Marker Of Atherosclerosis Research Articles

Influence of Persistently Elevated LDL Values on Carotid Intima Media Thickness in Elite Athletes.

Carotid IMT is a recognized marker for early atherosclerotic changes and a predictor of future CV events. Previous studies showed 11% increased risk of myocardial infarction with each 0.1mm incremental increase of carotid IMT. In general population, LDL cholesterol levels are positively correlated with carotid IMT in both cross-sectional and longitudinal studies while its role in elite athletes remains understudied. This study aimed to investigate the correlation between persistent lipid profile alterations and early markers of atherosclerosis, specifically carotid IMT, in a cohort of elite athletes. We included 302 athletes serially evaluated for a prolonged time period. Anthropometric data, blood tests for lipid profiles, and carotid IMT measurements were collected. Dyslipidemia was defined as LDL ≥ 116mg/dL, and persistent elevation when LDL values remained above the threshold limits in at least three pre-participation screenings. Categorical variables were expressed as frequencies and percentages and were compared using Fisher's exact test or Chi-square test, as appropriate. 91 athletes (30.1%) had persistently elevated LDL levels. Dyslipidemic athletes were older (30.7 ± 5.7 vs. 29.1 ± 4.1 years, p = 0.008), had higher BMI (p = 0.032), and a higher prevalence of obesity (5.5% vs. 0.5%, p = 0.004) compared to those with normal lipid profiles. Additionally, they had higher total cholesterol (p < 0.0001) and triglycerides (p < 0.0001) but similar HDL levels (p = 0.213). Globally, athletes with altered LDL profiles over long-time period showed higher IMT (0.60 ± 0.10mm vs. 0.57 ± 0.07mm, p = 0.014). In particular, longer exposure to elevated LDL was significantly associated with increased IMT (0.61 ± 0.12mm vs. 0.57 ± 0.06mm, p = 0.035). Our study highlights the association between persistently elevated LDL-C and increased carotid IMT in elite athletes, with longer exposure time correlating with more pronounced carotid changes. These findings underscore the importance of regular monitoring of blood lipid profiles and carotid IMT measurements as a non-invasive, cost-effective method to prevent atherosclerotic vascular disease.

Is Myocardial Work a Surrogate Marker for Functional Coronary Artery Stenosis or a Marker of Coronary Atherosclerosis?

Is Myocardial Work a Surrogate Marker for Functional Coronary Artery Stenosis or a Marker of Coronary Atherosclerosis?

Psoriasis treatments in the stabilization of atherosclerosis: a systematic review

Abstract This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA). Eligible studies were those involving human subjects over 18, written in English, that provided quantitative atherosclerosis markers, including CIMT, CCTA, arterial pulse wave velocity (aPWV), fat attenuation index (FAI), and augmentation index (Aix). From an initial pool of 217 studies, 21 were included, grouped by treatments, including TNF-α inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, DMARDs, phototherapy, and fumaric acid esters. The review found that TNF-α inhibitors significantly improved atherosclerosis markers such as CIMT, aPWV, FAI, and C-reactive protein (CRP), with reductions in these markers compared to no treatment, phototherapy, and IL-12/23 inhibitors. Additionally, IL-17 inhibitors demonstrated similar reductions in FAI compared to TNF-α inhibitors but showed a greater effect in reducing non-calcified plaque burden (12% vs. 5% for TNF-α inhibitors, p &lt; 0.001) and also decreased CRP levels. Fumaric acid improved cholesterol metabolism (p &lt; 0.04), and TNF-α inhibitors enhanced endothelial function (p &lt; 0.01). Mixed results were observed when compared to DMARDs, indicating that patient-specific factors should guide treatment choices. In conclusion, TNF-α inhibitors are highly effective in reducing atherosclerosis progression in psoriasis patients, consistently improving vascular health markers like CIMT, aPWV, FAI, and CRP. IL-17 inhibitors also show significant efficacy, particularly in reducing non-calcified plaque burden, making them a valuable alternative to TNF-α inhibitors. Fumaric acid’s role in cholesterol metabolism suggests its potential in combination therapies. These findings support integrating TNF-α and IL-17 inhibitors into treatment protocols for psoriasis patients with comorbid atherosclerosis, improving cardiovascular outcomes.

Effect of long term treatment with antiepileptic drugs on carotid intima-media thickness as an indicator of atherosclerosis

Purpose: The aim of current study was to investigate the possible relation between antiepileptic drugs (AEDs) and atheosclerotic risk factors and carotid intima media thickness (IMT) as a marker of atherosclerosis. Materials and Methods: Ninety-two patients, who had used carbamazepine (CBZ) and valproic acid (VPA) for three or more years and who had used a second AED (polytherapy) for two years in addition to CBZ or VPA monotherapy, were included in the study. The control group was composed of 31subjects with similiar demographics. Fasting blood glucose, liver and renal function tests, lipid profile, homocysteine, serum high sensitivity C-Reactive Protein (Hs-CRP), uric acid (UA), lipoprotein (a) (Lp (a)), folate and vitamine B12 levels were examined in both groups. Results: Homocysteine levels were higher in the VPA, CBZ and politherapy groups compared to the control group. UA levels were higher in the VPA monotherapy group when compared to the CBZ monotherapy and polytherapy group. In the CBZ monotherapy group, Hs-CRP levels were higher than in the VPA monotherapy, polytherapy and control groups. Total cholesterol levels were higher in the CBZ monotherapy group when compared to the VPA monotherapy and control groups. Conclusion: The findings showed no correlation between IMT values and duration of disease, duration of drug usage and dose, which suggests that long-term AED usage does not increase the development of atherosclerosis.

The relationship between residual insulin secretion and subclinical cardiovascular risk indices in young adults with type 1 diabetes.

Patients with type 1 diabetes (DM1), even in the setting of adequate glycaemic control, have an excess risk for developing cardiovascular disease. Residual insulin secretion (RIS), measured by detectable C-peptide levels in patients with DM1, might protect against diabetes-related complications. This study aimed to examine the relationship between residual insulin secretion and prognostic markers of cardiovascular complications in patients with DM1. A total of 137 patients with DM1 were included in this analysis. They were of young age (<45 years), with an established diagnosis of over two years before the study entry and without a history of cardiovascular complications. All patients underwent complete clinical and laboratory evaluation. A c-peptide measurement of ≥0.05 ng/ml was used to identify the presence of RIS. Pulse wave velocity (PWV), cardiac autonomic function assessed both at rest, by total power of heart rate variability and dynamically, by the expiration to inspiration (e/i) index, albumin to creatinine ratio (ACR), and high sensitivity CRP (hs-CRP) were used as predictive biomarkers of cardiovascular complications. Female participants represented 63.5% of the population [mean age: 29.7 (±8.1) years, mean HbA1c: 7.6% (±1.4), median diabetes duration:15 (10-21) years, median age at diabetes diagnosis: 13 (8-17) years]]. The median value of fasting c-peptide was 0.04 (0.03-0.05) ng/ml, and RIS was detected in 32 patients (23.4%). Patients with RIS had a shorter diabetes duration, an older age at diagnosis and a lower BMI, while no significant association was found between residual c-peptide and age or HbA1c. RIS was significantly associated with lower PWV values [8.1 m/s² (7-8.7) vs 9.2 m/s² (7.8-10.1), p <0,001], higher total power values [1124 Hz (600-3277) vs 577 Hz (207-2091), p <0,001], and higher E/I measurements [1.4 (1.2-1.5) vs. 1.3 (1.2-1.4), p=0.01]. No significant association was noted between RIS and either ACR or hs-CRP. In multivariable linear regression analysis, the association between RIS and lower PWV values remained significant (p= 0.007) regardless of age, sex, diabetes duration or age of diagnosis, blood pressure and BMI. Similarly, residual insulin secretion retained a significant independent association with total power (p= 0.032) and E/I (p=0.045). In young patients with DM1, free of macrovascular complications, residual insulin secretion is independently associated with more favorable prognostic markers of subclinical atherosclerosis and cardiac autonomic function.

Carotid artery intima-media thickness values in obese or overweight children: a meta-analysis.

Carotid artery intima-media thickness (IMT) is a non-invasive ultrasound marker of early atherosclerosis. This systematic review and meta-analysis aim to report the published differences in IMT values in children living with overweight or obesity compared to controls with normal weight. This review was conducted according to PRISMA guidelines, including only cohorts with normal controls. Inclusion criteria were IMT measured using B-mode or radiofrequency (RF) techniques and based on the four consensuses: American Heart Association, Association for European Pediatric Cardiology, Mannheim Consensus, and American Society of Echocardiography. We used the body mass index based on the World Health Organization growth standard definitions of obesity in children. Relevant articles were extracted from PubMed, Cochrane Library, Embase, and Web of Science searched from inception to February 2024. A meta-analysis was done by a biostatistician using the R-software version 4.0.2. We obtained 15 B-mode-based and two RF echo-tracking-based IMT measurement studies. IMT is significantly increased in children living with obesity. The mean IMT was 0.041 mm, 95% confidence interval (CI): 0.052; 0.031 higher in children with overweight/obesity, using the B-mode technique, and 0.045 mm, 95% CI: 0.062; 0.029 higher in children with overweight/obesity using RF technique. This meta-analysis shows that IMT is significantly increased in children with obesity compared to normal-weight children according to both techniques. Question IMT measured according to known consensuses is significantly increased in children living with obesity. Findings Mean IMT was 0.041 mm higher in children living with obesity using the B-mode technique and 0.045 mm using the RF technique. Clinical relevance There are different techniques to measure IMT in children. This meta-analysis, using cohorts of children living with obesity compared to normal weight controls, shows a significantly increased IMT in children living with obesity.

Effect of Low- and Moderate-Intensity Aerobic Training on Body Composition Cardiorespiratory Functions, Biochemical Risk Factors and Adipokines in Morbid Obesity.

Obesity poses an enormous public health and economic burden worldwide. Visceral fat accumulation is associated with various metabolic and cardiovascular consequences, resulting in an increased prevalence of atherosclerotic conditions. We aimed to examine the impact of low-and moderate-intensity aerobic training on several anthropometric and cardiorespiratory parameters and markers of atherosclerosis, including inflammation, serum levels of lipoproteins and adipokines of extremely obese patients in poor condition. Forty severely obese patients were recruited and randomized into two groups, Group 1 and Group 2, for a six-week inpatient study. Group 1 received moderate-intensity (40-60% heart rate reserve) and Group 2 received low-intensity (30-39% of heart rate reserve) aerobic training combined with resistance training. The patients' cardiorespiratory functions were assessed by ergospirometry. Anthropometric data were recorded, body composition was analyzed and functional tests were performed. We also investigated serum lipids and high-sensitive C-reactive protein levels and calculated the homeostatic model assessment-insulin resistance indices and adipokine levels as predictive biomarkers. Functional abilities and some biochemical parameters, such as homeostatic model assessment-insulin resistance, serum lipids, apolipoprotein A and apolipoprotein-B improved in both groups in a positive direction. However, cardiorespiratory capacity and the serum levels of high-sensitive C-reactive protein and Lipocalin-2 decreased, while irisin and paraoxonase 1 increased significantly, but only in Group 1. Six weeks of aerobic training, regardless of its intensity, could induce favorable changes in functional tests, body composition and serum lipids, even in severely obese, extremely unconditioned patients in both groups. However, moderate-intensity aerobic training should at least increase cardiorespiratory capacity and yield a better lipid profile oxidative status and inflammation profile.

Физиологические аспекты липидного обмена в условиях Арктической зоны Российской Федерации (обзор)

This article aimed to systematize data on lipid metabolism parameters in various population groups of the Arctic region in the historical aspect and in modern conditions. The materials were selected using international (Web of Science and Scopus) and Russian (Cyberleninka and eLIBRARY.RU) databases. The following keywords were searched for: Arctic, lipid metabolism, risk factors. The sample included 34 works on the changes in lipid metabolism in the inhabitants of the Arctic region published between 1979 and 2023. It has been shown that the indigenous population is more likely to have a favourable blood lipid profile, with a low content of lowdensity lipoproteins (LDL) and triglycerides (TG), but high content of high-density lipoproteins (HDL). In zerogeneration newcomers, when their adaptation is disrupted, atherogenic dyslipidaemia often develops, while in first- and second-generation newcomers, lipid metabolism occupies an intermediate position, approaching the parameters of the indigenous population. Along with climatic and geographical conditions, socio-economic factors (dietary changes, smoking and alcohol abuse) affect the human body, leading to atherogenic dyslipidaemia, which is the basis of cardiovascular diseases. An important role in assessing lipid metabolism disorders in the Arctic is played by determining more reliable markers of atherosclerosis, namely, the content of apolipoproteins (apoA and apoB) and fatty acids consumed. The indigenous inhabitants of the North typically have a protein- and fatrich diet characterized by increased levels of omega-3 and decreased levels of omega-6 polyunsaturated fatty acids (PUFAs). However, in recent decades, low levels of both omega-3 and omega-6 PUFAs have become more common. For early detection of signs of lipid metabolism disorders, we need to study not only the “traditional” parameters, i.e. total cholesterol, TG, LDL and HDL, but also apoA-I and apoB as well as omega-6 and omega-3 PUFAs in order to develop science-based diagnostic methods, differentiated wellness programmes and therapeutic measures.

Serum folate levels, but not vitamin B12, are associated with slower progression in carotid intima-media thickness in a population exposed to mandatory folic acid fortification

Background&AimsFolate and vitamin B12 are vitamins involved in one carbon metabolism. Carotid intima-media thickness (cIMT) is a non-invasive test and an early atherosclerosis marker. The relationship between these vitamins and cIMT is not well established. This study aimed to investigate the association between baseline vitamins and cIMT changes during a median follow-up of 8 years. MethodsProspective cohort study involving 5,061 ELSA-Brasil participants from São Paulo state aged 35-74 years at baseline. Serum folate and vitamin B12 levels and dietary intake were assessed at baseline. Ultrasound cIMT measurements were performed at baseline and wave 3. Linear mixed-effects models, adjusted for covariables, assessed the association between vitamins at baseline and changes in cIMT. Results4,260 participants were included; mean (SD) age was 51.4 (8.9) years and 54.5% were women. Folate (0.02%) and vitamin B12 (2.6%) deficiencies were almost nonexistent. Participants in the 4th quartile of serum folate had a slower cIMT increase during 8 years of follow-up than those in the 1st quartile (1st vs. 4th quartile comparison: β (95% CI): -0.015 (-0.026; -0.004), P: 0.006 for model 3). These findings remained the same after sensitivity analysis for overall dietary supplements and specifically multivitamins use. No association was found between vitamin B12 biomarker and the outcome. Dietary folate intake was also not associated with cIMT changes. ConclusionIn this population exposed to mandatory folic acid food fortification, prevalence of vitamins deficiencies was very low. Highest quartile of serum folate seemed to slow down the increment of cIMT measurements over time.

Circulating RBP4 and FABP4 concentrations in patients with chronic schizophrenia are associated with increased epicardial adipose tissue volume and metabolic syndrome.

Schizophrenia has been linked to an elevated cardiovascular risk profile and premature onset of cardiovascular disease. Quantifying epicardial adipose tissue (EAT) volume provides insight into its correlation with coronary artery disease (CAD) severity and associated risk factors. Previous research indicates higher pericardial adipose tissue in individuals with schizophrenia compared to non-schizophrenic counterparts. RBP4, FABP3, and FABP4 have been implicated in CAD pathogenesis. In this study, we examined the potential increase in EAT volume in individuals with chronic schizophrenia and aimed to elucidate the relationship between circulating levels of RBP4, FABP3, and FABP4 with EAT volume and coronary artery calcium score within this cohort. We recruited 186 consecutive patients with chronic schizophrenia and utilized enzyme-linked immunosorbent assay to assess plasma concentrations of RBP4, FABP3, and FABP4. Cardiac multislice computed tomography measured EAT volume and coronary artery calcium scores. Significantly higher EAT volume in patients with chronic schizophrenia compared to controls. RBP4 associated positively with metabolic factors and EAT volumes, while FABP3 associated positively with creatinine and coronary atherosclerosis markers. FABP4 showed positive associations with metabolic factors, hypertension, and EAT volumes, but negative associations with HDL-C and eGFR. Logistic regression identified RBP4 and FABP4 as independent factors associated with increased EAT volumes, even after adjusting for known biomarkers. Both RBP4 and FABP4 were significantly associated with metabolic syndrome components and EAT volume. This study elucidates the association between chronic schizophrenia and augmented EAT volume, suggesting plausible correlations with CAD-related health complications through RBP4 and FABP4 pathways.

Modeling the Impact of Extracellular Vesicle Cargoes in the Diagnosis of Coronary Artery Disease.

Objectives: We aimed to assess the relationship among circulating extracellular vesicles (EVs), hypoxia-related proteins, and the conventional risk factors of life-threatening coronary artery disease (CAD) to find more precise novel biomarkers. Methods: Patients were categorized based on coronary CT angiography. Patients with a Segment Involvement Score > 5 were identified as CAD patients. Individuals with a Segment Involvement Score < 5 were considered control subjects. The characterization of EVs and analysis of the plasma concentration of growth differentiation factor-15 were performed using multicolor or bead-based flow cytometry. The plasma protein levels of glycogen phosphorylase, muscle form, clusterin, and carboxypeptidase N subunit 1 were determined using an enzyme-linked immunosorbent assay. Multiple logistic regression was used to determine the association of the biomarkers with the CAD outcome after accounting for established risk factors. The analysis was built in three steps: first, we included the basic clinical and laboratory variables (Model 1), then we integrated the plasma protein values (Model 2), and finally, we complemented it with the circulating EV pattern (Model 3). To assess the discrimination value of the models, an area under (AUC) the receiver operating curve was calculated and compared across the three models. Results: The area under the curve (AUC) values were 0.68, 0.77, and 0.84 in Models 1, 2, and 3, respectively. The variables with the greatest impact on the AUC values were hemoglobin (0.2 (0.16-0.26)) in Model 1, carboxypeptidase N subunit 1 (0.12 (0.09-0.14)) in Model 2, and circulating CD41+/CD61+ EVs (0.31 (0.15-0.5)) in Model 3. A correlation analysis showed a significant impact of circulating CD41+/CD61+ platelet-derived EVs (p = 0.03, r = -0.4176) in Model 3. Conclusions: Based on our results, the circulating EV profile can be used as a supportive biomarker, along with the conventional laboratory markers of CAD, and it enables a more sensitive, non-invasive diagnostic analysis of CAD.

Abstract 4123501: Coronary Artery Calcium in Asymptomatic Arabs: Prevalence and Distribution

Background: Coronary artery calcification (CAC) is an established marker of subclinical atherosclerosis and predictor of cardiovascular events. Despite extensive research on CAC in various populations, data focusing on Arab populations, particularly asymptomatic individuals, is limited. Methods: We analyzed data from 2,739 asymptomatic self-referred Arabs included in the Kuwait Hospital Awareness Campaign for Early Detection of Atherosclerotic Coronary Artery Disease study. Traditional CVD risk factors were assessed, and ECG-gated cardiac CT imaging was used to measure using the Agatston method. Results: The mean±SD age of the sample was 48.4±9.8 and 41.8% were females. Kuwaitis comprised 61.6% of the sample, Egyptians 20.5%, and Levantines 16.4%. CAC was &gt;0 in 32.3%, ≥100 in 11.5%, and ≥400 in 4% of the sample. CAC prevalence increased with age and was higher in Arab males with a 12 year earlier onset in males than females. The 50 th , 75 th , 90 th and 95 th percentiles of CAC for Arab females were, 0, 0, 39, and 167 and for males were 0, 25, 191, and 470, respectively. The presence of CAC was associated with traditional risk factors including diabetes, smoking, hypertension and LDL-C. Levantines and Kuwaitis had the highest prevalence of CAC and CVD risk factors; these groups were independently associated with higher CAC levels. In all age and sex subgroups except older males, the 75 th percentiles of CAC were below 100. Therefore, a larger number of subjects were identified as high risk using the 75 th age- and sex-specific CAC percentile than with CAC≥100 (19.3% vs 11.5%). Conclusion: This study provides comprehensive insights into subclinical atherosclerosis in asymptomatic Arabs, emphasizing the importance of early risk stratification for primary CVD prevention using CAC scoring. Our findings highlight that Arabs are not a homogeneous group with regards to prevalence of CVD risk factors and CAC. This study underscores the need to consider both absolute and age- and sex-specific CAC percentile values to inform primary prevention strategies in this predominantly young population.

Abstract 4113617: Single-cell Analysis Reveals Endothelial Cell CD45 Deficiency Prevents Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis

Introduction: Protein-tyrosine-phosphatase CD45 is exclusively expressed in all nucleated cells of the hematopoietic system but is rarely expressed in endothelial cells (ECs). However, a recent study indicated that activation of the endogenous CD45 promoter in human endothelial colony forming cells induced expression of EndMT marker genes. Also, the CD45 phosphatase inhibitor blocked EndMT activities in TGFβ1-treated ovine mitral valve endothelial cells. EndMT contributes to atherosclerotic pathobiology and is associated with more complex plaques. We identified CD45-positive ECs undergoing EndMT in atherosclerotic ApoE-deficient (ApoE -/- ) mice. Here, we aim to investigate whether endothelial CD45-specific deletion can prevent EndMT in a mouse model of atherosclerosis. Methods and Results: We generated a tamoxifen-inducible EC-specific CD45-deficient mouse strain (EC-iCD45KO) on an ApoE -/- background (C57BL/6) and fed these mice a Western diet for 16 weeks. We isolated and enriched mouse aortic endothelial cells with CD31 beads to perform single-cell RNA-seq. Cells populated 15 major clusters after integrating the single-cell transcriptomic profiles. In the EC-iCD45KO group, the population of endothelial, resident macrophage, and mesenchymal-endothelial transition cells increased while vascular smooth muscle, EndMT, and fibroblast cells decreased. In EndMT cells, EC markers (Cdh5, Cldn5, Pecam1) increased, but SMC markers (Acta2) and EndMT markers (Col1a2 and Col3a1）decreased. In addition, we characterized EndMT cells into two sub-clusters: 1 and 2. EC-specific CD45 deletions reduced the cell numbers in the EndMT2 sub-cluster in atherosclerotic mice but had less impact on the EndMT1 sub-cluster. FGFR pathways were potentiated while TGFβ1 and Tgfbr2 decreased in EndMT1 sub-cluster， and the genes controlling endothelial cell development were upregulated but the genes controlling actin cytoskeleton organization were downregulated in both EndMT1 and 2 sub-clusters. Conclusion: Our single-cell analysis indicates that the loss of endothelial CD45 protects against EndMT-driven atherosclerosis, inhibiting TGFβ and EndoMT marker expression while stimulating FGFR pathways. Consistently, EC-iCD45KO/ApoE -/- mice showed reduced plaque macrophages, expression of cell adhesion molecules, foam cell formation, and lesion development when compared to ApoE -/- controls. Thus, targeting endothelial CD45 may be a novel therapeutic strategy for EndMT and atherosclerosis.

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

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

Associations Between Flavonoid Intake and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status. In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status. In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries.

Development of Landmark-Based Bit-State Model for Shape Analysis and Segmentation of Variations in Intima-Media Thickness of B-Mode Ultrasound Transverse Cross-Section of Carotid Artery Images

Central to the assessment of carotid artery health is the measurement of intima-media thickness (IMT), a valuable diagnostic marker for atherosclerosis. IMT quantifies the thickness of two arterial layers — the intima and media — providing insights into arterial wall health and atherosclerotic changes. Carotid ultrasound, a non-invasive imaging technique, is the primary modality for IMT measurement. However, it is not without its challenges, including operator dependency and segmentation difficulties. To surmount these limitations and advance our understanding of carotid artery health, in this research paper, we develop the Bit-State model by applying landmark-based geometric morphometrics (GM) that built upon the foundation of cardinal point symmetry landmark distributed models (CPS-LDM) which we have developed in our previous papers to comprehensively characterize and segment carotid artery IMT, unveiling essential insights into variations and alterations. The Bit-State (BS) Model, revolutionizes our approach to understanding carotid artery structural variations. In this paper, there are four regions of interest (ROI) in the B-Mode carotid artery image, hence we designated each ROI as a bit. Each bit is capable of existing in either of two states: bit 1 as thick-walled and bit 0 as thin-walled ROI. In adopting this binary characterization, we generated 16 different modalities and variations of the ROI of the carotid artery, we then proceed to use the CPS-LD Model to formulate 16 equations for the segmentation of the ROI the carotid artery images. This new model simplifies the complexity of B-Mode ultrasound carotid artery images. It systematically characterizes shape variations using CPS-LDM equations, offering an interpretable framework for comprehending arterial wall composition. This research represents a significant leap forward in carotid artery health assessment, promising more precise diagnoses and targeted interventions for cardiovascular health. It highlights the pivotal role of landmark-based GM in addressing the challenges posed by carotid artery diseases and atherosclerosis. By pioneering this innovative model, this research paves the way for a deeper understanding of carotid artery health and its implications for stroke prevention — a critical stride towards mitigating the global burden of cardiovascular diseases.

Ligustrazine alleviates the progression of coronary artery calcification by inhibiting caspase-3/GSDME mediated pyroptosis.

Coronary artery calcification (CAC) is an early marker for atherosclerosis and is mainly induced by the osteoblast-like phenotype conversion of vascular smooth muscle cells (VSMCs). Recent reports indicate that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis plays a significant role in the calcification of vascular smooth muscle cells (VSMCs), making it a promising target for treating calcific aortic valve disease (CAC). Ligustrazine, or tetramethylpyrazine (TMP), has been found effective in various cardiovascular and cerebrovascular diseases and is suggested to inhibit NLRP3-mediated pyroptosis. However, the function of TMP in CAC is unknown. Herein, influences of TMP on β-glycerophosphate (β-GP)-stimulated VSMCs and OPG-/- mice were explored. Mouse Aortic Vascular Smooth Muscle (MOVAS-1) cells were stimulated by β-GP with si- caspase-3, si- Gasdermin E (GSDME) or TMP. Increased calcification, reactive oxygen species (ROS) level, Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18) levels, lactate dehydrogenase (LDH) release, enhanced apoptosis, and activated cysteine-aspartic acid protease-3 (caspase-3)/GSDME signaling were observed in β-GP-stimulated MOVAS-1 cells, which was sharply alleviated by si-caspase-3, si-GSDME or TMP. Furthermore, the impact of TMP on the β-GP-induced calcification and injury in MOVAS-1 cells was abolished by raptinal, an activator of caspase-3. Subsequently, OPG-/- mice were dosed with TMP or TMP combined with raptinal. Calcium deposition, increased nodules, elevated IL-1β and IL-18 levels, upregulated CASP3 and actin alpha 2, smooth muscle (ACTA2), and activated caspase-3/GSDME signaling in OPG-/- mice were markedly alleviated by TMP, which were notably reversed by the co-administration of raptinal. Collectively, TMP mitigated CAC by inhibiting caspase-3/GSDME mediated pyroptosis.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p&amp;lt;0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p&amp;lt;0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p&amp;lt;0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p&amp;gt;0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT &amp; plaque burden

Importance and limits of cardiovascular risk factors on the prediction of SCD using machine learning approach

Abstract Background SCD is mainly due to lethal ventricular arrhythmias and occurs often among patients with ischemic heart disease. SCD and ischemic heart disease share a similar pattern of cardiovascular risk factors (CVRF). Commonly developed risk scores have been focused on cardiac-related risk factors. We aimed to investigate whether non-CVRF variables could enhance predictive performance beyond standard CVRF of SCD. Method We compared 2 different strategies for variable inclusion. First, we built a prediction model containing EHR data restricted to cardiovascular diseases and risk factors (CVD MR model) that occurred up to 5 years before SCD. We selected all available main cardiovascular variables as surrogate markers for coronary artery disease, stroke, diabetes, hypertension, smoking status, obesity, lipid disorders and chronic renal failure. On the other hand, our global approach (ALL MR model) includes all medical records codes, without any prior selection. To estimate the risk of SCD over three months, we trained a machine learning model on EHR data representing 8,566,229 drug prescriptions and 801,352 hospital diagnoses up to five years prior to SCD. The data were obtained from a cohort of 12,338 SCD in France and 12,338 controls from 2011 to 2015. We then validated the results on two external cohorts: one temporal in the same area between 2016 and 2020 with 11,620 SCD and 11,620 controls and one geographical from the USA with 892 SCD and 892 controls from 2013 to 2021. Results The CVD MR + ML model (CatBoost algorithm) yielded moderate performances with an AUC of 0.68 (95%CI 0.65-0.68), a sensitivity of 45%.(95%CI 42-47) and a specificity of 82% (95%CI 80-84). We found that the EHR model with all medical records (All MR + ML model) offered better performances. In the derivation cohort, this model achieved an AUC of 0.80 (95% CI: 0.78–0.82) with a sensitivity of 67% (95% CI 64-69), a specificity of 80% (95% CI 78-82) (Figure 1). The logistic regression (All MR + LR) applied on all medical records performed better than the CatBoost algorithm when restricted to CVD medical records (Figure 1). Conclusion The inclusion of all potential variables beyond the usual CVRF significantly improves the performances of SCD prediction models, independently of the methods (AI and logistic regression). Figure 1 : Receiver operating characteristic curves of the different models (ALL MR + ML, ALL MR + LR, CVD MR + ML and CVD MR + LR) in the derivation cohort and two validation cohorts (temporal and geographical)Figure 1.ROC curves

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.