Carotid Plaque Burden Research Articles

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR

Background and aimsElectronic cigarette (EC) use is popular among youth, touted as a safer alternative to smoking and promoted as a tool to aid in smoking cessation. EC cardiovascular safety however is not well established. The aim of this study was to examine cardiovascular consequences of EC use by evaluating their effect on the entire atherosclerotic cascade in young adults using noninvasive combined positron emission tomography (PET)/magnetic resonance imaging (MR) and comparing EC use with age matched smokers of traditional cigarettes and nonsmoking controls. MethodsCarotid PET/MR was applied to look at vascular inflammation (18-fluorodeoxyglucose (FDG)-PET) and plaque burden (multi-contrast MR of vessel wall) from 60 18-30 year-old subjects (20 electronic cigarette users, 20 traditional smokers and 20 nonsmokers). ResultsGroups were reasonably well balanced in terms of age, gender, demographics, cardiovascular risk and most biomarkers. There were no differences in vascular inflammation as measured by 18-FDG-PET target to background ratios (TBR) between EC users, traditional cigarette smokers and nonsmokers. However, measures of carotid plaque burden − wall area, normalized wall index, and wall thickness − measured from MR were significantly higher in both traditional smokers and EC users than in nonsmokers. ConclusionsYoung adult EC users, smokers and nonsmokers in our study did not exhibit vascular inflammation as defined by 18-F-FDG-PET TBR max, but smokers and EC users had significantly more carotid plaque burden compared to matched nonsmokers. Results could indicate that vaping does not cause an increase in vascular inflammation as measured by FDG-PET.

Carotid Plaque Burden by 3-Dimensional Vascular Ultrasound as a Risk Marker for Patients with Metabolic Syndrome

Our aim was to analyse the associations between carotid plaque burden (CPB), cardiovascular risk factors (CVRF), and surrogate markers of CV risk in subjects with metabolic syndrome (MetS). We consecutively included 75 asymptomatic outpatients with MetS components, <60 years old and non-smokers. We determined the presence of CVRF, left ventricular hypertrophy (LVH), carotid intima-media thickness (cIMT), albumin-creatinine ratio (ACR), coronary artery calcium score (CACS) and CPB by 3-dimensional vascular ultrasound (3DVUS) for comparison. A total of 50 (67%) subjects had MetS defined by harmonized criteria. A CPB >0 mm3 and a CACS >0 AU were the risk biomarkers most frequently observed (72% and 77%, respectively), followed by LVH (40%). CPB and CACS revealed association with cardiovascular risk (r = 0.308; p = 0.032 and r = 0.601 p < 0.01, respectively), and CPB also showed association with the burden of CVRF (r = 0.349; p = 0.014). CPB by 3DVUS was a prevalent CV risk marker, directly associated with CVRF and cardiovascular risk in MetS subjects.

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

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Subclinical Atherosclerosis and Brain Metabolism in Middle-Aged Individuals: The PESA Study

BackgroundAtherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored. ObjectivesThis study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals. MethodsThis study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography. Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3-dimensional vascular ultrasound. ResultsGlobal FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS) (β = −0.15, p < 0.001). This association was mainly driven by the presence of hypertension (d = 0.36, p < 0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β = −0.16, p < 0.001), even after adjusting for 30-year FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus. ConclusionsIn asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain’s midlife vulnerability to future cognitive dysfunction.

Measurement of carotid plaque burden: A tool for predicting and preventing dementia?

Carotid plaque burden is a strong predictor of stroke risk, and preventing stroke reduces the risk of dementia. Treating carotid plaque burden markedly reduces the risk of stroke. Among patients age 65-80 years attending a stroke prevention clinic, we identified those with a carotid plaque burden in the top 20% of Total Plaque Area (High TPA) and the bottom 20% (Low TPA) and performed cognitive tests: The Montreal Cognitive Assessment test (MoCA), the WAIS-III Digit Symbol-Coding Test (DSST) and Trail-Making Test (TMT) part A and B. There were 31 patients recruited; 11 Low TPA (5 men) and 20 High TPA (17 men), p=0.04. TPA was 35±25 mm2 in the Low TPA vs.392±169 mm2 in the High TPA group (0.0001). Patients with a high plaque burden had significantly worse performance on all the cognitive tests, all p< 0.05. A high carotid plaque burden identifies patients at risk of cognitive impairment. Because carotid plaque burden is treatable, and treating it markedly reduces the risk of stroke, we suggest that measurement of plaque burden is a useful tool for both prediction of cognitive impairment, and prevention of dementia.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events

It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. To assess associations of CA MRI plaque characteristics with incident CVD events. The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Increased exposure to air pollutants leads to greater atherosclerotic burden mediated by systemic inflammation

Abstract Introduction Air pollution has been a well-described environmental factor contributing significantly to the global disease burden. Purpose To examine the association of gaseous air pollutants with atherosclerosis, especially in subjects with coronary artery disease (CAD). Methods 2053 individuals enrolled in the Corinthia study underwent clinical and biochemical assessment followed by carotid ultrasonography to evaluate carotid intima-media thickness (cIMT) and plaque burden. Inflammation was estimated via measurement of C-Reactive protein (CRP). Air pollutants concentration analysis was performed in prespecified regions with respect to their proximity to heavy industries, highways and shipyards. Results A higher concentration of gaseous air pollutants was observed in Region 4 when compared to other regions (Table). Mean cIMT, maximum cIMT and carotid plaque burden were significantly increased in individuals of Region 4 (Table, Figure A and B), a result which remained unaffected after adjustment for cardiovascular confounders (Figure C). In parallel, inhabitants of Region 4 had higher levels of CRP (Region 1: 4.60±5.01mg/l; Region 2: 3.08±3.26mg/l; Region 3: 4.37±4.70mg/l, Region 4: 6.78±9.77mg/l, p&amp;lt;0.001). To examine the effect of air pollution on atherosclerosis in CAD, propensity scores were applied to match healthy controls with CAD subjects in terms of atherosclerosis risk factors resulting in two matched groups; one in regions 1, 2 and 3 -low air pollution areas (LAPA)- and another in region 4 -high air pollution area (HAPA). Interestingly, we noted substantially higher inter-area differences in mean cIMT of CAD individuals (Figure D). Conclusion Air pollution may significantly contribute to atherosclerosis progression, potentially via the induction of inflammation. A more pronounced effect was noted in CAD individuals exposed to high air pollution. Funding Acknowledgement Type of funding source: None

CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable plaque phenotype and remodelling

Abstract Background and purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules and members of the TNF receptor superfamily well known for their involvement in inflammatory and autoimmune diseases. This study uses two large human cohorts – the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) and the Carotid Plaque Imaging Project (CPIP) – to explore the potential of plasma or intra-plaque expression of CD40 and CD40L as biomarkers and to locally affect plaque stability. Methods Proximity Extension Assay (PEA) technique was used to measure soluble CD40 and CD40L (sCD40 and sCD40L) in plasma from 1437 subjects from the SUMMIT cohort, the majority of which (80%) with pre-existing cardiovascular disease, and in atherosclerotic plaque homogenates from 199 subjects of the CPIP cohort undergoing carotid endarterectomy. The Mann-Whitney U test was used to compare groups and Spearman's rank correlation/the Chi-square test was used to assess correlations. Multiple comparisons were corrected for using the Holm-Šídák test. A logistic regression model was used to test for associations with future cardiovascular events and mortality. Results In the SUMMIT cohort both plasma CD40 and CD40L levels were elevated in individuals with a history of stroke (p=0.000030 and p=0.020, respectively), while sCD40 levels also were higher in individuals with a prior acute myocardial infarction (p=0.016). Plasma levels of sCD40 correlated with carotid plaque burden (as measured by ultrasound imaging, r=0.355, p&amp;lt;1x10–16) and were associated with future cardiovascular events over a three year-follow up period (p=0.02, hazard ratio 1.3, 95% C.I: 1.042–1.625). sCD40 and sCD40L were associated with a plaque phenotype characterized by the strong presence of features both of vulnerability such as high content oxidized low-density lipoprotein (LDL; r=0.236, p=0.004 and r=0.259, p=0.0037, respectively) and pro-inflammatory cytokines (e.g. tumour necrosis factor-α: p=3.1x10–7 and p=0.0006, respectively) and low calcium content (r=−0.208, p=0.012 and r=0.268, p=0.00034, respectively). Conclusion High plasma CD40 and CD40L levels are associated with symptomatic cardiovascular disease. Plasma CD40 levels correlate with the severity of carotid atherosclerosis and are associated with an increased risk for future cardiovascular events. Additionally, intra-plaque levels are associated with a vulnerable plaque phenotype. Our findings thus support the value of sCD40 and sCD40L both as biomarkers and therapeutic targets for cardiovascular disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Swedish Heart and Lung Foundation (1) and the Swedish Research Council (2)

Association of habitual alcohol consumption with carotid atherosclerotic lesions: results from the Corinthia study

Abstract Introduction Alcohol is implicated in the pathophysiology of cardiovascular diseases. However, it is also believed to play a cardioprotective role if consumed in appropriate amounts. Purpose To assess the association between alcohol consumption and carotid atherosclerosis. Methods In the setting of the cross-sectional Corinthia study, volunteers filled in questionnaires regarding drinking habits and were characterized as social drinkers (SD) or habitual alcohol consumers (HAC). Furthermore, they underwent carotid ultrasonography examination to evaluate the carotid intima-media thickness (cIMT). Thickness of cIMT&amp;gt;1.5 mm or protrusion &amp;gt;50% compared to adjacent segments was considered as atherosclerotic plaque. Results HAC consumers were usually male (HAC: 61.1%, SD: 24.9%, p&amp;lt;0.001), smokers (HAC: 33.3%, SD: 23.5%, p&amp;lt;0.001) and frequently had a history of hypertension (HAC: 72.8%, SD: 67.5%, p=0.02) when compared to SD (Table 1). However, no significant differences were noted regarding other risk factors of atherosclerosis (Table). Notably, HAC had a greater extent of carotid atherosclerosis as demonstrated by an increased cIMT (HAC: 1.03±0.45mm, SD: 0.96±0.39mm, p&amp;lt;0.001) and carotid plaque burden (HAC: 27.7%, SD: 21.3%, p=0.004). Importantly, when taking into account the number of alcoholic drinks (in wine glasses), alcohol consumption of more than 1 wine glass resulted in significantly higher values of cIMT (1 wine glass: 1.00±0.42mm, &amp;gt;1 wine glass: 1.06±0.45mm, p=0.04) (Figure 1A) and extensive amount of carotid plaques (1 wine glass: 22.7%, &amp;gt;1 wine glass: 30.4%, p=0.02) when compared to consumption of 1 wine glass (Figure 1B). Conclusion Habitual alcohol consumption of more than one wine glass is associated with a higher carotid atherosclerotic burden. Figure 1 Funding Acknowledgement Type of funding source: None

New three-dimensional volumetric ultrasound probe for accurate quantification of atherosclerotic plaque volume

Abstract Background Atherosclerosis burden is directly related with the development of clinical cardiovascular events. Recent ESC guidelines endorse carotid and/or femoral plaque burden assessment as a complement for conventional cardiovascular risk evaluation. Compared with previous 3D probes, new 3D-matrix transducers for vascular ultrasound imaging are designed to improve functionality and image quality for an accurate study of atherosclerosis burden. Purpose We aimed to validate a commercially available 3D-matrix transducer for plaque volume measurement in early disease stages (small plaques) when accurate plaque detection and quantification is challenging, and intermediate-advanced (medium-large size) plaques in carotid and femoral arteries. Methods We performed an ex vivo study using carotid and femoral arterial specimens from a pig model of early atherosclerosis in which actual 3D vascular ultrasound (3DVUS) volume measurements obtained using the new 3D-matrix transducer (XL14–3) were correlated against gold-standard histological measurements. Moreover, we performed a clinical experiment in a subset of intermediate-high risk patients from the “Athero-Brain: Head to Heart (H2H)” study with patent carotid and femoral atherosclerosis for comparing plaque volume evaluated by the new XL14–3 3D-matrix transducer, based on “electronic” 3D-sweep technology, with that measured by previously validated VL13–5 “mechanical” 3D-sweep transducer that uses a mechanically steered linear-array. Results In the ex vivo setting, we evaluated 11 atherosclerotic plaques (6 carotid and 5 femoral plaques, mean plaque volume 16.5±22.5 mm3 ranging in size from 1 to 56 mm3), finding a strong correlation between 3DVUS measures and the histological gold-standard with an intraclass correlation coefficient (ICC) of 0.994 (95% CI [0.976; 0.998]). In the clinical setting, we measured 25 plaques (14 carotid and 11 femoral plaques; mean plaque volume 273.4±216.5 mm3 ranging in size from 10 to 859 mm3) from 8 patients (mean age 75±5 years old, 45% men) finding again a strong correlation between 3DVUS electronic-based and mechanical-based volume measurements (ICC=0.996 95% CI [0.991; 0.998]). Correlation and Bland-Altman plots for the measurements of both experiments are displayed in the figure and showed good agreement (Slope close to 1 in the Passing Bablock analysis) with small or lower than clinically relevant differences between measurements. Conclusions 3DVUS using new matrix technology accurately measures plaque volumes of early (small-size) to intermediate-advanced plaques located in superficial arteries like carotid and femoral arteries. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Carlos III Institute through an Integrated Excellence Project Grant

Prevalence and burden of carotid and femoral atherosclerosis in subjects older than 30 years-old without known cardiovascular disease determined by bidimensional vascular ultrasound

Abstract Introduction 2019 ESC guidelines on dyslipidemia (DLP) and diabetes (DM) recommend (class IIa) measurement of arterial (carotid and/or femoral) plaque burden with vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk with DLP and in asymptomatic patients with DM. However, there are no standard thresholds to categorize atherosclerosis burden (AB) measured by 2D-VUS, a simple, safe and spread technology. Purpose To explore carotid (c) and femoral (f) plaques prevalence and AB according to age, sex and cardiovascular risk factors (CVRF) in subjects older than 30 years-old without known atherosclerotic cardiovascular disease (ASCVD) Methods Among 9,987 consecutive individuals self-referred or referred by physicians for a cardiovascular workup, we present a cross-sectional analysis of 5,775 first visits of those between 30 and 80 years-old without known ASCVD. We registered prospectively information about CVRF, lifestyle and anthropometrics and determined the prevalence of atherosclerotic plaques evaluating bilateral carotid and femoral arteries with 2D-VUS, applying the Mannheim Consensus definition. Further, we estimated c-AB as the sum of all carotid plaque areas (in mm2), and f-AB according to the presence of unilateral, bilateral or no femoral plaques. Median c-AB and 25–75th percentiles by age and sex were determined. We finally examined the association of AB with number of CVRF adjusted by age. Results 61% were men, mean age was 51.3 (SD 10.6) years. CVRF were hypertension 53.3%, dyslipidemia 50.3%, sedentarism 56.9%, obesity 28.2%, smoking 16.6% and diabetes 7.3%. Near 10% had no CVRF, 23.1% had 1, 29.8% had 2 and 37.4% had ≥3 CVRF. 42% were medicated on antihypertensives and 17.8% on lipid-lowering drugs. Globally, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. There was an age-related increasing pattern in both sex, stepper in men compared to women before 50 years-old (see graph). Median cAB showed also increasing values with aging, starting at 40 years-old and being higher in men than women with nearly 8 to 10 years ahead of time. Likewise it was observed regarding the presence of uni and bilateral femoral plaques. Finally, there was an increasing prevalence of plaques by number of CVRF, higher in men than women, either in the whole population and in those younger than 50 years-old. However, plaques prevalence was elevated in subjects with 0 (44.9% in men and 35.2% in women) or 1 CVRF (59.2% in men and 44.4% in women), leveraged by age. Conclusions We observed a high prevalence of carotid or femoral atherosclerosis, higher in men than women, and a high AB in both sex, starting before the fourth decade of life and increasing with age. In spite of a significant association to classic CVRF, a significant number of subjects with paucity of CVRF were diagnosed with atherosclerosis Prevalence of carotid or femoral plaques Funding Acknowledgement Type of funding source: None

Depression in young adults is associated with increased carotid atherosclerotic burden: insights from the Corinthia study

Abstract Introduction Depression appears to have a detrimental effect not only on mental health but also in the progression of various diseases. Purpose The examination of a potential association between depression and atherosclerosis progression in a rural population. Methods In the context of the cross-sectional Corinthia study, volunteers fulfilled a questionnaire concerning emotional health. The Geriatric Depression Scale was used for individuals aged 60 or more while the Zung self-rating depression score was preferred in younger adults. Carotid ultrasonography examination was performed to evaluate the mean carotid intima-media thickness (cIMT). Thickness of cIMT&amp;gt;1.5 mm or protrusion &amp;gt;50% compared to adjacent segments was considered as atherosclerotic plaque. Results Young adults with significant depression were usually female and did not differ significantly on other risk factors of atherosclerosis compared to those with mild or no depressive disorder. Importantly, those with moderate-severe depression appeared to have increased mean cIMT (Mild-No depression: 0.85±0.30mm, Moderate-severe depression: 0.91±0.42mm, p=0.04) and a higher carotid plaque burden (Mild-No depression: 12.8%, Moderate-severe depression: 20.3%, p=0.04). With regards to the elderly, those with moderate-severe depression were usually smokers (Mild-No depression: 13.9%, Moderate-severe depression: 24.2%, p=0.01). However, mean cIMT (Mild-No depression: 1.11±0.47mm, Moderate-severe depression: 1.09±0.39mm, p=0.69) and carotid plaques (Mild-No depression: 31.1%, Moderate-severe depression: 36.1%, p=0.36) did not differ according to depression status in this subgroup. Conclusion Significant depressive disorder is associated with accelerated carotid atherosclerosis in young individuals. Funding Acknowledgement Type of funding source: None

Associations Between Carotid Plaque Characteristics and Improvement of Cerebral Blood Perfusion in Patients With Moderate to Severe Carotid Stenosis Undergoing Carotid Endarterectomy

The relationship between plaque characteristics and their predictive value for perioperative cerebral blood flow (CBF) are unknown. To investigate the relationship between carotid plaque characteristics and perioperative CBF utilizing MRI. Prospective. In all, 131 patients with carotid moderate-to-severe stenosis referred for carotid endarterectomy (CEA). 3T, black-blood T1 - and T2 -weighted, 3D time-of-flight, and simultaneous noncontrast angiography intraplaque hemorrhage. The relative CBF (rCBF = CBFindex-hemisphere /CBFcontralateral-hemisphere ) and the CBF difference ratio (DRCBF = [CBFpost-CEA - CBFpre-CEA ]/CBFpre-CEA ) in the middle cerebral artery territory were measured. The pre- and post-CEA CTP data were used as the assessment standard for CBF change. Carotid lipid-rich necrotic core (LRNC), intraplaque hemorrhage, calcification, fibrous cap rupture, maximum wall thickness, normalized wall index (NWI), and stenosis were determined. Pearson or Spearman correlation, Mann-Whitney U-test, and linear regression. Patients with LRNC had higher rCBFpre-CEA than those without (1.0 ± 0.1 vs. 0.9 ± 0.1, P < 0.05). NWI was weakly correlated with rCBFpre-CEA (r = -0.213, P < 0.05) and DRCBF (r = 0.185, P < 0.05) and marginally correlated with rCBFpost-CEA (r = 0.166, P = 0.057). LRNC was weakly correlated with rCBFpre-CEA (r = 0.179, P < 0.05). NWI was associated with rCBFpre-CEA (β = -0.035; 95% confidence interval [CI] [-0.064, -0.006]; P < 0.05), rCBFpost-CEA (β = 0.042; 95% CI [0.002, 0.081]; P < 0.05) and DRCBF (β = 0.105; 95% CI [0.026, 0.185]; P < 0.05). After adjusting for confounding factors, associations of NWI with rCBFpost-CEA (β = 0.059; 95% CI [0.016, 0.103]; P < 0.05) and DRCBF (β = 0.110; 95% CI [0.021, 0.199]; P < 0.05) remained statistically significant, while the association between NWI and rCBFpre-CEA was no longer significant (β = -0.026; 95% CI [-0.058, 0.006]; P = 0.112).The associations of LRNC with rCBFpre-CEA (β = 0.057; 95% CI [-0.0006, 0.114]; P = 0.052) and DRCBF (β = -0.157; 95% CI [-0.314, 0.001]; P = 0.051) were close to statistical significance. After adjusting for confounding factors, these associations were statistically significant (of LRNC vs. rCBFpre-CEA : β = 0.060; 95% CI [0.003, 0.118]; P < 0.05; LRNC vs. DRCBF : β = -0.205; 95% CI [-0.375, -0.036]; P < 0.05). Carotid plaque burden and components, particularly LRNC, might be effective indicators for CBF change following CEA. Level of Evidence 1 Technical Efficacy Stage 5.

Magnetic resonance imaging of carotid plaques: current status and clinical perspectives.

Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T1-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.

Short Communication: Carotid Artery Plaque Burden in HIV Is Associated with Soluble Mediators and Monocytes.

Maximum carotid plaque thickness (MCPT) measures the largest plaque thickness in the carotid artery and reflects atherosclerosis plaque burden. MCPT may be a better predictor of cardiovascular disease than carotid artery intima-media thickness (cIMT) because it identifies potential unstable arterial atherosclerosis plaques. We assessed the relationships of monocyte and T cell populations and plasma soluble mediators with MCPT measures. We performed a cross-sectional and small follow-up analysis in people living with HIV (PLWH) aged >40 years on stable antiretroviral therapy (ART) >6 months. MCPT was acquired by high-resolution B-mode ultrasound. Existing monocyte subsets and T cell activation frequencies were determined by flow cytometry and plasma mediators of inflammation and apolipoproteins were measured by Luminex assay. One hundred twenty-five ART-treated PLWH, 88% male, 55% Caucasian, with a median age of 51 years, median CD4 count of 477 cells/μL (Q1: 325, Q3: 612), 84% undetectable plasma HIV RNA (<50 copies/mL). Twenty-five PLWH had detectable carotid plaque. MCPT correlated with monocyte chemoattractant protein-1 (MCP-1; r = 0.487, p = .016), tumor necrosis factor-α (TNF-α; r = 0.474 p = .019), soluble vascular cell adhesion molecule-1 (sVCAM-1; r = 0.472, p = .020), apolipoprotein B6 (ApoB6; r = -0.473, p = .019), and interleukin-6 (IL-6; r = 0.455, p = .025). In a multivariable regression model, MCP-1, TNF-α, and sVCAM-1 remained significant after adjustment for age. Carotid plaque burden was associated with increased inflammatory, monocyte, and endothelial measures, including MCP-1, TNF-α, and sVCAM-1 levels. Further investigation on the evolution or severity of plaque burden in this population is warranted.

The Role of Carotid and Femoral Plaque Burden in the Diagnosis of Coronary Artery Disease.

With limitations of cardiovascular disease risk stratification by traditional risk factors, the role of noninvasive imaging techniques, such as vascular ultrasound, has emerged as a prominent utility for decision-making in coronary artery disease. A review of current guidelines and contemporary approaches for carotid and femoral plaque assessment is needed to better inform the diagnosis, management, and treatment of atherosclerosis in clinical practice. The recent consensus-based guidelines for carotid plaque assessment in coronary artery disease have been established, supported by some outcomes-based research. Currently, there is a gap of evidence on the use of femoral ultrasound to detect atherosclerosis, as well as predict adverse cardiovascular outcomes. The quantification and characterization of individualized plaque burden are important to stratify risk in asymptomatic or symptomatic atherosclerosis patients. Standardized quantification guidelines, supported by further outcomes-based research, are required to assess disease severity and progression.

Measurement of carotid plaque burden.

To describe the uses of measurement of carotid plaque burden, as total plaque area (TPA), total plaque volume (TPV), and vessel wall volume (VWV), which includes plaque burden and wall volume. Measurement of plaque burden is useful for risk stratification, research into the genetics and biology of atherosclerosis, for measuring effects of new therapies for atherosclerosis, and for treatment of high-risk patients with severe atherosclerosis. Measurement of plaque burden is far superior to measurement of carotid intima-media thickness (IMT) in many ways, and should replace it. Vessel wall volume can be measured in persons with no plaque as an alternative to IMT.

Uses of ultrasound in stroke prevention.

Ultrasound methods are useful in stroke prevention in several ways. Measurement of carotid plaque burden, as either total plaque area (TPA) or total plaque volume (TPV) are strong predictors of cardiovascular risk: much stronger than intima-media thickness, which does not represent true atherosclerosis, but a biologically and genetically distinct phenotype. Measurement of plaque burden is also useful for the study of genetics, and of new risk factors such as toxic products of the intestinal microbiome. Carotid plaque burden is highly correlated with and as predictive of risk as coronary calcium scores, but is less costly and does not require radiation. Furthermore, because carotid plaques change in time over a period of months, they can be used for a new approach to vascular prevention: "Treating arteries instead of treating risk factors". In high-risk patients with asymptomatic carotid stenosis (ACS), this approach, implemented in 2003 in our clinics, was associated with a >80% reduction of stroke and myocardial infarction over 2 years. "Treating arteries without measuring plaque would be like treating hypertension without measuring blood pressure". Ultrasound methods can also be used to assess plaque vulnerability, by detecting echolucency, ulceration and plaque inhomogeneity on assessment of plaque texture. Transcranial Doppler (TCD) embolus detection is useful for risk stratification in patients with ACS; patients with two or more microemboli in an hour of monitoring have a 1-year risk of 15.6%, vs. 1% without microemboli, so this very clearly distinguishes which patients with ACS could benefit from intervention. TCD saline studies are more sensitive than trans-esophageal echocardiography for detection of patent foramen ovale, and more predictive of recurrent stroke. These methods should be more widely used, to reduce the increasing burden of stroke in our aging populations.