Calcium Antagonists Research Articles

Heightened mitochondrial respiration in CF cells is normalised by triple CFTR modulator therapy through mechanisms involving calcium

BackgroundCystic fibrosis (CF) is associated with increased resting energy expenditure. However, the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has resulted in a paradigm shift in nutritional status for many people with CF, with increase body mass index and reduction in the need for nutritional support. While these changes are likely to reflect improved clinical status and an associated downregulation of energy expenditure, they may also reflect drug-induced alterations in metabolic perturbations within CF cells. We hypothesise that some of these changes relate to normalisation of mitochondrial respiration in CF. MethodsUsing wild-type (WT) and F508del/F508del CFTR human bronchial epithelial cell lines (HBE cell lines) and baby hamster kidney (BHK) cells we examined the impact of ETI on cellular metabolism. We monitored mitochondrial respiration, using Seahorse extracellular flux assays and monitored mitochondrial reactive oxygen species (mROS) and intracellular calcium levels by flow cytometry. ResultsIncreased mitochondrial respiration was found in HBE cell lines and BHK cells expressing CFTR F508del/F508del when assessing basal, maximal, spare respiratory capacities and ATP production, as well as increased mitochondrial ROS generated via forward electron transport. ETI significantly decreased basal, maximal, spare respiratory capacity and ATP production to WT levels or below. Calcium blocker, BAPTA-AM normalised mitochondrial respiration, suggesting a calcium-mediated mechanism. ETI decreased intracellular calcium levels in CF cells to the same extent as BAPTA-AM, highlighting the importance of calcium and chloride in mitochondrial respiration in CF. ConclusionsCF cell lines exhibit increased mitochondrial respiration, which can be downregulated by ETI therapy through mechanisms involving calcium.

Nimodipine Used with Vincristine: Protects Schwann Cells and Neuronal Cells from Vincristine-Induced Cell Death but Increases Tumor Cell Susceptibility.

The chemotherapeutic agent vincristine is commonly used for a variety of hematologic cancers, as well as solid tumors of the head and neck, bronchial carcinoma, as part of the procarbazine, lomustine and vincristine (PCV) regimen, for glioma. Damage to nerve tissue (neuropathy) is often dose-limiting and restricts treatment. Nimodipine is a calcium antagonist that has also shown neuroprotective properties in preliminary studies. In this approach here, we investigated the effects of the combination of vincristine and nimodipine on three cancer cell lines (A549, SAS and LN229) and neuronal cells (RN33B, SW10). Fluorescence microscopy, lactate dehydrogenase (LDH) assays and Western blot analyses were used. Nimodipine was able to enhance the cell death effects of vincristine in all tumor cells, while neuronal cells were protected and showed less cell death. There was an opposite change in the protein levels of Ak strain transforming/protein kinase B (AKT) in tumor cells (down) and neuronal cells (up), with simultaneous increased protein levels of cyclic adenosine monophosphate response element-binding protein (CREB) in all cell lines. In the future, this approach may improve tumor response to chemotherapy and reduce unwanted side effects such as neuropathy.

Influence of autonomic nervous dysfunction on eating during hemodialysis sessions: An observational study.

Although some studies have indicated that eating during hemodialysis may induce hypotension and cardiovascular events, some patients still consume food during their treatment. This prospective study was conducted to determine whether the need to eat during hemodialysis treatment was related to abnormal glucose metabolism and autonomic nerve dysfunction. Seventy patients were enrolled in this study, and their demographic features and various laboratory parameters were analyzed. At each routine hemodialysis visit, predialysis, intradialysis, and postdialysis blood pressure measurements were systematically conducted. A 24-hour ambulatory electrocardiogram (ECG) was performed during the hemodialysis interval, and heart rate variability (HRV) values were calculated. Additionally, whether the patients ate during the hemodialysis treatments was recorded. Another 20 people who underwent physical examinations during the same period and were matched for sex and age were included in the control group. The HRV values of the hemodialysis patients were generally lower than those of the control group. Univariate analysis revealed significant differences in sex, age, calcium antagonist use, blood calcium levels, insulin levels, diastolic blood pressure (DBP) measurements, and HRV indices between hemodialysis patients who ate and those who did not eat during hemodialysis (P < .05), whereas there were no significant differences in diabetes status or in the hemoglobin, albumin, blood glucose and C-peptide levels (P > .05). Multivariate analysis revealed that low values for very low frequency (VLF) and postdialysis DBP were risk factors for fasting intolerance during hemodialysis treatments. Autonomic dysfunction may affect whether hemodialysis patients tolerate fasting during dialysis. VLF evaluation may provide information that can be used to develop a more reasonable intradialytic nutritional supplementation method.

9: Extracorporeal Membrane Oxygenation Support in Adult Patients with Calcium Channel Blocker Toxicity - An ELSO Registry Analysis

9: Extracorporeal Membrane Oxygenation Support in Adult Patients with Calcium Channel Blocker Toxicity - An ELSO Registry Analysis

Pola Peresepan Obat Antihipertensi pada Pasien BPJS Kesehatan dibeberapa Apotek Daerah Bandung Periode November 2023

Hypertension is a non-communicable disease that always increases every year. Hypertension is known as a silent killer because patients who suffer from hypertension rarely feel the symptoms. Common symptoms of hypertension can be headaches in the back of the neck, blurred vision, and others. The blood pressure of hypertension sufferers is above 140/90 mmHg. This study aims to see the pattern of prescribing antihypertensive drugs in BPJS Kesehatan patients including gender, age, patient diagnosis, and combination of antihypertensive drug classes. The method used is descriptive observational research. This study was conducted using 195 prescriptions in the period November 2023. The results obtained were that hypertension sufferers were more dominated by women with a total of 131 sufferers with a percentage of 67% compared to men with a total of 64 sufferers with a percentage of 33%. The age most affected by hypertension is people aged 51 years - 75 years with a total of 143 people and a percentage of 73.33%. 92 of 195 (47.18%) patients did not have other diseases such as diabetes mellitus, hyperlipidemia, heart, GI, and asthma. Single therapy of antihypertensive drugs was most commonly prescribed by doctors with a total of 127 patients with a presentation of 65.13% compared to patients who used combination therapy of two or more antihypertensive drugs. Calcium antagonist or CCB drugs were most commonly used by BPJS patients at several pharmacies in the Bandung area used in the prescription analysis with a total of 107 patients with a percentage of 54.87%.

Evolving the Role of Black Race in Hypertension Therapeutics.

Black race has been used to guide antihypertensive drug selection for Black patients based on predominant between race (same drug) and intra-race (different drugs) blood pressure (BP) response patterns. Accordingly, thiazide diuretics and calcium antagonists have been recommended over renin-angiotensin system (RAS) inhibitors (angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors) and beta blockers for Black patients. Current antihypertensive drug prescribing reflects historical guidance as calcium antagonists and thiazide diuretics are prescribed more and RAS blockers less in Black than White patients. Hypertension control rates in Blacks, lag those for Whites despite their greater use of combination drug therapy and lesser use of monotherapy. This is also true across drug regimens containing any of the 4 recommended classes for initial therapy as well as for evidence-based combination drug therapy (calcium antagonist or thiazide diuretic + RAS blocker) regimens for which there is no known racial disparity in BP response. Current recommendations acknowledge the need for combination drug therapy in most, especially in Black patients. One exemplary comprehensive hypertension control program achieved >80% control rates in Black and White patients with minimal racial disparity while utilizing a race-agnostic therapeutic algorithm. Black patients manifest robust, if not outsized, BP responses to diet/lifestyle modifications. Importantly, race neither appears to be a necessary nor sufficient consideration for the selection of effective drug therapy. Accordingly, we urge the initiation of adequately intense race-agnostic drug therapy coupled with greater emphasis on diet/lifestyle modifications for Black patients as the cornerstone of a race-informed approach to hypertension therapeutics.

The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Long-Term Systemic Use of Calcium Channel Blockers and Incidence of Primary Open-Angle Glaucoma

PurposeTo evaluate the association between the systemic use of calcium channel blockers (CCBs) and primary open-angle glaucoma (POAG) using a diverse nationwide dataset. DesignRetrospective cohort study Subjects213,424 individuals aged 40 years and older in the National Institutes of Health (NIH) All of Us dataset, notable for its demographic, geographic and medical diversity and inclusion of historically underrepresented populations. Patients with a diagnosis of POAG prior to use of any kind of anti-hypertensive medication were excluded. MethodsBivariate and multivariable regression analyses were performed to evaluate associations between CCB use and POAG. CCB use was further divided into exposure to dihydropyridine CCBs and non-dihydropyridine CCBs, and subgroup analyses were performed using Chi-square and Fisher’s tests. Main Outcome MeasuresDiagnosis of POAG ResultsWithin our cohort, 2,772 participants (1.3%) acquired a diagnosis of POAG, while 210,652 (98.7%) did not. Among patients who developed POAG, the mean age was 73.3 years, 52.5% were female, and 48.2% identified as White. Among POAG patients, 32.6% used one or more CCB, 28.2% used a dihydropyridine CCB, and 2.2% used a non-dihydropyridine CCB. In bivariate analysis, use of any CCBs was associated with an increased risk of POAG (OR: 1.29, 95% CI: 1.27-1.31, p<0.001). In multivariable analysis adjusting for age, gender, race, ethnicity, and comorbidities such as diabetes, hyperlipidemia, and hypertension, use of any CCBs remained associated with an increased risk of developing POAG (OR: 1.52, 95% CI: 1.33-1.74, p<0.001). When stratified by type of CCB, the use of dihydropyridine CCBs (OR: 1.31, 95% CI: 1.14-1.50, p<0.001) was associated with increased POAG risk. ConclusionsUse of dihydropyridine calcium channel blockers was associated with a significantly higher risk of developing POAG, both before and while adjusting for demographic factors and comorbid medical conditions.

Quantification of Oversupply of Chronic Disease Medications among Patients Aged ≥55 Years in Japan.

Medication waste may be caused by medication oversupply; however, the degree of medication oversupply in Japan is unclear. This study aimed to quantify the degree of oversupply of chronic disease medications per patient, the proportion of oversupplied patients, and the excess days and costs of the oversupplied medications in Japan. This retrospective nationwide cohort study using a large insurance claims database from Japan was conducted in patients aged ≥55 years who received one or a combination of the following five classes of medications dispensed in FY 2019: third-generation calcium antagonists, angiotensin 2 receptor blockers, statins, dipeptidyl peptidase-4 inhibitors, and biguanides. Medications with the same ingredient having the same specification were treated as the same medication. Medication oversupply was defined as a medication possession ratio (MPR) during persistence >1.0. The proportions of oversupplied patients and excessively oversupplied patients with ≥30 excess days/year were approximately 16 and 1-2% for all drug classes, respectively. Three-quarters of the oversupplied patients had fewer excess day (≤14/year), and the median oversupplied medication cost was less than 1000 yen/year for all classes. However, there was a patient with oversupplied medication estimated as 983 excess days per year and a patient with oversupplied medication costs of nearly 90000 yen per year. Using the MPR and excess days as indicators, it is necessary to accelerate estimation of the oversupply per patient, as well as the development of patient intervention strategies and a national system to reduce medication oversupply.

Lifestyle counseling in patients with hypertension in primary health care and its association with antihypertensive pharmacotherapy.

The study aimed to investigate differences in hypertensive- and cardio-preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men=1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.

Identifying molecular subgroups of patients with preeclampsia through bioinformatics.

Preeclampsia (PE) is a pregnancy-related disorder associated with serious complications. Its molecular mechanisms remain undefined; hence, we aimed to identify molecular subgroups of patients with PE using bioinformatics to aid treatment strategies. R software was used to analyze gene expression data of 130 patients with PE and 138 healthy individuals from the Gene Expression Omnibus database. Patients with PE were divided into two molecular subgroups using the unsupervised clustering learning method. Clinical feature analysis of subgroups using weighted gene co-expression network analysis showed that the patients in subgroup I were primarily characterized by early onset of PE, severe symptoms at disease onset, and induced labor as the main delivery method. Patients in subgroup II primarily exhibited late PE onset, relatively mild symptoms, and natural delivery as the main delivery method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the significant enrichment of calcium ion channels in subgroup II indicated the potential efficacy of calcium antagonists and magnesium sulfate therapy. In conclusion, the establishment of PE molecular subgroups can aid in diagnosing and treating PE.

An Retrospective Study of Commonly Prescribed Antiepileptic Drugs and it’s Interaction with Other Drugs which are Already in use Respect to Other Disease

Antiepileptic drugs (AED) are increasingly used in the treatment of some non-epileptic neurological diseases and psychiatric diseases. Most of the available data on the use of these agents in clinical conditions other than epilepsy are from case series, uncontrolled studies, or small randomized clinical trials, and their apparent efficacy requires confirmation in well-designed large phase III trials. Interactions between antiepileptic drugs or between antiepileptic drugs and other drugs can be pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions include changes in absorption, distribution ,or eliminate , while pharmacodynamic interactions include synergism and antagonism at the site ,of action. Most clinically significant antiepileptic drug interactions are due to induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronide enzymes (as well as P-glycoprotein) and may reduce the effectiveness of concomitantly administered drugs such as oral anticoagulants, calcium antagonists, antimicrobial steroids. Mechanism Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties and less tendency to produce interactions mediated by enzyme induction. In contrast to enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, which can increase serum concentrations leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include valproic-induced increases in serum concentrations of phenobarbital and lamotrigine. There are also interactions where other drugs induce or inhibit the metabolism of antiepileptic drugs. Examples include an increase in serum carbamazepine concentration due to erythromycin and a decrease in serum lamotrigine concentration due to estrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the combined therapeutic synergy of valproic acid and lamotrigine, or adverse effects, such as the mutual potentiation of neurotoxicity in patients treated with a combination of sodium channel blocking antiepileptic drugs. AEDs are also used to treat psychiatric conditions, particularly bipolar disorder. To date, the AEDs most commonly used to treat this disorder have been carbamazepine and valproic acid, which have shown manic efficacy and likely long-term mood-stabilizing effects in many bipolar patients, including those who are lithium-intolerant. . The availability of new generation AEDs has expanded treatment options for bipolar disorder. Lamotrigine, oxcarbazepine, gabapentin, and topiramate appear to show promise in the treatment of bipolar disorder, both as monotherapy and in combination with traditional mood stabilizers. In addition, newer AEDs appear to have a more favorable tolerability and drug interaction profile than older compounds, thus improving compliance

European guidelines for the treatment of arterial hypertension 2023: new trends

The treatment strategy for arterial hypertension is aimed at controlling blood pressure levels, as well as preventing serious cardiovascular complications and affecting the prognosis of the disease. Therefore, pharmacotherapy of arterial hypertension is given great importance as a guide to the treatment of patients in real practice. The new 2023 European Society Guidelines for the diagnosis and treatment of hypertension were developed after a thorough analysis of studies in the field of arterial hypertension, and were not limited to RCTs only, but also included realistic studies (observational, cohort, administrative databases). The 2023 Guidelines support the proven value of five major classes of antihypertensive drugs: thiazide/thiazide-like diuretics, ACEIs, ARBs, calcium antagonists, and β-blockers. New data from meta-analyses support the greater clinical relevance of RAS blockers, calcium channel blockers, and thiazide/thiazide-like diuretics in preventing hypertension-related outcomes, leading to their preferred use in the pharmacotherapy of arterial hypertension, including various combinations of drugs. A new trend in the pharmacotherapy of arterial hypertension has been the inclusion of β-blockers among the main antihypertensive drugs, including their preferred use for a number of clinical conditions. New classes of drugs, such as SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists, are cited as having BP-lowering effects and with strong evidence of reduced cardiovascular and renal outcomes in patients with type 2 diabetes and, in the case of SGLT2 inhibitors, in non-diabetic patients. The 2023 Guidelines significantly updated information on available combination strategies for the treatment of arterial hypertension, and added data on the effectiveness of fixed combinations, including quadropills and polypills.

A Review on the Chemical Properties, Plant Sources, Anti-shock Effects, Pharmacokinetics, Toxicity, and Clinical Applications of Anisodamine.

Alkaloids are natural products that occur widely in many herbal plants. Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted from the roots of the Anisodus tanguticus Maxim. It is an antagonist to M-choline receptors and exhibits diverse pharmacological effects, such as cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a range of pharmacological effects akin to those of atropine and scopolamine. owing to its low toxicity and moderate efficacy in clinical to wide applications, especially for varieties of shock treatment. However, there remains a dearth of research regarding the in vivo pharmacokinetics, mechanism of action, and toxicity of anisodamine. Consequently, this paper provides a comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic characteristics of anisodamine to increase the understanding of its medicinal value, and provide reference and inspiration for the clinical application and further in-depth research of anisodamine.

Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

BackgroundRhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes. ObjectivesThis study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF. MethodsWe systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control–related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed. ResultsWe identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke. ConclusionsIn patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy.

Clinical Assessment of Early Morning Blood Pressure in Patients with Hypertension

A significant population experiencing hypertension, blood pressure (BP) demonstrates a significant rise during the awakening hours, it is linked to heightened cardiovascular complications during this time of the day. Many medications used to manage high BP fail to effectively control BP in the early morning, especially when administered once daily in the morning. Key factors to consider when choosing an efficient antihypertensive medication include the agent's pharmacokinetics, formulation, and timing of dosing. Examples of antihypertensive drugs with proven efficacy in regulating early morning BP include medications with extended pharmacologic half-lives, like telmisartan (an angiotensin II receptor blocker), amlodipine (a calcium antagonist), and bisoprolol (a beta-blocker). Administering chronotherapeutic preparations at bedtime has also been shown to be effective in managing early morning BP. There is a correlation between elevated early morning BP and cardiovascular risk, future clinical studies should emphasize evaluating the performance of antihypertensive drugs during this critical period of heightened risk. (Prev Cardiol. 2007;10:210−214) © 2007 Le Jacq. Medicine Today 2023 Vol.36 (1): 55-61

Review of international clinical guidelines for the management of hypertension in patients with diabetes mellitus?

Arterial hypertension (AH) is one of the leading problems of cardiological communities around the world. In patients with diabetes mellitus (DM), hypertension occurs 2 times more often than in the general population, being mutually aggravating diseases and leading risk factors for coronary heart disease, stroke, congestive heart failure and chronic kidney disease, which lead to disability and increased cardiovascular mortality. Various cardiological and endocrinological communities pay special attention to the management of hypertension in patients with DM, taking into account comorbidity. The present review examines modern approaches to the management of hypertension in DM patients based on current international clinical recommendations. Most of the current practical guidelines and clinical recommendations emphasize the need for early combined antihypertensive therapy for diabetes, which is due to the complex multifactorial pathogenesis and a more severe course of hypertension in disorders of carbohydrate metabolism. The main groups of antihypertensive drugs recommended for diabetes include: angiotensin converting enzyme inhibitors/angiotensin receptor blockers, thiazide/thiazide-like diuretics, calcium antagonists.

Diltiazem reduces levels of NT-proBNP and improves symptoms compared with metoprolol in patients with permanent atrial fibrillation.

Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation (AF) after 6 months. Men and women with permanent AF and preserved left ventricular systolic function were randomized to receive either diltiazem 360mg or metoprolol 100mg once daily. The primary endpoint was the level of NT-proBNP after a 6-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71±7 years, 28 women) were randomized. After 6-months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6-589.1, P<0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity. Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent AF.

SERUM CALCIUM IS ASSOCIATED WITH PERIPHERAL AND CENTRAL BLOOD PRESSURE IN DIFFERENT SAMPLES

Objective: Calcium homeostasis plays a crucial role in both contractility and relaxation mechanisms, determining the vasoconstriction and vasodilation of blood vessels. Some studies have reported a positive correlation between serum calcium and blood pressure (BP) levels, hypertension, metabolic syndrome, and type 2 diabetes, while others have not. Given these conflicting findings, we investigated the relationship between serum calcium and BP in three distinct samples. Our objective was to confirm the existence of a positive correlation between calcium levels and BP and to assess whether this relationship extends to central BP. Design and method: Serum calcium levels were measured in a restricted sample of patients referred to our ESH Excellence Center in Verona (n=56) with a suspicion of secondary hypertension, as well as in two large population-based studies from Sweden, the Malmö Preventive Project (MPP, n= 17,843) and from United Kingdom, the UK Biobank (UKB, n= 330,000). Central BP was estimated by tonometry performed with SphygmoCor Xcel. Results: In the Verona sample, the patients, predominantly receiving antihypertensive therapy based on calcium antagonists, serum calcium correlated with central systolic BP (r=0.37; p&lt;0.01), and this association persisted even after adjusting for age, sex, and BMI. In the MPP, baseline serum calcium was associated with both systolic (beta 0.60, 95% CI 0.30-0.89; p&lt;0.001) and diastolic BP (beta 0.44, 95% CI 0.26-0.62; p&lt;0.001) after adjustment for age, sex, BMI, and antihypertensive therapy. Similarly, in the UKB, the association between both systolic (beta 1.79, 95% CI 1.74-1.85; p&lt;10^15) and diastolic BP (beta 0.98, 95% CI 0.95-1.02; p&lt;10 ^15) and serum calcium was confirmed after the same adjustments. Conclusions: In different samples, serum calcium consistently associates with increased BP. Further studies are warranted to elucidate whether this association is influenced by hormones regulating this electrolyte and/or by dietary calcium intake.

Hypertension and arterial wall stiffness in clinical practice: literature review

Arterial stiffness, as a marker of subclinical target organ damage in patients with hypertension (HTN), is an important and independent predictor of mortality and cardiovascular morbidity. The review examines factors contributing to increased vascular wall stiffness with a focus on smoking, pathogenesis of increased arterial stiffness with aging, and the effect of arterial stiffness on increased systolic and pulse pressure. Particular attention is paid to the effect of pulse pressure on the risk of cardiovascular events, primarily on the incidence of stroke and cognitive impairment. Thiazide-like diuretics and calcium antagonists have the greatest evidence base in HTN treatment in the elderly due to their ability to reduce systolic and pulse pressure, reduce arterial stiffness and have a positive effect on prognosis. The use of amlodipine/indapamide retard combination promotes more effective treatment of elderly patients with HTN.