Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis

Objective: Persons with HIV have double the risk of developing cardiovascular disease compared with the general population. A persistent and heightened immune response to cytomegalovirus coinfection may be one contributing factor, but the relationship between cytomegalovirus replication, virus-specific immune cells, and plaque burden is unclear. Approach and Results: We assessed the relationship between CD4 + T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known cardiovascular disease. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1 + ~GPR56 + ~CD57 + (ie, C~G~C) + CD4 + T cells ( P =0.03), which is a marker combination associated with antiviral and cytotoxic responses. In addition, a median of 14.4% (IQR, 4.7%–32.7%) of the C~G~C + CD4 + T-cells expressed antigen receptors that recognized a single cytomegalovirus glycoprotein-B epitope. Using immunofluorescence staining, we found that CX3CR1 + CD4 + T cells were present in coronary plaque from deceased HIV-positive persons. C~G~C + CD4 + T cells were also present in cells isolated from the aorta of HIV-negative donors. Conclusions: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4 + T-cells expressing the C~G~C surface marker combination associated with antiviral and cytotoxic responses. These cells can be cytomegalovirus-specific and are also present in the aorta.

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Carotid Plaque Burden Is Shown To Predict Cardiovascular Death

Internal Medicine News ◽

10.1016/s1097-8690(05)71963-6 ◽

2005 ◽

Vol 38 (18) ◽

pp. 58

Author(s):

SHERRY BOSCHERT

Keyword(s):

Carotid Plaque ◽

Cardiovascular Death ◽

Plaque Burden

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Type 2 diabetic patients with diabetic retinopathy without previous cardiovascular disease show an increased carotid plaque burden

Atherosclerosis ◽

10.1016/j.atherosclerosis.2014.05.725 ◽

2014 ◽

Vol 235 (2) ◽

pp. e243

Author(s):

N. Alonso ◽

A. Traveset ◽

E. Rubinat ◽

M.V. Arcidiacono ◽

E. Ortega ◽

...

Keyword(s):

Cardiovascular Disease ◽

Diabetic Retinopathy ◽

Carotid Plaque ◽

Plaque Burden ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic

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Abstract 247: Association of Soluble RAGE Levels with Carotid Atherosclerosis: The Northern Manhattan Study (NOMAS)

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a247 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Barry I Hudson ◽

Hannah Gardener ◽

Wen Liu-Mares ◽

Chuanhui Dong ◽

Sandino Cespedes ◽

...

Keyword(s):

Carotid Plaque ◽

Minority Groups ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Serum Levels ◽

Plaque Morphology ◽

Disease States ◽

Soluble Rage ◽

Novel Target

Introduction The Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand receptor that propagates vascular cell dysfunction leading to proinflammatory disease states. RAGE is produced as a membrane bound and soluble isoform (soluble RAGE (sRAGE)), with the soluble isoform demonstrated to act as a RAGE decoy preventing cellular activation and atherosclerosis. Recent cohort studies have suggested that serum levels of sRAGE are associated with the risk of CVD and therefore may be a novel biomarker for cardiovascular disease states. Hypothesis We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in an ethnically diverse population. Methods We included 1,102 stroke-free participants from the multi-ethnic Northern Manhattan Study (NOMAS) who underwent high-resolution carotid B-mode ultrasound to measure carotid plaque phenotypes (density, thickness, and area) and carotid intima-media thickness (IMT). Plaque density was characterized by Gray Scale Median (GSM). Serum sRAGE was measured by ELISA and log-transformed to stabilize variance. Multiple linear and logistic regressions were employed to estimate sRAGE associations with IMT and plaque measures. Results The mean age at time of ultrasound was 70.7±8.6yrs; 65% were Hispanic, 19% black, and 16% white. The majority of subjects had carotid plaque present (54%) with the median GSM 38(0-190). Mean plaque thickness (IQR) was 1.30(0-3.99)mm and mean area (IQR) 2.43(0-96.75)mm2. Mean IMT was 0.93±0.09mm. High sRAGE levels were associated with more echolucent plaques (OR 1.2, 95% CI 1.03-1.42), especially among Hispanics (OR 1.26, 95% CI 1.04-1.54). These relationships remained after adjusting for sociodemographic and vascular risk factors. No association was seen between sRAGE levels and carotid IMT, plaque thickness or area. Conclusion In the present study, higher sRAGE levels were associated with echolucent (lower density) plaque, especially among Hispanic subjects. Our data suggest sRAGE levels may be associated with atherosclerotic plaque morphology and its vulnerability, especially among minority groups. These findings further support RAGE as a novel target for anti-atherosclerosis interventions.

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Abstract P210: Calcified Atherosclerotic Plaque and All Cause Mortality in Diabetes: Diabetes Heart Study

Circulation ◽

10.1161/circ.125.suppl_10.ap210 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Subhashish Agarwal ◽

David M Herrington ◽

Amanda J Cox ◽

Neal Jorgensen ◽

Jianzhao Xu ◽

...

Keyword(s):

Subclinical Atherosclerosis ◽

Principal Component ◽

Plaque Burden ◽

Chi Square ◽

Prediction Of Mortality ◽

Heart Study ◽

Calcified Plaque ◽

All Cause Mortality ◽

Diabetes Heart Study ◽

Vascular Beds

Introduction Coronary artery calcium (CAC), a measure of atherosclerosis predicts mortality in both diabetes and the general population. The incremental utility of measuring atherosclerosis across multiple vascular beds beyond CAC for the prediction of mortality has not been reported. In this study we derived a composite atherosclerosis score (CAS) from multiple vascular beds and compared it with CAC in predicting all-cause mortality. We hypothesized that this composite score will be significantly better than CAC in predicting mortality. Methods A total of 803 participants, ages 39–86, with complete data on diabetes and vascular imaging in the Diabetes Heart Study (DHS) were followed for an average of 7.4 years. Computed tomography (CT) scans were performed at baseline to obtain measures of carotid (CAAC), coronary (CAC) and abdominal aorta (AAC) Agatston scores. A principal component analysis using studentized residuals of log transformed (CAAC+1), (CAC+1), and (AAC+1) adjusting for age, race, and gender was performed. We selected the first principal component as the CAS. Seven-year risk estimates for mortality were obtained using logistic regression models. Model 1 included age, gender, smoking, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and ethnicity and CAS. Model 2 included these risk factors plus CAC. We compared the estimation of mortality in Model 1 with CAS vs. Model 2 with CAC using chi-square values. Results Overall, 14% (116/803) of participants died during follow-up. CAS explained 70% of the variance, (eigenvalue of 2.1 with loading, CAAC, 0.57; CAC, 0.57; and AAC, 0.59). After adjusting for potential confounders, the odds ratio (95% CI) of all-cause mortality for 1-standard deviation (SD) increment was 2.12 (1.64–2.78) for CAS and 2.38 (1.77–3.35) for CAC. The area under the curve (chi-square value) with CAS or CAC to predict mortality was 0.76 (36) vs 0.76 (37) respectively. Conclusion Subclinical atherosclerosis, as measured by CT determined calcified plaque burden has increasing evidence supporting its role as a tool to stratify future risk for mortality. Here we demonstrated that the diagnostic accuracy between CAS and CAC are comparable and the predictive value of CAC alone for mortality is not further enhanced by inclusion of calcified plaque burden in carotid or abdominal aortic territories.

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Abstract WP188: Impact of Carotid Plaque Burden on Long-Term Outcomes in Ischemic Stroke Patients With Atrial Fibrillation

Stroke ◽

10.1161/str.49.suppl_1.wp188 ◽

2018 ◽

Vol 49 (Suppl_1) ◽

Author(s):

Hyungjong Park ◽

Young Dae Kim ◽

Ji Joe Heo ◽

Hyo Suk Nam

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Carotid Plaque ◽

Plaque Burden ◽

Stroke Patients ◽

Long Term Outcomes

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Elevated serum sortilin is related to carotid plaque concomitant with calcification

Biomarkers in Medicine ◽

10.2217/bmm-2019-0472 ◽

2020 ◽

Vol 14 (5) ◽

pp. 381-389

Author(s):

Shanshan Huang ◽

Xingxing Yu ◽

Haiqing Wang ◽

Jianlei Zheng

Keyword(s):

Ischemic Stroke ◽

Carotid Plaque ◽

Elevated Serum ◽

Area Under The Curve ◽

Plaque Burden ◽

Multivariable Logistic Regression Analysis ◽

Characteristic Analysis ◽

Plaque Score ◽

Carotid Calcification

Aim: To explore whether elevated serum sortilin was associated with calcified carotid plaque and ischemic stroke. Methods: A total of 171 patients with cardiovascular risk factors were enrolled. Ultrasonography was performed to evaluate calcified plaques and noncalcified plaques. Serum sortilin concentration was measured by ELISA. Results: Serum sortilin level was higher in patients with calcified carotid plaque and positively related to carotid plaque burden, but not with ischemic stroke during the follow-up. Multivariable logistic regression analysis revealed serum sortilin level was an independent determinant for calcified carotid plaque (p = 0.001). Receiving operating characteristic analysis showed an area under the curve of sortilin for carotid calcification was 0.759. Conclusion: Higher serum sortilin level was associated with carotid calcification and severe carotid plaque score.

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0342 Self-Silencing within Intimate Relationships, Sleep, and Subclinical Atherosclerosis in Midlife Women

SLEEP ◽

10.1093/sleep/zsaa056.339 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A129-A130

Author(s):

K P Jakubowski ◽

Y Chang ◽

E Barinas-Mitchell ◽

K A Matthews ◽

P M Maki ◽

...

Keyword(s):

Sleep Quality ◽

Carotid Plaque ◽

Subclinical Atherosclerosis ◽

Sleep Onset ◽

Sleep Time ◽

Physical Symptoms ◽

Midlife Women ◽

Poor Sleep ◽

Multinomial Regression ◽

Health Indices

Abstract Introduction Social relationships are important for health. In some relationships, women learn to self-silence, or to inhibit self-expression to avoid conflict or loss. Self-silencing is associated with reported psychiatric and physical symptoms, but no studies have examined whether self-silencing is related to worse sleep or cardiovascular (CV) health. We tested relationships of self-silencing to sleep and carotid plaque in midlife women; secondary analyses examined whether sleep mediated or moderated relationships between self-silencing and plaque. Methods In an ongoing community-based study of nonsmoking women, 304 women aged 40-60 were assessed at baseline; 157 of these women have been assessed 5 years later. At baseline, women reported on self-expression in their current/last intimate relationship via the Silencing the Self Scale. At both visits, women provided self-reports (demographics, medical history, CESD depression, PSQI sleep quality), physical measures, actigraphy (total sleep time [TST], wake after sleep onset [WASO], and efficiency), and carotid artery ultrasound to quantify plaque. Relationships of self-silencing and subscales to sleep (subjective and actigraphic sleep at baseline and averaged across visits) and carotid plaque (0, 1, ≥2) were tested in linear regression and multinomial regression models, respectively, adjusted for demographic and health indices, including depressive symptoms and snoring. Results At baseline, women (72% White) were on average 54 years old; 44% reported poor sleep quality, 46% had plaque (24% score ≥2), and average TST, WASO, and efficiency were 6.2 hrs, 46 min, and 84%, respectively. At baseline, self-silencing (particularly the tendency to judge oneself by external standards) was related to worse sleep quality (p=.001), but better actigraphic WASO (p=.02) and efficiency (p=.02). Self-silencing was related to worse average sleep quality across visits (p=.001). Self-silencing related to higher odds of baseline plaque ≥2 [OR(95% CI)=1.14 (1.02,1.28), p=.02], yet sleep did not explain or moderate this relationship. Conclusion Self-silencing was associated with worse subjective, but better actigraphic sleep at baseline, and with poorer sleep quality over 5 years. Self-silencing related to carotid atherosclerosis, yet sleep did not appear to impact this relationship. Emotional expression is relevant to midlife women’s sleep and CV health. Support R01HL105647, K24123565 (RCT); RF1AG053504 (RCT & PM); T32MH018269 (KPJ)

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Extreme Phenotype Approach Suggests Taste Transduction Pathway for Carotid Plaque in a Multi-Ethnic Cohort

Stroke ◽

10.1161/strokeaha.120.028979 ◽

2020 ◽

Vol 51 (9) ◽

pp. 2761-2769

Author(s):

Nicole D. Dueker ◽

Brett Doliner ◽

Hannah Gardener ◽

Chuanhui Dong ◽

Ashley Beecham ◽

...

Keyword(s):

Risk Factors ◽

Ethnic Groups ◽

Pathway Analysis ◽

Carotid Plaque ◽

Vascular Risk Factors ◽

Plaque Burden ◽

Vascular Risk ◽

Data Set ◽

Gene Set ◽

Genome Wide

Background and Purpose: Carotid plaque is a heritable trait and a strong predictor of vascular events. Several loci have been identified for carotid plaque, however, studies in minority populations are lacking. Within a multi-ethnic cohort, we have identified individuals with extreme total carotid plaque area (TCPA), that is, higher or lower TCPA than expected based on traditional vascular risk factors (age, sex, smoking, diabetes mellitus, hypertension, etc). We hypothesized that these individuals are enriched with genetic variants accounting for the plaque burden that cannot be explained by traditional vascular risk factors. Herein, we sought to identify the genetic basis for TCPA using the multi-ethnic cohort. Methods: Three hundred forty participants (170 from each extreme group) from 3 race/ethnic groups (53% Hispanic, 29% non-Hispanic Black, and 18% non-Hispanic White) were genotyped using a genome-wide single-nucleotide polymorphism (SNP) array and imputed using 1000Genome data. SNP-based analyses using logistic regression and gene-based analyses using VEGAS2 were performed within each race/ethnic group and then meta-analyzed. Genes with P <0.001 were included in an overrepresentation enrichment pathway analysis using WebGestalt. Promising findings were tested for association with ischemic stroke using the MEGASTROKE Consortium data set. Results: No SNP or gene reached genome-wide significance. In the pathway analysis, GO:0050913 (sensory perception of bitter taste) gene set was significantly enriched ( P =4.5×10 −6 , false discovery rate=0.04), which was confirmed in MEGASTROKE ( P =0.01). Within the GO:0050913 gene set, 3 genes were associated with extreme TCPA in our study ( P <0.001): TAS2R20 , TAS2R50 , and ITPR3 . In TAS2R50 , rs1376251 is the top SNP and has been associated with myocardial infarction by others. In ITPR3 , a SNP with high regulatory potential (rs3818527, RegulomeScore=1f), and ITPR3 itself were among the top SNP-based and gene-based results and showed consistent evidence for association in all ethnic groups ( P <0.05). Conclusions: Extreme TCPA analysis identified new candidate genes for carotid plaque in understudied populations.

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