surveillance and stratification, our findings illustrate the potential of leveraging EHR data to conduct digital population surveillance in the realm of hypertension management.

[Beta-blockers and hypertension : an old actor returns to the stage]. / Bêtabloquants et hypertension artérielle : retour sur scène d'un vieil acteur.

For decades beta-blockers are a heterogenous group of drugs with diverse pharmacological properties, used in the treatment of high blood pressure. However, their benefit as therapy for hypertension without concomitant compelling indications is controversial. In this article we will discuss the concept of sympathetic overdrive and the theoretical rationale of the use of beta-blockers as antihypertensive drugs. The differences between beta-blockers' generations in terms of anti-hypertensive efficacy and side effects are discussed. Finally, we review the position of the last European guidelines published in 2023 about beta-blockers in the management of arterial hypertension.

Depuis des décennies, les bêtabloquants (BB) sont une gamme hétérogène de médicaments aux propriétés pharmacologiques diverses, utilisés dans le traitement de l'hypertension artérielle (HTA). Cependant, leur bénéfice, en tant que traitement de l'HTA en l'absence d'autre indication absolue à leur emploi, est controversé. Dans cet article, nous abordons le concept d'hyperactivité sympathique et la justification théorique de l'utilisation des BB comme médicaments antihypertenseurs. Les différences entre les générations de BB en termes d'efficacité antihypertensive et d'effets secondaires sont abordées. Enfin, nous revenons sur la position des dernières recommandations européennes publiées en 2023 sur les BB dans la prise en charge de l'hypertension artérielle.

[High blood pressure and glaucoma : an inextricable link]. / Hypertension artérielle et glaucome : un lien inextricable.

The relationship between glaucoma and hypertension is complex. Intraocular pressure is the main modifiable risk factor for glaucoma. Literature describes hypertension as being linked to glaucomatous damage, although the mechanisms are not fully understood. Therefore, glaucoma screening is recommended for hypertensive individuals over 60 years old. The relationships between ocular, arterial pressure, and ocular perfusion pressure, and their impact on optic nerve perfusion, make coordinated management of these elements crucial. Hypertension, hypotension, extreme variability, nocturnal dipping, and overtreatment with antihypertensive drugs can increase the incidence and/or progression of glaucoma. This critical review discusses the causative, clinical, and therapeutic elements to consider in the management of these two pathologies.

La relation entre le glaucome et l'hypertension artérielle (HTA) est complexe. La pression intraoculaire est le principal facteur de risque modifiable du glaucome. Selon la littérature, l'HTA entraînerait un dommage glaucomateux, sans que les mécanismes soient entièrement compris. Le dépistage du glaucome est ainsi recommandé chez les hypertendus de plus 60 ans. La relation entre pression oculaire, artérielle et pression de perfusion oculaire, ainsi que leur impact sur la perfusion du nerf optique, rendent fondamentale la gestion coordonnée de ces deux pathologies. L'HTA, l'hypotension artérielle, la variabilité extrême ou le dipping nocturne, tout comme le surtraitement par antihypertenseurs, peuvent augmenter l'incidence et/ou la progression du glaucome.. Cette revue critique discute des éléments causatifs, cliniques et thérapeutiques à considérer dans la prise en charge de ces deux pathologies.

Progress in diagnosis and treatment of hypertension combined with left ventricular hypertrophy.

BACKGROUND: Hypertension, a worldwide cardiovascular issue, is known to result in significant damage to the left ventricle. Left ventricular hypertrophy refers to an increase in ventricular mass, which is not only the primary independent risk factor for cardiovascular disease onset but also independently related to the risk of death. OBJECTIVES: We sought to synthesize the existing literature on the occurrence and correlation between hypertension and left ventricular hypertrophy and the progress. METHODS: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in the Pubmed database with no language restrictions, as of September 1, 2024. RESULTS: Of the 8110 articles retrieved, 110 were finally included. The selected articles were published between 1987 and 2024, with 55.5% (61/110) of the studies in the last five years and 14.5% (16/110) of 2024. The studies covered diagnosis, epidemiology, pathophysiology, prognosis, and treatment of hypertension with left ventricular hypertrophy. CONCLUSION: The literature reviewed suggests that studies on hypertension combined with left ventricular hypertrophy covered a variety of clinical progress, especially the clinical trial results of some new drugs that may bring great hope for treatment.

Continuous development of 3D echocardiographic technology may provide more accurate measurements; however, studies with the aim of establishing standard reference values remain in exploratory stages.The field of metabolomics offers a promising approach for studying biomarkers by detecting changes in metabolites associated with physiological or pathological processes induced by diseases. This avenue of research holds potential for the early diagnosis and assessment of LVH.Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin are initially indicated for conditions other than left ventricular hypertrophy (LVH); however, emerging evidence suggests that these medications may possess potential clinical value in reversing LVH.

Enhancing hypertension education of community health extension workers in Nigeria's federal capital territory: the impact of the extension for community healthcare outcomes model on primary care, a quasi-experimental study.

BACKGROUND: Healthcare workers (HCWs) including community health extension workers (CHEWs) in the Federal Capital Territory, Nigeria participated in a hypertension training series following the Extension for Community Healthcare Outcomes (ECHO) model which leverages technology and a practical peer-to-peer learning framework to virtually train healthcare practitioners. We sought to evaluate the patient-level effects of the hypertension ECHO series. METHODS: HCWs from 12 of 33 eligible primary healthcare centers (PHCs) in the Hypertension Treatment in Nigeria Program (NCT04158154) were selected to participate in a seven-part hypertension ECHO series from August 2022 to April 2023. Concurrent Hypertension Treatment in Nigeria Program patient data were used to evaluate changes in hypertension treatment and control rates, and adherence to Nigeria's hypertension treatment protocol. Outcomes were compared between the 12 PHCs in the ECHO program and the 21 which were not. RESULTS: Between July 2022 and June 2023, 16,691 PHC visits were documented among 4340 individuals (ECHO: n = 1428 [33%], non-ECHO: n = 2912 [67%]). Patients were on average (SD) 51.5 (12.0) years old, and one-third were male (n = 1372, 32%) with no differences between cohorts in either characteristic (p ≥ 0.05 for both). Blood pressures at enrollment were higher in the ECHO cohort compared to the non-ECHO cohort (systolic p < 0.0001 and diastolic p = 0.0001), and patients were less likely to be treated with multiple medications (p < 0.0001). Treatment rates were similar at baseline (ECHO: 94.0% and Non-ECHO: 94.7%) and increased at a higher rate (interaction p = 0.045) in the ECHO cohort over time. After adjustment for baseline and within site variation, the difference was attenuated (interaction p = 0.37). Over time, control rates increased and medication protocol adherence decreased, with no differences between cohorts. Staffing levels, adult patient visits, and rates of hypertension screening and empanelment were similar between ECHO and non-ECHO cohorts (p ≥ 0.05 for all). CONCLUSIONS: The ECHO series was associated with moderately increased hypertension treatment rates and did not adversely affect staffing or clinical capacity among PHCs in the Federal Capital Territory, Nigeria. These results may be used to inform strategies to support scaling hypertension education among frontline HCWs throughout Nigeria, and use of the ECHO model for CHEWs. TRIAL REGISTRATION: The Hypertension Treatment in Nigeria Program was prospectively registered on November 8, 2019 at www. CLINICALTRIALS: gov (NCT04158154; https://clinicaltrials.gov/ct2/show/NCT04158154 ).

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

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.

A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide. Methods: A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use. Findings: Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%). Interpretation: Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access.