Cortical inflammation and brain signs of high-risk atherosclerosis in a non-human primate model.

Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood-brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood-brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy.

Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review.

Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome: a randomized controlled trial.

BACKGROUND: Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. Restoring sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial blood pressure. METHODS: The aim of this study was to assess the efficacy and safety of minoxidil on Intima Media Thickness (IMT) on the right common carotid artery after twelve-month treatment in patient with Williams-Beuren syndrome. We performed a randomized placebo controlled double blind trial. All participants were treated for 12 months and followed for 18 months. The principal outcome was assessed by an independent adjudication committee blinded to the allocated treatment groups. RESULTS: The principal outcome was available for 9 patients in the placebo group and 8 patients in the minoxidil group. After 12-month treatment, the IMT in the minoxidil group increased by 0.03 mm (95% CI -0.002, 0.06) compared with 0.01 mm (95%CI - 0.02, 0.04 mm) in the placebo group (p = 0.4). Two serious adverse events unrelated to the treatment occurred, one in the minoxidil and 1 in the placebo group. After 18 months, the IMT increased by 0.07 mm (95% CI 0.04, 0.10 mm) in the minoxidil compared with 0.01 mm (95% CI -0.02, 0.04 mm) in the placebo group (p = 0.008). CONCLUSION: Our results suggest a slight increase after 12 and 18-month follow-up in IMT. More understanding of the biological changes induced by minoxidil should better explain its potential role on elastogenesis in Williams-Beuren syndrome. TRIALS REGISTRATION: US National Institutes of Health Clinical Trial Register (NCT00876200). Registered 3 April 2009 (retrospectively registered).

Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases.

BACKGROUND: The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity. OBJECTIVE: To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin. METHODS: Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data (LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment. RESULTS: The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm). CONCLUSION: Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the importance of having a global metabolic view and to evaluate the cardiovascular impact of the new enzymatic treatment.

A Fully-Automatic Method to Segment the Carotid Artery Layers in Ultrasound Imaging: Application to Quantify the Compression-Decompression Pattern of the Intima-Media Complex During the Cardiac Cycle.

The aim of this study was to introduce and evaluate a contour segmentation method to extract the interfaces of the intima-media complex in carotid B-mode ultrasound images. The method was applied to assess the temporal variation of intima-media thickness during the cardiac cycle. The main methodological contribution of the proposed approach is the introduction of an augmented dimension to process 2-D images in a 3-D space. The third dimension, which is added to the two spatial dimensions of the image, corresponds to the tentative local thickness of the intima-media complex. The method is based on a dynamic programming scheme that runs in a 3-D space generated with a shape-adapted filter bank. The optimal solution corresponds to a single medial axis representation that fully describes the two anatomical interfaces of the arterial wall. The method is fully automatic and does not require any input from the user. The method was trained on 60 subjects and validated on 184 other subjects from six different cohorts and four different medical centers. The arterial wall was successfully segmented in all analyzed images (average pixel size = 57 ± 20 mm), with average segmentation errors of 47 ± 70 mm for the lumen-intima interface, 55 ± 68 mm for the media-adventitia interface and 66 ± 90 mm for the intima-media thickness. The amplitude of the temporal variations in IMT during the cardiac cycle was significantly higher in the diseased population than in healthy volunteers (106 ± 48 vs. 86 ± 34 mm, p = 0.001). The introduced framework is a promising approach to investigate an emerging functional parameter of the arterial wall by assessing the cyclic compression-decompression pattern of the tissues.

Lipid profile and cardiovascular risk factors in pediatric liver transplant recipients.

Cardiovascular diseases induce long-term morbidity and mortality of adult LT recipients. The aim of this retrospective study was to assess CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT), more than 10 yr after pediatric LT. Thirty-one children who underwent LT between December 1990 and December 2000 were included. Median age at LT was 14 months (range 4-64), and median follow-up after LT was 11.9 yr (range 9.0-17.3). In our cohort, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients was smoker or diabetic. High TC and TG were both observed in 6.5% of the patients. The mean c-IMT for male patients was 1.22 ± 1.55 and 1.58 ± 1.23 mm in female patients. Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the 5th percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05). In conclusion, our results suggest that pediatric LT patients do not present significant CVRF; moreover, instead of hyperlipidemia, hypocholesterolemia (LDL-C) is frequent and immunosuppressive therapy is probably the cause.

Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis.

OBJECTIVE: Atherosclerotic plaque development in the arterial wall is the result of complex interaction between the wall's endothelial layer and blood hemodynamics. However, the interaction between hemodynamic parameters and inflammation in plaque evolution is not yet fully understood. The aim of the present study was to investigate the relation between wall shear stress (WSS) and vessel wall inflammation during atherosclerotic plaque development in a minipig model of carotid stenosis. METHODS: A surgical procedure was performed to create left common carotid artery stenosis by placement of a perivascular cuff in minipigs under atherogenic diet. Animals were followed up on 3T MRI, 1 week after surgery and 3, 6, and 8 months after initiation of the diet. Computational fluid dynamics simulation estimated WSS distribution for the first imaging point. Vascular geometries were co-registered for direct comparison of plaque development and features (Gadolinium- and USPIO-Contrast Enhanced MRI, for permeability and inflammation respectively) with the initial WSS. Histological analysis was performed and sections were matched to MR images, based on spatial landmarks. RESULTS: Vessel wall thickening, permeability and inflammation were observed distally from the stenosis. They were eccentric and facing regions of normal wall thickness. Histological analysis confirmed eccentric plaque formation with lipid infiltration, intimal thickening and medial degradation. High phagocytic activity in the stenosis region was co-localized with high WSS, corresponding to intense medial degradation observed on histology samples. CONCLUSION: Lower WSS promotes atherosclerotic plaque development distal to an induced stenosis. Vascular and perivascular inflammation locations were predominant in the high WSS stenosis segment, where medial thinning was the major consequence.

Real-time ultrasound-tagging to track the 2D motion of the common carotid artery wall in vivo.

PURPOSE: Tracking the motion of biological tissues represents an important issue in the field of medical ultrasound imaging. However, the longitudinal component of the motion (i.e., perpendicular to the beam axis) remains more challenging to extract due to the rather coarse resolution cell of ultrasound scanners along this direction. The aim of this study is to introduce a real-time beamforming strategy dedicated to acquire tagged images featuring a distinct pattern in the objective to ease the tracking. METHODS: Under the conditions of the Fraunhofer approximation, a specific apodization function was applied to the received raw channel data, in real-time during image acquisition, in order to introduce a periodic oscillations pattern along the longitudinal direction of the radio frequency signal. Analytic signals were then extracted from the tagged images, and subpixel motion tracking of the intima-media complex was subsequently performed offline, by means of a previously introduced bidimensional analytic phase-based estimator. RESULTS: The authors' framework was applied in vivo on the common carotid artery from 20 young healthy volunteers and 6 elderly patients with high atherosclerosis risk. Cine-loops of tagged images were acquired during three cardiac cycles. Evaluated against reference trajectories manually generated by three experienced analysts, the mean absolute tracking error was 98 ± 84 µm and 55 ± 44 µm in the longitudinal and axial directions, respectively. These errors corresponded to 28% ± 23% and 13% ± 9% of the longitudinal and axial amplitude of the assessed motion, respectively. CONCLUSIONS: The proposed framework enables tagged ultrasound images of in vivo tissues to be acquired in real-time. Such unconventional beamforming strategy contributes to improve tracking accuracy and could potentially benefit to the interpretation and diagnosis of biomedical images.

Progressive attenuation of the longitudinal kinetics in the common carotid artery: preliminary in vivo assessment.

Longitudinal kinetics (LOKI) of the arterial wall consists of the shearing motion of the intima-media complex over the adventitia layer in the direction parallel to the blood flow during the cardiac cycle. The aim of this study was to investigate the local variability of LOKI amplitude along the length of the vessel. By use of a previously validated motion-estimation framework, 35 in vivo longitudinal B-mode ultrasound cine loops of healthy common carotid arteries were analyzed. Results indicated that LOKI amplitude is progressively attenuated along the length of the artery, as it is larger in regions located on the proximal side of the image (i.e., toward the heart) and smaller in regions located on the distal side of the image (i.e., toward the head), with an average attenuation coefficient of -2.5 ± 2.0%/mm. Reported for the first time in this study, this phenomenon is likely to be of great importance in improving understanding of atherosclerosis mechanisms, and has the potential to be a novel index of arterial stiffness.

A new technique for the estimation of cardiac motion in echocardiography based on transverse oscillations: a preliminary evaluation in silico and a feasibility demonstration in vivo.

Quantification of regional myocardial motion and deformation from cardiac ultrasound is fostering considerable research efforts. Despite the tremendous improvements done in the field, all existing approaches still face a common limitation which is intrinsically connected with the formation of the ultrasound images. Specifically, the reduced lateral resolution and the absence of phase information in the lateral direction highly limit the accuracy in the computation of lateral displacements. In this context, this paper introduces a novel setup for the estimation of cardiac motion with ultrasound. The framework includes an unconventional beamforming technique and a dedicated motion estimation algorithm. The beamformer aims at introducing phase information in the lateral direction by producing transverse oscillations. The estimator directly exploits the phase information in the two directions by decomposing the image into two 2-D single-orthant analytic signals. An in silico evaluation of the proposed framework is presented on five ultra-realistic simulated echocardiographic sequences, where the proposed motion estimator is contrasted against other two phase-based solutions exploiting the presence of transverse oscillations and against block-matching on standard images. An implementation of the new beamforming strategy on a research ultrasound platform is also shown along with a preliminary in vivo evaluation on one healthy subject.

Simultaneous extraction of carotid artery intima-media interfaces in ultrasound images: assessment of wall thickness temporal variation during the cardiac cycle.

OBJECTIVES: The aim of this work is to present and evaluate a novel segmentation method for localizing the contours of the intima-media complex in the carotid artery wall through longitudinal ultrasound B-mode imaging. The method is used to investigate the association between atherosclerosis risk factors and the cyclic variation of the intima-media thickness during the heart beat. METHODS: The framework introduced is based on two main features. The first is a simultaneous extraction of both the lumen-intima and the media-adventitia interfaces, using the combination of an original shape-adapted filter bank and a specific dynamic programming scheme. The second is an innovative spatial transformation that eases the extraction of skewed and curved contours, and exploits the result from the previous image as a priori information, when processing the current image. The intima-media thickness is automatically derived from the estimated contours for each time step during the cardiac cycle. Our method was evaluated in vivo on 57 healthy volunteers and 25 patients at high cardiovascular risk. Reference contours were generated for each subject by averaging the tracings performed by three experienced observers. RESULTS: Segmentation errors were 29 ± 27 µm for the lumen-intima interface, 42 ± 38 µm for the media-adventitia interface, and 22 ± 16 µm for the intima-media thickness. This uncertainty was similar to inter- and intra-observer variability. Furthermore, the amplitude of the temporal variation in thickness of the intima-media layers during the cardiac cycle was significantly higher in at-risk patients compared to healthy volunteers (79 ± 36 vs. 64 ± 26 µm, p = 0.032). Conclusion: The method proposed may provide a relevant diagnostic aid for atherosclerosis screening in clinical studies.

Evaluation of a Kalman-based block matching method to assess the bi-dimensional motion of the carotid artery wall in B-mode ultrasound sequences.

We aim at investigating arterial diseases at early stage, by assessing the longitudinal (i.e. in the same direction as the blood flow) motion of the intima-media complex. This recently evidenced phenomenon has been shown to provide relevant and complementary information about vascular health. Our method assesses the longitudinal and radial motion from clinical in vivo B-mode ultrasound sequences. To estimate the trajectory of a selected point during the cardiac cycle, we introduce a block matching method that involves a temporal update of the reference block using a pixel-wise Kalman filter. The filter uses the initial gray-level of the pixel as control signal to avoid divergence due to cumulating errors. The block and search-window sizes are adapted to the tissue of interest. The method was evaluated on image sequences of the common carotid artery, acquired in 57 healthy volunteers and in 25 patients at high cardiovascular risk. Reference trajectories were generated for each sequence by averaging the tracings performed by three observers. Six different computerized techniques were also compared to our method. With a pixel size of 30 µm, the average absolute motion estimation errors were 84 ± 107 µm and 20 ± 19 µm for the longitudinal and radial directions, respectively. This accuracy was of the same order of magnitude as the inter- and intra-observers variability, and smaller than for the other methods. The estimated longitudinal motion amplitude was significantly reduced in at-risk patients compared with healthy volunteers (408 ± 281 µm vs. 643 ± 274 µm, p<0.0001). Our method can constitute a reliable and time-saving technique to investigate the arterial stiffness in clinical studies, in the objective to detect early-stage atherosclerosis.

Longitudinal displacement of the carotid wall and cardiovascular risk factors: associations with aging, adiposity, blood pressure and periodontal disease independent of cross-sectional distensibility and intima-media thickness.

The recently discovered longitudinal displacement of the common carotid arterial wall (i.e., the motion along the same plane as the blood flow), may be associated with incident cardiovascular events and represents a novel and relevant clinical information. At present, there have only been a few studies that have been conducted to investigate this longitudinal movement. We propose here a method to assess noninvasively the wall bi-dimensional (two-dimensional [2-D], cross-sectional and longitudinal) motion and present an original approach that combines a robust speckle tracking scheme to guidance by minimal path contours segmentation. Our method is well suited to large clinical population studies as it does not necessitate strong imaging prerequisites. The aim of this study is to describe the association between the longitudinal displacement of the carotid arterial wall and cardiovascular risk factors, among which periodontal disease. Some 126 Indigenous Australians with periodontal disease, an emerging risk factor, and 27 healthy age- and sex-matched non-indigenous control subjects had high-resolution ultrasound scans of the common carotid artery. Carotid intima-media thickness and arterial wall 2-D motion were then assessed using our method in ultrasound B-mode sequences. Carotid longitudinal displacement was markedly lower in the periodontal disease group than the control group (geometric mean (IQR): 0.15 mm (0.13) vs. 0.42 mm (0.30), respectively; p < 0.0001), independent of cardiovascular risk factors, cross-sectional distensibility and carotid intima-media thickness (p < 0.0001). A multivariable model indicated that the strongest correlates of carotid longitudinal displacement in adults with periodontal disease were age (ß-coefficient = -.235, p = .03), waist (ß-coefficient = -.357, p = 0.001), and pulse pressure (ß-coefficient = .175, p = 0.07), independent of other cardiovascular risk factors, cross-sectional distensibility and pulse wave velocity. Carotid longitudinal displacement, estimated with our approach, is impaired in the periodontal disease group, independent of established cardiovascular risk factors and other noninvasive measures of arterial stiffness, and may represent an important marker of cardiovascular risk.

Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus.

OBJECTIVES: REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. METHODS: Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. RESULTS: At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30 ± 0.80 to 7.77 ± 1.31 versus pioglitazone: from 8.30 ± 0.80 to 7.45 ± 1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. CONCLUSION: After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug.

Measurement of two-dimensional movement parameters of the carotid artery wall for early detection of arteriosclerosis: a preliminary clinical study.

The aim of this study was to clinically investigate the association between the risk factors of early-stage atherosclerosis and the two-dimensional (2-D) movement of the artery wall. To meet this objective, a speckle tracking approach for the estimation of the 2-D trajectory of the vessel wall was proposed and applied to B-mode ultrasound (US) sequences of the left common carotid artery (CCA). A deformable skeleton model was also introduced in the block matching scheme. Finally, the 2-D movements of both proximal and distal walls were investigated in three different local regions, with 1.5 × 0.3 mm(2) kernel blocks. A clinical study was conducted in which two different populations (26 young healthy volunteers and 26 older diabetic patients) were studied. The results show that the mean amplitude value of the diameter change ΔD, of the longitudinal displacement of the proximal wall ΔX(p) and of the longitudinal displacement of the distal wall ΔX(d) were 0.65 ± 0.17 vs. 0.41 ± 0.12 mm (p < 0.001), 0.48 ± 0.21 vs. 0.26 ± 0.18 mm (p < 0.001) and 0.48 ± 0.20 vs. 0.35 ± 0.23 mm (p = 0.006) for the young healthy volunteers and the older diabetic patients, respectively. The results of the three dynamic parameters ΔD, ΔX(p) and ΔX(d) were systematically and significantly lower for the diabetic subjects, respectively 37%, 46% and 27%. The method introduced in this feasibility study might constitute a pertinent approach to assess the presence of early-stage arteriosclerosis by the noninvasive estimation of the 2-D motion of the intima-media complex in the CCA.

Carotid intima-media and adventitial thickening: comparison of new and established ultrasound and magnetic resonance imaging techniques.

OBJECTIVE: Carotid intima-media thickness is a well established non-invasive surrogate marker of cardiovascular disease, however there is evidence that structural modification of the arterial adventitia also accompanies cardiovascular risk factors and might be involved causally in atherosclerosis. We sought to determine the relative contributions of the intima-media and adventitia to variation in ultrasound and magnetic resonance derived measures of carotid wall thickness. METHODS: Carotid ultrasound and magnetic resonance imaging were undertaken in 20 participants. Carotid intima-media thickness, carotid extra-media thickness (which incorporates the arterial adventitia) and total wall thickness (a combined near-wall intima-media thickness and carotid extra-media thickness) using high-resolution ultrasound, and wall thickness using magnetic resonance imaging, were obtained. RESULTS: All ultrasound-derived measures of the arterial wall thickness were highly correlated with wall thickness by magnetic resonance imaging (all P<0.001); as expected the total wall thickness by ultrasound measure was most tightly correlated (correlation coefficient=0.814, P<0.0001). In multivariable models, there was evidence that both carotid intima-media thickness and carotid extra-media thickness contributed independently to the variance in wall thickness by magnetic resonance imaging, especially for the most severe focal thickening. Measures of carotid wall thickness that incorporated all three layers of the arterial wall were more closely correlated with the number of cardiovascular risk factors than carotid intima-media thickness alone. CONCLUSIONS: These results indicate that the arterial adventitia is an important contributor to the wall thickness measure derived by magnetic resonance imaging, and that carotid extra-media thickness likely provides additional information concerning arterial structure than that obtained from carotid intima-media thickness alone.

Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: a preliminary study.

BACKGROUND: There is a need to identify diabetic patients at risk of cardiovascular events before symptom onset. AIMS: To evaluate the prevalence and characteristics of coronary atherosclerotic plaques in asymptomatic type 2 diabetic patients with coronary risk factors but without known coronary artery disease, using multidetector computed tomography. METHODS: High-resolution 40-slice coronary computed tomography was performed prospectively in 42 consecutive type 2 diabetic patients (mean age 62 years; range 50-77 years; 28 men) with over one or more carotid atherosclerotic plaque and no coronary artery disease symptoms. Computed tomography data were evaluated for calcium score and the presence of coronary plaques. Plaque type, distribution, extensive character and obstructive nature were determined per patient for each segment. RESULTS: No plaques were detected in 11 (26.2%) patients. Atherosclerotic plaques were detected in 31 (73.8%) patients. A total of 147 coronary segments with plaque were identified, of which 11 (7.5%) contained hypodense plaques, 28 (19%) mixed plaques and 108 (73.5%) calcified plaques. Hypodense plaques were noted in 4/15 (26.7%) patients without coronary calcifications. Most calcified and hypodense plaques resulted in lumen narrowing of less than 50%; most mixed plaques resulted in lumen narrowing greater than 50%. Obstructive disease was detected in 9/11 patients with a high calcium score (>400). CONCLUSION: This preliminary study demonstrates that a high proportion of asymptomatic type 2 diabetic patients present without coronary plaques detectable by multidetector computed tomography, despite concomitant carotid atherosclerotic lesions. Computed tomography seems to detect a high proportion of plaques compared with conventional angiography in these specific patients.

Noninvasive measurement of carotid extra-media thickness: associations with cardiovascular risk factors and intima-media thickness.

OBJECTIVES: We sought to develop a noninvasive technique to quantify the thickness of a segment of the carotid artery wall that incorporates the adventitia and to identify whether differences in this measure are associated with cardiovascular risk factors. BACKGROUND: There is increasing evidence that the arterial adventitia undergoes extensive structural alteration, including thickening, in response to arterial injury. However, there is currently no widely accepted noninvasive technique for studying the thickness of the arterial adventitia in humans. METHODS: The carotid artery and jugular vein were imaged simultaneously in longitudinal section with the use of high-resolution ultrasound. The distance from the jugular intima-lumen interface to the carotid media-adventitia margin was denominated as the carotid extra-media thickness (EMT). This measure includes the arterial adventitia but not the arterial intima or media. We measured the carotid EMT and intima-media thickness (IMT) in 175 subjects, including 54 with diabetes, 43 with dyslipidemia, 26 with other cardiovascular risk factors, and 52 healthy control subjects. RESULTS: When compared with control subjects, the EMT was increased in both the diabetes (p < 0.0001) and dyslipidemia (p = 0.04) groups. Multivariate linear regression analyses revealed that diabetes, high-density lipoprotein cholesterol (inverse association), and systolic blood pressure (J-shaped association) were the factors most strongly associated with EMT. These associations appear to be independent of carotid IMT. CONCLUSIONS: Carotid EMT can be assessed by ultrasonography. It is physically distinct from IMT and provides additional information concerning the vascular changes associated with cardiovascular risk factors. As such, the measurement of EMT, in addition to IMT, may provide a more complete indication of the structural modification of the vasculature associated with cardiovascular risk factors than that obtained by the measurement of carotid IMT alone.

Parity and carotid atherosclerosis in men and women: insights into the roles of childbearing and child-rearing.

BACKGROUND AND PURPOSE: Parity appears to be associated with carotid atherosclerosis in women aged 45 years and older. Studying this association among younger women and men may provide insight into whether this association relates predominantly to childbearing or child-rearing. METHODS: The association between parity and carotid atherosclerosis (intima-media thickness and presence of plaques) was assessed in a cohort consisting of 750 women and 1164 men, all with at least one traditional cardiovascular risk factor, aged 18 to 80 years of age. Traditional cardiovascular risk factors were also assessed, and the Framingham Risk Score calculated. RESULTS: In age-adjusted analyses, the number of children was associated with adiposity, fasting glucose, 2-hour glucose, Framingham risk score, and carotid atherosclerosis in women, but not in men. Multivariate linear regression models indicate that the prevalence of plaques was increased by 15% (95% CI, 2 to 29) per child among women, and 0% (95% CI, -10 to 11) among men, after adjustment for age, socioeconomic and lifestyle factors (including waist circumference). The association between parity and carotid intima-media thickness was similar in younger and older women (P(Heterogeneity)=0.20). CONCLUSIONS: A higher number of children is associated with increased carotid atherosclerosis in both younger and older women, but not among men. These findings indicate that childbearing, but not child-rearing, may be a risk factor for atherosclerosis, and suggest the potential importance of considering the number of children when assessing the level of cardiovascular risk in women.

Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in type 2 diabetic patients with coronary noncalcified plaques evaluated by multidetector computed tomography (MDCT).

OBJECTIVE: The combination of both morphological and cellular markers of subclinical atherosclerosis, in addition to conventional risk factors, may help to improve cardiovascular prevention in type 2 diabetic patients. The aim of our cross-sectional study was to evidence a putative increase in endothelial (EMP) or platelet (PMP) microparticles, in type 2 diabetic patients with coronary noncalcified plaques detected by multidetector CT (MDCT). METHODS AND RESULTS: Microparticles and coronary MDCT were assessed in 56 type 2 diabetic patients with different cardiovascular risk levels. Both EMP (r=0.35, p=0.022) and PMP (rho=0.34, p=0.022) were correlated with hsCRP. EMP were elevated in patients with acute coronary syndromes (p=0.034). EMP count was significantly higher in the presence of noncalcified diseased segments (p=0.01). By contrast, there was no association between hsCRP and noncalcified atheroma. This increase in EMP in noncalcified diseased segment carriers remained borderline significant after adjustment for coronary heart disease and hsCRP. Conversely, there was no association of PMP count with noncalcified diseased segments and no difference in PMP count between patients with and without acute coronary syndrome. No significant association between either EMP and PMP counts and mixed or calcified diseased segments was observed. CONCLUSIONS: We report for the first time an association between plasma EMP-CD144+ and coronary noncalcified plaques assessed by MDCT in a population of type 2 diabetic patients. EMP might be used as a surrogate marker of unstable plaques, and might help to improve cardiovascular prediction in diabetic patients with intermediate risk.