This study examines the relationship between carotid intima-media thickness (CIMT), carotid artery wall strain indices measured via ultrasound, and their associations with cardiovascular disease (CVD) risk factors in a low CVD risk population.

Eighty healthy volunteers (median age 35 y, 50% female) underwent carotid ultrasound imaging for CIMT and strain indices. Participants' clinical data, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, hemoglobin A1c, systolic blood pressure (SBP), diastolic blood pressure, body mass index and smoking status, were collected. Spearman Rho correlations assessed relationships between CIMT and strain indices. Multiple linear regression examined associations between strain indices and CVD risk factors, while Mann-Whitney U tests compared median differences between sexes. Statistical analyses were performed using SPSS.

No significant associations were seen between CIMT measurements and strain parameters. After adjustment for CVD risk factors, several strain indices were significantly associated with CVD risk factors. Age was inversely related to all strain parameters. SBP was significantly positively related to axial and shear strain. Hemoglobin A1c was significantly inversely related to most axial and shear strain (all p values <0.05). These relationships are consistent with previous findings in the literature. We also found that BMI was positively related to all strain parameters, which may be due to increased compliance with more gradual arterial remodeling.

Strain parameters remained significantly related to several CVD risk factors in fully adjusted models. All strain parameters are associated with age. Axial and shear parameters are associated with SBP and hemoglobin A1c. These findings suggest that strain measures may represent early mechanical changes in the arterial wall and have potential for use as a research tool to characterize arterial health.

Prevalence of cardiovascular diseases (CVDs) and depression is rising globally. Their co-occurrence associates with poorer outcomes, potentially due to shared metabolic pathways. This study aimed to identify metabolic pathways linking depression symptoms and CVD risk factors.

Data from the Young Finns Study (YFS, n = 1,599, mean age 37 ± 5, 54% female) served as input for a network (mixed graphical models). Confirmatory analysis through covariate-adjusted regression was done with UK Biobank (UKB, n = 69,513, mean age 63 ± 7, 64% female). Mendelian randomization assessed causality using genome-wide association studies data. The study examined 52 plasma metabolites measured by nuclear magnetic resonance spectroscopy. Outcomes included depression symptoms (BDI in YFS, PHQ-9 in UKB) and CVD risk factors [systolic/diastolic blood pressure, carotid intima-media thickness (cIMT)]. Mendelian randomization inferred causal links between metabolites and depression or (intermediate markers of) CVD. Two bridge metabolites were identified: glucose linked to sleep pattern (P = 0.034); omega-3 fatty acids (FAs) linked to appetite change (P < 0.001); and both connected to cIMT (both P = 0.002). Mendelian randomization suggested glucose as causal in coronary artery disease (CAD) risk, while omega-3 FAs showed potential causal links to CAD, coronary artery calcification, and cIMT.

This study integrated three statistical techniques and identified two metabolic markers (glucose, omega-3 FAs) connecting depression and CVD on a symptom and risk factor level. The associations, established in a relatively young cohort, were replicated in a predominantly middle-aged cohort and emphasize both the generalizability of the findings across different populations and value of symptom-level analysis in depression and CVD comorbidity research.

Pathogenic mechanisms involved in arterial hypertension (HT) promote the atherosclerosis development. Fatty acids (FAs) could modulate these processes. We investigated the association between dietary and serum FAs and early atherosclerosis development and their correlation with serum vascular inflammation markers in HT.

96 patients were included. Dietary information was collected through a validated food frequency questionnaire. Serum FAs were detected by gas chromatography. High-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6) and fibrinogen serum were determined by immunoturbidimetry, enzyme immunoassay and Clauss method, respectively. Carotid intima media-thickness (cIMT) was determined by ultrasound. Multivariate linear regression models were applied.

Patients showed an adverse health profile, with high caloric intake (3113 ± 1477 kcal/day), LDL cholesterol (126.0 ± 35.1 mg/dL), and overweight (BMI 31.1 ± 5.5 kg/t2), and also an inflam-matory process, characterised by higher hs-CRP (3.9 ± 2.7 mg/L) and fibrinogen (433.4 ± 84.6 mg/dL) concentrations. We found significant inverse correlations between dietary monounsaturated FAs (MUFAs), serum omega-3 polyunsaturated FAs (n-3 PUFAs), and hs-CRP (β = -3.59, [95% CI -6.87 to -0.32], p = 0.03 and β = -0.70, [95% CI -1.42-0.01], p = 0.05, respectively), significant positive associations between dietary MUFAs, serum saturated FAs (SFAs) and cIMT (β = 81.96, [95% CI 33.42-130.50], p = 0.002 and β = 36.71, [95% CI 6.34-67.08], p = 0.02, respectively), and significant inverse correlations between serum omega-6 polyunsaturated FAs (n-6 PUFAs) and cIMT (β = -91.44, [95% CI -168.01 to -14.88], p = 0.02 and β = -41.01, [95% CI -70.73-11.28], p = 0.01).

Serum n-3 PUFAs modulate hs-CRP levels, while n-6 PUFAs suggest antiatherosclerotic properties in HT. The ambiguous impact of MUFAs requires comprehensive research.

Black Americans suffer from disproportionately high rates of cardiovascular disease (CVD). Psychosocial stress contributes to this disparity. Previous studies reported that the Transcendental Meditation (TM) technique reduced CVD risk factors, surrogate endpoints, and clinical events in high-risk populations. However, no study has evaluated the effects of stress reduction with meditation on surrogate CVD markers such as carotid intima-media thickness (cIMT) along with CVD clinical events. Therefore, this randomized clinical trial evaluated the long-term effects of meditation and health education (HE) on cIMT and CVD events in high-risk Black adults.

Participants were Black women and men with CVD or at high risk who were randomized to either TM or HE. The primary outcome was a change in cIMT measured using B-mode ultrasound at baseline and 12 months. The main secondary outcome was major adverse cardiovascular events (MACE) at 5 years (maximum) of follow-up. Other secondary outcomes were MACE at 1 and 10 years of follow-up, blood pressure, and serum lipids after 1 year. Exploratory variables were a comparison of cIMT changes to historical controls and MACE after 14 years.

There were 197 randomized participants, of whom 136 completed posttest for cIMT. After 1 year, the TM and HE groups showed average cIMT changes of -0.0004 and -0.0003 mm, respectively, with no significant difference between the groups. Additionally, there were no significant differences between the groups in lipid levels or BP. However, both TM and HE groups showed prevention of progression of cIMT compared to historical controls at 12 months. In the survival analysis of MACE, there was a 65% relative risk reduction in the TM group after 5 (maximum) years of follow-up (HR = 0.346; 95% CI = 0.134-0.893; p = 0.017). At 1 and 10 years of follow-up, there were significant risk reductions in the TM vs. HE group, which was not significant at 14 years (all yearly maximums).

Both treatment groups demonstrated prevention of progression of cIMT over 12 months compared to historical controls. However, the TM group showed a relative risk reduction for MACE of 65% at 5 years. Therefore, as a lifestyle modification method, TM may be useful in the secondary prevention of CVD in this and possibly other high-risk groups.

ClinicalTrials.gov, NCT05642936.

Uric acid (UA), fibrinogen (FIB), and homocysteine (Hcy) are the main contributors to cardiovascular and cerebrovascular diseases, and are related to hypertension. Hypertension plays a role in atherosclerosis (CAS). We hence explored the correlations of UA, FIB, and Hcy levels with CAS in hypertensive patients.

Totally 170 hypertensive patients were retrospectively included and assigned into the Non-sclerosis, Thickened, and Plaque groups based on carotid intima-media thickness (cIMT), with serum UA, FIB, and Hcy compared. Correlations of UA, FIB, and Hcy with cIMT and carotid atherosclerotic plaque (CAP) were assessed using Spearman's correlation analysis. The risk factors of CAS were evaluated by logistic multivariate regression analysis. The predictive value of UA, FIB, and Hcy for CAS was estimated by the receiver operating characteristic (ROC) curve.

UA, FIB, and Hcy were up-regulated in the Plaque group vs. other two groups. Serum UA, FIB, and Hcy were positively linked to cIMT and CAP, and were independent risk factors for CAS. The area under ROC curve of UA, FIB, Hcy levels and their combination for predicting CAS were 0.889, 0.855, 0.902, and 0.958, respectively. Hypertensive patients with high levels of UA, FIB, or Hcy were more likely to develop CAS.

Serum UA, FIB, and Hcy are positively correlated with cIMT and CAP, and are independent risk factors for CAS in hypertensive patients. High UA, FIB and Hcy expression could assist in predicting CAS in patients with hypertension, and the combination of the three was more valuable than all three alone.

This study aimed to investigate the association between these Blood pressure (BP) components examined in this study, including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP), with the presence of multiple carotid plaques in a low-income rural Chinese population.

This population-based cross-sectional study was conducted from April 2014 to January 2015, involving participants from the Tianjin Brain Study. Participants aged 45 years and older with diagnosed carotid plaques were included. Data on demographics, medical history, and lifestyle factors were collected through interviews and existing records. Blood pressure measurements were taken in a quiet room, following the standard procedures recommended by the American Hypertension Association (AHA), and ultrasonographic examinations were performed to identify and quantify carotid plaques. Multivariate logistic regression model was used to explore the association between blood pressure components and multiple plaques. The blood pressure component with a positive univariate analysis was included in different models, each adjusted for age, sex, body mass index (BMI), and the ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C).

The study found that 41.8% of participants had multiple carotid plaques, with a higher prevalence in men compared to women. Multivariate logistic regression analysis revealed that each 1-mmHg increase in systolic BP (SBP) was associated with a 0.9% increase in the prevalence of multiple carotid plaques (OR = 1.009; 95% CI 1.004-1.014; P < 0.001). Each 1-mmHg increase in pulse pressure (PP) was associated with a 1.2% increase (OR = 1.012; 95% CI 1.006-1.018; P < 0.001), and each 1-mmHg increase in mean arterial pressure (MAP) was associated with a 1.1% increase (OR = 1.011; 95% CI 1.003-1.019; P = 0.005). Participants with a history of hypertension had a significantly higher prevalence of multiple carotid plaques compared to normotensive individuals. Notably, grade 2 hypertension showed a significant association with multiple carotid plaques (OR = 1.554; 95% CI 1.135-2.127; P = 0.006). In addition, male sex, older age, and low BMI were all associated with a higher risk of multiple carotid plaques (P all< 0.05).

This study provides critical evidence on the relationship between BP components and multiple carotid plaques, with significant implications for patients, physicians, and society. By prioritizing BP management, particularly focusing on PP, which demonstrates the strongest association with carotid plaques, as well as targeting higher-risk populations such as males, older individuals, and those with low BMI, preventive measures against carotid atherosclerosis can be enhanced. This will ultimately contribute to better cardiovascular health outcomes and reduce the societal burden of stroke and related diseases.

Higher-order relationships are a central concept in the science of complex systems. A popular method of attempting to estimate the higher-order relationships of synergy and redundancy from data is through the O-information. It is an information-theoretic measure composed of Shannon entropy terms that quantifies the balance between redundancy and synergy in a system. However, bias is not yet taken into account in the estimation of the O-information of discrete variables. In this paper, we explain where this bias comes from and explore it for fully synergistic, fully redundant, and fully independent simulated systems of n=3 variables. Specifically, we explore how the sample size and number of bins affect the bias in the O-information estimation. The main finding is that the O-information of independent systems is severely biased towards synergy if the sample size is smaller than the number of jointly possible observations. This could mean that triplets identified as highly synergistic may in fact be close to independent. A bias approximation based on the Miller-Maddow method is derived for the O-information. We find that for systems of n=3 variables the bias approximation can partially correct for the bias. However, simulations of fully independent systems are still required as null models to provide a benchmark of the bias of the O-information.

Carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, has been found to be associated with incident stroke. High-sensitivity C-reactive protein (CRP) and fibrinogen have been demonstrated to be associated with atherosclerosis. Previous studies on heritability estimates of IMT, CRP, and fibrinogen among Chinese populations are limited. This study aims to estimate the heritability of these risk factors in residents who participated in the Taichung Community Health Study (TCHS) and their family members. A total of 2671 study subjects from 805 families were enrolled in the study, selected from a random sample of TCHS participants and their family members. CRP, and fibrinogen were obtained from each participant, and a questionnaire interview was conducted. cIMT was measured by high-resolution B-mode ultrasound and expressed as the mean of the maximum. Heritability estimates and the familial correlation of cIMT, CRP, and fibrinogen among family pairs were determined with SAGE software. With multivariate adjustments, significant heritability was found for cIMT (h2 = 0.26, P < 0.001), CRP (h2 = 0.34, P < 0.001), and fibrinogen (h2 = 0.48, P < 0.001). The intrafamilial correlation coefficients for the three indexes in the parent-offspring pairs were significant (P < 0.001) and ranged from 0.17 to 0.41. The full sibship correlations were also significant (P < 0.001) for the three indexes and ranged from 0.19 to 0.47. This study indicates that a moderate proportion of the variability in CRP, fibrinogen, and cIMT can be attributed to genetic factors in Chinese populations. The findings suggest that CRP is associated with cIMT, whereas no significant association exists between fibrinogen and cIMT.

Carotid intima-media thickness (IMT) measurement is used to assess subclinical atherosclerosis. We aimed to examine the association between the maximum IMT by location and the occurrence of silent brain infarction (SBI).

Overall, 280 Japanese individuals (92 females, 52.6±5 years old) underwent a medical check-up at our hospital in Tokyo in 2015. Carotid IMT was measured at each site on ultrasound images (common carotid artery [CCA], internal carotid artery, or bifurcation). The risk factors for arterial dysfunction were evaluated. SBI was assessed using magnetic resonance imaging (MRI). The cross-sectional relationship between carotid maximum IMT and SBI was evaluated.

Of the 280 individuals, 18 (6.4%) were diagnosed with SBI on MRI. The mean age of the SBI(-) and SBI(+) groups was 51.9±10.6 and 63.6±18.6 years, respectively. The correlation coefficients between the carotid maximum IMT at each location were very weak (correlation coefficient range: 0.180-0.253). The percentage of participants with SBI increased significantly with increasing maximum CCA and bIMT values. After adjusting for confounders, SBI was found to be significantly associated with the maximum bIMT (per 0.1-mm increase) (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI]: 1.03-1.17). When bIMT was categorized according to three groups (＜1.0 mm, 1.0-＜2.0 mm, and ≥ 2.0 mm), a significant SBI risk was also observed with an increase by each category of bIMT (aOR: 3.96, 95% CI: 1.63-9.52, P=0.002).

The maximum bIMT was found to be the main determinant of SBI. A significant SBI risk was associated with an increase in each category of the maximum bIMT. Therefore, the maximum bIMT might be a useful predictor of future stroke in Japanese stroke-free medical check-up participants.

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.

Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives.

We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD = 16, control relatives = 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD = 21, control relatives = 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances.

Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p = 0.1333) despite elevated low-density lipoprotein cholesterol levels.

The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives.

This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.

Hemodialysis (HD) patients present an increased carotid intima-media thickness (CIMT) and calcified plaques, and studies have demonstrated that CIMT is predictor for cardiovascular death in this patient population; hence, the importance of identifying early non-invasive markers of atherosclerosis. We aim to propose a new three-perspective CIMT measuring method in HD population, and to further investigate the possible use and value of this method to predict outcomes.

A cross-sectional study was conducted, the CIMT was measured with duplex ultrasound during the perioperative access planning. Software provided maximum CIMT in a 10 mm (mm) width of the common carotid artery. CIMT was measured in Right (R) and Left (L) carotid arteries, both in anterior (a), lateral (l), and posterior (p) view. The sum of these values (Ra+Rl+Rp+La+Ll+Lp) was completed and termed as Sixth Carotid Intimal (SCI) score. We stratified either in low (summation <4) or high (>=4) SCI score groups. Demographics, patency rates, complications, and mortality were collected; chi-square test was used for our analysis.

A total of 30 patients (mean age 49 years and 56% females) that underwent access creation in the upper arm from 2010 to 2016 were selected and studied. A low SCI score was found 19 patients and 11 had high SCI, no significant difference was observed in demographics, history cardiovascular disease, and clinical outcomes as early thrombosis, and primary, primary-assisted patency at 12 months. Interestingly, during the follow up period of 36 months a significant higher difference in late thrombosis rates occurred (63.6% vs 26.3%, p = .044) and a higher all-cause mortality (54.4% vs 15.7%, p = .025) in patients with SCI score group above 4.

The SCI score method, might offer a screening tool for traditional cardiovascular risk factors in HD patients. In this study, we demonstrate an increased rate in late thrombosis and mortality in those with high SCI. Further research is necessary to better define the role of CIMT in vascular surgical procedures.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.

Atherosclerosis progression is possible in subjects with limited alteration of body weight, lipid profile, and oxidative stress. The ultrasound carotid thickness (IMT) and arterial wall modification (granulation and bubbles) are evident signs of the disease. Intestinal fats absorption shifting (IFAS) is expected to prevent or reduce the arterial damage. The aim of the registry was to evaluate the effects of a mild diet in association with lifestyle modifications (standard management [SM]) and SM+ a polyglucosamine biopolymer (BP) shifting the intestinal absorption of dietary fats.

The present is a two-year registry comparing two groups of otherwise healthy subjects, respectively 150 (SM) and 144 (SM+BP). BP was administered at the dosage of 3g/day. IMT and relative arterial damages were measured together with lipid profile, oxidative stress, anthropometric and vital measures.

The two groups at the baseline were comparable for all variables: 8 cases of drop out were found limited to SM. Compliance with BP was optimal (>97%) and no side effect were observed. IMT showed a significant decrease in thickness (P<0.05) using BP+SM, while increased in SM group. Intimal granulations and lipid wall bubbles were also significantly decreased with BP in comparison to SM only (P<0.05). BMI significantly decreased with BP (P<0.05) as well as BW, fat mass, lipid profile and oxidative stress in comparison to SM only. A positive variation in blood pressure and heart rate (P<0.05) was also observed.

BP allows IFAS to improve early subclinical arterial lesions that tend to progress to plaques and clinical events. The long-term and safe treatment of BP is effective on IMT, lipids, BW, and early lesions of the arterial wall structure in subjects with subclinical conditions. BP also reduces oxidative stress which contributes to lipid oxidation and deposition into the arterial wall layer in areas of high dynamic stress (arterial bifurcations).

Cognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear.

We investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity.

Carotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease.

People with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment.

This multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

United States South Asians constitute a fast-growing ethnic group with high prevalence of type 2 diabetes (T2D) despite lower mean BMI and other traditional risk factors compared to other races/ethnicities. Bilirubin has gained attention as a potential antioxidant, cardio-protective marker. Hence we sought to determine whether total bilirubin was associated with prevalent and incident T2D in U.S. South Asians.

We conducted a cross-sectional and prospective analysis of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Total bilirubin was categorized into gender-specific quartiles (Men: <0.6, 0.6, 0.7-0.8, >0.8; Women: <0.5, 0.5, 0.6, >0.6 mg/dl). We estimated odds of type 2 diabetes as well as other cardiovascular (CV) risk factors using multivariable logistic regression.

Among a total 1,149 participants (48% female, mean [SD] age of 57 [9] years), 38% had metabolic syndrome and 24% had T2D. Men and women in the lowest bilirubin quartile had 0.55% and 0.17% higher HbA1c than the highest quartile. Men, but not women, in the lowest bilirubin quartile had higher odds of T2D compared to the highest quartile (aOR [95% CI]; Men: 3.00 [1.72,5.23], Women: 1.15 [0.57,2.31]). There was no association between bilirubin and other CV risk factors.

Total bilirubin was inversely associated with T2D in SA men but not women. Longitudinal studies are needed to understand temporality of association.

Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta-analysis of the associations between different cIMT definitions and CVD.

A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA-IMT], internal carotid artery IMT [ICA-IMT], combined segments [combined-IMT], mean CCA-IMT, and maximum CCA-IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta-analysis. After adjusting for age and sex, a 1-SD increase in CCA-IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27-1.38]), MI (HR, 1.27 [95% CI, 1.22-1.33]), and CVD events (HR, 1.28 [95% CI, 1.19-1.37]). A 1-SD increase in ICA-IMT was related to future stroke (HR, 1.25 [95% CI, 1.11-1.42]) and CVD events (HR, 1.25 [95% CI, 1.04-1.50]) but not MI (HR, 1.26 [95% CI, 0.98-1.61]). A 1-SD increase in combined-IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08-1.57]) and CVD events (HR, 1.36 [95% CI, 1.23-1.49]). Maximum CCA-IMT was more strongly related than mean CCA-IMT with risk of MI, and both measures were similarly associated with stroke and CVD events.

Combined-IMT is more strongly associated with CVD events compared with single-segment cIMT definitions. Maximum CCA-IMT shows a stronger association with MI than mean CCA-IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.

There is a debate on how to evaluate carotid artery intima-media thickness (IMT). We here compared IMT of the common carotid artery (CCA) and bulb with plaque area regarding incident atherosclerotic disease.

In the PIVUS study (age 70 at baseline, 53% women, n = 856), IMT-CCA, IMT-bulb and plaque area were measured at ages 70, 75 and 80 years and these three measurements were used in updated Cox proportional hazard analysis.

Over 15 years follow-up, 135 individuals experienced a first-time atherosclerotic disease (myocardial infarction or ischemic stroke). IMT-CCA was not significantly related to this composite endpoint (p = 0.10). IMT-bulb was significantly related to the endpoint (p = 0.003), but this relationship was attenuated following adjustment for CVD risk factors (p = 0.02). On the contrary, plaque area was consistently related to incident atherosclerotic disease also following adjustment for CVD risk factors (p<0.001). When added on top of traditional risk factors, both IMT-bulb and plaque area, but not IMT-CCA, improved the discrimination compared to the traditional risk factors (+5.2%, p = 0.0026 for IMT-bulb, +3.8%, p = 0.013 for plaque area and 0.0% for IMT-CCA).

In elderly subjects, both IMT-bulb and plaque area improved the discrimination regarding incident atherosclerotic disease when added to traditional risk factors. This was not seen for IMT-CCA. IMT-CCA was therefore inferior compared to the other two carotid artery ultrasonographic measurements in this sample of elderly subjects.

Background and Objectives: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. Materials and Methods: The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. Results: Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and p = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and p = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and p < 0.001). Conclusions: The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.

We examined whether secondhand smoke exposure in childhood affects the risk of coronary heart disease (CHD) in adulthood.

In the Japan Collaborative Cohort Study, we analyzed data on 71,459 participants aged 40-79 years, with no history of CHD, stroke, or cancer at baseline (1988-1990) and who completed a lifestyle questionnaire including the number of smoking family members in childhood (0, 1, 2, and 3+ members) and followed them up until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of CHD mortality according to the number of smoking family members in childhood.

During the median 18.9 years' follow-up, 955 CHD deaths were reported. There was a dose-response relationship between the number of smoking family members at home and CHD mortality among middle-aged individuals (40-59 years); the multivariable HRs (95% CIs) were 1.08 (0.76-1.54) for 1, 1.35 (0.87-2.08) for 2, and 2.49 (1.24-5.00) for 3+ smoking family members compared with 0 members (p for trend=0.03). The association for 3+ smoking family members among the middle-aged group was more evident in men than in women (the multivariable HRs [95% CIs] were 2.97 [1.34-6.58] and 1.65 [0.36-7.52], respectively) and more evident in non-current smokers than in current smokers (the multivariable HRs [95% CIs] were 4.24 [1.57-11.45] and 1.93 [0.72-5.15], respectively).

Secondhand smoke exposure in childhood was associated with an increased risk of CHD mortality in adulthood, primarily in middle-aged men and non-current smokers.

Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population.

We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model.

After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years).

Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

Carotid atherosclerosis is an important etiological factor for ischemic stroke. Early carotid lesion detection may prevent further strokes. Doppler ultrasound measures carotid artery blood flow, intima-media thickness, stenosis, plaques, and lumen and wall changes.

The objective of this study is to determine the association of carotid plaque size (CPS), carotid intima-media thickness (CIMT), resistive index (RI), and pulsatility index (PI) with acute ischemic stroke.

A total of 60 participants were taken, including 30 cases and 30 age- and sex-matched controls. Patients with acute ischemic stroke were included as cases and age- and sex-matched healthy volunteers were included as controls. A carotid duplex study was done in both groups, and the findings were compared.

The mean age of the ischemic stroke cases was 63.33±10.79 years; more than half were aged >60 years. Male patients were 73.3% and female patients were 26.7% of the cases. Age and gender were statistically similar (p>0.05) in groups (cases and controls). The plaques were homogenous in 30% of patients, calcified in 26.7%, and mixed in 6.7%. About 36.6% of patients did not have any plaque. CPS was greater among cases than controls in the right and left internal and left common carotid arteries; however, it was not statistically significant (p>0.05). The mean CIMT was 0.79±0.10 mm on the right side and 0.90±0.17 mm on the left side among cases. CIMT was significantly higher in the cases group than in the controls (p<0.05). The mean RI was significantly greater in the left common carotid artery (CCA) among the cases than in the controls (p<0.05). Patients aged over 60 years had significantly higher RI and PI values in the left internal carotid artery (ICA) compared to the younger cases (p<0.05). Smoking history had a significant association with left CCA RI and PI values (p<0.05). However, RI, PI, CPS, and CIMT among cases were similar in different groups like diabetic, non-diabetic, hypertensive, and non-hypertensive patients (p>0.05).

CIMT was significantly thicker among the patients with ischemic stroke compared to the control group. RI in the left CCA was significantly greater among the stroke patients than in the control group. The age of the patient and smoking habit had an association with RI and PI values. Most of the parameters were found to be significant on the left side, suggesting carotid atherosclerosis may not be symmetrical. A large-scale further study is needed to see the association of these variables with ischemic stroke patients.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Metabolic syndrome (MetS), increasingly diagnosed among the Polish population, is a combination of factors that are associated with an increased risk of atherosclerosis and cardiovascular diseases. Intima-media thickness (IMT) of the common carotid artery has been suggested as, simply, a non-invasive and reproducible marker of the early stages of the atherosclerotic process. The carotid IMT can also be a strong predictor of future cerebral and cardiovascular events. The aim of our study was to evaluate atherosclerotic lesions in carotid vessels in patients with MetS depending on the presence of DMt2 and to assess which demographic factors affect the level of IMT. The study involved 335 subjects diagnosed with MetS, including 211 females (65%) and 124 males (37%) aged 37-82. The diagnosis of MetS was made on the basis of the International Diabetes Federation (IDF) criteria. The patients were divided into two subgroups: with DMt2 and without DMt2. The value of IMT depended on gender, education, and smoking status. We noticed that patients with DMt2 had the highest measurement of IMT compared with other groups (1.01 vs. 0.98). Additionally, a statistically significant difference between the subgroup with DMt2 and those without DMt2 was found (1.01 vs. 0.92; p < 0.005). Ultrasound assessment of the carotid IMT should be used more often in the diagnosis and monitoring of high cardiovascular risk and early progression of atherosclerosis, especially in patients with MetS with current DMt2.

In healthy adults, the association between the glycated hemoglobin A1c (HbA1c) level and intima-media thickness (IMT) is stronger in the femoral artery than that in the carotid artery. However, whether this differential strength of association also applies to adolescents with type 1 diabetes (T1D) is unknown. Therefore, this study aimed to examine whether IMT increases in extracarotid arteries (specifically in the lower extremities) prior to the carotid artery. In total, 286 adolescents with T1D (15.9 ± 4.9 years; 42.0% male participants) were enrolled, and the B-mode ultrasonographic measurement of IMT in the carotid, femoral, and popliteal arteries was performed. Cardiovascular risk factors, including blood pressure (BP), body mass index, lipid levels, and glycemic parameters, were evaluated. To evaluate the site-dependent relationship between IMT and cardiovascular risk factors, a linear mixed-effects model was developed with repeated IMT measurements at various arterial sites as fixed effects and participants as random effects. Glycemic parameters, lipids, uric acid, high-sensitivity C-reactive protein, and advanced glycation end-products were some cardiovascular risk factors that worsened with increasing HbA1c levels. Patients with a higher HbA1c level (>10% vs. ≤10%) had thicker IMT in the femoral artery but not in the carotid or popliteal arteries. Patients with poorer diabetic control exhibited significant changes in certain cardiovascular functions, including central systolic BP, left ventricular (LV) ejection time, LV dp/dt max, stroke volume, and brachial artery compliance. A standard mediation analysis revealed that none of the aforementioned cardiovascular functions mediated the relationship between higher HbA1c level and greater femoral IMT. In adolescents with T1D, cardiovascular risk factors deteriorate with worsening blood glucose control. In the early stages of T1D, femoral IMT may serve as a more sensitive surrogate marker for hyperglycemia-induced subclinical atherosclerosis, an effect that may not be mediated by alterations in cardiovascular functions.

The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis.

A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders.

Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014.

The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.

Intestinal fat absorption shifting (IFAS) can be obtained in hyperlipidemic subjects with polyglucosamine biopolymer (BP) able to segregate most metabolic fats in the gut, making them unavailable for intestinal interaction (shift). The aim of this study was to evaluate the effects of a SM (standard management) for hyperlipidemia in asymptomatic subjects for primary cardiovascular prevention focusing on arterial wall morphology (IMT thickness) in comparison to SM associated to the administration of the BP.

Two groups of comparable subjects (SM and SM+oral BP, 3 g/day) were considered; subjects were managed - in a supplement, pilot registry - for a year. Weight, fat mass, lipid profile, oxidative stress, IMT (carotids), the presence of granulations at the internal arterial layers and "near wall low density 'bubbles' were observed and compared at 1 year of management. A non-parallel, comparable group of subjects (102) using a statin for the same conditions was used as a reference population.

Two hundred eighty-four subjects completed one year (140 in the SM group and 144 in the SM+BP group). Compliance was optimal with (96.3% of the table correctly used) with no side effects. BMI, fat mass and oxidative stress decreased more in the SM+BP group (P<0.05). Cholesterol and triglycerides levels were significantly improved with BP (P<0.05). IMT measurements were significantly decreased (P<0.05) in the SM+BP group (as for the intimal granulation/bubbles) with minimal variations in the comparative SM group. In the statin group, the lipid profile was modified (P<0.05) but not the IMT and the rate of drop outs was higher (15.7%); these patients stopped the management; in 23% of these subjects muscular pain not seen with BP, was observed.

These results indicate positive effects of IFAS due to BP on IMT and arterial wall morphology and weight after 12 months. Fat shifting at intestinal level and the reduction of oxidative stress limit lipid oxidation/deposition into the arterial wall.

Atherosclerotic cardiovascular disease (ASCVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease (CHD) and stroke, while African Caribbean people have a lower risk of CHD but a higher risk of stroke.

To compare carotid atherosclerosis in EA, SA, and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by ASCVD risk factors.

Cardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid artery plaques and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using generalised linear models (GLMs), with and without adjustment for non-modifiable (age, sex) and modifiable risk factors (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking).

Prevalence of any plaque was similar in EA and SA, but lower in AC (16, 16, and 6%, respectively; p < 0.001). In those with plaque, total plaque area, numbers of plaques, plaque class, or greyscale median did not differ by ethnicity; adjustment for risk factors had minimal effects. cIMT was higher in AC than the other ethnic groups after adjustment for age and sex, adjustment for risk factors attenuated this difference.

Prevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. Lower plaque prevalence in in AC is consistent with their lower risk of CHD but not their higher risk of stroke. Higher cIMT in AC may be explained by risk factors. The similarity of plaque burden in SA and EA despite established differences in ASCVD risk casts some doubt on the utility of carotid ultrasound as a means of assessing risk across these ethnic groups.

Although protective in secondary stroke prevention of intracranial arterial stenosis (ICAS), it is uncertain if the benefits of leisure time physical activity (LTPA) extend to asymptomatic ICAS or extracranial carotid stenosis (ECAS). Therefore, we sought to determine LTPA's relationship with ECAS and ICAS in a stroke-free, race-ethnically diverse cohort.

This cross-sectional study included participants from the magnetic resonance imaging substudy of the Northern Manhattan Study, of whom 1274 had LTPA assessments at enrollment. LTPA was represented continuously as metabolic equivalent score (MET-score) and ordinally as model-based cluster analysis (LTPA-cluster), both based on the same LTPA assessments. We evaluated ECAS sonographically using carotid intima-media thickening and number of carotid plaques. ICAS was assessed with time-of-flight magnetic resonance angiograph and defined as ≥50% or ≥70% stenosis. We applied regression analyses to evaluate the association between LTPA with ECAS and ICAS, adjusting for confounders.

Of 1274 included participants (mean age 71±9 years; 60% women; 65% Hispanic), the mean MET-score was 10±16 and 60% were in a LTPA-cluster with any activity. Among those with carotid ultrasound (n=1234), the mean carotid intima-media thickening was 0.97±0.09 mm, and 56% of participants had at least one carotid plaque identified. Among those with magnetic resonance angiograph (n=1211), 8% had ≥50% ICAS and 5% had ≥70% ICAS. For ICAS, MET-score was associated with ≥70% ICAS (adjusted odds ratio per unit increase in MET-score [95% CI, 0.97 [0.94-0.99]) but not with ECAS measures (carotid intima-media thickening, adjusted β-estimate per unit increase in MET-score [95% CI], 0.002 [-0.003 to 0.006] or number of plaques, adjusted β-estimate [95% CI], 0.0001 [-0.0001 to 0.0003]). Substituting MET-score with LTPA-clusters replicated the association between ≥70% ICAS and LTPA (adjusted odds ratio per each increased LTPA-cluster [95% CI], 0.83 [0.70-0.99]).

In this diverse stroke-free population, we found LTPA most strongly associated with asymptomatic ≥70% ICAS. Given the high-risk nature of ≥70% ICAS, these findings may emphasize the role of LTPA in people at risk for ICAS.