Epigenetics is a rapidly developing science that has gained a lot of interest in recent years due to the correlation between characteristic epigenetic marks and cardiovascular diseases (CVDs). Epigenetic modifications contribute to a change in gene expression while maintaining the DNA sequence. The analysis of these modifications provides a thorough insight into the cardiovascular system from its development to its further functioning. Epigenetics is strongly influenced by environmental factors, including known cardiovascular risk factors such as smoking, obesity, and low physical activity. Similarly, conditions affecting the local microenvironment of cells, such as chronic inflammation, worsen the prognosis in cardiovascular diseases and additionally induce further epigenetic modifications leading to the consolidation of unfavorable cardiovascular changes. A deeper understanding of epigenetics may provide an answer to the continuing strong clinical impact of cardiovascular diseases by improving diagnostic capabilities, personalized medical approaches and the development of targeted therapeutic interventions. The aim of the study was to present selected epigenetic pathways, their significance in cardiovascular diseases, and their potential as a therapeutic target in specific medical conditions.
Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to right ventricular failure and, consequently, to death. The most common causes of PH include left heart disease and lung disease. Despite the significant development of medicine and related sciences observed in recent years, we still suffer from a lack of effective treatment that would significantly influence the prognosis and prolong life expectancy of patients with PH. One type of PH is pulmonary arterial hypertension (PAH). The pathophysiology of PAH is based on increased cell proliferation and resistance to apoptosis in the small pulmonary arteries, leading to pulmonary vascular remodeling. However, studies conducted in recent years have shown that epigenetic changes may also lie behind the pathogenesis of PAH. Epigenetics is the study of changes in gene expression that are not related to changes in the sequence of nucleotides in DNA. In addition to DNA methylation or histone modification, epigenetic research focuses on non-coding RNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Preliminary research results give hope that targeting epigenetic regulators may lead to new, potential therapeutic possibilities in the treatment of PAH.
Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019–2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.
The primary objective of the study was to evaluate the prognostic value of measuring plasma catestatin (CST) concentration in patients with heart failure with reduced ejection fraction (HFrEF) as a predictor of unplanned hospitalization and all-cause death independently and as a composite endpoint at 2-year follow-up. The study group includes 122 hospitalized Caucasian patients in NYHA classes II to IV. Patients who died during the 24-month follow-up period (n = 44; 36%) were significantly older on the day of enrollment, were more likely to be in a higher NYHA class, had lower TAPSE, hemoglobin concentration, hematocrit, and platelet count, higher concentrations of CST, NT-proBNP, troponin T, creatinine, and glucose, and higher red cell distribution width value and leukocyte and neutrocyte count than patients who survived the follow-up period. Plasma catestatin concentration increased with NYHA class (R = 0.58; p <0.001) and correlated significantly with blood NT-proBNP concentration (R = 0.44; p <0.001). We showed that higher plasma catestatin concentration increased the risk of all-cause death by more than five times. Plasma CST concentration is a valuable prognostic parameter in predicting death from all causes and unplanned hospitalization in patients with HFrEF.
Background/Objectives: The concentration of uric acid in the body of older adults may have various effects. Due to the multidirectional influence on metabolism, its significance in the daily functioning of older persons remains unclear. The present investigation explored whether serum uric acid levels are associated with scores on standard geriatric assessment scales in hospitalized older adults. Methods: In total, 77 patients admitted to the hospital for the Comprehensive Geriatric Assessment were recruited and classified into three groups: successfully treated for hyperuricemia, untreated or unsuccessfully treated with elevated uric acid levels, and untreated controls having normal uric acid levels. The analysis considered the relationship between the concentration of uric acid in patients from different study groups and the assigned classes defined by the ranges of the questionnaires used for the study. Results: Significant differences were shown in the distribution of classes defined by Addenbrooke’s Cognitive Examination III (ACE-III) and the MNA questionnaires concerning the study groups. Moreover, significant differences were confirmed when using compartmentalization based only on the screening test results for the ACE-III, the Mini Nutritional Assessment (MNA), and the Mini-Mental State Examination (MMSE). For ACE-III, a lower percentage of people with probable dementia was observed in the control group (34.5%) than in the group with elevated uric acid values (78.3%). Conclusions: Although the mechanisms related to uric acid’s influence on older people’s functioning require further research, the available evidence indicates a negative impact of elevated uric acid levels on cognitive functions and the nutritional status of older individuals.
Colchicine, a natural alkaloid, has emerged as a promising anti-inflammatory therapy with applications in cardiovascular diseases, dermatological conditions, and COVID-19 management. Its mechanisms, including the modulation of neutrophil activity, the inhibition of the NLRP3 inflammasome, and the mitigation of cytokine storms, have expanded its therapeutic potential beyond traditional uses. This review synthesizes current evidence on colchicine’s clinical applications and mechanisms of action. In cardiovascular medicine, colchicine has been shown to reduce risks of pericarditis, coronary artery disease and atrial fibrillation. In dermatology, most evidence derives from small-scale studies, case series, and retrospective analyses, suggesting potential benefits in conditions such as leukocytoclastic vasculitis, cutaneous amyloidosis, and pemphigus, although these findings require confirmation through randomized controlled trials (RCTs). Emerging studies also indicate a potential role for colchicine in improving outcomes in severe COVID-19. Overall, colchicine demonstrates broad therapeutic utility, warranting further research to clarify its effectiveness across diverse clinical settings.