Ischemic Cardiovascular Disease Research Articles

A Narrative Review on the FSTL-1 Protein and its Current Known Impact on Cardiovascular Ischaemic Disease

This narrative review investigates the potential therapeutic role of FSTL-1 in addressing severe cardiac issues following myocardial infarctions (MI). Despite advances in modern medicine, MI persist as a leading global cause of death, with stem cell therapy falling short of expectations since the early 2000s. In contrast, FSTL-1, an emerging bone morphogenetic protein, demonstrates promise based on successful studies. We conducted a qualitative narrative synthesis of studies published in PubMed, Scopus, and Web of Science between January 2000 and May 2022. This research explores the intricate scientific aspects of FSTL-1's contribution to myocardial regeneration, utilizing a chronological approach to trace its progression from biological pathways to broader scenarios. It examines the mechanisms regulated by FSTL-1 and its effects on cardiac tissue and cells, highlighting its potential as a therapeutic agent emphasizing its multifaceted role in cardiac regeneration. By deepening our comprehension of FSTL-1, this study significantly contributes to knowledge advancement, offering insights into its role in addressing severe cardiac issues post-MI. By consolidating current knowledge and proposing new avenues for investigation, this work offers valuable insights into FSTL-1's significance in advancing cardiovascular health and post-MI recovery.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells. A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional Dcbld1 knockout mice in vivo. Immunoblotting, immunofluorescence staining, plasma membrane subfraction isolation, Coimmunoprecipitation, and mass spectrum assay were performed to clarify the molecular mechanisms. Loss of Dcbld1 impaired VEGF (vascular endothelial growth factor) response and inhibited VEGF-induced endothelial cell proliferation and migration. Dcbld1 deletion interfered with adult and developmental angiogenesis. Mechanistically, DCBLD1 bound to VEGFR-2 and regulated the formation of VEGFR-2 complex with negative regulators: protein tyrosine phosphatases, E3 ubiquitin ligases (Nedd4 and c-Cbl), and also Dcbld1 knockdown promoted lysosome-mediated VEGFR-2 degradation in endothelial cells. These findings demonstrated the essential role of endothelial DCBLD1 in regulating VEGF signaling and provided evidence that DCBLD1 promotes VEGF-induced angiogenesis by limiting the dephosphorylation, ubiquitination, and lysosome degradation after VEGFR-2 endocytosis. We proposed that endothelial DCBLD1 is a potential therapeutic target for ischemic cardiovascular diseases by the modulation of angiogenesis through regulation of the VEGFR-2 endocytosis.

Impact of Dual Antithrombotic Therapy with Aspirin and Rivaroxaban on Secondary Cardiovascular Outcomes.

BACKGROUND Dual antiplatelet therapy is the main treatment for cardiovascular diseases (CADs). In this study, we evaluated the efficacy and safety of aspirin combined with low-dose rivaroxaban in the secondary prevention of high-risk ischemic cardiovascular diseases. MATERIAL AND METHODS In total, 168 patients who were diagnosed with acute myocardial infarction or multiple vessel disease 1 year after percutaneous coronary intervention were divided into 2 groups: the aspirin group (aspirin as acetylsalicylic acid: 100 mg once daily) and the aspirin + rivaroxaban group (aspirin: 100 mg once daily, rivaroxaban: 2.5 mg twice daily). The patients were followed up for 2 years to assess the clinical efficacy and safety of a new dual-channel antithrombotic treatment strategy. RESULTS The occurrence of MACE (recurrent myocardial infarction, in-stent restenosis, coronary target vessel revascularization, stent thrombosis, heart failure, rehospitalization, and all-cause mortality) in the rivaroxaban + aspirin group was lower than that in the aspirin group (3.57% of patients received aspirin + rivaroxaban treatment vs 13.10% of patients received aspirin treatment). There were not more adverse events in the rivaroxaban + aspirin group than in the aspirin group. Compared with patients administered aspirin, the coagulation function of patients taking aspirin + rivaroxaban was significantly changed. No heart failure occurred in either group of patients with CADs. CONCLUSIONS Aspirin + rivaroxaban had better primary outcome and secondary outcomes in patients with a high risk of ischemia. Our results provide a basis for evaluating the efficacy and safety of drugs used in secondary prevention among patients with high risk of ischemia.

Interplay between platelets and coagulation: from protective haemostasis to pathological arterial thrombosis

Abstract Haemostasis refers to the physiological process aimed at repairing vessel injury and preventing bleeding. It involves four interlinked stages culminating in the formation of a platelet–fibrin haemostatic plug that is eventually dissolved once the vessel heals. In contrast, arterial thrombosis is a pathological condition resulting from atheroma exposure, triggering the formation of a platelet-rich thrombus that may obstruct blood flow, leading to the clinical manifestations of ischaemic cardiovascular disease. The following review will provide a comprehensive overview of the finely regulated endogenous antithrombotic mechanisms responsible for maintaining the haemostatic balance and preventing intravascular thrombosis. Thereafter, it will further detail the different stages and mechanisms governing the intricate interplay between the vessel, platelets, and the coagulation cascade in haemostasis, highlighting the most recent advances in platelet biology and function, to further elucidate the differential traits and players contributing to pathological arterial thrombus growth. The review will also delve into the impact of emerging cardiovascular risk factors on tilting the haemostatic balance towards a pro-thrombotic state, thereby increasing the patient’s vulnerability to thrombotic events. Finally, it will underscore the importance of early screening for subclinical atherosclerosis through advanced imaging technologies capable of quantifying plaque burden and metabolic activity since they may set the stage for an increased thrombotic risk. Implementing proactive interventions to halt atherosclerosis progression or inducing its regression at early stages is crucial for preserving haemostasis and reducing the likelihood of ischaemic atherothrombotic disease.

Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration

BackgroundImmediate activated factor (F)X (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases. ObjectivesTherefore, we analyzed platelet-derived effects of long-term FXa inhibition in the setting of acute myocardial infarction (AMI) and stroke. MethodsWe evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following AMI and stroke in mice in vivo. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa nonvitamin K antagonist oral anticoagulant treatment and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of patients with AMI, we determined cardiovascular magnetic resonance based cardiac endpoints under FXa nonvitamin K antagonist oral anticoagulant effects on clinical endpoints in a cohort of patients with AMI. ResultsChronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24 hours after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced neutrophil extracellular trap formation in mice and patient samples. Proteome and RNA expression analysis of FXa inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet α and dense granule release. Subsequent, thromboinflammatory neutrophil extracellular trap density in thrombi isolated from stroke and myocardial infarction patients was reduced. Patients with AMI treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment. ConclusionLong-term FXa inhibition induces antithromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke.

Cardiovascular disease burden and risk factor management in cancer survivors: insights from a large-scale East London cohort

Abstract Introduction Improvements in cancer survival have led to an urgent need to address long-term health issues among survivors, notably increased risk of cardiovascular disease (CVD). Shared risk factors may underpin at least part of this excess risk. Aims To investigate differences in cardiovascular risk profile between cancer survivors and controls; and to assesses the management of hypertension and statin use among cancer survivors compared with controls in a multi-ethnic and socio-economically diverse population. Methods The data were obtained from electronic health records of 1.2 million people registered with general practices in East London. It provides a snapshot of health records at the time of data extraction (01/01/2023). We identify individuals with record of past cancer (grouped into 20 cancer types) and their cardiovascular profile. Each cancer-exposed patient was age- and sex-matched to four non-cancer comparators. Multivariable logistic regression, with extensive adjustment for demographic and health-related variables, was used to elucidate the independent associations of past cancer with a range of cardiovascular outcomes. Patterns of guideline-directed risk factor control among cancer patients with hypertension and ischaemic CVDs (vs non-cancer controls) were assessed. Results The study consisted of 18,839 cancer survivors and 75,356 matched controls (64±15 years, 43% male), with marked ethnic diversity (cancer survivors: 48% White, 24% Black and 22% Asian) and socio-economic deprivation. Compared to matched controls, patients with past cancer had a higher prevalence of hypertension (44% vs. 41%) and chronic kidney disease (18% vs. 14%). We observed a higher prevalence of CVDs including venous thromboembolism (VTE) (5.6% vs. 2.8%), atrial fibrillation (AF) (6.5% vs. 5%), and heart failure (HF) (4.4% vs. 3.4%) among cancer survivors. Regression models fully adjusted for shared risk factors demonstrated an increased risk of a range of CVDs in patients with (any) past cancer, including VTE (OR 2.01), HF (OR 1.31) and AF (OR 1.27). CVD risk varied across cancer types (Figure 1). For example, lung cancer survivors had an elevated risk of VTE (OR 4.02), AF (OR 2.47), IHD (OR 1.45) and peripheral artery disease (OR 1.67) while colorectal cancer survivors had increased risks of VTE (OR 2.68), HF (OR 1.4) and AF (OR 1.32). In subgroup analyses, control of blood pressure and cholesterol did not differ significantly across cancer survivors and matched controls with hypertension and ischaemic CVDs, respectively. Conclusion We show higher burden of VRFs and an increased risk of CVDs among cancer survivors compared with non-cancer controls, with notable variation across cancer types. The lack of difference in control of blood pressure and cholesterol between cancer survivors and controls suggests that these risk factors did not explain the increased risk. Suggesting that an individualised approach to risk management is likely to be warranted.Risk of CVDs in Cancer Survivors

Drug eluting stents trigger the secretion of inflammatory proteins in an experimental in vitro study

Abstract Introduction Ischemic cardiovascular diseases commonly appear following the occlusion of one or more of the coronary arteries. Drug eluting stents (DES) constitute the gold standard to help to keep open the arteries and maintain the blood flow. After their placement into the coronary arteries, they stay in direct contact with the blood stream, disturbing the physiological conditions and interacting with several cells and proteins within the surrounding blood and vessel wall. Besides the beneficial effects of DES, their clinical application is also associated with complications, such as (late) stent thromboses. Previous studies have shown that thrombosis and inflammation are tightly linked with each other by activating inflammatory cells and secreting cytokines and chemokines to further promote an inflammatory surrounding. However, the influence of DES and their components on the inflammatory cascade and their corresponding players was not investigated yet. Methods To investigate the inflammatory secretome in response to DES, we performed an in vitro study with isolated human peripheral blood mononuclear cells (PBMCs). Therefore, PBMCs were isolated from the whole blood of four healthy volunteers. In total, 63 stents were used in the study, including Medtronic Resolute Onyx (n=37), Abbott XIENCE Sierra (n=5), Boston Scientific SYNERGY (n=4), Terumo Ultimaster (n=3), and Biotronik Orsiro (n=14). We measured the secretion of cytokines and chemokines, including IL-1β, IL-6, TNF-α, IL-8, and IL-12, as well as ICAM-1, VCAM-1, and MCP-1 by commercially available enzyme-linked immunosorbent assay (ELISA). Results Our results showed that DES significantly increase the secretion of the cytokines IL-1β (p=0.0005), and IL-6 (p=0.0002), as well as the chemokine IL-8 (p=0.0010). Additionally, we also detected an elevation of the reaction product ICAM-1 (p=0.0003). Further analyses resulted in a reduced secretion of IL-1β, IL-6, TNF-α, IL-8, and ICAM-1 into the cells’ supernatants in response to Resolute Onyx stents, in comparison to the other stents. Moreover, multiple regression analysis revealed a high dependency of the inflammatory reaction on the elution drug, the polymer type and the stent’s length. Additionally, the material of the stent platform, as well as the polymer thickness further have impact on the cytokine and chemokine response of PBMCs. Conclusion Our study indicate that DES by themselves trigger an inflammatory reaction of blood cells by the secretion of cytokines and chemokines. Furthermore, we provided first insights into the composition of the inflammosome in response to DES. A triggered inflammation may increase the vulnerability for complications and the failure of the DES. As these complications were already observed in clinical studies, our results would potentially provide predictions about the application of certain DES designs and may help to choose the appropriate stents in the clinical setting.

Dual-Activated Photoacoustic Probe for Reliably Detecting Hydroxyl Radical in Ischemic Cardiovascular Disease in Mouse and Human Samples.

Cardiovascular disease (CVD) is a chronic disease characterized by the accumulation of lipids and fibrous tissue within the arterial walls, potentially leading to vascular obstruction and an increased risk of heart disease and stroke. Hydroxyl radicals play a significant role in the formation and progression of CVD as they can instigate lipid peroxidation, resulting in cellular damage and inflammatory responses. However, precisely detecting hydroxyl radicals in CVD lesions presents significant challenges due to their high reactivity and short lifespan. Herein, we present the development and application of a novel activatable optical probe, Cy-OH-LP, designed to detect hydroxyl radicals in lipid-rich environments specifically. Built on the Cy7 molecular skeleton, Cy-OH-LP exhibits near-infrared absorption and fluorescence characteristics, and its specific response to hydroxyl radicals enables a turn-on signal in both photoacoustic and fluorescence spectra. The probe demonstrated excellent selectivity and stability in various tests. Furthermore, Cy-OH-LP was successfully applied in an in vivo model to detect hydroxyl radicals in mouse models, providing a potential tool for diagnosing and monitoring AS. The biosafety of Cy-OH-LP was also verified, showing low cytotoxicity and no significant organ damage in mice. The findings suggest that Cy-OH-LP is a promising tool for the specific detection of hydroxyl radicals in lipid-rich environments, providing new possibilities for research and clinical applications in the field of oxidative stress-related diseases.

Long-Term Exposure to Arsenic in Community Water Supplies and Risk of Cardiovascular Disease among Women in the California Teachers Study.

Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of . We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards (, 1.00-2.99, 3.00-4.99, 5.00-9.99, ) and continuously using a log2-transformation (i.e., per doubling). Models were adjusted for baseline age, neighborhood socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. We also stratified analyses by age, BMI, and smoking status. Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, ) were 1.06 (95% CI: 1.00, 1.12), 1.05 (95% CI: 0.94, 1.17), 1.20 (95% CI: 1.02, 1.41), and 1.42 (95% CI: 1.10, 1.84) for , , , and , respectively. HRs for every doubling of wAs exposure were 1.04 (95% CI: 1.02, 1.06) for IHD and 1.02 (95% CI: 1.01, 1.04) for CVD. We observed statistically stronger risk among those vs. years of age at enrollment ( and 0.012 for IHD and CVD, respectively). Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410.

Impact of Age on Prescribing Patterns of Cardiovascular Medications in Older Japanese Patients with Non-Dialysis-Dependent Chronic Kidney Disease: A Cross-Sectional Study.

Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population. Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group. Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates. This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

Dynamically crosslinked ECM-like hydrogels loaded with ROS-responsive drug nanoparticles for treating inflammation in myocardial infarction and stroke

Following a myocardial infarction (MI) or stroke, the excessive generation of reactive oxygen species (ROS) within a brief timeframe may induce a pronounced inflammatory reaction, which exacerbates the progression of the disease. Thus, there is an urgent need to design a biomaterial to inhibit the inflammatory response associated with MI and stroke. In this study, we designed a reversible extracellular matrix (ECM)-like hydrogel via borate ester crosslinking, which responds to the inflammatory microenvironment affected by MI and stroke. At the same time, we developed a new type of loaded polymer nanoparticle (TK-DA) that can respond to ROS in ischemic regions and release the anti-inflammatory drug dexamethasone. Ultimately, we integrated the nanoparticles and ECM-like hydrogel to fabricate a functional hydrogel. To verify the therapeutic effect of the functional hydrogel, we established two models of typical ischemic diseases, MI and stroke. The results showed that the hydrogel substantially reduced ROS levels and inflammation in vitro. Moreover, the results of the two in vivo animal models demonstrated that this functional hydrogel can effectively treat MI and stroke by suppressing inflammatory responses, mitigating apoptosis, and promoting neovascularization. In conclusion, the functional hydrogel strategy presents a universally applicable treatment approach for ischemic cardiovascular and cerebrovascular diseases, which are not limited solely to the treatment of MI and stroke, but also hold future potential for clinical applications.

Influence of Clinical, Angiographic, and Developmental Characteristics and COVID-19 Severity and Vaccination Status on Young Patients with Acute Myocardial Infarction.

Atherosclerosis is the most common cause of ischemic cardiovascular disease (CVD). However, approximately 20%-40% of cases of acute myocardial infarction (AMI) in patients aged <50 years can be attributed to genetic factors, and coronavirus disease 2019 (COVID-19) is a risk factor for blood clots and AMI. We aimed to describe the clinical, angiographic, and developmental characteristics and COVID-19 severity and vaccination status in patients aged ≤45 years with AMI. We retrospectively analyzed 2624 patients with AMI by reviewing the results of coronary angiography and percutaneous coronary intervention and medical reports. The study included patients aged >18 years who met the universal definition of AMI but excluded those with missing medical records or coronary angiograms. In total, 2624 patients with AMI (aged 18-85 years) were included in the study and divided into two groups based on age: ≤45 (n = 1286) and >45 years (n = 1338). Total cholesterol and triglyceride levels were significantly higher in patients aged ≤45 years (5.6 ± 2.1 and 3.2 ± 2.1 mmol/L, respectively, P < 0.007) than in those aged >45 years (6.3 ± 1.8 and 3.1 ± 2.0 mmol/L, respectively, P < 0.001). Overall, 1745 and 879 patients were unvaccinated and fully vaccinated, respectively; severe and critical COVID-19 infections were more common among unvaccinated patients in both age groups. Younger patients with AMI were more likely to be smokers with no hypertension, diabetes mellitus, or previous AMI. In contrast, they were more likely to have hypercholesterolemia and hypertriglyceridemia, single-vessel disease, Type C lesions, and a history of drug-eluting stent use.

Peripheral Artery Disease among a High-Risk Asian Population with Ischaemic Stroke, Cardiovascular Disease, or Diabetes Mellitus.

Background: Peripheral artery disease (PAD) affects more than 100 million people globally. Most PAD studies have been performed among predominantly White populations-less is known about other ethnicities. The aim of this cross-sectional study was to determine the prevalence and risk factors of PAD in a high-risk Asian population with ischaemic stroke (IS), myocardial infarction, unstable angina (CVD), or diabetes mellitus (DM). Methods: Patients admitted for IS, CVD, or DM were recruited. Data were collected on age, sex, body mass index (BMI), index condition (CVD, IS, DM), history of hypertension, DM, hypercholesterolaemia, cigarette smoking, and claudication. The Edinburgh Claudication Questionnaire was administered, the ankle brachial index (ABI) was determined, and PAD was diagnosed if ABI was ≤0.9. Results: Of the 450 subjects recruited, 150 were placed in each index disease group, the mean age was 61.9 ± 10.32 years, 43.1% were female, and the mean BMI was 23.9 ± 4.3. Hypertension was reported in 59.3%, DM in 63.6%, hypercholesterolaemia in 39.6%, and smoking in 42.9% of patients. The prevalence of PAD was 27.1%, 22.0% in IS, 29.3% in CAD, and 30.0% in DM. PAD was associated with increasing age (adjusted odds ratio (aOR) 1.04/year, 95% confidence interval [CI] 1.01-1.06; p < 0.001), reduced BMI (aOR 0.94, 95% CI 0.89-0.99; p = 0.026), DM (aOR 1.59, 95% CI 1.20-3.18; p = 0.007), and hypercholesterolaemia (aOR 1.82, 95% CI 1.17-2.28; p = 0.007). It was more frequent in non-lacunar versus lacunar acute IS, non-ST segment elevation versus ST-segment elevation acute myocardial infarction, and insulin-treated versus non-insulin-treated DM. Conclusions: Our study showed a high prevalence of PAD among high-risk Asian patients. This was associated with increasing age, DM, and hypercholesterolaemia and inversely associated with BMI. Different rates were found in sub-groups of IS, CVD, and DM. Systematic approaches were used to identify these high-risk individuals and to improve their outcomes.

Serum anti‑KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

ПОВЫШЕНИЕ КРЕАТИНФОСФОКИНАЗЫ КАК ДИАГНОСТИЧЕСКАЯ ПРОБЛЕМА У МУЛЬТИМОРБИДНОГО ПАЦИЕНТА С COVID-19 (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

Background. Creatine phosphokinase is an enzyme that is often associated with muscle and myocardial disorders. However, other causes of elevated level of this enzyme are possible, such as stroke, hypothyroidism, paraneoplastic syndrome, as well as various pharmacological effects, including taking statins and the development of statin-associated muscle symptoms, the consequences of a previous coronavirus infection COVID-19. The aim of the work. To determine the cause of increased creatine phosphokinase in a patient after coronavirus infection associated with concomitant diseases; to carry out differential diagnosis of an increase in this enzyme. Results. We carried out an analysis of the patient’s medical history with a significantly increased creatine phosphokinase and subsequent differential diagnosis in order to identify the main causes of this change. The study was performed based on the assessment of general medical condition of the patient, as well as of the results of complete and bio-chemical blood counts (including the level of creatine phosphokinase and lactate dehydrogenase). Instrumental studies such as electroneuromyography, electrocardiography, echocardiography and ultrasound scanning were also carried out. The patient was diagnosed with ischemic cardiovascular disease and hypothyroidism. However, the increased creatine phosphokinase was not associated with statin use, since it was discontinued during observation, and the enzyme level increased over time. Other causes of increased creatine phosphokinase were also excluded, and the results indicate that the increase in this enzyme is likely caused by a previous coronavirus infection with concomitant diseases. Conclusion. The present study highlights the importance of a comprehensive approach to the differential diagnosis and treatment of increased creatine phosphokinase levels in patients with comorbid pathology, as this may be a con-sequence of various factors, including infections, concomitant diseases and pharmacological intervention.

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and risk stroke.

Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%). As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.

Time Series Forecasting of Cardiovascular Mortality: Machine Learning Based on State Economic and Local Medical Data.

This study focuses on the complex interplay of healthcare, economic factors, and population dynamics, addressing a research gap in regional-level models that integrate diverse features within a temporal framework. Our primary objective is to develop an advanced temporal model for predicting cardiovascular mortality in Russian regions by integrating global and local healthcare features with economic and population dynamics. Utilizing a dataset from the Almazov Center's Department of Mortality Performance Monitoring, covering 94 regions and 752 records from January 1, 2015, to December 31, 2023, our analysis incorporates key parameters such as angioplasty procedures, population morbidity rates, Ischemic Heart Disease (IHD) and Cardiovascular Diseases (CVD) monitoring, and demographic data. Employing XGBoost and a regression model, our methodology ensures the model's robustness and generalizability.

Waist-to-height ratio and body fat percentage as risk factors for ischemic cardiovascular disease: a prospective cohort study from UK Biobank

BackgroundThe independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain. ObjectivesThis study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD. MethodsThis prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR. ResultsIn total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS. ConclusionsWHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR.

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and stroke risk

Abstract Funding Acknowledgements None. Background Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. Methods We performed a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of two tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). Results After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia (12.8% vs. 4.7%; p=0.003), advanced atrioventricular block (13.2% vs. 6.0%; p=0.012), heart failure (28.5% vs. 18.7%; p=0.017), and cardiogenic shock (17.4% vs. 8.5%; p=0.006). In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p&amp;lt;0.001), without differences in stroke incidence (10.1% vs. 9.3%). Conclusion Patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-years follow up, they exhibit a high risk of AF recurrence, with no significant differences in stroke incidence.Kaplan Meier curves

Abstract 2007: Ischemic And Non-ischemic Cardiovascular Events Differentially Regulate Cross Disease Communication With Cancer

Cancer and cardiovascular disease (CVD) are the top two leading causes of death worldwide, exhibiting cross-disease communication that increases morbidity. Cancer patients are at significantly increased risk for CVD and recent studies by our lab and others indicate that CVDs like myocardial infarction (MI) or heart failure can in turn accelerate tumor growth. We previously showed this occurs through changes in the innate immune system or via tumor-promoting factors secreted from the damaged myocardium, which together have established the nascent field of Reverse CardioOncology. We hypothesized that ischemic and non-ischemic CVD injuries have distinctly different mechanisms underlying mammary tumor growth. To mimic these events, we modeled non-cardiac hind limb ischemic injury by femoral artery ligation (FAL) and non-ischemic cardiac injury by cardiac cryoinjury (CCI). To test our hypothesis, we introduced primary E0771 mouse mammary cancer cells into the mammary fat pad three days prior to FAL or CCI. Measurements of tumor over time showed significant increases in tumor growth after both FAL and CCI when compared to sham surgeries. However, only the ischemic injury, FAL, induced similar changes in immune cells to what we observed after MI (induced by left anterior descending coronary artery [LAD] ligation). This included significant increases in myeloid populations and decreased lymphocytes within the circulation. Additionally, flow cytometry of immune cells within tumors of mice exposed to FAL showed significantly increased myeloid cells and macrophages, as well as increased immunosuppressive T-regulatory cells. In contrast, while CCI showed significantly increased tumor burden and circulating leukocytes, there were no differences in the above-mentioned subsets of immune cells within the circulation or within the tumor. These data suggest that ischemic injury, via FAL or LAD, induces an immunosuppressive environment within the tumor that accelerates cancer growth that is distinct from the non-ischemic cardiac injury induced by CCI. Taken together, our data suggest that the immune reprogramming after ischemic CVDs is a risk factor for tumor growth and these data help to elucidate the mechanisms that underlie cancer risk in CVD patients.