Artery Atherosclerotic Plaques Research Articles

Conditional deletion of Ccl2 in smooth muscle cells does not reduce early atherosclerosis in mice

Background and aimsC–C motif chemokine ligand 2 (CCL2) is a pro-inflammatory chemokine important for monocyte recruitment to the arterial wall and atherosclerotic plaques. Global knockout of Ccl2 reduces plaque formation and macrophage content in mice, but the importance of different plaque cell types in mediating this effect has not been resolved. Smooth muscle cells (SMCs) can adopt a potentially pro-inflammatory function with expression of CCL2. The present study aimed to test the hypothesis that SMC-secreted CCL2 is involved in early atherogenesis in mice. MethodsSMC-restricted Cre recombinase was activated at 6 weeks of age in mice with homozygous floxed or wildtype Ccl2 alleles. Separate experiments in mice lacking the Cre recombinase transgene were conducted to control for genetic background effects. Hypercholesterolemia and atherosclerosis were induced by a tail vein injection of recombinant adeno-associated virus (rAAV) encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and a high-fat diet for 12 weeks. ResultsUnexpectedly, mice with SMC-specific Ccl2 deletion developed higher levels of plasma cholesterol and larger atherosclerotic plaques with more macrophages compared with wild-type littermates. When total cholesterol levels were incorporated into the statistical analysis, none of the effects on plaque development between groups remained significant. Importantly, changes in plasma cholesterol and atherosclerosis remained in mice lacking Cre recombinase indicating that they were not caused by SMC-specific CCL2 deletion but by effects of the floxed allele or passenger genes. ConclusionsSMC-specific deficiency of Ccl2 does not significantly affect early plaque development in hypercholesterolemic mice.

A Race Against Time: Coronary Computed Tomography Angiography Discovers a Highly Inflamed Plaque in 49-Year-Old Right Before STEMI

Abstract In the modern management of coronary artery disease (CAD), cardiac computed tomography angiography (CCTA) has emerged as a pivotal diagnostic tool, offering detailed visualization of coronary artery lumens and atherosclerotic plaques. We present the case of a 49-year-old woman, with no prior cardiovascular history but with several risk factors, in whom CCTA identified a highly inflamed atherosclerotic plaque, which led immediately to an acute myocardial infarction. Significantly, this case spotlights the vital role of perivascular inflammation mapping in CCTA, crucial for identifying high-risk plaques. The case emphasizes the necessity for a comprehensive, multifaceted diagnostic approach in the evaluation and management of CAD, incorporating advanced techniques like perivascular inflammation mapping for a more accurate and predictive assessment.

Extracranial carotid artery atherosclerotic plaque and APOE polymorphisms: a systematic review and meta-analysis.

Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque. A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between ε4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; p = .003]. Additionally, there was a significant association between patients possessing at least one ε4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; p = .03). Lastly, there was no association between ε4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; p = .30). APOE ε4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.

Association between visceral adiposity index and coronary artery calcification score and atherosclerotic plaque morphology.

The relationship between the visceral adipose index (VAI), a surrogate marker of visceral adipose tissue dysfunction, and coronary atherosclerotic plaque (CAP) morphology remains unclear. This study aimed to investigate the relationships between the VAI and the coronary artery calcification (CAC) score and CAP morphology in asymptomatic patients. We retrospectively assessed 782 patients between January 2012 and January 2020. CAC scores were determined at the threshold of 130 Hounsfield units according to the Agatston technique using 64-slice computed tomography. Patients were assigned to groups with no plaque (NP), fatty plaque (FP), calcified plaque (CP), and mixed plaque (MP). The median VAI levels were significantly different in each group (NP: 1.2 vs. FP: 1.7 vs. CP: 2.3 vs. MP: 2.8; P <0.001). An increased VAI level was an independent predictor of the CAC score. The threshold value of the VAI exhibited a gradual increase in predicting CAP morphology. VAI threshold values were >1.6 for the FP group (vs. the NP group), >2.1 for the CP group (vs. the FP group), and >2.6 for the MP group (vs. the CP group). High VAI levels independently predict an increased CAC score and CAP morphology. The VAI exhibits superior diagnostic performance in distinguishing the presence and morphology of CAP in asymptomatic patients and offers gradual cut-off values. Therefore, the VAI may be a potential screening tool for risk stratification and diagnosing CAP morphology in patients with suspected coronary artery disease.

Correlation of the middle cerebral artery atherosclerotic plaque characteristics with ischemic stroke recurrence: a vessel wall magnetic resonance imaging study.

This study aims to analyze the imaging features of atherosclerotic plaques in the middle cerebral artery (MCA) of patients with recurrent ischemic stroke using vessel wall magnetic resonance imaging (VWMRI) and investigate the correlation between these imaging features and the recurrence of ischemic stroke. Consecutive patients with ischemic stroke caused by atherosclerotic stenosis of the MCA were collected. The patients were divided into recurrent and non-recurrent ischemic stroke groups. We obtained VWMRI images of MCA plaques using 3.0T MRI by black-blood sequences, and the differences in VWMRI characteristics and clinical information between the two groups were compared. A binary Logistic regression model was used to analyze the VWMRI characteristics and clinical information related to ischemic stroke recurrence. 179 patients were collected from August 2018 to May 2020, and 81 patients were included in the study. The recurrent ischemic stroke group patients had a higher stenosis rate (0.69 vs 0.64). Meanwhile, the rate of centripetal wall thickening was significantly higher in patients with recurrent ischemic stroke (33.3% vs 11.7%). Binary Logistic regression analysis showed that sex (P=0.036, OR:2.983, CI:1.075-8.279), stenosis rate (P=0.038, OR:148.565, CI:1.331-16583.631), and vessel wall thickening pattern (P=0.012, OR:0.171, CI:0.043-0.678) were related to ischemic stroke recurrence. The patients with ischemic stroke caused by atherosclerotic stenosis of MCA, female patients, and those with concentric wall thickening and a high degree of stenosis have a higher risk of recurrence. Our results suggest that VWMRI is a valuable tool for predicting the risk of ischemic stroke recurrence in patients with MCA plaques.

Familial Hypercholesterolaemia in Children and Adolescents: Current and Future Perspectives.

Familial hypercholesterolemia (FH) is a genetic disease, the underlying cause of which is represented by mutations capable of influencing the metabolism of low-density lipoproteins (LDL). The distinguishing characteristic of FH has increased LDL cholesterol blood levels since birth, triggering early development of atherosclerosis-related diseases. Diagnosis of FH is frequently either missed or made with a considerable delay. Prompt identification of the disease is pivotal in implementing early prevention measures. Safe and effective drugs have been approved for use in children and adolescents, with statins, with or without ezetimibe, representing first-line therapy. At times, however, these medications may not be sufficient to achieve the therapeutic target, particularly in homozygous FH patients. Lipoprotein apheresis, which has proved safe and efficient, is strongly suggested in such cases. New drugs still at the investigational stage may represent a promising and personalised therapy. Lowering cholesterol levels in childhood hampers the formation of arterial atherosclerotic plaques, thus reducing cardiovascular events later in life. Accordingly, early detection, diagnosis, and therapy in FH subjects are priority aims.

Fluid-structure interaction study of hemodynamics and its biomechanical influence on carotid artery atherosclerotic plaque deposits

Atherosclerotic plaque deposits are common causes of blood flow disruption in the carotid artery bifurcation and the associated fluid mechanics has been extensively studied using Computational Fluid Dynamics (CFD) and Fluid Structure Interaction (FSI). However, the elastic responses of plaques to hemodynamics in the carotid artery bifurcation has not been deeply studied using either of the above-mentioned numerical techniques. In this study, a two-way FSI study was coupled with CFD technique, using Arbitrary-Lagrangian-Eulerian method, to study the biomechanics of blood flow on nonlinear and hyperelastic calcified plaque deposits in a realistic geometry of the carotid sinus. FSI parameters such as total mesh displacement and von Misses stress on the plaque, as well as flow velocity and blood pressure around the plaques, were analyzed and compared to variables such as velocity streamline, pressure and wall shear stress obtained from CFD simulation in a healthy model. The blood flow simulations reveal complete reversed blood flow behavior in the internal carotid artery, ICAs and external carotid artery, ECAs for both cases. In particular, this study suggests that plaques, irrespective of the masses, possess a high yielding response to hemodynamic forces at the attaching edges, while the surfaces are vulnerable to rupture.

Carotid atherosclerotic plaque segmentation in multi-weighted MRI using a two-stage neural network: advantages of training with high-resolution imaging and histology.

A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes. To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that consists of a convolutional neural network (CNN), followed by a Bayesian neural network (BNN). The rationale for the two-stage network approach is to account for the class imbalance of vessel wall and background by providing an attention mask to the BNN. A unique feature of the network training was to use ground truth defined by both high-resolution ex vivo MRI data and histopathology. More specifically, standard resolution 1.5 T in vivo MR image sets with corresponding high resolution 3.0 T ex vivo MR image sets and histopathology image sets were used to define ground-truth segmentations. Of these, data from 7 patients was used for training and from the remaining two was used for testing the proposed method. Next, to evaluate the generalizability of the method, we tested the method with an additional standard resolution 3.0 T in vivo data set of 23 patients obtained from a different scanner. Our results show that the proposed method yielded accurate segmentation of carotid atherosclerotic plaque and outperforms not only manual segmentation by trained readers, who did not have access to the ex vivo or histopathology data, but also three state-of-the-art deep-learning-based segmentation methods. Further, the proposed approach outperformed a strategy where the ground truth was generated without access to the high resolution ex vivo MRI and histopathology. The accurate performance of this method was also observed in the additional 23-patient dataset from a different scanner. In conclusion, the proposed method provides a mechanism to perform accurate segmentation of the carotid atherosclerotic plaque in multi-weighted MRI. Further, our study shows the advantages of using high-resolution imaging and histology to define ground truth for training deep-learning-based segmentation methods.

Predicting coronary atherosclerosis heart disease with pericoronary adipose tissue attenuation parameters based on dual-layer spectral detector computed tomography: a preliminary exploration.

Coronary atherosclerosis is a chronic inflammatory condition. Pericoronary adipose tissue (PCAT) attenuation is closely related to coronary inflammation. This study aimed to investigate the relationship between PCAT attenuation parameters and coronary atherosclerotic heart disease (CAD) using dual-layer spectral detector computed tomography (SDCT). This cross-sectional study included eligible patients who underwent coronary computed tomography angiography using SDCT at the First Affiliated Hospital of Harbin Medical University between April 2021 and September 2021. Patients were classified as CAD (with coronary artery atherosclerotic plaque) or non-CAD (without coronary artery atherosclerotic plaque). Propensity score matching was used to match the two groups. The fat attenuation index (FAI) was used to quantify PCAT attenuation. The FAI was measured on conventional images (120 kVp) and virtual monoenergetic images (VMI) by semiautomatic software. The slope of the spectral attenuation curve (λ) was calculated. Regression models were established to evaluate the predictive value of PCAT attenuation parameters for CAD. A total of 45 patients with CAD and 45 patients without CAD were enrolled. The PCAT attenuation parameters in the CAD group were significantly higher than those in the non-CAD group (all P values <0.05). The PCAT attenuation parameters of vessels with or without plaques in the CAD group were higher than those of vessels without plaques in the non-CAD group (all P values <0.05). In the CAD group, the PCAT attenuation parameters of vessels with plaques were slightly higher than those of vessels without plaques (all P values >0.05). In receiver operating characteristic curve analysis, the FAIVMI model achieved an area under the curve (AUC) of 0.8123 for discriminating between patients with and without CAD, which was higher than those of the FAI120 kVp model (AUC =0.7444) and the λ model (AUC =0.7230). However, the combined model of FAIVMI, FAI120 kVp, and λ obtained the best performance (AUC =0.8296) of all the models. PCAT attenuation parameters obtained using dual-layer SDCT can aid in distinguishing patients with and without CAD. By detecting increases in PCAT attenuation parameters, it might be possible to predict the formation of atherosclerotic plaques before they appear.

Sudden Sensorineural Hearing Loss due to Basilar Artery Atherosclerotic Plaque without Diffusion Restriction

Sudden Sensorineural Hearing Loss due to Basilar Artery Atherosclerotic Plaque without Diffusion Restriction

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulatedin calcific areas. We further demonstrated TCF21 expression wasincreased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Abstract Number ‐ 227: Retrograde embolism from a Subclavian Thrombus causing Acute Ischemic Stroke in the Middle Cerebral Artery

Introduction Intracranial embolism to the middle cerebral artery usually occurs because of embolization from the heart, carotid artery or the aorta. Here we describe a case of a subclavian thrombus, embolizing to the middle cerebral artery. Retrograde embolism is a rarely described mechanism of acute ischemic stroke. Methods A 49‐year‐old gentleman with a history of hyperlipidemia, peripheral artery disease, smoking, prior stroke, previously treated arteriovenous malformation (AVM) in the left parieto‐occipital region and active methamphetamine use presented with sudden onset dysarthria and left facial weakness (NIH stroke scale–3). CT angiogram (CTA) head and neck demonstrated a right M2 inferior division occlusion and noted nonocclusive thrombus attached to right subclavian artery atherosclerotic plaque, proximal to the origin of the right vertebral artery and otherwise minimal extracranial, and intracranial atherosclerotic disease. He was not a candidate for IV thrombolysis due to his AVM, or mechanical thrombectomy (MT) due to low NIHSS. Apixaban was started. Trans‐esophageal echocardiogram (TEE) demonstrated a grade 2 PFO. Venous doppler ultrasound performed of his upper and lower extremities was negative. On day 2 of hospitalization, his left hemiparesis and dysarthria worsened. Repeat CTA head and neck showed absence of the right subclavian thrombus and new distal M1‐MCA thrombus, suggestive of retrograde embolism from the right subclavian artery. The patient was started on IV heparin and aspirin. A stroke in young work‐up was sent including antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), homocysteine, hexagonal phase phospho proteins, antiphospholipid antibodies, HIV, rheumatoid factor, cryoglobulin, hepatitis B antibodies, hepatitis C antibodies, sickle cell screen, Sjogren’s syndrome antibodies, drug screen, and was negative. Results Embolism (cardioembolism and artery–artery embolism) to the intracranial vasculature is an important cause of acute ischemic stroke. Retrograde embolization is rarely described as a cause of ischemic stroke. Our patient presented initially with distal right M2 occlusion and subocclusive thrombus of the right subclavian artery, associated with focal atherosclerosis but otherwise patent extracranial and intracranial cerebral vessels. Work‐up including transesophageal echocardiogram, and hypercoagulable work‐up was unrevealing. Repeat CT angiogram obtained in view of worsening deficits revealed absence of his right subclavian thrombus and new distal M1‐MCA occlusion presumed retrograde embolism from the right subclavian artery. This is may represent the consequence of local turbulence and retrograde flow during diastole. Conclusions When considering sources of embolic stroke, retrograde embolism should be considered in patients with focal atherosclerosis.

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Vulnerable atherosclerotic plaque rupture is the principal mechanism that accounts for myocardial infarction and stroke. High matrix metalloproteinase-9 (MMP-9) expression and activity have been proven to lead to plaque instability. Metformin, a first-line treatment for type 2 diabetes, is beneficial to plaque vulnerability. However, the mechanism underlying its anti-atherogenic effect remains unclear. Molecular docking and surface plasmon resonance experiments showed that metformin directly interacts with MMP-9, and incubated MMP-9 overexpressing HEK293A cells with metformin (1 μmol·L-1) significantly attenuates MMP-9's activity using zymography and MMP activity assays. Moreover, metformin treatment drives MMP-9 degradation. Next, we constructed a carotid artery atherosclerotic plaque model and administered consecutive 14-day metformin (200 mg·kg-1·d-1) treatment by intragastric gavage. Immunofluorescence staining of the right carotid common artery and serum MMP activity assay results showed that metformin treatment decreased local plaque MMP-9 protein level and circulating MMP-9 activity, respectively. Histochemical staining revealed that after metformin treatment, the collagen content in plaque was significantly preserved, and the plaque vulnerability index decreased. These findings suggested that metformin improved atherosclerotic plaque stability by directly binding to MMP-9 and driving its degradation.

Carotid atherosclerosis in people of European, South Asian and African Caribbean ethnicity in the Southall and Brent revisited study (SABRE).

Atherosclerotic cardiovascular disease (ASCVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease (CHD) and stroke, while African Caribbean people have a lower risk of CHD but a higher risk of stroke. To compare carotid atherosclerosis in EA, SA, and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by ASCVD risk factors. Cardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid artery plaques and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using generalised linear models (GLMs), with and without adjustment for non-modifiable (age, sex) and modifiable risk factors (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking). Prevalence of any plaque was similar in EA and SA, but lower in AC (16, 16, and 6%, respectively; p < 0.001). In those with plaque, total plaque area, numbers of plaques, plaque class, or greyscale median did not differ by ethnicity; adjustment for risk factors had minimal effects. cIMT was higher in AC than the other ethnic groups after adjustment for age and sex, adjustment for risk factors attenuated this difference. Prevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. Lower plaque prevalence in in AC is consistent with their lower risk of CHD but not their higher risk of stroke. Higher cIMT in AC may be explained by risk factors. The similarity of plaque burden in SA and EA despite established differences in ASCVD risk casts some doubt on the utility of carotid ultrasound as a means of assessing risk across these ethnic groups.

Study of associations of blood proteins with development of unstable atherosclerotic plaques in coronary arteries by quantitative proteomics

Aim. To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries in patients with coronary artery disease using the quantitative proteomic analysis.Materials and methods. The study included patients with coronary artery disease (n = 40); the average age of patients was 58 ± 7 years. Material for the study was blood serum. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit (Cambridge Isotope Laboratories, USA). Protein fractions were identified using the liquid chromatograph and tandem mass spectrometer Q-TRAP 6500.Results. Mass spectrometry revealed an increased concentration of proteins, such as fibrinogen, fibulin-1, and complement factor H, in the serum samples of patients with unstable atherosclerotic plaques. It took place with a simultaneous decrease in the levels of α 2-antiplasmin, heparin cofactor II, coagulation factor XII, plasminogen, prothrombin, vitronectin, complement proteins (C1, C3, C7, C9), and complement factor B. The differences were considered significant at p &lt; 0.05. It was revealed that the presence of unstable atherosclerotic plaques was associated with the level of fibulin-1 (Exp(B) = 1.008; р = 0.05), plasminogen (Exp(В) = 0.995; р = 0.027), and coagulation factor X (Exp(В) = 0.973; р = 0.037).Conclusion. An increased concentration of fibulin-1 can be considered as a potential biomarker of unstable atherosclerotic plaque development in coronary artery disease. The possibility of using the studied proteins as biomarkers of unstable atherosclerotic plaques requires further studies on their potential role in the development of this disease.

Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study.

Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (β, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (β, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.

Wall Shear Stress Measurement in Carotid Artery Phantoms with Variation in Degree of Stenosis Using Plane Wave Vector Doppler

Wall shear stress (WSS) plays an important role in the formation, growth, and rupture of atherosclerotic plaques in arteries. This study measured WSS in diseased carotid artery phantoms with degrees of stenosis varying from 0 to 60% with both steady and pulsatile flow. Experiments were performed using in silico and real flow phantoms. Blood velocities were estimated using plane wave (PW) vector Doppler. Wall shear stress was then estimated from the velocity gradient near the wall multiplied by the viscosity of a blood-mimicking fluid. The estimated WSS using the in silico phantom agreed within 10% of the ground-truth values (root-mean-square error). The phantom experiment showed that the mean WSS and maximum WSS increased with the increasing degree of stenosis. The simulation and experiment results provide the necessary validation data to give confidence in WSS measurements in patients using the PW vector Doppler technique.

Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors.

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular diseasehas become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoproteinand low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity-triggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chain-enhancer of activated B cellstranscriptional factor, thus inducing interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby makingobese diabetic patients prone towardthe development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterolconcentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity-diabetes correlation.

Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy.

We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation.

High-risk features of basilar artery atherosclerotic plaque.

High-resolution magnetic resonance imaging (HR-MRI) is used to characterize atherosclerotic plaque. The present study aimed to determine the high-risk features of the basilar artery (BA) atherosclerotic plaque. Patients with advanced BA stenosis were screened. The features including the ruptured fibrous cap (RFC), lipid core, intraplaque hemorrhage (IPH), plaque enhancement, and calcification were assessed by using high-resolution MRI. The relationship between the features and acute infarction was analyzed. From 1 June 2014 to 31 December 2018, a total of 143 patients with 76 new strokes were included. RFC was identified in 25% of symptomatic and 10.4% of asymptomatic patients. IPH was identified in 48.7% of symptomatic and 25.4% of asymptomatic patients. RFC (3.157, 95% CI 1.062 to 9.382, p = 0.039) and IPH (2.78, 95% CI 1.127 to 6.505, p = 0.026) were independent risk factors for acute infarction. Our study showed that RFC and IPH of BA plaque were independent risk factors for acute infarction.