Management Of Cardiovascular Disease Research Articles

Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation

The science of cardiac rehabilitation and the secondary prevention of cardiovascular disease has progressed substantially since the most recent American Heart Association and American Association of Cardiovascular and Pulmonary Rehabilitation update on the core components of cardiac rehabilitation and secondary prevention programs was published in 2007. In addition, the advent of new care models, including virtual and remote delivery of cardiac rehabilitation services, has expanded the ways that cardiac rehabilitation programs can reach patients. In this scientific statement, we update the scientific basis of the core components of patient assessment, nutritional counseling, weight management and body composition, cardiovascular disease and risk factor management, psychosocial management, aerobic exercise training, strength training, and physical activity counseling. In addition, in recognition that high-quality cardiac rehabilitation programs regularly monitor their processes and outcomes and engage in an ongoing process of quality improvement, we introduce a new core component of program quality. High-quality program performance will be essential to improve widely documented low enrollment and adherence rates and reduce health disparities in cardiac rehabilitation access.

Fas Apoptosis Inhibitory Molecule 2 Inhibits Pathological Cardiac Hypertrophy by Regulating the MAPK Signaling Pathway.

Pathological cardiac hypertrophy stands as a pivotal mechanism contributing to diverse cardiovascular diseases, ultimately leading to heart failure. Despite its clinical significance, the intricate molecular mechanisms instigating pathological cardiac hypertrophy remain inadequately understood. In this study, we aim to further reveal its complex pathogenesis by exploring the role of Fas apoptotic inhibitory molecule 2 (FAIM2) in modulating pathological cardiac hypertrophy. We used phenylephrine-induced hypertrophic cardiomyocytes and also generated cardiac-specific knockout mice and adeno-associated virus serotype 9-Faim2 mice to evaluate the function of FAIM2 in pathological myocardial hypertrophy. Furthermore, unbiased RNA-sequencing analysis was used to identify the direct target and corresponding molecular events contributing to FAIM2 function. Ultimately, our study revealed a downregulation of FAIM2 expression in phenylephrine-induced hypertrophic cardiomyocytes and pressure overload-induced hypertrophic hearts. FAIM2 exhibited a significant attenuation of phenylephrine-induced enlargement of primary neonatal rat cardiomyocytes, whereas FAIM2 knockdown aggravated the hypertrophic response. Furthermore, Faim2 gene knockout significantly exacerbated cardiac hypertrophy and heart fibrosis invivo. Mechanistic investigations unveiled that FAIM2 exerts its inhibitory effect by suppressing TAK1-JNK1/2-p38 MAPK signaling cascades, thereby mitigating cardiac hypertrophy. Our findings position FAIM2 as a novel negative regulator of pathological cardiac hypertrophy through its inhibitory action on mitogen-activated protein kinase signaling activation. This identification of FAIM2's role provides crucial insights that may pave the way for the development of effective therapeutic strategies aimed at mitigating pathological cardiac hypertrophy, addressing a critical need in cardiovascular disease management.

Novel insights into RNA polymerase II transcription regulation: transcription factors, phase separation, and their roles in cardiovascular diseases.

Transcription factors (TFs) are specialized proteins that bind DNA in a sequence-specific manner and modulate RNA polymerase II (Pol II) in multiple steps of the transcription process. Phase separation is a spontaneous or driven process that can form membrane-less organelles called condensates. By creating different liquid phases at active transcription sites, the formation of transcription condensates can reduce the water content of the condensate and lower the dielectric constant in biological systems, which in turn alters the structure and function of proteins and nucleic acids in the condensate. In RNA Pol II transcription, phase separation formation shortens the time at which TFs bind to target DNA sites and promotes transcriptional bursting. RNA Pol II transcription is engaged in developing several diseases, such as cardiovascular disease, by regulating different TFs and mediating the occurrence of phase separation. This review aims to summarize the advances in the molecular mechanisms of RNA Pol II transcriptional regulation, in particular the effect of TFs and phase separation. The role of RNA Pol II transcriptional regulation in cardiovascular disease will be elucidated, providing potential therapeutic targets for the management and treatment of cardiovascular disease.

Advances in wearable biotechnology for cardiac monitoring

Wearable biotechnology is enhancing cardiac health monitoring by enabling continuous data collection for early detection and better management of cardiovascular diseases (CVDs). Recent advancements, such as multi-sensor integration, combine electrocardiography (ECG), heart rate variability, blood pressure, and oxygen saturation monitoring to provide a comprehensive cardiovascular assessment and improve diagnostic precision. Innovations in energy-harvesting technologies, like thermoelectric and piezoelectric materials, extend battery life, reducing the need for frequent recharging and increasing patient adherence. Despite these advances, challenges remain, particularly concerning data security, which requires robust encryption methods and secure data transmission protocols. Regulatory frameworks like the GDPR and HIPAA need to evolve to accommodate technological progress, ensuring new devices are safe and quickly brought to market. Enhancing interoperability with electronic health records (EHRs) is crucial to maximizing the clinical utility of wearable devices. Future research should focus on developing biochemical sensors to detect specific biomarkers in bodily fluids, refining AI algorithms for personalized diagnostics, and establishing standards for data sharing and integration. Collaboration among healthcare providers, regulatory bodies, and technology developers is essential to overcoming current barriers, expanding clinical applications, and ultimately improving patient outcomes and public health.

Abstract 4123370: Distance to a Cardiac Imaging Center and Likelihood of Imaging Receipt: Defining Imaging Deserts

Background: Cardiovascular imaging is critical for the diagnosis and management of cardiovascular disease. Whether geographic distance to a cardiovascular imaging center (CVIC) impacts access to care is unknown. Methods: We evaluated all Medicare beneficiaries (Fee-for-service and Medicare Advantage) from 2018-2022, excluding those < 65, without continuous Medicare enrollment in the previous year, individuals missing zip code of residence, or CVICs missing zip codes. We estimated distance from the centroid of an individual’s zip code of residence to the centroid of the zip code with the nearest CVIC (defined as > 10 imaging procedures/year). Multivariable regression models were used to estimate likelihood of imaging receipt by distance. Results/Data: A total of 64,260,530 individuals (age 73.0 ± 8 years, 54.6% female, 80.1% White) received care at 3,886 CVICS. The vast majority (95%) lived within 16 miles of a CVIC, but varied considerably by modality with substantially greater distances for cardiac CT, cardiac MRI, and PET (Median [IQR] distance in miles to CVIC, Echo: 3.4 [0.4-7.0]; SPECT: 3.8 [1.3-7.9]; cardiac CT: 8.1 [3.7-21.3]; cardiac MRI: 17.4 [7.3-43.3]; PET: 88.9 [26.2-194.6]). CVICs performing cardiac CT, cardiac MRI, or PET were nearly all in metropolitan locations. Likelihood of imaging receipt was triphasic: lowest within 0-10 miles of a CVIC (mainly metropolitan locations), greater within 10-15 miles, and then increasingly lower beyond 15 miles ( Figure 1 ). Sites beyond the 16-mile threshold were predominantly in the Midwest and West ( Figure 2 ). Conclusions: In this study of 64 million Medicare beneficiaries, 2018-2022, 95% of the US population was found to live within 16 miles of a CVIC, though varied by modality. While those living > 16 miles from a CVIC received less imaging, the lowest use was identified among individuals living in the same zip code as a CVIC, suggesting a possible disconnect between access to imaging care and proximity.

Abstract 4136758: Apabetalone: evaluating cardiovascular and safety outcomes in meta-analysis

Background: Epigenetic mechanisms play a pivotal role in the transcriptional programs associated with cardiovascular disease (CVD). Apabetalone, an orally available inhibitor of BET proteins that serve as key epigenetic readers, and modulating gene expression - holds promise as a therapeutic intervention in CVD management. Understanding its efficacy and tolerability is crucial for delineating its potential impact on disease progression and patient outcomes. Purpose: This systematic review and meta-analysis aimed to assess the impact of apabetalone in patients with cardiovascular disease. Methods: The meta-analysis was registered with PROSPERO (CRD42023423298). Databases searched included Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science. Three unique RCTs with total of 2897 patients were included, with trial durations ranging from 12 to 124 weeks. Primary outcomes assessed were all-cause mortality and non-fatal myocardial infarction (MI). Data analysis was performed using the inverse variance common effect model. Subgroup analyses were conducted based on the presence of atherosclerotic cardiovascular disease (ASCVD) or its increased risk. Results: Among the primary outcomes, no significant effects of apabetalone were observed on all-cause mortality (RR 0.88, 95% CI 0.63 to 1.23) or non-fatal MI (RR 0.83, 95% CI 0.62 to 1.11). Apabetalone demonstrated favorable effects on increasing Apo A1 (SMD 0.20, 95% CI 0.04 to 0.35) and HDL (SMD 0.29, 95% CI 0.09 to 0.49). However, no significant effects were observed for changes in Apo B, LDL, non-HDL, total cholesterol. Subgroup analysis did not reveal any significant differences in outcomes. Significant effects were noted in secondary outcomes. Apabetalone showed a significant increase in adverse events (AEs) leading to withdrawal (RR 1.61, 95% CI 1.21 to 2.15) and ALT and AST increases greater than three times the normal value (RR 4.50, 95% CI 2.73 to 7.41). Conclusion: Our meta-analysis highlights the significant impact of apabetalone on certain lipid parameters and adverse events. However, it did not demonstrate significant effects on all-cause mortality or non-fatal MI. Further well-designed and reported RCTs were warranted to elucidate the clinical implications of apabetalone in selected group of patients that might benefit the most from apabetalone that may also improve cardiovascular disease management.

Abstract 4136403: Impact of Coronary Artery Calcium Scores on Cardiovascular Risk and Preventive Therapies: A Systematic Review and Meta-Analysis

Introduction: Coronary artery calcium (CAC) serves as a key marker of atherosclerosis and is widely utilized in the noninvasive evaluation of coronary artery disease. We aim to compare cardiovascular risk outcomes and the likelihood of initiating or continuing pharmacological and lifestyle preventive therapies in asymptomatic and symptomatic patients with a CAC score greater than zero and those with a CAC score of zero with no established diagnosis of coronary artery disease. Methods: We performed systematic searches of PubMed, Scopus, Google Scholar, Cochrane Central, and ClinicalTrials.gov from inception to May 2024. Our search focused on randomized controlled trials and observational studies comparing outcomes between patients with a CAC score greater than zero and those with a CAC score of zero. Results: We included 53 observational studies, incorporating data from 210,672 asymptomatic and 32,477 symptomatic patients. Over a mean follow-up duration of 8.6 years, we observed that a CAC score greater than zero significantly correlated with an elevated risk of major adverse cardiovascular events (MACE) (OR: 5.58; 95% CI: 4.05–7.69; P < 0.00001). This association extended to all-cause mortality (OR: 3.90; 95% CI: 2.78–5.48; P < 0.00001), myocardial infarction (OR: 4.01; 95% CI: 3.45–4.65; P < 0.00001), and the need for revascularization (OR: 11.90; 95% CI: 6.82–20.78; P < 0.00001). Patients with a CAC score greater than zero were more likely to commence and continue aspirin therapy (OR: 2.45; 95% CI: 1.56–3.83; P < 0.0001 for initiation and OR: 1.71; 95% CI: 1.31–2.23; P < 0.0001 for continuation). Similar trends were noted for lipid-lowering medications (OR: 2.44; 95% CI: 1.57–3.79; P < 0.0001 for initiation and OR: 2.48; 95% CI: 1.53–4.01; P = 0.0002 for continuation), as well as the initiation of blood pressure medications (OR: 1.94; 95% CI: 1.61–2.33; P < 0.00001). Furthermore, a CAC score greater than zero was linked to increased adoption of lifestyle modifications, including enhanced physical activity (OR: 1.84; 95% CI: 1.41–2.41; P < 0.00001) and dietary changes (OR: 1.94; 95% CI: 1.52–2.49; P < 0.00001). Conclusion: Patients with elevated CAC scores are more likely to initiate and continue preventive pharmacological therapies and adopt beneficial lifestyle modifications. These findings underscore the importance of CAC scoring in guiding the management and prevention of cardiovascular disease in both asymptomatic and symptomatic populations.

Cardiovascular disease risk perception among community-dwelling adults in southwest Nigeria: A mixed-method study.

The rising prevalence of cardiovascular diseases (CVD) remains a global concern. In Nigeria, the current prevalence of CVD was 76.11% with its attendance burden. The CVD risk perception of individuals is a precursor to the desired lifestyle modification necessary for CVD prevention and management. This study assessed the CVD risk perception and sociodemographic determinants among rural and urban dwellers in southwest Nigeria. The study employed a convergent parallel mixed-methods design involving concurrent data collection. The participants' CVD risk perception was obtained using the Perception of Risk of Heart Disease Scale (quantitative data) and a validated focus group discussion (FGD) guide (qualitative data). Quantitative analysis was completed using descriptive statistics, Phi, Cramer's V, and multivariate linear regression, while the FGD was thematically analysed. The quantitative study involved 1,493 participants (62.4% women) with a mean age of 46.90±15.65 years, while the FGD involved 53 participants (52.8% women) with a mean age of 50.10±13.5 years. Over a quarter (28%) of the participants had a poor CVD risk perception; the mean score was 44.40±8.07. Rural residents had a significantly poorer CVD risk perception than their urban counterparts (Mean difference = -3.16, p<0.001). Having tertiary education (β = 0.100, p < 0.001), living in urban areas (β = 0.174, p<0.001), and living in Lagos (β = 0.074, p = 0.013) and in Oyo, other than Ogun state (β = -0.156, p<0.001) significantly predicted having a good perception of CVD risk. FGD produced three themes: knowledge about CVD, CVD risk factors, and CVD prevention. Participants had a fair understanding of the causes and prevention of CVD. Yet, a substantial portion underestimated their own risk of developing CVD, particularly rural dwellers and people with lower education. More public health education is required to improve the CVD risk perception in southwestern Nigeria.

Benefits of Camel Milk over Cow and Goat Milk for Infant and Adult Health in Fighting Chronic Diseases: A Review

The nutritional composition, antimicrobial properties, and health benefits of camel milk (CAM), cow milk (COM), and goat milk (GOM) have been extensively studied for their roles in managing diabetes and cardiovascular diseases (CVD). This review compares these milk types’ nutritional and therapeutic properties, emphasizing their applications in chronic disease management. CAM is rich in insulin-like proteins, vitamins, minerals, and bioactive compounds that benefit glycemic control and cardiovascular health. It also exhibits potent antioxidants, anti-inflammatory, and lipid-lowering effects, which are crucial for managing diabetes and reducing CVD risk factors. While COM and GOM provide essential nutrients, their impact on metabolic health differs. GOM is known for its digestibility and antihypertensive properties, whereas COM’s higher lactose content may be less suitable for diabetic patients. CAM’s unique nutritional profile offers distinct therapeutic benefits, particularly for diabetes and CVD management. Further research is needed to clarify its mechanisms of action and optimize its clinical application for chronic disease prevention and management.

Vascular Extracellular Matrix in Atherosclerosis

The extracellular matrix (ECM) plays a central role in the structural integrity and functionality of the cardiovascular system. Moreover, the ECM is involved in atherosclerotic plaque formation and stability. In fact, ECM remodeling affects plaque stability, cellular migration, and inflammatory responses. Collagens, fibronectin, laminin, elastin, and proteoglycans are crucial proteins during atherosclerosis development. This dynamic remodeling is driven by proteolytic enzymes such as matrix metalloproteinases (MMPs), cathepsins, and serine proteases. Exploring and investigating ECM dynamics is an important step to designing innovative therapeutic strategies targeting ECM remodeling mechanisms, thus offering significant advantages in the management of cardiovascular diseases. This review illustrates the structure and role of vascular ECM, presenting a new perspective on ECM remodeling and its potential as a therapeutic target in atherosclerosis treatments.

Epicardial Adipocytes in Cardiac Pathology and Healing.

Implications of epicardial adipose tissue (EAT) on the development of coronary artery disease (CAD) have garnered recent attention. Located between the myocardium and visceral pericardium, EAT possesses unique morphological and physiological contiguity to the heart. The transcriptome and secretome of EAT differ from that of other fat stores in the body. Physiologically, EAT protects the adjacent myocardium through its brown-fat-like thermogenic function and rapid fatty acid oxidation. However, EAT releases pro-inflammatory mediators acting on the myocardium and coronary vessels, thus contributing to the development and progression of cardiovascular diseases (CVD). Furthermore, EAT-derived mesenchymal stromal cells indicate promising regenerative capabilities that offer novel opportunities in cell-based cardiac regeneration. This review aims to provide a comprehensive understanding and unraveling of EAT mechanisms implicated in regulating cardiac function and regeneration under pathological conditions. A holistic understanding of the multifaceted nature of EAT is essential to the future development of pharmacological and therapeutic interventions for the management of CVD.

A Cross-talk between Nanomedicines and Cardiac Complications: Comprehensive View.

Cardiovascular Diseases (CVDs) are the leading cause of global morbidity and mortality, necessitating innovative approaches for both therapeutics and diagnostics. Nanoscience has emerged as a promising frontier in addressing the complexities of CVDs. This study aims to explorethe interaction of CVDs and Nanomedicine (NMs), focusing on applications in therapeutics and diagnostics. In the realm of therapeutics, nanosized drug delivery systems exhibit unique advantages, such as enhanced drug bioavailability, targeted delivery, and controlled release. NMs platform, including liposomes, nanoparticles, and carriers, allows the precise drug targeting to the affected cardiovascular tissues with minimum adverse effects and maximum therapeutic efficacy. Moreover, nanomaterial (NM) enables the integration of multifunctional components, such as therapeutic agents and target ligands, into a single system for comprehensive CVD management. Diagnostic fronts of NMs offer innovative solutions for early detection and monitoring of CVDs. Nanoparticles and nanosensors enable highly sensitive and specific detection of Cardiac biomarkers, providing valuable insights into a disease state, its progression, therapeutic outputs, etc. Further, nano-based technology via imaging modalities offers high high-resolution imaging, aiding in the vascularization of cardiovascular structures and abnormalities. Nanotechnology-based imaging modalities offer high-resolution imaging and aid in the visualization of cardiovascular structures and abnormalities. The cross-talk of CVDs and NMs holds tremendous potential for revolutionizing cardiovascular healthcare by providing targeted and efficient therapeutic interventions, as well as sensitive and early detection for the improvement of patient health if integrated with Artificial Intelligence (AI).

Multifaced roles of adipokines in endothelial cell function

Obesity significantly contributes to the progression of cardiovascular diseases (CVDs) and elevates the risk of cardiovascular mortality. Atherosclerosis, the primary pathogenic process underlying CVDs, initiates with vascular endothelial dysfunction, serving as the cornerstone of vascular lesions. Adipokines, bioactive molecules secreted by adipose tissue that regulate metabolic and endocrine functions, play a pivotal role in modulating endothelial function during atherosclerosis. This review comprehensively examines the distinct roles of various adipokines in regulating endothelial function in atherosclerosis. We categorize these adipokines into two main groups: protective adipokines, including adiponectin, FGF21, CTRP9, PGRN, Omentin, and Vaspin, and detrimental adipokines such as leptin, Chemerin, Resistin, FABP4, among others. Targeting specific adipokines holds promise for novel clinical interventions in the management of atherosclerosis-related CVDs, thereby providing a theoretical foundation for cardiovascular disease treatment strategies.

Impact of Genetic Risk Information for Cardiovascular Disease on Behavioural, Psychological Responses, and Risk Factor Modification: A Systematic Review.

Cardiovascular disease (CVD) remains a significant public health concern, influenced by both genetic susceptibility and lifestyle factors. Integrating genetic risk information into clinical practice shows promise but has yielded mixed results regarding its impact on CVD prevention and management. This systematic review aimed to assess the impact of providing genetic CVD risk information on health behaviours, psychological outcomes, and risk factors. Following JBI methodology and PRISMA 2020 guidelines, four electronic databases and two trial registries were searched for randomised controlled trials evaluating the impact of genetic risk information on the CVD risk profile. Data was synthesised using a narrative synthesis approach. Of the 3,596 articles retrieved, 11 studies were eligible. Genetic risk information showed modest improvements in dietary behaviour but had inconclusive effects on physical activity and medication adherence. Minimal changes in psychological outcomes were noted, including a slight decrease in depression. The impact on traditional risk factors, such as systolic blood pressure and total cholesterol was also limited. Bias across all studies was noted. Genetic CVD risk information has limited effects on clinical outcomes and psychological factors, despite its potential to encourage some health behaviour changes. These findings suggest that genetic risk information alone may not be sufficient to significantly reduce cardiovascular risk, highlighting the need for further research to better understand its long-term effects.

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

The use of PROMs (patient-reported outcome measures) and PREMs (patient-reported experience measures) in Cardiology: current state and applications to improve patient care

The integration of patient-reported outcomes and experiences through PROMs and PREMs tools represents a significant evolution in the quality of care and clinical practice. This article reviews the state of the art and the application experiences of these tools, focusing on their impact on the management of cardiovascular diseases. The use of PROMs and PREMs allows for a more comprehensive assessment of patient well-being by integrating with traditional clinical indicators. An increasing number of studies suggests that the systematic collection of these data can help physicians in better identifying individual patient's needs, improving doctor-patient communication, and personalizing therapies. In aggregate form, these data can be used to improve the quality of services. This article explores the main international experiences, starting from the activities carried out in this field by the European Society of Cardiology, the challenges in implementing such tools, and the prospects for a more widespread adoption in daily clinical practice. It emphasizes the activities carried out in Italy by the Fondazione Toscana Gabriele Monasterio and the Management and Healthcare Laboratory of the Scuola Superiore Sant'Anna of Pisa, highlighting the importance of validated tools, appropriate technologies, and a cultural change to promote patient-centered care.

Physical Activity Benchmarks for Implantable Loop Recorder Patients: The Role of ILRs in Cardiovascular Disease Management

Physical Activity Benchmarks for Implantable Loop Recorder Patients: The Role of ILRs in Cardiovascular Disease Management

PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions

PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions

The impact of X-rays on cardiac hydrometabolism and the regulatory role of AS-IV

BackgroundRadiation-induced cardiac injury has emerged as a significant pathological entity, with many studies focusing on the fibrotic changes in myocardial tissue. However, these do not offer solutions for the clinical prevention and treatment of radiation-induced heart disease. Regulating hydrometabolism presents a potential therapeutic target for the management of cardiovascular diseases. This research seeks to explore the impacts of irradiation on cardiac hydrometabolism and its regulatory mechanisms. MethodsThe impact of X-ray radiation on cardiac and cardiomyocyte hydrometabolism was studied through in vivo and in vitro experiments, examining the pharmacological effects and mechanisms of PX-478 and AS-IV interventions in cardiomyocytes. Results28 days after direct chest irradiation with 20 Gy X-rays, C57BL/6 mice exhibited an increased heart wet-to-dry weight ratio, significant enlargement of cardiomyocyte cross-sectional area, and elevated protein expression of HIF-1α, AQP1, AQP4, Cx43, Caspase3, and Bax, with decreased expression of Bcl-2. Irradiation with 6 Gy X-rays induced edema and damage in AC16 and HL-1 cardiomyocytes at 24, 48, and 72 h, with increased expression of HIF-1α, AQP1, AQP4, and Cx43 proteins post-radiation. Inhibition of HIF-1α ameliorated edema and apoptosis in AC16 and HL-1 cardiomyocytes, reducing the expression of HIF-1α, AQP1, AQP4, and Cx43 proteins. AS-IV demonstrated strong binding affinity with HIF-1α, and successfully attenuated the expression levels of HIF-1α, AQP1, AQP4, and Cx43 proteins, alleviating edema, mitochondrial swelling, and apoptosis in AC16 and HL-1 cardiomyocytes. Furthermore, AS-IV improved cardiomyocyte edema by restoring the activity of Na/K-ATPase. ConclusionAberrant activation of the HIF-1α/AQPs/Cx43 axis is a key mechanism in X-ray-induced cardiomyocyte edema and damage. AS-IV can ameliorate X-ray induced cardiac damage by regulating hydrometabolism.

Sodium-glucose cotransporter 2 inhibitors in cardiocerebrovascular disease

Cardiovascular disease is a leading cause of global mortality, necessitating effective strategies for prevention and treatment. The cardiovascular disease continuum concept highlights the progression from risk factors such as hypertension and diabetes mellitus to advanced stages, including heart failure (HF) and death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed to manage diabetes, have emerged as effective therapies across all stages of the cardiovascular disease continuum. Numerous cardiovascular outcome trials demonstrate that SGLT2 inhibitors significantly reduce major adverse cardiovascular events and hospitalizations for HF in patients with and without established atherosclerotic cardiovascular disease. Notably, SGLT2 inhibitors have shown remarkable benefits in reducing HF risk, even in patients without diabetes, including those with HF and preserved ejection fraction. Furthermore, recent studies in post–myocardial infarction patients suggest potential benefits in reducing hospitalizations for HF. Despite their widespread use, the precise mechanisms by which SGLT2 inhibitors confer cardiovascular protection remain unclear, suggesting the need for further investigation. In conclusion, SGLT2 inhibitors have revolutionized cardiovascular disease management, offering significant therapeutic potential across a broad spectrum of patients, and are expected to play an increasingly prominent role in both the prevention and treatment of cardiovascular disease.