Carotid Artery Atherosclerosis Research Articles

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. https://clinicaltrials.gov, identifier NCT04424706.

690 Residual In-stent Carotid Stenosis and Cigarette Smoking are Predictors of Restenosis After Stenting (CAS)

INTRODUCTION: Atherosclerosis of the internal carotid artery remains a significant contributor to stroke morbidity and mortality. While patient risk factors have been identified to be associated with carotid restenosis after carotid stenting (CAS), conflicting theroies exist on whether residual stenosis is an independent risk factor. METHODS: A single-center, prospectively maintained database was retrospectively reviewed for CAS procedures over a 12-year period. Patient demographic, procedural characteristics, radiographic and clinical details were noted. Comparison of baseline characteristics of patients with and without carotid restenosis were performed using chi-squared test for categorical variables and student t-test for continuous variables. Univariate and multivariate analyses were performed to determine risk factors associated with restenosis, defined as >70% on digital subtraction angiography. RESULTS: 1017 consecutive carotid artery stenting (CAS) procedures were performed in 905 patients over the 12-year period, with 738 CAS procedures in 632 patients included after exclusion criteria. Overall restenosis rate was 17%, with a 14% restenosis rate at 2 years-time. Multivariable analysis demonstrated former/current smoking status (OR=2.1 [95%CI 1.2-3.9]), moderate contralateral stenosis (OR 3.0 [95%CI 1.4-6.7]), severe contralateral stenosis (OR3.0 [1.4-6.3]), and residual stenosis (OR 454 [95% 85-2413]) were associated with restenosis. AUC for the multivariable model was 0.78. Cut-point degree for residual stenosis was ∼30%, where there was a 9% and 35% rate of restenosis in those less than, and greater than, 30% residual stenosis, respectively. CONCLUSIONS: We present the largest single-center data in the US to date on carotid artery stenosis treated with CAS, and factors associated with restenosis. Residual in-stent carotid stenosis and smoking history were independent predictors. Maximizing treatment of initial stenosis within stent for carefully selected patients and aggressive smoking cessation education are important steps in preventing future carotid restenosis.

Abstract 64: Risk Factors for Carotid Artery Lipid Deposition Measured by Gray Scale Median of the Intima-Media in Children and Young Adults Over the Life Course

Introduction: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media (GSM-IM), is a unitless measure that reflects lipid deposition in the arterial wall, with lower values indicating greater lipid deposition and atherosclerosis. Due to the relative novelty of GSM-IM, its progression and associated risk factors are incompletely understood. This study investigated the GSM profile in childhood and young adulthood using a longitudinal cohort of individuals followed over time, and conducted a priori analysis on the behavioral, psychosocial, and health risk factors for GSM. Methods: Data were collected as part of the Meta-Air2 follow-up study of participants enrolled in the Southern California Children’s Health Study. A total of 240 study participants underwent a carotid artery ultrasound examination in 2008 (mean age±standard deviation [ SD] : 11.2±0.6 years), and again between 2018 and 2023 (24.2±1.6 years) to assess changes in carotid artery health, including GSM-IM, carotid artery intima-media thickness (CIMT), and carotid artery distensibility. Participants self-reported lifestyle behaviors, psychosocial health, and underwent anthropometric and blood pressure measures at both time points. Mixed effects models were used to predict GSM-IM changes with repeated measurements of lifestyle behaviors, perceived stress, BMI, and blood pressure. Results: Means and SDs of GSM-IM were 110.0±27.4 in childhood, and 75.6±15.8 in adulthood, with an annual change rate of -2.6 per year. Individuals of Hispanic ethnicity, and those with lower parental education levels had significantly lower GSM-IM in both childhood and adulthood. GSM-IM was significantly correlated with other measures of carotid artery atherosclerosis, including CIMT (r=0.28; p <0.001) and carotid artery distensibility (r=0.36; p <0.001). Results of mixed effects models adjusting for covariates, indicated that higher BMI (β=-1.35; 95% confidence interval [CI], -1.70, -0.99; p <0.001) and systolic blood pressure (β=-0.32, 95% CI, -0.55, -0.09; p=0.007) were significantly associated with lower GSM-IM. A significant interaction between BMI and age (β difference=0.14; 95% CI, 0.09, 0.20; p <0.001) suggested that a per-unit change in BMI has a greater effect on GSM-IM among adolescents compared to young adults. Health compromising behaviors, including less sleeping time, smoking, drug use, and higher perceived stress were significantly associated with lower GSM-IM in unadjusted models. However, these associations were attenuated after adjustment for covariates. Conclusion: Our study highlights the influence of BMI, particularly during childhood, blood pressure and lifestyle behaviors on adverse changes in GSM-IM, indicative of greater lipid deposition. These risk factors may be key targets for early prevention for atherosclerosis.

Orosomucoid 2 as a biomarker of carotid artery atherosclerosis plaque vulnerability through its generation of reactive oxygen species and lipid accumulation in vascular smooth muscle cells

BackgroundOrosomucoid (ORM) has been reported as a biomarker of carotid atherosclerosis, but the role of ORM 2, a subtype of ORM, in carotid atherosclerotic plaque formation and the underlying mechanism have not been established. MethodsPlasma was collected from patients with carotid artery stenosis (CAS) and healthy participants and assessed using mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) technology to identify differentially expressed proteins. The key proteins and related pathways were identified via western blotting, immunohistochemistry, and polymerase chain reaction of carotid artery plaque tissues and in vitro experiments involving vascular smooth muscle cells (VSMCs). ResultsWe screened 33 differentially expressed proteins out of 535 proteins in the plasma. Seventeen proteins showed increased expressions in the CAS groups relative to the healthy groups, while 16 proteins showed decreased expressions during iTRAQ and bioinformatic analysis. The reactive oxygen species metabolic process was the most common enrichment pathway identified by Gene Ontology analysis, while ORM2, PRDX2, GPX3, HP, HBB, ANXA5, PFN1, CFL1, and S100A11 were key proteins identified by STRING and MCODE analysis. ORM2 showed increased expression in patients with CAS plaques, and ORM2 was accumulated in smooth muscle cells. Oleic acid increased the lipid accumulation and ORM2 and PRDX6 expressions in the VSMCs. The recombinant-ORM2 also increased the lipid accumulation and reactive oxygen species (ROS) in the VSMCs. The expressions of ORM2 and PRDX-6 were correlated, and MJ33 (an inhibitor of PRDX6-PLA2) decreased ROS production and lipid accumulation in VSMCs. ConclusionORM2 may be a biomarker for CAS; it induced lipid accumulation and ROS production in VSMCs during atherosclerosis plaque formation. However, the relationships between ORM2 and PRDX-6 underlying lipid accumulation-induced plaque vulnerability require further research.

Diagnostic Accuracy of Duplex Ultrasonography Versus Computed Tomographic Angiography in the Detection of Significant Carotid Artery Atherosclerosis

Objective: To determine the diagnostic accuracy Duplex of Ultrasonography in detecting clinically significant carotid atherosclerosis by keeping Computed Tomographic Angiography as a gold standard. Study Design: Cross-Sectional study Place and Duration of Study: Armed Forces Institute of Radiology and Imaging Rawalpindi Pakistan, from Jun to Nov 2019. Methodology: All patients referred with neurological symptoms during the study were included. Duplex (Doppler) ultrasound and Computed Tomographic Angiography of bilateral carotid arteries were performed on all these patients. The percentage of carotid stenosis was calculated for both modalities. Data was recorded separately for both right and left carotid arteries. Results: Out of 170 carotid arteries in 85 patients, Duplex ultrasound supported the diagnosis of clinically significant carotid atherosclerosis in 89 arteries (52.3%), and CTA confirmed it in 86 arteries (50.5%). Overall, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of Duplex ultrasonography in the detection of clinically significant carotid atherosclerosis by taking computed tomographic angiography (CTA) as a gold standard was 92.0%, 89.0%, 89.8%, 92.5% and 91.1% respectively Conclusion: Duplex ultrasonography is an accurate, non-invasive imaging investigation for detecting carotid atherosclerosis.

Dependence of local carotid arterial stiffness on the presence of atherosclerotic plaque in the carotid basin in hypertensive patients

Aim. To evaluate the viscoelastic properties of the common carotid arteries (CCA) in patients with stage II hypertension (HTN) and to compare these indicators between groups with and without carotid artery (CA) stenosis <50 %. Materials and methods. The study included 48 patients with stage II HTN, mean age – 55.9 years, 45.8 % men. Basic anthropometric data, laboratory parameters of lipid and carbohydrate metabolism, creatinine, quality intima-media thickness (QIMT), local stiffness indicators: artery diameter, distensibility, distensibility coefficient (DC), compliance coefficient (CC), stiffness indices α, β, local pulse wave velocity (PWV), pressure and augmentation index (using RF-QIMT, RF-QAS technologies) were studied. Statistical analysis was performed, p values of < 0.05 were considered statistically significant. Results. CA atheromas with stenosis up to 50 % were found in 48 % of the examined, they were older with higher parameters of vessel diameter by 4.6 %, QIMT – by 12.5 %, α index – by 28.0 %, β index – by 27.7 %, and PWV – by 14.7 %. A medium-strength positive correlation has been revealed for age, QIMT, HDL, creatinine level and local stiffness parameters (distensibility, CC, PWV, indices α, β). The atherosclerotic plaque (ASP) presence in the CA was associated with the limit levels of the left CCA QIMT over 698 μm (sensitivity 65.2 %, specificity 86.6 %, p < 0.01), of the right – over 598 μm (sensitivity 73.9 %, specificity 66.6 %, p < 0.01). However, a greater dependence on age than on the presence of atheroma has been proven. At the same time, the odds ratio of the ASP presence was 2.99-fold higher (p = 0.0065) with an increase in the CCA diameter of more than 7.94 mm, and in the multivariate model incorporating age – 2.6-fold higher (p = 0.036), while age has not impacted significantly (p = 0.301) the prognosis. Conclusions. In individuals with stage II HTN, the presence of CA atherosclerosis with stenosis up to 50 % is associated with a significant increase in vessel diameter regardless of age. CCA intima media thickness depends more on the age of hypertensive patients.

Abstract TP226: Analysis of the Association Between Lipoprotein(a) Levels and Carotid Plaque and Coronary Artery Calcium Using Health Checkup Data

Background: Lipoprotein a (Lp(a)) is known to be associated with coronary artery disease and carotid artery atherosclerosis. We analyzed the association between Lp(a) levels, coronary artery calcium score (CACS), and carotid plaque using data from individuals undergoing health check-ups. Methods: We enrolled patients who underwent all Lp(a) measurements, coronary artery calcium score computed tomography(CT), and carotid ultrasound at Gangnam Severance Hospital from January 2017 to December 2022. Lp(a) levels were categorized into two groups: below 50 mg/dl and 50 mg/dl or higher. Carotid ultrasound results were divided into two groups based on the presence or absence of plaque. Coronary artery calcium score CT results were analyzed in two groups: CACS=0 and CACS>0. Results: A total of 2620 subjects were enrolled. 1692 (64.6%) were male. Mean age was 57 years. Lp(a) levels of 50 or higher were found in 177 (6.8%) subjects. Carotid plaque was observed in 1140 (43.5%) subjects and CACS>0 in 1172 (44.7%) subjects. Multivariable logistic regression analysis was performed. There was an association between Lp(a) 50mg/dl or higher and carotid plaque (unadjusted odds ratio = 1.406, confidence interval = 1.036 - 1.908) (adjusted odds ratio = 1.383, confidence interval = 1.010 - 1.894). An association was also found between Lp(a) 50mg/dl or higher and CACS>0 (unadjusted odds ratio = 1.400, confidence interval = 1.031 - 1.900) (adjusted odds ratio = 1.378, confidence interval = 1.002 - 1.895). Carotid plaque and CACS>0 were associated (unadjusted odds ratio = 4.393, confidence interval = 3.725 - 5.182) (adjusted odds ratio = 2.380, confidence interval = 1.970 - 2.876). Conclusions: This study demonstrates that individuals with Lp(a) levels of 50 mg/dl or higher are at increased risk for carotid plaque and CACS. This association remains independent even after adjustment for factors such as statin use or low-density lipoprotein cholesterol (LDL-C) levels. Therefore, increased attention to the occurrence and progression of coronary artery disease and carotid artery atherosclerosis is necessary in individuals with Lp(a) levels of 50 mg/dl or higher, even if LDL-C levels are well controlled.

Abstract WP116: Plaque Features and Infarct Pattern in Ischemic Stroke With Bilateral Carotid Artery Atherosclerosis

Objective: to compare the carotid artery plaque characteristics between ipsilateral and contralateral infarct in ischemic stroke with bilateral carotid artery atherosclerosis, and explore the association between plaque characteristics and infarct pattern. Methods: a total of 186 ischemic stroke patients with bilateral carotid artery atherosclerosis were included, carotid artery plaque burden (the degree of stenosis, maximum wall thickness, lumen area, wall area, normalized wall index (NWI=wall area/[lumen area+ wall area]), and eccentricity index), and vulnerability (intraplaque hemorrhage [IPH], calcification, irregular surface, thin or ruptured fibrous cap[TRFC], and lipid-rich necrotic core[LRNC]) were obtained by MR vessel wall imaging, infarct pattern was divided as single and multiple/recurrent infarcts in infarct ipsilateral carotid artery. Ipsilateral and contralateral carotid artery plaque features were compared, then the carotid artery plaque characteristics on the infarct side were correlated with the infarct pattern. Results: the mean age of subjects included was 68 years old, 79.6% of them were male. Compared with contralateral carotid artery plaque, plaque burden at the ipsilateral carotid artery was much heavy, presented with a higher degree of stenosis, smaller lumen area (0.22±0.15 vs. 0.28±0.15), larger wall area (0.50±0.19 vs.0.42±0.17), and higher eccentricity index (0.67±0.13 vs. 0.58±0.23), all p values<0.05. The vulnerable plaques were also more prevalent at ipsilateral infarct, with a high percentage of IPH (47.8% vs. 19.8%), irregular surface (36.3% vs. 17.5%), TRFC (38.5% vs.12.3%), and LRNC (38.1% vs. 15.9%), all p values were <0.05. After adjusting for covariates, the degree of stenosis (OR=1.590, 95% CI 1.048-2.410) and LRNC (OR=0.259, 95% CI 0.087-0.769) were associated with multiple or recurrent infarcts independently. Conclusion: in ischemic stroke with bilateral carotid atherosclerosis, the atherosclerotic plaque burden at ipsilateral infarct was much heavier and more vulnerable. Both lumen stenosis and plaque components were correlated with multiple or recurrent infarcts in this population.

Association Between Clonal Hematopoiesis Driver Mutations, Immune Cell Function, and the Vasculometabolic Complications of Obesity.

Obesity is accompanied by dysregulated inflammation, which can contribute to vasculometabolic complications including metabolic syndrome and atherosclerosis. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular diseases. We aimed to determine how CHIP is related to immune cell function, systemic inflammation, and vasculometabolic complications in obese individuals. Two hundred ninety-seven individuals with overweight and obesity, between the ages of 54 and 81 years, were recruited in a cross-sectional study. Clonal hematopoiesis driver mutations (CHDMs) were identified with an ultrasensitive targeted assay. Assessment of carotid artery atherosclerosis was performed with ultrasound. Detailed immunological parameters, including cytokine production capacity of peripheral blood mononuclear cells, and targeted plasma proteomics analysis, were studied. Adipose tissue inflammation was determined in subcutaneous fat biopsies. Individuals with CHIP had higher concentrations of circulating IL (interleukin)-6. Total number of leukocytes and neutrophils were higher in individuals with CHIP. In contrast, exvivo cytokine production capacity of peripheral blood mononuclear cells was significantly lower in individuals with CHIP. Sex-stratified analysis showed that men with CHDMs had significantly higher leukocyte and neutrophil counts, and exvivo cytokine production capacity was lower in women with CHDMs. Surprisingly, the presence of atherosclerotic plaques was significantly lower in individuals with CHDMs. There was no relation between CHIP and metabolic syndrome. In individuals with overweight or obesity, CHDMs are not associated with vasculometabolic complications, but rather with a lower presence of carotid plaques. CHDMs associate with increased circulating inflammatory markers and leukocyte numbers, but a lower peripheral blood mononuclear cell cytokine production capacity.

Associations between atherosclerotic luminal stenosis in the distal internal carotid artery and diffuse wall thickening in its upstream segment.

Significant atherosclerotic stenosis or occlusion in the distal internalcarotid artery(ICA) may induce diffuse wall thickening (DWT) in the upstream arterial wall. This study aimed to assess the association of atherosclerotic steno-occlusive diseases in the distal ICA with DWT in the upstream ipsilateral ICA. Individuals with atherosclerotic stenosis in the distal ICA, detected by carotid MR vessel wall imaging using 3D pre- and post-contrast T1 volume isotropic turbo spin-echo acquisition (T1-VISTA) sequence, were enrolled. The associations of vessel wall thickening, the longitudinal extent of DWT, enhancement of the upstream ipsilateral ICA, and stenosis degree in the distal ICA were examined. Totally 64 arteries in 55 patients with atherosclerotic steno-occlusive distal ICAs were included. Significant correlations were found between distal ICA stenosis and DWT in the petrous ICA (r = 0.422, p = 0.001), DWT severity (r = 0.474, p < 0.001), the longitudinal extent of DWT in the ICA (r = 0.671, p < 0.001), enhancement in the petrous ICA (r = 0.409, p = 0.001), and enhancement degree (r = 0.651, p < 0.001). In addition, high degree of enhancement was correlated with both increased wall thickness and increased prevalence of DWT in the petrous ICA (both p < 0.001). DWT of the petrous ICA is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal ICA. The degree of stenosis in the distal ICA is associated with wall thickening and its longitudinal extent in the upstream segments. Diffuse wall thickening is a common secondary change in atherosclerotic steno-occlusive disease in the intracranial carotid. This phenomenon constitutes a confounding factor in the distinction between atherosclerosis and inflammatory vasculopathies, and could be reversed after alleviated atherosclerotic stenosis. • Diffuse wall thickening of the petrous internal carotid artery is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal internal carotid artery. • The phenomenon of diffuse wall thickening could be reversed after stenosis alleviation. • Carotid artery atherosclerosis with diffuse wall thickening should warrant a differential diagnosis from other steno-occlusive diseases, including moyamoya diseases and Takayasu aortitis.

Carotid Artery Ultrasonography as a Screening Tool for Predicting Coronary Artery Disease: A Cross-sectional Study from Hilly State of Northern India

Introduction: Coronary Artery Disease (CAD) is a major cause of morbidity and mortality worldwide; therefore, early diagnosis plays a crucial role in managing patients with CAD. Multidetector Computed Tomography (MDCT) allows non invasive visualisation of coronary arteries but has limited availability, involves radiation, and is costly. Carotid artery atherosclerosis can be assessed by Ultrasound (USG) in terms of Carotid Intima-media Thickness (CIMT) and carotid plaque assessment. These carotid USG parameters are associated with CAD and can be used to predict CAD in high-risk patients. Aim: To study the association and correlation between carotid artery atherosclerosis USG parameters (CIMT and carotid plaque) and CAD, using Computed Tomography Coronary Angiography (CTCA) as a reference. Materials and Methods: A cross-sectional study was conducted from January 2020 to October 2021 in the Department of Radiodiagnosis at Indira Gandhi Medical College, Shimla, Himachal Pradesh, India. In the present study, 31 patients with suspected CAD were enrolled. All patients underwent CTCA followed by carotid artery USG within two weeks. The association and correlation between carotid artery atherosclerosis on USG and CAD on CTCA were examined. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and accuracy were calculated using CTCA as the reference standard. Categorical data were analysed using the Chi-square test, with a p-value of &lt;0.05 considered statistically significant. Results: The mean age of the patients was 54.06±10.79 years. The CAD was observed in 14 (45.1%) cases, of which 13 (92.8%) had significant CAD. Nine patients had raised CIMT, of which eight had CAD. Raised CIMT and CAD showed a significant association with sensitivity, specificity, PPV, NPV, and accuracy of 57.14%, 94.12%, 88.89%, 72.73%, and 77.42%, respectively. A positive correlation was found between CIMT values and the number of vessels with significant CAD (r= +0.67). A total of 7 patients (22.5%) had the presence of carotid plaque, of which 6 (88.57%) had significant CAD. A significant association was found between CAD and the presence of carotid plaque. Carotid plaque had sensitivity, specificity, PPV, NPV, and accuracy of 50%, 100%, 100%, 70.83%, and 77.42%, respectively, in predicting CAD. A positive correlation was observed between carotid plaque burden and the number of vessels with significant CAD (r= +0.56). Conclusion: There is a significant association between carotid ultrasonography parameters (i.e., CIMT, carotid plaque) and CAD. CIMT is a more sensitive parameter than carotid plaque in predicting CAD. However, carotid plaque is more specific for predicting CAD. Carotid artery ultrasonography can be used as a screening tool for predicting CAD and should be included in the work-up of patients with suspected CAD.

Association of cardiorespiratory fitness level with vascular function and subclinical atherosclerosis in the elderly.

Physical exercise is crucial for healthy aging and plays a decisive role in the prevention of atherosclerotic cardiovascular disease (ASCVD). A higher level of cardiorespiratory fitness (CRF) in the elderly is associated with lower cardiovascular and all-cause mortality. This study investigated the association of CRF level with vascular function and cardiovascular risk factors in the elderly. We examined 79 apparently healthy and physically active subjects aged > 55years (64 ± 4years). Cardiovascular functional parameters assessed included brachial and central blood pressure (BP), pulse wave velocity (PWV), augmentation index (Aix), and ankle-brachial index. Sonography of the common carotid artery was performed. CRF level was determined by a cardiopulmonary exercise test, and everyday activity was quantified with an accelerometer. All participants had a higher CRF level than the reported age-specific normative values. Twenty-nine subjects had subclinical atherosclerosis of the common carotid artery. Compared with participants without atherosclerosis, they were older (p = 0.007), displayed higher brachial systolic BP (p = 0.006), and higher central systolic BP (p = 0.014). Lower brachial (p = 0.036) and central (p = 0.003) systolic BP, lower PWV (p = 0.004), lower Aix (p < 0.001), lower body fat percentage (< 0.001), and lower LDL cholesterol (p = 0.005) were associated with a higher CRF level. In this cohort of healthy and physically active individuals, subjects with subclinical atherosclerosis displayed higher systolic brachial and central BP. A higher CRF level was associated with enhanced vascular function, consistent with an influence of CRF on both BP and vascular function in the elderly.

Comparison of LASSO and random forest models for predicting the risk of premature coronary artery disease

PurposeWith the change of lifestyle, the occurrence of coronary artery disease presents a younger trend, increasing the medical and economic burden on the family and society. To reduce the burden caused by this disease, this study applied LASSO Logistic Regression and Random Forest to establish a risk prediction model for premature coronary artery disease(PCAD) separately and compared the predictive performance of the two models.MethodsThe data are obtained from 1004 patients with coronary artery disease admitted to a third-class hospital in Liaoning Province from September 2019 to December 2021. The data from 797 patients were ultimately evaluated. The dataset of 797 patients was randomly divided into the training set (569 persons) and the validation set (228 persons) scale by 7:3. The risk prediction model was established and compared by LASSO Logistic and Random Forest.ResultThe two models in this study showed that hyperuricemia, chronic renal disease, carotid artery atherosclerosis were important predictors of premature coronary artery disease. A result of the AUC between the two models showed statistical difference (Z = 3.47, P < 0.05).ConclusionsRandom Forest has better prediction performance for PCAD and is suitable for clinical practice. It can provide an objective reference for the early screening and diagnosis of premature coronary artery disease, guide clinical decision-making and promote disease prevention.

Complement C1q and von Willebrand factor interaction in atherosclerosis of human carotid artery.

Atherosclerosis is an inflammatory disease of the vessel wall, with cholesterol crystal (CC) deposition being a hallmark of the disease. As evidence for a cross-talk between complement activation and hemostasis on CC surfaces has been limited to in vitro data, the aim of this study was to demonstrate the presence of C1q-vWF complexes in human atherosclerosis ex vivo. We used immunofluorescence staining and a proximity ligation assay (PLA, Duolink®) to examine the presence, localization, and co-localization of C1q and vWF in frozen sections of human carotid arteries with atherosclerosis or without atherosclerotic changes as well as material from thrombendarteriectomy. We observed significantly higher levels of C1q and vWF in healthy tissue compared to diseased material and greater co-localization in the PLA in healthy samples than in diseased samples. In diseased samples, fluorescence signals were highest in locations encompassing atheroma and foam cells. While there was overall reduced signal in areas with CCs, the staining was spotty, and there was evidence of co-localization on individual CCs. Thus, we demonstrate the presence of C1q-vWF complexes in human carotid arteries ex vivo, which was most abundant in healthy endothelial and subendothelial space and reduced in diseased tissue. C1q-vWF interaction can also be demonstrated on the CC surface.

Modeling and computational fluid dynamics simulation of blood flow behavior based on MRI and CT for Atherosclerosis in Carotid Artery

Modeling and computational fluid dynamics simulation of blood flow behavior based on MRI and CT for Atherosclerosis in Carotid Artery

Ethanol extract of Rubia yunnanensis inhibits carotid atherosclerosis via the PI3K/AKT signaling pathway.

Atherosclerosis is a multifactorial vascular disease caused by endothelial dysfunction. Because of adverse reactions to drugs used to treat atherosclerosis. For example, statins, which significantly reduce the burden of atherosclerotic disease, have been associated with muscle toxicity. There is a need to identify novel drugs for the prevention and treatment of atherosclerosis Rubia yunnanensis is a herbs commonly used in Asian countries for its protective effects against cardiovascular diseases. However, the mechanism of action of R. yunnanensis extract in carotid artery atherosclerosis has not been found. The carotid artery is usually used as a site for clinical evaluation of atherosclerosis. The present study aimed to determine the mechanism of action of R. yunnanensis extract in the inhibition of carotid atherosclerosis in apolipoprotein E gene knockout (ApoE-/-) mice. The mechanism of atherosclerosis inhibition was elucidated by detecting the blood lipid level, carotid artery pathology, and the protein expression of PI3K and AKT. The present study demonstrated that ethanol extract of R. yunnanensis reduced lipid levels, intima damage and carotid lipid accumulation and increased p-PI3K/PI3K and p-AKT/AKT protein levels in ApoE-/- mice fed high-fat diet for 12 weeks. It was hypothesized that the effects of R. yunnanensis extract may be achieved by regulation of the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Ethanol extract of R. yunnanensis decreased carotid atherosclerosis in ApoE-/- mice fed a high-fat diet via the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Therefore, R. yunnanensis may be a promising option for treating atherosclerosis in the future.

In-silico study of drug delivery to atherosclerosis in the human carotid artery using metal–organic frameworks based on adhesion of nanocarriers

This study investigates nanocarriers (NCs) for drug delivery targeting carotid artery atherosclerosis. This targeted drug delivery mechanism is based on ligand–receptor bindings facilitated by coating NCs with P-selectin aptamers, which exhibit high affinities for P-selectin plaque receptors. Recognizing the significant advantages of metal–organic frameworks (MOFs), such as their high drug-loading percentages, we chose them as nanocarriers for this research. Our evaluation considers critical factors: NC surface density (the number of attached nanocarriers per unit of plaque area), toxicity (percentage of NCs missing the target), and efficient drug transfer to plaque tissue. Employing molecular dynamics (MD) for drug loading calculations via van der Waals interactions and computational fluid dynamics (CFD) for toxicity, surface density, and drug transfer assessments, we achieve a comprehensive analysis. A cardiac cycle-based metric guides optimal MOF release conditions, establishing an ideal dosage of 600 NCs per cycle. MOF-801 exhibits outstanding drug delivery performance, particularly in plaque targeting. While a magnetic field enhances NC adhesion, its impact on drug transfer is limited, emphasizing the need for further optimization in magnetic targeting for NC-based therapies. This study provides crucial insights into NC drug delivery performance in carotid artery atherosclerosis, advancing the field of targeted drug delivery for atherosclerosis treatment.

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

Abstract 116: Reversal of Acute Ocular Ischemic Syndrome Following Rescue Carotid Revascularization: A Case Report

Introduction Ocular ischemic syndrome (OIS) is a rare, vision‐threatening condition resulting from severe carotid artery disease secondary to severe atherosclerosis or arteritis. Common clinical features include acute/subacute to gradual vision loss, ocular pain, amaurosis fugax, photophobia and diplopia. We are presenting a case of acute ocular ischemic syndrome secondary to acute re‐occlusion of the right internal carotid artery (RICA) post Carotid Endarterectomy (CEA), that reversed with carotid revascularization. Methods Case Summary: 59‐year‐old male with history of T2DM, hyperlipidemia, tobacco use presented to an outside hospital with complaints of dizziness, blurry vision, left upper extremity weakness and multiple falls with head trauma. Exam revealed left lower quadrantanopia, mild left arm weakness and left hemineglect. Computed Tomography (CT) Head showed scattered right middle cerebral artery (MCA) territory infarcts. CT Angiography (CTA) revealed ulcerated plaque with a small focus of thrombus intraluminally in the RICA. Subsequently, the patient was initiated on heparin infusion and underwent CEA. On postoperative day (POD) 2, the patient experienced severe stabbing right eye pain with reduced visual acuity and worsening of left arm weakness. Imaging revealed complete occlusion of the right common carotid artery (RCCA). Perfusion imaging did not reveal a core or a penumbra. Given acute loss of vision likely secondary to ocular ischemic syndrome, decision was taken to proceed with rescue stenting. Using a transfemoral approach, an 8‐French balloon guide catheter was advanced into the proximal RCCA. A primary suction thrombectomy was performed under proximal flow arrest. After achieving a complete recanalization in one pass, we started the patient on cangrelor 30 mcg/kg intravenous bolus followed by 4 mcg/kg/min infusion. Post bolus, we placed a tandem closed‐cell carotid stent measuring 8x36mm &amp; 10x37mm. The patient reported immediate relief of ocular pain, vision and weakness following the procedure. He transitioned from cangrelor infusion to ticagrelor 90 mg twice daily and aspirin 81 mg daily. On post‐stenting day 7, the patient experienced acute onset headache, and imaging revealed re‐occlusion of the entire carotid artery sparing only the ophthalmic segment of the RICA which now filled retrograde via anterior communicating artery (AcoA) from the contralateral carotid artery. However, his visual acuity remained unchanged and reported no ocular pain. At one month follow‐up the patient remains symptom‐free. Results Discussion: Incidence of OIS is estimated to be 7.5 cases per million every year. Carotid artery atherosclerosis is the most common etiology. Majority of OIS (∼90%) present with gradual vision loss and approximately 40% present with ocular pain. Gradual vision loss is predominantly related to chronic ocular hypoperfusion and resultant iris neovascularization and glaucoma. In this case, patient suffered acute vision loss secondary to acute ICA occlusion following CEA. Emergent carotid revascularization resulted in restoration of vision and resolution of ocular pain. Conclusion Our main goal is to emphasize the importance of rescue stenting to address symptoms of aOIS. Immediately post‐stenting, there was remarkable improvement in ocular pain and visual acuity. Although, the carotid re‐occluded within seven days post‐stenting, we hypothesize that gradual re‐occlusion while on DAPT provided enough time recruit and preserve collaterals into the right ophthalmic artery via retrograde flow into the ophthalmic segment of RICA from the contralateral carotid artery via the AcoA which was subsequently confirmed on imaging.

A novel circular RNA, circSQSTM1, protects the endothelial function in atherosclerosis

A novel circRNA named circSQSTM1 (hsa_circRNA_075320) was screened out in atorvastatin (ATV) stimulated endothelial cells (ECs) by our group. Considering the anti-atherosclerotic function of ATV, we hypothesized the circSQSTM1 could protect ECs functions in AS progression. The effects of circSQSTM1 on ECs inflammation, oxidative stress and autophagy were measured by qRT-PCR, Western blotting, monocyte-endothelial adhesion assay, dichloro-dihydro-fluorescein diacetate and mCherry-GFP-LC3 labeling. A luciferase reporter assay, RNA immunoprecipitation, MS2-tagging system and fluorescence in situ hybridization were performed to identify the biological functions of circSQSTM1. The partial left carotid artery ligation model and atherosclerosis model were established to analyze the effects of circSQSTM1 on atherosclerosis progression in vivo. Our results revealed that ATV induced the accumulation of circSQSTM1 in ECs via suppressing m6A modified degradation. In the cytoplasm, circSQSTM1 could relieve Sirt1 by competitively sponging miR-23b-3p. In the nucleus, circSQSTM1 directly interacts with eIF4A3 and promoting the efficient nuclear export of FOXO1 mRNA, which encodes FOXO1 transcription factor to directly activate Sirt1 promoter activity. Hence, circSQSTM1 reduced inflammation, inhibited oxidative stress and promoted autophagy by upregulating Sirt1 in ECs. Moreover, circSQSTM1 overexpression in ECs attenuated the progression of atherosclerosis in ApoE−/− mice. Taken together, the unique noncoding RNA known as circSQSTM1 took a protective role to the ECs in atherosclerosis.