A novel thermotolerant L-rhamnose isomerase variant for biocatalytic conversion of D-allulose to D-allose.

A novel L-rhamnose isomerase was identified and cloned from an extreme-temperature aquatic habitat metagenome. The deduced amino acid sequence homology suggested the possible source of this metagenomic sequence to be Chloroflexus islandicus. The gene expression was performed in a heterologous host, Escherichia coli, and the recombinant protein L-rhamnose isomerase (L-RIM) was extracted and purified. The catalytic function of L-RIM was characterized for D-allulose to D-allose bioconversion. D-Allose is a sweet, rare sugar molecule with anti-tumour, anti-hypertensive, cryoprotective, and antioxidative properties. The characterization experiments showed L-RIM to be a Co++- or Mn++-dependent metalloenzyme. L-RIM was remarkably active (~ 80%) in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges. Optimal L-RIM activity with D-allulose as the substrate occurred at pH 7.0 and 75 °C. The enzyme was found to be excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively. L-RIM catalysis conducted at slightly acidic pH of 6.0 and 70 °C achieved biosynthesis of about 30 g L-1 from 100 g L-1 D-allulose in 3 h. KEY POINTS: • The present study explored an extreme temperature metagenome to identify a novel gene that encodes a thermostable l-rhamnose isomerase (L-RIM) • L-RIM exhibits substantial (80% or more) activity in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges • L-RIM is excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively.

Antihypertensive Effect of New Agonist of Adenosine Receptor in Spontaneously Hypertensive Rats. / Efeito Anti-Hipertensivo de Novos Agonistas do Receptor de Adenosina em Ratos Espontaneamente Hipertensos.

BACKGROUND: Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension. OBJECTIVE: To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors. METHODS: Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 µM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 µmol/kg of the selected compound LASSBio-2062. RESULTS: Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 µM, respectively. LASSBio-2062 (30 µmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062. CONCLUSIONS: The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension.

FUNDAMENTO: A hipertensão arterial sistêmica é um fator de risco para disfunções cardíacas, renais e metabólicas. A busca por novas estratégias para prevenir e tratar doenças cardiovasculares levou à síntese de novas N-acilidrazonas para produzir efeito anti-hipertensivo. Os receptores de adenosina são um alvo alternativo para reduzir a pressão arterial devido à sua ação vasodilatadora e propriedades antioxidantes, que podem reduzir o estresse oxidativo característico da hipertensão arterial sistêmica. OBJETIVO: Avaliar o perfil anti-hipertensivo de novos compostos contendo selênio desenvolvidos para melhorar sua interação com os receptores de adenosina. MÉTODOS: Foi avaliada a reatividade vascular, registrando-se a tensão isométrica da aorta torácica pré-contraída de ratos Wistar machos após exposição a concentrações crescentes de cada derivado (0,1 a 100 µM). Para investigar o efeito anti-hipertensivo em ratos espontaneamente hipertensos, foram determinadas a pressão arterial sistólica, pressão arterial diastólica, pressão arterial média e a frequência cardíaca após administração intravenosa de 10 e 30 µmol/kg do composto selecionado LASSBio-2062. RESULTADOS: Os compostos denominados LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092 e LASSBio-2093 promoveram vasodilatação com concentrações efetivas médias de 15,5 ± 6,5; 14,6 ± 2,9; 18,7 ± 9,6; 6,7 ± 4,1; > 100; 6,0 ± 3,6; 37,8 ± 11,8; e 15,9 ± 5,7 µM, respectivamente. O LASSBio-2062 (30 µmol/kg) reduziu a pressão arterial média em ratos espontaneamente hipertensos de 124,6 ± 8,6 para 72,0 ± 12,3 mmHg (p < 0,05). A ativação do receptor de adenosina subtipo A3 e dos canais de potássio parece estar envolvida no efeito anti-hipertensivo do LASSBio-2062. CONCLUSÕES: O novo agonista do receptor de adenosina e ativador dos canais de potássio é um potencial agente terapêutico para o tratamento da hipertensão arterial sistêmica.

Effects of Achieving Rapid, Intensive, and Sustained Blood Pressure Reduction in Intracerebral Hemorrhage Expansion and Functional Outcome.

BACKGROUND AND OBJECTIVES: The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. METHODS: Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP ≥150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement ≤60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score ≥4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. RESULTS: We included 312 patients (mean age 70.2 ± 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement ≤60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 ± 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). DISCUSSION: Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with spontaneous ICH and initial SBP ≥150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.

[ANMCO Scientific statement on combination therapies and polypill in secondary prevention]. / Scientific statement ANMCO sulla semplificazione del regime terapeutico farmacologico in prevenzione secondaria.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an ANMCO scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socioeconomic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Prevalence and associated risk factors of resistant hypertension among Chinese hypertensive patients in primary care setting.

INTRODUCTION: Hypertension (HT) is a major public health problem globally, and it is the commonest chronic disease with a prevalence of 27% among people aged 15 years or above in Hong Kong. There is emerging literature confirmed that patients with resistant hypertension (RHT) give its increased risk for adverse clinical outcomes and higher rate of documented target organ damage. This study aims to identify the prevalence of RHT among Chinese hypertensive patients managed in public primary care setting of Hong Kong and exploring its associated risk factors. METHODOLOGY: This is a cross-sectional descriptive study. Chinese hypertensive patients aged 30 or above with regular follow-up between 1st July 2019 and 30th June 2020 in 10 public primary care clinics under the Hospital Authority of Hong Kong were included. Demographic data, clinical parameters and drug profile of patients were retrieved from its computerized record system. The prevalence of RHT was identified and the associated risk factors of RHT were explored by multivariate logistic regression analysis. RESULTS: Among the 538 sampled Chinese hypertensive patients, the mean age was 67.4 ± 11.5 years old, and 51.9% were female. The mean duration of hypertension was 10.1 ± 6.4 years, with a mean systolic and diastolic blood pressure of 128.8 ± 12.3 and 72.9 ± 10.8 mmHg respectively. 40 out of 538 patients were found to have RHT, giving an overall prevalence of 7.43%. Four factors were found to be associated with increased risk of RHT, in ascending order of odds ratio: duration of hypertension (OR 1.08), male gender (OR 2.72), comorbid with type 2 diabetes mellitus (T2DM, OR 2.99), and congestive heart failure (CHF, OR 5.39). CONCLUSION: The prevalence of RHT among Chinese hypertensive patients in primary care setting of Hong Kong is 7.43%. RHT is more common in male patients, patients with longer duration of hypertension, concomitant T2DM and CHF. Clinicians should be vigilant when managing these groups of patients and provide aggressive treatment and close monitoring.

Should renin-angiotensin system inhibitors be held prior to major surgery?

Many patients undergoing surgical procedures have a history of hypertension, diabetes mellitus, heart failure, or a combination. Often, these conditions involve the chronic use of a renin-angiotensin system inhibitor, including angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Observational studies have suggested that continuing ACEIs/ARBs before major noncardiac surgery can increase the risk of intraoperative hypotension, which might drive postoperative complications such as acute kidney injury, myocardial injury, or stroke. Strong recommendations on how to manage ACEIs/ARBs before surgery are, however, lacking owing to insufficient evidence, mostly limited to data from observational studies. Recently, the SPACE trial investigated the impact of preoperative management of ACEIs/ARBs on postoperative myocardial injury. Myocardial injury occurred in 48.3% patients randomised to discontinue and 41.3% patients randomised to continue ACEI/ARB (odds ratio for continuing: 0.77, 95% confidence interval 0.45-1.31). Patients randomised to the 'Stop' group experienced more postoperative hypertension. In a post hoc analysis, patients randomised to the 'Continue' group with low preoperative NT-proBNP concentrations (<100 pg ml-1) experienced less myocardial injury after surgery than the 'Stop' group, whereas no significant difference was observed in patients with elevated preoperative NT-proBNP concentrations. The SPACE trial provides important and new reassuring data on the safety of continuing ACEIs/ARBs before major surgery, challenging previous beliefs.

Management of Inpatient Elevated Blood Pressures : A Systematic Review of Clinical Practice Guidelines.

BACKGROUND: Management of elevated blood pressure (BP) during hospitalization varies widely, with many hospitalized adults experiencing BPs higher than those recommended for the outpatient setting. PURPOSE: To systematically identify guidelines on elevated BP management in the hospital. DATA SOURCES: MEDLINE, Guidelines International Network, and specialty society websites from 1 January 2010 to 29 January 2024. STUDY SELECTION: Clinical practice guidelines pertaining to BP management for the adult and older adult populations in ambulatory, emergency department, and inpatient settings. DATA EXTRACTION: Two authors independently screened articles, assessed quality, and extracted data. Disagreements were resolved via consensus. Recommendations on treatment targets, preferred antihypertensive classes, and follow-up were collected for ambulatory and inpatient settings. DATA SYNTHESIS: Fourteen clinical practice guidelines met inclusion criteria (11 were assessed as high-quality per the AGREE II [Appraisal of Guidelines for Research & Evaluation II] instrument), 11 provided broad BP management recommendations, and 1 each was specific to the emergency department setting, older adults, and hypertensive crises. No guidelines provided goals for inpatient BP or recommendations for managing asymptomatic moderately elevated BP in the hospital. Six guidelines defined hypertensive urgency as BP above 180/120 mm Hg, with hypertensive emergencies requiring the addition of target organ damage. Hypertensive emergency recommendations consistently included use of intravenous antihypertensives in intensive care settings. Recommendations for managing hypertensive urgencies were inconsistent, from expert consensus, and focused on the emergency department. Outpatient treatment with oral medications and follow-up in days to weeks were most often advised. In contrast, outpatient BP goals were clearly defined, varying between 130/80 and 140/90 mm Hg. LIMITATION: Exclusion of non-English-language guidelines and guidelines specific to subpopulations. CONCLUSION: Despite general consensus on outpatient BP management, guidance on inpatient management of elevated BP without symptoms is lacking, which may contribute to variable practice patterns. PRIMARY FUNDING SOURCE: National Institute on Aging. (PROSPERO: CRD42023449250).

Current Trends in Hypertension Identification and Management: Insights from the National Health and Nutrition Examination Survey (NHANES) Following the 2017 ACC/AHA High Blood Pressure Guidelines.

BACKGROUND: Hypertension is a global health issue associated with increased cardiovascular morbidity and mortality. This study aimed to investigate contemporary hypertension identification and management trends following the 2017 American College of Cardiology/American Heart Association guidelines. METHODS AND RESULTS: Data from the National Health and Nutrition Examination Survey conducted from 2017 to 2020 were analyzed. Participants between 20 and 79 years of age were included. Participants were stratified into different treatment groups based on indication and guideline adherence. Descriptive statistics were used to compare medication use, diagnosis rates, and blood pressure control. A total of 265 402 026 people met the inclusion criteria, of which 19.0% (n=50 349 209) were undergoing guideline antihypertensive management. In the guideline antihypertensive management group, a single antihypertensive class was used to treat 45.7% of participants, and 55.2% had uncontrolled blood pressure. Participants not undergoing guideline antihypertensive management qualified for primary prevention in 11.5% (n=24 741 999) of cases and for secondary prevention in 2.4% (n=5 070 044) of cases; of these, 66.3% (n=19 774 007) did not know they may have hypertension and were not on antihypertensive medication. CONCLUSIONS: Adherence to guidelines for antihypertensive management is suboptimal. Over half of patients undergoing guideline treatment had uncontrolled blood pressure. One-third of qualifying participants may not be receiving treatment. Education and medical management were missing for 2 in 3 qualifying participants. Addressing these deficiencies is crucial for improving blood pressure control and reducing cardiovascular event outcomes.

Cost-Effectiveness of a Workplace-Based Hypertension Management Program in Real-World Practice in the Kailuan Study.

BACKGROUND: In 2009, a workplace-based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost-effectiveness of this program remains unclear. METHODS AND RESULTS: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10-year follow-up data, we estimated costs, quality-adjusted life years (QALYs), life-years, and incremental cost-effectiveness ratios (ICERs) for workplace-based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10-year follow-up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life-years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost-effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life-year gained, respectively, when comparing workplace-based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness-to-pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost-effective in 10 000 samples. CONCLUSIONS: Workplace-based management, compared with routine care for Chinese men with hypertension, could be cost-effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

Population Trends of New Prescriptions for Antihyperglycemics and Antihypertensives Between 2014 and 2022.

BACKGROUND: In the wake of pandemic-related health decline and health care disruptions, there are concerns that previous gains for cardiovascular risk factors may have stalled or reversed. Population-level excess burden of drug-treated diabetes and hypertension during the pandemic compared with baseline is not well characterized. We evaluated the change in incident prescription claims for antihyperglycemics and antihypertensives before versus during the pandemic. METHODS AND RESULTS: In this retrospective, serial, cross-sectional, population-based study, we used interrupted time series analyses to examine changes in the age- and sex-standardized monthly rate of incident prescriptions for antihyperglycemics and antihypertensives in patients aged ≥66 years in Ontario, Canada, before the pandemic (April 2014 to March 2020) compared with during the pandemic (July 2020 to November 2022). Incident claim was defined as the first prescription filled for any medication in these classes. The characteristics of patients with incident prescriptions of antihyperglycemics (n=151 888) or antihypertensives (n=368 123) before the pandemic were comparable with their pandemic counterparts (antihyperglycemics, n=97 015; antihypertensives, n=146 524). Before the pandemic, monthly rates of incident prescriptions were decreasing (-0.03 per 10 000 individuals [95% CI, -0.04 to -0.01] for antihyperglycemics; -0.14 [95% CI, -0.18 to -0.10] for antihypertensives). After July 2020, monthly rates increased (postinterruption trend 0.31 per 10 000 individuals [95% CI, 0.28-0.34] for antihyperglycemics; 0.19 [95% CI, 0.14-0.23] for antihypertensives). CONCLUSIONS: Population-level increases in new antihyperglycemic and antihypertensive prescriptions during the pandemic reversed prepandemic declines and were sustained for >2 years. Our findings are concerning for current and future cardiovascular health.

Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.

Treatment for Resistant Hypertension Under the Guidance of Pharmacogenomics: A Randomised Controlled Open-Label Trial.

OBJECTIVE: To evaluate the efficacy and safety of pharmacogenomics (PGx)-guided treatment in individuals with resistant hypertension (RH). STUDY DESIGN: Randomised controlled open-label study. Place and Duration of the Study: Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China, from June 2019 to November 2021. METHODOLOGY: The study assigned RH patients to two groups. The intervention group (IG) received 12 weeks of PGx-guided treatment, while the control group (CG) followed a consensus-based approach. Examining 10 genes and their alleles with 31 antihypertensive drugs in the IG, the study provided specific medication advice. The primary outcome measured the difference in office systolic blood pressure (SBP) change from baseline at 12 weeks. Secondary outcomes included changes in diastolic blood pressure (DBP), hepatic and renal function, and major adverse cardiovascular events. RESULTS: Fifty-nine patients from the First Hospital of China Medical University participated, with 29 in the IG and 30 in the CG. Significant differences were noted in SBP reduction (IG: 31.26 ± 18.64 mmHg; CG: 14.61 ± 17.74 mmHg; p=0.001) and DBP reduction (IG: 19.61 ± 17.32 mmHg; CG: 7.81 ± 11.23 mmHg; p = 0.003) after 12 weeks. One IG patient had a heart attack, and one CG subject developed heart failure. At week 12, hepatic insufficiency was observed in one IG patient and six CG patients, while renal insufficiency occurred in five patients of both groups. CONCLUSION: Treatment guided by PGx demonstrated significant reductions in both SBP and DBP compared to consensus-based treatment. KEY WORDS: Resistant hypertension, Treatment, Pharmacogenomics, Clinical study.

HELLP Syndrome at 20 Gestational Weeks Managed Using the Mississippi Protocol: A Case Report.

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.

Systematic Review Article: New Drug Strategies for Treating Resistant Hypertension-the Importance of a Mechanistic, Personalized Approach.

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs  as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.

Effectiveness of treatment of arterial hypertension in Central Europe from 1972 to 2022.

BACKGROUND: Hypertension is a leading cause of cardiovascular disease. This review examines the literature on hypertension control in the Czech Republic from 1972 to 2022 addressing limited data on its effectiveness. METHODS: A literature review was conducted covering the period from 1972 to 2022, utilizing MEDLINE (PubMed), Web of Science, and Scopus databases. Articles were selected based on title and abstract evaluations, with full-text reviews performed as needed. Thirteen studies involving 44,990 participants were included in this review. RESULTS: Control rates increased from 2.8% (men) and 5.2% (women) in 1985 to 32.3% (men) and 37.4% (women) from 2015 to 2018. Women showed better blood pressure control. Specialised centres achieved higher success (48%) than general practitioners (18.4%). Diabetic patients had a lower percentage (29.1%) of patients meeting their target values (<130/80 mmHg) compared to non-diabetic patients, who had a higher percentage (60.6%) meeting their target values (<140/90 mmHg). CONCLUSION: Hypertension treatment success rate in the Czech Republic improved significantly over the last 50 years and is currently comparable to that of other European countries with similar healthcare resources. However, it still remains suboptimal and lags behind the countries with the most successful treatment outcomes (Tab. 3, Fig. 1, Ref. 37). Text in PDF www.elis.sk Keywords: hypertension, treatment, effectiveness, Czech Republic, blood pressure.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife.

Importance: Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. Objective: To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. Design, Setting, and Participants: The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Exposures: Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Main Outcomes and Measures: Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Results: Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Conclusions and Relevance: Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Adherence to pharmacological therapy in patients with hypertension: protocol of a qualitative study by focus groups.

INTRODUCTION: Non-adherence to antihypertensive medication significantly contributes to inadequate blood pressure control. Regarding non-pharmacological interventions to improve medication adherence, the question remains of which interventions yield the highest efficacy.Understanding the complementary perspectives of patients and healthcare professionals can be valuable for designing strategies to enhance medication adherence. Few studies explored the perspectives of patients and healthcare professionals regarding medication adherence. None of them focused specifically on adherence to pharmacological therapy for hypertension in Portugal.Considering the high prevalence of non-adherence and its location-specific aspects, the priority should be identifying its barriers and developing tactics to address them.This study aims to gather the perspectives of patients with hypertension and healthcare professionals such as family doctors, nurses and community pharmacists from Portugal, regarding the most effective strategies to enhance antihypertensive medication adherence and to understand the factors contributing to non-adherence. METHODS AND ANALYSES: We will conduct qualitative research through synchronous online focus groups of 6-10 participants. Some groups will involve patients with hypertension, while others will include family doctors, nurses and community pharmacists. The number of focus groups will depend on the achievement of theoretical saturation. A purposive sample will be used. Healthcare participants will be recruited via email, while patients will be recruited through their family doctors.The moderator will maintain neutrality while ensuring interactive contributions from every participant. Participants will be encouraged to express their opinions on the meeting summary. Meetings will be recorded and transcribed.Two researchers will perform content analyses using MAXQDA V.12 through comparative analyses and subsequent consensus. A third researcher will review the analyses. The results will be presented narratively. ETHICS AND DISSEMINATION: The Ethics Committee of the University of Coimbra has approved this study with the number: CE-026/2021. The results will be disseminated via peer-reviewed publications and national and international conferences.