Atherosclerosis Research Articles

Formulation and Evaluation of Anti-Hyperlipidemic Tablet

Hyperlipidemia is one of the leading causes of mortality in developed as well as in developing countries like India. It attributes to the high risk of coronary heart disease and atherosclerosis which is referred as a silent killer. Herbal treatment for hyperlipidemia is inexpensive, readily available locally, and has no negative side effects. Medicinal plants are the "backbone" of traditional medicine so considered as good source of life for all people due to its wealthy therapeutic properties and being 100% natural. Several drugs in Siddha have been found to be beneficial in lowering lipid levels without any major adverse effects. Numerous plants like arjuna, ashwagandha, garlic, guggul, etc. have been reported to have lipid-lowering effects. The goal of the review paper is to examine the potential anti-hyperlipidemic effects of herbal plants using a variety of models. The anti-hyperlipidemic activity of the most well-known medicinal herbs is the focus of this review.

Increased caveolin 1 by human antigen R exacerbates Porphyromonas gingivali-induced atherosclerosis by modulating oxidative stress and inflammatory responses

Objective: Many different types of infectious oral diseases have been identified clinically, including chronic periodontitis. Porphyromonas gingivalis is the main pathogen causing chronic periodontitis, which is closely related to atherosclerosis (AS) and can promote the expression levels of caveolin 1 (Cav-1) and induced ribonucleic acid (RNA)-binding protein human antigen R (HuR). However, the roles of Cav-1 and its relationship with HuR in P. gingivalis-mediated AS progression remain largely unknown. Here, we aimed to detect the role and molecular mechanisms of Cav-1 in P. gingivalis-mediated AS. Material and Methods: To investigate the role of Cav-1 in P. gingivalis-mediated AS, we infected human umbilical vein endothelial cells (HUVECs) with P. gingivalis at a multiplicity of infection of 100:1 for 6, 12, and 24 h to simulate P. gingivalis-induced AS models in vitro and then transfected them with Cav-1 small interfering RNA to silence Cav-1. Combining molecular biology experimental techniques such as cell counting kit-8 assay, enzyme-linked immunosorbent assay, immunofluorescence staining, flow cytometry, Western blotting, and Oil Red O staining, and apolipoprotein E-deficient AS model mice, the impacts of Cav-1 on cell viability, inflammation, oxidative stress, apoptosis, Cav-1 and intercellular cell adhesion molecule-1 (ICAM-1) levels, and atherosclerotic plaque formation were investigated. Then, the relationship between Cav-1 and HuR was investigated through biotin pull-down and RNA immunoprecipitation assays, reverse transcription quantitative polymerase chain reaction, and Western blot. Results: P. gingivalis can induce Cav-1 expression in a time- and dose-dependent manner (P < 0.05). This effect can inhibit the proliferation of HUVECs (P < 0.05). Cav-1 interference repressed inflammatory response, reactive oxygen species (ROS) and ICAM-1 levels, and apoptosis in the HUVECs (P < 0.05). Cav-1 messenger RNA was stabilized by HuR, which can bind to the 3’ untranslated region of Cav-1. Increase in HuR level reversed the effects of Cav-1 silencing on ROS and ICAM-1 levels and apoptosis in the HUVECs (P < 0.05). In addition, the levels of inflammatory response, oxidative stress, and atherosclerotic plaque formation induced by P. gingivalis in the mouse model were significantly reduced after Cav-1 expression was inhibited (P < 0.05). Conclusion: HuR-activated Cav-1 may promote atherosclerotic plaque formation by modulating inflammatory response and oxidative stress, leading to AS.

Clonal haemopoiesis and venous thromboembolism risk.

Many cases of venous thromboembolism (VTE) are idiopathic and clonal haemopoiesis, a risk factor for atherosclerotic vascular disease, may be a contributing factor to VTE. The report by Englisch and colleagues suggests that clonal haemopoiesis is a risk factor for recurrent VTE, especially in people without identifiable thrombotic predisposition. Commentary on: Englisch etal. Association of clonal hematopoiesis with recurrent venous thromboembolism: A case-control study. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19871.

Moderately Increased Left Ventricular Filling Pressure Suggesting Early Stage of Heart Failure with Preserved Ejection Fraction in Patients with Invasively Assessed Coronary Microvascular Dysfunction

Background: With modern diagnostic tools, incidence ischemia with no obstructive coronary atherosclerosis (INOCA) and heart failure with preserved ejection fraction (HFpEF) are found to be much higher than previously believed, and—as they lead to adverse cardiovascular outcomes—their causes and development are subjects of ongoing research. There is growing evidence that coronary microvascular dysfunction might be the underlying cause of both INOCA and HFpEF. Methods: In 65 patients with effort angina but no obstructive coronary artery disease, the index of microvascular resistance and coronary flow reserve were measured invasively in the LAD. The echocardiographic parameters, including left atrial strain, left ventricular strain, and indices of left ventricular diastolic dysfunction, were compared between two groups of patients: those with normal coronary microcirculation parameters and those with impaired coronary microvascular function. Results: Patients with coronary microvascular dysfunction had higher a E/E′ index than those with normal microvessel reactivity. This finding was further confirmed by ROC analysis. The groups did not differ significantly in values of other echocardiographic parameters, including the left ventricular and left atrial strain. The prevalence of classical cardiovascular risk factors was similar in both groups. Conclusions: The coexistence of impaired coronary microvascular function with moderately elevated left ventricular filling pressures might correspond to the co-development of early stages of coronary microvascular dysfunction and HFpEF.

Chest-CT-based radiomics feature of epicardial adipose tissue for screening coronary atherosclerosis.

This study aims to investigate the diagnostic value of chest-CT epicardial adipose tissue (EAT) radiomics feature in coronary atherosclerotic stenosis. Clinical data from 215 individuals who underwent coronary angiography and chest-CT scan from January to July 2022 at our institution were retrospectively analyzed. Based on the coronary angiography results, the total population, men, and women were divided into the CAD group and non-CAD group. radiomics feature of EAT at the level of the bifurcation of the left-main coronary artery on the transverse level of chest CT were measured. The features contain both first-order feature and shape-order feature.The differences between groups were analyzed using the t test or Chi-square test. The diagnostic efficacy of each parameter in diagnosing atherosclerotic stenosis of coronary arteries was assessed by plotting the receiver operating characteristic (ROC) curve. First-order features: Mean, IntDen, Median, and RawIntDen; shape-order features: Area, Perim, Round, and BSA index; and clinical index: HbA1c showed statistical significance between the CAD group and the non-CAD group. The ROC curve analysis demonstrated high diagnostic efficacy, with the best for diagnostic efficacy being Median for the first-order feature parameter (AUC, 0.753; 95% confidence interval [CI], 0.689-0.817; t = 4.785, p < 0.001), Round for the shape-order feature (AUC, 0.775; 95% CI, 0.714-0.836; t = 7.842, p < 0.001), and HbA1c for the clinical index (AUC, 0.797; 95% CI, 0.783-0.856; t = 6.406, p < 0.001). After dividing the participants into male and female subgroups, the best diagnostic efficacy was observed with the BSA index for men (AUC, 0.743; 95% CI, 0.656-0.829; t = 5.128, p < 0.001) and Round for women (AUC, 0.871; 95% CI, 0.793-0.949; t = 7.247, p < 0.001). Median, Round in radiomics feature of EAT on chest CT may play a role in the assessment of coronary atherosclerotic stenosis.

2-Acetamidophenol (2-AAP) Suppresses the Progression of Atherosclerosis by Alleviating Hyperlipidemia and Attenuating the Ferroptosis Pathway

Hyperlipidemia and consequent endothelial inflammation, along with foam cell generation, promote the progression of atherosclerosis (AS). Here, we aimed to investigate the effects of 2-acetamidophenol (2-AAP), which was selected by zebrafish phenotypic screening, in alleviating AS by relieving hyperlipidemia and inhibiting foam cell formation, as well as the underlying mechanisms. In a zebrafish hyperlipidemia model, 2-AAP increased lipid-lowering efficacy; alleviated TC, TG, LDL-C, and MDA levels; elevated HDL-C and T-SOD levels; significantly improved intravascular macrophage aggregation; and improved blood flow. In an ox-LDL-induced RAW264.7 model, 2-AAP inhibited lipid phagocytosis in RAW264.7 cells; reduced the intracellular TC, TG, FC, and CE contents; and decreased the CE/TC ratio, thus slowing foam cell generation. In addition, 2-AAP alleviated intracellular ROS and ferrous ion accumulation in RAW264.7 cells, reduced the MDA content, and increased GPX4 viability. Furthermore, transcriptome analyses and gene expression validation showed 2-AAP treatment upregulates genes related to GSH synthesis and transport, such as gclc, gclm, gss, and gpx4a, and enhanced the expression levels of genes involved in the storage and transportation of iron ions, such as fpn1, fth, and g6pd, indicating that 2-AAP dramatically regulated the ferroptosis and glutathione metabolic pathways. Overall, our study demonstrated that 2-AAP demonstrated potential in AS by alleviating hyperlipidemia and attenuating the ferroptosis pathway and provided evidence supporting the future application of 2-AAP in AS treatment.

N-Acetylneuraminic acid triggers endothelial pyroptosis and promotes atherosclerosis progression via GLS2-mediated glutaminolysis pathway.

Vascular endothelial injury initiates atherosclerosis (AS) progression. N-Acetylneuraminic acid (Neu5Ac) metabolic disorder was found to intensify endothelial mitochondrial damage. And GLS2-associated glutaminolysis disorder contributed to mitochondrial dysfunction. However, mechanisms underlying Neu5Ac-associated mitochondrial dysfunction as well as its association with GLS2 remains unclear. In this study, we constructed GLS2-/-ApoE-/- mice by using HBLV-GLS2 shRNA injection. And methods like immunofluorescence, western blotting, transmission electron microscopy were applied to detect profiles of endothelial injury and AS progression both in vivo and in vitro. We demonstrated that Neu5Ac accumulation increased GLS2 expression and promoted glutaminolysis disorder, which further induced endothelial mitochondrial dysfunction via a pyroptosis-dependent pathway in vivo and in vitro. Mechanically, Neu5Ac interacted with SIRT3 and led to FOXO3a deacetylation and phosphorylation, further facilitated c-Myc antagonism and ultimately increased GLS2 levels. Inhibition of GLS2 could improve mitochondrial function and mitigate pyroptosis process. In addition, blocking Neu5Ac production using neuraminidases (NEUs) inhibitor could rescue endothelial damage and alleviate AS development in ApoE-/- mice. These findings proposed that Neu5Ac induced GLS2-mediated glutaminolysis disorder and then promoted mitochondrial dysfunction in a pyroptosis-dependent pathway. Targeting GLS2 or inhibiting Neu5Ac production could prevent AS progression.

Construction of Immune-Related circRNA-miRNA-mRNA Network and Identification of circRNAs as Biomarkers in Coronary Atherosclerotic Heart Disease

Circular RNAs (circRNAs) play crucial roles in the immune and inflammatory responses of many diseases by acting as competing endogenous RNAs (ceRNAs). However, the role of circRNAs as ceRNAs in the immune and inflammatory processes of coronary atherosclerosis heart disease (CHD) remains unclear. This study aimed to identify and validate the potential immune-related circRNAs as biomarkers for CHD. Firstly, we constructed a ceRNA regulatory network including 14 circRNAs, 24 miRNAs, and 15 genes through bioinformatics analysis. Four hub genes were identified and five candidate immune-related circRNAs were screened. Subsequently, the expression levels of these candidate circRNAs were detected by qRT-PCR. Notably, hsa_circRNA_101069 and hsa_circRNA_406053 showed significant up-regulation in CHD patients (p &lt; 0.001). The value of these circRNAs as biomarkers for CHD was evaluated by the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indexes. Adding circRNAs to a traditional CHD model significantly enhanced classification performance, with an IDI of 0.058 and an NRI of 0.280 for hsa_circRNA_101069 and an IDI of 0.051 and an NRI of 0.480 for hsa_circRNA_406053. Furthermore, hsa_circRNA_101069 was up-regulated in ox-LDL-induced THP-1 macrophages, and silencing hsa_circRNA_101069 significantly inhibited the apoptosis rates and the inflammatory cytokines levels. This study constructed an immune-related circRNA-miRNA-mRNA network and identified two circRNAs as biomarkers for CHD, with hsa_circRNA_101069 potentially contributing to the pathological basis of CHD.

Is soluble ST2 an useful biomarker for early diagnosis of coronary atherosclerosis?

Is soluble ST2 an useful biomarker for early diagnosis of coronary atherosclerosis?

Abstract 4135636: Age- and Sex-Related Coronary Atherosclerosis by Artificial Intelligence Quantitative Coronary CT Angiography from the INVICTUS Registry

Background: Coronary plaque analysis using artificial intelligence quantitative coronary CT (AI-QCT) is a promising tool to identify coronary atherosclerosis. However, there is insufficient data on coronary atherosclerosis volume and morphology using AI-QCT in patients who are at high risk of atherosclerosis. The purpose of this study is to clarify the differences in the volume and phenotypes of coronary atherosclerosis by age and gender using AI-QCT. Methods: The INVICTUS Registry is a multi-center registry enrolling patients who clinically underwent coronary CT angiography and invasive coronary angiography with invasive imaging modalities in Japan. Patients with a history of percutaneous coronary intervention or coronary artery bypass graft were excluded in this study. Using AI-QCT, the volume, and phenotypes (calcified, non-calcified, low-density non-calcified plaque [LD-NCP]) of coronary atherosclerosis were analyzed and assessed by age (&lt;55, 55-64, 65-74, and 75 and older) and gender. Results: A total of 982 patients were enrolled in the study. The mean age was 70.3 ± 10.8 years, 71.9% were male. Approximately two-thirds of patients had hypertension (73.3%) and dyslipidemia (71.5%), and 36.7% had diabetes. Mean total plaque volume (PV), calcified PV, non-calcified PV, and low-density PV were 745.5±529.8 mm 3 , 248.3±302.0 mm 3 , 482.2±340.6 mm 3 , and 15.0±29.4 mm 3 , respectively. The results of plaque volume and phenotypes by age are shown in the figure. Compared to those under 55 years of age, total PV increased gradually and significantly by about 10% for every 10 years of age (p=0.022). Though no significant difference was observed in non-calcified PV between the age groups (p=0.379), calcified PV progressively and significantly increases approximately 70% for every 10 years of age (p&lt;0.001). In contrast, the low-density plaque volume showed a trend toward a significant decrease with increasing age (p=0.073). These trends did not differ by gender. Conclusion: In a large cohort of patients at high risk for atherosclerosis analyzed by AI-QCT, total coronary PV increased with age, primarily calcified PV. While no change in non-calcified PV between the age groups, LD-NCPV was likely to decrease with increasing age. These findings may contribute to the guidance for the prevention of coronary artery diseases based on coronary atherosclerosis phenotype by age and gender.

Abstract 4134851: Demographic and regional disparities in cerebrovascular disease mortality among adult patients with pre-existing atherosclerosis in the United States from 1999-2020

Introduction: Atherosclerosis (ATH) is a major risk factor for cerebrovascular disease (CEVD), with persistent mortality disparities. Our study aims to identify vulnerable regions and demographics in the US adult population with pre-existing ATH at risk of CEVD. Methods: CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) was used to access National Vital Statistics System data from 1999 to 2020. ATH-related CEVD was identified using CEVD as the underlying cause of death and ATH as a contributing cause of death. Results were presented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to examine changes in trend and annual percentage change (APC). Results: A total of 325,408 CEVD occurred in patients with ATH from 1999 to 2020 (AAMR = 6.9, 95% CI: 6.8-7). Increased mortality rates were observed in males (AAMR = 6.3) as compared to females (AAMR = 5.1) (Figure, Panel A). AAMRs were highest in Non-Hispanic Whites [NHW] (5.7, 95% CI: 5.7 - 5.8), followed by non-Hispanic blacks [NHB] (5.5, 95% CI: 5.4 - 5.5), Hispanics (4.1, 95% CI: 4.0 - 4.1) and non-Hispanic American Indian/Alaska Native [NH-AIAN] (3.6, 95% CI: 3.4 - 3.8). Non-Hispanic Asian/Pacific Islander [NH-API] had the lowest mortality rates (3.4, 95% CI: 3.4 - 3.5). Region-wise analysis revealed that mortality rates were highest in the West (6.4, 95% CI: 6.3-6.4) and Midwest (6.2, 95% CI: 6.1-6.2). The South reported the rate of 5.5 (95% CI: 5.5-5.6), while the Northeast had the lowest rate (4.4, 95% CI: 4.3-4.4). Mortality rates were consistently higher in rural areas (6.1, 95% CI: 6.0-6.1) compared to urban areas (5.3, 95% CI: 5.3-5.4) throughout the study period. Overall AAMR rose from 9.0 in 1999 to 10.4 in 2001, then steadily declined before increasing to 3.6 from 2016 to 2020 (APC: 0.41). After an initial decline, AAMR increased in men (APC: 1.09) from 2016 and in women (APC: 5.09) from 2018. AAMR also increased among NH-API (APC: 8.9) and NHB (APC: 8.3) from 2018 onwards, and NHW (APC: 0.1) from 2016 (Figure, Panel B). Conclusions: Our study reveals significant mortality disparities from CEVD in patients with ATH, identifying males, NHW, and residents in the West and Midwest as particularly at increased risk. Rural areas consistently show higher mortality rates than urban areas. These findings highlight the need for targeted interventions and strategic provision of healthcare resources to improve outcomes for vulnerable populations.

Abstract 4141498: Coronary Atherosclerosis and Prostate Cancer: The Impact of Androgen Deprivation Therapy

Background: Men with prostate cancer (PC) who receive androgen-deprivation therapy (ADT), targeting the gonadotropin releasing hormone (GNRH) axis, are at higher risk of cardiovascular disease (CVD). However, the pathophysiology behind ADT cardiotoxicity is unclear. Hypothesis: We hypothesize that ADT is associated with accelerated atherosclerosis due to GNRH-mediated inflammatory cascade. Aims: To prospectively evaluate coronary plaque progression, using coronary computed tomography angiography (CCTA), in a cohort of PC men treated with versus without ADT. Methods: Sixty-eight men with localized PC receiving radiation (XRT) alone (n=17) or XRT+ADT (n=51) were prospectively enrolled. Patients underwent CCTA, as per clinical protocols , at baseline and 12-month follow-up. Plaque quantification was conducted, blinded to therapy and time-point, using semi-automated software (Coronary analysis research prototype, Siemens Healthineers, Forchheim, Germany), with assessment of total plaque volume (TPV) and plaque volume by subtype (calcified, CPV, high-density non-calcified, HD, low-density non-calcified, LD) on a per-patient basis. CAD-RADS was also evaluated. Results: At baseline, median (IQR) TPV, CPV, HD, LD (mm 3 ) and CAD-RADS among patients who received XRT alone versus XRT+ADT were 341.1 (118.5-778.2) vs 717.3 (207-1158.9), 22.2 (4.9-131.9) vs 74.3 (21.3-205.8), 306.6 (102.1-593.6) vs 585.8 (175-895.2), 14 (2.3-47) vs 22.6 (6.2-50.4), 1 (1-2) vs 2 (2-3), respectively. At 12-month follow-up, TPV, CPV, HD, LD, and CAD-RADS between XRT alone versus XRT+ADT were 410.1 (177-941) vs 904.6 (283.7-1402), 21 (12.1-195.1) vs 102.6 (30.5-259.4), 372.6 (157.6-721.6) vs 686.1 (242.7-1062.7), 11.7 (5.6-69.8) vs 34 (10.4-62.1), 2 (1-2) vs 3 (2-3). A statistically significant difference between baseline and follow-up was noted among patients treated with XRT+ADT for TPV, CPV, LD (p&lt;0.001), and HD (p=0.006). A significant difference in CAD-RADS grade was noted in both cohorts (p=0.025 for XRT and p&lt;0.001 for the XRT +ADT). There was no significant difference in any plaque volume between baseline and follow-up in the XRT alone cohort. Conclusion: Addition of ADT to XRT for localized PC treatment was associated with a significant progression of TPV, CPV, HD, LD, and CAD-RADS grade over a 12-month period. Insights on ADT cardiotoxicity may lead to enhanced cardioprotective strategies tailored to patients with PC undergoing combined therapy, potentially improving cardiac outcomes.

Microvascular resistance reserve in relation to total and vessel-specific atherosclerotic burden.

The relationship between coronary artery atherosclerosis and microvascular resistance remains unclear. This study aims to clarify the relationship between total atherosclerotic and vessel-specific atherosclerotic burden and microvascular resistance reserve (MRR). In this post-hoc analysis of the PACIFIC 1 trial, symptomatic patients without prior coronary artery disease (CAD) underwent [15O]H2O positron emission tomography, coronary computed tomography angiography (CCTA) and invasive fractional flow reserve (FFR). MRR was assessed across all three coronary branches, utilizing PET-derived coronary flow reserve and invasive FFR measurements. CCTA was used to assess patient and vessel-specific plaque volumes. Percentage atheroma volume (PAV) was defined as total plaque volume divided by vessel volume. The study included 142 patients (55% male, 57.5±8.6 years) with 426 vessels with a mean MRR of 3.77±1.64. While a significantly higher PAV was observed in the left anterior descending artery territory, MRR was similar across the three coronary branches. Generalized Estimating Equations without correction for cardiovascular risk factors identified that patient-specific PAV tertiles but not vessel-specific PAV tertiles were related to vessel-specific MRR. After correction for cardiovascular risk factors, compared to the first tertile of patient-specific PAV, the second tertile showed a vessel-specific MRR decrease of β=-0.362, p=0.018, and the third tertile showed a decrease of β=-0.347, p=0.024. In patients without prior CAD, patient-specific plaque burden was negatively associated to vessel-specific MRR; however, vessel-specific plaque burden was not related to vessel-specific MRR. Our findings suggest that the relation between atherosclerotic burden and an impaired microcirculatory function is of systemic origin.

Abstract 4120670: Pericoronary Adipose Tissue Inflammation as a Marker of Increased Coronary Plaque Burden in Patients With Chronic Coronary Artery Disease With Zero Calcium Score

Background: Dysfunctional or excess adiposity plays pivotal role in the development of coronary atherosclerosis. It remains unclear whether pericoroanry adipose tissue (PCAT) inflammation is associated with increased coronary plaque burden in its early stage of atherosclerosis, independent of traditional coronary risks or cardiovascular-kidney metabolic health. Purpose: To investigate the association of PCAT inflammation with coronary plaque burden in patients with newly suspected with chronic coronary artery disease (CAD) and zero calcium score who underwent coronary computed tomography angiography (CCTA). Methods: This retrospective CCTA study consists of 294 chronic CAD patients with zero calcium score (59 years, male 51 %). Chronic CAD was defined as stable condition with presence of increased non-calcified plaque burden on CCTA (Figure 1A-D). PCAT attenuation (PCATA) was assessed by fat attenuation index in the major three coronary arteries (right coronary artery, RCA; left anterior descending artery; LAD, and left circumflex coronary artery, LCX)(Figure 1C and D). Multivariable analysis using linear regression model was performed to determine independent predictors of increased %PV by adjusting for traditional coronary risks, metabolic risks, and chronic kidney disease (CKD). Hisayama Risk Score (HRS) was calculated to estimate 10-year cardiovascular risks. Results: Mean %plaque volume (PV) and PCATA-RCA was 44±4.0％ and -77±8.8 HU. %PV was correlated with age (p&lt;0.05), systolic blood pressure (p&lt;0.05), non-HDL cholesterol (p&lt;0.05), Hisayama risk score (p&lt;0.05, Figure 2), PCATA-RCA (p&lt;0.001, Figure 3), PCATA-LAD (p&lt;0.001), and LCX-PCATA (p&lt;0.001). In a multivariable linear regression model adjusting for age, sex, hypertension, diabetes, dyslipidemia, and current smoking (model 1), PCATA-RCA was independently associated with %PV [beta, 0.17; 95% confidential interval (CI) 0.115-0.217, p &lt; 0.001]. In a model adjusting for age, sex, metabolic syndrome, body mass index ≥23kg/mm 2 , and CKD (model 2), PCATA-RCA (beta, 0.18; 95% CI 0.128-0.232, p&lt;0.001) and high-risk HRS (beta, 3.1; 95% CI 1.35−4.87, p&lt;0.001) were independently associated with %PV. Similarly, independent associations of PCATA in LAD and LCX with %PV was observed. Conclusion: This study demonstrates that PCATA is a robust marker related to increased burden of coronary atherosclerosis even in the early stage of atherosclerosis as defined by zero coronary artery calcium score.

Commencement of Atorvastatin and Ezetimibe Immediately in Patients Presenting with Acute Coronary Syndrome

Lipids are implicated in the development of coronary atherosclerosis. Achieving a significant reduction in lipid levels remains a crucial aspect of secondary prevention following an acute coronary syndrome event. Novel lipid-lowering therapies now provide clinicians with a variety of therapeutic strategies to choose from and tailor to individual patient needs. This review focuses on evidence supporting the importance of early and intensive lipid-lowering therapy use in patients presenting with acute coronary syndrome, specifically addressing data relating to atorvastatin and ezetimibe use in this high-risk cohort of patients.

Abstract 4136032: Digital Biomarkers Associated With Coronary Artery Calcium And Traditional Risk Factors Extracted From Facial Photos Through Multi-Label Deep Learning For Detecting Coronary Artery Disease

Background: Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis. Aims: We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches. Methods: Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD. Results: A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC&gt;0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P&lt;0.001; 0.721 vs. 0.686, P=0.032), with further significant improvement when combined with these models (△AUC= +0.085, P&lt;0.001; △AUC= +0.068, P&lt;0.001). Conclusion: FacialCAD, a set of CAC and risk factors-associated novel digital biomarkers extracted from facial images, exhibited superior and incremental value to conventional clinical approaches in predicting CAD status.

The Trend of Modifiable Risk Factors of Ischemic Heart Disease in Pakistan from 2000 To 2022

Ischemic Heart Disease is the leading cause of mortality in Pakistan. It is cause by myocardial ischemia. Most cases of myocardial ischemia are as a result of coronary artery atherosclerosis. There are Modifiable and nonmodifiable risk factors of atherosclerosis. Here we discuss the trend of modifiable risk factors in Pakistan from 2000 to 2022. A Secondary analysis was conducted to find the trend of Modifiable risk factors and its relation with ischemic heart disease in Pakistan from 2000 to 2022. For this purpose, Literature review was performed using google scholar and PubMed, Data on trends of these risk factors was obtained from WHO Pakistan website. The trend of modifiable factors of ischemic heart disease, namely Tobacco smoking, Obesity, Alcohol consumption and Hypertension has been increasing in Pakistan, except for Tobacco smoking. Proper preventive measures must be taken to counter this specific death rate. This may include mass Health education, Health promotion, Dietary changes, and lifestyle changes.

New atherosclerosis progression markers in patients with post-Chernobyl metabolic syndrome

Relevance. As an epidemiologically proven consequence of the Chernobyl NPP accident, circulatory diseases are among the leading morbidities in liquidators. To predict the development of adverse cardiovascular events in patients with metabolic syndrome, there is the ongoing search for informative laboratory markers.The objective is to show how osteopontin, osteoprotegerin, fetuin-A, and risk factors for genetic circulatory disorders are associated with traditional risk factors for circulatory disorders in Chernobyl nuclear power plant accident liquidators suffering metabolic syndrome. Another objective is to explore the perspectives to use these indicators to forecast coronary atherosclerosis progression.Methods. The study group included 50 male liquidators of the Chernobyl nuclear power plant accident who suffered metabolic syndrome. The patients were split in two groups depending on osteopontin concentration in blood serum, i.e. above or under the upper reference limit. Medical history data, biochemical parameters, including inflammatory proteins, osteoprotegerin, fetuin-A, and genotyping of polymorphic variants of genes associated with the risk of circulatory diseases were analyzed. A control group of 30 conditionally healthy men was formed to determine the normal osteopontin, osteoprotegerin and fetuin-A values in blood serum.Results and discussion. With osteopontin value exceeding 21.4 ng/mL, the liquidators’ medical history showed 1.5 times higher frequency of myocardial infarction, 2.5 times higher frequent history of acute cerebral circulation disorder; ischemic heart disease was associated with type 2 diabetes mellitus. It was shown that the group of liquidators (osteopontin over 21.4 ng/ml) was characterized by a reliable increase in atherogenicity coefficient and osteoprotegerin level. Meanwhile, when compared to the control group, the same group of patients showed lower fetuin-A values and elevated high-sensitivity C-reactive protein, homocysteine, leptin and ghrelin. It was found that in liquidators, the presence of the A allele in the vitamin B12-dependent methionine synthase (MTR) gene (2756 A&gt;G) is associated with more pronounced biochemical markers of atherosclerosis progression compared to GG genotype carriers.Conclusion. Osteopontin performs a protective role in tissue damage, being is practically undetectable in normal conditions. However, in case of pathology its value increases dramatically. In patients with metabolic syndrome, decreased fetuin-A and osteopontin values exceeding 21.4 ng/mL require additional examination with a focus on cardiovascular pathology (coronary artery calcinosis), as well as a dual-energy X-ray absorptiometry to ensure early detection of diminished bone mineral density and body mass. It was found that in liquidators, the presence of A-allele (genotypes AA and AG) in the MTR 2756 A&gt;G gene is characterized by deeper atherogenic changes in the lipid spectrum, increased atherogenicity coefficient and decreased adiponectin content. This justifies the need for genotyping to build individual forecast for atherosclerosis progression in this category of patients.

A Novel Insight into Postmenopausal Hypercholesterolemia: Carnitine as a Key Player.

Background: Postmenopausal women (post-MW) are at a heightened risk of cardiovascular diseases, including hypercholesterolemia. This study aimed to investigate metabolomic variations to identify potential markers and targets for postmenopausal hypercholesterolemia. Methods: Sixty-two female volunteers aged 40-65 were recruited for this study. Metabolomic analysis using the Ultra-Performance Liquid Chromatography Quadrupole Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap MS) platform was conducted to investigate changes in endogenous substances in premenopause (n = 25) and postmenopause (n = 37) women. Following ovariectomy surgery, menopausal mice were monitored for changes in their biomarker levels, and the integrity of the large artery walls in each treatment group was observed through hematoxylin and eosin staining. In vitro cellular models were utilized to assess variations in lipid metabolism, reactive oxygen species (ROS) levels, and changes in the levels of superoxide dismutase and glutathione peroxidase enzymes in different cell groups postintervention using Western blot analysis. Results: Treatment with carnitine in postmenopausal mouse models led to increased plasma cholesterol and carnitine levels, as well as indicators of arterial sclerosis. In HepG2 cells, carnitine treatment resulted in heightened lipid levels, elevated ROS production, and decreased antioxidant enzyme levels. Conclusions: The findings suggest that carnitine may serve as a potential risk marker or therapeutic target for postmenopausal hypercholesterolemia. This study provides valuable insights into cardiovascular conditions in post-MW and offers new avenues for therapeutic interventions. Continued research in this area is crucial to enhance our understanding of cardiovascular diseases in post-MW and to explore additional treatment options.

Novel insights of disulfidptosis-mediated immune microenvironment regulation in atherosclerosis based on bioinformatics analyses

Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS.