Early Detection Of Atherosclerosis Research Articles

Kalman-Based Carotid-Artery Longitudinal-Kinetics Estimation and Pattern Recognition

Objectives. The context of the study is the early detection of atherosclerosis. The specific aim of the article is to estimate the longitudinal displacements of the carotid artery wall and assess the discriminative power of the estimated motion patterns to distinguish at-risk individuals from healthy subjects.Methods. Motion estimation builds on block matching with a Kalman filter updating the reference-block gray levels, and incorporates a Kalman filter controlling the trajectory via a model using cosine decomposition. The estimated motion patterns were normalized and provided as input features to a machine-learning-based classifier that automatically assigned healthy or at-risk labels.Results. Evaluated on 113 subjects, the method successfully estimated all but one trajectory, and classification achieved 70% sensitivity and 72% specificity.Conclusions. The proposed method is well suited to estimate 2D (longitudinal and radial) quasi-periodic displacements of the arterial wall in ultrasound image sequences. The estimated motion patterns can contribute to discriminate at-risk from healthy subjects.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker

BackgroundEarly vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis.MethodsThis cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5–18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls.ResultsOur B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03).ConclusionsSubclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.

The renal tubular damage marker urinary N-acetyl-\u03b2-d-glucosaminidase may be more closely associated with early detection of atherosclerosis than the glomerular damage marker albuminuria in patients with type 2 diabetes

BackgroundTo determine the association between urinary N-acetyl-β-d-glucosaminidase (NAG), a marker of renal tubulopathy, and carotid intima-media thickness (IMT) and plaques in patients with type 2 diabetes mellitus (T2D) and to compare the predictive value of NAG versus albuminuria, a marker of renal glomerulopathy.MethodsA total of 343 participants were enrolled in this retrospective cross-sectional study. We recruited participants with T2D who were tested for blood glucose parameters, urinary NAG, and urinary albumin-to-creatinine ratio (ACR) and had been checked for carotid ultrasonography.ResultsWe classified participants into a below-median urinary NAG group (Group I; n = 172) or an above-median group (Group II; n = 171). Mean, maximum, and mean of maximum carotid IMT and the proportion of patients with carotid plaques were significantly higher in Group II compared with Group I. In multiple linear regression analyses, high urinary NAG (Group II) was significantly associated with carotid IMT, independently of urinary ACR and other confounding factors. In terms of carotid plaques, both urinary NAG and ACR were significantly higher in participants with carotid plaques than in those without carotid plaques. After adjustment for confounding factors, both urinary NAG and ACR were significantly associated with the presence of carotid plaques.ConclusionsElevated urinary NAG, a marker of renal tubular damage, was related to increased carotid IMT and the presence of carotid plaques in patients with T2D. Urinary NAG may be a more sensitive biomarker than urinary albumin for early detection of atherosclerosis.

Predictive value of the augmentation index derived vascular age in patients with newly diagnosed atherosclerosis

Early detection of atherosclerosis, i.e., in occupational health screening programs could reduce the rate of cardiovascular events in the working population. Changes of the augmentation index (AIX) correlate with changes of the arterial stiffness induced by aging, atherosclerosis, or arterial hypertension and have a prognostic value for cardiovascular events. Their diagnostic yield should be increased by normalizing the AIX to age, in terms of a calculating the vascular age (VA). In this pilot study, 30 patients (mean age 65.3 ± 8.8 years, 21 male) with suspected coronary heart disease underwent a duplex ultrasound of the carotid arteries and a measurement of the ankle brachial index in addition to the coronary angiography. The AIX was recorded with a portable device (Vascular Explorer), and the VA was calculated. Atherosclerosis was found in 24 patients. They were older than the patients without atherosclerosis, but there was no age dependency found for the distribution pattern or severity of atherosclerosis. In patients with findings of atherosclerosis, the calculated VA was higher than the chronological age, and these differences were significant in patients below 65 years of age. Comparing patients in higher blood pressure classes with patients in lower classes, significantly higher AIX, VA, and differences to the chronological age were found. The VA, deduced from the noninvasively obtained AIX, is a promising candidate for screening programs for atherosclerosis, i.e., in occupational health screening programs.

Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis.

The aim of the present study was to identify an effective method for detecting early‑phase atherosclerosis (AS), as well as to provide useful DNA methylation profiles to serve as biomarkers for the detection of AS. A total of 300 individuals (150 AS patients and 150 healthy subjects) were recruited for peripheral blood DNA methylation analyses at 12gene promoter loci using nested methylation‑specific polymerase chain reaction in a test set. Based on the test set, the promoter methylation of TIMP metallopeptidase inhibitor1 (TIMP1), ATP binding cassette subfamily A member1 (ABCA1), and acetyl-CoA acetyltransferase1 (ACAT1) were determined to be candidate biomarkers; demonstrating the highest sensitivity (88%) and specificity (90%). The biomarkers that were candidates for early AS detection were validated in an independent validation set (n=100). In the validation set, the combination of TIMP1, ABCA1 and ACAT1 methylation achieved sensitivity, specificity and coincidence rate values of 88, 70 and 79%, respectively. In the current pilot study, the patterns of DNA methylation of AS‑associated genes were observed to be significantly altered in the peripheral blood of AS patients. Thus, the AS-specific methylation of the three‑gene panel (TIMP1, ABCA1, and ACAT1) may serve as a valuable biomarker for the early detection of AS.

Nanoparticles to diagnose and treat atherosclerosis

Researchers have developed nanoparticles that localize to arterial plaques and provide a possible new means to diagnose and treat atherosclerosis. Early detection of atherosclerosis is difficult and effective therapies are not available, making the condition a common cause of death worldwide. Plaques that are the hallmark of the disease form when white blood cells called macrophages attract cholesterol and agglomerate in arteries. These buildups can cause heart attacks, and when macrophages die, they can cause plaques to rupture and block blood flow, potentially causing strokes. High-density lipoprotein (HDL, or “good cholesterol”) deters plaque formation by promoting transport of cholesterol from plaques to the liver for excretion. In 2013, Shanta Dhar’s group at the University of Georgia reported the development of synthetic nanoparticles that mimic HDL functionally. In San Diego last week, Dhar and coworkers reported a modified version. The nanoparticles include a sugar-based macrophage-targeting ligan...

Effects of age and cardiovascular risk factors on (18)F-FDG PET/CT quantification of atherosclerosis in the aorta and peripheral arteries.

To quantify fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the aorta and peripheral arteries and assess the variation of (18)F-FDG uptake with age and cardiovascular risk factors. The subject population of this retrospective study comprises melanoma patients who underwent whole-body (18)F-FDG PET/CT scans. The patients' medical records were examined for cardiovascular risk factors and for a history of coronary artery disease or peripheral artery disease. Fluorine-18-FDG uptake in the peripheral arteries (iliac and femoral) and aorta was semi-quantified as a weighted-average mean standardized uptake value (wA-SUVmean), while background noise was accounted for by measuring mean venous blood pool SUV (V-SUVmean) in the superior vena cava. Atherosclerosis was semi-quantified by the tissue-to-background ratio (TBR) (wA-SUVmean divided by V-SUVmean). A regression model and t-test were used to evaluate the effect of age and location on the degree of atherosclerosis. To assess the effect of cardiovascular risk factors on atherosclerotic burden, the wA-SUVmean of patients with at least one of these risk factors was compared to that of patients without any risk factors. A total of 76 patients (46 men, 30 women; 22-91 years old) were included in this study. The average TBR of the aorta and peripheral arteries were 2.68 and 1.43, respectively, and increased with age in both locations. In regression analysis, the beta coefficients of age for TBR in the aorta and peripheral arteries were 0.55 (P<0.001) and 0.03 (P<0.001), respectively. In all age groups, the TBR of the aorta was significantly greater than that of the peripheral arteries. The Pearson correlation coefficients between the four age groups and the TBR of the aorta and peripheral arteries were 0.83 (P<0.001) and 0.75 (P<0.001), respectively. The wA-SUVmean of patients with cardiovascular risk factors was only significant (P<0.05) in the aorta. An increase in (18)F-FDG uptake was observed in the peripheral arteries and aorta with increasing age. Cardiovascular risk factors were significantly correlated with (18)F-FDG uptake in aorta. The early detection of atherosclerosis with (18)F-FDG PET may allow for the initiation of preventative interventions prior to the manifestation of significant structural abnormalities or symptoms of disease.

Evaluation of fetuin-A and carotid intima-media thickness in adolescent type 1 diabetic patients.

To evaluate fetuin-A level and carotid intima-media thickness (CIMT) in adolescent type 1 diabetics. The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin (HbA1), lipid profile, and fetuin-A. Urine sample was also taken for assessment of albumin/creatinine ratio. Anthropometric measurements were taken, including weight, height, and waist and hip circumference. CIMT was assessed for all patients and controls. Serum fetuin-A, Rt., Lt. and both CIMT were significantly higher in diabetics. Fetuin-A had a significant positive correlation with duration of disease, waist and hip circumference, BMI, BMI SDS, waist/height ratio, Rt., Lt. and both CIMT. Stepwise multiple regression analysis revealed that the duration of disease, waist/height ratio, and HDL-c were the factors related to fetuin-A. Adolescent type 1 diabetic patients have high fetuin-A levels and increased CIMT, with the latter representing the development of early atherosclerosis. In this light, adolescents with type 1 diabetes require frequent follow up for early detection of atherosclerosis.

GW25-e4220 Comparison of two methods for evaluating human carotid artery elasticity: Possible detection of early atherosclerosis In subjects with dyslipidemia

GW25-e4220 Comparison of two methods for evaluating human carotid artery elasticity: Possible detection of early atherosclerosis In subjects with dyslipidemia

Development and feasibility study of a two-dimensional ultrasonic-measurement-integrated blood flow analysis system for hemodynamics in carotid arteries.

Prevention and early detection of atherosclerosis are critical for protection against subsequent circulatory disease. In this study, an automated two-dimensional ultrasonic-measurement-integrated (2D-UMI) blood flow analysis system for clinical diagnosis was developed, and the feasibility of the system for hemodynamic analysis in a carotid artery was revealed. The system automatically generated a 2D computational domain based on ultrasound color Doppler imaging and performed a UMI simulation of blood flow field to visualize hemodynamics in the domain. In the UMI simulation, compensation of errors was applied by adding feedback signals proportional to the differences between Doppler velocities by measurement and computation while automatically estimating the cross-sectional average inflow velocity. The necessity of adjustment of the feedback gain was examined by analyzing blood flow in five carotid arteries: three healthy, one sclerosed, and one stenosed. The same feedback gain was generally applicable for the 2D-UMI simulation in all carotid arteries, depending on target variables. Thus, the present system was shown to be versatile in the sense that the parameter is patient independent. Moreover, the possibility of a new diagnostic method based on the hemodynamic information obtained by the 2D-UMI simulation, such as a waveform of the cross-sectional average inflow velocity and wall shear stress distributions, was suggested.

Early Detection of Atherosclerosis in Primary School Children

Purpose: The aim of this study was to determine the correlations of age, sex, anthropometric measurements, pulse rate, blood pressure, and family history of cardiovascular disease with early atherosclerosis in children. Methods: Between December 2011 and January 2012 we included 112 children of primary school aOsnovnaaola Bojana Ilicha Maribor´, whose parents consented and signed the inform consensus. We made a questionnaire about cardiovascular diseases in child's family. We measured blood pressure, pulse rate, body height, weight, waist circumference. We performed ultrasound measurement of carotid artery intima -media thickness (IMT). The data were processed using the SPSS statistical program. Results: Body mass index (BMI) (r=0.246;p<0.009), waist circumference ( r=0.198; p<0.036) systolic (r=0.282; p<0.003) and dias tolic bloodpressure (r=0.282; p<0.003) were positively correlated with carotid artery IMT. In addition, those with family history of cardiovascular diseases had higher carotid artery IMT (p<0.0001) at baseline. A multivariable logistic regression analysis revealed that family history of cardiovascular disease was associated withcarotid arteryIMT (p<0.0001). OriginalResearch Article

Local Arterial Stiffening Assessed by MRI Precedes Atherosclerotic Plaque Formation

Atherosclerosis is known to impair vascular function and cause vascular stiffening. The aim of this study was to evaluate the potential predictive role of vascular stiffening in the early detection of atherosclerosis. Therefore, we investigated the time course of early functional and morphological alterations of the vessel wall in a murine atherosclerosis model. Because initial lesions are distributed inhomogeneously in early-stage atherosclerosis, MR microscopy was performed to measure vascular elasticity locally, specifically the local pulse wave velocity and the arterial wall thickness. Local pulse wave velocity and the mean arterial wall thickness were determined in the ascending and the abdominal aortae of ApoE(-/-) and wild-type mice. In vivo MRI revealed that baseline pulse wave velocity and morphology were similar in 6-week-old ApoE(-/-) and WT mice, whereas at the age of 18 weeks, local pulse wave velocity was significantly elevated in ApoE(-/-) mice. Significantly increased vessel wall thickness was not found in ApoE(-/-) mice until the age of 30 weeks. Histological analysis of the aortae of ApoE(-/-) and WT mice showed that increased pulse wave velocity coincided with the fragmentation of the elastic laminae in the arterial wall, which is hypothesized to induce early vascular stiffening and may be promoted by macrophage-mediated matrix degradation. We newly report that the assessment of local pulse wave velocity via MRI provides early information about the local progression of atherosclerosis before macroscopic alterations of the vessel wall occur.

Early Atherosclerosis Detection in Asymptomatic Patients: A Comparison of Carotid Ultrasound, Coronary Artery Calcium Score, and Coronary Computed Tomography Angiography

BackgroundDetailed multimodality assessment of subclinical atherosclerosis in asymptomatic subjects referred for risk stratification has not been performed. We analyzed the detection of early atherosclerosis using 3 imaging modalities: coronary artery calcium (CAC) scoring, carotid ultrasound (US), and coronary computed tomography angiography (CCTA). MethodsAsymptomatic subjects free of known vascular disease scheduled to undergo a carotid US for risk stratification were invited to undergo CCTA/CAC. Subjects taking lipid-lowering medication were excluded. All images were assessed by experienced core laboratory personnel. Carotid intima media thickness ≥ 75th percentile for age and sex, CAC > 0, and detection of either carotid or coronary artery plaque were indicators of atherosclerosis. ResultsFifty patients were included with a median age of 53 years. Atherosclerosis was observed in 28%, 78%, and 90% of subjects using CAC, CCTA, and carotid US, respectively. All subjects showed atherosclerosis on at least 1 modality. In 36 patients with a CAC score = 0, 69% and 86% had atherosclerosis on CCTA and carotid US, respectively. ConclusionsIn this detailed analysis, all subjects identified to warrant further risk stratification had subclinical atherosclerosis on at least 1 imaging modality. Concordance between modalities was highly variable, dependent on the specific definition of atherosclerosis used. Carotid US and CCTA detection of plaque were significantly more sensitive than CAC > 0 in this middle-aged population. Considering the prevalence of subclinical disease on carotid US and CCTA, the threshold at which to treat warrants further research.

AB0372 Is routine ankle-brachial pressure index evaluation useful in rheumatoid arthritis?

BackgroundPatients with rheumatoid arthritis (RA) are at increased risk for cardiovascular mortality and may therefore benefit from early atherosclerosis detection. Ankle brachial pressure index (ABPI) measurement can detect asymptomatic peripheral...

Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

Introduction: Intima-media thickness (IMT) measurement of the common carotid artery (CCA) is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT).Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro). The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was &gt; 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (P&lt;0.001), followed by systolic blood pressure (P=0.001), diastolic blood pressure (P=0.003) and glucose blood level (P=0.048).Conclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

Waist circumference is associated with carotid intima media thickness in peritoneal dialysis patients

Atherosclerosis is responsible for the high mortality rate in end-stage renal disease patients. Defining risk factors for atherosclerosis may lead to reduction in cardiovascular disease through modification of these factors. Peritoneal dialysis (PD) patients are subjected to high glucose loads on a daily basis, which results in considerable weight gain and an increase in waist circumference (WC). WC as an indicator of abdominal obesity is a risk factor for atherosclerosis in the general population. Carotid artery intima media thickness (CIMT) measurement is a reliable method for the detection of early atherosclerosis. The aim of this study was to investigate the relationship between WC and CIMT and to define risk factors associated with CIMT in PD patients. Fifty-five PD patients and 40 healthy controls were included. Atherosclerosis was assessed using measurement of CIMT. Fasting blood was collected for analysis. Anthropometric parameters (age, weight, BMI, and WC) were measured. Peritoneal dialysis patients had higher WC (93.9 ± 1.7 vs. 87.3 ± 1.2 cm, p < 0.05) and CIMT (0.70 ± 0.02 vs. 0.57 ± 0.01 mm, p < 0.01) than the control group. On univariate analysis, age, WC, plaque formation, and D/P creatinine were positively correlated with CIMT, whereas residual renal function, albumin, ultrafiltration volume, and D/D0 glucose were negatively correlated. On multivariate analysis, only age, WC, and plaque formation showed correlation (p < 0.001). Carotid artery intima media thickness is associated with age, plaque formation, and WC in PD patients. WC measurement is a simple, inexpensive, reproducible, and reliable method of evaluating atherosclerosis risk in PD patients and should be assessed at every visit. Appropriate counsel should be provided to patients with greater WC who are deemed to be at risk for atherosclerosis.

MONITORING THE PROGRESSION OF ATHEROSCLEROSIS IN RABBITS MODEL WITH TARGETED ULTRASOUND DETECTION OF VASCULAR CELL ADHESION MOLECULE-1

ObjectivesThe aim of our study was to investigate the use of targeted contrast-enhanced high-frequency ultrasonography for molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression on carotid artery in a...

Fatty streak assessed by optical coherence tomography: early atherosclerosis detection

Macrophage plays a crucial role for atherosclerotic plaque and its measurement is important. Fatty streak consists of macrophage foam cells, but its assessment by optical coherence tomography (OCT) has not been established in vivo . These images were derived from an aorta of Watanabe heritable hyperlipidaemia rabbit ex vivo . OCT …

Segmentation of the Common Carotid Artery Walls Based on a Frequency Implementation of Active Contours

Atherosclerosis is one of the most extended cardiovascular diseases nowadays. Although it may be unnoticed during years, it also may suddenly trigger severe illnesses such as stroke, embolisms or ischemia. Therefore, an early detection of atherosclerosis can prevent adult population from suffering more serious pathologies. The intima-media thickness (IMT) of the common carotid artery (CCA) has been used as an early and reliable indicator of atherosclerosis for years. The IMT is manually computed from ultrasound images, a process that can be repeated as many times as necessary (over different ultrasound images of the same patient), but also prone to errors. With the aim to reduce the inter-observer variability and the subjectivity of the measurement, a fully automatic computer-based method based on ultrasound image processing and a frequency-domain implementation of active contours is proposed. The images used in this work were obtained with the same ultrasound scanner (Philips iU22 Ultrasound System) but with different spatial resolutions. The proposed solution does not extract only the IMT but also the CCA diameter, which is not as relevant as the IMT to predict future atherosclerosis evolution but it is a statistically interesting piece of information for the doctors to determine the cardiovascular risk. The results of the proposed method have been validated by doctors, and these results are visually and numerically satisfactory when considering the medical measurements as ground truth, with a maximum deviation of only 3.4 pixels (0.0248 mm) for IMT.

Cardiovascular Molecular Imaging: The Road Ahead

Despite significant advancements in medical and device-based therapies, cardiovascular disease remains the number one cause of death in the United States. Early detection of atherosclerosis, prevention of myocardial infarction and sudden cardiac death, and modulation of adverse ventricular remodeling still remain elusive goals. Molecular imaging focuses on identifying critical cellular and molecular targets and therefore plays an integral role in understanding these biologic processes in vivo. Because many imaging targets are upregulated before irreversible tissue damage occurs, early detection could ultimately lead to development of novel, preventive therapeutic strategies. This review addresses recent work on radionuclide imaging of cardiovascular inflammation, infection, and infarct healing. We further discuss opportunities provided by multimodality approaches such as PET/MRI and PET/optical imaging.