Abstract: Hemodialysis (HD) remains the cornerstone of renal replacement therapy for patients with End-Stage Kidney Disease (ESKD). Over the past two decades, conventional HD has been followed by more advanced dialysis modalities, including online hemodiafiltration (HDF) and expanded hemodialysis (HDx). These have been introduced to improve solute clearance and clinical outcomes. Yet cardiovascular events, mortality, and symptom burden remain unacceptably high, and it remains unclear which modality is optimal. Studies so far have shown that HDF, which combines diffusive and convective transport, is associated with lower all-cause and cardiovascular mortality than conventional HD. This is particularly the case when HDF achieves adequate convection volume and in patients with certain characteristics. HDx, which employs medium cut-off membranes, enables the clearance of larger middle molecules and may reduce inflammation, hospitalization, and symptom burden, data on hard cardiovascular and survival endpoints remain limited. Across modalities, studies assessing quality of life, symptom relief, and treatment tolerability are few and often underpowered, leaving important patient priorities underexplored. In parallel, the implementation of resourceintensive modalities such as HDF raises concerns about water, energy, and plastic use. This underscores the need for overall environmental sustainability in a growing dialysis population. Current evidence supports an individualized, outcome-driven approach to prescribing HD, HDF, and HDx, balancing potential cardiovascular and survival advantages of high-volume HDF and HDx against feasibility, cost, and environmental impact. This narrative review synthesizes evidence from randomized controlled trials and large observational cohorts comparing conventional low- and high-flux HD with post-dilution HDF and HDx, highlighting key clinical and methodological controversies.
Background: The progressive aging of the global population has been accompanied by a parallel increase in both dementia and atrial fibrillation (AF), two conditions that frequently coexist and are linked through complex cerebrovascular and systemic mechanisms. Beyond overt ischemic stroke, AF has been increasingly associated with subclinical brain injury and cognitive decline. Objective: This review examines the relationship between AF, oral anticoagulation, and cognitive outcomes, with a particular focus on elderly patients and those with cognitive impairment. Methods: Study Design and Literature Search Strategy: This article is a narrative review based on a structured literature search conducted in PubMed/MEDLINE, Scopus, and relevant guideline databases. The search focused on studies addressing atrial fibrillation, oral anticoagulation, cognitive decline, dementia, silent cerebral infarction, cerebral microbleeds, and neurovascular injury. Priority was given to systematic reviews, meta-analyses, randomized controlled trials, observational cohort studies, and current international guidelines. Relevant English-language articles published up to 2025 were considered. We performed a narrative synthesis of the current evidence addressing the biological pathways connecting AF and neurodegeneration, as well as clinical studies evaluating the impact of oral anticoagulant therapy on cognitive trajectories. Results: Oral anticoagulation remains central to stroke prevention in AF, yet its role in modulating cognitive decline remains incompletely defined. Observational data suggest that direct oral anticoagulants (DOACs) may be associated with a lower incidence of dementia, potentially through the reduction of microembolism and silent cerebral ischemia. However, these findings are not conclusive and should be interpreted with caution. Concerns regarding bleeding risk, particularly intracerebral hemorrhage, continue to influence treatment decisions, especially in frail and cognitively impaired populations. Conclusion: Managing anticoagulation in patients with AF and cognitive impairment requires a careful balance between preventing blood clots and minimizing bleeding risk. A comprehensive, patientfocused approach, supported by multidisciplinary collaboration, may improve clinical decisionmaking. More research is needed to understand the long-term cognitive effects of anticoagulant treatments in this vulnerable group.
Pericarditis is a common disease caused by various factors such as viral infections, systemic diseases, or drugs. A diagnosis of pericarditis is rendered in up to 5% of Emergency Room (ER) visits for non-ischemic chest pain. It is diagnosed when pleuritic chest pain is present, accentuated in the supine position, accompanied by ECG changes comprising new extensive ST-segment elevation and PR depression, a pericardial friction rub, and new or increased pericardial effusion on echocardiography. In North America and Western Europe, the most common causes of acute pericarditis are idiopathic or viral, followed by post-procedural (iatrogenic) pericarditis, radiation therapy, and cardiac surgery. Tuberculosis is the most common cause of pericarditis in endemic areas and is managed with antituberculosis therapy, with corticosteroids used when there is concurrent constrictive pericarditis. New diagnostic techniques have aided the sampling and analysis of pericardial fluid and in determining its cause. Treatment of pericarditis comprises high-dose Non-Steroidal AntiInflammatory Drugs (NSAIDs) for uncomplicated cases, with doses tapered when symptoms have subsided and C-reactive protein level has normalized, typically over several weeks. Colchicine (often a 3-6-month course) is needed to both alleviate symptoms and decrease recurrences, while glucocorticoids and newer therapies with interleukin-1 blockers are reserved for recurrences and/or failures of prior therapies. Integrated use of new imaging methods facilitates more precise detection and better management of complications such as pericardial effusion or constriction. The diagnostic yield of extensive laboratory evaluation and pericardiocentesis remains low; hence, invasive procedures should be limited mostly to patients in whom a therapeutic intervention is needed. The majority of pericardial effusions can be safely drained with an echo-guided percutaneous technique. Pericardiectomy remains the definitive treatment for constrictive pericarditis and provides symptomatic relief in most cases. Importantly, differentiation of constrictive pericarditis from restrictive cardiomyopathy remains a clinical challenge, but is facilitated by tissue Doppler and colour M-mode echocardiography. All these issues are reviewed herein.
Work is a social determinant of Cardiovascular (CV) and general health and can both influence and be influenced by health. The type of work, working conditions, and work environment are fundamental social determinants of CV and general health status. Climate change presents an urgent and increasing threat to workers' health, via both direct exposure to environmental risks and the indirect worsening of social and health inequalities. Occupational health, which focuses on the promotion of mental and physical health and well-being of workers, and the avoidance of occupationrelated health risks, is a crucial but less discussed concern and component of human health. Relevant research at the intersection of climate change and occupational health remains scarce. Additionally, mitigation of climate change and adaptation efforts are driving forces for rapid transformations in the workplace, including shifts towards sustainability and circular economy models. These transitions are creating new occupational hazards, including those concerning renewable energy and the circular economy sectors. Investment in occupational health research and surveillance should be increased to address the evolving influences of both climate change and the green transition, to enhance and protect workers' CV and general health. Among the work-related factors that play an important role in patients with CVD, the following seem crucial: work participation, physical and mental work capability, appropriate work, support from and flexibility of the work environment, inter-personal communication, person-centered milieu, and interdisciplinary communication. A moderate leisure-time physical activity combined with moderate occupational physical activity may be a more plausible way to combine these two activities to sustain and/or improve CV health. Such an approach may be able to ameliorate workrelated outcomes in patients with CVD. Finally, lifestyle interventions targeting multiple behaviors are also most important to prevent CVD and attain cardiometabolic health. All these issues of occupational CVD are herein reviewed, and relevant meta-analyses are tabulated and discussed.
Introduction/Objective Kidney transplantation is a vital therapeutic option for individuals with end-stage renal disease. Among the various immunosuppressive agents available, everolimus, a selective inhibitor of the mammalian target of rapamycin, is widely used. While previous studies have reported an increased risk of venous thromboembolism (VTE) in heart and lung transplant recipients treated with everolimus, its impact in kidney transplant patients remains less explored. This study aimed to investigate the association between everolimus and VTE in renal transplant recipients.Methods This study is a retrospective observational analysis combining a single-center case series of kidney transplant recipients and a review of cases retrieved from the French National Pharmacovigilance Database.Results From February 2017 to February 2022, in our center, 5 VTE occurred in five kidney transplant patients treated with everolimus. Among them, 3 patients had recurrent VTE. The median time between everolimus initiation and VTE onset was 11 months [IQR 3.8-15.0]. Everolimus was discontinued in one patient (20.0%) following the VTE event. From the French pharmacovigilance database, 16 additional cases of VTE associated with everolimus in the context of organ transplantation were identified. Among these, 12 (75.0%) patients were male, with a median age of 63 years [IQR 56.5-69.0]. Transplanted organs included heart (43.8%), lung (18.8%), and kidney (18.8%). Pulmonary embolism was the most common presentation, occurring in 11 (68.8%) patients, while 2 (12.5%) patients had isolated lower-limb DVT. Thrombosis at unusual sites was reported in three cases: one upper-limb DVT, one jugular vein thrombosis, and one right ventricular intracardiac thrombus. The median time to VTE onset after everolimus initiation was 24 months [IQR 7.5-42.0]. Everolimus therapy was continued in 13 (81.2%) patients, with dose reduction in 2 (12.5%) and discontinuation in 3 (18.9%).Discussion Everolimus may increase the risk of VTE in kidney transplant recipients. This risk appears to be higher in patients with a prior history of VTE before transplantation and during the first year following everolimus initiation.Conclusion Our findings suggest that everolimus may increase the risk of VTE in kidney transplant recipients. Further studies are needed to confirm this association and to evaluate the benefit-risk profile of everolimus compared with other immunosuppressive therapies in renal transplant patients.Type of Research Single-center and Pharmacovigilance Retrospective Observational Studies
Vascular remodeling, a common feature of hypertension and its complications, involves the reconstruction of blood vessel layers through mechanisms of vascular matrix degradation and reorganization. This process is an important step in development, morphogenesis, and tissue repair. Normally, it is regulated by physiological conditions, but when dysregulated, it may contribute to the pathogenesis of several diseases, such as arthritis, cancer, chronic ulcers, and fibrosis. Uncontrolled remodeling of the extracellular matrix (ECM) in the myocardium and vasculature is characteristic of cardiovascular diseases (CVDs). Matrix metalloproteinases (MMPs) have been highlighted as an important class of enzymes with cleavage capacity linked to remodeling processes in CVDs. These proteolytic enzymes are involved in collagen degradation, contribute to the formation and breakdown of various ECM proteins, and participate in cell migration and growth regulation. They are present in several cell types and tissues, including vascular smooth muscle cells, fibroblasts, endothelium, and inflammatory cells. Activation of the renin-angiotensin-aldosterone system affects vascular structure by promoting fibrosis and growth and is also an important regulator of inflammation and vascular remodeling. In this context, this review aims to provide insight into the biological role of MMPs (focusing on MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMPs) in the development and progression of CVDs, as well as the severe implications of acute blood pressure elevations, such as eclampsia, stroke, and other related conditions, highlighting the varied roles of MMPs in vascular remodeling processes.
INTRODUCTION:Cardiovascular Diseases (CVDs) are the predominant chronic illness among the aged population. One in five people died from CDV in 2022, with approximately 700000 people losing their lives to the condition. Chitosan-saponin-bentonite nanocomposites (CSB-NC ) exhibit antioxidant, anti-inflammatory effects, as well as anti-proliferative and anti-apoptotic properties. The present study aims to examine the cardioprotective effects of CSB-NC against the cardiovascular toxicity associated with doxorubicin (Dox). METHODS:Cardiovascular toxicity was induced in rats following the administration of Dox (3 mg/kg body weight, i.p.) on days 2, 4, 6, 8, 10, and 12. Thirty-six rats were divided into six groups, each consisting of six rats. The groups included: control, Dox, Dox + chitosan (60 mg/kg, orally), Dox + bentonite (60 mg/kg, orally), Dox + saponins (60 mg/kg, orally), and Dox + CSB-NC (60 mg/kg, orally). RESULTS:Following CSB-NC treatment, the ST segment of the ECG exhibited partial normalization. CSB-NC reduced the levels of cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, nitric oxide, DNA fragmentation, and caspase-3, while it elevated glutathione, reduced catalase, nuclear factor erythroid 2-related factor 2 (Nrf2) expression, and Bcell leukemia/lymphoma 2 (Bcl-2). The CSB-NC-treated group exhibited a normal histological structure of cardiac muscle. DISCUSSION:CSB-NC demonstrated a protective effect on the heart against Dox toxicity by enhancing the Nrf2 pathway, supporting the internal antioxidant system, and inhibiting the apoptotic pathway by reducing caspase-3 and stimulating Bcl-2 expression. CONCLUSION:CSB-NC showed a synergistic protective effect against cardiovascular toxicity induced by Dox when combined with saponin, chitosan, and bentonite.
BACKGROUND:End-stage renal disease (ESRD) patients on hemodialysis are at higher risk for cardiovascular complications due to the increased risk of atherosclerosis. This study aims to evaluate the factors associated with poor outcomes in this group of patients with Peripheral arterial disease (PAD) regarding survival and rates of lower limb amputation, which is an important determinant of morbidity and quality of life. METHODS:A retrospective analysis was performed using hospital databases from 2010 to 2021. ESRD patients who were diagnosed with PAD during this period were studied; diagnosis was done through CT-angiography. Predefined endpoints were death and amputation. RESULTS:The mean age for the patients was 65.9 (SD 12.96) and 66.7% were males. Most patients had either DM (84.6%) or HTN (91%). The prevalence of amputation was 44.7%, 32.9% were males (P=0.33); using univariate analysis DM was a strong predictor for amputation (P=0.001) as long as coronary artery disease (P=0.001) while other comorbidities like HTN (P=0.66), heart failure (P=0.86), atrial fibrillation (P=0.81), Dyslipidemia (P=0.95) and stroke (P=0.16) were not associated with amputation. On multivariate analysis, only DM (P=0.003) was associated with a higher prevalence of amputation Time to death was 16.9 months (SDܸ25.6), 11.3 months (SDܸ9.1) for patients with amputation vs. 21.1 (SDܸ32.7) for those without amputation. CONCLUSION:End-stage renal disease patients with PVD, especially with PVD, have higher mortality, and the majority are diabetic, which necessitates earlier recognition of PVD and modified risk factors like better control of DM and its complications in addition to other risk factors like HTN, dyslipidemia, and metabolic disorders of CKD.
INTRODUCTION:This study evaluates dyslipidaemia management in the Arabian Gulf region. METHODS:The multicentre, multinational longitudinal Gulf ACTION registry includes adults (≥18 years old) on lipid-lowering therapy (LLT) recruited from outpatient clinics at 14 tertiary care centres and 9 primary care clinics across five Arabian Gulf countries. RESULTS:A total of 2884 patients were enrolled (mean age 58±12 years); 63% were male. The median first follow-up was 7 (6-11) months, and the median second follow-up was 14 (12-23) months. Among the cohort, 52% of patients were very high risk, 21% of whom achieved their LDL-C target; 40% were high risk, 24% achieved their LDL-C target; 2% were moderate risk, 72% achieved their LDL-C target; and 6% were low risk, 78% achieved their LDL-C target. Only 24% of the overall cohort and 30% of the very high-risk group were treated with combination LLT. DISCUSSION:Similar to international data from the SANTORINI and INTERASPIRE studies, our study showed that only one-fourth of the very high-risk group and one-third of the high-risk group achieved their LDL-C targets. Potential reasons include lower use of combination therapy, poor health behaviors, and psychosocial factors. The variability in practice patterns across the Arabian Gulf and even among study sites is a limitation. CONCLUSION:Very high- and high-risk groups were less likely to achieve their LDL-C target. The low use of combination LLT, unhealthy lifestyle, and social factors in the Gulf region were the main reasons for such poor control. Strategies are needed to achieve current guideline-recommended LDL-C targets.
INTRODUCTION:Statins exhibit pleiotropic effects with potential benefits in several infectious diseases, but their role in infective endocarditis (IE) remains unclear. We evaluated the impact of statin use on the frequency of IE and on key clinical outcomes in patients with IE, specifically embolic events (EE) and mortality. METHODS:We conducted a meta-analysis in which the primary outcome was the frequency of IE among statin users compared with non-users. Secondary outcomes included EE and follow-up mortality (6 months to 1 year). RESULTS:Eleven observational studies, eight retrospective and three prospective, were included, comprising a total of 35,844 patients. The frequency of IE was significantly lower in patients receiving statins compared with non-users (odds ratio (OR): 0.52; 95% confidence interval (CI): 0.34-0.80; P=0.003). Statin-treated IE patients also had fewer EE than non-users (OR: 0.50; 95% CI: 0.26-0.96; P=0.04). Follow-up mortality was significantly reduced in IE patients using statins compared with non-users (hazard ratio (HR): 0.70; 95% CI: 0.61-0.80; P<0.00001). DISCUSSION:Statins exert anti-inflammatory, endothelial-stabilizing, and antithrombotic effects that counteract key pathological mechanisms underlying IE. In this meta-analysis, statin use was associated with a lower frequency of IE, fewer EE, and reduced follow-up mortality. CONCLUSION:This meta-analysis suggests that statins may offer protective benefits against the incidence of IE and its complications. However, these findings should be interpreted with caution and highlight the need for further research.
INTRODUCTION:Circadian rhythm influences the clinical spectrum of stroke. Despite extensive research, studies examining the circadian influences on stroke occurrence, focusing on demographic factors and common risk factors, are limited. This study aims to examine the distribution and circadian patterns of ischemic stroke onset times and to analyze demographic factors and risk factors related to stroke timing. METHODS:Conducted at Shanghai East Hospital, an affiliated hospital of Tongji University, this study analyzed electronic medical records from 2021 and 2022, screening 1,320 patients. A total of 406 patients met the inclusion criteria: >18 years old, Chinese nationality, diagnosed with acute ischemic stroke, and without liver disease. Stroke occurrences were categorized into six time intervals for Cosinor analysis and chi-square tests. RESULTS:Among 406 patients (62.1% male, mean age 68.7 years), stroke occurrences showed a clear circadian pattern, peaking between 08:00 and 11:59 (36.2%) and occurring predominantly during daylight hours (75.9%). Cosinor analysis confirmed significant circadian rhythmicity. Hypertension (67.5%) and diabetes (33%) were not significantly associated with stroke onset timing. No significant differences in stroke timing were observed across gender or age groups. DISCUSSION:Patients with a history of previous stroke demonstrated a significant association with late afternoon onset (p = 0.038), a pattern infrequently reported in prior studies that may reflect altered vulnerability or treatment-related factors. CONCLUSION:This study demonstrates a pronounced circadian pattern in ischemic stroke, with a latemorning peak. The observed late-afternoon signal among patients with prior stroke warrants further investigation to clarify underlying mechanisms and implications for prevention strategies.
Chronic obstructive pulmonary disease (COPD) remains a significant global public health challenge, plagued by substantial morbidity and mortality worldwide; it is one of the main causes of death worldwide, especially during episodes of severe exacerbation. There is a higher COPD burden noted in regions with high smoking prevalence, air pollution, and faster socioeconomic development. There is also a high number of cardiovascular (CV) comorbidities among these patients, pointing to a need for routine CV screening in such circumstances. These two diseases, COPD and CV disease (CVD), are associated via an intricate and multifactorial interplay characterized by convergent risk factors, systemic inflammation, and interlinked pathophysiological mechanisms, with atherosclerosis being a principal inflammatory process linking these two disorders, driven by systemic inflammation, oxidative stress, and endothelial dysfunction. Importantly, despite the fact that CVD is common in COPD, it remains underdiagnosed and undertreated due to overlapping respiratory and cardiac symptomatology. The latter issue is accentuated in the case of heart failure (HF) and coronary artery disease (CAD), whereby HF atypical symptoms may mimic the clinical picture of COPD exacerbation and CAD presenting with atypical symptomatology such as dyspnea on exertion and/or fatigue, which may point to HF/COPD worsening. Thus, a structured CV assessment and management following exacerbations of COPD is needed in order to identify CAD and/or other new heart disease in these patients and guide appropriate management. These issues are discussed with relevant metaanalyses and key guidelines tabulated, and the involved interrelated mechanisms are pictorially illustrated.
INTRODUCTION:Metabolic dysfunction-associated steatotic liver disease (MASLD) and peripheral arterial disease (PAD) are highly prevalent conditions that increase cardiovascular risk. This review aims to summarize current evidence on the association between MASLD and PAD, with a particular focus on clinical studies. A critical appraisal of this association will enhance understanding of MASLD as a multi-system disease and provide potential therapeutic implications. METHODS:A literature search was performed using the PubMed database. RESULTS:Both MASLD and PAD are multifactorial diseases that share common risk factors and pathogenic mechanisms. Most relevant clinical studies support an association between MASLD and PAD, particularly in the context of hepatic steatosis. Data regarding steatohepatitis or hepatic fibrosis are limited, largely due to the scarcity of studies with biopsy-proven MASLD. Management strategies for MASLD and PAD overlap, emphasizing lifestyle modifications such as a balanced diet, regular exercise, and smoking cessation. Additionally, certain medications used for PAD (e.g., statins, aspirin) or under investigation for MASLD (e.g., glucagon-like peptide-1 receptor agonists, dual and triple peptide agonists) may have beneficial effects on both conditions. DISCUSSION:Until clinical trials specifically evaluate medications for patients with concomitant MASLD and PAD, priority should be given to lifestyle interventions and the management of shared comorbidities, including obesity, type 2 diabetes mellitus, arterial hypertension, and dyslipidemia, which may confer benefits for both diseases. CONCLUSIONS:MASLD and PAD frequently coexist. Targeting both conditions is expected to reduce the elevated cardiovascular risk observed in patients affected by both MASLD and PAD.
BACKGROUND:Several scores have been developed to facilitate risk stratification and early discharge following primary angioplasty, particularly the Zwolle Risk Score (ZRS). However, validation in large-sized studies is still lacking. Therefore, the aim of the current study was to validate the use of the ZRS in a contemporary global population, including patients who were treated during the SARS-CoV-2 pandemic and enrolled in a large intercontinental observational study. METHODS:The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving primary PCI centers from Europe, Latin America, South-East Asia, and NorthAfrica, including patients treated from March 1st until June 30th, in 2019 and 2020]. ZRS was calculated for each patient. The patients were additionally categorized according to the following values of the ZRS [≤3; 4-6; 7-9; ≥10]. Our study outcomes were in-hospital and 30-day mortality. The discriminatory capacity of the ZRS was assessed by the area under the ROC curve [c statistic] as an index of model performance. RESULTS:Our population is represented by 16084 STEMI patients undergoing mechanical reperfusion enrolled in 109 centers. The score showed a very good performance in the predicting mortality both in-hospital [AUC=0.83 [0.82-0.85], p<0.0001] and at 30- day follow-up [AUC=0.82 [0.81-0.84, p<0.0001]. The results were confirmed when the ZRS was separately applied to patients treated in 2019 and 2020, with good stability across time. ZRS was able to identify a large cohort [n=10672, 66.3%] of low-risk patients [score ≤3] with a very low mortality rate at 2 days [1%] and between 3 and 10 days [0.7%], with a very good negative predictive value for in-hospital [98.3%] and 30-day mortality [97.7%], with similar results in 2019 and 2020. CONCLUSION:This study is the first to demonstrate the good prognostic performance of the ZRS in a large-scale contemporary global multicenter validation set. Similar results were obtained both in the pre-pandemic and the COVID-19 era. ZRS ≤3 identified a very low-risk population that could be discharged early, even during the COVID-19 pandemic, with expected advantages in the availability of hospital beds and nursing staff, costs of medical care, and in-hospital risk of contagion.
AIMS:Our study was to investigate the association between statin use and the prevalence of abdominal aortic calcification (AAC). METHODS:The population was enrolled in the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). The statin use was determined from the questionnaire inquiring the medications taken in the past month. The presence of AAC and severe AAC were assessed based on the AAC score measured by abdominal dual-energy X-ray absorptiometry (DXA). Logistic regression analysis was performed to evaluate the association between statin treatment and AAC after adjustment for potential confounders. RESULTS:The study included a total of 2074 individuals; the average age 61.6±11.8 years old and 922 (44.5%) were male. AAC (AAC score >0) was present in 35.4% of the population and 12.0% had severe AAC. There were 836 (40.3%) statin users. After adjustment for demographics, lifestyles, comorbidities, and laboratory examinations, statin use was associated with higher odds of AAC (OR 1.28, 95%CI 1.02-1.62; P=0.034) and severe AAC (OR 1.78, 95%CI 1.24-2.55; P=0.002), respectively. Subgroup analysis revealed that the association was stronger in male, non-diabetic participants and those aged >60 years old. CONCLUSION:Stain use was associated with a greater presence of AAC and severe AAC. This association was stronger for male, non-diabetic participants and those aged >60 years.
Aims This study aimed to evaluate clinical outcomes, including recurrent acute coronary syndrome (ACS) and mortality, in ACS patients with varying HbA1c levels, addressing the controversy over optimal targets in those with newly diagnosed and pre-existing diabetes mellitus (DM).Methods From January 2005 to December 2019, a total of 33,990 patients were identified with ACS in the Chang Gung Research Database based on their medical history. After excluding patients without DM and baseline or subsequent HbA1C data, a cohort of 11,870 DM patients was divided into two groups: one consisting of 6,089 patients with newly diagnosed DM and the other comprising 5,781 patients with pre-existing DM.Results During the three-year follow-up, the pre-existing DM group experienced worse clinical outcomes, such as increased rates of re-ACS, major bleeding, cardiovascular (CV) events, and all-cause mortality. Optimal HbA1c levels for mitigating re-ACS and/or CV mortality and all-cause mortality appeared to differ between the two DM cohorts. Re-ACS and CV mortality reached their highest at an HbA1c of 6.8% for all DM patients, 6.6% for newly diagnosed, and 6.7% for pre-existing cases. The greatest all-cause mortality risk was at an HbA1c of 7.4% for all DM patients, 7.0% in newly diagnosed, and 8.2% in pre-existing patients.Conclusion Upon comparing newly diagnosed DM patients with those with pre-existing DM, a poorer prognosis was observed in the latter group, attributed to older age and a higher burden of comorbidities. Throughout the follow-up period, maintaining consistently low HbA1c levels did not reduce the incidence of re-ACS nor enhance survival rates.
Background: Hepatic fibrosis, a chronic pathological condition, is associated with adverse outcomes in stroke patients. Cardioembolism (CE) is a common etiology of stroke, yet the association between hepatic fibrosis and CE remains understudied. Aim: This study aims to investigate the association between hepatic fibrosis and CE-induced stroke, as well as its impact on stroke patient prognosis. Methods: This retrospective study included 344 acute ischemic stroke (AIS) patients who underwent thrombolytic therapy. Hepatic fibrosis was assessed using the Fibrosis-4 (FIB-4) index and the Aspartate Aminotransferase-Platelet Ratio Index (APRI). Mediation analysis examined the role of CE in the association between hepatic fibrosis and 3-month functional outcomes. Results: Among 344 patients, 319 were classified using the Trial of Org 10172 in Acute Stroke Treatment criteria. Severe fibrosis (FIB-4 ≥ 2.01) was observed in 131 patients (38.08%), and CE was identified in 79 patients. FIB-4 was an independent predictor of CE (OR: 2.038, 95%CI: 1.507- 2.757, p < 0.001) and poor 3-month functional outcome (OR: 1.477, 95%CI: 1.103-1.978, p = 0.009) after adjusting for confounders. The effect of FIB-4 on poor 3-month functional outcomes was partially mediated by CE, with a mediation proportion of 30.63%. Conclusions: Hepatic fibrosis is a significant predictor of short-term functional outcomes in AIS, particularly cardioembolic stroke. The association between hepatic fibrosis and stroke outcomes is partially mediated through CE. These findings highlight the importance of assessing hepatic fibrosis in stroke patients, particularly those with CE etiology.
Pericytes, also known as mural cells, are cells embedded between endothelial cells and the basement membrane of capillaries, where they orchestrate the morphological and functional homeostasis of blood vessels. Within the tumor microenvironment, pericytes interact closely with various cellular components, including tumor cells, stromal cells, and immune cells. Through these dynamic interactions, pericytes are activated and subsequently transform into tumor-associated pericytes (TPCs). The origin of TPCs varies depending on the tissue and tumor type, contributing to their phenotypic and functional heterogeneity. TPCs play pivotal roles in facilitating tumor progression, metastasis, immune evasion, and therapeutic resistance by promoting angiogenesis, engaging in reciprocal interactions with tumor cells, remodeling the extracellular matrix, and fostering an immunosuppressive microenvironment. This review synthesizes the latest significant advancements in targeted therapies against TPCs. It underscores the challenges inherent in developing effective anti-TPC therapies, which include the heterogeneity and pluripotency of TPCs, the absence of specific markers for precise TPC targeting, and the limited understanding of how current anti-tumor therapies affect TPCs and vice versa. This review furnishes a comprehensive understanding of the origins, markers, and functions of TPCs, and their interplays within the tumor microenvironment, providing prospective strategies for more effective anti-tumor therapy.
INTRODUCTION/OBJECTIVE:Both fasting and postprandial hypertriglyceridemia are associated with atherosclerotic cardiovascular disease (ASCVD). The Hellenic Postprandial Lipemia Study (HPLS, NCT02163044) is the largest prospective cohort trial assessing the effects of statin therapy on postprandial lipemia. METHODS:Individuals at high or very high risk for ASCVD were evaluated, and their characteristics were recorded at baseline (Visit 1). At Visit 2 (2-4 weeks after Visit 1) and Visit 3 (3-4 months after Visit 2), serum triglyceride (TG) levels were measured after a 12-hour fast (fTG) as well as 4 hours after the ingestion of a commercially available oral fat tolerance test meal (pTG). After Visit 2, all individuals were treated with a statin. RESULTS AND DISCUSSION:Among 900 participants, 699 completed all 3 visits, and of these, 209 (29.9%) had an abnormal pTG response. The mean (standard deviation, SD) total- and low-density lipoprotein cholesterol concentrations were 225 (50) and 148 (46) mg/dL at Visit 1, 231 (42) and 156 (40) mg/dL at Visit 2, and 171 (28) and 101 (27) mg/dL at Visit 3. At Visit 2, the mean fTG level was 127 (45) mg/dL and pTG was 188 (73) mg/dL with a mean difference of 58 mg/dL (P<0.001). At Visit 3, the mean fTG concentration was 110 (40) mg/dL, while pTG was 140 (54) mg/dL (mean difference: 29 mg/dL; P<0.001). Fasting glucose levels had no impact on pTG response in statin-treated individuals with abnormal postprandial lipemia. CONCLUSION:Nearly 30% of individuals at high-/very high-risk for ASCVD had postprandial hypertriglyceridemia. Statin treatment normalized abnormal postprandial lipemia in 75.6% of participants, and decreased pTG concentration even in those with normal fTG levels.
BACKGROUND:Patients with adult growth hormone deficiency (AGHD) show accelerated atherosclerosis. While growth hormone replacement therapy (GHRT) may help mitigate this process, the mechanisms driving atherosclerosis progression in GHRT-treated patients with AGHD remain unclear. METHODS:Thirty-one patients with AGHD on daily GHRT for ≥5 years were assessed in this crosssectional study. Carotid intima-media thickness (cIMT) was evaluated by ultrasound. Reactive hyperemia index (RHI) was measured using peripheral arterial tonometry. Associations between vascular measures and clinical, pituitary, treatment, body composition, and laboratory parameters were evaluated. RESULTS:cIMT correlated with body mass index (r=0.584, p=0.001) and visceral adipose tissue area (r=0.791, p<0.001), while demonstrating nominally significant associations with triglyceride levels, insulin resistance index, smoking history, and arterial hypertension. Neither the current nor the 5-year mean insulin-like growth factor 1 standard deviation score directly correlated with vascular parameters. Median cIMT was higher in adult-onset compared with child-onset AGHD (0.70 vs. 0.58 mm; p=0.020), while median RHI was lower in genetic than structural etiology (1.58 vs. 2.18; p=0.010); however, both associations were nominally significant. DISCUSSION:Several of the identified cardiovascular risk factors associated with cIMT are unlikely to be sufficiently controlled through GHRT. Pituitary disease characteristics may play a role in atherogenesis; however, the subgroups defined by disease onset timing and etiology were small and not fully comparable. CONCLUSION:In long-term GHRT-treated patients, cIMT is linked to well-established cardiovascular risk factors rather than features of the pituitary disorder and its management, highlighting the need for targeted cardiovascular risk management alongside GHRT in AGHD.
