Correlation Between Intracoronary Vascular Ultrasound Indexes in Patients with Coronary Heart Disease.

Background: Coronary atherosclerosis is a serious and progressive condition characterized by the accumulation of plaques, consisting of fat, cholesterol, and other substances, within the arteries that supply blood to the heart. These plaques can harden and narrow the arteries, leading to reduced blood flow to the heart muscle. Objective: The primary objective of this study is to investigate the correlation between specific cardiovascular parameters and intracoronary vascular ultrasound indexes in patients diagnosed with coronary heart disease. This investigation aims to explore the relationships between intracoronary vascular ultrasound measurements and three key cardiovascular parameters: epicardial fat pad thickness, mono-platelet polymer levels, and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. Methods: In this investigation, we applied a comprehensive method to evaluate atherosclerotic plaque characteristics in patients with diverse stages of coronary heart disease (CHD), contrasting these profiles with those of healthy individuals. Our study included 80 acute myocardial infarction (AMI) patients, 145 with unstable angina pectoris (UAP), 175 with stable angina pectoris (SAP), and 100 controls. We utilized intravascular ultrasound (IVUS), an advanced imaging technique that surpasses traditional angiography by providing detailed, high-resolution images of both the coronary artery lumen and wall, including plaque composition. This approach is pivotal for assessing plaque stability, a key factor in the risk of rupture and subsequent cardiovascular events, indicated by features like lipid-rich cores and thin fibrous caps. During IVUS, we quantified parameters such as plaque area, load, and the remodeling index, the latter offering insights into vascular adaptation to plaque buildup. Additionally, we conducted a correlation analysis between IVUS indices and three cardiovascular markers: epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels. The goal was to ascertain the predictive value of these markers in tandem with IVUS for determining the stability of coronary artery atherosclerotic plaques. This integrative approach enhances understanding of plaque formation and destabilization, potentially informing more effective CHD prevention and management strategies. Results: Our study revealed distinct variations in key parameters across patient groups with different forms of CHD and healthy controls. Notably, we observed significant differences in gender distribution, hypertension, and diabetes mellitus prevalence among these groups. In terms of IVUS indexes and cardiovascular parameters, the SAP group exhibited markedly different results compared to the AMI and UAP groups. Specifically, the SAP patients showed the lowest values for EMMA, plaque area, plaque burden, reconstruction index, and positive remodeling. Additionally, they exhibited the thickest fibrous caps. In contrast, the AMI and UAP groups presented similar outcomes in these aspects. Regarding the epicardial fat pad thickness, the positive rate of monocyte-platelet aggregates, and the levels of sdLDL-C, there were no significant differences between the AMI and UAP groups. However, these parameters were notably higher in the AMI and UAP groups compared to the SAP group. Crucially, we established a significant correlation between the thickness of the epicardial fat pad, the positive rate of monocyte-platelet aggregates, and the sdLDL-C levels with plaque loading rate and remodeling index. These correlations underscore the potential utility of these parameters as indicators of plaque stability and cardiovascular risk in patients with CHD. This highlights the complexity of atherosclerotic disease progression and underscores the importance of a multifaceted approach to assessing and managing CHD. Conclusion: Our research delineates the critical role of the remodeling index, epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels as key prognostic tools for assessing coronary plaque stability in coronary artery disease (CAD). These biomarkers collectively provide an enhanced perspective on plaque vulnerability, an essential aspect in the genesis of acute coronary events. Clinically, these findings are pivotal. They offer a refined approach to CAD management and risk evaluation, allowing for the precise identification of patients at increased risk of plaque rupture, a precursor to acute coronary syndromes. This precision facilitates the adoption of more individualized treatment strategies, focusing on aggressive interventions for high-risk patients and more conservative management for those with stable plaques.

Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Navigating the landscape: Prospects and hurdles in targeting vascular smooth muscle cells for atherosclerosis diagnosis and therapy.

Vascular smooth muscle cells (VSMCs) have emerged as pivotal contributors throughout all phases of atherosclerotic plaque development, effectively dispelling prior underestimations of their prevalence and significance. Recent lineage tracing studies have unveiled the clonal nature and remarkable adaptability inherent to VSMCs, thereby illuminating their intricate and multifaceted roles in the context of atherosclerosis. This comprehensive review provides an in-depth exploration of the intricate mechanisms and distinctive characteristics that define VSMCs across various physiological processes, firmly underscoring their paramount importance in shaping the course of atherosclerosis. Furthermore, this review offers a thorough examination of the significant strides made over the past two decades in advancing imaging techniques and therapeutic strategies with a precise focus on targeting VSMCs within atherosclerotic plaques, notably spotlighting meticulously engineered nanoparticles as a promising avenue. We envision the potential of VSMC-targeted nanoparticles, thoughtfully loaded with medications or combination therapies, to effectively mitigate pro-atherogenic VSMC processes. These advancements are poised to contribute significantly to the pivotal objective of modulating VSMC phenotypes and enhancing plaque stability. Moreover, our paper also delves into recent breakthroughs in VSMC-targeted imaging technologies, showcasing their remarkable precision in locating microcalcifications, dynamically monitoring plaque fibrous cap integrity, and assessing the therapeutic efficacy of medical interventions. Lastly, we conscientiously explore the opportunities and challenges inherent in this innovative approach, providing a holistic perspective on the potential of VSMC-targeted strategies in the evolving landscape of atherosclerosis research and treatment.

Predictive Value of Carotid Plaque Contrast-Enhanced Ultrasound Score and Homocysteine in Senile Metabolic Syndrome Complicated by Cerebral Infarction.

OBJECTIVE: To investigate the predictive value of the carotid plaque contrast-enhanced ultrasound (CEUS) score and blood homocysteine (HCY) in senile metabolic syndrome (MetS) complicated by cerebral infarction. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Ultrasound Imaging, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, China, from July 2020 to December 2021. METHODOLOGY: A total of 118 senile MetS patients complicated by cerebral infarction were selected as Group A, and 103 senile MetS patients without cerebral infarction were selected as Group B. Both groups were compared in terms of cardiovascular risk factors and ultrasonic examination of carotid plaques. The independent risk factors for cerebral infarction among senile MetS patients were analysed using logistic regression. An ROC curve was used to assess the predictive value of statistically significant risk factors in senile MetS complicated by cerebral infarction. RESULTS: Significant differences were observed in smoking, abdominal circumference, blood pressure, HCY, fasting blood glucose, high-density and low-density lipoprotein cholesterol, triacylglycerol, carotid plaque thickness, CEUS score, lumen stenosis, and ulcer plaque between the two groups. Logistic regression analysis showed that the plaque CEUS score and HCY were independent risk factors for senile MetS complicated by cerebral infarction. The areas under the ROC curve for the CEUS score and HCY were 0.795 and 0.812, respectively, and was 0.858 for the combined diagnosis of both. When the CEUS score was ≥2 and HCY was ≥16.45 mmol/l, the sensitivity and specificity of predicted senile MetS complicated by cerebral infarction were 83.1% and 74.8%, respectively. CONCLUSION: The carotid plaque CEUS score and blood HCY exhibit a substantial predictive capacity for cerebral infarction in elderly MetS patients. The combined diagnostic efficacy of the two is superior. KEY WORDS: Contrast-enhanced ultrasound, Homocysteine, Elderly, Metabolic syndrome, Cerebral infarction, Carotid plaque.

High-field magnetic resonance microscopy of aortic plaques in a mouse model of atherosclerosis.

OBJECTIVES: Pre-clinical models of human atherosclerosis are extensively used; however, traditional histological methods do not allow for a holistic view of vascular lesions. We describe an ex-vivo, high-resolution MRI method that allows the 3 dimensional imaging of the vessel for aortic plaque visualization and quantification. MATERIALS AND METHODS: Aortas from apolipoprotein-E-deficient (apoE-/-) mice fed an atherogenic diet (group 1) or a control diet (group 2) were subjected to 14 T MR imaging using a 3D gradient echo sequence. The obtained data sets were reconstructed (Matlab), segmented, and analyzed (Avizo). The aortas were further sectioned and subjected to traditional histological analysis (Oil-Red O and hematoxylin staining) for comparison. RESULTS: A resolution up to 15 × 10x10 µm3 revealed that plaque burden (mm3) was significantly (p < 0.05) higher in group 1 (0.41 ± 0.25, n = 4) than in group 2 (0.01 ± 0.01, n = 3). The achieved resolution provided similar detail on the plaque and the vessel wall morphology compared with histology. Digital image segmentation of the aorta's lumen, plaque, and wall offered three-dimensional visualizations of the entire, intact aortas. DISCUSSION: 14 T MR microscopy provided histology-like details of pathologically relevant vascular lesions. This work may provide the path research needs to take to enable plaque characterization in clinical applications.

Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques-A Comparison between Women and Men in the Population-Based Hamburg City Health Study.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45-74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.

Quantification of Local Vessel Wall and Plaque Volume Change for Assessment of Effects of Therapies on Carotid Atherosclerosis Based on 3-D Ultrasound Imaging.

We developed a new method to measure the voxel-based vessel-wall-plus-plaque volume (VWV). In addition to quantifying local thickness change as in the previously introduced vessel-wall-plus-plaque thickness (VWT) metric, voxel-based VWV further considers the circumferential change associated with vascular remodeling. Three-dimensional ultrasound images were acquired at baseline and 1 y afterward. The vessel wall region was divided into small voxels with the voxel-based VWV change (ΔVVol%) computed by taking the percentage volume difference between corresponding voxels in the baseline and follow-up images. A 3-D carotid atlas was developed to allow visualization of the local thickness and circumferential change patterns in the pomegranate versus the placebo groups. A new patient-based biomarker was obtained by computing the mean ΔVVol% over the entire 3-D map for each patient (ΔVVol%¯). ΔVVol%¯ detected a significant difference between patients randomized to pomegranate juice/extract and placebo groups (p = 0.0002). The number of patients required by ΔVVol%¯ to establish statistical significance was approximately a third of that required by the local VWT biomarker. The increased sensitivity afforded by the proposed biomarker improves the cost-effectiveness of clinical studies evaluating new anti-atherosclerotic treatments.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

BACKGROUND AND AIMS: There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. MATERIALS AND METHODS: We retrospectively analyzed 1,636 Korean individuals (mean age 52.6 ± 7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥ 140/90 mmHg, fasting blood glucose ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, body mass index ≥ 25.0 kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤ 3.2, 3.3 - 3.6, and ≥ 3.7 mg/dL). RESULTS: 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149 - 2.308; p = 0.006) and third (OR: 1.645; 95% CI: 1.093 - 2.476; p = 0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124 - 2.292; p = 0.009) and third (OR 1.790; 95% CI 1.179 - 2.716; p = 0.006) SPC tertiles. CONCLUSION: In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

Correlation between Characteristics of Coronary Plaque and Chinese Medicine Syndromes of Coronary Heart Disease: A Cross-Sectional Study Analysed by Intravascular Ultrasound.

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). CONCLUSIONS: Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology　- A Serial Computed Tomography Angiography Study.

BACKGROUND: Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results: This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. CONCLUSIONS: In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Ferrite-encapsulated nanoparticles with stable photothermal performance for multimodal imaging-guided atherosclerotic plaque neovascularization therapy.

Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis.

Three-dimensional ultrasound assessment of effects of therapies on carotid atherosclerosis using vessel wall thickness maps.

We present a new method for assessing the effects of therapies on atherosclerosis, by measuring the weighted average of carotid vessel-wall-plus-plaque thickness change (ΔVWT¯Weighted) in 120 patients randomized to pomegranate juice/extract versus placebo. Three-dimensional ultrasound images were acquired at baseline and one year after. Three-dimensional VWT maps were reconstructed and then projected onto a carotid template to obtain two-dimensional VWT maps. Anatomic correspondence on the two-dimensional VWT maps was optimized to reduce misalignment for the same subject and across subjects. A weight was computed at each point on the two-dimensional VWT map to highlight anatomic locations likely to exhibit plaque progression/regression, resulting in ΔVWT¯Weighted for each subject. The weighted average of VWT-Change measured from the two-dimensional VWT maps with correspondence alignment (ΔVWT¯Weighted,MDL) detected a significant difference between the pomegranate and placebo groups (P = 0.008). This method improves the cost-effectiveness of proof-of-concept studies involving new therapies for atherosclerosis.

Meta-Analysis Comparing the Effect of Combined Omega-3 + Statin Therapy Versus Statin Therapy Alone on Coronary Artery Plaques.

Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 µm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.

ACR appropriateness criteria asymptomatic patient at risk for coronary artery disease: 2021 update

Coronary atherosclerotic disease is a leading cause of mortality and morbidity due to major cardiovascular events in the United States and abroad. Risk stratification and early preventive measures can reduce major cardiovascular events given the long latent asymptomatic period. Imaging tests can detect subclinical coronary atherosclerosis and aid initiation of targeted preventative efforts based on patient risk. A summary of available imaging tests for low-, intermediate-, and high-risk asymptomatic patients is outlined in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Prevalence and Characterization of Subclinical Coronary Atherosclerotic Plaque with CT among Individuals with HIV: Results from the Canadian HIV and Aging Cohort Study.

Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography (n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors. Results There were 181 PLWH (mean age, 56 years ± 7; 167 men) and 84 healthy volunteers (mean age, 57 years ± 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively; P = .45), as were CAC score (odds ratio [OR], 1.06; 95% CI: 0.58, 1.94; P = .85) and overall plaque prevalence (prevalence ratio, 1.07; 95% CI: 0.86, 1.32; P = .55) after adjustment for cardiovascular risk. Noncalcified plaque prevalence (prevalence ratio, 2.5; 95% CI: 1.07, 5.67; P = .03) and volume (OR, 2.8; 95% CI: 1.05, 7.40; P = .04) were higher in PLWH. Calcified plaque frequency was reduced in PLWH (OR, 0.6; 95% CI: 0.40, 0.91; P = .02). Treatment with protease inhibitors was associated with higher volume of overall (OR, 1.8; 95% CI: 1.09, 2.85; P = .02) and mixed plaque (OR, 1.6; 95% CI: 1.04, 2.45; P = .03). Conclusion Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in asymptomatic people living with HIV without known cardiovascular disease compared with healthy volunteers without HIV. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lai in this issue.

Platelet-Mimicking Therapeutic System for Noninvasive Mitigation of the Progression of Atherosclerotic Plaques.

Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment.

Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE-/- mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

New carotid plaque, but not the progression of intima-media thickness, predicts the progression of high-risk coronary plaque.

BACKGROUND: Carotid intima-media thickness (CIMT) is regarded as a controversial risk marker for cardiovascular disease (CVD). We aimed to evaluate the role of CIMT and carotid plaque progression as predictors for the progression of coronary plaque and compositions. METHODS: In the Garlic 4 study, asymptomatic patients with intermediate CVD risk (Framingham risk score 6-20%) were recruited for a serial carotid ultrasound, and coronary artery calcium score (CAC)/coronary computed tomography angiography (CCTA) studies for subclinical atherosclerosis at a baseline and 1 year. The association between progression of quantitatively measured coronary plaque compositions and the progression of CIMT/carotid plaque was analyzed. A P value <0.05 is considered as statistically significant. RESULTS: Forty-seven consecutive patients were included. The mean age was 58.5 ± 6.6 years, and 69.1 % were male. New carotid plaque appeared in 34.0 % (n = 16) of participants, and 55.3 % (n = 26) of subjects had coronary plaque progression. In multilinear regression analysis, adjusted by age, gender, and statin use, the development of new carotid plaque was significantly associated with an increase in noncalcified coronary plaque [ß (SE) 2.0 (0.9); P = 0.025] and necrotic core plaque (1.7 (0.6); P = 0.009). In contrast, CIMT progression was not associated with the progression of coronary plaque, or coronary artery calcium (CAC) (P = NS). CONCLUSION: Compared to CIMT, carotid plaque is a better indicator of coronary plaque progression. The appearance of a new carotid plaque is associated with significant progression of necrotic core and noncalcified plaque, which are high-risk coronary plaque components.

Digestive n-6 Lipid Oxidation, a Key Trigger of Vascular Dysfunction and Atherosclerosis in the Western Diet: Protective Effects of Apple Polyphenols.

SCOPE: A main risk factor of atherosclerosis is a Western diet (WD) rich in n-6 polyunsaturated fatty acids (PUFAs) sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde. An increased 4-HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApolipoproteinE (ApoE-/- ) mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins. METHODS AND RESULTS: ApoE-/- mice are fed during 12 weeks with a WD with or without n-6 PUFAs. Moreover, two WD + n-6 PUFAs groups are supplemented with apple puree or phenolic extract. An increase in digestive 4-HNE production associated with a rise in plasmatic 4-HNE and oxidized LDL concentrations is reported. Oxidizable n-6 PUFAs consumption is associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress. CONCLUSION: n-6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy can limit 4-HNE formation during digestion and thus durably protect vascular function.