Carotid Total Plaque Area Research Articles

Assessment of total carotid plaque area progression in patients with chronic kidney disease. Good practices for decision-making.

Chronic kidney disease (CKD) increases cardiovascular risk, however,traditional cardiovascular risk factors cannot entirely explain it. A real-world investigation examined the concept that renal function decline is linked to carotid total plaque area progression, which strongly confirms cardiovascular risk. We analyzed CKD patients in stages 1-3 to find risk factor relationships before the onset of severe CKD. We monitored 328 patients for 16 ± 5months. Participants were classified at baseline by estimated glomerular filtration rate (eGFR) stage: G1 (≥ 90), G2 (60-89), and G3 (30-59ml/min/1.73m2). Ultrasound-guided total plaque area tracked atherosclerosis. Age, sex, blood pressure, lipids, and HbA1c were covariates. Total plaque area and variables were measured on day 1 and at the conclusion of observation. We used a multilevel mixed effects model to assess biological and behavioral factors on total plaque area progression in the general population. For validation, this research was conducted on 73 CKD patients with optimal traditional cardiovascular risk factor management during 15 ± 5months. Multiple analyses showed an inverse relationship between eGFR decline and total plaque area progression [β-exponent = 0.99 (95% CI = 0.98-0.99)], regardless of age, lipid profile, blood pressure, smoking, diabetes, or hypertension. The correlation remainedsignificant in the 73-patient sample with optimal traditional cardiovascular risk factor management (β-exponent = 0.99; 95% CI 0.97-0.99). Although traditional cardiovascular risk factor management was excellent, total plaque area increased considerably in G2-G3 patients compared to G1. CKD, total plaque area, and eGFR are inversely correlated, independent of traditional cardiovascular risk factors, suggesting that non-traditional mechanisms are responsible for resistant atherosclerosis. The combination of eGFR and total plaque area may be useful in identifying high-risk patients.

Effect of lipid-lowering therapy on carotid plaque burden in older adults

BackgroundLittle is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75. MethodsData was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan–Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis. ResultsIn total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan–Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57). ConclusionLipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

Adherence to Dietary Patterns and Cardiovascular Disease Risk: A Cross-Sectional Study of Total Carotid Plaque Area in Argentina.

Assessing subclinical atherosclerosis (sAT) is crucial for preventing cardiovascular disease. The Mediterranean diet is considered the gold standard for cardiovascular protection, but cultural and economic barriers can hinder adherence to it. The prudent dietary pattern (DP) has been associated with protective effects against chronic diseases. However, its impact on primary cardiovascular prevention remains uncertain. This study examined adherence to various DPs and their effect on sAT, measured by total carotid plaque area (TPA). This cross-sectional study included 116 adults enrolled in a cardiovascular prevention program. Demographic, clinical, laboratory, and TPA data were collected. Adherence to DPs was assessed using a food frequency questionnaire. Participants were categorized according to their adherence to 4 mutually exclusive DPs: prudent, traditional, sweet, and mixed. Generalized linear models were used to assess the effect of DPs on TPA, adjusting for relevant cardiovascular variables. The traditional, sweet, and mixed DPs were associated with higher TPA values than the prudent DP, with medians (interquartile range) of 27 (99), 39 (49), 27.5 (58), and 0 (36) mm2, respectively. Gamma regression analysis found that the beta exponents for the traditional, sweet, and mixed DPs versus the prudent DP were 3.78 (p=0.046); 3.73 (p=0.013), and 2.20 (p=0.072), respectively. Systolic blood pressure values were higher for the sweet and mixed DPs than for the prudent DP (133.9±11.7; 132.5±13.9 and 122.7±8.8 mmHg, respectively; p<0.05). These findings underscore the importance of additional research and targeted interventions to promote healthier DPs to promote improvements in cardiovascular health.

Ultrasound carotid plaque segmentation via image reconstruction-based self-supervised learning with limited training labels.

Carotid total plaque area (TPA) is an important contributing measurement to the evaluation of stroke risk. Deep learning provides an efficient method for ultrasound carotid plaque segmentation and TPA quantification. However, high performance of deep learning requires datasets with many labeled images for training, which is very labor-intensive. Thus, we propose an image reconstruction-based self-supervised learning algorithm (IR-SSL) for carotid plaque segmentation when few labeled images are available. IR-SSL consists of pre-trained and downstream segmentation tasks. The pre-trained task learns region-wise representations with local consistency by reconstructing plaque images from randomly partitioned and disordered images. The pre-trained model is then transferred to the segmentation network as the initial parameters in the downstream task. IR-SSL was implemented with two networks, UNet++ and U-Net, and evaluated on two independent datasets of 510 carotid ultrasound images from 144 subjects at SPARC (London, Canada) and 638 images from 479 subjects at Zhongnan hospital (Wuhan, China). Compared to the baseline networks, IR-SSL improved the segmentation performance when trained on few labeled images (n = 10, 30, 50 and 100 subjects). For 44 SPARC subjects, IR-SSL yielded Dice-similarity-coefficients (DSC) of 80.14-88.84%, and algorithm TPAs were strongly correlated (r=0.962-0.993, p < 0.001) with manual results. The models trained on the SPARC images but applied to the Zhongnan dataset without retraining achieved DSCs of 80.61-88.18% and strong correlation with manual segmentation (r=0.852-0.978, p < 0.001). These results suggest that IR-SSL could improve deep learning when trained on small labeled datasets, making it useful for monitoring carotid plaque progression/regression in clinical use and trials.

Carotid total plaque area as an independent predictor of short-term subclinical polyvascular atherosclerosis progression and major adverse cardiac and cerebrovascular events.

The use of ultrasound-based methods for imaging of subclinical atherosclerosis, including measurement of carotid plaque burden (cPB), is a promising direction for further improvement of major adverse cardiac and cerebrovascular events (MACCE) prediction. The aim of the study was to research the prognostic values' significance of cPB indicators with regard to the short-term progression of polyvascular subclinical atherosclerosis and the long-term onset of MACCE. Single-center prospective cohort study. The study included patients 40-64 years of age. All patients underwent duplex scanning (DS) of the carotid and lower limb arteries. The following cPB indicators were determined: carotid plaque score (cPS), maximum carotid plaque thickness (cPTmax), and carotid total plaque area (cTPA). The combined endpoint included the following components: cardiovascular death; nonfatal myocardial infarction; nonfatal stroke or transient ischemic attack (TIA); revascularization of the coronary and/or peripheral arteries. The study included 387 patients, among whom 142 (36.7%) patients underwent repeated DS after 12-24 months. The median follow-up time was 20.0 (13.0; 36.5) months. MACCE were recorded in 33 (8.52%) of patients. cTPA and cPTmax, but not cPS, were independently associated with the progression of subclinical polyvascular atherosclerosis over a period of 13.9 months of follow-up. cTPA, but not cPTmax and cPS, was independently associated with the development of MACCE over a period of 20.0 months of follow-up. Only a cTPA > 42.0 mm2 proved to be an independent predictor of both the progression of subclinical polyvascular atherosclerosis and MACCE. In patients from 40 to 64 years of age with various cardiovascular risks, among the indicators of the cPB, only an increase in cTPA > 42.0 mm2 was shown to be independently associated with an increase in the relative risk (RR) of progression of subclinical polyvascular atherosclerosis by 2.38 (1.08-5.25) times, as well as with the development of MACCE by 3.10 (1.54-6.26) times.

Vascular Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Vascular Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Liver Stiffness Is Associated with the Burden of Carotid and Systemic Atherosclerosis in an Unorganized Cohort of Patients 40-64 Years Old.

Background: The aim of the study is to research the relationship between the severity of liver fibrosis and the burden of carotid and systemic atherosclerosis. Methods: The study includes 163 patients 40 to 64 years of age without atherosclerotic CVD or liver disease. All patients underwent duplex scanning of the carotid and lower limb arteries. All patients underwent transient liver elastometry using the FibroScan (Echosens, France). Results: Carotid plaque was detected in 110 (67.5%) patients. Based on the results of linear regression analysis, relationships between liver stiffness and carotid total plaque area (r = 0.21; p = 0.025) were found. Significant relationships were established between liver stiffness and atherosclerosis burden score based on the results of linear regression (r = 0.17; p = 0.029). Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis. An increase in liver stiffness >4.5 kPa was associated with an odds ratio of generalized atherosclerosis of 3.48 (95% CI 1.07–11.3; p = 0.038) after adjusting confounding factors. Conclusion: Among patients 40–64 years of age without established atherosclerotic CVD and liver disease, liver stiffness directly correlates with the burden of carotid and systemic atherosclerosis. Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis.

Association of Cardiac Biomarkers With Cardiovascular Outcomes in Patients With Psoriatic Arthritis and Psoriasis: A Longitudinal Cohort Study.

ObjectiveIn patients with psoriatic disease (PsD), we determined whether cardiac troponin I (cTnI) and N‐terminal pro–brain natriuretic peptide (NT‐proBNP) were associated with carotid plaque burden and the development of cardiovascular events independent of the Framingham Risk Score (FRS).MethodsAmong 1,000 patients with PsD, carotid total plaque area (TPA) was measured in 358 participants at baseline. Cardiac troponin I and NT‐proBNP were measured using automated clinical assays. The association between cardiac biomarkers and carotid atherosclerosis was assessed by multivariable regression after adjusting for cardiovascular risk factors. Improvement in the prediction of cardiovascular events beyond the FRS was tested using measures of risk discrimination and reclassification.ResultsIn univariate analyses, cTnI (β coefficient 0.52 [95% confidence interval (95% CI) 0.3, 0.74], P < 0.001) and NT‐proBNP (β coefficient 0.24 [95% CI 0.1, 0.39], P < 0.001) were associated with TPA. After adjusting for cardiovascular risk factors, the association remained statistically significant for cTnI (adjusted β coefficient 0.21 [95% CI 0, 0.41], P = 0.047) but not for NT‐proBNP (P = 0.21). Among the 1,000 patients with PsD assessed for cardiovascular risk prediction, 64 patients had incident cardiovascular events. When comparing a base model (with the FRS alone) to expanded models (with the FRS plus cardiac biomarkers), there was no improvement in predictive performance.ConclusionIn patients with PsD, cTnI may reflect the burden of atherosclerosis, independent of traditional cardiovascular risk factors. Cardiac troponin I and NT‐proBNP are associated with incident cardiovascular events independent of the FRS, but further study of their role in cardiovascular risk stratification is warranted.

Relationship between Atherosclerosis and Cancer: An observational outcome study

Background and aims: It was investigated whether there is a relationship between advanced atherosclerosis of the carotid artery and cancer. Method: The carotid Total Plaque Area (TPA), the maximum plaque thickness, and the cardiovascular risk based on Framingham calculator using body-mass-index were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was collected as part of occupational health check-ups. Result: In 4207 healthy men aged 35-65 years (50±8 years) we found 578 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 566 (97.9%) subjects. The average follow-up time was 48 months (range 0 to 139 months). Ten subjects were excluded because of missing data on treatment. A total number of 230 subjects was treated with a statin, 326 received no statin. Within the group of these subjects (54±6 years), 33 men died (15 cancer, 4 strokes, 11 heart attacks, 1 COPD, 1 sepsis, 1 cirrhosis of the liver). In the group with CVD death, two subjects were treated with a statin, 13 were untreated. In the group with cancer death, two subjects were treated with a statin, 13 were untreated. The death rate because of cancer and CVD was 1.7% for the treated subjects and 8.0% for the untreated subjects. In the group with low risk (n= 1890), six men died (2 traffic accidents, 1aneurysm bleeding, 2 cancer, 1 unclear, a follow-up examination has been completed for 43.9% (n= 830) of the subjects, mean follow-up time of 65 months (0-137 months). One man died (Parkinson) within the group with intermediate risk. In this group (n= 482) a follow-up examination has been completed for 55% (n= 265) with a mean follow-up time of 55 months (total range: 0-130 months). In the reference group (no atherosclerosis; n= 1257) follow-up has been completed in 38.3% (n= 482) with a mean follow-up time of 60 (0-145) months and nobody died. In 3203 healthy women aged 35-65 years nobody died of cancer. Conclusion: The development of cancer in men with advanced atherosclerosis of the carotid artery appears to be noticeable. The question of whether there is a causal relationship requires further investigations.

Skin autofluorescence, a measure of tissue accumulation of advanced glycation end products, is associated with subclinical atherosclerosis in coronary and carotid arteries

Background and aimsSkin autofluorescence (AF), a measure of tissue accumulation of advanced glycation end products (AGEs), has been associated with diabetes and cardiovascular disease. However, the association of skin AF with subclinical coronary atherosclerosis in the general population is largely unknown. Our study aimed to examine the associations between skin AF and subclinical atherosclerosis in coronary and carotid arteries in a middle-aged population. MethodsSkin AF and subclinical atherosclerosis were measured in 4416 subjects (aged 50–64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Skin AF was measured non-invasively using an autofluorescence reader. Subclinical atherosclerosis was assessed by ultrasonography of carotid arteries for evaluation of carotid plaques and computed tomography for the evaluation of the coronary artery calcium score (CACS). ResultsA total of 615 (13.9%) individuals had CACS >100 and 1340 (30.3%) subjects had bilateral carotid plaques (median total plaque area: 8 mm2). After controlling for confounding factors, there were significant associations between skin AF (per 1 standard deviation (SD) increase) and CACS >100: odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.06–1.29, p = 0.001. Total carotid plaque area and occurrence of bilateral carotid plaques (OR per 1 SD increase: 1.10, 95%CI: 1.01–1.19, p = 0.02) were similarly associated with skin AF after multivariable adjustments. ConclusionsElevated skin AF was significantly associated with subclinical atherosclerosis in coronary and carotid arteries independently of conventional risk factors. Skin AF, a measure of accumulation of AGEs, could be a marker for the identification of middle-aged subjects with elevated atherosclerotic risk.

Carotid plaque is strongly associated with coronary artery calcium and predicts incident coronary heart disease in a population-based cohort

Background and aimsCoronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events. MethodsThe REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1–100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors. ResultsCombined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories. ConclusionsCarotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype.

Background and PurposeCD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. MethodsSoluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. ResultsBoth plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. ConclusionsHigher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

Carotid total plaque area as a marker of asymptomatic lower extremity arterial disease

Objective: to examine the prognostic value of ultrasound markers of carotid atherosclerosis in relation to the presence of asymptomatic lower extremity peripheral artery disease (PAD). Materials and Methods: the study included 193 patients with carotid atherosclerosis. All patients underwent duplex ultrasound scanning (DUS) of carotid and lower limb arteries. The carotid plaque score (cPS) was determined as the total height of all plaques in the carotid arteries. The carotid total plaque area (cTPA) was estimated in the longitudinal position, the area of plaque was measured in the manual trace mode.Results: asymptomatic lower extremity PAD was diagnosed in 31.6% of patients. The increase in cTPA, in contrast to cPS and the degree of carotid stenosis, was independent predictor of lower extremity PAD and was associated with an increase in the relative risk of its presence by 6.78 times (95% CI 2.48-18.5; p &lt;0.0001). cTPA ≥42.5 mm2 made it possible to diagnose asymptomatic lower extremity PAD with a sensitivity of 70.2% and specificity of 73.0%. Conclusion: In patients with carotid atherosclerosis among carotid atherosclerosis markers only cTPA, in contrast to cPS and the degree of carotid stenosis, had an independent predictive value regarding the presence of asymptomatic lower extremity PAD.

Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study

IntroductionPatients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methodsPart of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. ResultsWe included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. ConclusionsA significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Factores de riesgo asociados a la calcificación valvular en pacientes con enfermedad renal crónica. Análisis del Estudio Nefrona

IntroductionPatients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methodsPart of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. ResultsWe included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33ml/min with significant decrease to 30.9ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. ConclusionsA significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Carotid total plaque area as a promising marker of asymptomatic peripheral artery disease

Background and Aims: In current guidelines on the diagnosis and treatment of peripheral arterial diseases (PAD) there is no decision-making algorithm for screening for lower extremity PAD in patients with carotid atherosclerosis due to insufficient data. Aim of the study was to examine the prognostic value of various ultrasound markers of atherosclerosis of the carotid arteries in relation to the presence of asymptomatic lower extremity PAD.

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

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

Achilles Tendon Thickness Is an Independent Predictor of Carotid Atherosclerosis and Is Associated With a Carotid Plaque Burden.

The aim of the study was to research the relationship between carotid atherosclerosis markers and ultrasound parameters of Achilles tendons (AT). The study included 150 patients at high and very high cardiovascular risk (CVR). All patients underwent a carotid ultrasound scanning. We evaluated carotid plaque, carotid plaque score (cPS), carotid total plaque area (cTPA), and the percentage of stenosis. All patients underwent AT ultrasound with an assessment of thickness (Achilles tendon thickness [ATT]), width (Achilles tendon width), and cross-sectional area. An increase in the ATT ≥5.07 mm was associated with a 4.55-fold increase in the relative risk of carotid atherosclerosis (sensitivity 68.3% and specificity 62.5%). Direct correlations between the ATT and carotid stenosis (r = 0.277; P = .004), cPS (r = 0.225; P = .035), and cTPA (r = 0.305; P = .004) were determined. An increase in the mean ATT by 1 mm was associated with an increase in cTPA by 8.09 mm2 (95% CI: 2.26-13.9; P = .007) and carotid stenosis by 4.11% (95% CI: 0.64-7.60; P = .021). Thus, in patients with high and very high CVR, an increase in ATT is an independent predictor of carotid atherosclerosis. The ATT directly correlates with the markers of carotid plaque burden.

Interaction of smoking, hyperhomocysteinemia, and metabolic syndrome with carotid atherosclerosis: A cross-sectional study in 972 non-diabetic patients.

Little is known about the interactions between hyperhomocysteinemia and metabolic syndrome (MetS) in individuals at risk for atherosclerosis. The aim of this study was to assess the burden of atherosclerosis in patients with MetS and hyperhomocysteinemia. We assessed the interaction of MetS with other risk factors including hyperhomocysteinemia in 972 patients with a history of stroke, transient ischemic attack, or carotid stenosis. MetS was defined as by the International Diabetes Federation as body mass index ≥30 kg/m² and two or more of the following: hypertension, high triacylglycerides, and low high-density lipoprotein. We defined hyperhomocysteinemia as plasma total homocysteine ≥14 µmol/L. Patients with diabetes were excluded. Carotid total plaque area (TPA), a strong predictor of cardiovascular risk, was measured by carotid ultrasound. The association of TPA with MetS, and interaction with related risk factors, was assessed by multiple linear regression. Complete data were available on 972 non-diabetic patients. Of these, 179 (18.4%) had MetS. Patients with MetS and hyperhomocysteinemia (P < 0.001) or smoking (P=0.02) had a higher TPA compared with those with MetS and normal plasma total homocysteine levels. In linear regression, there was a significant association of MetS (P=0.004), hyperhomocysteinemia (P=0.01), and smoking (P=0.004) with increased TPA. Patients with MetS and smoking or hyperhomocysteinemia are at particularly high cardiovascular risk. Targeted atherosclerosis prevention should include identification and treatment of MetS, smoking, and hyperhomocysteinemia (including that due to unrecognized metabolic vitamin B12 deficiency).

Traffic-Related Air Pollution and Carotid Plaque Burden in a Canadian City With Low-Level Ambient Pollution.

BackgroundThe association between fine particulate matter and cardiovascular disease has been convincingly demonstrated. The role of traffic‐related air pollutants is less clear. To better understand the role of traffic‐related air pollutants in cardiovascular disease development, we examined associations between NO2, carotid atherosclerotic plaque, and cardiometabolic disorders associated with cardiovascular disease.Methods and ResultsCross‐sectional analyses were conducted among 2227 patients (62.9±13.8 years; 49.5% women) from the Stroke Prevention and Atherosclerosis Research Centre (SPARC) in London, Ontario, Canada. Total carotid plaque area measured by ultrasound, cardiometabolic disorders, and residential locations were provided by SPARC medical records. Long‐term outdoor residential NO2 concentrations were generated by a land use regression model. Associations between NO2, total carotid plaque area, and cardiometabolic disorders were examined using multiple regression models adjusted for age, sex, smoking, and socioeconomic status. Mean NO2 was 5.4±1.6 ppb in London, Ontario. NO2 was associated with a significant increase in plaque (3.4 mm2 total carotid plaque area per 1 ppb NO2), exhibiting a linear dose‐response. NO2 was also positively associated with triglycerides, total cholesterol, and the ratio of low‐ to high‐density lipoprotein cholesterol (P<0.05). Diabetes mellitus mediated the relationship between NO2 and total carotid plaque area (P<0.05).ConclusionsOur results demonstrate that even low levels of traffic‐related air pollutants are linked to atherosclerotic plaque burden, an association that may be partially attributable to pollution‐induced diabetes mellitus. Our findings suggest that reducing ambient concentrations in cities with NO2 below current standards would result in additional health benefits. Given the billions of people exposed to traffic emissions, our study supports the global public health significance of reducing air pollution.