Coronary Artery Disease Patients Research Articles

Prolonged L-NAME exposure changes the vasodilator factor from NO to H2O2 in human arterioles in response to A23187

The Ca2+ ionophore A23187 induces endothelium-dependent and non-receptor-mediated vasodilation in human adipose arterioles (HAAs). The purpose of this study was to determine the mechanism of A23187-induced dilation in HAAs from patients with and without coronary artery disease (CAD). HAAs were freshly isolated from adipose tissues obtained from non-CAD (n = 25) and CAD (n = 14) patients, and vascular reactivity was studied by videomicroscopy. No difference in baseline dose response to A23187 was observed between non-CAD and CAD subjects. However, acute (30 min) incubation with N(omega)-nitro-l-arginine methyl ester (L-NAME), NO synthase inhibitor strongly reduced A23187-induced dilation in non-CAD arterioles, while catalase, an H2O2 scavenger, largely abolished dilation in CAD. Surprising, prolonged (90 min) incubation with L-NAME restored A23187 response in non-CAD subjects, which was subsequently inhibited by catalase. The action of prolonged L-NAME exposure was not reversible after washing with Krebs while the effect of acute L-NAME exposure was largely reversible. To further determine the role of mitochondria-derived ROS in A23187-induced dilation, arterioles were treated with rotenone, an inhibitor of complex I of the electron transport chain. Rotenone abolished A23187 response in CAD patients and in non-CAD arterioles after prolonged L-NAME, but not in non-CAD controls. These data indicate that NO contributes to A23187-induced dilation in HAAs from non-CAD patients and H2O2 contributes to the dilation in CAD patients. Prolonged L-NAME exposure induces a NO-H2O2 switch in the mechanism of dilation in non-CAD subjects. Moreover, the effect of prolonged L-NAME exposure is not readily reversible, while the action of acute L-NAME exposure is reversible.

Long-Term Impacts of Complete Revascularization on Clinical Outcomes in Patients with Coronary Chronic Total Occlusion

The impact of complete revascularization (CR), achieved through the recanalization of coronary chronic total occlusions (CTOs), on long-term patient outcomes remains uncertain.To evaluate this in patients who achieved CR after CTO-PCI with those who did not due to deferred CTO-PCI, the Asan Medical Center Registry was reviewed to identify coronary artery disease (CAD) patients with CTOs treated between January 2003 and December 2018. Patients were included with single-vessel disease with CTO and with multivessel disease who had undergone revascularization for non-CTO lesions. These subjects were divided into those who achieved CR with CTO-PCI and those who did not due to deferred CTO-PCI. Their outcomes were compared following 1:1 propensity score matching. Of the 2,746 enrolled CAD patients with CTOs, 1,837 achieved CR with CTO-PCI and 909 did not. Propensity score matching yielded 653 patient pairs. The CR-achieving group had a significantly lower 10-year risk of the primary composite outcome of death, myocardial infarction, stroke, or repeat revascularization (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.46–0.72; P < 0.001), as well as significantly lower risks of death (HR: 0.66; 95% CI: 0.51–0.87; P = 0.003) and repeat revascularization (HR: 0.67; 95% CI: 0.48–0.95; P = 0.023). CR was beneficial in all subgroups, including patients with major cardiovascular risk factors such as older age, hypertension, diabetes, and advanced CAD. Compared with incomplete revascularization, CR may significantly reduce the 10-year incidence of major adverse cardiac events in patients with CTO.

Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients

In a recent untargeted clinical lipidomics study of platelets of coronary artery disease (CAD) patients, medium-chain phosphatidylcholines (MCPCs) with C8 and C10 fatty acyl residues were found significantly upregulated in the patient group with acute coronary syndrome (ACS) as compared to chronic coronary syndrome (CCS) and healthy controls. To support this finding, this work presents the development and optimization of a targeted UHPLC-QTrap-MS/MS method with multiple reaction monitoring acquisition for the quantitative analysis of MCPCs (PC 10:0/8:0, PC 16:0/8:0, PC 10:0/20:4 and PC 10:0/10:0) in platelets for biomarker validation. A systematic optimization of chromatographic and mass spectrometric parameters was performed. A charged surface hybrid CSH C18 (1.7 µm, 130 Å) column and fine-tuned gradient elution with 2-propanol/acetonitrile and ammonium acetate as additive to the mobile phase was employed in the final method in ESI negative mode. Four selected PC standards (PC 6:0/6:0, PC 8:0/8:0, PC 10:0/10:0 and PC 12:0/12:0), which cover well the carbon and retention rime range of the target analytes, were used for the optimization process and calibration. Quantification was based on matrix-matched calibration with these four selected commercially available MCPC standards as surrogate calibrants and PC 6:0/6:0 (d22) as internal standard. Furthermore, an organic solvent and fatty acyl carbon number-corrected response factor approach gave also accuracies within acceptance limits of bioanalytical validation guidelines and has more generic applicability. Compared to the previous untargeted RPLC-ESI-QTOF-MS/MS method, the optimized targeted UHPLC-QTrap-MS/MS assay showed increased sensitivity and selectivity for the detection of medium-chain PCs in platelet samples of CAD (LOQs in the range of 0.5-5 nmol/L). The method performance parameters indicated its suitability for a future biomarker validation study of MCPCs in platelets.

Remnant Cholesterol and Long-Term Incidence of Death in Coronary Artery Disease Patients

Remnant Cholesterol and Long-Term Incidence of Death in Coronary Artery Disease Patients

Endometriosis, Anxiety, and Atherosclerosis: A study of eight million young hospitalized women in United States.

In recent years, several studies have proposed an association between endometriosis and various cardiovascular diseases. Our study evaluated the association between endometriosis and atherosclerosis in patients under 35 years of age using a large population database. This was a retrospective population-based study. We used the data of more than eight million hospitalized women under 35 years of age who were registered in one of the hospitals participating in the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP NIS) during the study period of 2007 to 2014. The prevalence of endometriosis, atherosclerosis and related conditions was estimated, and logistic regression model was used to examine the association. In the period of study, we noted an upward pattern for the prevalence of atherosclerosis and a downward trend for endometriosis. Adjusting the analysis for sociodemographic characteristics and comorbidities, the probability of being diagnosed with atherosclerosis was 42% higher in patients with endometriosis (OR=1.421; 95%CI 1.058-1.910); 35% higher in patients with anxiety (OR=1.352; 95%CI 1.249-1.464); and 3 times higher in women with both endometriosis and anxiety (OR=3.075; 95%CI 1.969-4.803) compared to women without those conditions. In HCUP NIS databases some information such as the severity of disease, laboratory findings, or medical treatment is not available. The strong association between endometriosis and atherosclerosis suggests that they may share a similar mechanism possibly endothelial dysfunction related to chronic inflammation. Further studies on the potential role of psychologic conditions, such as anxiety, on systemic inflammatory diseases are also deemed timely and important.

Guanxinning for Residual Inflammation of Stable Coronary Artery Disease: A Pilot Randomized Controlled Trial.

Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients. In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP). Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P<0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P<0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P<0.05). The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.

УРОВЕНЬ Р-СЕЛЕКТИНА, ИНТЕГРИНА-Β3 В ПЛАЗМЕ КРОВИ У ПАЦИЕНТОВ С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА ПОСЛЕ ЧРЕСКОЖНОГО КОРОНАРНОГО ВМЕШАТЕЛЬСТВА

Background. Coronary artery disease (CAD) is a leading cause of mortality and disability worldwide. Modern treatment methods, such as percutaneous coronary intervention (PCI), have significantly improved patients’ outcomes. However, the risk of stent restenosis remains a significant problem. Objective. To determine the levels of biochemical markers (P-selectin and integrin-β3) in the plasma of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI), and to evaluate the effectiveness of various models for predicting in-stent restenosis. Material and methods. The study included 209 CAD patients divided into four groups: healthy individuals, patients with chronic CAD without indications for invasive coronary angiography, patients with CAD who underwent elective PCI, and patients with in-stent restenosis. Plasma levels of P-selectin and integrin-β3 were measured using enzymelinked immunosorbent assay (ELISA). Results. In-stent restenosis occurred in 12 patients (8.05%) after elective PCI. Analysis showed that P-selectin and integrin-β3 levels did not have statistically significant differences between patient groups. The predictive model including BMI, ventricular extrasystole, number of stents, diabetes mellitus, and multifocal atherosclerotic coronary artery disease showed the best key metrics efficiency. Conclusion. P-selectin and integrin-β3 levels did not show significant differences in patients with in-stent restenosis. The model including BMI, VE, number of stents, DM, and MFCAD is the most effective for predicting restenosis recurrence.

Distinct Metabolites in Atherosclerosis Based on Metabolomics: A Systematic Review and Meta-analysis Primarily in Chinese Population

AimsAtherosclerosis is a life-threatening disease that develops when a plaque builds up inside an artery and progresses silently. Identifying the early pathological changes and the biomarkers of atherosclerosis deserves attention. We aimed to systematically study and integrate the various metabolites of atherosclerosis in the level of disease to provide more evidences to support early prevention and treatment of atherosclerosis. Data synthesisThe protocol was registered with PROPSERO (CRD42023441845). We searched 14985 records via EMBASE, PubMed, Web of Science, WanFang data, VIP data, and CNKI databases. The collected metabolites were for qualitative and quantitative meta-analysis. The I2 statistic estimated heterogeneity, with over 50% considered to adopt the random-effects model. A total of 49 articles were included in the meta-analysis. We finally integrated 83 and 16 metabolites presented more than two times in inclusion studies, respectively in blood (plasma and serum) and urine. Among them, the level of citric acid (SMD=-10.35 [95%CI -15.03, -5.67], p<0.001), lactic acid (SMD= 6.32 [95%CI 0.12, 12.52], p<0.001) and TMAO (SMD= 1.40 [95%CI 0.27, 2.53], p<0.001) had significant differences between atherosclerosis and controls. And we observed blood stasis syndrome of atherosclerosis patients present arterial ischemia and energy disorder obviously. ConclusionsThe study provides an in-depth understanding of the roles of metabolites on atherosclerosis progression and prediction primarily in Chinese population, which contributing to development of prevention and therapeutic potential in the future.

High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state.

Neutrophil extracellular trap (NET) formation is involved in atherothrombosis. We sought to investigate whether statins affect neutrophil extracellular traps activation and release (NETosis) in coronary artery disease (CAD), and whether such changes show associations with statin‑induced additional effects. We studied 130 patients with advanced CAD before and at least 6 months after initiation of high‑dose statin therapy with rosuvastatin 40 mg/d or atorvastatin 80 mg/d. The levels of circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO), and neutrophil elastase (NE) were assessed as proteins associated with NETosis along with thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis inhibitors. Following statin therapy intensification, we observed reduced accumulation of H3cit (-30.4%), MPO (-28.1%), and NE (-25.5%; all P <0.001), all not associated with low‑density lipoprotein cholesterol (LDL‑C) lowering (-25%). However, H3cit level was lower in 50 patients (38.5%) who achieved the target LDL‑C below 1.8 mmol/l (-16.5%; P = 0.004), and in 19 patients (14.6%) with LDL‑C below 1.4 mmol/l (-25.5%; P = 0.001), as compared with the remaining individuals. The reductions in H3cit and MPO levels were associated with a 42.9% decrease in C‑reactive protein (CRP) level on high‑dose statins (R = 0.855; P <0.001 and R = 0.25; P = 0.004, respectively), along with increases in Ks and reduction in thrombin activatable fibrinolysis inhibitor (TAFI) activity, but not with CLT or thrombin generation (all |R|, 0.24-0.4; P <0.01). In multivariable analysis, changes in CRP (β = 0.771; P <0.001), TAFI activity (β = 0.125; P = 0.013), and fibrinogen level (β = 0.106; P = 0.034) were independently associated with a decrease in H3cit concentration. We showed for the first time that high‑dose statins can reduce the level of NET‑related proteins in association with anti‑inflammatory and antithrombotic actions in CAD patients.

Bibliometric and visual analysis of SGLT2 inhibitors in cardiovascular diseases.

Cardiovascular diseases (CVD) pose a significant threat to human health due to their high mortality and morbidity rates. Despite advances in treatments, the prevalence and impact of cardiovascular disease continue to increase. Sodium-glucose transporter 2 inhibitors (SGLT2i), initially approved for the treatment of type 2 diabetes, have important research value and promising applications in reducing CVD risk, especially in heart failure (HF) and atherosclerosis patients with cardiovascular disease (ASCVD). This study aims to comprehensively review the latest progress, research trends, cutting-edge hot spots, and future development directions of SGLT2i in the field of CVD through bibliometric analysis. Articles related to MSCs in cardiovascular diseases were sourced from the Web of Science. The bibliometric analysis was conducted using CiteSpace and VOSviewer, and a knowledge map was created based on the data obtained from the retrieved articles. In this article, we screened 3,476 relevant studies, including 2,293 articles and 1,183 reviews. The analysis found that the number of papers related to the application of SGLT2i in CVD has generally increased, peaking in 2022. The United States and China contributed the largest number of papers, with the United States accounting for 36.97% of the total and also ranking first in terms of the number of citations. However, China's high-quality papers are slightly lacking and need further improvement. Keyword analysis showed that empagliflozin, dapagliflozin, diabetes, and heart failure were the most common terms, reflecting the main research interests in currently published papers in this field. Bibliometric analysis showed a robust and growing interest in the application of SGLT2i for treating CVD. By summarizing the latest progress of SGLT2i in the field of CVD, exploring research hotspots, and looking forward to future research development trends, this article provides valuable insights for thinking about research prospects.

Lesion Characterization by 99mTc-MIBI Myocardial Perfusion Imaging (MPI) &amp; 18F-FDG Cardiac PET Following Myocardial Infarction Before Revascularization &amp; Outcome Prediction: Initial Experience in Bangladesh

99mTc-MIBI SPECT myocardial perfusion imaging (MPI) and 18F-FDG cardiac positron emission tomography (Cardiac PET) can assess the extent and severity of myocardial perfusion and metabolic defect following myocardial infarction (MI) and also able to predict the outcome before revascularization in known coronary artery disease patients. About 135 cases of known coronary artery disease patients were enrolled here for combined nuclear imaging tests, rest only ECG gated MPI and FDG cardiac PET to assess myocardial perfusion and viability status following MI prior to revascularization. In this study we want to figure out the utility of this combined protocol for myocardial lesion characterization and its role for clinical decision-making in-patient selection prior to revascularization and treatment planning. We are also intended to share the initial outcome in available follow up cases. J Inv Clin Cardiol 2023; 5(2): 45-52

Cost effectiveness and functional outcomes of smartphone cardiac rehabilitation assisted self-management versus centre based cardiac rehabilitation among patients with coronary heart disease in Southern India: a multicentre randomized clinical trial protocol

Background: To attain the world specific indicators of quality on programs which brings rehabilitation for cardiac diseases and surgeries in India are to be brought to meet the international standards. Dearth of published research on cost effectiveness of smart phone application oriented CR assisted self-management (SCRAM) over centre based (CBCR) in Indian Population drives this study to be done. This study aims to analyze cost effectiveness of SCRAM versus CBCR in coronary artery disease (CAD) patients. Methods: In this multicentre randomized clinical trial, 100 subjects with uncomplicated CAD will be recruited through purposive sampling and divided into group A and B through block randomization. Group A will be treated with CBCR whereas group B with SCRAM. Outcome measures of 6 minutes’ walk test distance, talk test values and SF 36 scores, high density lipoprotein level and 3 months’ average blood glucose level were documented pre and post interventions and 3, 6, 12 months follow up for data analysis. This study will follow human study ethical consideration based on Declaration of Helsinki. Conclusions: Cost effectiveness of experimental group where SCRAM given as intervention may be better post intervention than control group where CBCR given. By this way this RCT protocol may bring the execution cost down with coronary heart disease patients which play a major role in participation of these patients in CR programs. Trial registration: The trial was registered with CTRI – Clinical Trial Registry of India (ICMR) - CTRI/2022/11/047143 (registered on: 09 November 2022) - trial registered prospectively.

Association between average glucose concentration or glucose variability and acute kidney injury among CAD patients with prediabetes

Abstract Background Prediabetes, impacting approximately 10% of adults, lacks comprehensive attention, and there is limited data on effective glycemic control strategies. Meta-analysis suggests that intensive glycemic control is linked to a lower incidence of major adverse cardiovascular events, mainly driven by decreased reinfarction and reduced microvascular complications in coronary artery disease (CAD) patients. However, despite these associations, existing evidence does not conclusively establish the efficacy of intensive glycemic control in enhancing cardio-renal outcomes. Purpose In the present study, we aimed to validate the utility of intensive glycaemic control on acute kidney injury (AKI) prevention using a prospective, pragmatic clinical data of patients with CAD. Methods This study utilized data from the Prospective Registry of the Current Status of Care for Patients with Coronary Artery Disease database, a nationwide and pragmatic registry project initiated on January 17th, 2022. Data, including demographics, medical history, and lab results, were collected from electronic medical records. The time-weighted average glucose (TWAG) and glucose variability (CV) for each patient to assess glycaemic control, and outcomes including AKI were assessed. Statistical analysis involved logistic models and sensitivity analyses. SAS 9.4 and R software were used, with p&amp;lt;0.05 considered significant. Results Between January 2022 and June 2023, 2,454 CAD patients with prediabetes were included for final analysis. Among them, the average age was 62.6 ± 10.3 years, of whom 27.1% were females. In univariate model, the incidence of AKI was 1.51 (1.36,1.68) times higher in patients with an increasing TWAG per mmol/L. After the stepwise adjusting of covariates, the OR was 1.50 (1.35,1.67). CV of glucose also had positive association with AKI. An increasing of 0.1 unit of CV increased the risk of about 44%. When adjusting the TWAG and CV of glucose at the same time, both still had positive association with AKI. A restricted cubic splines plot showed an increasing trend of the ORs for AKI as both TWAG and CV of glucose increased. Subgroups analyses also showed stable positive association between TWAG, CV and AKI. Conclusions Our study reveals an association between TWAG or CV and AKI in individuals with both CAD and prediabetes. These findings underscore the importance of continuous glucose monitoring and the implementation of intensive glycaemic control for CAD patients coexistence of prediabetes.Restricted cubic splines function

Prognostic significance of coexistent coronary artery disease in patients undergoing transcatheter aortic valve implantation for aortic stenosis

Abstract Background The optimal management of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) is uncertain. As TAVI expands into lower risk cohorts with longer life expectancies there is increasing need to determine the prognostic significance of coexistent CAD and identify which lesions may benefit from revascularisation. Purpose To evaluate the prognostic significance of coexistent CAD in patients with AS undergoing TAVI stratified according to myocardial territories at risk. Methods Using a retrospective, single-centre, observational registry, patients undergoing TAVI for severe AS between 2015 and 2020 were included. CAD was angiographically determined using computed tomography or invasive coronary angiography. CAD was stratified into 1) low-risk: &amp;lt;70% stenosis in all major epicardial coronary arteries or &amp;lt;50% in the left main (LM); 2) intermediate-risk: ≥70% stenosis in one or two arteries, except the proximal left anterior descending (LAD) and LM; 3) high-risk: ≥70% stenosis in the proximal LAD, ≥70% stenosis in 3 arteries or LM stenosis ≥50%. Patients with previous CABG were categorised as high-risk if: ≥70% stenosis of 3 coronary grafts or graft supplying a proximally stenosed LAD; and intermediate-risk if: ≥70% stenosis of 1 or 2 non-LAD grafts. Baseline characteristics and procedural outcomes were compared between the 3 cohorts, with the impact of CAD on outcomes evaluated after adjustment for demographics and comorbidities. Results 1805 patients were included; median age 84 (79-88), 51% male sex, median logistic Euroscore 13 (8-21). 1281 (71%), 384 (21%) and 140 (8%) patients were characterised as low-, intermediate- and high-risk coronary anatomy respectively. High risk patients were older than the other groups, however, did not have the highest prevalence of comorbidities (Table 1). Other than pacemaker implantation (9% vs 12% vs 6%, p=0.04), there were no differences in procedural complications or in-hospital mortality between groups (Table 1). At a median follow-up of 3.5 (2.3-4.8) years, 920 patients (51%) died, 292 (16%) had hospitalisation for heart failure (HHF) and 565 patients (31%) had a major adverse coronary event (MACE); defined as either myocardial infarction, HHF or cardiovascular death. Coronary anatomical stratification was associated with MACE (Log rank p&amp;lt;0.001) (Figure 1). After multivariate adjustment, high-risk anatomy was associated with all-cause mortality (hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.06-1.68, p=0.013), HHF (HR: 1.49, 95% CI: 1.01-2.21, p=0.046) and MACE (HR: 1.68, 95% CI: 1.27-2.21, p&amp;lt;0.001). Conclusions Whilst the presence of CAD does not impact TAVI procedural safety, untreated high-risk coronary anatomy is associated with future adverse events and may warrant intensive medical therapy and/or revascularisation.

Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Abstract Introduction Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Methods This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients are primary prevention patients and among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non-contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by immunonephelometric method. Results The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin usage to %32 and statin usage to %96) within the population. 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study highlights the influence of subclinical atherosclerosis on treatment approaches, as demonstrated by the notable rise in statin and aspirin utilization observed after screening.Clinical and biochemical characteristicsSubclinical Atherosclerosis Rates

Gene Expression Changes in CAD Patients Due to Smoking Using Matched Samples

Abstract Background Smoking is a well-known risk factor for coronary artery disease (CAD). However, the effects of smoking on gene expression in the blood of CAD patients in Hungary have not been extensively studied. Aim To identify differentially expressed genes associated with smoking in CAD patients. Methods Eleven matched samples, based on age and gender, were selected for analysis in this study. All patients were non-obese, non-alcoholic, non-diabetic, and non-hypertensive and had moderate to severe stenosis of one or more coronary arteries, confirmed by coronary angiography. Whole blood samples were collected using PAXgene tubes. Next-generation sequencing was employed using the NextSeq 500 system to generate high-throughput sequencing data for transcriptome profiling. The differentially expressed genes were analyzed using the R programming language. Results The median age of patients was 67 years (range: 54-75). RNA sequencing was performed on two groups: smokers and non-smokers. After quality control and filtering, gene expression data were obtained for all samples. Using DESeq2, we identified 279 differentially expressed genes with a p-value ≤ 0.05 and a log2 fold change ≥1. Of these genes, 160 were upregulated in the smokers, and 119 were downregulated compared to non-smokers. Gene ontology analysis revealed that the upregulated genes were enriched for pathways related to immune responses and activities (FDR&amp;lt; 0.03). Specifically, upregulated genes were involved in keratinocyte differentiation, cornification, and epidermis development. The downregulated genes were enriched for cell-cardiac muscle cell adhesion (FDR= 0.004) and epithelium development (FDR= 0.001) pathways. Conclusions This research illuminates smoking’s biological effects, aiding personalized medicine for predicting and treating smoking-related diseases. Key messages • Smoking alters gene expression in CAD patients’ blood, identifying 279 differentially expressed genes, revealing smoking’s biological effects. • The study underscores gene expression profiles’ role in personalized medicine, predicting smoking-related disease risks and tailoring CAD patient treatments.

Diabetes Mellitus influence in Lipoprotein(a) gene expression and association to coronary artery disease

Abstract Introduction Lp(a) and type 2 diabetes mellitus are both known and established risk factors for the development of coronary artery disease (CAD). Lp(a) levels are 75% to 95% heritable and predominately determined by single-nucleotide variants at the LPA gene; rs3798220 is one of the most studied variants and accounts for a significant portion of Lp(a) levels. Whether diabetes could influence the LPA rs3798220 account for Lp(a) levels is unknown. Aim Evaluate whether there is a different association between polymorphism LPA rs3798220 T&amp;gt;C and Lp(a) levels and their association with CAD in diabetic and non-diabetic populations. Methods 3,209 subjects (mean age 59.3±8.9 years, 76.3% male were selected from the data set of the Research Center. The LPA rs3798220 T&amp;gt;C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This genetic variant has a minor allele frequency (MAF) &amp;lt;2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Lp(a) biochemical levels were measured in all participants. From the 3,209 participants, 810 had diabetes, and 2399 were no diabetics. For each group, chi-squared tests were used to determine the association of CAD prevalence by genotype, and t-tests were used to evaluate differences in CAD prevalence by Lp(a) levels. Results In non-diabetic subjects, LPA TC was significantly associated with CAD in non-diabetic subjects compared with TT (p&amp;lt;0.0001). Similarly, Lp(a) was higher in the CAD population (37.2±39.7) compared to the healthy population (25.6±30.0) (p&amp;lt;0.0001). In diabetic group, Lp(a) was higher in the CAD population (38.5±41.4) compared to the population without CAD (23.9±29.2) (p&amp;lt;0.0001). Nevertheless, there was no difference in genotype between CAD and non-CAD patients (p=0.710). Conclusion The LPA rs3798220 T&amp;gt;C variant in non-diabetic group can explain high Lp(a) levels and their association with CAD. However, in patients with diabetes, Lp(a) is elevated in CAD patients besides the fact that no significant genotype differences were displayed. Non-genetic influences like behavioural factors or even epigenetic changes may probably explain high Lp(a) levels in this population.

Association of Sleep Apnea and cardiovascular mortality in CAD patients

Abstract Background A growing body of epidemiological and clinical research has uncovered a significant relationship between sleep apnea and the exacerbation of cardiovascular outcomes, notably myocardial infarction, stroke, and cardiac death. Individuals diagnosed with coronary artery disease (CAD) alongside sleep apnea are identified to have a heightened likelihood of experiencing recurrent cardiovascular events. Despite these associations, the link between sleep apnea and an elevated risk of mortality among CAD patients remains insufficiently explored. Purpose Our study aims to shed light on the impact of sleep apnea on mortality rates within this patient population, potentially guiding future therapeutic strategies. Methods Our cohort study leveraged data from the TriNetX multinational electronic health record network, focusing on patients aged 18 and above diagnosed with coronary artery disease. Participants were stratified into two groups based on the diagnosis of sleep apnea. To ensure a fair comparison, we adjusted for prevalent risk factors such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease, which are commonly observed in CAD patients. Results The study encompassed 1,799,812 patients, equally divided into two groups of 899,906 individuals each, one with sleep apnea and the other without. Over a 5-year observation period, the primary endpoint, defined as event-free survival, was significantly lower in the sleep apnea group (74.385%) compared to the non-sleep apnea group (76.606%), with a Log Rank confidence interval of 1.128 to 1.148 and a p-value of &amp;lt;0.0001. This outcome highlights a association between sleep apnea and increased mortality rates in CAD patients. Conclusion The findings from our large cohort study underscore the critical impact of sleep apnea on mortality among patients with coronary artery disease. The diagnosis of sleep apnea in CAD patients within the TriNetX cohort was significantly associated with a higher mortality rate over a span of five years. These insights emphasize the need for integrated care strategies that not only address the primary cardiovascular conditions but also prioritize the diagnosis and management of sleep apnea to potentially improve survival outcomes in this vulnerable patient group. Our study calls for heightened clinical awareness and further research to elucidate the mechanisms behind this association and to explore the benefits of targeted sleep apnea interventions in reducing mortality rates among CAD patients.5-year Kaplan-Meier curves for mortality

Is the HNF4A gene variant paradoxically associated with better prognostic in CAD patients?

Abstract Background The Hepatocyte nuclear factor 4 A (HNF4A) gene was considered to be associated with susceptibility to atherosclerosis and coronary artery disease (CAD). It encodes a protein HNF4α, a genetic transcription factor regulating the genetic expression of thousands of genes playing essential roles in glucose and lipid metabolism. Its abnormal expression is emerging as a critical factor in diabetes, dyslipidemia, and cancer. Loss of function of specific mutations could attenuate its role in CAD pathogenesis and the progression of atherosclerosis. Aim To investigate whether a genetic variant (HNF4α rs1884613 C&amp;gt;G) could be associated with a low genetic function and, paradoxically, a better prognostic in CAD patients. Methods A cohort of 1,718 patients with coronary angiography (&amp;gt;70% stenosis of at least one main coronary vessel) from the GENEMACOR Study was investigated. Thirty-three genetic variants were genotyped using TaqMan assay methodology and HNF4A rs1884613 C&amp;gt;G genotype models were individually studied regarding the occurrence of Major Adverse Cardiovascular Events (MACEs). We used bivariate analysis to evaluate genotypic and allelic differences. Multivariate Cox regression analysis estimated variables independently associated with MACE, and Kaplan-Meier estimate methodology assessed the survival. Results Of the 1,718 CAD patients with the CC wild type, 73.4% had MACE, compared with 66.5% without. CG had 25.2% compared with 30.5% without. Finally, in the GG genotype, only 1.4% had events compared with 3.0% without (p=0.004). Cox regression analysis showed that GG genotype (mutated) is significantly and independently associated with 56% of MACE protection with a hazard ratio (HR) of 0.436; p=0.014. Physical inactivity and type-2 Diabetes remained independently associated with MACE occurrence (Fig.1). Kaplan-Meier cumulative event analysis disclosed that the carriers of the GG genotype were significantly associated with a better event-free time, and CC discloses a worse event-free time (Breslow test, p=0.001) (Fig.2). Conclusions The rs1884613 genetic variant of HNF4A is associated with a better CAD prognosis. This variant could probably induce gene downregulation and HNF4A gene function loss. Modifying and modulating hepatic lipase and lipid metabolism positively affected atherosclerosis progression. Future bioactive modulators for HNF4A variants could raise the possibility that diseases involving diabetes, lipid disorders, and cancer might be amenable to pharmacologic intervention.

Human macrophages are immunnoprofiled by pericardial fluid small extracellular vesicles modulating lipid metabolism mechanisms

Abstract Background Coronary artery disease (CAD) is the main cause of myocardial infarction and consequent ischemic heart disease (IHD). Macrophages are central to CAD. Small extracellular vesicles (sEVs) can shuttle microRNAs and other molecular cargos from cell to cell, mediating response in target cells. Recent evidence supports the sEVs role in modulating macrophage phenotype. The pericardial fluid (PF) contains sEVs and immune cells including cavity-like macrophages. Purpose This study investigates whether PF-sEVs regulate macrophages, contributing to a specific immunophenotype in CAD patients. Methods PF was collected from CAD patients undergoing coronary bypass surgery (CABG) and non-atherosclerotic patients operated for mitral valve repair (control group). sEVs were isolated and characterised for size (Nanosight tracking analysi), tetrasapanin content (Nanoview chips) and microRNA content (RNA seq analysis). Monocytes from healthy donors were isolated from buffy coats and differentiated into macrophages following established protocols. Macrophages were incubated with either CAD-sEVs or non-CAD sEVs for 24h at 37oC. The cells were collected and processed for mRNA analyses (qRT-PCR) and flow cytometry. Further bioinformatics were employed to understand functional pathways targeted by PF-sEVs-miRNA. Results In line with the human-PF macrophages profile, exposure to CAD-sEVs reduces the anti-inflammatory profile of human macrophages. CAD-sEVs treated macrophages showed a CCR2-, CD36+low, CD206+low profile. While non-CAD-sEVs did not statistically differ from PBS nor untouched groups, CAD-sEVs increased the mRNA level of IL1a, IL1b, TNFa and decreased MRC1. Bioinformatic analysis showed that 861 miRNAs were decreased in the PF-sEVs from CAD patients compared to non-CAD. miRNA targets prediction and pathway analyses reported that clusters of PF-miRNAs could regulate CD36, decreased in PF-macrophages. Conclusions We demonstrate, that sEVs isolated from PF-CAD reduce the anti-inflammatory profile of human macrophages, and target crucial lipid metabolism pathways. These clinically relevant results could drive to decipher improved therapeutics to modulate the epicardial/myocardial immune response in CAD patients.