Gray-scale Median Research Articles

Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia. Results: The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1). Conclusions: Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.

Efficacy of acupuncture in patients with carotid atherosclerosis: a randomized controlled clinical trial

BackgroundThe current clinical management of carotid atherosclerosis is based on the control of risk factors and medicine. However, the risk of adverse events associated with the medicine resulting in concerns and low medication compliance makes it necessary to seek a safer alternative therapy. This study assessed the effectiveness and safety of acupuncture as a treatment for carotid atherosclerosis.MethodsIn this randomized controlled trial, patients with carotid atherosclerotic plaques were included and randomly assigned (1:1) to receive real acupuncture or sham acupuncture for 12 weeks. The follow-up period was 12 weeks. The primary outcome included carotid intima-media thickness (cIMT), plaque score (PS), plaque volume (PV) and grey-scale median (GSM). Secondary outcome was pulse wave velocity (PWV). Adverse events results were recorded as safety outcomes.ResultsFrom January 2021 to February 2022, 60 eligible patients were included. 55 patients (91.7%) completed the intervention and the 12-week follow-up and there was no statistical difference in demographics between the groups. At the end of treatment, the real acupuncture group had significantly reduced PS (P = 0.002), PV (P = 0.000), and improved GSM (P = 0.044). There was no significant difference in the reduction in cIMT (Left cIMT: P = 0.338, Right cIMT: P = 0.204) and PWV between the groups (the left BS: P = 0.429; the left ES: P = 0.701; the right BS: P = 0.211; the right ES: P = 0.083). Three mild adverse reactions occurred during the study.ConclusionThis study found that acupuncture had a certain effect on reducing the thickness and volume of carotid plaque and improving the stability of plaque with minor side effects. These findings suggest that acupuncture may be a potential alternative therapy for carotid atherosclerosis.Trial registrationThis trial has been registered at ClinicalTrials.gov (ChiCTR2100041762). Submitted 30 December 2020, Registered 4 January 2021 Prospectively registered.

Carotid Artery Wall Echogenicity Measured by Gray Scale Median of the Intima-Media Complex From Childhood to Young Adulthood.

Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media complex (IM-GSM), is a novel subclinical atherosclerosis marker with lower values indicating greater lipid deposition. Our longitudinal study investigated IM-GSM from childhood to adulthood and its associated risk factors. A total of 240 participants from the Southern California CHS (Children's Health Study) underwent carotid artery ultrasounds in 2008 (mean age±SD): (11.2±0.6 years), and again around 2022 (24.2±1.6 years) to assess IM-GSM, carotid artery intima-media thickness, and carotid artery distensibility. Questionnaires and anthropometric and blood pressure measurements were completed by participants at both times. Mean and SD of IM-GSM were 108.2±24.6 in childhood and 75.6±15.8 in adulthood. Each 1-year increase in age was associated with -2.52 change in IM-GSM (95% CI, -2.76 to -2.27). Childhood and adulthood IM-GSMs were highly correlated (β=0.13 [95% CI, 0.05-0.22]). In childhood, Hispanic ethnicity, lower parental education levels and prenatal father smoking were significantly associated with lower IM-GSM. In adulthood, higher systolic blood pressure, carotid artery intima-media thickness, hypertension, and lower distensibility were significantly associated with lower IM-GSM. Weight status exhibited a consistent association with both childhood and adulthood IM-GSM. During the transition from childhood to adulthood, individuals who shifted from normal weight to overweight/obese or normal blood pressure to hypertension or experienced an increase in carotid artery intima-media thickness displayed lower levels of IM-GSM in adulthood. IM-GSM decreases with age. Maintaining healthy weight and blood pressure levels in children could potentially aid in preventing subclinical atherosclerosis.

Association Between Cardiovascular Health and Subclinical Atherosclerosis Among Young Adults Using the American Heart Association's "Life's Essential 8" Metrics.

This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults. This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 μm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10-6×m2/N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 μm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics. Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.

Gray-Scale Median in Patients with Symptomatic and Asymptomatic Carotid Atherosclerosis-Risk Factors and Diagnostic Potential.

The identification of clinical factors affecting the gray-scale median (GSM) and determination of GSM diagnostic utility for differentiating between symptomatic and asymptomatic internal carotid artery (ICA) stenosis. This study included 45 patients with asymptomatic and 40 patients with symptomatic ICA stenosis undergoing carotid endarterectomy (CEA). Echolucency of carotid plaque was determined using computerized techniques for the GSM analysis. Study groups were compared in terms of clinical risk factors, coexisting comorbidities, and used pharmacotherapy. Mean GSM values in the symptomatic group were significantly lower than in the asymptomatic group (p < 0.001). Both in the univariate as well as in the multiple regression analysis, GSM was significantly correlated with D-dimers and fasting plasma glucose levels and tended to correlate with β-adrenoceptor antagonist use in the symptomatic group. In asymptomatic patients, GSM was associated with the presence of grade 2 and grade 3 hypertension, and tended to correlate with the use of metformin, sulfonylureas, and statin. Independent factors for GSM in this group remained as grade 3 hypertension and statin's therapy. The receiver operating characteristic (ROC) analysis revealed that GSM differentiated symptomatic from asymptomatic ICA stenosis with sensitivity and specificity of 73% and 80%, respectively. The completely diverse clinical parameters may affect GSM in symptomatic and asymptomatic patients undergoing CEA, whose clinical characteristics were similar in terms of most of the compared parameters. GSM may be a clinically useful parameter for differentiating between symptomatic and asymptomatic ICA stenosis.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition

Circulating amyloid-beta 1–40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data.

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima-media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54-79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima-media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.

Echogenicity of atherosclerotic plaque - a criterion for assessing the dynamics and prognosis of cardiovascular diseases

Aim: to measure the echogenicity of atherosclerotic plaques (AP) of carotid arteries to assess the dynamics of atherosclerosis and risk of cardiovascular outcomes (CVO) in patients with different CVD risk.Materials and methods. The study included 223 patients: 80 patients (47 males) with moderate CVD risk (mean age: 53 years, range: 39-66) (Group 1) and 143 patients (123 males) with acute coronary syndrome (ACS) and high CVD risk (mean age: 57, range: 32-83) years (Group 2). All patients were examined at the Chazov National Medical Research Center of Cardiology. Patients underwent a standard clinical examination, biochemical blood test with lipid profile determination, and ultrasound duplex scanning. Patients with ACS were re-examined after 1-1.5 years and patients with moderate CVD risk were re-examined after 1 and 7 years.Results. We analyzed 181 APs in Group 1 and 378 APs in Group 2. Analysis of gray-scale median (GSM) at the first and second visit showed a significant increase in GSM in both groups: from 67.02 [54.13; 82.85] to 73.5 [59.5; 88.7] (p&lt;0.0001) in Group 1, and from 49.3 [39.73;63.64] to 50.7 [40.04;66.54] (p&lt;0.05) in Group 2. An increase in GSM was observed in 79% of patients in Group 1, in 53% of patients in Group 2. Unfavorable CVO (CVO+) developed after 7 years in 7 (8.8%) patients in Group 1, and after 1 year in 23 (23%) patients in Group 2. In Group 1, an increase in GSM was observed only in patients with favorable prognosis (CVO-): from 67.7[52.13; 79.0] to 77.5[64.12; 91.0] (n=148 AP, p&lt;0.05), in patients with CVO+, GSM increased non-significantly from 60.1[53.5; 66.5] to 66.5[55.0; 71.6] (n=18 AP, p=NS). In Group 2, a significant increase in GSM was observed in patients with CVO-: from 48.7[39.0; 63.4] to 51.3[40.0; 67.4] (n=141 AP, p&lt;0.01), in patients with CVO+, GSM decreased from 51.6[42.9; 72.5] to 50.2[40.4; 65.0] (n=43 AP, p=NS). In Group 2, GSM significantly increased by 2.75 (6.05%) from the initial value (p&lt;0.05) in patients with CVO-, while patients with CVO+ showed a significant decrease in the average GSM of AP by 3.33 (7.8%) (p&lt;0.05). Using ROC analysis, a Δ% GSM value of 6.96% was found (area under the curve 0.628 ± 0.0465 [95% CI 0.556 - 0.696], p = 0.0058). According to Cox regression analysis, the risk of CVO increased by 2.16 times with a decrease in GSM AP in the carotid arteries over time by ≥ 6.96% (НR=2.16; 95% CI=1.331 – 3.507); p=0.009.Conclusion. The ultrasound method of measuring the echogenicity of an atherosclerotic plaque of the carotid artery using GSM parameter can be effective for assessing the dynamics of atherosclerosis and prognosis of adverse cardiovascular events in patients with high and moderate CVD risk

Abstract P533: Association Between Cardiovascular Health and Carotid Arterial Ultrasound Markers Among Young Adults Using AHA’s “Life’s Essential 8” Metrics

Background: In 2022, the American Heart Association (AHA) published a new set of cardiovascular health (CVH) guidelines, named Life's Essential 8 (LE8), as an update to the AHA’s previous definition of ideal CVH, Life’s Simple 7 (LS7). This study used both LE8 and LS7 scores to investigate associations between CVH and carotid markers among young adults. Methods: This cross-sectional study included 240 young adults (age 24.2±1.6) who underwent a carotid ultrasound between 2018 to 2022. LE8 score was calculated from 8 metrics including four health factors (body mass index (BMI), non-high density lipid (non-HDL) levels, fasting glucose, and blood pressure), and four health behaviors (physical activity, dietary pattern, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better adherence to CVH guidelines. Carotid artery intima-media thickness (CIMT), arterial stiffness (CAS), and lipid deposition (determined by gray scale median, GSM) were evaluated by carotid ultrasound. Linear regression analyses were conducted to assess the association of LE8 and LS7 with carotid markers, adjusting for age, sex, race/ethnicity, and parents’ highest degree. Results: After adjusting for covariates, a one standard deviation (SD) increase in LE8 score was associated with 11.11μm lower CIMT (95% confidence interval[ CI] , -19.91 -2.30; p , 0.014), 1.20 (10 -6 xm 2 /N) greater distensibility (95% CI , 0.12 2.29; p 0.030), and 2.62 greater GSM (95% CI , 0.51 4.73; p 0.015). Analyses using LS7 score demonstrated consistent findings. Individual health factor metrics demonstrated stronger association with carotid markers, as compared to individual behavior metrics. One-SD increase in LE8 BMI score was associated with 19.37μm lower CIMT (95% CI , -27.66 -11.07; p &lt;0.001), 2.33 greater distensibility (95% CI , 1.31 3.35; p 0.001), and 6.10 greater GSM (95% CI, 4.18 8.03; p &lt;0.001). Similar trends were observed for LE8 scores for lipids and blood pressure with carotid measures. Conclusion: Greater adherence to CVH guidelines is associated with better carotid arterial health in young adults, evidenced by lower CIMT, less arterial stiffness, and less lipid deposition. LE8 and LS7 demonstrated comparable associations with carotid markers, with LE8 displaying a slightly stronger association with CIMT.

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

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

Carotid plaque characteristics in the CREST-2 trial

BackgroundThe modest stroke prevention from surgery for asymptomatic carotid disease has prompted a search for predictors that may improve risk stratification beyond luminal stenosis. Plaque disruption and atheroembolization are associated with unique anatomical and histological changes. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) collects information on duplex ultrasound (DUS) plaque biomarkers with the goal of evaluating their relationship to the periprocedural and long-term risks of stroke. In this study, we examine the reliability with which carotid plaque features can be measured from DUS images, and report baseline carotid DUS-derived stenosis and plaque features using semiautomated digital image analysis of patients enrolled in CREST-2. MethodsWe studied the first 503 patients in CREST-2. Patients underwent standardized carotid DUS evaluation pre-enrollment. B-Mode images were scaled linearly to normalize brightness. Plaques were outlined manually. Dedicated software automatically measured the longitudinal sectional area (mm2), grayscale median (GSM), Gray-Weale classification, and tissue composition (mm2) of intraplaque hemorrhage (IPH), lipid, fibrous tissue, muscle, and calcium. We present the mean, standard deviation, median, interquartile range, minimum and maximum range, and proportions of carotid peak systolic velocities (PSVs) and plaque morphological features. We tested for autocorrelation among plaque features and computed the proportion of potentially unstable plaques in the cohort. Reliability of the image analysis techniques was tested in 100 patients using Bland-Altman plots and intraclass and interclass correlation coefficients. ResultsMost patients were male (58.4%), older (mean age of 69.3 years), White (87.5%), and had a PSV of ≥230 cm/s (98.6%); the 1.4% with a PSV of <230 cm/s were enrolled based on catheter angiography. Plaques in this study were large; the mean longitudinal sectional area was 62 ± 37 mm2 (range, 6.2–256.5 mm2). The mean GSM was 58 ± 30 (unitless) (range, 0–168) and Gray-Weale classification was 3.5 ± 0.9 (range, 1–5). The mean areas of tissue types were IPH 5.3 ± 8.9 mm2, lipid 9.3 ± 8.6 mm2, fibrous tissue 10 ± 10 mm2, muscle 17 ± 12 mm2, and calcium 1.6 ± 4.1 mm2. The PSV of patients showed poor correlation with plaque features. The proportion of plaques with a GSM of ≤35 was 22.8%, IPH of ≥5 mm2 was 30.0%, and a lipid-rich necrotic core of ≥40% was 3.0% of the cohort. Plaque measurements could be performed with high reliability with good interobserver and intraobserver correlations. ConclusionsSite-generated, core laboratory-interpreted ultrasound examination provides a reliable way of characterizing carotid plaque morphological features across studies performed at many CREST-2 sites. The initial cohort of patients randomized in CREST-2 had heterogeneity of plaque features despite causing high-grade stenosis. Completion of the trial will provide an opportunity to assess whether plaque heterogeneity interacts with response to revascularization and medical management.

Qualitative and quantitative ultrasound parameters of carotid atherosclerotic plaques in patients with moderate cardiovascular risk according to the SCORE scale: 7-year prospective follow-up study

Aim. To assess asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk over a 7-year prospective follow-up using non-invasive ultrasound markers.Material and methods. Eighty patients (47 men and 33 women) aged 53,1±5,9 years with moderate Systematic Coronary Risk Evaluation (SCORE) level, low-density lipoprotein cholesterol (LDL-C) of 2,7-4,8 mmol/l and asymptomatic hemodynamically insignificant (stenosis &lt;50%) carotid atherosclerosis (CA). Patients underwent CA ultrasound (PHILIPS IU22) at baseline and after 7 years. Plaque number, maximum plaque height, total plaque height, total CA stenosis, visual plaque morphology, gray-scale median (GSM), and intima- media thickness of the right and left common CAs were assessed. All patients were prescribed atorvastatin therapy at a dose of 10-40 mg until a target LDL-С level &lt;2,6 mmol/l was achieved.Results. During the follow-up period, a significant increase was noted in the number of plaques, the maximum and total plaque height, total CA stenosis, and intima- media thickness of the right and left common CAs. An increase in GSM was detected in 79% of plaques on statin therapy. Plaque echoicity increased by 4,90 [0,51; 17,41] (p &lt;0,001) or 7,2% [0,7%; 29%] (p&lt;0,001) over seven years. Regression analysis adjusted for sex and age showed the dependence of GSM changes (ΔGSM) on changes in the LDL-C level (ΔLDL-C) (p=0,049). With a decrease in LDL-C by 1 mmol/l, an increase in average GSM was noted by 5,9 (0,03-11,78). The maximum plaque height increased significantly after 7-year follow-up from 1,80 [1,50; 2,20] to 2,00 [1,63; 2,68] mm (p=0,044). In patients who reached a LDL-C level of 1,8 mmol/l, the maximum plaque height decreased more than in patients who did not reach this level (-0,07 [-0,45; 0,14] mm and 0,20 [-0,05; 0,40] mm, respectively (p=0,028)). Regression analysis adjusted for sex and age did not reveal a relationship between the change of maximum plaque height with ΔLDL-C and Δhigh-density lipoprotein cholesterol, but with LDL-C level after 7 years.Conclusion. Statin therapy in patients with CA stenosis &lt;50% stabilizes the plaques due to echogenicity increase. LDL-C &lt;1,8 mmol/l can lead to a decrease in maximum plaque height.

Plasma levels of amyloid beta 1-40 are associated with ultrasonographic morphological characteristics related with carotid plaque vulnerability in individuals without cardiovascular disease

Abstract Background Amyloid-beta (1-40) (Αb40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical atherosclerotic cardiovascular disease (ASCVD) and with major adverse cardiac events in both primary and secondary prevention settings conferring additive and reclassification value over traditional risk factors and risk scores. This evidence supports the hypothesis that Ab40 could be a biomarker of ASCVD. However, mechanistic data on the association of Αb40 with in vivo morphological characteristics of atherosclerosis related with plaque vulnerability are not available. Purpose To examine the association of Ab40 levels with characteristics of the carotid artery wall in the general population. Methods In the settings of the Athens Vascular registry, subjects without clinically overt ASCVD were consecutively recruited (n=301). Subclinical carotid atherosclerosis was assessed by ultrasonography and the images were subsequently analyzed using a dedicated software (AMS v3.03). The sum and maximal area of atherosclerotic plaques (PLQ) and the minimum echogenicity using grey scale median (GSM) of intima-media thickness (IMT, IMT_GSM) and atherosclerotic plaques (PLQ_GSM) were used as the main endpoints of the analysis. Αb40 was measured in plasma samples. Results Subjects with Ab40 levels in the highest tertile had higher prevalence of male sex, presence of carotid plaque atherosclerosis, higher sum and maximal PLQ are and lower GFR HDL-C levels and lower PLQ_GSM (p&amp;lt;0.05 for all). Ab40 in the highest vs. lower tertile was associated with higher sum and maximal plaque area (b-coefficient= 22.9 95% CI: 0.72, 45.1, p=0.43 and b-coefficient= 10.5 95% CI: 1.77, 19.3, p=0.019, for sum and maximal plaque area, respectively) after adjustment for traditional cardiovascular risk factors and GFR (core model). Moreover, Ab40 in the highest tertile was associated with decreased GSM of both IMT and PLQ in the carotid arteries (b-coefficient= -6.0 95% CI: -9.6, -2.36, p=0.001, for IMT and b-coefficient= -8.66 95% CI: -16.5, -0.79, p=0.31, for PLQ) after adjustment for the core model. Conclusion In individuals without clinically overt ASCVD, higher levels of Ab40 are associated with the larger atherosclerotic burden and with ultrasonographic characteristics related to higher plaque vulnerability. These findings suggest a mechanistic background for the established association of Ab40 with major adverse cardiovascular events.

Abstract 15400: Association of Cardiovascular Health With Early Carotid Artery Changes in Young Adults From Disadvantaged Social Backgrounds: The Future of Families and Child Wellbeing Study (FFCWS)

Introduction: Associations of cardiovascular health (CVH), as measured by the AHA’s Life’s Essential 8 (LE8) score, with early markers of arterial injury have not been described in young adults. Methods: The FFCWS enrolled 4898 mother-baby dyads at delivery in 20 US cities in 1998-2000, oversampling mothers who were unmarried, including a disproportionate number of minority and low-income families. In 2021-23, offspring were invited to attend an in-person exam to measure CVH and perform carotid artery ultrasound. Individual CVH metric and overall LE8 scores (except sleep) were calculated for each participant (ppt). Carotid imaging was performed by 2 trained sonographers and images were analyzed by a core lab. We examined cross-sectional associations of LE8 scores with measures of carotid intima-media thickness (IMT), gray scale (a measure of early arterial injury), and distensibility, using linear regression. Results: Among 1211 offspring ppts, mean age was 22y, &gt;50% self-identified as female, and &gt;75% as Black or Hispanic. Black and Hispanic ppts had lower, and ppts from Other racial/ethnic groups had higher, overall LE8 scores compared with White ppts (all P≤0.01; Table 1A). In unadjusted analyses, Black ppts had thicker carotid IMT and lower Young’s elastic modulus measures. Prevalence of diagnostic plaque was low. In analyses adjusted for age, sex, and race/ethnicity (Table 1B), LE8 scores were significantly associated with lower carotid IMT, higher gray scale median, and lower Young’s elastic modulus. For example, for each 10 point higher (better) LE8 score, mean-maximal carotid IMT was lower by 0.008 mm. Conclusions: Among young adults largely from disadvantaged social backgrounds, the LE8 score was associated with early measures of carotid arterial injury. LE8 may be an important surrogate measure for monitoring long-term CVH and may help identify young adults with emerging subclinical disease and higher long-term cardiovascular risk.

Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes

Aims/hypothesisPrevious studies have suggested that glucose variability may accelerate atherosclerosis progression in people with type 2 diabetes. Current guidelines recommend assessing glycaemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycaemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and atherosclerosis progression is not entirely clear.MethodsThis exploratory study used baseline data and data obtained after 104 weeks from an ongoing prospective, multicentre, observational study. Six hundred study participants with type 2 diabetes and no apparent history of symptomatic cardiovascular disease underwent CGM and ultrasonographic atherosclerosis measurements of the carotid arteries, including the intima–media thickness (IMT) and grey-scale median (GSM), at baseline and 104 weeks. Non-invasive ultrasonic tissue characterisation of the carotid artery wall or plaque using the GSM reflects vascular composition. Multivariate regression models were used to analyse the association between CGM-derived indices, mainly time in range (TIR) and CV, and changes in carotid atherosclerosis index values.ResultsOver the 104-week study period, there were modest increases in mean IMT (from 0.759±0.153 to 0.773±0.152 mm, p<0.001) and thickened-lesion GSM (from 43.5±19.5 to 53.9±23.5 units, p<0.001), but no significant changes in common carotid artery maximum-IMT (from 1.109±0.442 to 1.116±0.469 mm, p=0.453) or mean GSM (from 48.7±19.3 to 49.8±20.8 units, p=0.092). In a linear regression model with adjustment for possible atherosclerotic risk factors, including HbA1c, TIR and CV at baseline were significantly associated with the annual change in mean GSM (regression coefficient per 10% increase in TIR 0.52; 95% CI 0.06, 0.98; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV −0.12; 95% CI −0.22, −0.02; Hochberg-adjusted p value 0.038). TIR and CV at baseline were also significantly associated with the annual change in thickened-lesion GSM (regression coefficient per 10% increase in TIR 0.95; 95% CI 0.12, 1.79; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV −0.19; 95% CI −0.36, −0.01; Hochberg-adjusted p value 0.038). Participants who achieved target CGM-derived metrics at baseline, as proposed by an international consensus, showed significant annual changes in mean GSM compared with those who did not (0.94±6.88 vs −0.21±6.19 units/year, p=0.007).Conclusions/interpretationTIR and CV were significantly associated with changes in the tissue characteristics of the carotid artery wall.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, number UMIN000032325Graphical

Novel Biomarkers and Imaging Indices for the "Vulnerable Patient" with Carotid Stenosis: A Single-Center Study.

We investigated the relationship of matrix metalloproteinases (MMPs), cardio-ankle vascular index (CAVI), and Gray-Scale Median (GSM) score with the severity and vulnerability of carotid atherosclerosis and major adverse cardiovascular events (MACE) during follow-up of carotid artery revascularization. We enrolled 262 patients undergoing carotid revascularization therapy (GRT), 109 asymptomatic patients with low-grade carotid stenosis (40-70%) receiving conservative treatment (GCT), and 92 age- and sex-matched control subjects without carotid atherosclerosis (GCO). All participants underwent carotid ultrasound and we assessed at baseline clinical parameters, metabolic profile, CAVI, GSM, and circulating levels of hsCRP, MMP-3,-7,-9, and TIMP-1. Both GRT and GCT presented with elevated CAVI, MMPs, and TIMP-1 levels compared to GCO (p < 0.001). The escalation highly correlated to the presence of symptoms or paralleled the degree of carotid stenosis (p < 0.001). During follow-up (mean duration: 55 months), 51 GRT patients experienced MACE unrelated to the revascularization procedure. Within GRT, diabetes (HR: 2.07; CI: 1.55-2.78, p < 0.001), smoking (HR: 1.67; CI: 1.35-1.95, p < 0.001), high CAVI (HR: 1.22; CI: 1.09-1.43, p = 0.023) and MMP-9 (HR: 1.44; CI: 1.29-2.15, p = 0.005), and low GSM (HR: 1.40; CI: 1.16-2.12, p = 0.002) independently predicted MACE occurrences, despite the optimum medical therapy. Novel imaging and biochemical biomarkers were positively associated with atherosclerosis severity, while CAVI, MMP-9, and low GSM showed a positive, independent relationship with MACE after carotid revascularization, describing "vulnerable patients".

Serum sLOX-1 levels negatively correlate with gray-scale median (GSM) scoring in patients undergoing carotid endarterectomy

Serum sLOX-1 levels negatively correlate with gray-scale median (GSM) scoring in patients undergoing carotid endarterectomy

Circulating obesity-induced MCP-1 affects gray-scale median (GSM) scoring in patients undergoing carotid endarterectomy

Circulating obesity-induced MCP-1 affects gray-scale median (GSM) scoring in patients undergoing carotid endarterectomy

Serum Uric Acid Levels Are Associated with the Echogenic Features of Carotid Plaque Vulnerability in Elderly Patients with Atherosclerotic Disease.

Uric acid is a marker of inflammation and a risk factor for atherosclerosis that has been suggested to play a role in carotid plaque instability. Reduced atherosclerotic plaque echogenicity at ultrasound examination is associated with alarming histopathological features and inflammation. In this study, we investigated the relationship between serum uric acid (SUA) levels and echogenic patterns of plaque instability in elderly subjects with carotid atherosclerosis. Since uric acid metabolism largely depends on renal function, SUA levels were indexed for serum creatinine levels (SUA/SCr). We enrolled 108 patients aged 65 years or more (72.7 ± 5.9 years; 50 females and 58 males) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by greyscale median (GSM). The regression analysis demonstrated a significant inverse association between the GSM and the SUA/SCr ratio (β: -0.567; 95% CI -0.751 to -0.384 and p < 0.0001). Stepwise multivariate regression showed that the SUA/SCr ratio explained 30.3% of GSM variability (β: -0.600; 95% CI -0.777/-0.424, p < 0.0001, and semi-partial correlation 0.303). After a mean period of 3.5 ± 0.5 years, 48 patients were reevaluated according to the same baseline study protocol. The regression analysis demonstrated a still significant inverse association between the GSM and the SUA/SCr ratio (β: -0.462; 95% CI -0.745 to -0.178 and p = 0.002). Stepwise multivariate regression showed that the SUA/SCr ratio explained 28.0% of GSM variability (coefficient -0.584, 95% CI -0.848/-0.319, p < 0.0001, and semi-partial R2 0.280). In conclusion, this study demonstrates that SUA levels indexed for serum creatinine are associated with the echogenic features of carotid plaque vulnerability in elderly patients with atherosclerotic disease. These data could suggest an influential role for uric acid metabolism in carotid plaque biology.

Enhanced Carotid Plaque Echolucency Is Associated with Reduced Cognitive Performance in Elderly Patients with Atherosclerotic Disease Independently on Metabolic Profile.

Vulnerable carotid atherosclerotic plaques are related to an increased risk of cognitive impairment and dementia in advanced age. In this study, we investigated the relationship between the echogenicity of carotid plaques and cognitive performance in patients with asymptomatic carotid atherosclerotic plaques. We enrolled 113 patients aged 65 years or more (72.4 ± 5.9 years) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by grey-scale median (GSM) and neuropsychological tests to assess cognitive function. The GSM values at baseline were inversely correlated with the number of seconds required to complete Trail Makin Test (TMT) A (rho: -0.442; p < 0.0001), TMT B (rho: -0.460; p < 0.0001) and TMT B-A (rho: -0.333; p < 0.0001) and directly correlated with Mini Mental State Examination (MMSE) and Verbal Fluency Test (VFT) score (rho: 0.217; p = 0.021 and rho: 0.375; p < 0.0001, respectively) and the composite cognitive z-score (rho: 0.464; p < 0.0001). After a mean period of 3.5 ± 0.5 years, 55 patients were reevaluated according to the same baseline study protocol. Patients with baseline GSM value higher than the median value of 29 did not show any significant variation in the z-score. Instead, those with GSM ≤ 29 showed a significant worsening of z-score (-1.2; p = 0.0258). In conclusion, this study demonstrates the existence of an inverse relationship between the echolucency of carotid plaques and cognitive function in elderly patients with atherosclerotic carotid disease. These data suggest that the assessment of plaque echogenicity if used appropriately, might aid in identifying subjects at increased risk for cognitive dysfunction.